WorldWideScience

Sample records for abrogates son binding

  1. Tyrosine phosphorylation of Munc18c on residue 521 abrogates binding to Syntaxin 4

    Directory of Open Access Journals (Sweden)

    Bryant Nia J

    2011-05-01

    Full Text Available Abstract Background Insulin stimulates exocytosis of GLUT4 from an intracellular store to the cell surface of fat and muscle cells. Fusion of GLUT4-containing vesicles with the plasma membrane requires the SNARE proteins Syntaxin 4, VAMP2 and the regulatory Sec1/Munc18 protein, Munc18c. Syntaxin 4 and Munc18c form a complex that is disrupted upon insulin treatment of adipocytes. Munc18c is tyrosine phosphorylated in response to insulin in these cells. Here, we directly test the hypothesis that tyrosine phosphorylation of Munc18c is responsible for the observed insulin-dependent abrogation of binding between Munc18c and Syntaxin 4. Results We show that Munc18c is directly phosphorylated by recombinant insulin receptor tyrosine kinase in vitro. Using pull-down assays, we show that phosphorylation abrogates binding of Munc18c to both Syntaxin 4 and the v-SNARE VAMP2, as does the introduction of a phosphomimetic mutation into Munc18c (Y521E. Conclusion Our data indicate that insulin-stimulated tyrosine phosphorylation of Munc18c impairs the ability of Munc18c to bind its cognate SNARE proteins, and may therefore represent a regulatory step in GLUT4 traffic.

  2. HCV NS5A abrogates p53 protein function by interfering with p53-DNA binding

    Institute of Scientific and Technical Information of China (English)

    Guo-Zhong Gong; Yong-Fang Jiang; Yan He; Li-Ying Lai; Ying-Hua Zhu; Xian-Shi Su

    2004-01-01

    AIM: To evaluate the inhibition effect of HCV NS5A on p53 transactivation on p21 promoter and explore its possible mechanism for influencing p53 function.METHODS: p53 function of transactivation on p21 promoter was studied with a luciferase reporter system in which the luciferase gene is driven by p21 promoter, and the p53-DNA binding ability was observed with the use of electrophoretic mobility-shift assay (EMSA). Lipofectin mediated p53 or HCV NS5A expression vectors were used to transfect hepatoma cell lines to observe whether HCV NS5A could abrogate the binding ability of p53 to its specific DNA sequence and p53 transactivation on p21 promoter.Western blot experiment was used for detection of HCV NS5A and p53 proteins expression.RESULTS: Relative luciferase activity driven by p21 promoter increased significantly in the presence of endogenous p53 protein. Compared to the control group, exogenous p53 protein also stimulated p21 promoter driven luciferase gene expression in a dose-dependent way. HCV NS5A protein gradually inhibited both endogenous and exogenous p53 transactivation on p21 promoter with increase of the dose of HCV NS5A expression plasmid. By the experiment of EMSA, we could find p53 binding to its specific DNA sequence and, when co-transfected with increased dose of HCV NS5A expression vector, the p53 binding affinity to its DNA gradually decreased and finally disappeared. Between the Huh 7 cells transfected with p53 expression vector alone or co-transfected with HCV NS5A expression vector, there was no difference in the p53 protein expression.CONCLUSION: HCV NS5A inhibits p53 transactivation on p21 promoter through abrogating p53 binding affinity to its specific DNA sequence. It does not affect p53 protein expression.

  3. NS1-binding protein abrogates the elevation of cell viability by the influenza A virus NS1 protein in association with CRKL

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, Masaya [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Nishihara, Hiroshi, E-mail: hnishihara@med.hokudai.ac.jp [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Hasegawa, Hideki [Department of Pathology, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan); Tashiro, Masato [Influenza Virus Research Center, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan); Wang, Lei [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Kimura, Taichi; Tanino, Mishie; Tsuda, Masumi [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Tanaka, Shinya [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan)

    2013-11-29

    Highlights: •NS1 induced excessive phosphorylation of ERK and elevated cell viability. •NS1-BP expression and CRKL knockdown abolished survival effect of NS1. •NS1-BP and NS1 formed the complex through the interaction with CRKL-SH3(N). -- Abstract: The influenza A virus non-structural protein 1 (NS1) is a multifunctional virulence factor consisting of an RNA binding domain and several Src-homology (SH) 2 and SH3 binding motifs, which promotes virus replication in the host cell and helps to evade antiviral immunity. NS1 modulates general host cell physiology in association with various cellular molecules including NS1-binding protein (NS1-BP) and signaling adapter protein CRK-like (CRKL), while the physiological role of NS1-BP during influenza A virus infection especially in association with NS1 remains unclear. In this study, we analyzed the intracellular association of NS1-BP, NS1 and CRKL to elucidate the physiological roles of these molecules in the host cell. In HEK293T cells, enforced expression of NS1 of A/Beijing (H1N1) and A/Indonesia (H5N1) significantly induced excessive phosphorylation of ERK and elevated cell viability, while the over-expression of NS1-BP and the abrogation of CRKL using siRNA abolished such survival effect of NS1. The pull-down assay using GST-fusion CRKL revealed the formation of intracellular complexes of NS1-BP, NS1 and CRKL. In addition, we identified that the N-terminus SH3 domain of CRKL was essential for binding to NS1-BP using GST-fusion CRKL-truncate mutants. This is the first report to elucidate the novel function of NS1-BP collaborating with viral protein NS1 in modulation of host cell physiology. In addition, an alternative role of adaptor protein CRKL in association with NS1 and NS1-BP during influenza A virus infection is demonstrated.

  4. A novel thromboxane A2 receptor D304N variant that abrogates ligand binding in a patient with a bleeding diathesis

    Science.gov (United States)

    Mumford, Andrew D.; Dawood, Ban B.; Daly, Martina E.; Murden, Sherina L.; Williams, Michael D.; Protty, Majd B.; Spalton, Jennifer C.; Wheatley, Mark; Mundell, Stuart J.; Watson, Steve P.

    2015-01-01

    We investigated the cause of mild mucocutaneous bleeding in a 14-year-old male patient (P1). Platelet aggregation and ATP secretion induced by arachidonic acid and the thromboxane A2 receptor (TxA2R) agonist U46619 were reduced in P1 compared with controls, whereas the responses to other platelet agonists were retained. P1 was heterozygous for a transversion within the TBXA2R gene predictive of a D304N substitution in the TxA2R. In Chinese hamster ovary-K1 cells expressing the variant D304N TxA2R, U46619 did not increase cytosolic free Ca2+ concentration, indicating loss of receptor function. The TxA2R antagonist [3H]-SQ29548 showed an approximate 50% decrease in binding to platelets from P1 but absent binding to Chinese hamster ovary-K1 cells expressing variant D304N TxA2R. This is the second naturally occurring TxA2R variant to be associated with platelet dysfunction and the first in which loss of receptor function is associated with reduced ligand binding. D304 lies within a conserved NPXXY motif in transmembrane domain 7 of the TxA2R that is a key structural element in family A G protein-coupled receptors. Our demonstration that the D304N substitution causes clinically significant platelet dysfunction by reducing ligand binding establishes the importance of the NPXXY motif for TxA2R function in vivo. PMID:19828703

  5. A single amino acid substitution (Trp(666)-->Ala) in the interbox1/2 region of the interleukin-6 signal transducer gp130 abrogates binding of JAK1, and dominantly impairs signal transduction.

    Science.gov (United States)

    Haan, C; Hermanns, H M; Heinrich, P C; Behrmann, I

    2000-07-01

    gp130 is the common signal-transducing receptor chain of interleukin (IL)-6-type cytokines. Here we describe, for the first time, a single amino acid substitution (Trp(666)-->Ala) in the membrane-proximal interbox1/2 region that abrogates activation of STAT (signal transducer and activator of transcription) transcription factors and the proliferative response of pro-B-cell transfectants. Moreover, association of the Janus kinase JAK1 is prevented. No signalling of heterodimeric IL-5 receptor (IL-5R)/gp130 chimaeras occurs in COS-7 cells, even when only a single cytoplasmic chain of a gp130 dimer contains the Trp(666)Ala mutation, indicating that it acts dominantly.

  6. Son: Part One

    Directory of Open Access Journals (Sweden)

    Jennifer Higgie

    2004-08-01

    Full Text Available It is 1842. Two Englishman set out on a Grand Tour of Europe and the Middle East. One is a young, gifted artist; the other a Gentleman. By the time they return to England, the artist has become a devotee of the Egyptian god Osiris. One night, after dining together in a small inn in Cobham, he violently murders his beloved father, believing him to be an imposter. Why? Son is a novel inspired by the life of Richard Dadd, one of the greatest Victorian painters and inmate of Bethlem Hospital - more commonly known as Bedlam. Part Two of Son will be published in Portal vol. 2, no. 1, January 2005.

  7. Son: Part Two

    Directory of Open Access Journals (Sweden)

    Jennifer Higgie

    2005-03-01

    Full Text Available It is 1842. Two Englishman set out on a Grand Tour of Europe and the Middle East. One is a young, gifted artist; the other a Gentleman. By the time they return to England, the artist has become a devotee of the Egyptian god Osiris. One night, after dining together in a small inn in Cobham, he violently murders his beloved father, believing him to be an imposter. Why? Son is a novel inspired by the life of Richard Dadd, one of the greatest Victorian painters and inmate of Bethlem Hospital - more commonly known as Bedlam. Part one of Son was published in PORTAL vol. 1, no. 2, in July 2004. This is the second and concluding part of the novel.

  8. Son, Sent, and Servant

    Directory of Open Access Journals (Sweden)

    Truls Åkerlund

    2015-11-01

    Full Text Available This study challenges the claim that Jesus is the archetypical servant leader as described in contempo-rary leadership literature. Based on a theological reading of the Fourth Gospel, the paper suggests that, as a servant, Jesus cannot be understood apart from his mission and obedience to God. Consequently, Jesus was not primarily a servant leader but rather the Son who was sent to the world to enact the Fa-ther’s will. In this regard, the Fourth Gospel provides a unique perspective that is barely noted in the current discourse on servant leadership modelled on the example of Christ. Although certain aspects of servant leadership theory correspond to John’s portrayal of Jesus, the study concludes that other de-scriptions of him as a servant leader suffer from a one-sided and reductionist Christology. Implications of this view for Christian ministry are briefly sketched out.

  9. À chacun son puzzle

    Directory of Open Access Journals (Sweden)

    Jean-Noël Ferrié

    2012-05-01

    Full Text Available Le texte soutient que le « tournant naturaliste » que l’on nous invite à négocier ne donne aucun moyen supplémentaire pour parvenir à une description perspicace de ce que les gens font dans des circonstances précises, l’existence humaine pouvant être considérée comme une collection de circonstances précises. Sans doute le naturalisme nous permet-il de comprendre comment certaines actions humaines sont possibles, mais cela ne nous dit pas pourquoi et comment elles font sens pour tout un chacun. La méthodologie nécessaire pour éclaircir le premier point obscurcit généralement le second. Le mieux est donc de considérer que les deux approches ne vont pas de pair. Ce point de vue est soutenu à partir d’exemple tirés de l’anthropologie de la religion.To each one his puzzle. For a serene methodological pluralismThe text argues that the « naturalistic turn » that we are invited to negotiate does not give any additional means to achieve an insightful description of what people do in specific circumstances, and human existence can be considered as a collection of specific circumstances. Probably naturalism allows us to understand how some human actions are possible, but that does not tell us why and how they make sense for everyone. The methodology needed to clarify the first point usually obscures the second one. The best way is to consider that the two approaches do not go together. The text supports this view from an example drawn from the anthropology of religion.A cada uno su rompecabezas. En favor de un pluralismo metodológico serenoEl texto argumenta que la inflexión naturalista a la que se nos invita a participar no proporciona ningún medio suplementario que desemboque en una descripción perspicaz de lo que la gente hace en circunstancias concretas ya que la existencia humana puede ser considerada como una concatenación de circunstancias concretas. Sin duda el naturalismo nos permite comprender como son

  10. Nutritional abrogation of photoimmunosuppression: in vivo investigations.

    Science.gov (United States)

    Pilkington, Suzanne M; Gibbs, Neil K; Friedmann, Peter S; Rhodes, Lesley E

    2014-01-01

    Skin cancer is a major public health concern, and the primary aetiological factor in the majority of skin cancers is ultraviolet radiation (UVR) exposure. UVR not only induces potentially mutagenic DNA damage but also suppresses cell-mediated immunity (CMI), allowing cancerous cells to escape destruction and progress to tumours. A considerable proportion of an individual's annual sun exposure is obtained outside the vacation period when topical and physical measures for photoprotection are irregularly used. Certain nutrients could provide an adjunctive protective role, and evidence is accruing from experimental studies to support their use in abrogation of photoimmunosuppression. Moreover, developments in clinical research methods to evaluate impact of solar-simulated radiation on cutaneous CMI allow the immune protective potential of nutritional agents to be examined in humans in vivo. This article summarises the mediation of CMI and its suppression by UVR, evaluates the methodology for quantitative assessment in vivo, reviews the human studies reported on nutritional abrogation of photoimmunosuppression including recent randomized controlled trials and discusses the mechanisms of photoprotection by the nutrients. This includes, in addition to antioxidants, novel studies of omega-3 polyunsaturated fatty acids and nicotinamide.

  11. Determinants of mitotic catastrophe on abrogation of the G2 DNA damage checkpoint by UCN-01.

    Science.gov (United States)

    On, Kin Fan; Chen, Yue; Ma, Hoi Tang; Chow, Jeremy P H; Poon, Randy Y C

    2011-05-01

    Genotoxic stress such as ionizing radiation halts entry into mitosis by activation of the G(2) DNA damage checkpoint. The CHK1 inhibitor 7-hydroxystaurosporine (UCN-01) can bypass the checkpoint and induce unscheduled mitosis in irradiated cells. Precisely, how cells behave following checkpoint abrogation remains to be defined. In this study, we tracked the fates of individual cells after checkpoint abrogation, focusing in particular on whether they undergo mitotic catastrophe. Surprisingly, while a subset of UCN-01-treated cells were immediately eliminated during the first mitosis after checkpoint abrogation, about half remained viable and progressed into G(1). Both the delay of mitotic entry and the level of mitotic catastrophe were dependent on the dose of radiation. Although the level of mitotic catastrophe was specific for different cell lines, it could be promoted by extending the mitosis. In supporting this idea, weakening of the spindle-assembly checkpoint, by either depleting MAD2 or overexpressing the MAD2-binding protein p31(comet), suppressed mitotic catastrophe. Conversely, delaying of mitotic exit by depleting either p31(comet) or CDC20 tipped the balance toward mitotic catastrophe. These results underscore the interplay between the level of DNA damage and the effectiveness of the spindle-assembly checkpoint in determining whether checkpoint-abrogated cells are eliminated during mitosis.

  12. Achalasia in father and son.

    Science.gov (United States)

    Mackler, D; Schneider, R

    1978-11-01

    Achalasia has not been previously reported in father and son. A man, age 38, and his father, age 66, presented two years apart with symptoms of dysphagia and aspiration. The diagnosis of achalasia was made on the basis of x-ray and endoscopic findings and on esophageal motility studies performed on the father. Both responded well to pneumatic dilatation and have been asymptomatic for 24 months and 6 months, respectively. These cases again suggest a genetic basis for achalasia.

  13. Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation

    DEFF Research Database (Denmark)

    Connolly, Brian M; Choi, Eun Young; Gårdsvoll, Henrik;

    2010-01-01

    the interaction between endogenous uPA and uPAR is selectively abrogated, whereas other functions of both the protease and its receptor are retained. Specifically, we introduced 4 amino acid substitutions into the growth factor domain (GFD) of uPA that abrogate uPAR binding while preserving the overall structure...... of the domain. Analysis of Plau(GFDhu/GFDhu) mice revealed an unanticipated role of the uPA-uPAR interaction in suppressing inflammation secondary to fibrin deposition. In contrast, leukocyte recruitment and tissue regeneration were unaffected by the loss of uPA binding to uPAR. This study identifies...

  14. New discoveries of old SON: a link between RNA splicing and cancer.

    Science.gov (United States)

    Hickey, Christopher J; Kim, Jung-Hyun; Ahn, Eun-Young Erin

    2014-02-01

    The SON protein is a ubiquitously expressed DNA- and RNA-binding protein primarily localized to nuclear speckles. Although several early studies implicated SON in DNA-binding, tumorigenesis and apoptosis, functional significance of this protein had not been recognized until recent studies discovered SON as a novel RNA splicing co-factor. During constitutive RNA splicing, SON ensures efficient intron removal from the transcripts containing suboptimal splice sites. Importantly, SON-mediated splicing is required for proper processing of selective transcripts related to cell cycle, microtubules, centrosome maintenance, and genome stability. Moreover, SON regulates alternative splicing of RNAs from the genes involved in apoptosis and epigenetic modification. In addition to the role in RNA splicing, SON has an ability to suppress transcriptional activation at certain promoter/enhancer DNA sequences. Considering the multiple SON target genes which are directly involved in cell proliferation, genome stability and chromatin modifications, SON is an emerging player in gene regulation during cancer development and progression. Here, we summarize available information from several early studies on SON, and highlight recent discoveries describing molecular mechanisms of SON-mediated gene regulation. We propose that our future effort on better understanding of diverse SON functions would reveal novel targets for cancer therapy.

  15. Son huasteco e identidad regional

    Directory of Open Access Journals (Sweden)

    Rosa María Bonilla Burgos

    2013-01-01

    Full Text Available La población de la región Huasteca es partícipe de manifestaciones musicales en diferentes ámbitos, lo cual permite reconocer que entre todos los géneros utilizados destaca el son huasteco y su correspondiente bailable llamado huapango. Dichas expresiones musicales se impregnan de los ambientes tanto físico como social que viven constantemente. Es a través de las letras de los sones huastecos que se desarrolla el mecanismo para reflejar el mundo natural que perciben, y los acontecimientos que les suceden, cobrando una importancia que deriva en una identificación que trasciende. Conciben su entorno y lo refieren con sentido de pertenencia-apropiación, que les permite recrear su vida y fundirse en una identificación cultural a la que se le llamará "identidad regional". La relevancia de considerar una expresión musical de estas características radica en que se preserva y enriquece constantemente unificando un área de México que no necesariamente corresponde a límites políticos establecidos en las diferentes etapas históricas.

  16. Policy-based SON management demonstrator

    NARCIS (Netherlands)

    Lohmuller, S.; Eisenblatter, A.; Frenzel, C.; Gotz, D.; Hahn, S.; Kurner, T.; Litjens, R.; Lobinger, A.; Sas, B.; Schmelz, L.C.; Turke, U.

    2015-01-01

    A Self-Organising Network (SON) represents an approach where the optimisation of a mobile radio network is automated through a set of independently operating SON functions. These SON functions, however, require to be configured in order to allow for an optimised network performance with respect to t

  17. Are we ready to abrogate compulsory vaccinations for children?

    Science.gov (United States)

    Martinelli, Domenico; Tafuri, Silvio; Fortunato, Francesca; Cozza, Vanessa; Germinario, Cinzia A; Prato, Rosa

    2015-01-01

    In Italy, vaccination against diphtheria, tetanus, polio and hepatitis B is compulsory for infants countrywide, except in Veneto region where since 2007 Health Authorities have experimented the suspension of mandatory vaccination. In light of the recent discussion on the potential abrogation in other regions, we explored the opinion of family pediatricians who play a crucial role in promoting immunization programmes in Italy. In November 2009, we interviewed by phone the family pediatricians working in Puglia region using a standardised, ad hoc and piloted questionnaire. Of the 596 contacted, 502 (84.2%) completed the questionnaire (54% female, median age = 52 y). Among the respondents, 72 (14.3%) would agree on the hypothesis of abrogation. This judgment was associated with having a good opinion on the level of awareness of the importance of vaccinations in the general public (OR = 6.6; 95% CI: 3.6-12.1) and having the perception of adequate organization of Vaccination Services in supporting the abrogation (OR = 3.6; 95% CI: 1.7-5.9). Family pediatricians appeared really sceptical about the abrogation of compulsory vaccination that could be hypothesized only increasing public awareness, communication skills and capability of Vaccination Services personnel in offering vaccinations.

  18. Preference for sons: past and present.

    Science.gov (United States)

    Li, D

    1997-10-01

    This brief article discusses the present and past preference for sons in China. The preference for sons is rooted in feudal views that men are superior to women. Preference for sons dates back to the Warring States Period, in about 500 B.C. Clan brotherhoods of men have existed for centuries. Historical records mention the practice of female infanticide. Patriarchal families believed that women were economically dependent on men and thus became their subjects. Daughters married, lived in their husband's home, and did not carry the responsibility of caring for their own parents. Couples with only daughters would seek a son-in-law to support them in old age. Rural families with no sons were looked down upon. Sons were expected to carry on the family lineage, increase the reputation of the family, and protect the family's interests. The lack of sons was a sign of humiliation and a curse. The founding of the People's Republic of China brought changes to son preference. The government attempted to increase women's status. In rural areas, women were given equal access to the land. Job opportunities were created for women during the industrialization drive. The Chinese government encouraged the repudiation of the negative impacts of the doctrines of Confucius and Mencius. Efforts were made to give men and women equal pay for equal work. Legislation was passed prohibiting arranged marriage, polygyny, and early marriage. A side effect of fertility decline is the renewed preference for sons. In Huangyan and Haining in Zhejiang, a developed province, the sex ratio at birth is normal. Sexual division of labor reinforces son preference.

  19. Carbamoylation abrogates the antioxidant potential of hydrogen sulfide.

    Science.gov (United States)

    Praschberger, Monika; Hermann, Marcela; Laggner, Christian; Jirovetz, Leopold; Exner, Markus; Kapiotis, Stylianos; Gmeiner, Bernhard M K; Laggner, Hilde

    2013-11-01

    Hydrogen sulfide (H2S) has been identified as the third gasotransmitter. Beside its role as signaling molecule in the cardiovascular and nervous system the antioxidant and cyto-protective properties of H2S have gained much attention. In the present study we show that cyanate, an uremic toxin which is found in abundant concentration in sera of patients suffering from chronic kidney disease (CKD), can abrogate the antioxidant and cytoprotective activity of H2S via S-carbamoylation reaction, a reaction that previously has only been shown to have a physiological effect on cysteine groups, but not on H2S. Carbamoylation strongly inhibited the free radical scavenging (ABTS(+·) and alkylperoxyl ROO(·)) properties of H2S. The extent of intracellular ROS formation induced by ROO(·) was diminished by H2S whereas carbamoylation counteracted the protective effect. Reagent HOCl was rapidly inactivated by H2S in contrast to the carbamoylated compound. Protein modification by HOCl was inhibited by H2S but carbamoylation significantly reduced the effect. Thus, S-carbamoylation of low molecular weight thiols by abrogating their antioxidant potential may contribute to the higher oxidative stress observed in CKD.

  20. Neuroblastoma-targeted nanocarriers improve drug delivery and penetration, delay tumor growth and abrogate metastatic diffusion.

    Science.gov (United States)

    Cossu, Irene; Bottoni, Gianluca; Loi, Monica; Emionite, Laura; Bartolini, Alice; Di Paolo, Daniela; Brignole, Chiara; Piaggio, Francesca; Perri, Patrizia; Sacchi, Angelina; Curnis, Flavio; Gagliani, Maria Cristina; Bruno, Silvia; Marini, Cecilia; Gori, Alessandro; Longhi, Renato; Murgia, Daniele; Sementa, Angela Rita; Cilli, Michele; Tacchetti, Carlo; Corti, Angelo; Sambuceti, Gianmario; Marchiò, Serena; Ponzoni, Mirco; Pastorino, Fabio

    2015-11-01

    Selective tumor targeting is expected to enhance drug delivery and to decrease toxicity, resulting in an improved therapeutic index. We have recently identified the HSYWLRS peptide sequence as a specific ligand for aggressive neuroblastoma, a childhood tumor mostly refractory to current therapies. Here we validated the specific binding of HSYWLRS to neuroblastoma cell suspensions obtained either from cell lines, animal models, or Schwannian-stroma poor, stage IV neuroblastoma patients. Binding of the biotinylated peptide and of HSYWLRS-functionalized fluorescent quantum dots or liposomal nanoparticles was dose-dependent and inhibited by an excess of free peptide. In animal models obtained by the orthotopic implant of either MYCN-amplified or MYCN single copy human neuroblastoma cell lines, treatment with HSYWLRS-targeted, doxorubicin-loaded Stealth Liposomes increased tumor vascular permeability and perfusion, enhancing tumor penetration of the drug. This formulation proved to exert a potent antitumor efficacy, as evaluated by bioluminescence imaging and micro-PET, leading to (i) delay of tumor growth paralleled by decreased tumor glucose consumption, and (ii) abrogation of metastatic spreading, accompanied by absence of systemic toxicity and significant increase in the animal life span. Our findings are functional to the design of targeted nanocarriers with potentiated therapeutic efficacy towards the clinical translation.

  1. "Mama's Boy; Preacher's Son": A Memoir

    Science.gov (United States)

    Whitlock, Reta Ugena

    2010-01-01

    "Mama's Boy; Preacher's Son" is Kevin Jennings's autobiographical account of growing up gay in the Southern United States. In his memoir, Jennings shares formative experiences relating to his impoverished childhood and his career as teacher and social activist. His rich description of the influence of family relationships on his personal and…

  2. Cuidados invisibles: ¿son suficientemente reconocidos?

    Directory of Open Access Journals (Sweden)

    Rosanna de la Rosa Eduardo

    Full Text Available Los cuidados invisibles son un elemento central y fundamental de la práctica de la Enfermería y son la base de su identidad profesional. La Enfermería ha sufrido un importante y positivo proceso de profesionalización en los últimos 150 años, sin embargo, los cuidados invisibles siguen siendo poco reconocidos, a pesar de su importancia en la recuperación y en la calidad de vida de los usuarios. En este trabajo se analizan brevemente las grandes transformaciones sociales actuales que obligan a replantearse la necesidad de visibilizar los cuidados invisibles, se plantean interrogantes clave para abordar esta discusión y se proponen una serie de acciones concretas para avanzar en este reconocimiento.

  3. Compression des fichiers son de type wave.

    OpenAIRE

    BAKLI, Meriem

    2014-01-01

    Ce travail de projet de fin d’étude s’intéresse à une étude comparative sur la compression d’un fichier son. La compression est l'action utilisée pour réduire la taille physique d'un bloc d'information.. Il existe plusieurs algorithmes pour la compression comme HUFFMAN, …etc. Nous avons fait la compression d’un fichier son de format WAVE non compressé à un fichier MP3 compressé avec différent format de codage, différent frame et quelque soit le fichier mono où stéréo. A partir ...

  4. Paradox of Denials in All My Sons

    Institute of Scientific and Technical Information of China (English)

    雷慧慧

    2014-01-01

    Arthur Miller, who was one of the greatest American playwrights of the 20th century. In All My Sons, different sorts of denials lead to the family’s collapse and Keller’s death. Paradoxically, the very denial that is designed to protect him from prose-cution and incarceration is followed by a chain of events that lead to Keller’s own self-imprisonment and self-imposed execu-tion. Denial also exists in the history of some countries, such as Germany, Japan and America and so on. My paper aims to ex-plore the paradox of denial both in our history and in literature works. My paper will demonstrate that denial has some negative effects both on the outer-world and the inner-world through thorough analysis on the characters in All My Sons.

  5. Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.

    Science.gov (United States)

    Sankrityayan, Himanshu; Majumdar, Anuradha S

    2016-01-01

    Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 μg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels.

  6. Epithelial inactivation of Yy1 abrogates lung branching morphogenesis.

    Science.gov (United States)

    Boucherat, Olivier; Landry-Truchon, Kim; Bérubé-Simard, Félix-Antoine; Houde, Nicolas; Beuret, Laurent; Lezmi, Guillaume; Foulkes, William D; Delacourt, Christophe; Charron, Jean; Jeannotte, Lucie

    2015-09-01

    Yin Yang 1 (YY1) is a multifunctional zinc-finger-containing transcription factor that plays crucial roles in numerous biological processes by selectively activating or repressing transcription, depending upon promoter contextual differences and specific protein interactions. In mice, Yy1 null mutants die early in gestation whereas Yy1 hypomorphs die at birth from lung defects. We studied how the epithelial-specific inactivation of Yy1 impacts on lung development. The Yy1 mutation in lung epithelium resulted in neonatal death due to respiratory failure. It impaired tracheal cartilage formation, altered cell differentiation, abrogated lung branching and caused airway dilation similar to that seen in human congenital cystic lung diseases. The cystic lung phenotype in Yy1 mutants can be partly explained by the reduced expression of Shh, a transcriptional target of YY1, in lung endoderm, and the subsequent derepression of mesenchymal Fgf10 expression. Accordingly, SHH supplementation partially rescued the lung phenotype in vitro. Analysis of human lung tissues revealed decreased YY1 expression in children with pleuropulmonary blastoma (PPB), a rare pediatric lung tumor arising during fetal development and associated with DICER1 mutations. No evidence for a potential genetic interplay between murine Dicer and Yy1 genes during lung morphogenesis was observed. However, the cystic lung phenotype resulting from the epithelial inactivation of Dicer function mimics the Yy1 lung malformations with similar changes in Shh and Fgf10 expression. Together, our data demonstrate the crucial requirement for YY1 in lung morphogenesis and identify Yy1 mutant mice as a potential model for studying the genetic basis of PPB.

  7. ?Cuales son las amenazas o peligros volcanicos?

    Science.gov (United States)

    Myers, Bobbie; Brantley, Steven R.; Stauffer, Peter; Hendley, James W.

    2000-01-01

    Los volcanes son capaces de producir numerosos peligros geologicos e hidrologicos. Los cientificos del Servicio Geologico de los EE. UU. (USGS, por sus siglas en ingles) y de otras instituciones alrededor del mundo estan estudiando los peligros de muchos de los centenares de volcanes activos y potencialmente activos del mundo. Estos cientificos vigilan muy de cerca la actividad de algunos de los volcanes mas peligrosos, por lo que estan preparados para alertar a las autoridades y/o a la poblacion en caso de que aumente sustancialmente la probabilidad de que ocurra una erupcion u otro evento peligroso.

  8. My Son 22.10.11

    Directory of Open Access Journals (Sweden)

    Rebecca Baillie

    2013-01-01

    Full Text Available 'My Son 22.10.11' was made immediately following a miscarriage 8 weeks into pregnancy. After bleeding lightly for a couple of hours, I went to the toilet and a large bloody mass fell from within me. I knew that I could not flush this away, and that to retrieve the mass was my only chance to connect with the unborn foetus. I fished the contents from the bottom of the toilet bowl using my hands and carried them into my small studio. I found some paper and began to dissect the mass. At the centre, I found the tiny, cold, hard foetus. I kissed it and then began to use it as a kind of painting tool, drawing the outline of the lost child using its very own flesh and blood. I knew that to create a lasting and tangible portrait of 'my son' was the best way to understand the somewhat unreal and fleeting experience of miscarriage. I thought of Frida Kahlo while making the work, thinking 'thank God' that I had a reference to miscarriage before it happened to me. I also thought of my childhood days spent on our family pig farm, and of all the dead pig foetuses that I had seen at various stages of development. Before the miscarriage, I thought little about the subject; afterwards, I recognise the profundity of the creation of a life that is never born. The experience is so common, yet so very rarely discussed or depicted.

  9. Mutations Abrogating VP35 Interaction with Double-Stranded RNA Render Ebola Virus Avirulent in Guinea Pigs

    Energy Technology Data Exchange (ETDEWEB)

    Prins, Kathleen C.; Delpeut, Sebastien; Leung, Daisy W.; Reynard, Olivier; Volchkova, Valentina A.; Reid, St. Patrick; Ramanan, Parameshwaran; Cárdenas, Washington B.; Amarasinghe, Gaya K.; Volchkov, Viktor E.; Basler, Christopher F. (CNRS-INSERM); (Mount Sinai Hospital); (LB-Ecuador); (Iowa State)

    2010-10-11

    Ebola virus (EBOV) protein VP35 is a double-stranded RNA (dsRNA) binding inhibitor of host interferon (IFN)-{alpha}/{beta} responses that also functions as a viral polymerase cofactor. Recent structural studies identified key features, including a central basic patch, required for VP35 dsRNA binding activity. To address the functional significance of these VP35 structural features for EBOV replication and pathogenesis, two point mutations, K319A/R322A, that abrogate VP35 dsRNA binding activity and severely impair its suppression of IFN-{alpha}/{beta} production were identified. Solution nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography reveal minimal structural perturbations in the K319A/R322A VP35 double mutant and suggest that loss of basic charge leads to altered function. Recombinant EBOVs encoding the mutant VP35 exhibit, relative to wild-type VP35 viruses, minimal growth attenuation in IFN-defective Vero cells but severe impairment in IFN-competent cells. In guinea pigs, the VP35 mutant virus revealed a complete loss of virulence. Strikingly, the VP35 mutant virus effectively immunized animals against subsequent wild-type EBOV challenge. These in vivo studies, using recombinant EBOV viruses, combined with the accompanying biochemical and structural analyses directly correlate VP35 dsRNA binding and IFN inhibition functions with viral pathogenesis. Moreover, these studies provide a framework for the development of antivirals targeting this critical EBOV virulence factor.

  10. L'astronomie et son histoire

    CERN Document Server

    Roy, Jean-René

    1982-01-01

    Le livre de Jean-René Roy nous présente une vaste synthèse des connaissances présentes en astronomie. Le grand mérite du livre est de dérouler son sujet en parallèle avec une histoire de l'astronomie. Le côté historique est ici beaucoup plus qu'un luxe. Il redonne leurs dimensions vraies aux réponses qu'apporte l'astronomie. Pour bien sentir la nature d'une étape franchie, il faut aussi avoir vécu la situation telle qu'elle se présentait avant. Et les fiches personnelles incluses dans le livre ont l'intérêt de nous rapprocher encore plus du "" feu de l'action "". Écrit dans un style direct et

  11. Lo que son mujeres en los escenarios

    Directory of Open Access Journals (Sweden)

    González Cañal, Rafael

    2007-06-01

    Full Text Available In this article I review the publishing and stage trajectory of one of Rojas Zorrilla’s most significant plays: Lo que son mujeres. As well as collecting a list of the different editions, I emphasize the 1822 version by the Mexican Manuel Eduardo de Gorostiza, which started a new renaissance period for this play on stage. I also analyze the 1899 one-act version by Emilio Bobadilla. Finally, I include all the different productions between the 17th and the 19th centuries, and address the little interest aroused in the 20th century–suffice to say that it has not been staged even during these early years of the 21st century when the centenary of Rojas Zorrilla is being celebrated.En este artículo se hace un repaso detallado de la fortuna editorial y escénica de una de las obras más significativas de Rojas Zorrilla: Lo que son mujeres. Aparte de recoger las diferentes ediciones de la misma, se hace hincapié en la refundición del mexicano Manuel Eduardo de Gorostiza, estrenada en 1822, que abrió un período de cierta recuperación de este texto dramático en los escenarios. Se analiza también la refundición que llevó a cabo en un solo acto Emilio Bobadilla en 1899. Finalmente, se registran todas las representaciones conocidas de la obra desde el siglo XVII hasta el siglo XIX y se constata el poco interés que ha despertado en los escenarios del siglo XX. Incluso en los últimos años, en los que los montajes de obras de Rojas comienzan a ser más frecuentes, esta obra no ha sido todavía llevada a escena.

  12. Natural Mutations in Streptococcus agalactiae Resulting in Abrogation of β Antigen Production.

    Science.gov (United States)

    Vasilyeva, Anastasia; Santos Sanches, Ilda; Florindo, Carlos; Dmitriev, Alexander

    2015-01-01

    Streptococcus agalactiae genome encodes 21 two-component systems (TCS) and a variety of regulatory proteins in order to control gene expression. One of the TCS, BgrRS, comprising the BgrR DNA-binding regulatory protein and BgrS sensor histidine kinase, was discovered within a putative virulence island. BgrRS influences cell metabolism and positively control the expression of bac gene, coding for β antigen at transcriptional level. Inactivation of bgrR abrogated bac gene expression and increased virulence properties of S. agalactiae. In this study, a total of 140 strains were screened for the presence of bac gene, and the TCS bgrR and bgrS genes. A total of 53 strains carried the bac, bgrR and bgrS genes. Most of them (48 strains) expressed β antigen, while five strains did not express β antigen. Three strains, in which bac gene sequence was intact, while bgrR and/or bgrS genes had mutations, and expression of β antigen was absent, were complemented with a constructed plasmid pBgrRS(P) encoding functionally active bgrR and bgrS gene alleles. This procedure restored expression of β antigen indicating the crucial regulatory role of TCS BgrRS. The complemented strain A49V/BgrRS demonstrated attenuated virulence in intraperitoneal mice model of S. agalactiae infection compared to parental strain A49V. In conclusion we showed that disruption of β antigen expression is associated with: i) insertion of ISSa4 upstream the bac gene just after the ribosomal binding site; ii) point mutation G342A resulting a stop codon TGA within the bac gene and a truncated form of β antigen; iii) single deletion (G) in position 439 of the bgrR gene resulting in a frameshift and the loss of DNA-binding domain of the BgrR protein, and iv) single base substitutions in bgrR and bgrS genes causing single amino acid substitutions in BgrR (Arg187Lys) and BgrS (Arg252Gln). The fact that BgrRS negatively controls virulent properties of S. agalactiae gives a novel clue for understanding of S

  13. Sons fricativos surdos Voiceless fricatives sounds

    Directory of Open Access Journals (Sweden)

    Carla Aparecida Cielo

    2008-01-01

    Full Text Available TEMA: características dos sons fricativos surdos. OBJETIVO: propor uma revisão da literatura pertinente às características acústicas, fonéticas e fonológicas dos fonemas fricativos surdos que integram o sistema fonológico do Português. Além disso, são descritas suas aplicações na terapia vocal. CONCLUSÕES: os fricativos são fonemas agudos, abrangendo de 2500 a 8000Hz; são plenamente adquiridos até os 3:7 anos de idade; o /s/ que também é o mais afetado em casos de frênulo lingual curto; a omissão do /s/ é uma das ocorrências mais freqüentes na alfabetização; sendo que, no desvio fonológico e na fissura lábio-palatina, freqüentemente ocorre comprometimento de toda a classe de fricativos. Na avaliação de voz, os fricativos são mencionados com as medidas de TMF e relação s/z, bem como seu uso como sons de apoio na fonoterapia.BACKGROUND: characteristics of voiceless fricative sounds PURPOSE: to review the literature related to acoustic, phonetics and phonological characteristics of voiceless fricative sounds that are part of the phonological system of the Portuguese Language. Furthermore, it describes the use of these sounds in voice therapy. CONCLUSIONS: fricatives are acute phonemes comprised between 2500 and 8000 Hz; they are fully acquired up to the age of 3:7 years; the /s/, which is the most affected in cases of short lingual frenum; omission of the /s/ is one of the most frequent occurrences during literacy education; and in the phonological deviation and labial-palatine fissure the entire class of fricatives is frequently affected. In voice assessment, fricative sounds are mentioned as TMF measurements and s/z relationship, and their use as support sounds in speech therapy.

  14. Adolescents with Nonresident Fathers: Are Daughters more Disadvantaged than Sons?

    OpenAIRE

    Mitchell, Katherine Stamps; Booth, Alan; KING, VALARIE

    2009-01-01

    This study examined sons' and daughters' involvement with nonresident fathers and associated outcomes (N=4,663). Results indicate that sons and daughters report equal involvement with nonresident fathers on most measures of father investment, although sons report more overnight visits, sports, and movies, and feeling closer to their fathers compared to daughters. Sons and daughters generally benefit from nonresident father involvement in the same way in internalizing and externalizing problem...

  15. Adolescents with Nonresident Fathers: Are Daughters More Disadvantaged than Sons?

    Science.gov (United States)

    Mitchell, Katherine Stamps; Booth, Alan; King, Valarie

    2009-01-01

    This study examined sons' and daughters' involvement with nonresident fathers and associated outcomes (N = 4,663). Results indicated that sons and daughters reported equal involvement with nonresident fathers on most measures of father investment, although sons reported more overnight visits, sports, and movies and feeling closer to their fathers…

  16. Peroxisome proliferator-activated receptor-gamma abrogates Smad-dependent collagen stimulation by targeting the p300 transcriptional coactivator.

    Science.gov (United States)

    Ghosh, Asish K; Bhattacharyya, Swati; Wei, Jun; Kim, Suyeon; Barak, Yaacov; Mori, Yasuji; Varga, John

    2009-09-01

    Ligands of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) abrogate the stimulation of collagen gene transcription induced by transforming growth factor-beta (TGF-beta). Here, we delineate the mechanisms underlying this important novel physiological function for PPAR-gamma in connective tissue homeostasis. First, we demonstrated that antagonistic regulation of TGF-beta activity by PPAR-gamma ligands involves cellular PPAR-gamma, since 15-deoxy-Delta12,14-prostaglandin J(2) (15d-PGJ(2)) failed to block TGF-beta-induced responses in either primary cultures of PPAR-gamma-null murine embryonic fibroblasts, or in normal human skin fibroblasts with RNAi-mediated knockdown of PPAR-gamma. Next, we examined the molecular basis underlying the abrogation of TGF-beta signaling by PPAR-gamma in normal human fibroblasts in culture. The results demonstrated that Smad-dependent transcriptional responses were blocked by PPAR-gamma without preventing Smad2/3 activation. In contrast, the interaction between activated Smad2/3 and the transcriptional coactivator and histone acetyltransferase p300 induced by TGF-beta, and the accumulation of p300 on consensus Smad-binding DNA sequences and histone H4 hyperacetylation at the COL1A2 locus, were all prevented by PPAR-gamma. Wild-type p300, but not a mutant form of p300 lacking functional histone acetyltransferase, was able to restore TGF-beta-induced stimulation of COL1A2 in the presence of PPAR-gamma ligands. Collectively, these results indicate that PPAR-gamma blocked Smad-mediated transcriptional responses by preventing p300 recruitment and histone H4 hyperacetylation, resulting in the inhibition of TGF-beta-induced collagen gene expression. Pharmacological activation of PPAR-gamma thus may represent a novel therapeutic approach to target p300-dependent TGF-beta profibrotic responses such as stimulation of collagen gene expression.

  17. Is the distant relationship of fathers and homosexual sons related to the sons' erotic preference for male partners, or to the sons' atypical gender identity, or to both?

    Science.gov (United States)

    Freund, K; Blanchard, R

    1983-01-01

    Study 1 compared the retrospectively reported father-son relationships of four groups of adult males: (a) Gynephiles (males who erotically prefer physically mature females), (b) androphiles (who prefer physically mature males), (c) a combined group of heterosexual pedophiles and pedohebephiles (the latter being attracted to pubescent as well as prepubescent females), and (d) a combined group of homosexual pedophiles and pedohebephiles (the latter attracted to pubescent as well as prepubescent males). The gynephiles were paid volunteers; the latter three groups were patients. The androphiles, the only group among those compared known to exhibit a measurably greater degree of cross gender identity in childhood, were also the only group to report significantly poorer father-son relations. The homosexual pedo/pedohebephiles, who also prefer male partners but who exhibit typical male gender identity in childhood, did not differ in father-son relations from the gynephiles or the heterosexual pedo/pedohebephiles. Study 2 showed that, within a sample of nonpatient volunteer androphiles, those individuals who reported the greatest degree of cross gender behavior in childhood also tended to report the worst relationships with their fathers. This correlation was replicated within a sample of androphilic patients in Study 3. The consistent pattern of results obtained from these three studies suggests that the emotionally distant relationships of fathers and androphilic sons relate to the sons' atypical childhood gender identity (or observable gender role behavior) rather than to the sons' erotic preference for male partners per se.

  18. Enhancement and abrogation : modifications of host immune status influence IL-2 and LAK cell immunotherapy

    NARCIS (Netherlands)

    E.P. Steller (Erick)

    1988-01-01

    textabstractThis thesis will discuss the role immune cells and the host immune system can play in enhancement and abrogation of this novel immunotherapy with interleukin 2 and lymphokine-activated killer cells. Chapter 3 and 4 will discuss the scoring methods in this intraperitoneal cancer and immun

  19. Son preference in rural China: patrilineal families and socioeconomic change.

    Science.gov (United States)

    Murphy, Rachel; Tao, Ran; Lu, Xi

    2011-01-01

    This article draws on a survey conducted in six provinces in summer 2008 to investigate the determinants of son preference in rural China. The analysis confirms the conventional wisdom that son preference is embedded within patrilineal family structures and practices. We extend our analysis by exploring specific aspects of variation within patrilineal family culture. We find that the patrilineal group (clan) composition of villages and family participation in practices such as building ancestral halls and updating genealogies significantly influence son preference. Yet even though son preference is embedded within patrilineal family culture, our analysis suggests that over time the attenuation of son preference is likely. This is because determinants associated with socioeconomic change—for instance, higher levels of education, direct exposure to official policy education materials, higher income (a proxy for rural industrialization), and agricultural mechanization—all attenuate son preference. Being younger and female are also associated with weaker son preference, and both characteristics are likely to interact with education and industrialization to further dilute son preference in the longer term. Nevertheless, our findings suggest that concerted efforts are needed to ameliorate institutional discrimination against rural people in welfare provisioning and in labor markets, and to promote multiple dimensions of gender equality, including in land rights, wage rates, and education.

  20. Like Godfather, Like Son: Exploring the Intergenerational Nature of Crime

    Science.gov (United States)

    Hjalmarsson, Randi; Lindquist, Matthew J.

    2012-01-01

    Sons (daughters) with criminal fathers have 2.06 (2.66) times higher odds of having a criminal conviction than those with noncriminal fathers. One additional paternal sentence increases sons' (daughters') convictions by 32 (53) percent. Compared to traditional labor market measures, the intergenerational transmission of crime is lower than that…

  1. Hepatitis C virus core protein abrogates the DDX3 function that enhances IPS-1-mediated IFN-beta induction.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Oshiumi

    Full Text Available The DEAD box helicase DDX3 assembles IPS-1 (also called Cardif, MAVS, or VISA in non-infected human cells where minimal amounts of the RIG-I-like receptor (RLR protein are expressed. DDX3 C-terminal regions directly bind the IPS-1 CARD-like domain as well as the N-terminal hepatitis C virus (HCV core protein. DDX3 physically binds viral RNA to form IPS-1-containing spots, that are visible by confocal microscopy. HCV polyU/UC induced IPS-1-mediated interferon (IFN-beta promoter activation, which was augmented by co-transfected DDX3. DDX3 spots localized near the lipid droplets (LDs where HCV particles were generated. Here, we report that HCV core protein interferes with DDX3-enhanced IPS-1 signaling in HEK293 cells and in hepatocyte Oc cells. Unlike the DEAD box helicases RIG-I and MDA5, DDX3 was constitutively expressed and colocalized with IPS-1 around mitochondria. In hepatocytes (O cells with the HCV replicon, however, DDX3/IPS-1-enhanced IFN-beta-induction was largely abrogated even when DDX3 was co-expressed. DDX3 spots barely merged with IPS-1, and partly assembled in the HCV core protein located near the LD in O cells, though in some O cells IPS-1 was diminished or disseminated apart from mitochondria. Expression of DDX3 in replicon-negative or core-less replicon-positive cells failed to cause complex formation or LD association. HCV core protein and DDX3 partially colocalized only in replicon-expressing cells. Since the HCV core protein has been reported to promote HCV replication through binding to DDX3, the core protein appears to switch DDX3 from an IFN-inducing mode to an HCV-replication mode. The results enable us to conclude that HCV infection is promoted by modulating the dual function of DDX3.

  2. Hepatitis C virus core protein abrogates the DDX3 function that enhances IPS-1-mediated IFN-beta induction.

    Science.gov (United States)

    Oshiumi, Hiroyuki; Ikeda, Masanori; Matsumoto, Misako; Watanabe, Ayako; Takeuchi, Osamu; Akira, Shizuo; Kato, Nobuyuki; Shimotohno, Kunitada; Seya, Tsukasa

    2010-12-08

    The DEAD box helicase DDX3 assembles IPS-1 (also called Cardif, MAVS, or VISA) in non-infected human cells where minimal amounts of the RIG-I-like receptor (RLR) protein are expressed. DDX3 C-terminal regions directly bind the IPS-1 CARD-like domain as well as the N-terminal hepatitis C virus (HCV) core protein. DDX3 physically binds viral RNA to form IPS-1-containing spots, that are visible by confocal microscopy. HCV polyU/UC induced IPS-1-mediated interferon (IFN)-beta promoter activation, which was augmented by co-transfected DDX3. DDX3 spots localized near the lipid droplets (LDs) where HCV particles were generated. Here, we report that HCV core protein interferes with DDX3-enhanced IPS-1 signaling in HEK293 cells and in hepatocyte Oc cells. Unlike the DEAD box helicases RIG-I and MDA5, DDX3 was constitutively expressed and colocalized with IPS-1 around mitochondria. In hepatocytes (O cells) with the HCV replicon, however, DDX3/IPS-1-enhanced IFN-beta-induction was largely abrogated even when DDX3 was co-expressed. DDX3 spots barely merged with IPS-1, and partly assembled in the HCV core protein located near the LD in O cells, though in some O cells IPS-1 was diminished or disseminated apart from mitochondria. Expression of DDX3 in replicon-negative or core-less replicon-positive cells failed to cause complex formation or LD association. HCV core protein and DDX3 partially colocalized only in replicon-expressing cells. Since the HCV core protein has been reported to promote HCV replication through binding to DDX3, the core protein appears to switch DDX3 from an IFN-inducing mode to an HCV-replication mode. The results enable us to conclude that HCV infection is promoted by modulating the dual function of DDX3.

  3. Causal Attributions and Parents' Acceptance of Their Homosexual Sons.

    Science.gov (United States)

    Belsky, Yael; Diamond, Gary M

    2015-01-01

    This Internet-based study examined the association between Israeli parents' attributions regarding the cause of their son's homosexuality and their level of acceptance of their homosexual son. The sample (N = 57) was recruited via Internet Web sites (gay forums and support groups). Findings suggest that more essentialist (versus constructivist) causal attributions were associated with higher levels of parental acceptance. Length of time parents knew of their son's homosexual orientation predicted the degree to which their attributions were essentialist. Implications are discussed.

  4. An exon 53 frameshift mutation in CUBN abrogates cubam function and causes Imerslund-Gräsbeck syndrome in dogs.

    Science.gov (United States)

    Fyfe, John C; Hemker, Shelby L; Venta, Patrick J; Fitzgerald, Caitlin A; Outerbridge, Catherine A; Myers, Sherry L; Giger, Urs

    2013-08-01

    Cobalamin malabsorption accompanied by selective proteinuria is an autosomal recessive disorder known as Imerslund-Gräsbeck syndrome in humans and was previously described in dogs due to amnionless (AMN) mutations. The resultant vitamin B12 deficiency causes dyshematopoiesis, lethargy, failure to thrive, and life-threatening metabolic disruption in the juvenile period. We studied 3 kindreds of border collies with cobalamin malabsorption and mapped the disease locus in affected dogs to a 2.9Mb region of homozygosity on canine chromosome 2. The region included CUBN, the locus encoding cubilin, a peripheral membrane protein that in concert with AMN forms the functional intrinsic factor-cobalamin receptor expressed in ileum and a multi-ligand receptor in renal proximal tubules. Cobalamin malabsorption and proteinuria comprising CUBN ligands were demonstrated by radiolabeled cobalamin uptake studies and SDS-PAGE, respectively. CUBN mRNA and protein expression were reduced ~10 fold and ~20 fold, respectively, in both ileum and kidney of affected dogs. DNA sequencing demonstrated a single base deletion in exon 53 predicting a translational frameshift and early termination codon likely triggering nonsense mediated mRNA decay. The mutant allele segregated with the disease in the border collie kindred. The border collie disorder indicates that a CUBN mutation far C-terminal from the intrinsic factor-cobalamin binding site can abrogate receptor expression and cause Imerslund-Gräsbeck syndrome.

  5. Mother-son incest as a defence against psychosis.

    Science.gov (United States)

    Bachmann, K M; Bossi, J

    1993-09-01

    In the following, a case of mother-adult son incest is described and explained from a psychoanalytical viewpoint. Two theories are put forward: (a) Mother-son incest may occur as a defence against psychosis, and (b) the incest represents an unconscious search for triangulation, a process in which external authorities (such as, for example, a court of law) may function as surrogates for persons who have been missed in the pre-oedipal past. It is therefore possible to understand mother-son incest symbolically as an indicator of pre-oedipal needs of the son and of the mother's longing for the absent partner. The incest is, however, not only a cry for help; it is also to be regarded as an attempt to solve the problem for both people involved. Looked at in this way, new ways of understanding and new possibilities for therapy emerge.

  6. Cryptorchidism and hypospadias in sons of gardeners and farmers

    DEFF Research Database (Denmark)

    Weidner, I S; Møller, H; Jensen, Tina Kold

    1998-01-01

    Cryptorchidism and hypospadias have been related to prenatal estrogen exposure in animal models. Some chemicals used in farming and gardening have been shown to possess estrogenic and other hormone-disrupting effects. Earlier studies have indicated increased risks of urogenital malformations...... in the sons of pesticide appliers. In the present study, parental occupation in the farming and gardening industry among 6,177 cases of cryptorchidism, 1,345 cases of hypospadias, and 23,273 controls, born live from 1983 to 1992 in Denmark, was investigated in a register-based case-control study....... A significantly increased risk of cryptorchidism but not hypospadias was found in sons of women working in gardening (adjusted odds ratio = 1.67; 95% confidence interval, 1.14-2.47). The risks were not increased in sons of men working in farming or gardening. The increased risk of cryptorchidism among sons...

  7. The Telephone Connection: An Interview with Ernest Hemingway's Son.

    Science.gov (United States)

    Workman, Brooke

    1979-01-01

    Relates how a conference call to Ernest Hemingway's son, Gregory, resolved questions and brought understanding and excitement to a group of Iowa high school students enrolled in a 12-week Hemingway seminar. (FL)

  8. The discovery and exploration of Hang Son Doong

    Energy Technology Data Exchange (ETDEWEB)

    Limbert, H.; Limbert, D.; Hieu, N.; Phai, V. V.; Kinh Bac, D.; Phuong, T. H.; Granger, D.

    2016-08-01

    Hang Son Doong is located in the Phong Nha Ke Bang Limestone Massif in Quang Binh Province, Central Vietnam. Cave exploration by British cavers has been continuous in this area since 1990. Hang Son Doong is part of the Phong Nha Cave system which runs from the southern end of the National Park near the Lao border to the final resurgence at Phong Nha Cave. (Author)

  9. Remarks on Psychological Analyses of Sons and Lovers

    Institute of Scientific and Technical Information of China (English)

    杨艳微

    2007-01-01

    Sons and Lovers is considered to be D.H.Lawrene's first masterpiece. Social critique and psychological exploration are two props of creative works of D.H.Lawrence. There are two points of view in literature world about the novel Sons and Lovers: One is its critical function which criticizes the destroy of capitalistic industrial civilization to human body and mind. The other is psychological analyses. The tragedy of the characters attributes to the Oedipus complex.

  10. Conglutinin binds the HIV-1 envelope glycoprotein gp 160 and inhibits its interaction with cell membrane CD4

    DEFF Research Database (Denmark)

    Andersen, Ove; Sørensen, A M; Svehag, S E;

    1991-01-01

    was calcium-dependent, which is characteristic of the binding of a C-type lectin to its ligand, and the binding was inhibited in a dose-dependent manner with N-acetyl-D-glucosamine. Deglycosylation of rgp160 abrogated the conglutinin binding. In addition, conglutinin exerted a dose-dependent inhibition...

  11. THE MOTIF OF THE PRODIGAL SON IN IVAN TURGENEV'S NOVELS

    Directory of Open Access Journals (Sweden)

    Valentina Ivanovna Gabdullina

    2013-11-01

    Full Text Available The author questions the perception of Ivan Turgenev as a “non- Christian writer” and studies the problem of the prodigal son motif functioning in a series of his novels. In his novels, Turgenev pictured different phases of the archetypal story, originating from the Gospel parable of the prodigal son. In the novel Rudin he depicted the phase of spiritual wanderings of the hero who had lost touch with his native land — Russia. In his next novels (Home of the Gentry, Fathers and Sons and Smoke, after leading his hero in circles and sending him back to his paternal home, Turgenev reconstructs the model of human behavior, represented in the parable, thereby recognizing the immutability of the idea formalized in the Gospel. The motif of the return to Russian land gets its completion in Turgenev's last novel Virgin Soil, in which the author paradoxically connects the Westernist idea with the Gospel imperative. Solomin, the son of a deacon, sent by his wise father out to Europe “to get education”, studies in England, masters the European knowledge and returns back “to his native land” to establish his own business in inland Russia. Thus, a series of Turgenev's novels, in which he portrayed different phases of social life, are interlinked with the motif of the prodigal son, who is represented by novels' main characters.

  12. Violating Bell's inequality beyond Cirel'son's bound

    CERN Document Server

    Cabello, A

    2002-01-01

    Cirel'son inequality states that the absolute value of the combination of quantum correlations appearing in the Clauser-Horne-Shimony-Holt (CHSH) inequality is bound by $2 \\sqrt 2$. It is shown that the correlations of two qubits belonging to a three-qubit system can violate the CHSH inequality beyond $2 \\sqrt 2$. Such a violation is not in conflict with Cirel'son's inequality because it requires a choice of pairs of qubits which is only meaningful in a local-realistic theory. The maximum allowed violation of the CHSH inequality, 4, can be achieved using the Greenberger-Horne-Zeilinger state.

  13. Origins, Form, and Development of the Son Jarocho: Veracruz, Mexico.

    Science.gov (United States)

    Loza, Steven J.

    1982-01-01

    Son Jarocho (specifically from Veracruz) is a song-and-dance form originating in Spain and implanted in Mexico during 17th- and 18th-century colonization. The jarocho style of music today is one of Latin America's most unique forms, using one to four instruments and characterized by its distinctive rhythm. (LC)

  14. The culture of referendum in Albania: Technical and theoritecal reflections on the abrogative referendum

    Directory of Open Access Journals (Sweden)

    Valbona Pajo Bala

    2014-01-01

    Full Text Available The aim of this paper is to analyse the Albanian constitutional and legal framework on referenda, in general, focusing special attention to the abrogative referenda of a law or part thereof. Given the absence of any concrete case of an abrogative referenda held in Albania, which does not creates very much room for discussion in that regard, the paper, through a comparative approach on the referenda culture in other european states, aims at offering to the reader a more complete view on the mechanisms and guarantees enjoyed by voters and the effective way of their use, in order to give life to the direct democracy, but without replacing the representative one. In addition, part of the analyses will be the powers of the Constitutional Court for the ex ante constitutional review of the issue subject to a referendum, the review of constitutionality of the referndum and of its results. In this context, the paper will focus on the constitutional case-law as a tool for increasing the referenda culture and shaping the constitional order, as well as a source of standards and values. Another objective of the paper is to open a discussion on the need for the reception of referenda-related standards elaborated in those European countries, where the culture of helding a referenda and the case-law on the regard is enriched and may serve as a qualitative basis for further reference.

  15. Maternal smoking in pregnancy and reproductive hormones in adult sons.

    Science.gov (United States)

    Ramlau-Hansen, C H; Thulstrup, A M; Olsen, J; Ernst, E; Andersen, C Y; Bonde, J P

    2008-12-01

    Smoking during pregnancy has been reported to alter levels of reproductive hormones in adult sons. From a Danish pregnancy cohort established in 1984-1987, 347 out of 5109 sons were selected according to their exposure to tobacco smoke in foetal life. From February 2005 to January 2006, a blood sample from each young man (18-21 years) was collected and analysed for reproductive hormones. There were no apparent trends of increasing or decreasing hormonal levels with increased exposure to maternal tobacco smoking during pregnancy. Only the free testosterone/free estradiol ratios increased with increased maternal smoking during pregnancy (p for trend = 0.05). No trends for increasing odds ratios for high follicle-stimulating hormone (> or =25 percentile) or low inhibin B (hormones later in life, but the data may suggest a shift in the hypothalamo-pituitary-gonadal axis towards higher androgenicity. This result was, however, of only borderline significance and could be because of chance.

  16. Conflicts between Spirit and Body in Sons and Lovers

    Institute of Scientific and Technical Information of China (English)

    赵佳

    2009-01-01

    The purpose of this paper is to analyze the conflicts between spirit and body that exist among characters in Sons and Lovers. By stating the complicated relationships of Mr. and Mrs. Morel, two sons and their mother, and the protagonist Paul and two women, Miriam and Clara, spirit and body collides and conflicts emerge from time to time. Conflicts between blood ties and lovers' affairs, moral principles and incest, and chastity and lust are reflected on char-acters, especially Paul in the novel. It concludes that Mrs. Morel's influence on Paul's spirit and thought is great. Her spiritual domination on Paul is the main factor for these conflicts. Her death at the end of the story will be a brand-new start of Paul's life.

  17. An ecological reading of the sons and lovers

    Institute of Scientific and Technical Information of China (English)

    徐萌萌

    2012-01-01

    1 .Introduction D.H. Lawrence is one of the greatest writers in the English lit- erature history. The author makes a textual analysis of the novel-- Sons and Lovers, David Herbert Lawrence's third novel Which is also his first masterpiece. The novel is recognized as the pioneer work among English novels and now has become one of the most widespread readings. As his representative, sons and lovers is a work filled with ecological elements, which discovered lots of social and psychological problems through the description of the character Paul's growing. Under the backgrounds of the author's own growing experiences and Industry Revolution, the natural circumstances has been ruined, the sick relationship in the worker's family,

  18. Private Transfers within the Family: Mothers, Fathers, Sons and Daughters

    OpenAIRE

    Donald Cox

    2003-01-01

    Despite recent advances in data collection and the growing number of empirical studies that examine private intergenerational transfers, there still exist significant gaps in our knowledge. Who transfers what to whom, and why do they it? I argue that some of these gaps could be filled by departing from the standard parent-child framework and concentrating instead on fathers, mothers, sons and daughters in a way that accounts for fundamental--and sometimes obvious--male-female differences in c...

  19. Like Father, Like Son? Intergenerational Educational Mobility in India.

    Science.gov (United States)

    Azam, Mehtabul; Bhatt, Vipul

    2015-12-01

    Using the nationally representative India Human Development Survey (IHDS), we create a unique son-father matched data set that is representative of the entire adult male population (aged 20-65) in India. We use these data to document the evolution of intergenerational transmission of educational attainment in India over time, among different castes and states for the birth cohorts of 1940-1985. We find that educational persistence, as measured by the regression coefficient of father's education as a predictor of son's education, has declined over time. This implies that increases in average educational attainment are driven primarily by increases among children of less-educated fathers. However, we do not find such a declining trend in the correlation between educational attainment of sons and fathers, which is another commonly used measure of persistence. To understand the source of such a discrepancy between the two measures of educational persistence, we decompose the intergenerational correlation and find that although persistence has declined at the lower end of the fathers' educational distribution, it has increased at the top end of that distribution.

  20. Son preference in Indian families: absolute versus relative wealth effects.

    Science.gov (United States)

    Gaudin, Sylvestre

    2011-02-01

    The desire for male children is prevalent in India, where son preference has been shown to affect fertility behavior and intrahousehold allocation of resources. Economic theory predicts less gender discrimination in wealthier households, but demographers and sociologists have argued that wealth can exacerbate bias in the Indian context. I argue that these apparently conflicting theories can be reconciled and simultaneously tested if one considers that they are based on two different notions of wealth: one related to resource constraints (absolute wealth), and the other to notions of local status (relative wealth). Using cross-sectional data from the 1998-1999 and 2005-2006 National Family and Health Surveys, I construct measures of absolute and relative wealth by using principal components analysis. A series of statistical models of son preference is estimated by using multilevel methods. Results consistently show that higher absolute wealth is strongly associated with lower son preference, and the effect is 20%-40% stronger when the household's community-specific wealth score is included in the regression. Coefficients on relative wealth are positive and significant although lower in magnitude. Results are robust to using different samples, alternative groupings of households in local areas, different estimation methods, and alternative dependent variables.

  1. Immunosuppression abrogates resistance of young rabbits to Rabbit Haemorrhagic Disease (RHD).

    Science.gov (United States)

    Marques, Raquel M; Teixeira, Luzia; Aguas, Artur P; Ribeiro, Joana C; Costa-e-Silva, António; Ferreira, Paula G

    2014-02-04

    Rabbit Haemorrhagic Disease (RHD) is caused by a calicivirus (RHDV) that kills 90% of infected adult European rabbits within 3 days. Remarkably, young rabbits are resistant to RHD. We induced immunosuppression in young rabbits by treatment with methylprednisolone acetate (MPA) and challenged the animals with RHDV by intramuscular injection. All of these young rabbits died within 3 days of infection due to fulminant hepatitis, presenting a large number of RHDV-positive dead or apoptotic hepatocytes, and a significant seric increase in cytokines, features that are similar to those of naïve adult rabbits infected by RHDV. We conclude that MPA-induced immunosuppression abrogates the resistance of young rabbits to RHD, indicating that there are differences in the innate immune system between young and adult rabbits that contribute to their distinct resistance/susceptibility to RHDV infection.

  2. ¿Son las mujeres una minoría?

    OpenAIRE

    Osborne, Raquel

    1996-01-01

    Not available.

    El clásico tratamiento de las mujeres como minoría desde la sociología se halla contemporáneamente interrelacionado con las políticas de igualdad tejidas en torno a las mujeres. Pasado y presente, teoría y práctica se unen para mostrar que las teorías no son accidentales ni fortuitas sino que acarrean importantes consecuencias en la acción, pudiendo dar lugar a intervenciones en la vida pública, que es lo que, a mi entender, confiere su sentido a la. sociolog...

  3. [Bladder cancer at an early age in father and son].

    Science.gov (United States)

    Ovsiannikov, D; Stöhr, R; Hartmann, A; Böttrich, R; Hengstler, J G; Golka, K

    2011-12-01

    Bladder cancer may be caused by external factors like tobacco smoking, but may also be familial. We report on a father and son who developed this tumour at the ages of 45 and 35. Testing various genetic markers including the mismatch repair proteins MLH1, MSH2 and MSH6, whose loss is associated with a higher risk for hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome), did not point to a familial disease. Thus the heavy smoking habits of the two patients must be considered as causal.

  4. Experimental Violation of Bell Inequality beyond Cirel'son's Bound

    CERN Document Server

    Chen, Y A; Pan, J W; Yang, T; Zhang, A N; Zhao, Z; Cabello, Adan; Chen, Yu-Ao; Pan, Jian-Wei; Yang, Tao; Zhang, An-Ning; Zhao, Zhi

    2006-01-01

    The correlations between two qubits belonging to a three-qubit system can violate the Clauser-Horne-Shimony-Holt-Bell inequality beyond Cirel'son's bound [A. Cabello, Phys. Rev. Lett. 88, 060403 (2002)]. We experimentally demonstrate such a violation by 7 standard deviations by using a three-photon polarization-entangled Greenberger-Horne-Zeilinger state produced by Type-II spontaneous parametric down-conversion. In addition, using part of our results, we obtain a violation of the Mermin inequality by 39 standard deviations.

  5. Male-mediated infertility in sons of building painters and gardeners

    DEFF Research Database (Denmark)

    Ramlau-Hansen, Cecilia; Stoltenberg, Christian Ditlev G; Hougaard, K S

    2012-01-01

    To investigate whether sons of gardeners and building painters have increased risk of infertility in comparison with sons of bricklayers, carpenters and electricians.......To investigate whether sons of gardeners and building painters have increased risk of infertility in comparison with sons of bricklayers, carpenters and electricians....

  6. Son preference, sex selection, and kinship in Vietnam.

    Science.gov (United States)

    Guilmoto, Christophe Z

    2012-01-01

    This article examines the recent rise in the sex ratio at birth in Vietnam and relates its emergence to kinship systems and ethnic composition using 2009 census micro-data. Presentation of the main socioeconomic and ethnic differentials in birth masculinity is followed by a review of the three intermediate factors leading to increases in the sex ratio at birth: prenatal technology, declining fertility, and gender bias. An indirect measurement of fertility behavior is used to demonstrate the close association between levels of the sex ratio at birth and the intensity of son preference. Data on household composition indicate that Vietnam is characterized by the co-existence of kinship patterns typical of East and Southeast Asia. Son preference in Vietnam is found to be related to the prevalence of more traditional patrilineal systems. The article concludes by considering the implications of the cultural dimensions of prenatal sex selection for policy responses and for the likely future change in the sex ratio at birth.

  7. Tetrandrine: A Potent Abrogator of G2 Checkpoint Function in Tumor Cells and Its Mechanism

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To assess the ability of tetrandrine (Tet) to enhance the sensitivity to irradiation and its mechanism in cell lines of human breast cancer p53-mutant MCF-7/ADR, p53-wild-type MCF-7 and human colon carcinoma p53-mutant HT-29 as well as in C26 colorectal carcinoma-bearing BALB/c mice. Methods MCF-7/ADR, HT-29 and MCF-7 cells were exposed to irradiation in the absence or presence of tetrandrine. The effect of Tet on the cytotoxicity of X-irradiation in these three cells was determined and the effect of tetrandrine on cell cycle arrest induced by irradiation in its absence or presence was studied by flow cytometry, Moreover, mitotic index measurement determined mitosis of cells to enter mitosis. Western blotting was employed to detect cyclin B1 and Cdc2 proteins in extracts from irradiated or non-irradiated cells of MCF-7/ADR, HT-29 and MCF-7 treated with tetrandrine at various concentrations. Tumor growth delay assay was conducted to determine the radio-sensitization of tetrandrine in vivo. Results Clonogenic assay showed that tetrandrine markedly enhanced the lethal effect of X-rays on p53-mutant MCF-7/ADR and HT-29 cells and the sensitization enhancement ratio (SER) of tetrandrine was 1.51 and 1.63, but its SER was only 1.1 in p53-wt MCF-7 cells. Irradiated p53-mutant MCF-7/ADR and HT-29 cells were only arrested in G2/M phase while MCF-7 cells were arrested in G1 and G2/M phases. Radiation-induced G2 phase arrests were abrogated by tetrandrine in a concentration-dependent manner in MCF-7/ADR and HT-29 cells,whereas redistribution within MCF-7 cell cycle changed slightly. The proportion of cells in M phase increased from 1.3% to 14.7% in MCF-7/ADR cells, and from 1.5% to 13.2% in HT-29 cells, but 2.4% to 7.1% in MCF-7 cells. Furthermore, the levels of cyclin B 1 and Cdc2 expression decreased after X-irradiation in MCF-7/ADR and HT-29 cells, and the mitotic index was also lower. Tet could reverse the decrease and induce the irradiated cells to enter mitosis

  8. Herpesvirus telomerase RNA (vTR with a mutated template sequence abrogates herpesvirus-induced lymphomagenesis.

    Directory of Open Access Journals (Sweden)

    Benedikt B Kaufer

    2011-10-01

    Full Text Available Telomerase reverse transcriptase (TERT and telomerase RNA (TR represent the enzymatically active components of telomerase. In the complex, TR provides the template for the addition of telomeric repeats to telomeres, a protective structure at the end of linear chromosomes. Human TR with a mutation in the template region has been previously shown to inhibit proliferation of cancer cells in vitro. In this report, we examined the effects of a mutation in the template of a virus encoded TR (vTR on herpesvirus-induced tumorigenesis in vivo. For this purpose, we used the oncogenic avian herpesvirus Marek's disease virus (MDV as a natural virus-host model for lymphomagenesis. We generated recombinant MDV in which the vTR template sequence was mutated from AATCCCAATC to ATATATATAT (vAU5 by two-step Red-mediated mutagenesis. Recombinant viruses harboring the template mutation replicated with kinetics comparable to parental and revertant viruses in vitro. However, mutation of the vTR template sequence completely abrogated virus-induced tumor formation in vivo, although the virus was able to undergo low-level lytic replication. To confirm that the absence of tumors was dependent on the presence of mutant vTR in the telomerase complex, a second mutation was introduced in vAU5 that targeted the P6.1 stem loop, a conserved region essential for vTR-TERT interaction. Absence of vTR-AU5 from the telomerase complex restored virus-induced lymphoma formation. To test if the attenuated vAU5 could be used as an effective vaccine against MDV, we performed vaccination-challenge studies and determined that vaccination with vAU5 completely protected chickens from lethal challenge with highly virulent MDV. Taken together, our results demonstrate 1 that mutation of the vTR template sequence can completely abrogate virus-induced tumorigenesis, likely by the inhibition of cancer cell proliferation, and 2 that this strategy could be used to generate novel vaccine candidates

  9. Terapia vocal e sons nasais: efeitos sobre disfonias hiperfuncionais

    Directory of Open Access Journals (Sweden)

    Simone Rattay Andrade

    2016-02-01

    Full Text Available RESUMO Buscou-se verificar os efeitos de um programa fonoterapêutico que incluiu orientação vocal e postural, adequação da função respiratória e a técnica de sons nasais em disfonias hiperfuncionais. Foi realizado um estudo de casos clínicos, observacional, longitudinal, não controlado, de caráter quantitativo que analisou três sujeitos do sexo feminino com idade média de 31,33 anos que apresentavam disfonias hiperfuncionais. Os sujeitos foram submetidos a: videolaringoscopia, avaliação vocal perceptivoauditiva e acústica, coleta de tempos máximos de fonação, triagem postural e determinação do tipo respiratório durante a fala, antes e após um programa terapêutico composto por orientação, conscientização e treinamento vocal com sons nasais durante 16 sessões de fonoterapia, uma vez na semana com treinamento em domicílio. Os dados foram analisados por meio dos testes não-paramétricos Mann-Whitney e Qui-quadrado, com nível de significância de 5%. Pós-terapia, observou-se que a postura corporal passou de desalinhada para alinhada e o tipo respiratório de superior para costodiafragmático abdominal; houve diminuição das medidas acústicas em relação ao grau e número de subharmônicos na maioria significante dos sujeitos, além de melhoras teciduais e diminuição do edema na mucosa das pregas vocais e na região aritenoide, e melhora da coaptação glótica. Após a execução de um programa fonoterapêutico com orientação vocal e postural, adequação da função respiratória e uso da técnica de sons nasais em disfonias hiperfuncionais, observou-se melhora significante da postura corporal, do tipo respiratório, das medidas acústicas sugestivas de ruído à emissão vocal, e efeitos positivos sobre o tecido e o fechamento das pregas vocais.

  10. Ethics of intergenerational (father-to-son) sperm donation.

    Science.gov (United States)

    Bredenoord, Annelien L; Lock, Matthias T W T; Broekmans, Frank J M

    2012-05-01

    In the ever changing field of reproductive medicine, clinics are regularly confronted with requests for novel variants of medically assisted reproduction. Particularly third-party (assisted) reproduction, which requires the involvement of an oocyte or sperm donor, is ethically and psychologically complex due to the parties involved, but nevertheless widely accepted. A particular type of third party reproduction concerns intrafamilial medically assisted reproduction (IMAR), where the donor is a family member of the recipients. In IMAR, some of the ethical and psychological issues associated with third party reproduction are intensified. The precise impact and consequences, however, remain speculative due to the lack of information regarding IMAR. Both the ESHRE Task Force on Ethics and Law and the Human Fertilization and Embryology Authority have recently highlighted the lack of information and the need for debate. In order to contribute to the discussion and knowledge on IMAR, we present a couple that recently visited our academic clinic with a request for a very particular variant of IMAR: first degree, intergenerational father-to-son sperm donation. As our academic hospital did not have experience with this variant of IMAR, our interdisciplinary Ethics Committee for Reproductive Medicine extensively discussed the request, resulting in an advisory report on the ethics of IMAR in general and father-to-son sperm donation in particular. Here, we will first present the andrological and social background of the couple and subsequently discuss the ethical considerations that led to the approval of their request. We will conclude the paper with recommendations for a morally sound practice of IMAR.

  11. Abrogation of CC chemokine receptor 9 ameliorates ventricular remodeling in mice after myocardial infarction.

    Science.gov (United States)

    Huang, Yan; Wang, Dandan; Wang, Xin; Zhang, Yijie; Liu, Tao; Chen, Yuting; Tang, Yanhong; Wang, Teng; Hu, Dan; Huang, Congxin

    2016-01-01

    CC chemokine receptor 9 (CCR9), which is a unique receptor for CC chemokine ligand (CCL25), is mainly expressed on lymphocytes, dendritic cells (DCs) and monocytes/macrophages. CCR9 mediates the chemotaxis of inflammatory cells and participates in the pathological progression of inflammatory diseases. However, the role of CCR9 in the pathological process of myocardial infarction (MI) remains unexplored; inflammation plays a key role in this process. Here, we used CCR9 knockout mice to determine the functional significance of CCR9 in regulating post-MI cardiac remodeling and its underlying mechanism. MI was induced by surgical ligation of the left anterior descending coronary artery in CCR9 knockout mice and their CCR9+/+ littermates. Our results showed that the CCR9 expression levels were up-regulated in the hearts of the MI mice. Abrogation of CCR9 improved the post-MI survival rate and left ventricular (LV) dysfunction and decreased the infarct size. In addition, the CCR9 knockout mice exhibited attenuated inflammation, apoptosis, structural and electrical remodeling compared with the CCR9+/+ MI mice. Mechanistically, CCR9 mainly regulated the pathological response by interfering with the NF-κB and MAPK signaling pathways. In conclusion, the data reveal that CCR9 serves as a novel modulator of pathological progression following MI through NF-κB and MAPK signaling.

  12. Lipoteichoic acid synthesis inhibition in combination with antibiotics abrogates growth of multidrug-resistant Enterococcus faecium.

    Science.gov (United States)

    Paganelli, Fernanda L; van de Kamer, Tim; Brouwer, Ellen C; Leavis, Helen L; Woodford, Neil; Bonten, Marc J M; Willems, Rob J L; Hendrickx, Antoni P A

    2017-03-01

    Enterococcus faecium is a multidrug-resistant (MDR) nosocomial pathogen causing significant morbidity in debilitated patients. New antimicrobials are needed to treat antibiotic-resistant E. faecium infections in hospitalised patients. E. faecium incorporates lipoteichoic acid (LTA) (1,3-polyglycerol-phosphate linked to glycolipid) in its cell wall. The small-molecule inhibitor 1771 [2-oxo-2-(5-phenyl-1,3,4-oxadiazol-2-ylamino)ethyl 2-naphtho[2,1-b]furan-1-ylacetate] specifically blocks the activity of Staphylococcus aureus LtaS synthase, which polymerises 1,3-glycerolphosphate into LTA polymers. Here we characterised the effects of the small-molecule inhibitor 1771 on the growth of E. faecium isolates, alone (28 strains) or in combination with the antibiotics vancomycin, daptomycin, ampicillin, gentamicin or linezolid (15 strains), and on biofilm formation (16 strains). Inhibition of LTA synthesis at the surface of the cell by compound 1771 in combination with current antibiotic therapy abrogates enterococcal growth in vitro but does not affect mature E. faecium biofilms. Targeting LTA synthesis may provide new possibilities to treat MDR E. faecium infections.

  13. Telomerase expression abrogates rapamycin-induced irreversible growth arrest of uterine fibroid smooth muscle cells.

    Science.gov (United States)

    Suo, Guangli; Sadarangani, Anil; Tang, Wingchung; Cowan, Bryan D; Wang, Jean Y J

    2014-09-01

    Uterine fibroids are the most common solid tumors found in women of reproductive age. It has been reported that deregulation of the mammalian target of rapamycin (mTOR) pathway plays an important role in the etiology of leiomyoma. Here, we investigated the effect of rapamycin, an inhibitor of mTORC1, on the growth of primary fibroid smooth muscle cells (fSMCs) and human telomerase reverse transcriptase (hTERT)-transduced and immortalized fSMCs. With the primary fSMCs, a 24-hour treatment with rapamycin was sufficient to trigger a growth arrest that was not reversible upon drug removal. By contrast, the growth inhibitory effect of rapamycin on the hTERT-transduced fSMCs was readily reversible, as these cells resumed proliferation upon the withdrawal of the drug. These results suggest that rapamycin-induced irreversible growth arrest of fSMCs is dependent on the senescence barrier that is abrogated by the ectopic expression of telomerase.

  14. Secoisolariciresinol diglucoside abrogates oxidative stress-induced damage in cardiac iron overload condition.

    Directory of Open Access Journals (Sweden)

    Stephanie Puukila

    Full Text Available Cardiac iron overload is directly associated with cardiac dysfunction and can ultimately lead to heart failure. This study examined the effect of secoisolariciresinol diglucoside (SDG, a component of flaxseed, on iron overload induced cardiac damage by evaluating oxidative stress, inflammation and apoptosis in H9c2 cardiomyocytes. Cells were incubated with 50 μ5M iron for 24 hours and/or a 24 hour pre-treatment of 500 μ M SDG. Cardiac iron overload resulted in increased oxidative stress and gene expression of the inflammatory mediators tumor necrosis factor-α, interleukin-10 and interferon γ, as well as matrix metalloproteinases-2 and -9. Increased apoptosis was evident by increased active caspase 3/7 activity and increased protein expression of Forkhead box O3a, caspase 3 and Bax. Cardiac iron overload also resulted in increased protein expression of p70S6 Kinase 1 and decreased expression of AMP-activated protein kinase. Pre-treatment with SDG abrogated the iron-induced increases in oxidative stress, inflammation and apoptosis, as well as the increased p70S6 Kinase 1 and decreased AMP-activated protein kinase expression. The decrease in superoxide dismutase activity by iron treatment was prevented by pre-treatment with SDG in the presence of iron. Based on these findings we conclude that SDG was cytoprotective in an in vitro model of iron overload induced redox-inflammatory damage, suggesting a novel potential role for SDG in cardiac iron overload.

  15. Upregulation of neurovascular communication through filamin abrogation promotes ectopic periventricular neurogenesis

    Science.gov (United States)

    Houlihan, Shauna L; Lanctot, Alison A; Guo, Yan; Feng, Yuanyi

    2016-01-01

    Neuronal fate-restricted intermediate progenitors (IPs) are derived from the multipotent radial glia (RGs) and serve as the direct precursors for cerebral cortical neurons, but factors that control their neurogenic plasticity remain elusive. Here we report that IPs’ neuron production is enhanced by abrogating filamin function, leading to the generation of periventricular neurons independent of normal neocortical neurogenesis and neuronal migration. Loss of Flna in neural progenitor cells (NPCs) led RGs to undergo changes resembling epithelial-mesenchymal transition (EMT) along with exuberant angiogenesis that together changed the microenvironment and increased neurogenesis of IPs. We show that by collaborating with β-arrestin, Flna maintains the homeostatic signaling between the vasculature and NPCs, and loss of this function results in escalated Vegfa and Igf2 signaling, which exacerbates both EMT and angiogenesis to further potentiate IPs’ neurogenesis. These results suggest that the neurogenic potential of IPs may be boosted in vivo by manipulating Flna-mediated neurovascular communication. DOI: http://dx.doi.org/10.7554/eLife.17823.001 PMID:27664421

  16. Abrogation of plasminogen activator inhibitor-1-vitronectin interaction ameliorates acute kidney injury in murine endotoxemia.

    Directory of Open Access Journals (Sweden)

    Kamlesh K Gupta

    Full Text Available Sepsis-induced acute kidney injury (AKI contributes to the high mortality and morbidity in patients. Although the pathogenesis of AKI during sepsis is poorly understood, it is well accepted that plasminogen activator inhibitor-1 (PAI-1 and vitronectin (Vn are involved in AKI. However, the functional cooperation between PAI-1 and Vn in septic AKI has not been completely elucidated. To address this issue, mice were utilized lacking either PAI-1 (PAI-1-/- or expressing a PAI-1-mutant (PAI-1R101A/Q123K in which the interaction between PAI-1 and Vn is abrogated, while other functions of PAI-1 are retained. It was found that both PAI-1-/- and PAI-1R101A/Q123K mice are associated with decreased renal dysfunction, apoptosis, inflammation, and ERK activation as compared to wild-type (WT mice after LPS challenge. Also, PAI-1-/- mice showed attenuated fibrin deposition in the kidneys. Furthermore, a lack of PAI-1 or PAI-1-Vn interaction was found to be associated with an increase in activated Protein C (aPC in plasma. These results demonstrate that PAI-1, through its interaction with Vn, exerts multiple deleterious mechanisms to induce AKI. Therefore, targeting of the PAI-1-Vn interaction in kidney represents an appealing therapeutic strategy for the treatment of septic AKI by not only altering the fibrinolytic capacity but also regulating PC activity.

  17. Niacinamide abrogates the organ dysfunction and acute lung injury caused by endotoxin.

    Science.gov (United States)

    Kao, Shang-Jyh; Liu, Demeral David; Su, Chain-Fa; Chen, Hsing I

    2007-09-01

    Poly (ADP-ribose) synthabse (PARS) or polymerase (PARP) is a cytotoxic enzyme causing cellular damage. Niacinamide inhibits PARS or PARP. The present experiment tests the effects of niacinamide (NCA) on organ dysfunction and acute lung injury (ALI) following lipopolysaccharide (LPS). LPS was administered to anesthetized rats and to isolated rat lungs. In anesthetized rats, LPS caused systemic hypotension and increased biochemical factors, nitrate/nitrite (NOx), methyl guanidine (MG), tumor necrosis factoralpha (TNFalpha), and interleukin-1beta (IL-1beta). In isolated lungs, LPS increased lung weight (LW) to body weight ratio, LW gain, protein and dye tracer leakage, and capillary permeability. The insult also increased NOx, MG, TNFalpha, and IL-1beta in lung perfusate, while decreased adenosine triphosphate (ATP) content with an increase in PARP activity in lung tissue. Pathological examination revealed pulmonary edema with inflammatory cell infiltration. These changes were abrogated by posttreatment (30 min after LPS) with NCA. Following LPS, the inducible NO synthase (iNOS) mRNA expression was increased. NCA reduced the iNOS expression. Niacinamide exerts protective effects on the organ dysfunction and ALI caused by endotoxin. The mechanisms may be mediated through the inhibition on the PARP activity, iNOS expression and the subsequent suppression of NO, free radicals, and proinflammatory cytokines with restoration of ATP.

  18. Effector T Cells Abrogate Stroma-Mediated Chemoresistance in Ovarian Cancer.

    Science.gov (United States)

    Wang, Weimin; Kryczek, Ilona; Dostál, Lubomír; Lin, Heng; Tan, Lijun; Zhao, Lili; Lu, Fujia; Wei, Shuang; Maj, Tomasz; Peng, Dongjun; He, Gong; Vatan, Linda; Szeliga, Wojciech; Kuick, Rork; Kotarski, Jan; Tarkowski, Rafał; Dou, Yali; Rattan, Ramandeep; Munkarah, Adnan; Liu, J Rebecca; Zou, Weiping

    2016-05-19

    Effector T cells and fibroblasts are major components in the tumor microenvironment. The means through which these cellular interactions affect chemoresistance is unclear. Here, we show that fibroblasts diminish nuclear accumulation of platinum in ovarian cancer cells, resulting in resistance to platinum-based chemotherapy. We demonstrate that glutathione and cysteine released by fibroblasts contribute to this resistance. CD8(+) T cells abolish the resistance by altering glutathione and cystine metabolism in fibroblasts. CD8(+) T-cell-derived interferon (IFN)γ controls fibroblast glutathione and cysteine through upregulation of gamma-glutamyltransferases and transcriptional repression of system xc(-) cystine and glutamate antiporter via the JAK/STAT1 pathway. The presence of stromal fibroblasts and CD8(+) T cells is negatively and positively associated with ovarian cancer patient survival, respectively. Thus, our work uncovers a mode of action for effector T cells: they abrogate stromal-mediated chemoresistance. Capitalizing upon the interplay between chemotherapy and immunotherapy holds high potential for cancer treatment.

  19. Galangin Abrogates Ovalbumin-Induced Airway Inflammation via Negative Regulation of NF-κB

    Directory of Open Access Journals (Sweden)

    Wang-Jian Zha

    2013-01-01

    Full Text Available Persistent activation of nuclear factor κB (NF-κB has been associated with the development of asthma. Galangin, the active pharmacological ingredient from Alpinia galanga, is reported to have a variety of anti-inflammatory properties in vitro via negative regulation of NF-κB. This study aimed to investigate whether galangin can abrogate ovalbumin- (OVA- induced airway inflammation by negative regulation of NF-κB. BALB/c mice sensitized and challenged with OVA developed airway hyperresponsiveness (AHR and inflammation. Galangin dose dependently inhibited OVA-induced increases in total cell counts, eosinophil counts, and interleukin-(IL- 4, IL-5, and IL-13 levels in bronchoalveolar lavage fluid, and reduced serum level of OVA-specific IgE. Galangin also attenuated AHR, reduced eosinophil infiltration and goblet cell hyperplasia, and reduced expression of inducible nitric oxide synthase and vascular cell adhesion protein-1 (VCAM-1 levels in lung tissue. Additionally, galangin blocked inhibitor of κB degradation, phosphorylation of the p65 subunit of NF-κB, and p65 nuclear translocation from lung tissues of OVA-sensitized mice. Similarly, in normal human airway smooth muscle cells, galangin blocked tumor necrosis factor-α induced p65 nuclear translocation and expression of monocyte chemoattractant protein-1, eotaxin, CXCL10, and VCAM-1. These results suggest that galangin can attenuate ovalbumin-induced airway inflammation by inhibiting the NF-κB pathway.

  20. CK2 abrogates the inhibitory effects of PRH/HHEX on prostate cancer cell migration and invasion and acts through PRH to control cell proliferation

    Science.gov (United States)

    Siddiqui, Y H; Kershaw, R M; Humphreys, E H; Assis Junior, E M; Chaudhri, S; Jayaraman, P-S; Gaston, K

    2017-01-01

    PRH/HHEX (proline-rich homeodomain protein/haematopoietically expressed homeobox protein) is a transcription factor that controls cell proliferation, cell differentiation and cell migration. Our previous work has shown that in haematopoietic cells, Protein Kinase CK2-dependent phosphorylation of PRH results in the inhibition of PRH DNA-binding activity, increased cleavage of PRH by the proteasome and the misregulation of PRH target genes. Here we show that PRH and hyper-phosphorylated PRH are present in normal prostate epithelial cells, and that hyper-phosphorylated PRH levels are elevated in benign prostatic hyperplasia, prostatic adenocarcinoma, and prostate cancer cell lines. A reduction in PRH protein levels increases the motility of normal prostate epithelial cells and conversely, PRH over-expression inhibits prostate cancer cell migration and blocks the ability of these cells to invade an extracellular matrix. We show that CK2 over-expression blocks the repression of prostate cancer cell migration and invasion by PRH. In addition, we show that PRH knockdown in normal immortalised prostate cells results in an increase in the population of cells capable of colony formation in Matrigel, as well as increased cell invasion and decreased E-cadherin expression. Inhibition of CK2 reduces PRH phosphorylation and reduces prostate cell proliferation but the effects of CK2 inhibition on cell proliferation are abrogated in PRH knockdown cells. These data suggest that the increased phosphorylation of PRH in prostate cancer cells increases both cell proliferation and tumour cell migration/invasion. PMID:28134934

  1. Genetic and biochemical evidences reveal novel insights into the mechanism underlying Saccharomyces cerevisiae Sae2-mediated abrogation of DNA replication stress

    Indian Academy of Sciences (India)

    INDRAJEET GHODKE; K MUNIYAPPA

    2016-12-01

    In Saccharomyces cerevisiae, the Mre11-Rad50-Xrs2 (MRX) protein complex plays pivotal roles in double-strandbreak (DSB) repair, replication stress and telomere length maintenance. Another protein linked to DSB repair is Sae2,which regulates MRX persistence at DSBs. However, very little is known about its role in DNA replication stress andrepair. Here, we reveal a crucial role for Sae2 in DNA replication stress. We show that different mutant alleles of SAE2cause hypersensitivity to genotoxic agents, and when combined with Δmre11 or nuclease-defective mre11 mutantalleles, the double mutants are considerably more sensitive suggesting that the sae2 mutations synergize with mre11mutations. Biochemical studies demonstrate that Sae2 exists as a dimer in solution, associates preferentially withsingle-stranded and branched DNA structures, exhibits structure-specific endonuclease activity and cleaves thesesubstrates from the 5′ end. Furthermore, we show that the nuclease activity is indeed intrinsic to Sae2. Interestingly,sae2G270D protein possesses DNA-binding activity, but lacks detectable nuclease activity. Altogether, our data suggesta direct role for Sae2 nuclease activity in processing of the DNA structures that arise during replication and DNAdamage and provide insights into the mechanism underlying Mre11-Sae2-mediated abrogation of replication stress-relateddefects in S. cerevisiae.

  2. ¿Son las mujeres una minoría?

    Directory of Open Access Journals (Sweden)

    Osborne, Raquel

    1996-10-01

    Full Text Available Not available.

    El clásico tratamiento de las mujeres como minoría desde la sociología se halla contemporáneamente interrelacionado con las políticas de igualdad tejidas en torno a las mujeres. Pasado y presente, teoría y práctica se unen para mostrar que las teorías no son accidentales ni fortuitas sino que acarrean importantes consecuencias en la acción, pudiendo dar lugar a intervenciones en la vida pública, que es lo que, a mi entender, confiere su sentido a la. sociología y, en particular, a la sociología del género. El título alude a la existencia de un importante desarrollo en sociología de la temática de las minorías, que traemos a colación por cuanto desde muy temprano dicha ciencia refirió este tema a las mujeres, desarrollo que seguiremos en este artículo. La conceptualización de las mujeres como minoría se traducirá, en términos de políticas públicas, en lo que se conoce como medidas de acción o discriminación positiva impulsadas, en lo que a las mujeres atañe, por el movimiento feminista.

  3. Jean Alesi and his son Giuliano visited CERN

    CERN Multimedia

    Emma Jones

    2010-01-01

    Jean Alesi, former F1 racing driver, and his kids visited CERN on Monday 1st February 2010. The Bulletin and the Video productions team had the opportunity to meet him. The video interview is transcribed for your convenience. What attracted you to CERN, what was it that made you want to come? We talked at home with the children about places to see close to us, like CERN, where they are seeking to reproduce the origins of the world. These things are so far removed from what we ordinarily think and talk about, that they captured our imagination and made us want to come see for ourselves. We know that your son (Giuliano, 9 years) is interested in what is happening at CERN, so we'd like to ask him: how did he find out about it? Giuliano: I am very interested in the technologies used in laboratories, and the exploration of the Universe. Plus, I wanted to see some of the incredible machines. I enjoyed my visit a lot. I found out about CERN from my mother. She showed me a video that I really liked, so I wanted to...

  4. Mammalian target of rapamycin inhibitor abrogates abnormal osteoclastogenesis in neurofibromatosis type 1

    Institute of Scientific and Technical Information of China (English)

    LIU Ning; XU Ning; WEI Li-hui; CHAI Guo-lin

    2013-01-01

    Background Neurofibromatosis type 1 (NF1) is the most common genetic syndrome predisposing patients to various tumors due to dysregulation of the Ras signaling pathway.Recent research has shown NF1 patients also suffer a spectrum of bone pathologies.The pathogenesis of NF1 bone diseases is largely unknown.There is no current treatment.By Nf1 heterozygote (Nf1+/-) mice and Nf1 conditional knockout mice,we and other groups demonstrated abnormal osteoblast and osteoclast function due to dysregulation of Ras signaling.However,the specific downstream effector pathways linked to NF1 abnormal osteoblastogenesis and osteoclastogenesis have not been defined.In this study,we investigated the Ras downstream effector related with NF1 bone disease.Methods We used Nf1+/+ and Nf1+/-mice as normal and NF1 models.Bone stromal cells extracted from Nf1+/+ and Nf1+/-mice were induced osteoclasts.The osteoclast cell was stained by tartrate resistant acid phosphatase staining.The osteoclast cell number was counted and the surface area of osteoclast cells was calculated under the microscope.The mRNA of mammalian target of rapamycin (mTOR) was determined by quantitative reverse-transcription-polymerase chain reaction.The presence of ribosomal protein S6 kinase was determined by Western blotting.Results Compared with Nf1+/+ mice,Nf1+/-mice had about 20% more of osteoclast cells.These osteoclast cells werelarger in size with more nuclei.Hyperactive mTOR was detected in Nf1+/-osteoclast cells.Inhibition of mTOR signalingby rapamycin in Nf1+/-osteoclasts abrogated abnormalities in cellular size and number.Conclusion mTOR pathway inhibition may represent a viable therapy for NF1 bone diseases.

  5. Targeting ILK and {beta}4 integrin abrogates the invasive potential of ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yoon Pyo; Kim, Baek Gil [BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Gao, Ming-Qing; Kang, Suki [Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cho, Nam Hoon, E-mail: cho1988@yuhs.ac [BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer The potential of targeting ILK and integrins for highly aggressive ovarian cancer. Black-Right-Pointing-Pointer Unanticipated synergistic effect for the combination of ILK/{beta}4 integrin. Black-Right-Pointing-Pointer Combination of ILK/{beta}4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. Black-Right-Pointing-Pointer Targeting of {beta}4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of {beta}1 and {beta}4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of {beta}1 and {beta}4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of {beta}4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of {beta}4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting {beta}4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.

  6. Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Ahad, Amjid [Lipid Metabolism Laboratory, Department of Biochemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Ganai, Ajaz Ahmad [Department of Biotechnology, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Mujeeb, Mohd [Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Siddiqui, Waseem Ahmad, E-mail: was.sid121@gmail.com [Lipid Metabolism Laboratory, Department of Biochemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India)

    2014-08-15

    Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16 weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-kB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway. - Highlights: • Chrysin reduced renal oxidative stress and inflammation in diabetic rats. • Chrysin reduced serum levels of pro-inflammatory in diabetic rats. • Chrysin exhibited renal protective effect by suppressing the TNF-α pathway.

  7. Mothers' Predictions of Their Son's Executive Functioning Skills: Relations to Child Behavior Problems

    Science.gov (United States)

    Johnston, Charlotte

    2011-01-01

    This study examined mothers' ability to accurately predict their sons' performance on executive functioning tasks in relation to the child's behavior problems. One-hundred thirteen mothers and their 4-7 year old sons participated. From behind a one-way mirror, mothers watched their sons perform tasks assessing inhibition and planning skills.…

  8. Abrogation of anti-retinal autoimmunity in IL-10 transgenic mice due to reduced T cell priming and inhibition of disease effector mechanisms.

    Science.gov (United States)

    Agarwal, Rajeev K; Horai, Reiko; Viley, Angelia M; Silver, Phyllis B; Grajewski, Rafael S; Su, Shao Bo; Yazdani, Arrash T; Zhu, Wei; Kronenberg, Mitchell; Murray, Peter J; Rutschman, Robert L; Chan, Chi-Chao; Caspi, Rachel R

    2008-04-15

    Experimental autoimmune uveitis (EAU) induced by immunization of animals with retinal Ags is a model for human uveitis. The immunosuppressive cytokine IL-10 regulates EAU susceptibility and may be a factor in genetic resistance to EAU. To further elucidate the regulatory role of endogenous IL-10 in the mouse model of EAU, we examined transgenic (Tg) mice expressing IL-10 either in activated T cells (inducible) or in macrophages (constitutive). These IL-10-Tg mice and non-Tg wild-type controls were immunized with a uveitogenic regimen of the retinal Ag interphotoreceptor retinoid-binding protein. Constitutive expression of IL-10 in macrophages abrogated disease and reduced Ag-specific immunological responses. These mice had detectable levels of IL-10 in sera and in ocular extracts. In contrast, expression of IL-10 in activated T cells only partially protected from EAU and marginally reduced Ag-specific responses. All IL-10-Tg lines showed suppression of Ag-specific effector cytokines. APC from Tg mice constitutively expressing IL-10 in macrophages exhibited decreased ability to prime naive T cells, however, Ag presentation to already primed T cells was not compromised. Importantly, IL-10-Tg mice that received interphotoreceptor retinoid-binding protein-specific uveitogenic T cells from wild-type donors were protected from EAU. We suggest that constitutively produced endogenous IL-10 ameliorates the development of EAU by suppressing de novo priming of Ag-specific T cells and inhibiting the recruitment and/or function of inflammatory leukocytes, rather than by inhibiting local Ag presentation within the eye.

  9. SysSon: A Sonification Platform for Climate Data

    Science.gov (United States)

    Visda, Goudarzi; Hanns Holger, Rutz; Katharina, Vogt

    2014-05-01

    Climate data provide a challenging working basis for sonification. Both model data and measured data are assessed in collaboration with the Wegener Center for Climate and Global Change. The multi dimensionality and multi variety of climate data has a great potential for auditory displays. Furthermore, there is consensus on global climate change and the necessity of intensified climate research today in the scientific community and general public. Sonification provides a new means to communicate scientific results and inform a wider audience. SysSon is a user centered auditory platform for climate scientists to analyze data. It gives scientists broader insights by extracting hidden patterns and features from data that is not possible using a single modal visual interface. A variety of soundscapes to chose from lessens the fatigue that comes with repeated and sustained listening to long streams of data. Initial needs assessments and user tests made the work procedures and the terminology of climate scientists clear and informed the architecture of our system. Furthermore, experiments evaluated the sound design which led to a more advanced soundscape and improvement of the auditory display. We present a novel interactive sonification tool which combines a workspace for the scientists with a development environment for sonification models. The tool runs on different operating systems and is released as open source. In the standalone desktop application, multiple data sources can be imported, navigated and manipulated either via text or a graphical interface, including traditional plotting facilities. Sound models are built from unit generator graphs which are enhanced with matrix manipulation functions. They allow us to systematically experiment with elements known from the visual domain, such as range selections, scaling, thresholding, markers and labels. The models are organized in an extensible library, from which the user can choose and parametrize. Importance is

  10. ¿Son los MOOC una alternativa de aprendizaje?

    Directory of Open Access Journals (Sweden)

    Antonio Ramón Bartolomé Pina

    2015-01-01

    Full Text Available Este trabajo reflexiona sobre los MOOC como entornos de aprendizaje. El número de cursos masivos abiertos y en línea (MOOC ha crecido exponencialmente en pocos años desde que fueron introducidos. Los MOOC son considerados una nueva forma de entornos virtuales de aprendizaje potenciados por la tecnología. Se consideran dos tipos de MOOC: unos los organizados por Siemens y Downes (cMOOC y otros los desarrollados en lugares como Stanford, con muchos estudiantes y loables objetivos (xMOOC; estos tienen también sus debilidades. Aunque han sido recibidos con altas expectativas, también han encontrado una fuerte oposición que está aumentando con el tiempo, lo que nos permite estudiar este fenómeno en profundidad. Aunque todavía hay pocas investigaciones empíricas sobre los efectos de los MOOC en el aprendizaje, este estudio trata de arrojar luz sobre el tema desde un punto de vista teórico. En primer lugar exploraremos las expectativas positivas y negativas generadas. Los MOOC pueden constituir una buena propuesta a gran escala, lo que solo es posible para unas pocas grandes instituciones. No hay estudio de mercado, ni modelo de negocio, ni investigaciones empíricas que permitan confirmar los anuncios de sus efectos positivos. Revisaremos las teorías del aprendizaje recientes y clásicas respecto a su capacidad para explicar el proceso de aprendizaje y compararemos los cursos en línea tradicionales, los xMOOC y los cMOOC en relación a su potencial para apoyar el aprendizaje y su auto-regulación.

  11. On the“Oedipus Complex”in Sons and Lovers-Mother is a lover of her son

    Institute of Scientific and Technical Information of China (English)

    王瑞瑒

    2014-01-01

    Sons and Lovers is one of Lawrence’s most famous novels. It mainly concerns about the love affairs among the main character-Paul, his mother and his two girlfriends. The mother’s strange love has affected the boys for a long time, which even has made him lose the ability to love other girls. As a result, Paul gradually has the“Oedipus Complex”towards his mother, and it has influenced the whole lifetime of himself. During the competition of grasp the heart of Paul, Miriam and Clara are all the los-ers, while they both can’t drag Paul out of the influence from his mother. It is not until the death of his mother does Paul finally escape from the control of his mother. All the origins can be concluded into one thing-that is the Paul’s“Oedipus Complex”towards his mother. What is the“Oedipus Complex”, and how does it reflect in the main content? How does it influence the emotions of Paul step by step? This essay will elaborate it in detail.

  12. De Novo Truncating Variants in SON Cause Intellectual Disability, Congenital Malformations, and Failure to Thrive.

    Science.gov (United States)

    Tokita, Mari J; Braxton, Alicia A; Shao, Yunru; Lewis, Andrea M; Vincent, Marie; Küry, Sébastien; Besnard, Thomas; Isidor, Bertrand; Latypova, Xénia; Bézieau, Stéphane; Liu, Pengfei; Motter, Connie S; Melver, Catherine Ward; Robin, Nathaniel H; Infante, Elena M; McGuire, Marianne; El-Gharbawy, Areeg; Littlejohn, Rebecca O; McLean, Scott D; Bi, Weimin; Bacino, Carlos A; Lalani, Seema R; Scott, Daryl A; Eng, Christine M; Yang, Yaping; Schaaf, Christian P; Walkiewicz, Magdalena A

    2016-09-01

    SON is a key component of the spliceosomal complex and a critical mediator of constitutive and alternative splicing. Additionally, SON has been shown to influence cell-cycle progression, genomic integrity, and maintenance of pluripotency in stem cell populations. The clear functional relevance of SON in coordinating essential cellular processes and its presence in diverse human tissues suggests that intact SON might be crucial for normal growth and development. However, the phenotypic effects of deleterious germline variants in SON have not been clearly defined. Herein, we describe seven unrelated individuals with de novo variants in SON and propose that deleterious variants in SON are associated with a severe multisystem disorder characterized by developmental delay, persistent feeding difficulties, and congenital malformations, including brain anomalies.

  13. Genistein abrogates G2 arrest induced by curcumin in p53 deficient T47D cells

    Directory of Open Access Journals (Sweden)

    Astuti Puji

    2012-11-01

    Full Text Available Abstract Background The high cost and low level of cancer survival urge the finding of new drugs having better mechanisms. There is a high trend of patients to be “back to nature” and use natural products as an alternative way to cure cancer. The fact is that some of available anticancer drugs are originated from plants, such as taxane, vincristine, vinblastine, pacitaxel. Curcumin (diferuloylmethane, a dietary pigment present in Curcuma longa rizhome is reported to induce cell cycle arrest in some cell lines. Other study reported that genistein isolated from Glycine max seed inhibited phosphorylation of cdk1, gene involved during G2/M transition and thus could function as G2 checkpoint abrogator. The inhibition of cdk1 phosphorylation is one of alternative strategy which could selectively kill cancer cells and potentially be combined with DNA damaging agent such as curcumin. Methods T47D cell line was treated with different concentrations of curcumin and genistein, alone or in combination; added together or with interval time. Flow Cytometry and MTT assay were used to evaluate cell cycle distribution and viability, respectively. The presence of apoptotic cells was determined using acridine orange-ethidium bromide staining. Results In this study curcumin induced G2 arrest on p53 deficient T47D cells at the concentration of 10 μM. Increasing concentration up to 30 μM increased the number of cell death. Whilst genistein alone at low concentration (≤10 μM induced cell proliferation, addition of genistein (20 μM 16 h after curcumin resulted in more cell death (89%, 34% higher than that administered at the same time (56%. The combination treatment resulted in apoptotic cell death. Combining curcumin with high dose of genistein (50 μM induced necrotic cells. Conclusions Genistein increased the death of curcumin treated T47D cells. Appropriate timing of administration and concentration of genistein determine the outcome of

  14. Dessiner son parcours professionnel, pour en tirer des enseignements

    Directory of Open Access Journals (Sweden)

    Pascale Corten-Gualtieri

    2011-02-01

    Full Text Available Dans le cadre de la formation continue pour des enseignants du supérieur, une activité d’expression visuelle a soutenu une posture réflexive à propos du développement professionnel de chacun. Il a été demandé aux enseignants de dessiner leur parcours professionnel en le comparant à un parcours routier. Ce dessin a ensuite servi de support aux enseignants pour dégager les leviers et les freins de leur développement professionnel, puis pour clarifier leur(s perspective(s d’évolution professionnelle. Cadrage théorique et échanges en binômes ont enrichi ce regard distancié. L’ensemble de ces activités constitue une préparation efficace et motivante à la rédaction d’un portfolio dans lequel l’enseignant analyse ses pratiques et son développement professionnels. Cet article décrit le cadre théorique et les modalités de cet ensemble d’activités ; il analyse ensuite les résultats obtenus, essentiellement à partir de l’étude du corpus de dessins réalisés par les enseignants, et d’une enquête d’évaluation réalisée auprès de ceux-ci.A recent visual creative activity carried out during a continuous education programme for teachers in higher education enhances reflective practice regarding professional development. Teachers were asked to draw their professional path as they would draw a route map. On the basis of this drawing, they were able to highlight the levers and obstacles in their professional development and then clarify their perspectives in terms of professional growth. This analysis was emphasized using a theoretical framework and exchanges in teams of two. All activities comprised an effective and stimulating preparation for writing a portfolio in which the teachers analyzed their professional practices and development. This article describes the theoretical framework and methods used during these activities; it then analyzes the results obtained based on the study of the various drawings made

  15. Abrogation of p53-induced apoptosis by the hepatitis B virus X gene.

    NARCIS (Netherlands)

    X.W. Wang (Xin Wei); M.K. Gibson (Michael); W. Vermeulen (Wim); H. Yeh; K. Forrester; H.-W. Stürzbecher; J.H.J. Hoeijmakers (Jan); C.C. Harris

    1996-01-01

    textabstractThe p53 tumor suppressor gene product is a transcriptional transactivator and a potent apoptotic inducer. The fact that many of the DNA tumor virus oncoproteins bind to p53 and affect these p53 functions indicates that this interaction is an important step in oncogenic transformation. We

  16. Artonin E and Structural Analogs from Artocarpus Species Abrogates Estrogen Receptor Signaling in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Imaobong Etti

    2016-06-01

    Full Text Available The increasing rate of mortality ensued from breast cancer has encouraged research into safer and efficient therapy. The human Estrogen receptor α has been implicated in the majority of reported breast cancer cases. Molecular docking employing Glide, Schrodinger suite 2015, was used to study the binding affinities of small molecules from the Artocarpus species after their drug-like properties were ascertained. The structure of the ligand-binding domain of human Estrogen receptor α was retrieved from Protein Data Bank while the structures of compounds were collected from PubChem database. The binding interactions of the studied compounds were reported as well as their glide scores. The best glide scored ligand, was Artonin E with a score of −12.72 Kcal when compared to other studied phytomolecules and it evoked growth inhibition of an estrogen receptor positive breast cancer cells in submicromolar concentration (3.8–6.9 µM in comparison to a reference standard Tamoxifen (18.9–24.1 µM within the tested time point (24–72 h. The studied ligands, which had good interactions with the target receptor, were also drug-like when compared with 95% of orally available drugs with the exception of Artoelastin, whose predicted physicochemical properties rendered it less drug-like. The in silico physicochemical properties, docking interactions and growth inhibition of the best glide scorer are indications of the anti-breast cancer relevance of the studied molecules.

  17. The Plasminogen-Binding Group A Streptococcal M Protein-Related Protein Prp Binds Plasminogen via Arginine and Histidine Residues▿

    Science.gov (United States)

    Sanderson-Smith, Martina L.; Dowton, Mark; Ranson, Marie; Walker, Mark J.

    2007-01-01

    The migration of the human pathogen Streptococcus pyogenes (group A streptococcus) from localized to deep tissue sites may result in severe invasive disease, and sequestration of the host zymogen plasminogen appears crucial for virulence. Here, we describe a novel plasminogen-binding M protein, the plasminogen-binding group A streptococcal M protein (PAM)-related protein (Prp). Prp is phylogenetically distinct from previously described plasminogen-binding M proteins of group A, C, and G streptococci. While competition experiments indicate that Prp binds plasminogen with a lower affinity than PAM (50% effective concentration = 0.34 μM), Prp nonetheless binds plasminogen with high affinity and at physiologically relevant concentrations of plasminogen (Kd = 7.8 nM). Site-directed mutagenesis of the putative plasminogen binding site indicates that unlike the majority of plasminogen receptors, Prp does not interact with plasminogen exclusively via lysine residues. Mutagenesis to alanine of lysine residues Lys96 and Lys101 reduced but did not abrogate plasminogen binding by Prp. Plasminogen binding was abolished only with the additional mutagenesis of Arg107 and His108 to alanine. Furthermore, mutagenesis of Arg107 and His108 abolished plasminogen binding by Prp despite the presence of Lys96 and Lys101 in the binding site. Thus, binding to plasminogen via arginine and histidine residues appears to be a conserved mechanism among plasminogen-binding M proteins. PMID:17012384

  18. The plasminogen-binding group A streptococcal M protein-related protein Prp binds plasminogen via arginine and histidine residues.

    Science.gov (United States)

    Sanderson-Smith, Martina L; Dowton, Mark; Ranson, Marie; Walker, Mark J

    2007-02-01

    The migration of the human pathogen Streptococcus pyogenes (group A streptococcus) from localized to deep tissue sites may result in severe invasive disease, and sequestration of the host zymogen plasminogen appears crucial for virulence. Here, we describe a novel plasminogen-binding M protein, the plasminogen-binding group A streptococcal M protein (PAM)-related protein (Prp). Prp is phylogenetically distinct from previously described plasminogen-binding M proteins of group A, C, and G streptococci. While competition experiments indicate that Prp binds plasminogen with a lower affinity than PAM (50% effective concentration = 0.34 microM), Prp nonetheless binds plasminogen with high affinity and at physiologically relevant concentrations of plasminogen (K(d) = 7.8 nM). Site-directed mutagenesis of the putative plasminogen binding site indicates that unlike the majority of plasminogen receptors, Prp does not interact with plasminogen exclusively via lysine residues. Mutagenesis to alanine of lysine residues Lys(96) and Lys(101) reduced but did not abrogate plasminogen binding by Prp. Plasminogen binding was abolished only with the additional mutagenesis of Arg(107) and His(108) to alanine. Furthermore, mutagenesis of Arg(107) and His(108) abolished plasminogen binding by Prp despite the presence of Lys(96) and Lys(101) in the binding site. Thus, binding to plasminogen via arginine and histidine residues appears to be a conserved mechanism among plasminogen-binding M proteins.

  19. Maternal pre-pregnancy body mass index and pubertal development among sons

    DEFF Research Database (Denmark)

    Hounsgaard, M L; Håkonsen, L B; Vested, A;

    2013-01-01

    Maternal overweight and obesity in pregnancy has been associated with earlier age of menarche in daughters as well as reduced semen quality in sons. We aimed at investigating pubertal development in sons born by mothers with a high body mass index (BMI). The study included 2522 sons of mothers...... that during pregnancy in 1984-1987 were enrolled in a mother-child cohort and gave information on their pre-pregnancy height and weight from which we calculated their BMI. Information on sons' pubertal development, assessed by age when starting regular shaving, voice break, acne and first nocturnal emission...... indicators of pubertal development, results also indicated earlier pubertal development among sons of obese mothers. After excluding sons of underweight mothers in a subanalysis, we observed an inverse trend between maternal pre-pregnancy BMI and age at regular shaving, acne and first nocturnal emission...

  20. SON68 glass dissolution driven by magnesium silicate precipitation

    Science.gov (United States)

    Fleury, Benjamin; Godon, Nicole; Ayral, André; Gin, Stéphane

    2013-11-01

    Experimental results are reported on the effect of magnesium silicate precipitation on the mechanisms and rate of borosilicate glass dissolution. Leaching experiments with SON68 glass, a borosilicate containing no Mg, were carried out in initially deionized water at 50 °C with a glass-surface-area-to-solution-volume ratio of 20,000 m-1. After 29 days of alteration the experimental conditions were modified by the addition of Mg to trigger the precipitation of Mg-silicate. Additional experiments were conducted to investigate the importance of other parameters such as pH or dissolved silica on the mechanisms of precipitation of Mg-silicates and their consequences on the glass dissolution rate. Mg-silicates precipitate immediately after Mg is added. The amount of altered glass increases with the quantity of added Mg, and is smaller when silicon is added in solution. A time lag is observed between the addition of magnesium and the resumption of glass alteration because silicon is first provided by partial dissolution of the previously formed alteration gel. It is shown that nucleation does not limit Mg-silicate precipitation. A pH above 8 is necessary for the phase to precipitate under the investigated experimental conditions. On the other hand the glass alteration kinetics limits the precipitation if the magnesium is supplied in solution at a non-limiting rate. The concentration of i in solution was analyzed as well as that of boron. The quantity of i released from the glass is estimated with the assumption that i and B are released congruently at the glass dissolution front. The remained quantity of the element i is then supposed to be in the gel or in the secondary phase. In this paper, we do not make a difference between gel and hydrated glass using the same word 'gel' whereas Gin et al. [40] makes this difference. Recent papers [40,41] discussed about different key issues related to the passivation properties of the alteration layer including the hydrated glass

  1. Comparison of father-son relationship in Chinese and American films

    Institute of Scientific and Technical Information of China (English)

    倪秀飞

    2015-01-01

    The depiction of human emotions is never lacking in filmography, and affection between family members accounts for the top spot to become the most deeply touching one, especially the father-son relationship. Compared with mother-daughter and mother-son relationship, father-son relationship is often full of tension, turning out to be more introverted. So, in which way do films and television shows at home and broad represent vividly and truly about the father-child relationship?

  2. Binding Procurement

    Science.gov (United States)

    Rao, Gopalakrishna M.; Vaidyanathan, Hari

    2007-01-01

    This viewgraph presentation reviews the use of the binding procurement process in purchasing Aerospace Flight Battery Systems. NASA Engineering and Safety Center (NESC) requested NASA Aerospace Flight Battery Systems Working Group to develop a set of guideline requirements document for Binding Procurement Contracts.

  3. Dietary chlorophyllin abrogates TGFβ signaling to modulate the hallmark capabilities of cancer in an animal model of forestomach carcinogenesis.

    Science.gov (United States)

    Thiyagarajan, Paranthaman; Kavitha, Krishnamurthy; Thautam, Avaneesh; Dixit, Madhulika; Nagini, Siddavaram

    2014-07-01

    Transforming growth factor (TGF) β signaling pathway plays a central role in the regulation of a wide range of cellular processes involved in the acquisition of the malignant phenotype. The objective of the present study was to examine the effect of chlorophyllin, a semisynthetic derivative of chlorophyll on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)--induced rat forestomach carcinogenesis based on the modulation of TGFβ signaling and the downstream target genes associated with cell proliferation, apoptosis evasion, angiogenesis, invasion, and metastasis. We determined the effect of dietary chlorophyllin on TGFβ signaling and the downstream events-cell proliferation, apoptosis evasion, angiogenesis, invasion, and metastasis by semiquantitative and quantitative reverse transcription (RT)-PCR, Western blot, and immunohistochemical analyses. We further validated the inhibition of TGFβ signaling by chlorophyllin by performing molecular docking studies. We found that dietary supplementation of chlorophyllin at 4-mg/kg bw inhibits the development of MNNG-induced forestomach carcinomas by downregulating the expression of TGFβ RI, TGFβ RII, and Smad 2 and 4 and upregulating Smad 7, thereby abrogating canonical TGFβ signaling. Docking interactions also confirmed the inhibition of TGFβ signaling by chlorophyllin via inactivating TGFβ RI. Furthermore, attenuation of TGFβ signaling by chlorophyllin also blocked cell proliferation, angiogenesis, invasion, and metastasis, and induced mitochondria-mediated cell death. Dietary chlorophyllin that simultaneously abrogates TGFβ signaling pathway and the key hallmark events of cancer appear to be an ideal candidate for cancer chemoprevention.

  4. IL-4 abrogates TH17 cell-mediated inflammation by selective silencing of IL-23 in antigen-presenting cells

    Science.gov (United States)

    Guenova, Emmanuella; Skabytska, Yuliya; Hoetzenecker, Wolfram; Weindl, Günther; Sauer, Karin; Tham, Manuela; Kim, Kyu-Won; Park, Ji-Hyeon; Seo, Ji Hae; Ignatova, Desislava; Cozzio, Antonio; Levesque, Mitchell P.; Volz, Thomas; Köberle, Martin; Kaesler, Susanne; Thomas, Peter; Mailhammer, Reinhard; Ghoreschi, Kamran; Schäkel, Knut; Amarov, Boyko; Eichner, Martin; Schaller, Martin; Clark, Rachael A.; Röcken, Martin; Biedermann, Tilo

    2015-01-01

    Interleukin 4 (IL-4) can suppress delayed-type hypersensitivity reactions (DTHRs), including organ-specific autoimmune diseases in mice and humans. Despite the broadly documented antiinflammatory effect of IL-4, the underlying mode of action remains incompletely understood, as IL-4 also promotes IL-12 production by dendritic cells (DCs) and IFN-γ–producing TH1 cells in vivo. Studying the impact of IL-4 on the polarization of human and mouse DCs, we found that IL-4 exerts opposing effects on the production of either IL-12 or IL-23. While promoting IL-12–producing capacity of DCs, IL-4 completely abrogates IL-23. Bone marrow chimeras proved that IL-4–mediated suppression of DTHRs relies on the signal transducer and activator of transcription 6 (STAT6)-dependent abrogation of IL-23 in antigen-presenting cells. Moreover, IL-4 therapy attenuated DTHRs by STAT6- and activating transcription factor 3 (ATF3)-dependent suppression of the IL-23/TH17 responses despite simultaneous enhancement of IL-12/TH1 responses. As IL-4 therapy also improves psoriasis in humans and suppresses IL-23/TH17 responses without blocking IL-12/TH1, selective IL-4–mediated IL-23/TH17 silencing is promising as treatment against harmful inflammation, while sparing the IL-12–dependent TH1 responses. PMID:25646481

  5. Radiosensitization of metformin in pancreatic cancer cells via abrogating the G2 checkpoint and inhibiting DNA damage repair.

    Science.gov (United States)

    Wang, Zheng; Lai, Song-Tao; Ma, Ning-Yi; Deng, Yun; Liu, Yong; Wei, Dong-Ping; Zhao, Jian-Dong; Jiang, Guo-Liang

    2015-12-01

    Recent evidences have demonstrated the potential of metformin as a novel agent for cancer prevention and treatment. Here, we investigated its ability of radiosensitization and the underlying mechanisms in human pancreatic cancer cells. In this study, we found that metformin at 5 mM concentration enhanced the radiosensitivity of MIA PaCa-2 and PANC-1 cells, with sensitization enhancement ratios of 1.39 and 1.27, respectively. Mechanistically, metformin caused abrogation of the G2 checkpoint and increase of mitotic catastrophe, associated with suppression of Wee1 kinase and in turn CDK1 Tyr15 phosphorylation. Furthermore, metformin inhibited both expression and irradiation-induced foci formation of Rad51, a key player in homologous recombination repair, ultimately leading to persistent DNA damage, as reflected by γ-H2AX and 53BP1 signaling. Finally, metformin-mediated AMPK/mTOR/p70S6K was identified as a possible upstream pathway controlling translational regulation of Wee1 and Rad51. Our data suggest that metformin radiosensitizes pancreatic cancer cells in vitro via abrogation of the G2 checkpoint and inhibition of DNA damage repair. However, the in vivo study is needed to further confirm the findings from the in vitro study.

  6. African-American Fathers' Perspectives on Facilitators and Barriers to Father-Son Sexual Health Communication.

    Science.gov (United States)

    Randolph, Schenita D; Coakley, Tanya; Shears, Jeffrey; Thorpe, Roland J

    2017-02-21

    African-American males ages 13 through 24 are disproportionately affected by sexually transmitted infections (STIs) and human immunodeficiency virus (HIV), accounting for over half of all HIV infections in this age group in the United States. Clear communication between African-American parents and their youth about sexual health is associated with higher rates of sexual abstinence, condom use, and intent to delay initiation of sexual intercourse. However, little is known about African-American fathers' perceptions of what facilitates and inhibits sexual health communication with their preadolescent and adolescent sons. We conducted focus groups with 29 African-American fathers of sons ages 10-15 to explore perceived facilitators and barriers for father-son communication about sexual health. Participants were recruited from barbershops in metropolitan and rural North Carolina communities highly affected by STIs and HIV, and data were analyzed using content analysis. Three factors facilitated father-son communication: (a) fathers' acceptance of their roles and responsibilities; (b) a positive father-son relationship; and (c) fathers' ability to speak directly to their sons about sex. We also identified three barriers: (a) fathers' difficulty in initiating sexual health discussions with their sons; (b) sons' developmental readiness for sexual health information; and (c) fathers' lack of experience in talking with their own fathers about sex. These findings have implications for father-focused prevention interventions aimed at reducing risky sexual behaviors in adolescent African-American males. © 2017 Wiley Periodicals, Inc.

  7. 78 FR 6128 - Accreditation of R. Markey & Sons, Inc., Markan Laboratories, as a Commercial Laboratory

    Science.gov (United States)

    2013-01-29

    ... SECURITY U.S. Customs and Border Protection Accreditation of R. Markey & Sons, Inc., Markan Laboratories, as a Commercial Laboratory AGENCY: U.S. Customs and Border Protection, Department of Homeland Security. ACTION: Notice of accreditation of R. Markey & Sons, Inc., Markan Laboratories, as a...

  8. Pathways to prevention: improving nonresident African American fathers' parenting skills and behaviors to reduce sons' aggression.

    Science.gov (United States)

    Howard Caldwell, Cleopatra; Antonakos, Cathy L; Assari, Shervin; Kruger, Daniel; De Loney, E Hill; Njai, Rashid

    2014-01-01

    This study describes a test of the Fathers and Sons Program for increasing intentions to avoid violence and reducing aggressive behaviors in 8- to 12-year-old African American boys by enhancing the parenting skills satisfaction and parenting behaviors of their nonresident fathers. The study included 158 intervention and 129 comparison group families. Structural equation model results indicated that the intervention was effective for improving fathers' parenting skills satisfaction, which was positively associated with sons' satisfaction with paternal engagement. Sons' paternal engagement satisfaction was positively associated with their intentions to avoid violence. Although aggressive behaviors were lower for comparison group sons, the intervention effectively reduced sons' aggressive behaviors indirectly by enhancing fathers' parenting behaviors. Support for family-centered youth violence prevention efforts is discussed.

  9. Polyandrous females produce sons that are successful at post-copulatory competition.

    Science.gov (United States)

    Klemme, I; Bäumer, J; Eccard, J A; Ylönen, H

    2014-03-01

    Some of the genetic benefit hypotheses put forward to explain multiple male mating (polyandry) predict that sons of polyandrous females will have an increased competitive ability under precopulatory or post-copulatory competition via paternally inherited traits, such as attractiveness or fertilization efficiency. Here, we tested these predictions by comparing the competitive ability of sons of experimentally monandrous and polyandrous female bank voles (Myodes glareolus), while controlling for potential material and maternal effects. In female choice experiments, we found no clear preference for sons of either monandrous or polyandrous mothers. Moreover, neither male type was dominant over the other, indicating no advantage in precopulatory male contest competition. However, in competitive matings, sons of polyandrous mothers significantly increased their mating efforts (mating duration, intromission number). In line with this, paternity success was biased towards sons of polyandrous mothers. Because there was no evidence for maternal effects, our results suggest that female bank voles gain genetic benefits from polyandry.

  10. Synaptotagmin-1 binds to PIP(2)-containing membrane but not to SNAREs at physiological ionic strength.

    Science.gov (United States)

    Park, Yongsoo; Seo, Jong Bae; Fraind, Alicia; Pérez-Lara, Angel; Yavuz, Halenur; Han, Kyungreem; Jung, Seung-Ryoung; Kattan, Iman; Walla, Peter Jomo; Choi, MooYoung; Cafiso, David S; Koh, Duk-Su; Jahn, Reinhard

    2015-10-01

    The Ca(2+) sensor synaptotagmin-1 is thought to trigger membrane fusion by binding to acidic membrane lipids and SNARE proteins. Previous work has shown that binding is mediated by electrostatic interactions that are sensitive to the ionic environment. However, the influence of divalent or polyvalent ions, at physiological concentrations, on synaptotagmin's binding to membranes or SNAREs has not been explored. Here we show that binding of rat synaptotagmin-1 to membranes containing phosphatidylinositol 4,5-bisphosphate (PIP2) is regulated by charge shielding caused by the presence of divalent cations. Surprisingly, polyvalent ions such as ATP and Mg(2+) completely abrogate synaptotagmin-1 binding to SNAREs regardless of the presence of Ca(2+). Altogether, our data indicate that at physiological ion concentrations Ca(2+)-dependent synaptotagmin-1 binding is confined to PIP2-containing membrane patches in the plasma membrane, suggesting that membrane interaction of synaptotagmin-1 rather than SNARE binding triggers exocytosis of vesicles.

  11. Intestinal microbiota shifts towards elevated commensal Escherichia coli loads abrogate colonization resistance against Campylobacter jejuni in mice.

    Directory of Open Access Journals (Sweden)

    Lea-Maxie Haag

    Full Text Available BACKGROUND: The zoonotic pathogen Campylobacter jejuni is a leading cause of bacterial foodborne enterocolitis in humans worldwide. The understanding of immunopathology underlying human campylobacteriosis is hampered by the fact that mice display strong colonization resistance against the pathogen due to their host specific gut microbiota composition. METHODOLOGY/PRINCIPAL FINDINGS: Since the microbiota composition changes significantly during intestinal inflammation we dissected factors contributing to colonization resistance against C. jejuni in murine ileitis, colitis and in infant mice. In contrast to healthy animals C. jejuni could stably colonize mice suffering from intestinal inflammation. Strikingly, in mice with Toxoplasma gondii-induced acute ileitis, C. jejuni disseminated to mesenteric lymphnodes, spleen, liver, kidney, and blood. In infant mice C. jejuni infection induced enterocolitis. Mice suffering from intestinal inflammation and C. jejuni susceptible infant mice displayed characteristical microbiota shifts dominated by increased numbers of commensal Escherichia coli. To further dissect the pivotal role of those distinct microbiota shifts in abrogating colonization resistance, we investigated C. jejuni infection in healthy adult mice in which the microbiota was artificially modified by feeding live commensal E. coli. Strikingly, in animals harboring supra-physiological intestinal E. coli loads, colonization resistance was significantly diminished and C. jejuni infection induced enterocolitis mimicking key features of human campylobacteriosis. CONCLUSION/SIGNIFICANCE: Murine colonization resistance against C. jejuni is abrogated by changes in the microbiota composition towards elevated E. coli loads during intestinal inflammation as well as in infant mice. Intestinal inflammation and microbiota shifts thus represent potential risk factors for C. jejuni infection. Corresponding interplays between C. jejuni and microbiota might

  12. Older parents enjoy better filial piety and care from daughters than sons in China

    DEFF Research Database (Denmark)

    Zeng, Yi; George, Linda; Sereny, Melanie

    2016-01-01

    with having son(s), having daughter(s) is significantly more beneficial at older ages in China, with regard to maintaining higher cognitive capacity and reducing mortality risk. Such daughter advantages in providing emotional care to older parents are more profound among the oldest-old aged 80+ as compared......OBJECTIVE: To examine whether older parents in China would benefit more from daughters' care than from sons' emotional care. METHOD: Analysis of the unique data sets of the Chinese Longitudinal Healthy Longevity Survey conducted in 2002, 2005, and 2008-2009 in 22 provinces. RESULTS: As compared...

  13. Parent-son decision-making about human papillomavirus vaccination: a qualitative analysis

    Directory of Open Access Journals (Sweden)

    Alexander Andreia B

    2012-12-01

    Full Text Available Abstract Background Licensed for use in males in 2009, Human Papillomavirus (HPV vaccination rates in adolescent males are extremely low. Literature on HPV vaccination focuses on females, adult males, or parents of adolescent males, without including adolescent males or the dynamics of the parent-son interaction that may influence vaccine decision-making. The purpose of this paper is to examine the decision-making process of parent-son dyads when deciding whether or not to get vaccinated against HPV. Methods Twenty-one adolescent males (ages 13–17, with no previous HPV vaccination, and their parents/guardians were recruited from adolescent primary care clinics serving low to middle income families in a large Midwestern city. Dyad members participated in separate semi-structured interviews assessing the relative role of the parent and son in the decision regarding HPV vaccination. Interviews were recorded, transcribed, and coded using inductive content analysis. Results Parents and sons focused on protection as a reason for vaccination; parents felt a need to protect their child, while sons wanted to protect their own health. Parents and sons commonly misinterpreted the information about the vaccine. Sons were concerned about an injection in the penis, while some parents and sons thought the vaccine would protect them against other sexually transmitted infections including Herpes, Gonorrhea, and HIV. Parents and sons recalled that the vaccine prevented genital warts rather than cancer. The vaccine decision-making process was rapid and dynamic, including an initial reaction to the recommendation for HPV vaccine, discussion between parent and son, and the final vaccine decision. Provider input was weighed in instances of initial disagreement. Many boys felt that this was the first health care decision that they had been involved in. Dyads which reported shared decision-making were more likely to openly communicate about sexual issues than those

  14. Sequence similarity between the erythrocyte binding domain 1 of the Plasmodium vivax Duffy binding protein and the V3 loop of HIV-1 strain MN reveals binding residues for the Duffy Antigen Receptor for Chemokines

    Directory of Open Access Journals (Sweden)

    Garry Robert F

    2011-01-01

    Full Text Available Abstract Background The surface glycoprotein (SU, gp120 of the human immunodeficiency virus (HIV must bind to a chemokine receptor, CCR5 or CXCR4, to invade CD4+ cells. Plasmodium vivax uses the Duffy Binding Protein (DBP to bind the Duffy Antigen Receptor for Chemokines (DARC and invade reticulocytes. Results Variable loop 3 (V3 of HIV-1 SU and domain 1 of the Plasmodium vivax DBP share a sequence similarity. The site of amino acid sequence similarity was necessary, but not sufficient, for DARC binding and contained a consensus heparin binding site essential for DARC binding. Both HIV-1 and P. vivax can be blocked from binding to their chemokine receptors by the chemokine, RANTES and its analog AOP-RANTES. Site directed mutagenesis of the heparin binding motif in members of the DBP family, the P. knowlesi alpha, beta and gamma proteins abrogated their binding to erythrocytes. Positively charged residues within domain 1 are required for binding of P. vivax and P. knowlesi erythrocyte binding proteins. Conclusion A heparin binding site motif in members of the DBP family may form part of a conserved erythrocyte receptor binding pocket.

  15. Risk of cryptorchidism among sons of horticultural workers and farmers in Denmark

    DEFF Research Database (Denmark)

    Jørgensen, Kristian Tore; Jensen, Morten Søndergaard; Toft, Gunnar Vase;

    2014-01-01

    OBJECTIVES: Previous studies indicate an increased risk of cryptorchidism, incomplete testicular descent, among sons of women working with pesticides. This study assessed the risk of cryptorchidism among boys of parents employed as horticultural workers and farmers using nationwide registers...... on occupation and cryptorchidism. METHODS: The cohort consisted of >600 000 boys born in Denmark from 1980-2007 with a parent in employment during pregnancy. These boys were followed for cryptorchidism from 1980-2009 comparing risks among sons of horticultural workers and farmers with sons of parents in other...... of mothers in other occupations (15 511 cases). Paternal occupation as farmer was unrelated to the risk among sons. Maternal occupation as a horticultural worker was associated with a non-significantly increased risk (72 cases; HR 1.20, 95% CI 0.95-1.52). A similar association was found for paternal...

  16. Charcot's son, commander Jean-Baptiste Charcot: from neurology to "Pourquoi Pas?".

    Science.gov (United States)

    Teive, Hélio A G; Munhoz, Renato P; Simões, Jefferson C

    2012-04-01

    Charcot name became very famous around the world, firstly because of the work of Professor Jean-Martin Charcot, the founder of Clinical Neurology, and, secondly, because of his son, Jean-Baptiste, the world famous maritime explorer.

  17. SON controls cell-cycle progression by coordinated regulation of RNA splicing.

    Science.gov (United States)

    Ahn, Eun-Young; DeKelver, Russell C; Lo, Miao-Chia; Nguyen, Tuyet Ann; Matsuura, Shinobu; Boyapati, Anita; Pandit, Shatakshi; Fu, Xiang-Dong; Zhang, Dong-Er

    2011-04-22

    It has been suspected that cell-cycle progression might be functionally coupled with RNA processing. However, little is known about the role of the precise splicing control in cell-cycle progression. Here, we report that SON, a large Ser/Arg (SR)-related protein, is a splicing cofactor contributing to efficient splicing of cell-cycle regulators. Downregulation of SON leads to severe impairment of spindle pole separation, microtubule dynamics, and genome integrity. These molecular defects result from inadequate RNA splicing of a specific set of cell-cycle-related genes that possess weak splice sites. Furthermore, we show that SON facilitates the interaction of SR proteins with RNA polymerase II and other key spliceosome components, suggesting its function in efficient cotranscriptional RNA processing. These results reveal a mechanism for controlling cell-cycle progression through SON-dependent constitutive splicing at suboptimal splice sites, with strong implications for its role in cancer and other human diseases.

  18. Que son las Cochinillas de los Cotrus (Naranjos, Limoneros, Mandarinos, etc. y como se Combaten.

    Directory of Open Access Journals (Sweden)

    Posada Sinisterra. Belisario

    1942-04-01

    Full Text Available Las cochinillas son insectos de aspecto variado. Son llamados también insectos-escamas porque la mayoría de ellos viven protegidos por una concha o escama de forma y coloración diversa. Las especies que en seguida se describen tienen un ciclo biológico muy similar. Se reproducen por medio de huevos que depositan las hembras bajo la escama.

  19. Sons or Daughters? Endogenous Sex Preferences and the Reversal of the Gender Educational Gap

    OpenAIRE

    Hazan, Moshe; ZOABI, Hosny

    2012-01-01

    This paper provides a new explanation for the narrowing and reversal of the gender education gap. It highlights the indirect effect of returns to human capital on parents' preferences for sons and the resulting demand for children and education. We assume that parents maximize the full income of their children and that males have an additional income, independently of their level of education. This additional income has two effects. First, it biases parental preferences towards sons. Second, ...

  20. Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence.

    Science.gov (United States)

    Vo, Uybach; Vajpai, Navratna; Flavell, Liz; Bobby, Romel; Breeze, Alexander L; Embrey, Kevin J; Golovanov, Alexander P

    2016-01-22

    The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly (15)N-labeled Ras as well as [(13)C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions.

  1. Daughters increase longevity of fathers, but daughters and sons equally reduce longevity of mothers.

    Science.gov (United States)

    Jasienska, Grazyna; Nenko, Ilona; Jasienski, Michal

    2006-01-01

    Reproduction is energetically and physiologically expensive, and an individual investing resources into producing offspring should suffer costs such as deterioration in health condition and possibly shorter life span. Since the energetic and nutritional demands of pregnancy and breastfeeding render reproductive costs much higher in women than in men, women with a large number of children should show signs of deterioration in condition, while men with large families should not. However, whether reproductive costs reduce longevity in women is still questionable, and in men this issue has not been adequately addressed. In addition, since sons are energetically more expensive to produce than daughters, having sons should have a more pronounced negative impact on maternal longevity than having daughters. Here we document a striking disparity in the impact of children on the life span of mothers and fathers in a Polish rural population. We show for the first time that number of daughters was positively related to a longer life span of their fathers, increasing their longevity on average by 74 weeks per daughter born, while number of sons did not have a significant effect on paternal longevity. In contrast, in women, the number of daughters and number of sons reduced maternal longevity and did so to the same extent, on average by 95 weeks per son or daughter, indicating that for women, the costs of having sons and daughters are similar.

  2. Some reflections on a case of mother/adolescent son incest.

    Science.gov (United States)

    Shengold, L

    1980-01-01

    A rare case of mother/adolescent son incest is presented. The son, treated in analysis, was not psychotic. Questions are raised about why father/daughter incest appears to be much more common than mother/son incest. Part of the answer, I speculate, has to do with the special psychic dangers for both mother and son, perhaps phylogenetically-based, which attach to the fantasy and the possibility of impregnating the mother. Where the incest taboo is violated, the primary responsibility would appear to be the parent's; the parent is frequently motivated by a compulsion to repeat his or her own incestuous past. In the case presented the probably psychotic mother had raised her son to look like a girl for several years, and he had been the victim of a homosexual assault at the age of 6. The incest at puberty seems to have helped him reverse a psychic position of subjection to the pre-oedipal mother, to have modified his rage and reinforced his masculinity. It also produced some of the arrogance, alongside a need for failure and punishment that evoke the legend of Oedipus. The mother, fearful of the possibility of getting pregnant, had abruptly stopped the incest. It had been repressed, and became conscious again when the son entered analysis. He then left his treatment without being able to work through much of the terror consequent to the consummation of incest, and with some of the feeling of oedipal triumph retained.

  3. Like daughter, like son? Fertility decline and the transformation of gender systems in the family

    Directory of Open Access Journals (Sweden)

    Keera Allendorf

    2012-10-01

    Full Text Available BACKGROUND An important question for population research is whether fertility decline transforms gender systems. OBJECTIVE This paper contributes to answering this broad question by examining how fertility decline may change the relative value and roles of daughters versus sons in families. First, I outline theoretical pathways, suggesting that a key factor is the gender composition of families. As fertility declines, the proportion of families with children of only one gender increases, which may facilitate greater gender symmetry between daughters and sons. Second, I explore how fertility decline may be transforming the relative value and roles of sons and daughters in practice in one place. METHODS The analysis draws primarily on semi-structured interviews with 30 respondents living in one Indian village. RESULTS In recent decades, fertility has declined to at least replacement levels. Respondents also perceive changes in the gender system, including less son preference, more equal schooling for sons and daughters, more freedom in marriage and pre-marital relationships, and perhaps greater daughter support of parents in old age. CONCLUSIONS The results describe changes in the relative value, treatment, and behavior of sons and daughters that are consistent with the theorized effects of fertility decline. Future research is needed, however, to determine whether fertility decline makes a unique causal contribution to changes in the gender system.

  4. Abrogation of Chk1-mediated S/G2 checkpoint by UCN-01 enhances ara-C-induced cytotoxicity in human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Rong-guang SHAO; Chun-Xia CAO; Yves POMMIER

    2004-01-01

    AIM: To investigate whether 7-hydroxystaurosporine (UCN-01) affects cell cycle progression in arabinosylcytosine (ara-C) treated human colon carcinoma HT-29 cells. METHODS: Cytotoxicity, DNA synthesis, cell cycle distribution,protein level, and kinase activity were determined by clonogenic assay, flow cytometry, DNA synthesis assay,immunoblotting, and kinase assays, respectively. RESULTS: UCN-01 abrogated an S/G2-phase checkpoint in HT29 cells treated with ara-C. When UCN-01 was added after treatment with ara-C, the rate of recovery of DNA synthesis was enhanced and colony-forming ability diminished. Thus, premature recovery of DNA synthesis was associated with increased cytotoxicity. Measurements of cyclin A and B protein levels, Cdk2 and Cdc2 kinase activities, Cdc25C phosphorylation, and Chkl kinase activity were consistent with UCN-01-induced abrogation of the S/G2-phase checkpoint in ara-C treated cells. CONCLUSION: The abrogation of the S/G2 checkpoint may be due to inhibition of Chkl kinase by UCN-01. The enhanced cytotoxicity produced when UCN-01 was combined with ara-C suggested a rationale for the use of this drug combination for tumors that might be susceptible to cell cycle checkpoint abrogation.

  5. Has Their Son Been Vaccinated? Beliefs About Other Parents Matter for Human Papillomavirus Vaccine.

    Science.gov (United States)

    Schuler, Christine L; Coyne-Beasley, Tamera

    2016-07-01

    The goal of this study was to determine if parents' beliefs about social norms of human papillomavirus (HPV) vaccination for sons were associated with knowledge of HPV, intention to vaccinate sons, or beliefs about side effects. A cross-sectional, survey-based study of parents with sons was performed in 2010. Fisher's exact tests were used to examine associations between demographics and responses about social norms. Multivariate logistic regression models examined beliefs about social norms of male HPV vaccination and primary outcomes. Few parents agreed that others were vaccinating sons (n = 31/267, 12%), including 1% responding strongly agree and 11% responding agree. Most parents, 52%, disagreed that others were vaccinating (40% disagree, 11% strongly disagree), and 37% chose prefer not to answer regarding others' vaccination practices. Hispanic parents and those with a high school education or less were significantly more likely to choose prefer not to answer than their respective counterparts regarding vaccination norms. In multivariate models, parents agreeing others were vaccinating sons had greater odds of having high knowledge of HPV (adjusted odds ratio [aOR] high vs low knowledge 3.15, 95% confidence interval [CI] 1.13, 8.77) and increased intention to vaccinate sons (n = 243, aOR = 4.41, 95% CI = 1.51, 12.89). Beliefs about side effects were not significantly associated with beliefs about social norms. Parents' beliefs about others' vaccination practices are important with regard to knowledge of HPV and intention to vaccinate sons. Studying how various public messages about HPV vaccine may influence normative beliefs could be relevant to improving vaccination coverage.

  6. Son Preference in India: Shedding Light on the North-South Gradient

    Directory of Open Access Journals (Sweden)

    Daniela Klaus

    2014-12-01

    Full Text Available Dieser Beitrag liegt nur in englischer Sprache vor. Son preference is widespread in India and deep-rooted in its history. It is a matter of concern because it produces an imbalanced juvenile sex ratio. There are far fewer girls than boys. The figures vary greatly among the Indian states suggesting a major north-south gradient in son preference accompanied by a minor west-east gradient. The aim of this paper is to explain the regional pattern. We provide an application of the value of children-approach according to which the decision to have children is made on the calculus of benefits and costs related to children. In the light of the socioeconomic and sociocultural background in India, we propose that (potential parents’ expectations of benefits and costs are biased in favour of sons. This is suggested, therefore, as the key motivation for the preference for male offspring. However, region-specifics in the level of affluence, the educational level, the mode of production, the meaning and importance of religion, and the kinship regime are assumed to produce stronger son preference in north India compared to south India. This mediation-model is tested using the Indian sub-sample of the international Value of Children-study. Data were collected in Uttar Pradesh (north-central India and Puducherry (south-east India. Mothers aged 16 to 65 were interviewed in 2002 and 2010. Based on 1,173 respondents, a structural equation model was carried out to test the hypothesised composition effects related to the region and the mediating position of sex-specific benefits and costs. Initial findings confirm that the national son preference pattern is more likely to be found among north Indian mothers than south Indian mothers. As assumed, the sex-specific balance of benefits and costs contributes to the explanation of son preference. However, there is little evidence that the benefits and costs mediate between the region-specific socioeconomic and

  7. The Relationship Between Sexual Function and Quality of Sleep in Caregiving Mothers of Sons with Duchenne Muscular Dystrophy

    OpenAIRE

    Nozoe, Karen T.; Helena Hachul, MD, PhD; Camila Hirotsu, PhD; Daniel N. Polesel, MSc; Gustavo A. Moreira, MD, PhD; Sergio Tufik, MD, PhD; Monica L. Andersen, PhD

    2014-01-01

    Introduction: The task of the caregiver, especially a caregiving mother of a son with a chronic and fatal disease, may interfere with their quality of sleep, sexuality, and some hormone levels. Aim: The aim of this study was to evaluate the sexual function and the quality of sleep of caregiving mothers of sons with Duchenne muscular dystrophy (DMD). Methods: We evaluated 20 caregiving mothers of sons with DMD and 20 caregiving mothers of sons without any neuromuscular or chronic disease...

  8. Two Dimensional Analytical Modeling for SOI and SON MOSFET and Their Performance Comparison

    Directory of Open Access Journals (Sweden)

    Saptarsi Ghosh

    2011-01-01

    Full Text Available During last few decade continuous device performance improvements have been achieved through a combination of device scaling, new device structures and material property improvement to its fundamental limits. Conventional silicon (bulk CMOS technology can’t overcome the fundamental physical limitations belong to sub-micro or nanometer region which leads to alternative device technology like Silicon-on-Insulator (SOI technology and its recent innovative modification Silicon-On-Nothing (SON MOSFET. Analytical simulation is very important to understand the relative performance of those devices under different structural and operational parameter variations. For present analytical simulation asymmetric structure of Silicon-On-Insulator (SOI MOSFET and Silicon-On-Nothing (SON MOSFET are considered. The proposed structure of SON MOSFET is similar to that of the SOI MOSFET with the only exception being the oxide layer here is substituted with air which has much lower permittivity than Silicon-dioxide. Variation of threshold voltage against effective channel lengths is compared for both the structures. From our simulation it is observed that the proposed SON model has lower drain to source current (IDS than SOI model. In our modeling based on solution of two dimensional Poisson’s equation short channel effects such as DIBL and fringing field effects are also taken into account. SON is found to provide better suppression of SCE s than SOI. The results predicted by our analytical simulation hold good agreement with experimental results.

  9. Inhibition of MARCH5 ubiquitin ligase abrogates MCL1-dependent resistance to BH3 mimetics via NOXA.

    Science.gov (United States)

    Subramanian, Aishwarya; Andronache, Adrian; Li, Yao-Cheng; Wade, Mark

    2016-03-29

    BH3 mimetic compounds induce tumor cell death through targeted inhibition of anti-apoptotic BCL2 proteins. Resistance to one such compound, ABT-737, is due to increased levels of anti-apoptotic MCL1. Using chemical and genetic approaches, we show that resistance to ABT-737 is abrogated by inhibition of the mitochondrial RING E3 ligase, MARCH5. Mechanistically, this is due to increased expression of pro-apoptotic BCL2 family member, NOXA, and is associated with MARCH5 regulation of MCL1 ubiquitylation and stability in a NOXA-dependent manner. MARCH5 expression contributed to an 8-gene signature that correlates with sensitivity to the preclinical BH3 mimetic, navitoclax. Furthermore, we observed a synthetic lethal interaction between MCL1 and MARCH5 in MCL1-dependent breast cancer cells. Our data uncover a novel level at which the BCL2 family is regulated; furthermore, they suggest targeting MARCH5-dependent signaling will be an effective strategy for treatment of BH3 mimetic-resistant tumors, even in the presence of high MCL1.

  10. CD40-signalling abrogates induction of RORγt+ Treg cells by intestinal CD103+ DCs and causes fatal colitis

    Science.gov (United States)

    Barthels, Christian; Ogrinc, Ana; Steyer, Verena; Meier, Stefanie; Simon, Ferdinand; Wimmer, Maria; Blutke, Andreas; Straub, Tobias; Zimber-Strobl, Ursula; Lutgens, Esther; Marconi, Peggy; Ohnmacht, Caspar; Garzetti, Debora; Stecher, Bärbel; Brocker, Thomas

    2017-01-01

    Immune homeostasis in intestinal tissues depends on the generation of regulatory T (Treg) cells. CD103+ dendritic cells (DCs) acquire microbiota-derived material from the gut lumen for transport to draining lymph nodes and generation of receptor-related orphan γt+ (RORγt+) Helios−-induced Treg (iTreg) cells. Here we show CD40-signalling as a microbe-independent signal that can induce migration of CD103+ DCs from the lamina propria (LP) to the mesenteric lymph nodes. Transgenic mice with constitutive CD11c-specific CD40-signalling have reduced numbers of CD103+ DCs in LP and a low frequency of RORγt+Helios− iTreg cells, exacerbated inflammatory Th1/Th17 responses, high titres of microbiota-specific immunoglobulins, dysbiosis and fatal colitis, but no pathology is detected in other tissues. Our data demonstrate a CD40-dependent mechanism capable of abrogating iTreg cell induction by DCs, and suggest that the CD40L/CD40-signalling axis might be able to intervene in the generation of new iTreg cells in order to counter-regulate immune suppression to enhance immunity. PMID:28276457

  11. L-carnitine, a diet component and organic cation transporter OCTN ligand, displays immunosuppressive properties and abrogates intestinal inflammation.

    Science.gov (United States)

    Fortin, G; Yurchenko, K; Collette, C; Rubio, M; Villani, A-C; Bitton, A; Sarfati, M; Franchimont, D

    2009-04-01

    Allele variants in the L-carnitine (LCAR) transporters OCTN1 (SLC22A4, 1672 C --> T) and OCTN2 (SLC22A5, -207 G --> C) have been implicated in susceptibility to Crohn's disease (CD). LCAR is consumed in the diet and transported actively from the intestinal lumen via the organic cation transporter OCTN2. While recognized mainly for its role in fatty acid metabolism, several lines of evidence suggest that LCAR may also display immunosuppressive properties. This study sought to investigate the immunomodulatory capacity of LCAR on antigen-presenting cell (APC) and CD4+ T cell function by examining cytokine production and the expression of activation markers in LCAR-supplemented and deficient cell culture systems. The therapeutic efficacy of its systemic administration was then evaluated during the establishment of colonic inflammation in vivo. LCAR treatment significantly inhibited both APC and CD4+ T cell function, as assessed by the expression of classical activation markers, proliferation and cytokine production. Carnitine deficiency resulted in the hyperactivation of CD4+ T cells and enhanced cytokine production. In vivo, protection from trinitrobenzene sulphonic acid colitis was observed in LCAR-treated mice and was attributed to the abrogation of both innate [interleukin (IL)-1beta and IL-6 production] and adaptive (T cell proliferation in draining lymph nodes) immune responses. LCAR therapy may therefore represent a novel alternative therapeutic strategy and highlights the role of diet in CD.

  12. The Relationship between Paul and His Mother in Sons and Lovers

    Institute of Scientific and Technical Information of China (English)

    ZhangYanxia

    2010-01-01

    Sons and lovers is the greatest work written by D.H.Lawrence.In the novel,the mother,Mrs Morel devotes all her love on her sons,first on William,who dies after leaving home,then on her second son,Paul,and he also has the affection upon his mother.Thus it makes him incapable of dealing the relationship with other women.This Oedipus complex influences his life and emotion.How does this kind of emotion come into being? Why does Paul have this kind of abnormal love? Maybe there are a lot of reasons,and they will be discussed in detail in the following paragraphs.

  13. Impaired Reproductive Development in Sons of Women Occupationally Exposed to Pesticides during Pregnancy

    DEFF Research Database (Denmark)

    Andersen, Helle Raun; Schmidt, Ida M.; Grandjean, Philippe

    2008-01-01

    OBJECTIVES: The aim of this prospective study was to investigate whether occupational pesticide exposure during pregnancy causes adverse effects on the reproductive development in the male infants. DESIGN AND MEASUREMENTS: Pregnant women employed in greenhouses in Denmark were consecutively...... recruited, and 113 mother-son pairs were included. The mothers were categorized as occupationally exposed (91 sons) or unexposed (22 sons) to pesticides during pregnancy. Testicular position and volume, penile length, and position of urethral opening were determined at 3 months of age using standardized...... techniques. Concentrations of reproductive hormones in serum from the boys were analyzed. RESULTS: The prevalence of cryptorchidism at 3 months of age was 6.2% [95% confidence interval (CI), 3.0-12.4]. This prevalence was considerably higher than among Danish boys born in the Copenhagen area (1.9%; 95% CI, 1...

  14. Maternal distancing strategies toward twin sons, one with mild hearing loss: a case study.

    Science.gov (United States)

    Muñoz-Silva, Alicia; Sánchez-García, Manuel

    2004-01-01

    The authors apply descriptive and sequential analyses to a mother's distancing strategies toward her 3-year-old twin sons in puzzle assembly and book reading tasks. One boy had normal hearing and the other a mild hearing loss (threshold: 30 dB). The results show that the mother used more distancing behaviors with the son with a hearing loss, and thus gave greater encouragement to this son's cognitive development. These results differ from those of previous studies of deaf or hard of hearing children, whose participants generally had severe or profound hearing loss. In those studies, parents of deaf children used more low-level distancing than parents of normally hearing children. The results of the present study are discussed in terms of their implications for the parenting of twins and of children with mild hearing loss.

  15. Vaccinating sons against HPV: results from a U.S. national survey of parents.

    Directory of Open Access Journals (Sweden)

    Jaime L Taylor

    Full Text Available PURPOSE: The quadrivalent HPV vaccination was approved for use in males ages 9 to 26 in 2009 and recommended for routine administration in 2011. The purpose of this study was to uncover predictable commonalities amongst parents who chose to vaccinate their 11-17 year old sons against HPV. METHODS: We compiled data from a U.S. national sample of 779 parents with sons 11-17 years old using a web-based survey to gather information about behavioral and sociodemographic factors which predicted receipt of 1 or more HPV vaccine doses based on parental report. Predictors were first modeled individually for univariable associations. Significant predictors (p<0.10 were combined in a multivariable model. RESULTS: In the adjusted model, independent predictors included receipt of flu vaccination, health insurance coverage and sexual health topic discussions with sons. Sons who had received a flu shot in the last two years more frequently received at least one dose of the vaccine (OR 1.82; 95% CI 1.45-2.26. Sons covered by private health insurance had decreased odds of HPV vaccination (OR 0.56 95% CI 0.37-0.83. Lastly, parents who had discussed sexual health topics with their sons were more likely to vaccinate (OR 1.61; 95% CI 1.37-1.89. CONCLUSIONS: Male vaccination rates in the U.S. have increased, but males continue to be under-immunized. Utilization of health care is an important factor in HPV vaccine uptake; therefore, health care providers should use every contact as an opportunity to vaccinate. Communication about sexual health topics may provide a forum for parents and health care providers to have conversations about HPV vaccination as those more comfortable discussing these topics may also be more comfortable discussing HPV vaccination.

  16. Les descripteurs d'un son Librairie Matlab SPL et fichiers de descriptions ".sig""

    OpenAIRE

    Lemaitre, Guillaume; Gallo, Emmanuel

    2006-01-01

    Le traitement du signal audio rapide travaille avec des descriptions compactes des sons plutôt qu'avec les sons eux-mêmes. Dans une première partie nous introduisons cette notion de description et nous proposons un état de l'art des différents types de description utilisés. Ces descriptions incorporent le plus souvent des quantités telles que l'énergie ou le spectre de puissance à court-terme. Cependant, énergie et puissance sont des concepts qui sont souvent confondus ou mal interprétés, et ...

  17. Proyecto de consolidación de Son Espases Vell, Palma de Mallorca

    OpenAIRE

    ANTÓN ESTEVE, NURIA

    2011-01-01

    Trabajo científico técnico. El presente proyecto se centra en la consolidación de una casa pallesa, antigua casa de aperos, situada en el solar de Son Espases, de proporciones humildes y con diversas intervenciones a lo largo de distintas épocas, y que guarda muchos de los elementos tradicionales de la arquitectura popular mallorquina, así como sus sistemas constructivos. Antón Esteve, N. (2011). Proyecto de consolidación de Son Espases Vell, Palma de Mallorca. http://hdl.handle.net/10251/...

  18. An Analysis on Paul's Emotional Experience with Freud's Psychoanalytical Theory in Sons and Lovers

    Institute of Scientific and Technical Information of China (English)

    胡嘉薏; 范丽娟

    2016-01-01

    David Herbert Lawrence is one of the most important and controversial writers. Sons and Lovers, one of .his most influential novels, is his first full-length and semi-autobiographical novel. This novel describes the growing process and the emotional experiences of a coal mine worker's son Paul. This paper takes Freud's psychoanalytic theory as the theoretical basis. By analyzing three different patterns of relationships among Paul and three women, including mother Morel, lover Miriam and mistress Clara, this paper finally comes to a conclusion that the real love should be based on the harmony of the personality structure and the unity of the body and the soul.

  19. Jarana y Fandango son símbolos de la nueva identidad de México

    OpenAIRE

    Bruno Bartra

    2015-01-01

    En la última década el son jarocho, música originaria del Estado mexicano de Veracruz, se ha abierto paso en la escena musical neoyorquina. Vinculada a una diáspora de clase media conformada por músicos profesionales, intérpretes y profesores, así como por empresarios cuyos lujosos restaurantes en Manhattan o Brooklyn sirven como foros para estos artistas, lideran esta escena Bandas como Radio Jarocho o Jarana Beat, que comparten dos objetivos musicales: por un lado, fusionar el son jarocho c...

  20. Plasma membrane Toll-like receptor activation increases bacterial uptake but abrogates endosomal Lactobacillus acidophilus induction of interferon-β.

    Science.gov (United States)

    Boye, Louise; Welsby, Iain; Lund, Lisbeth Drozd; Goriely, Stanislas; Frøkiaer, Hanne

    2016-11-01

    Lactobacillus acidophilus induces a potent interferon-β (IFN-β) response in dendritic cells (DCs) by a Toll-like receptor 2 (TLR2) -dependent mechanism, in turn leading to strong interleukin-12 (IL-12) production. In the present study, we investigated the involvement of different types of endocytosis in the L. acidophilus-induced IFN-β and IL-12 responses and how TLR2 or TLR4 ligation by lipopolysaccharide and Pam3/4CSK4 influenced endocytosis of L. acidophilus and the induced IFN-β and IL-12 production. Lactobacillus acidophilus was endocytosed by constitutive macropinocytosis taking place in the immature cells as well as by spleen tyrosine kinase (Syk) -dependent phagocytosis but without involvement of plasma membrane TLR2. Stimulation with TLR2 or TLR4 ligands increased macropinocytosis in a Syk-independent manner. As a consequence, incubation of DCs with TLR ligands before incubation with L. acidophilus enhanced the uptake of the bacteria. However, in these experimental conditions, induction of IFN-β and IL-12 was strongly inhibited. As L. acidophilus-induced IFN-β depends on endocytosis and endosomal degradation before signalling and as TLR stimulation from the plasma membrane leading to increased macropinocytosis abrogates IFN-β induction we conclude that plasma membrane TLR stimulation leading to increased macropinocytosis decreases endosomal induction of IFN-β and speculate that this is due to competition between compartments for molecules involved in the signal pathways. In summary, endosomal signalling by L. acidophilus that leads to IFN-β and IL-12 production is inhibited by TLR stimulation from the plasma membrane.

  1. Combined inhibition of p38 and Akt signaling pathways abrogates cyclosporine A-mediated pathogenesis of aggressive skin SCCs

    Energy Technology Data Exchange (ETDEWEB)

    Arumugam, Aadithya; Walsh, Stephanie B.; Xu, Jianmin; Afaq, Farrukh [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019 (United States); Elmets, Craig A. [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019 (United States); Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019 (United States); Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer p38 and Akt are the crucial molecular targets in the pathogenesis of SCCs in OTRs. Black-Right-Pointing-Pointer Combined inhibition of these targets diminished tumor growth by 90%. Black-Right-Pointing-Pointer Inhibition of these targets act through downregulating mTOR signaling pathway. -- Abstract: Non-melanoma skin cancers (NMSCs) are the most common neoplasm in organ transplant recipients (OTRs). These cancers are more invasive and metastatic as compared to those developed in normal cohorts. Previously, we have shown that immunosuppressive drug, cyclosporine A (CsA) directly alters tumor phenotype of cutaneous squamous cell carcinomas (SCCs) by activating TGF-{beta} and TAK1/TAB1 signaling pathways. Here, we identified novel molecular targets for the therapeutic intervention of these SCCs. We observed that combined blockade of Akt and p38 kinases-dependent signaling pathways in CsA-promoted human epidermoid carcinoma A431 xenograft tumors abrogated their growth by more than 90%. This diminution in tumor growth was accompanied by a significant decrease in proliferation and an increase in apoptosis. The residual tumors following the combined treatment with Akt inhibitor triciribine and p38 inhibitors SB-203580 showed significantly diminished expression of phosphorylated Akt and p38 and these tumors were less invasive and highly differentiated. Diminished tumor invasiveness was associated with the reduced epithelial-mesenchymal transition as ascertained by the enhanced E-cadherin and reduced vimentin and N-cadherin expression. Consistently, these tumors also manifested reduced MMP-2/9. The decreased p-Akt expression was accompanied by a significant reduction in p-mTOR. These data provide first important combinatorial pharmacological approach to block the pathogenesis of CsA-induced highly aggressive cutaneous neoplasm in OTRs.

  2. Oral delivery of Brucella spp. recombinant protein U-Omp16 abrogates the IgE-mediated milk allergy

    Science.gov (United States)

    Smaldini, Paola Lorena; Ibañez, Andrés Esteban; Fossati, Carlos Alberto; Cassataro, Juliana; Docena, Guillermo Horacio

    2014-01-01

    Food allergies are increasingly common disorders and no therapeutic strategies are yet approved. The unlipidated Omp16 (U-Omp16) is the outer membrane protein of 16 kDa from B. abortus and possesses a mucosal adjuvant property. In this study, we aimed to examine the U-Omp16 capacity to abrogate an allergen-specific Th2 immune response when it is administered as an oral adjuvant in a mouse model of food allergy.   Balb/c mice were sensitized with cholera toxin and cow’s milk proteins (CMP) by gavage and simultaneously treated with U-Omp16 and CMP. Oral challenge with CMP was performed to evaluate the allergic status of mice. Symptoms, local (small bowel cytokine and transcription factor gene expression) and systemic (specific isotypes and spleen cell-secreted cytokines) parameters, and skin tests were done to evaluate the immune response. We found that the oral administration of U-Omp16 with CMP during sensitization dampened the allergic symptoms, with negativization of immediate skin test and increased skin DTH response. Serum specific IgE and IL-5 were inhibited and a Th1 response was promoted (specific IgG2a antibodies and CMP-induced IFN-γ secretion). We found at the mucosal site an inhibition of the gene expression corresponding to IL-13 and Gata-3, with an induction of IFN-γ and T-bet. These results indicated that the oral administration of U-Omp16 significantly controlled the allergic response in sensitized mice with a shift of the balance of Th1- and Th2-T cells toward Th1 predominance. These findings suggest that U-Omp16 may be useful as a Th1-directing adjuvant in an oral vaccine. PMID:25424811

  3. Antioxidants Abrogate Alpha-Tocopherylquinone-Mediated Down-Regulation of the Androgen Receptor in Androgen-Responsive Prostate Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Alexandra M Fajardo

    Full Text Available Tocopherylquinone (TQ, the oxidation product of alpha-tocopherol (AT, is a bioactive molecule with distinct properties from AT. In this study, AT and TQ are investigated for their comparative effects on growth and androgenic activity in prostate cancer cells. TQ potently inhibited the growth of androgen-responsive prostate cancer cell lines (e.g., LAPC4 and LNCaP cells, whereas the growth of androgen-independent prostate cancer cells (e.g., DU145 cells was not affected by TQ. Due to the growth inhibitory effects induced by TQ on androgen-responsive cells, the anti-androgenic properties of TQ were examined. TQ inhibited the androgen-induced activation of an androgen-responsive reporter and inhibited the release of prostate specific antigen from LNCaP cells. TQ pretreatment was also found to inhibit AR activation as measured using the Multifunctional Androgen Receptor Screening assay. Furthermore, TQ decreased androgen-responsive gene expression, including TM4SF1, KLK2, and PSA over 5-fold, whereas AT did not affect the expression of androgen-responsive genes. Of importance, the antiandrogenic effects of TQ on prostate cancer cells were found to result from androgen receptor protein down-regulation produced by TQ that was not observed with AT treatment. Moreover, none of the androgenic endpoints assessed were affected by AT. The down-regulation of androgen receptor protein by TQ was abrogated by co-treatment with antioxidants. Overall, the biological actions of TQ were found to be distinct from AT, where TQ was found to be a potent inhibitor of cell growth and androgenic activity in androgen-responsive prostate cancer cells.

  4. A combination of an anti-SLAMF6 antibody and ibrutinib efficiently abrogates expansion of chronic lymphocytic leukemia cells

    Science.gov (United States)

    Yigit, Burcu; Halibozek, Peter J.; Chen, Shih-Shih; O'Keeffe, Michael S.; Arnason, Jon; Avigan, David; Gattei, Valter; Bhan, Atul; Cen, Osman; Longnecker, Richard; Chiorazzi, Nicholas; Wang, Ninghai; Engel, Pablo; Terhorst, Cox

    2016-01-01

    The signaling lymphocyte activation molecule family [SLAMF] of cell surface receptors partakes in both the development of several immunocyte lineages and innate and adaptive immune responses in humans and mice. For instance, the homophilic molecule SLAMF6 (CD352) is in part involved in natural killer T cell development, but also modulates T follicular helper cell and germinal B cell interactions. Here we report that upon transplantation of a well-defined aggressive murine B220+CD5+ Chronic Lymphocytic Leukemia (CLL) cell clone, TCL1-192, into SCID mice one injection of a monoclonal antibody directed against SLAMF6 (αSlamf6) abrogates tumor progression in the spleen, bone marrow and blood. Similarly, progression of a murine B cell lymphoma, LMP2A/λMyc, was also eliminated by αSlamf6. But, surprisingly, αSLAMF6 neither eliminated TCL1-192 nor LMP2A/λMyc cells, which resided in the peritoneal cavity or omentum. This appeared to be dependent upon the tumor environment, which affected the frequency of sub-populations of the TCL1-192 clone or the inability of peritoneal macrophages to induce Antibody Dependent Cellular Cytotoxicity (ADCC). However, co-administering αSlamf6 with the Bruton tyrosine kinase (Btk) inhibitor, ibrutinib, synergized to efficiently eliminate the tumor cells in the spleen, bone marrow, liver and the peritoneal cavity. Because an anti-human SLAMF6 mAb efficiently killed human CLL cells in vitro and in vivo, we propose that a combination of αSlamf6 with ibrutinib should be considered as a novel therapeutic approach for CLL and other B cell tumors. PMID:27029059

  5. Non-commutative Poisson Algebra Structures on the Lie Algebra son(CQ)

    Institute of Scientific and Technical Information of China (English)

    Jie Tong; Quanqin Jin

    2007-01-01

    Non-commutative Poisson algebras are the algebras having both an associativealgebra structure and a Lie algebra structure together with the Leibniz law.In this paper,the non-commutative poisson algebra structures on son(CQ) are determined.

  6. Charcot's son, commander Jean-Baptiste Charcot: from neurology to "Pourquoi Pas?"

    Directory of Open Access Journals (Sweden)

    Hélio A. G. Teive

    2012-04-01

    Full Text Available Charcot name became very famous around the world, firstly because of the work of Professor Jean-Martin Charcot, the founder of Clinical Neurology, and, secondly, because of his son, Jean-Baptiste, the world famous maritime explorer.

  7. The risk of cryptorchidism among sons of women working in horticulture in Denmark

    DEFF Research Database (Denmark)

    Gabel, Pernille; Jensen, Morten Søndergaard; Andersen, Helle Raun;

    2011-01-01

    Androgens are crucial for normal testicular descent. Studies show that some pesticides have estrogenic or antiandrogenic effects, and that female workers exposed to pesticides have increased risk of having a boy with cryptorchidism. The main objective of the present study was to investigate wheth...... pregnant women exposed to pesticides due to their work in horticulture experience excess risk of having sons with cryptorchidism....

  8. Terascale Physics Opportunities at a High Statistics, High Energy Neutrino Scattering Experiment: NuSOnG

    CERN Document Server

    Adams, T; Bugel, L; Camilleri, L; Conrad, J M; De Gouvêa, A; Fisher, P H; Formaggio, J A; Jenkins, J; Karagiorgi, G; Kobilarcik, T R; Kopp, S; Kyle, G; Loinaz, W A; Mason, D A; Milner, R; Moore, R; Morfín, J G; Nakamura, M; Naples, D; Nienaber, P; Olness, F I; Owens, J F; Pate, S F; Pronin, A; Seligman, W G; Shaevitz, M H; Schellman, H; Schienbein, I; Syphers, M J; Tait, T M P; Takeuchi, T; Tan, C Y; Van de Water, R G; Yamamoto, R K; Yu, J Y

    2008-01-01

    This article presents the physics case for a new high-energy, ultra-high statistics neutrino scattering experiment, NuSOnG (Neutrino Scattering on Glass). This experiment uses a Tevatron-based neutrino beam to obtain over an order of magnitude higher statistics than presently available for the purely weak processes $\

  9. Better-surviving barn swallow mothers produce more and better-surviving sons.

    Science.gov (United States)

    Romano, Andrea; Costanzo, Alessandra; Caprioli, Manuela; Parolini, Marco; Ambrosini, Roberto; Rubolini, Diego; Saino, Nicola

    2016-05-01

    Sex allocation theory predicts that parents are selected to bias their progeny sex ratio (SR) toward the sex that will benefit the most from parental quality. Because parental quality may differentially affect survival of sons and daughters, a pivotal test of the adaptive value of SR adjustment is whether parents overproduce offspring of the sex that accrues larger fitness advantages from high parental quality. However, this crucial test of the long-term fitness consequences of sex allocation decisions has seldom been performed. In this study of the barn swallow (Hirundo rustica), we showed a positive correlation between the proportion of sons and maternal annual survival. We then experimentally demonstrated that this association did not depend on the differential costs of rearing offspring of either sex. Finally, we showed that maternal lifespan positively predicted lifespan of sons but not of daughters. Because in barn swallows lifespan is a strong determinant of lifetime reproductive success, the results suggest that mothers overproduce offspring of the sex that benefits the most from maternal quality. Hence, irrespective of mechanisms causing the SR bias and mother-son covariation in lifespan, we provide strong evidence that sex allocation decisions of mothers can highly impact on their lifetime fitness.

  10. Analysis of the Female Images in Sons and Lovers from the Feminist Perspective

    Institute of Scientific and Technical Information of China (English)

    付晓芳

    2015-01-01

    This thesis is an attempt to analyze the novel Sons and Lovers from the feminist perspective to expose women's suppressed and subordinate situation as “the other” in the patriarchal society, and to unmask the repression and predicament of immanent women.

  11. Men as caregivers of the elderly: support for the contributions of sons

    Directory of Open Access Journals (Sweden)

    Collins CR

    2014-11-01

    Full Text Available Cynthia R Collins Loyola University New Orleans, College of Social Sciences/School of Nursing, New Orleans, LA, USA Abstract: Emerging practice research on filial sources of health care support has indicated that there is a growing trend for sons to assume some responsibility for the health care needs of their aging parents. The purpose of this work is to propose that outcomes observed through a secondary analysis of data from a previous mixed methods research project, conducted with a sample of 60 elderly women residing in independent living centers, supports this concept in elder care. The present study is a retrospective interpretation utilizing the original database to examine the new question, “What specific roles do sons play in caregiving of their elderly mothers?” While daughters presently continue to emerge in existing health care studies as the primary care provider, there is a significant pattern in these data for older patients to depend upon sons for a variety of instrumental activities of daily living. As the baby-boomers age, there is more of cohort trend for their families to be smaller, adult daughters to be employed, and for adult children to be more geographically mobile. These factors may combine to make health care support networks more limited for the current aging population, challenging the elderly and their health care providers to revisit the cultural gender norms that are used to identify caregivers. Keywords: sons as caregivers, male caregivers, aging parents, filial support, informal caregivers 

  12. Attention deficit hyperactivity disorder associated with orbitofrontal epilepsy in a father and a son.

    Science.gov (United States)

    Powell, A L; Yudd, A; Zee, P; Mandelbaum, D E

    1997-04-01

    The authors report on a father and son with frontal lobe epilepsy and symptoms of attention deficit hyperactivity disorder (ADHD). Attention deficit hyperactivity is a syndrome defined by criteria that include inattention, impulsive behavior, impaired concentration and motor restlessness. It does not require medical or neurobehavioral evaluation to determine an underlying etiology. The father is a 45-year-old man evaluated for possible ADHD. His referral came after the diagnosis of ADHD in his 6-year-old son who responded well to treatment with methylphenidate HCL. Neurobehavioral evaluation of the father suggested frontal lobe dysfunction. Magnetic resonance imaging and electroencephalography (EEG) were normal. Brain 99mTc HMPAO single-photon emission computed tomography (SPECT) revealed left orbitofrontal hypoperfusion. Additional history from his wife revealed episodic symptoms suggestive of nonconvulsive epilepsy that included nonresponsive staring, complex automatic behavior, and amnesic lacunas. Treatment of the father with carbmazepine produced dramatic improvement. Subsequent evaluation of his son, currently on maintenance treatment with methylphenidate HCL for ADHD, elicited a history consistent with atonic and simple motor partial epilepsy. The son's brain SPECT revealed bilateral orbitofrontal hypoperfusion defects. Attention deficit hyperactivity disorder is a syndrome that may be caused by frontal lobe lesions or epilepsy. In the setting of possible ADHD, neurological evaluation is warranted. Although overreliance on structural imaging or EEG in such an evaluation must be discouraged, brain SPECT may be useful to evaluate patients with symptoms of attention disorders for frontal epilepsy.

  13. Poetics of Narrative: A Study on the "Sons of the Wind" by Laila Al Atrash

    Science.gov (United States)

    Al Zuraigat, Asma M.; Zeidanin, Hussein Hasan

    2015-01-01

    This study aims at identifying the poetic devices overlapping with the genre of fiction in Laila Al Atrash's novel "The Sons of the Wind". The devices the study explores are the poetics of the title, poetics of the prologue and poetics of the language upon which the writer relies to support her point of view about the topics and issues…

  14. Slit-Dependent Endocytic Trafficking of the Robo Receptor Is Required for Son of Sevenless Recruitment and Midline Axon Repulsion.

    Science.gov (United States)

    Chance, Rebecca K; Bashaw, Greg J

    2015-09-01

    Understanding how axon guidance receptors are activated by their extracellular ligands to regulate growth cone motility is critical to learning how proper wiring is established during development. Roundabout (Robo) is one such guidance receptor that mediates repulsion from its ligand Slit in both invertebrates and vertebrates. Here we show that endocytic trafficking of the Robo receptor in response to Slit-binding is necessary for its repulsive signaling output. Dose-dependent genetic interactions and in vitro Robo activation assays support a role for Clathrin-dependent endocytosis, and entry into both the early and late endosomes as positive regulators of Slit-Robo signaling. We identify two conserved motifs in Robo's cytoplasmic domain that are required for its Clathrin-dependent endocytosis and activation in vitro; gain of function and genetic rescue experiments provide strong evidence that these trafficking events are required for Robo repulsive guidance activity in vivo. Our data support a model in which Robo's ligand-dependent internalization from the cell surface to the late endosome is essential for receptor activation and proper repulsive guidance at the midline by allowing recruitment of the downstream effector Son of Sevenless in a spatially constrained endocytic trafficking compartment.

  15. Slit-Dependent Endocytic Trafficking of the Robo Receptor Is Required for Son of Sevenless Recruitment and Midline Axon Repulsion.

    Directory of Open Access Journals (Sweden)

    Rebecca K Chance

    2015-09-01

    Full Text Available Understanding how axon guidance receptors are activated by their extracellular ligands to regulate growth cone motility is critical to learning how proper wiring is established during development. Roundabout (Robo is one such guidance receptor that mediates repulsion from its ligand Slit in both invertebrates and vertebrates. Here we show that endocytic trafficking of the Robo receptor in response to Slit-binding is necessary for its repulsive signaling output. Dose-dependent genetic interactions and in vitro Robo activation assays support a role for Clathrin-dependent endocytosis, and entry into both the early and late endosomes as positive regulators of Slit-Robo signaling. We identify two conserved motifs in Robo's cytoplasmic domain that are required for its Clathrin-dependent endocytosis and activation in vitro; gain of function and genetic rescue experiments provide strong evidence that these trafficking events are required for Robo repulsive guidance activity in vivo. Our data support a model in which Robo's ligand-dependent internalization from the cell surface to the late endosome is essential for receptor activation and proper repulsive guidance at the midline by allowing recruitment of the downstream effector Son of Sevenless in a spatially constrained endocytic trafficking compartment.

  16. Major ion chemistry of the Son River, India: Weathering processes, dissolved fluxes and water quality assessment

    Indian Academy of Sciences (India)

    Chinmaya Maharana; Sandeep Kumar Gautam; Abhay Kumar Singh; Jayanth K Tripathi

    2015-08-01

    River Son, draining diverse lithologies in the subtropical climate of the peninsular sub-basin of the Ganga basin, is one of the major tributaries of the Ganga River. The chemistry of major ions in the surface water of the Son River was studied in detail to determine various source(s) and processes controlling its water chemistry, seasonal and spatial variations in water chemistry, dissolved fluxes and chemical denudation rate (CDR). The study shows that Ca2+, Mg2+ and HCO$^{-}_{3}$ are major ionic species in the river water. Most of the measured parameters exhibit a relatively lower concentration in the post-monsoon as compared to pre-monsoon season. The water chemistry highlights the influence of continental weathering aided by secondary contributions from ground water, saline/alkaline soils and anthropogenic activities in the catchment. Results also reflect the dominance of carbonate weathering over silicate weathering in controlling water composition. The Son River delivers about 4.2 million tons of dissolved loads annually to the Ganga River, which accounts for ∼6% of the total annual load carried by the Ganga River to the Bay of Bengal. The average CDR of the Son River is 59.5 tons km−2 yr−1, which is less than the reported 72 tons km−2 yr−1 of the Ganga River and higher than the global average of 36 tons km−2 yr−1. The water chemistry for the pre-monsoon and post-monsoon periods shows a strong seasonal control on solute flux and CDR values. The water chemistry indicates that the Son River water is good to excellent in quality for irrigation and also suitable for drinking purposes.

  17. Hepatitis C Virus Core Protein Abrogates the DDX3 Function That Enhances IPS-1-Mediated IFN–Beta Induction

    OpenAIRE

    2010-01-01

    The DEAD box helicase DDX3 assembles IPS-1 (also called Cardif, MAVS, or VISA) in non-infected human cells where minimal amounts of the RIG-I-like receptor (RLR) protein are expressed. DDX3 C-terminal regions directly bind the IPS-1 CARD-like domain as well as the N-terminal hepatitis C virus (HCV) core protein. DDX3 physically binds viral RNA to form IPS-1-containing spots, that are visible by confocal microscopy. HCV polyU/UC induced IPS-1-mediated interferon (IFN)-beta promoter activation,...

  18. Abrogation of E-cadherin-mediated cellular aggregation allows proliferation of pluripotent mouse embryonic stem cells in shake flask bioreactors.

    Directory of Open Access Journals (Sweden)

    Lisa Mohamet

    Full Text Available BACKGROUND: A fundamental requirement for the exploitation of embryonic stem (ES cells in regenerative medicine is the ability to reproducibly derive sufficient numbers of cells of a consistent quality in a cost-effective manner. However, undifferentiated ES cells are not ideally suited to suspension culture due to the formation of cellular aggregates, ultimately limiting scalability. Significant advances have been made in recent years in the culture of ES cells, including automated adherent culture and suspension microcarrier or embryoid body bioreactor culture. However, each of these methods exhibits specific disadvantages, such as high cost, additional downstream processes or reduced cell doubling times. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that abrogation of the cell surface protein E-cadherin, using either gene knockout (Ecad-/- or the neutralising antibody DECMA-1 (EcadAb, allows culture of mouse ES cells as a near-single cell suspension in scalable shake flask culture over prolonged periods without additional media supplements. Both Ecad-/- and EcadAb ES cells exhibited adaptation phases in suspension culture, with optimal doubling times of 7.3 h±0.9 and 15.6 h±4.7 respectively and mean-fold increase in viable cell number of 95.1±2.0 and 16±0.9-fold over 48 h. EcadAb ES cells propagated as a dispersed cell suspension for 15 d maintained expression of pluripotent markers, exhibited a normal karyotype and high viability. Subsequent differentiation of EcadAb ES cells resulted in expression of transcripts and proteins associated with the three primary germ layers. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration of the culture of pluripotent ES cells as a near-single cell suspension in a manual fed-batch shake flask bioreactor and represents a significant improvement on current ES cell culture techniques. Whilst this proof-of-principle method would be useful for the culture of human ES and iPS cells, further steps are

  19. Instabilities of Spherical Solutions with Multiple Galileons and SO(N) Symmetry

    CERN Document Server

    Andrews, Melinda; Khoury, Justin; Trodden, Mark

    2010-01-01

    The 4-dimensional effective theory arising from an induced gravity action for a co-dimension greater than one brane consists of multiple galileon fields pi^I, I=1...N, invariant under separate Galilean transformations for each scalar, and under an internal SO(N) symmetry. We study the viability of such models by examining spherically symmetric solutions. We find that for general, non-derivative couplings to matter invariant under the internal symmetry, such solutions exist and exhibit a Vainshtein screening effect. By studying perturbations about such solutions, we find both an inevitable gradient instability and fluctuations propagating at superluminal speeds. These findings suggest that more general, derivative couplings to matter are required for the viability of SO(N) galileon theories.

  20. Mesure ambulatoire de la pression artérielle, son utilité en pratique quotidienne

    OpenAIRE

    Krzesinski, Jean-Marie

    1994-01-01

    Si la nécessité du traitement de l'hypertension artérielle est un fait accepté de façon universelle, la question à propos des niveaux de pression artérielle qui méritent une intervention reste débattue. Cette difficulté trouve son origine dans une telle variabilité de la pression artérielle que les mesures au cabinet de consultation représentent seulement une vue limitée de son réel profil sur 24 heures. Le développement d'enregistreurs portatifs de la pression artérielle par méthode non i...

  1. Planning a Career in Engineering: Parental Effects on Sons and Daughters

    Directory of Open Access Journals (Sweden)

    Jerry A. Jacobs

    2017-01-01

    Full Text Available This paper examines the extent to which prospective engineers follow in their parents’ footsteps. Specifically, we investigate the connection between fathers’ and mothers’ employment in the engineering profession and the career plans of sons and daughters. We develop a number of reasons to expect an occupation-specific intergenerational association in this field, as well as hypotheses regarding gender-specific role-modeling. Data are drawn from the UCLA HERI Freshman Survey data spanning 1971 to 2011. The results point to clear and substantial effects on sons and daughters’ plans to pursue engineering, connections that cannot be explained by typical pathways such as social background, education and values. The evidence points to a pattern of increasing salience of mothers with respect to the career plans of their children, especially their daughters. The implications of these findings for the under-representation of women in engineering and for gender-specific family dynamics are discussed in the conclusion.

  2. Experiences of parents whose sons or daughters have (had) attempted suicide

    DEFF Research Database (Denmark)

    Buus, Niels; Caspersen, Jimmy; Hansen, Rasmus;

    2014-01-01

    problem and relatives are understood as playing an important role in suicide prevention; however, suicide and suicidal behaviour affect the relatives' lives profoundly, both emotionally and socially, and the psychosocial impact on families is underresearched. DESIGN: Focus groups with parents of sons...... in the conversational interactions. The findings were interpreted and discussed within an interactionist framework. FINDINGS: The participants in the study described their experiences as a double trauma, which included the trauma of the suicide attempt(s) and the subsequent psychosocial impact on the family's well......AIM: The aim of this exploratory study was to gain further insights into the experiences of parents of sons or daughters who have attempted suicide and how these parents respond to the increased psychosocial burden following the suicide attempt(s). BACKGROUND: Suicide is a major public health...

  3. ‘Lest we forget’*: a veteran and son share a ‘warfare tourism’ experience

    OpenAIRE

    Fallon, Paul; Robinson, Peter

    2016-01-01

    Warfare tourism’ represents an increasingly significant dimension of contemporary tourism. This paper provides a fresh perspective on participation in ‘warfare tourism’ by investigating the behaviour and experiences of a living veteran and his son returning to two theatres of war in which the veteran had served in the Royal Navy during the Second World War. Active interviews with the two family members were used to gather rich data regarding the two extended trips, which had been funded by ‘H...

  4. The mystery of the perpetual motion clock of Geiser and Son

    Science.gov (United States)

    Piguet, Jean-Michel

    A description of the operation and mechanisms of a so called perpetual motion clock is given. At the end of the 18th and beginning of the 19th century, the achievement of perpetual motion was one of the Neuchatel clockmakers' great interests. Some watchmakers presented scientists and the public with constructions which, at first sight, seemed to have solved the problem. In 1815 a really interesting clock mechanism invented by Jean Geiser and his son was presented in Neuchatel.

  5. Pragmatic Analysis of a Dialogue in Laurence’s Sons and Lovers

    Institute of Scientific and Technical Information of China (English)

    李桂芝; 马宏

    2008-01-01

    This article provides a pragmatic analysis of a dialogue in Laurence’s Sons and Lovers from the perspectives of turn-taking,cooperative principle,politeness principle and speech act theory. A detailed analysis shows that pragmatic theories provide a good approach to the appreciation of fiction and that such kind of analysis based on a relatively precise methodology proves to be an effective approach to capture the richness of characters.

  6. Views of Astronaut (Col.) Joe Engle and son Jon with L-5 Piper Cub

    Science.gov (United States)

    1981-01-01

    Views of Astronaut (Col.) Joe Engle and son Jon with L-5 Piper Cub at Clover Airport. Photos includes Jon Engle sitting on side door frame working on portion of wing. Joe Engle is behind him working on a wing strut (34329); Joe Engle works on tightening bolt (34330); Jon Engle works on portion of wing which connects to the cockpit. Joe Engle works on connecting strut to wing (34331).

  7. Paternal antisocial behavior and sons' cognitive ability: a population-based quasiexperimental study.

    Science.gov (United States)

    Latvala, Antti; Kuja-Halkola, Ralf; Långström, Niklas; Lichtenstein, Paul

    2015-01-01

    Parents' antisocial behavior is associated with developmental risks for their offspring, but its effects on their children's cognitive ability are unknown. We used linked Swedish register data for a large sample of adolescent men (N = 1,177,173) and their parents to estimate associations between fathers' criminal-conviction status and sons' cognitive ability assessed at compulsory military conscription. Mechanisms behind the association were tested in children-of-siblings models across three types of sibling fathers with increasing genetic relatedness (half-siblings, full siblings, and monozygotic twins) and in quantitative genetic models. Sons whose fathers had a criminal conviction had lower cognitive ability than sons whose fathers had no conviction (any crime: Cohen's d = -0.28; violent crime: Cohen's d = -0.49). As models adjusted for more genetic factors, the association was gradually reduced and eventually eliminated. Nuclear-family environmental factors did not contribute to the association. Our results suggest that the association between men's antisocial behavior and their children's cognitive ability is not causal but is due mostly to underlying genetic factors.

  8. Son Preference and Family Planning Practices among Married Men in Mumbai, India

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To study son preferences and the contraceptive knowledge, attitude and practices of Indian Male Subjects & Methods The data was obtained through a semi-structured interview schedule caried out in 2 687 married men at Mumbai City, India in 1999.Results About 80% of men felt two children as their ideal family size, while 82%desired two children i.e. one son and one daughter. 8. 2% of men had strong prefer ence for two or more sons because of family lineage, old age support and to support each other.23. 1% of the couples had used contraceptives in the past, 48% of couples were not using any contraceptive method at the time of survey. Male participation in spacing contraceptive methods was 23% i.e. condom 21.9% and withdrawal 1.1%. Though awareness (99. 9% ) and knowledge (95. 2% ) of condom was high, only 42. 8% of subjects knew use the correct of the method. Only 2. 4% of them thought about accept ing vasectomy, while others reported various misconception.Conclusion This study suggests a pressing need for effective intervention strategies,both at the community level and the clinic level, backed with efficient motivation, coun seling and provision of quality services in urban areas.

  9. A Stylistic Analysis of D.H. Lawrence’s ‘Sons and Lovers’

    Directory of Open Access Journals (Sweden)

    Nozar Niazi

    2013-07-01

    Full Text Available This paper aims at analyzing D.H. Lawrence’s ‘Sons and Lovers’ using a stylistic approach. Stylistics is a study of the amalgamation of form with content. The stylistic analysis of a novel goes beyond the traditional, intuitive interpretation, because it combines intuition and detailed linguistic analysis of the text. The defining elements of modern language are within the text itself, not prescribed from outside. With modernist texts, usually understanding comes from close study of the language system defined within the text itself. Form, technique and style are considered not as a mere vehicle of the content of the story, but an integral part of the work’s meaning and value. In our analysis of ‘Sons and Lovers’ the resources of language: lexis, syntax, phonology, figurative language, cohesion and coherence, are discussed in relation to the style of discourse in order to explore hidden meanings in the text. The resources of language are shown to be an essential part of the meaning of the novel. Key words: stylistics, D.H. Lawrence, Sons and Lovers

  10. Multivariate Multiple Regression Models for a Big Data-Empowered SON Framework in Mobile Wireless Networks

    Directory of Open Access Journals (Sweden)

    Yoonsu Shin

    2016-01-01

    Full Text Available In the 5G era, the operational cost of mobile wireless networks will significantly increase. Further, massive network capacity and zero latency will be needed because everything will be connected to mobile networks. Thus, self-organizing networks (SON are needed, which expedite automatic operation of mobile wireless networks, but have challenges to satisfy the 5G requirements. Therefore, researchers have proposed a framework to empower SON using big data. The recent framework of a big data-empowered SON analyzes the relationship between key performance indicators (KPIs and related network parameters (NPs using machine-learning tools, and it develops regression models using a Gaussian process with those parameters. The problem, however, is that the methods of finding the NPs related to the KPIs differ individually. Moreover, the Gaussian process regression model cannot determine the relationship between a KPI and its various related NPs. In this paper, to solve these problems, we proposed multivariate multiple regression models to determine the relationship between various KPIs and NPs. If we assume one KPI and multiple NPs as one set, the proposed models help us process multiple sets at one time. Also, we can find out whether some KPIs are conflicting or not. We implement the proposed models using MapReduce.

  11. The Experiences and Meanings That Shape Heterosexual Fathers' Relationships With Their Gay Sons in South Africa.

    Science.gov (United States)

    Livingston, Jacques; Fourie, Eduard

    2016-12-01

    Gay men's relationships with their mothers are likely to be more positive than their relationships with their fathers, and fathers are less likely to be told, less likely to be told first, and more likely to react negatively to disclosure than mothers. Drawing on an interpretivist approach, an individual in-depth interview strategy was adopted in the study as a means of gathering data from six Afrikaans-speaking White fathers, between the ages of 53 and 61 years (median: 55.5 years), residing in Gauteng, South Africa. Interviews were audio-recorded and transcribed for later coding and analysis. Through thematic network analysis, eight organizing themes emerged and were explored. For the purpose of this article only three organizing themes are discussed, namely "subliminal awareness prior to coming out," "epistemic rupture of internal systems of ideas/beliefs," and "acceptance as a complex and ongoing dialectical and reconciliatory process." The themes support the view that most parents are neither totally rejecting nor fully accepting of their gay sons. Although the fathers may have attained a level of "loving denial" in the relationships with their gay sons, most continue to struggle with the meaning and expression of same-sex sexuality. Despite these challenges, it is recognized that the fathers are adapting to changing circumstances and are trying to find ways to tolerate, accommodate, and in some ways accept their gay sons.

  12. Human papillomavirus type 16 E7 oncoprotein engages but does not abrogate the mitotic spindle assembly checkpoint

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Yueyang [Division of Infectious Diseases, Brigham and Women' s Hospital and Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115 (United States); Munger, Karl, E-mail: kmunger@rics.bwh.harvard.edu [Division of Infectious Diseases, Brigham and Women' s Hospital and Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115 (United States)

    2012-10-10

    The mitotic spindle assembly checkpoint (SAC) ensures faithful chromosome segregation during mitosis by censoring kinetochore-microtubule interactions. It is frequently rendered dysfunctional during carcinogenesis causing chromosome missegregation and genomic instability. There are conflicting reports whether the HPV16 E7 oncoprotein drives chromosomal instability by abolishing the SAC. Here we report that degradation of mitotic cyclins is impaired in cells with HPV16 E7 expression. RNAi-mediated depletion of Mad2 or BubR1 indicated the involvement of the SAC, suggesting that HPV16 E7 expression causes sustained SAC engagement. Mutational analyses revealed that HPV16 E7 sequences that are necessary for retinoblastoma tumor suppressor protein binding as well as sequences previously implicated in binding the nuclear and mitotic apparatus (NuMA) protein and in delocalizing dynein from the mitotic spindle contribute to SAC engagement. Importantly, however, HPV16 E7 does not markedly compromise the SAC response to microtubule poisons.

  13. RhoA Activation Sensitizes Cells to Proteotoxic Stimuli by Abrogating the HSF1-Dependent Heat Shock Response.

    Directory of Open Access Journals (Sweden)

    Roelien A M Meijering

    Full Text Available The heat shock response (HSR is an ancient and highly conserved program of stress-induced gene expression, aimed at reestablishing protein homeostasis to preserve cellular fitness. Cells that fail to activate or maintain this protective response are hypersensitive to proteotoxic stress. The HSR is mediated by the heat shock transcription factor 1 (HSF1, which binds to conserved heat shock elements (HSE in the promoter region of heat shock genes, resulting in the expression of heat shock proteins (HSP. Recently, we observed that hyperactivation of RhoA conditions cardiomyocytes for the cardiac arrhythmia atrial fibrillation. Also, the HSR is annihilated in atrial fibrillation, and induction of HSR mitigates sensitization of cells to this disease. Therefore, we hypothesized active RhoA to suppress the HSR resulting in sensitization of cells for proteotoxic stimuli.Stimulation of RhoA activity significantly suppressed the proteotoxic stress-induced HSR in HL-1 atrial cardiomyocytes as determined with a luciferase reporter construct driven by the HSF1 regulated human HSP70 (HSPA1A promoter and HSP protein expression by Western Blot analysis. Inversely, RhoA inhibition boosted the proteotoxic stress-induced HSR. While active RhoA did not preclude HSF1 nuclear accumulation, phosphorylation, acetylation, or sumoylation, it did impair binding of HSF1 to the hsp genes promoter element HSE. Impaired binding results in suppression of HSP expression and sensitized cells to proteotoxic stress.These results reveal that active RhoA negatively regulates the HSR via attenuation of the HSF1-HSE binding and thus may play a role in sensitizing cells to proteotoxic stimuli.

  14. Analyzing binding data.

    Science.gov (United States)

    Motulsky, Harvey J; Neubig, Richard R

    2010-07-01

    Measuring the rate and extent of radioligand binding provides information on the number of binding sites, and their affinity and accessibility of these binding sites for various drugs. This unit explains how to design and analyze such experiments.

  15. Complicated grief and manic comorbidity in the aftermath of the loss of a son.

    Science.gov (United States)

    Carmassi, Claudia; Shear, M Katherine; Socci, Chiara; Corsi, Martina; Dell'osso, Liliana; First, Michael B

    2013-09-01

    Based on the recommendations of the sub-workgroup on trauma and dissociative disorders, the American Psychiatric Association (APA) removed the "bereavement exclusion" from the criteria for major depression in DSM-5. In addition, proposed DSM-5 research criteria for persistent complex bereavement disorder (PCBD) were included in the new manual in a section for conditions and criteria needing further research. We describe a case that warranted such a diagnosis. The patient was a 52- year-old woman who was admitted to the inpatient unit of our clinic on the birthday of her son who had died 18 months earlier. She was diagnosed with a manic episode with psychotic symptoms according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria and was treated accordingly. Three months after discharge, she made a suicide attempt and was admitted and re-assessed. During this admission, she completed the Inventory of Complicated Grief (ICG), the Mood-Spectrum Rating Scale (MOODS-SR), and the Trauma and Loss Spectrum questionnaire (TALS-SR). She endorsed symptoms of intense yearning for her son, feelings of shock and disbelief, anger and bitterness related to his death, estrangement from others, auditory, tactile and visual hallucinations of the deceased, and intense emotional reactivity to memories of her son. These symptoms were sufficiently prolonged and severe to meet criteria for complicated grief. While complicated grief appeared to be the primary diagnosis for this patient, when she was diagnosed using only DSMIV-TR criteria, her treatment failed to address herprimary problem. This case draws attention to the occurrence of manic-like symptoms as well as depression-like manifestations following bereavement and highlights the importance of including the syndrome of complicated grief in the diagnostic nomenclature.

  16. The Tragic Marriage of the Morel Couple in Sons and Lovers

    Institute of Scientific and Technical Information of China (English)

    YUAN Shuai

    2016-01-01

    In Sons and Lovers, one of William Faulkner’s most famous novels, the marriage between Walter Morel and Gertrude Coppard was inarguably a tragic one. However, as for the reason, it was not explicitly represented in the novel. This paper at-tempts to delve into the reason of this failed marriage and put forward an argument that this failure could be attributed to the con-flict between sex and social class with the help of the theory of dominance and subordinance put forward by Kate Millett.

  17. Acercamiento al son guatemalteco tradicional desde una perspectiva histórica

    OpenAIRE

    de Gandarias, Igor

    2015-01-01

    Este artículo recorre sintéticamente la ruta histórica seguida por el son guatemalteco tradicional, a partir de la ubicación temporal de sus com- portamientos musicales dentro de los procesos históricos de occidenta- lización y mestizaje que los originaron. Inicia con el sustrato tímbrico de instrumentos sonoros mayas prehispánicos que perviven en un sector de la producción conocida. Le siguen, además de otros instrumentos musicales, los aportes tonales, rítmicos y texturales de origen europe...

  18. Autismo y Programa Son-Rise: Intervención sobre un caso

    OpenAIRE

    López Camarero, Irene

    2013-01-01

    En este documento se estudian los distintos tipos de trastorno del espectro autista, distinguiendo las características de cada uno de ellos y las posibles causas que pueden originarlos. Partiendo de esta base, se plantean distintos métodos o programas existentes en nuestra sociedad para trabajar con este colectivo y lograr que desarrollen sus capacidades en el máximo nivel posible. Tras una breve explicación de algunos de ellos, nos centramos en el Programa Son-Rise, método poco conocid...

  19. The Tragedy of Hamlet, Son of an Organic Chemist of Denmark

    Science.gov (United States)

    Brisbois, Ronald G.

    2004-04-01

    Once faced with structure reactivity relationships in the context of nucleophilic substitution at sp 3 carbon, introductory organic chemistry students must compare and contrast the various attributes and ramifications of S N 2 versus S N 1 reaction pathways. The dramatic (even melodramatic) way in which some students ask such comparative questions inspired a parody of Hamlet's famous to be or not to be soliloquy. Herein, Hamlet (the son of an organic chemist of Denmark) is the surrogate of any and every student as he uses a thoroughly Shakespearian approach to sorting out some of the key distinguishing features of S N 2 versus S N 1 reactions.

  20. THE EPITHESIS IN THE LOAN WORDS ALINTI KELİMELERDE SON TÜREME

    Directory of Open Access Journals (Sweden)

    Gülden SAĞOL YÜKSEKKAYA

    2010-01-01

    Full Text Available Anaptyxis is a sound appearing that is not found in the original structure of the word. There are three types of anaptyxis: prothesis, epenthesis and epithesis. Epithesis is a vowel or consonant appearing at the end of a word which is not found in the original structure of it. Although, there isn’t not so much example, both vowel and consonant reproduction is seen even in the last sound of the word; but the derivative sound isn’t the same, standard in the whole dialects and accents. Nevertheless some derivative sounds have an intense in a specific region, they aren’t seen in the other areas or has rare example. In this study, the epithesis in the loan words in Turkish will be emphasized. Bir kelimede aslında bulunmayan bir sesin sonradan ortaya çıkmasına ses türemesi denir. Ses türemesinin üç çeşidi vardır: ön türeme, iç türeme, son türeme. Son türeme, kelimenin aslında bulunmayan bir ünlü veya ünsüzün kelime sonunda belirmesidir. Örneği fazla olmamakla birlikte son seste de hem ünlü hem de ünsüz türemesi görülür. Ancak türeyen sesler standart olarak bütün lehçe ve ağızlarda ortak değildir. Türeyen bazı sesler belli bir bölge içerisinde yoğunlaşırken, bazı bölgelerde görülmemekte veya sadece birkaç, hatta bir örnekle sınırlı kalabilmektedir. Bu çalışmada Türkçede alıntı kelimelerdeki son türeme örnekleri üzerinde durulacaktır.

  1. THE APOCOPE IN THE LOAN WORDS ALINTI KELİMELERDE SON SES DÜŞMESİ

    Directory of Open Access Journals (Sweden)

    Aylin KOÇ

    2010-10-01

    Full Text Available Disappearance is the loss of a sound in structure of the word with some reasons. There are three types of disappearance: apheresis, syncope and apocope. The apocope is disappearance of a vowel or consonant at the end of a word. This situation isn’t standard in whole dialects and accents. Some dropping sounds, have an intense in a spesific region, they aren’t seen in the other areas or have rare examples. This is rather common in the dialects. In this study will be handled the apocope in the loan words with the examples in Turkey Turkish and contemporary Turkish dialects. Bir kelimedeki seslerden birinin, çeşitli nedenlerle düşmesine ses düşmesi denir. Ses düşmesi üç çeşittir: ön ses düşmesi, iç ses düşmesi ve son ses düşmesi. Son ses düşmesi, kelimede son ses durumunda olan ünlü veya ünsüzün düşmesidir. Bu durum, bütün lehçelerde ve ağızlarda standart değildir. Düşen bazı sesler, belli bir bölge içinde yoğunlaşırken, bazı bölgelerde görülmemekte ve hatta birkaç ya da bir örnekle sınırlı kalabilmektedir. Bu daha çok ağızlarda görülür. Çalışmada, Türkiye Türkçesinde ve Çağdaş Türk Lehçelerinde alıntı kelimelerde son ses düşmesi bahsi örnekleriyle ele alınacaktır.

  2. ¿Son las creencias religiosas razonables? : verificación o falsación

    OpenAIRE

    2008-01-01

    Este trabajo está orientado a responder la pregunta ¿son la creencias religiosas razonables? Para ello, se hace un esbozo, primero de qué significan las creencias en general, para luego abarcar las creencias religiosas en particular. En este punto se realiza una descripción de las teorías de la verificación y la falsación. Posteriormente, se detallan las distintas posiciones relacionadas con las expresiones religiosas. Finalmente, se presenta un enfrentamiento entre aquellos que consideran la...

  3. Performance of the Birmingham Solar-Oscillations Network (BiSON)

    CERN Document Server

    Hale, S J; Chaplin, W J; Davies, G R; Elsworth, Y P

    2015-01-01

    The Birmingham Solar-Oscillations Network (BiSON) has been operating with a full complement of six stations since 1992. Over 20 years later, we look back on the network history. The meta-data from the sites have been analysed to assess performance in terms of site insolation, with a brief look at the challenges that have been encountered over the years. We explain how the international community can gain easy access to the ever-growing dataset produced by the network, and finally look to the future of the network and the potential impact of nearly 25 years of technology miniaturisation.

  4. Data and Analysis Methods of the Son-O-Mermaid and MERMAID Experiments

    Science.gov (United States)

    Simon, J. D.; Simons, F. J.; Nolet, G.

    2014-12-01

    Here we present, for the first time, the results from pilot deployments of the Son-O-Mermaid project, an autonomously drifting, oceangoing data-collection platform that can be cheaply deployed without the need for a costly research vessel, and that records and transmits hydroacoustic signals (with a target of those generated by teleseismic earthquakes) in near real-time. Both deployments employ three identical hydrophones spaced about 70 cm apart at the end of a 700 m long cable attached to a surface buoy that houses electronics, communications, and a GPS location package. The maiden voyage occurred October 8, 2012, in Exuma Bay, Bahamas and returned 25 hours of acoustic data. A second deployment is to take place in September 2014, with near-immediate data relay via Iridium modem. The experimental setup is different from the MERMAID instrument, which sinks to a midcolumn depth and surfaces to transmit waveforms when an event detection algorithm is triggered. MERMAIDs have recorded hundreds of seismic traces from 18 active floats in the Indian and Mediterranean Oceans with a signal-to-noise ratio suitable for global tomography. As with earthquake early-warning studies, both Son-O-Mermaid and MERMAID benefit from rapid and accurate event detection, discrimination, and measurement technology. With this triple purpose in mind we continue to improve methods (in the time-domain, via spectrogram analysis and using wavelets) that we illustrate on the latest and some of the older data, as well. While hydroacoustic data have numerous other applications beyond seismology (whale calls, ice calving, weather patterns, and so on) the Son-O-Mermaid and MERMAID instruments may potentially revolutionize seismic data collection in the oceans. Moreover, in the near future they will be fitted with more or different instruments, becoming multipurpose and multidisciplinary platforms for all types of scientific research in and of the oceans. In seismology we envision a future when the

  5. Failed Mothers, Monster Sons. Reading Shakespeare’S Richard Iii as a Fairy Tale

    Directory of Open Access Journals (Sweden)

    Percec Dana

    2014-03-01

    Full Text Available The paper looks at Shakespeare’s historical play Richard III and its fairy tale-like character given by the configuration of the main character as an arch-villain and the presence of motifs and patterns typically associated with the fairy tale genre. More specifically, it considers the mother-son relationship between the Duchess of York and Richard in the light of the motif of monstrous birth. It is not a coincidence that the emergence of such motifs coincides with the historical contexts of the early modern period. Reading Richard III in this key is related to the revisionist approach to chronicle plays.

  6. ¿Son fiables los productos que encontramos en los supermercados?

    OpenAIRE

    Olivares Zabalandicoechea, Maitane; Zuloaga Zubieta, Olatz

    2012-01-01

    Duración (en horas): De 21 a 30 horas. Destinatario: Estudiante En este recurso didáctico se presenta la metodología en base a proyectos utilizada en el proceso de enseñanza-aprendizaje de la asignatura optativa "Cromatografía y Técnicas Afines" que se imparte en el segundo ciclo de la Licenciatura de Química. El proyecto, que lleva como título "¿Son fiables los productos que encontramos en los supermercados?", permite al alumno aprender los distintos métodos analíticos para el a...

  7. Two qubits of a W state violate Bell's inequality beyond Cirel'son's bound

    CERN Document Server

    Cabello, A

    2002-01-01

    It is shown that the correlations between two qubits selected from a trio prepared in a W state violate the Clauser-Horne-Shimony-Holt inequality more than the correlations between two qubits in any quantum state. Such a violation beyond Cirel'son's bound is smaller than the one achieved by two qubits selected from a trio in a Greenberger-Horne-Zeilinger state [A. Cabello, Phys. Rev. Lett. 88, 060403 (2002)]. However, it has the advantage that all local observers can know from their own measurements whether their qubits belongs or not to the selected pair.

  8. Guillaume Rondelet (1507-1566): Cardinal physician and anatomist who dissected his own son.

    Science.gov (United States)

    Mian, Asma; Watanabe, Koichi; Shoja, Mohammadali M; Loukas, Marios; Tubbs, R Shane

    2014-04-01

    The 16th century French anatomist Guillaume Rondelet will be remembered as a great naturalist and a founder of ichthyology. Little known to most is that Rondelet was a proficient anatomist and contemporary to Vesalius and in fact, both studied anatomy under Johannes Guinter. Even less known is that he established the first dissecting theatre at Montpellier and it was here that he would dissect his infant son in an attempt to identify the cause of death. In this article, we review the life and contributions to anatomy of Rondelet.

  9. LA SABIDURIA DEL SILENCIO. HACIA EL DIÁLOGO... ¡OTROS MUNDOS SON POSIBLES!

    Directory of Open Access Journals (Sweden)

    Juan Carlos Valverde Campos

    2012-05-01

    Full Text Available A Occidentales y Orientales nos cobija un mismo techo. Sin embargo, la manera de concebir el mundo y, por ende, de actuar, es diferente. La sociedad globalizada en la que vivimos quiere hacer de este mundo uno solo, con un solo corazón y una sola manera de actuar y pensar. Occidente ha impuesto su mundo cuando en realidad son muchos y debemos conocerlos. El pensamiento oriental tiene mucho qué decirnos a los occidentales. En todo caso, el silencio que impone la escucha es fundamental en eso que tantos llaman hoy el diálogo.

  10. CHIRAL RING OF Sp(N) AND SO(N) SUPERSYMMETRIC GAUGE THEORY IN FOUR DIMENSIONS

    Institute of Scientific and Technical Information of China (English)

    E. WITTEN

    2003-01-01

    The chiral ring of classical supersymmetric Yang-Mills theory with gauge group Sp(N) or SO(N) is computed, extending previous work (of Cachazo, Douglas, Seiberg, and the author)for SU(N). The result is that, as has been conjectured, the ring is generated by the usualglueball superfield S ~ Tr WαWα, with the relation Sh = 0, h being the dual Coxeter number.Though this proposition has important implications for the behavior of the quantum theory,the statement and (for the most part) the proofs amount to assertions about Lie groups withno direct reference to gauge theory.

  11. Non-Abelian Vortices in SO(N) and USp(N) Gauge Theories

    CERN Document Server

    Eto, Minoru; Gudnason, Sven Bjarke; Konishi, Kenichi; Nagashima, Takayuki; Nitta, Muneto; Ohashi, Keisuke; Vinci, Walter

    2009-01-01

    Non-Abelian BPS vortices in SO(N) x U(1) and USp(2N) x U(1) gauge theories are constructed in maximally color-flavor locked vacua. We study in detail their moduli and transformation properties under the exact symmetry of the system. Our results generalize non-trivially those found earlier in supersymmetric U(N) gauge theories. The structure of the moduli spaces turns out in fact to be considerably richer here than what was found in the U(N) theories. We find that vortices are generally of the semi-local type, with power-like tails of profile functions.

  12. The risk of cryptorchidism among sons of women working in horticulture in Denmark: a cohort study

    Directory of Open Access Journals (Sweden)

    Gabel Pernille

    2011-11-01

    Full Text Available Abstract Background Androgens are crucial for normal testicular descent. Studies show that some pesticides have estrogenic or antiandrogenic effects, and that female workers exposed to pesticides have increased risk of having a boy with cryptorchidism. The main objective of the present study was to investigate whether pregnant women exposed to pesticides due to their work in horticulture experience excess risk of having sons with cryptorchidism. Methods We conducted a cohort study of pregnant women working in horticulture using four cohorts including one cohort established with data from the departments of occupational medicine in Jutland and Funen and three existing mother-child cohorts (n = 1,468. A reference group was established from the entire Danish population of boys born in the period of 1986-2007 (n = 783,817. Nationwide Danish health registers provided information on birth outcome, cryptorchidism diagnosis and orchiopexy. The level of occupational exposure to pesticides was assessed by expert judgment blinded towards outcome status. Risk of cryptorchidism among exposed horticulture workers compared to the background population and to unexposed horticulture workers was assessed by Cox regression models. Results Pesticide exposed women employed in horticulture had a hazard ratio (HR of having cryptorchid sons of 1.39 (95% CI 0.84; 2.31 and a HR of orchiopexy of 1.34 (0.72; 2.49 compared to the background population. Analysis divided into separate cohorts revealed a significantly increased risk of cryptorchidism in cohort 2: HR 2.58 (1.07;6.20 and increased risk of orchiopexy in cohort 4: HR 2.76 (1.03;7.35, but no significant associations in the other cohorts. Compared to unexposed women working in horticulture, pesticide exposed women had a risk of having sons with cryptorchidism of 1.34 (0.30; 5.96 and of orchiopexy of 1.93 (0.24;15.4. Conclusions The data are compatible with a slightly increased risk of cryptorchidism in sons of women

  13. Trust and disclosure of sexual orientation in gay males' mother-son relationships.

    Science.gov (United States)

    Miller, R J; Boon, S D

    2000-01-01

    This study explored the possibility that changes in feelings of trust for mother are associated with gay males' decisions to disclose (or withhold) their sexual orientation in their mother-son relationships. Fifty gay and bisexual males completed a questionnaire about their coming out experiences in the context of their relationships with their mothers. As part of this questionnaire, they completed a retrospective graphical trust history task that involved plotting the degree of trust they felt for their mothers over time and across important events (such as disclosure). Results are discussed in terms of gay men's expectations about their mothers' responses to disclosure, the evidence for stability versus change in their memories regarding the nature of their feelings of maternal trust over time, the complexity of the trust histories participants drew, similarity between disclosers and non-disclosers in the shape of their trust curves, and the types of events and experiences that constituted the timeline or "plot" in the stories participants told about their mother-son relationships. This study offers the first empirical evidence to support speculations linking disclosure of sexual orientation to the climate of trust that exists in the relationship between discloser and target (e.g., Holtzen, Kenny & Mahalik, 1995).

  14. Symbolism of the Shadows in Son of Man by Roa Bastos

    Institute of Scientific and Technical Information of China (English)

    Patricia G. Montenegro

    2015-01-01

    In his novel Son of Man, Augusto Roa Bastos uses images and symbols of shadows to represent the ramifications ofthe Paraguayan Dr. Jose Rodriguez de Francia's dictatorship. Rodriguez de Francia's legacy, which begins duringthe postcolonial years and extends well into the 20th century, resonates in the novel in soeio-political structures andcharacters' ideologies and behaviors. It allows for plantation owners to enslave workers and their families; itconfines and oppresses people through unfounded legends and myths; and among other things, it creates a falseidea of purpose and patriotism in the Chaco War (1932-1935), which in the end lets down the soldiers. Tocounteract these deleterious social conditions, Roa Bastos creates surreal characters, such as a fantastic helper whoaids plantation workers to escape dehumanizing situations. Roa Bastos also narrates how the people in Itapr, asmall town, make an idol of a Christ statue carved by one of their own. However, when the two Goiburfl brothersreplace the statue by crucifying their sister's rapist, the people's myth is destroyed. Likewise, Roa Bastos availshimself of Christian and Catholic concepts and symbols to transpose them into a humanistic ideology so as toconvey hope to his people through a new perspective. In this way, a new Annunciation takes place when the son ofa raped woman is born. In the end, Roa Bastos lets the course of these warped transpositions take their logicaldenouement: In the absence of a purpose beyond an earthly existence, death becomes the narrator's option.

  15. Malaria and enterobiasis among Karen Long-neck tribe in Mae Hong Son Province.

    Science.gov (United States)

    Nithikathkul, Choosak; Polseela, Panida; Poodendan, Wilawan; Brodsky, Marc; Rakprapapant, Derek; Chadchatreechan, Suparp; Phethleart, Aree; Sukthana, Yaowalark; Leemingsawat, Somjai

    2003-01-01

    In Thailand, Mae Hong Son Province is highly endemic for malaria. Knowing this, the local Health Department has introduced a program to educate local residents about the risk factors, in particular the dangers and symptoms of malaria. This study was conducted to evaluate these efforts, by determining the number of malaria infections in a segment of the population, and also by testing for enterobiasis among a group of its children. Two villages in Mae Hong Son Province were chosen for this purpose with a combined population of about 300. Of these, 195 were screened for malaria. Two subjects were diagnosed positive for malaria by microscopy. One of these two villages was chosen to screen for Enterobius vermicularis infection in children as well. Out of 69 stool samples, five (7%) showed infection with E. vermicularis: three with a low number of eggs (1-50), and two with a high number of eggs (>100). Compared with infection rates in similar studies, the results of this study indicate that the Health Department's efforts are meeting with relative success. The low prevalence of infection indicates that the villagers are using the information they have received to help combat infection.

  16. Seismic Interpretation of the Nam Con Son Basin and its Implication for the Tectonic Evolution

    Directory of Open Access Journals (Sweden)

    Nguyen Quang Tuan

    2016-08-01

    Full Text Available The Nam Con Son Basin covering an area of circa 110,000 km2 is characterized by complex tectonic settings of the basin which has not fully been understood. Multiple faults allowed favourable migration passageways for hydrocarbons to go in and out of traps. Despite a large amount of newly acquired seismic and well data there is no significant update on the tectonic evolution and history of the basin development. In this study, the vast amount of seismic and well data were integrated and reinterpreted to define the key structural events in the Nam Con Son Basin. The results show that the basin has undergone two extentional phases. The first N - S extensional phase terminated at around 30 M.a. forming E - W trending grabens which are complicated by multiple half grabens filled by Lower Oligocene sediments. These grabens were reactivated during the second NW - SE extension (Middle Miocene, that resulted from the progressive propagation of NE-SW listric fault from the middle part of the grabens to the margins, and the large scale building up of roll-over structure. Further to the SW, the faults of the second extentional phase turn to NNE-SSW and ultimately N - S in the SW edge of the basin. Most of the fault systems were inactive by Upper Miocene except for the N - S fault system which is still active until recent time.

  17. Self-Organizing Networks (SON) Self-Planning, Self-Optimization and Self-Healing for GSM, UMTS and LTE

    CERN Document Server

    Ramiro, Juan

    2011-01-01

    With the current explosion in network traffic, and mounting pressure on operators' business case, Self-Organizing Networks (SON) play a crucial role. They are conceived to minimize human intervention in engineering processes and at the same time improve system performance to maximize Return-on-Investment (ROI) and secure customer loyalty. Written by leading experts in the planning and optimization of Multi-Technology and Multi-Vendor wireless networks, this book describes the architecture of Multi-Technology SON for GSM, UMTS and LTE, along with the enabling technologies for SON planning, opti

  18. Molecular Determinants for Antibody Binding on Group 1 House Dust Mite Allergens

    Energy Technology Data Exchange (ETDEWEB)

    Chruszcz, Maksymilian; Pomés, Anna; Glesner, Jill; Vailes, Lisa D.; Osinski, Tomasz; Porebski, Przemyslaw J.; Majorek, Karolina A.; Heymann, Peter W.; Platts-Mills, Thomas A.E.; Minor, Wladek; Chapman, Martin D. (INDOOR Bio.); (UV); (UVHS)

    2012-07-11

    House dust mites produce potent allergens, Der p 1 and Der f 1, that cause allergic sensitization and asthma. Der p 1 and Der f 1 are cysteine proteases that elicit IgE responses in 80% of mite-allergic subjects and have proinflammatory properties. Their antigenic structure is unknown. Here, we present crystal structures of natural Der p 1 and Der f 1 in complex with a monoclonal antibody, 4C1, which binds to a unique cross-reactive epitope on both allergens associated with IgE recognition. The 4C1 epitope is formed by almost identical amino acid sequences and contact residues. Mutations of the contact residues abrogate mAb 4C1 binding and reduce IgE antibody binding. These surface-exposed residues are molecular targets that can be exploited for development of recombinant allergen vaccines.

  19. Leukotriene A4 hydrolase: Selective abrogation of leukotriene B4 formation by mutation of aspartic acid 375

    Science.gov (United States)

    Rudberg, Peter C.; Tholander, Fredrik; Thunnissen, Marjolein M. G. M.; Samuelsson, Bengt; Haeggström, Jesper Z.

    2002-01-01

    Leukotriene A4 (LTA4, 5S-trans-5,6-oxido-7,9-trans-11,14-cis-eicosatetraenoic acid) hydrolase (LTA4H)/aminopeptidase is a bifunctional zinc metalloenzyme that catalyzes the final and rate-limiting step in the biosynthesis of leukotriene B4 (LTB4, 5S,12R-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid), a classical chemoattractant and immune modulating lipid mediator. Two chemical features are key to the bioactivity of LTB4, namely, the chirality of the 12R-hydroxyl group and the cis-trans-trans geometry of the conjugated triene structure. From the crystal structure of LTA4H, a hydrophilic patch composed of Gln-134, Tyr-267, and Asp-375 was identified in a narrow and otherwise hydrophobic pocket, believed to bind LTA4. In addition, Asp-375 belongs to peptide K21, a previously characterized 21-residue active site-peptide to which LTA4 binds during suicide inactivation. In the present report we used site-directed mutagenesis and x-ray crystallography to show that Asp-375, but none of the other candidate residues, is specifically required for the epoxide hydrolase activity of LTA4H. Thus, mutation of Asp-375 leads to a selective loss of the enzyme's ability to generate LTB4 whereas the aminopeptidase activity is preserved. We propose that Asp-375, possibly assisted by Gln-134, acts as a critical determinant for the stereoselective introduction of the 12R-hydroxyl group and thus the biological activity of LTB4. PMID:11917124

  20. Bad Mothers and Monstrous Sons: Autistic Adults, Lifelong Dependency, and Sensationalized Narratives of Care.

    Science.gov (United States)

    Allen, Holly

    2017-03-01

    Sensationalized representations of autistic families in film and other media frequently feature violent encounters between mothers and sons. This essay analyzes two media stories and three films that suggest how limited-and therefore misleading-popular representations of the autism family are. Except for one of the films, these representations blame the problem of adult autistic dependency on either monstrous autism or bad mothering. Doing so elides collective social responsibility for autism care and denies the reality that autistic adults continue to have complex dependency needs that families cannot always meet. Narratives that sensationalize youth and adults with autism or scapegoat their maternal caregivers also diminish opportunities for social inclusion and for autistic people to live fully and dependently.

  1. Supersymmetric SO(N) from a Planck-scale statistical theory

    CERN Document Server

    Allen, Roland E

    2010-01-01

    Several refinements are made in a theory which starts with a Planck-scale statistical picture and ends with supersymmetry and a coupling of fundamental fermions and bosons to SO(N) gauge fields. In particular, more satisfactory treatments are given for (1) the transformation from the initial Euclidean form of the path integral for fermionic fields to the usual Lorentzian form, (2) the corresponding transformation for bosonic fields (which is much less straightforward), (3) the transformation from an initial primitive supersymmetry to the final standard form (containing, e.g., scalar sfermions and their auxiliary fields), (4) the initial statistical picture, and (5) the transformation to an action which is invariant under general coordinate transformations.

  2. El vídeoclip, l'art d'unir imatges i sons

    OpenAIRE

    2011-01-01

    Aquest projecte es basa en la cerca, estudi i realització d’un vídeo musical com a obra artística que uneix imatges i sons. Primerament s’analitza el videoclip, l’origen, la finalitat, les classes de videoclips i el mercat actual. Posteriorment es selecciona una versió de la cançó Boadicea d’Enya per realitzar-ne el vídeo musical i es fa una pre-producció on s’idea l’esquema del videoclip i les imatges que es gravaran. Després de la producció es realitza la post-producció amb la unió de le...

  3. CUENTOS QUE NO SON CUENTOS...UN RECORRIDO POR SAN ZENÓN (MAGDALENA

    Directory of Open Access Journals (Sweden)

    Tania Ximena Salcedo Goméz

    2013-07-01

    Full Text Available Es de tarde y el sol inclemente de febrero se refleja sobre Las cálidas aguas del río Magdalena; sus visos en naranja y rojo se inmortalizan en el tapiz del cielo, mientras en tierra, esta gama de luz iridescente se forja en la piel de los hombres y mujeres de San Zenón. Los árboles desnudos han sido bañados por el frío invierno. Las ciénagas y el río han dejado sus marcas a través del marrón 330 de sus cortezas. Las pocas hojas que quedan son solo un breve recuerdo de un amanecer con sombra. El asfalto y la pasividad del viento, quienes amenazan la lucidez.

  4. CUENTOS QUE NO SON CUENTOS...UN RECORRIDO POR SAN ZENÓN (MAGDALENA)

    OpenAIRE

    Tania Ximena Salcedo Goméz

    2013-01-01

    Es de tarde y el sol inclemente de febrero se refleja sobre Las cálidas aguas del río Magdalena; sus visos en naranja y rojo se inmortalizan en el tapiz del cielo, mientras en tierra, esta gama de luz iridescente se forja en la piel de los hombres y mujeres de San Zenón. Los árboles desnudos han sido bañados por el frío invierno. Las ciénagas y el río han dejado sus marcas a través del marrón 330 de sus cortezas. Las pocas hojas que quedan son solo un breve recuerdo de un amanecer con sombra....

  5. Padoue et son contado (Xe-XIIIe siècle)

    OpenAIRE

    Rippe, Gérard

    2013-01-01

    L'ouvrage traite d’un objet classique – une cité et son contado – à l’aide des concepts mis au point par l’historiographie récente. Après avoir décrit le cadre territorial hérité de l’Antiquité et du haut Moyen Âge, elle analyse l’évolution de ce territoire et de ses institutions du Xe au XIIe siècle, notamment la naissance et la constitution d’une société féodale à laquelle s’intègrent même les « arimanni » , puis l’« incastellamento » et sa signification démographique et politique, enfin l’...

  6. Pincio y los Estados Unidos que no son los Estados Unidos

    Directory of Open Access Journals (Sweden)

    Franco Zangrilli

    2015-07-01

    Full Text Available Lo neofantástico en Tommaso Pincio se distingue de lo fantástico posmoderno de nuestros escritores. Se basa en la realidad estadounidense contemporánea; la introduce en un proceso de elaboraciones enfáticas, mezclas, transfiguraciones, y la convierte en el símbolo de otro mundo, de un planeta extraño. Pincio llega a esta operación creativa gracias a su conocimiento de las tradiciones y de las costumbres, de la historia, de la cultura y de la literatura de los Estados Unidos. De todo eso quiere darse una idea en este ensayo, analizando la segunda novela de Pincio, Spazio sfinito, en la que se representa a unos Estados Unidos que no son Estados Unidos.

  7. L’emploi industriel en France et son évolution 1994-2004

    Directory of Open Access Journals (Sweden)

    Régis Guillaume

    2008-07-01

    Full Text Available Le déclin de l’emploi industriel est souvent appréhendé comme le symbole des difficultés de la France à maintenir son rang dans une économie toujours plus mondialisée et plus concurrentielle. L’article vise, à partir des statistiques de l’emploi, à montrer que la diminution des effectifs est loin d’être homogène et que, depuis une dizaine d’années, elle s’accompagne d’un redéploiement géographique de forte intensité. On a construit à cet effet des agrégats spécifiques permettant de prendre en compte le devenir des filières productives majeures.

  8. JOURNEY OF A WORKING MOTHER AND HER SON WITH DOWN SYNDROME.

    Science.gov (United States)

    Shahzad, Saadia

    2015-01-01

    Trisomy 21, chromosomal disorder related with Down syndrome (DS), is the most common cause leading to learning disability among all races and all human population. Having a child with Down syndrome in developed world has now become less of an unfortunate incidence in the lives of the parents; not because they do not realize the tough road ahead for their child as compared to other siblings but due to the fact that they have got a comprehensive and cohesive support system running for these children at every stage of life that builds up the child to his/her full potential. The present special communication is about personal experience of a working mother with her son with Down syndrome.

  9. Inhibitory effect of morphine on excitatory synaptic transmission via presynaptic mechanism in rat SON neurons in brain slices

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-bin; HU San-jue; JU Gong

    2001-01-01

    To observe the effects of morphine on the excitatory postsynaptic currents (EPSCs) and miniature EPSCs (mEPSCs) in rat supraoptic nucleus (SON) neurons and to explore its synaptic mechanism. Methods: Using whole-cell voltage-clamp recording technique in the brain slices, the EPSCS and mEPSCs of rat SON neurons were recorded, respectively. Results: Morphine (20 μmol/L) decreased the frequency of EPSCs and mEPSCs (by 65% for EPSCS and by 45% for mEPSCs), and reduced the amplitude of EPSCs by 44% in all SON neurons, but the amplitude distribution ofmEPSCs was not affected. Conclusion: Morphine inhibits the excitatory transmissions via presynaptic mechanisms in SON neurons from rat brain slices.

  10. Fathers' Trait Verbal Aggressiveness and Argumentativeness as Predictors of Adult Sons' Perceptions of Fathers' Sarcasm, Criticism, and Verbal Aggressiveness.

    Science.gov (United States)

    Beatty, Michael J.; And Others

    1994-01-01

    Finds that approximately 40% of the variance in adult sons' reports of fathers' messages (sarcasm, criticism, and verbal aggressiveness) was attributable to fathers' self-reported argumentativeness and verbal aggression. (SR)

  11. L'art de faire parler les pierres : Bande-son de Bertrand de la Peine

    Directory of Open Access Journals (Sweden)

    Isabelle Dangy

    2012-12-01

    Full Text Available Bande-Son, de Bertrand de la Peine, fait défiler trois figures de l’artiste qui suggèrent pour l’activité artistique un domaine de définition. À la pointe de la contemporanéité, Sven Langhens est un acousticien qui s’attache à rendre audible le chant de l’infime, celui des bêtes minuscules et même celui des pierres. Avant lui, au XVIIIe siècle, Rudolf Erich Raspe, auteur des Aventures du baron de Munchhausen, s’était déjà lancé sur les traces de pierres chantantes. Enfin, légèrement en retrait par rapport à ces deux figures originales dont il orchestre les rapports, le narrateur propose une poétique reflétant et court-circuitant à la fois les recherches de ses deux personnages. Leur interaction culminera dans une installation en Provence, qui, transcendant la distinction entre les différents sujets de l’art et leur objet, parviendra à piéger dans un miroir la force du vent.Bertrand de la Peine Bande-Son scrolls three artist figures who suggest a domain of definition for artistic activity. At the forefront of the contemporary, Sven Langhens is an acoustician who strives to make audible the voice of the tiny, tiny animals and even the stones. Before him, in the eighteenth century, Rudolf Erich Raspe, author of The Surprising Adventures of Baron Munchausen, had already run on the footsteps of singing stones. Finally, slightly down compared to the two original figures, the narrator reports their relationships and offers a poetic reflecting and bypassing his characters research. Their interaction will culminate in an installation in Provence, which transcends the distinction between the different subjects of art and object, succeeding in trapping the wind by a mirror’s force.

  12. [Suh Yang Park, who became a doctor as a son of a butcher].

    Science.gov (United States)

    Park, Hyoung Woo; Hong, Jung Wan

    2006-12-01

    Dr. Suh Yang Park was born in 1885 as a son of a butcher, which was the lowest class at that time in Korea. However, contact with western missionaries, including Dr. 0. R. Avison, provided him with an understanding of western civilization. After entering Chejungwon Medical School in 1900, Dr. Park learned basic sciences, basic medical sciences like anatomy and physiology, and other Western medical specialties such as internal medicine and surgery. He graduated from medical school in 1908 and received Government Certificate from Home Office, the first in Korea in this field, which granted the right to practice medicine. His certificate number was 4th overall. As both a doctor and a talented musician, Dr. Park actively participated in the social enlightenment movement. He was quite progressive in his time, having surpassed the social limitations as a son of a butcher, as well as actively propagating his knowledge of Western civilization onto others. After graduation, he had served as a professor at the school he graduated from, until he went into exile in Manchuria in 1917 due to the annexation of Korea by Japan in 1910. There, he opened a hospital and provided medical treatment for Koreans. He also established a school for young Koreans, inspiring them with a sense of nationalism. Also, Dr. Park was an active member of various Independence Movement Organizations in Manchuria. Then in 1932, at the time when Japan took control of Manchuria, his school was closed down. As a result, Dr. Park couldn't help but stop his anti-Japanese activities. In 1936, he returned to his homeland and passed away in 1940, just five years before the liberation of Korea from Japanese occupation.

  13. Suh Yang Park, who Became a Doctor as a Son of a Butcher

    Directory of Open Access Journals (Sweden)

    PARK Hyoung Woo

    2006-12-01

    Full Text Available Dr. Suh Yang Park was born in 1885 as a son of a butcher, which was the lowest class at that time in Korea. However, contact with western missionaries, including Dr. O. R. Avison, provided him with an understanding of western civilization. After entering Chejungwon Medical School in 1900, Dr. Park learned basic sciences, basic medical sciences like anatomy and physiology, and other Western medical specialties such as internal medicine and surgery. He graduated from medical school in 1908 and received Government Certificate from Home Office, the first in Korea in this field, which granted the right to practice medicine. His certificate number was 4th overall. As both a doctor and a talented musician, Dr. Park actively participated in the social enlightenment movement. He was quite progressive in his time, having surpassed the social limitations as a son of a butcher, as well as actively propagating his knowledge of Western civilization onto others. After graduation, he had served as a professor at the school he graduated from, until he went into exile in Manchuria in 1917 due to the annexation of Korea by Japan in 1910. There, he opened a hospital and provided medical treatment for Koreans. He also established a school for young Koreans, inspiring them with a sense of nationalism. Also, Dr. Park was an active member of various Independence Movement Organizations in Manchuria. Then in 1932, at the time when Japan took control of Manchuria, his school was closed down. As a result, Dr. Park couldn't help but stop his anti-Japanese activities. In 1936, he returned to his homeland and passed away in 1940, just five years before the liberation of Korea from Japanese occupation.

  14. "Fathers" and "sons" of theories in cell physiology: the membrane theory.

    Science.gov (United States)

    Matveev, V V; Wheatley, D N

    2005-12-16

    The last 50 years in the history of life sciences are remarkable for a new important feature that looks as a great threat for their future. A profound specialization dominating in quickly developing fields of science causes a crisis of the scientific method. The essence of the method is a unity of two elements, the experimental data and the theory that explains them. To us, "fathers" of science, classically, were the creators of new ideas and theories. They were the true experts of their own theories. It is only they who have the right to say: "I am the theory". In other words, they were carriers of theories, of the theoretical knowledge. The fathers provided the necessary logical integrity to their theories, since theories in biology have still to be based on strict mathematical proofs. It is not true for sons. As a result of massive specialization, modern experts operate in very confined close spaces. They formulate particular rules far from the level of theory. The main theories of science are known to them only at the textbook level. Nowadays, nobody can say: "I am the theory". With whom, then is it possible to discuss today on a broader theoretical level? How can a classical theory--for example, the membrane one--be changed or even disproved under these conditions? How can the "sons" with their narrow education catch sight of membrane theory defects? As a result, "global" theories have few critics and control. Due to specialization, we have lost the ability to work at the experimental level of biology within the correct or appropriate theoretical context. The scientific method in its classic form is now being rapidly eroded. A good case can be made for "Membrane Theory", to which we will largely refer throughout this article.

  15. The Relationship Between Sexual Function and Quality of Sleep in Caregiving Mothers of Sons with Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Karen T. Nozoe

    2014-08-01

    Conclusions: This study indicates that caregiving mothers of sons with DMD show major risk for sexual dysfunction and a reduction in their quality of sleep mediated in part by the hormonal changes related to stress. Nozoe KT, Hachul H, Hirotsu C, Polesel DN, Moreira GA, Tufik S, and Andersen ML. The relationship between sexual function and quality of sleep in caregiving mothers of sons with Duchenne muscular dystrophy. Sex Med 2014;2:133–140.

  16. Membrane translocation of t-SNARE protein syntaxin-4 abrogates ground-state pluripotency in mouse embryonic stem cells

    Science.gov (United States)

    Hagiwara-Chatani, Natsumi; Shirai, Kota; Kido, Takumi; Horigome, Tomoatsu; Yasue, Akihiro; Adachi, Naoki; Hirai, Yohei

    2017-01-01

    Embryonic stem (ES) and induced pluripotent stem (iPS) cells are attractive tools for regenerative medicine therapies. However, aberrant cell populations that display flattened morphology and lose ground-state pluripotency often appear spontaneously, unless glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase kinase (MEK1/2) are inactivated. Here, we show that membrane translocation of the t-SNARE protein syntaxin-4 possibly is involved in this phenomenon. We found that mouse ES cells cultured without GSK3β/MEK1/2 inhibitors (2i) spontaneously extrude syntaxin-4 at the cell surface and that artificial expression of cell surface syntaxin-4 induces appreciable morphological changes and mesodermal differentiation through dephosphorylation of Akt. Transcriptome analyses revealed several candidate elements responsible for this, specifically, an E-to P-cadherin switch and a marked downregulation of Zscan4 proteins, which are DNA-binding proteins essential for ES cell pluripotency. Embryonic carcinoma cell lines F9 and P19CL6, which maintain undifferentiated states independently of Zscan4 proteins, exhibited similar cellular behaviors upon stimulation with cell surface syntaxin-4. The functional ablation of E-cadherin and overexpression of P-cadherin reproduced syntaxin-4-induced cell morphology, demonstrating that the E- to P-cadherin switch executes morphological signals from cell surface syntaxin-4. Thus, spontaneous membrane translocation of syntaxin-4 emerged as a critical element for maintenance of the stem-cell niche. PMID:28057922

  17. Combinatorial treatment using targeted MEK and SRC inhibitors synergistically abrogates tumor cell growth and induces mesenchymal-epithelial transition in non-small-cell lung carcinoma.

    Science.gov (United States)

    Chua, Kian Ngiap; Kong, Li Ren; Sim, Wen Jing; Ng, Hsien Chun; Ong, Weijie Richard; Thiery, Jean Paul; Huynh, Hung; Goh, Boon Cher

    2015-10-01

    Oncogenesis in non-small cell lung cancer (NSCLC) is regulated by a complex signal transduction network. Single-agent targeted therapy fails frequently due to treatment insensitivity and acquired resistance. In this study, we demonstrate that co-inhibition of the MAPK and SRC pathways using a PD0325901 and Saracatinib kinase inhibitor combination can abrogate tumor growth in NSCLC. PD0325901/Saracatinib at 0.25:1 combination was screened against a panel of 28 NSCLC cell lines and 68% of cell lines were found to be sensitive (IC50 cell migration and matrigel invasion. The co-inhibition of MAPK and SRC induced strong G1/G0 cell cycle arrest in the NSCLC lines, inhibited anchorage independent growth and delayed tumor growth in H460 and H358 mouse xenografts. These data provide rationale for further investigating the combination of MAPK and SRC pathway inhibitors in advanced stage NSCLC.

  18. Isolation of a cdc28 mutation that abrogates the dependence of S phase on completion of M phase of the budding yeast cell cycle

    Indian Academy of Sciences (India)

    Santanu Kumar Ghosh; Pratima Sinha

    2000-01-01

    We have isolated a mutation in the budding yeast Saccharomyces cerevisisae CDC28 gene that allows cdc13 cells, carrying damaged DNA, to continue with the cell division cycle. While cdc13 mutant cells are arrested as large-budded cells at the nonpermissive temperature 37°C, the cdc13 cdc28 double mutant culture showed cells with one or more buds, most of which showed apical growth. The additional buds emerged without the intervening steps of nuclear division and cell separation. We suggest that the cdc28 mutation abrogates a checkpoint function and allows cells with damaged or incompletely replicated DNA an entry to another round of cell cycle and bypasses the mitotic phase of the cell cycle.

  19. Membrane binding domains

    OpenAIRE

    Hurley, James H.

    2006-01-01

    Eukaryotic signaling and trafficking proteins are rich in modular domains that bind cell membranes. These binding events are tightly regulated in space and time. The structural, biochemical, and biophysical mechanisms for targeting have been worked out for many families of membrane binding domains. This review takes a comparative view of seven major classes of membrane binding domains, the C1, C2, PH, FYVE, PX, ENTH, and BAR domains. These domains use a combination of specific headgroup inter...

  20. Estructuras de pobreza en el agro ¿por qué son pobres los campesinos?

    Directory of Open Access Journals (Sweden)

    Eugenio Pedro Giovenardi

    1992-01-01

    Full Text Available La pobreza campesina persiste a pesar de los programas de carácter especial que se adelantan desde hace muchos años, tanto por iniciativa de los gobiernos latinoamericanos, como de organismos internacionales. Las fórmulas, las medidas, las estrategias adoptadas hasta ahora para aminorar la pobreza, se enmarcan en un cuadro de soluciones coyunturales o segmentarias, sin un conducto lógico que permita influir positivamente los elementos de un plan global e integral de acción. Son programas de crédito individual para la producción, pero sin estrategias de comercialización. Otros son de capacitación y educación, pero desconectados de la realidad económica que envuelve los campesinos. En el presente ensayo, se busca formular una estrategia de carácter estructural, analizando el conjunto de las relaciones económicas del complejo rural, escenario donde actúan todos los agentes responsables de la producción agrícola desde la siembra hasta el consumo. Se analizan las causas estructurales de la riqueza, los puntos de acumulación o agregados y su capacidad de generar y retener los valores que se van creando alrededor del producto, y su expresión corno centros de decisión de precios, de políticas económicas y de reinversión de los excedentes producidos. Se examinan la mecánica de la transferencia de valores de un agregado a otro y los elementos de decisión de cada punto de acumulación. Se recogen algunas inquietudes del poco éxito de los programas de desarrollo rural y se reafirma la convicción de que los campesinos pueden llegar a ser ricos, sin miedo de emplear este término, siempre y cuando el gobierno y la sociedad civil se decidan a tornar medidas integrales capaces de erradicar las causas de la pobreza. En otras palabras, introducir la actividad campesina en las estructuras de riqueza, a través de empresas asociativas planificadas para administrar el complejo económico rural.

  1. Poesía y filosofía son de palabra

    Directory of Open Access Journals (Sweden)

    Santamaría Pargada, Antonio

    2006-04-01

    Full Text Available The imaginary and sinister concentration-camp chief Otto Friedrich Zur Linde was conceived by Jorge-Luis Borges as an example of misunderstanding philosophy and life, by seeing in them only the power of fight. This conception is compared with a dynamic understanding of philosophy. For Mr. Zur Linde Aristotle and Plato represent this confrontation, and each philosophical debate in history could be considered as a moment in it. But now, in the last fight, the will to power of man has gone beyond all the limits, even of morality. However some modern techniques of appropriation of ancient philosophy are completely opposed to this conception, namely Paul Ricoeur’s theory of fiction and Heidegger’s Sein und Schein,. Ultimately, the close relationship between poetry and philosophy since its origins speak against this thesis. A closer analysis of Nietzsche and Hölderlin will help to enlighten how wrong Zur Linde´s conception is..El siniestro jefe de un campo de concentración Otto Friedrich Zur Linde, concebido por Borges como ejemplo de una interpretación de la filosofía y la vida en la que la lucha es el único motor, es confrontado con una concepción de la filosofía dinámica. Zur Linde mantiene que Aristóteles y Platón son el enfrentamiento filosófico paradigmático. En el último momento del enfrentamiento la voluntad de poder de un nuevo superhombre ha rebasado todos los límites, incluso el de la conciencia. A esto se oponen las técnicas de apropiación filosófica del mundo griego por parte de la modernidad, a saber: el poder de la ficción, el Schein y el Sein así como el nacimiento de la filosofía, tan cercano a la poesía. Bajo este prisma cabe un análisis de Nietzsche y Hölderlin, que reniega de la interpretación de Zur Linde y clarifica que ante todo poetas y filósofos son seres de palabra.

  2. Bats (Mammalia: Chiroptera of the southeastern Truong Son Mountains, Quang Ngai Province, Vietnam

    Directory of Open Access Journals (Sweden)

    Nguyen Truong Son

    2016-07-01

    Full Text Available Bat communities of mainland Southeast Asia can be highly diverse. Many are under threat. Despite this, regional faunal composition is not well documented for many areas, including regions of Vietnam.  We assessed the biodiversity of bats in a watershed protection forest in the southeastern Truong Son (Annamite Mountains, southwestern Quang Ngai Province, Vietnam in 2011–2013.  Twenty species of insectivorous bats were documented including a high diversity of Murina species Tube-nosed Bats.  Diversity and abundance indices were compared with that recorded previously in two nature reserves and one national park in Vietnam, and were higher or comparable in several measures despite the lack of a karst substrate for roosts.  Reproduction in the insectivorous bat fauna coincided with the early rainy season.  In the late dry season, pregnant females of several species were observed but volant juveniles were not present, whereas in the early wet season adult females were lactating or post-lactating and volant juveniles of nine species were detected.  We recorded echolocation calls of 14 bat species; for each species, we compared features of calls with those reported previously in other Asian localities.  For some species we found discrepancies in call metrics among studies, perhaps suggesting a greater hidden biodiversity of bats in Southeast Asia.

  3. Two sons and a daughter: sex composition and women's reproductive behaviour in Madhya Pradesh, India.

    Science.gov (United States)

    Edmeades, Jeffrey; Pande, Rohini; Macquarrie, Kerry; Falle, Tina; Malhotra, Anju

    2012-11-01

    This article examines how the sex composition of women's current children at the start of a pregnancy interval influences both fertility desires and the full range of reproductive actions women may take to realize them, including temporary contraception, abortion and sterilization, in Madhya Pradesh, India, where popular notions of ideal family size and sex composition are dominated by son preference. The analysis is conducted using a dataset of 9127 individual pregnancy intervals from a 2002 statewide representative survey of 2444 women aged 15-39 with at least one child. The results indicate that women's preferences go beyond a singular preference for male children, with the preferred composition of children being two boys and one girl. Women with this composition are 90% less likely to report having wanted another pregnancy (OR 0.097, p < 0.01) relative to those with two girls. These preferences have significant implications for reproductive actions. While sex composition has no statistically significant effect on the use of temporary contraception, those with the preferred sex composition are twice as likely to attempt abortion (OR 2.436, p < 0.01) and twelve times more likely to be sterilized (OR 12.297, p < 0.01) relative to those with two girls only.

  4. Mothers, fathers, sons and daughters: parental sensitivity in families with two children.

    Science.gov (United States)

    Hallers-Haalboom, Elizabeth T; Mesman, Judi; Groeneveld, Marleen G; Endendijk, Joyce J; van Berkel, Sheila R; van der Pol, Lotte D; Bakermans-Kranenburg, Marian J

    2014-04-01

    Most studies on early childhood parenting include only mothers. Fathers are rarely observed in interaction with their young children, although they play an important role in the socialization of their children. In this study, we observed parenting of mothers and fathers toward their sons and daughters in families with two children, using a within-family approach in a sample with systematically varying family constellations. Participants included 389 families with two children (1 and 3 years of age). Parenting practices were coded during free play using the Emotional Availability Scales (Biringen, 2008). Findings revealed that mothers showed higher levels of sensitivity and lower levels of intrusiveness toward their children than fathers. Furthermore, mothers and fathers were more sensitive and less intrusive toward their oldest child than toward their youngest child. Fathers' higher intrusiveness toward the youngest child was only found in the case of a youngest boy. Child gender was not related to parenting in any of the other analyses. Our results suggest that parent gender is more salient than child gender in the prediction of parenting practices in early childhood.

  5. Complicity to Hegemonic Masculinity in D.H. Lawrence’s Sons and Lovers

    Directory of Open Access Journals (Sweden)

    Angelina Subrayan

    2016-04-01

    Full Text Available Men have long been associated with dominance, strength and confidence and the issue regarding being compliant to the acceptable masculine ideal has always been part of a culture’s social identity. This study focuses on the critical discussion on masculinity studies in the classic fiction of D.H Lawrence.  Drawing on narrative data from his novel Sons and Lovers (1913, the study examines how hegemonic masculinity is conformed by the male protagonist, Walter Morel, in his gendered relationship. More specifically, the analysis focuses on how the male character aligns himself with the hegemonically authoritarian philosophy of ‘tough’ masculinity. The effects of social practices and socio-historical context in which Lawrence wrote these novels are also examined. The study utilises Connell’s theory of hegemonic masculinity to explicate Lawrence’s depiction of dominant masculinity through his character. The findings reveal that Lawrence aligns his male protagonist to the dominant role by sanctioning aggressiveness, autonomy and violence. Keywords: Hegemonic Masculinity, Dominant Masculinity, Patriarchy, Gender, Power

  6. Une pensée en action du son au théâtre

    Directory of Open Access Journals (Sweden)

    Jean-Paul Quéinnec

    2011-09-01

    Full Text Available En cherchant à ne plus soumettre le son à l’action dramatique, le statut de la dramaturgie théâtrale (textuelle et scénique se met à dériver. Un glissement de la pensée comme de la pratique qui appelle une écoute à d’autres références théoriques et méthodologiques. Cet article s’appuie sur une recherche création en dramaturgie sonore qui explore la notion d’intermédialité et la création performative au théâtre. Un vécu expérientiel de la matérialité sonore (texte, objet, espace qui développe un concept que nous nommons « dramaturgie informe » car le théâtre contemporain devenu matière vive et complexe s’avère difficile à isoler pour être défini.

  7. A Novel Stochastic Learning Automata Based SON Interference Mitigation Framework for 5G HetNets

    Directory of Open Access Journals (Sweden)

    M. N. Qureshi

    2016-12-01

    Full Text Available Long Term Evolution Advanced (LTE-A Heterogeneous Networks (HetNet are an important aspect of 5th generation mobile communication systems. They consists of high power macrocells along with low power cells i.e. picocells and femtocells to fill up macrocell coverage gaps. HetNet permit deployment of femtocells by users for added flexibility, but then interference issues between neighbouring cells have to be addressed as all femtocells use the same frequency channels for transmission. To mitigate this problem, LTE-A standard offers two new features, one is carrier aggregation in which Component Carriers (CC form the basic aggregate units shared among cells and the other is enhanced Inter-Cell Interference Co-ordination (eICIC through X2 interface. The physical implementation of these features is left open to research. This paper investigates two distinct techniques for orthogonal CC selection through Stochastic Cellular Learning Automata (SCLA to improve the QoS performance of a femtocell. The first, technique uses SCLA with user feedback, and the second technique uses SCLA with a central publishing server where all cells upload their past used CC vectors. SCLA methods are better suited for Self Organizing Network (SON as they do not require synchronized cell coordination, have low complexity and have good optimization characteristics. The simulation results show that the techniques enhance the cell edge performance considerably.

  8. Los saberes indígenas son patrimonio de la humanidad

    Directory of Open Access Journals (Sweden)

    José Narciso Jamioy Muchavisoy

    1997-10-01

    Full Text Available Bajo la premisa de que narrar en pocas palabras los saberes milenarios de los distintos pueblos es irrespetuoso e irresponsable, ya que se puede caer en interpretaciones superficiales y erradas sobre aquellos conocimientos que para ellos son sagrados, el autor se limita a presentar un panorama muy general de cómo dichos conocimientos generan vida e identidad en las nuevas generaciones mediante procesos de tradición oral por los padres, abuelos, tíos y, en especial, por los ancianos sabedores de los pueblos y comunidades indígenas. La explicación es fruto de sus experiencias como hijo de una familia que conservó la tradición Kamëntsá, como acompañante en algunas actividades de reflexión realizadas con voceros del ordennacional y con las comunidades de los pueblos Arhuaco, Paéz, Guambiano,Pastos, Ticuna, Cofán e Inga. Así mismo, de sus vivencias como estudian- te, docente de colegio, catedrático universitario e investigador.

  9. A Novel Dynamic Adjusting Algorithm for Load Balancing and Handover Co-Optimization in LTE SON

    Institute of Scientific and Technical Information of China (English)

    Wen-Yu Li; Xiang Zhang; Shu-Cong Jia; Xin-Yu Gu; Lin Zhang; Xiao-Yu Duan; Jia-Ru Lin

    2013-01-01

    With the development of mobile internet and multi-media service,advanced techniques need to be applied in wireless network to improve user experience.Long term evolution (LTE) systems,which can offer up to 100Mbps downlink date rates,have been deployed in USA and Korea.However,because plenty of complex physical layer algorithms are utilized,network planning and optimization become heavy burdens for LTE network operators.Self-organizing network (SON) is a promising method to overcome this problem by automatically selecting and adjusting key parameters in LTE systems.In this paper,we present a dynamic adjusting algorithm to improve both handover and load balancing performance by introducing a weighted co-satisfaction factor (CSF).Analysis and system level simulation are conducted to exhibit the performance improvement of the proposed scheme.Results show that the proposed method outperforms the conventional solutions in terms of the network handover success ratio and load balancing gains significantly.

  10. Violencia cometida por los adolescentes en la familia o cuando son los hijos los que maltratan

    Directory of Open Access Journals (Sweden)

    Helena Morales Ortega

    2011-12-01

    Full Text Available Este estudio de tipo cualitativo, de corte deductivo, se propuso realizar un acercamiento al fenómeno de la violencia ejercida por los jóvenes menores de 18 años en el ámbito familiar, para establecer su ocurrencia en la ciudad de Barranquilla, Colombia, describir las características de los jóvenes implicados, la dinámica familiar y algunos aspectos del entorno social que podrían estar facilitando la ocurrencia de la misma. El estudio fue realizado en el Centro de Reeducación del Adolescente Infractor "Oasis", de esta ciudad; se examinaron expedientes de jóvenes judicializados por los delitos de violencia intrafamiliar, hurto, lesiones personales y daño en bien ajeno, donde la víctima había sido un familiar; igualmente, se realizaron entrevistas semiestructuradas con profundidad a madres de jóvenes que al momento de la investigación se hallaban internos en el centro por violencia en la familia. Los resultados indican que son pocos los estudios criminológicos realizados sobre el tema; se trata de jóvenes con edades promedio de 14 a 17 años, provenientes de familias desintegradas, con carencias tanto materiales como afectivas, con dinámicas y estilos de crianza inadecuados; es frecuente en estos jóvenes el consumo de sustancias alucinógenas o alcohol.

  11. Maternal Child Sexual Abuse Is Associated With Lower Maternal Warmth Toward Daughters but Not Sons.

    Science.gov (United States)

    Cross, Dorthie; Kim, Ye Ji; Vance, L Alexander; Robinson, Gabriella; Jovanovic, Tanja; Bradley, Bekh

    2016-01-01

    Mothers with a history of child sexual abuse report less warmth toward their children, but whether this association differs by child gender is unknown. We examined the association of maternal child sexual abuse and warmth across child gender, accounting for depression, post-traumatic stress disorder, and child physical abuse. We verbally administered self-report measures to a cross-sectional sample of 154 mothers with a child between 8 and 12 years old. Eighty-five mothers based warmth responses on a son, and 69 on a daughter. We conducted a hierarchical multiple regression, including child gender, maternal child sexual abuse, child physical abuse, depression, post-traumatic stress disorder, and 4 two-way interaction terms with child gender. Maternal depression predicted decreased warmth, regardless of child gender, and maternal child sexual abuse predicted decreased warmth, but only toward daughters. Given previous research suggesting that maternal warmth predicts child well-being, the current finding may represent an important avenue of intergenerational transmission of risk in girls.

  12. Analyzing radioligand binding data.

    Science.gov (United States)

    Motulsky, Harvey; Neubig, Richard

    2002-08-01

    Radioligand binding experiments are easy to perform, and provide useful data in many fields. They can be used to study receptor regulation, discover new drugs by screening for compounds that compete with high affinity for radioligand binding to a particular receptor, investigate receptor localization in different organs or regions using autoradiography, categorize receptor subtypes, and probe mechanisms of receptor signaling, via measurements of agonist binding and its regulation by ions, nucleotides, and other allosteric modulators. This unit reviews the theory of receptor binding and explains how to analyze experimental data. Since binding data are usually best analyzed using nonlinear regression, this unit also explains the principles of curve fitting with nonlinear regression.

  13. The role of God in the father/son relationship during identity formation – a Gestalt theoretical perspective

    Directory of Open Access Journals (Sweden)

    H.B. Grobler

    2010-07-01

    Full Text Available This article is based on research done within the Afrikaansspeaking community in the area of the Drakenstein Municipality, Western Cape province, South Africa. The focus falls specifically on one concept that was outlined during the research, namely the perceptions of fathers and adolescent sons on identity formation within their relationship as well as the role that God plays. Combined qualitative/quantitative research was conducted with emphasis on semi-structured interviews with fathers (n=4 and adolescent boys (n=4 and an auto-ethnography of the author as the dominant component. The lessdominant quantitative component consisted of questionnaires completed by fathers (n=42 and adolescent boys (n=180. Metatheoretical assumptions and theoretical assumptions as grounding for the male identity are discussed as part of the author’s paradigmatic perspective. Furthermore, empirical findings are discussed and recommendations are made. From the discussions with fathers and their sons it was clear that both fathers and sons have a need to stand in close relationship to each other and to God. It is within this relationship where their identities are formed. However, fathers seemed to be resistant of transferring their beliefs to their sons. Adolescent boys also indicated no need to one day transfer learned behaviour from their fathers to their sons.

  14. Analytical Modeling of SON MOSFET and Realization Inverter Circuit for High Speed and Ultra Dense Low Power Circuits

    Directory of Open Access Journals (Sweden)

    Kousik Naskar

    2012-06-01

    Full Text Available In the recent years, there has been considerable interest in the realization of high speed, small-size and low-power consuming devices and systems. As a consequence, the search for new principle of operation of the small-size, high speed and low-power device is becoming more and more important. In our earlier paper, it has been established that SON technology, not only improve the dc performance with reduce a short-channel effect and threshold voltage, it also improves the frequency response due to improvement in conductance and reduced parasitic effect. Further, it is already in our knowledge that SCEs are suppressed in dual material gate MOSFETs because of the perceivable step in the surface-potential profile, which screens the drain potential. The concept of dual material gate has been applied to SON MOSFETs structure and the features exhibited by resulting new SON structure has been examined for the first time by developing an analytical model and the result agree well with the MEDICI simulation values. In order to substantiate the merits of the proposed SON MOSFETs, a MOS Inverter is realized using the SON MOSFETs and its performance is investigated as an aid to the high-speed, ultra-dense and low-power circuit related work.

  15. Effect of Multiple Mutations in the Hemoglobin- and Hemoglobin-Haptoglobin-Binding Proteins, HgpA, HgpB, and HgpC, of Haemophilus influenzae Type b

    OpenAIRE

    Morton, Daniel J; Whitby, Paul W.; Jin, Hongfan; Ren, Zhen; Stull, Terrence L.

    1999-01-01

    Haemophilus influenzae requires heme for growth and can utilize hemoglobin and hemoglobin-haptoglobin as heme sources. We previously identified two hemoglobin- and hemoglobin-haptoglobin-binding proteins, HgpA and HgpB, in H. influenzae HI689. Insertional mutation of hgpA and hgpB, either singly or together, did not abrogate the ability to utilize or bind either hemoglobin or the hemoglobin-haptoglobin complex. A hemoglobin affinity purification method was used to isolate a protein of approxi...

  16. The Gelfand-Zeitlin integrable system and its action on generic elements of gl(n) and so(n)

    CERN Document Server

    Colarusso, Mark

    2008-01-01

    In recent work Bertram Kostant and Nolan Wallach ([KW1], [KW2]) have defined an interesting action of a simply connected Lie group $A$ isomorphic to \\mathbb{C}^{{n\\choose 2}} on gl(n) using a completely integrable system derived from Gelfand-Zeitlin theory. In this paper we show that an analogous action of \\mathbb{C}^{d} exists on the complex orthogonal Lie algebra so(n), where d is half the dimension of a regular adjoint orbit in so(n). In [KW1], Kostant and Wallach describe the orbits of $A$ on a certain Zariski open subset of regular semisimple elements in gl(n). We extend these results to the case of so(n). We also make brief mention of the author's results in [Col1], which describe all $A$-orbits of dimension {n\\choose 2} in gl(n).

  17. Design and Analysis of a High Speed, Power Efficient 8 Bit ALU Based on SOI / SON MOSFET Technology

    Directory of Open Access Journals (Sweden)

    Subhramita Basak

    2014-01-01

    Full Text Available This paper shows an overall performance comparative analysis in terms of Average Power Consumption, Average Delay and Power-Delay Product for an 8 bit Arithmetic Logic Unit (ALU using bulk MOS, Silicon-on-Insulator (SOI and Silicon-on-Nothing (SON technology. The entire design is done in 32nm technology for all the three cases (Bulk, SOI & SON and then compared. The comparisons have been carried out with the help of the simulation runs on Synopsys HSpice tool, and that clearly indicates, for lower Supply Voltages (Vdd, SOI / SON technology provides a significant reduction in Average Power Consumption, Average Delay and Power-Delay Product compared to that of Bulk MOS technology.

  18. Ureaplasma urealyticum binds mannose-binding lectin.

    Science.gov (United States)

    Benstein, Barbara D; Ourth, Donald D; Crouse, Dennis T; Shanklin, D Radford

    2004-10-01

    Mannose-binding C-type lectin (MBL) is an important component of innate immunity in mammals. Mannose-binding lectin (MBL), an acute phase protein, acts as an opsonin for phagocytosis and also activates the mannan-binding lectin complement pathway. It may play a particularly significant role during infancy before adequate specific protection can be provided by the adaptive immune system. Ureaplasma urealyticum has been linked to several diseases including pneumonia and chronic lung disease (CLD) in premature infants. We therefore investigated the ability of U. urealyticum to bind MBL. A guinea pig IgG anti-rabbit-MBL antiserum was produced. An immunoblot (dot-blot) assay done on nitrocellulose membrane determined that the anti-MBL antibody had specificity against both rabbit and human MBL. Pure cultures of U. urealyticum, serotype 3, were used to make slide preparations. The slides containing the organisms were then incubated with nonimmune rabbit serum containing MBL. Ureaplasma was shown to bind rabbit MBL with an immunocytochemical assay using the guinea pig IgG anti-rabbit MBL antiserum. Horseradish peroxidase (HRP)-labeled anti-guinea pig IgG was used to localize the reaction. The anti-MBL antiserum was also used in an immunocytochemical assay to localize U. urealyticum in histological sections of lungs from mice specifically infected with this organism. The same method also indicated binding of MBL by ureaplasma in human lung tissue obtained at autopsy from culture positive infants. Our results demonstrate that ureaplasma has the capacity to bind MBL. The absence of MBL may play a role in the predisposition of diseases related to this organism.

  19. Ligand binding mechanics of maltose binding protein.

    Science.gov (United States)

    Bertz, Morten; Rief, Matthias

    2009-11-13

    In the past decade, single-molecule force spectroscopy has provided new insights into the key interactions stabilizing folded proteins. A few recent studies probing the effects of ligand binding on mechanical protein stability have come to quite different conclusions. While some proteins seem to be stabilized considerably by a bound ligand, others appear to be unaffected. Since force acts as a vector in space, it is conceivable that mechanical stabilization by ligand binding is dependent on the direction of force application. In this study, we vary the direction of the force to investigate the effect of ligand binding on the stability of maltose binding protein (MBP). MBP consists of two lobes connected by a hinge region that move from an open to a closed conformation when the ligand maltose binds. Previous mechanical experiments, where load was applied to the N and C termini, have demonstrated that MBP is built up of four building blocks (unfoldons) that sequentially detach from the folded structure. In this study, we design the pulling direction so that force application moves the two MBP lobes apart along the hinge axis. Mechanical unfolding in this geometry proceeds via an intermediate state whose boundaries coincide with previously reported MBP unfoldons. We find that in contrast to N-C-terminal pulling experiments, the mechanical stability of MBP is increased by ligand binding when load is applied to the two lobes and force breaks the protein-ligand interactions directly. Contour length measurements indicate that MBP is forced into an open conformation before unfolding even if ligand is bound. Using mutagenesis experiments, we demonstrate that the mechanical stabilization effect is due to only a few key interactions of the protein with its ligand. This work illustrates how varying the direction of the applied force allows revealing important details about the ligand binding mechanics of a large protein.

  20. A Possible Link Between the Pubertal Growth of Girls and Prostate Cancer in Their Sons

    Science.gov (United States)

    BARKER, DAVID J.P.; OSMOND, CLIVE; THORNBURG, KENT L.; KAJANTIE, EERO; ERIKSSON, JOHAN G.

    2012-01-01

    Objectives Among women attending antenatal clinics during 1934–1944 a large intercristal diameter, the maximum distance between the pelvic iliac crests, was associated with a raised incidence of breast and ovarian cancer in the daughters in later life. At puberty, the intercristal diameter of girls enlarges rapidly under the influence of estrogen. We speculated that high maternal estrogen concentrations during pregnancy initiate hormonal cancers in their daughters. Here, we examine the association between the mothers’ intercristal diameters and prostate cancer in their sons. Methods Using the national cancer registry we identified 221 cases of prostate cancer among 6,975 men born during 1934–1944 in Helsinki, Finland. Four thousand four hundred and one of these men had their mother’s bony pelvic measurements recorded: there were 149 cases among them. Results Hazard ratios for prostate cancer rose as the mother’s intercristal diameter increased; but this association was restricted to men who were born before 40 weeks of gestation. Among these men the hazard ratio was 1.27 (95% CI 1.09–1.48; P = 0.002). The hazard ratio was 2.2 (1.3–3.7; P < 0.001) in men whose mothers weighed more than 80 kg in late pregnancy compared with those whose mothers weighed 60 kg or less. Conclusions These findings are consistent with a conceptual framework for the origins of hormonally dependent cancers that invokes exposure of embryonic tissue to maternal sex hormones followed by resetting of the fetal hypothalamic-gonadotropin axis in late gestation. We hypothesize that compensatory prepubertal growth among girls is associated with hormonal cancers in the next generation. PMID:22287160

  1. ¿Son los Planes de Desarrollo un mecanismo eficaz para el fortalecimiento de las democracias participativas?

    OpenAIRE

    2011-01-01

    El autor se interroga acerca de si el Consejo Nacional de Planeación, al igual que los consejos territoriales, son escenarios para el ejercicio de la democracia y si su participación, en la construcción de los planes de desarrollo, constituye un instrumento eficaz para su fortalecimiento o son, por el contrario, un espejismo en la praxis de la democracia en Colombia. En la primera parte se mencionan algunas versiones de democracia desde Lincoln, pasando por las versiones de Tocqueville, Shump...

  2. Son de mar : Aproximación al universo narrativo de Manuel Vicent

    OpenAIRE

    Ferrer, Margarita Maria

    2014-01-01

    Son de mar –premio Alfaguara 1999– es una novela que se ubica aproximadamente “nel mezzo del camin” de la producción narrativa de Manuel Vicent, a 33 años de la publicación de su primer obra, El resuello (1966). Son de mar es una novela de la madurez, y en ella podemos analizar algunas cuestiones que caracterizan el universo narrativo de Vicent, universo que incluye novelas, relatos, artículos y columnas periodísticas recopiladas y publicadas en libros. El término universo apunta a una noción...

  3. Protein Binding Pocket Dynamics.

    Science.gov (United States)

    Stank, Antonia; Kokh, Daria B; Fuller, Jonathan C; Wade, Rebecca C

    2016-05-17

    The dynamics of protein binding pockets are crucial for their interaction specificity. Structural flexibility allows proteins to adapt to their individual molecular binding partners and facilitates the binding process. This implies the necessity to consider protein internal motion in determining and predicting binding properties and in designing new binders. Although accounting for protein dynamics presents a challenge for computational approaches, it expands the structural and physicochemical space for compound design and thus offers the prospect of improved binding specificity and selectivity. A cavity on the surface or in the interior of a protein that possesses suitable properties for binding a ligand is usually referred to as a binding pocket. The set of amino acid residues around a binding pocket determines its physicochemical characteristics and, together with its shape and location in a protein, defines its functionality. Residues outside the binding site can also have a long-range effect on the properties of the binding pocket. Cavities with similar functionalities are often conserved across protein families. For example, enzyme active sites are usually concave surfaces that present amino acid residues in a suitable configuration for binding low molecular weight compounds. Macromolecular binding pockets, on the other hand, are located on the protein surface and are often shallower. The mobility of proteins allows the opening, closing, and adaptation of binding pockets to regulate binding processes and specific protein functionalities. For example, channels and tunnels can exist permanently or transiently to transport compounds to and from a binding site. The influence of protein flexibility on binding pockets can vary from small changes to an already existent pocket to the formation of a completely new pocket. Here, we review recent developments in computational methods to detect and define binding pockets and to study pocket dynamics. We introduce five

  4. EGFR-targeted plasmonic magnetic nanoparticles suppress lung tumor growth by abrogating G2/M cell-cycle arrest and inducing DNA damage

    Science.gov (United States)

    Kuroda, Shinji; Tam, Justina; Roth, Jack A; Sokolov, Konstantin; Ramesh, Rajagopal

    2014-01-01

    Background We have previously demonstrated the epidermal growth factor receptor (EGFR)-targeted hybrid plasmonic magnetic nanoparticles (225-NP) produce a therapeutic effect in human lung cancer cell lines in vitro. In the present study, we investigated the molecular mechanism of 225-NP-mediated antitumor activity both in vitro and in vivo using the EGFR-mutant HCC827 cell line. Methods The growth inhibitory effect of 225-NP on lung tumor cells was determined by cell viability and cell-cycle analysis. Protein expression related to autophagy, apoptosis, and DNA-damage were determined by Western blotting and immunofluorescence. An in vivo efficacy study was conducted using a human lung tumor xenograft mouse model. Results The 225-NP treatment markedly reduced tumor cell viability at 72 hours compared with the cell viability in control treatment groups. Cell-cycle analysis showed the percentage of cells in the G2/M phase was reduced when treated with 225-NP, with a concomitant increase in the number of cells in Sub-G1 phase, indicative of cell death. Western blotting showed LC3B and PARP cleavage, indicating 225-NP-treatment activated both autophagy- and apoptosis-mediated cell death. The 225-NP strongly induced γH2AX and phosphorylated histone H3, markers indicative of DNA damage and mitosis, respectively. Additionally, significant γH2AX foci formation was observed in 225-NP-treated cells compared with control treatment groups, suggesting 225-NP induced cell death by triggering DNA damage. The 225-NP-mediated DNA damage involved abrogation of the G2/M checkpoint by inhibiting BRCA1, Chk1, and phospho-Cdc2/CDK1 protein expression. In vivo therapy studies showed 225-NP treatment reduced EGFR phosphorylation, increased γH2AX foci, and induced tumor cell apoptosis, resulting in suppression of tumor growth. Conclusion The 225-NP treatment induces DNA damage and abrogates G2/M phase of the cell cycle, leading to cellular apoptosis and suppression of lung tumor growth

  5. EGFR-targeted plasmonic magnetic nanoparticles suppress lung tumor growth by abrogating G2/M cell-cycle arrest and inducing DNA damage

    Directory of Open Access Journals (Sweden)

    Kuroda S

    2014-08-01

    Full Text Available Shinji Kuroda,1 Justina Tam,2 Jack A Roth,1 Konstantin Sokolov,2 Rajagopal Ramesh3–5 1Department of Thoracic and Cardiovascular Surgery, 2Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Department of Pathology, 4Graduate Program in Biomedical Sciences, 5Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA Background: We have previously demonstrated the epidermal growth factor receptor (EGFR-targeted hybrid plasmonic magnetic nanoparticles (225-NP produce a therapeutic effect in human lung cancer cell lines in vitro. In the present study, we investigated the molecular mechanism of 225-NP-mediated antitumor activity both in vitro and in vivo using the EGFR-mutant HCC827 cell line. Methods: The growth inhibitory effect of 225-NP on lung tumor cells was determined by cell viability and cell-cycle analysis. Protein expression related to autophagy, apoptosis, and DNA-damage were determined by Western blotting and immunofluorescence. An in vivo efficacy study was conducted using a human lung tumor xenograft mouse model. Results: The 225-NP treatment markedly reduced tumor cell viability at 72 hours compared with the cell viability in control treatment groups. Cell-cycle analysis showed the percentage of cells in the G2/M phase was reduced when treated with 225-NP, with a concomitant increase in the number of cells in Sub-G1 phase, indicative of cell death. Western blotting showed LC3B and PARP cleavage, indicating 225-NP-treatment activated both autophagy- and apoptosis-mediated cell death. The 225-NP strongly induced γH2AX and phosphorylated histone H3, markers indicative of DNA damage and mitosis, respectively. Additionally, significant γH2AX foci formation was observed in 225-NP-treated cells compared with control treatment groups, suggesting 225-NP induced cell death by triggering DNA damage. The 225-NP-mediated DNA damage involved abrogation of the

  6. Inhibition of lanthanide nanocrystal-induced inflammasome activation in macrophages by a surface coating peptide through abrogation of ROS production and TRPM2-mediated Ca(2+) influx.

    Science.gov (United States)

    Yao, Han; Zhang, Yunjiao; Liu, Liu; Xu, Youcui; Liu, Xi; Lin, Jun; Zhou, Wei; Wei, Pengfei; Jin, Peipei; Wen, Long-Ping

    2016-11-01

    Lanthanide-based nanoparticles (LNs) hold great promise in medicine. A variety of nanocrystals, including LNs, elicits potent inflammatory response through activation of NLRP3 inflammasome. We have previously identified an LNs-specific surface coating peptide RE-1, with the sequence of 'ACTARSPWICG', which reduced nanocrystal-cell interaction and abrogated LNs-induced autophagy and toxicity in both HeLa cells and liver hepatocytes. Here we show that RE-1 coating effectively inhibited LNs-induced inflammasome activation, mostly mediated by NLRP3, in mouse bone marrow derived macrophage (BMDM) cells, human THP-1 cells and mouse peritoneal macrophages and also reduced LNs-elicited inflammatory response in vivo. RE-1 coating had no effect on cellular internalization of LNs in BMDM cells, in contrast to the situation in HeLa cells where cell uptake of LNs was significantly inhibited by RE-1. To elucidate the molecular mechanism underlying the inflammasome-inhibiting effect of RE-1, we assessed several parameters known to influence nanocrystal-induced NLRP3 inflammasome activation. RE-1 coating did not reduce potassium efflux, which occurred after LNs treatment in BMDM cells and was necessary but insufficient for LNs-induced inflammasome activation. RE-1 did decrease lysosomal damage induced by LNs, but the inhibitor of cathepsin B did not affect LNs-elicited caspase 1 activation and IL-1β release, suggesting that lysosomal damage was not critically important for LNs-induced inflammasome activation. On the other hand, LNs-induced elevation of intracellular reactive oxygen species (ROS), critically important for inflammasome activation, was largely abolished by RE-1 coating, with the reduction on NADPH oxidase-generated ROS playing a more prominent role for RE-1's inflammasome-inhibiting effect than the reduction on mitochondria-generated ROS. ROS generation further triggered Ca(2+) influx, an event that was mediated by Transient Receptor Potential M2 (TRPM2) and was

  7. Python bindings for libcloudph++

    OpenAIRE

    Jarecka, Dorota; Arabas, Sylwester; Del Vento, Davide

    2015-01-01

    This technical note introduces the Python bindings for libcloudph++. The libcloudph++ is a C++ library of algorithms for representing atmospheric cloud microphysics in numerical models. The bindings expose the complete functionality of the library to the Python users. The bindings are implemented using the Boost.Python C++ library and use NumPy arrays. This note includes listings with Python scripts exemplifying the use of selected library components. An example solution for using the Python ...

  8. Mutational analysis of hemoglobin binding and heme utilization by a bacterial hemoglobin receptor.

    Science.gov (United States)

    Fusco, W G; Choudhary, N R; Council, S E; Collins, E J; Leduc, I

    2013-07-01

    Iron is an essential nutrient for most living organisms. To acquire iron from their environment, Gram-negative bacteria use TonB-dependent transporters that bind host proteins at the bacterial surface and transport iron or heme to the periplasm via the Ton machinery. TonB-dependent transporters are barrel-shaped outer membrane proteins with 22 transmembrane domains, 11 surface-exposed loops, and a plug domain that occludes the pore. To identify key residues of TonB-dependent transporters involved in hemoglobin binding and heme transport and thereby locate putative protective epitopes, the hemoglobin receptor of Haemophilus ducreyi HgbA was used as a model of iron/heme acquisition from hemoglobin. Although all extracellular loops of HgbA are required by H. ducreyi to use hemoglobin as a source of iron/heme, we previously demonstrated that hemoglobin binding by HgbA only involves loops 5 and 7. Using deletion, substitution, and site-directed mutagenesis, we were able to differentiate hemoglobin binding and heme acquisition by HgbA. Deletion or substitution of the GYEAYNRQWWA region of loop 5 and alanine replacement of selected histidines affected hemoglobin binding by HgbA. Conversely, mutation of the phenylalanine in the loop 7 FRAP domain or substitution of the NRQWWA motif of loop 5 significantly abrogated utilization of heme from hemoglobin. Our findings show that hemoglobin binding and heme utilization by a bacterial hemoglobin receptor involve specific motifs of HgbA.

  9. Python bindings for libcloudph++

    CERN Document Server

    Jarecka, Dorota; Del Vento, Davide

    2015-01-01

    This technical note introduces the Python bindings for libcloudph++. The libcloudph++ is a C++ library of algorithms for representing atmospheric cloud microphysics in numerical models. The bindings expose the complete functionality of the library to the Python users. The bindings are implemented using the Boost.Python C++ library and use NumPy arrays. This note includes listings with Python scripts exemplifying the use of selected library components. An example solution for using the Python bindings to access libcloudph++ from Fortran is presented.

  10. DNS & Bind Cookbook

    CERN Document Server

    Liu, Cricket

    2011-01-01

    The DNS & BIND Cookbook presents solutions to the many problems faced by network administrators responsible for a name server. Following O'Reilly's popular problem-and-solution cookbook format, this title is an indispensable companion to DNS & BIND, 4th Edition, the definitive guide to the critical task of name server administration. The cookbook contains dozens of code recipes showing solutions to everyday problems, ranging from simple questions, like, "How do I get BIND?" to more advanced topics like providing name service for IPv6 addresses. It's full of BIND configuration files that yo

  11. Por qué ser justos. ¿Son las normas de justicia sociales o morales?

    Directory of Open Access Journals (Sweden)

    Rodríguez López, Blanca

    2013-08-01

    Full Text Available In the last few years, there has been a good amount of theoretical work around the concept of social norm. The work of Cristina Bicchieri and Jon Elster has been specially interesting and intense in this field. Although their respective approaches present substantive differences, they both agree in defining social norms in contrast with other related concepts, such as moral norms. Notwithstanding this basic agreement, they disagree when classifying norms of justice. For Bicchieri these are social norms, while Elster’s view is more complex and he classifies different norms of justice in different categories: some are social while others are semi moral o moral. In this paper I focus on the treatment of one specific norm of justice, the norm of egalitarian distribution, which is a social norm for Bichieri but a moral norm from Elster’s view. With the aid of some recent experiments, I conclude that Elster’s view is more promising, at least when analyzing this particular norm.Durante los últimos años, el concepto de norma social ha sido objeto de un intenso trabajo teórico, en el que cabe destacar las aportaciones de Cristina Bicchieri y Jon Elster. Pese a las diferencias de sus respectivos planteamientos, ambos coinciden en definir el concepto por oposición a otro tipo de normas, en especial las morales. Este acuerdo no impide, sin embargo, que clasifiquen las normas de justicia de manera diferente: mientras que para Bicchieri se trata de normas sociales, Elster clasifica distintas normas de justicia en distintas categorías (sociales, cuasi morales y morales.En este trabajo, y con ayuda de algunos experimentos recientes, se analiza el caso de una norma de justicia, la norma de reparto igualitario, y se defiende que, pese a que los experimentos no son concluyentes, hay algunos factores que apuntan a la mayor validez de la teoría de Elster para el tratamiento y la conceptualización de esta norma.

  12. Le developpement de flexorage et son devenir industriel The Development of Flexodrilling

    Directory of Open Access Journals (Sweden)

    Thiery J. R.

    2006-11-01

    Full Text Available Après un rappel des avantages et inconvénients comparés du forage rotary et du flexoforage, cet article retrace l'historique du développement, par l'Institut Français du Pétrole (IFP du flexoforage. La première période a vu la mise au point du flexoforage léger, et son application à la reconnaissance des fonds marins. Dans la deuxième phase, les composants principaux du flexoforage profond ont été créés par l'IFP et expérimentés en URSS dans le cadre d'un accord de coopération franco-soviétique. La troisième phase du développement correspond en fait, à l'industrialisation du procédé. Elle a été marquée, en 1974, par la création de la société Foraflex et la réalisation de deux campagnes de forage pour la compagnie Nam à Groningue. L'article décrit les étapes actuellement en cours de cette industrialisation et les perspectives relatives au devenir industriel du procédé. After reviewing the comparative advantages of rotary drilling and flexodrilling, this article tracesthe historical developmentof flexodrilling by Institut Français du Pétrole(IFP. During the first phase, light flexodrilling was developed and applied ta seabed reconnaissance. In the second phase, IFP created the main components of deep flexodrilling which were experimented in lheSoviet Union under the terms of the French-Soviet Cooperation Agreement. The third phase of development actually corresponds to the industrialization of the process. In 1974 is was mdrked by the creation of Société Floraflex and two drilling campaigns for Nom at Groningen,the Netherlands. The article describes the current stages of this industrialization and the industrial outlook for the process.

  13. Mothers' and Fathers' Perceptions of Change and Continuity in their Relationships with Young Adult Sons and Daughters

    Science.gov (United States)

    Proulx, Christine M.; Helms, Heather M.

    2008-01-01

    Guided by contemporary feminist revisions of individual theories on adolescent development, interviews with 142 parent dyads were conducted to better understand the variation in mothers' and fathers' perceptions of changes and continuities in their relationships with their firstborn young adult sons and daughters. A between-families content…

  14. Superb fairy-wren (Malurus cyaneus sons and daughters acquire song elements of mothers and social fathers

    Directory of Open Access Journals (Sweden)

    Christine eEvans

    2016-02-01

    Full Text Available Birdsong is regarded as a classic example of a sexually-selected trait and has been primarily studied in systems with male song. Complex solo female song is emerging from the shadows of overlooked phenomena. In males, rearing conditions affect male song complexity, and males with complex songs are often more successful at mate attraction and territorial defense. Little is known about the ontogeny or function of complex female song. Here we examine song elements in fledgling superb fairy-wrens (Malurus cyaneus in relation to the song elements of adult tutors. Male and female superb fairy-wrens produce solo song year-round to defend a territory. We ask if sons and daughters acquire song elements from sex-specific vocal tutors. We found that sons and daughters produced the song elements of their mothers and social fathers, and that sons and daughters had comparable song element repertoires at age 7-10 weeks. We conclude that sons and daughters increase their song element repertoire when vocally imitating elements from several vocal tutors, and that both sexes acquire elements from male and female vocal tutors in this system.

  15. Self-Regulation in Early Adolescence: Relations with Mother-Son Relationship Quality and Maternal Regulatory Support and Antagonism

    Science.gov (United States)

    Moilanen, Kristin L.; Shaw, Daniel S.; Fitzpatrick, Amber

    2010-01-01

    The purpose of the current investigation was to examine relations among maternal regulatory support, maternal antagonism, and mother-son relationship quality in relation to boys' self-regulation during early adolescence. As part of a larger longitudinal study on 263 low-income, ethnically diverse boys, multiple informants and methods were used to…

  16. 77 FR 72906 - Chessie Logistics Co., LLC-Acquisition and Operation Exemption-J. Emil Anderson & Son, Inc.

    Science.gov (United States)

    2012-12-06

    ... Surface Transportation Board Chessie Logistics Co., LLC--Acquisition and Operation Exemption-- J. Emil Anderson & Son, Inc. Chessie Logistics Co., LLC (Chessie), a noncarrier, has filed a verified notice of... copy of each pleading must be served on Ariel A. Erbacher, Legal Counsel, Chessie Logistics Co.,...

  17. Literature as an exploration of the phenomenology of schizophrenia: disorder and recovery in Denis Johnson's Jesus' Son.

    Science.gov (United States)

    Hamm, Jay A; Leonhardt, Bethany L; Fogley, Rebecca L; Lysaker, Paul H

    2014-12-01

    When read as a fictional psychosis narrative, Jesus' Son, a collection of short stories by Denis Johnson, reveals important elements of the phenomenology of schizophrenia and recovery. It is possible that Jesus' Son, as a work of fiction, may be able to uniquely add depth and nuance to an understanding of the phenomenology of schizophrenia involving a state of psychological fragmentation, an ever-changing interpersonal field and a loss of personal agency. In addition, by following the protagonist in Jesus' Son as he begins to resolve some of his difficulties, the book also offers an individualised account of recovery. The authors detail how the book reveals these insights about schizophrenia and recovery and suggest that these elements are intertwined in such a manner that leads to a profound disruption of self-experience, characterised by a collapse of metacognitive processes. Jesus' Son may add depth to our understanding of the subjective experience of schizophrenia and recovery, and also may serve as one example in which the study of humanities offers an opportunity to explore the human elements in the most profound forms of suffering.

  18. Return Migration, Investment in Children, and Intergenerational Mobility: Comparing Sons of Foreign- and Native-Born Fathers

    Science.gov (United States)

    Dustmann, Christian

    2008-01-01

    This paper studies parental investment in education and intergenerational earnings mobility for father-son pairs with native- and foreign-born fathers. We illustrate within a simple model that for immigrants, investment in their children is related to their return migration probability. In our empirical analysis, we include a measure for return…

  19. A two-dimensional analytical-model-based comparative threshold performance analysis of SOI-SON MOSFETs

    Institute of Scientific and Technical Information of China (English)

    Sanjoy Deb; Saptarsi Ghosh; N Basanta Singh; A K De; Subir Kumar Sarkar

    2011-01-01

    A generalized threshold voltage model based on two-dimensional Poisson analysis has been developed for SOI/SON MOSFETs.Different short channel field effects,such as fringing fields,junction-induced lateral fields and substrate fields,are carefully investigated,and the related drain-induced barrier-lowering effects are incorporated in the analytical threshold voltage model.Through analytical model-based simulation,the threshold voltage roll-off and subthreshold slope for both structures are compared for different operational and structural parameter variations.Results of analytical simulation are compared with the results of the ATLAS 2D physicsbased simulator for verification of the analytical model.The performance of an SON MOSFET is found to be significantly different from a conventional SOI MOSFET.The short channel effects are found to be reduced in an SON,thereby resulting in a lower threshold voltage roll-offand a smaller subthreshold slope.This type of analysis is quite useful to figure out the performance improvement of SON over SOI structures for next generation short channel MOS devices.

  20. Pathways to Prevention: Improving Nonresident African American Fathers' Parenting Skills and Behaviors to Reduce Sons' Aggression

    Science.gov (United States)

    Caldwell, Cleopatra Howard; Antonakos, Cathy L.; Assari, Shervin; Kruger, Daniel; De Loney, E. Hill; Njai, Rashid

    2014-01-01

    This study describes a test of the Fathers and Sons Program for increasing intentions to avoid violence and reducing aggressive behaviors in 8-to 12-year-old African American boys by enhancing the parenting skills satisfaction and parenting behaviors of their nonresident fathers. The study included 158 intervention and 129 comparison group…

  1. Cutting edge: trans-signaling via the soluble IL-6R abrogates the induction of FoxP3 in naive CD4+CD25 T cells.

    Science.gov (United States)

    Dominitzki, Sabine; Fantini, Massimo C; Neufert, Clemens; Nikolaev, Alexei; Galle, Peter R; Scheller, Jürgen; Monteleone, Giovanni; Rose-John, Stefan; Neurath, Markus F; Becker, Christoph

    2007-08-15

    Chronic inflammatory diseases may develop when regulatory T cells (Tregs) fail to control the balance between tolerance and immunity. Alternatively, activated immune cells might prevent the induction or activation of Tregs in such diseases. In this study, we demonstrate that trans-signaling into T cells via the soluble IL-6 receptor completely abrogates the de novo induction of adaptive Tregs. Mechanistically, IL-6 trans-signaling augmented the expression of the TGF-beta signaling inhibitor SMAD7. Consequently, SMAD7 overexpression in T cells using newly created transgenic mice rendered CD4(+)CD25(-) T cells resistant to the induction of FoxP3. Finally, IL-6 trans-signaling inhibited Treg-mediated suppression in a murine model of colitis. In summary, IL-6 trans-signaling into T cells emerges as a key pathway for blockade of the development of adaptive Tregs and thus may play a pivotal role in shifting the balance between effector and regulatory T cell numbers in chronic inflammatory and autoimmune diseases.

  2. PilN Binding Modulates the Structure and Binding Partners of the Pseudomonas aeruginosa Type IVa Pilus Protein PilM.

    Science.gov (United States)

    McCallum, Matthew; Tammam, Stephanie; Little, Dustin J; Robinson, Howard; Koo, Jason; Shah, Megha; Calmettes, Charles; Moraes, Trevor F; Burrows, Lori L; Howell, P Lynne

    2016-05-20

    Pseudomonas aeruginosa is an opportunistic bacterial pathogen that expresses type IVa pili. The pilus assembly system, which promotes surface-associated twitching motility and virulence, is composed of inner and outer membrane subcomplexes, connected by an alignment subcomplex composed of PilMNOP. PilM binds to the N terminus of PilN, and we hypothesize that this interaction causes functionally significant structural changes in PilM. To characterize this interaction, we determined the crystal structures of PilM and a PilM chimera where PilM was fused to the first 12 residues of PilN (PilM·PilN(1-12)). Structural analysis, multiangle light scattering coupled with size exclusion chromatography, and bacterial two-hybrid data revealed that PilM forms dimers mediated by the binding of a novel conserved motif in the N terminus of PilM, and binding PilN abrogates this binding interface, resulting in PilM monomerization. Structural comparison of PilM with PilM·PilN(1-12) revealed that upon PilN binding, there is a large domain closure in PilM that alters its ATP binding site. Using biolayer interferometry, we found that the association rate of PilN with PilM is higher in the presence of ATP compared with ADP. Bacterial two-hybrid data suggested the connectivity of the cytoplasmic and inner membrane components of the type IVa pilus machinery in P. aeruginosa, with PilM binding to PilB, PilT, and PilC in addition to PilN. Pull-down experiments demonstrated direct interactions of PilM with PilB and PilT. We propose a working model in which dynamic binding of PilN facilitates functionally relevant structural changes in PilM.

  3. On Binding Domains

    NARCIS (Netherlands)

    Everaert, M.B.H.

    2005-01-01

    In this paper I want to explore reasons for replacing Binding Theory based on the anaphor-pronoun dichotomy by a Binding Theory allowing more domains restricting/defining anaphoric dependencies. This will, thus, have consequences for the partitioning of anaphoric elements, presupposing more types of

  4. Melanin-binding radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Packer, S; Fairchild, R G; Watts, K P; Greenberg, D; Hannon, S J

    1980-01-01

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed. (PSB)

  5. DNS BIND Server Configuration

    Directory of Open Access Journals (Sweden)

    Radu MARSANU

    2011-01-01

    Full Text Available After a brief presentation of the DNS and BIND standard for Unix platforms, the paper presents an application which has a principal objective, the configuring of the DNS BIND 9 server. The general objectives of the application are presented, follow by the description of the details of designing the program.

  6. Mutational definition of binding requirements of an hnRNP-like protein in Arabidopsis using fluorescence correlation spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Leder, Verena [Molecular Cell Physiology, Faculty of Biology, Bielefeld University (Germany); Biomolecular Photonics, Faculty of Physics, Bielefeld University (Germany); Lummer, Martina [Molecular Cell Physiology, Faculty of Biology, Bielefeld University (Germany); Tegeler, Kathrin [Molecular Cell Physiology, Faculty of Biology, Bielefeld University (Germany); Biomolecular Photonics, Faculty of Physics, Bielefeld University (Germany); Humpert, Fabian [Biomolecular Photonics, Faculty of Physics, Bielefeld University (Germany); Lewinski, Martin [Molecular Cell Physiology, Faculty of Biology, Bielefeld University (Germany); Schüttpelz, Mark [Biomolecular Photonics, Faculty of Physics, Bielefeld University (Germany); Staiger, Dorothee, E-mail: dorothee.staiger@uni-bielefeld.de [Molecular Cell Physiology, Faculty of Biology, Bielefeld University (Germany)

    2014-10-10

    Highlights: • We use FCS to investigate binding site requirements for the hnRNP-like protein AtGRP7. • We identify three nucleotides critical for AtGRP7 binding to its own intron. • Mutation of the conserved R{sup 49} abolishes binding altogether. • The paralogue AtGRP8 binds to an overlapping motif with different sequence requirement. • The glycine-rich stretch of a plant hnRNP-like protein contributes to binding. - Abstract: Arabidopsis thaliana glycine-rich RNA binding protein 7 (AtGRP7) is part of a negative feedback loop through which it regulates alternative splicing and steady-state abundance of its pre-mRNA. Here we use fluorescence correlation spectroscopy to investigate the requirements for AtGRP7 binding to its intron using fluorescently-labelled synthetic oligonucleotides. By systematically introducing point mutations we identify three nucleotides that lead to an increased K{sub d} value when mutated and thus are critical for AtGRP7 binding. Simultaneous mutation of all three residues abrogates binding. The paralogue AtGRP8 binds to an overlapping motif but with a different sequence preference, in line with overlapping but not identical functions of this protein pair. Truncation of the glycine-rich domain reduces the binding affinity of AtGRP7, showing for the first time that the glycine-rich stretch of a plant hnRNP-like protein contributes to binding. Mutation of the conserved R{sup 49} that is crucial for AtGRP7 function in pathogen defence and splicing abolishes binding.

  7. Thermodynamics of fragment binding.

    Science.gov (United States)

    Ferenczy, György G; Keserű, György M

    2012-04-23

    The ligand binding pockets of proteins have preponderance of hydrophobic amino acids and are typically within the apolar interior of the protein; nevertheless, they are able to bind low complexity, polar, water-soluble fragments. In order to understand this phenomenon, we analyzed high resolution X-ray data of protein-ligand complexes from the Protein Data Bank and found that fragments bind to proteins with two near optimal geometry H-bonds on average. The linear extent of the fragment binding site was found not to be larger than 10 Å, and the H-bonding region was found to be restricted to about 5 Å on average. The number of conserved H-bonds in proteins cocrystallized with multiple different fragments is also near to 2. These fragment binding sites that are able to form limited number of strong H-bonds in a hydrophobic environment are identified as hot spots. An estimate of the free-energy gain of H-bond formation versus apolar desolvation supports that fragment sized compounds need H-bonds to achieve detectable binding. This suggests that fragment binding is mostly enthalpic that is in line with their observed binding thermodynamics documented in Isothermal Titration Calorimetry (ITC) data sets and gives a thermodynamic rationale for fragment based approaches. The binding of larger compounds tends to more rely on apolar desolvation with a corresponding increase of the entropy content of their binding free-energy. These findings explain the reported size-dependence of maximal available affinity and ligand efficiency both behaving differently in the small molecule region featured by strong H-bond formation and in the larger molecule region featured by apolar desolvation.

  8. ¿Son seres humanos los puentes de fábrica?

    Directory of Open Access Journals (Sweden)

    Bauder, E.

    2006-03-01

    éndole cualidades humanas a lo largo de su ciclo vital, a la vez que desempeña el papel de creador, padre, defensor, médico o psicólogo según las situaciones en que se encuentre o los problemas a que se enfrente su puente-hijo. Además, se quiere poner de manifiesto que la abundante utilización de esta metáfora y las correspondencias terminológicas derivadas de ella no son un fenómeno extraño, sino el resultado lógico de la interdisciplinaridad natural entre la técnica constructiva, la medicina (psicología incluida, la terminología y el lenguaje.

  9. Compared study of the local structure of alteration products of SON 68 glass and natural gels; Etude comparee de la structure locale des produits d'alteration du verre SON 68 et de gels naturels

    Energy Technology Data Exchange (ETDEWEB)

    Pellegrin, E

    2000-07-01

    This study is a contribution in the understanding of the long time behavior of alteration products of the glass SON 68, used to simulate the nuclear glass R7T7. The local structure around Zirconium and iron has been probed using X-ray absorption spectroscopy in altered surface layer of glass SON 68. Alteration products of this glass have been prepared for short (3 hours to 7 days) and long (17 months) time, using various indexes of saturation for the leaching solution with respect to the Si content of the glass (from 0 to 90 %). The evolution of the local structure around Fe has also been studied in recent and old natural ferric gels. Zr, Fe- L{sub 2,3} XANES and Zr, Fe-K EXAFS spectroscopies have shown that, in the pristine glass, these elements are connected to the polymeric network. Zr is found in an environment close to that of a zircon-silicate containing Na and Ca. Trivalent Fe is a network former. The leached layer of glass SON 68 is constituted of poorly ordered Zr-and Fe-(oxi-hydr)oxides that may have been formed by a mechanism of dissolution/precipitation; a relict phase with the same Zr local structure as that observed in the pristine glass, probably obtained thanks to in-situ solid condensation. The structural characteristics of the leached layer are observed from the first steps of alteration for Zr and Fe. Conversely to Fe, the structural status of Zr depends on the leaching kinetic as well as the contents of Ca and Si in the solid. Fe-K EXAFS results in recent natural ferri-hydrides present a clear structural similarity with that determined in glass SON 68 leached products. The study of old paleosols (between 1,800 and 200,000 years) has demonstrated the long time stability of ferric gels, although an increase of medium range order around Fe is seen. (author)

  10. Applicability of the SON-R 6-40 Non-verbal Intelligence Test in China%SON-R6-40非言语智力测验在中国的适用性

    Institute of Scientific and Technical Information of China (English)

    徐建平; 郭枝; 王茜; Peter Tellegen

    2014-01-01

    SON-R 6-40非言语智力测验是以非文字形式测量个体推理与空间能力的智力评估工具.研究旨在考查SON-R6-40在中国的适用性.根据全国人口分布,在中国六大行政区6至40岁年龄人群中施测了1721人,通过与荷兰/德国混合样本比较,分析该测验的跨文化等值水平.结果表明:(1)测验信度与结构跨样本一致,说明该测验在两种文化下结构等值;(2)多样本验证性因素分析证明了该测验的测量单位等值性.因此,SON-R 6-40适合在中国推广使用以及用于智力的跨文化比较研究.

  11. Insights into dynamic mitotic chromatin organization through the NIMA kinase suppressor SonC, a chromatin-associated protein involved in the DNA damage response.

    Science.gov (United States)

    Larson, Jennifer R; Facemyer, Eric M; Shen, Kuo-Fang; Ukil, Leena; Osmani, Stephen A

    2014-01-01

    The nuclear pore complex proteins SonA and SonB, the orthologs of mammalian RAE1 and NUP98, respectively, were identified in Aspergillus nidulans as cold-sensitive suppressors of a temperature-sensitive allele of the essential mitotic NIMA kinase (nimA1). Subsequent analyses found that sonB1 mutants exhibit temperature-dependent DNA damage sensitivity. To understand this pathway further, we performed a genetic screen to isolate additional conditional DNA damage-sensitive suppressors of nimA1. We identified two new alleles of SonA and four intragenic nimA mutations that suppress the temperature sensitivity of the nimA1 mutant. In addition, we identified SonC, a previously unstudied binuclear zinc cluster protein involved with NIMA and the DNA damage response. Like sonA and sonB, sonC is an essential gene. SonC localizes to nuclei and partially disperses during mitosis. When the nucleolar organizer region (NOR) undergoes mitotic condensation and removal from the nucleolus, nuclear SonC and histone H1 localize in a mutually exclusive manner with H1 being removed from the NOR region and SonC being absent from the end of the chromosome beyond the NOR. This region of chromatin is adjacent to a cluster of nuclear pore complexes to which NIMA localizes last during its progression around the nuclear envelope during initiation of mitosis. The results genetically extend the NIMA regulatory system to include a protein with selective large-scale chromatin location observed during mitosis. The data suggest a model in which NIMA and SonC, its new chromatin-associated suppressor, might help to orchestrate global chromatin states during mitosis and the DNA damage response.

  12. Exploring Mothers’ and Fathers’ Relationships with Sons Versus Daughters: Links to Adolescent Adjustment in Mexican Immigrant Families

    Science.gov (United States)

    Updegraff, Kimberly A.; Delgado, Melissa Y.; Wheeler, Lorey A.

    2009-01-01

    Drawing on ecological and gender socialization perspectives, this study examined mothers’ and fathers’ relationships with young adolescents, exploring differences between mothers and fathers, for sons versus daughters, and as a function of parents’ division of paid labor. Mexican immigrant families (N = 162) participated in home interviews and seven nightly phone calls. Findings revealed that mothers reported higher levels of acceptance toward adolescents and greater knowledge of adolescents’ daily activities than did fathers, and mothers spent more time with daughters than with sons. Linkages between parent-adolescent relationship qualities and youth adjustment were moderated by adolescent gender and parents’ division of paid labor. Findings revealed, for example, stronger associations between parent–adolescent relationship qualities and youth adjustment for girls than for boys. PMID:19779582

  13. Exploring Mothers' and Fathers' Relationships with Sons Versus Daughters: Links to Adolescent Adjustment in Mexican Immigrant Families.

    Science.gov (United States)

    Updegraff, Kimberly A; Delgado, Melissa Y; Wheeler, Lorey A

    2009-04-01

    Drawing on ecological and gender socialization perspectives, this study examined mothers' and fathers' relationships with young adolescents, exploring differences between mothers and fathers, for sons versus daughters, and as a function of parents' division of paid labor. Mexican immigrant families (N = 162) participated in home interviews and seven nightly phone calls. Findings revealed that mothers reported higher levels of acceptance toward adolescents and greater knowledge of adolescents' daily activities than did fathers, and mothers spent more time with daughters than with sons. Linkages between parent-adolescent relationship qualities and youth adjustment were moderated by adolescent gender and parents' division of paid labor. Findings revealed, for example, stronger associations between parent-adolescent relationship qualities and youth adjustment for girls than for boys.

  14. Mitochondrial DNA analysis on remains of a putative son of Louis XVI, King of France and Marie-Antoinette.

    Science.gov (United States)

    Jehaes, E; Decorte, R; Peneau, A; Petrie, J H; Boiry, P A; Gilissen, A; Moisan, J P; Van den Berghe, H; Pascal, O; Cassiman, J J

    1998-01-01

    Carl Wilhelm Naundorff was buried in 1845 in Delft as Louis Charles, Duc de Normandie, 'Louis XVII'. However, the son of Louis XVI and Marie-Antoinette-Louis XVII--officially died in the Temple of Paris in 1795. In order to resolve the identity of Naundorff, mitochondrial DNA (mtDNA) D-loop sequences of his remains were compared with the sequences obtained from the hairs of two sisters of Marie-Antoinette, Marie-Antoinette herself, and with the sequences obtained from DNA samples of two living maternal relatives. The mtDNA sequence of a bone sample from Naundorff showed two nucleotide differences from the sequences of the three sisters and four differences from the sequences of living maternal relatives. Based on this evidence it becomes very unlikely that Naundroff is the son of Marie-Antoinette.

  15. QCD Precision Measurements and Structure Function Extraction at a High Statistics, High Energy Neutrino Scattering Experiment: NuSOnG

    CERN Document Server

    Adams, T; Bugel, L; Camilleri, L; Conrad, J M; De Gouvêa, A; Fisher, P H; Formaggio, J A; Jenkins, J; Karagiorgi, G; Kobilarcik, T R; Kopp, S; Kyle, G; Loinaz, W A; Mason, D A; Milner, R; Moore, R; Morfín, J G; Nakamura, M; Naples, D; Nienaber, P; Olness, F I; Owens, J F; Pate, S F; Pronin, A; Seligman, W G; Shaevitz, M H; Schellman, H; Schienbein, I; Syphers, M J; Tait, T M P; Takeuchi, T; Tan, C Y; Van de Water, R G; Yamamoto, R K; Yu, J Y

    2009-01-01

    We extend the physics case for a new high-energy, ultra-high statistics neutrino scattering experiment, NuSOnG (Neutrino Scattering On Glass) to address a variety of issues including precision QCD measurements, extraction of structure functions, and the derived Parton Distribution Functions (PDFs). This experiment uses a Tevatron-based neutrino beam to obtain a sample of Deep Inelastic Scattering (DIS) events which is over two orders of magnitude larger than past samples. We outline an innovative method for fitting the structure functions using a parameterized energy shift which yields reduced systematic uncertainties. High statistics measurements, in combination with improved systematics, will enable NuSOnG to perform discerning tests of fundamental Standard Model parameters as we search for deviations which may hint of "Beyond the Standard Model" physics.

  16. Kauffman Knot Invariant from SO(N) or Sp(N) Chern-Simons theory and the Potts Model

    CERN Document Server

    Astorino, Marco

    2010-01-01

    The expectation value of Wilson loop operators in three-dimensional SO(N) Chern-Simons gauge theory gives a known knot invariant: the Kauffman polynomial. Here this result is derived, at the first order, via a simple variational method. With the same procedure the skein relation for Sp(N) are also obtained. Jones polynomial arises as special cases: Sp(2), SO(-2) and SL(2,R). These results are confirmed and extended up to the second order, by means of perturbation theory, which moreover let us establish a duality relation between SO(+/-N) and Sp(-/+N) invariants. A correspondence between the firsts orders in perturbation theory of SO(-2), Sp(2) or SU(2) Chern-Simons quantum holonomies and the partition function of the Q=4 Potts Model is built.

  17. QCD Precision Measurements and Structure Function Extraction at a High Statistics, High Energy Neutrino Scattering Experiment: NuSOnG

    Energy Technology Data Exchange (ETDEWEB)

    Adams, T.; /Florida State U.; Batra, P.; /Columbia U.; Bugel, Leonard G.; /Columbia U.; Camilleri, Leslie Loris; /Columbia U.; Conrad, Janet Marie; /MIT; de Gouvea, A.; /Northwestern U.; Fisher, Peter H.; /MIT; Formaggio, Joseph Angelo; /MIT; Jenkins, J.; /Northwestern U.; Karagiorgi, Georgia S.; /MIT; Kobilarcik, T.R.; /Fermilab /Texas U.

    2009-06-01

    We extend the physics case for a new high-energy, ultra-high statistics neutrino scattering experiment, NuSOnG (Neutrino Scattering On Glass) to address a variety of issues including precision QCD measurements, extraction of structure functions, and the derived Parton Distribution Functions (PDFs). This experiment uses a Tevatron-based neutrino beam to obtain a sample of Deep Inelastic Scattering (DIS) events which is over two orders of magnitude larger than past samples. We outline an innovative method for fitting the structure functions using a parameterized energy shift which yields reduced systematic uncertainties. High statistics measurements, in combination with improved systematics, will enable NuSOnG to perform discerning tests of fundamental Standard Model parameters as we search for deviations which may hint of 'Beyond the Standard Model' physics.

  18. SCH529074, a small molecule activator of mutant p53, which binds p53 DNA binding domain (DBD), restores growth-suppressive function to mutant p53 and interrupts HDM2-mediated ubiquitination of wild type p53.

    Science.gov (United States)

    Demma, Mark; Maxwell, Eugene; Ramos, Robert; Liang, Lianzhu; Li, Cheng; Hesk, David; Rossman, Randall; Mallams, Alan; Doll, Ronald; Liu, Ming; Seidel-Dugan, Cynthia; Bishop, W Robert; Dasmahapatra, Bimalendu

    2010-04-02

    Abrogation of p53 function occurs in almost all human cancers, with more than 50% of cancers harboring inactivating mutations in p53 itself. Mutation of p53 is indicative of highly aggressive cancers and poor prognosis. The vast majority of mutations in p53 occur in its core DNA binding domain (DBD) and result in inactivation of p53 by reducing its thermodynamic stability at physiological temperature. Here, we report a small molecule, SCH529074, that binds specifically to the p53 DBD in a saturable manner with an affinity of 1-2 microm. Binding restores wild type function to many oncogenic mutant forms of p53. This small molecule reactivates mutant p53 by acting as a chaperone, in a manner similar to that previously reported for the peptide CDB3. Binding of SCH529074 to the p53 DBD is specifically displaced by an oligonucleotide with a sequence derived from the p53-response element. In addition to reactivating mutant p53, SCH529074 binding inhibits ubiquitination of p53 by HDM2. We have also developed a novel variant of p53 by changing a single amino acid in the core domain of p53 (N268R), which abolishes binding of SCH529074. This amino acid change also inhibits HDM2-mediated ubiquitination of p53. Our novel findings indicate that through its interaction with p53 DBD, SCH529074 restores DNA binding activity to mutant p53 and inhibits HDM2-mediated ubiquitination.

  19. A Brief Introduction to Paul in Sons and Lovers——From Self-absence to Self-realization

    Institute of Scientific and Technical Information of China (English)

    张灵机

    2008-01-01

    Paul,the main character in the novel Sons and Lovers,experiences a tough psychological development.At the beginning,he relies heavily on his mother and serves as the medium of her dream and ambitions,leading him to a lost self.Whereas,in his attempt,though it is painful,he finally finds a true self of his own maintaining a harmonious unity with various social relations.

  20. Keampferol-3-O-rhamnoside abrogates amyloid beta toxicity by modulating monomers and remodeling oligomers and fibrils to non-toxic aggregates

    Directory of Open Access Journals (Sweden)

    Sharoar Md

    2012-12-01

    Full Text Available Abstract Background Aggregation of soluble, monomeric β- amyloid (Aβ to oligomeric and then insoluble fibrillar Aβ is a key pathogenic feature in development of Alzheimer’s disease (AD. Increasing evidence suggests that toxicity is linked to diffusible Aβ oligomers, rather than to insoluble fibrils. The use of naturally occurring small molecules for inhibition of Aβ aggregation has recently attracted significant interest for development of effective therapeutic strategies against the disease. A natural polyphenolic flavone, Kaempferol-3-O-rhamnoside (K-3-rh, was utilized to investigate its effects on aggregation and cytotoxic effects of Aβ42 peptide. Several biochemical techniques were used to determine the conformational changes and cytotoxic effect of the peptide in the presence and absence of K-3-rh. Results K-3-rh showed a dose-dependent effect against Aβ42 mediated cytotoxicity. Anti-amyloidogenic properties of K-3-rh were found to be efficient in inhibiting fibrilogenesis and secondary structural transformation of the peptide. The consequence of these inhibitions was the accumulation of oligomeric structural species. The accumulated aggregates were smaller, soluble, non-β-sheet and non-toxic aggregates, compared to preformed toxic Aβ oligomers. K-3-rh was also found to have the remodeling properties of preformed soluble oligomers and fibrils. Both of these conformers were found to remodel into non-toxic aggregates. The results showed that K-3-rh interacts with different Aβ conformers, which affects fibril formation, oligomeric maturation and fibrillar stabilization. Conclusion K-3-rh is an efficient molecule to hinder the self assembly and to abrogate the cytotoxic effects of Aβ42 peptide. Hence, K-3-rh and small molecules with similar structure might be considered for therapeutic development against AD.

  1. Betaine supplementation mitigates cisplatin-induced nephrotoxicity by abrogation of oxidative/nitrosative stress and suppression of inflammation and apoptosis in rats.

    Science.gov (United States)

    Hagar, Hanan; Medany, Azza El; Salam, Reem; Medany, Gamila El; Nayal, Omina A

    2015-02-01

    Cisplatin is one of the most potent chemotherapeutic antitumor drugs used in the treatment of a wide range of solid tumors. Its primary dose-limiting side effect is nephrotoxicity. This study aims to investigate the effect of betaine supplementation on cisplatin-induced nephrotoxicity. A single intraperitoneal injection of cisplatin (5mg/kg) deteriorated the kidney functions as reflected by elevated blood urea nitrogen and serum creatinine levels. Oxidative/nitrosative stress was evident in cisplatin group by increased renal thiobarbituric acid-reactive substances (TBARS), an indicator of lipid peroxidation, reduced renal total antioxidant status and increased renal nitrite concentration. Cisplatin resulted in a decline in the concentrations of reduced glutathione, glutathione peroxidase, catalase, and superoxide dismutase in renal tissues. Renal tumor necrosis factor-α (TNF-α) was also elevated. Expressions of nuclear factor-kappa B (NF-κB) and caspase-3 were up-regulated in renal tissues as indicated by immunohistochemical analysis. Histopathological changes were observed in cisplatin group. Betaine supplementation (250 mg/kg/day) orally via gavage for 21 days prior to cisplatin injection was able to protect against deterioration in kidney function, abrogate the decline in antioxidants enzymes and suppressed the increase in TBARS, nitrite and TNF-α concentrations. Moreover, betaine inhibited NF-κB and caspase-3 activation and improved the histological changes induced by cisplatin. Thus, the present study demonstrated the renoprotective nature of betaine by attenuating the pro-inflammatory and apoptotic mediators and improving antioxidant competence in kidney tissues of cisplatin treated rats. Betaine could be a beneficial dietary supplement to attenuate cisplatin nephrotoxicity.

  2. TGF-β1 induced epithelial to mesenchymal transition (EMT in human bronchial epithelial cells is enhanced by IL-1β but not abrogated by corticosteroids

    Directory of Open Access Journals (Sweden)

    Zuraw Bruce L

    2009-10-01

    Full Text Available Abstract Background Chronic persistent asthma is characterized by ongoing airway inflammation and airway remodeling. The processes leading to airway remodeling are poorly understood, and there is increasing evidence that even aggressive anti-inflammatory therapy does not completely prevent this process. We sought to investigate whether TGFβ1 stimulates bronchial epithelial cells to undergo transition to a mesenchymal phenotype, and whether this transition can be abrogated by corticosteroid treatment or enhanced by the pro-inflammatory cytokine IL-1β. Methods BEAS-2B and primary normal human bronchial epithelial cells were stimulated with TGFβ1 and expression of epithelial and mesenchymal markers assessed by quantitative real-time PCR, immunoblotting, immunofluorescence microscopy and zymography. In some cases the epithelial cells were also incubated with corticosteroids or IL-1β. Results were analyzed using non-parametric statistical tests. Results Treatment of BEAS-2B or primary human bronchial epithelial cells with TGFβ1 significantly reduced the expression level of the epithelial adherence junction protein E-cadherin. TGFβ1 then markedly induced mesenchymal marker proteins such as collagen I, tenascin C, fibronectin and α-smooth muscle actin mRNA in a dose dependant manner. The process of mesenchymal transition was accompanied by a morphological change towards a more spindle shaped fibroblast cell type with a more motile and invasive phenotype. Corticosteroid pre-treatment did not significantly alter the TGFβ1 induced transition but IL-1β enhanced the transition. Conclusion Our results indicate, that TGFβ1 can induce mesenchymal transition in the bronchial epithelial cell line and primary cells. Since asthma has been strongly associated with increased expression of TGFβ1 in the airway, epithelial to mesenchymal transition may contribute to the contractile and fibrotic remodeling process that accompanies chronic asthma.

  3. Interference of daratumumab in monitoring multiple myeloma patients using serum immunofixation electrophoresis can be abrogated using the daratumumab IFE reflex assay (DIRA).

    Science.gov (United States)

    van de Donk, Niels W C J; Otten, Henny G; El Haddad, Omar; Axel, Amy; Sasser, A Kate; Croockewit, Sandra; Jacobs, Joannes F M

    2016-06-01

    Daratumumab is a fully human anti-CD38 IgG1-κ monoclonal antibody (mAb) currently being evaluated in several Phase 2 and 3 clinical studies for the treatment of multiple myeloma (MM). In this clinical case study we demonstrate that daratumumab can be detected as an individual monoclonal band in serum immunofixation electrophoresis (IFE). M-protein follow-up by IFE is part of the International Myeloma Working Group (IMWG) criteria to assess treatment response. Therefore, it is crucial that the daratumumab band is not confused with the endogenous M-protein of the patient during IFE interpretation. Moreover, a significant number of IgG-κ M-proteins co-migrate with daratumumab. Co-migration introduces a bias in the M-protein quantification since pharmacokinetic studies show that daratumumab peak plasma concentrations reach up to 1 g/L. More importantly, co-migration can mask clearance of the M-protein by IFE which is necessary for classification of complete response by IMWG criteria (negative serum IFE). For optimal M-protein monitoring the laboratory specialist needs to be informed when patients receive daratumumab, and it is essential that the laboratory specialist is aware that a slow migrating band in the γ-region in those patients may be derived from the daratumumab. A daratumumab specific IFE reflex assay (DIRA) has been developed and can be utilized to abrogate interference. The here described mAb interference is not limited to daratumumab, and as therapeutic antibodies gain approval and enter into common clinical practice, laboratory specialists will need additional processes to characterize IFE interference and distinguish endogenous M-protein from therapeutic antibodies.

  4. Salvia miltiorrhiza water-soluble extract, but not its constituent salvianolic acid B, abrogates LPS-induced NF-κB signalling in intestinal epithelial cells

    Science.gov (United States)

    Kim, J S; Narula, A S; Jobin, C

    2005-01-01

    Herbal medicine has become an increasing popular therapeutic alternative among patients suffering from various inflammatory disorders. The Salvia miltiorrhizae water-soluble extract (SME) have been shown to possess antioxidant and anti-inflammatory properties in vitro. However, the mechanism of action and impact of SME on LPS-induced gene expression is still unknown. We report that SME significantly abrogated LPS-induced IκB phosphorylation/degradation, NF-κB transcriptional activity and ICAM-1 gene expression in rat IEC-18 cells. Chromatin immunoprecipitation assay demonstrated that LPS-induced RelA recruitment to the ICAM-1 gene promoter was inhibited by SME. Moreover, in vitro kinase assay showed that SME directly inhibits LPS induced IκB kinase (IKK) activity in IEC-18 cells. To investigate the physiological relevance of SME inhibitory activity on NF-κB signalling, we used small intestinal explants and primary intestinal epithelial cells derived from a transgenic mouse expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-κB cis-elements (cis-NF-κBEGFP). SME significantly blocked LPS-induced EGFP expression and IκBα phosphorylation in intestinal explants and primary IECs, respectively. However, salvianolic acid B, an activate component of SME did not inhibit NF-κB transcriptional activity and IκB phosphorylation/degradation in IEC-18 cells. These results indicate that SME blocks LPS-induced NF-κB signalling pathway by targeting the IKK complex in intestinal epithelial cells. Modulation of bacterial product-mediated NF-κB signalling by natural plant extracts may represent an attractive strategy towards the prevention and treatment of intestinal inflammation. PMID:15996193

  5. Abrogating phosphorylation of eIF4B is required for EGFR and mTOR inhibitor synergy in triple-negative breast cancer.

    Science.gov (United States)

    Madden, Julie M; Mueller, Kelly L; Bollig-Fischer, Aliccia; Stemmer, Paul; Mattingly, Raymond R; Boerner, Julie L

    2014-09-01

    Triple-negative breast cancer (TNBC) patients suffer from a highly malignant and aggressive disease. They have a high rate of relapse and often develop resistance to standard chemotherapy. Many TNBCs have elevated epidermal growth factor receptor (EGFR) but are resistant to EGFR inhibitors as monotherapy. In this study, we sought to find a combination therapy that could sensitize TNBC to EGFR inhibitors. Phospho-mass spectrometry was performed on the TNBC cell line, BT20, treated with 0.5 μM gefitinib. Immunoblotting measured protein levels and phosphorylation. Colony formation and growth assays analyzed the treatment on cell proliferation, while MTT assays determined the synergistic effect of inhibitor combination. A Dual-Luciferase reporter gene plasmid measured translation. All statistical analysis was done on CalucuSyn and GraphPad Prism using ANOVAs. Phospho-proteomics identified the mTOR pathway to be of interest in EGFR inhibitor resistance. In our studies, combining gefitinib and temsirolimus decreased cell growth and survival in a synergistic manner. Our data identified eIF4B, as a potentially key fragile point in EGFR and mTOR inhibitor synergy. Decreased eIF4B phosphorylation correlated with drops in growth, viability, clonogenic survival, and cap-dependent translation. Taken together, these data suggest EGFR and mTOR inhibitors abrogate growth, viability, and survival via disruption of eIF4B phosphorylation leading to decreased translation in TNBC cell lines. Further, including an mTOR inhibitor along with an EGFR inhibitor in TNBC with increased EGFR expression should be further explored. Additionally, translational regulation may play an important role in regulating EGFR and mTOR inhibitor synergy and warrant further investigation.

  6. Chitosan-shelled oxygen-loaded nanodroplets abrogate hypoxia dysregulation of human keratinocyte gelatinases and inhibitors: New insights for chronic wound healing

    Energy Technology Data Exchange (ETDEWEB)

    Khadjavi, Amina [Dipartimento di Neuroscienze, Università di Torino, Torino (Italy); Magnetto, Chiara [Istituto Nazionale di Ricerca Metrologica (INRIM), Torino (Italy); Panariti, Alice [Dipartimento di Scienze della Salute, Università di Milano Bicocca, Monza (Italy); Argenziano, Monica [Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Torino (Italy); Gulino, Giulia Rossana [Dipartimento di Oncologia, Università di Torino, Torino (Italy); Rivolta, Ilaria [Dipartimento di Scienze della Salute, Università di Milano Bicocca, Monza (Italy); Cavalli, Roberta [Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Torino (Italy); Giribaldi, Giuliana [Dipartimento di Oncologia, Università di Torino, Torino (Italy); Guiot, Caterina [Dipartimento di Neuroscienze, Università di Torino, Torino (Italy); Prato, Mauro, E-mail: mauro.prato@unito.it [Dipartimento di Neuroscienze, Università di Torino, Torino (Italy); Dipartimento di Scienze della Sanità Pubblica e Pediatriche, Università di Torino, Torino (Italy)

    2015-08-01

    Background: : In chronic wounds, efficient epithelial tissue repair is hampered by hypoxia, and balances between the molecules involved in matrix turn-over such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are seriously impaired. Intriguingly, new oxygenating nanocarriers such as 2H,3H-decafluoropentane-based oxygen-loaded nanodroplets (OLNs) might effectively target chronic wounds. Objective: : To investigate hypoxia and chitosan-shelled OLN effects on MMP/TIMP production by human keratinocytes. Methods: : HaCaT cells were treated for 24 h with 10% v/v OLNs both in normoxia or hypoxia. Cytotoxicity and cell viability were measured through biochemical assays; cellular uptake by confocal microscopy; and MMP and TIMP production by enzyme-linked immunosorbent assay or gelatin zymography. Results: : Normoxic HaCaT cells constitutively released MMP-2, MMP-9, TIMP-1 and TIMP-2. Hypoxia strongly impaired MMP/TIMP balances by reducing MMP-2, MMP-9, and TIMP-2, without affecting TIMP-1 release. After cellular uptake by keratinocytes, nontoxic OLNs abrogated all hypoxia effects on MMP/TIMP secretion, restoring physiological balances. OLN abilities were specifically dependent on time-sustained oxygen diffusion from OLN core. Conclusion: : Chitosan-shelled OLNs effectively counteract hypoxia-dependent dysregulation of MMP/TIMP balances in human keratinocytes. Therefore, topical administration of exogenous oxygen, properly encapsulated in nanodroplet formulations, might be a promising adjuvant approach to promote healing processes in hypoxic wounds. - Highlights: • Hypoxia impairs MMP9/TIMP1 and MMP2/TIMP2 balances in HaCaT human keratinocytes. • Chitosan-shelled oxygen-loaded nanodroplets (OLNs) are internalised by HaCaT cells. • OLNs are not toxic to HaCaT cells. • OLNs effectively counteract hypoxia effects on MMP/TIMP balances in HaCaT cells. • OLNs appear as promising and cost-effective therapeutic tools for hypoxic

  7. 养儿防老和母以子贵:是儿子还是儿女双全?%Old- age Support and Mother's Family Status. Sons Only or Both Sons and Daughters?

    Institute of Scientific and Technical Information of China (English)

    尹银

    2012-01-01

    了解养儿防老、母以子贵等传统生育文化的影响对中国稳定低生育水平至关重要。使用2008年中国老年人健康因素跟踪调查数据,通过logistic回归分析子女性别对老年父亲、母亲生活质量(包括生活满意度和婚姻满意度)、家庭地位(包括经济决策权和自我决策权)的影响发现,儿子的作用大大下降,儿女双全除了增加老年父亲的婚姻满意度以外,并没有提高老年人的生活质量,养儿未必能防老;生育儿子或儿女双全并没有提高老年母亲的家庭地位,甚至有儿子的老年母亲的经济决策权还更低;老年人自身的社会经济因素显著提高了老年人的生活质量和家庭地位。养儿防老、母以子贵等传统生育文化影响逐渐减弱,这对中国稳定低生育水平是一个利好的消息。%It is important to study the influences of traditional fertility culture (such as old - age sup- port and mother' s status depending on sons) on China's fertility. Using 2008 Chinese Longitudinal Healthy Longevity Survey, the paper analyzes the impact of sex of children on life quality of elderly par- ents (including life satisfaction and marital satisfaction) and family status (including economic decision - making power and self decision - making authority). Regression results show that son' s influence has decreased. Having both sons and daughters does not improve life quality of the elderly parents, but increases marital satisfaction of the elderly fathers. Bringing up sons not necessarily provides sup- port for ageing parents. Having sons or both sons and daughters may not help to improve family status of the elderly mothers, and the elderly mothers having sons only have even lower economic decision - making power. Social and economic situation of the elderly significantly improves their life quality and family status. Thus, influences of traditional fertility culture have been gradually weakening

  8. BALTIMORE’S M.S. LEVY AND SONS: Straw Hat Makers to the World, 1870-1960

    Directory of Open Access Journals (Sweden)

    Jessica I. Elfenbein

    2008-01-01

    Full Text Available From 1860 to 1960, Baltimore was an important center of the men’s ready-to- wear clothing industries. German-speaking Jews created many businesses that manufactured and sold underwear, men’s suits, and specialty items like hats and umbrellas. The straw hat making firm started by M.S. Levy is an interesting example of a Baltimore-based, family-owned niche business that existedfor 90 years, through three generations ofa singlefamily. The M.S. Levy and Sons story has two main chapters. The first covers the period from its founding by Michael Simon Levy in the 1870s through his son Julius’ death in 1926. This is the story of ascension. A premonition about the coming popularity of straw hats, together with a small but important technological breakthrough, positioned a family and a small industry for significant expansion. The second period began in 1930 with the introduction of wool felt hats and the death of William, M.S. Levy’s oldest son, and includes the Great Depression, unionization, merger, third generation leadership, and finally, in 1959, the family’s withdrawal from the industry. This later period, as told by grandsons of the founder, is the story of struggle followed by decline.

  9. SHBG (Sex Hormone Binding Globulin)

    Science.gov (United States)

    ... as: Testosterone-estrogen Binding Globulin; TeBG Formal name: Sex Hormone Binding Globulin Related tests: Testosterone , Free Testosterone, ... I should know? How is it used? The sex hormone binding globulin (SHBG) test may be used ...

  10. Mothers, fathers, sons, and daughters: gender differences in factors associated with parent-child communication about sexual topics

    Directory of Open Access Journals (Sweden)

    Koo Helen P

    2010-12-01

    Full Text Available Abstract Background In the United States, nearly half of high school students are sexually active, and adolescents experience high rates of unintended pregnancy and sexually transmitted diseases. Parents can have an important influence on their children's sexual behaviour, but many parents do not talk with their children about sexual topics. Research has shown significant differences in parent-child communication about sexual topics depending on the gender of both the parent and the child. Little is known, however, about the reasons for these gender differences. The purpose of this paper is to describe how factors associated with parent-child communication about sexual topics differ by gender. Methods Data are from a nationwide online survey with 829 fathers and 1,113 mothers of children aged 10 to 14. For each of the four gender groups (fathers of sons, fathers of daughters, mothers of sons, mothers of daughters, we calculated the distribution of responses to questions assessing (1 parent-child communication about sex-related topics, and (2 factors associated with that communication. We used chi-square tests to determine whether the distributions differed and the false discovery rate control to reduce the likelihood of type I errors. Results With both sons and daughters, fathers communicated less about sexual topics than mothers did. Fathers also had lower levels of many characteristics that facilitate communication about sex (e.g., lower self-efficacy and lower expectations that talking to their children about sex would have positive outcomes. Compared with parents of sons, parents of daughters (both mothers and fathers talked more about sexual topics, were more concerned about potential harmful consequences of sexual activity, and were more disapproving of their child having sex at an early age. Conclusions Using a large national sample, this study confirms findings from previous studies showing gender differences in parent

  11. Effect of Callovo-Oxfordian clay rock on the dissolution rate of the SON68 simulated nuclear waste glass

    Energy Technology Data Exchange (ETDEWEB)

    Neeway, James J., E-mail: James.Neeway@pnnl.gov [SUBATECH, Unité Mixte de Recherche 6457, École des Mines de Nantes, CNRS/IN2P3, Université de Nantes, BP 20722, 44307 Nantes cedex 3 (France); Abdelouas, Abdesselam; Ribet, Solange; El Mendili, Yassine [SUBATECH, Unité Mixte de Recherche 6457, École des Mines de Nantes, CNRS/IN2P3, Université de Nantes, BP 20722, 44307 Nantes cedex 3 (France); Schumacher, Stéphan [ANDRA, Parc de la Croix Blanche, 1/7 rue Jean Monnet, 92298 Châtenay-Malabry (France); Grambow, Bernd [SUBATECH, Unité Mixte de Recherche 6457, École des Mines de Nantes, CNRS/IN2P3, Université de Nantes, BP 20722, 44307 Nantes cedex 3 (France)

    2015-04-15

    Long-term storage of high-level nuclear waste glass in France is expected to occur in an engineered barrier system (EBS) located in a subsurface Callovo-Oxfordian (COx) clay rock formation in the Paris Basin in northeastern France. Understanding the behavior of glass dissolution in the complex system is critical to be able to reliably model the performance of the glass in this complex environment. To simulate this multi-barrier repository scenario in the laboratory, several tests have been performed to measure glass dissolution rates of the simulated high-level nuclear waste glass, SON68, in the presence of COx claystone at 90 °C. Experiments utilized a High-Performance Liquid Chromatography (HPLC) pump to pass simulated Bure site COx pore water through a reaction cell containing SON68 placed between two COx claystone cores for durations up to 200 days. Silicon concentrations at the outlet were similar in all experiments, even the blank experiment with only the COx claystone (∼4 mg/L at 25 °C and ∼15 mg/L at 90 °C). The steady-state pH of the effluent, measured at room temperature, was roughly 7.1 for the blank and 7.3–7.6 for the glass-containing experiments demonstrating the pH buffering capacity of the COx claystone. Dissolution rates for SON68 in the presence of the claystone were elevated compared to those obtained from flow-through experiments conducted with SON68 without claystone in silica-saturated solutions at the same temperature and similar pH values. Additionally, through surface examination of the monoliths, the side of the monolith in direct contact with the claystone was seen to have a corrosion thickness 2.5× greater than the side in contact with the bulk glass powder. Results from one experiment containing {sup 32}Si-doped SON68 also suggest that the movement of Si through the claystone is controlled by a chemically coupled transport with a Si retention factor, K{sub d}, of 900 mL/g.

  12. CARBOHYDRATE-CONTAINING COMPOUNDS WHICH BIND TO CARBOHYDRATE BINDING RECEPTORS

    DEFF Research Database (Denmark)

    1995-01-01

    Carbohydrate-containing compounds which contain saccharides or derivatives thereof and which bind to carbohydrate binding receptors are useful in pharmaceutical products for treatment of inflammatory diseases and other diseases.......Carbohydrate-containing compounds which contain saccharides or derivatives thereof and which bind to carbohydrate binding receptors are useful in pharmaceutical products for treatment of inflammatory diseases and other diseases....

  13. The in vitro biological activity of the HLA-DR-binding clinical IgG4 antibody 1D09C3 is a consequence of the disruption of cell aggregates and can be abrogated by Fab arm exchange.

    NARCIS (Netherlands)

    Hansen, K.; Ruttekolk, I.R.R.; Glauner, H.B.; Becker, F.; Brock, R.E.; Hannus, S.

    2009-01-01

    Antibodies of the IgG4 subclass, directed against cell surface antigens have received attention as therapeutic molecules due to their poor induction of the complement system. The MHC class II-directed IgG4 antibody 1D09C3 has been explored for the treatment of lymphomas. The mechanism-of-action is s

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

    NARCIS (Netherlands)

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

    2003-01-01

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

  15. 75 FR 5359 - In the Matter of L. Luria & Son, Inc., Lew Corp. (n/k/a Questus Global Limited), Library Bureau...

    Science.gov (United States)

    2010-02-02

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION In the Matter of L. Luria & Son, Inc., Lew Corp. (n/k/a Questus Global Limited), Library Bureau... current and accurate information concerning the securities of L. Luria & Son, Inc. because it has...

  16. Activation of p38 and JNK MAPK pathways abrogates requirement for new protein synthesis for phorbol ester mediated induction of select MMP and TIMP genes.

    Science.gov (United States)

    Sampieri, Clara L; Nuttall, Robert K; Young, David A; Goldspink, Deborah; Clark, Ian M; Edwards, Dylan R

    2008-03-01

    The human matrix metalloproteinase (MMP) gene family includes 24 genes whose regulated expression, together with that of four tissue inhibitors of metalloproteinases (TIMPs), is essential in tissue remodelling and cell signalling. Quantitative real-time-PCR (qPCR) analysis was used to evaluate the shared and unique patterns of control of these two gene families in human MRC-5 and WI-38 fibroblasts in response to the protein kinase C (PKC) activator phorbol-12-myristate-13-acetate (PMA). The requirement for ongoing translation was analysed using three protein synthesis inhibitors, anisomycin, cycloheximide and emetine. PMA induced MMP1, 3, 8, 9, 10, 12, 13, 14 and TIMP1 and TIMP3 RNAs after 4-8 h, and induction of all except MMP9 and TIMP3 was blocked by all protein synthesis inhibitors. However, even though all inhibitors effectively blocked translation, PMA-induction of MMP9 and TIMP3 was blocked by emetine but was insensitive to cycloheximide and anisomycin. Anisomycin alone induced MMP9 and TIMP3, along with MMP25 and MMP19. The extracellular signal-regulated kinases (ERKs)-1/2 were strongly activated by PMA, while anisomycin activated the c-Jun N-terminal kinase (JNK) and p38 pathways, and cycloheximide activated p38, but emetine had no effect on the stress-activated mitogen-activated protein kinase (MAPK) pathways. The involvement of the p38 and JNK pathways in the selective effects of anisomycin and cycloheximide on MMP/TIMP expression was supported by use of pharmacological inhibitors. These data confirm that most inducible MMPs and TIMP1 behave as "late" activated, protein synthesis-dependent genes in fibroblasts. However, the requirement of protein synthesis for PMA-induction of MMPs and TIMPs is not universal, since it is abrogated for MMP9 and TIMP3 by stimulation of the stress-activated MAPK pathways. The definition of clusters of co-regulated genes among the two gene families will aid in bioinformatic dissection of control mechanisms.

  17. Depo-provera treatment does not abrogate protection from intravenous SIV challenge in female macaques immunized with an attenuated AIDS virus.

    Directory of Open Access Journals (Sweden)

    Meritxell Genescà

    Full Text Available BACKGROUND: In a previous study, progesterone treatment of female monkeys immunized with live, attenuated SHIV89.6 abrogated the generally consistent protection from vaginal simian immunodeficiency virus (SIV challenge. The mechanisms responsible for the loss of protection remain to be defined. The objective of the present study was to determine whether Depo-Provera administration alters protection from intravenous SIV challenge in SHIV-immunized female macaques. METHODS AND FINDINGS: Two groups of female macaques were immunized with attenuated SHIV89.6 and then challenged intravenously with SIVmac239. Four weeks before challenge, one animal group was treated with Depo-Provera, a commonly used injectable contraceptive progestin. As expected, SHIV-immunized monkeys had significantly lower peak and set-point plasma viral RNA levels compared to naïve controls, but in contrast to previously published findings with vaginal SIV challenge, the Depo-Provera SHIV-immunized animals controlled SIV replication to a similar, or even slightly greater, degree than did the untreated SHIV-immunized animals. Control of viral replication from week 4 to week 20 after challenge was more consistent in the progesterone-treated, SHIV-immunized animals than in untreated, SHIV-immunized animals. Although levels of interferon-gamma production were similar, the SIV-specific CD8(+ T cells of progesterone-treated animals expressed more functions than the anti-viral CD8(+ T cells from untreated animals. CONCLUSIONS: Depo-Provera did not diminish the control of viral replication after intravenous SIV challenge in female macaques immunized with a live-attenuated lentivirus. This result contrasts with the previously reported effect of Depo-Provera(R on protection from vaginal SIV challenge and strongly implies that the decreased protection from vaginal challenge is due to effects of progesterone on the genital tract rather than to systemic effects. Further, these results

  18. The BRCA1 variant p.Ser36Tyr abrogates BRCA1 protein function and potentially confers a moderate risk of breast cancer.

    Science.gov (United States)

    Christou, Charita M; Hadjisavvas, Andreas; Kyratzi, Maria; Flouri, Christina; Neophytou, Ioanna; Anastasiadou, Violetta; Loizidou, Maria A; Kyriacou, Kyriacos

    2014-01-01

    The identification of variants of unknown clinical significance (VUS) in the BRCA1 gene complicates genetic counselling and causes additional anxiety to carriers. In silico approaches currently used for VUS pathogenicity assessment are predictive and often produce conflicting data. Furthermore, functional assays are either domain or function specific, thus they do not examine the entire spectrum of BRCA1 functions and interpretation of individual assay results can be misleading. PolyPhen algorithm predicted that the BRCA1 p.Ser36Tyr VUS identified in the Cypriot population was damaging, whereas Align-GVGD predicted that it was possibly of no significance. In addition the BRCA1 p.Ser36Tyr variant was found to be associated with increased risk (OR = 3.47, 95% CI 1.13-10.67, P = 0.02) in a single case-control series of 1174 cases and 1109 controls. We describe a cellular system for examining the function of exogenous full-length BRCA1 and for classifying VUS. We achieved strong protein expression of full-length BRCA1 in transiently transfected HEK293T cells. The p.Ser36Tyr VUS exhibited low protein expression similar to the known pathogenic variant p.Cys61Gly. Co-precipitation analysis further demonstrated that it has a reduced ability to interact with BARD1. Further, co-precipitation analysis of nuclear and cytosolic extracts as well as immunofluorescence studies showed that a high proportion of the p.Ser36Tyr variant is withheld in the cytoplasm contrary to wild type protein. In addition the ability of p.Ser36Tyr to co-localize with conjugated ubiquitin foci in the nuclei of S-phase synchronized cells following genotoxic stress with hydroxyurea is impaired at more pronounced levels than that of the p.Cys61Gly pathogenic variant. The p.Ser36Tyr variant demonstrates abrogated function, and based on epidemiological, genetic, and clinical data we conclude that the p.Ser36Tyr variant is probably associated with a moderate breast cancer risk.

  19. La importancia del deporte y los eventos deportivos. ¿Son realmente dinamizadores socioeconómicos?

    OpenAIRE

    2015-01-01

    El deporte es una industria muy potente y transversal que genera muchos beneficios económicos y sociales. Uno de los grandes responsables de que el deporte produzca beneficios en la economía así como en la sociedad son los eventos deportivos. En el presente documento se introducirá el deporte como sector económico para tener una idea de lo amplio que es, quien interviene y hacia dónde se dirige; se analizará el impacto socioeconómico de los grandes eventos deportivos, aquellos eventos globale...

  20. Indicadores regionales de desarrollo sustentable en Chile: ¿Hasta qué punto son útiles y necesarios?

    Directory of Open Access Journals (Sweden)

    Hernán Blanco

    2001-09-01

    Full Text Available Cada vez más necesitamos maneras de asegurar patrones de desarrollo que sean sustentables, es decir, que sean ambiental, social y económicamente apropiados para nosotros y para las generaciones venideras. Los indicadores de desarrollo sustentable son una herramienta promisoria que permitiría "aterrizar" el concepto de sustentabilidad, apoyando la manera en que se toman las decisiones. En Chile existen pocas experiencias sobre el tema. Este artículo presenta el trabajo realizado para desarrollar indicadores de desarrollo sustentable en cuatro regiones del país. El artículo se centra en las lecciones que han surgido de la experiencia

  1. Sons of the Buddha. Continuities and Ruptures in a Burmese Monastic Tradition, Jason A. Carbine

    Directory of Open Access Journals (Sweden)

    Guillaume Rozenberg

    2012-11-01

    Full Text Available Version sensiblement remaniée d’une thèse de doctorat, l’ouvrage de Jason Carbine envisage la « culture religieuse bouddhique birmane » sous l’angle de l’institution monastique, de ses représentations et de ses rouages. Il se concentre sur une branche particulière de la communauté monastique birmane, la branche Shwegyin, du nom du village natal de son fondateur, le moine Ashin Jāgara (1822-1894. Cette branche, établie vers 1860, comptait 40 000 membres (novices et moines en 1999, soit 10 % ...

  2. Activation and transfer of sulfate in biological systems (1960); Activation biologique du sulfate et son transfert (1960)

    Energy Technology Data Exchange (ETDEWEB)

    Chapeville, F. [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

    1960-07-01

    It examines in this review the successive stages of active sulfate formation and its role in biological synthesis of sulfuric esters. The possible role of active sulfate as intermediary in sulfate reduction is also discussed. (author) [French] On examine dans cette etude les stades successifs de la mise en evidence du sulfate actif, son role dans la formation des esters sulfuriques de natures diverses, ainsi que sa participation eventuelle comme intermediaire au cours de la reduction du sulfate. On decrit aussi un procede de preparation du systeme biologique, generateur du sulfate actif et une methode de synthese chimique. (auteur)

  3. In the Name of the Son (and the Daughter): Intergenerational Mobility in the United States, 1850-1930

    OpenAIRE

    2013-01-01

    This paper provides a new perspective on intergenerational mobility in the United States in the late 19th and early 20th centuries. We devise an empirical strategy that allows to calculate intergenerational elasticities between fathers and children of both sexes. The key insight of our approach is that the information about socio-economic status conveyed by first names can be used to create a pseudo-link not only between fathers and sons, but also between fathers and daughters. The latter is ...

  4. "Daughter and son: a completely different story”? Gender as a moderator of the relationship between sexism and parental attitudes

    Directory of Open Access Journals (Sweden)

    Małgorzata Lipowska

    2016-09-01

    Full Text Available Background During childhood, parents are the first and most important individuals who form the base of the content of gender stereotypes in children. A parent’s expectations about the extent a child’s behaviour should be line with gender stereotypes also depends on the intensity of a parent’s sexism. A parent’s sexism may be exhibited in parental attitudes. Hence, in our study we analysed the relationship between parental ambivalent sexism and parental attitudes within dyads of mothers and fathers with a special focus on the role of the gender of both parents and children. Participants and procedure Two hundred and ninety-four couples of parents of five-year-olds (153 girls, 141 boys participated. The Ambivalent Sexism Inventory (ASI was used to measure levels of sexism, and the Parental Attitudes Scale (SPR was used to assess parental attitudes. Results In terms of the profile of parental attitudes, regardless of the child’s sex, mothers and fathers scored highest for inconsequent and demanding attitudes, and lowest for overprotective and autonomy attitudes. The child’s sex is also not important for the overall levels of parents’ sexism – fathers exhibit higher levels of hostile sexism in comparison to mothers. Only the mothers’ education level is important for levels of sexism – women with higher education exhibited the lowest levels of hostile sexism. The child’s sex moderates relationships between parents’ sexism and parental attitudes. In the case of mothers of sons, the intensity of benevolent sexism is negatively related to overprotective and demanding attitudes. The more educated the mothers of sons, the more demanding they were. For fathers of sons, the inconsequence attitude increases under the influence of both hostile and benevolent sexism. Among fathers of daughters, hostile sexism strengthens the overprotective attitude, while levels of both benevolent and hostile sexism as well as education influence the

  5. "Los homosexuales no son como los champiñones. El problema del anacronismo en Historia de las Ciencias"

    OpenAIRE

    Vázquez García, Francisco

    2013-01-01

    Consideramos en principio que, del mismo modo que una persona puede caracterizarse por el color de su pelo o de sus ojos, puede ser también clasificada a partir de su “orientación sexual”, siendo así heterosexual, homosexual o bisexual. Es decir, estimamos que la orientación sexual es un rasgo “natural”, de modo que homosexuales, heterosexuales y bisexuales son otros tantos objetos naturales, del mismo modo que las manzanas, las piñas o los champiñones. Por eso, los biólogos que estudian el c...

  6. Assessment of snapper (Pagrus auratus) natural IgM binding to bromelain treated sheep erythrocytes.

    Science.gov (United States)

    Morrison, Richard N; Bruce Lyons, A; Nowak, Barbara F; Hayball, John D

    2005-01-01

    Normal snapper (Pagrus auratus Bloch and Schneider) serum was examined for natural IgM that binds to protease (bromelain) treated sheep erythrocytes (BrSRBC) in a model assay system that has been used to appraise natural IgM of various mammals. Normal snapper serum lysed BrSRBC while haemolysis was abrogated by heat inactivation of serum and in divalent cation-deficient conditions, indicative of classical complement mediated lysis. In addition, heat inactivated normal snapper serum agglutinated BrSRBC while phosphatidylcholine (PtC) liposomes partially inhibited both haemolysis and agglutination. Inhibition of haemolysis and agglutination may have been mediated by an interaction between immunoglobulin (Ig) and PtC as protein A purified snapper Ig bound to PtC liposomes. However it is not known if this binding was PtC specific nor if the binding was initiated by either the Fab and/or Fc domains of snapper Ig. BrSRBC plaque forming cells (PFC) were detected in the peritoneal cavity, spleen, head kidney and peripheral blood of normal snapper. The greatest proportion of BrSRBC PFC per B cell was within the peritoneal cavity followed by the spleen, peripheral blood and head kidney. Together, these data suggest that normal snapper serum may contain natural Ig that binds BrSRBC, activating the classical complement cascade.

  7. Universal stress protein Rv2624c alters abundance of arginine and enhances intracellular survival by ATP binding in mycobacteria

    Science.gov (United States)

    Jia, Qiong; Hu, Xinling; Shi, Dawei; Zhang, Yan; Sun, Meihao; Wang, Jianwei; Mi, Kaixia; Zhu, Guofeng

    2016-01-01

    The universal stress protein family is a family of stress-induced proteins. Universal stress proteins affect latency and antibiotic resistance in mycobacteria. Here, we showed that Mycobacterium smegmatis overexpressing M. tuberculosis universal stress protein Rv2624c exhibits increased survival in human monocyte THP-1 cells. Transcriptome analysis suggested that Rv2624c affects histidine metabolism, and arginine and proline metabolism. LC-MS/MS analysis showed that Rv2624c affects the abundance of arginine, a modulator of both mycobacteria and infected THP-1 cells. Biochemical analysis showed that Rv2624c is a nucleotide-binding universal stress protein, and an Rv2624c mutant incapable of binding ATP abrogated the growth advantage in THP-1 cells. Rv2624c may therefore modulate metabolic pathways in an ATP-dependent manner, changing the abundance of arginine and thus increasing survival in THP-1 cells. PMID:27762279

  8. Cell surface syndecan-1 contributes to binding and function of macrophage migration inhibitory factor (MIF) on epithelial tumor cells.

    Science.gov (United States)

    Pasqualon, Tobias; Lue, Hongqi; Groening, Sabine; Pruessmeyer, Jessica; Jahr, Holger; Denecke, Bernd; Bernhagen, Jürgen; Ludwig, Andreas

    2016-04-01

    Surface expressed proteoglycans mediate the binding of cytokines and chemokines to the cell surface and promote migration of various tumor cell types including epithelial tumor cells. We here demonstrate that binding of the chemokine-like inflammatory cytokine macrophage migration inhibitory factor (MIF) to epithelial lung and breast tumor cell lines A549 and MDA-MB231 is sensitive to enzymatic digestion of heparan sulphate chains and competitive inhibition with heparin. Moreover, MIF interaction with heparin was confirmed by chromatography and a structural comparison indicated a possible heparin binding site. These results suggested that proteoglycans carrying heparan sulphate chains are involved in MIF binding. Using shRNA-mediated gene silencing, we identified syndecan-1 as the predominant proteoglycan required for the interaction with MIF. MIF binding was decreased by induction of proteolytic shedding of syndecan-1, which could be prevented by inhibition of the metalloproteinases involved in this process. Finally, MIF induced the chemotactic migration of A549 cells, wound closure and invasion into matrigel without affecting cell proliferation. These MIF-induced responses were abrogated by heparin or by silencing of syndecan-1. Thus, our study indicates that syndecan-1 on epithelial tumor cells promotes MIF binding and MIF-mediated cell migration. This may represent a relevant mechanism through which MIF enhances tumor cell motility and metastasis.

  9. Selective toxicity of MKT-077 to cancer cells is mediated by its binding to the hsp70 family protein mot-2 and reactivation of p53 function.

    Science.gov (United States)

    Wadhwa, R; Sugihara, T; Yoshida, A; Nomura, H; Reddel, R R; Simpson, R; Maruta, H; Kaul, S C

    2000-12-15

    MKT-077, a cationic rhodacyanine dye analogue has been under preclinical cancer therapeutical trials because of its selective toxicity to cancer cells. Its cellular targets and mechanism of action remain poorly understood. Here we report that MKT-077 binds to an hsp70 family member, mortalin (mot-2), and abrogates its interactions with the tumor suppressor protein, p53. In cancer cells, but not in normal cells, MKT-077 induced release of wild-type p53 from cytoplasmically sequestered p53-mot-2 complexes and rescued its transcriptional activation function. Thus, MKT-077 may be particularly useful for therapy of cancers with wild-type p53.

  10. Binding of thrombin-activated platelets to a fibrin scaffold through α(IIbβ₃ evokes phosphatidylserine exposure on their cell surface.

    Directory of Open Access Journals (Sweden)

    Tomasz Brzoska

    Full Text Available Recently, by employing intra-vital confocal microscopy, we demonstrated that platelets expose phosphatidylserine (PS and fibrin accumulate only in the center of the thrombus but not in its periphery. To address the question how exposure of platelet anionic phospholipids is regulated within the thrombus, an in-vitro experiment using diluted platelet-rich plasma was employed, in which the fibrin network was formed in the presence of platelets, and PS exposure on the platelet surface was analyzed using Confocal Laser Scanning Microscopy. Almost all platelets exposed PS after treatment with tissue factor, thrombin or ionomycin. Argatroban abrogated fibrin network formation in all samples, however, platelet PS exposure was inhibited only in tissue factor- and thrombin-treated samples but not in ionomycin-treated samples. FK633, an α(IIbβ₃ antagonist, and cytochalasin B impaired platelet binding to the fibrin scaffold and significantly reduced PS exposure evoked by thrombin. Gly-Pro-Arg-Pro amide abrogated not only fibrin network formation, but also PS exposure on platelets without suppressing platelet binding to fibrin/fibrinogen. These results suggest that outside-in signals in platelets generated by their binding to the rigid fibrin network are essential for PS exposure after thrombin treatment.

  11. Terms of Binding

    NARCIS (Netherlands)

    Sevcenco, A.

    2006-01-01

    The present dissertation aimed at achieving two goals. First, it constitutes an attempt to widen the search for phenomena that bear relevance to the idea that binding has a syntactic residue and is not, therefore, an exclusively semantic matter. Second, it tried to provide the technical means to acc

  12. Binding and Bulgarian

    NARCIS (Netherlands)

    Schürcks-Grozeva, Lilia Lubomirova

    2003-01-01

    In haar proefschrift analyseert Lilia Schürcks de anaforische verschijnselen in de Bulgaarse taal. Het gaat dan om wederkerende aspecten, uitgedrukt bij woorden als ‘zich’ en ‘elkaar’. De situatie in het Bulgaars blijkt moeilijk in te passen in de klassieke Binding Theory van Noam Chomsky. Bron: RUG

  13. MD-2 binds cholesterol.

    Science.gov (United States)

    Choi, Soo-Ho; Kim, Jungsu; Gonen, Ayelet; Viriyakosol, Suganya; Miller, Yury I

    2016-02-19

    Cholesterol is a structural component of cellular membranes, which is transported from liver to peripheral cells in the form of cholesterol esters (CE), residing in the hydrophobic core of low-density lipoprotein. Oxidized CE (OxCE) is often found in plasma and in atherosclerotic lesions of subjects with cardiovascular disease. Our earlier studies have demonstrated that OxCE activates inflammatory responses in macrophages via toll-like receptor-4 (TLR4). Here we demonstrate that cholesterol binds to myeloid differentiation-2 (MD-2), a TLR4 ancillary molecule, which is a binding receptor for bacterial lipopolysaccharide (LPS) and is indispensable for LPS-induced TLR4 dimerization and signaling. Cholesterol binding to MD-2 was competed by LPS and by OxCE-modified BSA. Furthermore, soluble MD-2 in human plasma and MD-2 in mouse atherosclerotic lesions carried cholesterol, the finding supporting the biological significance of MD-2 cholesterol binding. These results help understand the molecular basis of TLR4 activation by OxCE and mechanisms of chronic inflammation in atherosclerosis.

  14. Sequential memory: Binding dynamics

    Science.gov (United States)

    Afraimovich, Valentin; Gong, Xue; Rabinovich, Mikhail

    2015-10-01

    Temporal order memories are critical for everyday animal and human functioning. Experiments and our own experience show that the binding or association of various features of an event together and the maintaining of multimodality events in sequential order are the key components of any sequential memories—episodic, semantic, working, etc. We study a robustness of binding sequential dynamics based on our previously introduced model in the form of generalized Lotka-Volterra equations. In the phase space of the model, there exists a multi-dimensional binding heteroclinic network consisting of saddle equilibrium points and heteroclinic trajectories joining them. We prove here the robustness of the binding sequential dynamics, i.e., the feasibility phenomenon for coupled heteroclinic networks: for each collection of successive heteroclinic trajectories inside the unified networks, there is an open set of initial points such that the trajectory going through each of them follows the prescribed collection staying in a small neighborhood of it. We show also that the symbolic complexity function of the system restricted to this neighborhood is a polynomial of degree L - 1, where L is the number of modalities.

  15. Cellulose binding domain proteins

    Science.gov (United States)

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc; Doi, Roy

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  16. ¿Qué hogares colombianos son pobres? una aproximación desde la ECV del 2003

    Directory of Open Access Journals (Sweden)

    Adriana Carolina Silva Arias

    2007-01-01

    Full Text Available Este artículo analizó los conceptos y medidas de pobreza. A partir de esta perspectiva, se estudió quiénes son pobres en Colombia y qué características de los hogares determinan dicha condición para el 2003. A partir de la Encuesta de Calidad de Vida, se realizó un análisis logit para identifi car y medir la incidencia de algunos factores en la probabilidad de que un hogar sea clasifi cado como pobre. Estas estimaciones mostraron que los hogares que tienen más probabilidad de considerarse como pobres son aquellos en los que los jefes de hogar eran analfabetas, mujeres, los que se ocuparon en labores agrícolas o que hacían parte de alguna etnia. Adicionalmente, se encontró que los hogares que tenían menores de 12 años tuvieron más de probabilidad de ser pobres. Finalmente, los hogares cuyo jefe de hogar tenía mayor nivel educativo, tenían menor probabilidad de ser pobres, siendo mayor el efecto educativo de su cónyuge.

  17. Application of the GRAAL model to leaching experiments with SON68 nuclear glass in initially pure water

    Energy Technology Data Exchange (ETDEWEB)

    Frugier, P., E-mail: pierre.frugier@cea.f [CEA Marcoule, DTCD/SECM/LCLT, BP 17171, 30207 Bagnols-sur-Ceze Cedex (France); Chave, T. [ICSM Site de Marcoule, DEN/MAR/ICSM/LSFC, UMR 5257, BP 17171, 30207 Bagnols-sur-Ceze Cedex (France); Gin, S. [CEA Marcoule, DTCD/SECM/LCLT, BP 17171, 30207 Bagnols-sur-Ceze Cedex (France); Lartigue, J.-E. [CEA Cadarache, DEN/CAD/DTN/SMTM/LMTE, 13108 Saint-Paul-Lez-Durance Cedex (France)

    2009-08-01

    Based on a review of the current state of knowledge concerning the aqueous alteration of SON68 nuclear glass we have proposed a mechanistic model, GRAAL (Glass Reactivity with Allowance for the Alteration Layer) [P. Frugier, S. Gin, Y. Minet, T. Chave, B. Bonin, N. Godon, J.E. Lartigue, P. Jollivet, A. Ayral, L. De Windt, G. Santarini, J. Nucl. Mater. 380 (2008) 8]. This article describes how the GRAAL model hypotheses are solved using a calculation code coupling chemistry and transport. The geochemical solution of this model combines three major phenomena: chemical equilibria in solution, water and ion transport by convection or diffusion, and element diffusion through the passivating reactive interphase. The model results are compared with experimental data for SON68 glass leached in initially pure water both in a closed system and in renewed media. The comparison shows the model very satisfactorily accounts for variations in the pH and the element concentrations in solution as a function of time, the glass surface area in contact with solution, and the solution renewal rate. This success is due to the fact that the diffusion of elements through the alteration gel is taken into account in the model. This mechanism cannot be disregarded under most experimental conditions - if only to predict the solution pH - and must therefore be an integral part of the geochemical model.

  18. Expression of Multiple Sexual Signals by Fathers and Sons in the East-Mediterranean Barn Swallow: Are Advertising Strategies Heritable?

    Science.gov (United States)

    Vortman, Yoni; Safran, Rebecca J.; Reiner Brodetzki, Tali; Dor, Roi; Lotem, Arnon

    2015-01-01

    The level of expression of sexually selected traits is generally determined by genes, environment and their interaction. In species that use multiple sexual signals which may be costly to produce, investing in the expression of one sexual signal may limit the expression of the other, favoring the evolution of a strategy for resource allocation among signals. As a result, even when the expression of sexual signals is condition dependent, the relative level of expression of each signal may be heritable. We tested this hypothesis in the East-Mediterranean barn swallow (Hirundo rustica transitiva), in which males have been shown to express two uncorrelated sexual signals: red-brown ventral coloration, and long tail streamers. We show that variation in both signals may partially be explained by age, as well as by paternal origin (genetic father-son regressions), but that the strongest similarity between fathers and sons is the relative allocation towards one trait or the other (relative expression index), rather than the expression of the traits themselves. These results suggest that the expression of one signal is not independent of the other, and that genetic strategies for resource allocation among sexual signals may be selected for during the evolution of multiple sexual signals. PMID:25679206

  19. Expression of multiple sexual signals by fathers and sons in the East-Mediterranean barn swallow: are advertising strategies heritable?

    Directory of Open Access Journals (Sweden)

    Yoni Vortman

    Full Text Available The level of expression of sexually selected traits is generally determined by genes, environment and their interaction. In species that use multiple sexual signals which may be costly to produce, investing in the expression of one sexual signal may limit the expression of the other, favoring the evolution of a strategy for resource allocation among signals. As a result, even when the expression of sexual signals is condition dependent, the relative level of expression of each signal may be heritable. We tested this hypothesis in the East-Mediterranean barn swallow (Hirundo rustica transitiva, in which males have been shown to express two uncorrelated sexual signals: red-brown ventral coloration, and long tail streamers. We show that variation in both signals may partially be explained by age, as well as by paternal origin (genetic father-son regressions, but that the strongest similarity between fathers and sons is the relative allocation towards one trait or the other (relative expression index, rather than the expression of the traits themselves. These results suggest that the expression of one signal is not independent of the other, and that genetic strategies for resource allocation among sexual signals may be selected for during the evolution of multiple sexual signals.

  20. SON 68 nuclear glass alteration kinetics between pH 7 and pH 11.5

    Science.gov (United States)

    Gin, S.; Mestre, J. P.

    2001-05-01

    The effect of the pH was investigated on the mechanisms of SON 68 (R7T7-type) glass alteration under `saturation' conditions in order to delimit the pH range within which a stable, protective gel is formed. Static experiments were conducted at 90°C with an S/ V ratio of 50 cm-1 at various imposed pH values: 7, 8, 9.5, 10, 10.5, 11 and 11.5. An additional experiment was conducted with no restriction on the pH. The kinetic study showed that a protective gel formed in all the test media, although its stability was pH-dependent: at pH 11 or higher, the precipitation of a potassium and sodium aluminosilicate led to the degradation of the gel and the lose of its protective properties. This phenomenon resulted in renewed glass alteration, leading to complete and rapid degradation of the glass into alteration products. The aluminosilicate precipitation was found to be limited by the solubility of aluminum. Below pH 10, this type of secondary phase is unlikely to precipitate and the gel should remain stable. This study, based on thermodynamic and kinetic considerations, suggests that aqueous alteration of the French SON 68 nuclear glass results in the formation of a protective gel with long-term stability between pH 7 and pH 10.

  1. Aging parents' caregiving and rehabilitating a brain-injured son: an autoethnography of a 10-year journey.

    Science.gov (United States)

    Hassan, Syed Tajuddin Syed; Jamaludin, Husna

    2014-01-01

    This autoethnography withdraws from information accumulated through a 10-year period of daily-weekly-monthly descriptive observation-recording (triangulated- parents & house-helper) of caregiving and rehabilitating of our brain injured son (survivor/care-receiver). We present it as an interactive voice of verbal conversation, thoughts, insights, and interpretations. It is delivered as a series of articulation intra-pulsated with our interrogation of societal-cultural-religious perspectives, norms and biases, and aligns with the CAP (Creative Analytical Practices) method of Ellis. This autoethnography glows from the richness of information which encapsulates the challenges confronting us the aging parent caregivers, the gradual incremental mind mending achievement of our son, and the interactive verbalizations and thoughts, of the caregivers, care-receiver, and other persons. The overwhelming mental and physical pain and struggle of the survivor and the aging caregivers and their sense of celebratory-satisfaction with rehabilitation progress are highlighted. Interpretation and valuation of positive and negative responses of other persons provide a critical matrix to this autoethnography. We intend to inform other caregivers and relevant healthcare professionals through this autoethnography.

  2. Aging parents’ caregiving and rehabilitating a brain-injured son: an autoethnography of a 10-year journey

    Science.gov (United States)

    Hassan, Syed Tajuddin Syed; Jamaludin, Husna

    2014-01-01

    This autoethnography withdraws from information accumulated through a 10-year period of daily-weekly-monthly descriptive observation-recording (triangulated- parents & house-helper) of caregiving and rehabilitating of our brain injured son (survivor/care-receiver). We present it as an interactive voice of verbal conversation, thoughts, insights, and interpretations. It is delivered as a series of articulation intra-pulsated with our interrogation of societal-cultural-religious perspectives, norms and biases, and aligns with the CAP (Creative Analytical Practices) method of Ellis. This autoethnography glows from the richness of information which encapsulates the challenges confronting us the aging parent caregivers, the gradual incremental mind mending achievement of our son, and the interactive verbalizations and thoughts, of the caregivers, care-receiver, and other persons. The overwhelming mental and physical pain and struggle of the survivor and the aging caregivers and their sense of celebratory-satisfaction with rehabilitation progress are highlighted. Interpretation and valuation of positive and negative responses of other persons provide a critical matrix to this autoethnography. We intend to inform other caregivers and relevant healthcare professionals through this autoethnography. PMID:25763170

  3. Megalin binds and mediates cellular internalization of folate binding protein

    DEFF Research Database (Denmark)

    Birn, Henrik; Zhai, Xiaoyue; Holm, Jan;

    2005-01-01

    Folate is an essential vitamin involved in a number of biological processes. High affinity folate binding proteins (FBPs) exist both as glycosylphosphatidylinositol-linked, membrane associated folate binding proteins and as soluble FBPs in plasma and some secretory fluids such as milk, saliva...... to bind and mediate cellular uptake of FBP. Surface plasmon resonance analysis shows binding of bovine and human milk FBP to immobilized megalin, but not to low density lipoprotein receptor related protein. Binding of (125)I-labeled folate binding protein (FBP) to sections of kidney proximal tubule, known...

  4. Targeting of MAPK-associated molecules identifies SON as a prime target to attenuate the proliferation and tumorigenicity of pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Furukawa Toru

    2012-12-01

    Full Text Available Abstract Background Pancreatic cancer is characterized by constitutive activation of mitogen-activated protein kinase (MAPK. Activation of MAPK is associated with the upregulation of genes implicated in the proliferation and survival of pancreatic cancer cells. We hypothesized that knockdown of these MAPK-associated molecules could produce notable anticancer phenotypes. Methods A RNA interference-mediated knockdown screening of 78 MAPK-associated molecules previously identified was performed to find molecules specifically associated with proliferation of pancreatic cancer cells in vitro. Expression of an identified molecule in pancreatic cancer tissues was examined by immunohistochemistry. In vivo tumorigenicity of cancer cells with stable knockdown of the molecule was assayed by using xenograft models. Flow cytometry and live cell imaging were employed to assess an association of the molecule with cell cycle. Results The knockdown screening revealed that knockdown of SON, the gene encoding SON, which is a large serine/arginine-rich protein involved in RNA processing, substantially suppressed pancreatic cancer cell proliferation and survival in vitro and tumorigenicity in vivo. SON expression was higher in ductal adenocarcinomas than in cells of normal ducts and precursor lesions in pancreatic cancer tissues. Knockdown of SON induced G2/M arrest and apoptosis in cultured cancer cells. The suppressive effect of SON knockdown on proliferation was less pronounced in cultured normal duct epithelial cells. SON formed nuclear speckles in the interphase of the cell cycle and dispersed in the cytoplasm during mitosis. Live cell imaging showed that SON diffusely dispersed in the early mitotic phase, accumulated in some foci in the cytoplasm in the late mitotic phase, and gradually reassembled into speckles after mitosis. Conclusion These results indicate that SON plays a critical role in the proliferation, survival, and tumorigenicity of pancreatic

  5. It Is Necessary to Abrogate All the International Basic Standards of Seals%必需废除所有国际密封基础标准

    Institute of Scientific and Technical Information of China (English)

    徐长祥; 张晓忠; 陈佑军

    2016-01-01

    According to the definitions in the international standard JCGM 200,physical quanti-ties are the quantifiable properties of phenomenon,obj ect,or material,which could be classified into two - basic quantity and export quantity.Basic quantity cannot be the one expressed by u-sing other quantity,and the export quantity is the one defined by using the basic quantity in its system,and the basic quantity and export quantity in its system are correlated with through law and its equation.In unit on international system,the sealing tightness,the leakage resistance,is the exported quantity established by sealing or leakage,and is the product of time t and pressure p,the time which is consumed by the leaked unit volume fluid in pressure vessel under constant pressure or in the system through sealed joint.Absolutely,it is not the reciprocal of “leakage rate”fabricated in existing international standard.The difference of inner pipe flow routing,the external obj ect flow routing and leakage flow routing is only their flow (leakage)resistance and reactance.It is hardly to make difference and control flow routing before the leakage resistance and reactance unknown.The international sealing basic standard has been set up under the condi-tion of the leakage resistance (tightness)and qualified sealing unknown,and thence how to de-sign,install and acceptance inspection of sealing.So,the basic standard cannot be relied upon to provide efficient control of pressure or system leakage.It is the must to abrogate it in a quick ac-tion.%按照国际标准JCGM 200定义,物理量是现象、物体或物质的可量化属性,可以分为基本量和导出量两种;基本量是不可用其它量表达的量,导出量是可用其系统基本量定义的量;系统内的基本量和导出量可以通过定律及其方程进行相关联。在国际单位制中,密封紧密度即漏阻是由密封或泄漏定律确立的导出量,是恒压状态下压力容器或系统穿过密

  6. Surface localization of high-mobility group nucleosome-binding protein 2 on leukemic B cells from patients with chronic lymphocytic leukemia is related to secondary autoimmune hemolytic anemia.

    Science.gov (United States)

    Morande, Pablo E; Borge, Mercedes; Abreu, Cecilia; Galletti, Jeremías; Zanetti, Samanta R; Nannini, Paula; Bezares, Raimundo F; Pantano, Sergio; Dighiero, Guillermo; Oppezzo, Pablo; Gamberale, Romina; Giordano, Mirta

    2015-04-01

    Chronic lymphocytic leukemia (CLL) is the main cause of autoimmune hemolytic anemia (AHA). However, the cellular basis underlying this strong association remains unclear. We previously demonstrated that leukemic B cells from patients with CLL recognize the erythrocyte protein Band 3, a prevalent autoantigen in AHA. Here we show that the major binding site of Band 3 on leukemic cells is an extrinsic protein identified as high-mobility group nucleosome binding protein 2 (HMGN2), a nucleosome-interacting factor which has not been previously reported at the cell surface. T lymphocytes do not express HMGN2 or bind Band 3. Removal of HMGN2 from the cell membrane abrogated the capacity of Band 3-pulsed CLL cells to induce CD4 + T cell proliferation. We conclude that surface HMGN2 in leukemic B cells is involved in Band 3 binding, uptake and presentation to CD4 + T lymphocytes, and as such may favor the initiation of AHA secondary to CLL.

  7. Red Son Rising.

    Science.gov (United States)

    Arnold, Adele R.

    Among the Native Americans, few tribes were as warlike as the Apaches of the Southwest. The courage and ferocity of Apache warriors like Geronimo, Cochise, Victorio, and Mangas Coloradas is legendary. Based on a true story, this book is about an Apache boy who was captured by an enemy tribe and sold to a white man. Carlos Gentile, a photographer…

  8. Sons & Lumieres / Ivar Jung

    Index Scriptorium Estoniae

    Jung, Ivar

    2004-01-01

    Näitus "Hääl ja valgus" Pariisi Pompidou keskuses 22. IX 2004-3. I 2005. Väljas on 99 kunstniku (Paul Klee, Frantishek Kupka, Vassili Kandinsky, Laszlo Moholy-Nagy, Raoul Hausmann, Bill Viola, Robert Rauschenberg, Joseph Beuys, Rodney Graham jne.) tööd ajavahemikust 1910-2004. Kuraatorid Sophie Duplaix ja Marcella Lista

  9. Vider son Verdun trait

    Directory of Open Access Journals (Sweden)

    Olivier Parenteau

    2009-09-01

    Full Text Available « Le bataillon, fleuri comme un grand cimetière,avait traversé la ville à la débandade. »Roland Dorgelès, Les Croix de boisLa trahison des poètesEn France, comme ce fut le cas dans toutes les sociétés belligérantes, la Première Guerre mondiale a engendré la production d’un important arsenal de textes poétiques. Cet engouement lyrique, qui s’est manifesté dès les premiers jours d’août 1914, s’est maintenu tout au long du conflitet n’a pas perdu de sa vigueur aussitôt les armes déposées. Ces po...

  10. Sweet Sorrow's Son.

    Science.gov (United States)

    Brothers, Deborah

    1997-01-01

    Presents an award-winning essay about a teacher's relationship with a troubled student placed in his alternative classroom. Shows how the two worked together on science, math, and "Romeo and Juliet." (TB)

  11. Sensitive mother-to-adolescent disclosures after divorce: is the experience of sons different from that of daughters?

    Science.gov (United States)

    Koerner, Susan Silverberg; Wallace, Sara; Lehman, Stephanie Jacobs; Lee, Sun-A; Escalante, Kristine A

    2004-03-01

    This study addressed two main questions: (a) Are adolescent sons and daughters exposed to sensitive maternal disclosures after divorce with similar frequency and in similar detail? and (b) Does gender act as a moderator in the association between maternal disclosures and adolescent adjustment difficulties? Forced-choice and open-ended data were collected from 194 adolescents within 2 years after their parents' divorce. Quantitative analyses revealed that although the majority of adolescents experience some level of maternal disclosure, neither frequency nor detail of maternal disclosure differed as a function of adolescent gender. Frequent and detailed maternal disclosures were associated with adolescent adjustment difficulties, primarily psychological distress. Gender did not moderate that significant association. Qualitative analysis shed light on the link between maternal disclosures and adolescent distress, suggested the importance of how disclosures are made, and revealed several gender differences in reactions to maternal disclosures. Implications of the findings are discussed.

  12. Différences inter-individuelles en latéralisation de sons basse fréquence

    OpenAIRE

    Savel, Sophie

    2010-01-01

    National audience; La plupart des études sur la localisation auditive en champ libre ou la latéralisation au casque ont été menées sur un très faible effectif d'auditeurs, sur-entraînés à la tâche. Nous avons récemment décelé d'importantes différences entre 50 individus naïfs dans la capacité à localiser un son basse fréquence en champ libre, et identifié un lien entre sexe ou latéralité manuelle et asymétrie gauche/droite de cette capacité (Savel, 2009, Hearing Research). Dans l'étude présen...

  13. Integrable String Models in Terms of Chiral Invariants of SU(n, SO(n, SP(n Groups

    Directory of Open Access Journals (Sweden)

    Victor D. Gershun

    2008-05-01

    Full Text Available We considered two types of string models: on the Riemmann space of string coordinates with null torsion and on the Riemman-Cartan space of string coordinates with constant torsion. We used the hydrodynamic approach of Dubrovin, Novikov to integrable systems and Dubrovin solutions of WDVV associativity equation to construct new integrable string equations of hydrodynamic type on the torsionless Riemmann space of chiral currents in first case. We used the invariant local chiral currents of principal chiral models for SU(n, SO(n, SP(n groups to construct new integrable string equations of hydrodynamic type on the Riemmann space of the chiral primitive invariant currents and on the chiral non-primitive Casimir operators as Hamiltonians in second case. We also used Pohlmeyer tensor nonlocal currents to construct new nonlocal string equation.

  14. La segregación residencial urbana en estudios latinoamericanos y bogotanos. ¿Son necesarias nuevas miradas?

    Directory of Open Access Journals (Sweden)

    Esperanza Cifuentes Ardila

    2015-12-01

    Full Text Available En América Latina, las lecturas sobre la segregación residencial urbana concluyen que las ciudades de la región son ámbitos territoriales segregados por razones económicas: las inequidades se expresan en la organización urbana. Este artículo tiene como propósito mostrar que, incluso en regiones tan desiguales como la nuestra, la estructura simbólica incide en la configuración de la segregación residencial urbana, pues la valoración que los agentes sociales dan a determinados lugares y grupos humanos es decisiva para su localización en el espacio urbano.

  15. Giving birth to life--again!: bereaved parents' experiences with children born following the death of an adult son.

    Science.gov (United States)

    Hamama-Raz, Yaira; Rosenfeld, Sarah; Buchbinder, Eli

    2010-01-01

    This article is based on a qualitative study examining the experiences of parents that lost a son during military service in Israel and consequently choose to give birth to another child. Seven couples and 3 mothers were interviewed for the study, and their interviews were analyzed using a phenomenological-hermeneutic approach. Three main themes were extracted from parents' descriptions of their experiences: (a) "From the place where pain and sadness was sown, a new smile was grown," relating to transforming the experience of loss into a new meaning for life; (b) "No to a child memorial," focusing on parents' awareness of the burden placed on the child who was born; and (c) "Different parenting," dealing with participant's parenting following their loss. The study's findings are discussed in the context of literature dealing with reconstructing meaning through coping and bereavement.

  16. Action audio-visual for the promotion of between mother attachment seropositivity for HIV and his son

    Directory of Open Access Journals (Sweden)

    Camila Nayane de Carvalho Lima

    2012-09-01

    Full Text Available The study aimed at evaluating the effects of the educational video use to promote the attachment between HIV positive mother and her son after six months of contact between them.This is an exploratory-descriptive study with a qualitative approach. Data was collected through semi-structured interviews. The sampling was intentional. The plan of analysis consisted of the following steps: the constitution of the corpus, definition of unit analysis, data categorization and analysis through categories. This study showed that, despite the difficulties and obstacles imposed by HIV / AIDS, by the treatment and the doubts present in daily life, HIV mothers develop strategies that enable them to live and better deal with the disease, without forgetting their role as a mother.

  17. Trajectories and Determinants of Elder Care in Rural China During an 8-Year Period: Why Having Sons Makes a Difference.

    Science.gov (United States)

    Guo, Man; Chi, Iris; Silverstein, Merril

    2016-07-01

    Using 8-year panel data for 1,355 older adults in rural Anhui province, China, this study examined the trajectories and determinants of elder care provided by adult children to their older parents. The results of two-level latent variable growth models showed that trajectories of elder care differed by the gender of children, with an increase in care from sons but a decrease in care from daughters over time. Children's life stages influenced their care provision but differed by gender. Functional impairment of parents and care provided by siblings in the family also affected the care provided by each child. The findings reflect the patrilineal nature of Chinese family systems and demonstrate the linkages between critical life events and caregiving behaviors of adult children. Findings of this study can inform the formulation of elder care policies that meet the needs of families with different structures and at different life stages.

  18. Cognitive ability correlates positively with son birth and predicts cross-cultural variation of the offspring sex ratio.

    Science.gov (United States)

    Dama, Madhukar Shivajirao

    2013-06-01

    Human populations show remarkable variation in the sex ratio at birth which is believed to be related to the parental condition. In the present study, the global variation of sex ratio at birth (SRB, proportion of male offspring born) was analyzed with respect to indirect measure of condition, the intelligence quotient (IQ). IQ correlates strongly with lifespan across nations, which makes it a good indicator of health of the large populations. Relation between three standard measures of average national IQ and SRB was studied using multiple linear regression models. Average national IQ was positively correlated with SRB (r = 0.54 to 0.57, p wealth, son preference, latitude, low birth weight, and neonatal mortality in the regression models. These results suggest that the striking variation of offspring sex ratio across nations could be caused in part by the difference in general condition of populations.

  19. Disruption of NAD~+ binding site in glyceraldehyde 3-phosphate dehydrogenase affects its intranuclear interactions

    Institute of Scientific and Technical Information of China (English)

    Manali; Phadke; Natalia; Krynetskaia; Anurag; Mishra; Carlos; Barrero; Salim; Merali; Scott; A; Gothe; Evgeny; Krynetskiy

    2015-01-01

    AIM:To characterize phosphorylation of human glyceraldehyde 3-phosphate dehydrogenase(GAPDH),and mobility of GAPDH in cancer cells treated with chemotherapeutic agents. METHODS:We used proteomics analysis to detect and characterize phosphorylation sites within human GAPDH. Site-specific mutagenesis and alanine scanning was then performed to evaluate functional significance of phosphorylation sites in the GAPDH polypeptide chain. Enzymatic properties of mutated GAPDH variants were assessed using kinetic studies. Intranuclear dynamics parameters(diffusion coefficient and the immobile fraction) were estimated using fluorescence recovery after photobleaching(FRAP) experiments and confocal microscopy. Molecular modeling experiments were performed to estimate the effects of mutations on NAD+ cofactor binding.RESULTS:Using MALDI-TOF analysis,we identified novel phosphorylation sites within the NAD+ binding center of GAPDH at Y94,S98,and T99. Using polyclonal antibody specific to phospho-T99-containing peptide within GAPDH,we demonstrated accumulation of phospho-T99-GAPDH inthe nuclear fractions of A549,HCT116,and SW48 cancer cel s after cytotoxic stress. We performed site-mutagenesis,and estimated enzymatic properties,intranuclear distribution,and intranuclear mobility of GAPDH mutated variants. Site-mutagenesis at positions S98 and T99 in the NAD+ binding center reduced enzymatic activity of GAPDH due to decreased affinity to NAD+(Km = 741 ± 257 μmol/L in T99 I vs 57 ± 11.1 μmol/L in wild type GAPDH. Molecular modeling experiments revealed the effect of mutations on NAD+ binding with GAPDH. FRAP(fluorescence recovery after photo bleaching) analysis showed that mutations in NAD+ binding center of GAPDH abrogated its intranuclear interactions. CONCLUSION:Our results suggest an important functional role of phosphorylated amino acids in the NAD+ binding center in GAPDH interactions with its intranuclear partners.

  20. SON68 nuclear glass dissolution kinetics: Current state of knowledge and basis of the new GRAAL model

    Energy Technology Data Exchange (ETDEWEB)

    Frugier, P. [CEA Marcoule, DTCD/SECM/LCLT, BP 17171, 30207 Bagnols-sur-Ceze cedex (France)], E-mail: pierre.frugier@cea.fr; Gin, S.; Minet, Y.; Chave, T. [CEA Marcoule, DTCD/SECM/LCLT, BP 17171, 30207 Bagnols-sur-Ceze cedex (France); Bonin, B. [CEA Saclay, DEN/DIR/DS, 91191 Gif-sur-Yvette cedex (France); Godon, N.; Lartigue, J.-E.; Jollivet, P. [CEA Marcoule, DTCD/SECM/LCLT, BP 17171, 30207 Bagnols-sur-Ceze cedex (France); Ayral, A. [IEM/CNRS-ENSCM Universite Montpellier 2, CC 047, Place Eugene Bataillon, 34095 Montpellier cedex 5 (France); De Windt, L. [ENSMP, CG, 35 rue St Honore, 77305 Fontainebleau cedex (France); Santarini, G. [CEA Saclay HC/CAB, 91191 Gif-sur-Yvette cedex (France)

    2008-10-15

    This article summarizes the present state of knowledge concerning aqueous alteration of R7T7-type nuclear containment glasses, represented mainly by the inactive reference glass designated SON68. Based on this review, we propose to describe the glass alteration kinetics up to and including the final residual rate regime by means of a new mechanistic model known as GRAAL (glassreactivitywithallowanceforthealterationlayer). Phenomenological analysis findings are reviewed for the various glass alteration regimes: interdiffusion, initial rate, rate drop, residual rate and, under very particular circumstances, resumption of alteration. These alteration regimes are associated with predominant mechanisms. Published work interpreting and modeling these mechanisms was examined in detail. There is a broad consensus on the general mechanisms of the initial rate and even the interdiffusion regime, whereas the mechanisms controlling the rate drop remain a subject of dispute not only with regard to nuclear glasses but also for the dissolution of silicate minerals. The reaction affinity responsible for the rate drop is expressed differently by different authors and depending on the underlying theories. The disagreement concerns the nature of the phase (glass or gel) or the activated complex controlling the rate drop, which in turn determines the elements that must be taken into account in the overall affinity term. Progress in recent years, especially in identifying the mechanisms responsible for the residual rate, has shed new light on these issues, allowing us to propose new theoretical foundations for modeling the different kinetic regimes of SON68 nuclear glass dissolution. The GRAAL model considers that water diffusion in the passivating reaction zone (the gel formed under saturation conditions) is a rate-limiting step in the overall glass dissolution kinetics. Moreover, this passivation zone is a soluble phase whose stability is directly dependent on the nature of the

  1. Binding Principles A and B

    Institute of Scientific and Technical Information of China (English)

    陈源

    2014-01-01

    This paper focuses on the discussion of how Binding Principle A and Binding Principe B help with the interpretation of reference in English and Chinese. They are supposedly universal across languages.

  2. Construction and validation of the SON-R 5 1/2-17, the Snijders-Oomen non-verbal intelligence test

    NARCIS (Netherlands)

    Laros, Jacob Arie; Tellegen, Peter Johannes

    1991-01-01

    In this thesis the construction and validation of the SON-R 5,5-17 is described, the recent revision of the Snijders-Oomen non-verbal intelligence test. The SON-R is an individual test of (non-verbal) intelligence for children in the ages of 51/2 to 17 years. The test was published in 1989 with an e

  3. The requirement of the glutamic acid residue at the third position from the carboxyl termini of the laminin gamma chains in integrin binding by laminins.

    Science.gov (United States)

    Ido, Hiroyuki; Nakamura, Aya; Kobayashi, Reiko; Ito, Shunsuke; Li, Shaoliang; Futaki, Sugiko; Sekiguchi, Kiyotoshi

    2007-04-13

    Laminins are the major cell-adhesive proteins in the basement membrane, consisting of three subunits termed alpha, beta, and gamma. The putative binding site for integrins has been mapped to the G domain of the alpha chain, although trimerization with beta and gamma chains is necessary for the G domain to exert its integrin binding activity. The mechanism underlying the requirement of beta and gamma chains in integrin binding by laminins remains poorly understood. Here, we show that the C-terminal region of the gamma chain is involved in modulation of the integrin binding activity of laminins. We found that deletion of the C-terminal three but not two amino acids within the gamma1 chain completely abrogated the integrin binding activity of laminin-511. Furthermore, substitution of Gln for Glu-1607, the amino acid residue at the third position from the C terminus of the gamma1 chain, also abolished the integrin binding activity, underscoring the role of Glu-1607 in integrin binding by the laminin. We also found that the conserved Glu residue of the gamma2 chain is necessary for integrin binding by laminin-332, suggesting that the same mechanism operates in the modulation of the integrin binding activity of laminins containing either gamma1 or gamma2 chains. However, the peptide segment modeled after the C-terminal region of gamma1 chain was incapable of either binding to integrin or inhibiting integrin binding by laminin-511, making it unlikely that the Glu residue is directly recognized by integrin. These results, together, indicate a novel mechanism operating in ligand recognition by laminin binding integrins.

  4. Single nucleotide polymorphisms in microRNA binding sites of oncogenes: implications in cancer and pharmacogenomics.

    Science.gov (United States)

    Manikandan, Mayakannan; Munirajan, Arasambattu Kannan

    2014-02-01

    Cancer, a complex genetic disease involving uncontrolled cell proliferation, is caused by inactivation of tumor suppressor genes and activation of oncogenes. A vast majority of these cancer causing genes are known targets of microRNAs (miRNAs) that bind to complementary sequences in 3' untranslated regions (UTR) of messenger RNAs and repress them from translation. Single Nucleotide Polymorphisms (SNPs) occurring naturally in such miRNA binding regions can alter the miRNA:mRNA interaction and can significantly affect gene expression. We hypothesized that 3'UTR SNPs in miRNA binding sites of proto-oncogenes could abrogate their post-transcriptional regulation, resulting in overexpression of oncogenic proteins, tumor initiation, progression, and modulation of drug response in cancer patients. Therefore, we developed a systematic computational pipeline that integrates data from well-established databases, followed stringent selection criteria and identified a panel of 30 high-confidence SNPs that may impair miRNA target sites in the 3' UTR of 54 mRNA transcripts of 24 proto-oncogenes. Further, 8 SNPs amidst them had the potential to determine therapeutic outcome in cancer patients. Functional annotation suggested that altogether these SNPs occur in proto-oncogenes enriched for kinase activities. We provide detailed in silico evidence for the functional effect of these candidate SNPs in various types of cancer.

  5. Son Excellence Madame Elisabeth Laurin Ambassadeur Représentant permanent de la France auprès de l’Office des Nations Unies et des autres organisations internationales en Suisse République française Son Excellence Monsieur Roberto Balzaretti Ambassadeur Directeur

    CERN Document Server

    AUTHOR|(CDS)2099575

    2016-01-01

    Son Excellence Madame Elisabeth Laurin Ambassadeur Représentant permanent de la France auprès de l’Office des Nations Unies et des autres organisations internationales en Suisse République française Son Excellence Monsieur Roberto Balzaretti Ambassadeur Directeur,

  6. Carboplatin binding to histidine

    Energy Technology Data Exchange (ETDEWEB)

    Tanley, Simon W. M. [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom); Diederichs, Kay [University of Konstanz, D-78457 Konstanz (Germany); Kroon-Batenburg, Loes M. J. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Levy, Colin [University of Manchester, 131 Princess Street, Manchester M1 7DN (United Kingdom); Schreurs, Antoine M. M. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Helliwell, John R., E-mail: john.helliwell@manchester.ac.uk [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom)

    2014-08-29

    An X-ray crystal structure showing the binding of purely carboplatin to histidine in a model protein has finally been obtained. This required extensive crystallization trials and various novel crystal structure analyses. Carboplatin is a second-generation platinum anticancer agent used for the treatment of a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine (in hen egg-white lysozyme; HEWL) showed the partial conversion of carboplatin to cisplatin owing to the high NaCl concentration used in the crystallization conditions. HEWL co-crystallizations with carboplatin in NaBr conditions have now been carried out to confirm whether carboplatin converts to the bromine form and whether this takes place in a similar way to the partial conversion of carboplatin to cisplatin observed previously in NaCl conditions. Here, it is reported that a partial chemical transformation takes place but to a transplatin form. Thus, to attempt to resolve purely carboplatin binding at histidine, this study utilized co-crystallization of HEWL with carboplatin without NaCl to eliminate the partial chemical conversion of carboplatin. Tetragonal HEWL crystals co-crystallized with carboplatin were successfully obtained in four different conditions, each at a different pH value. The structural results obtained show carboplatin bound to either one or both of the N atoms of His15 of HEWL, and this particular variation was dependent on the concentration of anions in the crystallization mixture and the elapsed time, as well as the pH used. The structural details of the bound carboplatin molecule also differed between them. Overall, the most detailed crystal structure showed the majority of the carboplatin atoms bound to the platinum centre; however, the four-carbon ring structure of the cyclobutanedicarboxylate moiety (CBDC) remained elusive. The potential impact of the results for the administration of carboplatin as an anticancer agent are described.

  7. ‘Unkind and cruel, to deceive your Son | In borrow’d Shapes, and his Embrace to shun’: Mother-son love in T. S. Eliot’s ‘La Figlia Che Piange’

    Directory of Open Access Journals (Sweden)

    Matthew Geary

    2015-01-01

    Full Text Available T. S. Eliot's "La Figlia Che Piange" (1916 is a curious anomaly in his early works. It stands out as a love poem of outstanding grace portraying a more positive relationship to the feminine compared to other poems contemporaneous with its writing such as "The Love Song of St. Sebastian" (1914 and "Hysteria" (1915. This essay shows the import of Eliot's chosen epigraph for "La Figlia" taken from Virgil's Aeneid to have been largely neglected or misread by critics. As a consequence, it argues that critical readings have crucially missed the presence of a shrouded maternal aspect within the poem. Through the lens of Lacanian psychoanalysis and the work of adherents to Lacanian theory — such as Bruce Fink, Shoshana Felman and Slavoj Zizek — this paper newly argues that the poem's meditation on the issues of union and separation between two lovers is in fact a screen for deeper unconscious ambivalent feelings between mother and son. That is to say, Eliot's "La Figlia Che Piange" shows a failed attempt to reconstruct, traverse and separate from the "fundamental fantasy" unconsciously orientating the male speaker of the poem and his desire.

  8. SON68 nuclear glass dissolution kinetics: Current state of knowledge and basis of the new GRAAL model

    Energy Technology Data Exchange (ETDEWEB)

    Frugier, P.; Gin, S.; Minet, Y.; Chave, T. [CEA Marcoule, DTCD SECM LCLT, 30 (France)

    2009-06-15

    Complete text of publication follows: Based on a review of the current state of knowledge concerning the aqueous alteration of SON68 nuclear glass GRAAL (Glass Reactivity with Allowance for the Alteration Layer) mechanistic model has been proposed [1]: An amorphous layer at the glass/solution interface gradually reorganized by hydrolysis and condensation mechanisms constitutes a barrier against the transport of water toward the glass and of solvated glass ions into solution [2]. The existence of this transport-inhibiting effect rapidly causes this layer to control glass alteration. The reaction affinity responsible for the glass alteration rate drop is expressed with respect to this passivating reactive interphase (PRI). Some glass constituent elements precipitate as crystallized secondary phases on the external surface and can sustain glass alteration. Correctly modeling the seat of recondensation (PRI or secondary crystallized phases) of elements is a key point for understanding their effect on glass alteration. Describing not only (1) solution chemistry but also ion transport (2) in solution by at a macroscopic scale and (3) by reactive interdiffusion in the PRI at a nanometer scale by means of a single model at each point in space and time is a complex task. Most existing models describe only one or two of these aspects. GRAAL describes a simple and still effective manner of coupling theses three phenomena using a calculation code coupling chemistry and transport HYTEC [3]. The model results are compared with experimental data for SON68 glass leached in initially pure water both in a closed system and in renewed media. The comparison shows the model very satisfactorily accounts for variations in the pH and the element concentrations in solution as a function of time, glass surface area in contact with solution, and solution renewal rate. Interdiffusion through the PRI cannot be disregarded under most experimental conditions - if only to predict the solution p

  9. False-positive myeloperoxidase binding activity due to DNA/anti-DNA antibody complexes: a source for analytical error in serologic evaluation of anti-neutrophil cytoplasmic autoantibodies.

    Science.gov (United States)

    Jethwa, H S; Nachman, P H; Falk, R J; Jennette, J C

    2000-09-01

    Anti-myeloperoxidase antibodies (anti-MPO) are a major type of anti-neutrophil cytoplasmic antibody (ANCA). While evaluating anti-MPO monoclonal antibodies from SCG/Kj mice, we observed several hybridomas that appeared to react with both MPO and DNA. Sera from some patients with systemic lupus erythematosus (SLE) also react with MPO and DNA. We hypothesized that the MPO binding activity is a false-positive result due to the binding of DNA, contained within the antigen binding site of anti-DNA antibodies, to the cationic MPO. Antibodies from tissue culture supernatants from 'dual reactive' hybridomas were purified under high-salt conditions (3 M NaCl) to remove any antigen bound to antibody. The MPO and DNA binding activity were measured by ELISA. The MPO binding activity was completely abrogated while the DNA binding activity remained. The MPO binding activity was restored, in a dose-dependent manner, by the addition of increasing amount of calf-thymus DNA (CT-DNA) to the purified antibody. Sera from six patients with SLE that reacted with both MPO and DNA were treated with DNase and showed a decrease in MPO binding activity compared with untreated samples. MPO binding activity was observed when CT-DNA was added to sera from SLE patients that initially reacted with DNA but not with MPO. These results suggest that the DNA contained within the antigen binding site of anti-DNA antibodies could bind to the highly cationic MPO used as substrate antigen in immunoassays, resulting in a false-positive test.

  10. Pan-HER - an antibody mixture targeting EGFR, HER2, and HER3 abrogates preformed and ligand-induced EGFR homo- and heterodimers

    DEFF Research Database (Denmark)

    Ellebaek, Sofie; Pedersen, Susanne Brix; Grandal, Michael

    2016-01-01

    Abs is development of acquired resistance through mechanisms such as alterated receptor dimerization patterns and dependencies. Pan-HER is a mixture of six mAbs simultaneously targeting epidermal growth factor receptor (EGFR), HER2, and HER3 with two mAbs against each receptor. Pan-HER has previously demonstrated....... The effect of Pan-HER on cell proliferation and HER-family receptor degradation was superior to treatment with single mAbs targeting either single receptor, and similar to targeting a single receptor with two non-overlapping antibodies. Furthermore, changes in EGFR-dimerization patterns after treatment......-HER and the EGFR-targeting mAb mixture also blocked EGF-binding and thereby ligand-induced changes in EGFR-dimerization levels. These results suggest that Pan-HER reduces the cellular capability to switch HER-dependency and dimerization pattern in response to treatment and thus hold promise for future clinical...

  11. Lipoxin A4 inhibits immune cell binding to salivary epithelium and vascular endothelium.

    Science.gov (United States)

    Chinthamani, Sreedevi; Odusanwo, Olutayo; Mondal, Nandini; Nelson, Joel; Neelamegham, Sriram; Baker, Olga J

    2012-04-01

    Lipoxins are formed by leukocytes during cell-cell interactions with epithelial or endothelial cells. Native lipoxin A(4) (LXA(4)) binds to the G protein-coupled lipoxin receptors formyl peptide receptor 2 (FPR2)/ALX and CysLT1. Furthermore, LXA(4) inhibits recruitment of neutrophils, by attenuating chemotaxis, adhesion, and transmigration across vascular endothelial cells. LXA(4) thus appears to serve as an endogenous "stop signal" for immune cell-mediated tissue injury (Serhan CN; Annu Rev Immunol 25: 101-137, 2007). The role of LXA(4) has not been addressed in salivary epithelium, and little is known about its effects on vascular endothelium. Here, we determined that interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) receptor activation in vascular endothelium and salivary epithelium upregulated the expression of adhesion molecules that facilitates the binding of immune cells. We hypothesize that the activation of the ALX/FPR2 and/or CysLT1 receptors by LXA(4) decreases this cytokine-mediated upregulation of cell adhesion molecules that enhance lymphocyte binding to both the vascular endothelium and salivary epithelium. In agreement with this hypothesis, we observed that nanomolar concentrations of LXA(4) blocked IL-1β- and TNF-α-mediated upregulation of E-selectin and intercellular cell adhesion molecule-1 (ICAM-1) on human umbilical vein endothelial cells (HUVECs). Binding of Jurkat cells to stimulated HUVECs was abrogated by LXA(4). Furthermore, LXA(4) preincubation with human submandibular gland cell line (HSG) also blocked TNF-α-mediated upregulation of vascular cell adhesion molecule-1 (VCAM-1) in these cells, and it reduced lymphocyte adhesion. These findings suggest that ALX/FPR2 and/or CysLT1 receptor activation in endothelial and epithelial cells blocks cytokine-induced adhesion molecule expression and consequent binding of lymphocytes, a critical event in the pathogenesis of Sjögren's syndrome (SS).

  12. Indicadores regionales de desarrollo sustentable en Chile: ¿Hasta qué punto son útiles y necesarios?

    Directory of Open Access Journals (Sweden)

    Hernán Blanco

    2001-09-01

    Full Text Available Cada vez más necesitamos maneras de asegurar patrones de desarrollo que sean sustentables, es decir, que sean ambiental, social y económicamente apropiados para nosotros y para las generaciones venideras. Los indicadores de desarrollo sustentable son una herramienta promisoria que permitiría "aterrizar" el concepto de sustentabilidad, apoyando la manera en que se toman las decisiones. En Chile existen pocas experiencias sobre el tema. Este artículo presenta el trabajo realizado para desarrollar indicadores de desarrollo sustentable en cuatro regiones del país. El artículo se centra en las lecciones que han surgido de la experienciaWe are increasingly needing ways to secure patterns of development that be sustainable, that is, environmentally, socially and economically appropriate for us and for future generations. Sustainability indicators are a promising tool that would allow us to "land" the concept, supporting the way in which decisions are made. In Chile there are few experiences on the subject. This paper presents the work carried out to develop sustainability indicators in four regions. The paper focuses on the lessons that have been drawn from the experience

  13. Tectonomagnetic study in the seismoactive area of Narmada–Son lineament, central India: Preliminary results on repeat field observations

    Indian Academy of Sciences (India)

    S Y Waghmare; S D Pimprikar; P B Gawali; L Carlo; A G Patil

    2009-06-01

    Repeated measurements of the total geomagnetic field on the five profiles have revealed a picture of stress-induced tectonomagnetic effect in the form of secular variation of the total geomagnetic field in the tectonically and seismically active area of Jabalpur and adjoining areas of the Narmada-Son lineament (NSL),central India.For this experiment,a reference base station was established within the study area at Jabalpur.Using proton precession magnetometers with a sensitivity of 0.1 nT, simultaneous measurements of total geomagnetic field were made annually at the base and all field stations.Five cycles of repeated observations have been performed between 2003 and 2007.For data analysis,a difference method has been applied and the residuals have been calculated as secular variations of the total geomagnetic field with values ranging from ± 0.1nT to about > ± 14.6nT/yr over the different stations.The anomalies in secular variation of the total geomagnetic field may be related to anomalous accumulation of tectonic stresses and tensions on the deep fault zones and crustal blocks due to recent geodynamic processes and active geological inhomogeneities in the NSL.

  14. Household opportunity costs of protecting and developing forest lands in Son La and Hoa Binh Provinces, Vietnam

    Directory of Open Access Journals (Sweden)

    Le Ngoc Lan

    2016-09-01

    Full Text Available Vietnam has pilot-tested a payment for forest environmental services (PFES program in an effort to restore and protect forest areas, some of which have been severely degraded by the excessive cutting of trees by small-scale farmers planting annual crops on steep, sloping lands. The pilot program implemented in southern Vietnam seems to be successful, yet the program in northern Vietnam has not produced the desired rates of planting and maintaining forest areas. The reasons for these mixed results include differences in socio-economic characteristics and also the production and marketing opportunities available to rural households in the project areas. To gain insight regarding program participation, we examine the household-level opportunity costs of planting and ­maintaining small plots of forest trees in northern Vietnam. We find that small-scale farmers in Hoa Binh Province, with limited financial resources, prefer the annual revenue stream provided by crops such as maize and cassava, rather than waiting for 7 years to obtain revenue from a forest planting. Farmers in Son La Province, with limited access to markets, prefer annual crops because they are not able to sell bamboo shoots and other forest products harvested from their small plots. In both provinces, the payments offered for planting and maintaining forest trees are smaller than the opportunity costs of planting and harvesting annual crops. Thus, most households likely would choose not to participate in the PFES program, at current payment rates, if given the opportunity to decline.

  15. 2-D Crustal thermal structure along Thuadara–Sindad DSS profile across Narmada– Son lineament, central India

    Indian Academy of Sciences (India)

    S N Rai; S Thiagarajan

    2007-08-01

    Central India is traversed by a WSW–ENE trending Narmada–Son lineament (NSL) which is characterized by the presence of numerous hot springs, feeder dykes for Deccan Traps and seismicity all along its length. It is divided in two parts by the Barwani–Sukta Fault (BSF). To the west of this fault a graben exists, whereas to the east the basement is uplifted between Narmada North Fault (NNF) and Narmada South Fault (NSF). The present work deals with the 2-D thermal modeling to delineate the crustal thermal structure of the western part of NSL region along the Thuadara–Sindad Deep Seismic Sounding (DSS) profile which runs almost in the N–S direction across the NSL. Numerical results of the model reveal that the conductive surface heat flow value in the region under consideration varies between 45 and 47mW/m2. Out of which 23mW/m2 is the contribution from the mantle heat flow and the remaining from within the crust. The Curie depth is found to vary between 46 and 47 km and is in close agreement with the earlier reported Curie depth estimated from the analysis of MAGSAT data. The Moho temperature varies between 470 and 500°C. This study suggests that this western part of central Indian region is characterized by low mantle heat flow which in turn makes the lower crust brittle and amenable to the occurrence of deep focused earthquakes such as Satpura (1938) earthquake.

  16. Precios de los medicamentos: cómo se establecen y cuáles son sus sistemas de control

    Directory of Open Access Journals (Sweden)

    Joan Rovira Forns

    2015-01-01

    Full Text Available El precio es una de las principales barreras de acceso a los medicamentos. Por ello es importante conocer cómo se forman los precios y qué factores determinan su cuantía y también qué formas de intervención y regulación son las más adecuadas teniendo en cuenta sus efectos, tanto sobre el acceso, como sobre la innovación, la producción local y otros posibles objetivos de la política de medicamentos. El análisis económico ha desarrollado un conjunto de modelos de mercado que permiten explicar el comportamiento de los precios, aunque los mercados reales divergen sustancialmente de los modelos teóricos. La regulación de precios está justificada por los llamados “fallos de mercado”; la regulación de precios basada en el costo de producción, la modalidad de control de precios más tradicional, ha caído en desuso a favor de los sistemas de precios de referencia internacionales y por la fijación del precio basada en el valor.

  17. ¿SON EFECTIVOS LOS CONSEJOS DE ADMINISTRACIÓN? LA EFICACIA DEL CONSEJO Y LOS RESULTADOS DE LA EMPRESA

    Directory of Open Access Journals (Sweden)

    Barroso Castro, C.

    2010-01-01

    Full Text Available Numerosos trabajos han estudiado la influencia del consejo de administración en las decisiones y resultados de sus empresas. No obstante, la enorme popularidad alcanzada en el campo del gobierno corporativo por estos estudios, no viene acompañada por sus resultados, que han sido ambiguos y, a veces, conflictivos En esta investigación proponemos que la efectividad de los consejos depende de las experiencias y conocimientos de los consejeros que lo conforman, así como de la estructura de estos consejos. Entendemos que ambas dimensiones (composición y estructura no son “por si” suficientes para el logro de consejos plenamente efectivos, pero si se definen como elementos necesarios para ello. Desde nuestra perspectiva, constituyen el potencial que permitirá lograr una adecuada capacidad estratégica por parte del consejo. Nuestros resultados muestran la importancia de las variables que conforman la estructura y composición del consejo (tamaño del consejo, permanencia, experiencia de los consejeros a la hora de explicar los resultados empresariales.

  18. Facies, dissolution seams and stable isotope compositions of the Rohtas Limestone (Vindhyan Supergroup) in the Son valley area, central India

    Indian Academy of Sciences (India)

    S Banerjee; S K Bhattacharya; S Sarkar

    2005-02-01

    The early Mesoproterozoic Rohtas Limestone in the Son valley area of central India represents an overall shallowing-upward carbonate succession. Detailed facies analysis of the limestone reveals outer- to inner-shelf deposition in an open marine setting. Wave-ripples, hummocky cross strat- ifications and edgewise conglomerates argue against a deep marine depositional model for the Rohtas Limestone proposed earlier. Stable isotope analysis of the limestone shows that 13C and 18O values are compatible with the early Mesoproterozoic open seawater composition. The ribbon limestone facies in the Rohtas Limestone is characterized by micritic beds, each decoupled in a lower band enriched and an upper band depleted in dissolution seams. Band-wise isotopic analysis reveals systematic short-term variations. Comparative enrichment of the heavier isotopes in the upper bands is attributed to early cementation from sea water and water derived from the lower band undergoing dissolution because of lowering of pH at depth. The short-term positive shifts in isotopic compositions in almost every upward gradational transition from a seamed band to a non-seamed band support the contention that dissolution seams here are of early diagenetic origin, although their formation was accentuated under overburden pressure.

  19. "Now if you have only sons you are dead": migration, gender, and family economy in twentieth century northwestern Ghana.

    Science.gov (United States)

    Abdul-Korah, Gariba B

    2011-01-01

    This article explores the interconnectedness between labor migration, gender, and the family economy in northwestern Ghana in the 20th century. It focuses specifically on the Dagaaba of the Nadowli and Jirapa administrative districts of what is now the Upper West Region (UWR). It examines how the relationships between men and women in terms of roles, status, access to productive resources and inheritance, changed in tandem with broader changes in society in the 20th century; changes that over time produced enhanced value and elevated status for women in the family. These changes in gender relations are reflected increasingly in the belief among elderly men that ‘now if you have only sons, you are dead’. By focusing on the lived experiences of ordinary women and men in the migration process, it argues that even though indigenous social structures privileged men over women in almost all spheres of life, Dagaaba women were nonetheless significantly active in shaping the history of their communities and that gender relations in Dagaaba communities were not static — they changed over time and generation. This article contributes to the ongoing discussion of the internal migration phenomenon in West Africa, which has so far attracted scant historical analysis.

  20. Analytic QCD Binding Potentials

    CERN Document Server

    Fried, H M; Grandou, T; Sheu, Y -M

    2011-01-01

    This paper applies the analytic forms of a recent non-perturbative, manifestly gauge- and Lorentz-invariant description (of the exchange of all possible virtual gluons between quarks ($Q$) and/or anti-quarks ($\\bar{Q}$) in a quenched, eikonal approximation) to extract analytic forms for the binding potentials generating a model $Q$-$\\bar{Q}$ "pion", and a model $QQQ$ "nucleon". Other, more complicated $Q$, $\\bar{Q}$ contributions to such color-singlet states may also be identified analytically. An elementary minimization technique, relevant to the ground states of such bound systems, is adopted to approximate the solutions to a more proper, but far more complicated Schroedinger/Dirac equation; the existence of possible contributions to the pion and nucleon masses due to spin, angular momentum, and "deformation" degrees of freedom is noted but not pursued. Neglecting electromagnetic and weak interactions, this analysis illustrates how the one new parameter making its appearance in this exact, realistic formali...

  1. Metallothionein and a peptide modeled after metallothionein, EmtinB, induce neuronal differentiation and survival through binding to receptors of the low-density lipoprotein receptor family

    DEFF Research Database (Denmark)

    Ambjørn, Malene; Asmussen, Johanne W; Lindstam, Mats;

    2007-01-01

    Accumulating evidence suggests that metallothionein (MT)-I and -II promote neuronal survival and regeneration in vivo. The present study investigated the molecular mechanisms underlying the differentiation and survival-promoting effects of MT and a peptide modeled after MT, EmtinB. Both MT...... and EmtinB directly stimulated neurite outgrowth and promoted survival in vitro using primary cultures of cerebellar granule neurons. In addition, expression and surface localization of megalin, a known MT receptor, and the related lipoprotein receptor-related protein-1 (LRP) are demonstrated in cerebellar...... granule neurons. By means of surface plasmon resonance MT and EmtinB were found to bind to both megalin and LRP. The bindings were abrogated in the presence of receptor-associated protein-1, an antagonist of the low-density lipoprotein receptor family, which also inhibited MT- and EmtinB-induced neurite...

  2. Biophysical studies on calcium and carbohydrate binding to carbohydrate recognition domain of Gal/GalNAc lectin from Entamoeba histolytica: insights into host cell adhesion.

    Science.gov (United States)

    Yadav, Rupali; Verma, Kuldeep; Chandra, Mintu; Mukherjee, Madhumita; Datta, Sunando

    2016-09-01

    Entamoeba histolytica, an enteric parasite expresses a Gal/GalNAc-specific lectin that contributes to its virulence by establishing adhesion to host cell. In this study, carbohydrate recognition domain of Hgl (EhCRD) was purified and biophysical studies were conducted to understand the thermodynamic basis of its binding to carbohydrate and Ca(++) Here, we show that carbohydrate recognition domain (CRD) of the lectin binds to calcium through DPN motif. To decipher the role of calcium in carbohydrate binding and host cell adhesion, biophysical and cell-based studies were carried out. We demonstrated that the presence of the cation neither change the affinity of the lectin for carbohydrates nor alters its conformation. Mutation of the calcium-binding motif in EhCRD resulted in complete loss of ability to bind calcium but retained its affinity for carbohydrates. Purified EhCRD significantly diminished adhesion of the amebic trophozoites to Chinese Hamster Ovary (CHO) cells as well as triggered red blood cell agglutination. The calcium-binding defective mutant abrogated amebic adhesion to CHO cells similar to the wild-type protein, but it failed to agglutinate RBCs suggesting a differential role of the cation in these two processes. This study provides the first molecular description of the role of calcium in Gal/GalNAc mediated host cell adhesion.

  3. In silico analysis reveals sequential interactions and protein conformational changes during the binding of chemokine CXCL-8 to its receptor CXCR1.

    Directory of Open Access Journals (Sweden)

    Je-Wen Liou

    Full Text Available Chemokine CXCL-8 plays a central role in human immune response by binding to and activate its cognate receptor CXCR1, a member of the G-protein coupled receptor (GPCR family. The full-length structure of CXCR1 is modeled by combining the structures of previous NMR experiments with those from homology modeling. Molecular docking is performed to search favorable binding sites of monomeric and dimeric CXCL-8 with CXCR1 and a mutated form of it. The receptor-ligand complex is embedded into a lipid bilayer and used in multi ns molecular dynamics (MD simulations. A multi-steps binding mode is proposed: (i the N-loop of CXCL-8 initially binds to the N-terminal domain of receptor CXCR1 driven predominantly by electrostatic interactions; (ii hydrophobic interactions allow the N-terminal Glu-Leu-Arg (ELR motif of CXCL-8 to move closer to the extracellular loops of CXCR1; (iii electrostatic interactions finally dominate the interaction between the N-terminal ELR motif of CXCL-8 and the EC-loops of CXCR1. Mutation of CXCR1 abrogates this mode of binding. The detailed binding process may help to facilitate the discovery of agonists and antagonists for rational drug design.

  4. Classificação de sons cardíacos usando Motifs: desenvolvimento de uma aplicação móvel

    OpenAIRE

    Oliveira, Soraia Carvalho da Cruz

    2014-01-01

    Este documento foi redigido no âmbito da Tese, do Mestrado em Engenharia Informática na área de Tecnologias do Conhecimento e Decisão, do Departamento de Engenharia Informática, do ISEP, cujo tema é classificação de sons cardíacos usando motifs. Neste trabalho, apresenta-se um algoritmo de classificação de sons cardíacos, capaz de identificar patologias cardíacas. A classificação do som cardíaco é um trabalho desafiante dada a dificuldade em separar os sons ambiente (vozes, respiração, con...

  5. Inhibition of factor-dependent transcription termination in Escherichia coli might relieve xenogene silencing by abrogating H-NS-DNA interactions in vivo

    Indian Academy of Sciences (India)

    Deepti Chandraprakash; Aswin Sai Narain Seshasayee

    2014-03-01

    Many horizontally acquired genes (xenogenes) in the bacterium Escherichia coli are maintained in a silent transcriptional state by the nucleoid-associated transcription regulatory protein H-NS. Recent evidence has shown that antibiotic-mediated inhibition of the transcription terminator protein Rho leads to de-repression of horizontally acquired genes, akin to a deletion of hns. The mechanism behind this similarity in outcomes between the perturbations of two distinct processes remains unclear. Using ChIP-seq of H-NS in wild-type cells, in addition to that in cells treated with bicyclomycin – a specific inhibitor of Rho, we show that bicyclomycin treatment leads to a decrease in binding signal for H-NS to the E. coli chromosome. Rho inhibition leads to RNA polymerase readthrough, which in principle could displace H-NS from the DNA, thus leading to transcriptional derepression of H-NS-silenced genes. Other possible mediators of the effect of Rho on H-NS are discussed. A possible positive feedback between Rho and H-NS might help reinforce xenogene silencing.

  6. Clonage de l'IGF-I et de son récepteur chez le turbot (Psetta maxima

    Directory of Open Access Journals (Sweden)

    ELIES G.

    1998-07-01

    Full Text Available Les IGF, leurs récepteurs et leurs protéines de liaison constituent une famille moléculaire qui joue un rôle essentiel dans la régulation de la croissance et du développement. Nous nous sommes intéressés à la caractérisation moléculaire de l'IGF-l et de son récepteur (IGF-1R chez le turbot (Psetta maxima, un poisson plat téléostéen. Par RT-PCR, nous avons clone un ADNc codant pour les quatre domaines de l'IGF-l mature. La protéine présente 70 à 96 % d'identité avec les autres IGF-I de vertébrés. Le clonage de la séquence codante entière du récepteur a nécessité la construction d'une banque d'ADNc d'embryons de turbots. Le récepteur est organisé en domaines dont la taille et les caractéristiques sont semblables à celles des autres récepteurs aux IGF de type 1 décrits chez les mammifères et le poulet. La région catalytique est particulièrement conservée. Dans certains domaines, notamment dans la région C-terminale du précurseur, quelques différences qui pourraient avoir une importance fonctionnelle sont cependant observées. Enfin, par RT-PCR, nous avons mis en évidence une régulation ontogénique du statut de polyadénylation des ARNm IGF-1R.

  7. Comment Hobbes tente de rendre son matérialisme acceptable dans les appendices du Léviathan

    Directory of Open Access Journals (Sweden)

    Anne Staquet

    2011-11-01

    Full Text Available Le Léviathan de Hobbes [1651] a subi de nombreuses attaques, au point qu’il est jugé responsable de la grande peste de 1665 et de l’incendie de Londres l’année suivante et que le parlement ouvre une procédure contre l’ouvrage. Aussi, lorsqu’en 1666, Thomas Hobbes veut publier la traduction latine de ce livre, il y adjoint trois appendices. La version latine de l’œuvre est généralement jugée plus acceptable que le texte originaire anglais. En étudiant la manière dont Hobbes traite de son matérialisme dans ces appendices, je tente de montrer que les addenda latins ne constituent en aucune manière un retour en arrière du texte, mais que le philosophe enrobe simplement davantage des propos que, par ailleurs, il rend plus radicaux.Hobbes’s Leviathan [1651] has been critiqued so much that it was held responsible for the Great Plague of 1665 and the Fire of London during the following year, resulting in the Parliament instituting proceedings against the book. Therefore, when in 1666 Thomas Hobbes wanted to publish a Latin translation of this book, he added three appendices. Generally, the Latin version of the work is considered more acceptable than the English original text. By studying how Hobbes deals with his materialism in these appendices, I try to show that the Latin additions are in no way a reversal of the text, but that the philosopher simply veiled more propositions, while at the same time making them more radical.

  8. Alteracions respiratòries durant el son inflamació i canvis fenotípics al múscul intercostal extern /

    OpenAIRE

    Pallàs i Villaronga, Josep Oriol

    2012-01-01

    En pacients amb Malaltia Pulmonar Obstructiva Crònica (MPOC) la disfunció muscular, tant a nivell dels músculs perifèrics com respiratoris, ha estat estudiada per múltiples grups d'investigació, però les alteracions musculars en els trastorns respiratoris durant el son (Síndrome d'Apnees i Hipopnees del Son -SAHS- i Overlap Syndrome respiratori -OS-) són poc conegudes. Aquesta tesi estudia els canvis inflamatoris i de l'estructura muscular que es produeixen en un dels principals músculs respi...

  9. The putative effector-binding site of Leishmania mexicana pyruvate kinase studied by site-directed mutagenesis.

    Science.gov (United States)

    Hannaert, Véronique; Yernaux, Cédric; Rigden, Daniel J; Fothergill-Gilmore, Linda A; Opperdoes, Fred R; Michels, Paul A M

    2002-03-13

    The activity of pyruvate kinase of Leishmania mexicana is allosterically regulated by fructose 2,6-bisphosphate (F-2,6-P(2)), contrary to the pyruvate kinases from other eukaryotes that are usually stimulated by fructose 1,6-bisphosphate (F-1,6-P(2)). Based on the comparison of the three-dimensional structure of Saccharomyces cerevisiae pyruvate kinase crystallized with F-1,6-P(2) present at the effector site (R-state) and the L. mexicana enzyme crystallized in the T-state, two residues (Lys453 and His480) were proposed to bind the 2-phospho group of the effector. This hypothesis was tested by site-directed mutagenesis. The allosteric activation by F-2,6-P(2) appeared to be entirely abrogated in the mutated enzymes confirming our predictions.

  10. Abrogation of heat-shock protein (HSP)70 expression induced cell growth inhibition and apoptosis in human androgen-independent prostate cancer cell line PC-3m

    Institute of Scientific and Technical Information of China (English)

    Zhi-GangZhao; Qing-ZhengMa; Chun-XiaoXu

    2004-01-01

    Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC3m cells were treated with 0-16μmol/L antisense HSP70 oligomers for 0-100 hr. Cell growth inhibition was analyzed using a trypan blue dye exclusion test. Apoptotic cells were detected and confirmed by flow cytometric analysis and DNA fragmentation analysis. The protein expression of HSP70 and bcl-2 affected by antisense HSP70 oligomers were determined using Western blot. Results: Antisense HSP70 oligomer induced apoptosis and then inhibited proliferation of PC-3m cells in a dose- and time-dependent manner. Ladder-like patterns of DNA fragments were observed in PC-3m cells treated with 10μmol/L antisense HSP70 oligomer for 48 hr or 8μtmol/L for 72 hr on agarose gel electrophoresis. Antisense HSP70 oligomer pretreatment enhanced the subsequent induction of apoptosis by heat shock in PC-3m cells. In addition, undetectable HSP70 expression was observed at a concentration of 10μtmol/L antisense HSP70 oligomer treatment for 48 hr or 8μtmol/L for 72 hr in Western blot, which was paralleled by decreased expression levels of anti-apoptotic protein bcl-2. Conclusion: HSP70 antisense oligomer treatment abro-gates the expression of HSP70, which may disrupt HSP70-bcl-2-interactions and further down-regulate bcl-2 expression,in turn inducing apoptosis and inhibiting cell growth in PC-3m cells. (Asian JAndro12004 Dec;6:319-324)

  11. 5-Methoxyl Aesculetin Abrogates Lipopolysaccharide-Induced Inflammation by Suppressing MAPK and AP-1 Pathways in RAW 264.7 Cells

    Directory of Open Access Journals (Sweden)

    Lei Wu

    2016-03-01

    Full Text Available For the first time, a pale amorphous coumarin derivative, 5-methoxyl aesculetin (MOA, was isolated from the dried bark of Fraxinus rhynchophylla Hance (Oleaceae. MOA modulates cytokine expression in lipopolysaccharide (LPS-treated RAW 264.7 macrophages, but the precise mechanisms are still not fully understood. We determined the effects of MOA on the production of inflammatory mediators and pro-inflammatory cytokines in the LPS-induced inflammatory responses of RAW 264.7 macrophages. MOA significantly inhibited the LPS-induced production of nitric oxide (NO, prostaglandin E2 (PGE2, tumor necrosis factor-α (TNF-α, interleukin-6, and interleukin-1β. It also effectively attenuated inducible nitric oxide (NO synthase, cyclooxygenase-2, and TNF-α mRNA expression and significantly decreased the levels of intracellular reactive oxygen species. It inhibited phosphorylation of the extracellular signal-regulated kinase (ERK1/2, thus blocking nuclear translocation of activation protein (AP-1. In a molecular docking study, MOA was shown to target the binding site of ERK via the formation of three hydrogen bonds with two residues of the kinase, which is sufficient for the inhibition of ERK. These results suggest that the anti-inflammatory effects of MOA in RAW 264.7 macrophages derive from its ability to block both the activation of mitogen-activated protein kinases (MAPKs and one of their downstream transcription factors, activator protein-1 (AP-1. Our observations support the need for further research into MOA as a promising therapeutic agent in inflammatory diseases.

  12. Pan-HER-An antibody mixture targeting EGFR, HER2 and HER3 abrogates preformed and ligand-induced EGFR homo- and heterodimers.

    Science.gov (United States)

    Ellebaek, Sofie; Brix, Susanne; Grandal, Michael; Lantto, Johan; Horak, Ivan D; Kragh, Michael; Poulsen, Thomas Tuxen

    2016-11-01

    The human epidermal growth factor receptor (HER)-family is involved in development of many epithelial cancers. Therefore, HER-family members constitute important targets for anti-cancer therapeutics such as monoclonal antibodies (mAbs). A limitation to the success of single HER-targeting mAbs is development of acquired resistance through mechanisms such as alterted receptor dimerization patterns and dependencies. Pan-HER is a mixture of six mAbs simultaneously targeting epidermal growth factor receptor (EGFR), HER2 and HER3 with two mAbs against each receptor. Pan-HER has previously demonstrated broader efficacy than targeting single or dual receptor combinations also in resistant settings. In light of this broad efficacy, we decided to investigate the effect of Pan-HER compared with single HER-targeting with single and dual mAbs on HER-family cross-talk and dimerization focusing on EGFR. The effect of Pan-HER on cell proliferation and HER-family receptor degradation was superior to treatment with single mAbs targeting either single receptor, and similar to targeting a single receptor with two non-overlapping antibodies. Furthermore, changes in EGFR-dimerization patterns after treatment with Pan-HER were investigated by in situ proximity ligation assay and co-immunoprecipitation, demonstrating that Pan-HER and the EGFR-targeting mAb mixture efficiently down-regulate basal EGFR homo- and heterodimerization in two tested cell lines, whereas single mAbs had limited effects. Pan-HER and the EGFR-targeting mAb mixture also blocked EGF-binding and thereby ligand-induced changes in EGFR-dimerization levels. These results suggest that Pan-HER reduces the cellular capability to switch HER-dependency and dimerization pattern in response to treatment and thus hold promise for future clinical development of Pan-HER in resistant settings.

  13. Binding Energy and Enzymatic Catalysis.

    Science.gov (United States)

    Hansen, David E.; Raines, Ronald T.

    1990-01-01

    Discussed is the fundamental role that the favorable free energy of binding of the rate-determining transition state plays in catalysis. The principle that all of the catalytic factors discussed are realized by the use of this binding energy is reviewed. (CW)

  14. 心理干预提高独生子女士兵适应能力的研究%A Study on Psychological Intervention to Improve the Adaptability of the Only Son Recruits

    Institute of Scientific and Technical Information of China (English)

    李权超; 蓝新友; 何英强; 蒋忠军; 谭终意; 李兴国

    2002-01-01

    Objective: To study the effects of psychological intervention on the adaptability of the only son recruits. Methods: Mental status of the only son recruits and non-only son recruits were assessed using Symptom Checklist-90, Social Support Questionnaire and Simplified Coping Style Questionnaire before and after psychological intervention. Results: The only son recruits scored significantly higher on depression, anxiety, and interpersonal sensitivity prior to psychological intervention, when compared to the non-only son recruits (P<0.05 or 0.01). The scores of negative emotion decreased and the scores of positive coping style increased significantly in the only son recruits after psychological intervention (P<0.05 or0.01).Conclusion: Psychological intervention could improve the psychological status and adaptability of the only son recruits.

  15. Transitional changes in the CRP structure lead to the exposure of proinflammatory binding sites

    Science.gov (United States)

    Braig, David; Nero, Tracy L.; Koch, Hans-Georg; Kaiser, Benedict; Wang, Xiaowei; Thiele, Jan R.; Morton, Craig J.; Zeller, Johannes; Kiefer, Jurij; Potempa, Lawrence A.; Mellett, Natalie A.; Miles, Luke A.; Du, Xiao-Jun; Meikle, Peter J.; Huber-Lang, Markus; Stark, G. Björn; Parker, Michael W.; Peter, Karlheinz; Eisenhardt, Steffen U.

    2017-01-01

    C-reactive protein (CRP) concentrations rise in response to tissue injury or infection. Circulating pentameric CRP (pCRP) localizes to damaged tissue where it leads to complement activation and further tissue damage. In-depth knowledge of the pCRP activation mechanism is essential to develop therapeutic strategies to minimize tissue injury. Here we demonstrate that pCRP by binding to cell-derived microvesicles undergoes a structural change without disrupting the pentameric symmetry (pCRP*). pCRP* constitutes the major CRP species in human-inflamed tissue and allows binding of complement factor 1q (C1q) and activation of the classical complement pathway. pCRP*–microvesicle complexes lead to enhanced recruitment of leukocytes to inflamed tissue. A small-molecule inhibitor of pCRP (1,6-bis(phosphocholine)-hexane), which blocks the pCRP–microvesicle interactions, abrogates these proinflammatory effects. Reducing inflammation-mediated tissue injury by therapeutic inhibition might improve the outcome of myocardial infarction, stroke and other inflammatory conditions. PMID:28112148

  16. The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins

    Directory of Open Access Journals (Sweden)

    Ning Li

    2015-12-01

    Full Text Available Members of the Msi family of RNA-binding proteins have recently emerged as potent oncoproteins in a range of malignancies. MSI2 is highly expressed in hematopoietic cancers, where it is required for disease maintenance. In contrast to the hematopoietic system, colorectal cancers can express both Msi family members, MSI1 and MSI2. Here, we demonstrate that, in the intestinal epithelium, Msi1 and Msi2 have analogous oncogenic effects. Further, comparison of Msi1/2-induced gene expression programs and transcriptome-wide analyses of Msi1/2-RNA-binding targets reveal significant functional overlap, including induction of the PDK-Akt-mTORC1 axis. Ultimately, we demonstrate that concomitant loss of function of both MSI family members is sufficient to abrogate the growth of human colorectal cancer cells, and Msi gene deletion inhibits tumorigenesis in several mouse models of intestinal cancer. Our findings demonstrate that MSI1 and MSI2 act as functionally redundant oncoproteins required for the ontogeny of intestinal cancers.

  17. Beyond Ribosomal Binding: The Increased Polarity and Aberrant Molecular Interactions of 3-epi-deoxynivalenol

    Science.gov (United States)

    Hassan, Yousef I.; Zhu, Honghui; Zhu, Yan; Zhou, Ting

    2016-01-01

    Deoxynivalenol (DON) is a secondary fungal metabolite and contaminant mycotoxin that is widely detected in wheat and corn products cultivated around the world. Bio-remediation methods have been extensively studied in the past two decades and promising ways to reduce DON-associated toxicities have been reported. Bacterial epimerization of DON at the C3 carbon was recently reported to induce a significant loss in the bio-toxicity of the resulting stereoisomer (3-epi-DON) in comparison to the parental compound, DON. In an earlier study, we confirmed the diminished bio-potency of 3-epi-DON using different mammalian cell lines and mouse models and mechanistically attributed it to the reduced binding of 3-epi-DON within the ribosomal peptidyl transferase center (PTC). In the current study and by inspecting the chromatographic behavior of 3-epi-DON and its molecular interactions with a well-characterized enzyme, Fusarium graminearum Tri101 acetyltransferase, we provide the evidence that the C3 carbon epimerization of DON influences its molecular interactions beyond the abrogated PTC binding. PMID:27618101

  18. Androgen receptor serine 81 phosphorylation mediates chromatin binding and transcriptional activation.

    Science.gov (United States)

    Chen, Shaoyong; Gulla, Sarah; Cai, Changmeng; Balk, Steven P

    2012-03-01

    Our previous findings indicated that androgen receptor (AR) phosphorylation at serine 81 is stimulated by the mitotic cyclin-dependent kinase 1 (CDK1). In this report, we extended our previous study and confirmed that Ser-81 phosphorylation increases during mitosis, coincident with CDK1 activation. We further showed blocking cell cycle at G(1) or S phase did not disrupt androgen-induced Ser-81 phosphorylation and AR-dependent transcription, consistent with a recent report that AR was phosphorylated at Ser-81 and activated by the transcriptional CDK9. To assess the function of Ser-81 phosphorylation in prostate cancer (PCa) cells expressing endogenous AR, we developed a ligand switch strategy using a ligand-binding domain mutation (W741C) that renders AR responsive to the antagonist bicalutamide. An S81A/W741C double mutant AR stably expressed in PCa cells failed to transactivate the endogenous AR-regulated PSA or TMPRSS2 genes. ChIP showed that the S81A mutation prevented ligand-induced AR recruitment to these genes, and cellular fractionation revealed that the S81A mutation globally abrogated chromatin binding. Conversely, the AR fraction rapidly recruited to chromatin after androgen stimulation was highly enriched for Ser-81 phosphorylation. Finally, inhibition of CDK1 and CDK9 decreased AR Ser-81 phosphorylation, chromatin binding, and transcriptional activity. These findings indicate that Ser-81 phosphorylation by CDK9 stabilizes AR chromatin binding for transcription and suggest that CDK1-mediated Ser-81 phosphorylation during mitosis provides a pool of Ser-81 phosphorylation AR that can be readily recruited to chromatin for gene reactivation and may enhance AR activity in PCa.

  19. Influence of gamma irradiation effects on the residual alteration rate of the French SON68 nuclear glass

    Energy Technology Data Exchange (ETDEWEB)

    Rolland, S. [CEA/DEN/DTCD/SECM, BP 17171, 30207 Bagnols sur Cèze cedex (France); Tribet, M., E-mail: magaly.tribet@cea.fr [CEA/DEN/DTCD/SECM, BP 17171, 30207 Bagnols sur Cèze cedex (France); Jollivet, P.; Jégou, C.; Broudic, V.; Marques, C. [CEA/DEN/DTCD/SECM, BP 17171, 30207 Bagnols sur Cèze cedex (France); Ooms, H. [Instrumentation Department SCK-CEN, Belgian Nuclear Research Centre, Boeretang 200, B-2400 Mol (Belgium); Toulhoat, P. [Université de Lyon 1, CNRS/ISA, UFR de Chimie Biochimie, 69622 Villeurbanne cedex (France); INERIS, Parc Technologique Alata, BP 2, 60550 Verneuil en Halatte (France)

    2013-02-15

    The residual rate regime of SON68 nuclear glass has been investigated here by static experiments under external irradiation. The experiments were carried out in a gamma irradiator with {sup 60}Co sources. Four dose rates were studied: two high dose rates (5 and 10 kGy h{sup −1}) to exacerbate electronic radiation effects, and two lower dose rates (0.8 and 0.05 kGy h{sup −1}). The objective of this work is not to assess potential LET effects but to assess more widely electronic effects on the residual rate regime which controls the long term stability of the glass under geological disposal. Fresh glasses were leached in argon atmosphere at 90 °C and at a high surface-area-to-volume ratio (SA/V = 10 000 m{sup −1}). Under these conditions the system quickly reaches the residual alteration rate regime. The alteration rate was monitored by solution analyses: the release of glass alteration tracer elements—in particular boron, sodium and lithium—was measured by ICP-AES. The hydrogen peroxide produced by water radiolysis was quantified by chemiluminescence. Radiation effects on the glass and its gel network were characterized by scanning electron microscopy (SEM) and Transmission Electron Microscopy (TEM). Higher H{sub 2}O{sub 2} concentrations were measured on irradiated samples in the presence of glass, suggesting an irradiation effect on the glass and its alteration layer. However, the data obtained on glass alteration show that potential defects or changes induced by gamma irradiation do not modify the kinetics of alteration up to a gamma dose rate of 10 kGy h{sup −1}: the residual rates measured for the different dose rates studied are similar and comparable to experiments performed without irradiation. Moreover, these observations are consistent with SEM and TEM characterizations which show that the alteration layer formed under gamma irradiation is similar to the alteration layer formed without irradiation. This study demonstrates that species produced

  20. Le problème du mal dans le Guide des Perplexes et son arrière-plan talmudique

    Directory of Open Access Journals (Sweden)

    Costa, José

    2010-12-01

    Full Text Available At first sight, the question of evil is regarded in the Guide for the Perplexed in a paradoxical manner. Thus, in Guide I, 2, Maimonides examines the notions of good and evil as subjective evaluations possessing neither the rigour not the exactness of the notions of true and false. However, the question of evil occupies an essential place in the Guide, as various modern authors have shown. This question is important to Maimonides because he is, in this respect, the heir of the rabbinic tradition and his conception of evil is largely based on an interaction with the Talmudic and Midrašic texts. Therefore, we would like to review thirty-nine rabbinic ‘quotes’ which appear in chapters 8 to 24 in the third part of the Guide and deal with the origin of evil, the meaning of suffering and the evil inclination. Maimonides reappropriates the midrašim that are susceptible of being in agreement with his rationalist positions and also quotes some rabbinic traditions that are too close to mu ͑tazilism, undoubtedly aware of the more profound resemblance that exists between the rabbinic and mu ͑tazilite doctrines of evil and retribution.A primera vista, el problema del mal es abordado en la Guía de Perplejos de manera paradójica. Para Maimónides, las nociones de bien y mal son subjetivas y no resultan ni rigorosas ni exactas, a la inversa de las nociones de verdad y falsedad (Guía I, 2. Sin embargo, el problema del mal es muy importante en la Guía, como lo demostraran varios autores. Maimónides es el heredero de la tradición rabínica y existe en la Guía una interacción entre la filosofia de Maimónides y los textos talmúdicos y midrásicos. Es particularmente el caso de las treinta y nueve citas rabínicas de la Guía II, 8-24, que tratan del origen del mal, del significado del sufrimiento y de la inclinación al mal. Maimónides cita los midrašim que concuerdan con sus posiciones racionalistas y evoca también algunas tradiciones rab

  1. Biological effect of Acidithiobacillus thiooxidans on some potentially toxic elements during alteration of SON 68 nuclear glass

    Science.gov (United States)

    Bachelet, M.; Crovisier, J. L.; Stille, P.; Vuilleumier, S.; Geoffroy, V.

    2009-04-01

    Although underground nuclear waste repositories are not expected to be favourable places for microbial activity, one should not exclude localized action of extremophilic bacteria on some materials involved in the storage concept. Among endogenous or accidentally introduced acidophiles, some are susceptible to lead to a locally drastic decreased in pH, with potential consequences on materials corrosion. Experiments were performed with Acidithiobacillus thiooxidans on 100-125 m french reference nuclear glass SON68 grains in a mineral medium under static conditions during 60 days at 25degC. Growth medium was periodically renewed and analyzed by ICP-AES and ICP-MS spectrometry for both major, trace and ultra-trace elements. Biofilm formation was evidenced by confocal laser microscopy, staining DNA with ethidium bromide and exopolysaccharides with calcofluor white. Biofilm thickness around material grains exceeded 20 m under the chosen experimental conditions. It can be noticed that while numerous studies on biofilm formation upon interaction between Acidithiobacillus ferrooxidans and materials are found in the literature, evidence for biofilm formation is still scarce for the case of the acidophilic bacterium A. thiooxidans. Presence of biofilm is a key parameter for material alteration at the solid/solution interface in biotic systems. Indeed, various constitutive elements of materials trapped in the polyanionic polymer of biofilm may also influence the alteration process. In particular, biofilm may reduce the alteration rate of materials by forming a protective barrier at their surface (Aouad et al., 2008). In this study, glass alteration rates, determined using strontium as tracer, showed that the progressive formation of a biofilm on the surface of glass has a protective effect against its alteration. Uranium and rare earth elements (REE) are efficiently trapped in the biogenic compartment of the system (exopolysaccharides + bacterial cells). Besides, the ratio

  2. ¿Son válidas las curvas y tablas de crecimiento españolas actuales?

    Directory of Open Access Journals (Sweden)

    T. Durá Travé

    Full Text Available Objetivo: Modificar los resultados del Estudio longitudinal del crecimiento en Navarra (NA 09 mediante la exclusión en la muestra poblacional de los casos de obesidad; así como realizar un análisis comparativo con las curvas de crecimiento españolas e internacionales más cualificadas. Material y métodos: De los 930 participantes del NA-09 se han excluido todos los casos de obesidad según los estándares de Cole et al., siendo la muestra definitiva de 782 participantes (371 varones y 411 mujeres. Los resultados obtenidos se comparan con los estudios españoles de Serra-Majem et al (estudio enKid, Carrascosa et al (ESP 08 y NA 09, que no excluyen los casos de obesidad; así como, con las tablas del Center for Disease Control and Prevention (CDC, 2000 y de la OMS (WHO, 2007 que aplican criterios de depuración de valores antropométricos poco saludables (obesidad y malnutrición. Resultados: Se exponen los valores medios modificados de la talla, peso e IMC con su distribución percentilada, en ambos sexos. Al compararlos con los estudios españoles se observa que los valores evolutivos de los percentiles 3 y 50 correspondientes a la talla, peso e IMC son prácticamente similares; sin embargo, los valores evolutivos del percentil 97 correspondientes al peso e IMC se van distanciando progresivamente. Al compararlos con los estándares internaciones los valores evolutivos de los percentiles 3, 50 y 97 correspondientes al IMC se intercalaban entre ambas referencias. Conclusiones: Para que las curvas y tablas de crecimiento puedan servir como patrones de referencia convendría también excluir en su elaboración a todos los pacientes con obesidad; ya que, de otra manera, podrían llegar a considerarse como estudios meramente descriptivos de una población con una reconocida tendencia al exceso de peso corporal y, por tanto, su aplicabilidad clínica quedaría en entredicho.

  3. ¿Son los chilenos igualmente solidarios?la influencia de los recursos personales en las donaciones de dinero

    Directory of Open Access Journals (Sweden)

    Juan Carlos Castillo

    2012-06-01

    Full Text Available En el discurso público comúnmente se asume que Chile es un país solidario, un supuesto que se confunde con la idea de una cierta homogeneidad en lo que respecta a valores solidarios y conductas de ayuda en el país. El presente trabajo apunta a cuestionar esta idea de homogeneidad respecto de solidaridad, proponiendo que las conductas solidarias se relacionan con los recursos que las personas poseen, los que a su vez se asocian al lugar que las personas ocupan en la estructura de estratificación social. Tomando los datos de la Encuesta de Solidaridad realizada en 2009 por el Centro de Medición MIDE UC de la Pontificia Universidad Católica de Chile, el trabajo se centra en un tipo de conducta de ayuda particular: las donaciones en dinero. El análisis se focaliza en la influencia de recursos personales como ingreso, educación y pertenencia a redes sobre este tipo de donaciones. Los resultados indican que los individuos con mayores recursos son más proclives a las donaciones, donde el nivel educacional alcanzado juega un papel preponderante.In the public discourse it is commonly assumed that Chile is a solidary country, an assumption that is mixed with the idea of homogeneity in the country as far as helping behavior and solidarity values is concerned. The present paper is aimed at challenging this homogeneity assumption by proposing that helping behavior is associated to personal resources, which at the same time are linked to the position in the social stratification structure. Using data from the Solidarity Survey implemented by the assessment center MIDE UC of the Pontificia Universidad Católica de Chile in 2009, the paper focuses on a specific type of helping behavior: money donations. The analysis centers on the influence of personal resources such as income, education and networks on this kind of donations. Results indicate that individuals with greater resources are more given to donate, whereby the educational level plays a key

  4. Alternative Constructions of Treason in the Angevin Political World: Traïson in the History of William Marshal

    Directory of Open Access Journals (Sweden)

    Stephen D. WHITE

    2007-05-01

    Full Text Available After some nobles and other fighting men surrendered Rochester castle to King John in 1215, John wanted to hang the nobles but refrained from doing so on the advice of one of his military captains. Would hanging the nobles for making war on the king have been lawful? This question about the law of treason has provoked inconclusive debate among historians who have sought to determine whether, in this period, making war against the English king was legally classified as lèse-majesté (crimen laesae majestatis, proditio or infidelitas. This article, however, asks whether the nobles whom John wanted to hang were guilty of traïson, as this vernacular term was used in the History of William Marshal (c. 1230. On this basis, the paper concludes that in all probability, the nobles who held Rochester against the king would not have been condemned as traitors, at least by their aristocratic peers.Cuando en 1215 ciertos nobles y otros combatientes se rindieron y entregaron el castillo de Rochester al rey Juan éste quiso colgarles, pero el consejo de uno de sus nobles le hizo absternerse. ¿Habría sido legítimo condenar a la horca a los que habían guerreado contra el rey? Cuestiones relativas al derecho de traición al intentar determinar si la guerra contra el rey de Inglaterra fue considerada en la época un crimen laesae majestatis, proditio, o infidelitas, según la definición que dan a estos términos las fuentes latinas, han suscitado debates interminables entre los historiadores. Este artículo, por el contrario, se pregunta si los nobles que el rey Juan deseaba colgar eran o no culpables de traición, en el sentido vernáculo del término que es usado en L’histoire de Guillaume le Maréchal (hacia 1230. Sobre esta base, la conclusión del artículo es que los nobles que ocuparon el castillo de Rochester, casi con total seguridad, no habrían sido condenados como traidores, al menos por sus pares.

  5. La structure iconographique d’un art rupestre est-elle une clef pour son interprétation?

    Directory of Open Access Journals (Sweden)

    Georges SAUVET

    2009-12-01

    Full Text Available RÉSUMÉ: L’hypothèse émise par R. Layton selon laquelle la structure des arts rupestres diffère profondément, en termes de fréquence des motifs et de leur distribution entre les sites, en fonction de la religion et de l’organisation sociale des groupes humains est réexaminée dans ce travail collectif, à l’aide d’une documentation renouvelée et augmentée provenant d’Afrique et d’Australie, mais aussi d’une analyse approfondie de l’art pariétal paléolithique d’Europe occidentale. Il ressort de cette étude que l’hétérogénéité des sites (distribution géographique des motifs et la diversité de l’iconographie (fréquence des motifs sont des critères importants indubitablement liés à la structure sociale, aux croyances et à l’économie des sociétés, mais qu’ils ne permettent pas de trancher en faveur d’une organisation totémique ou de pratiques chamaniques.RESUMEN: La hipótesis de R. Layton según la cual la estructura de las artes rupestres difiere mucho en términos de frecuencia de los motivos y de su distribución entre los sitios, en función de la religión y de la organización social de los grupos humanos es examinada de nuevo en este trabajo colectivo, a la luz de una documentación nueva y aumentada procedente de África y Australia y de un análisis pormenorizado del arte parietal paleolítico de Europa occidental. Resulta de este estudio que la heterogeneidad de los sitios (distribución geográfica de los motivos y la diversidad de la iconografía (frecuencia de los motivos son criterios efectivamente ligados a la estructura social, a las creencias y a la economía de las sociedades, pero no permiten decidir a favor de una organización totémica o de prácticas chamánicas.

  6. Bilateral Brown's syndrome in a mother and her son: case report Síndrome de Brown bilateral em mãe e filho: relato de caso

    Directory of Open Access Journals (Sweden)

    Rosália Maria Simões Antunes-Foschini

    2008-08-01

    Full Text Available This case report describes clinical data from mother and son with bilateral Brown's syndrome and highlights possible genetically determined predispositions.Este relato de caso descreve achados clínicos de mãe e filho com síndrome de Brown bilateral e discute a possibilidade de predisposição genética.

  7. On the Relationship between Father and Son in Seize the Day%《只争朝夕》中的父子关系分析

    Institute of Scientific and Technical Information of China (English)

    吴丽聪

    2014-01-01

    Saul Bellow’s novel Seize the Day represents an extraordinary contribution to the relationship between father and son as a theme in fiction. This paper tries to analyze the relationship between the hero and his father in order to help the reader have a better understanding of the novel.

  8. Understanding Gender Differences in Children's Risk Taking and Injury: A Comparison of Mothers' and Fathers' Reactions to Sons and Daughters Misbehaving in Ways that Lead to Injury

    Science.gov (United States)

    Morrongiello, Barbara A.; Zdzieborski, Daniel; Normand, Jackie

    2010-01-01

    This study compared reactions of mothers and fathers to the risk taking behavior of sons and daughters. Mother-father pairs (N = 52) imagined their 2-year-old boy or girl behaving in risky ways in common home situations that could, and did, result in injury. Emotional and parenting reactions to the behaviors were assessed before and after injury.…

  9. «¿Quién soy yo? ¿Quiénes son ellos/as?». Personajes en busca de identidad

    Directory of Open Access Journals (Sweden)

    Caretti, Laura

    2006-12-01

    Full Text Available Who am I? Who are they? These are the questions haunting the characters, created by writers such as Ibsen, Pirandello, Beckett and others, whose emblematic search for identity is explored in the article. The complex interconnections between subjectivity and alterity are focused within the coordinates of space (society and time (memory in their outward and inward movement. The characters are seen on stage relating also to the otherness of actors and spectators. Particular relief is given to the difference between the female and male search for identity in the light of contemporary historical changes.¿Quién soy yo? ¿Quiénes son ellos/as? Estas son las cuestiones que obsesionan a los personajes creados por escritores como Ibsen, Pirandello, Beckett y otros, cuya emblemática búsqueda de identidad se explora a lo largo de este artículo. Las complejas interconexiones entre subjetividad y alteridad son analizadas con las coordenadas del espacio (sociedad y el tiempo (memoria en su movimiento interno y externo. Los personajes son vistos en el escenario desde la alteridad de actores y espectadores. Un particular relieve se otorga a la diferencia entre la búsqueda de la identidad femenina y masculina a la luz de los cambios históricos contemporáneos.

  10. Sons conceived by assisted reproduction techniques inherit deletions in the azoospermia factor (AZF) region of the Y chromosome and the DAZ gene copy number

    DEFF Research Database (Denmark)

    Mau Kai, C; Juul, A; McElreavey, K

    2008-01-01

    number, supplemented with haplogroup typing in deleted patients, were performed, in combination with clinical assessments in 264 fathers and their sons conceived by assisted reproduction techniques (ART), and in 168 fertile men with normal sperm concentration. RESULTS: In the ART fathers group...

  11. El desequilibrio de importancia entre las lenguas oficiales de Bolivia ¿ Por qué existen lenguas que son más oficiales que otras?

    DEFF Research Database (Denmark)

    Cancino, Rita

    EL DESEQUILIBRIO DE IMPORTANCIA ENTRE LAS LENGUAS OFICIALES DE BOLIVIA ¿ POR QUÉ EXISTEN LENGUAS QUE SON MÁS OFICIALES QUE OTRAS? Con la Constitución de Bolivia muchas lenguas originarias fueron declaradas oficiales y levantadas a un nivel de lengua oficial en paridad con el español. En el Artículo...

  12. Toward the Autonomous Recording and Transmission of Seismic Data from the Oceans: Testing the Son-O-Mermaid Float in the Sargasso Sea

    Science.gov (United States)

    Simon, J. D.; Simons, F. J.; Vincent, H. T.; Nolet, G.

    2015-12-01

    We report on the deployment of two new Son-O-Mermaid floats into theSargasso Sea during a cruise aboard the R/V Atlantic Explorer, whichdeparted from Bermuda in May of 2015. Son-O-Mermaid is a freelyfloating and autonomous oceangoing system composed of a surface buoyconnected to a length of cable from which a three-hydrophone array issuspended. The main objective of the Son-O-Mermaid project is torecord signals suitable for global tomography in the deep ocean andprovide the seismic community with an abundance of novel raypaths frompreviously unsampled regions of the Earth. The Son-O-Mermaid float,with its ability to continually record, analyze, and transmit seismicdata from the oceans in near-real time has the potential torevolutionize the field of seismology. We analyze new data returnedfrom this deployment, a previous Son-O-Mermaid test, as well as theongoing MERMAID mission in the time, spectral, and wavelet domains. Afull description of the float and deployment report will be presented.A short-term goal of the project is determining realistic magnitude,distance, and pressure relationships for teleseismic earthquakes thatare recorded in the water column. Our analysis of this question isaided by synthetics created using SPECFEM2D and guided by the data,especially noise records recorded by Son-O-Mermaid and MERMAID fromoceans throughout the world. Synthetics provide an idealized waveformuseful for understanding the often very messy and noisy arrivalscommon in midcolumn acoustic recordings. Notably, synthetics allowthe confirmation or rejection of unlikely phases which are matched toearthquake databases after arrivals are detected by automatic pickingalgorithms. Additionally, marine-acoustic processing techniques willbe improved once the underwater acoustic field is better modeled usingrealistic signal-to-noise ratios and noise spectra returned fromSon-O-Mermaid and MERMAID missions. This analysis, particularly whenimplemented in the wavelet domain, is proving

  13. Cooperative binding: a multiple personality.

    Science.gov (United States)

    Martini, Johannes W R; Diambra, Luis; Habeck, Michael

    2016-06-01

    Cooperative binding has been described in many publications and has been related to or defined by several different properties of the binding behavior of the ligand to the target molecule. In addition to the commonly used Hill coefficient, other characteristics such as a sigmoidal shape of the overall titration curve in a linear plot, a change of ligand affinity of the other binding sites when a site of the target molecule becomes occupied, or complex roots of the binding polynomial have been used to define or to quantify cooperative binding. In this work, we analyze how the different properties are related in the most general model for binding curves based on the grand canonical partition function and present several examples which highlight differences between the cooperativity characterizing properties which are discussed. Our results mainly show that among the presented definitions there are not two which fully coincide. Moreover, this work poses the question whether it can make sense to distinguish between positive and negative cooperativity based on the macroscopic binding isotherm only. This article shall emphasize that scientists who investigate cooperative effects in biological systems could help avoiding misunderstandings by stating clearly which kind of cooperativity they discuss.

  14. Evidências de validade convergente do SON-R 2½-7[a] com o WPPSI-III e WISC-III Evidences of convergent validity of SON-R 2½-7[a] with WPPSI-III and WISC-III

    Directory of Open Access Journals (Sweden)

    Camila Akemi Karino

    2011-01-01

    Full Text Available Um processo de validação adequado é fundamental para assegurar uma interpretação correta dos resultados de um teste. Assim, este estudo investigou a validade convergente do teste não-verbal de inteligência SON-R 2½-7[a] com o WPPSI-III e o WISC-III. O teste é a versão abreviada do SON-R 2½-7, de origem holandesa, normatizado e validado em vários países da Europa. No total, 109 crianças de três estados brasileiros participaram do estudo. A correlação entre o SON-R 2½-7[a] e o WPPSI-III foi igual a 0,75 e com o WISC-III foi de 0,69. Esses coeficientes de validade são muito semelhantes aos encontrados em estudos feitos com o SON-R 2½-7 em outros países. Conclui-se que os resultados indicam uma validade convergente satisfatória do teste SON-R 2½-7[a].An adequate validation process is fundamental to ensure sound interpretations of test results. Thus, this study aimed to investigate the convergent validity of the SON-R 2½-7[a] with the WPPSI-III and the WISC-III. The test is an abridged edition of the SON-R 2½-7, a Dutch non-verbal intelligence test, with normatization and validation studies done in several European countries. A total of 109 children from three Brazilian states participated in the study. The correlations of the SON-R 2½-7[a] with the WPPSI-III and with the WISC-III were .75 and .69, respectively. The validation coefficients encountered are very similar to the ones found in studies with the SON-R 2½-7 in other countries. The results imply a satisfactory convergent validity of the SON-R 2½-7[a].

  15. Binding of cellular export factor REF/Aly by Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 protein is not required for efficient KSHV lytic replication.

    Science.gov (United States)

    Li, Da-Jiang; Verma, Dinesh; Swaminathan, Sankar

    2012-09-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 protein is expressed early during lytic KSHV replication, enhances expression of many KSHV genes, and is essential for virus production. ORF57 is a member of a family of proteins conserved among all human and many animal herpesviruses that are multifunctional regulators of gene expression and act posttranscriptionally to increase accumulation of their target mRNAs. The mechanism of ORF57 action is complex and may involve effects on mRNA transcription, stability, and export. ORF57 directly binds to REF/Aly, a cellular RNA-binding protein component of the TREX complex that mediates RNA transcription and export. We analyzed the effects of an ORF57 mutation known to abrogate REF/Aly binding and demonstrate that the REF-binding mutant is impaired in activation of viral mRNAs and noncoding RNAs confined to the nucleus. Although the inability to bind REF leads to decreased ORF57 activity in enhancing gene expression, there is no demonstrable effect on nuclear export of viral mRNA or the ability of ORF57 to support KSHV replication and virus production. These data indicate that REF/Aly-ORF57 interaction is not essential for KSHV lytic replication but may contribute to target RNA stability independent of effects on RNA export, suggesting a novel role for REF/Aly in viral RNA metabolism.

  16. Acute myeloid leukemia targeting by myxoma virus in vivo depends on cell binding but not permissiveness to infection in vitro.

    Science.gov (United States)

    Madlambayan, Gerard J; Bartee, Eric; Kim, Manbok; Rahman, Masmudur M; Meacham, Amy; Scott, Edward W; McFadden, Grant; Cogle, Christopher R

    2012-05-01

    Some oncolytic viruses, such as myxoma virus (MYXV), can selectively target malignant hematopoietic cells, while sparing normal hematopoietic cells. This capacity for discrimination creates an opportunity to use oncolytic viruses as ex vivo purging agents of autologous hematopoietic cell grafts in patients with hematologic malignancies. However, the mechanisms by which oncolytic viruses select malignant hematopoietic cells are poorly understood. In this study, we investigated how MYXV specifically targets human AML cells. MYXV prevented chloroma formation and bone marrow engraftment of two human AML cell lines, KG-1 and THP-1. The reduction in human leukemia engraftment after ex vivo MYXV treatment was dose-dependent and required a minimum MOI of 3. Both AML cell lines demonstrated MYXV binding to leukemia cell membranes following co-incubation: however, evidence of productive MYXV infection was observed only in THP-1 cells. This observation, that KG-1 can be targeted in vivo even in the absence of in vitro permissive viral infection, contrasts with the current understanding of oncolytic virotherapy, which assumes that virus infection and productive replication is a requirement. Preventing MYXV binding to AML cells with heparin abrogated the purging capacity of MYXV, indicating that binding of infectious virus particles is a necessary step for effective viral oncolysis. Our results challenge the current dogma of oncolytic virotherapy and show that in vitro permissiveness to an oncolytic virus is not necessarily an accurate predictor of oncolytic potency in vivo.

  17. Lineage-affiliated transcription factors bind the Gata3 Tce1 enhancer to mediate lineage-specific programs.

    Science.gov (United States)

    Ohmura, Sakie; Mizuno, Seiya; Oishi, Hisashi; Ku, Chia-Jui; Hermann, Mary; Hosoya, Tomonori; Takahashi, Satoru; Engel, James Douglas

    2016-03-01

    The transcription factor GATA3 is essential for the genesis and maturation of the T cell lineage, and GATA3 dysregulation has pathological consequences. Previous studies have shown that GATA3 function in T cell development is regulated by multiple signaling pathways and that the Notch nuclear effector, RBP-J, binds specifically to the Gata3 promoter. We previously identified a T cell-specific Gata3 enhancer (Tce1) lying 280 kb downstream from the structural gene and demonstrated in transgenic mice that Tce1 promoted T lymphocyte-specific transcription of reporter genes throughout T cell development; however, it was not clear if Tce1 is required for Gata3 transcription in vivo. Here, we determined that the canonical Gata3 promoter is insufficient for Gata3 transcriptional activation in T cells in vivo, precluding the possibility that promoter binding by a host of previously implicated transcription factors alone is responsible for Gata3 expression in T cells. Instead, we demonstrated that multiple lineage-affiliated transcription factors bind to Tce1 and that this enhancer confers T lymphocyte-specific Gata3 activation in vivo, as targeted deletion of Tce1 in a mouse model abrogated critical functions of this T cell-regulatory element. Together, our data show that Tce1 is both necessary and sufficient for critical aspects of Gata3 T cell-specific transcriptional activity.

  18. Asymmetric cation-binding catalysis

    DEFF Research Database (Denmark)

    Oliveira, Maria Teresa; Lee, Jiwoong

    2017-01-01

    and KCN, are selectively bound to the catalyst, providing exceptionally high enantioselectivities for kinetic resolutions, elimination reactions (fluoride base), and Strecker synthesis (cyanide nucleophile). Asymmetric cation-binding catalysis was recently expanded to silicon-based reagents, enabling...... solvents, thus increasing their applicability in synthesis. The expansion of this concept to chiral polyethers led to the emergence of asymmetric cation-binding catalysis, where chiral counter anions are generated from metal salts, particularly using BINOL-based polyethers. Alkali metal salts, namely KF...

  19. Cytoplasmic polyadenylation-element-binding protein (CPEB)1 and 2 bind to the HIF-1alpha mRNA 3'-UTR and modulate HIF-1alpha protein expression.

    Science.gov (United States)

    Hägele, Sonja; Kühn, Uwe; Böning, Melanie; Katschinski, Dörthe M

    2009-01-01

    The heterodimeric HIF (hypoxia-inducible factor)-1 is a transcriptional master regulator of several genes involved in mammalian oxygen homoeostasis. Besides the well described regulation of the HIF-1alpha subunit via hydroxylation-mediated protein stability in hypoxia, there are several indications of an additional translational control of the HIF-1alpha mRNA, especially after growth factor stimulation. We identified an interaction of CPEB (cytoplasmic polyadenylation-element-binding protein) 1 and CPEB2 with the 3'-UTR (untranslated region) of HIF-1alpha mRNA. Overexpression of CPEB1 and CPEB2 affected HIF-1alpha protein levels mediated by the 3'-UTR of HIF-1alpha mRNA. Stimulation of neuroblastoma SK-N-MC cells with insulin and thus activation of endogenous CPEBs increased the expression of a luciferase reporter gene fused to the 3'-UTR of HIF-1alpha as well as endogenous HIF-1alpha protein levels. This could be abrogated by treating the cells with CPEB1 or CPEB2 siRNAs (short interfering RNAs). Injection of HIF-1alpha cRNA into Xenopus oocytes verified the elongation of the poly(A)+ (polyadenylated) tail by cytoplasmic polyadenylation. Thus CPEB1 and CPEB2 are involved in the regulation of HIF-1alpha following insulin stimulation.

  20. Evaluación de anemia ferropénica en la primera infancia del Municipio de Sonsón-Antioquia, 2007

    OpenAIRE

    Tulia Isabel Castillo Salgado; Rocío Pérez Escobar

    2016-01-01

    Objetivo: Determinar la prevalencia de anemia por deficiencia de hierro en niños de la primera infancia del municipio de Sonsón – Antioquia, en el año 2007. Metodología: Se realizó un estudio descriptivo transversal en 391 niños de 0 a 84 meses de edad del Municipio de Sonsón, Antioquia. Se estudiaron los parámetros de hemoglobina y ferritina sérica utilizando puntos de corte de la Organización Mundial de la Salud (OMS). Se calcularon las medidas de frecuencia y de resumen y los intervalos de...

  1. Los estudios de género de los hombres y las masculinidades: ¿qué son y qué estudian?

    Directory of Open Access Journals (Sweden)

    Guillermo Núñez Noriega

    2016-01-01

    Full Text Available En este artículo se presenta una visión comprensiva de los estudios de género de los varones y las masculinidades a partir de dos reflexiones relacionadas: a el vínculo con el feminismo y los estudios lgbtti, y b el objeto de estudio. La propuesta se realiza desde la epistemología constructivista realista y desde el planteo teórico posestructuralista. Se plantea que estos estudios son un subcampo de los estudios de género y que su objeto no son ni los hombres, ni las masculinidades por sí solos, sino los procesos socioculturales y de poder (androcéntrico y/o heterosexista, de inscripción/resistencia/transformación del género en los cuerpos/subjetividades de los humanos machos y/o socialmente “hombres”, y en el tejido social todo.

  2. Parental choice: what parents want in a son-in-law and a daughter-in-law across 67 pre-industrial societies.

    Science.gov (United States)

    Apostolou, Menelaos

    2010-11-01

    Parents are influential over mate choice, and in most human societies they choose spouses for their offspring according to their own preferences. However, surprising little is known about the qualities which make a woman desirable as a daughter-in-law and a man desirable as a son-in-law. Using evidence from 67 societies such traits are identified and three hypotheses are tested: first, the hypothesis is tested that parents desire in an in-law qualities which are beneficial to them and their kin. Second, it is hypothesized that such preferences are contingent upon the sex of the in-law, as traits are weighted differently in a daughter-in-law and in a son-in-law. The third hypothesis tested is that parental preferences vary according to the subsistence type of a given society, as traits are valued differently in agropastoral societies and foraging societies. The evidence presented here provides support for all three hypotheses.

  3. La riqueza y la pobreza de las naciones. ¿Por qué algunas son tan ricas y otras tan pobres?

    Directory of Open Access Journals (Sweden)

    Abel Ignacio López

    2010-08-01

    Full Text Available Landes, David. La riqueza y la pobreza de las naciones. ¿Por qué algunas son tan ricas y otras son tan pobres?, Barcelona, Editorial Crítica, 1999, 604 páginas. ¿Porqué hay naciones pobres y naciones ricas y cuál es la contribución de la historia en la comprensión de esta cuestión? El autor entiende por cultura el espíritu de empresa, el conjunto de valores que guían la conducta de una población, el dominio de la ciencia, la tecnología y el espíritu racional.

  4. La riqueza y la pobreza de las naciones. ¿por qué algunas son tan ricas y otras tan pobres?

    OpenAIRE

    Abel Ignacio López.

    2010-01-01

    Landes, David. La riqueza y la pobreza de las naciones. ¿Por qué algunas son tan ricas y otras son tan pobres?, Barcelona, Editorial Crítica, 1999, 604 páginas. ¿Porqué hay naciones pobres y naciones ricas y cuál es la contribución de la historia en la comprensión de esta cuestión? El autor entiende por cultura el espíritu de empresa, el conjunto de valores que guían la conducta de una población, el dominio de la ciencia, la tecnología y el espíritu racional.

  5. De Masaccio à Stalker: pour une esthétique du seuil et de son franchissement 

    Directory of Open Access Journals (Sweden)

    Sylvie Castets

    2010-04-01

    Full Text Available Le seuil,abordé en tant que sujet représenté, est ici le moyen d’envisager la question  de la limite et de son dépassement dans le territoire de l’œuvre peinte, de l’installation et de la performance. La fresque de Masaccio, intitulée « Adam et Ève chassés du Paradis », réalisée vers 1425, constitue une étape décisive dans le traitement de l’espace de représentation. La suggestion d’une  profondeur, mais également, d’une épaisseur, apparaît, faisant basculer la peinture vers le naturalisme. Ainsi, au réalisme intellectuel du Moyen Age, se substitue un nouveau mode de figuration. L’artiste de la Renaissance quitte donc un territoire artistique pour explorer et poser les bases d’un art inédit. Dès lors, la toile, telle une zone de friction, se place et agit dans l’interstice séparant l’espace réel et l’espace représenté. La vision du spectateur, face au tableau, franchit ainsi le barrage de l’œuvre pour coloniser une fable topique amenée par l’illusion de la profondeur. La peinture est également le lieu où l’artiste révèle au spectateur, par le biais de stratagèmes plastiques, ses conditions de réalisation. A partir de là, une rupture s’opère entre la représentation et le fait de présenter. Art et vie s’interpénètrent alors, dans des installations ou des performances, offrant au spectateur un lieu milieu, dans lequel il est amené à s’affranchir de ces modèles. L’oeuvre est donc un seuil qu’il faut «traverser pour apprendre la solitude. » (Serres. Elle vibre d’instabilité et cristallise l’état singulier du changement. Enfin, elle conduit inéluctablement vers un devenir autre.The threshold as theme of representation is in this article used as a way to question the limit and its crossing in the territory of the painted work, of the installation and the performance. Masaccio’s fresco “The Expulsion from the Garden of Eden” of 1425 constitutes a decisive

  6. Yo no soy marinero, soy capitán:Usos sociopolíticos contemporáneos del fandango y el son jarocho

    Directory of Open Access Journals (Sweden)

    Rafael Figueroa­ Hernández

    2015-01-01

    Siguiendo las reglas musicales y líricas tradicionales del son jarocho, un creciente grupo de personas han estado usando el fandango como una manera de participar en protestas sociales de varias maneras: a creando o manteniendo identidad entre grupos subalternos, b diseminando ideas políticas y sociales a través de letras basadas en formas tradicionales y c mediante la participación directa en manifestaciones y marchas entre otras.

  7. Notice sur Madame Dr A.A. Weber née van Bosse à l’occasion de son 90ième anniversaire

    NARCIS (Netherlands)

    Koster, Joséphine Th.; Benthem Jutting, van Tera S.S.

    1942-01-01

    Anne Antoinette van Bosse, fille de M. Jacob van Bosse et de Mme Jaqueline Jeanne née Reynvaan, naquit à Amsterdam le 27 mars 1852. Très jeune encore elle perdit sa mère; sa soeur, son ainée de 10 ans, prit sa place aussi bien qu’elle put. Outre cette soeur elle avait trois frères. Selon l’usage de

  8. ¿Son asimétricas las reacciones de política monetaria de un banco central? El caso del BCE

    Directory of Open Access Journals (Sweden)

    Jesús Manuel García-Iglesias

    2013-01-01

    Full Text Available Una gran parte de los bancos centrales adopta sus decisiones conforme a determinados objetivos, fundamentalmente de inflación y crecimiento económico. La pregunta que nos hacemos es si son igual de intensas las reacciones de esos institutos centrales cuando las desviaciones respecto a los objetivos señalados son positivas, en comparación con el caso en que sean negativas, o si, por el contrario, las reacciones son asimétricas. Para responder a esta cuestión, con base en los planteamientos taylorianos de la función de reacción de política monetaria, analizamos las posibles causas de comportamientos asimétricos y establecemos una metodología para determinar si las decisiones de un banco central han sido asimétricas, o no. Empíricamente, analizamos el caso del Banco Central Europeo (BCE, para concluir que en el caso de éste no es posible afirmar que haya reaccionado asimétricamente en el periodo1999-2008.

  9. Genetic data and de novo mutation rates in father-son pairs of 23 Y-STR loci in Southern Brazil population.

    Science.gov (United States)

    Da Fré, Nicole Nascimento; Rodenbusch, Rodrigo; Gastaldo, André Zoratto; Hanson, Erin; Ballantyne, Jack; Alho, Clarice Sampaio

    2015-11-01

    We evaluated haplotype and allele frequencies, as well as statistical forensic parameters, for 23 Y-chromosome short tandem repeats (STRs) loci of the PowerPlex®Y23 system (DYS19, DYS385a/b, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, Y-GATA-H4, DYS481, DYS533, DYS549, DYS570, DYS576, DYS643) in a sample of 150 apparently healthy males, resident in South Brazil. A total of 150 different haplotypes were identified. The highest gene diversity (GD) was observed for the single locus marker DYS570 (GD = 0.7888) and for a two-locus system DYS385 (GD = 0.9009). We also examined 150 father-son pairs by the same system, and a total of 13 mutations were identified in the 3450 father-son allelic transfers, with an overall mutation rate across the 23 loci of 3.768 × 10(-3) (95% CI: 3.542 × 10(-3) to 3.944 × 10(-3)). In all cases there was only one locus mutated with gain/loss of repeats in the son (5 one-repeat gains, and 7 one-repeat and 1 two-repeat losses); we observed no instances of mutations involving a non-integral number of repeats.

  10. Cholesterol binding to ion channels

    Directory of Open Access Journals (Sweden)

    Irena eLevitan

    2014-02-01

    Full Text Available Numerous studies demonstrated that membrane cholesterol is a major regulator of ion channel function. The goal of this review is to discuss significant advances that have been recently achieved in elucidating the mechanisms responsible for cholesterol regulation of ion channels. The first major insight that comes from growing number of studies that based on the sterol specificity of cholesterol effects, show that several types of ion channels (nAChR, Kir, BK, TRPV are regulated by specific sterol-protein interactions. This conclusion is supported by demonstrating direct saturable binding of cholesterol to a bacterial Kir channel. The second major advance in the field is the identification of putative cholesterol binding sites in several types of ion channels. These include sites at locations associated with the well-known cholesterol binding motif CRAC and its reversed form CARC in nAChR, BK, and TRPV, as well as novel cholesterol binding regions in Kir channels. Notably, in the majority of these channels, cholesterol is suggested to interact mainly with hydrophobic residues in non-annular regions of the channels being embedded in between transmembrane protein helices. We also discuss how identification of putative cholesterol binding sites is an essential step to understand the mechanistic basis of cholesterol-induced channel regulation. Clearly, however, these are only the first few steps in obtaining a general understanding of cholesterol-ion channels interactions and their roles in cellular and organ functions.

  11. The prion protein binds thiamine.

    Science.gov (United States)

    Perez-Pineiro, Rolando; Bjorndahl, Trent C; Berjanskii, Mark V; Hau, David; Li, Li; Huang, Alan; Lee, Rose; Gibbs, Ebrima; Ladner, Carol; Dong, Ying Wei; Abera, Ashenafi; Cashman, Neil R; Wishart, David S

    2011-11-01

    Although highly conserved throughout evolution, the exact biological function of the prion protein is still unclear. In an effort to identify the potential biological functions of the prion protein we conducted a small-molecule screening assay using the Syrian hamster prion protein [shPrP(90-232)]. The screen was performed using a library of 149 water-soluble metabolites that are known to pass through the blood-brain barrier. Using a combination of 1D NMR, fluorescence quenching and surface plasmon resonance we identified thiamine (vitamin B1) as a specific prion ligand with a binding constant of ~60 μM. Subsequent studies showed that this interaction is evolutionarily conserved, with similar binding constants being seen for mouse, hamster and human prions. Various protein construct lengths, both with and without the unstructured N-terminal region in the presence and absence of copper, were examined. This indicates that the N-terminus has no influence on the protein's ability to interact with thiamine. In addition to thiamine, the more biologically abundant forms of vitamin B1 (thiamine monophosphate and thiamine diphosphate) were also found to bind the prion protein with similar affinity. Heteronuclear NMR experiments were used to determine thiamine's interaction site, which is located between helix 1 and the preceding loop. These data, in conjunction with computer-aided docking and molecular dynamics, were used to model the thiamine-binding pharmacophore and a comparison with other thiamine binding proteins was performed to reveal the common features of interaction.

  12. Galectin-3-Binding and Metastasis

    Science.gov (United States)

    Nangia-Makker, Pratima; Balan, Vitaly; Raz, Avraham

    2013-01-01

    i. Summary Galectin-3 is a member of a family of carbohydrate-binding proteins. It is present in the nucleus, the cytoplasm and also extracellular matrix of many normal and neoplastic cell types. Arrays of reports show an upregulation of this protein in transformed and metastatic cell lines (1, 2). Moreover, in many human carcinomas, an increased expression of galectin-3 correlates with progressive tumor stages (3–6). Several lines of analysis have demonstrated that the galectins participate in cell-cell and cell-matrix interactions by recognizing and binding complimentary glycoconjugates and thereby play a crucial role in normal and pathological processes. Elevated expression of the protein is associated with an increased capacity for anchorage-independent growth, homotypic aggregation, and tumor cell lung colonization (7–9). In this chapter we describe the methods of purification of galectin-3 from transformed E. coli and some of the commonly used functional assays for analyzing galectin-3 binding. PMID:22674139

  13. The meningococcal vaccine candidate neisserial surface protein A (NspA binds to factor H and enhances meningococcal resistance to complement.

    Directory of Open Access Journals (Sweden)

    Lisa A Lewis

    Full Text Available Complement forms an important arm of innate immunity against invasive meningococcal infections. Binding of the alternative complement pathway inhibitor factor H (fH to fH-binding protein (fHbp is one mechanism meningococci employ to limit complement activation on the bacterial surface. fHbp is a leading vaccine candidate against group B Neisseria meningitidis. Novel mechanisms that meningococci employ to bind fH could undermine the efficacy of fHbp-based vaccines. We observed that fHbp deletion mutants of some meningococcal strains showed residual fH binding suggesting the presence of a second receptor for fH. Ligand overlay immunoblotting using membrane fractions from one such strain showed that fH bound to a approximately 17 kD protein, identified by MALDI-TOF analysis as Neisserial surface protein A (NspA, a meningococcal vaccine candidate whose function has not been defined. Deleting nspA, in the background of fHbp deletion mutants, abrogated fH binding and mAbs against NspA blocked fH binding, confirming NspA as a fH binding molecule on intact bacteria. NspA expression levels vary among strains and expression correlated with the level of fH binding; over-expressing NspA enhanced fH binding to bacteria. Progressive truncation of the heptose (Hep I chain of lipooligosaccharide (LOS, or sialylation of lacto-N-neotetraose LOS both increased fH binding to NspA-expressing meningococci, while expression of capsule reduced fH binding to the strains tested. Similar to fHbp, binding of NspA to fH was human-specific and occurred through fH domains 6-7. Consistent with its ability to bind fH, deleting NspA increased C3 deposition and resulted in increased complement-dependent killing. Collectively, these data identify a key complement evasion mechanism with important implications for ongoing efforts to develop meningococcal vaccines that employ fHbp as one of its components.

  14. Computational Prediction of RNA-Binding Proteins and Binding Sites.

    Science.gov (United States)

    Si, Jingna; Cui, Jing; Cheng, Jin; Wu, Rongling

    2015-01-01

    Proteins and RNA interaction have vital roles in many cellular processes such as protein synthesis, sequence encoding, RNA transfer, and gene regulation at the transcriptional and post-transcriptional levels. Approximately 6%-8% of all proteins are RNA-binding proteins (RBPs). Distinguishing these RBPs or their binding residues is a major aim of structural biology. Previously, a number of experimental methods were developed for the determination of protein-RNA interactions. However, these experimental methods are expensive, time-consuming, and labor-intensive. Alternatively, researchers have developed many computational approaches to predict RBPs and protein-RNA binding sites, by combining various machine learning methods and abundant sequence and/or structural features. There are three kinds of computational approaches, which are prediction from protein sequence, prediction from protein structure, and protein-RNA docking. In this paper, we review all existing studies of predictions of RNA-binding sites and RBPs and complexes, including data sets used in different approaches, sequence and structural features used in several predictors, prediction method classifications, performance comparisons, evaluation methods, and future directions.

  15. Computational Prediction of RNA-Binding Proteins and Binding Sites

    Directory of Open Access Journals (Sweden)

    Jingna Si

    2015-11-01

    Full Text Available Proteins and RNA interaction have vital roles in many cellular processes such as protein synthesis, sequence encoding, RNA transfer, and gene regulation at the transcriptional and post-transcriptional levels. Approximately 6%–8% of all proteins are RNA-binding proteins (RBPs. Distinguishing these RBPs or their binding residues is a major aim of structural biology. Previously, a number of experimental methods were developed for the determination of protein–RNA interactions. However, these experimental methods are expensive, time-consuming, and labor-intensive. Alternatively, researchers have developed many computational approaches to predict RBPs and protein–RNA binding sites, by combining various machine learning methods and abundant sequence and/or structural features. There are three kinds of computational approaches, which are prediction from protein sequence, prediction from protein structure, and protein-RNA docking. In this paper, we review all existing studies of predictions of RNA-binding sites and RBPs and complexes, including data sets used in different approaches, sequence and structural features used in several predictors, prediction method classifications, performance comparisons, evaluation methods, and future directions.

  16. MYB elongation is regulated by the nucleic acid binding of NFκB p50 to the intronic stem-loop region.

    Directory of Open Access Journals (Sweden)

    Lloyd A Pereira

    Full Text Available MYB transcriptional elongation is regulated by an attenuator sequence within intron 1 that has been proposed to encode a RNA stem loop (SLR followed by a polyU tract. We report that NFκBp50 can bind the SLR polyU RNA and promote MYB transcriptional elongation together with NFκBp65. We identified a conserved lysine-rich motif within the Rel homology domain (RHD of NFκBp50, mutation of which abrogated the interaction of NFκBp50 with the SLR polyU and impaired NFκBp50 mediated MYB elongation. We observed that the TAR RNA-binding region of Tat is homologous to the NFκBp50 RHD lysine-rich motif, a finding consistent with HIV Tat acting as an effector of MYB transcriptional elongation in an SLR dependent manner. Furthermore, we identify the DNA binding activity of NFκBp50 as a key component required for the SLR polyU mediated regulation of MYB. Collectively these results suggest that the MYB SLR polyU provides a platform for proteins to regulate MYB and reveals novel nucleic acid binding properties of NFκBp50 required for MYB regulation.

  17. Murine anti-vaccinia virus D8 antibodies target different epitopes and differ in their ability to block D8 binding to CS-E.

    Directory of Open Access Journals (Sweden)

    Michael H Matho

    2014-12-01

    Full Text Available The IMV envelope protein D8 is an adhesion molecule and a major immunodominant antigen of vaccinia virus (VACV. Here we identified the optimal D8 ligand to be chondroitin sulfate E (CS-E. CS-E is characterized by a disaccharide moiety with two sulfated hydroxyl groups at positions 4' and 6' of GalNAc. To study the role of antibodies in preventing D8 adhesion to CS-E, we have used a panel of murine monoclonal antibodies, and tested their ability to compete with CS-E for D8 binding. Among four antibody specificity groups, MAbs of one group (group IV fully abrogated CS-E binding, while MAbs of a second group (group III displayed widely varying levels of CS-E blocking. Using EM, we identified the binding site for each antibody specificity group on D8. Recombinant D8 forms a hexameric arrangement, mediated by self-association of a small C-terminal domain of D8. We propose a model in which D8 oligomerization on the IMV would allow VACV to adhere to heterogeneous population of CS, including CS-C and potentially CS-A, while overall increasing binding efficiency to CS-E.

  18. High-affinity binding of southern African HIV type 1 subtype C envelope protein, gp120, to the CCR5 coreceptor.

    Science.gov (United States)

    Fromme, Bernhard J; Coetsee, Marla; Van Der Watt, Pauline; Chan, Mei-Chi; Sperling, Karin M; Katz, Arieh A; Flanagan, Colleen A

    2008-12-01

    HIV-1 subtype C is the fastest spreading subtype worldwide and predominantly uses the CCR5 coreceptor, showing minimal transition to the X4 phenotype. This raises the possibility that envelope proteins of HIV-1 subtype C have structural features that favor interaction with CCR5. Preference for CCR5 could arise from enhanced affinity of HIV-1 subtype C for CCR5. To test this, we have characterized the interaction of gp120 envelope proteins from HIV-1 subtype C clones with CD4 and CCR5. Recombinant gp120 proteins from isolates of HIV-1 subtypes B and C were expressed, purified, and assessed in a CD4 binding assay and a CCR5 chemokine competition binding assay. All gp120 proteins bound to CD4-expressing cells, except one, 97ZA347ts, which had Arg substituted for the Cys239 in the conserved C2 loop. Reconstitution of Cys239, using site-directed mutagenesis, restored CD4 binding, while introducing Arg or Ser into position 239 of the functional Du151 gp120 protein abrogated CD4 binding. This shows that the Cys228-Cys239 disulfide bond of gp120 is required for high-affinity binding to CD4. Recombinant gp120 proteins from two HIV-1 subtype B clones bound CCR5 in the presence of CD4, while gp120 from the X4-tropic, HxB2, clone did not bind CCR5. gp120 from two functional HIV-1 subtype C clones, Du151 and MOLE1, bound CCR5 with high affinity in the presence of CD4 and Du151 showed significant CCR5 binding in the absence of CD4. A gp120 from a nonfunctional subtype C clone had lower affinity for CCR5. These results indicate that HIV-1 subtype C proteins have high affinity for CCR5 with variable dependence on CD4.

  19. An antibody against the surfactant protein A (SP-A)-binding domain of the SP-A receptor inhibits T cell-mediated immune responses to Mycobacterium tuberculosis.

    Science.gov (United States)

    Samten, Buka; Townsend, James C; Sever-Chroneos, Zvjezdana; Pasquinelli, Virginia; Barnes, Peter F; Chroneos, Zissis C

    2008-07-01

    Surfactant protein A (SP-A) suppresses lymphocyte proliferation and IL-2 secretion, in part, by binding to its receptor, SP-R210. However, the mechanisms underlying this effect are not well understood. Here, we studied the effect of antibodies against the SP-A-binding (neck) domain (alpha-SP-R210n) or nonbinding C-terminal domain (alpha-SP-R210ct) of SP-R210 on human peripheral blood T cell immune responses against Mycobacterium tuberculosis. We demonstrated that both antibodies bind to more than 90% of monocytes and 5-10% of CD3+ T cells in freshly isolated PBMC. Stimulation of PBMC from healthy tuberculin reactors [purified protein derivative-positive (PPD+)] with heat-killed M. tuberculosis induced increased antibody binding to CD3+ cells. Increased antibody binding suggested enhanced expression of SP-R210, and this was confirmed by Western blotting. The antibodies (alpha-SP-R210n) cross-linking the SP-R210 through the SP-A-binding domain markedly inhibited cell proliferation and IFN-gamma secretion by PBMC from PPD+ donors in response to heat-killed M. tuberculosis, whereas preimmune IgG and antibodies (alpha-SP-R210ct) cross-linking SP-R210 through the non-SP-A-binding, C-terminal domain had no effect. Anti-SP-R210n also decreased M. tuberculosis-induced production of TNF-alpha but increased production of IL-10. Inhibition of IFN-gamma production by alpha-SP-R210n was abrogated by the combination of neutralizing antibodies to IL-10 and TGF-beta1. Together, these findings support the hypothesis that SP-A, via SP-R210, suppresses cell-mediated immunity against M. tuberculosis via a mechanism that up-regulates secretion of IL-10 and TGF-beta1.

  20. Coinvasion of dentinal tubules by Porphyromonas gingivalis and Streptococcus gordonii depends upon binding specificity of streptococcal antigen I/II adhesin.

    Science.gov (United States)

    Love, R M; McMillan, M D; Park, Y; Jenkinson, H F

    2000-03-01

    Cell wall-anchored polypeptides of the antigen I/II family are produced by many species of oral streptococci. These proteins mediate adhesion of streptococci to salivary glycoproteins and to other oral microorganisms and promote binding of cells to collagen type I and invasion of dentinal tubules. Since infections of the root canal system have a mixed anaerobic bacterial etiology, we investigated the hypothesis that coadhesion of anaerobic bacteria with streptococci may facilitate invasive endodontic disease. Porphyromonas gingivalis ATCC 33277 cells were able to invade dentinal tubules when cocultured with Streptococcus gordonii DL1 (Challis) but not when cocultured with Streptococcus mutans NG8. An isogenic noninvasive mutant of S. gordonii, with production of SspA and SspB (antigen I/II family) polypeptides abrogated, was deficient in binding to collagen and had a 40% reduced ability to support adhesion of P. gingivalis. Heterologous expression of the S. mutans SpaP (antigen I/II) protein in this mutant restored collagen binding and tubule invasion but not adhesion to P. gingivalis or the ability to promote P. gingivalis coinvasion of dentin. An isogenic afimbrial mutant of P. gingivalis had 50% reduced binding to S. gordonii cells but was unaffected in the ability to coinvade dentinal tubules with S. gordonii wild-type cells. Expression of the S. gordonii SspA or SspB polypeptide on the surface of Lactococcus lactis cells endowed these bacteria with the abilities to bind P. gingivalis, penetrate dentinal tubules, and promote P. gingivalis coinvasion of dentin. The results demonstrate that collagen-binding and P. gingivalis-binding properties of antigen I/II polypeptides are discrete functions. Specificity of antigen I/II polypeptide recognition accounts for the ability of P. gingivalis to coinvade dentinal tubules with S. gordonii but not with S. mutans. This provides evidence that the specificity of interbacterial coadhesion may influence directly the etiology

  1. Synthetic heparin-binding growth factor analogs

    Science.gov (United States)

    Pena, Louis A.; Zamora, Paul; Lin, Xinhua; Glass, John D.

    2007-01-23

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

  2. The Dishevelled, EGL-10 and pleckstrin (DEP domain-containing protein DEPDC7 binds to CARMA2 and CARMA3 proteins, and regulates NF-κB activation.

    Directory of Open Access Journals (Sweden)

    Egildo Luca D'Andrea

    Full Text Available The molecular complexes containing BCL10, MALT1 and CARMA proteins (CBM complex have been recently identified as a key component in the signal transduction pathways that regulate activation of Nuclear Factor kappaB (NF-κB transcription factor. Herein we identified the DEP domain-containing protein DEPDC7 as cellular binding partners of CARMA2 and CARMA3 proteins. DEPDC7 displays a cytosolic distribution and its expression induces NF-κB activation. Conversely, shRNA-mediated abrogation of DEPDC7 results in impaired NF-κB activation following G protein-coupled receptors stimulation, or stimuli that require CARMA2 and CARMA3, but not CARMA1. Thus, this study identifies DEPDC7 as a CARMA interacting molecule, and provides evidence that DEPDC7 may be required to specifically convey on the CBM complex signals coming from activated G protein-coupled receptors.

  3. The Dishevelled, EGL-10 and pleckstrin (DEP) domain-containing protein DEPDC7 binds to CARMA2 and CARMA3 proteins, and regulates NF-κB activation.

    Science.gov (United States)

    D'Andrea, Egildo Luca; Ferravante, Angela; Scudiero, Ivan; Zotti, Tiziana; Reale, Carla; Pizzulo, Maddalena; De La Motte, Luigi Regenburgh; De Maio, Chiara; Mazzone, Pellegrino; Telesio, Gianluca; Vito, Pasquale; Stilo, Romania

    2014-01-01

    The molecular complexes containing BCL10, MALT1 and CARMA proteins (CBM complex) have been recently identified as a key component in the signal transduction pathways that regulate activation of Nuclear Factor kappaB (NF-κB) transcription factor. Herein we identified the DEP domain-containing protein DEPDC7 as cellular binding partners of CARMA2 and CARMA3 proteins. DEPDC7 displays a cytosolic distribution and its expression induces NF-κB activation. Conversely, shRNA-mediated abrogation of DEPDC7 results in impaired NF-κB activation following G protein-coupled receptors stimulation, or stimuli that require CARMA2 and CARMA3, but not CARMA1. Thus, this study identifies DEPDC7 as a CARMA interacting molecule, and provides evidence that DEPDC7 may be required to specifically convey on the CBM complex signals coming from activated G protein-coupled receptors.

  4. Cellulose binding domain fusion proteins

    Science.gov (United States)

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  5. Caseins from bovine colostrum and milk strongly bind piscidin-1, an antimicrobial peptide from fish.

    Science.gov (United States)

    Kütt, Mary-Liis; Stagsted, Jan

    2014-09-01

    A model system of bovine colostrum and piscidin, a fish-derived antimicrobial peptide, was developed to study potential interactions of antimicrobial peptides in colostrum. We did not detect any antimicrobial activity of colostrum using the radial plate diffusion assay; in fact colostrum completely abrogated activity of added piscidin. This could not be explained by degradation of piscidin by colostrum, which was less than ten percent. We found that colostrum even protected piscidin against degradation by added proteases. We further observed that colostrum and milk rapidly quenched the fluorescence of fluorescein-piscidin but not that of fluorescein. This effect was not seen with BSA and the specific quenching of fluorescein-piscidin by colostrum was saturably inhibited with unlabeled piscidin. Size exclusion chromatography indicated that fluorescein-piscidin bound to casein micelles with no apparent binding to IgG or whey proteins. Further, addition of pure caseins was able to quench fluorescence of fluorescein-piscidin and to inhibit the antimicrobial activity of piscidin. The interaction between caseins and piscidin could be dissociated by guanidine hydrochloride and recovered piscidin had antimicrobial activity against bacteria. Based on our results we propose that caseins could be carriers for antimicrobial peptides in colostrum and milk.

  6. Protein binding assay for hyaluronate

    Energy Technology Data Exchange (ETDEWEB)

    Lacy, B.E.; Underhill, C.B.

    1986-11-01

    A relatively quick and simple assay for hyaluronate was developed using the specific binding protein, hyaluronectin. The hyaluronectin was obtained by homogenizing the brains of Sprague-Dawley rats, and then centrifuging the homogenate. The resulting supernatant was used as a source of crude hyaluronectin. In the binding assay, the hyaluronectin was mixed with (/sup 3/H)hyaluronate, followed by an equal volume of saturated (NH/sub 4/)/sub 2/SO/sub 4/, which precipitated the hyaluronectin and any (/sup 3/H)hyaluronate associated with it, but left free (/sup 3/H)hyaluronate in solution. The mixture was then centrifuged, and the amount of bound (/sup 3/H)hyaluronate in the precipitate was determined. Using this assay, the authors found that hyaluronectin specifically bound hyaluronate, since other glycosaminoglycans failed to compete for the binding protein. In addition, the interaction between hyaluronectin and hyaluronate was of relatively high affinity, and the size of the hyaluronate did not appear to substantially alter the amount of binding. To determine the amount of hyaluronate in an unknown sample, they used a competition assay in which the binding of a set amount of (/sup 3/H)hyaluronate was blocked by the addition of unlabeled hyaluronate. By comparing the degree of competition of the unknown samples with that of known amounts of hyaluronate, it was possible to determine the amount of hyaluronate in the unknowns. They have found that this method is sensitive to 1 ..mu..g or less of hyaluronate, and is unaffected by the presence of proteins.

  7. Evaluación de anemia ferropénica en la primera infancia del Municipio de Sonsón-Antioquia, 2007

    Directory of Open Access Journals (Sweden)

    Tulia Isabel Castillo Salgado

    2016-08-01

    Full Text Available Objetivo: Determinar la prevalencia de anemia por deficiencia de hierro en niños de la primera infancia del municipio de Sonsón – Antioquia, en el año 2007. Metodología: Se realizó un estudio descriptivo transversal en 391 niños de 0 a 84 meses de edad del Municipio de Sonsón, Antioquia. Se estudiaron los parámetros de hemoglobina y ferritina sérica utilizando puntos de corte de la Organización Mundial de la Salud (OMS. Se calcularon las medidas de frecuencia y de resumen y los intervalos de confianza para proporciones y las pruebas de estadística paramétrica y no paramétrica. Resultados: La prevalencia de anemia ferropénica fue de 4,3% y la media de ferritina sérica y de hemoglobina para la población del estudio fue de 29,9 ng/mL y 12,6 g/dL respectivamente. Adicionalmente se halló significancia estadística de la prevalencia de anemia ferropénica por grupo de edad (p<0,0001; pero no se encontró significancia estadística de la  prevalencia de anemia con el sexo (p= 1,0000.  Conclusión: La prevalencia de anemia ferropénica en los niños de la primera infancia del Municipio de Sonsón fue baja de acuerdo con los parámetros de hemoglobina y ferritina sérica establecidos por la OMS, hay variación de la anemia ferropénica por grupo de edad pero no por sexo.

  8. Daniel John Cunningham (1850-1909): anatomist and textbook author, whose sons achieved distinction in the Army, Navy and Indian Medical Service.

    Science.gov (United States)

    Kaufman, Matthew H

    2008-02-01

    Daniel John Cunningham was a son of the manse. His father John (1819-93) was the parish priest at Crieff, Perthshire from 1845 and was to remain there for 41 years. In 1886 he was appointed Principal of St Mary's College of the University of St Andrews and Moderator of the Church of Scotland. Daniel was educated at Crieff Academy before he progressed to the University of Edinburgh. He graduated MB CM with First-class Honours in 1874 and then proceeded MD in 1876 when he was awarded a Gold Medal for his thesis. He acted as Demonstrator to Professor Turner (1832-1916) in Edinburgh for eight years until 1882 and was then appointed to the Chair of Anatomy at the Royal College of Surgeons of Ireland, in Dublin. After only one year there, he transferred to Trinity College, Dublin, where he occupied a similar position for 20 years. In 1903, on the appointment of Sir William Turner to the post of Principal and Vice-Chancellor of the University of Edinburgh, Daniel was invited to succeed him as Professor of Anatomy in Edinburgh. Daniel held this post until his premature death in 1909. He had three sons and two daughters. Each of his three sons achieved distinction in different fields - one in the Army, another in the Navy and the third in the Indian Medical Service. One of Daniel's daughters married Dr Edwin Bramwell (1873-1952), who was later to occupy the Moncrieff Arnott Chair of Clinical Medicine in the University of Edinburgh.

  9. No son víctimas hasta no demuestren lo contrario : Un análisis de los debates sobre la ley de trata de personas en Argentina

    OpenAIRE

    Molina, Claudia Patricia

    2009-01-01

    En las últimas décadas asistimos a un proceso de crecimiento exponencial del tráfico y trata de personas en todo el mundo. Se cuentan por millones las personas traficadas y millonarios son los dividendos que promueve este delito, sólo comparables con los márgenes de ganancias producidos por el tráfico de armas y drogas con el que suele estar asociado. La trata de mujeres no es un fenómeno novedoso en nuestro país. A finales del siglo XIX en la región del Rio de La Plata se conformaron las ...

  10. Eu não posso ser dois : uma perspectiva sobre o conceito de gameplay a partir de experimentos com o jogo Brothers : a tale of two sons

    OpenAIRE

    Mariana Amaro Cruz

    2016-01-01

    Esta pesquisa concentra-se, fundamentalmente, no conceito de gameplay, tendo como objetivo principal compreender como as materialidades próprias da situação de jogo, as mecânicas e dinâmicas de jogo influenciam e caracterizam o gameplay a partir de experiências com o jogo digital Brothers – A Tale of Two Sons (Starbreeze Studios, 2013). O referencial teórico é divido em quatro partes: na primeira se faz um breve histórico sobre os Game Studies; na segunda é feita uma articulação entre os conc...

  11. ¿Son las TIC un factor clave en la adquisición de competencias? Un análisis con evaluaciones por ordenador

    OpenAIRE

    Mauro Mediavilla; Josep Oriol Escardíbul

    2015-01-01

    Este artículo analiza los efectos de la tenencia y uso de las tecnologías de la información y la comunicación (TIC) en la adquisición de competencias (evaluadas por ordenador en la prueba de PISA de 2012). Los principales resultados son los siguientes. En primer lugar, se constata que las variables TIC inciden en mayor medida en la adquisición de matemáticas que en el resto de competencias evaluadas (comprensión lectora y ciencias). En segundo lugar, resulta relevante la variable TIC utilizad...

  12. Familial ainhum: A case report of multiple toe involvement in a father and son, staging of ainhum with insight into different types of constricting bands

    Directory of Open Access Journals (Sweden)

    B T Priya

    2015-01-01

    Full Text Available Ainhum, also known as dactylolysis spontanea, is a painful constriction of the base of the fifth toe, frequently followed by spontaneous amputation a few years later. The disease is often symmetrical on both the feet, but, occasionally, other toes are also affected and rarely the distal phalanx of the fifth finger. Pseudoainhum is a similar condition that occurs as a secondary event resulting from certain hereditary and nonhereditary diseases that lead to annular constriction of digits. We hereby present a case of familial ainhum in father and son with multiple toes affected, autoamputation, and more involvement of fourth toe than the fifth toe, which is a very rare finding.

  13. Familial ainhum: a case report of multiple toe involvement in a father and son, staging of ainhum with insight into different types of constricting bands.

    Science.gov (United States)

    Priya, Bt; Suganthy, Rajakumari R; Manimegalai, M; Krishnaveni, A

    2015-01-01

    Ainhum, also known as dactylolysis spontanea, is a painful constriction of the base of the fifth toe, frequently followed by spontaneous amputation a few years later. The disease is often symmetrical on both the feet, but, occasionally, other toes are also affected and rarely the distal phalanx of the fifth finger. Pseudoainhum is a similar condition that occurs as a secondary event resulting from certain hereditary and nonhereditary diseases that lead to annular constriction of digits. We hereby present a case of familial ainhum in father and son with multiple toes affected, autoamputation, and more involvement of fourth toe than the fifth toe, which is a very rare finding.

  14. Tumor susceptibility gene 101 (TSG101 is a novel binding-partner for the class II Rab11-FIPs.

    Directory of Open Access Journals (Sweden)

    Conor P Horgan

    Full Text Available The Rab11-FIPs (Rab11-family interacting proteins; henceforth, FIPs are a family of Rab11a/Rab11b/Rab25 GTPase effector proteins implicated in an assortment of intracellular trafficking processes. Through proteomic screening, we have identified TSG101 (tumor susceptibility gene 101, a component of the ESCRT-I (endosomal sorting complex required for transport complex, as a novel FIP4-binding protein, which we find can also bind FIP3. We show that α-helical coiled-coil regions of both TSG101 and FIP4 mediate the interaction with the cognate protein, and that point mutations in the coiled-coil regions of both TSG101 and FIP4 abrogate the interaction. We find that expression of TSG101 and FIP4 mutants cause cytokinesis defects, but that the TSG101-FIP4 interaction is not required for localisation of TSG101 to the midbody/Flemming body during abscission. Together, these data suggest functional overlap between Rab11-controlled processes and components of the ESCRT pathway.

  15. EGCG debilitates the persistence of EBV latency by reducing the DNA binding potency of nuclear antigen 1

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ya-Lin; Tsai, Hsing-Lyn [Department of Life Sciences, Tzu-Chi University, 701 Chung-Yang Rd. Sec 3, Hualien 97004, Taiwan (China); Peng, Chih-Wen, E-mail: pengcw@mail.tcu.edu.tw [Department of Life Sciences, Tzu-Chi University, 701 Chung-Yang Rd. Sec 3, Hualien 97004, Taiwan (China)

    2012-01-20

    Highlights: Black-Right-Pointing-Pointer Two cell-based reporter platforms were established for screening of EBNA1 inhibitors. Black-Right-Pointing-Pointer EGCG acts as an inhibitor to block EBNA1 binding with the cognate oriP sequence. Black-Right-Pointing-Pointer EGCG debilitates EBNA1-dependent transcription enhancement and episome maintenance. Black-Right-Pointing-Pointer EGCG impairs persistence of EBV latency. Black-Right-Pointing-Pointer EGCG is a potent anti-EBV agent for targeting the latent cascade of EBV. -- Abstract: Because the expression of EBNA1 is prevalent in all EBV-associated tumors, it has become one of the most attractive drug targets for the discovery of anti-EBV compounds. In a cell-based reporter system, EBNA1 consistently upregulated the transcription of an oriP-Luc mini-EBV episome by 6- to 8-fold. The treatment of cells with 50 {mu}M EGCG effectively blocked the binding of EBNA1 to oriP-DNA both in vivo and in vitro, which led to the abrogation of EBNA1-dependent episome maintenance and transcriptional enhancement. Importantly, the anti-EBNA1 effects caused by EGCG ultimately impaired the persistence of EBV latent infection. Our data suggest that the inhibition of EBNA1 activity by EGCG could be a promising starting point for the development of new protocols for anti-EBV therapy.

  16. Modern Dönem Nesih Tartışmaları ve İbn Kesîr’in Neshe Yaklaşımı / Discussions of Naskh (Abrogation in Modern Studies and Ibn Kathīr’s Perception of Naskh

    Directory of Open Access Journals (Sweden)

    Melek

    2016-12-01

    Full Text Available Abrogation (naskh is one of the controversial themes of Islamic studies, especially in later period that of principle of exegesis (uṣūl al-tafsīr. However, the recent studies on abrogation (naskh do not offer a comprehensive analysis on the concept. In fact, the problem of naskh (abrogation is in need of a systematic and holistic approach, which would only be possible with a detailed study on how the concept of abrogation (naskh is understood in Islamic interpretive tradition (tafsīr. With this purpose in mind, this article intends to examine two points regarding the term abrogation: first, the article will offer a analytical reflection on the diverse views of naskh, and then it will highlight how Ibn Kathīr (d. 1373 understood and applied this term to his hermeneutical framework. By doing so, the present study aims to show Ibn Kathīr’s position in Islamic interpretive tradition on the matter of naskh. The key conclusion of this study is that although Ibn Kathīr is one of the representatives of the traditional riwayah (sound transmission through a chain of exegetes exegesis, he advances his interpretive hermeneutics with multiple aspects that also involves dirayah (personal opinion exegesis (tafsīr. SUMMARY The problem of naskh (abrogation is one of the most important and controversial themes of science and principle of exegesis (ʿilm wan a-l uṣūl al-tafsīr in Islamic tradition. In order to understand naskh, which is claimed to be occurred in the Qur’ānic text, it is necessary to involve the time of the revelation of the Qur’ān. An analysis of this period reveals that first Muslims regard the naskh as a natural process of the revelation and do not dispute over this matter. In other words, the controversial theme naskh is perceived by first addresses of the Qur’ān as a hermeneutical characteristic of the Qur’ānic revelation. Therefore, naskh was not considered as a controversial concept and debated its origins based on

  17. AutoCAD 3D pour l'architecture et le design : conception d'une maison et de son mobilier

    CERN Document Server

    Riccio, Michel

    2010-01-01

    Module 3D d'AutoCAD, logiciel leader de dessin assisté par ordinateur, AutoCAD 3D est l'outil indispensable des architectes qui souhaitent présenter leurs travaux en trois dimensions. Voici donc un livre très pédagogique qui leur fera découvrir ses principales fonctionnalités (versions 2006 à 2010) à travers un projet de conception de maison contemporaine. Riche de 700 plans, schémas et dessins, il explique quels outils employer pour modéliser les façades d'une villa, sa piscine et sa terrasse, ainsi que son architecture intérieure et son mobilier. Dès les premières pages, le lecteur se retrouve ainsi plongé dans la pratique, voyant se construire au fil des 17 ateliers un édifice tridimensionnel complexe, qu'il aura la satisfaction d'avoir créé lui-même. A qui s'adresse ce livre ? Aux bureaux d'architectes qui souhaitent présenter leurs projets en 3D ; À tous les étudiants en écoles d'architecture ; Aux utilisateurs 2D d'AutoCAD qui désirent connaître les fonctions 3D de ce logiciel.

  18. When Parents Separate and One Parent 'Comes Out' as Lesbian, Gay or Bisexual: Sons and Daughters Engage with the Tension that Occurs When Their Family Unit Changes.

    Directory of Open Access Journals (Sweden)

    Siobhán C Daly

    Full Text Available The experiences of Irish sons and daughters born into heterosexually-organised parental partnerships/unions whose parents have separated and one has come out as Lesbian, Gay or Bisexual (LGB were explored through a grounded theory approach. 15 adult children (over the age of 18 years, who varied in age when their parents separated and one disclosed as LGB, were interviewed. The primary concern that emerged centred on participants having to adjust to their parents' being separated, as opposed to their parent being LGB. This involved engaging with the tension that arose from the loss of the parental union, which involved changes to the home environment and adapting to new parental partners and family units. Heightened reflection on sexual orientation and an increased sensitivity to societal LGB prejudice were specifically associated with a parent coming out as LGB. How parents negotiated disclosing the changes to others, the level of support available to parents, and how capable parents were at maintaining the parent-child relationship had an impact on the tension experienced by sons and daughters. Participants moved from initially avoiding and resisting the family changes that were occurring to gradual consonance with their altered family environments. Concluding directions for research and clinical considerations are suggested.

  19. Parents think their sons are brighter than their daughters: sex differences in parental self-estimations and estimations of their children's multiple intelligences.

    Science.gov (United States)

    Furnham, Adrian; Reeves, Emma; Budhani, Salima

    2002-03-01

    In this study, 156 participants, predominantly White British adults (M age = 44.3 years) rated themselves on overall IQ and on H. Gardner's (1983) 7 intelligence subtypes. Parents (n = 120) also estimated the intelligence of their children. Men's self-estimates were significantly higher than women's (110.15 vs. 104.84). Participants thought their verbal, mathematical, and spatial intelligence scores were the best indicators of their own overall intelligence. Parents estimated that their sons had significantly higher IQs than their daughters (115.21 vs. 107.49). Self-estimates and estimates of children's multiple intelligences were higher for men and sons, significantly so for logical-mathematical and spatial intelligence. Parents rated 2nd-born daughters as having significantly higher verbal and musical intelligence than their male counterparts. Higher parental IQ self-estimates corresponded with higher IQ estimates for children. Results for 1st-born children were clearest and showed the most significant differences. The findings are interpreted in terms of sociocultural and familial influences and the possibility of actual sex differences in particular abilities.

  20. ¿Son las transferencias del sector hidroeléctrico un instrumento eficaz para la protección de los recursos naturales?

    Directory of Open Access Journals (Sweden)

    Luis Diego Vélez Gómez

    2015-02-01

    Full Text Available Las transferencias del sector eléctrico son uno de los instrumentos financieros más importantes con los que cuentan las Corporaciones Autónomas Regionales (CAR para financiar su presupuesto. Este instrumento suscita actualmente un debate acerca de su capacidad para remunerar el capital natural aportado por los territorios en el desarrollo del sector eléctrico. En este artículo se explica cómo funcionan las CAR y la importancia de las transferencias del sector eléctrico para ellas. Se ofrece un escenario comparativo de las transferencias calculadas de acuerdo al proyecto de Ley 88 de 2010, para observar diferencias significativas en cuanto a la remuneración del capital natural de acuerdo con el artículo 45 de la Ley 99 de 1993. Sin embargo, más allá del simple aspecto remunerativo de la Ley, se pretende mostrar que las CAR no son organizaciones aptas para el cumplimiento de sus funciones, lo cual hace que el tema de su financiamiento sea desplazado ante evidentes fallas de gestión de sus recursos y en algunos casos problemas de corrupción que hacen que las transferencias no cumplan su objetivo.

  1. Human plasminogen binding protein tetranectin

    DEFF Research Database (Denmark)

    Kastrup, J S; Rasmussen, H; Nielsen, B B;

    1997-01-01

    The recombinant human plasminogen binding protein tetranectin (TN) and the C-type lectin CRD of this protein (TN3) have been crystallized. TN3 crystallizes in the tetragonal space group P4(2)2(1)2 with cell dimensions a = b = 64.0, c = 75.7 A and with one molecule per asymmetric unit. The crystals...... to at least 2.5 A. A full data set has been collected to 3.0 A. The asymmetric unit contains one monomer of TN. Molecular replacement solutions for TN3 and TN have been obtained using the structure of the C-type lectin CRD of rat mannose-binding protein as search model. The rhombohedral space group indicates...

  2. Pituitary tumor transforming gene binding factor: a new gene in breast cancer.

    Science.gov (United States)

    Watkins, Rachel J; Read, Martin L; Smith, Vicki E; Sharma, Neil; Reynolds, Gary M; Buckley, Laura; Doig, Craig; Campbell, Moray J; Lewy, Greg; Eggo, Margaret C; Loubiere, Laurence S; Franklyn, Jayne A; Boelaert, Kristien; McCabe, Christopher J

    2010-05-01

    Pituitary tumor transforming gene (PTTG) binding factor (PBF; PTTG1IP) is a relatively uncharacterized oncoprotein whose function remains obscure. Because of the presence of putative estrogen response elements (ERE) in its promoter, we assessed PBF regulation by estrogen. PBF mRNA and protein expression were induced by both diethylstilbestrol and 17beta-estradiol in estrogen receptor alpha (ERalpha)-positive MCF-7 cells. Detailed analysis of the PBF promoter showed that the region -399 to -291 relative to the translational start site contains variable repeats of an 18-bp sequence housing a putative ERE half-site (gcccctcGGTCAcgcctc). Sequencing the PBF promoter from 122 normal subjects revealed that subjects may be homozygous or heterozygous for between 1 and 6 repeats of the ERE. Chromatin immunoprecipitation and oligonucleotide pull-down assays revealed ERalpha binding to the PBF promoter. PBF expression was low or absent in normal breast tissue but was highly expressed in breast cancers. Subjects with greater numbers of ERE repeats showed higher PBF mRNA expression, and PBF protein expression positively correlated with ERalpha status. Cell invasion assays revealed that PBF induces invasion through Matrigel, an action that could be abrogated both by siRNA treatment and specific mutation. Furthermore, PBF is a secreted protein, and loss of secretion prevents PBF inducing cell invasion. Given that PBF is a potent transforming gene, we propose that estrogen treatment in postmenopausal women may upregulate PBF expression, leading to PBF secretion and increased cell invasion. Furthermore, the number of ERE half-sites in the PBF promoter may significantly alter the response to estrogen treatment in individual subjects.

  3. Probing protein phosphatase substrate binding

    DEFF Research Database (Denmark)

    Højlys-Larsen, Kim B.; Sørensen, Kasper Kildegaard; Jensen, Knud Jørgen;

    2012-01-01

    Proteomics and high throughput analysis for systems biology can benefit significantly from solid-phase chemical tools for affinity pull-down of proteins from complex mixtures. Here we report the application of solid-phase synthesis of phosphopeptides for pull-down and analysis of the affinity...... around the phosphorylated residue are important for the binding affinity of ILKAP. We conclude that solid-phase affinity pull-down of proteins from complex mixtures can be applied in phosphoproteomics and systems biology....

  4. Anion binding in biological systems

    Science.gov (United States)

    Feiters, Martin C.; Meyer-Klaucke, Wolfram; Kostenko, Alexander V.; Soldatov, Alexander V.; Leblanc, Catherine; Michel, Gurvan; Potin, Philippe; Küpper, Frithjof C.; Hollenstein, Kaspar; Locher, Kaspar P.; Bevers, Loes E.; Hagedoorn, Peter-Leon; Hagen, Wilfred R.

    2009-11-01

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L3 (2p3/2) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  5. Anion binding in biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Feiters, Martin C [Department of Organic Chemistry, Institute for Molecules and Materials, Faculty of Science, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen (Netherlands); Meyer-Klaucke, Wolfram [EMBL Hamburg Outstation at DESY, Notkestrasse 85, D-22607 Hamburg (Germany); Kostenko, Alexander V; Soldatov, Alexander V [Faculty of Physics, Southern Federal University, Sorge 5, Rostov-na-Donu, 344090 (Russian Federation); Leblanc, Catherine; Michel, Gurvan; Potin, Philippe [Centre National de la Recherche Scientifique and Universite Pierre et Marie Curie Paris-VI, Station Biologique de Roscoff, Place Georges Teissier, BP 74, F-29682 Roscoff cedex, Bretagne (France); Kuepper, Frithjof C [Scottish Association for Marine Science, Dunstaffnage Marine Laboratory, Oban, Argyll PA37 1QA, Scotland (United Kingdom); Hollenstein, Kaspar; Locher, Kaspar P [Institute of Molecular Biology and Biophysics, ETH Zuerich, Schafmattstrasse 20, Zuerich, 8093 (Switzerland); Bevers, Loes E; Hagedoorn, Peter-Leon; Hagen, Wilfred R, E-mail: m.feiters@science.ru.n [Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft (Netherlands)

    2009-11-15

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L{sub 3} (2p{sub 3/2}) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  6. The C-terminal domain of the Arabinosyltransferase Mycobacterium tuberculosis EmbC is a lectin-like carbohydrate binding module.

    Directory of Open Access Journals (Sweden)

    Luke J Alderwick

    2011-02-01

    Full Text Available The D-arabinan-containing polymers arabinogalactan (AG and lipoarabinomannan (LAM are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis. Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl (Araf transferases whose structures are largely uncharacterised, despite the fact that several of them are pharmacological targets of ethambutol, a frontline drug in tuberculosis therapy. Herein, we present the crystal structure of the C-terminal hydrophilic domain of the ethambutol-sensitive Araf transferase M. tuberculosis EmbC, which is essential for LAM synthesis. The structure of the C-terminal domain of EmbC (EmbC(CT encompasses two sub-domains of different folds, of which subdomain II shows distinct similarity to lectin-like carbohydrate-binding modules (CBM. Co-crystallisation with a cell wall-derived di-arabinoside acceptor analogue and structural comparison with ligand-bound CBMs suggest that EmbC(CT contains two separate carbohydrate binding sites, associated with subdomains I and II, respectively. Single-residue substitution of conserved tryptophan residues (Trp868, Trp985 at these respective sites inhibited EmbC-catalysed extension of LAM. The same substitutions differentially abrogated binding of di- and penta-arabinofuranoside acceptor analogues to EmbC(CT, linking the loss of activity to compromised acceptor substrate binding, indicating the presence of two separate carbohydrate binding sites, and demonstrating that subdomain II indeed functions as a carbohydrate-binding module. This work provides the first step towards unravelling the structure and function of a GT-C-type glycosyltransferase that is essential in M. tuberculosis.

  7. Mesothelin-MUC16 binding is a high affinity, N-glycan dependent interaction that facilitates peritoneal metastasis of ovarian tumors

    Directory of Open Access Journals (Sweden)

    Sathyanarayana Bangalore K

    2006-10-01

    Full Text Available Abstract Background The mucin MUC16 and the glycosylphosphatidylinositol anchored glycoprotein mesothelin likely facilitate the peritoneal metastasis of ovarian tumors. The biochemical basis and the kinetics of the binding between these two glycoproteins are not clearly understood. Here we have addressed this deficit and provide further evidence supporting the role of the MUC16-mesothelin interaction in facilitating cell-cell binding under conditions that mimic the peritoneal environment. Results In this study we utilize recombinant-Fc tagged human mesothelin to measure the binding kinetics of this glycoprotein to MUC16 expressed on the ovarian tumor cell line OVCAR-3. OVCAR-3 derived sublines that did not express MUC16 showed no affinity for mesothelin. In a flow cytometry-based assay mesothelin binds with very high affinity to the MUC16 on the OVCAR-3 cells with an apparent Kd of 5–10 nM. Maximum interaction occurs within 5 mins of incubation of the recombinant mesothelin with the OVCAR-3 cells and significant binding is observed even after 10 sec. A five-fold molar excess of soluble MUC16 was unable to completely inhibit the binding of mesothelin to the OVCAR-3 cells. Oxidation of the MUC16 glycans, removal of its N-linked oligosaccharides, and treatment of the mucin with wheat germ agglutinin and erythroagglutinating phytohemagglutinin abrogates its binding to mesothelin. These observations suggest that at least a subset of the MUC16-asscociated N-glycans is required for binding to mesothelin. We also demonstrate that MUC16 positive ovarian tumor cells exhibit increased adherence to A431 cells transfected with mesothelin (A431-Meso+. Only minimal adhesion is observed between MUC16 knockdown cells and A431-Meso+ cells. The binding between the MUC16 expressing ovarian tumor cells and the A431-Meso+ cells occurs even in the presence of ascites from patients with ovarian cancer. Conclusion The strong binding kinetics of the mesothelin-MUC16

  8. Probing into the binding interaction between medroxyprogesterone acetate and bovine serum albumin (BSA): spectroscopic and molecular docking methods.

    Science.gov (United States)

    Fang, Fang; Pan, Dong-Qi; Qiu, Min-Jie; Liu, Ting-Ting; Jiang, Min; Wang, Qi; Shi, Jie-Hua

    2016-09-01

    To further understand the mechanism of action and pharmacokinetics of medroxyprogesterone acetate (MPA), the binding interaction of MPA with bovine serum albumin (BSA) under simulated physiological conditions (pH 7.4) was studied using fluorescence emission spectroscopy, synchronous fluorescence spectroscopy, circular dichroism and molecular docking methods. The experimental results reveal that the fluorescence of BSA quenches due to the formation of MPA-BSA complex. The number of binding sites (n) and the binding constant for MPA-BSA complex are ~1 and 4.6 × 10(3)  M(-1) at 310 K, respectively. However, it can be concluded that the binding process of MPA with BSA is spontaneous and the main interaction forces between MPA and BSA are van der Waals force and hydrogen bonding interaction due to the negative values of ΔG(0) , ΔH(0) and ΔS(0) in the binding process of MPA with BSA. MPA prefers binding on the hydrophobic cavity in subdomain IIIA (site II'') of BSA resulting in a slight change in the conformation of BSA, but BSA retaining the α-helix structure. Copyright © 2016 John Wiley & Sons, Ltd.

  9. El delito de aborto son inconstitucionales (los abortos son homicidios

    Directory of Open Access Journals (Sweden)

    Gustavo González Solano

    2002-09-01

    Full Text Available El voto 2306-2000 (sobre la fecundación in vitro de la Sala Constitucional, ha dado un giro "copernicano" al concepto de "persona" y la protección que a ellas se les ofrece, en el campo jurídico. La Sala generalizó el uso de la palabra "persona" a todos los seres humanos ya nacidos y a "no nacidos" llamados en nuestra legislación "fetos". Tal definición, modifica de plano el Código Civil que expresa: "La existencia de lapersonafisicaprincipia al nacer viva... "y con ello, toda la aplicación de la materia no solo civil sino también la de Derecho de Familia, al otorgarle una serie de derechos y obligaciones a esta categoría de seres humanos (los no nacidos que antes no les ofrecía.The 2306-2006 vote of the Costa Rican Constitutional Court ( about the in vitro fecundation, has made "Copernicans" revolution on the concept of "human person" and the legal protection given to them. The Court spread the use of the word "human person" to every human being including the unborn, called in our legislation, "fetus". This definition modified the Civil Code which expresses " The existence of the human person are begins at a living birth" and affects as well the Family Code because the rights and obligations now given to the unborn.

  10. Engineering RNA-binding proteins for biology

    OpenAIRE

    Chen,Yu; Varani, Gabriele

    2013-01-01

    RNA-binding proteins play essential roles in the regulation of gene expression. Many have modular structures and combine relatively few common domains in various arrangements to recognize RNA sequences and/or structures. Recent progress in engineering the specificity of the PUF class RNA-binding proteins has shown that RNA-binding domains may be combined with various effector or functional domains to regulate the metabolism of targeted RNAs. Designer RNA-binding proteins with tailored sequenc...

  11. The structure of cytomegalovirus immune modulator UL141 highlights structural Ig-fold versatility for receptor binding

    Energy Technology Data Exchange (ETDEWEB)

    Nemčovičová, Ivana [La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037 (United States); Slovak Academy of Sciences, Dúbravská cesta 9, SK 84505 Bratislava (Slovakia); Zajonc, Dirk M., E-mail: dzajonc@liai.org [La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037 (United States)

    2014-03-01

    The crystal structure of Human cytomegalovirus immune modulator UL141 was solved at 3.25 Å resolution. Here, a detailed analysis of its intimate dimerization interface and the biophysical properties of its receptor (TRAIL-R2 and CD155) binding interactions are presented. Natural killer (NK) cells are critical components of the innate immune system as they rapidly detect and destroy infected cells. To avoid immune recognition and to allow long-term persistence in the host, Human cytomegalovirus (HCMV) has evolved a number of genes to evade or inhibit immune effector pathways. In particular, UL141 can inhibit cell-surface expression of both the NK cell-activating ligand CD155 as well as the TRAIL death receptors (TRAIL-R1 and TRAIL-R2). The crystal structure of unliganded HCMV UL141 refined to 3.25 Å resolution allowed analysis of its head-to-tail dimerization interface. A ‘dimerization-deficient’ mutant of UL141 (ddUL141) was further designed, which retained the ability to bind to TRAIL-R2 or CD155 while losing the ability to cross-link two receptor monomers. Structural comparison of unliganded UL141 with UL141 bound to TRAIL-R2 further identified a mobile loop that makes intimate contacts with TRAIL-R2 upon receptor engagement. Superposition of the Ig-like domain of UL141 on the CD155 ligand T-cell immunoreceptor with Ig and ITIM domains (TIGIT) revealed that UL141 can potentially engage CD155 similar to TIGIT by using the C′C′′ and GF loops. Further mutations in the TIGIT binding site of CD155 (Q63R and F128R) abrogated UL141 binding, suggesting that the Ig-like domain of UL141 is a viral mimic of TIGIT, as it targets the same binding site on CD155 using similar ‘lock-and-key’ interactions. Sequence alignment of the UL141 gene and its orthologues also showed conservation in this highly hydrophobic (L/A)X{sub 6}G ‘lock’ motif for CD155 binding as well as conservation of the TRAIL-R2 binding patches, suggesting that these host

  12. Partial deficiency of thyroxine-binding globulin-Allentown is due to a mutation in the signal peptide.

    Science.gov (United States)

    Fingerhut, Anja; Reutrakul, Sirimon; Knuedeler, Sebastian D; Moeller, Lars C; Greenlee, Carol; Refetoff, Samuel; Janssen, Onno E

    2004-05-01

    We present an unusual variant of T(4)-binding globulin (TBG) found in a family from Allentown, Pennsylvania (TBG-AT). The heterozygous proposita presented serum total T(4) and TBG levels ranging from low to normal. TBG gene sequencing revealed a C-to-T substitution in codon -2 (CAC to TAC) leading to the substitution of the normal histidine by a tyrosine within the signal peptide. No mutation within the mature peptide was found. Allele-specific PCR confirmed the H(-2)Y mutation in the propositas mother and son. T(4)-binding analysis of TBG in serum from the proposita and son showed normal affinity but reduced capacity when compared with the unaffected father. Heat stability and isoelectric focusing of TBG-AT were normal. In vitro expression of a recombinant TBG-AT in Xenopus oocytes revealed a diminished secretory efficiency and confirmed the normal binding affinity and heat stability of the small amount of secreted TBG-AT. This study has defined impaired cotranslational processing as a hitherto unrecognized cause of hereditary TBG deficiency.

  13. Feature-Based Binding and Phase Theory

    Science.gov (United States)

    Antonenko, Andrei

    2012-01-01

    Current theories of binding cannot provide a uniform account for many facts associated with the distribution of anaphors, such as long-distance binding effects and the subject-orientation of monomorphemic anaphors. Further, traditional binding theory is incompatible with minimalist assumptions. In this dissertation I propose an analysis of…

  14. Binding of Alphaherpesvirus Glycoprotein H to Surface α4β1-Integrins Activates Calcium-Signaling Pathways and Induces Phosphatidylserine Exposure on the Plasma Membrane

    Science.gov (United States)

    Gramatica, Andrea; Herrmann, Andreas; Osterrieder, Nikolaus

    2015-01-01

    ABSTRACT Intracellular signaling connected to integrin activation is known to induce cytoplasmic Ca2+ release, which in turn mediates a number of downstream signals. The cellular entry pathways of two closely related alphaherpesviruses, equine herpesviruses 1 and 4 (EHV-1 and EHV-4), are differentially regulated with respect to the requirement of interaction of glycoprotein H (gH) with α4β1-integrins. We show here that binding of EHV-1, but not EHV-4, to target cells resulted in a rapid and significant increase in cytosolic Ca2+ levels. EHV-1 expressing EHV-4 gH (gH4) in lieu of authentic gH1 failed to induce Ca2+ release, while EHV-4 with gH1 triggered significant Ca2+ release. Blocking the interaction between gH1 and α4β1-integrins, inhibiting phospholipase C (PLC) activation, or blocking binding of inositol 1,4,5-triphosphate (IP3) to its receptor on the endoplasmic reticulum (ER) abrogated Ca2+ release. Interestingly, phosphatidylserine (PS) was exposed on the plasma membrane in response to cytosolic calcium increase after EHV-1 binding through a scramblase-dependent mechanism. Inhibition of both Ca2+ release from the ER and scramblase activation blocked PS scrambling and redirected virus entry to the endocytic pathway, indicating that PS may play a role in facilitating virus entry directly at the plasma membrane. PMID:26489864

  15. Elucidation of the structural determinants responsible for the specific formation of heterodimeric Mxd1/Max b-HLH-LZ and its binding to E-box sequences.

    Science.gov (United States)

    Montagne, Martin; Naud, Jean-François; Lavigne, Pierre

    2008-02-08

    The proteins of the Mxd family (formally known as Mad) are antagonists of the oncoprotein c-Myc. They compete with c-Myc for their obligate partner Max to prevent the c-Myc/Max heterodimer from binding to E-box sequences in the target gene promoters. In cancer cells, where Myc is overexpressed, the expression of Mxd proteins is usually insufficient or abrogated. However, the reintroduction of Mxd1 expression in these cells prevents growth and proliferation. While the antagonism of c-Myc functions by Mxd proteins is of potential relevance for the development of cancer treatment strategies, the structural determinants responsible for the specific heterodimerization between the Mxd and the Max b-helix-loop-helix-leucine zippers are not fully understood. Moreover, whether the heterodimer is assembled on DNA or in the nucleoplasm prior to DNA binding is under debate. In this article, we demonstrate that Mxd1 D112a and Max N78a and H81d, which are located in the leucine zippers of the proteins, can dictate the specificity of heterodimerization and whether or not the Mxd1/Max/DNA complex forms. Our results also indicate that additional specific determinants exist in the helix-loop-helix domains of Max and Mxd1. Finally, we provide evidence that heterodimerization must precede DNA binding in vivo.

  16. Biomolecular interaction study of hydralazine with bovine serum albumin and effect of β-cyclodextrin on binding by fluorescence, 3D, synchronous, CD, and Raman spectroscopic methods.

    Science.gov (United States)

    Bolattin, Mallavva B; Nandibewoor, Sharanappa T; Chimatadar, Shivamurti A

    2016-07-01

    Spectrofluoremetric technique was employed to study the binding behavior of hydralazine with bovine serum albumin (BSA) at different temperatures. Binding study of bovine serum albumin with hydralazine has been studied by ultraviolet-visible spectroscopy, fluorescence spectroscopy and confirmed by three-dimensional, synchronous, circular dichroism, and Raman spectroscopic methods. Effect of β-cyclodextrin on binding was studied. The experimental results showed a static quenching mechanism in the interaction of hydralazine with bovine serum albumin. The binding constant and the number of binding sites are calculated according to Stern-Volmer equation. The thermodynamic parameters ∆H(o) , ∆G(o) , ∆S(o) at different temperatures were calculated. These indicated that the hydrogen bonding and weak van der Waals forces played an important role in the interaction. Based on the Förster's theory of non-radiation energy transfer, the binding average distance, r, between the donor (BSA) and acceptor (hydralazine) was evaluated and found to be 3.95 nm. Spectral results showed that the binding of hydralazine to BSA induced conformational changes in BSA. The effect of common ions on the binding of hydralazine to BSA was also examined. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Ferney et son nouveau visage

    CERN Multimedia

    2004-01-01

    Ferney-Voltaire's third annual fête in h. of Voltaire will take place on 26 June. The theme this year is Newton and the emblem is the apple. CERN, which is celebrating its fiftieth anniversary this year, will be participating in the fête, and has sent a magnet to be displayed outside the Town Hall (1 paragraph)

  18. Cuando son muchas las voces

    Directory of Open Access Journals (Sweden)

    Cruz, Manuel

    2003-12-01

    Full Text Available The work departs from an approach to the genesis of the concept of responsibility. Some features of the concept that have today become obvious can already come into sight in this first approach. The work devotes itself then to point out the implications (and, most of all, the consequences involved in openly ascribing responsibility to the Modern Age and to the rise of industrial civilization. One of these main consequences is perhaps to have to deal with a number of theoretical topics in a necessary connexion with another axial topic of modern thought, namely, identity. Besides, the essay points also to a number of topics, such as the problem of the alleged collective responsibilities and also that of evil, just to quote two of them, whose magnitude may serve as an indicator to the relevance of the concept of responsibility in contemporary thought.

    Tras una inicial aproximación a la génesis del concepto de responsabilidad, génesis en la que se empiezan a percibir algunos de los rasgos del mismo que terminarán por hacerse explícitos en nuestros días, el trabajo se centra en señalar las implicaciones (y, sobre todo, las consecuencias que tiene adscribir decididamente la responsabilidad a la época moderna y, en concreto, al surgimiento de la civilización industrial. Acaso una de las más importantes sea la de obligarnos a plantear toda una serie de asuntos en conexión necesaria con otro tema-eje del pensamiento moderno, el de la identidad. Junto a dicho tema, en el texto quedan apuntados otros, como el de la justa escala en la que abordar tales asuntos (o, lo que viene a ser lo mismo, el problema de las presuntas responsabilidades colectivas o el del mal, por citar sólo dos, cuya envergadura puede servir como indicador de la importancia que presenta el concepto de responsabilidad en el pensamiento contemporáneo.

  19. Integración, turismo y discapacidad: ¿son accesibles los hoteles para las personas con discapacidad física?

    Directory of Open Access Journals (Sweden)

    Raquel Suriá Martínez

    2014-01-01

    Full Text Available En este estudio examinamos los obstaculos que se encuentran las personas con discapacidad física durante su estancia en un hotel. Se examinó la influencia del género y edad. Participaron 41 personas con discapacidad motora pertenencientes a la confederación de discapacitados de la provincia de Alicante. Utilizamos un cuestionario diseñado had hoc para el estudio. Los resultados indicaron que la mayor dificultad que los participantes encuentran en los hoteles son los escalones y el personal. se encontraron diferencias según el género y edad. Ello revela la existencia de obstáculos que impiden la accesibilidad hotelera para las personas con discapacidad. Estas dificultades pueden solucionarse con una adecuada predisposición por parte de los responsables hoteleros.

  20. Performance of brain MRI of a two generation father-and-son family with long-term smoking caffeinum natrio benzoicum

    Institute of Scientific and Technical Information of China (English)

    SUN Wan-li; ZHANG Li-fang; LIU Hong; ZHAO Li-yun; XING Yu-ping; YUAN Ning

    2010-01-01

    @@ Since the 1970s, some people in north, northeast,northwest areas began to smoke caffeinum natrio benzoicum (CNB) and started to abuse CNB. As a common ingredient that can be found in drugs or drinks,many studies on the safety of CNB have been investigated, but no one has shown significant abnormality in the brain of a CNB abuser by using neuroimaging. In our study, three subjects from of a two generation father-and-son family with long-term smoking CNB were enrolled. Combining with the clinical data and taking the cocaine animal trial model and toxicology as the reference, we wanted to observe the performance of brain MRI and MRS of patients with long-term smoking CNB.

  1. La prose fran(c)aise avec son profond humanisme%法兰西散文的流变和人文精神

    Institute of Scientific and Technical Information of China (English)

    程依荣

    2003-01-01

    Le terme de la prose désigne ici tous les genres littéraires en prose non romantisée, à coté des trois genres “majeurs” que sont la poésie, le théatre et le roman. La prose francaise a une trés longue tradition, et elle a connu des grands auteurs tels que Montaigne, R.F. de Chateaubriand, J. J. Rousseau, F. Mauriac etc. qui avaient créé des oeuvres de réputation mondiale. Tout au long de son histoire, la prose francaise est marquée par un profond humanisme qui se renouvelle sans cesse, et par des écrits artistiques raffinés et variés.

  2. Transplantation rénale au Maroc: l'hémodialysé et son entourage sont-ils suffisamment informés?

    OpenAIRE

    Noto-Kadou-Kaza, Béfa; Sabi, Kossi Akomola; Imangue, Ghislain; Al-Torayhi, Mays Hadi; Amekoudi, Eyram Yoan Makafui; Tsevi, Claude Mawufemo; Zamd, Mohamed; Medkouri, Ghislaine; Benghanem, Mohamed Gharbi; Ramdani, Benyounes

    2014-01-01

    Introduction La transplantation rénale constitue le traitement idéal de l'insuffisance rénale chronique. Cependant il existe une insuffisance de donneurs contrairement aux receveurs dont le nombre ne cesse de s'accroitre. La méconnaissance de la transplantation par les hémodialysés et leur entourage pourrait être l'une des causes. Notre but était d’évaluer les connaissances et opinions de l'hémodialysé et de son entourage sur la transplantation rénale. Méthodes L'enquête menée en Aout 2013 av...

  3. ¿Cuáles son las variables clave en la adopción del marketing de relaciones? Una investigación en el contexto colombiano

    Directory of Open Access Journals (Sweden)

    César Augusto Salazar

    2015-10-01

    Full Text Available El objetivo de esta investigación es descubrir cuáles son las variables clave en la aplicación del marketing de relaciones en las empresas colombianas. Se aplica un instrumento comparativo a compañías pertenecientes a diferentes sectores y con distintos tamaños, en ese país, en dos olas: el primero, denominado ‘ola 1’, corresponde a los años 2003 y 2004; el segundo, denominado ‘ola 2’, corresponde a los años 2010 y 2011. La técnica utilizada para validar el constructo propuesto fue el análisis factorial de componentes principales.

  4. ¿Cuáles son las revistas, libros y personas más influyentes en la biología latinoamericana?

    OpenAIRE

    Monge-Nájera, Julián; Benavides-Varela, Catalina; Morera, Bernal

    2014-01-01

    Para identificar las revistas, libros y personas más influyentes en la biología latinoamericana, se envió por correo electrónico una encuesta a 553 personas dedicadas el tema, según la base de datos de la Revista de Biología Tropical. Un tercio de ellas respondió, concluyéndose que la Revista de Biología Tropical, es la más influyente de la región según las personas consultadas. Con esta excepción, la mayoría de las revistas influyentes son publicadas en países desarrollados. La distribución ...

  5. ¿Qué es la investigación en Educación Matemática y cuáles son sus resultados? II

    OpenAIRE

    1994-01-01

    En el pasado número de este boletín presenté un resumen de las conferencias y discusiones que tuvieron lugar en mayo de 1994, durante la Conferencia ICMI 1994 alrededor del tema ¿Qué es la investigación en educación matemática y cuáles son sus resultados? En ese artículo presento algunos apartes del documento que Paul Ernest (Ernest, 1994) presentó en esta reunión con el propósito de dar respuesta a estas preguntas. Me centraré tan sólo en algunos de los puntos de su documento, dejando por fu...

  6. Synthetic heparin-binding factor analogs

    Science.gov (United States)

    Pena, Louis A.; Zamora, Paul O.; Lin, Xinhua; Glass, John D.

    2010-04-20

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain, and preferably two peptide chains branched from a dipeptide branch moiety composed of two trifunctional amino acid residues, which peptide chain or chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a linker, which may be a hydrophobic linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  7. Defining Starch Binding by Glucan Phosphatases

    DEFF Research Database (Denmark)

    Auger, Kyle; Raththagala, Madushi; Wilkens, Casper

    2015-01-01

    phosphatases. The main objective of this study was to quantify the binding affinity of different enzymes that are involved in this cyclic process. We established a protocol to quickly, reproducibly, and quantitatively measure the binding of the enzymes to glucans utilizing Affinity Gel Electrophoresis (AGE...... glucan phosphatases showed similar affinities for the short oligosaccharide β-cyclodextrin. We performed structure-guided mutagenesis to define the mechanism of these differences. We found that the carbohydrate binding module (CBM) domain provided a stronger binding affinity compared to surface binding...

  8. Statistics for Transcription Factor Binding Sites

    OpenAIRE

    2008-01-01

    Transcription factors (TFs) play a key role in gene regulation. They interact with specific binding sites or motifs on the DNA sequence and regulate expression of genes downstream of these binding sites. In silico prediction of potential binding of a TF to a binding site is an important task in computational biology. From a statistical point of view, the DNA sequence is a long text consisting of four different letters ('A','C','G', and 'T'). The binding of a TF to the sequence corresponds to ...

  9. Mutation of Asp(171) and Asp(262) of the chemokine receptor CXCR4 impairs its coreceptor function for human immunodeficiency virus-1 entry and abrogates the antagonistic activity of AMD3100

    DEFF Research Database (Denmark)

    Hatse, S; Princen, K; Gerlach, L O

    2001-01-01

    that the antagonistic action of AMD3100 against CXCR4--as assessed by the inhibitory effects of the compound on stromal cell-derived factor (SDF-1) binding to its receptor and on SDF-1-induced intracellular calcium signaling, and by displacement of the CXCR4-specific antibody, clone 12G5--was greatly reduced...

  10. DBD2BS: connecting a DNA-binding protein with its binding sites

    OpenAIRE

    2012-01-01

    By binding to short and highly conserved DNA sequences in genomes, DNA-binding proteins initiate, enhance or repress biological processes. Accurately identifying such binding sites, often represented by position weight matrices (PWMs), is an important step in understanding the control mechanisms of cells. When given coordinates of a DNA-binding domain (DBD) bound with DNA, a potential function can be used to estimate the change of binding affinity after base substitutions, where the changes c...

  11. Infinite sets and double binds.

    Science.gov (United States)

    Arden, M

    1984-01-01

    There have been many attempts to bring psychoanalytical theory up to date. This paper approaches the problem by discussing the work of Gregory Bateson and Ignacio Matte-Blanco, with particular reference to the use made by these authors of Russell's theory of logical types. Bateson's theory of the double bind and Matte-Blanco's bilogic are both based on concepts of logical typing. It is argued that the two theories can be linked by the idea that neurotic symptoms are based on category errors in thinking. Clinical material is presented from the analysis of a middle-aged woman. The intention is to demonstrate that the process of making interpretations can be thought of as revealing errors in thinking. Changes in the patient's inner world are then seen to be the result of clarifying childhood experiences based on category errors. Matte-Blanco's theory of bilogic and infinite experiences is a re-evaluation of the place of the primary process in mental life. It is suggested that a combination of bilogic and double bind theory provides a possibility of reformulating psychoanalytical theory.

  12. Protection against Mitochondrial and Metal Toxicity Depends on Functional Lipid Binding Sites in ATP13A2

    Directory of Open Access Journals (Sweden)

    Shaun Martin

    2016-01-01

    Full Text Available The late endo-/lysosomal P-type ATPase ATP13A2 (PARK9 is implicated in Parkinson’s disease (PD and Kufor-Rakeb syndrome, early-onset atypical Parkinsonism. ATP13A2 interacts at the N-terminus with the signaling lipids phosphatidic acid (PA and phosphatidylinositol (3,5 bisphosphate (PI(3,5P2, which modulate ATP13A2 activity under cellular stress conditions. Here, we analyzed stable human SHSY5Y cell lines overexpressing wild-type (WT or ATP13A2 mutants in which three N-terminal lipid binding sites (LBS1–3 were mutated. We explored the regulatory role of LBS1–3 in the cellular protection by ATP13A2 against mitochondrial stress induced by rotenone and found that the LBS2-3 mutants displayed an abrogated protective effect. Moreover, in contrast to WT, the LBS2 and LBS3 mutants responded poorly to pharmacological inhibition of, respectively, PI(3,5P2 and PA formation. We further demonstrate that PA and PI(3,5P2 are also required for the ATP13A2-mediated protection against the toxic metals Mn2+, Zn2+, and Fe3+, suggesting a general lipid-dependent activation mechanism of ATP13A2 in various PD-related stress conditions. Our results indicate that the ATP13A2-mediated protection requires binding of PI(3,5P2 to LBS2 and PA to LBS3. Thus, targeting the N-terminal lipid binding sites of ATP13A2 might offer a therapeutic approach to reduce cellular toxicity of various PD insults including mitochondrial stress.

  13. Structural and Functional Characterization of Cargo-Binding Sites on the μ4-Subunit of Adaptor Protein Complex 4

    Science.gov (United States)

    Ross, Breyan H.; Lin, Yimo; Corales, Esteban A.; Burgos, Patricia V.; Mardones, Gonzalo A.

    2014-01-01

    Adaptor protein (AP) complexes facilitate protein trafficking by playing key roles in the selection of cargo molecules to be sorted in post-Golgi compartments. Four AP complexes (AP-1 to AP-4) contain a medium-sized subunit (μ1-μ4) that recognizes YXXØ-sequences (Ø is a bulky hydrophobic residue), which are sorting signals in transmembrane proteins. A conserved, canonical region in μ subunits mediates recognition of YXXØ-signals by means of a critical aspartic acid. Recently we found that a non-canonical YXXØ-signal on the cytosolic tail of the Alzheimer's disease amyloid precursor protein (APP) binds to a distinct region of the μ4 subunit of the AP-4 complex. In this study we aimed to determine the functionality of both binding sites of μ4 on the recognition of the non-canonical YXXØ-signal of APP. We found that substitutions in either binding site abrogated the interaction with the APP-tail in yeast-two hybrid experiments. Further characterization by isothermal titration calorimetry showed instead loss of binding to the APP signal with only the substitution R283D at the non-canonical site, in contrast to a decrease in binding affinity with the substitution D190A at the canonical site. We solved the crystal structure of the C-terminal domain of the D190A mutant bound to this non-canonical YXXØ-signal. This structure showed no significant difference compared to that of wild-type μ4. Both differential scanning fluorimetry and limited proteolysis analyses demonstrated that the D190A substitution rendered μ4 less stable, suggesting an explanation for its lower binding affinity to the APP signal. Finally, in contrast to overexpression of the D190A mutant, and acting in a dominant-negative manner, overexpression of μ4 with either a F255A or a R283D substitution at the non-canonical site halted APP transport at the Golgi apparatus. Together, our analyses support that the functional recognition of the non-canonical YXXØ-signal of APP is limited to the non

  14. Adaptive evolution of transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Berg Johannes

    2004-10-01

    Full Text Available Abstract Background The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks in the evolution of complex regulatory networks. We study a theoretical model for the sequence evolution of binding sites by point mutations. The approach is based on biophysical models for the binding of transcription factors to DNA. Hence we derive empirically grounded fitness landscapes, which enter a population genetics model including mutations, genetic drift, and selection. Results We show that the selection for factor binding generically leads to specific correlations between nucleotide frequencies at different positions of a binding site. We demonstrate the possibility of rapid adaptive evolution generating a new binding site for a given transcription factor by point mutations. The evolutionary time required is estimated in terms of the neutral (background mutation rate, the selection coefficient, and the effective population size. Conclusions The efficiency of binding site formation is seen to depend on two joint conditions: the binding site motif must be short enough and the promoter region must be long enough. These constraints on promoter architecture are indeed seen in eukaryotic systems. Furthermore, we analyse the adaptive evolution of genetic switches and of signal integration through binding cooperativity between different sites. Experimental tests of this picture involving the statistics of polymorphisms and phylogenies of sites are discussed.

  15. Gamma Oscillations and Visual Binding

    Science.gov (United States)

    Robinson, Peter A.; Kim, Jong Won

    2006-03-01

    At the root of visual perception is the mechanism the brain uses to analyze features in a scene and bind related ones together. Experiments show this process is linked to oscillations of brain activity in the 30-100 Hz gamma band. Oscillations at different sites have correlation functions (CFs) that often peak at zero lag, implying simultaneous firing, even when conduction delays are large. CFs are strongest between cells stimulated by related features. Gamma oscillations are studied here by modeling mm-scale patchy interconnections in the visual cortex. Resulting predictions for gamma responses to stimuli account for numerous experimental findings, including why oscillations and zero-lag synchrony are associated, observed connections with feature preferences, the shape of the zero-lag peak, and variations of CFs with attention. Gamma waves are found to obey the Schroedinger equation, opening the possibility of cortical analogs of quantum phenomena. Gamma instabilities are tied to observations of gamma activity linked to seizures and hallucinations.

  16. Sex hormone binding globulin phenotypes

    DEFF Research Database (Denmark)

    Cornelisse, M M; Bennett, Patrick; Christiansen, M

    1994-01-01

    Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection....... This method of detection was used to determine the distribution of SHBG phenotypes in healthy controls of both sexes and in five different pathological conditions characterized by changes in the SHBG level or endocrine disturbances (malignant and benign ovarian neoplasms, hirsutism, liver cirrhosis...... on the experimental values. Differences in SHBG phenotypes do not appear to have any clinical significance and no sex difference was found in the SHBG phenotype distribution....

  17. DNA binding hydroxyl radical probes

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Vicky J.; Konigsfeld, Katie M.; Aguilera, Joe A. [Department of Radiology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0610 (United States); Milligan, Jamie R., E-mail: jmilligan@ucsd.edu [Department of Radiology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0610 (United States)

    2012-01-15

    The hydroxyl radical is the primary mediator of DNA damage by the indirect effect of ionizing radiation. It is a powerful oxidizing agent produced by the radiolysis of water and is responsible for a significant fraction of the DNA damage associated with ionizing radiation. There is therefore an interest in the development of sensitive assays for its detection. The hydroxylation of aromatic groups to produce fluorescent products has been used for this purpose. We have examined four different chromophores, which produce fluorescent products when hydroxylated. Of these, the coumarin system suffers from the fewest disadvantages. We have therefore examined its behavior when linked to a cationic peptide ligand designed to bind strongly to DNA. - Highlights: > Examined four aromatic groups as a means to detect hydroxyl radicals by fluorescence. > Coumarin system suffers from the fewest disadvantages. > Characterized its reactivity when linked to a hexa-arginine peptide.

  18. Why tight-binding theory?

    Science.gov (United States)

    Harrison, Walter A.

    2002-12-01

    In the context of computational physics other methods are more accurate, but tight-binding theory allows very direct physical interpretation and is simple enough to allow much more realistic treatments beyond the local density approximation. We address several important questions of this last category: How does the gap enhancement from Coulomb correlations vary from material to material? Should the enhanced gap be used for calculating the dielectric constant? For calculating the effective mass in k-dot-p theory? How valid is the scissors approximation? How does one line up bands at an interface? How should we match the envelope function at interfaces in effective-mass theory? Why can the resulting quantum-well states seem to violate the uncertainty principle? How should f-shell electrons be treated when they are intermediate between band-like and core-like? The answers to all of these questions are given and discussed.

  19. Synthetic LPS-Binding Polymer Nanoparticles

    Science.gov (United States)

    Jiang, Tian

    Lipopolysaccharide (LPS), one of the principal components of most gram-negative bacteria's outer membrane, is a type of contaminant that can be frequently found in recombinant DNA products. Because of its strong and even lethal biological effects, selective LPS removal from bioproducts solution is of particular importance in the pharmaceutical and health care industries. In this thesis, for the first time, a proof-of-concept study on preparing LPS-binding hydrogel-like NPs through facile one-step free-radical polymerization was presented. With the incorporation of various hydrophobic (TBAm), cationic (APM, GUA) monomers and cross-linkers (BIS, PEG), a small library of NPs was constructed. Their FITC-LPS binding behaviors were investigated and compared with those of commercially available LPS-binding products. Moreover, the LPS binding selectivity of the NPs was also explored by studying the NPs-BSA interactions. The results showed that all NPs obtained generally presented higher FITC-LPS binding capacity in lower ionic strength buffer than higher ionic strength. However, unlike commercial poly-lysine cellulose and polymyxin B agarose beads' nearly linear increase of FITC-LPS binding with particle concentration, NPs exhibited serious aggregation and the binding quickly saturated or even decreased at high particle concentration. Among various types of NPs, higher FITC-LPS binding capacity was observed for those containing more hydrophobic monomers (TBAm). However, surprisingly, more cationic NPs with higher content of APM exhibited decreased FITC-LPS binding in high ionic strength conditions. Additionally, when new cationic monomer and cross-linker, GUA and PEG, were applied to replace APM and BIS, the obtained NPs showed improved FITC-LPS binding capacity at low NP concentration. But compared with APM- and BIS-containing NPs, the FITC-LPS binding capacity of GUA- and PEG-containing NPs saturated earlier. To investigate the NPs' binding to proteins, we tested the NPs

  20. Peptide binding specificity of the chaperone calreticulin

    DEFF Research Database (Denmark)

    Sandhu, N.; Duus, K.; Jorgensen, C.S.;

    2007-01-01

    Calreticulin is a molecular chaperone with specificity for polypeptides and N-linked monoglucosylated glycans. In order to determine the specificity of polypeptide binding, the interaction of calreticulin with polypeptides was investigated using synthetic peptides of different length and composit......Calreticulin is a molecular chaperone with specificity for polypeptides and N-linked monoglucosylated glycans. In order to determine the specificity of polypeptide binding, the interaction of calreticulin with polypeptides was investigated using synthetic peptides of different length...... and composition. A large set of available synthetic peptides (n=127) was tested for binding to calreticulin and the results analysed by multivariate data analysis. The parameter that correlated best with binding was hydrophobicity while beta-turn potential disfavoured binding. Only hydrophobic peptides longer...... a peptide-binding specificity for hydrophobic sequences and delineate the fine specificity of calreticulin for hydrophobic amino acid residues....

  1. The helical structure of DNA facilitates binding

    Science.gov (United States)

    Berg, Otto G.; Mahmutovic, Anel; Marklund, Emil; Elf, Johan

    2016-09-01

    The helical structure of DNA imposes constraints on the rate of diffusion-limited protein binding. Here we solve the reaction-diffusion equations for DNA-like geometries and extend with simulations when necessary. We find that the helical structure can make binding to the DNA more than twice as fast compared to a case where DNA would be reactive only along one side. We also find that this rate advantage remains when the contributions from steric constraints and rotational diffusion of the DNA-binding protein are included. Furthermore, we find that the association rate is insensitive to changes in the steric constraints on the DNA in the helix geometry, while it is much more dependent on the steric constraints on the DNA-binding protein. We conclude that the helical structure of DNA facilitates the nonspecific binding of transcription factors and structural DNA-binding proteins in general.

  2. EXPLICAR LA CALIDAD DEMOCRÁTICA: ¿QUÉ TAN RELEVANTES SON LAS TRADICIONES AUTORITARIAS? Explaining Democratic Quality: How Relevant is the Authoritarian Legacy?

    Directory of Open Access Journals (Sweden)

    Leonardo Morlino

    2007-01-01

    Full Text Available Esta es una versión revisada de la lectura abierta dada por el autor el año 2004, en la conferencia de la sociedad italiana de Ciencia política en Padua. En la primera sección se discute la principal definición de democracia y calidad democrática, como estado de derecho, accountability electoral, accountability interins titucional, responsiveness, libertad y equidad/solidaridad. En la segunda parte surge una pregunta clave: si nosotros quisiéramos explicar la calidad de la democracia, ¿cuán relevantes son las tradiciones políticas previas? también son sugeridos otros factores explicativos que complementan el rol de los legados autoritarios, proponiendo pequeñas hipótesis clave. En la última sección se analiza el impacto del legado autoritario sobre la calidad de las democracias contemporáneas en países del sur de Europa como Portugal, España e Italia y el Cono Sur de Latinoamérica tal como Chile, Argentina, Uruguay y BrasilThis is the revised draft ofthe opening lecture given by the author atthe 2004 Conference of Italian Society of Political Science in Padua. Inthe first sectionthe main definitions of democracy and democratic qualities rule of law, electoral accountability, inter-ins titutional accountability, responsiveness, freedom and equality/solidarity are discussed. Inthe second a key ques tion is addressed: if we would liketo explainthe qualities of a democracy how much arethe previous politicaltraditions ofthe country relevant? Other explanatory factors, which complementthe role of an authoritarian legacy, are also sugges ted and a few key hypotheses are proposed.the final section does not provide any comprehensive explanation, but analyses ofthe impact of authoritarian legacy in a few countries of Southern Europe, such as Portugal, Spain, and Italy (but not Greece where it is not relevant and inthe Southern Cone as Chile, Argentina, Uruguay, Brazil, wherethe quality of contemporary democracies is ques tioned

  3. ¿Son viables los créditos ects otorgados a las matemáticas en los nuevos planes de estudio de LADE?

    Directory of Open Access Journals (Sweden)

    Álvarez Martínez, Pedro

    2006-01-01

    Full Text Available EL nuevo plan de estudios para la Administración y Dirección de Empresas (ADE va encaminado a resolver los problemas de la vida real en las empresas. Las disciplinas que lo contemplan están reguladas por los créditos ECTS (European Credit Transfer System, establecidos por la Commission of the European Community, con objeto de proporcionar procedimientos comunes que garanticen un reconocimiento académico de los estudios en los distintos paises que la integran. La presencia de las Matemáticas en los Planes es debido a su carácter instrumental, sus contenidos son utilizados por la demás disciplinas y le otorga el papel de ser una asignatura de servicio y “transversal”. El presente trabajo desarrolla una metodología empírica, determinando la temporización docente/discente de los contenidos matemáticos que son utilizados por todas las disciplinas que componen la titulación de ADE. Dichos contenidos han sido contabilizados y cuantificado en términos de créditos ECTS, aplicando los criterios que caracterizan su definición. El resultado obtenido pone de manifiesto que los créditos del nuevo plan no satisfacen las exigencias que caracterizan a los créditos ECTS para el aprendizaje de las matemáticas. Dado que los contenidos matemáticos no han cambiado, por exigencias de las disciplinas de ADE, los resultados obtenidos con datos experimentales, tras la reducción de horas de docencia, muestran lo siguiente: Con el Plan del 1973 (10 horas semanales de clase de Matemáticas se necesitaban 3 convocatorias para aprobar, con el plan actual (4 horas semanales de clase se necesitan 6 convocatorias. La reducción ha supuesto para el alumno un incremento de año y medio de estancia en la universidad, y como consecuencia aumenta el coste. Estudiar matemáticas para ADE era mas barato “antes” que “ahora”. La propuesta de los nuevos planes hace inviable el aprendizaje de las matemáticas en ADE.

  4. Predicted metal binding sites for phytoremediation

    OpenAIRE

    Sharma, Ashok; Roy, Sudeep; Tripathi, Kumar Parijat; Roy, Pratibha; Mishra, Manoj; Khan, Feroz; Meena, Abha

    2009-01-01

    Metal ion binding domains are found in proteins that mediate transport, buffering or detoxification of metal ions. The objective of the study is to design and analyze metal binding motifs against the genes involved in phytoremediation. This is being done on the basis of certain pre-requisite amino-acid residues known to bind metal ions/metal complexes in medicinal and aromatic plants (MAP's). Earlier work on MAP's have shown that heavy metals accumulated by aromatic and medicinal plants do no...

  5. A computational model for feature binding

    Institute of Scientific and Technical Information of China (English)

    SHI ZhiWei; SHI ZhongZhi; LIU Xi; SHI ZhiPing

    2008-01-01

    The "Binding Problem" is an important problem across many disciplines, including psychology, neuroscience, computational modeling, and even philosophy. In this work, we proposed a novel computational model, Bayesian Linking Field Model, for feature binding in visual perception, by combining the idea of noisy neuron model, Bayesian method, Linking Field Network and competitive mechanism.Simulation Experiments demonstrated that our model perfectly fulfilled the task of feature binding in visual perception and provided us some enlightening idea for future research.

  6. A computational model for feature binding

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The "Binding Problem" is an important problem across many disciplines, including psychology, neuroscience, computational modeling, and even philosophy. In this work, we proposed a novel computational model, Bayesian Linking Field Model, for feature binding in visual perception, by combining the idea of noisy neuron model, Bayesian method, Linking Field Network and competitive mechanism. Simulation Experiments demonstrated that our model perfectly fulfilled the task of feature binding in visual perception and provided us some enlightening idea for future research.

  7. Lead-Binding Proteins: A Review

    Directory of Open Access Journals (Sweden)

    Harvey C. Gonick

    2011-01-01

    Full Text Available Lead-binding proteins are a series of low molecular weight proteins, analogous to metallothionein, which segregate lead in a nontoxic form in several organs (kidney, brain, lung, liver, erythrocyte. Whether the lead-binding proteins in every organ are identical or different remains to be determined. In the erythrocyte, delta-aminolevulinic acid dehydratase (ALAD isoforms have commanded the greatest attention as proteins and enzymes that are both inhibitable and inducible by lead. ALAD-2, although it binds lead to a greater degree than ALAD-1, appears to bind lead in a less toxic form. What may be of greater significance is that a low molecular weight lead-binding protein, approximately 10 kDa, appears in the erythrocyte once blood lead exceeds 39 μg/dL and eventually surpasses the lead-binding capacity of ALAD. In brain and kidney of environmentally exposed humans and animals, a cytoplasmic lead-binding protein has been identified as thymosin β4, a 5 kDa protein. In kidney, but not brain, another lead-binding protein has been identified as acyl-CoA binding protein, a 9 kDa protein. Each of these proteins, when coincubated with liver ALAD and titrated with lead, diminishes the inhibition of ALAD by lead, verifying their ability to segregate lead in a nontoxic form.

  8. Drug binding properties of neonatal albumin

    DEFF Research Database (Denmark)

    Brodersen, R; Honoré, B

    1989-01-01

    Neonatal and adult albumin was isolated by gel chromatography on Sephacryl S-300, from adult and umbilical cord serum, respectively. Binding of monoacetyl-diamino-diphenyl sulfone, warfarin, sulfamethizole, and diazepam was studied by means of equilibrium dialysis and the binding data were analyzed...... by the method of several acceptable fitted curves. It was found that the binding affinity to neonatal albumin is less than to adult albumin for monoacetyl-diamino-diphenyl sulfone and warfarin. Sulfamethizole binding to the neonatal protein is similarly reduced when more than one molecule of the drug is bound...

  9. Advances on Plant Pathogenic Mycotoxin Binding Proteins

    Institute of Scientific and Technical Information of China (English)

    WANG Chao-hua; DONG Jin-gao

    2002-01-01

    Toxin-binding protein is one of the key subjects in plant pathogenic mycotoxin research. In this paper, new advances in toxin-binding proteins of 10 kinds of plant pathogenic mycotoxins belonging to Helminthosporium ,Alternaria ,Fusicoccum ,Verticillium were reviewed, especially the techniques and methods of toxin-binding proteins of HS-toxin, HV-toxin, HMT-toxin, HC-toxin. It was proposed that the isotope-labeling technique and immunological chemistry technique should be combined together in research of toxin-binding protein, which will be significant to study the molecular recognition mechanism between host and pathogenic fungus.

  10. Retinoid-binding proteins: similar protein architectures bind similar ligands via completely different ways.

    Directory of Open Access Journals (Sweden)

    Yu-Ru Zhang

    Full Text Available BACKGROUND: Retinoids are a class of compounds that are chemically related to vitamin A, which is an essential nutrient that plays a key role in vision, cell growth and differentiation. In vivo, retinoids must bind with specific proteins to perform their necessary functions. Plasma retinol-binding protein (RBP and epididymal retinoic acid binding protein (ERABP carry retinoids in bodily fluids, while cellular retinol-binding proteins (CRBPs and cellular retinoic acid-binding proteins (CRABPs carry retinoids within cells. Interestingly, although all of these transport proteins possess similar structures, the modes of binding for the different retinoid ligands with their carrier proteins are different. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we analyzed the various retinoid transport mechanisms using structure and sequence comparisons, binding site analyses and molecular dynamics simulations. Our results show that in the same family of proteins and subcellular location, the orientation of a retinoid molecule within a binding protein is same, whereas when different families of proteins are considered, the orientation of the bound retinoid is completely different. In addition, none of the amino acid residues involved in ligand binding is conserved between the transport proteins. However, for each specific binding protein, the amino acids involved in the ligand binding are conserved. The results of this study allow us to propose a possible transport model for retinoids. CONCLUSIONS/SIGNIFICANCE: Our results reveal the differences in the binding modes between the different retinoid-binding proteins.

  11. Crustal thickness mapping in Raipur–Katni area of Narmada–Son lineament in central India derived from 3D Euler deconvolution of magnetic data

    Indian Academy of Sciences (India)

    G K Ghosh; C L Singh

    2013-10-01

    The Narmada–Son lineament (NSL) is one of the most prominent tectonic features which divides the Indian peninsula into two subcontinents, northern and southern India since Precambrian times. The area is seismically active and geologically complex with different geological formations. Magnetic data divides the area into two parts and more prominent magnetic highs are observed near Tikwa, Mau and Amarpur regions with 800, 600 and 400 nT, respectively due to the presence of the crystalline basement rock. Tectonic resettlement and lithological changes causes upwarpment of Mahakoshal rocks. In the present study, magnetic data interpretation is carried out for locating depth of causative body and delineating structural fault/dyke boundaries using Euler deconvolution technique. Most of the faults are oriented in the ENE–WSW direction; however, few more faults are identified which are oriented in the SE to NW direction. These fault patterns suggest that the area is exaggerated by tectonic turmoil and distressed both sedimentary to basement rocks isolating the area into numerous faulted blocks. The maximum depths (< 4.5 km) observed at Katni and Umaria area and moderate depths (between 4.0 and 4.5 km) observed towards east of Katni, Ramnagar, Burwa and east of Umaria and Sarna area.

  12. Evidence for an extensive intrusive component of the Deccan Large Igneous Province in the Narmada Son Lineament region, India from three dimensional magnetotelluric studies

    Science.gov (United States)

    Patro, Prasanta K.; Sarma, S. V. S.

    2016-10-01

    The crustal electrical structure beneath the western segment of Narmada-Son lineament zone in Central India has been imaged using magnetotelluric (MT) data set of 153 stations distributed over a grid (∼7-8 km site spacing). Three dimensional modeling of this data set brought out several major crustal conductors with different geometries at different depth levels in the crustal column. The conductive features, correlating with gravity high anomalies and high seismic velocity zones are interpreted to be mafic-ultramafic bodies derived from mantle. We infer that these bodies represent the intrusive component of the Large Igneous Province (LIP) of the Deccan volcanic episode triggered by the passage of the Indian continent over the Reunion hot spot during the Late Cretaceous. The disposition and the geometry of the subsurface magmatic bodies, which must have served as magma chambers for outpouring of the Deccan lavas, suggest that they are closely related to the plumbing geometry of the LIP of the Deccan volcanic episode.

  13. The incandescent lamps in Mexico; are they really a beneficial technology?; Las lamparas incandescentes en Mexico: son realmente una tecnologia benefica?

    Energy Technology Data Exchange (ETDEWEB)

    Ramirez Rivero, A. G. [Genertek, S.A. de C.V., Mexico, D. F. (Mexico)

    1995-12-31

    The versatility of the incandescent lamps has originated a sustained increment of its population all over the world. Because of its characteristics they continue being irreplaceable in numberless applications, that go from the movies up to the medicine. Nevertheless the greatest population are represented by the incandescent lamps A-19 with the well-known negative effects to the environment and the economy caused by the electric power generation by conventional methods. No doubt about it, the best option to substitute them are the compact fluorescent lamps (CFL), but the economical barriers, the market and the performance do not permit its massive application in Mexico. In this paper a proposal is set forth that might bring high benefits with a minimum investment and rapid implementation. [Espanol] La versatilidad de las lamparas incandescentes ha causado un incremento sostenido de su poblacion en todo el mundo. Dadas sus caracteristicas continua siendo insustituible en un sinnumero de aplicaciones, que van desde el cine hasta la medicina. Sin embargo, la mayor poblacion la representan las ineficientes lamparas incandescentes A19 con los consabidos efectos negativos en el medio ambiente y la economia, causados por la generacion de energia electrica por medios convencionales. Sin duda, la mejor opcion para sustituirlas son las lamparas compacto fluorescentes (LCF), pero las barreras economicas, de mercado y de desempeno no permiten su aplicacion masiva en Mexico. En este trabajo se hace una propuesta que puede permitir grandes beneficios con minima inversion y rapida implementacion.

  14. Nommer le conflit. Le cas de l’Alsace pendant son annexion de fait au Troisième Reich, 1940-1945

    Directory of Open Access Journals (Sweden)

    Anne-Ségolène Verneret

    2011-12-01

    Full Text Available L’étude des comportements et opinions de la population en Alsace entre 1940 et 1945 fait appel à la nécessité de nommer une conflictualité parfois floue, ambivalente et qui évolue au cours de la période. Il convient de s’interroger sur l’adaptation des outils de définition des comportements développés en France et en Allemagne pour la situation alsacienne pendant l’annexion de fait de son territoire.   Alsace 1940-1945, oppositions au nazisme, comportements collectifsDie Erforschung des Verhaltens und der Meinung der Bevölkerung im Elsass zwischen 1940-1945 bringt die Notwendigkeit mit sich, eine zuweilen undurchsichtige, zweideutige Konfliktträchtigkeit zu benennen, die sich im Zeitraum der Annektierung zudem entwickelte. Die methodischen Werkzeuge zur Definition kollektiven Verhaltens, die in Frankreich und Deutschland für diesen elsässischen Fall entwickelt wurden, müssen hierbei angepasst werden.

  15. Materials characterization activities for %E2%80%9CTake Our Sons&Daughters to Work Day%E2%80%9D 2013.

    Energy Technology Data Exchange (ETDEWEB)

    Mowry, Curtis Dale; Pimentel, Adam S.; Sparks, Elizabeth Schares; Hanlon, Brittany Paula

    2013-09-01

    We created interactive demonstration activities for Take Our Daughters&Sons to Work Day (TODSTWD) 2013 in order to promote general interest in chemistry and also generate awareness of the type of work our laboratories can perform. %E2%80%9CCurious about Mars Rover Curiosity?%E2%80%9D performed an elemental analysis on rocks brought to our lab using the same technique utilized on the planet Mars by the NASA robotic explorer Curiosity. %E2%80%9CFood is Chemistry?%E2%80%9D utilized a mass spectrometer to measure, in seconds, each participant's breath in order to identify the food item consumed for the activity. A total of over 130 children participated in these activities over a 3 hour block, and feedback was positive. This document reports the materials (including handouts), experimental procedures, and lessons learned so that future demonstrations can benefit from the baseline work performed. We also present example results used to prepare the Food activity and example results collected during the Curiosity demo.

  16. 《土生子》与《看不见的人》里的象征艺术%Symbolism in Native Son and Invisible Man

    Institute of Scientific and Technical Information of China (English)

    黄春英

    2007-01-01

    Richard Wright and Ralph Allison were two famous contemporary American black novelists. The frequent use of symbolism is a common feature in their literary writing.Through the analysis of the use of symbolism in Richard Wright's Native Son and Ralph Allison's Invisible Man, the writer reveals that a close link between the two novelists' literary creation is an objective existence which is hard to deny.%理查德·赖特和拉尔夫·埃里森,是美国当代两位最著名的黑人作家.大量运用象征,是他们创作的一个共同点.本文主要通过对赖特和埃里森这两部小说里象征艺术的对比分析,指出两位作家创作的密切联系的确是难以否认的客观存在.

  17. n torno a la globalización. ¿Cuáles son los cambios para interpretar las instituciones políticas?

    Directory of Open Access Journals (Sweden)

    Francisco Roberto García Samaniego

    2005-01-01

    Full Text Available Actualmente existen líneas de investigación sobre aquellos fenómenos presentes que son producto de la globalización, los cambios y los efectos que le siguen producen en la política, la sociedad y la cultura. En este caso haremos referencia a lo colectivo, en tanto y en cuanto, trae parejos profundos conflictos afectivos del entorno individual de algunos seres humanos que afrontan dichos cambios que repolitizan lo público. Y dichos efectos globales entorno a la democracia, y sus instituciones, replantea las formas de interpretar el conflicto social, su visión política y sus efectos sociales a largo plazo. Es decir, la globalización económica y tecnológica de los medios y las redes electrónicas permiten una multiculturalidad que hace desestructurar los referentes tradicionales de identidad. Y al desestructurar el sujeto social unificado que representaba las figuras del pueblo y de nación se descubre el carácter conflictivo que hoy adquiere las configuraciones de lo colectivo y de lo público-político.

  18. Sex allocation and secondary sex ratio in Cuban boa ( Chilabothrus angulifer): mother's body size affects the ratio between sons and daughters

    Science.gov (United States)

    Frynta, Daniel; Vejvodová, Tereza; Šimková, Olga

    2016-06-01

    Secondary sex ratios of animals with genetically determined sex may considerably deviate from equality. These deviations may be attributed to several proximate and ultimate factors. Sex ratio theory explains some of them as strategic decisions of mothers improving their fitness by selective investment in sons or daughters, e.g. local resource competition hypothesis (LRC) suggests that philopatric females tend to produce litters with male-biased sex ratios to avoid future competition with their daughters. Until now, only little attention has been paid to examine predictions of sex ratio theory in snakes possessing genetic sex determination and exhibiting large variance in allocation of maternal investment. Cuban boa is an endemic viviparous snake producing large-bodied newborns (˜200 g). Extremely high maternal investment in each offspring increases importance of sex allocation. In a captive colony, we collected breeding records of 42 mothers, 62 litters and 306 newborns and examined secondary sex ratios (SR) and sexual size dimorphism (SSD) of newborns. None of the examined morphometric traits of neonates appeared sexually dimorphic. The sex ratio was slightly male biased (174 males versus 132 females) and litter sex ratio significantly decreased with female snout-vent length. We interpret this relationship as an additional support for LRC as competition between mothers and daughters increases with similarity of body sizes between competing snakes.

  19. SO(n)规范势的可分解理论%General Decomposition Theory of SO(n) Gauge Potential

    Institute of Scientific and Technical Information of China (English)

    李希国; 段一士; 等

    2001-01-01

    使用几何代数方法,研究了n维紧致黎曼流形上SO(n)规范势(自旋联络)的一般分解理论,建立了SO(n)规范场用球丛上单位矢量场n分解的一般表达式. 由此,分别得到了U(1)规范场和U(2)规范场用单位矢量场n分解的一般形式.%By means of devices of geometry algebra the general decomposition of gauge potential (spin connection) on a compact n-dimension Riemannian manifold has been studied in detail. A general decomposition formula of SO(n) gauge potential in terms of a unit vector field on the sphere bundle has been established. Using same local structure between SO(2) and U(1), SO(3) and SU(2) the general decomposition formula of U(1) and SU(2) gauge potential in terms of the unit vector field has been also given respectively

  20. 父与子的神话:霍尔顿的双重身份%A Modern Father-Son Myth: Dual Identities of Holden Caulfield

    Institute of Scientific and Technical Information of China (English)

    罗灿

    2006-01-01

    霍尔顿体现了一个成长中的少年的种种问题:厌恶成人世界,不愿长大,急切地在寻找一个"父亲"来指导未来的生活.虽然寻找精神上的父亲是徒劳的,霍尔顿自己却在不知不觉中充当了父亲的角色,具有敏锐的观察力,不断地试图去关怀他人,保护他人.儿子和父亲两种截然不同甚至有些矛盾的角色同时存在于霍尔顿身上,使其形象复杂,充满争议,同时也正是其魅力所在.%As a teenager,Holden Caulfield complains about the phoniness of adult world and searches desperately for a spiritual father who can help him cross the road,that is,grow up without losing his innocence.Yet at the same time,as he himself dreams,Holden Caulfield is a catcher,or a father figure who offers facilitating and guiding help.As a son figure and father figure combined,Holden is an entity of contradiction.The success and controversy of Holden in part consist in his very contradiction and inexplicability.