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Sample records for abrogates son binding

  1. 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.

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

    International Nuclear Information System (INIS)

    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

  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. Interruption of intrachromosomal looping by CCCTC binding factor decoy proteins abrogates genomic imprinting of human insulin-like growth factor II

    Science.gov (United States)

    Zhang, He; Niu, Beibei; Ge, Shengfang; Wang, Haibo; Li, Tao; Ling, Jianqun; Steelman, Brandon N.; Qian, Guanxiang

    2011-01-01

    Monoallelic expression of IGF2 is regulated by CCCTC binding factor (CTCF) binding to the imprinting control region (ICR) on the maternal allele, with subsequent formation of an intrachromosomal loop to the promoter region. The N-terminal domain of CTCF interacts with SUZ12, part of the polycomb repressive complex-2 (PRC2), to silence the maternal allele. We synthesized decoy CTCF proteins, fusing the CTCF deoxyribonucleic acid–binding zinc finger domain to CpG methyltransferase Sss1 or to enhanced green fluorescent protein. In normal human fibroblasts and breast cancer MCF7 cell lines, the CTCF decoy proteins bound to the unmethylated ICR and to the IGF2 promoter region but did not interact with SUZ12. EZH2, another part of PRC2, was unable to methylate histone H3-K27 in the IGF2 promoter region, resulting in reactivation of the imprinted allele. The intrachromosomal loop between the maternal ICR and the IGF2 promoters was not observed when IGF2 imprinting was lost. CTCF epigenetically governs allelic gene expression of IGF2 by orchestrating chromatin loop structures involving PRC2. PMID:21536749

  5. "Abrogation of Rulings” Methodology: A Critique

    OpenAIRE

    Gasser Auda

    2004-01-01

    Surveying the subject of abrogation (naskh) in the Qur’ān, ḥādīth and Islamic literature, it is clear that most abrogation cases were introduced after the Prophetic era in order to interpret certain Qur’ānic verses and Prophetic narrations (aḥādīth) that some scholars perceived as “conflicting.” Two striking examples are “The Verse of the Sword” (āyat al-saif) and “The Verse of the Barrier” (āyat al-ḥijāb). The Qur’ānic verses and aḥādīth,...

  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. 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.

  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. PMID:24283330

  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. TNIK inhibition abrogates colorectal cancer stemness

    Science.gov (United States)

    Masuda, Mari; Uno, Yuko; Ohbayashi, Naomi; Ohata, Hirokazu; Mimata, Ayako; Kukimoto-Niino, Mutsuko; Moriyama, Hideki; Kashimoto, Shigeki; Inoue, Tomoko; Goto, Naoko; Okamoto, Koji; Shirouzu, Mikako; Sawa, Masaaki; Yamada, Tesshi

    2016-01-01

    Canonical Wnt/β-catenin signalling is essential for maintaining intestinal stem cells, and its constitutive activation has been implicated in colorectal carcinogenesis. We and others have previously identified Traf2- and Nck-interacting kinase (TNIK) as an essential regulatory component of the T-cell factor-4 and β-catenin transcriptional complex. Consistent with this, Tnik-deficient mice are resistant to azoxymethane-induced colon tumorigenesis, and Tnik−/−/Apcmin/+ mutant mice develop significantly fewer intestinal tumours. Here we report the first orally available small-molecule TNIK inhibitor, NCB-0846, having anti-Wnt activity. X-ray co-crystal structure analysis reveals that NCB-0846 binds to TNIK in an inactive conformation, and this binding mode seems to be essential for Wnt inhibition. NCB-0846 suppresses Wnt-driven intestinal tumorigenesis in Apcmin/+ mice and the sphere- and tumour-forming activities of colorectal cancer cells. TNIK is required for the tumour-initiating function of colorectal cancer stem cells. Its inhibition is a promising therapeutic approach. PMID:27562646

  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. 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.

  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. 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.

  18. Antibody-mediated neutralization of virus is abrogated by mycoplasma.

    OpenAIRE

    Dickson, C; Elkington, J; Hales, A.; Weiss, R.

    1980-01-01

    The ability of a mouse mammary tumor cell line to abrogate antibody neutralization of vesicular stomatitis virus was shown to be due to the presence of mycoplasma. The mycoplasma was isolated from the cell line and typed as Mycoplasma orale. Colonies of this mycoplasma were used to deliberately infect cell cultures which then gained the capacity to reactivate antibody-neutralized virus. The extent of the reactivation depended on the source of neutralizing antiserum. Other species of mycoplasm...

  19. Should attractive males have more sons?

    NARCIS (Netherlands)

    Fawcett, T.W.; Kuijper, A.L.W.; Pen, I.R.; Weissing, F.J.

    2007-01-01

    It is often argued that females with attractive partners should produce more sons because these sons will inherit their father's attractiveness. Numerous field and laboratory studies have addressed this hypothesis, with inconsistent results, but there is surprisingly little theoretical work on the t

  20. On the Themes of Sons and Lovers

    Institute of Scientific and Technical Information of China (English)

    路颖

    2015-01-01

    The current research attempts to explore the main themes of Lawrence's masterpiece Sons and Lovers from five the following aspects:Man/woman Love, the maturation of an artist, class conflict, Industrial life Vs. nature and Opposite forces: light and dark. It is great hope that this paper will make a small contribution to assist anyone who appreciates Sons and Lovers.

  1. Father-son incest: underreported psychiatric problem?

    Science.gov (United States)

    Dixon, K N; Arnold, L E; Calestro, K

    1978-07-01

    Six families are described in which 10 sons were involved incestuously with a natural father (N=4) or step-father (N=2). Father-son incest as a part of the spectrum of child abuse appears to be a more frequent clinical entity than was thought previously. PMID:665796

  2. 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.

  3. Relaxin requires the angiotensin II type 2 receptor to abrogate renal interstitial fibrosis.

    Science.gov (United States)

    Chow, Bryna S Man; Kocan, Martina; Bosnyak, Sanja; Sarwar, Mohsin; Wigg, Belinda; Jones, Emma S; Widdop, Robert E; Summers, Roger J; Bathgate, Ross A D; Hewitson, Tim D; Samuel, Chrishan S

    2014-07-01

    Fibrosis is a hallmark of chronic kidney disease, for which there is currently no effective cure. The hormone relaxin is emerging as an effective antifibrotic therapy; however, its mechanism of action is poorly understood. Recent studies have shown that relaxin disrupts the profibrotic actions of transforming growth factor-β1 (TGF-β1) by its cognate receptor, relaxin family peptide receptor 1 (RXFP1), extracellular signal-regulated kinase phosphorylation, and a neuronal nitric oxide synthase-dependent pathway to abrogate Smad2 phosphorylation. Since angiotensin II also inhibits TGF-β1 activity through its AT2 receptor (AT2R), we investigated the extent to which relaxin interacts with the AT2R. The effects of the AT2R antagonist, PD123319, on relaxin activity were examined in primary rat kidney myofibroblasts, and in kidney tissue from relaxin-treated male wild-type and AT2R-knockout mice subjected to unilateral ureteric obstruction. Relaxin's antifibrotic actions were significantly blocked by PD123319 in vitro and in vivo, or when relaxin was administered to AT2R-knockout mice. While heterodimer complexes were formed between RXFP1 and AT2Rs independent of ligand binding, relaxin did not directly bind to AT2Rs but signaled through RXFP1-AT2R heterodimers to induce its antifibrotic actions. These findings highlight a hitherto unrecognized interaction that may be targeted to control fibrosis progression. PMID:24429402

  4. 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.

  5. Satisfied Working Mothers and Their Preschool Sons.

    Science.gov (United States)

    Henggeler, Scott W.; Borduin, Charles M.

    1981-01-01

    Studied the effects of maternal employment on mother-child relations and children's psychosocial functioning. Mother-son pairs (N=28) were divided into maternal working versus maternal nonworking groups. Groups were observed at home and in a laboratory. Results indicated no significant main effects or interaction effects for maternal working…

  6. "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…

  7. 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. PMID:26571019

  8. 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.

  9. 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.

  10. 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. PMID:26329601

  11. ?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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. Mate-sampling costs and sexy sons.

    Science.gov (United States)

    Kokko, H; Booksmythe, I; Jennions, M D

    2015-01-01

    Costly female mating preferences for purely Fisherian male traits (i.e. sexual ornaments that are genetically uncorrelated with inherent viability) are not expected to persist at equilibrium. The indirect benefit of producing 'sexy sons' (Fisher process) disappears: in some models, the male trait becomes fixed; in others, a range of male trait values persist, but a larger trait confers no net fitness advantage because it lowers survival. Insufficient indirect selection to counter the direct cost of producing fewer offspring means that preferences are lost. The only well-cited exception assumes biased mutation on male traits. The above findings generally assume constant direct selection against female preferences (i.e. fixed costs). We show that if mate-sampling costs are instead derived based on an explicit account of how females acquire mates, an initially costly mating preference can coevolve with a male trait so that both persist in the presence or absence of biased mutation. Our models predict that empirically detecting selection at equilibrium will be difficult, even if selection was responsible for the location of the current equilibrium. In general, it appears useful to integrate mate sampling theory with models of genetic consequences of mating preferences: being explicit about the process by which individuals select mates can alter equilibria. PMID:25399634

  17. Having a Son Promotes Clean Cooking Fuel Use in Urban India: Women's Status and Son Preference

    OpenAIRE

    Avinash Kishore; Dean Spears

    2014-01-01

    Urban Indian households with a male first child are approximately 2 percentage points more likely to use clean cooking fuel than comparable households with a female first child. Given Indian son preference, there are at least two mechanisms by which child sex could affect fuel choice: by improving the intrahousehold status of women, who bear more of the costs of traditional fuels, or by presenting an opportunity to invest in children's health, in the context of a preference for healthier boys...

  18. 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.

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

    OpenAIRE

    Valbona Pajo Bala

    2014-01-01

    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 me...

  20. 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.

  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. 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.

  3. A Letter from a Black Mom to Her Son

    Science.gov (United States)

    Watson, Dyan

    2012-01-01

    An African American mother and teacher educator uses examples from her own childhood to describe how she hopes her child will be treated by teachers, and what she fears. In her letter to her son, the African American mom expresses how she want teachers to know her son's journey to school--metaphorically and physically. She wants them to know that…

  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. PMID:23746554

  5. 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.

  6. 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. PMID:26177158

  7. 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.

  8. The role of son preference in reproductive behaviour in Pakistan.

    Science.gov (United States)

    Hussain, R; Fikree, F F; Berendes, H W

    2000-01-01

    The sex of surviving children is an important determinant of reproductive behaviour in South Asia in general and Pakistan in particular. This cohort study evaluates the role of the sex of children on reproductive intentions and subsequent behaviour of women in urban slums of Karachi, Pakistan. The analysis is based on two rounds of surveys conducted in 1990-91 and 1995 of a cohort of married women aged 15-49 years. The results show that pregnancies became increasingly unwanted as the number of surviving sons increased. The sex of surviving children was strongly correlated with subsequent fertility and contraceptive behaviour. However, rather than an exclusive son preference, couples strove for one or more sons and at least one surviving daughter. The policy implications of the link between overt son preference and low status of women are discussed. PMID:10812738

  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. 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)

  11. 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...

  12. Abrogation of the Transactivation Activity of p53 by BCCIP Down-regulation*

    OpenAIRE

    Meng, Xiangbing; Yue, Jingyin; Liu, Zhihe; Shen, Zhiyuan

    2006-01-01

    The tumor suppression function of p53 is mostly conferred by its transactivation activity, which is inactivated by p53 mutations in ~50% of human cancers. In cancers harboring wild type p53, the p53 transactivation activity may be compromised by other mechanisms. Identifying the mechanisms by which wild type p53 transactivation activity can be abrogated may provide insights into the molecular etiology of cancers harboring wild type p53. In this report, we show that BCCIP, a BRCA2 and CDKN1A-i...

  13. Vpliv sončnih elektrarn na napetostni profil

    OpenAIRE

    Zupanc, Karel

    2013-01-01

    Z vključevanjem sončnih fotonapetostnih elektrarn v elektroenergetski sistem lahko vplivamo na smer pretoka moči in posledično napetostni profil vzdolž nizkonapetostnega omrežja. Cilj magistrskega dela je bil na podlagi meritev in analitičnega orodja prepoznati ter ovrednotiti eventualne negativne vplive na napetostni profil. Ugotovili smo, da sončne fotonapetostne elektrarne na obravnavanem področju vplivajo na napetostni profil, vendar v mejah dovoljenega. To pa ne pomeni, da negativne...

  14. Identification of a minimal transforming domain of p53: negative dominance through abrogation of sequence-specific DNA binding.

    OpenAIRE

    Shaulian, E; Zauberman, A; Ginsberg, D; Oren, M.

    1992-01-01

    Mutations in the p53 gene are most frequent in cancer. Many p53 mutants possess transforming activity in vitro. In cells transformed by such mutants, the mutant protein is oligomerized with endogenous cell p53. To determine the relevance of oligomerization for transformation, miniproteins containing C-terminal portions of p53 were generated. These miniproteins, although carrying no point mutation, transformed at least as efficiently as full-length mutant p53. Transforming activity was coupled...

  15. Observations of a Father: My Son Has Spina Bifida.

    Science.gov (United States)

    Remmel, Carl L.

    1982-01-01

    The author reviews his experiences as the father of a child with spina bifida, a congenital problem in which the spine is not completely enclosed. He recounts his feelings upon first finding out about the condition and his son's subsequent surgeries and crises. (CL)

  16. ¿Qué son los "massive open online courses"?

    OpenAIRE

    Luján Mora, Sergio

    2012-01-01

    Conferencia "¿Qué son los "massive open online courses"?" impartida en las Segundas Jornadas de la Facultad de Ingeniería y Ciencias Agropecuarias en la Universidad de las Américas (Quito, Ecuador) el 28 de mayo de 2012.

  17. African American Single Mothers Raising Sons: Implications for Family Therapy

    Science.gov (United States)

    Gantt, Ann L.; Greif, Geoffrey L.

    2009-01-01

    Being raised by a single mother is one factor that has been suggested as contributing to the plight of African American males. Yet few studies have focused specifically on African American single mothers' experiences with raising sons. This qualitative study explored the following questions: (1) What are the experiences of African American single…

  18. 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.

  19. 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,

  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. 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.

  2. 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. PMID:21302027

  3. 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....

  4. [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.

  5. Son-Yamamoto relation and Holographic RG flows

    CERN Document Server

    Dubinkin, O; Milekhin, A

    2014-01-01

    Motivated by the Son-Yamamoto (SY) relation which connects the three point and two-point correlators we consider the holographic RG flows in the bottom-up approach to holographic QCD via the Hamilton-Jacobi (HJ) equation with respect to the radial coordinate . It is shown that the SY relation is diagonal with respect to the RG flow in the 5d YM-CS model while the RG equation acquires the inhomogeneous term in the model with the additional scalar field which encodes the chiral condensate.

  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...

  7. 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

  8. 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

  9. 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.

  10. miR-143 interferes with ERK5 signaling, and abrogates prostate cancer progression in mice.

    Directory of Open Access Journals (Sweden)

    Cyrielle Clapé

    Full Text Available BACKGROUND: Micro RNAs are small, non-coding, single-stranded RNAs that negatively regulate gene expression at the post-transcriptional level. Since miR-143 was found to be down-regulated in prostate cancer cells, we wanted to analyze its expression in human prostate cancer, and test the ability of miR-43 to arrest prostate cancer cell growth in vitro and in vivo. RESULTS: Expression of miR-143 was analyzed in human prostate cancers by quantitative PCR, and by in situ hybridization. miR-143 was introduced in cancer cells in vivo by electroporation. Bioinformatics analysis and luciferase-based assays were used to determine miR-143 targets. We show in this study that miR-143 levels are inversely correlated with advanced stages of prostate cancer. Rescue of miR-143 expression in cancer cells results in the arrest of cell proliferation and the abrogation of tumor growth in mice. Furthermore, we show that the effects of miR-143 are mediated, at least in part by the inhibition of extracellular signal-regulated kinase-5 (ERK5 activity. We show here that ERK5 is a miR-143 target in prostate cancer. CONCLUSIONS: miR-143 is as a new target for prostate cancer treatment.

  11. JAK Kinase Inhibition Abrogates STAT3 Activation and Head and Neck Squamous Cell Carcinoma Tumor Growth

    Directory of Open Access Journals (Sweden)

    Malabika Sen

    2015-03-01

    Full Text Available Aberrant activation of the Janus kinase (JAK/signal transducer and activator of transcription (STAT 3 has been implicated in cell proliferation and survival of many cancers including head and neck squamous cell carcinoma (HNSCC. AZD1480, an orally active pharmacologic inhibitor of JAK1/JAK2, has been tested in several cancer models. In the present study, the in vitro and in vivo effects of AZD1480 were evaluated in HNSCC preclinical models to test the potential use of JAK kinase inhibition for HNSCC therapy. AZD1480 treatment decreased HNSCC proliferation in HNSCC cell lines with half maximal effective concentration (EC50 values ranging from 0.9 to 4 μM in conjunction with reduction of pSTAT3Tyr705 expression. In vivo antitumor efficacy of AZD1480 was demonstrated in patient-derived xenograft (PDX models derived from two independent HNSCC tumors. Oral administration of AZD1480 reduced tumor growth in conjunction with decreased pSTAT3Tyr705 expression that was observed in both PDX models. These findings suggest that the JAK1/2 inhibitors abrogate STAT3 signaling and may be effective in HNSCC treatment approaches.

  12. 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.

  13. Beclin1-induced autophagy abrogates radioresistance of lung cancer cells by suppressing osteopontin

    International Nuclear Information System (INIS)

    Osteopontin (OPN) serves as an indicator of resistance to radiotherapy. However, the role of OPN in the development of acquired radioresistance in human lung cancer cells has not yet been fully elucidated. Therefore, the potential importance of OPN as a marker of lung cancer with a potential significant role in the development of radioresistance against repeated radiotherapy has prompted us to define the pathways by which OPN regulates lung cancer cell growth. In addition, autophagy has been reported to play a key role in the radiosensitization of cancer cells. Here, we report that increased OPN expression through induction of nuclear p53 following irradiation was inhibited by exogenous beclin-1 (BECN1). Our results clearly show that BECN1 gene expression led to induction of autophagy and inhibition of cancer cell growth and angiogenesis. Our results suggest that the induction of autophagy abrogated the radioresistance of the cancer cells. Interestingly, we showed that knockdown of OPN by lentivirus-mediated shRNA induced the autophagy of human lung cancer cell. Taken together, these results suggest that OPN and BECN1 can be molecular targets for overcoming radioresistance by controlling autophagy. (author)

  14. 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.

  15. 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.

  16. 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.

  17. SysSon - A Framework for Systematic Sonification Design

    Science.gov (United States)

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

    2015-04-01

    SysSon is a research approach on introducing sonification systematically to a scientific community where it is not yet commonly used - e.g., in climate science. Thereby, both technical and socio-cultural barriers have to be met. The approach was further developed with climate scientists, who participated in contextual inquiries, usability tests and a workshop of collaborative design. Following from these extensive user tests resulted our final software framework. As frontend, a graphical user interface allows climate scientists to parametrize standard sonifications with their own data sets. Additionally, an interactive shell allows to code new sonifications for users competent in sound design. The framework is a standalone desktop application, available as open source (for details see http://sysson.kug.ac.at/) and works with data in NetCDF format.

  18. ¿Otras palabras, otra mirada, son otros?

    OpenAIRE

    Giglio, Martín

    2011-01-01

    ¿Integrar o Incluir? O mejor dicho: ¿Qué hacemos con este otro? En este relato trabajamos sobre las conceptualizaciones teóricas de términos muy usados en los terrenos de la discapacidad, como lo son: integración e inclusión y diversidad. Su uso y entendimiento histórico y las prácticas que producen. Desentrañamos la mirada del docente y la pretensión cultural de la sociedad, como determinante en la construcción de un cuerpo normal. Y proponemos un cambio en la mirada de la construcción de...

  19. Transgenerational effects of nutrition are different for sons and daughters.

    Science.gov (United States)

    Zizzari, Z V; van Straalen, N M; Ellers, J

    2016-07-01

    Food shortage is an important selective factor shaping animal life-history trajectories. Yet, despite its role, many aspects of the interaction between parental and offspring food environments remain unclear. In this study, we measured developmental plasticity in response to food availability over two generations and tested the relative contribution of paternal and maternal food availability to the performance of offspring reared under matched and mismatched food environments. We applied a cross-generational split-brood design using the springtail Orchesella cincta, which is found in the litter layer of temperate forests. The results show adverse effects of food limitation on several life-history traits and reproductive performance of both parental sexes. Food conditions of both parents contributed to the offspring phenotypic variation, providing evidence for transgenerational effects of diet. Parental diet influenced sons' age at maturity and daughters' weight at maturity. Specifically, being born to food-restricted parents allowed offspring to alleviate the adverse effects of food limitation, without reducing their performance under well-fed conditions. Thus, parents raised on a poor diet primed their offspring for a more efficient resource use. However, a mismatch between maternal and offspring food environments generated sex-specific adverse effects: female offspring born to well-fed mothers showed a decreased flexibility to deal with low-food conditions. Notably, these maternal effects of food availability were not observed in the sons. Finally, we found that the relationship between age and size at maturity differed between males and females and showed that offspring life-history strategies in O. cincta are primed differently by the parents. PMID:27018780

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

    International Nuclear Information System (INIS)

    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

  1. 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.

  2. 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.

  3. KNK437, abrogates hypoxia-induced radioresistance by dual targeting of the AKT and HIF-1{alpha} survival pathways

    Energy Technology Data Exchange (ETDEWEB)

    Oommen, Deepu, E-mail: oommen1978@gmail.com [Centre for Cancer Research and Cell Biology, Queen' s University Belfast, Belfast, Northern Ireland (United Kingdom); Prise, Kevin M. [Centre for Cancer Research and Cell Biology, Queen' s University Belfast, Belfast, Northern Ireland (United Kingdom)

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer KNK437, a benzylidene lactam compound, is a novel radiosensitizer. Black-Right-Pointing-Pointer KNK437 inhibits AKT signaling and abrogates the accumulation of HIF-1{alpha} under hypoxia. Black-Right-Pointing-Pointer KNK437 abrogates hypoxia induced resistance to radiation. -- Abstract: KNK437 is a benzylidene lactam compound known to inhibit stress-induced synthesis of heat shock proteins (HSPs). HSPs promote radioresistance and play a major role in stabilizing hypoxia inducible factor-1{alpha} (HIF-1{alpha}). HIF-1{alpha} is widely responsible for tumor resistance to radiation under hypoxic conditions. We hypothesized that KNK437 sensitizes cancer cells to radiation and overrides hypoxia-induced radioresistance via destabilizing HIF-1{alpha}. Treatment of human cancer cells MDA-MB-231 and T98G with KNK437 sensitized them to ionizing radiation (IR). Surprisingly, IR did not induce HSPs in these cell lines. As hypothesized, KNK437 abrogated the accumulation of HIF-1{alpha} in hypoxic cells. However, there was no induction of HSPs under hypoxic conditions. Moreover, the proteosome inhibitor MG132 did not restore HIF-1{alpha} levels in KNK437-treated cells. This suggested that the absence of HIF-1{alpha} in hypoxic cells was not due to the enhanced protein degradation. HIF-1{alpha} is mainly regulated at the level of post-transcription and AKT is known to modulate the translation of HIF-1{alpha} mRNA. Interestingly, pre-treatment of cells with KNK437 inhibited AKT signaling. Furthermore, down regulation of AKT by siRNA abrogated HIF-1{alpha} levels under hypoxia. Interestingly, KNK437 reduced cell survival in hypoxic conditions and inhibited hypoxia-induced resistance to radiation. Taken together, these data suggest that KNK437 is an effective radiosensitizer that targets multiple pro-survival stress response pathways.

  4. ¿Las agencias son unidades administrativas especiales?

    Directory of Open Access Journals (Sweden)

    Consuelo Sarria

    2015-06-01

    Full Text Available Al plantearse como tema del artículo el de si las agencias son unidades administrativas especiales, el trabajo debe abordar dos conceptos aparentemente diferentes en cuanto al contenido y la génesis, pues de un lado se tiene conocimiento de las unidades administrativas especiales creadas con la finalidad de realizar actividades propias de un ministerio o departamento administrativo, y que, en consecuencia, siguiendo lineamientos jurisprudenciales, debían formar parte de la estructura de aquellos o estos. No obstante el reproche doctrinal referido a que a ciertas unidades administrativas se les otorgaba personería jurídica, llama la atención el cambio de criterio jurisprudencial que las avaló, y la manera en que a partir de la Constitución de 1991 se regularon unidades con o sin personería jurídica. Al abordar el tema de las agencias del Estado resulta relevante el origen anglosajón del término y la ausencia de características que las identifiquen, y la ausencia de un régimen común. Se hace especial mención a la reforma de 2011 y a cómo se crearon varias Agencias del Estado, algunas definidas como Unidades Administrativas Especiales, ante lo que cabe interrogarse sobre la correspondencia entre ambas nociones.

  5. 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...

  6. 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

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

    Science.gov (United States)

    2012-01-01

    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 treatment and this method

  8. 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.

  9. 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. PMID:27545676

  10. 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.

  11. 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

  12. ¿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.

  13. 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

  14. Like father like son? Sons of patients of European or Indian origin with coronary artery disease reflect their parents' risk factor patterns.

    OpenAIRE

    Shaukat, N.; de Bono, D P; Jones, D R

    1995-01-01

    OBJECTIVE--To investigate the extent to which risk factor patterns associated with coronary artery disease (CAD) in patients of Indian origin and in those of North European origin undergoing coronary angiography for suspected angina were reflected in their apparently healthy sons aged 15-30 years. DESIGN--Prospective study in which risk markers were measured in patients of Indian origin and in matched European patients undergoing angiography and in their sons. SETTING--Patients attending a re...

  15. Galectin-9 Signaling through TIM-3 Is Involved in Neutrophil-Mediated Gram-Negative Bacterial Killing: An Effect Abrogated within the Cystic Fibrosis Lung

    Science.gov (United States)

    Vega-Carrascal, Isabel; Bergin, David A.; McElvaney, Oliver J.; McCarthy, Cormac; Banville, Nessa; Pohl, Kerstin; Hirashima, Mitsuomi; Kuchroo, Vijay K.; Reeves, Emer P.; McElvaney, Noel G.

    2016-01-01

    The T cell Ig and mucin domain–containing molecule (TIM) family of receptors have emerged as potential therapeutic targets to correct abnormal immune function in chronic inflammatory conditions. TIM-3 serves as a functional receptor in structural cells of the airways and via the ligand galectin-9 (Gal-9) can modulate the inflammatory response. The aim of this study was to investigate TIM-3 expression and function in neutrophils, focusing on its potential role in cystic fibrosis (CF) lung disease. Results revealed that TIM-3 mRNA and protein expression values of circulating neutrophils were equal between healthy controls (n = 20) and people with CF (n = 26). TIM-3 was detected on resting neutrophil membranes by FACS analysis, and expression levels significantly increased post IL-8 or TNF-α exposure (p < 0.05). Our data suggest a novel role for TIM-3/Gal-9 signaling involving modulation of cytosolic calcium levels. Via TIM-3 interaction, Gal-9 induced neutrophil degranulation and primed the cell for enhanced NADPH oxidase activity. Killing of Pseudomonas aeruginosa was significantly increased upon bacterial opsonization with Gal-9 (p < 0.05), an effect abrogated by blockade of TIM-3 receptors. This mechanism appeared to be Gram-negative bacteria specific and mediated via Gal-9/ LPS binding. Additionally, we have demonstrated that neutrophil TIM-3/Gal-9 signaling is perturbed in the CF airways due to proteolytic degradation of the receptor. In conclusion, results suggest a novel neutrophil defect potentially contributing to the defective bacterial clearance observed in the CF airways and suggest that manipulation of the TIM-3 signaling pathway may be of therapeutic value in CF, preferably in conjunction with antiprotease treatment. PMID:24477913

  16. Are simple tests of son preference useful? An evaluation using data from Vietnam

    OpenAIRE

    Jonathan Haughton; Dominique Haughton

    1998-01-01

    Son preference is widespread although not universal. Where it occurs it may lead to higher fertility rates. Ideally son preference should be measured in the context of a hazards or parity progression model of fertility, or a logistic model of contraceptive use. Such models require large amounts of survey data, particularly to measure the covariates. Can son preference be discerned reliably using tests which rely on more limited information? The answer is yes, based on applying eight simple te...

  17. 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?

  18. Self-coordination of parameter conflicts in D-SON architectures: A Markov Decision Process Framework

    OpenAIRE

    Moysen, Jessica; Giupponi, Lorenza

    2015-01-01

    We consider a distributed SON (D-SON) architecture where the interaction of different self-organizing network (SON) functions negatively affect the performances of the system. This is referred to in 3rd Generation Partnership Project (3GPP) as a SON conflict, which needs to be handled by means of a self-coordination framework. We focus on a functional architecture and a theoretical framework based on the theory of Markov decision process (MDP) for the self-coordination of different actions ta...

  19. 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. PMID:26304716

  20. 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.

  1. 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

  2. Factors Promoting Secure Attachment Relationships between Employed Mothers and Their Sons.

    Science.gov (United States)

    Benn, Rita K.

    1986-01-01

    Investigates factors associated with outcomes in attachment relationships between 30 well-educated, full-time working mothers and their 18-month-old firstborn sons. Suggests maternal employment effects on mother-son attachment are mediated primarily by a woman's affective state, which becomes manifested in her style of caregiving and child-care…

  3. 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.

  4. 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.

  5. 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

  6. Abrogation of Age-Induced MicroRNA-195 Rejuvenates the Senescent Mesenchymal Stem Cells by Reactivating Telomerase.

    Science.gov (United States)

    Okada, Motoi; Kim, Ha Won; Matsu-ura, Kaoru; Wang, Yi-Gang; Xu, Meifeng; Ashraf, Muhammad

    2016-01-01

    Previously, we reported that a novel subpopulation of young mesenchymal stem cells (YMSCs) existed in old bone marrow, which possessed high antiaging properties as well as excellent efficacy for cardiac repair. MicroRNAs (miRNAs) have emerged as key regulators in post-transcriptional gene expression programs, and however, it is unknown whether miRNAs directly control stem cell senescence. Here we present the first evidence that miR-195 overexpressed in old MSCs (OMSCs) induces stem cell senescence deteriorating their regenerative ability by directly deactivating telomerase reverse transcriptase (Tert), and abrogation of miR-195 can reverse stem cell aging. MiRNAs profiling analysis in YMSCs and OMSCs by microarray showed that miR-140, miR-146a/b, and miR-195 were significantly upregulated in OMSCs, which led us to hypothesize that these are age-induced miRNAs involved in stem cell senescence. Of these miRNAs, we found miR-195 directly targeted 3'-untranslated region of Tert gene by computational target prediction analysis and luciferase assay, and knockdown of miR-195 significantly increased Tert expression in OMSCs. Strikingly, miR-195 inhibition significantly induced telomere relengthening in OMSCs along with reduced expression of senescence-associated β-galactosidase. Moreover, silencing miR-195 in OMSCs by transfection of miR-195 inhibitor significantly restored antiaging factors expression including Tert and Sirt1 as well as phosphorylation of Akt and FOXO1. Notably, abrogation of miR-195 markedly restored proliferative abilities in OMSCs. Transplantation of OMSCs with knocked out miR-195 reduced infarction size and improved LV function. In conclusion, rejuvenation of aged stem cells by miR-195 inhibition would be a promising autologous therapeutic strategy for cardiac repair in the elderly patients. PMID:26390028

  7. Abrogation of prostaglandin E-EP4 signaling in osteoblasts prevents the bone destruction induced by human prostate cancer metastases.

    Science.gov (United States)

    Watanabe, Kenta; Tominari, Tsukasa; Hirata, Michiko; Matsumoto, Chiho; Maruyama, Takayuki; Murphy, Gillian; Nagase, Hideaki; Miyaura, Chisato; Inada, Masaki

    2016-09-01

    The metastasis of tumors to bone is known to be promoted by prostaglandin E2 (PGE2) produced by the tumor host stromal tissue. Although bone metastases frequently occur in prostate cancer patients, the significance of PGE2 in stromal responses to the tumor is not known. In this study, we report that PGE2 and its receptor EP4 play a pivotal role in bone destruction and metastasis in an experimental metastasis model of prostate cancer in nude mice. Using human prostate cancer PC-3 cells that are stably transfected with luciferase, we showed that the development of bone metastasis was accompanied by increased osteoclastic bone resorption in the bone metastasis microenvironment, and could be abrogated by an EP4 receptor antagonist. The growth of PC-3 cells in vitro was not influenced by PGE2 or by the EP4 receptor. However, cell-cell interactions between fixed PC-3 cells and host osteoblasts induced PGE2 production and RANKL expression in the osteoblasts. Addition of an EP4 antagonist suppressed both PGE2 and RANKL expression induced by the PC3-osteoblast interaction, which would have consequent effects on osteoclast activation and osteolysis. These results indicate that the blockage of PGE2-EP4 signaling prevents the bone destruction required for prostate cancer metastases, and that this is, in part due to the abrogation of bone cell responses. The study provides further evidence that an EP4 antagonist is a candidate for the treatment of prostate cancer in the blockade of bone metastasis. PMID:27450806

  8. MMP-9 cleaves SP-D and abrogates its innate immune functions in vitro.

    Directory of Open Access Journals (Sweden)

    Preston E Bratcher

    Full Text Available Possession of a properly functioning innate immune system in the lung is vital to prevent infections due to the ongoing exposure of the lung to pathogens. While mechanisms of pulmonary innate immunity have been well studied, our knowledge of how these systems are altered in disease states, leading to increased susceptibility to infections, is limited. One innate immune protein in the lung, the pulmonary collectin SP-D, has been shown to be important in innate immune defense, as well as clearance of allergens and apoptotic cells. MMP-9 is a protease with a wide variety of substrates, and has been found to be dysregulated in a myriad of lung diseases ranging from asthma to cystic fibrosis; in many of these conditions, there are decreased levels of SP-D. Our results indicate that MMP-9 is able to cleave SP-D in vitro and this cleavage leads to loss of its innate immune functions, including its abilities to aggregate bacteria and increase phagocytosis by mouse alveolar macrophages. However, MMP-9-cleaved SP-D was still detected in a solid-phase E. coli LPS-binding assay, while NE-cleaved SP-D was not. In addition, MMP-9 seems to cleave SP-D much more efficiently than NE at physiological levels of calcium. Previous studies have shown that in several diseases, including cystic fibrosis and asthma, patients have increased expression of MMP-9 in the lungs as well as decreased levels of intact SP-D. As patients suffering from many of the diseases in which MMP-9 is over-expressed can be more susceptible to pulmonary infections, it is possible that MMP-9 cleavage of SP-D may contribute to this phenotype.

  9. 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...... with the young-old aged 65 to 79 and surprisingly more profound in rural areas as compared with urban areas, even though son preference is much more common among rural residents. DISCUSSION: We describe how educational campaigns aimed at informing the public about the benefits of daughter(s) for older parents...

  10. 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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...

  12. 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.

  13. 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.

  14. On the domain wall partition functions of level-1 affine so(n) vertex models

    OpenAIRE

    Dow, A.; Foda, O.

    2006-01-01

    We derive determinant expressions for domain wall partition functions of level-1 affine so(n) vertex models, n >= 4, at discrete values of the crossing parameter lambda = m pi / 2(n-3), m in Z, in the critical regime.

  15. 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.

  16. 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.

  17. The Demand for Sons: Evidence from Divorce, Fertility, and Shotgun Marriage

    OpenAIRE

    Gordon B. Dahl; Moretti, Enrico

    2004-01-01

    This paper shows how parental preferences for sons versus daughters affect divorce, child custody, marriage, shotgun marriage when the sex of the child is known before birth, and fertility stopping rules. We document that parents with girls are significantly more likely to be divorced, that divorced fathers are more likely to have custody of their sons, and that women with only girls are substantially more likely to have never been married. Perhaps the most striking evidence comes from the an...

  18. Transcendence and Son Jarocho as Practiced in the San Francisco Bay Area

    OpenAIRE

    Sacolick, Robin

    2016-01-01

    AbstractTranscendence and Son Jarocho as Practiced in the San Francisco Bay AreaRobin SacolickPeople of emerging or non-dominant ethnicities in multicultural, diasporic societies need ways to establish identities, merge strengths, and transcend difficulties. This study explores one way: community practices, by Latina/os and others in the Bay Area, of son jarocho, a centuries-old genre of Mexican music, dance and poetry. While their project revives traditional folklore, it also offers experien...

  19. Child Gender and Parental Inputs: No More Son Preference in Korea?

    OpenAIRE

    Eleanor Jawon Choi; Jisoo Hwang

    2015-01-01

    Sex ratio at birth remains highly skewed in Asian countries due to son preference. In South Korea, however, it has declined to the natural ratio. In this paper, we investigate whether son preference has disappeared in Korea by analyzing parents' time and monetary inputs by the sex of their child. We exploit randomness of the first child's sex to overcome potential bias from endogenous fertility decisions. Our findings show that mothers are more likely to work after having a girl, girls spend ...

  20. La notion de zone de connexion biologique. Son application en aménagement du territoire

    Directory of Open Access Journals (Sweden)

    Philippe Ménard

    2001-12-01

    Full Text Available La notion de zone de connexion biologique a été définie comme un espace fonctionnel d'échange biologique permettant le maintien des biodiversités locales. Nous avons testé son intérêt et son application dans le cas d'un paysage complexe très fragmenté, traversé par un projet autoroutier.

  1. 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.

  2. 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.

  3. Repression of Runx2 by Androgen Receptor (AR) in Osteoblasts and Prostate Cancer Cells: AR Binds Runx2 and Abrogates Its Recruitment to DNA

    OpenAIRE

    Baniwal, Sanjeev K.; Khalid, Omar; Sir, Donna; Buchanan, Grant; Coetzee, Gerhard A.; Frenkel, Baruch

    2009-01-01

    Runx2 and androgen receptor (AR) are master transcription factors with pivotal roles in bone metabolism and prostate cancer (PCa). We dissected AR-mediated repression of Runx2 in dihydrotestosterone (DHT)-treated osteoblastic and PCa cells using reporter assays and endogenous Runx2 target genes. Repression required DHT, but not AR’s transactivation function, and was associated with nuclear colocalization of the two proteins. Runx2 and AR coimmunoprecipitated and interacted directly in glutath...

  4. 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.

  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. PMID:25595021

  6. 29 CFR 825.122 - Definitions of spouse, parent, son or daughter, next of kin of a covered servicemember, adoption...

    Science.gov (United States)

    2010-07-01

    ... of a covered servicemember, adoption, foster care, son or daughter on active duty or call to active..., adoption, foster care, son or daughter on active duty or call to active duty status, son or daughter of a... at 29 CFR 1630.2(h), (i), and (j), issued by the Equal Employment Opportunity Commission under...

  7. The Power of a Single Mother: The Influence of Black Women on Their Sons' Academic Performance

    Science.gov (United States)

    Robinson, Quintin L.; Werblow, Jacob

    2013-01-01

    This study examines the ways single Black mothers contribute to the educational success of their 11th-grade sons, despite the fact that their sons are enrolled in "failing schools." Data from five interviews and one focus group reveal common characteristics of how single-Black mothers help their sons beat the odds.

  8. Fibronectin induction abrogates the BRAF inhibitor response of BRAF V600E/PTEN-null melanoma cells.

    Science.gov (United States)

    Fedorenko, I V; Abel, E V; Koomen, J M; Fang, B; Wood, E R; Chen, Y A; Fisher, K J; Iyengar, S; Dahlman, K B; Wargo, J A; Flaherty, K T; Sosman, J A; Sondak, V K; Messina, J L; Gibney, G T; Smalley, K S M

    2016-03-10

    The mechanisms by which some melanoma cells adapt to Serine/threonine-protein kinase B-Raf (BRAF) inhibitor therapy are incompletely understood. In the present study, we used mass spectrometry-based phosphoproteomics to determine how BRAF inhibition remodeled the signaling network of melanoma cell lines that were BRAF mutant and PTEN null. Short-term BRAF inhibition was associated with marked changes in fibronectin-based adhesion signaling that were PTEN dependent. These effects were recapitulated through BRAF siRNA knockdown and following treatment with chemotherapeutic drugs. Increased fibronectin expression was also observed in mouse xenograft models as well as specimens from melanoma patients undergoing BRAF inhibitor treatment. Analysis of a melanoma tissue microarray showed loss of PTEN expression to predict for a lower overall survival, with a trend for even lower survival being seen when loss of fibronectin was included in the analysis. Mechanistically, the induction of fibronectin limited the responses of these PTEN-null melanoma cell lines to vemurafenib, with enhanced cytotoxicity observed following the knockdown of either fibronectin or its receptor α5β1 integrin. This in turn abrogated the cytotoxic response to BRAF inhibition via increased AKT signaling, which prevented the induction of cell death by maintaining the expression of the pro-survival protein Mcl-1. The protection conveyed by the induction of FN expression could be overcome through combined treatment with a BRAF and PI3K inhibitor. PMID:26073081

  9. Silencing of poly(ADP-ribose) glycohydrolase sensitizes lung cancer cells to radiation through the abrogation of DNA damage checkpoint

    Energy Technology Data Exchange (ETDEWEB)

    Nakadate, Yusuke [Shien-Lab, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Kodera, Yasuo; Kitamura, Yuka [Shien-Lab, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Tachibana, Taro [Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Tamura, Tomohide [Division of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Koizumi, Fumiaki, E-mail: fkoizumi@ncc.go.jp [Division of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan)

    2013-11-29

    Highlights: •Radiosensitization by PARG silencing was observed in multiple lung cancer cells. •PAR accumulation was enhanced by PARG silencing after DNA damage. •Radiation-induced G2/M arrest and checkpoint activation were impaired by PARG siRNA. -- Abstract: Poly(ADP-ribose) glycohydrolase (PARG) is a major enzyme that plays a role in the degradation of poly(ADP-ribose) (PAR). PARG deficiency reportedly sensitizes cells to the effects of radiation. In lung cancer, however, it has not been fully elucidated. Here, we investigated whether PARG siRNA contributes to an increased radiosensitivity using 8 lung cancer cell lines. Among them, the silencing of PARG induced a radiosensitizing effect in 5 cell lines. Radiation-induced G2/M arrest was largely suppressed by PARG siRNA in PC-14 and A427 cells, which exhibited significantly enhanced radiosensitivity in response to PARG knockdown. On the other hand, a similar effect was not observed in H520 cells, which did not exhibit a radiosensitizing effect. Consistent with a cell cycle analysis, radiation-induced checkpoint signals were not well activated in the PC-14 and A427 cells when treated with PARG siRNA. These results suggest that the increased sensitivity to radiation induced by PARG knockdown occurs through the abrogation of radiation-induced G2/M arrest and checkpoint activation in lung cancer cells. Our findings indicate that PARG could be a potential target for lung cancer treatments when used in combination with radiotherapy.

  10. ERK5 signalling rescues intestinal epithelial turnover and tumour cell proliferation upon ERK1/2 abrogation

    Science.gov (United States)

    de Jong, Petrus R.; Taniguchi, Koji; Harris, Alexandra R.; Bertin, Samuel; Takahashi, Naoki; Duong, Jen; Campos, Alejandro D.; Powis, Garth; Corr, Maripat; Karin, Michael; Raz, Eyal

    2016-01-01

    The ERK1/2 MAPK signalling module integrates extracellular cues that induce proliferation and differentiation of epithelial lineages, and is an established oncogenic driver, particularly in the intestine. However, the interrelation of the ERK1/2 module relative to other signalling pathways in intestinal epithelial cells and colorectal cancer (CRC) is unclear. Here we show that loss of Erk1/2 in intestinal epithelial cells results in defects in nutrient absorption, epithelial cell migration and secretory cell differentiation. However, intestinal epithelial cell proliferation is not impeded, implying compensatory mechanisms. Genetic deletion of Erk1/2 or pharmacological targeting of MEK1/2 results in supraphysiological activity of the ERK5 pathway. Furthermore, targeting both pathways causes a more effective suppression of cell proliferation in murine intestinal organoids and human CRC lines. These results suggest that ERK5 provides a common bypass route in intestinal epithelial cells, which rescues cell proliferation upon abrogation of ERK1/2 signalling, with therapeutic implications in CRC. PMID:27187615

  11. 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

  12. 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.

  13. The deconfining phase transition of SO(N) gauge theories in 2+1 dimensions

    Science.gov (United States)

    Lau, Richard; Teper, Michael

    2016-03-01

    We calculate the deconfining temperature of SO(N ) gauge theories in 2+1 dimensions, and determine the order of the phase transition as a function of N , for various values of N ∈ [4 , 16]. We do so by extrapolating our lattice results to the infinite volume limit, and then to the continuum limit, for each value of N. We then extrapolate to the N =∞ limit and observe that the SO(N) and SU(N) deconfining temperatures agree in that limit. We find that the the deconfining temperatures of all the SO(N ) gauge theories appear to follow a single smooth function of N , despite the lack of a non-trivial centre for odd N . We also compare the deconfining temperatures of SO(6) with SU(4), and of SO(4) with SU(2) × SU(2), motivated by the fact that these pairs of gauge theories share the same Lie algebras.

  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. 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.

  16. Chapitre II. La reproduction du son dans la légende

    OpenAIRE

    Pisano, Giusy

    2013-01-01

    La captation du son possède ses propres mythes et légendes, car, avant d’aboutir à une réalisation technique, une longue période de tentatives fantaisistes et maladroites s’est écoulée. Saisir le son de la voix humaine, pouvoir le conserver et le réécouter, est l’un de ces rêves qui rapprochent l’homme du domaine du sacré et le projettent dans un espace proche des forces mystérieuses de la nature. En fait, séparer la voix de son appareil physiologique et la réduire à une simple sonorité serai...

  17. 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

    occupations. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Cox regression adjusting for parental age, birth years, parity, and geographical region. RESULTS: Sons of maternal farmers were at increased risk of cryptorchidism (157 cases; HR 1.31, 95% CI 1.12-1.53) compared to boys...... 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......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...

  18. The relation of son preference and religion to induced abortion: the case of South Korea.

    Science.gov (United States)

    Chung, Woojin

    2007-09-01

    This paper explores the factors that influence the practice of induced abortion in a very low fertility society, with particular emphasis on son preference and three distinct religions: Confucianism, Buddhism and Christianity. Using multivariate logistic regression models fitted by the generalized estimating equation (GEE) method, this paper analysed the data collected by the 2000 Korea National Fertility and Family Health Survey of 6348 married women aged 15-49 years with a total of 1217 pregnancy outcomes. The results showed that the likelihood of induced abortions in women with two or more children, compared with those with one child, was significantly influenced by the sex composition of the previous children: odds ratio (OR)=12.71 (95% CI=5.49, 29.42) for women with only son(s), and OR=3.91 (95% CI=1.67, 9.14) for women with only daughter(s). At parity two, women with two sons were much more likely to have induced abortions than women with two daughters (OR=5.88, 95% CI=2.70, 12.85). Although Buddhist women were not significantly different from Confucian women in induced abortion practice, Christian women were much less likely than Confucian women to have an induced abortion (OR=0.39, 95% CI=0.18, 0.88 for women with only sons and OR=0.44, 95% CI=0.24, 0.81 for women with two children). This suggests that even in this very low fertility society, son preference and religious affiliation are significant predictors of women's practice of induced abortion. PMID:17381891

  19. Particle Swarm Optimization for Mobility Load Balancing SON in LTE Networks

    OpenAIRE

    Altman, Zwi; SALLEM, Soumaya; Nasri, Ridha; Sayrac, Berna; Clerc, Maurice

    2013-01-01

    This paper presents a self-optimizing solution for Mobility Load Balancing (MLB). The MLB-SON is performed in two phases. In the first, a MLB controller is designed using Multi-Objective Particle Swarm Optimization (MO-PSO) which incorporates a priori expert knowledge to considerably reduce the search space and optimization time. The dynamicity of the optimization phase is addressed. In the second phase, the controller is pushed into the base stations to implement the MLB SON. The method is a...

  20. Particle Swarm Optimization for Mobility Load Balancing SON in LTE Networks

    OpenAIRE

    Altman, Zwi; SALLEM, Soumaya; Nasri, Ridha; Sayrac, Berna; Clerc, Maurice

    2014-01-01

    This paper presents a self-optimizing solution for Mobility Load Balancing (MLB). The MLB-SON is performed in two phases. In the first, a MLB controller is designed using Multi-Objective Particle Swarm Optimization (MO-PSO) which incorporates a priori expert knowledge to considerably reduce the search space and optimization time. The dynamicity of the optimization phase is addressed. In the second phase, the controller is pushed into the base stations to implement the MLB SON. The method is a...

  1. The Legend, The Madman, and the Prophet a Memoir about Fathers and Sons

    OpenAIRE

    Thalman, Erik K.

    2015-01-01

    The Legend, the Madman, and the Prophet is a memoir about fathers and sons, about the experience of being a son of a man of the Rocky Mountains, a legend grown old. The narrative centers around my struggle with the fact that my father had grown old and sick while I was still young, and my consequent search for other fathers, employing two primary examples—a martial-arts instructor from my high-school years who was later exposed as a pedophile, and the eccentric figure of my ex-girlfriend’s we...

  2. La communication publique dans le monde arabe. Essai d’analyse de son émergence et de son développement

    OpenAIRE

    Hammami, Sadock

    2011-01-01

    Ce texte examine l’émergence et le développement de la communication publique dans le monde arabe. L’essor de la communication publique est lié à une série de dynamiques : construction et crise de l’Etat postcolonial, transformations des organisations publiques et mutations de la sphère des médias. Situé dans son contexte sociétal, l’essor de la communication publique nous renseigne sur les changements des modes de gestion politique et sur le statut des organisations publiques dans des sociét...

  3. 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.

  4. 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

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

    International Nuclear Information System (INIS)

    Highlights: ► p38 and Akt are the crucial molecular targets in the pathogenesis of SCCs in OTRs. ► Combined inhibition of these targets diminished tumor growth by 90%. ► 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-β 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.

  6. 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

  7. 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

    2016-05-01

    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

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

    OpenAIRE

    Doerner, Astrid M; Zuraw, Bruce L

    2009-01-01

    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 o...

  9. 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.

  10. Fathers Are Important People: A Study of Father-Son Sexual Communication

    Science.gov (United States)

    DiIorio, Colleen; Lehr, Sally; Wasserman, Jill L.; Eichler, Michelle; Cherry, Chauncey; Denzmore, Pamela

    2006-01-01

    The purpose of this study was to examine the perceived role of African-American fathers in educating their sons about sex and HIV prevention. Given that some studies have shown a relationship between parent-adolescent sexual communication and adolescent sexual behavior, and the disproportionately high rates of teen pregnancy and HIV (and other…

  11. 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 whether...... pregnant women exposed to pesticides due to their work in horticulture experience excess risk of having sons with cryptorchidism....

  12. 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 

  13. 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.

  14. Marriage Form and Son Preference in Rural China: An Investigation in Three Counties

    Science.gov (United States)

    Jin, Xiaoyi; Li, Shuzhuo; Feldman, Marcus W.

    2007-01-01

    Using data from two surveys in three counties among which the prevalence of uxorilocal marriage varies greatly, this paper analyzes effects of marriage form, as well as individual, family, and social factors on son preference in the context of strict birth control in rural China. It is shown that, under the Chinese patrilineal joint family system,…

  15. 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. PMID:26990898

  16. Evaluation of performance of Son Tek Argonaut acoustic doppler velocity log in tow tank and sea

    Digital Repository Service at National Institute of Oceanography (India)

    Joseph, A.; Madhan, R.; Mascarenhas, A.A.M.Q.; Desai; VijayKumar, K.; Dias, M.; Tengali, S.; Methar, A.

    of Performance of SonTek Argonaut Acoustic Doppler Velocity Log in Tow Tank and Sea Antony Joseph, R. Madhan, Antonio Mascaranhas, R.G. Prabhu Desai, Vijaykumar, Mathew Dias, Suryakant Tengali, and Anand Methar National Institute of Oceanography, Dona Paula...

  17. 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 $\

  18. 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.

  19. Does Father Know Best? Mothers and Fathers Teaching Their Preschool Sons and Daughters.

    Science.gov (United States)

    Frankel, Marc T.; And Others

    The interactional teaching patterns of 36 fathers and mothers with their 6-year-old sons and daughters were studied. Parents were asked to play (in parent-child dyads) with their child on a jigsaw puzzle and to teach the child to remember 25 picture cards that could be divided into conceptual categories. It was found that parents' instructional…

  20. 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.

  1. The Putative Son's Attractiveness Alters the Perceived Attractiveness of the Putative Father.

    Science.gov (United States)

    Prokop, Pavol

    2015-08-01

    A body of literature has investigated female mate choice in the pre-mating context (pre-mating sexual selection). Humans, however, are long-living mammals forming pair-bonds which sequentially produce offspring. Post-mating evaluations of a partner's attractiveness may thus significantly influence the reproductive success of men and women. I tested herein the theory that the attractiveness of putative sons provides extra information about the genetic quality of fathers, thereby influencing fathers' attractiveness across three studies. As predicted, facially attractive boys were more frequently attributed to attractive putative fathers and vice versa (Study 1). Furthermore, priming with an attractive putative son increased the attractiveness of the putative father with the reverse being true for unattractive putative sons. When putative fathers were presented as stepfathers, the effect of the boy's attractiveness on the stepfather's attractiveness was lower and less consistent (Study 2). This suggests that the presence of an attractive boy has the strongest effect on the perceived attractiveness of putative fathers rather than on non-fathers. The generalized effect of priming with beautiful non-human objects also exists, but its effect is much weaker compared with the effects of putative biological sons (Study 3). Overall, this study highlighted the importance of post-mating sexual selection in humans and suggests that the heritable attractive traits of men are also evaluated by females after mating and/or may be used by females in mate poaching. PMID:25731909

  2. 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.

  3. Los que son y no son: percorsi di identità (sonate nella Cuba della seconda metà del XIX secolo e inizi del XX

    Directory of Open Access Journals (Sweden)

    Irene Campagna

    2011-12-01

    Full Text Available The son is configured into the orbit of Cuban popular music as the mulatto music genre par excellence,  thanks to the amalgam of musical elements and structural features of Spanish and African origins.In its heyday - when are defined new modes of interpretation and new sonic possibilities - shares political and cultural unrest of vanguards that, through the recognition of the African component, try to build a coherent concept of nation, highlighting the contribution of black people to cultural and political processes. This work is based on the hypotheses suggested in some cuban studies recently published, about the causal relationship between the son’s development and the shape of national identity in the period of the Wars of Independence, to come to find through the  thematic analysis of representative texts the genre's functioning within this perspective.

  4. Možnost uporabe tekstilij za izkoriščanje sončne energije

    OpenAIRE

    Dretar, Nina

    2014-01-01

    Diplomsko delo obravnava možnost uporabe ploskih tekstilij v namene izkoriščanja sončne energije. V teoretičnem delu naloge so najprej predstavljene osnove sončnega sevanja, fotovoltaika, tj. veda, ki preučuje pretvorbo energije svetlobe v elektriko, ter zgradba in delovanje sončne celice. Osrednji del diplomskega dela se nanaša na stanje raziskav na področju uporabe tekstilij kot fotonapetostnih sistemov za izkoriščanje sončne energije. V nadaljevanju so predstavljeni načini izdelave tekstil...

  5. 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.

  6. The deconfining phase transition of SO(N) gauge theories in 2+1 dimensions

    CERN Document Server

    Lau, Richard

    2015-01-01

    We calculate the deconfining temperature of SO(N) gauge theories in 2+1 dimensions, and determine the order of the phase transition as a function of N, for various values of N in the range [4,16]. We do so by extrapolating our lattice results to the infinite volume limit, and then to the continuum limit, for each value of N. We then extrapolate to the N=infinity limit and compare the SO(N) and SU(N) deconfining temperatures in that limit. We also compare the deconfining temperatures of SO(6) with SU(4), and of SO(4) with SU(2)xSU(2), motivated by the fact that these pairs of gauge theories share the same Lie algebras.

  7. L’eau à Damas et dans son environnement rural au xviiie siècle

    OpenAIRE

    Marino, Brigitte; Meier, Astrid

    2013-01-01

    Le système hydraulique qui alimente la ville de Damas et son environnement rural est très ancien. Mais il est en constante évolution et l’on peut difficilement accréditer l’idée de son caractère immuable. À partir de diverses sources juridiques, cet article s’interroge sur les règles, les pratiques et les procédures administratives et juridiques qui sont en vigueur dans le domaine de la distribution de l’eau à Damas et dans sa campagne au xviiie siècle. Il montre le rôle des autorités juridiq...

  8. Patterns of Parental Spending: Do Parents Spend More Money on Sons or Daughters?

    OpenAIRE

    Batten, George P

    2013-01-01

    This study examines the spending patterns of parents, indentifying differences in the amount of money that parents spend on select items for sons compared to daughters. Using secondary data from the "Consumer Expenditure Survey: Diary Survey" dataset from 2008 through 2010, this study tests the hypothesis that parents with adolescent girls spend more money on apparel, beauty and hygiene products, health care, and education compared to parents with adolescent boys. An interaction effect for ge...

  9. Living with foster siblings: the adjustment of adolescent sons and daughters in families who foster.

    OpenAIRE

    Richardson, J.

    2007-01-01

    This paper aims to review how fostering affects the adjustment of adolescent sons and daughters in families who foster. The research is presented within a developmental psychopathology framework, addressing individual, parent-child and sibling factors that affect adolescents' adjustment. These factors are initially discussed in the context of 'normative' families and stepfamilies, as a prelude for understanding the adjustment of adolescents in reconstituted foster families. Secondly, fifteen ...

  10. 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.

  11. 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.

  12. Integrating Equality - Globalization, Women’s Rights, Son Preference and Human Trafficking

    OpenAIRE

    Cho, Seo-Young

    2011-01-01

    Employing economic and social globalization indicators, we empirically analyze whether globalization affects women’s rights in the economic and social dimensions. Using panel data from 150 countries over the 1981-2008 period, we find that social globalization positively affects both women’s economic and social rights, while the impact of economic globalization disappears when controlling for social globalization. Furthermore, we find that social globalization also reduces ‘son preference’ pro...

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

    OpenAIRE

    Angelina Subrayan; Wan Roselezam Wan Yahya

    2016-01-01

    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...

  14. Girl adoption in China-A less-known side of son preference.

    Science.gov (United States)

    Chen, Yuyu; Ebenstein, Avraham; Edlund, Lena; Li, Hongbin

    2015-01-01

    In 1987, 4 per cent of girls were adopted within China. Why? Unlike infanticide, abandonment rids parents of daughters while preserving the supply of potential brides. In fact, an erstwhile tradition common in Fujian and Jiangxi provinces had parents of sons adopting an infant girl to serve as a future daughter-in-law and household help. Analysing a nationally representative 1992 survey of children, we found that: (1) girl adoptions were concentrated in the above-mentioned provinces; (2) girls were predominantly adopted by families with sons; (3) adopted girls faced substantial disadvantage as measured by school attendance at ages 8-13. In the 1990s, as the sex ratio at birth climbed, were girls aborted rather than abandoned? Observing that in the 2000 census too many girls appear in families with older sons, we estimated that at least 1/25 girls were abandoned in the 1990s, a proportion that in Fujian and Jiangxi may have peaked at 1/10 in 1994. PMID:25789605

  15. Mutation rate at 17 Y-STR loci in "Father/Son" pairs from moroccan population.

    Science.gov (United States)

    Laouina, Adil; Nadifi, Sellama; Boulouiz, Redouane; El Arji, Marzouk; Talbi, Jalal; El Houate, Brahim; Yahia, Hakima; Chbel, Faiza

    2013-09-01

    Precise knowledge of mutation rate at Y-STRs loci is essential for a correct evaluation of typing results in forensic casework and specially kinship genetic studies. In this study, we have examined 252 confirmed and unrelated father/son sample pairs from Moroccan population using the 17 Y-STR markers DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385a, DYS385b, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, and Y-GATA-H4 of the AmpFlSTR Yfiler™ kit used in routine casework. We observed a total of 15 single repeat mutations between fathers and sons as mutational events. Nine mutations resulted in the gain of a repeat in the son and six resulted in a loss of a repeat. The average mutation rate in the studied sample is 3.5×10(-3) (95% CI 2-5.8×10(-3)). Furthermore, Y-STRs mutation occurrence seems to be 4 times more frequent than autosomal STRs mutation in this sample. PMID:23623014

  16. 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.

  17. 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.

  18. Serum and plasma fibronectin binds to complement reacted immune complexes primarily via Clq

    DEFF Research Database (Denmark)

    Baatrup, G; Svehag, S E

    1986-01-01

    The binding of fibronectin to human Clq, C3b, and complement-reacted immune complexes (IC) was investigated by enzyme-linked immunosorbent assays. Microplates were coated with BSA followed by incubation with rabbit-anti-BSA IgG or F(ab')2 fragments of rabbit anti-BSA. Incubation of the solid phase...... with serum at 37 degrees C caused attachment of Clq and C3b. Addition of EDTA to the serum inhibited the binding of C3b, but not Clq, whereas substitution of the anti-BSA IgG on the solid phase with the F(ab')2 fragments abrogated the Clq, but not the C3b binding. Fibronectin binding was observed after...

  19. 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.

  20. A Pyrococcus homolog of the leucine-responsive regulatory protein, LrpA, inhibits transcription by abrogating RNA polymerase recruitment

    OpenAIRE

    Dahlke, Isabell; Thomm, Michael

    2002-01-01

    The genomes of Archaea harbor homologs of the global bacterial regulator leucine-responsive regulatory protein (Lrp). Archaeal Lrp homologs are helix–turn–helix DNA-binding proteins that specifically repress the transcription of their own genes in vitro. Here, we analyze the interaction of Pyrococcus LrpA with components of the archaeal transcriptional machinery at the lrpA promoter. DNA–protein complexes can be isolated by electrophoretic mobility shift assays that contain both LrpA and the ...

  1. 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.

  2. Calmodulin binds to and inhibits the activity of phosphoglycerate kinase.

    Science.gov (United States)

    Myre, Michael A; O'Day, Danton H

    2004-09-17

    Phosphoglycerate kinase (PGK) functions as a cytoplasmic ATP-generating glycolytic enzyme, a nuclear mediator in DNA replication and repair, a stimulator of Sendai virus transcription and an extracellular disulfide reductase in angiogenesis. Probing of a developmental expression library from Dictyostelium discoideum with radiolabelled calmodulin led to the isolation of a cDNA encoding a putative calmodulin-binding protein (DdPGK) with 68% sequence similarity to human PGK. Dictyostelium, rabbit and yeast PGKs bound to calmodulin-agarose in a calcium-dependent manner while DdPGK constructs lacking the calmodulin-binding domain (209KPFLAILGGAKVSDKIKLIE228) failed to bind. The calmodulin-binding domain shows 80% identity between diverse organisms and is situated beside the hinge and within the ATP binding domain adjacent to nine mutations associated with PGK deficiency. Calmodulin addition inhibits yeast PGK activity in vitro while the calmodulin antagonist W-7 abrogates this inhibition. Together, these data suggest that PGK activity may be negatively regulated by calcium and calmodulin signalling in eukaryotic cells. PMID:15363631

  3. The Impact of Birth Order on Intergenerational Transmission of Attitudes from Parents to Adolescent Sons: The Israeli Case

    Science.gov (United States)

    Kulik, Liat

    2004-01-01

    This study deals with birth order and its impact on intergenerational transmission of parental attitudes to adolescent sons in Israeli society. The sample included 294 participants (including 98 mothers, 98 fathers, and 98 sons). The attitudes chosen were key issues of concern in Israeli society: gender role attitudes, ethnic stereotypes, and…

  4. 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

    OpenAIRE

    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

    2010-01-01

    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 sat...

  5. 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.

  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. 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.

  8. Healing of the royal official’s son in John 4:46-54

    Directory of Open Access Journals (Sweden)

    Jan Van der Watt

    2012-01-01

    Full Text Available The healing of the royal official’s son (4:46-54 is one of the neglected sections in John’s Gospel. Although it is considered in commentaries and it is often used in sermons it is rarely the subject of wider discussion. This article considers the narratological, social and historical aspects of this brief miracle narrative. The complex structure of the narrative is considered, its relation to parallels in the Synoptics and possible shared sources are investigated, and possibilities for understanding the narrative are discussed.

  9. 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.

  10. L'entrepreneuriat immigré et son accompagnement en France,

    OpenAIRE

    Levy-Tadjine, Thierry

    2004-01-01

    Partant du constat que la littérature anglo-saxonne sur l'entrepreneuriat ethnique et immigré est insatisfaisante pour rendre compte du phénomène entrepreneurial immigré dans le contexte français et de son accompagnement, nous proposons un modèle dialectique et téléologique de l'Entrepreneuriat Immigré fondé sur la Psycho-Sociologie de l'Interculturel et sur la Théorie des conventions. Ce modèle rend compte de la diversité des trajectoires entrepreneuriales des publics issus de l'immigration....

  11. 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...

  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. Lowest-energy states in parity-transformation eigenspaces of SO(N) spin chain

    OpenAIRE

    Tigran Hakobyan

    2015-01-01

    We expand the symmetry of the open finite-size SO(N) symmetric spin chain to O(N). We partition its space of states into the eigenspaces of the parity transformations in the flavor space, generating the subgroup $Z_2^{\\times(N-1)}$. It is proven that the lowest-energy states in these eigenspaces are nondegenerate and assemble in antisymmetric tensors or pseudotensors. At the valence-bond solid point, they constitute the $2^{N-1}$-fold degenerate ground state with fully broken parity-transform...

  14. Were king Stefan the First-Crowned and his son Radoslav co-rulers?

    OpenAIRE

    Bubalo Đorđe

    2009-01-01

    The Serbian historiography considers the issue of the co-ruling of King Stefan the First-Crowned and his son Radoslav as the one finally resolved. The suggested solution on the co-rule of Stefan and Radoslav may be most succinctly expressed as following: as early as in the year of 1220, due to the frail health of Stefan the First-Crowned and Radoslav's marriage to Anne the Epirus princess, Radoslav was crowned to be the king and positioned to co-rule with his father after the Byzantine model ...

  15. Deformations of fundamental group representations and earthquakes on $SO(n,1)$ surface groups

    OpenAIRE

    Ho, Son Lam

    2016-01-01

    In this article we construct a type of deformations of representations $\\pi_1(M)\\rightarrow G$ where $G$ is an arbitrary lie group and $M$ is a large class of manifolds including CAT(0) manifolds. The deformations are defined based on codimension 1 hypersurfaces with certain conditions, and also on disjoint union of such hypersurfaces, i.e. multi-hypersurfaces. We show commutativity of deforming along disjoint hypersurfaces. As application, we consider Anosov surface groups in $SO(n,1)$ and s...

  16. The $1/N$ expansion for $SO(N)$ lattice gauge theory at strong coupling

    CERN Document Server

    Chatterjee, Sourav

    2016-01-01

    The $1/N$ expansion is an asymptotic series expansion for certain quantities in large-$N$ lattice gauge theories. This article gives a rigorous formulation and proof of the $1/N$ expansion for Wilson loop expectations in $SO(N)$ lattice gauge theory in the strong coupling regime in any dimension. The terms in the expansion are expressed as sums over trajectories of strings in a lattice string theory, establishing an explicit gauge-string duality. The trajectories trace out surfaces of genus zero for the first term in the expansion, and surfaces of higher genus for the higher terms.

  17. 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.

  18. 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

  19. Étude de son 3D pour une interaction audio-visuelle en environnement virtuel enrichi

    OpenAIRE

    Ortega González, Erik Vladimir

    2011-01-01

    La plupart des applications qui intègrent le son 3D en environnement virtuel sont limitées à la simulation acoustique. L'objectif de cette thèse est d'étudier l'apport du son 3D dans l'interaction en environnement virtuel. Nous avons développé une technique de stimulation sonore appelée: Sensation Artificielle Spatialisée Auditive (SASA), basée sur la création d'effets sonores. Cette technique restitue des sensations de spatialisation de son permettant la localisation précise (en azimut et en...

  20. 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.

  1. Léon Bardalès: Sa vie et son œuvre

    Directory of Open Access Journals (Sweden)

    Ilias Taxidis

    2011-07-01

    Full Text Available Cette étude comprend la présentation et l’édition critique de deux lettres et six poèmes de Léon Bardalès qui fut l’un des dignitaires impériaux byzantins de la fin du XIIIe et du début du XIVe siècle. Pour l’occasion, toutes les données concernant l’auteur et son activité politique et littéraire sont réévaluées conformément aux informations fournies par les lettres que Bardalès a reçues d’épistoliers connus de son époque, comme Maxime Planude, Nicéphore Choumnos et Nicéphore Grégoras. Dans l’édition, les erreurs et fautes d’inattention des éditeurs précédents sont corrigées, et un apparat des sources est ajouté.

  2. 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.

  3. Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK–PKC–CBP signaling cascade

    Directory of Open Access Journals (Sweden)

    Arya A

    2016-03-01

    Full Text Available Aditya Arya,1 Anamika Gangwar,1 Sushil Kumar Singh,2 Manas Roy,3,4 Mainak Das,3 Niroj Kumar Sethy,1 Kalpana Bhargava1 1Peptide and Proteomics Division, Defense Institute of Physiology and Allied Sciences, 2Functional Materials Division, Solid State Physics Laboratory, Defense Research and Development Organization, Timarpur, Delhi, 3Biological Science and Bioengineering, Indian Institute of Technology, Kanpur, 4Department of Chemistry, Indian Institute of Engineering Science and Technology, Howrah, India Abstract: Structural and functional integrity of the brain is adversely affected by reduced oxygen saturation, especially during chronic hypoxia exposure and often encountered by altitude travelers or dwellers. Hypoxia-induced generation of reactive nitrogen and oxygen species reportedly affects the cortex and hippocampus regions of the brain, promoting memory impairment and cognitive dysfunction. Cerium oxide nanoparticles (CNPs, also known as nanoceria, switch between +3 and +4 oxidation states and reportedly scavenge superoxide anions, hydrogen peroxide, and peroxynitrite in vivo. In the present study, we evaluated the neuroprotective as well as the cognition-enhancing activities of nanoceria during hypobaric hypoxia. Using polyethylene glycol-coated 3 nm nanoceria (PEG-CNPs, we have demonstrated efficient localization of PEG-CNPs in rodent brain. This resulted in significant reduction of oxidative stress and associated damage during hypoxia exposure. Morris water maze-based memory function tests revealed that PEG-CNPs ameliorated hypoxia-induced memory impairment. Using microscopic, flow cytometric, and histological studies, we also provide evidences that PEG-CNPs augmented hippocampus neuronal survival and promoted neurogenesis. Molecular studies revealed that PEG-CNPs promoted neurogenesis through the 5'-adenine monophosphate-activated protein kinase–protein kinase C–cyclic adenosine monophosphate response element-binding protein

  4. On the N-dependence of SO(N) and SU(N) gauge theories in 2+1 dimensions

    CERN Document Server

    Athenodorou, Andreas; Teper, Michael

    2015-01-01

    We compare (continuum) mass ratios of the lightest `glueballs' as a function of N for SO(N) and SU(N) lattice gauge theories in D=2+1. We observe that the leading large N correction is usually sufficient to describe the N-dependence both of SO(N) for N greater than or equal to 3, and of SU(N) for N greater than or equal to 2. Moreover the coefficient of this correction is found to be remarkably small in both cases. We point out that this can follow naturally from the strong constraints that one naively expects from the Lie algebra equivalence between certain SO(N) and SU(N') theories. The same argument for a weak N-dependence can apply to SU(N) and SO(N) gauge theories in D=3+1.

  5. The Psychoanalytic Study of the Personality Development of Paul Morel in D.H.Lawrence‘s Novel Sons and Lovers

    OpenAIRE

    Zaira Wahab; Shumaila Mazhar; Fozia Sultana

    2012-01-01

    We investigate D. H. Lawrence’s delineation of Paul’s personality development and its harmony with Freudian concept in the novel Sons and Lovers. The study has approached the novel from psychological perspective particularly emphasizing Freudian Theory of Psychosexual Development. The qualitative research paradigm is adopted focusing on textual data analysis of the novel Sons and Lovers. The findings of the study revealed how Paul’s early childhood trauma caused by his father’s brutal treatme...

  6. 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.

  7. Deconfining temperatures in SO(N) and SU(N) gauge theories

    CERN Document Server

    Lau, Richard

    2015-01-01

    We present our current results for the deconfining temperatures in SO(N) gauge theories in 2+1 dimensions. SO(2N) theories may help us to understand QCD at finite chemical potential since there is a large-N orbifold equivalence between SO(2N) QCD-like theories and SU(N) QCD, and SO(2N) theories do not have the sign problem present in QCD. We show that the deconfining temperatures in these two theories match at the large-N limit. We also present results for SO(2N+1) gauge theories and compare results for SO(6) with SU(4) gauge theories, which have the same Lie algebras but different centres.

  8. 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.

  9. La linguistique marriste et son onomastique. Le cas de la Géorgie

    OpenAIRE

    Van Elverdinghe, Emmanuel

    2014-01-01

    Les théories linguistiques de Nikolaj Marr ont profondément imprégné la vie intellectuelle soviétique jusque dans les années 1950. Ce succès s’explique à la fois par une série de facteurs conjoncturels et par la personnalité même du savant géorgien. En plus d’une chronologie périodisée de l’évolution du « marrisme », il est possible de distinguer des fils de trame invariants, qui depuis ses débuts sous-tendent son développement. L’étude des ethnonymes et des toponymes constituait pour Marr un...

  10. The death of a young son in violent circumstance: understanding the experience of the mother.

    Science.gov (United States)

    Alarcão, Ana Carolina Jacinto; Carvalho, Maria Dalva de Barros; Pelloso, Sandra Marisa

    2008-01-01

    This study was aimed at understanding the life of a mother who lost their child in violent circumstances. The methodological proceedings were supported on phenomenology. The study population was constituted by five mothers who had lost its young children for homicide. These homicides occurred different times ranging from 50 days to 10 years. I used as instrument of collection of data open interview the phenomenological method guided by a orienting question. The analysis phenomenology in their discourses showed the comprehension of essential meanings which were systematized in categories: the child's mummification in the memory; the two ways followed by the publicity concerning the death; fondness to spirituality to endure the pain from the child's death; maternal complicity and impunity. The results of this study can contribute to elaboration of intervention proposals close to the mothers in the sense of helping them in the reorganization of their lives after son's death. PMID:18695804

  11. 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.

  12. 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.

  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

    .2-3.0) examined by the same procedure. Boys of pesticide-exposed mothers showed decreased penile length, testicular volume, serum concentrations of testosterone, and inhibin B. Serum concentrations of sex hormone-binding globulin, follicle-stimulating hormone, and the luteinizing hormone:testosterone ratio were...

  14. Bill project aiming at abrogating exclusive search permits for unconventional hydrocarbon searches, and at prohibiting their exploration and exploitation of the national territory; Proposition de Loi visant a abroger les permis exclusifs de recherches d'hydrocarbures non conventionnels et a interdire leur exploration et leur exploitation sur le territoire national

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-01

    After having briefly recalled the origin of shale gases, their extraction process and the evolution of their production in the USA, the authors outline the extremely negative environmental impacts of the fracking technique (hydraulic fracturing): water pollution, air pollution, soil pollution, existence of numerous drilling sites which would degrade landscapes, water and soil contamination risks. As some search permits have already been awarded, and while taking these negative consequences into account, the authors propose a bill project to prohibit these explorations, to abrogate the existing permits, and to ensure public information before bestowing such search permits and exploitation concessions

  15. Total iron binding capacity

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003489.htm Total iron binding capacity To use the sharing features on this page, please enable JavaScript. Total iron binding capacity (TIBC) is a blood test to ...

  16. La structure de la population après son lieu de naissance

    Directory of Open Access Journals (Sweden)

    Maria-Magdalena LUPCHIAN

    2008-10-01

    Full Text Available La capacité de polarisation de la ville de Suceava a agrandi d`une manière significative pendant la deuxième moitie de la XXème siècle, grâce au développement de la fonction industrielle de la ville entre 1960 et 1970. L`analyse de la structure de la population après le lieu de naissance a été possible grâceaux données fournies par les recensements de la population de 1930, 1966, 1977, 1992 et 2002(pour toute la ville et grâce aux données fournies par l`enquête réalisée en 2005 sur enéchantillon qui a dépassé 3000 personnes (pour l`analyse au niveau intra urbaine.Dans une première étape, l`aire de provenance de la population de la ville dépassaitles limites du département de Suceava. La ville a consolide son pouvoir d`attraction au niveaudu département et au niveau du Plateau de Suceava après les années `70. Pendant ce période(1950 – 1990, des déplacements très stables se sont développé entre les départements deBotoşani et de Neamţ et le département de Suceava.L`analyse de l`aire de provenance de la population née dans le département deSuceava relève le fait que la ville a représenté et représente encore un pole d`attraction pour lamoitie de plateau du département de Suceava. La ville chef lieu de département est enconcurrence avec les villes plus petites mais viables (Rădăuţi, Fălticeni, situées en proximité.L`analyse de la structure de la population après son lieu de naissance au niveau intraurbaine démontre l`opposition qui existe entre les vieux quartiers d`habitat individuel (ou lapopulation née en ville est majoritaire et les nouveaux quartiers, d`habitat collectif, édifiésdans les années d`industrialisation de la ville – Burdujeni, George Enescu – où le pourcentagede ceux nes dans le milieu rural est maximal.On remarque aussi la position intermédiaire du quartier Centre et des quartierspéricentraux, mais aussi du nouveau quartier Obcine, avec des pourcentage sur la

  17. 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.

  18. 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.

  19. 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.

  20. Plant Hormone Binding Sites

    OpenAIRE

    Napier, Richard

    2004-01-01

    • Aims Receptors for plant hormones are becoming identified with increasing rapidity, although a frustrating number remain unknown. There have also been many more hormone‐binding proteins described than receptors. This Botanical Briefing summarizes what has been discovered about hormone binding sites, their discovery and descriptions, and will not dwell on receptor functions or activities except where these are relevant to understand binding.

  1. Analysis of binding heterogeneity.

    NARCIS (Netherlands)

    Nederlof, M.M.

    1992-01-01

    Binding heterogeneity, due to different functional groups on a reactive surface, plays an important role in the binding of small molecules or ions to many adsorbents, both in industrial processes and in natural environments. The binding heterogeneity is described by a distribution of affinity consta

  2. "There is such a thing as too many daughters, but not too many sons": A qualitative study of son preference and fetal sex selection among Indian immigrants in the United States.

    Science.gov (United States)

    Puri, Sunita; Adams, Vincanne; Ivey, Susan; Nachtigall, Robert D

    2011-04-01

    In response to concerns from feminists, demographers, bioethicists, journalists, and health care professionals, the Indian government passed legislation in 1994 and 2003 prohibiting the use of sex selection technology and sex-selective abortion. In contrast, South Asian families immigrating to the United States find themselves in an environment where reproductive choice is protected by law and technologies enabling sex selection are readily available. Yet there has been little research exploring immigrant Indian women's narratives about the pressure they face to have sons, the process of deciding to utilize sex selection technologies, and the physical and emotional health implications of both son preference and sex selection. We undertook semi-structured, in-depth interviews with 65 immigrant Indian women in the United States who had pursued fetal sex selection on the East and West coasts of the United States between September 2004 and December 2009. Women spoke of son preference and sex selection as separate though intimately related phenomena, and the major themes that arose during interviews included the sociocultural roots of son preference; women's early socialization around the importance of sons; the different forms of pressure to have sons that women experienced from female in-laws and husbands; the spectrum of verbal and physical abuse that women faced when they did not have male children and/or when they found out they were carrying a female fetus; and the ambivalence with which women regarded their own experience of reproductive "choice." We found that 40% of the women interviewed had terminated prior pregnancies with female fetuses and that 89% of women carrying female fetuses in their current pregnancy pursued an abortion. These narratives highlight the interaction between medical technology and the perpetuation of this specific form of violence against women in an immigrant context where women are both the assumed beneficiaries of reproductive choice

  3. Evolution of the local environment of lanthanum during simplified SON68 glass leaching

    Energy Technology Data Exchange (ETDEWEB)

    Jollivet, P.; Delaye, J.M. [CEA, Lab Comportement Long Terme, F-30207 Bagnols Sur Ceze (France); Den Auwer, C. [CEA, Lab Concept Architectures Mol, F-30207 Bagnols Sur Ceze (France); Simoni, E. [Inst Phys Nucl, F-91406 Orsay (France)

    2007-03-15

    The evolution of the short- and medium-range local environment of lanthanum was determined by L-III-edge X-ray absorption spectroscopy (XAS) during leaching of simplified SON68-type glasses. In glass without phosphorus, lanthanum is found in a silicate environment, and its first coordination sphere comprises eight oxygen atoms at a mean distance of 2.51 angstrom. When this glass was leached at a high renewal rate, the lanthanum local environment was significantly modified: it was present at hydroxy-carbonate and silicate sites with a mean La-O distance of 2.56 angstrom, and the second neighbors consisted of La atoms instead of Si for the glass. Conversely, in the gel formed at low renewal rates, lanthanum was found in a silicate environment similar to that of the glass. In phosphorus-doped glass, lanthanum is found in a phosphate environment, although the Si/P atomic ratio is 20:1. Lanthanum is surrounded by seven oxygen atoms at a mean distance of 2.37 angstrom. When phosphorus-doped glass is leached, regardless of the leaching solution flow rate, the short- and medium-range lanthanum local environment remains almost constant; the most significant change is a 0.05 angstrom increase in the La-O distance. (authors)

  4. Evolution of the local environment of cerium and neodymium during simplified SON68 glass alteration

    Energy Technology Data Exchange (ETDEWEB)

    Jollivet, Patrick [Commissariat a l' Energie Atomique (CEA), Rhone Valley Research Center, BP 17171, 30207 Bagnols-sur-Ceze (France)]. E-mail: patrick.jollivet@cea.fr; Lopez, Christophe [Commissariat a l' Energie Atomique (CEA), Rhone Valley Research Center, BP 17171, 30207 Bagnols-sur-Ceze (France); Auwer, Christophe Den [Commissariat a l' Energie Atomique (CEA), Rhone Valley Research Center, BP 17171, 30207 Bagnols-sur-Ceze (France); Simoni, Eric [Institut de Physique Nucleaire, Batiment 100, 91406 Orsay cedex (France)

    2005-11-15

    The evolution of the sites occupied by cerium and neodymium (coordination numbers and Ce, Nd-O distances) during alteration of simplified SON68 glass specimens was determined by L{sub III}-edge XAS. Cerium and neodymium are situated in a silicate environment in the glass, surrounded by eight oxygen atoms at an average distance of 2.44 and 2.48 A, respectively. These two rare earth elements exhibit different leaching behavior, however. The main environment of cerium becomes a silicate (d {sub Ce-O} = 2.19 A) with a second oxide or more probably oxyhydroxide site (d {sub Ce-O} = 2.32 A). The cerium coordination number increases by 1 to 3 compared with the glass, depending on the leaching conditions. Neodymium is found mainly in a hydroxycarbonate environment (d {sub Nd-O} = 2.46 A); the second site is a silicate (d {sub Nd-O} = 2.54 A). The neodymium coordination number increases by 1 compared with the glass. When glass containing neodymium is doped with phosphorus, Nd is situated in a phosphate environment; this change is also reflected in the coordination number and Nd-O distance (seven oxygen atoms at 2.42 A). During glass leaching, neodymium is present at two different sites, phosphate (d {sub Nd-O} = 2.52 A) and hydroxycarbonate (d {sub Nd-O} = 2.40 A)

  5. Evolution of the local environment of lanthanum during simplified SON68 glass leaching

    International Nuclear Information System (INIS)

    The evolution of the short- and medium-range local environment of lanthanum was determined by L-III-edge X-ray absorption spectroscopy (XAS) during leaching of simplified SON68-type glasses. In glass without phosphorus, lanthanum is found in a silicate environment, and its first coordination sphere comprises eight oxygen atoms at a mean distance of 2.51 angstrom. When this glass was leached at a high renewal rate, the lanthanum local environment was significantly modified: it was present at hydroxy-carbonate and silicate sites with a mean La-O distance of 2.56 angstrom, and the second neighbors consisted of La atoms instead of Si for the glass. Conversely, in the gel formed at low renewal rates, lanthanum was found in a silicate environment similar to that of the glass. In phosphorus-doped glass, lanthanum is found in a phosphate environment, although the Si/P atomic ratio is 20:1. Lanthanum is surrounded by seven oxygen atoms at a mean distance of 2.37 angstrom. When phosphorus-doped glass is leached, regardless of the leaching solution flow rate, the short- and medium-range lanthanum local environment remains almost constant; the most significant change is a 0.05 angstrom increase in the La-O distance. (authors)

  6. 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.

  7. 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.

  8. 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.

  9. Meta-analysis suggests choosy females get sexy sons more than "good genes".

    Science.gov (United States)

    Prokop, Zofia M; Michalczyk, Łukasz; Drobniak, Szymon M; Herdegen, Magdalena; Radwan, Jacek

    2012-09-01

    Female preferences for specific male phenotypes have been documented across a wide range of animal taxa, including numerous species where males contribute only gametes to offspring production. Yet, selective pressures maintaining such preferences are among the major unknowns of evolutionary biology. Theoretical studies suggest that preferences can evolve if they confer genetic benefits in terms of increased attractiveness of sons ("Fisherian" models) or overall fitness of offspring ("good genes" models). These two types of models predict, respectively, that male attractiveness is heritable and genetically correlated with fitness. In this meta-analysis, we draw general conclusions from over two decades worth of empirical studies testing these predictions (90 studies on 55 species in total). We found evidence for heritability of male attractiveness. However, attractiveness showed no association with traits directly associated with fitness (life-history traits). Interestingly, it did show a positive correlation with physiological traits, which include immunocompetence and condition. In conclusion, our results support "Fisherian" models of preference evolution, while providing equivocal evidence for "good genes." We pinpoint research directions that should stimulate progress in our understanding of the evolution of female choice. PMID:22946794

  10. 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.

  11. 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.

  12. 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. PMID:24635666

  13. Chemical Precipitation of Ammonia and Phosphatefrom Nam Son Landfill Leachate, Hanoi

    Directory of Open Access Journals (Sweden)

    Nguyen Manh Khai

    2012-01-01

    Full Text Available Leachate from municipal landfills of the city is often contaminated heavily, especially for parameters such as organic components, heavy metals, microorganisms. However, leachate also contains amounts of valuable nutrients (e.g. N, P, K which can be used for agriculture as fertilizers. Precipitated of N and P in the form of struvite (MgNH4PO4.6H2O might be applied as a technique for removal a huge amount of N as well as P in wastewater. This study investigated the recovery ability of N, P in leachate from Nam Son municipal landfill of Hanoi city. Different pH values, anaerobic time and stoichiometric Mg2+: NH4+: PO43- was tested to determine the optimal conditions for precipitating struvite. The effect of pH on the forming of struvite was between pH 9 to 11. The results showed that nutrients in landfill leachate could be recovered with the optimum pH around 9.5 and the optimum Mg2+: NH4+: PO43- molar ratio as 1.15: 1: 1. With the anaerobic interval of 21 days, COD value in landfill leachate was decreased to 60%, the retrieval reached 80.6% for nitrogen and 82.7% for phosphorus. According to estimates, with the application of struvite precipitation technique, the average annual retrieval amount of NH4+ and PO43- can reach 263 tons and 25 tons, respectively.

  14. 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

  15. 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.

  16. Otočno obratovanje sončne elektrarne enodružinske hiše

    OpenAIRE

    Koncilja, Rok

    2016-01-01

    Tema moje diplomske naloge je otočno delovanje sončne elektrarne enodružinske hiše. V uvodu izvemo nekaj o samooskrbi z električno energijo ter o samem delovanju manjše sončne elektrarne. V glavnem delu naloge je najprej, s pomočjo tlorisnih načrtov enodružinske hiše, opisana dnevna poraba električne energije. V nadaljevanju sem pri izračunu sončnega obsevanja za naš solarni sistem upošteval konkretne parametre, pomagal pa sem si s podatki meteoroloških postaj. Rezultat so dnevne vrednost...

  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. En realidades sociales de múltiples pobrezas cómo son el juego y las relaciones de poder

    OpenAIRE

    Madueño, Juan Agustín

    2013-01-01

    En realidades sociales de "múltiples pobrezas", como son el juego y las relaciones de poder con sujetos adolescentes y jóvenes que concurren a las prácticas en recreación durante el 2000 al 2005. Con un sentido de criterio etnográfico, y bajo una mirada de un enfoque cualitativo, como son los cruces en lo atañe a las actividades recreativas y los juegos en esas poblaciones, y cual es la microfísica de poder que se establecen en las relaciones con las coordinaciones de los estudiantes en recre...

  19. Alexander Falconer Sr Seamen's missionary in New Zealand, son Alexander Falconer medical superintendent for mentally ill, grandson Murray Falconer neurosurgeon.

    Science.gov (United States)

    Hawgood, Barbara J

    2016-08-01

    Alexander Falconer Sr (1843-1915) came from Scotland to New Zealand. A practical Christian, he set up places of relaxation for miners, sailors and soldiers; he became the Seamen's Missionary. Son, Dr Alexander Falconer (1874-1955) trained at Otago University Medical School. As medical superintendent for the mentally ill, he urged the early introduction of psychotherapy. His son, Murray Falconer (1910-1977) was the first Nuffield Dominions Clinical Fellow, training in neurosurgery in Oxford. He was the first director of the Guy's-Maudsley Neurosurgical Unit in London and was internationally known for the surgical management of temporal lobe epilepsy in adults and children. PMID:26025843

  20. 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

  1. Knockdown of platinum-induced growth differentiation factor 15 abrogates p27-mediated tumor growth delay in the chemoresistant ovarian cancer model A2780cis

    International Nuclear Information System (INIS)

    Molecular mechanisms underlying the development of resistance to platinum-based treatment in patients with ovarian cancer remain poorly understood. This is mainly due to the lack of appropriate in vivo models allowing the identification of resistance-related factors. In this study, we used human whole-genome microarrays and linear model analysis to identify potential resistance-related genes by comparing the expression profiles of the parental human ovarian cancer model A2780 and its platinum-resistant variant A2780cis before and after carboplatin treatment in vivo. Growth differentiation factor 15 (GDF15) was identified as one of five potential resistance-related genes in the A2780cis tumor model. Although A2780-bearing mice showed a strong carboplatin-induced increase of GDF15 plasma levels, the basal higher GDF15 plasma levels of A2780cis-bearing mice showed no further increase after short-term or long-term carboplatin treatment. This correlated with a decreased DNA damage response, enhanced AKT survival signaling and abrogated cell cycle arrest in the carboplatin-treated A2780cis tumors. Furthermore, knockdown of GDF15 in A2780cis cells did not alter cell proliferation but enhanced cell migration and colony size in vitro. Interestingly, in vivo knockdown of GDF15 in the A2780cis model led to a basal-enhanced tumor growth, but increased sensitivity to carboplatin treatment as compared to the control-transduced A2780cis tumors. This was associated with larger necrotic areas, a lobular tumor structure and increased p53 and p16 expression of the carboplatin-treated shGDF15-A2780cis tumors. Furthermore, shRNA-mediated GDF15 knockdown abrogated p27 expression as compared to control-transduced A2780cis tumors. In conclusion, these data show that GDF15 may contribute to carboplatin resistance by suppressing tumor growth through p27. These data show that GDF15 might serve as a novel treatment target in women with platinum-resistant ovarian cancer

  2. 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

  3. Son preference among the historical Sandžak Muslim population

    Directory of Open Access Journals (Sweden)

    Čvorović Jelena

    2012-01-01

    Full Text Available This paper attempts to explain parental son preferences among historical Muslim population in the Sandžak region, southwestern Serbia. The paper draws upon data collected in the course of anthropological fieldwork studies in the region. The fieldwork was performed among Muslim and Christian families in Serbian rural area of Sandžak, measuring maternal fitness in relation to several variables. The data set comes from 120 women born between 1880-1924, representing so a historical demographic data based on individual and lineage records. These data were complemented with official records from Archive of Novi Pazar, whenever possible. In this Serbian rural area, land is still considered as an abundant resource, useful in establishing a family, livestock or agriculture. In the past, in spite of yearly fluctuations in production, lands and labor constituted a stable source of wealth from generation to generation. In this study, the data include the socio-economic status of each woman, assigned according to her husband’s family economic status: land-ownership vs. landless. This represents differences in resource availability in terms of nutrition, wealth and workload among these women. As the results show, the Muslim families, on average, left more surviving descendants through sons, in contrast with their Christian counterparts. The basic research question, then, is why? Furthermore, what were the impacts of particular behaviors on reproductive and lineage success, under particular social and ecological conditions? In this sample, regarding the Muslim families, the family structure was/is traditional and stratified, characterized by a large disparity in the status of males and females. Patrilineal inheritance, the concentration of wealth and power in males and the social restriction of women all characterize even today this patriarchal family arrangement. This supports the Trivers-Willard hypothesis, especially in terms of sex-biased parental

  4. Activation of the ATR kinase by the RPA-binding protein ETAA1

    DEFF Research Database (Denmark)

    Haahr, Peter; Hoffmann, Saskia; Tollenaere, Maxim A X;

    2016-01-01

    Activation of the ATR kinase following perturbations to DNA replication relies on a complex mechanism involving ATR recruitment to RPA-coated single-stranded DNA via its binding partner ATRIP and stimulation of ATR kinase activity by TopBP1. Here, we discovered an independent ATR activation pathway...... in vertebrates, mediated by the uncharacterized protein ETAA1 (Ewing's tumour-associated antigen 1). Human ETAA1 accumulates at DNA damage sites via dual RPA-binding motifs and promotes replication fork progression and integrity, ATR signalling and cell survival after genotoxic insults. Mechanistically......, this requires a conserved domain in ETAA1 that potently and directly stimulates ATR kinase activity independently of TopBP1. Simultaneous loss of ETAA1 and TopBP1 gives rise to synthetic lethality characterized by massive genome instability and abrogation of ATR-dependent signalling. Our findings demonstrate...

  5. PF573,228 inhibits vascular tumor cell growth, migration as well as angiogenesis, induces apoptosis and abrogates PRAS40 and S6RP phosphorylation.

    Science.gov (United States)

    Mabeta, Peace

    2016-09-01

    PF573,228 is a compound that targets focal adhesion kinase (FAK), a non-receptor protein kinase, which is over-expressed in various tumors. The aim of this study was to evaluate the effects of PF573,228 on the cells derived from mouse vascular tumors, namely, endothelioma cells. The treatment of endothelioma cells with PF573,228 reduced their growth with an IC50 of approximately 4.6 μmol L-1 and inhibited cell migration with an IC50 of about 0.01 μmol L-1. Microscopic studies revealed morphological attributes of apoptosis. These observations were confirmed by ELISA, which showed increased caspase-3 activity. PF573,228 also inhibited angiogenesis in a dose-dependent manner, with an IC50 of approximately 3.7 μmol L-1, and abrogated the phosphorylation of cell survival proteins, proline-rich Akt substrate (PRAS40) and S6 ribosomal protein (S6RP). Array data further revealed that PF573,228 induced caspase-3 activation, thus promoting apoptosis. Since all the processes inhibited by PF573,228 provide important support to tumor survival and progression, the drug may have a potential role in the treatment of vascular tumors. PMID:27383888

  6. ATP binding to the pseudokinase domain of JAK2 is critical for pathogenic activation.

    Science.gov (United States)

    Hammarén, Henrik M; Ungureanu, Daniela; Grisouard, Jean; Skoda, Radek C; Hubbard, Stevan R; Silvennoinen, Olli

    2015-04-14

    Pseudokinases lack conserved motifs typically required for kinase activity. Nearly half of pseudokinases bind ATP, but only few retain phosphotransfer activity, leaving the functional role of nucleotide binding in most cases unknown. Janus kinases (JAKs) are nonreceptor tyrosine kinases with a tandem pseudokinase-kinase domain configuration, where the pseudokinase domain (JAK homology 2, JH2) has important regulatory functions and harbors mutations underlying hematological and immunological diseases. JH2 of JAK1, JAK2, and TYK2 all bind ATP, but the significance of this is unclear. We characterize the role of nucleotide binding in normal and pathogenic JAK signaling using comprehensive structure-based mutagenesis. Disruption of JH2 ATP binding in wild-type JAK2 has only minor effects, and in the presence of type I cytokine receptors, the mutations do not affect JAK2 activation. However, JH2 mutants devoid of ATP binding ameliorate the hyperactivation of JAK2 V617F. Disrupting ATP binding in JH2 also inhibits the hyperactivity of other pathogenic JAK2 mutants, as well as of JAK1 V658F, and prevents induction of erythrocytosis in a JAK2 V617F myeloproliferative neoplasm mouse model. Molecular dynamic simulations and thermal-shift analysis indicate that ATP binding stabilizes JH2, with a pronounced effect on the C helix region, which plays a critical role in pathogenic activation of JAK2. Taken together, our results suggest that ATP binding to JH2 serves a structural role in JAKs, which is required for aberrant activity of pathogenic JAK mutants. The inhibitory effect of abrogating JH2 ATP binding in pathogenic JAK mutants may warrant novel therapeutic approaches. PMID:25825724

  7. 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…

  8. 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…

  9. The Quest of Father and Son: Illuminating Character Identity, Motivation, and Conflict in Cormac McCarthy's "The Road"

    Science.gov (United States)

    Gilbert, Chris

    2012-01-01

    "The Road" has been an important part of the author's English IV Honors course for several years now. Undeniably bleak, it details a father and son's journey through a seared, post-apocalyptic wasteland. As they travel through the burnt remains of America, they are threatened by starvation, dehydration, and scattered, hostile humans. Although his…

  10. 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…

  11. Examination of the Film "My Father and My Son" According to the Basic Concepts of Multigenerational Family Therapy

    Science.gov (United States)

    Acar, Tulin; Voltan-Acar, Nilufer

    2013-01-01

    The aim of this study was to evaluate the basic concepts of multigenerational Family Therapy and to evaluate the scenes of the film ''My Father and My Son'' according to these concepts. For these purposes firstly basic concepts of Multigenerational Family Therapy such as differentiation of self, triangles/triangulation, nuclear…

  12. 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.,...

  13. 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…

  14. An evolutionary psychological investigation of parental distress and reproductive coercion during the "coming out" of gay sons.

    Science.gov (United States)

    Wisniewski, Timothy J; Robinson, Thomas N; Deluty, Robert H

    2010-01-01

    The lack of success of the "coming out" studies over the last three decades to explain and predict parental responses has motivated an evolutionary psychological reconceptualization. According to this reconceptualization, it was predicted that (a) biological mothers would experience more distress and apply more pressure on gay sons to change than would biological fathers and; (b) obligate investment for fathers on dependent sons would cause fathers to experience more distress and apply more pressure on gay sons to change than it would fathers without this obligate investment. In contrast, a cultural-norm hypothesis predicted that fathers would experience more distress and apply more pressure on gay sons to change than mothers. The majority of predictions were tested using 787 participants from two-biological parent families, who were drawn from a total sample of 891 participants from various family backgrounds. As predicted by the evolutionary hypothesis, biological mothers were reported to have been more distressed and coercive than biological fathers, in spite of a strong, societal expectation to the contrary. Furthermore, the results supported the obligate investment argument for paternal reactions. The model not only correctly explained and predicted parental behavior during coming out, but also was shown to unify within its theoretical framework discrepant results from the literature previously considered inconsistent. PMID:20069499

  15. BiSON data preparation: A correction for differential extinction and the weighted averaging of contemporaneous data

    CERN Document Server

    Davies, G R; Elsworth, Y; Hale, S J

    2014-01-01

    The Birmingham Solar Oscillations Network (BiSON) has provided high-quality high-cadence observations from as far back in time as 1978. These data must be calibrated from the raw observations into radial velocity and the quality of the calibration has a large impact on the signal-to-noise ratio of the final time series. The aim of this work is to maximise the potential science that can be performed with the BiSON data set by optimising the calibration procedure. To achieve better levels of signal-to-noise ratio we perform two key steps in the calibration process: we attempt a correction for terrestrial atmospheric differential extinction; and the resulting improvement in the calibration allows us to perform weighted averaging of contemporaneous data from different BiSON stations. The improvements listed produce significant improvement in the signal-to-noise ratio of the BiSON frequency-power spectrum across all frequency ranges. The reduction of noise in the power spectrum will allow future work to provide gr...

  16. Beating the Odds: How Single Black Mothers Influence the Educational Success of Their Sons Enrolled in Failing Schools

    Science.gov (United States)

    Robinson, Quintin L.; Werblow, Jacob

    2012-01-01

    The academy has given little attention to academically successful Black males and the factors that may lead to their successes. This multiple case study design, however, examined the ways in which single-Black mothers influence the educational success of their sons by focusing on the mothers of academically successful 11th grade Black males. Data…

  17. "My Son Is Reliable": Young Drivers' Parents' Optimism and Views on the Norms of Parental Involvement in Youth Driving

    Science.gov (United States)

    Guttman, Nurit

    2013-01-01

    The high crash rates among teenage drivers are of great concern across nations. Parents' involvement is known to help increase their young drivers' driving safety. In particular, parents can place restrictions on their son's/daughter's driving (e.g., restrict night time driving), which can enable the young driver to gain driving experience in…

  18. 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 ...

  19. 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

  20. 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.

  1. 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.

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

    International Nuclear Information System (INIS)

    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 R49 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 Kd 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 R49 that is crucial for AtGRP7 function in pathogen defence and splicing abolishes binding

  3. 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.

  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. 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)

  7. 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.

  8. 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.

  9. 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.

  10. A Combination Supplement of Fructo- and Xylo-Oligosaccharides Significantly Abrogates Oxidative Impairments and Neurotoxicity in Maternal/Fetal Milieu Following Gestational Exposure to Acrylamide in Rat.

    Science.gov (United States)

    Krishna, Gokul; Divyashri, Gangaraju; Prapulla, S G; Muralidhara

    2015-09-01

    Prebiotic oligosaccharides are demonstrated to confer a wide spectrum of physiological benefits during pregnancy. In view of this, focused attempts are being directed towards understanding their role as modulators of brain chemistry and behavior. Epidemiological studies have identified that exposure to neurotoxins during prenatal/early life can profoundly impact neurodevelopment/function. In this context, we have tested the hypothesis that a combination of prebiotic supplements during gestation has the propensity to attenuate acrylamide (ACR) induced oxidative impairments, mitochondrial dysfunction and neurotoxicity in maternal and fetal brain of rats. To achieve this, pregnant dams given oral supplements of a combination of fructo- and xylooligosaccharides (FOS + XOS, 3 g/kg/day) during gestation days (GD 0-19) were exposed to ACR (200 ppm in drinking water, GD 6-19). The behavioral analysis revealed that ACR dams fed prebiotics displayed higher exploratory behavior in the open field test. The prenatal evaluation showed that ACR-induced decrements of placental/fetal weights were markedly restored with prebiotic feeding. Prebiotics significantly offset markers of oxidative stress, restored enzymic antioxidants, cholinergic and mitochondrial function in the maternal and fetal brain. Concomitantly, prebiotics restored ACR-induced depletion in the levels of dopamine and γ-aminobutyric acid in the maternal cortex that positively correlated with cecal bacterial numbers. Collectively, these data suggest that prenatal prebiotic oligosaccharide supplements protect developing brain against oxidative stress-mediated neurotoxicity. While the underlying mechanism/s by which prebiotics abrogate the impact of neurotoxicants in the developing brain merits further studies, we speculate that it may be mediated predominantly through attenuation of oxidative stress and proliferation of enteric microbiota. PMID:26248513

  11. 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

  12. ¿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.

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

    OpenAIRE

    Zuraw Bruce L; Doerner Astrid M

    2009-01-01

    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 tr...

  14. 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.

  15. KLEIN (André), David Ortlieb (1797-1875) : un artiste alsacien en son époque

    OpenAIRE

    Esch, Christine

    2013-01-01

    L’Association pour la restauration des édifices historiques de Colmar et son président André Klein font découvrir à travers cette importante monographie l’artiste peintre colmarien singulier qu’est David Ortlieb (1797-1875). Aucun ouvrage conséquent ne lui avait été consacré jusqu’alors : il fallait se contenter d’écrits épars et de sources clairsemées. Au fil des pages, André Klein resitue l’artiste et son œuvre dans le temps et l’espace. Il propose des fragments biographiques agrémentés de ...

  16. 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.

  17. Alteration kinetics of the glass-ceramic zirconolite and role of the alteration film Comparison with the SON68 glass

    Science.gov (United States)

    Martin, C.; Ribet, I.; Frugier, P.; Gin, S.

    2007-06-01

    The glass-ceramic zirconolite is being considered for specific conditioning of plutonium or the minor actinides. The actinides are distributed throughout the zirconolite crystals and the residual glass phase. Since zirconolite alteration is extremely limited, actinide release from the glass-ceramic material is mainly attributable to alteration of the residual glass. Specimens corresponding to the residual glass phase alone were therefore altered under different conditions to compare their kinetics with the one of the SON68 glass (inactive R7T7 type glass). Glass-ceramic zirconolite presents a more important rate decrease occuring more rapidly and that induces a quantity of glass altered at least 10 times as small as for SON68 glass. This slowdown of the alteration rate is attributed to the formation of an alteration film that has been the subject of a specific study. We have in particular identified a dense phase enriched in titanium and neodymium that probably influences deeply the kinetics.

  18. Parents who have lost a son or daughter through suicide : towards improved care and restored psychological health

    OpenAIRE

    Larsson Omerov, Pernilla

    2014-01-01

    Background Parents that have lost a son or daughter through suicide are at risk of developing psychological morbidity that may become long-lasting and even life-threatening. Despite this the aftermath of a suicidal loss is yet to be carefully studied. One reason for the lack of studies is that trauma-related surveys may be hindered when the risks of asking participants are overestimated and the benefits not considered. Another reason is methodological difficulties. The goa...

  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. Bargaining over Sons and Daughters: Child Labor, School Attendance and Intra-Household Gender Bias in Brazil

    OpenAIRE

    Emerson, Patrick M.; Andre Portela Souza

    2002-01-01

    In this paper we examine intra-household gender differences and the incidence of child labor and children�s school attendance in Brazil to test whether the unitary model of household allocations is suitable in the child labor context. We begin by building an intra-household allocation model where fathers and mothers may affect the education investment and the child labor participation of their sons and daughters differently due to differences in the children's human capital technologies and...

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

    OpenAIRE

    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’...

  2. Conserved Cysteine Residue in the DNA-Binding Domain of the Bovine Papillomavirus Type 1 E2 Protein Confers Redox Regulation of the DNA- Binding Activity in Vitro

    Science.gov (United States)

    McBride, Alison A.; Klausner, Richard D.; Howley, Peter M.

    1992-08-01

    The bovine papillomavirus type 1 E2 open reading frame encodes three proteins involved in viral DNA replication and transcriptional regulation. These polypeptides share a carboxyl-terminal domain with a specific DNA-binding activity; through this domain the E2 polypeptides form dimers. In this study, we demonstrate the inhibition of E2 DNA binding in vitro by reagents that oxidize or otherwise chemically modify the free sulfydryl groups of reactive cysteine residues. However, these reagents had no effect on DNA-binding activity when the E2 polypeptide was first bound to DNA, suggesting that the free sulfydryl group(s) may be protected by DNA binding. Sensitivity to sulfydryl modification was mapped to a cysteine residue at position 340 in the E2 DNA-binding domain, an amino acid that is highly conserved among the E2 proteins of different papillomaviruses. Replacement of this residue with other amino acids abrogated the sensitivity to oxidation-reduction changes but did not affect the DNA-binding property of the E2 protein. These results suggest that papillomavirus DNA replication and transcriptional regulation could be modulated through the E2 proteins by changes in the intracellular redox environment. Furthermore, a motif consisting of a reactive cysteine residue carboxyl-terminal to a lysine residue in a basic region of the DNA-binding domain is a feature common to a number of transcriptional regulatory proteins that, like E2, are subject to redox regulation. Thus, posttranslational regulation of the activity of these proteins by the intracellular redox environment may be a general phenomenon.

  3. 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

  4. Direct Demonstration That Loop1 of Scap Binds to Loop7: A CRUCIAL EVENT IN CHOLESTEROL HOMEOSTASIS.

    Science.gov (United States)

    Zhang, Yinxin; Lee, Kwang Min; Kinch, Lisa N; Clark, Lindsay; Grishin, Nick V; Rosenbaum, Daniel M; Brown, Michael S; Goldstein, Joseph L; Radhakrishnan, Arun

    2016-06-10

    Cholesterol homeostasis is mediated by Scap, a polytopic endoplasmic reticulum (ER) protein that transports sterol regulatory element-binding proteins from the ER to Golgi, where they are processed to forms that activate cholesterol synthesis. Scap has eight transmembrane helices and two large luminal loops, designated Loop1 and Loop7. We earlier provided indirect evidence that Loop1 binds to Loop7, allowing Scap to bind COPII proteins for transport in coated vesicles. When ER cholesterol rises, it binds to Loop1. We hypothesized that this causes dissociation from Loop7, abrogating COPII binding. Here we demonstrate direct binding of the two loops when expressed as isolated fragments or as a fusion protein. Expressed alone, Loop1 remained intracellular and membrane-bound. When Loop7 was co-expressed, it bound to Loop1, and the soluble complex was secreted. A Loop1-Loop7 fusion protein was also secreted, and the two loops remained bound when the linker between them was cleaved by a protease. Point mutations that disrupt the Loop1-Loop7 interaction prevented secretion of the Loop1-Loop7 fusion protein. These data provide direct documentation of intramolecular Loop1-Loop7 binding, a central event in cholesterol homeostasis. PMID:27068746

  5. 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.

  6. 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 ...

  7. 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

  8. 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.

  9. Parameterization of an effective potential for protein-ligand binding from host-guest affinity data.

    Science.gov (United States)

    Wickstrom, Lauren; Deng, Nanjie; He, Peng; Mentes, Ahmet; Nguyen, Crystal; Gilson, Michael K; Kurtzman, Tom; Gallicchio, Emilio; Levy, Ronald M

    2016-01-01

    Force field accuracy is still one of the "stalemates" in biomolecular modeling. Model systems with high quality experimental data are valuable instruments for the validation and improvement of effective potentials. With respect to protein-ligand binding, organic host-guest complexes have long served as models for both experimental and computational studies because of the abundance of binding affinity data available for such systems. Binding affinity data collected for cyclodextrin (CD) inclusion complexes, a popular model for molecular recognition, is potentially a more reliable resource for tuning energy parameters than hydration free energy measurements. Convergence of binding free energy calculations on CD host-guest systems can also be obtained rapidly, thus offering the opportunity to assess the robustness of these parameters. In this work, we demonstrate how implicit solvent parameters can be developed using binding affinity experimental data and the binding energy distribution analysis method (BEDAM) and validated using the Grid Inhomogeneous Solvation Theory analysis. These new solvation parameters were used to study protein-ligand binding in two drug targets against the HIV-1 virus and improved the agreement between the calculated and the experimental binding affinities. This work illustrates how benchmark sets of high quality experimental binding affinity data and physics-based binding free energy models can be used to evaluate and optimize force fields for protein-ligand systems. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26256816

  10. 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

  11. 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

  12. 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.

  13. 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

  14. Stretch regulates expression and binding of chymotrypsin-like elastase 1 in the postnatal lung.

    Science.gov (United States)

    Joshi, Rashika; Liu, Sheng; Brown, Montell D; Young, Sarah M; Batie, Matthew; Kofron, J Matthew; Xu, Yan; Weaver, Timmothy E; Apsley, Karen; Varisco, Brian M

    2016-02-01

    Lung stretch is critical for normal lung development and for compensatory lung growth after pneumonectomy (PNX), but the mechanisms by which strain induces matrix remodeling are unclear. Our prior work demonstrated an association of chymotrypsin-like elastase 1 (Cela1) with lung elastin remodeling, and that strain triggered a near-instantaneous elastin-remodeling response. We sought to determine whether stretch regulates Cela1 expression and Cela1 binding to lung elastin. In C57BL/6J mice, Cela1 protein increased 176-fold during lung morphogenesis. Cela1 was covalently bound to serpin peptidase inhibitor, clade A, member 1, resulting in a higher molecular mass in lung homogenate compared to pancreas homogenate. Post-PNX, Cela1 mRNA increased 6-fold, protein 3-fold, and Cela1-positive cells 2-fold. Cela1 was expressed predominantly in alveolar type II cells in the embryonic lung and predominantly in CD90-positive lung fibroblasts postnatally. During compensatory lung growth, Cela1 expression was induced in nonproliferative mesenchymal cells. In ex vivo mouse lung sections, stretch increased Cela1 binding to lung tissue by 46%. Competitive inhibition with soluble elastin completely abrogated this increase. Areas of stretch-induced elastase activity and Cela1 binding colocalized. The stretch-dependent expression and binding kinetics of Cela1 indicate an important role in stretch-dependent remodeling of the peripheral lung during development and regeneration. PMID:26443822

  15. 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.

  16. The CHR promoter element controls cell cycle-dependent gene transcription and binds the DREAM and MMB complexes.

    Science.gov (United States)

    Müller, Gerd A; Quaas, Marianne; Schümann, Michael; Krause, Eberhard; Padi, Megha; Fischer, Martin; Litovchick, Larisa; DeCaprio, James A; Engeland, Kurt

    2012-02-01

    Cell cycle-dependent gene expression is often controlled on the transcriptional level. Genes like cyclin B, CDC2 and CDC25C are regulated by cell cycle-dependent element (CDE) and cell cycle genes homology region (CHR) promoter elements mainly through repression in G(0)/G(1). It had been suggested that E2F4 binding to CDE sites is central to transcriptional regulation. However, some promoters are only controlled by a CHR. We identify the DREAM complex binding to the CHR of mouse and human cyclin B2 promoters in G(0). Association of DREAM and cell cycle-dependent regulation is abrogated when the CHR is mutated. Although E2f4 is part of the complex, a CDE is not essential but can enhance binding of DREAM. We show that the CHR element is not only necessary for repression of gene transcription in G(0)/G(1), but also for activation in S, G(2) and M phases. In proliferating cells, the B-myb-containing MMB complex binds the CHR of both promoters independently of the CDE. Bioinformatic analyses identify many genes which contain conserved CHR elements in promoters binding the DREAM complex. With Ube2c as an example from that screen, we show that inverse CHR sites are functional promoter elements that can bind DREAM and MMB. Our findings indicate that the CHR is central to DREAM/MMB-dependent transcriptional control during the cell cycle. PMID:22064854

  17. The CHR promoter element controls cell cycle-dependent gene transcription and binds the DREAM and MMB complexes

    Science.gov (United States)

    Müller, Gerd A.; Quaas, Marianne; Schümann, Michael; Krause, Eberhard; Padi, Megha; Fischer, Martin; Litovchick, Larisa; DeCaprio, James A.; Engeland, Kurt

    2012-01-01

    Cell cycle-dependent gene expression is often controlled on the transcriptional level. Genes like cyclin B, CDC2 and CDC25C are regulated by cell cycle-dependent element (CDE) and cell cycle genes homology region (CHR) promoter elements mainly through repression in G0/G1. It had been suggested that E2F4 binding to CDE sites is central to transcriptional regulation. However, some promoters are only controlled by a CHR. We identify the DREAM complex binding to the CHR of mouse and human cyclin B2 promoters in G0. Association of DREAM and cell cycle-dependent regulation is abrogated when the CHR is mutated. Although E2f4 is part of the complex, a CDE is not essential but can enhance binding of DREAM. We show that the CHR element is not only necessary for repression of gene transcription in G0/G1, but also for activation in S, G2 and M phases. In proliferating cells, the B-myb-containing MMB complex binds the CHR of both promoters independently of the CDE. Bioinformatic analyses identify many genes which contain conserved CHR elements in promoters binding the DREAM complex. With Ube2c as an example from that screen, we show that inverse CHR sites are functional promoter elements that can bind DREAM and MMB. Our findings indicate that the CHR is central to DREAM/MMB-dependent transcriptional control during the cell cycle. PMID:22064854

  18. 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.

  19. Review of the execution of the extension of the Sonček kindergarten in Semič project

    OpenAIRE

    Konda, Anja

    2012-01-01

    The thesis demonstrates a review of the running of the project titled The Extension of the Sonček Kindergarten in Semič. The author of the thesis monitored the course of the construction work up to the completion of its third phase. First, the organisation of the project and the conditions for the construction have been demonstrated. What follows is the presentation of the organisation of the technological construction process: it describes the methods of executing the individual phases of co...

  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. Hamlet på motorcyklar : En komparativ analys av TV-serien Sons of Anarchy och Shakespeares drama Hamlet

    OpenAIRE

    Sander, Johanna

    2010-01-01

    In 2008 Fox first aired its hit show Sons of Anarchy, a drama series about a Californian motorcycle club. The main thrust is about the club’s vice-president and his struggle to find his place in a life of violence. According to creator Kurt Sutter the series is partly based on Shakespeare’s 16th century drama Hamlet - Prince of Denmark, which causes the show to often be referred to as ”Hamlet on Harleys”. Focusing on the first two seasons of the series, this essay looks into the relationship ...

  2. Cirugía cardiaca en el hospital universitario Son Dureta: Análisis de morbimortalidad y factores asociados

    OpenAIRE

    Riera Sagrera, María

    2011-01-01

    La morbimortalidad de la cirugía cardiaca y el análisis de los factores pronósticos muestran resultados discrepantes. Se analizaron las complicaciones postoperatorias y la mortalidad hospitalaria y a medio plazo, en relación con la edad y otros factores de riesgo asociados. Se realizó en el hospital universitario Son Dureta (Palma de Mallorca), con una unidad de cuidados intensivos específica para dicho paciente. La mortalidad hospitalaria y a medio plazo fue menor, comparada con otras series...

  3. "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

  4. ¿SON LOS PADRES Y PROFESORES BUENOS DETECTORES DE LAS ALTAS CAPACIDADES INTELECTUALES DE LOS ALUMNOS?

    OpenAIRE

    Fernández-Sánchez, Inmaculada

    2013-01-01

    Los alumnos con altas capacidades intelectuales son una población con posibles dificultades adaptativas a la escuela, ya que un porcentaje elevado de ellos presentan un síndrome de bajo rendimiento, debido, entre otras cosas, a sus características psiconeurológicas y a la falta de formación del profesorado para identificarlos y para intervenir con las medidas educativas apropiadas. Este trabajo tiene como objetivo conocer la adecuación de los procesos de identificación de al...

  5. The IkB kinase inhibitor nuclear factor-kB essential modulator–binding domain peptide for inhibition of balloon injury-induced neointimal formation

    OpenAIRE

    Grassia, G.; Maddaluno, M.; Musilli, C.; De Stefano, D.; Carnuccio, R.; Di Lauro, M.V.; Parratt, C.A.; Kennedy, S.; di Meglio, P; Ianaro, A; Maffia, P.; Parenti., A; Ialenti, A.

    2010-01-01

    Objective—The activation of nuclear factor-kB (NF-kB) is a crucial step in the arterial wall’s response to injury. The identification and characterization of the NF-kB essential modulator– binding domain (NBD) peptide, which can block the activation of the IkB kinase complex, have provided an opportunity to selectively abrogate the inflammation-induced activation of NF-kB. The aim of the present study was to evaluate the effect of the NBD peptide on neointimal formation. Method...

  6. 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.

  7. Familial defective apolipoprotein B-100: low density lipoproteins with abnormal receptor binding

    International Nuclear Information System (INIS)

    Previous in vivo turnover studies suggested that retarded clearance of low density lipoproteins (LDL) from the plasma of some hypercholesterolemic patients is due to LDL with defective receptor binding. The present study examined this postulate directly by receptor binding experiments. The LDL from a hypercholesterolemic patient (G.R.) displayed a reduced ability to bind to the LDL receptors on normal human fibroblasts. The G.R. LDL possessed 32% of normal receptor binding activity. Likewise, the G.R. LDL were much less effective than normal LDL in competing with 125I-labeled normal LDL for cellular uptake and degradation and in stimulating intracellular cholesteryl ester synthesis. The defect in LDL binding appears to be due to a genetic abnormality of apolipoprotein B-100: two brothers of the proband possess LDL defective in receptor binding, whereas a third brother and the proband's son have normally binding LDL. Further, the defect in receptor binding does not appear to be associated wit an abnormal lipid composition or structure of the LDL. Normal and abnormal LDL subpopulations were partially separated from plasma of two subjects by density-gradient ultracentrifugation, a finding consistent with the presence of a normal and a mutant allele. The affected family members appear to be heterozygous for this disorder, which has been designated familial defective apolipoprotein B-100. These studies indicate that the defective receptor binding results in inefficient clearance of LDL and the hypercholesterolemia observed in these patients

  8. 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

  9. 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

  10. 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.

  11. (Alpha, gamma) irradiation effect on the alteration of high-level radioactive wastes matrices (UO2, hollandite, glass SON68)

    International Nuclear Information System (INIS)

    The aim of this work is to determine the effect of irradiation on the alteration of high level nuclear waste forms matrices. The matrices investigated are UO2 to simulate the spent fuel, the hollandite for the specific conditioning of Cs, and the inactive glass SON68 representing the nuclear glass R7T7) The alpha irradiation experiments on UO2 colloids in aqueous carbonate media have enabled to distinguish between the oxidation of UO2 matrix as initial and dissolution as subsequent step. The simultaneous presence of carbonate and H2O2 (product resulting from water radiolysis) increased the dissolution rate of UO2 to its maximum value governed by the oxidation rate. ii) The study of hollandite alteration under gamma irradiation confirmed the good retention capacity for Cs and Ba. Gamma irradiation had brought only a little influence on releasing of Cs and Ba in solution. Electronic irradiation had conducted to the amorphization of the hollandite only for a dose 1000 times higher than the auto-induced dose of Ba over millions of years. iii) The experiences of glass irradiation under alpha beam and of helium implantation in the glass SON68 were analyzed by positon annihilation spectroscopy. No effect has been observed on the solid surface for an irradiation dose equal to 1000 years of storage. (author)

  12. 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

  13. When mothers make sons sexy: maternal effects contribute to the increased sexual attractiveness of extra-pair offspring.

    Science.gov (United States)

    Tschirren, Barbara; Postma, Erik; Rutstein, Alison N; Griffith, Simon C

    2012-03-22

    Quality differences between offspring sired by the social and by an extra-pair partner are usually assumed to have a genetic basis, reflecting genetic benefits of female extra-pair mate choice. In the zebra finch (Taeniopygia guttata), we identified a colour ornament that is under sexual selection and appears to have a heritable basis. Hence, by engaging in extra-pair copulations with highly ornamented males, females could, in theory, obtain genes for increased offspring attractiveness. Indeed, sons sired by extra-pair partners had larger ornaments, seemingly supporting the genetic benefit hypothesis. Yet, when comparing ornament size of the social and extra-pair partners, there was no difference. Hence, the observed differences most likely had an environmental basis, mediated, for example, via differential maternal investment of resources into the eggs fertilized by extra-pair and social partners. Such maternal effects may (at least partly) be mediated by egg size, which we found to be associated with mean ornament expression in sons. Our results are consistent with the idea that maternal effects can shape sexual selection by altering the genotype-phenotype relationship for ornamentation. They also caution against automatically attributing greater offspring attractiveness or viability to an extra-pair mate's superior genetic quality, as without controlling for differential maternal investment we may significantly overestimate the role of genetic benefits in the evolution of extra-pair mating behaviour. PMID:21957136

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. Cellulose binding domain proteins

    Energy Technology Data Exchange (ETDEWEB)

    Shoseyov, Oded (Karmey Yosef, IL); Shpiegl, Itai (Rehovot, IL); Goldstein, Marc (Davis, CA); Doi, Roy (Davis, CA)

    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.

  19. 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.

  20. Lectin binding in meningiomas.

    Science.gov (United States)

    Kleinert, R; Radner, H

    1987-01-01

    Forty-two meningiomas of different morphological sub-type were examined to determine their pattern of binding to 11 different lectins which characterize cell surface components such as carbohydrate residues. Histiocytic and xanthoma cells within meningiomas could be demonstrated with six different lectins: wheat germ agglutinin (WGA), peanut agglutinin (PNA) Bauhinia purpurea agglutinin (BPA), Helix pomatia agglutinin (HPA), Vicia fava agglutinin (VFA) and Soyabean agglutinin (SBA). Vascular elements including endothelial cells and intimal cells, bound Ulex europaeus agglutinin type 1 (UEA 1), WGA and HPA. The fibrous stroma in fibrous and fibroblastic meningiomas bound PNA, Laburnum alpinum agglutinin (LAA) and SBA. Tumour cells in meningotheliomatous meningiomas and some areas of anaplastic meningiomas bound Concanavalin A, PNA, LAA and VFA whereas tumour cells in fibrous and fibroblastic meningiomas bound BPA, LAA and VFA. Lectin binding has proved to be of value in detecting histiocytic and xanthoma cells together with vascular elements within meningiomas. In addition, the different lectin binding patterns allow different histological sub-types of meningioma to be distinguished although the biological significance of the binding patterns is unclear. PMID:3658105

  1. Riad al-Solh en son temps (Riyâd Al-Sulh fî zamâni-hi, Beyrouth, Dar An-Nahar, 2011

    Directory of Open Access Journals (Sweden)

    Ahmad Beydoun

    2011-10-01

    Full Text Available Riad al-Solh a été assassiné à l’âge de cinquante-sept ans. Au cours des dernières années de sa vie, il tint à rappeler son parcours et son expérience à ses jeunes collègues du Parlement, cherchant ainsi à aiguiser leur discernement. Son engagement précoce en politique (que l’on nommait jihad à cette époque, puis son départ, avaient occupé toute sa vie. Elles lui conféraient l’aura d’un vieux sage. Ces quarante années de carrière avaient conduit le jeune étudiant en droit d’un bureau d’Istan...

  2. 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.

  3. Batroxobin binds fibrin with higher affinity and promotes clot expansion to a greater extent than thrombin.

    Science.gov (United States)

    Vu, Trang T; Stafford, Alan R; Leslie, Beverly A; Kim, Paul Y; Fredenburgh, James C; Weitz, Jeffrey I

    2013-06-01

    Batroxobin is a thrombin-like serine protease from the venom of Bothrops atrox moojeni that clots fibrinogen. In contrast to thrombin, which releases fibrinopeptide A and B from the NH2-terminal domains of the Aα- and Bβ-chains of fibrinogen, respectively, batroxobin only releases fibrinopeptide A. Because the mechanism responsible for these differences is unknown, we compared the interactions of batroxobin and thrombin with the predominant γA/γA isoform of fibrin(ogen) and the γA/γ' variant with an extended γ-chain. Thrombin binds to the γ'-chain and forms a higher affinity interaction with γA/γ'-fibrin(ogen) than γA/γA-fibrin(ogen). In contrast, batroxobin binds both fibrin(ogen) isoforms with similar high affinity (Kd values of about 0.5 μM) even though it does not interact with the γ'-chain. The batroxobin-binding sites on fibrin(ogen) only partially overlap with those of thrombin because thrombin attenuates, but does not abrogate, the interaction of γA/γA-fibrinogen with batroxobin. Furthermore, although both thrombin and batroxobin bind to the central E-region of fibrinogen with a Kd value of 2-5 μM, the α(17-51) and Bβ(1-42) regions bind thrombin but not batroxobin. Once bound to fibrin, the capacity of batroxobin to promote fibrin accretion is 18-fold greater than that of thrombin, a finding that may explain the microvascular thrombosis that complicates envenomation by B. atrox moojeni. Therefore, batroxobin binds fibrin(ogen) in a manner distinct from thrombin, which may contribute to its higher affinity interaction, selective fibrinopeptide A release, and prothrombotic properties. PMID:23612970

  4. 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

    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 a principal in vivo role of the uPA-uPAR interaction in cell-associated fibrinolysis critical for suppression of fibrin accumulation and fibrin-associated inflammation and provides a valuable model for further exploration of this multifunctional receptor....

  5. Effects of mono- and divalent metal ions on DNA binding and catalysis of human apurinic/apyrimidinic endonuclease 1.

    Science.gov (United States)

    Miroshnikova, Anastasia D; Kuznetsova, Alexandra A; Vorobjev, Yuri N; Kuznetsov, Nikita A; Fedorova, Olga S

    2016-05-26

    Here, we used stopped-flow fluorescence techniques to conduct a comparative kinetic analysis of the conformational transitions in human apurinic/apyrimidinic endonuclease 1 (APE1) and in DNA containing an abasic site in the course of their interaction. Effects of monovalent (K(+)) and divalent (Mg(2+), Mn(2+), Ca(2+), Zn(2+), Cu(2+), and Ni(2+)) metal ions on DNA binding and catalytic stages were studied. It was shown that the first step of substrate binding (corresponding to formation of a primary enzyme-substrate complex) does not depend on the concentration (0.05-5.0 mM) or the nature of divalent metal ions. In contrast, the initial DNA binding efficiency significantly decreased at a high concentration (5-250 mM) of monovalent K(+) ions, indicating the involvement of electrostatic interactions in this stage. It was also shown that Cu(2+) ions abrogated the DNA binding ability of APE1, possibly, due to a strong interaction with DNA bases and the sugar-phosphate backbone. In the case of Ca(2+) ions, the catalytic activity of APE1 was lost completely with retention of binding potential. Thus, the enzymatic activity of APE1 is increased in the order Zn(2+) < Ni(2+) < Mn(2+) < Mg(2+). Circular dichroism spectra and calculation of the contact area between APE1 and DNA reveal that Mg(2+) ions stabilize the protein structure and the enzyme-substrate complex. PMID:27063150

  6. 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 maternal age, polygyny prevalence, 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.

  7. Clonage de l'IGF-I et de son récepteur chez le turbot (Psetta maxima)

    OpenAIRE

    ELIES G.; Duval, H.; GROIGNO L.; Wolff, J.; Boeuf, G.; BOUJARD D.

    1998-01-01

    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 verté...

  8. 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.

  9. 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.

  10. L’analyse du discours et ses entre-deux : notes sur son histoire au Brésil

    OpenAIRE

    Puccinelli Orlandi, Eni

    2014-01-01

    À Paul Henry pour l’excellence théorique avec laquelle, dès le début, il a exploré la force et les nuances de l’analyse du discours. Introduction Mettant hors du champ de la réflexion discursive la notion d’« intervalle », je propose une pratique matérialiste de l’analyse du discours par son inscription dans un espace d’« entre-deux », jusqu’au sein même de l’histoire des théories linguistiques. À la différence de celle d’intervalle, l’idée d’entre-deux renvoie à des espaces simultanément hab...

  11. El drama de ser mujer en Todas las historias son de amor de Adolfo Torres

    OpenAIRE

    Gutiérrez García, Rosa María.

    2010-01-01

    La ideología expresa y se reproduce en la sociedad a través del discurso; en esa dirección, el espíritu que guía este análisis es el concepto de ideología asociado al discurso y será utilizado en el sentido de noción general de creencias, ya que pretendemos encontrar en el discurso del drama Todas las historias son de amor, de Adolfo Torres, las marcas de ideología relacionadas con el género. Nuestro objetivo particular es examinar cuál es la idea que sobre la mujer se tiene y cómo aparece en...

  12. 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.

  13. The Sun-as-a-star observations: GOLF & VIRGO on SoHO, and BiSON network

    CERN Document Server

    Garcia, R A; Jimenez, A; Ballot, J; Mathur, S; Salabert, D; Chaplin, W J; Elsworth, Y; Regulo, C; Turck-Chieze, S

    2013-01-01

    Sun-as-a-star observations are very important for the study of the conditions within the Sun and in particular for the deep interior where higher degree modes do not penetrate. They are also of significance in this era of dramatic advances in stellar asteroseismology as they are comparable to those measured in other stars by asteroseismic missions such as CoRoT, Kepler, and MOST. More than 17 years of continuous measurements of SoHO and more than 30 years of BiSON observations provide very long data sets of uninterrupted helioseismic observations. In this work, we discuss the present status of all these facilities that continue to provide state- of-the-art measurements and invaluable data to improve our knowledge of the deepest layers of the Sun and its structural changes during the activity cycle.

  14. ¿También los extranjeros son iguales ante la ley? = Foreigners: are they equal before the law?

    OpenAIRE

    Mora Alemañy, Rosario

    2013-01-01

    «Los españoles son iguales ante la ley» (art. 14 CE). La recentísima STC 17/2013 señala que «los extranjeros gozan en España del derecho fundamental derivado del artículo 18.4 CE en las mismas condiciones que los españoles»; pero, como señala el voto particular del Magistrado Pérez Tremps, al que se unen otros tres magistrados, la regulación avalada por el Tribunal Constitucional en esta sentencia «pone de manifiesto una notable limitación del contenido esencial del derec...

  15. 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.

  16. 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.

  17. Simulated alteration tests on non-radioactive SON 68 nuclear glass in the presence of corrosion products and environmental materials

    International Nuclear Information System (INIS)

    Alteration tests with non-radioactive French SON 68 (R7T7-type) nuclear glass in the presence of simulated metal canister corrosion products (CP) or environmental materials (EM) were simulated using the LIXIVER2 computer code. The code incorporates hypotheses concerning glass alteration in aqueous media based on the first-order kinetic law for total silicon with variable silicon retention in the gel and silicon diffusion in the gel interstitial water, coupled with silicon adsorption and diffusion in the materials in contact with the glass. The canister CP are considered as a localized medium with a mass adsorption capacity Rad, while the EM are considered as a porous medium with a diffusion coefficient Dp and a distribution coefficient Kd. LIXIVER2 simulates these media in one-dimensional Cartesian geometry. The Kd values determined by simulating alteration tests logically increase with the aggressiveness of the materials with respect to the glass

  18. 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

  19. Deletion of locus D15S113 in a mother and son without features of Angelman syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Michaelis, R.C.; Tarleton, J.C.; Donlon, T.A.; Simensen, R.J. [Greenwood Gneetic Center, SC (United States)] [and others

    1994-09-01

    Deletions of the proximal long arm of chromosome 15 result in Angelman syndrome when inherited from the mother and Prader-Willi syndrome when inherited from the father. The minimal critical deletion region for Angelman syndrome has been reported to include D15S74 (B1.5), D15S10 (TD3-21), and D15S113 (LS6-1). We report a mother and son who have deletions that include D15S113 but who do not have features of Angelman syndrome. D.H. is a 10-year-old white male referred for genetic evaluation due to mental retardation. He has mild to moderate mental retardation and minor dysmorphic features, including downslanting palpebral fissures, prominent nose, broad forehead, small chin, midface hypoplasia, and large ears. His mother (B.S.) has slightly downslanting palpebral fissures and a borderline intellectual deficit. Neither individual has the seizures, excessive laughter, hand clapping, ataxia or facial dysmorphism which are characteristic of Angelman syndrome. The linear order of probes mapping to 15q11-q13 is 15cen-D15S11-D15S13-D15S10-D15S113-GABRB3-D15S12-tel. The proximal border of the deletion in our patients lies between D15S10 and D15S113. The fact that these two individuals do not have Angelman syndrome, despite deletion of D15S113, suggests that the Angelman syndrome critical deletion region should be further refined to exclude the D15S113 locus. In addition, the findings of a more severe intellectual impairment in the son than in the mother suggests that the region immediately telomeric to the critical deletion region for Angelman syndrome may contain imprintable genes that influence intellectual function.

  20. CD36 mediates proximal tubular binding and uptake of albumin and is upregulated in proteinuric nephropathies.

    Science.gov (United States)

    Baines, Richard J; Chana, Ravinder S; Hall, Matthew; Febbraio, Maria; Kennedy, David; Brunskill, Nigel J

    2012-10-01

    Dysregulation of renal tubular protein handling in proteinuria contributes to the development of chronic kidney disease. We investigated the role of CD36 as a novel candidate mediator of albumin binding and endocytosis in the kidney proximal tubule using both in vitro and in vivo approaches, and in nephrotic patient renal biopsy samples. In CD36-transfected opossum kidney proximal tubular cells, both binding and uptake of albumin were substantially enhanced. A specific CD36 inhibitor abrogated this effect, but receptor-associated protein, which blocks megalin-mediated endocytosis of albumin, did not. Mouse proximal tubular cells expressed CD36 and this was absent in CD36 null animals, whereas expression of megalin was equal in these animals. Compared with wild-type mice, CD36 null mice demonstrated a significantly increased urinary protein-to-creatinine ratio and albumin-to-creatinine ratio. Proximal tubular cells expressed increased CD36 when exposed to elevated albumin concentrations in culture medium. Expression of CD36 was studied in renal biopsy tissue obtained from adult patients with heavy proteinuria due to minimal change disease, membranous nephropathy, or focal segmental glomerulosclerosis. Proximal tubular CD36 expression was markedly increased in proteinuric individuals. We conclude that CD36 is a novel mediator influencing binding and uptake of albumin in the proximal tubule that is upregulated in proteinuric renal diseases. CD36 may represent a potential therapeutic target in proteinuric nephropathy. PMID:22791331

  1. 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.

  2. 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)

  3. 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

  4. 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...... to express high levels of megalin, is inhibitable by excess unlabeled FBP and by receptor associated protein, a known inhibitor of binding to megalin. Immortalized rat yolk sac cells, representing an established model for studying megalin-mediated uptake, reveal (125)I-labeled FBP uptake which is inhibited...

  5. 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.

  6. 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.

  7. 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

  8. De Novo Mutations in SON Disrupt RNA Splicing of Genes Essential for Brain Development and Metabolism, Causing an Intellectual-Disability Syndrome.

    Science.gov (United States)

    Kim, Jung-Hyun; Shinde, Deepali N; Reijnders, Margot R F; Hauser, Natalie S; Belmonte, Rebecca L; Wilson, Gregory R; Bosch, Daniëlle G M; Bubulya, Paula A; Shashi, Vandana; Petrovski, Slavé; Stone, Joshua K; Park, Eun Young; Veltman, Joris A; Sinnema, Margje; Stumpel, Connie T R M; Draaisma, Jos M; Nicolai, Joost; Yntema, Helger G; Lindstrom, Kristin; de Vries, Bert B A; Jewett, Tamison; Santoro, Stephanie L; Vogt, Julie; Bachman, Kristine K; Seeley, Andrea H; Krokosky, Alyson; Turner, Clesson; Rohena, Luis; Hempel, Maja; Kortüm, Fanny; Lessel, Davor; Neu, Axel; Strom, Tim M; Wieczorek, Dagmar; Bramswig, Nuria; Laccone, Franco A; Behunova, Jana; Rehder, Helga; Gordon, Christopher T; Rio, Marlène; Romana, Serge; Tang, Sha; El-Khechen, Dima; Cho, Megan T; McWalter, Kirsty; Douglas, Ganka; Baskin, Berivan; Begtrup, Amber; Funari, Tara; Schoch, Kelly; Stegmann, Alexander P A; Stevens, Servi J C; Zhang, Dong-Er; Traver, David; Yao, Xu; MacArthur, Daniel G; Brunner, Han G; Mancini, Grazia M; Myers, Richard M; Owen, Laurie B; Lim, Ssang-Taek; Stachura, David L; Vissers, Lisenka E L M; Ahn, Eun-Young Erin

    2016-09-01

    The overall understanding of the molecular etiologies of intellectual disability (ID) and developmental delay (DD) is increasing as next-generation sequencing technologies identify genetic variants in individuals with such disorders. However, detailed analyses conclusively confirming these variants, as well as the underlying molecular mechanisms explaining the diseases, are often lacking. Here, we report on an ID syndrome caused by de novo heterozygous loss-of-function (LoF) mutations in SON. The syndrome is characterized by ID and/or DD, malformations of the cerebral cortex, epilepsy, vision problems, musculoskeletal abnormalities, and congenital malformations. Knockdown of son in zebrafish resulted in severe malformation of the spine, brain, and eyes. Importantly, analyses of RNA from affected individuals revealed that genes critical for neuronal migration and cortex organization (TUBG1, FLNA, PNKP, WDR62, PSMD3, and HDAC6) and metabolism (PCK2, PFKL, IDH2, ACY1, and ADA) are significantly downregulated because of the accumulation of mis-spliced transcripts resulting from erroneous SON-mediated RNA splicing. Our data highlight SON as a master regulator governing neurodevelopment and demonstrate the importance of SON-mediated RNA splicing in human development. PMID:27545680

  9. A case study of conflict management in bonobos: how does a bonobo (Pan paniscus) mother manage conflicts between her sons and her female coalition partner?

    Science.gov (United States)

    Legrain, L; Stevens, J; Alegria Iscoa, J; Destrebecqz, A

    2011-01-01

    Female coalitions are an important part of the social organization of bonobos. The strength of the mother-son relationship is another essential part of this social structure. A bonobo mother is therefore facing a dilemma when a conflict arises between her sons and her female coalition partners. Will she take her coalition partner's side and favour the social organization of the group or support her son in order to defend her offspring? In order to address this issue, we performed an observational study of the captive group at Planckendael (Belgium) and used social grooming and proximity to assess the relationship between individuals. As a case study, we focused on the relationships between Hortense, one of the group's mothers, her 3 sons Redi, Vifijo and Zamba, and her coalition partner Hermien. Surprisingly, we observed that Hortense preferentially supported her female coalition partner. For Hortense's social status in the group, it may be more important to maintain the strong relationship with her higher-ranking female coalition partner than to support her sons. PMID:22286277

  10. 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.

  11. 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.

  12. How parasitoid females produce sexy sons: a causal link between oviposition preference, dietary lipids and mate choice in Nasonia.

    Science.gov (United States)

    Blaul, Birgit; Ruther, Joachim

    2011-11-01

    Sexual selection theory predicts that phenotypic traits used to choose a mate should reflect honestly the quality of the sender and thus, are often costly. Physiological costs arise if a signal depends on limited nutritional resources. Hence, the nutritional condition of an organism should determine both its quality as a potential mate and its ability to advertise this quality to the choosing sex. In insects, the quality of the offspring's nutrition is often determined by the ovipositing female. A causal connection, however, between the oviposition decisions of the mother and the mating chances of her offspring has never been shown. Here, we demonstrate that females of the parasitic wasp Nasonia vitripennis prefer those hosts for oviposition that have been experimentally enriched in linoleic acid (LA). We show by (13)C-labelling that LA from the host diet is a precursor of the male sex pheromone. Consequently, males from LA-rich hosts produce and release higher amounts of the pheromone and attract more virgin females than males from LA-poor hosts. Finally, males from LA-rich hosts possess three times as many spermatozoa as those from LA-poor hosts. Hence, females making the right oviposition decisions may increase both the fertility and the sexual attractiveness of their sons. PMID:21429922

  13. ¿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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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...

  19. TGF-β and IL-6 signals modulate chromatin binding and promoter occupancy by acetylated FOXP3

    Science.gov (United States)

    Samanta, Arabinda; Li, Bin; Song, Xiaomin; Bembas, Kathryn; Zhang, Geng; Katsumata, Makoto; Saouaf, Sandra J.; Wang, Qiang; Hancock, Wayne W.; Shen, Yuan; Greene, Mark I.

    2008-01-01

    Expression of FOXP3, a potent gene-specific transcriptional repressor, in regulatory T cells is required to suppress autoreactive and alloreactive effector T cell function. Recent studies have shown that FOXP3 is an acetylated protein in a large nuclear complex and FOXP3 actively represses transcription by recruiting enzymatic corepressors, including histone modification enzymes. The mechanism by which extracellular stimuli regulate the FOXP3 complex ensemble is currently unknown. Although TGF-β is known to induce murine FOXP3+ Treg cells, TGF-β in combination with IL-6 attenuates the induction of FOXP3 functional activities. Here we show that TCR stimuli and TGF-β signals modulate the disposition of FOXP3 into different subnuclear compartments, leading to enhanced chromatin binding in human CD4+CD25+ regulatory T cells. TGF-β treatment increases the level of acetylated FOXP3 on chromatin and site-specific recruitment of FOXP3 on the human IL-2 promoter. However, the proinflammatory cytokine IL-6 down-regulates FOXP3 binding to chromatin in the presence of TGF-β. Moreover, histone deacetylation inhibitor (HDACi) treatment abrogates the down-regulating effects of IL-6 and TGF-β. These studies indicate that HDACi can enhance regulatory T cell function via promoting FOXP3 binding to chromatin even in a proinflammatory cellular microenvironment. Collectively, our data provide a framework of how different signals affect intranuclear redistribution, posttranslational modifications, and chromatin binding patterns of FOXP3. PMID:18779564

  20. TGF-beta and IL-6 signals modulate chromatin binding and promoter occupancy by acetylated FOXP3.

    Science.gov (United States)

    Samanta, Arabinda; Li, Bin; Song, Xiaomin; Bembas, Kathryn; Zhang, Geng; Katsumata, Makoto; Saouaf, Sandra J; Wang, Qiang; Hancock, Wayne W; Shen, Yuan; Greene, Mark I

    2008-09-16

    Expression of FOXP3, a potent gene-specific transcriptional repressor, in regulatory T cells is required to suppress autoreactive and alloreactive effector T cell function. Recent studies have shown that FOXP3 is an acetylated protein in a large nuclear complex and FOXP3 actively represses transcription by recruiting enzymatic corepressors, including histone modification enzymes. The mechanism by which extracellular stimuli regulate the FOXP3 complex ensemble is currently unknown. Although TGF-beta is known to induce murine FOXP3(+) Treg cells, TGF-beta in combination with IL-6 attenuates the induction of FOXP3 functional activities. Here we show that TCR stimuli and TGF-beta signals modulate the disposition of FOXP3 into different subnuclear compartments, leading to enhanced chromatin binding in human CD4(+)CD25(+) regulatory T cells. TGF-beta treatment increases the level of acetylated FOXP3 on chromatin and site-specific recruitment of FOXP3 on the human IL-2 promoter. However, the proinflammatory cytokine IL-6 down-regulates FOXP3 binding to chromatin in the presence of TGF-beta. Moreover, histone deacetylation inhibitor (HDACi) treatment abrogates the down-regulating effects of IL-6 and TGF-beta. These studies indicate that HDACi can enhance regulatory T cell function via promoting FOXP3 binding to chromatin even in a proinflammatory cellular microenvironment. Collectively, our data provide a framework of how different signals affect intranuclear redistribution, posttranslational modifications, and chromatin binding patterns of FOXP3. PMID:18779564

  1. 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.

  2. 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.

  3. 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. PMID:27008865

  4. 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.

  5. Bill project aiming at prohibiting the exploration and exploitation of unconventional hydrocarbons, and at abrogating exclusive search permits for liquid or gaseous hydrocarbon mines, and aiming at ensuring transparency in the issue of search permits and concessions

    International Nuclear Information System (INIS)

    As offshore drillings and the search for unconventional gas has faced a strong opposition by part of the French population, this bill project (presented mainly by the Socialist group) aims at prohibiting these practices in France, and notably at abrogating some exclusive search permits which have been recently awarded. The authors outline the main motivations of this bill project: these exploitation and mining techniques are very expensive; they have several negative impacts with respect to environment protection commitments like the Grenelle de l'Environnement and the Grenelle de la Mer; these techniques have also an impact on water resources, and generate pollution which impacts water quality as well as ecosystems and biodiversity; some chemical products used by these techniques are carcinogenic (as it already appeared in the USA and in Canada); and finally, the exploitation of unconventional hydrocarbons has a bad carbon assessment. This presentation if followed by the bill project text

  6. 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...

  7. 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.

  8. 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)

  9. Y a-t-il un rapport entre les étymologies du Cratyle et les figures de son et anagrammes d’Héraclite ?

    OpenAIRE

    Mouraviev, Serge

    2014-01-01

    Platon dépeint Cratyle comme un disciple d’Héraclite en se fondant principalement sur son adhésion à la soi-disant théorie du flux universel de ce dernier. Nulle part dans le Cratyle, ni Socrate ni Cratyle ne lui attribuent une croyance dans une correction naturelle des noms. Mais c’est un fait bien établi qu’Héraclite utilisait largement dans son livre, entre autres figures de rhétorique, des structures phoniques extrêmement élaborées, et proposait nombre de jeux de mots « étymologiques » qu...

  10. Ürünlerde Son Kullanma Tarihinin Tüketicilerce Algılanmasına Yönelik Bir Araştırma

    OpenAIRE

    Açıkgözoğlu, Semih

    2006-01-01

    Bu çalışma ürünlerde son kullanma tarihinin tüketicilerce algılanmasına yönelik bir araştırmadır. Anket yoluyla elde edilen bilgilerin istatiksel anlamda ilişkileri incelenmiştir. Sonuç olarak tüketicilerin son kullanma tarihine dikkat ettikleri ve tüketicilik bilincinin ülkemizde de oluşmaya başladığı anlaşılmıştır.

  11. Quarkonium Binding and Entropic Force

    CERN Document Server

    Satz, Helmut

    2015-01-01

    A Q-Qbar bound state represents a balance between repulsive kinetic and attractive potential energy. In a hot quark-gluon plasma, the interaction potential experiences medium effects. Color screening modifies the attractive binding force between the quarks, while the increase of entropy with Q-Qbar separation gives rise to a growing repulsion. We study the role of these phenomena for in-medium Q-Qbar binding and dissociation. It is found that the relevant potential for Q-Qbar binding is the free energy F; with increasing Q-Qbar separation, further binding through the internal energy U is compensated by repulsive entropic effects.

  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. 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. PMID:27342948

  14. 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.

  15. 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.

  16. 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.

  17. Alcohol Binding to the Odorant Binding Protein LUSH: Multiple Factors Affecting Binding Affinities

    OpenAIRE

    Ader, Lauren; Jones, David N. M.; Lin, Hai

    2010-01-01

    Density function theory (DFT) calculations have been carried out to investigate the binding of alcohols to the odorant binding protein LUSH from Drosophila melanogaster. LUSH is one of the few proteins known to bind to ethanol at physiologically relevant concentrations and where high-resolution structural information is available for the protein bound to alcohol at these concentrations. The structures of the LUSH–alcohol complexes identify a set of specific hydrogen-bonding interactions as cr...

  18. 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

  19. Programming of neurotoxic cofactor CXCL-10 in HIV-1-associated dementia: abrogation of CXCL-10-induced neuro-glial toxicity in vitro by PKC activator

    Directory of Open Access Journals (Sweden)

    Mehla Rajeev

    2012-10-01

    Full Text Available Abstract Background More than 50% of patients undergoing lifelong suppressive antiviral treatment for HIV-1 infection develop minor HIV-1-associated neurocognitive disorders. Neurological complications during HIV-1 infection are the result of direct neuronal damage by proinflammatory products released from HIV-1-infected or -uninfected activated lymphocytes, monocytes, macrophages, microglia and astrocytes. The specific pro-inflammatory products and their roles in neurotoxicity are far from clear. We investigated proinflammatory cytokines and chemokines in the cerebrospinal fluid (CSF of HIV-demented (HIV-D and HIV-nondemented (HIV-ND patients and studied their affect on neuroglial toxicity. Methods and results Bioplex array showed elevated levels of signatory chemokines or cytokines (IL-6, IFN-γ, CXCL10, MCP-1 and PDGF in the CSF of HIV-D patients (n = 7 but not in that of HIV-ND patients (n = 7. Among the signatory cytokines and chemokines, CXCL10 was distinctly upregulated in-vitro in HIV-1 (NLENG1-activated human fetal astrocytes, HIV-1 (Ba-L-infected macrophages, and HIV-1 (NLENG1-infected lymphocytes. Virus-infected macrophages also had increased levels of TNF-α. Consistently, human fetal astrocytes treated with HIV-1 and TNF-α induced the signatory molecules. CXCL10 in combination with HIV-1 synergistically enhanced neuronal toxicity and showed chemotactic activity (~ 40 fold for activated peripheral blood mononuclear cells (PBMC, suggesting the intersection of signaling events imparted by HIV-1 and CXCL10 after binding to their respective surface receptors, CXCR4 and CXCR3, on neurons. Blocking CXCR3 and its downstream MAP kinase (MAPK signaling pathway suppressed combined CXCL10 and HIV-1-induced neurotoxicity. Bryostatin, a PKC modulator and suppressor of CXCR4, conferred neuroprotection against combined insult with HIV-1 and CXCL10. Bryostatin also suppressed HIV-1 and CXCL10-induced PBMC chemotaxis. Although, therapeutic targeting

  20. 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.

  1. «¿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.

  2. 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.

  3. Polyandrous females provide sons with more competitive sperm: Support for the sexy-sperm hypothesis in the rattlebox moth (Utetheisa ornatrix).

    Science.gov (United States)

    Egan, Andrea L; Hook, Kristin A; Reeve, H Kern; Iyengar, Vikram K

    2016-01-01

    Given the costs of multiple mating, why has female polyandry evolved? Utetheisa ornatrix moths are well suited for studying multiple mating in females because females are highly polyandrous over their life span, with each male mate transferring a substantial spermatophore with both genetic and nongenetic material. The accumulation of resources might explain the prevalence of polyandry in this species, but another, not mutually exclusive, possibility is that females mate multiply to increase the probability that their sons will inherit more-competitive sperm. This latter "sexy-sperm" hypothesis posits that female multiple mating and male sperm competitiveness coevolve via a Fisherian runaway process. We tested the sexy-sperm hypothesis by using competitive double matings to compare the sperm competition success of sons of polyandrous versus monandrous females. In accordance with sexy-sperm theory, we found that in 511 offspring across 17 families, the male whose polyandrous mother mated once with each of three different males sired significantly more of all total offspring (81%) than did the male whose monandrous mother was mated thrice to a single male. Interestingly, sons of polyandrous mothers had a significantly biased sex ratio of their brood toward sons, also in support of the hypothesis. PMID:26626578

  4. 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.

  5. 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

    ... COMMISSION In the Matter of L. Luria & Son, Inc., Lew Corp. (n/k/a Questus Global Limited), Library Bureau...., Lindatech, Inc., Littlefield, Adams & Company, and Liuski International, Inc.; Order of Suspension of... Lew Corp. (n/k/a Questus Global Limited) because it has not filed any periodic reports since...

  6. "We Txt 2 Sty Cnnectd": An African American Mother and Son Communicate: Digital Literacies, Meaning-Making, and Activity Theory Systems

    Science.gov (United States)

    Lewis, Tisha Y.

    2013-01-01

    This research demonstrated how an African American mother and son communicated via texting and instant messaging at home. Data from a 2007 larger ethnographic case study of a family's digital literacy practices were collected and analyzed. Situated within the framework of New Literacy Studies and multimodality, this research explored: (a) how and…

  7. 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, a...

  8. 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)

  9. Legacies and Memorializations in the Intergenerational Transmission of Psychic Life: Psychoanalytic Notes on Some of the Ways in Which Sons Assume Their Father's Mantle.

    Science.gov (United States)

    Barratt, Barnaby B

    2016-04-01

    The intergenerational transmission of psychic life has been difficult to explore psychoanalytically given that a treatment of both parent and child is rarely, if ever, feasible. Here the issue is explored in terms of father-son relationships. Three legendary fathers (Abraham, Laius, Shiva) are discussed as illustrating the filicidal legacy they imposed psychically and corporeally on their sons. Three contemporary case vignettes are then presented, indicating ways in which sons ambivalently memorialize their fathers. This material provides a model as to some of the ways in which sons assume the mantle of the father's conscious and unconscious dynamics in the course of their personal history. Paternal legacies generate "memorializations" that express profound and poignant conflicts animating the son's psychic life. In the context of this investigation, the significance of the distinction between actual fathers or father figures (who are mortal, who possess some sort of gendered qualities, and who may be present or absent, emotionally and physically) and the "symbolic father" (who is the locus of the phallus that organizes the possibility of representational discourse) is discussed. It is suggested that boys and men typically develop in terms of confusions around this distinction. The oedipal conundrum and challenge of the boy's passage into manhood is then formulated as follows: Masculinity involves both the integration of patricidal desire (in response to the paternal legacy) and the mourning of actual fathers or father figures. It also involves the acceptance of the human condition, which is both that of mortality and of our "castratedness" in relation to the "symbolic father" as the locus of the phallus (the only one who knows whereof "He" speaks and acts, and who can neither be mourned nor surpassed). PMID:27042981

  10. DNA binding and condensation properties of the herpes simplex virus type 1 triplex protein VP19C.

    Directory of Open Access Journals (Sweden)

    Alakesh Bera

    Full Text Available Herpesvirus capsids are regular icosahedrons with a diameter of a 125 nm and are made up of 162 capsomeres arranged on a T = 16 lattice. The capsomeres (VP5 interact with the triplex structure, which is a unique structural feature of herpesvirus capsid shells. The triplex is a heterotrimeric complex; one molecule of VP19C and two of VP23 form a three-pronged structure that acts to stabilize the capsid shell through interactions with adjacent capsomeres. VP19C interacts with VP23 and with the major capsid protein VP5 and is required for the nuclear localization of VP23. Mutation of VP19C results in the abrogation of capsid shell synthesis. Analysis of the sequence of VP19C showed the N-terminus of VP19C is very basic and glycine rich. It was hypothesized that this domain could potentially bind to DNA. In this study an electrophoretic mobility shift assay (EMSA and a DNA condensation assay were performed to demonstrate that VP19C can bind DNA. Purified VP19C was able to bind to both a DNA fragment of HSV-1 origin as well as a bacterial plasmid sequence indicating that this activity is non-specific. Ultra-structural imaging of the nucleo-protein complexes revealed that VP19C condensed the DNA and forms toroidal DNA structures. Both the DNA binding and condensing properties of VP19C were mapped to the N-terminal 72 amino acids of the protein. Mutational studies revealed that the positively charged arginine residues in this N-terminal domain are required for this binding. This DNA binding activity, which resides in a non-conserved region of the protein could be required for stabilization of HSV-1 DNA association in the capsid shell.

  11. 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

  12. 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.

  13. ¿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

  14. 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

  15. ¿Son válidas las curvas y tablas de crecimiento españolas actuales?

    Directory of Open Access Journals (Sweden)

    T. Durá Travé

    2012-02-01

    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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. [3]tetrahydrotrazodone binding. Association with serotonin binding sites

    International Nuclear Information System (INIS)

    High (17 nM) and low (603 nM) affinity binding sites for [3]tetrahydrotrazodone ([3] THT), a biologically active analogue of trazodone, have been identified in rat brain membranes. The substrate specificity, concentration, and subcellular and regional distributions of these sites suggest that they may represent a component of the serotonin transmitter system. Pharmacological analysis of [3]THT binding, coupled with brain lesion and drug treatment experiments, revealed that, unlike other antidepressants, [3] THT does not attach to either a biogenic amine transporter or serotonin binding sites. Rather, it would appear that [3]THT may be an antagonist ligand for the serotonin binding site. This probe may prove of value in defining the mechanism of action of trazodone and in further characterizing serotonin receptors

  1. 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

    2016-01-01

    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. PMID:26808502

  2. 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.

  3. Structure-function analysis of the extracellular domains of the Duffy antigen/receptor for chemokines: characterization of antibody and chemokine binding sites.

    Science.gov (United States)

    Tournamille, Christophe; Filipe, Anne; Wasniowska, Kazimiera; Gane, Pierre; Lisowska, Elwira; Cartron, Jean-Pierre; Colin, Yves; Le Van Kim, Caroline

    2003-09-01

    The Duffy antigen/receptor for chemokines (DARC), a seven-transmembrane glycoprotein carrying the Duffy (Fy) blood group, acts as a widely expressed promiscuous chemokine receptor. In a structure-function study, we analysed the binding of chemokines and anti-Fy monoclonal antibodies (mAbs) to K562 cells expressing 39 mutant forms of DARC with alanine substitutions spread out on the four extracellular domains (ECDs). Using synthetic peptides, we defined previously the Fy6 epitope (22-FEDVW-26), and we characterized the Fya epitope as the linear sequence 41-YGANLE-46. In agreement with these results, mutations of F22-E23, V25 and Y41, G42, N44, L45 on ECD1 abolished the binding of anti-Fy6 and anti-Fya mAbs to K562 cells respectively, Anti-Fy3 binding was abolished by D58-D59 (ECD1), R124 (ECD2), D263 and D283 (ECD4) substitutions. Mutations of C51 (ECD1), C129 (ECD2), C195 (ECD3) and C276 (ECD4 severely reduced anti-Fy3 and CXC-chemokine ligand 8 (CXCL-8) binding. CXCL-8 binding was also abrogated by mutations of F22-E23, P50 (ECD1) and D263, R267, D283 (ECD4). These results defined the Fya epitope and suggested that (1) two disulphide bridges are involved in the creation of an active chemokine binding pocket; (2) a limited number of amino acids in ECDs 1-4 participate in CXCL-8 binding; and (3) Fy3 is a conformation-dependent epitope involving all ECDs. We also showed that N-glycosylation of DARC occurred on N16SS and did not influence antibody and chemokine binding. PMID:12956774

  4. Structural studies of sugar binding proteins

    OpenAIRE

    Sooriyaarachchi, Sanjeewani

    2010-01-01

    Binding proteins, which are themselves non-enzymatic, play an important role in enzymatic reactions as well as non-enzymatic processes by providing a binding platform for the specific recognition of particular molecules. For example, periplasmic binding proteins play a vital role in nutrient uptake in Gram-negative bacteria. In the present study, three sugar binding proteins, including two periplasmic binding proteins and a β-glucan binding protein, are described. The glucose/galactose bindin...

  5. 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.

  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. 现代文明中的爱情悲剧%The Traglc Love in Modern Civilization·On lawrence's Sons and Lovers

    Institute of Scientific and Technical Information of China (English)

    曾文雄

    2001-01-01

    Lawrence's Sons and Lover reflects the people in modern civilization are killed off their capacity and emotions to respond to the natural beauty and the loveliness in the human being. There are conflicts in pursuing :instinct, rationality and spirituality.Through the discussion on the hero's tragiclove stories, we can find only if hese conflicts can be solved,perfect humanity will be gained·

  8. A Buffett turns to farming in Africa: Warren's son Howard has quietly become a player in the fight against global hunger

    OpenAIRE

    Kilman, S.; Thurow, R.

    2009-01-01

    Metadata only record Warren Buffet's fourth son, Howard Buffet is an unassuming Illinois soybean and corn farmer. However, he plays a behind the scenes role in the global war against hunger. With a small portion of his father's fortune he spends much of the year traveling through Africa. Mr. Buffett is looking for ways to help African farmers increase their harvests without increasing their costs, thus his interest in developing plants that resist disease and drought.

  9. A new family of N dimensional superintegrable double singular oscillators and quadratic algebra Q(3) ⨁ so(n) ⨁ so(N-n)

    International Nuclear Information System (INIS)

    We introduce a new family of N dimensional quantum superintegrable models consisting of double singular oscillators of type (n, N-n). The special cases (2,2) and (4,4) have previously been identified as the duals of 3- and 5-dimensional deformed Kepler–Coulomb systems with u(1) and su(2) monopoles, respectively. The models are multiseparable and their wave functions are obtained in (n, N-n) double-hyperspherical coordinates. We obtain the integrals of motion and construct the finitely generated polynomial algebra that is the direct sum of a quadratic algebra Q(3) involving three generators, so(n), so(N-n) (i.e. Q(3) ⨁ so(n) ⨁ so(N-n)). The structure constants of the quadratic algebra itself involve the Casimir operators of the two Lie algebras so(n) and so(N-n). Moreover, we obtain the finite dimensional unitary representations (unirreps) of the quadratic algebra and present an algebraic derivation of the degenerate energy spectrum of the superintegrable model. (paper)

  10. 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.

  11. Phosphorylation of HPV-16 E2 at serine 243 enables binding to Brd4 and mitotic chromosomes.

    Directory of Open Access Journals (Sweden)

    Szu-Wei Chang

    Full Text Available The papillomavirus E2 protein is involved in the maintenance of persistent infection and known to bind either to cellular factors or directly to mitotic chromosomes in order to partition the viral genome into the daughter cells. However, how the HPV-16 E2 protein acts to facilitate partitioning of the viral genome remains unclear. In this study, we found that serine 243 of HPV-16 E2, located in the hinge region, is crucial for chromosome binding during mitosis. Bromodomain protein 4 (Brd4 has been identified as a cellular binding target through which the E2 protein of bovine papillomavirus type 1 (BPV-1 tethers the viral genome to mitotic chromosomes. Mutation analysis showed that, when the residue serine 243 was substituted by glutamic acid or aspartic acid, whose negative charges mimic the effect of constitutive phosphorylation, the protein still can interact with Brd4 and colocalize with Brd4 in condensed metaphase and anaphase chromosomes. However, substitution by the polar uncharged residues asparagine or glutamine abrogated Brd4 and mitotic chromosome binding. Moreover, following treatment with the inhibitor JQ1 to release Brd4 from the chromosomes, Brd4 and E2 formed punctate foci separate from the chromosomes, further supporting the hypothesis that the association of the HPV-16 E2 protein with the chromosomes is Brd4-dependent. In addition, the S243A E2 protein has a shorter half-life than the wild type, indicating that phosphorylation of the HPV-16 E2 protein at serine 243 also increases its half-life. Thus, phosphorylation of serine 243 in the hinge region of HPV-16 E2 is essential for interaction with Brd4 and required for host chromosome binding.

  12. 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

  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. 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.

  15. Probing protein phosphatase substrate binding

    DEFF Research Database (Denmark)

    Højlys-Larsen, Kim B.; Sørensen, Kasper Kildegaard; Jensen, Knud Jørgen;

    2012-01-01

    profile of the integrin-linked kinase associated phosphatase (ILKAP), a member of the protein phosphatase 2C (PP2C) family. Phosphatases can potentially dephosphorylate these phosphopeptide substrates but, interestingly, performing the binding studies at 4 °C allowed efficient binding to phosphopeptides...... 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.......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...

  16. Water binding in legume seeds

    Science.gov (United States)

    Vertucci, C. W.; Leopold, A. C.

    1987-01-01

    The physical status of water in seeds has a pivotal role in determining the physiological reactions that can take place in the dry state. Using water sorption isotherms from cotyledon and axis tissue of five leguminous seeds, the strength of water binding and the numbers of binding sites have been estimated using van't Hoff analyses and the D'Arcy/Watt equation. These parameters of water sorption are calculated for each of the three regions of water binding and for a range of temperatures. Water sorption characteristics are reflective of the chemical composition of the biological materials as well as the temperature at which hydration takes place. Changes in the sorption characteristics with temperature and hydration level may suggest hydration-induced structural changes in cellular components.

  17. 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

  18. 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.

  19. 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.

  20. Skyrmions with low binding energies

    Directory of Open Access Journals (Sweden)

    Mike Gillard

    2015-06-01

    Full Text Available Nuclear binding energies are investigated in two variants of the Skyrme model: the first replaces the usual Skyrme term with a term that is sixth order in derivatives, and the second includes a potential that is quartic in the pion fields. Solitons in the first model are shown to deviate significantly from ansätze previously assumed in the literature. The binding energies obtained in both models are lower than those obtained from the standard Skyrme model, and those obtained in the second model are close to the experimental values.

  1. Skyrmions with low binding energies

    Energy Technology Data Exchange (ETDEWEB)

    Gillard, Mike, E-mail: m.n.gillard@leeds.ac.uk; Harland, Derek, E-mail: d.g.harland@leeds.ac.uk; Speight, Martin, E-mail: speight@maths.leeds.ac.uk

    2015-06-15

    Nuclear binding energies are investigated in two variants of the Skyrme model: the first replaces the usual Skyrme term with a term that is sixth order in derivatives, and the second includes a potential that is quartic in the pion fields. Solitons in the first model are shown to deviate significantly from ansätze previously assumed in the literature. The binding energies obtained in both models are lower than those obtained from the standard Skyrme model, and those obtained in the second model are close to the experimental values.

  2. 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.

  3. Inhibition of calcineurin abrogates while inhibition of mTOR promotes regulatory T cell expansion and graft-versus-host disease protection by IL-2 in allogeneic bone marrow transplantation.

    Directory of Open Access Journals (Sweden)

    Atsushi Satake

    Full Text Available Regulatory T cells (Tregs attenuate excessive immune responses, making their expansion beneficial in immune-mediated diseases including allogeneic bone marrow transplantation (BMT-associated graft-versus-host disease (GVHD. We have recently reported that Treg expansion does not require phospholipase Cγ activation when IL-2 is provided. As such, the combination of IL-2 and a calcineurin inhibitor (Cyclosporine A; CsA expands Tregs while inhibiting Tconv proliferation and protects against a mouse model of multiple sclerosis. However, CsA inhibits Treg proliferation in the presence of a TCR stimulus, suggesting that CsA may negatively impact Treg proliferation when they receive strong allogeneic MHC-mediated TCR signals. In this study, we show that CsA inhibits Treg proliferation and inducible Treg generation in allogeneic but not in syngeneic BMT when IL-2 is provided. In contrast to CsA, the mTOR inhibitor (Rapamycin almost completely suppressed IL-2-mediated Treg proliferation. However, CsA and Rapamycin inhibited Treg proliferation to a similar extent when TCR stimulation was provided. Furthermore, Rapamycin promoted Treg expansion and inducible Treg generation in allogeneic BMT recipients treated with IL-2. Consistent with these observations, CsA abrogated while Rapamycin promoted the protective effect of IL-2 on allogeneic BMT-induced GVHD. These results suggest that while CsA permits IL-2-induced Treg proliferation in the syngeneic setting (absence of strong TCR signals, CsA in combination with IL-2 may be detrimental for Treg proliferation in an allogeneic setting. Thus, in allogeneic settings, an mTOR inhibitor such as Rapamycin is a better choice for adjunct therapy with IL-2 in expansion of Tregs and protection against allogeneic BMT-induced GVHD.

  4. 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. PMID:25036607

  5. 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.

  6. 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. PMID:25391811

  7. 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.

  8. 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...

  9. BINDING ISOTHERMS SURFACTANT-PROTEINS

    OpenAIRE

    Elena Irina Moater; Cristiana Radulescu; Ionica Ionita

    2011-01-01

    The interactions between surfactants and proteins shows some similarities with interactions between surfactants and polymers, but the hydrophobic amphoteric nature of proteins and their secondary and tertiary structure components make them different from conventional polymer systems. Many studies from the past about surfactant - proteins bonding used the dialysis techniques. Other techniques used to determine the binding isotherm, included ultrafiltration, ultracentrifugation, potentiometry, ...

  10. Cellulose binding domain fusion proteins

    Energy Technology Data Exchange (ETDEWEB)

    Shoseyov, Oded (Karmey Yosef, IL); Shpiegl, Itai (Rehovot, IL); Goldstein, Marc A. (Davis, CA); Doi, Roy H. (Davis, CA)

    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.

  11. Poškodbe mladih sadik navadnega divjega kostanja (Aesculus hippocastanum L.) zaradi sončevega ožiga

    OpenAIRE

    Žitnik, Denis

    2014-01-01

    Pri pregledu zdravstvenega stanja drevoreda navadnih divjih kostanjev (Aesculus hippocastanum L.) na Cesti v mestni log v Mestni občini Ljubljana smo opazili številne neprerasle poškodbe na deblih dreves zaradi sončevega ožiga. Za potrebe nadaljnjih raziskav je bilo meseca aprila 2009 iz drevoreda odstranjenih sedem dreves. Drevesa so bila podrobno preiskana, nato pa smo jihrazžagali na kolute iz katerih smo pridobili posamezne vzorce za naše raziskave. Vlažnost lesa smo določili gravimetričn...

  12. The Portrayal of White Organized Racists Characters on Television : How White Organized Racist Characters are Portrayed in Oz, Sons of Anarchy, and Justified

    OpenAIRE

    2012-01-01

    The purpose of this thesis is to look at how white organized racist characters are portrayed on television by taking a closer look at the white organized racist characters portrayed in Oz, Sons of Anarchy and Justified. It will look closer at how the social class and social status of these characters have been defined and portrayed. It will also look at how the white organized racist characters perform their gender and what types of masculinity they display, and analyze the usage of racist sy...

  13. Relation entre la carie du blé (Tilletia spp.) et son environnement, et propositions de recherches futures pour des agriculteurs en mode de production biologique

    OpenAIRE

    Vidal, Alix

    2012-01-01

    Le rapport se divise en cinq grandes parties : Présentation du contexte de l’étude, recherche bibliographique, matériel et méthodes, résultats et discussion et enfin, les perspectives pour la recherche future. Cette étude comporte deux objectifs principaux. Le premier est de mettre en relation la carie du blé (causée par Tilletia spp.)avec son environnement au sens large. Le second est de proposer des nouveaux angles d’approches pour la recherche future, en accord avec les agriculteurs en mod...

  14. Funciones del sueño en un auto de Calderón: Sueños hay que verdad son (1670)

    OpenAIRE

    Gilbert, Françoise

    2005-01-01

    International audience SUMMARY:This study seeks to analyze the different functions of dream in the auto of Calderón, Sueños hay que verdad son (1670), which is based on some episodes from Josef's life in Genesis. Beginning with the structuring function of dream, in Bible stories, I study the dramatic function of this motif in this auto, within the sacramental frame of a double reading: historial and allegorical. After first establishing the structure of the work based on its metrical organ...

  15. Proposal of a new model for dose calculation due to the inhalation of Ru-222, Ru-220 and their sons with brief half-life

    International Nuclear Information System (INIS)

    The consequences of the radiation interactions upon the human body are studied. In order to simulate by computer the radiation interaction of the atoms of radon and thoron atoms and their Sons with a brief half life inhaled with the cells, the compartimental dosimetric model is used. The metabolic pathway of those radionuclides is described by continuous medium dynamic differential equation. The energy transfer processes are seen in details. The individual retention function is determined by bio-analysis. The results of internal dosimetry are consistents with the new international recommendations from ICRP-32. (L.F.S.)

  16. Death of a Son is Associated With Risk of Suicide Among Parous Women in Taiwan: A Nested Case-Control Study

    OpenAIRE

    Chen, Chih-Cheng; Kuo, Chien-Chun; Wu, Trong-Neng; Yang, Chun-Yuh

    2012-01-01

    Background The impact of the sex of a deceased child on maternal suicide has not been studied. We examined whether the death of a child, especially a son, increased the risk of suicide among parous Taiwanese women. Methods This matched case-control study was done within a cohort of 1 292 462 Taiwanese women who experienced a first and singleton childbirth between 1 January 1978 and 31 December 1987 and were followed up until 31 December 2008. From the cohort, 2701 suicide cases were identifie...

  17. ¿SON LAS CAJAS DE AHORROS DE CASTILLA Y LEÓN SOCIALMENTE RESPONSABLES?. INFLUENCIA DE SU OBRA SOCIAL EN EL DESEMPEÑO EMPRESARIAL /

    OpenAIRE

    Marbella Sánchez, F.; Martínez Campillo, A.; Cabeza García, L.

    2008-01-01

    Los objetivos de este trabajo son realizar un estudio descriptivo de la evolución del gasto en obra social de las Cajas de Ahorros de Castilla y León durante el periodo 2000-2004, así como analizar el efecto de dicha inversión sobre el desempeño empresarial. Los resultados obtenidos muestran un crecimiento relativamente bajo de la dotación a obra social, siendo el área que más presupuesto recibe la de Cultura y Tiempo Libre, y una influencia positiva y significativa de la misma sobre la cuota...

  18. Influência das vogais na estimulabilidade dos sons líquidos Vowels influence in the stimulability for liquid sounds

    Directory of Open Access Journals (Sweden)

    Márcia Mathias de Castro

    2009-01-01

    Full Text Available OBJETIVO: verificar o número de crianças, entre 5:0 e 11:6 anos, com e sem Transtorno Fonológico, falantes do Português Brasileiro que imitaram corretamente os sons líquidos no teste de estimulabilidade considerando cada uma das vogais subsequentes. MÉTODOS: a estimulabilidade foi medida por uma prova de imitação de 63 sílabas com os sons com as sete vogais orais, em três repetições. Foi analisada a porcentagem de sujeitos que produziu corretamente os sons em função da vogal subsequente. RESULTADOS: o foi o som com mais produções corretas, independente da vogal subsequente; o foi melhor produzido com as vogais subsequentes [ε, ó], parecendo ser a altura da língua em posição média-baixa facilitadora da produção desse som; o foi melhor produzido com as vogais subsequentes arredondadas [o, ó, u] evidenciando que o gesto articulatório de arredondamento dos lábios facilita a produção deste som, assim como a posição média-alta e posterior da língua. CONCLUSÃO: as vogais subsequentes aos sons líquidos estudados evidenciam influências em suas produções, de forma a facilitá-las.PURPOSE: to check the number of children, between 5:0 and 11:6-year old, with and without Phonological Disorder, Brazilian Portuguese speaking children that imitated correctly the liquid sounds in the stimulability test considering each one of the subsequent vowels. METHODS: the stimulability was measured in syllable imitation of 63 syllables with the sounds with seven oral vowels. We analyzed the percentage of subjects that produced correctly the sounds as a function of the subsequent vowel. RESULTS: the was the sound with more correct productions, independent of the sequent vowel; the was better produced with the vowels [ε, ó], and it seems that the medium-lower position height of the tongue is make easier the production of this sound; the was better produced with the vowels [o, ó, u], it seems that the round position of the lips

  19. Diseño de un sistema integrado de aprovechamiento de aguas grises y pluviales en el hotel rural de Son Xotano (Sencelles, Mallorca)

    OpenAIRE

    Ramonell Fernández, Pedro

    2007-01-01

    El presente proyecto estudia y analiza la gestión del agua en una instalación hotelera de pequeña envergadura, con el objetivo de conseguir un ahorro de dicho recurso mediante la reutilización principalmente. La edificación estudiada es el hotel rural Son Xotano****, en el término municipal de Sencelles (Mallorca), ubicado en el centro de la isla. Para conseguir dicho objetivo, se ha basado el trabajo en una de las soluciones que se barajan actualmente para tal fin: el reciclaj...

  20. 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.

  1. Selection of IgE-binding aptameric green fluorescent protein (Ap-GFP) by the ribosome display (RD) platform

    International Nuclear Information System (INIS)

    GFP-Cκ fusion protein was previously shown selectable on ribosome display platform with solid phase antibodies against GFP determinant [Y.-M. Yang, T.J. Barankiewicz, M. He, M. Taussig, S.-S. Chen, Selection of antigenic markers on a GFP-Cκ fusion scaffold with high sensitivity by eukaryotic ribosome display, Biochem. Biophys. Res. Commun. 359 (2007) 251-257]. Herein, we show that members of aptameric peptide library constructed within the site 6 and site 8/9 loops of GFP of the ribosome display construct are selectable upon binding to the solid phase IgE antigen. An input of 1.0 μg of the dual site aptameric GFP library exhibiting a diversity of 7.5 x 1011 was transcribed, translated and incubated with solid phase IgE. RT-PCR products were amplified from mRNA of the aptamer-ribosome-mRNA (ARM) complex captured on the solid phase IgE. Clones of aptameric GFP were prepared from RT-PCR product of ARM complex following repetitive selection. Recombinant aptameric GFP proteins from the selected clones bind IgE coated on the 96-well plate, and the binding was abrogated by incubation with soluble human IgE but not human IgG. Selected aptameric GFP proteins also exhibit binding to three different sources of human IgE (IgE PS, BED, and JW8) but not irrelevant proteins. These observations indicate that appropriately selected aptameric GFP on a solid phase ligand by ribosome display may serve as an affinity reagent for blocking reactivity of a biological ligand

  2. 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.

  3. Antimicrobial Peptide-Lipid Binding Interactions and Binding Selectivity

    OpenAIRE

    Lad, Mitaben D.; Birembaut, Fabrice; Clifton, Luke A.; Frazier, Richard A.; Webster, John R. P.; Green, Rebecca J.

    2007-01-01

    Surface pressure measurements, external reflection-Fourier transform infrared spectroscopy, and neutron reflectivity have been used to investigate the lipid-binding behavior of three antimicrobial peptides: melittin, magainin II, and cecropin P1. As expected, all three cationic peptides were shown to interact more strongly with the anionic lipid, 1,2 dihexadecanoyl-sn-glycerol-3-(phosphor-rac-(1-glycerol)) (DPPG), compared to the zwitterionic lipid, 1,2 dihexadecanoyl-sn-glycerol-3-phosphocho...

  4. Characteristics of human erythrocyte insulin binding sites.

    OpenAIRE

    Okada, Yoshio

    1981-01-01

    Insulin and human erythrocyte cell membrane interactions were studied with respect to binding and dissociation. The per cent of specific binding of 125I-labeled insulin to erythrocytes was directly proportional to the cell concentration. The optimum pH for binding was 8.1. The initial binding rate was directly proportional to, and the steady state insulin binding was reversely proportional to, the incubation temperature. The per cent of specific binding of 125I-labeled insulin was 12.10 +/- 1...

  5. 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.

  6. 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. PMID:11952262

  7. 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.

  8. 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.

    Science.gov (United States)

    Daly, Siobhán C; MacNeela, Pádraig; MacNeela, Pádriag; Sarma, Kiran M

    2015-01-01

    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. PMID:26710277

  9. 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.

  10. 论余华小说中的父子关系%On Father and Son in YuHua's Works

    Institute of Scientific and Technical Information of China (English)

    阮崇友; 刘永松

    2015-01-01

    余华小说中的父子关系从充满冷漠、仇视、暴力、死亡的怪异的父子关系,到善良坚强,关爱呵护血浓于水的舐犊情深。形态各异,变化万千,给读者带来了阅读上的革命,本文论述了余华作品中的种种父子关系。从这些关系中让我们更好地了解余华及余华的小说。%In YuHua's works,the relationship between father and son presents different patterns,various changes,which en-dues the readers a revolution in reading.The relationship varys from indifference,hatred,violence,the strange death to kind-ness,strong will,loving care,and the viewpoint of blood is thicker than water and so on.This paper discusses a variety of the relationship between father and son in YuHua's works,from which the readers can understand the author and his works better.

  11. Deletion involving D15S113 in a mother and son without Angelman syndrome: Refinement of the Angelman syndrome critical deletion region

    Energy Technology Data Exchange (ETDEWEB)

    Michaelis, R.C.; Skinner, S.A.; Lethco, B.A. [Greenwood Genetic Center, SC (United States)] [and others

    1995-01-02

    Deletions of 15q11-q13 typically result in Angelman syndrome when inherited from the mother and Prader-Willi syndrome when inherited from the father. The critical deletion region for Angelman syndrome has recently been restricted by a report of an Angelman syndrome patient with a deletion spanning less than 200 kb around the D15S113 locus. We report here on a mother and son with a deletion of chromosome 15 that includes the D15S113 locus. The son has mild to moderate mental retardation and minor anomalies, while the mother has a borderline intellectual deficit and slightly downslanting palpebral fissures. Neither patient has the seizures, excessive laughter and hand clapping, ataxia or the facial anomalies which are characteristic of Angelman syndrome. The proximal boundary of the deletion in our patients lies between the D15S10 and The D15S113 loci. Our patients do not have Angelman syndrome, despite the deletion of the D15S113 marker. This suggests that the Angelman syndrome critical deletion region is now defined as the overlap between the deletion found in the previously reported Angelman syndrome patient and the region that is intact in our patients. 28 refs., 6 figs.

  12. Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Gang G.; Song, Jikui; Wang, Zhanxin; Dormann, Holger L.; Casadio, Fabio; Li, Haitao; Luo, Jun-Li; Patel, Dinshaw J.; Allis, C. David; (MSKCC); (Scripps); (Rockefeller)

    2009-07-21

    Histone H3 lysine4 methylation (H3K4me) has been proposed as a critical component in regulating gene expression, epigenetic states, and cellular identities. The biological meaning of H3K4me is interpreted by conserved modules including plant homeodomain (PHD) fingers that recognize varied H3K4me states. The dysregulation of PHD fingers has been implicated in several human diseases, including cancers and immune or neurological disorders. Here we report that fusing an H3K4-trimethylation (H3K4me3)-binding PHD finger, such as the carboxy-terminal PHD finger of PHF23 or JARID1A (also known as KDM5A or RBBP2), to a common fusion partner nucleoporin-98 (NUP98) as identified in human leukaemias, generated potent oncoproteins that arrested haematopoietic differentiation and induced acute myeloid leukaemia in murine models. In these processes, a PHD finger that specifically recognizes H3K4me3/2 marks was essential for leukaemogenesis. Mutations in PHD fingers that abrogated H3K4me3 binding also abolished leukaemic transformation. NUP98-PHD fusion prevented the differentiation-associated removal of H3K4me3 at many loci encoding lineage-specific transcription factors (Hox(s), Gata3, Meis1, Eya1 and Pbx1), and enforced their active gene transcription in murine haematopoietic stem/progenitor cells. Mechanistically, NUP98-PHD fusions act as 'chromatin boundary factors', dominating over polycomb-mediated gene silencing to 'lock' developmentally critical loci into an active chromatin state (H3K4me3 with induced histone acetylation), a state that defined leukaemia stem cells. Collectively, our studies represent, to our knowledge, the first report that deregulation of the PHD finger, an 'effector' of specific histone modification, perturbs the epigenetic dynamics on developmentally critical loci, catastrophizes cellular fate decision-making, and even causes oncogenesis during mammalian development.

  13. Functional evolution of IGF2:IGF2R domain 11 binding generates novel structural interactions and a specific IGF2 antagonist.

    Science.gov (United States)

    Frago, Susana; Nicholls, Ryan D; Strickland, Madeleine; Hughes, Jennifer; Williams, Christopher; Garner, Lee; Surakhy, Mirvat; Maclean, Rory; Rezgui, Dellel; Prince, Stuart N; Zaccheo, Oliver J; Ebner, Daniel; Sanegre, Sabina; Yu, Sheng; Buffa, Francesca M; Crump, Matthew P; Hassan, Andrew Bassim

    2016-05-17

    Among the 15 extracellular domains of the mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF2R), domain 11 has evolved a binding site for IGF2 to negatively regulate ligand bioavailability and mammalian growth. Despite the highly evolved structural loops of the IGF2:domain 11 binding site, affinity-enhancing AB loop mutations suggest that binding is modifiable. Here we examine the extent to which IGF2:domain 11 affinity, and its specificity over IGF1, can be enhanced, and we examine the structural basis of the mechanistic and functional consequences. Domain 11 binding loop mutants were selected by yeast surface display combined with high-resolution structure-based predictions, and validated by surface plasmon resonance. We discovered previously unidentified mutations in the ligand-interacting surface binding loops (AB, CD, FG, and HI). Five combined mutations increased rigidity of the AB loop, as confirmed by NMR. When added to three independently identified CD and FG loop mutations that reduced the koff value by twofold, these mutations resulted in an overall selective 100-fold improvement in affinity. The structural basis of the evolved affinity was improved shape complementarity established by interloop (AB-CD) and intraloop (FG-FG) side chain interactions. The high affinity of the combinatorial domain 11 Fc fusion proteins functioned as ligand-soluble antagonists or traps that depleted pathological IGF2 isoforms from serum and abrogated IGF2-dependent signaling in vivo. An evolved and reengineered high-specificity M6P/IGF2R domain 11 binding site for IGF2 may improve therapeutic targeting of the frequent IGF2 gain of function observed in human cancer. PMID:27140600

  14. 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.

  15. 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

  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. Dissection of the Critical Binding Determinants of Cellular Retinoic Acid Binding Protein II by Mutagenesis and Fluorescence Binding Assay

    OpenAIRE

    Vasileiou, Chrysoula; Lee, Kin Sing Stephen; Crist, Rachael M.; Vaezeslami, Soheila; Goins, Sarah M.; Geiger, James H.; Borhan, Babak

    2009-01-01

    The binding of retinoic acid to mutants of Cellular Retinoic Acid Binding Protein II (CRABPII) was evaluated to better understand the importance of the direct protein/ligand interactions. The important role of Arg111 for the correct structure and function of the protein was verified and other residues that directly affect retinoic acid binding have been identified. Furthermore, retinoic acid binding to CRABPII mutants that lack all previously identified interacting amino acids was rescued by ...

  18. 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...

  19. Binding effects and nuclear shadowing

    OpenAIRE

    Indumathi, D.; Wei ZHU

    1996-01-01

    The effects of nuclear binding on nuclear structure functions have so far been studied mainly at fixed target experiments, and there is currently much interest in obtaining a clearer understanding of this phenomenon. We use an existing dynamical model of nuclear structure functions, that gives good agreement with current data, to study this effect in a kinematical regime (low $x$, high $Q^2$) that can possibly be probed by an upgrade of {\\sc hera} at {\\sc desy} into a nuclear accelerator.

  20. Calcium binding by dietary fibre

    International Nuclear Information System (INIS)

    Dietary fibre from plants low in phytate bound calcium in proportion to its uronic-acid content. This binding by the non-cellulosic fraction of fibre reduces the availability of calcium for small-intestinal absorption, but the colonic microbial digestion of uronic acids liberates the calcium. Thus the ability to maintain calcium balance on high-fibre diets may depend on the adaptive capacity on the colon for calcium. (author)

  1. Material Binding Peptides for Nanotechnology

    Directory of Open Access Journals (Sweden)

    Urartu Ozgur Safak Seker

    2011-02-01

    Full Text Available Remarkable progress has been made to date in the discovery of material binding peptides and their utilization in nanotechnology, which has brought new challenges and opportunities. Nowadays phage display is a versatile tool, important for the selection of ligands for proteins and peptides. This combinatorial approach has also been adapted over the past decade to select material-specific peptides. Screening and selection of such phage displayed material binding peptides has attracted great interest, in particular because of their use in nanotechnology. Phage display selected peptides are either synthesized independently or expressed on phage coat protein. Selected phage particles are subsequently utilized in the synthesis of nanoparticles, in the assembly of nanostructures on inorganic surfaces, and oriented protein immobilization as fusion partners of proteins. In this paper, we present an overview on the research conducted on this area. In this review we not only focus on the selection process, but also on molecular binding characterization and utilization of peptides as molecular linkers, molecular assemblers and material synthesizers.

  2. 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.

  3. 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.

  4. 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

  5. Bu-Shen-Ning-Xin decoction: inhibition of osteoclastogenesis by abrogation of the RANKL-induced NFATc1 and NF-κB signaling pathways via selective estrogen receptor α

    Directory of Open Access Journals (Sweden)

    Wang L

    2015-07-01

    in osteoclast precursor cells; the inhibitory effect was abolished by methyl-piperidino-pyrazole but not the estrogen receptor β antagonist or androgen receptor antagonist.Conclusion: These results collectively suggest that administration of BSNXD presents inhibitory effects on osteoclast differentiation by abrogating the RANKL-induced nuclear factor of activated T-cells, cytoplasmic 1 and NF-κB signaling pathways downstream of estrogen receptor α, thereby contributing to the inhibitory effect on bone resorption.Keywords: herbal formula, osteoclastogenesis, estrogen receptor α, NF-κB, NFATc1

  6. Solute-vacancy binding in aluminum

    International Nuclear Information System (INIS)

    Previous efforts to understand solute-vacancy binding in aluminum alloys have been hampered by a scarcity of reliable, quantitative experimental measurements. Here, we report a large database of solute-vacancy binding energies determined from first-principles density functional calculations. The calculated binding energies agree well with accurate measurements where available, and provide an accurate predictor of solute-vacancy binding in other systems. We find: (i) some common solutes in commercial Al alloys (e.g., Cu and Mg) possess either very weak (Cu), or even repulsive (Mg), binding energies. Hence, we assert that some previously reported large binding energies for these solutes are erroneous. (ii) Large binding energies are found for Sn, Cd and In, confirming the proposed mechanism for the reduced natural aging in Al-Cu alloys containing microalloying additions of these solutes. (iii) In addition, we predict that similar reduction in natural aging should occur with additions of Si, Ge and Au. (iv) Even larger binding energies are found for other solutes (e.g., Pb, Bi, Sr, Ba), but these solutes possess essentially no solubility in Al. (v) We have explored the physical effects controlling solute-vacancy binding in Al. We find that there is a strong correlation between binding energy and solute size, with larger solute atoms possessing a stronger binding with vacancies. (vi) Most transition-metal 3d solutes do not bind strongly with vacancies, and some are even energetically strongly repelled from vacancies, particularly for the early 3d solutes, Ti and V

  7. Erythropoietin binding protein from mammalian serum

    Energy Technology Data Exchange (ETDEWEB)

    Clemons, G.K.

    1997-04-29

    Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described. 11 figs.

  8. Erythropoietin binding protein from mammalian serum

    Energy Technology Data Exchange (ETDEWEB)

    Clemons, Gisela K. (Berkeley, CA)

    1997-01-01

    Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described.

  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. 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.

  11. El delito de aborto son inconstitucionales (los abortos son homicidios)

    OpenAIRE

    Gustavo González Solano

    2002-01-01

    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 ...

  12. 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.

  13. Conceptualisation de l'esprit entrepreneurial et identification des facteurs de son développement à l'université.

    OpenAIRE

    Rajhi, Nadia,

    2011-01-01

    Cette thèse est consacrée d'une part à la conceptualisation de l'esprit entrepreneurial et d'autre part à l'identification des facteurs de son développement à l'université. L'étude théorique nous a amené à considérer l'esprit entrepreneurial comme un processus mental composé d'un ensemble d'attitudes et de sentiments de compétence favorable à une orientation entrepreneuriale. L'université à côté d'autres facteurs de socialisation pourrait le développer. Et ce en évoluant vers une université e...

  14. 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.

  15. 3 minutes pour développer son intelligence émotionnelle: journal filmé avec une classe d'enfants porteurs d'un handicap physique

    OpenAIRE

    Kozma, Kim; Savoy, Bernard

    2015-01-01

    Comment faire entrer le bonheur, le bien-être et le plaisir d’être ensemble dans ma classe d’enseignement spécialisé avec des enfants porteurs d’un handicap physique ? A la recherche d’une approche différente qui valorise l’humain plutôt que ses performances, je me suis intéressée à une autre forme d’intelligence. Le bonheur est aujourd’hui un sujet qui fascine le grand public et les scientifiques. Que de méthodes pour trouver son équilibre ! Une seule constance : cet équilibre passe par l’ac...

  16. ¿Qué es la investigación en Educación Matemática y cuáles son sus resultados? I

    OpenAIRE

    Gómez, Pedro

    1994-01-01

    Entre el 8 y el 11 de mayo de 1994 tuvo lugar en la Universidad de Maryland la Conferencia ICMI 1994 alrededor del tema ÀQué es la investigación en educación matemática y cuáles son sus resultados? El ICMI es la principal organización internacional de educación matemática. Además de ser el organizador de los ICME, los congresos mundiales de educación matemática que tienen lugar cada cuatro años, el ICMI organiza estudios sobre diferentes temas de la educación matemática. Estos estudios toman ...

  17. Rich Man's Sons and Daughters: Dance with the Soul%《财主底儿女们》:舞蹈着的心灵

    Institute of Scientific and Technical Information of China (English)

    陈传芝

    2012-01-01

    Rich Man's Sons and Daughters presented the spirit as "dance with the soul", which shows not only the vigorous action of the characters, the struggle of the wilderness, backwardness and hesitation of the heavy affection; but also shows the clumsy narration of the young authors.%《财主底儿女们》所呈现的精神样态为“舞蹈着的心灵”,这既表现为作品人物“前进”中的奋力突进、旷野中的挣扎、沉重的温柔所带来的滞缓与迟疑,又表现为年轻的作者呈舞蹈之姿的稚拙叙事。

  18. 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.

  19. 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.

  20. 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 per albumin molecule, and binding of the first sulfamethizole molecule is possibly reduced as well. Diazepam binds with equal affinity to the fetal and adult proteins. Among the two main albumin drug-binding functions, for warfarin and diazepam, the former is thus compromised in the newborn...

  1. 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)

  2. 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.

  3. 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

  4. 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.

  5. Erythropoietin binding sites in human foetal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Pekonen, F.; Rosenloef, K.; Rutanen, E.-M.

    1987-01-01

    Using /sup 125/I labelled recombinant DNA human erythropoietin (EP), we have explored the presence and properties of EP binding sites in foetal human tissues. The EP binding site is present in the foetal liver already during the first trimester of pregnancy. The binding site has a equilibrium association constant of 4.1-6.2 x 10/sup 9/l/mol and is specific for EP. The cross-reactivities of FSH, TSH, hCG, insulin and renin substrate were less than 0.01%. The EP binding capacity of foetal liver was 5.4-16 fmol/mg membrane protein. In foetal lung tissue, a slight EP binding activity was observed, whereas foetal spleen, muscle, brain, thyroid and placental tissues were virtually devoid of EP binding capacity. The same level of binding was reached at 37 deg. C in 1 h and at 4 deg. C in 24 h. The binding was pH-dependent with maximal specific binding at pH 7.7. SDS-PAGE gel electrophoresis analysis of covalently cross-linked /sup 125/I-EP to foetal liver membranes suggested that the EP binding site was composed of two subunits with an apparent mol wt of 41000 and 86000 dalton, respectively.

  6. Binding characteristics of swine erythrocyte insulin receptors

    International Nuclear Information System (INIS)

    Crossbred gilts had 8.8 +/- 1.1% maximum binding of [125I]insulin to insulin receptors on erythrocytes. The number of insulin-binding sites per cell was 137 +/- 19, with a binding affinity ranging from 7.4 X 10(7)M-1 to 11.2 X 10(7)M-1 and mean of 8.8 X 10(7)M-1. Pregnant sows had a significant increase in maximum binding due to an increase in number of receptor sites per cell. Lactating sows fed a high-fiber diet and a low-fiber diet did not develop a significant difference in maximum binding of insulin. Sows fed the low-fiber diet had a significantly higher number of binding sites and a significantly lower binding affinity than did sows fed a high-fiber diet. Receptor-binding affinity was lower in the low-fiber diet group than in cycling gilts, whereas data from sows fed the high-fiber diet did not differ from data for cycling gilts. Data from this study indicated that insulin receptors of swine erythrocytes have binding characteristics similar to those in other species. Pregnancy and diet will alter insulin receptor binding in swine

  7. Erythropoietin binding sites in human foetal tissues

    International Nuclear Information System (INIS)

    Using 125I labelled recombinant DNA human erythropoietin (EP), we have explored the presence and properties of EP binding sites in foetal human tissues. The EP binding site is present in the foetal liver already during the first trimester of pregnancy. The binding site has a equilibrium association constant of 4.1-6.2 x 109l/mol and is specific for EP. The cross-reactivities of FSH, TSH, hCG, insulin and renin substrate were less than 0.01%. The EP binding capacity of foetal liver was 5.4-16 fmol/mg membrane protein. In foetal lung tissue, a slight EP binding activity was observed, whereas foetal spleen, muscle, brain, thyroid and placental tissues were virtually devoid of EP binding capacity. The same level of binding was reached at 37 deg. C in 1 h and at 4 deg. C in 24 h. The binding was pH-dependent with maximal specific binding at pH 7.7. SDS-PAGE gel electrophoresis analysis of covalently cross-linked 125I-EP to foetal liver membranes suggested that the EP binding site was composed of two subunits with an apparent mol wt of 41000 and 86000 dalton, respectively. (author)

  8. 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.

  9. Two distinct classes of IgG Fc receptors on a human monocyte line (U937) defined by differences in binding of murine IgG subclasses at low ionic strength

    International Nuclear Information System (INIS)

    Two distinct classes of IgG Fc receptors (FcR) on cells of a human monocytic line (U937) by analyzing the direct binding of murine IgG subclasses in medium of low ionic strength. Four lines of evidence support this contention. (1) The binding of aggregated murine IgB2b (AggmIgG2b) to U937 and Daudi cells was enhanced at low ionic strength, whereas monomeric murine IgG2a (mIgG2a) did not bind to Daudi cells and its high affinity binding to U937 cells was unaffected by changes in ionic strength. (2) Double reciprocal inhibition experiments with U937 cells indicated that the binding of both ligands was inhibited 30 to 135 times more efficiently by the homologous ligand than by the heterologous one. That is, the binding of 125I-AggmIgG2b was inhibited 50% by 3.5 μg/ml of AggmIgG2b and 100 μg/ml of mIgG2a. Similarly, the binding of 125I-mIgG2a was inhibited 50% by 2.5 μg/ml of mIgG2a and only 44% by 243 μg/ml of AggmIgG2b. (3) A monoclonal antibody of the IgG2b subclass raised against an IgG FcR on K562 cells inhibited binding to U937 cells of AggmIgG2b but not of mIgG2a. (4) Trypsinization of U937 cells abrogated by 32% the binding of mIgG2a but did not affect the binding of AggmIgG2b. Human IgG inhibited binding of both AggmIgG2b and mIgG2a t U937 cells. They propose that the newly recognized FcR that binds AggmIgG2b is the human homologue of the murine macrophage IgG2b/1 FcR (FcRII), and that the previously described 72,000 dalton high-affinity FcR on U937 cells that binds mIgG2a is the human equivalent of the murine macrophage IgG2a FcR (FcRI)

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. ¿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.

  16. 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

  17. Methods for Improving Aptamer Binding Affinity

    OpenAIRE

    Hijiri Hasegawa; Nasa Savory; Koichi Abe; Kazunori Ikebukuro

    2016-01-01

    Aptamers are single stranded oligonucleotides that bind a wide range of biological targets. Although aptamers can be isolated from pools of random sequence oligonucleotides using affinity-based selection, aptamers with high affinities are not always obtained. Therefore, further refinement of aptamers is required to achieve desired binding affinities. The optimization of primary sequences and stabilization of aptamer conformations are the main approaches to refining the binding properties of a...

  18. Collective bargaining under non-binding contracts

    OpenAIRE

    Dobbelaere, S.; Luttens, R.I.

    2011-01-01

    We introduce collective bargaining in a static framework where the firm and its risk-neutral employees negotiate over wages in a non-binding contract setting. Our main result is the equivalence between the non-binding collective equilibrium wage-employment contract and the equilibrium contract under binding risk-neutral efficient bargaining. We also demonstrate that our non-cooperative equilibrium wages and profits coincide with the Owen values of the corresponding cooperative game with the c...

  19. 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.

  20. 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.