WorldWideScience

Sample records for mechanism underlying breast

  1. Mechanical response of human female breast skin under uniaxial stretching.

    Science.gov (United States)

    Kumaraswamy, N; Khatam, Hamed; Reece, Gregory P; Fingeret, Michelle C; Markey, Mia K; Ravi-Chandar, Krishnaswamy

    2017-10-01

    Skin is a complex material covering the entire surface of the human body. Studying the mechanical properties of skin to calibrate a constitutive model is of great importance to many applications such as plastic or cosmetic surgery and treatment of skin-based diseases like decubitus ulcers. The main objective of the present study was to identify and calibrate an appropriate material constitutive model for skin and establish certain universal properties that are independent of patient-specific variability. We performed uniaxial tests performed on breast skin specimens freshly harvested during mastectomy. Two different constitutive models - one phenomenological and another microstructurally inspired - were used to interpret the mechanical responses observed in the experiments. Remarkably, we found that the model parameters that characterize dependence on previous maximum stretch (or preconditioning) exhibited specimen-independent universal behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    DEFF Research Database (Denmark)

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER......'-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk....

  3. Steroid sulfatase inhibition success and limitation in breast cancer clinical assays: an underlying mechanism.

    Science.gov (United States)

    Sang, Xiaoye; Han, Hui; Poirier, Donald; Lin, Sheng Xiang

    2018-05-24

    Steroid sulfatase is detectable in most hormone-dependent breast cancers. STX64, an STS inhibitor, induced tumor reduction in animal assay. Despite success in phase І clinical trial, the results of phase II trial were not that significant. Breast Cancer epithelial cells (MCF-7 and T47D) were treated with two STS inhibitors (STX64 and EM1913). Cell proliferation, cell cycle, and the concentrations of estradiol and 5α-dihydrotestosterone were measured to determine the endocrinological mechanism of sulfatase inhibition. Comparisons were made with inhibitions of reductive 17β-hydroxysteroid dehydrogenases (17β-HSDs). Proliferation studies showed that DNA synthesis in cancer cells was modestly decreased (approximately 20%), accompanied by an up to 6.5% in cells in the G0/G1 phase and cyclin D1 expression reduction. The concentrations of estradiol and 5α-dihydrotestosterone were decreased by 26% and 3% respectively. However, supplementation of 5α-dihydrotestosterone produced a significant increase (approximately 35.6%) in the anti-proliferative effect of sulfatase inhibition. This study has clarified sex-hormone control by sulfatase in BC, suggesting that the different roles of estradiol and 5α-dihydrotestosterone can lead to a reduction in the effect of sulfatase inhibition when compared with 17β-HSD7 inhibition. This suggests that combined treatment of sulfatase inhibitors with 17β-HSD inhibitors such as the type7 inhibitor could hold promise for hormone-dependent breast cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Identification of the Mechanisms Underlying Antiestrogen Resistance: Breast Cancer Research Partnership between FIU-UM Braman Family Breast Cancer Institute

    National Research Council Canada - National Science Library

    Roy, Deodutta

    2008-01-01

    This research proposal has two primary objectives which are to (1) increase FIU investigators' research expertise and competitive ability to succeed as independent breast cancer researchers; and (2...

  5. Mechanisms underlying differential expression of interleukin-8 in breast cancer cells

    Science.gov (United States)

    Freund, Ariane; Jolivel, Valérie; Durand, Sébastien; Kersual, Nathalie; Chalbos, Dany; Chavey, Carine; Vignon, Françoise; Lazennec, Gwendal

    2004-01-01

    We have recently reported that Interleukin-8 (IL-8) expression was inversely correlated to estrogen-receptor (ER)-status and was overexpressed in invasive breast cancer cells. In the present study, we show that IL-8 overexpression in breast cancer cells involves a higher transcriptional activity of IL-8 gene promoter. Cloning of IL-8 promoter from MDA-MB-231 and MCF-7 cells expressing high and low levels of IL-8, respectively, shows the integrity of the promoter in both cell lines. Deletion and site-directed mutagenesis of the promoter demonstrate that NF-κB and AP-1 and to a lesser extent C/EBP binding sites play a crucial role in the control of IL-8 promoter activity in MDA-MB-231 cells. Knock-down of NF-κB and AP-1 activities by adenovirus-mediated expression of a NF-κB super-repressor and RNA interference, respectively, decreased IL-8 expression in MDA-MB-231 cells. On the contrary, restoration of Fra-1, Fra-2, c-Jun, p50, p65, C/EBPα and C/EBPβ expression levels in MCF-7 cells led to a promoter activity comparable to that observed in MDA-MB-231 cells. Our data constitute the first extensive study of IL-8 gene overexpression in breast cancer cells and suggest that the high expression of IL-8 in invasive cancer cells requires a complex cooperation between NF-κB, AP-1 and C/EBP transcription factors. PMID:15208657

  6. Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2 inhibitor celecoxib in human breast cancer cells

    International Nuclear Information System (INIS)

    Basu, Gargi D; Pathangey, Latha B; Tinder, Teresa L; Gendler, Sandra J; Mukherjee, Pinku

    2005-01-01

    Inhibitors of cyclo-oxygenase (COX)-2 are being extensively studied as anticancer agents. In the present study we evaluated the mechanisms by which a highly selective COX-2 inhibitor, celecoxib, affects tumor growth of two differentially invasive human breast cancer cell lines. MDA-MB-231 (highly invasive) and MDA-MB-468 (moderately invasive) cell lines were treated with varying concentrations of celecoxib in vitro, and the effects of this agent on cell growth and angiogenesis were monitored by evaluating cell proliferation, apoptosis, cell cycle arrest, and vasculogenic mimicry. The in vitro results of MDA-MB-231 cell line were further confirmed in vivo in a mouse xenograft model. The highly invasive MDA-MB-231 cells express higher levels of COX-2 than do the less invasive MDA-MB-468 cells. Celecoxib treatment inhibited COX-2 activity, indicated by prostaglandin E 2 secretion, and caused significant growth arrest in both breast cancer cell lines. In the highly invasive MDA-MB-231 cells, the mechanism of celecoxib-induced growth arrest was by induction of apoptosis, associated with reduced activation of protein kinase B/Akt, and subsequent activation of caspases 3 and 7. In the less invasive MDA-MB-468 cells, growth arrest was a consequence of cell cycle arrest at the G 0 /G 1 checkpoint. Celecoxib-induced growth inhibition was reversed by addition of exogenous prostaglandin E 2 in MDA-MB-468 cells but not in MDA-MB-231 cells. Furthermore, MDA-MB-468 cells formed significantly fewer extracellular matrix associated microvascular channels in vitro than did the high COX-2 expressing MDA-MB-231 cells. Celecoxib treatment not only inhibited cell growth and vascular channel formation but also reduced vascular endothelial growth factor levels. The in vitro findings corroborated in vivo data from a mouse xenograft model in which daily administration of celecoxib significantly reduced tumor growth of MDA-MB-231 cells, which was associated with reduced vascularization and

  7. Parallel evolution under chemotherapy pressure in 29 breast cancer cell lines results in dissimilar mechanisms of resistance.

    Directory of Open Access Journals (Sweden)

    Bálint Tegze

    Full Text Available BACKGROUND: Developing chemotherapy resistant cell lines can help to identify markers of resistance. Instead of using a panel of highly heterogeneous cell lines, we assumed that truly robust and convergent pattern of resistance can be identified in multiple parallel engineered derivatives of only a few parental cell lines. METHODS: Parallel cell populations were initiated for two breast cancer cell lines (MDA-MB-231 and MCF-7 and these were treated independently for 18 months with doxorubicin or paclitaxel. IC50 values against 4 chemotherapy agents were determined to measure cross-resistance. Chromosomal instability and karyotypic changes were determined by cytogenetics. TaqMan RT-PCR measurements were performed for resistance-candidate genes. Pgp activity was measured by FACS. RESULTS: All together 16 doxorubicin- and 13 paclitaxel-treated cell lines were developed showing 2-46 fold and 3-28 fold increase in resistance, respectively. The RT-PCR and FACS analyses confirmed changes in tubulin isofom composition, TOP2A and MVP expression and activity of transport pumps (ABCB1, ABCG2. Cytogenetics showed less chromosomes but more structural aberrations in the resistant cells. CONCLUSION: We surpassed previous studies by parallel developing a massive number of cell lines to investigate chemoresistance. While the heterogeneity caused evolution of multiple resistant clones with different resistance characteristics, the activation of only a few mechanisms were sufficient in one cell line to achieve resistance.

  8. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    NARCIS (Netherlands)

    K. Lawrenson (Kate); S. Kar (Siddhartha); K. McCue (Karen); Kuchenbaeker, K. (Karoline); K. Michailidou (Kyriaki); J.P. Tyrer (Jonathan); J. Beesley (Jonathan); S.J. Ramus (Susan); Li, Q. (Qiyuan); Delgado, M.K. (Melissa K.); J.M. Lee (Janet M.); K. Aittomäki (Kristiina); I.L. Andrulis (Irene); H. Anton-Culver (Hoda); Arndt, V. (Volker); B.K. Arun (Banu); B. Arver (Brita Wasteson); E.V. Bandera (Elisa); M. Barile (Monica); Barkardottir, R.B. (Rosa B.); D. Barrowdale (Daniel); M.W. Beckmann (Matthias); J. Benítez (Javier); A. Berchuck (Andrew); M. Bisogna (Maria); L. Bjorge (Line); C. Blomqvist (Carl); W.J. Blot (William); N.V. Bogdanova (Natalia); Bojesen, A. (Anders); S.E. Bojesen (Stig); M.K. Bolla (Manjeet K.); B. Bonnani (Bernardo); A.-L. Borresen-Dale (Anne-Lise); H. Brauch (Hiltrud); P. Brennan (Paul); H. Brenner (Hermann); F. Bruinsma (Fiona); J. Brunet (Joan); S.A.B.S. Buhari (Shaik Ahmad Bin Syed); B. Burwinkel (Barbara); R. Butzow (Ralf); S.S. Buys (Saundra); Q. Cai (Qiuyin); T. Caldes (Trinidad); I. Campbell (Ian); Canniotto, R. (Rikki); J. Chang-Claude (Jenny); Chiquette, J. (Jocelyne); Choi, J.-Y. (Ji-Yeob); K.B.M. Claes (Kathleen B.M.); L.S. Cook (Linda S.); A. Cox (Angela); D.W. Cramer (Daniel); S.S. Cross (Simon); C. Cybulski (Cezary); K. Czene (Kamila); M.B. Daly (Mary B.); F. Damiola (Francesca); A. Dansonka-Mieszkowska (Agnieszka); H. Darabi (Hatef); J. Dennis (Joe); P. Devilee (Peter); O. Díez (Orland); J.A. Doherty (Jennifer A.); S.M. Domchek (Susan); C.M. Dorfling (Cecilia); T. Dörk (Thilo); M. Dumont (Martine); H. Ehrencrona (Hans); B. Ejlertsen (Bent); S.D. Ellis (Steve); C. Engel (Christoph); E. Lee (Eunjung); Evans, D.G. (D. Gareth); P.A. Fasching (Peter); L. Feliubadaló (L.); J.D. Figueroa (Jonine); D. Flesch-Janys (Dieter); O. Fletcher (Olivia); H. Flyger (Henrik); L. Foretova (Lenka); F. Fostira (Florentia); W.D. Foulkes (William); B.L. Fridley (Brooke); E. Friedman (Eitan); D. Frost (Debra); Gambino, G. (Gaetana); P.A. Ganz (Patricia A.); J. Garber (Judy); M. García-Closas (Montserrat); A. Gentry-Maharaj (Aleksandra); M. Ghoussaini (Maya); G.G. Giles (Graham); R. Glasspool (Rosalind); A.K. Godwin (Andrew K.); M.S. Goldberg (Mark); D. Goldgar (David); A. González-Neira (Anna); E.L. Goode (Ellen); M.T. Goodman (Marc); M.H. Greene (Mark H.); J. Gronwald (Jacek); P. Guénel (Pascal); C.A. Haiman (Christopher A.); P. Hall (Per); Hallberg, E. (Emily); U. Hamann (Ute); T.V.O. Hansen (Thomas); P. harrington (Patricia); J.M. Hartman (Joost); N. Hassan (Norhashimah); S. Healey (Sue); P.U. Heitz; J. Herzog (Josef); E. Høgdall (Estrid); C.K. Høgdall (Claus); F.B.L. Hogervorst (Frans); A. Hollestelle (Antoinette); J.L. Hopper (John); P.J. Hulick (Peter); T. Huzarski (Tomasz); E.N. Imyanitov (Evgeny); C. Isaacs (Claudine); H. Ito (Hidemi); A. Jakubowska (Anna); R. Janavicius (Ramunas); A. Jensen (Allan); E.M. John (Esther); Johnson, N. (Nichola); M. Kabisch (Maria); D. Kang (Daehee); M.K. Kapuscinski (Miroslav K.); Karlan, B.Y. (Beth Y.); S. Khan (Sofia); L.A.L.M. Kiemeney (Bart); M. Kjaer (Michael); J.A. Knight (Julia); I. Konstantopoulou (I.); V-M. Kosma (Veli-Matti); V. Kristensen (Vessela); J. Kupryjanczyk (Jolanta); A. Kwong (Ava); M. de La Hoya (Miguel); Y. Laitman (Yael); Lambrechts, D. (Diether); N.D. Le (Nhu D.); K. De Leeneer (Kim); K.J. Lester (Kathryn); D.A. Levine (Douglas); J. Li (Jingmei); A. Lindblom (Annika); J. Long (Jirong); A. Lophatananon (Artitaya); J.T. Loud (Jennifer); K.H. Lu (Karen); J. Lubinski (Jan); A. Mannermaa (Arto); S. Manoukian (Siranoush); L. Le Marchand (Loic); S. Margolin (Sara); F. Marme (Frederick); L.F. Massuger (Leon); K. Matsuo (Keitaro); S. Mazoyer (Sylvie); L. McGuffog (Lesley); C.A. McLean (Catriona Ann); I. McNeish (Iain); A. Meindl (Alfons); U. Menon (Usha); Mensenkamp, A.R. (Arjen R.); R.L. Milne (Roger); M. Montagna (Marco); K.B. Moysich (Kirsten); K.R. Muir (K.); A.-M. Mulligan (Anna-Marie); K.L. Nathanson (Katherine); R.B. Ness (Roberta); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); S. Nord (Silje); R.L. Nussbaum (Robert L.); K. Odunsi (Kunle); K. Offit (Kenneth); E. Olah; O.I. Olopade (Olufunmilayo I.); J.E. Olson (Janet); C. Olswold (Curtis); D.M. O'Malley (David M.); I. Orlow (Irene); N. Orr (Nick); A. Osorio (Ana); Park, S.K. (Sue Kyung); C.L. Pearce (Celeste); T. Pejovic (Tanja); P. Peterlongo (Paolo); G. Pfeiler (Georg); C. Phelan (Catherine); E.M. Poole (Elizabeth); K. Pykäs (Katri); P. Radice (Paolo); J. Rantala (Johanna); M.U. Rashid (Muhammad); G. Rennert (Gad); V. Rhenius (Valerie); K. Rhiem (Kerstin); H. Risch (Harvey); G.C. Rodriguez (Gustavo); M.A. Rossing (Mary Anne); Rudolph, A. (Anja); H.B. Salvesen (Helga); Sangrajrang, S. (Suleeporn); Sawyer, E.J. (Elinor J.); J.M. Schildkraut (Joellen); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); T.A. Sellers (Thomas A.); C.M. Seynaeve (Caroline); Shah, M. (Mitul); C.-Y. Shen (Chen-Yang); X.-O. Shu (Xiao-Ou); W. Sieh (Weiva); C.F. Singer (Christian); O. Sinilnikova (Olga); S. Slager (Susan); H. Song (Honglin); Soucy, P. (Penny); M.C. Southey (Melissa); M. Stenmark-Askmalm (Marie); D. Stoppa-Lyonnet (Dominique); C. Sutter (Christian); A.J. Swerdlow (Anthony ); Tchatchou, S. (Sandrine); P.J. Teixeira; S.-H. Teo (Soo-Hwang); K.L. Terry (Kathryn); M.B. Terry (Mary Beth); M. Thomassen (Mads); M.G. Tibiletti (Maria Grazia); L. Tihomirova (Laima); S. Tognazzo (Silvia); A.E. Toland (Amanda); I.P. Tomlinson (Ian); D. Torres (Diana); T. Truong (Thérèse); C.-C. Tseng (Chiu-Chen); N. Tung (Nadine); Tworoger, S.S. (Shelley S.); C. Vachon (Celine); Van Den Ouweland, A.M.W. (Ans M.W.); Van Doorn, H.C. (Helena C.); E.J. van Rensburg (Elizabeth); L.J. van 't Veer (Laura); A. Vanderstichele (Adriaan); I. Vergote (Ignace); J. Vijai (Joseph); Wang, Q. (Qin); S. Wang-Gohrke (Shan); J.N. Weitzel (Jeffrey); N. Wentzensen (N.); A.S. Whittemore (Alice); H. Wildiers (Hans); R. Winqvist (Robert); A.H. Wu (Anna); Yannoukakos, D. (Drakoulis); S.-Y. Yoon (Sook-Yee); J-C. Yu (Jyh-Cherng); W. Zheng (Wei); Y. Zheng (Ying); Khanna, K.K. (Kum Kum); J. Simard (Jacques); A.N.A. Monteiro (Alvaro N.); J.D. French (Juliet); F.J. Couch (Fergus); M. Freedman (Matthew); D.F. Easton (Douglas F.); A.M. Dunning (Alison); P.D.P. Pharoah (Paul); S.L. Edwards (Stacey); G. Chenevix-Trench (Georgia); A.C. Antoniou (Antonis C.); S.A. Gayther (Simon); D. Bowtell (David); A. DeFazio (Anna); P. Webb (Penny); M.-A. Collonge-Rame; Damette, A. (Alexandre); E. Barouk-Simonet (Emmanuelle); F. Bonnet (Françoise); V. Bubien (Virginie); N. Sevenet (Nicolas); M. Longy (Michel); P. Berthet (Pascaline); D. Vaur (Dominique); L. Castera (Laurent); S.F. Ferrer; Y.-J. Bignon (Yves-Jean); N. Uhrhammer (Nancy); F. Coron (Fanny); L. Faivre (Laurence); Baurand, A. (Amandine); Jacquot, C. (Caroline); Bertolone, G. (Geoffrey); Lizard, S. (Sarab); D. Leroux (Dominique); H. Dreyfus (Hélène); C. Rebischung (Christine); Peysselon, M. (Magalie); J.-P. Peyrat; J. Fournier (Joëlle); F. Révillion (Françoise); C. Adenis (Claude); L. Vénat-Bouvet (Laurence); M. Léone (Mélanie); N. Boutry-Kryza (N.); A. Calender (Alain); S. Giraud (Sophie); C. Verny-Pierre (Carole); C. Lasset (Christine); V. Bonadona (Valérie); Barjhoux, L. (Laure); H. Sobol (Hagay); V. Bourdon (Violaine); Noguchi, T. (Tetsuro); A. Remenieras (Audrey); I. Coupier (Isabelle); P. Pujol (Pascal); J. Sokolowska (Johanna); M. Bronner (Myriam); C.D. Delnatte (Capucine); Bézieau, S. (Stéphane); Mari, V. (Véronique); M. Gauthier-Villars (Marion); B. Buecher (Bruno); E. Rouleau (Etienne); L. Golmard (Lisa); V. Moncoutier (Virginie); M. Belotti (Muriel); A. de Pauw (Antoine); Elan, C. (Camille); Fourme, E. (Emmanuelle); Birot, A.-M. (Anne-Marie); Saule, C. (Claire); Laurent, M. (Maïté); C. Houdayer (Claude); F. Lesueur (Fabienne); N. Mebirouk (Noura); F. Coulet (Florence); C. Colas (Chrystelle); F. Soubrier; Warcoin, M. (Mathilde); F. Prieur (Fabienne); M. Lebrun (Marine); C. Kientz (Caroline); D.W. Muller (Danièle); J.P. Fricker (Jean Pierre); C. Toulas (Christine); R. Guimbaud (Rosine); L. Gladieff (Laurence); V. Feillel (Viviane); I. Mortemousque (Isabelle); B. Bressac-de Paillerets (Brigitte); O. Caron (Olivier); M. Guillaud-Bataille (Marine); H. Gregory (Helen); Z. Miedzybrodzka (Zosia); P.J. Morrison (Patrick); A. Donaldson (Alan); M.T. Rogers (Mark); M.J. Kennedy (John); M.E. Porteous (Mary); A. Brady (A.); J. Barwell (Julian); Foo, C. (Claire); F. Lalloo (Fiona); L. Side (Lucy); J. Eason (Jacqueline); Henderson, A. (Alex); L.J. Walker (Lisa); J. Cook (Jackie); Snape, K. (Katie); A. Murray (Alexandra); E. McCann (Emma); M.A. Rookus (Matti); F.E. van Leeuwen (F.); L. van der Kolk (Lizet); M.K. Schmidt (Marjanka); N.S. Russell (Nicola); J.L. de Lange (J.); Wijnands, R.; J.M. Collée (Margriet); M.J. Hooning (Maartje); Seynaeve, C.; C.H.M. van Deurzen (Carolien); A.I.M. Obdeijn (Inge-Marie); C.J. van Asperen (Christi); R.A.E.M. Tollenaar (Rob); T.C.T.E.F. van Cronenburg; C.M. Kets; M.G.E.M. Ausems (Margreet); C. van der Pol (Carmen); T.A.M. van Os (Theo); Q. Waisfisz (Quinten); E.J. Meijers-Heijboer (Hanne); E.B. Gómez García (Encarna); J.C. Oosterwijk (Jan); M.J. Mourits (Marjan); G.H. de Bock (Geertruida); H. Vasen (Hans); Siesling, S.; Verloop, J.; L.I.H. Overbeek (Lucy); S.B. Fox (Stephen); J. Kirk (Judy); G.J. Lindeman; M. Price (Melanie)

    2016-01-01

    textabstractA locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 ×

  9. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    DEFF Research Database (Denmark)

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER-n...

  10. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    OpenAIRE

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J.; Li, Qiyuan; Delgado, Melissa K.; Lee, Janet M.; Aittomaki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10...

  11. A finite element-based machine learning approach for modeling the mechanical behavior of the breast tissues under compression in real-time.

    Science.gov (United States)

    Martínez-Martínez, F; Rupérez-Moreno, M J; Martínez-Sober, M; Solves-Llorens, J A; Lorente, D; Serrano-López, A J; Martínez-Sanchis, S; Monserrat, C; Martín-Guerrero, J D

    2017-11-01

    This work presents a data-driven method to simulate, in real-time, the biomechanical behavior of the breast tissues in some image-guided interventions such as biopsies or radiotherapy dose delivery as well as to speed up multimodal registration algorithms. Ten real breasts were used for this work. Their deformation due to the displacement of two compression plates was simulated off-line using the finite element (FE) method. Three machine learning models were trained with the data from those simulations. Then, they were used to predict in real-time the deformation of the breast tissues during the compression. The models were a decision tree and two tree-based ensemble methods (extremely randomized trees and random forest). Two different experimental setups were designed to validate and study the performance of these models under different conditions. The mean 3D Euclidean distance between nodes predicted by the models and those extracted from the FE simulations was calculated to assess the performance of the models in the validation set. The experiments proved that extremely randomized trees performed better than the other two models. The mean error committed by the three models in the prediction of the nodal displacements was under 2 mm, a threshold usually set for clinical applications. The time needed for breast compression prediction is sufficiently short to allow its use in real-time (<0.2 s). Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. ROS-dependent mitochondria molecular mechanisms underlying antitumor activity of Pleurotus abalonus acidic polysaccharides in human breast cancer MCF-7 cells.

    Directory of Open Access Journals (Sweden)

    Xiaolong Shi

    Full Text Available BACKGROUND: A greater reduction in cancer risk associated with mushroom diet rich in fungus polysaccharides is generally accepted. Meanwhile, edible Pleurotus abalonus as a member of Abalone mushroom family is a popular nutritional supplement that purportedly prevents cancer occurrence. However, these anecdotal claims are supported by limited studies describing tumor-inhibitory responses to the promising polysaccharides, and the molecular mechanisms underlying these properties have not yet been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: We here fractionated the crude polysaccharide preparation from the fruiting bodies of P. abalonus into three fractions, namely PAP-1, PAP-2 and PAP-3, and tested these fractions for antiproliferative activity in human breast cancer MCF-7 cells. The largest PAP-3, an acidic polysaccharide fraction with a molecular mass of 3.68×10(5 Da, was the most active in inhibiting MCF-7 cancer cells with an IC50 of 193 µg/mL. The changes in cell normal morphology were observed by DAPI staining and the PAP-3-induced apoptosis was confirmed by annexin V/propidium iodide staining. The apoptosis was involved in mitochondria-mediated pathway including the loss of mitochondrial membrane potential (Δψm, the increase of Bax/Bcl-2 ratio, caspase-9/3 activation, and poly(ADP-ribose polymerase (PARP degradation, as well as intracellular ROS production. PAP-3 also induced up-regulation of p53, and cell cycle arrest at the S phase. The incubation of MCF-7 cells with antioxidant superoxide dismutase (SOD and N-acetylcysteine (NAC significantly attenuated the ROS generation and apoptosis caused by PAP-3, indicating that intracellular ROS plays a pivotal role in cell death. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the polysaccharides, especially acidic PAP-3, are very important nutritional ingredients responsible for, at least in part, the anticancer health benefits of P. abalonus via ROS-mediated mitochondrial apoptotic

  13. Mechanism of immune evasion in breast cancer

    Science.gov (United States)

    Wang, Mozhi; Zhang, Changwang; Song, Yongxi; Wang, Zhenning; Wang, Yaojia; Luo, Fang; Xu, Yujie; Zhao, Yi; Wu, Zhonghua; Xu, Yingying

    2017-01-01

    Breast cancer (BC) is the most common malignant tumor among women, with high morbidity and mortality. Its onset, development, metastasis, and prognosis vary among individuals due to the interactions between tumors and host immunity. Many diverse mechanisms have been associated with BC, with immune evasion being the most widely studied to date. Tumor cells can escape from the body’s immune response, which targets abnormal components and foreign bodies, using different approaches including modification of surface antigens and modulation of the surrounding environment. In this review, we summarize the mechanisms and factors that impact the immunoediting process and analyze their functions in detail. PMID:28352189

  14. Under treated Breast Cancer in the Elderly

    International Nuclear Information System (INIS)

    Malik, M.K.; Tartter, P.I.; Belfer, R.

    2013-01-01

    The effect of under treatment with adjuvant hormonal therapy, chemotherapy, or radiation was studied in elderly women with breast cancer. A prospectively maintained database was used to identify women undergoing potentially curative surgery between 1978 and 2012. The presentation, pathologic findings, treatment, and outcomes of 382 women over 70 were compared to the findings in 2065 younger patients. Subsequently, conventionally treated and under treated elderly patients were identified and their characteristics and outcomes were compared. Both young and old patients presented most frequently with mammographic findings, but older patients presented more frequently with mammographic masses while younger patients presented more frequently with mammographic calcifications. Cancers of older patients were significantly more favorable than cancers in younger patients: smaller, with more infiltrating lobular, fewer ductal carcinoma in situ, and more frequently estrogen receptor positive and fewer were poorly differentiated. Elderly patients had less axillary sampling, fewer mastectomies, less adjuvant radiation therapy, and more hormonal therapy. Fifty-one percent of the 382 elderly patients were under treated by conventional criteria. Under treated patients were more frequently in situ, better differentiated, smaller, and more often estrogen receptor positive. Forty-four percent of the under treated patients died during followup without disease recurrence. Despite under treatment, local and distant disease-free survival was comparable to patients who were not under treated.

  15. Acousto-Mechanical Imaging for Breast Cancer Detection

    National Research Council Canada - National Science Library

    Emelianov, Stanislav Y

    2002-01-01

    The underlying hypothesis of our study is that quantitative breast elasticity imaging is possible and provides unique information, which could increase the detection, characterization and monitoring...

  16. Acousto-Mechanical Imaging for Breast Cancer Detection

    National Research Council Canada - National Science Library

    Emelianov, Stanislav Y

    2003-01-01

    The underlying hypothesis of our study is that quantitative breast elasticity imaging is possible and provides unique information, which could increase the detection, characterization and monitoring...

  17. A Physical Mechanism and Global Quantification of Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Chong Yu

    Full Text Available Initiation and progression of cancer depend on many factors. Those on the genetic level are often considered crucial. To gain insight into the physical mechanisms of breast cancer, we construct a gene regulatory network (GRN which reflects both genetic and environmental aspects of breast cancer. The construction of the GRN is based on available experimental data. Three basins of attraction, representing the normal, premalignant and cancer states respectively, were found on the phenotypic landscape. The progression of breast cancer can be seen as switching transitions between different state basins. We quantified the stabilities and kinetic paths of the three state basins to uncover the biological process of breast cancer formation. The gene expression levels at each state were obtained, which can be tested directly in experiments. Furthermore, by performing global sensitivity analysis on the landscape topography, six key genes (HER2, MDM2, TP53, BRCA1, ATM, CDK2 and four regulations (HER2⊣TP53, CDK2⊣BRCA1, ATM→MDM2, TP53→ATM were identified as being critical for breast cancer. Interestingly, HER2 and MDM2 are the most popular targets for treating breast cancer. BRCA1 and TP53 are the most important oncogene of breast cancer and tumor suppressor gene, respectively. This further validates the feasibility of our model and the reliability of our prediction results. The regulation ATM→MDM2 has been extensive studied on DNA damage but not on breast cancer. We notice the importance of ATM→MDM2 on breast cancer. Previous studies of breast cancer have often focused on individual genes and the anti-cancer drugs are mainly used to target the individual genes. Our results show that the network-based strategy is more effective on treating breast cancer. The landscape approach serves as a new strategy for analyzing breast cancer on both the genetic and epigenetic levels and can help on designing network based medicine for breast cancer.

  18. Indications for breast imaging in women under age 35

    International Nuclear Information System (INIS)

    Harris, V.J.; Jackson, V.P.

    1988-01-01

    Many women under age 35 years undergo breast imaging, and the vast majority of studies are normal or compatible with benign disease. In our series of 649 patients aged 13 - 34, the only significant indicators were a palpable mass or infection. In the 383 patients with either of these indications, mammographic and/or US findings were normal in 53%, compatible with benign disease in 14%, and suggestive of malignancy in 33%. Biopsy performed in 80 of these women revealed breast cancer in five (6%). None of the 266 women with low-yield indications (pain, modularity, galactorrhea, fibrocystic disease, screening) had significant imaging findings or clinical or surgical evidence of breast cancer

  19. In silico analysis of the potential mechanism of telocinobufagin on breast cancer MCF-7 cells.

    Science.gov (United States)

    Dang, Yi-Wu; Lin, Peng; Liu, Li-Min; He, Rong-Quan; Zhang, Li-Jie; Peng, Zhi-Gang; Li, Xiao-Jiao; Chen, Gang

    2018-05-01

    The extractives from a ChanSu, traditional Chinese medicine, have been discovered to possess anti-inflammatory and tumor-suppressing abilities. However, the molecular mechanism of telocinobufagin, a compound extracted from ChanSu, on breast cancer cells has not been clarified. The aim of this study is to investigate the underlying mechanism of telocinobufagin on breast cancer cells. The differentially expressed genes after telocinobufagin treatment on breast cancer cells were searched and downloaded from Gene Expression Omnibus (GEO), ArrayExpress and literatures. Bioinformatics tools were applied to further explore the potential mechanism of telocinobufagin in breast cancer using the Kyoto Encyclopedia of genes and genomes (KEGG) pathway, Gene ontology (GO) enrichment, panther, and protein-protein interaction analyses. To better comprehend the role of telocinobufagin in breast cancer, we also queried the Connectivity Map using the gene expression profiles of telocinobufagin treatment. One GEO accession (GSE85871) provided 1251 differentially expressed genes after telocinobufagin treatment on MCF-7 cells. The pathway of neuroactive ligand-receptor interaction, cell adhesion molecules (CAMs), intestinal immune network for IgA production, hematopoietic cell lineage and calcium signaling pathway were the key pathways from KEGG analysis. IGF1 and KSR1, owning to higher protein levels in breast cancer tissues, IGF1 and KSR1 could be the hub genes related to telocinobufagin treatment. It was indicated that the molecular mechanism of telocinobufagin resembled that of fenspiride. Telocinobufagin might regulate neuroactive ligand-receptor interaction pathway to exert its influences in breast cancer MCF-7 cells, and its molecular mechanism might share some similarities with fenspiride. This study only presented a comprehensive picture of the role of telocinobufagin in breast cancer MCF-7 cells using big data. However, more thorough and deeper researches are required to add

  20. Usefulness of ultrasonography for detection of breast cancer in patients under 30 years of age

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Hyung; Oh, Ki Keun; Yoon, Sang Wook [Yongdong Severance Hospital, Seoul (Korea, Republic of)

    1995-04-15

    The purpose of this study was to compare mammography and breast sonography in detection of breast cancer and to suggest reasonable guideline of breast imaging in breast cancer patients under 30 years of age in whom breast cancer shows different clinicopathologic characteristics compared with breast cancer in older women. Authors reviewed medical records of 27 patients under 30 years of age with pathologically-proven breast cancer. Age, family history, physical examination findings, indications for breast sonography were reviewed. Cases in whom breast cancer lesion is detectable and cases in whom not detectable using mammography or breast sonography were reviewed. And then, authors evaluated the usefulness of each method and reasons for nonvisualization of lesion on mammography. Among 27 patients, 25 patients had palpable breast mass as indication of mammography and breast sonography. Cancer lesions were detectable in 16 of 25 patients (64%) on mammography and 24 of 25 patients (96%) on breast ultrasonography. Reasons for nonvisualization of cancer lesions on mammography were dense breast with nodular parenchyma pattern and minimal breast change of ductal carcinoma in situ. In breast cancer patients under 30 years of age who have palpable breast mass as a initial, and main clinical problem, breast ultrasonography is superior to mammography in detecting and diagnosing breast cancer. We suggest that guidelines can avoid unnecessary mammography in these patients.

  1. Usefulness of ultrasonography for detection of breast cancer in patients under 30 years of age

    International Nuclear Information System (INIS)

    Kim, Ji Hyung; Oh, Ki Keun; Yoon, Sang Wook

    1995-01-01

    The purpose of this study was to compare mammography and breast sonography in detection of breast cancer and to suggest reasonable guideline of breast imaging in breast cancer patients under 30 years of age in whom breast cancer shows different clinicopathologic characteristics compared with breast cancer in older women. Authors reviewed medical records of 27 patients under 30 years of age with pathologically-proven breast cancer. Age, family history, physical examination findings, indications for breast sonography were reviewed. Cases in whom breast cancer lesion is detectable and cases in whom not detectable using mammography or breast sonography were reviewed. And then, authors evaluated the usefulness of each method and reasons for nonvisualization of lesion on mammography. Among 27 patients, 25 patients had palpable breast mass as indication of mammography and breast sonography. Cancer lesions were detectable in 16 of 25 patients (64%) on mammography and 24 of 25 patients (96%) on breast ultrasonography. Reasons for nonvisualization of cancer lesions on mammography were dense breast with nodular parenchyma pattern and minimal breast change of ductal carcinoma in situ. In breast cancer patients under 30 years of age who have palpable breast mass as a initial, and main clinical problem, breast ultrasonography is superior to mammography in detecting and diagnosing breast cancer. We suggest that guidelines can avoid unnecessary mammography in these patients

  2. COPING MECHANISM OF CAREER WOMEN WITH BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Rosnani Rosnani

    2017-06-01

    Full Text Available Introduction: Patients with cancer may experience psychological disorders such as depression, anxiety, anger, helplessness, and unappreciated, so in certain situations require defense mechanisms (coping mechanism to oppose or resist feelings of anxiety, fear or stress that haunt her. The aim of this study was to know the coping mechanism of career women with breast cancer reviewed by phenomenology in Palembang 2016. Method: Type of this study was a qualitative study with a phenomenological approach. Total samples were 8 participants with inclusion criteria: career women, productive age range, health physic and physiologic. Independent variable was a coping mechanism, and the dependent variable was breast cancer. The instrument used the voice recorder, and interview guides. Data analyze used verbatim transcript with credibility, dependability, and confirmability. Result: The results showed that working women who have breast cancer have a coping strategy that is adjusted to the psychological condition and physical reactions of the therapy in progress. Psychologically, the coping mechanism is in the form of rejecting, drawing closer to Allah SWT, seeking the opinion of other health workers, discussing conditions with spouse and family, seeking alternative treatment and asking for doctor's direction. The coping mechanism of the body's reaction to therapy is done by taking medicine according to the rules and remember Allah SWT. Conclusions: Need the support of the coping mechanism in patients with breast cancer and nursing care approach with the pattern of coping mechanisms with the involvement of the family.

  3. Trichostatin A enhances estrogen receptor-alpha repression in MCF-7 breast cancer cells under hypoxia

    International Nuclear Information System (INIS)

    Noh, Hyunggyun; Park, Joonwoo; Shim, Myeongguk; Lee, YoungJoo

    2016-01-01

    Estrogen receptor (ER) is a crucial determinant of resistance to endocrine therapy, which may change during the progression of breast cancer. We previously showed that hypoxia induces ESR1 gene repression and ERα protein degradation via proteasome-mediated pathway in breast cancer cells. HDAC plays important roles in the regulation of histone and non-histone protein post-translational modification. HDAC inhibitors can induce epigenetic changes and have therapeutic potential for targeting various cancers. Trichostatin A exerts potent antitumor activities against breast cancer cells in vitro and in vivo. In this report, we show that TSA augments ESR1 gene repression at the transcriptional level and downregulates ERα protein expression under hypoxic conditions through a proteasome-mediated pathway. TSA-induced estrogen response element-driven reporter activity in the absence of estrogen was synergistically enhanced under hypoxia; however, TSA inhibited cell proliferation under both normoxia and hypoxia. Our data show that the hypoxia-induced repression of ESR1 and degradation of ERα are enhanced by concomitant treatment with TSA. These findings expand our understanding of hormone responsiveness in the tumor microenvironment; however, additional in-depth studies are required to elucidate the detailed mechanisms of TSA-induced ERα regulation under hypoxia. - Highlights: • TSA augments ESR1 gene repression at the transcriptional level under hypoxia. • TSA downregulates ERα protein expression under hypoxia. • TSA-induced ERα regulation under hypoxia is essential for understanding the behavior and progression of breast cancer.

  4. Trichostatin A enhances estrogen receptor-alpha repression in MCF-7 breast cancer cells under hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Hyunggyun; Park, Joonwoo; Shim, Myeongguk; Lee, YoungJoo, E-mail: yjlee@sejong.ac.kr

    2016-02-12

    Estrogen receptor (ER) is a crucial determinant of resistance to endocrine therapy, which may change during the progression of breast cancer. We previously showed that hypoxia induces ESR1 gene repression and ERα protein degradation via proteasome-mediated pathway in breast cancer cells. HDAC plays important roles in the regulation of histone and non-histone protein post-translational modification. HDAC inhibitors can induce epigenetic changes and have therapeutic potential for targeting various cancers. Trichostatin A exerts potent antitumor activities against breast cancer cells in vitro and in vivo. In this report, we show that TSA augments ESR1 gene repression at the transcriptional level and downregulates ERα protein expression under hypoxic conditions through a proteasome-mediated pathway. TSA-induced estrogen response element-driven reporter activity in the absence of estrogen was synergistically enhanced under hypoxia; however, TSA inhibited cell proliferation under both normoxia and hypoxia. Our data show that the hypoxia-induced repression of ESR1 and degradation of ERα are enhanced by concomitant treatment with TSA. These findings expand our understanding of hormone responsiveness in the tumor microenvironment; however, additional in-depth studies are required to elucidate the detailed mechanisms of TSA-induced ERα regulation under hypoxia. - Highlights: • TSA augments ESR1 gene repression at the transcriptional level under hypoxia. • TSA downregulates ERα protein expression under hypoxia. • TSA-induced ERα regulation under hypoxia is essential for understanding the behavior and progression of breast cancer.

  5. Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms.

    Science.gov (United States)

    Kravchenko, Julia; Akushevich, Igor; Seewaldt, Victoria L; Abernethy, Amy P; Lyerly, H Kim

    2011-07-01

    The observed bimodal patterns of breast cancer incidence in the U.S. suggested that breast cancer may be viewed as more than one biological entity. We studied the factors potentially contributing to this phenomenon, specifically focusing on how disease heterogeneity could be linked to breast carcinogenesis mechanisms. Using empirical analyses and population-based biologically motivated modeling, age-specific patterns of incidence of ductal and lobular breast carcinomas from the SEER registry (1990-2003) were analyzed for heterogeneity and characteristics of carcinogenesis, stratified by race, stage, grade, and estrogen (ER)/progesterone (PR) receptor status. The heterogeneity of breast carcinoma age patterns decreased after stratification by grade, especially for grade I and III tumors. Stratification by ER/PR status further reduced the heterogeneity, especially for ER(+)/PR(-) and ER(-)/(-) tumors; however, the residual heterogeneity was still observed. The number of rate-limiting events of carcinogenesis and the latency of ductal and lobular carcinomas differed, decreasing from grade I to III, with poorly differentiated tumors associated with the least number of carcinogenesis stages and the shortest latency. Tumor grades play important role in bimodal incidence of breast carcinoma and have distinct mechanisms of carcinogenesis. Race and cancer subtype could play modifying role. ER/PR status contributes to the observed heterogeneity, but is subdominant to tumor grade. Further studies on sources of "remaining" heterogeneity of population with breast cancer (such as genetic/epigenetic characteristics) are necessary. The results of this study could suggest stratification rather than unification of breast cancer prevention strategies, risk assessment, and treatment.

  6. Pain in Breast Cancer Treatment: Aggravating Factors and Coping Mechanisms

    Directory of Open Access Journals (Sweden)

    Maria de Fatima Guerreiro Godoy

    2014-01-01

    Full Text Available The objective of this study was to evaluate pain in women with breast cancer-related lymphedema and the characteristics of aggravating factors and coping mechanisms. The study was conducted in the Clinica Godoy, São Jose do Rio Preto, with a group of 46 women who had undergone surgery for the treatment of breast cancer. The following variables were evaluated: type and length of surgery; number of radiotherapy and chemotherapy sessions; continued feeling of the removed breast (phantom limb, infection, intensity of pain, and factors that improve and worsen the pain. The percentage of events was used for statistical analysis. About half the participants (52.1% performed modified radical surgery, with 91.3% removing only one breast; 82.6% of the participants did not perform breast reconstruction surgery. Insignificant pain was reported by 32.60% of the women and 67.3% said they suffered pain; it was mild in 28.8% of the cases (scale 1–5, moderate in 34.8% (scale 6–9, and severe in 4.3%. The main mechanisms used to cope with pain were painkillers in 41.30% of participants, rest in 21.73%, religious ceremonies in 17.39%, and chatting with friends in 8.69%. In conclusion, many mastectomized patients with lymphedema complain of pain, but pain is often underrecognized and undertreated.

  7. Metacognitive mechanisms underlying lucid dreaming.

    Science.gov (United States)

    Filevich, Elisa; Dresler, Martin; Brick, Timothy R; Kühn, Simone

    2015-01-21

    Lucid dreaming is a state of awareness that one is dreaming, without leaving the sleep state. Dream reports show that self-reflection and volitional control are more pronounced in lucid compared with nonlucid dreams. Mostly on these grounds, lucid dreaming has been associated with metacognition. However, the link to lucid dreaming at the neural level has not yet been explored. We sought for relationships between the neural correlates of lucid dreaming and thought monitoring. Human participants completed a questionnaire assessing lucid dreaming ability, and underwent structural and functional MRI. We split participants based on their reported dream lucidity. Participants in the high-lucidity group showed greater gray matter volume in the frontopolar cortex (BA9/10) compared with those in the low-lucidity group. Further, differences in brain structure were mirrored by differences in brain function. The BA9/10 regions identified through structural analyses showed increases in blood oxygen level-dependent signal during thought monitoring in both groups, and more strongly in the high-lucidity group. Our results reveal shared neural systems between lucid dreaming and metacognitive function, in particular in the domain of thought monitoring. This finding contributes to our understanding of the mechanisms enabling higher-order consciousness in dreams. Copyright © 2015 the authors 0270-6474/15/351082-07$15.00/0.

  8. Molecular Mechanisms Underlying Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Christian Trepo

    2009-11-01

    Full Text Available Hepatocarcinogenesis is a complex process that remains still partly understood. That might be explained by the multiplicity of etiologic factors, the genetic/epigenetic heterogeneity of tumors bulks and the ignorance of the liver cell types that give rise to tumorigenic cells that have stem cell-like properties. The DNA stress induced by hepatocyte turnover, inflammation and maybe early oncogenic pathway activation and sometimes viral factors, leads to DNA damage response which activates the key tumor suppressive checkpoints p53/p21Cip1 and p16INK4a/pRb responsible of cell cycle arrest and cellular senescence as reflected by the cirrhosis stage. Still obscure mechanisms, but maybe involving the Wnt signaling and Twist proteins, would allow pre-senescent hepatocytes to bypass senescence, acquire immortality by telomerase reactivation and get the last genetic/epigenetic hits necessary for cancerous transformation. Among some of the oncogenic pathways that might play key driving roles in hepatocarcinogenesis, c-myc and the Wnt/β-catenin signaling seem of particular interest. Finally, antiproliferative and apoptosis deficiencies involving TGF-β, Akt/PTEN, IGF2 pathways for instance are prerequisite for cancerous transformation. Of evidence, not only the transformed liver cell per se but the facilitating microenvironment is of fundamental importance for tumor bulk growth and metastasis.

  9. Weight gain following breast cancer diagnosis: Implication and proposed mechanisms

    Science.gov (United States)

    Makari-Judson, Grace; Braun, Barry; Jerry, D Joseph; Mertens, Wilson C

    2014-01-01

    Weight gain occurs in the majority of women following breast cancer treatment. An overview of studies describing weight gain amongst women treated with early to modern chemotherapy regimens is included. Populations at higher risk include women who are younger, closer to ideal body weight and who have been treated with chemotherapy. Weight gain ranges between 1 to 5 kg, and may be associated with change in body composition with gain in fat mass and loss in lean body mass. Women are unlikely to return to pre-diagnosis weight. Possible mechanisms including inactivity and metabolic changes are explored. Potential interventions are reviewed including exercise, dietary changes and pharmacologic agents. Although breast cancer prognosis does not appear to be significantly impacted, weight gain has negative consequences on quality of life and overall health. Future studies should explore change in body composition, metabolism and insulin resistance. Avoiding weight gain in breast cancer survivors following initial diagnosis and treatment should be encouraged. PMID:25114844

  10. Effect of acadesine on breast cancer cells under hypoxia

    Directory of Open Access Journals (Sweden)

    A. M. Shcherbakov

    2017-01-01

    Full Text Available The riboside derivative acadesine (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside is currently being tested in clinical trials as a promising anti-tumor drug. Intracellular target of acadesine is adenosine monophosphate-activated protein kinase (АМРК, an important regulatory molecule of energy metabolism. It is expected that acadesine would be active in tumors under hypoxia conditions. In normoxia (cells incubated in 21 % oxygen, acadesine inhibited proliferation and induced cell death of breast adenocarcinoma, including the triple negative breast cancer line. When oxygen partial pressure was decreased to 1 % (experimental hypoxia, acadesine inhibited activation of reporter construct responsive to HIF-1α (hypoxia inducible factor 1 alpha transcription factor. This effect was observed for acadesine in concentrations close to cytotoxic. Acadesine retained cytotoxicity under hypoxia and decreased the survival of the MDA-MB-231 cell line when used in combination with cisplatin. These results considerably widen acadesine’s field of application and allow to assume its efficacy in chemotherapy combination regimens for breast cancer, including the tumors with low oxygenation.

  11. Breast density does not impact the ability of Videssa® Breast to detect breast cancer in women under age 50.

    Directory of Open Access Journals (Sweden)

    David E Reese

    Full Text Available Breast density is associated with reduced imaging resolution in the detection of breast cancer. A biochemical approach that is not affected by density would provide an important tool to healthcare professionals who are managing women with dense breasts and suspicious imaging findings. Videssa® Breast is a combinatorial proteomic biomarker assay (CPBA, comprised of Serum Protein Biomarkers (SPB and Tumor Associated Autoantibodies (TAAb integrated with patient-specific clinical data to produce a diagnostic score that reliably detects breast cancer (BC as an adjunctive tool to imaging. The performance of Videssa® Breast was evaluated in the dense (a and b and non-dense (c and d groups in a population of n = 545 women under age 50. The sensitivity and specificity in the dense breast group were calculated to be 88.9% and 81.2%, respectively, and 92.3% and 86.6%, respectively, for the non-dense group. No significant differences were observed in the sensitivity (p = 1.0 or specificity (p = 0.18 between these groups. The NPV was 99.3% and 99.1% in non-dense and dense groups, respectively. Unlike imaging, Videssa® Breast does not appear to be impacted by breast density; it can effectively detect breast cancer in women with dense and non-dense breasts alike. Thus, Videssa® Breast provides a powerful tool for healthcare providers when women with dense breasts present with challenging imaging findings. In addition, Videssa® Breast provides assurance to women with dense breasts that they do not have breast cancer, reducing further anxiety in this higher risk patient population.

  12. Deciphering the Cognitive and Neural Mechanisms Underlying ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Deciphering the Cognitive and Neural Mechanisms Underlying Auditory Learning. This project seeks to understand the brain mechanisms necessary for people to learn to perceive sounds. Neural circuits and learning. The research team will test people with and without musical training to evaluate their capacity to learn ...

  13. Peeling mechanism of tomato under infrared heating

    Science.gov (United States)

    Critical behaviors of peeling tomatoes using infrared heat are thermally induced peel loosening and subsequent cracking. However, the mechanism of peel loosening and cracking due to infrared heating remains unclear. This study aimed at investigating the mechanism of peeling tomatoes under infrared h...

  14. Molecular Mechanisms of Anticancer Effects of Phytoestrogens in Breast Cancer.

    Science.gov (United States)

    Hsieh, Chia-Jung; Hsu, Ya-Ling; Huang, Ya-Fang; Tsai, Eing-Mei

    2018-01-01

    Phytoestrogens derived from plants exert estrogenic as well as antiestrogenic effects and multiple actions within breast cancer cells. Chemopreventive properties of phytoestrogens have emerged from epidemiological observations. In recent clinical research studies, phytoestrogens are safe and may even protect against breast cancer. In this brief review, the molecular mechanisms of phytoestrogens on regulation of cell cycle, apoptosis, estrogen receptors, cell signaling pathways, and epigenetic modulations in relation to breast cancer are discussed. Phytoestrogens have a preferential affinity for estrogen receptor (ER)-β, which appears to be associated with antiproliferative and anticarcinogenic effects. Moreover, while phytoestrogens not only inhibit ER-positive but also ER-negative breast cancer cells, the possibility of epigenetic modulation playing an important role is also discussed. In conclusion, as there are multiple targets and actions of phytoestrogens, extensive research is still necessary. However, due to low toxicity, low cost, and easy availability, their potent chemoprevention effects deserve further study. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Mechanical properties of cork under contact stresses

    International Nuclear Information System (INIS)

    Parralejo, A. D.; Guiberteau, F.; Fortes, M. A.; Rosa, M. E.

    2001-01-01

    In this work our interest is focussed on the mechanical behaviour of natural cork under contact stresses. Many of the applications of this curious material are related with its mechanical response under such a stress field, however this topic has not been still sufficiently considered in the scientific literature. For this purpose, we proposed the use of Hertzian indentation tests. By using this mythology we have investigated the cork structure influence on the corresponding mechanical properties. Our results reveal a clear mechanical anisotropy effect. Moreover, the elastic modulus corresponding to specific directions have been estimated. Several are the main advantages of this specific test mythology versus traditional uniaxial compression tests, specially simplicity and local character. (Author) 9 refs

  16. Mechanisms driving local breast cancer recurrence in a model of breast-conserving surgery.

    LENUS (Irish Health Repository)

    Smith, Myles J

    2012-02-03

    OBJECTIVE: We aimed to identify mechanisms driving local recurrence in a model of breast-conserving surgery (BCS) for breast cancer. BACKGROUND: Breast cancer recurrence after BCS remains a clinically significant, but poorly understood problem. We have previously reported that recurrent colorectal tumours demonstrate altered growth dynamics, increased metastatic burden and resistance to apoptosis, mediated by upregulation of phosphoinositide-3-kinase\\/Akt (PI3K\\/Akt). We investigated whether similar characteristics were evident in a model of locally recurrent breast cancer. METHODS: Tumours were generated by orthotopic inoculation of 4T1 cells in two groups of female Balb\\/c mice and cytoreductive surgery performed when mean tumour size was above 150 mm(3). Local recurrence was observed and gene expression was examined using Affymetrix GeneChips in primary and recurrent tumours. Differential expression was confirmed with quantitative real-time polymerase chain reaction (qRT-PCR). Phosphorylation of Akt was assessed using Western immunoblotting. An ex vivo heat shock protein (HSP)-loaded dendritic cell vaccine was administered in the perioperative period. RESULTS: We observed a significant difference in the recurrent 4T1 tumour volume and growth rate (p < 0.05). Gene expression studies suggested roles for the PI3K\\/Akt system and local immunosuppression driving the altered growth kinetics. We demonstrated that perioperative vaccination with an ex vivo HSP-loaded dendritic cell vaccine abrogated recurrent tumour growth in vivo (p = 0.003 at day 15). CONCLUSION: Investigating therapies which target tumour survival pathways such as PI3K\\/Akt and boost immune surveillance in the perioperative period may be useful adjuncts to contemporary breast cancer treatment.

  17. Mechanisms of Twist 1-Induced Invasion in Breast Cancer Metastasis

    Science.gov (United States)

    2011-01-01

    affect breast cancer metastasis with a subcutaneous mouse tumor implantation model of breast cancer metastasis. HMLE -Twist1 cells expressing shRNAs...13 4 Introduction Distant metastases are responsible for the vast majority of breast cancer deaths. This process...to migrate and invade is therefore essential to the metastatic process. The initial steps of breast cancer metastasis, local invasion and

  18. Dissecting the Mechanisms of Drug Resistance in BRCA1/2-Mutant Breast Cancers

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0600 TITLE: Dissecting the Mechanisms of Drug Resistance in BRCA1/2-Mutant Breast Cancers PRINCIPAL INVESTIGATOR: Dr...2017 4. TITLE AND SUBTITLE Dissecting the Mechanisms of Drug Resistance in BRCA1/2- Mutant Breast Cancers 5a. CONTRACT NUMBER W81XWH-16-1-0600 5b...therapeutic modality for targeting homologous recombination (HR) deficient tumors such as BRCA1 and BRCA2-mutated triple negative breast cancers

  19. Surface Damage Mechanism of Monocrystalline Si Under Mechanical Loading

    Science.gov (United States)

    Zhao, Qingliang; Zhang, Quanli; To, Suet; Guo, Bing

    2017-03-01

    Single-point diamond scratching and nanoindentation on monocrystalline silicon wafer were performed to investigate the surface damage mechanism of Si under the contact loading. The results showed that three typical stages of material removal appeared during dynamic scratching, and a chemical reaction of Si with the diamond indenter and oxygen occurred under the high temperature. In addition, the Raman spectra of the various points in the scratching groove indicated that the Si-I to β-Sn structure (Si-II) and the following β-Sn structure (Si-II) to amorphous Si transformation appeared under the rapid loading/unloading condition of the diamond grit, and the volume change induced by the phase transformation resulted in a critical depth (ductile-brittle transition) of cut (˜60 nm ± 15 nm) much lower than the theoretical calculated results (˜387 nm). Moreover, it also led to abnormal load-displacement curves in the nanoindentation tests, resulting in the appearance of elbow and pop-out effects (˜270 nm at 20 s, 50 mN), which were highly dependent on the loading/unloading conditions. In summary, phase transformation of Si promoted surface deformation and fracture under both static and dynamic mechanical loading.

  20. DNA under Force: Mechanics, Electrostatics, and Hydration

    Directory of Open Access Journals (Sweden)

    Jingqiang Li

    2015-02-01

    Full Text Available Quantifying the basic intra- and inter-molecular forces of DNA has helped us to better understand and further predict the behavior of DNA. Single molecule technique elucidates the mechanics of DNA under applied external forces, sometimes under extreme forces. On the other hand, ensemble studies of DNA molecular force allow us to extend our understanding of DNA molecules under other forces such as electrostatic and hydration forces. Using a variety of techniques, we can have a comprehensive understanding of DNA molecular forces, which is crucial in unraveling the complex DNA functions in living cells as well as in designing a system that utilizes the unique properties of DNA in nanotechnology.

  1. Gas Bubble Dynamics under Mechanical Vibrations

    Science.gov (United States)

    Mohagheghian, Shahrouz; Elbing, Brian

    2017-11-01

    The scientific community has a limited understanding of the bubble dynamics under mechanical oscillations due to over simplification of Navier-Stockes equation by neglecting the shear stress tensor and not accounting for body forces when calculating the acoustic radiation force. The current work experimental investigates bubble dynamics under mechanical vibration and resulting acoustic field by measuring the bubble size and velocity using high-speed imaging. The experimental setup consists of a custom-designed shaker table, cast acrylic bubble column, compressed air injection manifold and an optical imaging system. The mechanical vibrations resulted in accelerations between 0.25 to 10 times gravitational acceleration corresponding to frequency and amplitude range of 8 - 22Hz and 1 - 10mm respectively. Throughout testing the void fraction was limited to <5%. The bubble size is larger than resonance size and smaller than acoustic wavelength. The amplitude of acoustic pressure wave was estimated using the definition of Bjerknes force in combination with Rayleigh-Plesset equation. Physical behavior of the system was capture and classified. Bubble size, velocity as well as size and spatial distribution will be presented.

  2. Dissociation of decision making under ambiguity and decision making under risk in breast cancer patients receiving adjuvant chemotherapy: a neuropsychological study.

    Science.gov (United States)

    Chen, Xingui; Zhu, Chunyan; Li, Jingjing; Qiu, Linlin; Zhang, Long; Yu, Fengqiong; Ye, Rong; Zhang, Jingjie; Wang, Kai

    2013-10-02

    There is evidence that women with breast cancer show a cognitive impairment after having undergone chemotherapy treatment; this cognitive impairment may result in behavioral deficits. However, the neural mechanism of this cognitive impairment remains unclear. The present study investigated the neural basis of the cognitive impairment caused by chemotherapy treatment by exploring the decision-making function of the executive subcomponents under ambiguity and risk in breast cancer survivors. Participants included breast cancer patients who had undergone chemotherapy (CT, N=63) or patients who did not undergo chemotherapy (non-CT, N=62), as well as matched healthy controls (HC, N=61). All participants were examined using the Iowa Gambling Task (IGT) to assess their decision-making under ambiguity, the Game of Dice Task (GDT) to assess their decision-making under risk and neuropsychological background tests. Our results indicated that during the IGT test, the chemotherapy-treated breast cancer patients selected from the disadvantageous decks with a higher frequency than the non-treated breast cancer patients or healthy controls, whereas all three groups performed at the same level when performing the GDT. The CT group demonstrated significantly lower scores in several cognitive tasks, including attention, memory, executive functions and cognitive processing, when compared with the other two groups. In addition, within the CT group, significant correlations were found between the IGT performance and information processing, as well as with working memory. This study demonstrated that breast cancer survivors treated with chemotherapy may have selective reductions in IGT performance but unimpaired GDT performance and that these deficits may result from dysfunctions in the limbic loop rather than in the dorsolateral prefrontal loop. © 2013 Elsevier B.V. All rights reserved.

  3. Deformation Mechanisms of Gum Metals Under Nanoindentation

    Science.gov (United States)

    Sankaran, Rohini Priya

    defect structures to applied loading, we perform ex-situ nanoindentation. Nanoindentation is a convenient method as the plastic deformation is localized and probes a nominally defect free volume of the material. We subsequently characterize the defect structures in these alloys with both conventional TEM and advanced techniques such as HAADF HRSTEM and nanoprobe diffraction. These advanced techniques allow for a more thorough understanding of the observed deformation features. The main findings from this investigation are as follows. As expected we observe that a non-equilibrium phase, o, is present in the leaner beta-stabilized alloy, ST Ref-1. We do not find any direct evidence of secondary phases in STGM, and we find the beta phase in CWGM, along with lath microstructure with subgrain structure consisting of dislocation cell networks. Upon nanoindentation, we find twinning accompanied by beta nucleation on the twin boundary in ST Ref-1 samples. This result is consistent with previous findings and is reasonable considering the alloy is unstable with respect to beta transformation. We find deformation nanotwinning in cold worked gum metals under nanoindentation, which is initially surprising. We argue that when viewed as a nanocrystalline material, such a deformation mechanism is consistent with previous work, and furthermore, a deformation nanotwinned structure does not preclude an ideal shear mechanism from operating in the alloy. Lastly, we observe continuous lattice rotations in STGM under nanoindentation via nanoprobe diffraction. With this technique, for the first time we can demonstrate that the lattice rotations are truly continuous at the nanoscale. We can quantify this lattice rotation, and find that even though the rotation is large, it may be mediated by a reasonable geometrically necessary dislocation density, and note that similar rotations are typically observed in other materials under nanoindentation. HRSTEM and conventional TEM data confirm the

  4. Mechanisms underlying UV-induced immune suppression

    International Nuclear Information System (INIS)

    Ullrich, Stephen E.

    2005-01-01

    Skin cancer is the most prevalent form of human neoplasia. Estimates suggest that in excess of one million new cases of skin cancer will be diagnosed this year alone in the United States (www.cancer.org/statistics). Fortunately, because of their highly visible location, skin cancers are more rapidly diagnosed and more easily treated than other types of cancer. Be that as it may, approximately 10,000 Americans a year die from skin cancer. The cost of treating non-melanoma skin cancer is estimated to be in excess of US$ 650 million a year [J.G. Chen, A.B. Fleischer, E.D. Smith, C. Kancler, N.D. Goldman, P.M. Williford, S.R. Feldman, Cost of non-melanoma skin cancer treatment in the United States, Dermatol. Surg. 27 (2001) 1035-1038], and when melanoma is included, the estimated cost of treating skin cancer in the United States is estimated to rise to US$ 2.9 billion annually (www.cancer.org/statistics). Because the morbidity and mortality associated with skin cancer is a major public health problem, it is important to understand the mechanisms underlying skin cancer development. The primary cause of skin cancer is the ultraviolet (UV) radiation found in sunlight. In addition to its carcinogenic potential, UV radiation is also immune suppressive. In fact, data from studies with both experimental animals and biopsy proven skin cancer patients suggest that there is an association between the immune suppressive effects of UV radiation and its carcinogenic potential. The focus of this manuscript will be to review the mechanisms underlying the induction of immune suppression following UV exposure. Particular attention will be directed to the role of soluble mediators in activating immune suppression

  5. Two distinct neural mechanisms underlying indirect reciprocity.

    Science.gov (United States)

    Watanabe, Takamitsu; Takezawa, Masanori; Nakawake, Yo; Kunimatsu, Akira; Yamasue, Hidenori; Nakamura, Mitsuhiro; Miyashita, Yasushi; Masuda, Naoki

    2014-03-18

    Cooperation is a hallmark of human society. Humans often cooperate with strangers even if they will not meet each other again. This so-called indirect reciprocity enables large-scale cooperation among nonkin and can occur based on a reputation mechanism or as a succession of pay-it-forward behavior. Here, we provide the functional and anatomical neural evidence for two distinct mechanisms governing the two types of indirect reciprocity. Cooperation occurring as reputation-based reciprocity specifically recruited the precuneus, a region associated with self-centered cognition. During such cooperative behavior, the precuneus was functionally connected with the caudate, a region linking rewards to behavior. Furthermore, the precuneus of a cooperative subject had a strong resting-state functional connectivity (rsFC) with the caudate and a large gray matter volume. In contrast, pay-it-forward reciprocity recruited the anterior insula (AI), a brain region associated with affective empathy. The AI was functionally connected with the caudate during cooperation occurring as pay-it-forward reciprocity, and its gray matter volume and rsFC with the caudate predicted the tendency of such cooperation. The revealed difference is consistent with the existing results of evolutionary game theory: although reputation-based indirect reciprocity robustly evolves as a self-interested behavior in theory, pay-it-forward indirect reciprocity does not on its own. The present study provides neural mechanisms underlying indirect reciprocity and suggests that pay-it-forward reciprocity may not occur as myopic profit maximization but elicit emotional rewards.

  6. Molecular mechanics of silk nanostructures under varied mechanical loading.

    Science.gov (United States)

    Bratzel, Graham; Buehler, Markus J

    2012-06-01

    Spider dragline silk is a self-assembling tunable protein composite fiber that rivals many engineering fibers in tensile strength, extensibility, and toughness, making it one of the most versatile biocompatible materials and most inviting for synthetic mimicry. While experimental studies have shown that the peptide sequence and molecular structure of silk have a direct influence on the stiffness, toughness, and failure strength of silk, few molecular-level analyses of the nanostructure of silk assemblies, in particular, under variations of genetic sequences have been reported. In this study, atomistic-level structures of wildtype as well as modified MaSp1 protein from the Nephila clavipes spider dragline silk sequences, obtained using an in silico approach based on replica exchange molecular dynamics and explicit water molecular dynamics, are subjected to simulated nanomechanical testing using different force-control loading conditions including stretch, pull-out, and peel. The authors have explored the effects of the poly-alanine length of the N. clavipes MaSp1 peptide sequence and identify differences in nanomechanical loading conditions on the behavior of a unit cell of 15 strands with 840-990 total residues used to represent a cross-linking β-sheet crystal node in the network within a fibril of the dragline silk thread. The specific loading condition used, representing concepts derived from the protein network connectivity at larger scales, have a significant effect on the mechanical behavior. Our analysis incorporates stretching, pull-out, and peel testing to connect biochemical features to mechanical behavior. The method used in this study could find broad applications in de novo design of silk-like tunable materials for an array of applications. Copyright © 2011 Wiley Periodicals, Inc.

  7. Neural Mechanisms Underlying Risk and Ambiguity Attitudes.

    Science.gov (United States)

    Blankenstein, Neeltje E; Peper, Jiska S; Crone, Eveline A; van Duijvenvoorde, Anna C K

    2017-11-01

    Individual differences in attitudes to risk (a taste for risk, known probabilities) and ambiguity (a tolerance for uncertainty, unknown probabilities) differentially influence risky decision-making. However, it is not well understood whether risk and ambiguity are coded differently within individuals. Here, we tested whether individual differences in risk and ambiguity attitudes were reflected in distinct neural correlates during choice and outcome processing of risky and ambiguous gambles. To these ends, we developed a neuroimaging task in which participants ( n = 50) chose between a sure gain and a gamble, which was either risky or ambiguous, and presented decision outcomes (gains, no gains). From a separate task in which the amount, probability, and ambiguity level were varied, we estimated individuals' risk and ambiguity attitudes. Although there was pronounced neural overlap between risky and ambiguous gambling in a network typically related to decision-making under uncertainty, relatively more risk-seeking attitudes were associated with increased activation in valuation regions of the brain (medial and lateral OFC), whereas relatively more ambiguity-seeking attitudes were related to temporal cortex activation. In addition, although striatum activation was observed during reward processing irrespective of a prior risky or ambiguous gamble, reward processing after an ambiguous gamble resulted in enhanced dorsomedial PFC activation, possibly functioning as a general signal of uncertainty coding. These findings suggest that different neural mechanisms reflect individual differences in risk and ambiguity attitudes and that risk and ambiguity may impact overt risk-taking behavior in different ways.

  8. Vascular Adventitia Calcification and Its Underlying Mechanism.

    Directory of Open Access Journals (Sweden)

    Na Li

    Full Text Available Previous research on vascular calcification has mainly focused on the vascular intima and media. However, we show here that vascular calcification may also occur in the adventitia. The purpose of this work is to help elucidate the pathogenic mechanisms underlying vascular calcification. The calcified lesions were examined by Von Kossa staining in ApoE-/- mice which were fed high fat diets (HFD for 48 weeks and human subjects aged 60 years and older that had died of coronary heart disease, heart failure or acute renal failure. Explant cultured fibroblasts and smooth muscle cells (SMCswere obtained from rat adventitia and media, respectively. After calcification induction, cells were collected for Alizarin Red S staining. Calcified lesions were observed in the aorta adventitia and coronary artery adventitia of ApoE-/-mice, as well as in the aorta adventitia of human subjects examined. Explant culture of fibroblasts, the primary cell type comprising the adventitia, was successfully induced for calcification after incubation with TGF-β1 (20 ng/ml + mineralization media for 4 days, and the phenotype conversion vascular adventitia fibroblasts into myofibroblasts was identified. Culture of SMCs, which comprise only a small percentage of all cells in the adventitia, in calcifying medium for 14 days resulted in significant calcification.Vascular calcification can occur in the adventitia. Adventitia calcification may arise from the fibroblasts which were transformed into myofibroblasts or smooth muscle cells.

  9. Investigating Mechanisms of Alkalinization for Reducing Primary Breast Tumor Invasion

    Directory of Open Access Journals (Sweden)

    Ian F. Robey

    2013-01-01

    Full Text Available The extracellular pH (pHe of many solid tumors is acidic as a result of glycolytic metabolism and poor perfusion. Acidity promotes invasion and enhances metastatic potential. Tumor acidity can be buffered by systemic administration of an alkaline agent such as sodium bicarbonate. Tumor-bearing mice maintained on sodium bicarbonate drinking water exhibit fewer metastases and survive longer than untreated controls. We predict this effect is due to inhibition of tumor invasion. Reducing tumor invasion should result in fewer circulating tumor cells (CTCs. We report that bicarbonate-treated MDA-MB-231 tumor-bearing mice exhibited significantly lower numbers of CTCs than untreated mice (. Tumor pHe buffering may reduce optimal conditions for enzymes involved in tumor invasion such as cathepsins and matrix metalloproteases (MMPs. To address this, we tested the effect of transient alkalinization on cathepsin and MMP activity using enzyme activatable fluorescence agents in mice bearing MDA-MB-231 mammary xenografts. Transient alkalinization significantly reduced the fluorescent signal of protease-specific activatable agents in vivo (. Alkalinization, however, did not affect expression of carbonic anhydrase IX (CAIX. The findings suggest a possible mechanism in a live model system for breast cancer where systemic alkalinization slows the rate of invasion.

  10. Mechanism of c-Src Synergy with the EGFR In Breast Cancer

    National Research Council Canada - National Science Library

    Tice, David

    1999-01-01

    ... on tumorigenicity and growth of breast tumor cells. Furthermore, we have discovered a mechanism of c-Src synergy with the EGFR and located specific points at which the pathway can be interdicted...

  11. Aspiration of breast abscess under ultrasound guidance: outcome obtained and factors affecting success.

    Science.gov (United States)

    Elagili, Faisal; Abdullah, Norlia; Fong, Liew; Pei, Tan

    2007-01-01

    To assess ultrasonographically (US) guided needle aspiration of breast abscesses as an alternative to surgical incision and drainage. In our prospective study, 30 patients with 31 breast abscesses (one patient had bilateral breast abscess) underwent percutaneous breast abscess drainage under US guidance with local anaesthesia and oral antibiotics between 1 January 2004 and 31 March 2005. These patients consisted of 16 (53.3%) non-lactating and 14 (46.7%) lactating women, with ages ranging from 18 to 68 years (median, 28 years). The racial distribution comprised 26 (86.7%) Malays, three (10%) Chinese and one (3.3%) Indian. All patients had the chief complaint of breast swelling and 25 (83.3%) had breast pain. Clinically, 28 (93.3%) were found to have a palpable mass. Nine (30%) lesions were in the upper outer quadrant of the left breast. US diameters ranged from 1 to 15 cm (median, 4 cm). The pus volumes varied from 1 to 200 mL (median, 14 mL). Fifteen (50%) patients required only a single aspiration, 10 required multiple aspirations and five required incision and drainage. Those patients in whom needle aspiration failed had multiloculated lesions irrespective of abscess volume and size. Needle aspiration with ultrasound guidance is an effective treatment for breast abscess irrespective of abscess volume and size.

  12. Adaptive Breast Radiation Therapy Using Modeling of Tissue Mechanics: A Breast Tissue Segmentation Study

    International Nuclear Information System (INIS)

    Juneja, Prabhjot; Harris, Emma J.; Kirby, Anna M.; Evans, Philip M.

    2012-01-01

    Purpose: To validate and compare the accuracy of breast tissue segmentation methods applied to computed tomography (CT) scans used for radiation therapy planning and to study the effect of tissue distribution on the segmentation accuracy for the purpose of developing models for use in adaptive breast radiation therapy. Methods and Materials: Twenty-four patients receiving postlumpectomy radiation therapy for breast cancer underwent CT imaging in prone and supine positions. The whole-breast clinical target volume was outlined. Clinical target volumes were segmented into fibroglandular and fatty tissue using the following algorithms: physical density thresholding; interactive thresholding; fuzzy c-means with 3 classes (FCM3) and 4 classes (FCM4); and k-means. The segmentation algorithms were evaluated in 2 stages: first, an approach based on the assumption that the breast composition should be the same in both prone and supine position; and second, comparison of segmentation with tissue outlines from 3 experts using the Dice similarity coefficient (DSC). Breast datasets were grouped into nonsparse and sparse fibroglandular tissue distributions according to expert assessment and used to assess the accuracy of the segmentation methods and the agreement between experts. Results: Prone and supine breast composition analysis showed differences between the methods. Validation against expert outlines found significant differences (P<.001) between FCM3 and FCM4. Fuzzy c-means with 3 classes generated segmentation results (mean DSC = 0.70) closest to the experts' outlines. There was good agreement (mean DSC = 0.85) among experts for breast tissue outlining. Segmentation accuracy and expert agreement was significantly higher (P<.005) in the nonsparse group than in the sparse group. Conclusions: The FCM3 gave the most accurate segmentation of breast tissues on CT data and could therefore be used in adaptive radiation therapy-based on tissue modeling. Breast tissue segmentation

  13. Adaptive Breast Radiation Therapy Using Modeling of Tissue Mechanics: A Breast Tissue Segmentation Study

    Energy Technology Data Exchange (ETDEWEB)

    Juneja, Prabhjot, E-mail: Prabhjot.Juneja@icr.ac.uk [Joint Department of Physics, Institute of Cancer Research, Sutton (United Kingdom); Harris, Emma J. [Joint Department of Physics, Institute of Cancer Research, Sutton (United Kingdom); Kirby, Anna M. [Department of Academic Radiotherapy, Royal Marsden National Health Service Foundation Trust, Sutton (United Kingdom); Evans, Philip M. [Joint Department of Physics, Institute of Cancer Research, Sutton (United Kingdom)

    2012-11-01

    Purpose: To validate and compare the accuracy of breast tissue segmentation methods applied to computed tomography (CT) scans used for radiation therapy planning and to study the effect of tissue distribution on the segmentation accuracy for the purpose of developing models for use in adaptive breast radiation therapy. Methods and Materials: Twenty-four patients receiving postlumpectomy radiation therapy for breast cancer underwent CT imaging in prone and supine positions. The whole-breast clinical target volume was outlined. Clinical target volumes were segmented into fibroglandular and fatty tissue using the following algorithms: physical density thresholding; interactive thresholding; fuzzy c-means with 3 classes (FCM3) and 4 classes (FCM4); and k-means. The segmentation algorithms were evaluated in 2 stages: first, an approach based on the assumption that the breast composition should be the same in both prone and supine position; and second, comparison of segmentation with tissue outlines from 3 experts using the Dice similarity coefficient (DSC). Breast datasets were grouped into nonsparse and sparse fibroglandular tissue distributions according to expert assessment and used to assess the accuracy of the segmentation methods and the agreement between experts. Results: Prone and supine breast composition analysis showed differences between the methods. Validation against expert outlines found significant differences (P<.001) between FCM3 and FCM4. Fuzzy c-means with 3 classes generated segmentation results (mean DSC = 0.70) closest to the experts' outlines. There was good agreement (mean DSC = 0.85) among experts for breast tissue outlining. Segmentation accuracy and expert agreement was significantly higher (P<.005) in the nonsparse group than in the sparse group. Conclusions: The FCM3 gave the most accurate segmentation of breast tissues on CT data and could therefore be used in adaptive radiation therapy-based on tissue modeling. Breast tissue

  14. Mechanism of RhoB/FTI Action in Breast Cancer

    National Research Council Canada - National Science Library

    Kamasani, Uma

    2003-01-01

    .... What factors dictate FTI efficacy? Work completed earlier in this project defined rules for RhoB and its downstream effector kinase PRK in mediating growth inhibition by FTI in epithelial cells, including human breast epithelial cells...

  15. Magnetization reversal mechanisms under oblique magnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    Ntallis, N.; Efthimiadis, K.G., E-mail: kge@auth.gr

    2017-03-01

    In this work finite element micromagnetic simulations were performed in order to study the reversal mechanisms of spherical ferromagnetic particles with uniaxial magnetocrystalline anisotropy, when they are magnetized along an oblique direction with respect to the anisotropy axis. Magnetization loops are taken in different directions of external magnetic field, at different anisotropy constants and particle sizes. In the simulation results, the three reversal mechanisms (coherent, curling and domains) are observed and new phenomena arise due to the action of oblique magnetic fields. Moreover, the dependence of the critical fields with respect to the angle of the external field is presented. - Highlights: • Finite element micromagnetic simulation of the three different reversal mechanisms. • For the curling mechanism, the new phenomenon is the rotation of the vortex. • In the domain reversal mechanism, the formed domain wall is smaller than 180°. • In soft ferromagnetic particles a rearrangement of the magnetic domains is observed.

  16. Shear-wave elastographic features of breast cancers: comparison with mechanical elasticity and histopathologic characteristics.

    Science.gov (United States)

    Lee, Su Hyun; Moon, Woo Kyung; Cho, Nariya; Chang, Jung Min; Moon, Hyeong-Gon; Han, Wonshik; Noh, Dong-Young; Lee, Jung Chan; Kim, Hee Chan; Lee, Kyoung-Bun; Park, In-Ae

    2014-03-01

    The objective of this study was to compare the quantitative and qualitative shear-wave elastographic (SWE) features of breast cancers with mechanical elasticity and histopathologic characteristics. This prospective study was conducted with institutional review board approval, and written informed consent was obtained. Shear-wave elastography was performed for 30 invasive breast cancers in 30 women before surgery. The mechanical elasticity of a fresh breast tissue section, correlated with the ultrasound image, was measured using an indentation system. Quantitative (maximum, mean, minimum, and standard deviation of elasticity in kilopascals) and qualitative (color heterogeneity and presence of signal void areas in the mass) SWE features were compared with mechanical elasticity and histopathologic characteristics using the Pearson correlation coefficient and the Wilcoxon signed rank test. Maximum SWE values showed a moderate correlation with maximum mechanical elasticity (r = 0.530, P = 0.003). There were no significant differences between SWE values and mechanical elasticity in histologic grade I or II cancers (P = 0.268). However, SWE values were significantly higher than mechanical elasticity in histologic grade III cancers (P masses were present in 43% of breast cancers (13 of 30) and were correlated with dense collagen depositions (n = 11) or intratumoral necrosis (n = 2). Quantitative and qualitative SWE features reflect both the mechanical elasticity and histopathologic characteristics of breast cancers.

  17. Supersymmetric quantum mechanics under point singularities

    International Nuclear Information System (INIS)

    Uchino, Takashi; Tsutsui, Izumi

    2003-01-01

    We provide a systematic study on the possibility of supersymmetry (SUSY) for one-dimensional quantum mechanical systems consisting of a pair of lines R or intervals [-l, l] each having a point singularity. We consider the most general singularities and walls (boundaries) at x = ±l admitted quantum mechanically, using a U(2) family of parameters to specify one singularity and similarly a U(1) family of parameters to specify one wall. With these parameter freedoms, we find that for a certain subfamily the line systems acquire an N = 1 SUSY which can be enhanced to N = 4 if the parameters are further tuned, and that these SUSY are generically broken except for a special case. The interval systems, on the other hand, can accommodate N = 2 or N = 4 SUSY, broken or unbroken, and exhibit a rich variety of (degenerate) spectra. Our SUSY systems include the familiar SUSY systems with the Dirac δ(x)-potential, and hence are extensions of the known SUSY quantum mechanics to those with general point singularities and walls. The self-adjointness of the supercharge in relation to the self-adjointness of the Hamiltonian is also discussed

  18. Stress and Coping Mechanisms Among Breast Cancer Patients and ...

    African Journals Online (AJOL)

    Sitwala

    the leading cause of cancer mortality, representing. 14.1%. In Zambia ... focused on coping with breast cancer, 5 on stress and adaptation to .... relying on prayer, avoiding negative people, ... responses among women from three ethnic groups; ... common strategy among African Americans. .... Global Cancer Statistics, 2002.

  19. Clinicopathological and imaging features of breast cancer in Korean Women under 40 years of age

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jun Woo; Jang, Mi Jung; Kim, Sun Mi; Yun, Bo La; Lee, Jong Yoon; Kim, Eun Kyu; Kang, Eun Young; Park, So Yeon [Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2017-06-15

    To evaluate the clinicopathological and imaging features of mammography, ultrasonography, and magnetic resonance imaging (MRI) for breast cancer in Korean women under 40 years of age according to molecular subtypes. We included 183 breast cancers in 176 consecutive women under 40 years old who had been diagnosed with breast cancer between January 2012 and November 2014. The patients' clinical and pathologic records were available as electronic medical records. A retrospective review of the pre-operative imaging studies was performed with 177 mammographies, 183 ultrasonographies, and 178 MRIs. Eighty-six percent (158/183) of lesions were symptomatic, with masses (147/183) as the most common presentation. Eighty percent (22/25) of the asymptomatic lesions were diagnosed via screening ultrasonography. The luminal A subtype was the most common (n = 79, 43%), human epidermal growth factor receptor 2-enriched subtype showed indistinct margins on mammography (p = 0.006), the triple negative subtype depicted a posterior enhancement on ultrasonography (p < 0.001) and rim enhancement on MRI (p < 0.001). Breast cancers in Korean women under 40 years of age are commonly presented with a palpable mass, and luminal A is the most common molecular subtype. In our study, the imaging and pathologic characteristics of breast cancer in younger women were similar to those previously reported for older patients.

  20. Clinicopathological and imaging features of breast cancer in Korean Women under 40 years of age

    International Nuclear Information System (INIS)

    Kim, Jun Woo; Jang, Mi Jung; Kim, Sun Mi; Yun, Bo La; Lee, Jong Yoon; Kim, Eun Kyu; Kang, Eun Young; Park, So Yeon

    2017-01-01

    To evaluate the clinicopathological and imaging features of mammography, ultrasonography, and magnetic resonance imaging (MRI) for breast cancer in Korean women under 40 years of age according to molecular subtypes. We included 183 breast cancers in 176 consecutive women under 40 years old who had been diagnosed with breast cancer between January 2012 and November 2014. The patients' clinical and pathologic records were available as electronic medical records. A retrospective review of the pre-operative imaging studies was performed with 177 mammographies, 183 ultrasonographies, and 178 MRIs. Eighty-six percent (158/183) of lesions were symptomatic, with masses (147/183) as the most common presentation. Eighty percent (22/25) of the asymptomatic lesions were diagnosed via screening ultrasonography. The luminal A subtype was the most common (n = 79, 43%), human epidermal growth factor receptor 2-enriched subtype showed indistinct margins on mammography (p = 0.006), the triple negative subtype depicted a posterior enhancement on ultrasonography (p < 0.001) and rim enhancement on MRI (p < 0.001). Breast cancers in Korean women under 40 years of age are commonly presented with a palpable mass, and luminal A is the most common molecular subtype. In our study, the imaging and pathologic characteristics of breast cancer in younger women were similar to those previously reported for older patients

  1. Physical and chemical mechanisms underlying hematoma evolution

    International Nuclear Information System (INIS)

    Cho, K.J.; Fanders, B.L.; Smid, A.R.; McLaughlin, P.

    1986-01-01

    Angiostat, a new collagen embolic material supplied at a concentration of 35 mg/ml (Target Therapeutics, Los Angeles) was used for flow-directed hepatic artery embolization in a series of rabbits to examine its acute effects on hepatic microcirculation. Arteriograms were obtained both before and after embolization. The aorta and portal vein were perfused with two different colors of Microfil after the animals were killed,. Cleared liver specimens were examined under a dissection microscope. Extent of dearterialization, status of portal sinusoidal perfusion, and collateral formation after embolization with Angiostat were evaluated. Results will be compared with results achieved using other liquid and particulate embolic agents

  2. Noninvasive In-Vivo Quantification of Mechanical Heterogeneity of Invasive Breast Carcinomas.

    Directory of Open Access Journals (Sweden)

    Tengxiao Liu

    Full Text Available Heterogeneity is a hallmark of cancer whether one considers the genotype of cancerous cells, the composition of their microenvironment, the distribution of blood and lymphatic microvasculature, or the spatial distribution of the desmoplastic reaction. It is logical to expect that this heterogeneity in tumor microenvironment will lead to spatial heterogeneity in its mechanical properties. In this study we seek to quantify the mechanical heterogeneity within malignant and benign tumors using ultrasound based elasticity imaging. By creating in-vivo elastic modulus images for ten human subjects with breast tumors, we show that Young's modulus distribution in cancerous breast tumors is more heterogeneous when compared with tumors that are not malignant, and that this signature may be used to distinguish malignant breast tumors. Our results complement the view of cancer as a heterogeneous disease on multiple length scales by demonstrating that mechanical properties within cancerous tumors are also spatially heterogeneous.

  3. Epigenetic Mechanisms of Folate Nutrition in Breast Cancer

    Science.gov (United States)

    2012-04-01

    MDAMB231 clones that express non-leaky TetR systems. Test effects of folate deficiency on global and gene specific DNA methylation and gene...cellular differentiation and function. Aberrant DNA methylation is a characteristic of cancer cells, including mammary tumors. The B vitamin folate ...relationships between folate , one-carbon metabolism, DNA methylation , and gene expression within the context of breast cancer. We hypothesize that

  4. V1 mechanisms underlying chromatic contrast detection

    Science.gov (United States)

    Hass, Charles A.

    2013-01-01

    To elucidate the cortical mechanisms of color vision, we recorded from individual primary visual cortex (V1) neurons in macaque monkeys performing a chromatic detection task. Roughly 30% of the neurons that we encountered were unresponsive at the monkeys' psychophysical detection threshold (PT). The other 70% were responsive at threshold but on average, were slightly less sensitive than the monkey. For these neurons, the relationship between neurometric threshold (NT) and PT was consistent across the four isoluminant color directions tested. A corollary of this result is that NTs were roughly four times lower for stimuli that modulated the long- and middle-wavelength sensitive cones out of phase. Nearly one-half of the neurons that responded to chromatic stimuli at the monkeys' detection threshold also responded to high-contrast luminance modulations, suggesting a role for neurons that are jointly tuned to color and luminance in chromatic detection. Analysis of neuronal contrast-response functions and signal-to-noise ratios yielded no evidence for a special set of “cardinal color directions,” for which V1 neurons are particularly sensitive. We conclude that at detection threshold—as shown previously with high-contrast stimuli—V1 neurons are tuned for a diverse set of color directions and do not segregate naturally into red–green and blue–yellow categories. PMID:23446689

  5. Physiological mechanisms underlying animal social behaviour.

    Science.gov (United States)

    Seebacher, Frank; Krause, Jens

    2017-08-19

    Many species of animal live in groups, and the group represents the organizational level within which ecological and evolutionary processes occur. Understanding these processes, therefore, relies on knowledge of the mechanisms that permit or constrain group formation. We suggest that physiological capacities and differences in physiology between individuals modify fission-fusion dynamics. Differences between individuals in locomotor capacity and metabolism may lead to fission of groups and sorting of individuals into groups with similar physiological phenotypes. Environmental impacts such as hypoxia can influence maximum group sizes and structure in fish schools by altering access to oxygenated water. The nutritional environment determines group cohesion, and the increase in information collected by the group means that individuals should rely more on social information and form more cohesive groups in uncertain environments. Changing environmental contexts require rapid responses by individuals to maintain group coordination, which are mediated by neuroendocrine signalling systems such as nonapeptides and steroid hormones. Brain processing capacity may constrain social complexity by limiting information processing. Failure to evaluate socially relevant information correctly limits social interactions, which is seen, for example, in autism. Hence, functioning of a group relies to a large extent on the perception and appropriate processing of signals from conspecifics. Many if not all physiological systems are mechanistically linked, and therefore have synergistic effects on social behaviour. A challenge for the future lies in understanding these interactive effects, which will improve understanding of group dynamics, particularly in changing environments.This article is part of the themed issue 'Physiological determinants of social behaviour in animals'. © 2017 The Author(s).

  6. Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer

    Science.gov (United States)

    1997-07-01

    immune system? Ann N Y Acad Sci, JR, 1986, The role of NK cells in tumour growth and 741, 212-15. metastasis in beige mice. Nature, 284, 622-4. 89. Stone ...77. Simmons ML and Brick JO, 1969, The Laboratory 96. Senger DR, Brown LF, Claffey KP and Dvorak HF, Mouse. Hollaender A, ed. Englewood Cliffs, NJ...ranfe of huan tumo sme I I su ding the human chromosome 11 into the highly metastatic MDA-MB-435 breast tumorigenic phenotype of several tumor lines

  7. Reduced expression of p27 is a novel mechanism of docetaxel resistance in breast cancer cells

    International Nuclear Information System (INIS)

    Brown, Iain; Shalli, Kawan; McDonald, Sarah L; Moir, Susan E; Hutcheon, Andrew W; Heys, Steven D; Schofield, Andrew C

    2004-01-01

    Docetaxel is one of the most effective chemotherapeutic agents in the treatment of breast cancer. Breast cancers can have an inherent or acquired resistance to docetaxel but the causes of this resistance remain unclear. However, apoptosis and cell cycle regulation are key mechanisms by which most chemotherapeutic agents exert their cytotoxic effects. We created two docetaxel-resistant human breast cancer cell lines (MCF-7 and MDA-MB-231) and performed cDNA microarray analysis to identify candidate genes associated with docetaxel resistance. Gene expression changes were validated at the RNA and protein levels by reverse transcription PCR and western analysis, respectively. Gene expression cDNA microarray analysis demonstrated reduced p27 expression in docetaxel-resistant breast cancer cells. Although p27 mRNA expression was found to be reduced only in MCF-7 docetaxel-resistant sublines (2.47-fold), reduced expression of p27 protein was noted in both MCF-7 and MDA-MB-231 docetaxel-resistant breast cancer cells (2.83-fold and 3.80-fold, respectively). This study demonstrates that reduced expression of p27 is associated with acquired resistance to docetaxel in breast cancer cells. An understanding of the genes that are involved in resistance to chemotherapy may allow further development in modulating drug resistance, and may permit selection of those patients who are most likely to benefit from such therapies

  8. Regulation of matrix stiffness on the epithelial-mesenchymal transition of breast cancer cells under hypoxia environment

    Science.gov (United States)

    Lv, Yonggang; Chen, Can; Zhao, Boyuan; Zhang, Xiaomei

    2017-06-01

    Substrate stiffness and hypoxia are associated with tumor development and progression, respectively. However, the synergy of them on the biological behavior of human breast cancer cell is still largely unknown. This study explored how substrate stiffness regulates the cell phenotype, viability, and epithelial-mesenchymal transition (EMT) of human breast cancer cells MCF-7 under hypoxia (1% O2). TRITC-phalloidin staining showed that MCF-7 cells transformed from round to irregular polygon with stiffness increase either in normoxia or hypoxia. While being accompanied with the upward tendency from a 0.5- to a 20-kPa substrate, the percentage of cell apoptosis was significantly higher in hypoxia than that in normoxia, especially on the 20-kPa substrate. Additionally, it was hypoxia, but not normoxia, that promoted the EMT of MCF-7 by upregulating hypoxia-inducible factor-1α (HIF-1α), vimentin, Snail 1, and matrix metalloproteinase 2 (MMP 2) and 9 (MMP 9), and downregulating E-cadherin simultaneously regardless of the change of substrate stiffness. In summary, this study discovered that hypoxia and stiffer substrate (20 kPa) could synergistically induce phenotype change, apoptosis, and EMT of MCF-7 cells. Results of this study have an important significance on further exploring the synergistic effect of stiffness and hypoxia on the EMT of breast cancer cells and its molecular mechanism.

  9. Nutritional value of breast and thigh muscle of chukar partridge (Alectoris chukar under intensive fattening conditions

    Directory of Open Access Journals (Sweden)

    Radovan Jůzl

    2012-01-01

    Full Text Available The aim of our study was to evaluate the nutritional value of the breast and thigh muscle of chukar partridge (Alectoris chukar under intensive fattening conditions. Commercial feeding mixtures for broilers were used. Live weight of 60 partridges (birds were not sexed was controlled during 90 days of fattening. After the fattening was finished, 30 birds were selected to monitor the carcass yield. Breast and thigh muscle were used for chemical analysis of crude protein (Kjeldahl method, total lipids (fat analyser ANKOMXT10, ash (Muffle furnace - 550° C and gross energy (calorimetry. Average values ​​of live weight were increasing in the course of fattening; at the end of fattening the live weight reached 0.452 kg. The carcass yield, breast muscle yield and thigh yield were evaluated (73.72%, 18.09%, 20.80%, respectively. Chemical analysis showed a highly significant difference (P ≤ 0.01 between the breast and thigh muscle for crude protein, fat, ash and gross energy. The ash content demonstrated a significant difference (P ≤ 0.05 between the breast and thigh muscle. This study brings new data on the nutritional value of the meat of chukar partridge that can be used for reccomendation of a suitable feeding mixture.

  10. Breast cancer features in women under the age of 40 years

    Directory of Open Access Journals (Sweden)

    Deise Santiago Girão Eugênio

    Full Text Available Summary Objective: To describe the clinical features, imaging findings and pathological aspects of breast cancer diagnosed in women under the age of 40 years. Method: A retrospective, descriptive study was performed through analysis of medical records between November 2008 and August 2012. One hundred and twenty (120 patients were included, of whom 112 underwent mammography, 113 underwent ultrasonography, and 105 underwent magnetic resonance imaging (MRI. The histopathological data was obtained in most cases from post-surgical analysis, which was available for 113 patients. Results: The mean age at diagnosis of primary breast cancer was 34 years. Only 11 patients (9.0% had a family history of breast or ovarian cancer in first-degree relative. Ninety-two (92 patients sought medical attention after showing breast symptoms, and the presence of a palpable nodule was the main complaint. One hundred and twenty-two (122 primary tumors were diagnosed, of which 112 were invasive (95%. The most common histological type was invasive ductal carcinoma (73.8%. Luminal B was the predominant molecular subtype (42.6%. Ultrasonography was positive in 94.5% of the cases and the most common finding were nodules (94.8%. At mammography, the malignancy was observed in 92.8% and the presence of suggestive calcifications was the dominant feature. The MRI was positive in 98% of patients, and mass lesions were the most common. Conclusion: Most cases of breast cancer diagnosed in patients under the age of 40 years, in our population, had symptoms at diagnosis and tumor with more aggressive biological behavior. Despite the ultrasound has been the most widely used method, we found improved characterization of breast lesions when also used mammography and MRI.

  11. Crack assessment of pipe under combined thermal and mechanical load

    International Nuclear Information System (INIS)

    Song, Tae Kwang; Kim, Yun Jae

    2009-01-01

    In this paper, J-integral and transient C(t)-integral, which were key parameters in low temperature and high temperature fracture mechanics, under combined thermal and mechanical load were estimated via 3-dimensional finite element analyses. Various type of thermal and mechanical load, material hardening were considered to decrease conservatism in existing solutions. As a results, V-factor and redistribution time for combined thermal and mechanical load were proposed to calculate J-integral and C(t)-integral, respectively.

  12. Mechanical properties of metastatic breast cancer cells invading into collagen I matrices

    Science.gov (United States)

    Ros, Robert

    2014-03-01

    Mechanical interactions between cells and the extracellular matrix (ECM) are critical to the metastasis of cancer cells. To investigate the mechanical interplay between the cells and ECM during invasion, we created thin bovine collagen I hydrogels ranging from 0.1-5 kPa in Young's modulus that were seeded with highly metastatic MDA-MB-231 breast cancer cells. Significant population fractions invaded the matrices either partially or fully within 24 h. We then combined confocal fluorescence microscopy and indentation with an atomic force microscope to determine the Young's moduli of individual embedded cells and the pericellular matrix using novel analysis methods for heterogeneous samples. In partially embedded cells, we observe a statistically significant correlation between the degree of invasion and the Young's modulus, which was up to an order of magnitude greater than that of the same cells measured in 2D. ROCK inhibition returned the cells' Young's moduli to values similar to 2D and diminished but did not abrogate invasion. This provides evidence that Rho/ROCK-dependent acto-myosin contractility is employed for matrix reorganization during initial invasion, and suggests the observed cell stiffening is due to an attendant increase in actin stress fibers. This work was supported by the National Cancer Institute under the grant U54 CA143862.

  13. Breast infection

    Science.gov (United States)

    Mastitis; Infection - breast tissue; Breast abscess ... must continue to breastfeed or pump to relieve breast swelling from milk production. In case if the abscess does not go away, needle aspiration under ultrasound ...

  14. The Acinar Cage: Basement Membranes Determine Molecule Exchange and Mechanical Stability of Human Breast Cell Acini.

    Directory of Open Access Journals (Sweden)

    Aljona Gaiko-Shcherbak

    Full Text Available The biophysical properties of the basement membrane that surrounds human breast glands are poorly understood, but are thought to be decisive for normal organ function and malignancy. Here, we characterize the breast gland basement membrane with a focus on molecule permeation and mechanical stability, both crucial for organ function. We used well-established and nature-mimicking MCF10A acini as 3D cell model for human breast glands, with ether low- or highly-developed basement membrane scaffolds. Semi-quantitative dextran tracer (3 to 40 kDa experiments allowed us to investigate the basement membrane scaffold as a molecule diffusion barrier in human breast acini in vitro. We demonstrated that molecule permeation correlated positively with macromolecule size and intriguingly also with basement membrane development state, revealing a pore size of at least 9 nm. Notably, an intact collagen IV mesh proved to be essential for this permeation function. Furthermore, we performed ultra-sensitive atomic force microscopy to quantify the response of native breast acini and of decellularized basement membrane shells against mechanical indentation. We found a clear correlation between increasing acinar force resistance and basement membrane formation stage. Most important native acini with highly-developed basement membranes as well as cell-free basement membrane shells could both withstand physiologically relevant loads (≤ 20 nN without loss of structural integrity. In contrast, low-developed basement membranes were significantly softer and more fragile. In conclusion, our study emphasizes the key role of the basement membrane as conductor of acinar molecule influx and mechanical stability of human breast glands, which are fundamental for normal organ function.

  15. Underlying mechanisms of improving physical activity behavior after rehabilitation

    NARCIS (Netherlands)

    van der Ploeg, H.P.; Streppel, K.R.; van der Beek, A.J.; van der Woude, L.H.V.; van Harten, W.H.; van Mechelen, W.

    2008-01-01

    Background: Regular physical activity is beneficial for the health and functioning of people with a disability. Effective components of successful physical activity promotion interventions should be identified and disseminated. Purpose: To study the underlying mechanisms of the combined sport

  16. Underlying Mechanisms of Improving Physical Activity Behavior after Rehabilitation

    NARCIS (Netherlands)

    van der Ploeg, Hidde P.; Streppel, Kitty R.M.; van der Beek, Allard J.; Woude, Luc H.V.; van Harten, Willem H.; Vollenbroek-Hutten, Miriam Marie Rosé; van Mechelen, Willem

    2008-01-01

    Background: Regular physical activity is beneficial for the health and functioning of people with a disability. Effective components of successful physical activity promotion interventions should be identified and disseminated. Purpose: To study the underlying mechanisms of the combined sport

  17. Nonlinear Mechanics of MEMS Rectangular Microplates under Electrostatic Actuation

    KAUST Repository

    Saghir, Shahid

    2016-01-01

    The first objective of the dissertation is to develop a suitable reduced order model capable of investigating the nonlinear mechanical behavior of von-Karman plates under electrostatic actuation. The second objective is to investigate the nonlinear

  18. Animal behavior models of the mechanisms underlying antipsychotic atypicality.

    NARCIS (Netherlands)

    Geyer, M.A.; Ellenbroek, B.A.

    2003-01-01

    This review describes the animal behavior models that provide insight into the mechanisms underlying the critical differences between the actions of typical vs. atypical antipsychotic drugs. Although many of these models are capable of differentiating between antipsychotic and other psychotropic

  19. Control of a perturbed under-actuated mechanical system

    KAUST Repository

    Zayane, Chadia; Laleg-Kirati, Taous-Meriem; Chemori, Ahmed

    2015-01-01

    In this work, the trajectory tracking problem for an under-actuated mechanical system in presence of unknown input disturbances is addressed. The studied inertia wheel inverted pendulum falls in the class of non minimum phase systems. The proposed

  20. Infection of PTFE mesh 15 years following pedicled TRAM flap breast reconstruction: mechanism and aetiology.

    Science.gov (United States)

    Elfaki, A; Gkorila, A; Khatib, M; Malata, C M

    2018-01-01

    The pedicled transverse rectus abdominis myocutaneous (TRAM) flap procedure is still widely used for breast reconstruction. The repair of the flap harvest site in the transverse rectus abdominis muscle and sheath is often assisted by the use of prosthetic meshes. This decreases the risk of abdominal wall weakness and herniation but, being a foreign body, it also carries the risk of infection. In this report, we describe the case of a 63-year-old patient who, whilst receiving chemotherapy for metastatic breast cancer, presented with an infected polytetrafluoroethylene mesh 15 years after pedicled TRAM flap immediate breast reconstruction. This necessitated mesh removal to treat the infection. Following a thorough review of the English literature, this is the longest recorded presentation of an abdominal prosthetic mesh infection. The mechanism and aetiology of such a late complication are discussed.

  1. Withaferin A and sulforaphane regulate breast cancer cell cycle progression through epigenetic mechanisms.

    Science.gov (United States)

    Royston, Kendra J; Paul, Bidisha; Nozell, Susan; Rajbhandari, Rajani; Tollefsbol, Trygve O

    2018-07-01

    Little is known about the effects of combinatorial dietary compounds on the regulation of epigenetic mechanisms involved in breast cancer prevention. The human diet consists of a multitude of components, and there is a need to elucidate how certain compounds interact in collaboration. Withaferin A (WA), found in the Indian winter cherry and documented as a DNA methyltransferase (DNMT) inhibitor, and sulforaphane (SFN), a well-known histone deacetylase (HDAC) inhibitor found in cruciferous vegetables, are two epigenetic modifying compounds that have only recently been studied in conjunction. The use of DNMT and HDAC inhibitors to reverse the malignant expression of certain genes in breast cancer has shown considerable promise. Previously, we found that SFN + WA synergistically promote breast cancer cell death. Herein, we determined that these compounds inhibit cell cycle progression from S to G2 phase in MDA-MB-231 and MCF-7 breast cancer. Furthermore, we demonstrate that this unique combination of epigenetic modifying compounds down-regulates the levels of Cyclin D1 and CDK4, and pRB; conversely, the levels of E2F mRNA and tumor suppressor p21 are increased independently of p53. We find these events coincide with an increase in unrestricted histone methylation. We propose SFN + WA-induced breast cancer cell death is attributed, in part, to epigenetic modifications that result in the modulated expression of key genes responsible for the regulation of cancer cell senescence. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. The frequency of malignancy in breast lumps on fnac in females under 35 years of age

    International Nuclear Information System (INIS)

    Iqbal, M.; Iqbal, M.

    2014-01-01

    Breast carcinoma is one of the common malignancies in females and its incidence is increasing in younger age. Diagnosis of carcinoma breast includes clinical evaluation, imaging and pathology. Fine Needle Aspiration Cytology is the first line pathological investigation in the diagnosis with excellent results. Objective: To determine the frequency of malignancy in breast lumps on FNAC in females under 35 years of age. Descriptive cross sectional study. Setting:Department of pathology Fatima Jinnah Medical College (FJMC), Lahore. Duration: Six months from 20th July, 2011 till 20th January, 2012.Methods: 150 female patients 35 years of age or less, presenting to the OPD and Indoor of Sir Ganga Ram Hospital Lahore, an affiliated hospital of FJMC Lahore, with breast lumps were included in the study. Demographic features and consent of the patients were noted. FNAC of the patients was performed as per advice of the consultant. Diagnosis of malignant cases was further confirmed on histology.Results: Out of all, 124 lumps (82.7%) were benign and 26 lumps (17.3%) were malignant. Amongst the benign lumps, 77(62.1%) were fibroadenomas, 28(22.6%) were fibrocystic changes, 08(06.5%) were inflammatory lesions, 07(05.6%) showed pyogenic abscess and 04 lumps (03.2%) were galactoceles. Amongst the malignant lumps, 22(84.6%) were ductal carcinoma, 02(07.7%) colloid carcinoma and 02(07.7%) were malignant phylloides. Conclusions: The frequency of malignancy in breast lumps in Pakistan is significantly high in females under 35 years of age. Appropriate measures are needed for prevention and early diagnosis and treatment in young females. (author)

  3. Lumpectomy and sentinel lymph node navigation surgery for breast cancer under local anesthesia

    International Nuclear Information System (INIS)

    Nakajima, Hiroo; Fujiwara, Ikuya; Mizuta, Naruhiko; Sakaguchi, Koichi; Hachimine, Yasushi; Nakatsukasa, Katsuhiro; Kobayashi, Aya

    2007-01-01

    We studied and analyzed therapeutic outcomes of a radical surgery under local anesthesia for breast cancer in our department. Subjects were 53 patients with breast cancer whose diagnoses were definitely made before surgery. Indications were: localized ductal carcinoma in situ (DCIS) diagnosed preoperatively; invasive carcinoma less than 3 cm in tumor diameter on ultrasound and magnetic resonance imaging scan; and clinically tumors with negative axillary lymph nodes. Operative procedures included microdochectomy or lumpectomy associated with sentinel lymph node navigation biopsy (SLNB). We could perform the operation under local anesthesia in all the 53 patients, and were not demanded to shift from local to general anesthesia. Surgical stumps were positive in 10 patients (18.9%). Of the ten patients, additional resection was performed in one, and irradiation was added to the remaining nine patients. SLNB was performed in a total of 39 patients, six (15.4%) patients of them had metastasis and two out of the six patients underwent additional axillary lymph node dissection. None of serious complications were encountered. Local recurrence and hepatic metastasis occurred in each one patient in an averaged observation period of 15.1 months. This day's radical operation under local anesthesia for breast cancer is a useful procedure as minimally invasive surgery as for the indications employed in this study. (author)

  4. Molecular Mechanisms of Breast Cancer Metastasis and Potential Anti-metastatic Compounds.

    Science.gov (United States)

    Tungsukruthai, Sucharat; Petpiroon, Nalinrat; Chanvorachote, Pithi

    2018-05-01

    Throughout the world, breast cancer is among the major causes of cancer-related death and is the most common cancer found in women. The development of cancer molecular knowledge has surpassed the novel concept of cancer biology and unraveled principle targets for anticancer drug developments and treatment strategies. Metastatic breast cancer cells acquire their aggressive features through several mechanisms, including augmentation of survival, proliferation, tumorigenicity, and motility-related cellular pathways. Clearly, natural product-derived compounds have since long been recognized as an important source for anticancer drugs, several of which have been shown to have promising anti-metastasis activities by suppressing key molecular features supporting such cell aggressiveness. This review provides the essential details of breast cancer, the molecular-based insights into metastasis, as well as the effects and mechanisms of potential compounds for breast cancer therapeutic approaches. As the abilities of cancer cells to invade and metastasize are addressed as the hallmarks of cancer, compounds possessing anti-metastatic effects, together with their defined molecular drug action could benefit the development of new drugs as well as treatment strategies. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  5. Believing versus interacting: Behavioural and neural mechanisms underlying interpersonal coordination

    DEFF Research Database (Denmark)

    Konvalinka, Ivana; Bauer, Markus; Kilner, James

    When two people engage in a bidirectional interaction with each other, they use both bottom-up sensorimotor mechanisms such as monitoring and adapting to the behaviour of the other, as well as top-down cognitive processes, modulating their beliefs and allowing them to make decisions. Most research...... in joint action has investigated only one of these mechanisms at a time – low-level processes underlying joint coordination, or high-level cognitive mechanisms that give insight into how people think about another. In real interactions, interplay between these two mechanisms modulates how we interact...

  6. Mammotome biopsy under ultrasound control in the diagnostics and treatment of nodular breast lesions - own experience.

    Science.gov (United States)

    Kibil, Wojciech; Hodorowicz-Zaniewska, Diana; Kulig, Jan

    2012-05-01

    Mammotome biopsy is an effective, minimally invasive, novel technique used in the verification of breast lesions.The aim of the study was to assess the value of ultrasound-guided vacuum-assisted core needle biopsy (mammotome biopsy) in the diagnostics and treatment of nodular breast lesions, considering own data.Material and methods. Analysis comprised 1183 mammotome biopsies under ultrasound control performed in 1177 female patients during the period between 2000 and 2010, at the Regional Clinic for Early Diagnostics and Treatment of Breast Lesions, I Chair and Department of General Surgery, Jagiellonian University, Collegium Medicum.Results. The average patient age amounted to 41.7 years. The size of the investigated lesions ranged between 4 and 65 mm (mean - 12 mm). The histopathological examination result was as follows: fibrocystic lesions (n=285), adenofibroma (n=477), adenosis sclerosans (n=188), hyperplasia without atypy (n=58), phyllode tumor (n=2), papilloma (n=14), hamartoma (n=1), atypical hyperplasia (n=25), in situ ductal carcinoma (n=4), in situ lobular carcinoma (n=5), infiltrating ductal carcinoma (n=114), infiltrating lobular carcinoma (n=4), non-diagnostic result (n=6). The histopathological diagnosis was obtained in 99.5% of cases. Patients diagnosed with atypical hyperplasia or cancer were qualified for surgery, according to accepted standards. The presence of a hematoma was the most common complication after the biopsy, observed in 16.5% of patients.Conclusions. The obtained results confirmed the high value of ultrasound-guided biopsies in the diagnostics of nodular breast lesions. The method is safe, minimally invasive, with few complications, providing a good cosmetic effect. In case of benign lesions with a diameter of less than 15 mm the mammotome biopsy enables to completely excise the lesions, being an alternative to open surgical biopsies. The mammotome biopsy should become the method of choice considering the diagnostics of nodular

  7. A comprehensive sensitivity analysis of microarray breast cancer classification under feature variability

    Directory of Open Access Journals (Sweden)

    Reinders Marcel JT

    2009-11-01

    Full Text Available Abstract Background Large discrepancies in signature composition and outcome concordance have been observed between different microarray breast cancer expression profiling studies. This is often ascribed to differences in array platform as well as biological variability. We conjecture that other reasons for the observed discrepancies are the measurement error associated with each feature and the choice of preprocessing method. Microarray data are known to be subject to technical variation and the confidence intervals around individual point estimates of expression levels can be wide. Furthermore, the estimated expression values also vary depending on the selected preprocessing scheme. In microarray breast cancer classification studies, however, these two forms of feature variability are almost always ignored and hence their exact role is unclear. Results We have performed a comprehensive sensitivity analysis of microarray breast cancer classification under the two types of feature variability mentioned above. We used data from six state of the art preprocessing methods, using a compendium consisting of eight diferent datasets, involving 1131 hybridizations, containing data from both one and two-color array technology. For a wide range of classifiers, we performed a joint study on performance, concordance and stability. In the stability analysis we explicitly tested classifiers for their noise tolerance by using perturbed expression profiles that are based on uncertainty information directly related to the preprocessing methods. Our results indicate that signature composition is strongly influenced by feature variability, even if the array platform and the stratification of patient samples are identical. In addition, we show that there is often a high level of discordance between individual class assignments for signatures constructed on data coming from different preprocessing schemes, even if the actual signature composition is identical

  8. Amount of fear extinction changes its underlying mechanisms.

    Science.gov (United States)

    An, Bobae; Kim, Jihye; Park, Kyungjoon; Lee, Sukwon; Song, Sukwoon; Choi, Sukwoo

    2017-07-03

    There has been a longstanding debate on whether original fear memory is inhibited or erased after extinction. One possibility that reconciles this uncertainty is that the inhibition and erasure mechanisms are engaged in different phases (early or late) of extinction. In this study, using single-session extinction training and its repetition (multiple-session extinction training), we investigated the inhibition and erasure mechanisms in the prefrontal cortex and amygdala of rats, where neural circuits underlying extinction reside. The inhibition mechanism was prevalent with single-session extinction training but faded when single-session extinction training was repeated. In contrast, the erasure mechanism became prevalent when single-session extinction training was repeated. Moreover, ablating the intercalated neurons of amygdala, which are responsible for maintaining extinction-induced inhibition, was no longer effective in multiple-session extinction training. We propose that the inhibition mechanism operates primarily in the early phase of extinction training, and the erasure mechanism takes over after that.

  9. Breast

    International Nuclear Information System (INIS)

    Ribeiro, G.G.

    1985-01-01

    The treatment of malignant disease of the breast arouses more controversy and emotion than that of any other form of malignant disease. Many clinical trials have been carried out and others are still in progress. In addition, research work continues in regard to other aspects of the disease, such as epidemiology, population screening, and endocrine factors; yet little is really known about the true biological nature of carcinoma of the breast. A vast amount of literature has accumulated on the treatment of ''operable'' carcinoma of the breast, but it is not proposed to discuss here the merits or demerits of the various suggested treatments. Instead this chapter will be confined to the practical management of carcinoma of the breast as seen from the point of view of radiotherapist. For this reason greater attention will be paid to the radiotherapy techniques as practised at the Christie Hospital

  10. Proteomics Characterization of the Molecular Mechanisms of Mutant P53 Reactivation with PRIMA-1 in Breast Cancer Cells

    National Research Council Canada - National Science Library

    Daoud, Sayed S

    2006-01-01

    The main purpose of the study is to identify novel protein-protein interactions in various locations of cells to establish the molecular mechanisms of mutant p53 reactivation with PRIMA-1 in breast cancer cells...

  11. PI3K/Akt/mTOR Intracellular Pathway and Breast Cancer: Factors, Mechanism and Regulation.

    Science.gov (United States)

    Sharma, Var Ruchi; Gupta, Girish Kumar; Sharma, A K; Batra, Navneet; Sharma, Daljit K; Joshi, Amit; Sharma, Anil K

    2017-01-01

    The most recurrent and considered second most frequent cause of cancer-related deaths worldwide in women is the breast cancer. The key to diagnosis is early prediction and a curable stage but still treatment remains a great clinical challenge. Origin of the Problem: A number of studies have been carried out for the treatment of breast cancer which includes the targeted therapies and increased survival rates in women. Essential PI3K/mTOR signaling pathway activation has been observed in most breast cancers. The cell growth and tumor development in such cases involve phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) complex intracellular pathway. Through preclinical and clinical trials, it has been observed that there are a number of other inhibitors of PI3K/Akt/mTOR pathway, which either alone or in combination with cytotoxic agents can be used for endocrine therapies. Structure and regulation/deregulation of mTOR provides a greater insight into the action mechanism. Also, through this review, one could easily scan first and second generation inhibitors for PI3K/Akt/mTOR pathway besides targeted therapies for breast cancer and the precise role of mTOR. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Depression and Chronic Liver Diseases: Are There Shared Underlying Mechanisms?

    Directory of Open Access Journals (Sweden)

    Xiaoqin Huang

    2017-05-01

    Full Text Available The occurrence of depression is higher in patients with chronic liver disease (CLD than that in the general population. The mechanism described in previous studies mainly focused on inflammation and stress, which not only exists in CLD, but also emerges in common chronic diseases, leaving the specific mechanism unknown. This review was to summarize the prevalence and risk factors of depression in CLD including chronic hepatitis B, chronic hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease, and to point out the possible underlying mechanism of this potential link. Clarifying the origins of this common comorbidity (depression and CLD may provide more information to understand both diseases.

  13. Resveratrol for breast cancer prevention and therapy: Preclinical evidence and molecular mechanisms.

    Science.gov (United States)

    Sinha, Dona; Sarkar, Nivedita; Biswas, Jaydip; Bishayee, Anupam

    2016-10-01

    Globally, breast cancer is the most frequently diagnosed cancer among women. The major unresolved problems with metastatic breast cancer is recurrence after receiving objective response to chemotherapy, drug-induced side effects of first line chemotherapy and delayed response to second line of treatment. Unfortunately, very few options are available as third line treatment. It is clear that under such circumstances there is an urgent need for new and effective drugs. Phytochemicals are among the most promising chemopreventive treatment options for the management of cancer. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a non-flavonoid polyphenol present in several dietary sources, including grapes, berries, soy beans, pomegranate and peanuts, has been shown to possess a wide range of health benefits through its effect on a plethora of molecular targets.The present review encompasses the role of resveratrol and its natural/synthetic analogue in the light of their efficacy against tumor cell proliferation, metastasis, epigenetic alterations and for induction of apoptosis as well as sensitization toward chemotherapeutic drugs in various in vitro and in vivo models of breast cancer. The roles of resveratrol as a phytoestrogen, an aromatase inhibitor and in stem cell therapy as well as adjuvent treatment are also discussed. This review explores the full potential of resveratrol in breast cancer prevention and treatment with current limitations, challenges and future directions of research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Damage mechanisms in PBT-GF30 under thermo-mechanical cyclic loading

    International Nuclear Information System (INIS)

    Schaaf, A.; De Monte, M.; Hoffmann, C.; Vormwald, M.; Quaresimin, M.

    2014-01-01

    The scope of this paper is the investigation of damage mechanisms at microscopic scale on a short glass fiber reinforced polybutylene terephthalate (PBT-GF30) under thermo-mechanical cyclic loading. In addition the principal mechanisms are verified through micro mechanical FE models. In order to investigate the fatigue behavior of the material both isothermal strain controlled fatigue (ISCF) tests at three different temperatures and thermo-mechanical fatigue (TMF) tests were conducted on plain and notched specimens, manufactured by injection molding. The goal of the work is to determine the damage mechanisms occurring under TMF conditions and to compare them with the mechanisms occurring under ISCF. For this reason fracture surfaces of TMF and ISCF samples loaded at different temperature levels were analyzed using scanning electron microscopy. Furthermore, specimens that failed under TMF were examined on microsections revealing insight into both crack initiation and crack propagation. The findings of this investigation give valuable information about the main damage mechanisms of PBT-GF30 under TMF loading and serve as basis for the development of a TMF life estimation methodology

  15. Study on Mechanical Properties of Barite Concrete under Impact Load

    Science.gov (United States)

    Chen, Z. F.; Cheng, K.; Wu, D.; Gan, Y. C.; Tao, Q. W.

    2018-03-01

    In order to research the mechanical properties of Barite concrete under impact load, a group of concrete compression tests was carried out under the impact load by using the drop test machine. A high-speed camera was used to record the failure process of the specimen during the impact process. The test results show that:with the increase of drop height, the loading rate, the peak load, the strain under peak load, the strain rate and the dynamic increase factor (DIF) all increase gradually. The ultimate tensile strain is close to each other, and the time of impact force decreases significantly, showing significant strain rate effect.

  16. Asymmetry in family history implicates nonstandard genetic mechanisms: application to the genetics of breast cancer.

    Directory of Open Access Journals (Sweden)

    Clarice R Weinberg

    2014-03-01

    Full Text Available Genome-wide association studies typically target inherited autosomal variants, but less studied genetic mechanisms can play a role in complex disease. Sex-linked variants aside, three genetic phenomena can induce differential risk in maternal versus paternal lineages of affected individuals: 1. maternal effects, reflecting the maternal genome's influence on prenatal development; 2. mitochondrial variants, which are inherited maternally; 3. autosomal genes, whose effects depend on parent of origin. We algebraically show that small asymmetries in family histories of affected individuals may reflect much larger genetic risks acting via those mechanisms. We apply these ideas to a study of sisters of women with breast cancer. Among 5,091 distinct families of women reporting that exactly one grandmother had breast cancer, risk was skewed toward maternal grandmothers (p<0.0001, especially if the granddaughter was diagnosed between age 45 and 54. Maternal genetic effects, mitochondrial variants, or variant genes with parent-of-origin effects may influence risk of perimenopausal breast cancer.

  17. Anti-EGFR Therapy: Mechanism and Advances in Clinical Efficacy in Breast Cancer

    Directory of Open Access Journals (Sweden)

    John F. Flynn

    2009-01-01

    Full Text Available This review will focus on recent advances in the application of antiepidermal growth factor receptor (anti-EGFR for the treatment of breast cancer. The choice of EGFR, a member of the ErbB tyrosine kinase receptor family, stems from evidence pinpointing its role in various anti-EGFR therapies. Therefore, an increase in our understanding of EGFR mechanism and signaling might reveal novel targets amenable to intervention in the clinic. This knowledge base might also improve existing medical treatment options and identify research gaps in the design of new therapeutic agents. While the approved use of drugs like the dual kinase inhibitor Lapatinib represents significant advances in the clinical management of breast cancer, confirmatory studies must be considered to foster the use of anti-EGFR therapies including safety, pharmacokinetics, and clinical efficacy.

  18. Mechanical behavior of silicon carbide nanoparticles under uniaxial compression

    Energy Technology Data Exchange (ETDEWEB)

    He, Qiuxiang; Fei, Jing; Tang, Chao; Zhong, Jianxin; Meng, Lijun, E-mail: ljmeng@xtu.edu.cn [Xiangtan University, Hunan Key Laboratory for Micro-Nano Energy Materials and Devices, Faculty of School of Physics and Optoelectronics (China)

    2016-03-15

    The mechanical behavior of SiC nanoparticles under uniaxial compression was investigated using an atomic-level compression simulation technique. The results revealed that the mechanical deformation of SiC nanocrystals is highly dependent on compression orientation, particle size, and temperature. A structural transformation from the original zinc-blende to a rock-salt phase is identified for SiC nanoparticles compressed along the [001] direction at low temperature. However, the rock-salt phase is not observed for SiC nanoparticles compressed along the [110] and [111] directions irrespective of size and temperature. The high-pressure-generated rock-salt phase strongly affects the mechanical behavior of the nanoparticles, including their hardness and deformation process. The hardness of [001]-compressed nanoparticles decreases monotonically as their size increases, different from that of [110] and [111]-compressed nanoparticles, which reaches a maximal value at a critical size and then decreases. Additionally, a temperature-dependent mechanical response was observed for all simulated SiC nanoparticles regardless of compression orientation and size. Interestingly, the hardness of SiC nanocrystals with a diameter of 8 nm compressed in [001]-orientation undergoes a steep decrease at 0.1–200 K and then a gradual decline from 250 to 1500 K. This trend can be attributed to different deformation mechanisms related to phase transformation and dislocations. Our results will be useful for practical applications of SiC nanoparticles under high pressure.

  19. A possible realization of Einstein's causal theory underlying quantum mechanics

    International Nuclear Information System (INIS)

    Yussouff, M.

    1979-06-01

    It is shown that a new microscopic mechanics formulated earlier can be looked upon as a possible causal theory underlying quantum mechanics, which removes Einstein's famous objections against quantum theory. This approach is free from objections raised against Bohm's hidden variable theory and leads to a clear physical picture in terms of familiar concepts, if self interactions are held responsible for deviations from classical behaviour. The new level of physics unfolded by this approach may reveal novel frontiers in high-energy physics. (author)

  20. Frictional behaviour of polymer films under mechanical and electrostatic loads

    International Nuclear Information System (INIS)

    Ginés, R; Christen, R; Motavalli, M; Bergamini, A; Ermanni, P

    2013-01-01

    Different polymer foils, namely polyimide, FEP, PFA and PVDF were tested on a setup designed to measure the static coefficient of friction between them. The setup was designed according to the requirements of a damping device based on electrostatically tunable friction. The foils were tested under different mechanically applied forces and showed reproducible results for the static coefficient of friction. With the same setup the measurements were performed under an electric field as the source of the normal force. Up to a certain electric field the values were in good agreement. Beyond this field discrepancies were found. (paper)

  1. Reliability Issues and Solutions in Flexible Electronics Under Mechanical Fatigue

    Science.gov (United States)

    Yi, Seol-Min; Choi, In-Suk; Kim, Byoung-Joon; Joo, Young-Chang

    2018-03-01

    Flexible devices are of significant interest due to their potential expansion of the application of smart devices into various fields, such as energy harvesting, biological applications and consumer electronics. Due to the mechanically dynamic operations of flexible electronics, their mechanical reliability must be thoroughly investigated to understand their failure mechanisms and lifetimes. Reliability issue caused by bending fatigue, one of the typical operational limitations of flexible electronics, has been studied using various test methodologies; however, electromechanical evaluations which are essential to assess the reliability of electronic devices for flexible applications had not been investigated because the testing method was not established. By employing the in situ bending fatigue test, we has studied the failure mechanism for various conditions and parameters, such as bending strain, fatigue area, film thickness, and lateral dimensions. Moreover, various methods for improving the bending reliability have been developed based on the failure mechanism. Nanostructures such as holes, pores, wires and composites of nanoparticles and nanotubes have been suggested for better reliability. Flexible devices were also investigated to find the potential failures initiated by complex structures under bending fatigue strain. In this review, the recent advances in test methodology, mechanism studies, and practical applications are introduced. Additionally, perspectives including the future advance to stretchable electronics are discussed based on the current achievements in research.

  2. Turing mechanism underlying a branching model for lung morphogenesis.

    Science.gov (United States)

    Xu, Hui; Sun, Mingzhu; Zhao, Xin

    2017-01-01

    The mammalian lung develops through branching morphogenesis. Two primary forms of branching, which occur in order, in the lung have been identified: tip bifurcation and side branching. However, the mechanisms of lung branching morphogenesis remain to be explored. In our previous study, a biological mechanism was presented for lung branching pattern formation through a branching model. Here, we provide a mathematical mechanism underlying the branching patterns. By decoupling the branching model, we demonstrated the existence of Turing instability. We performed Turing instability analysis to reveal the mathematical mechanism of the branching patterns. Our simulation results show that the Turing patterns underlying the branching patterns are spot patterns that exhibit high local morphogen concentration. The high local morphogen concentration induces the growth of branching. Furthermore, we found that the sparse spot patterns underlie the tip bifurcation patterns, while the dense spot patterns underlies the side branching patterns. The dispersion relation analysis shows that the Turing wavelength affects the branching structure. As the wavelength decreases, the spot patterns change from sparse to dense, the rate of tip bifurcation decreases and side branching eventually occurs instead. In the process of transformation, there may exists hybrid branching that mixes tip bifurcation and side branching. Since experimental studies have reported that branching mode switching from side branching to tip bifurcation in the lung is under genetic control, our simulation results suggest that genes control the switch of the branching mode by regulating the Turing wavelength. Our results provide a novel insight into and understanding of the formation of branching patterns in the lung and other biological systems.

  3. Mechanical Behaviour of Bolted Joints Under Impact Rates of Loading

    Science.gov (United States)

    2012-01-01

    M. (1995). Bearing Strength of Autoclave and oven cured kevlar / epoxy laminates under static and dynamic loading. Compostes, 451-456. Kretsis, G...Joints in Glass Fibre/ Epoxy Laminates. Composites, Volume 16. No 2. Kolsky, H. (1949). An Investigation of the Mechanical Properties of Materials at...elongating the pulse width. The responses are read by the strain gages bonded on the incident and transmission bar with Vishay AE-10 epoxy . The gages

  4. Control of a perturbed under-actuated mechanical system

    KAUST Repository

    Zayane, Chadia

    2015-11-05

    In this work, the trajectory tracking problem for an under-actuated mechanical system in presence of unknown input disturbances is addressed. The studied inertia wheel inverted pendulum falls in the class of non minimum phase systems. The proposed high order sliding mode control architecture including a controller and differentiator allows to track accurately the predefined trajectory and to stabilize the internal dynamics. The robustness of the proposed approach is illustrated through different perturbation and output noise configurations.

  5. Neural mechanisms underlying morphine withdrawal in addicted patients: a review

    Directory of Open Access Journals (Sweden)

    Nima Babhadiashar

    2015-06-01

    Full Text Available Morphine is one of the most potent alkaloid in opium, which has substantial medical uses and needs and it is the first active principle purified from herbal source. Morphine has commonly been used for relief of moderate to severe pain as it acts directly on the central nervous system; nonetheless, its chronic abuse increases tolerance and physical dependence, which is commonly known as opiate addiction. Morphine withdrawal syndrome is physiological and behavioral symptoms that stem from prolonged exposure to morphine. A majority of brain regions are hypofunctional over prolonged abstinence and acute morphine withdrawal. Furthermore, several neural mechanisms are likely to contribute to morphine withdrawal. The present review summarizes the literature pertaining to neural mechanisms underlying morphine withdrawal. Despite the fact that morphine withdrawal is a complex process, it is suggested that neural mechanisms play key roles in morphine withdrawal.

  6. An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development

    Directory of Open Access Journals (Sweden)

    Xinglong Gu

    2016-01-01

    Full Text Available In the mammalian brain, GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here, we report that NMDA-type ionotropic glutamate receptors (NMDARs in individual immature neurons are the upstream signaling molecules essential for GABAergic synapse development, which requires signaling via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. Interestingly, in neurons lacking NMDARs, whereas GABAergic synaptic transmission is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA receptors is increased, suggesting a compensatory mechanism for the lack of synaptic inhibition. These results demonstrate a crucial role for NMDARs in specifying the development of inhibitory synapses, and suggest an important mechanism for controlling the establishment of the balance between synaptic excitation and inhibition in the developing brain.

  7. Fracture mechanics of hydroxyapatite single crystals under geometric confinement.

    Science.gov (United States)

    Libonati, Flavia; Nair, Arun K; Vergani, Laura; Buehler, Markus J

    2013-04-01

    Geometric confinement to the nanoscale, a concept that refers to the characteristic dimensions of structural features of materials at this length scale, has been shown to control the mechanical behavior of many biological materials or their building blocks, and such effects have also been suggested to play a crucial role in enhancing the strength and toughness of bone. Here we study the effect of geometric confinement on the fracture mechanism of hydroxyapatite (HAP) crystals that form the mineralized phase in bone. We report a series of molecular simulations of HAP crystals with an edge crack on the (001) plane under tensile loading, and we systematically vary the sample height whilst keeping the sample and the crack length constant. We find that by decreasing the sample height the stress concentration at the tip of the crack disappears for samples with a height smaller than 4.15nm, below which the material shows a different failure mode characterized by a more ductile mechanism with much larger failure strains, and the strength approaching that of a flaw-less crystal. This study directly confirms an earlier suggestion of a flaw-tolerant state that appears under geometric confinement and may explain the mechanical stability of the reinforcing HAP platelets in bone. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Giant panda׳s tooth enamel: Structure, mechanical behavior and toughening mechanisms under indentation.

    Science.gov (United States)

    Weng, Z Y; Liu, Z Q; Ritchie, R O; Jiao, D; Li, D S; Wu, H L; Deng, L H; Zhang, Z F

    2016-12-01

    The giant panda׳s teeth possess remarkable load-bearing capacity and damage resistance for masticating bamboos. In this study, the hierarchical structure and mechanical behavior of the giant panda׳s tooth enamel were investigated under indentation. The effects of loading orientation and location on mechanical properties of the enamel were clarified and the evolution of damage in the enamel under increasing load evaluated. The nature of the damage, both at and beneath the indentation surfaces, and the underlying toughening mechanisms were explored. Indentation cracks invariably were seen to propagate along the internal interfaces, specifically the sheaths between enamel rods, and multiple extrinsic toughening mechanisms, e.g., crack deflection/twisting and uncracked-ligament bridging, were active to shield the tips of cracks from the applied stress. The giant panda׳s tooth enamel is analogous to human enamel in its mechanical properties, yet it has superior hardness and Young׳s modulus but inferior toughness as compared to the bamboo that pandas primarily feed on, highlighting the critical roles of the integration of underlying tissues in the entire tooth and the highly hydrated state of bamboo foods. Our objective is that this study can aid the understanding of the structure-mechanical property relations in the tooth enamel of mammals and further provide some insight on the food habits of the giant pandas. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Breast Carcinoma Progression and Tumour Vascular Markers Related to Apoptotic Mechanisms

    Directory of Open Access Journals (Sweden)

    Miroslava Bilecova-Rabajdova

    2014-01-01

    Full Text Available Background. In the last few years, the cancer research had tried to identify and characterize new biochemical and molecular pathways in which the inhibition induces prosurvival mechanisms. Our work describes the expression of two different members of apoptotic regulatory pathway and their relationship with a progression of breast carcinoma. Materials and Methods. We compared expression of genes related to apoptosis (DR6 and Gpm6B in the blood of patients suffering from stage I of breast cancer in different grades (I–IV, with healthy controls. After isolation of mRNA, transcription of mRNA into the cDNA was performed. The quantification of gene expression changes in DR6 and Gpm6B was detected by RT-PCR method. Analysis at the protein level was performed by the Western blot.Results. In statistical analysis of Dr6 mRNA level changes we detected significant increase starting in Grading 1 (G1 and reached maximal level in G3.This expression on mRNA levels was similar to protein levels, which copy rising tendency with maximal value in G3. The results of Gpm6B were significantly lower.Conclusion. This result showed that antiapoptotic signalling during neovascularization is increased significantly. It would be advisable in the future to study the influence of cytostatic treatment on the expression of genes related to apoptotic pathways and their relationship with progression of breast cancer tumours.

  10. Mechanical properties of graphene nanoribbons under uniaxial tensile strain

    Science.gov (United States)

    Yoneyama, Kazufumi; Yamanaka, Ayaka; Okada, Susumu

    2018-03-01

    Based on the density functional theory with the generalized gradient approximation, we investigated the mechanical properties of graphene nanoribbons in terms of their edge shape under a uniaxial tensile strain. The nanoribbons with armchair and zigzag edges retain their structure under a large tensile strain, while the nanoribbons with chiral edges are fragile against the tensile strain compared with those with armchair and zigzag edges. The fracture started at the cove region, which corresponds to the border between the zigzag and armchair edges for the nanoribbons with chiral edges. For the nanoribbons with armchair edges, the fracture started at one of the cove regions at the edges. In contrast, the fracture started at the inner region of the nanoribbons with zigzag edges. The bond elongation under the tensile strain depends on the mutual arrangement of covalent bonds with respect to the strain direction.

  11. Social networks, social support mechanisms, and quality of life after breast cancer diagnosis.

    Science.gov (United States)

    Kroenke, Candyce H; Kwan, Marilyn L; Neugut, Alfred I; Ergas, Isaac J; Wright, Jaime D; Caan, Bette J; Hershman, Dawn; Kushi, Lawrence H

    2013-06-01

    We examined mechanisms through which social relationships influence quality of life (QOL) in breast cancer survivors. This study included 3,139 women from the Pathways Study who were diagnosed with breast cancer from 2006 to 2011 and provided data on social networks (the presence of a spouse or intimate partner, religious/social ties, volunteering, and numbers of close friends and relatives), social support (tangible support, emotional/informational support, affection, positive social interaction), and QOL, measured by the FACT-B, approximately 2 months post diagnosis. We used logistic models to evaluate associations between social network size, social support, and lower versus higher than median QOL scores. We further stratified by stage at diagnosis and treatment. In multivariate-adjusted analyses, women who were characterized as socially isolated had significantly lower FACT-B (OR = 2.18, 95 % CI: 1.72-2.77), physical well-being (WB) (OR = 1.61, 95 % CI: 1.27-2.03), functional WB (OR = 2.08, 95 % CI: 1.65-2.63), social WB (OR = 3.46, 95 % CI: 2.73-4.39), and emotional WB (OR = 1.67, 95 % CI: 1.33-2.11) scores and higher breast cancer symptoms (OR = 1.48, 95 % CI: 1.18-1.87) compared with socially integrated women. Each social network member independently predicted higher QOL. Simultaneous adjustment for social networks and social support partially attenuated associations between social networks and QOL. The strongest mediator and type of social support that was most predictive of QOL outcomes was "positive social interaction." However, each type of support was important depending on outcome, stage, and treatment status. Larger social networks and greater social support were related to higher QOL after a diagnosis of breast cancer. Effective social support interventions need to evolve beyond social-emotional interventions and need to account for disease severity and treatment status.

  12. Social networks, social support mechanisms, and quality of life after breast cancer diagnosis

    Science.gov (United States)

    Kroenke, Candyce H; Kwan, Marilyn L.; Neugut, Alfred I.; Ergas, Isaac J.; Wright, Jaime D.; Caan, Bette J.; Hershman, Dawn; Kushi, Lawrence H.

    2013-01-01

    Purpose We examined mechanisms through which social relationships influence quality of life (QOL) in breast cancer survivors. Methods This study included 3,139 women from the Pathways Study who were diagnosed with breast cancer from 2006-2011 and provided data on social networks (presence of spouse or intimate partner, religious/social ties, volunteering, and numbers of close friends and relatives), social support (tangible, emotional/informational, affection, positive social interaction), and quality of life (QOL), measured by the FACT-B, approximately two months post-diagnosis. We used logistic models to evaluate associations between social network size, social support, and lower vs. higher than median QOL scores. We further stratified by stage at diagnosis and treatment. Results In multivariate-adjusted analyses, women who were characterized as socially isolated had significantly lower FACT-B (OR=2.18, 95%CI:1.72-2.77), physical well-being (WB) (OR=1.61, 95%CI:1.27-2.03), functional WB (OR=2.08, 95%CI:1.65-2.63), social WB (OR=3.46, 95%CI:2.73-4.39), and emotional WB (OR=1.67, 95%CI:1.33-2.11) scores and higher breast cancer symptoms (OR=1.48, 95%CI:1.18-1.87), compared with socially integrated women. Each social network member independently predicted higher QOL. Simultaneous adjustment for social networks and social support partially attenuated associations between social networks and QOL. The strongest mediator and type of social support that was most predictive of QOL outcomes was “positive social interaction”. However, each type of support was important depending on outcome, stage, and treatment status. Conclusions Larger social networks and greater social support were related to higher QOL after a diagnosis of breast cancer. Effective social support interventions need to evolve beyond social-emotional interventions and need to account for disease severity and treatment status. PMID:23657404

  13. Peripheral Receptor Mechanisms Underlying Orofacial Muscle Pain and Hyperalgesia

    Science.gov (United States)

    Saloman, Jami L.

    Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) are severely debilitating and affect approximately 12% of the population. Identifying peripheral nociceptive mechanisms underlying mechanical hyperalgesia, a prominent feature of persistent muscle pain, could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. This study provides evidence of functional interactions between ligand-gated channels, P2X3 and TRPV1/TRPA1, in trigeminal sensory neurons, and proposes that these interactions underlie the development of mechanical hyperalgesia. In the masseter muscle, direct P2X3 activation, via the selective agonist αβmeATP, induced a dose- and time-dependent hyperalgesia. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810, or the TRPA1 antagonist, AP18. P2X3 was co-expressed with both TRPV1 and TRPA1 in masseter muscle afferents confirming the possibility for intracellular interactions. Moreover, in a subpopulation of P2X3 /TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly potentiated following P2X3 activation. Inhibition of Ca2+-dependent kinases, PKC and CaMKII, prevented P2X3-mechanical hyperalgesia whereas blockade of Ca2+-independent PKA did not. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal sensory neurons. Significant phosphorylation was observed at 15 minutes, the time point at which behavioral hyperalgesia was prominent. Similar data were obtained regarding another nonselective cation channel, the NMDA receptor (NMDAR). Our data propose P2X3 and NMDARs interact with TRPV1 in a facilitatory manner, which could contribute to the peripheral sensitization underlying masseter hyperalgesia. This study offers novel mechanisms by which individual pro-nociceptive ligand

  14. Taxane resistance in breast cancer: mechanisms, predictive biomarkers and circumvention strategies.

    Science.gov (United States)

    Murray, S; Briasoulis, E; Linardou, H; Bafaloukos, D; Papadimitriou, C

    2012-11-01

    Taxanes are established in the treatment of metastatic breast cancer (MBC) and early breast cancer (EBC) as potent chemotherapy agents. However, their therapeutic usefulness is limited by de-novo refractoriness or acquired resistance, which are common drawbacks to most anti-cancer cytotoxics. Considering that the taxanes will remain principle chemotherapeutic agents for the treatment of breast cancer, we reviewed known mechanisms of resistance in with an outlook of optimizing their clinical use. We searched the PubMed and MEDLINE databases for articles (from inception through to 9th January 2012; last search 10/01/2012) and journals known to publish information relevant to taxane chemotherapy. We imposed no language restrictions. Search terms included: cancer, breast cancer, response, resistance, taxane, paclitaxel, docetaxel, taxol. Due to the possibility of alternative mechanisms of resistance all combination chemotherapy treated data sets were removed from our overview. Over-expression of the MDR-1 gene product Pgp was extensively studied in vitro in association with taxane resistance, but data are conflicting. Similarly, the target components microtubules, which are thought to mediate refractoriness through alterations of the expression pattern of tubulins or microtubule associated proteins and the expression of alternative tubulin isoforms, failed to confirm such associations. Little consensus has been generated for reported associations between taxane-sensitivity and mutated p53, or taxane-resistance and overexpression of Bcl-2, Bcl-xL or NFkB. In contrary sufficient in vitro data support an association of spindle assembly checkpoint (SAC) defects with resistance. Clinical data have been limited and inconsistent, which relate to the variety of methods used, lack of standardization of cut-offs for quantitation, differences in clinical endpoints measured and in methods of tissue collection preparation and storage, and study/patient heterogeneity. The most

  15. Cell-Nonautonomous Mechanisms Underlying Cellular and Organismal Aging.

    Science.gov (United States)

    Medkour, Younes; Svistkova, Veronika; Titorenko, Vladimir I

    2016-01-01

    Cell-autonomous mechanisms underlying cellular and organismal aging in evolutionarily distant eukaryotes have been established; these mechanisms regulate longevity-defining processes within a single eukaryotic cell. Recent findings have provided valuable insight into cell-nonautonomous mechanisms modulating cellular and organismal aging in eukaryotes across phyla; these mechanisms involve a transmission of various longevity factors between different cells, tissues, and organisms. Herein, we review such cell-nonautonomous mechanisms of aging in eukaryotes. We discuss the following: (1) how low molecular weight transmissible longevity factors modulate aging and define longevity of cells in yeast populations cultured in liquid media or on solid surfaces, (2) how communications between proteostasis stress networks operating in neurons and nonneuronal somatic tissues define longevity of the nematode Caenorhabditis elegans by modulating the rates of aging in different tissues, and (3) how different bacterial species colonizing the gut lumen of C. elegans define nematode longevity by modulating the rate of organismal aging. Copyright © 2016. Published by Elsevier Inc.

  16. Mechanisms Regulating Acid-Base Transporter Expression in Breast- and Pancreatic Cancer

    DEFF Research Database (Denmark)

    Gorbatenko, Andrej

    , characteristics of which are a shift towards glycolytic metabolism and increased acid production. HER2 receptor overexpression in breast cancer leads to further increased glycolysis, invasion and metastasis, drug resistance and poor prognosis. Increased tumor glycolysis requires acquisition of mechanisms...... for dealing with excess acid production. In this light, evidence accumulates on the importance of pH regulatory proteins to cancer cell survival and motility. Our group previously demonstrated upregulation of the Na+/HCO3 - co-transporter NBCn1 (SLC4A7) by a constitutively active form of HER2 receptor (p95HER...

  17. Mechanisms of breast cancer risk in shift workers: association of telomere shortening with the duration and intensity of night work.

    Science.gov (United States)

    Samulin Erdem, Johanna; Notø, Heidi Ødegaard; Skare, Øivind; Lie, Jenny-Anne S; Petersen-Øverleir, Marte; Reszka, Edyta; Pepłońska, Beata; Zienolddiny, Shanbeh

    2017-08-01

    Occupational factors such as shiftwork and especially night work that involves disruption of the circadian rhythm may contribute to increased breast cancer risk. Circadian disruption may also affect telomere length (TL). While short TL generally is associated with increased cancer risk, its association with breast cancer risk is inconclusive. We suggest that working schedules might be an important factor in assessment of effects of TL on breast cancer risk. Moreover, telomere shortening might be a potential mechanism for night work-related breast cancer. In this study, effects of shift work on TL and its association with breast cancer risk were investigated in a nested breast cancer case-control study of Norwegian nurses. TL was assessed by qPCR in DNA from 563 breast cancer patients and 619 controls. Here, we demonstrate that TL is affected by intensive night work schedules, as work with six consecutive night for a period of more than 5 years was associated with decreased telomere lengths (-3.18, 95% CI: -6.46 to -0.58, P = 0.016). Furthermore, telomere shortening is associated with increased breast cancer risk in workers with long periods of consecutive night shifts. Thus, nurses with longer telomere lengths had a lower risk for breast cancer if they had worked more than four (OR: 0.37, 95% CI: 0.16-0.79, P = 0.014) or five (OR: 0.31, 95% CI: 0.10-0.83, P = 0.029) consecutive night shifts for a period of 5 years or more. These data suggest that telomere shortening is associated with the duration and intensity of night work and may be a contributing factor for breast cancer risk among female shift workers. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  18. Temporomandibular disorders and painful comorbidities: clinical association and underlying mechanisms.

    Science.gov (United States)

    Costa, Yuri Martins; Conti, Paulo César Rodrigues; de Faria, Flavio Augusto Cardoso; Bonjardim, Leonardo Rigoldi

    2017-03-01

    The association between temporomandibular disorders (TMDs) and headaches, cervical spine dysfunction, and fibromyalgia is not artefactual. The aim of this review is to describe the comorbid relationship between TMD and these three major painful conditions and to discuss the clinical implications and the underlying pain mechanisms involved in these relationships. Common neuronal pathways and central sensitization processes are acknowledged as the main factors for the association between TMD and primary headaches, although the establishment of cause-effect mechanisms requires further clarification and characterization. The biomechanical aspects are not the main factors involved in the comorbid relationship between TMD and cervical spine dysfunction, which can be better explained by the neuronal convergence of the trigeminal and cervical spine sensory pathways as well as by central sensitization processes. The association between TMD and fibromyalgia also has supporting evidence in the literature, and the proposed main mechanism underlying this relationship is the impairment of the descending pain inhibitory system. In this particular scenario, a cause-effect relationship is more likely to occur in one direction, that is, fibromyalgia as a risk factor for TMD. Therefore, clinical awareness of the association between TMD and painful comorbidities and the support of multidisciplinary approaches are required to recognize these related conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Vascular mechanisms underlying the hypotensive effect of Rumex acetosa.

    Science.gov (United States)

    Qamar, Hafiz Misbah-Ud-Din; Qayyum, Rahila; Salma, Umme; Khan, Shamim; Khan, Taous; Shah, Abdul Jabbar

    2018-12-01

    Rumex acetosa L. (Polygonaceae) is well known in traditional medicine for its therapeutic efficacy as an antihypertensive. The study investigates antihypertensive potential of crude methanol extract (Ra.Cr) and fractions of Rumex acetosa in normotensive and hypertensive rat models and probes the underlying vascular mechanisms. Ra.Cr and its fractions were tested in vivo on normotensive and hypertensive Sprague-Dawley rats under anaesthesia for blood pressure lowering effect. In vitro experiments on rat and Oryctolagus cuniculus rabbit aortae were employed to probe the underlying vasorelaxant mechanism. In normotensive rats under anaesthesia, Ra.Cr caused fall in MAP (40 mmHg) at 50 mg/kg with % fall of 27.88 ± 4.55. Among the fractions tested, aqueous fraction was more potent at the dose of 50 mg/kg with % fall of 45.63 ± 2.84. In hypertensive rats under similar conditions, extract and fractions showed antihypertensive effect at same doses while aqueous fraction being more potent, exhibited 68.53 ± 4.45% fall in MAP (70 mmHg). In isolated rat aortic rings precontracted with phenylephrine (PE), Ra.Cr and fractions induced endothelium-dependent vasorelaxation, which was partially blocked in presence of l-NAME, indomethacin and atropine. In isolated rabbit aortic rings pre-contracted with PE and K + -(80 mM), Ra.Cr induced vasorelaxation and shifted Ca 2+ concentration-response curves to the right and suppressed PE peak formation, similar to verapamil, in Ca 2+ -free medium. The data indicate that l-NAME and atropine-sensitive endothelial-derived NO and COX enzyme inhibitors and Ca 2+ entry blocking-mediated vasodilator effect of the extract explain its antihypertensive potential.

  20. Detection of Breast Microcalcifications Under Ultrasound Using Power Doppler and Acoustic Resonance Imaging

    National Research Council Canada - National Science Library

    Weinstein, Susan

    2003-01-01

    .... Our goal with our current project was to utilize breast sonography coupled with the technique of acoustic resonance to image and evaluate the breast micorcalcifications in patients prior to biopsy...

  1. The mechanism underlying fast germination of tomato cultivar LA2711.

    Science.gov (United States)

    Yang, Rongchao; Chu, Zhuannan; Zhang, Haijun; Li, Ying; Wang, Jinfang; Li, Dianbo; Weeda, Sarah; Ren, Shuxin; Ouyang, Bo; Guo, Yang-Dong

    2015-09-01

    Seed germination is important for early plant morphogenesis as well as abiotic stress tolerance, and is mainly controlled by the phytohormones abscisic acid (ABA) and gibberellic acid (GA). Our previous studies identified a salt-tolerant tomato cultivar, LA2711, which is also a fast-germinating genotype, compared to its salt-sensitive counterpart, ZS-5. In an effort to further clarify the mechanism underlying this phenomenon, we compared the dynamic levels of ABA and GA4, the transcript abundance of genes involved in their biosynthesis and catabolism as well as signal transduction between the two cultivars. In addition, we tested seed germination sensitivity to ABA and GAs. Our results revealed that insensitivity of seed germination to exogenous ABA and low ABA content in seeds are the physiological mechanisms conferring faster germination rates of LA2711 seeds. SlCYP707A2, which encodes an ABA catabolic enzyme, may play a decisive role in the fast germination rate of LA2711, as it showed a significantly higher level of expression in LA2711 than ZS-5 at most time points tested during germination. The current results will enable us to gain insight into the mechanism(s) regarding seed germination of tomato and the role of fast germination in stress tolerance. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Mechanisms underlying astringency: introduction to an oral tribology approach

    Science.gov (United States)

    Upadhyay, Rutuja; Brossard, Natalia; Chen, Jianshe

    2016-03-01

    Astringency is one of the predominant factors in the sensory experience of many foods and beverages ranging from wine to nuts. The scientific community is discussing mechanisms that explain this complex phenomenon, since there are no conclusive results which correlate well with sensory astringency. Therefore, the mechanisms and perceptual characteristics of astringency warrant further discussion and investigation. This paper gives a brief introduction of the fundamentals of oral tribology forming a basis of the astringency mechanism. It discusses the current state of the literature on mechanisms underlying astringency describing the existing astringency models. The review discusses the crucial role of saliva and its physiology which contributes significantly in astringency perception in the mouth. It also provides an overview of research concerned with the physiological and psychophysical factors that mediate the perception of this sensation, establishing the ground for future research. Thus, the overall aim of the review is to establish the critical roles of oral friction (thin-film lubrication) in the sensation of astringency and possibly of some other specific sensory features.

  3. Failure Mechanisms of Brittle Rocks under Uniaxial Compression

    Science.gov (United States)

    Liu, Taoying; Cao, Ping

    2017-09-01

    The behaviour of a rock mass is determined not only by the properties of the rock matrix, but mostly by the presence and properties of discontinuities or fractures within the mass. The compression test on rock-like specimens with two prefabricated transfixion fissures, made by pulling out the embedded metal inserts in the pre-cured period was carried out on the servo control uniaxial loading tester. The influence of the geometry of pre-existing cracks on the cracking processes was analysed with reference to the experimental observation of crack initiation and propagation from pre-existing flaws. Based on the rock fracture mechanics and the stress-strain curves, the evolution failure mechanism of the fissure body was also analyzed on the basis of exploring the law of the compression-shear crack initiation, wing crack growth and rock bridge connection. Meanwhile, damage fracture mechanical models of a compression-shear rock mass are established when the rock bridge axial transfixion failure, tension-shear combined failure, or wing crack shear connection failure occurs on the specimen under axial compression. This research was of significance in studying the failure mechanism of fractured rock mass.

  4. Underlying mechanism in the water chemistry of nuclear systems

    International Nuclear Information System (INIS)

    Walton, G.N.

    1978-01-01

    The equilibrium between dissolved hydrogen and oxygen in the molecular decomposition of water, and the equilibrium between hydrogen ions and hydroxyl ions in the ionic dissociation of water, both constitute important underlying mechanisms in the corrosion behaviour of water. The two equilibria, and the rates of the reactions involved in water and steam, will be compared and contrasted as a function of temperature, pressure and radiation. The effects of the equilibria on the hydrolysis and solubility of ferrous and ferric ions, and the ions of other metals, will be discussed in relation to the control of conditions in the coolant circuits of nuclear reactors. A third mechanism to discussed is the electrochemical exchange reactions that can contribute to the contamination of circuits. (author)

  5. Mechanical Design of AM Fabricated Prismatic Rods under Torsion

    Directory of Open Access Journals (Sweden)

    Manzhirov Alexander V.

    2017-01-01

    Full Text Available We study the stress-strain state of viscoelastic prismatic rods fabricated or repaired by additive manufacturing technologies under torsion. An adequate description of the processes involved is given by methods of a new scientific field, mechanics of growing solids. Three main stages of the deformation process (before the beginning of growth, in the course of growth, and after the termination of growth are studied. Two versions of statement of two problems are given: (i given the torque, find the stresses, displacements, and torsion; (ii given the torsion, find the stresses, displacements, and torque. Solution methods using techniques of complex analysis are presented. The results can be used in mechanical and instrument engineering.

  6. Mechanisms underlying KCNQ1channel cell volume sensitivity

    DEFF Research Database (Denmark)

    Hammami, Sofia

    Cells are constantly exposed to changes in cell volume during cell metabolism, nutrient uptake, cell proliferation, cell migration and salt and water transport. In order to cope with these perturbations, potassium channels in line with chloride channels have been shown to be likely contributors...... to the process of cell volume adjustments. A great diversity of potassium channels being members of either the 6TM, 4 TM or 2 TM K+ channel gene family have been shown to be strictly regulated by small, fast changes in cell volume. However, the precise mechanism underlying the K+ channel sensitivity to cell...... volume alterations is not yet fully understood. The KCNQ1 channel belonging to the voltage gated KCNQ family is considered a precise sensor of volume changes. The goal of this thesis was to elucidate the mechanism that induces cell volume sensitivity. Until now, a number of investigators have implicitly...

  7. Nanomaterials modulate stem cell differentiation: biological interaction and underlying mechanisms.

    Science.gov (United States)

    Wei, Min; Li, Song; Le, Weidong

    2017-10-25

    Stem cells are unspecialized cells that have the potential for self-renewal and differentiation into more specialized cell types. The chemical and physical properties of surrounding microenvironment contribute to the growth and differentiation of stem cells and consequently play crucial roles in the regulation of stem cells' fate. Nanomaterials hold great promise in biological and biomedical fields owing to their unique properties, such as controllable particle size, facile synthesis, large surface-to-volume ratio, tunable surface chemistry, and biocompatibility. Over the recent years, accumulating evidence has shown that nanomaterials can facilitate stem cell proliferation and differentiation, and great effort is undertaken to explore their possible modulating manners and mechanisms on stem cell differentiation. In present review, we summarize recent progress in the regulating potential of various nanomaterials on stem cell differentiation and discuss the possible cell uptake, biological interaction and underlying mechanisms.

  8. Biochemical mechanisms of signaling: perspectives in plants under arsenic stress.

    Science.gov (United States)

    Islam, Ejazul; Khan, Muhammad Tahir; Irem, Samra

    2015-04-01

    Plants are the ultimate food source for humans, either directly or indirectly. Being sessile in nature, they are exposed to various biotic and abiotic stresses because of changing climate that adversely effects their growth and development. Contamination of heavy metals is one of the major abiotic stresses because of anthropogenic as well as natural factors which lead to increased toxicity and accumulation in plants. Arsenic is a naturally occurring metalloid toxin present in the earth crust. Due to its presence in terrestrial and aquatic environments, it effects the growth of plants. Plants can tolerate arsenic using several mechanisms like phytochelation, vacuole sequestration and activation of antioxidant defense systems. Several signaling mechanisms have evolved in plants that involve the use of proteins, calcium ions, hormones, reactive oxygen species and nitric oxide as signaling molecules to cope with arsenic toxicity. These mechanisms facilitate plants to survive under metal stress by activating their defense systems. The pathways by which these stress signals are perceived and responded is an unexplored area of research and there are lots of gaps still to be filled. A good understanding of these signaling pathways can help in raising the plants which can perform better in arsenic contaminated soil and water. In order to increase the survival of plants in contaminated areas there is a strong need to identify suitable gene targets that can be modified according to needs of the stakeholders using various biotechnological techniques. This review focuses on the signaling mechanisms of plants grown under arsenic stress and will give an insight of the different sensory systems in plants. Furthermore, it provides the knowledge about several pathways that can be exploited to develop plant cultivars which are resistant to arsenic stress or can reduce its uptake to minimize the risk of arsenic toxicity through food chain thus ensuring food security. Copyright © 2015

  9. Surgical excision of the breast giant fibroadenoma under regional anesthesia by Pecs II and internal intercostal plane block: a case report and brief technical description: a case report.

    Science.gov (United States)

    Kim, Hyungtae; Shim, Junho; Kim, Ikthae

    2017-02-01

    A 22-years-old female patient at 171 cm and 67 kg visited the Department of Breast Surgery of the hospital with a mass accompanied with pain on the left side breast as chief complaints. Since physical examination revealed a suspected huge mass, breast surgeon decided to perform surgical excision and requested anesthesia to our department. Surgery of breast tumor is often under local anesthesia. However, in case of big size tumor, surgery is usually performed under general anesthesia. The patient feared general anesthesia. Unlike abdominal surgery, there is no need to control visceral pain for breast and anterior thoracic wall surgery. Therefore, we decided to perform resection under regional anesthesia. Herein, we report a successful anesthetic and pain management of the patient undergoing excision of a huge breast fibroadenoma under regional anesthesia using Pecs II and internal intercostal plane block.

  10. Behavior of duplex stainless steel casting defects under mechanical loadings

    International Nuclear Information System (INIS)

    Jayet-Gendrot, S.; Gilles, P.

    2000-01-01

    Several components in the primary circuit of pressurized water reactors are made of cast duplex stainless steels. This material contains small casting defects, mainly shrinkage cavities, due to the manufacturing process. In safety analyses, the structural integrity of the components is studied under the most severe assumptions: presence of a large defect, accidental loadings and end-of-life material properties accounting for its thermal aging embrittlement at the service temperature. The casting defects are idealized as semi-circular surface cracks or notches that have envelope dimensions. In order to assess the real severity of the casting defects under mechanical loadings, an experimental program was carried out. It consisted of testing, under both cyclic and monotonic solicitations, three-point bend specimens containing either a natural defect (in the form of a localized cluster of cavities) or a machined notch having the dimensions of the cluster's envelope. The results show that shrinkage cavities are far less harmful than envelope notches thanks to the metal bridges between cavities. Under fatigue loadings, the generalized initiation of a cluster of cavities (defined when the cluster becomes a crack of the same global size) is reached for a number of cycles that is much higher than the one leading to the initiation of a notch. In the case of monotonic loadings, specimens with casting defects offer a very high resistance to ductile tearing. The tests are analyzed in order to develop a method that takes into account the behavior of casting defects in a more realistic fashion than by an envelope crack. Various approaches are investigated, including the search of equivalent defects or of criteria based on continuum mechanics concepts, and compared with literature data. This study shows the conservatism of current safety analyses in modeling casting defects by envelope semi-elliptical cracks and contributes to the development of alternative approaches. (orig.)

  11. Candidate mechanisms accounting for effects of physical activity on breast carcinogenesis.

    Science.gov (United States)

    Thompson, Henry J; Jiang, Weiqin; Zhu, Zongjian

    2009-09-01

    Evidence is strong that a reduction in risk for breast cancer is associated with moderate to vigorous physical activity (PA); however, there is limited understanding of the role of type, intensity, duration, and frequency of PA and their mechanisms in accounting for this health benefit. The objective of this review is to stimulate investigations of candidate mechanisms that may account for the effects of the intensity and duration of aerobic PA on breast cancer risk and tumor burden. Three hypotheses are considered: 1) the mTOR network hypothesis: PA inhibits carcinogenesis by suppressing the activation of the mTOR signaling network in mammary carcinomas; 2) the hormesis hypothesis: the carcinogenic response to PA is nonlinear and accounted for by a physiological cellular stress response; and 3) the metabolic reprogramming hypothesis: PA limits the amount of glucose and glutamine available to mammary carcinomas thereby inducing apoptosis because tumor-associated metabolic programming is reversed. To link these hypotheses to systemic effects of PA, it is recommended that consideration be given to determining: 1) what contracting muscle releases into circulation or removes from circulation that would directly modulate the carcinogenic process in epithelial cells; 2) whether the effects of muscle contraction on epithelial cell carcinogenesis are exerted in an endocrine, paracrine, autocrine, or intracrine manner; and 3) if the effects of muscle contraction on malignant cells differ from effects on normal or premalignant cells that do not manifest the hallmarks of malignancy. (c) 2009 IUBMB

  12. Inhibitory effects and molecular mechanisms of tetrahydrocurcumin against human breast cancer MCF-7 cells

    Directory of Open Access Journals (Sweden)

    Xiao Han

    2016-02-01

    Full Text Available Background: Tetrahydrocurcumin (THC, an active metabolite of curcumin, has been reported to have similar biological effects to curcumin, but the mechanism of the antitumor activity of THC is still unclear. Methods: The present study was to investigate the antitumor effects and mechanism of THC in human breast cancer MCF-7 cells using the methods of MTT assay, LDH assay, flow cytometry analysis, and western blot assay. Results: THC was found to have markedly cytotoxic effect and antiproliferative activity against MCF-7 cells in a dose-dependent manner with the IC50 for 24 h of 107.8 μM. Flow cytometry analysis revealed that THC mediated the cell-cycle arrest at G0/G1 phase, and 32.8% of MCF-7 cells entered the early phase of apoptosis at 100 μM for 24 h. THC also dose-dependently led to apoptosis in MCF-7 cells via the mitochondrial pathway, as evidenced by the activation of caspase-3 and caspase-9, the elevation of intracellular ROS, a decrease in Bcl-2 and PARP expression, and an increase in Bax expression. Meanwhile, cytochrome C was released to cytosol and the loss of mitochondria membrane potential (Δψm was observed after THC treatment. Conclusion: THC is an excellent source of chemopreventive agents in the treatment of breast cancer and has excellent potential to be explored as antitumor precursor compound.

  13. The effect of marital status on breast cancer-related outcomes in women under 65: A SEER database analysis.

    Science.gov (United States)

    Hinyard, Leslie; Wirth, Lorinette Saphire; Clancy, Jennifer M; Schwartz, Theresa

    2017-04-01

    Marital status is strongly associated with improved health and longevity. Being married has been shown to be positively associated with survival in patients with multiple different types of malignancy; however, little is known about the relationship between marital status and breast cancer in younger women. The purpose of this study is to investigate the effect of marital status on diagnosis, and survival of women under the age of 65 with breast cancer. The SEER 18 regions database was used to identify women between the ages of 25-64 diagnosed with invasive breast cancer in the years 2004-2009. Logistic regression was used to predict later stage diagnosis by marital status and Cox proportional hazards models were used to compare breast cancer-related and all-cause survival by marital status classification. Models were stratified by AJCC stage. After adjusting for age, race, and ER status, unmarried women were 1.18 times more likely to be diagnosed at a later stage than married women (95% CI 1.15, 1.20). In adjusted analysis unmarried women were more likely to die of breast cancer and more likely to die of all causes than married women across all AJCC stages. Younger unmarried women with breast cancer may benefit from additional counseling, psychosocial support and case management at the time of diagnosis to ensure their overall outcomes are optimized. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Age differences in the underlying mechanisms of stereotype threat effects.

    Science.gov (United States)

    Popham, Lauren E; Hess, Thomas M

    2015-03-01

    The goals of the present study were to (a) examine whether age differences exist in the mechanisms underlying stereotype threat effects on cognitive performance and (b) examine whether emotion regulation abilities may buffer against threat effects on performance. Older and younger adults were exposed to positive or negative age-relevant stereotypes, allowing us to examine the impact of threat on regulatory focus and working memory. Self-reported emotion regulation measures were completed prior to the session. Older adults' performance under threat suggested a prevention-focused approach to the task, indexed by increased accuracy and reduced speed. The same pattern was observed in younger adults, but the effects were not as strong. Age differences emerged when examining the availability of working memory resources under threat, with young adults showing decrements, whereas older adults did not. Emotion regulation abilities moderated threat effects in young adults but not in older adults. The results provide support for the notion that stereotype threat may lead to underperformance through somewhat different pathways in older and younger adults. Future research should further examine whether the underlying reason for this age difference is rooted in age-related improvements in emotion regulation. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Elucidation of the Molecular Mechanisms for Aberrant Expression of Breast Cancer Specific Gene 1 in Invasive and Metastatic Breast Carcinomas

    National Research Council Canada - National Science Library

    Liu, Jingwen

    2005-01-01

    ...%) of tumor tissues of diversified cancer types including liver, esophagus, colon, gastric, lung, prostate, cervical, and breast cancer but rarely expressed in tumor matched non neoplastic adjacent tissues (NNAT) (0.6...

  16. Functional screen for genes responsible for tamoxifen resistance in human breast cancer cells

    NARCIS (Netherlands)

    Meijer, Danielle; van Agthoven, Ton; Bosma, Peter T.; Nooter, Kees; Dorssers, Lambert C. J.

    2006-01-01

    Antiestrogens, such as tamoxifen, are widely used for endocrine treatment of estrogen receptor-positive breast cancer. However, as breast cancer progresses, development of tamoxifen resistance is inevitable. The mechanisms underlying this resistance are not well understood. To identify genes

  17. Genomic interrogation of mechanism(s) underlying cellular responses to toxicants

    International Nuclear Information System (INIS)

    Amin, Rupesh P.; Hamadeh, Hisham K.; Bushel, Pierre R.; Bennett, Lee; Afshari, Cynthia A.; Paules, Richard S.

    2002-01-01

    Assessment of the impact of xenobiotic exposure on human health and disease progression is complex. Knowledge of mode(s) of action, including mechanism(s) contributing to toxicity and disease progression, is valuable for evaluating compounds. Toxicogenomics, the subdiscipline which merges genomics with toxicology, holds the promise to contributing significantly toward the goal of elucidating mechanism(s) by studying genome-wide effects of xenobiotics. Global gene expression profiling, revolutionized by microarray technology and a crucial aspect of a toxicogenomic study, allows measuring transcriptional modulation of thousands of genes following exposure to a xenobiotic. We use our results from previous studies on compounds representing two different classes of xenobiotics (barbiturate and peroxisome proliferator) to discuss the application of computational approaches for analyzing microarray data to elucidate mechanism(s) underlying cellular responses to toxicants. In particular, our laboratory demonstrated that chemical-specific patterns of gene expression can be revealed using cDNA microarrays. Transcript profiling provides discrimination between classes of toxicants, as well as, genome-wide insight into mechanism(s) of toxicity and disease progression. Ultimately, the expectation is that novel approaches for predicting xenobiotic toxicity in humans will emerge from such information

  18. Aluminium and breast cancer: Sources of exposure, tissue measurements and mechanisms of toxicological actions on breast biology.

    Science.gov (United States)

    Darbre, Philippa D; Mannello, Ferdinando; Exley, Christopher

    2013-11-01

    This review examines recent evidence linking exposure to aluminium with the aetiology of breast cancer. The human population is exposed to aluminium throughout daily life including through diet, application of antiperspirants, use of antacids and vaccination. Aluminium has now been measured in a range of human breast structures at higher levels than in blood serum and experimental evidence suggests that the tissue concentrations measured have the potential to adversely influence breast epithelial cells including generation of genomic instability, induction of anchorage-independent proliferation and interference in oestrogen action. The presence of aluminium in the human breast may also alter the breast microenvironment causing disruption to iron metabolism, oxidative damage to cellular components, inflammatory responses and alterations to the motility of cells. The main research need is now to investigate whether the concentrations of aluminium measured in the human breast can lead in vivo to any of the effects observed in cells in vitro and this would be aided by the identification of biomarkers specific for aluminium action. © 2013.

  19. Insights into the Mechanisms Underlying Boron Homeostasis in Plants

    Directory of Open Access Journals (Sweden)

    Akira Yoshinari

    2017-11-01

    Full Text Available Boron is an essential element for plants but is toxic in excess. Therefore, plants must adapt to both limiting and excess boron conditions for normal growth. Boron transport in plants is primarily based on three transport mechanisms across the plasma membrane: passive diffusion of boric acid, facilitated diffusion of boric acid via channels, and export of borate anion via transporters. Under boron -limiting conditions, boric acid channels and borate exporters function in the uptake and translocation of boron to support growth of various plant species. In Arabidopsis thaliana, NIP5;1 and BOR1 are located in the plasma membrane and polarized toward soil and stele, respectively, in various root cells, for efficient transport of boron from the soil to the stele. Importantly, sufficient levels of boron induce downregulation of NIP5;1 and BOR1 through mRNA degradation and proteolysis through endocytosis, respectively. In addition, borate exporters, such as Arabidopsis BOR4 and barley Bot1, function in boron exclusion from tissues and cells under conditions of excess boron. Thus, plants actively regulate intracellular localization and abundance of transport proteins to maintain boron homeostasis. In this review, the physiological roles and regulatory mechanisms of intracellular localization and abundance of boron transport proteins are discussed.

  20. Mechanisms Underlying the Antidepressant Response and Treatment Resistance

    Directory of Open Access Journals (Sweden)

    Marjorie Rose Levinstein

    2014-06-01

    Full Text Available Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance.

  1. Behavior of duplex stainless steel casting defects under mechanical loadings

    Energy Technology Data Exchange (ETDEWEB)

    Jayet-Gendrot, S [Electricite de France, 77 - Moret-sur-Loing (France). Dept. of Materials Study; Gilles, P; Migne, C [Societe Franco-Americaine de Constructions Atomiques (FRAMATOME), 92 - Paris-La-Defense (France)

    1997-04-01

    Several components in the primary circuit of pressurized water reactors are made of cast duplex stainless steels. This material contains small casting defects, mainly shrinkage cavities, due to the manufacturing process. In safety analyses, the structural integrity of the components is studied. In order to assess the real severity of the casting defects under mechanical loadings, an experimental program was carried out. It consisted of testing, under both cyclic and monotonic solicitations, three-point bend specimens containing either a natural defect (in the form of a localized cluster of cavities) or a machined notch having the dimensions of the cluster`s envelope. The tests are analyzed in order to develop a method that takes into account the behavior of castings defects in a more realistic fashion than by an envelope crack. Various approaches are investigated, including the search of equivalent defects or of criteria based on continuum mechanics concepts, and compared with literature data. This study shows the conservatism of current safety analyses in modelling casting defects by envelope semi-elliptical cracks and contributes to the development of alternative approaches. (author) 18 refs.

  2. Hardening and softening mechanisms of pearlitic steel wire under torsion

    International Nuclear Information System (INIS)

    Zhao, Tian-Zhang; Zhang, Shi-Hong; Zhang, Guang-Liang; Song, Hong-Wu; Cheng, Ming

    2014-01-01

    Highlights: • Mechanical behavior of pearlitic steel wire is studied using torsion. • Work hardening results from refinement lamellar pearlitic structure. • Softening results from recovery, shear bands and lamellar fragmentations. • A microstructure based analytical flow stress model is established. - Abstract: The mechanical behaviors and microstructure evolution of pearlitic steel wires under monotonic shear deformation have been investigated by a torsion test and a number of electron microscopy techniques including scanning electron microscopy (SEM) and transmission electron microscopy (TEM), with an aim to reveal the softening and hardening mechanisms of a randomly oriented pearlitic structure during a monotonic stain path. Significantly different from the remarkable strain hardening in cold wire drawing, the strain hardening rate during torsion drops to zero quickly after a short hardening stage. The microstructure observations indicate that the inter-lamellar spacing (ILS) decreases and the dislocations accumulate with strain, which leads to hardening of the material. Meanwhile, when the strain is larger than 0.154, the enhancement of dynamic recovery, shear bands (SBs) and cementite fragmentations results in the softening and balances the strain hardening. A microstructure based analytical flow stress model with considering the influence of ILS on the mean free path of dislocations and the softening caused by SBs and cementite fragmentations, has been established and the predicted flow shear curve meets well with the measured curve in the torsion test

  3. Autophagy as a Possible Underlying Mechanism of Nanomaterial Toxicity

    Directory of Open Access Journals (Sweden)

    Vanessa Cohignac

    2014-07-01

    Full Text Available The rapid development of nanotechnologies is raising safety concerns because of the potential effects of engineered nanomaterials on human health, particularly at the respiratory level. Since the last decades, many in vivo studies have been interested in the pulmonary effects of different classes of nanomaterials. It has been shown that some of them can induce toxic effects, essentially depending on their physico-chemical characteristics, but other studies did not identify such effects. Inflammation and oxidative stress are currently the two main mechanisms described to explain the observed toxicity. However, the exact underlying mechanism(s still remain(s unknown and autophagy could represent an interesting candidate. Autophagy is a physiological process in which cytoplasmic components are digested via a lysosomal pathway. It has been shown that autophagy is involved in the pathogenesis and the progression of human diseases, and is able to modulate the oxidative stress and pro-inflammatory responses. A growing amount of literature suggests that a link between nanomaterial toxicity and autophagy impairment could exist. In this review, we will first summarize what is known about the respiratory effects of nanomaterials and we will then discuss the possible involvement of autophagy in this toxicity. This review should help understand why autophagy impairment could be taken as a promising candidate to fully understand nanomaterials toxicity.

  4. Exploration of mechanisms underlying the strain-rate-dependent mechanical property of single chondrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Trung Dung; Gu, YuanTong, E-mail: yuantong.gu@qut.edu.au [School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, Queensland (Australia)

    2014-05-05

    Based on the characterization by Atomic Force Microscopy, we report that the mechanical property of single chondrocytes has dependency on the strain-rates. By comparing the mechanical deformation responses and the Young's moduli of living and fixed chondrocytes at four different strain-rates, we explore the deformation mechanisms underlying this dependency property. We found that the strain-rate-dependent mechanical property of living cells is governed by both of the cellular cytoskeleton and the intracellular fluid when the fixed chondrocytes are mainly governed by their intracellular fluid, which is called the consolidation-dependent deformation behavior. Finally, we report that the porohyperelastic constitutive material model which can capture the consolidation-dependent behavior of both living and fixed chondrocytes is a potential candidature to study living cell biomechanics.

  5. ASPN and GJB2 Are Implicated in the Mechanisms of Invasion of Ductal Breast Carcinomas

    Directory of Open Access Journals (Sweden)

    Bàrbara Castellana, Daniel Escuin, Gloria Peiró, Bárbara Garcia-Valdecasas, Tania Vázquez, Cristina Pons, Maitane Pérez-Olabarria, Agustí Barnadas, Enrique Lerma

    2012-01-01

    Full Text Available The mechanism of progression from ductal carcinoma in situ (DCIS to invasive ductal carcinoma (IDC remains largely unknown. We compared gene expression in tumors with simultaneous DCIS and IDC to decipher how diverse proteins participate in the local invasive process.Twenty frozen tumor specimens with concurrent, but separated, DCIS and IDC were microdissected and evaluated. Total RNA was extracted and microarray analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST Arrays. Microarray data were validated by quantitative real time reverse transcription-PCR (qRT-PCR and immunohistochemistry. Controls included seven pure in situ carcinomas, eight fragments from normal breast tissue, and a series of mouse breast carcinomas (MMTV-PyMT.Fifty-six genes were differentially expressed between DCIS and IDC samples. The genes upregulated in IDC samples, and probably associated with invasion, were related to the epithelial-mesenchymal transition (ASPN, THBS2, FN1, SPARC, and COL11A1, cellular adhesion (GJB2, cell motility and progression (PLAUR, PLAU, BGN, ADAMTS16, and ENPP2, extracellular matrix degradation (MMP11, MMP13, and MMP14, and growth/proliferation (ST6GAL2. qRT-PCR confirmed the expression patterns of ASPN, GJB2, ENPP2, ST6GAL2, and TMBS10. Expression of the ASPN and GJB2 gene products was detected by immunohistochemistry in invasive carcinoma foci. The association of GJB2 protein expression with invasion was confirmed by qRT-PCR in mouse tumors (P < 0.05.Conclusions: The upregulation of ASPN and GJB2 may play important roles in local invasion of breast ductal carcinomas.

  6. Validation of feasibility and quality of chicken breast meat cooked under various water-cooking conditions.

    Science.gov (United States)

    Chumngoen, Wanwisa; Chen, Hsin-Yi; Tan, Fa-Jui

    2016-12-01

    Under laboratory conditions, the qualities of boneless chicken breasts are commonly determined by placing them in a bag and cooking them in a water bath. The results are often applied as references for comparing the influences of cooking techniques. However, whether a sample cooked under this "laboratory" condition actually represents the meat cooked under the "real-life" condition in which meat is frequently cooked directly in water without packaging remains unclear. Whether the two cooking conditions lead to comparable results in meat quality should be determined. This study evaluated the influence of cooking conditions, including "placed-in-bag and cooked in a water bath (BC)" and "cooked directly in hot water (WC)" conditions, on the quality of chicken meat. The results reveal that BC samples had a longer cooking time. Deboned-and-skinless BC samples had a higher cooking loss and lower protein solubility (P < 0.01). BC samples with bone and skin had a higher lightness in both skin and muscle. No significant differences were observed in attributes, including shear force, collagen solubility, microstructures, redness, yellowness and descriptive sensory characteristics between treatments. Based on the results, considering the quality attributes that might be influenced, is critical when conducting relevant research. © 2016 Japanese Society of Animal Science.

  7. Mechanisms of Acquired Resistance to Trastuzumab Emtansine in Breast Cancer Cells.

    Science.gov (United States)

    Li, Guangmin; Guo, Jun; Shen, Ben-Quan; Bumbaca Yadav, Daniela; Sliwkowski, Mark X; Crocker, Lisa M; Lacap, Jennifer A; Lewis Phillips, Gail D

    2018-04-25

    The receptor tyrosine kinase HER2 is overexpressed in approximately 20% of breast cancer, and its amplification is associated with reduced survival. Trastuzumab emtansine (Kadcyla®, T-DM1), an antibody-drug conjugate that is comprised of trastuzumab covalently linked to the anti-mitotic agent DM1 through a stable linker, was designed to selectively deliver DM1 to HER2-overexpressing tumor cells. T-DM1 is approved for the treatment of patients with HER2-positive metastatic breast cancer following progression on trastuzumab and a taxane. Despite the improvement in clinical outcome, many patients who initially respond to T-DM1 treatment eventually develop progressive disease. The mechanisms that contribute to T-DM1 resistance are not fully understood. To this end, we developed T-DM1-resistant in vitro models to examine the mechanisms of acquired T-DM1 resistance. We demonstrate that decreased HER2 and up-regulation of MDR1 contribute to T-DM1 resistance in KPL-4 T-DM1 resistant cells. In contrast, both loss of SLC46A3 and PTEN deficiency play a role in conferring resistance in BT-474M1 T-DM1 resistant cells. Our data suggest that these two cell lines acquire resistance through distinct mechanisms. Furthermore, we show that the KPL-4 T-DM1 resistance can be overcome by treatment with an inhibitor of MDR1, whereas a PI3K inhibitor can rescue PTEN loss-induced resistance in T-DM1-resistant BT-474M1 cells. Our results provide a rationale for developing therapeutic strategies to enhance T-DM1 clinical efficacy by combining T-DM1 and other inhibitors that target signaling transduction or resistance pathways. Copyright ©2018, American Association for Cancer Research.

  8. Evaluation of Potential Mechanisms Controlling the Catalase Expression in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Christophe Glorieux

    2018-01-01

    Full Text Available Development of cancer cell resistance against prooxidant drugs limits its potential clinical use. MCF-7 breast cancer cells chronically exposed to ascorbate/menadione became resistant (Resox cells by increasing mainly catalase activity. Since catalase appears as an anticancer target, the elucidation of mechanisms regulating its expression is an important issue. In MCF-7 and Resox cells, karyotype analysis showed that chromosome 11 is not altered compared to healthy mammary epithelial cells. The genomic gain of catalase locus observed in MCF-7 and Resox cells cannot explain the differential catalase expression. Since ROS cause DNA lesions, the activation of DNA damage signaling pathways may influence catalase expression. However, none of the related proteins (i.e., p53, ChK was activated in Resox cells compared to MCF-7. The c-abl kinase may lead to catalase protein degradation via posttranslational modifications, but neither ubiquitination nor phosphorylation of catalase was detected after catalase immunoprecipitation. Catalase mRNA levels did not decrease after actinomycin D treatment in both cell lines. DNMT inhibitor (5-aza-2′-deoxycytidine increased catalase protein level in MCF-7 and its resistance to prooxidant drugs. In line with our previous report, chromatin remodeling appears as the main regulator of catalase expression in breast cancer after chronic exposure to an oxidative stress.

  9. Mechanisms underlying epithelium-dependent relaxation in rat bronchioles

    DEFF Research Database (Denmark)

    Kroigaard, Christel; Dalsgaard, Thomas; Simonsen, Ulf

    2010-01-01

    This study investigated the mechanisms underlying epithelium-derived hyperpolarizing factor (EpDHF)-type relaxation in rat bronchioles. Immunohistochemistry was performed, and rat bronchioles and pulmonary arteries were mounted in microvascular myographs for functional studies. An opener of small...... (SK(Ca)) and intermediate (IK(Ca))-conductance calcium-activated potassium channels, NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) was used to induce EpDHF-type relaxation. IK(Ca) and SK(Ca)3 positive immunoreactions were observed mainly in the epithelium and endothelium of bronchioles and arteries......, respectively. In 5-hydroxytryptamine (1 microM)-contracted bronchioles (828 +/- 20 microm, n = 84) and U46619 (0.03 microM)-contracted arteries (720 +/- 24 microm, n = 68), NS309 (0.001-10 microM) induced concentration-dependent relaxations that were reduced by epithelium/endothelium removal and by blocking IK...

  10. Neural mechanisms underlying human consensus decision-making.

    Science.gov (United States)

    Suzuki, Shinsuke; Adachi, Ryo; Dunne, Simon; Bossaerts, Peter; O'Doherty, John P

    2015-04-22

    Consensus building in a group is a hallmark of animal societies, yet little is known about its underlying computational and neural mechanisms. Here, we applied a computational framework to behavioral and fMRI data from human participants performing a consensus decision-making task with up to five other participants. We found that participants reached consensus decisions through integrating their own preferences with information about the majority group members' prior choices, as well as inferences about how much each option was stuck to by the other people. These distinct decision variables were separately encoded in distinct brain areas-the ventromedial prefrontal cortex, posterior superior temporal sulcus/temporoparietal junction, and intraparietal sulcus-and were integrated in the dorsal anterior cingulate cortex. Our findings provide support for a theoretical account in which collective decisions are made through integrating multiple types of inference about oneself, others, and environments, processed in distinct brain modules. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Physical effects of mechanical design parameters on photon sensitivity and spatial resolution performance of a breast-dedicated PET system.

    Science.gov (United States)

    Spanoudaki, V C; Lau, F W Y; Vandenbroucke, A; Levin, C S

    2010-11-01

    This study aims to address design considerations of a high resolution, high sensitivity positron emission tomography scanner dedicated to breast imaging. The methodology uses a detailed Monte Carlo model of the system structures to obtain a quantitative evaluation of several performance parameters. Special focus was given to the effect of dense mechanical structures designed to provide mechanical robustness and thermal regulation to the minuscule and temperature sensitive detectors. For the energies of interest around the photopeak (450-700 keV energy window), the simulation results predict a 6.5% reduction in the single photon detection efficiency and a 12.5% reduction in the coincidence photon detection efficiency in the case that the mechanical structures are interspersed between the detectors. However for lower energies, a substantial increase in the number of detected events (approximately 14% and 7% for singles at a 100-200 keV energy window and coincidences at a lower energy threshold of 100 keV, respectively) was observed with the presence of these structures due to backscatter. The number of photon events that involve multiple interactions in various crystal elements is also affected by the presence of the structures. For photon events involving multiple interactions among various crystal elements, the coincidence photon sensitivity is reduced by as much as 20% for a point source at the center of the field of view. There is no observable effect on the intrinsic and the reconstructed spatial resolution and spatial resolution uniformity. Mechanical structures can have a considerable effect on system sensitivity, especially for systems processing multi-interaction photon events. This effect, however, does not impact the spatial resolution. Various mechanical structure designs are currently under evaluation in order to achieve optimum trade-off between temperature stability, accurate detector positioning, and minimum influence on system performance.

  12. POSSIBLE MECHANISMS UNDERLYING THE THERAPEUTIC EFFECTS OF TRANSCRANIAL MAGNETIC STIMULATION

    Directory of Open Access Journals (Sweden)

    Alexander eChervyakov

    2015-06-01

    Full Text Available Transcranial magnetic stimulation (TMS is an effective method used to diagnose and treat many neurological disorders. Although repetitive TMS (rTMS has been used to treat a variety of serious pathological conditions including stroke, depression, Parkinson's disease, epilepsy, pain, and migraines, the pathophysiological mechanisms underlying the effects of long-term TMS remain unclear. In the present review, the effects of rTMS on neurotransmitters and synaptic plasticity are described, including the classic interpretations of TMS effects on synaptic plasticity via long-term potentiation (LTP and long-term depression (LTD. We also discuss the effects of rTMS on the genetic apparatus of neurons, glial cells and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth and sprouting and neurotrophic factors are described, including change in brain-derived neurotrophic factor (BDNF concentration under the influence of rTMS. Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception, the macromolecular effects of TMS, and the electromagnetic theory of consciousness. Finally, we discuss possible interpretations of TMS effects according to dynamical systems theory. Evidence suggests that a rTMS-induced magnetic field should be considered a separate physical factor that can be impactful at the subatomic level and that rTMS is capable of significantly altering the reactivity of molecules (radicals. It is thought that these factors underlie the therapeutic benefits of therapy with TMS. Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols.

  13. Possible Mechanisms Underlying the Therapeutic Effects of Transcranial Magnetic Stimulation

    Science.gov (United States)

    Chervyakov, Alexander V.; Chernyavsky, Andrey Yu.; Sinitsyn, Dmitry O.; Piradov, Michael A.

    2015-01-01

    Transcranial magnetic stimulation (TMS) is an effective method used to diagnose and treat many neurological disorders. Although repetitive TMS (rTMS) has been used to treat a variety of serious pathological conditions including stroke, depression, Parkinson’s disease, epilepsy, pain, and migraines, the pathophysiological mechanisms underlying the effects of long-term TMS remain unclear. In the present review, the effects of rTMS on neurotransmitters and synaptic plasticity are described, including the classic interpretations of TMS effects on synaptic plasticity via long-term potentiation and long-term depression. We also discuss the effects of rTMS on the genetic apparatus of neurons, glial cells, and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth and sprouting and neurotrophic factors are described, including change in brain-derived neurotrophic factor concentration under the influence of rTMS. Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception, the macromolecular effects of TMS, and the electromagnetic theory of consciousness. Finally, we discuss possible interpretations of TMS effects according to dynamical systems theory. Evidence suggests that a rTMS-induced magnetic field should be considered a separate physical factor that can be impactful at the subatomic level and that rTMS is capable of significantly altering the reactivity of molecules (radicals). It is thought that these factors underlie the therapeutic benefits of therapy with TMS. Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols. PMID:26136672

  14. Simulated airplane headache: a proxy towards identification of underlying mechanisms.

    Science.gov (United States)

    Bui, Sebastian Bao Dinh; Petersen, Torben; Poulsen, Jeppe Nørgaard; Gazerani, Parisa

    2017-12-01

    Airplane Headache (AH) occurs during flights and often appears as an intense, short lasting headache during take-off or landing. Reports are limited on pathological mechanisms underlying the occurrence of this headache. Proper diagnosis and treatments would benefit from identification of potential pathways involved in AH pathogenesis. This study aimed at providing a simulated airplane headache condition as a proxy towards identification of its underlying mechanisms. Fourteen participants including 7 volunteers suffering from AH and 7 healthy matched controls were recruited after meeting the diagnostic and safety criteria based on an approved study protocol. Simulation of AH was achieved by entering a pressure chamber with similar characteristics of an airplane flight. Selected potential biomarkers including salivary prostaglandin E 2 (PGE 2 ), cortisol, facial thermo-images, blood pressure, pulse, and saturation pulse oxygen (SPO) were defined and values were collected before, during and after flight simulation in the pressure chamber. Salivary samples were analyzed with ELISA techniques, while data analysis and statistical tests were handled with SPSS version 22.0. All participants in the AH-group experienced a headache attack similar to AH experience during flight. The non-AH-group did not experience any headaches. Our data showed that the values for PGE 2 , cortisol and SPO were significantly different in the AH-group in comparison with the non-AH-group during the flight simulation in the pressure chamber. The pressure chamber proved useful not only to provoke AH-like attack but also to study potential biomarkers for AH in this study. PGE 2 , and cortisol levels together with SPO presented dysregulation during the simulated AH-attack in affected individuals compared with healthy controls. Based on these findings we propose to use pressure chamber as a model to induce AH, and thus assess new potential biomarkers for AH in future studies.

  15. Nonlinear Mechanics of MEMS Rectangular Microplates under Electrostatic Actuation

    KAUST Repository

    Saghir, Shahid

    2016-12-01

    The first objective of the dissertation is to develop a suitable reduced order model capable of investigating the nonlinear mechanical behavior of von-Karman plates under electrostatic actuation. The second objective is to investigate the nonlinear static and dynamic behavior of rectangular microplates under small and large actuating forces. In the first part, we present and compare various approaches to develop reduced order models for the nonlinear von-Karman rectangular microplates actuated by nonlinear electrostatic forces. The reduced-order models aim to investigate the static and dynamic behavior of the plate under small and large actuation forces. A fully clamped microplate is considered. Different types of basis functions are used in conjunction with the Galerkin method to discretize the governing equations. First we investigate the convergence with the number of modes retained in the model. Then for validation purpose, a comparison of the static results is made with the results calculated by a nonlinear finite element model. The linear eigenvalue problem for the plate under the electrostatic force is solved for a wide range of voltages up to pull-in. In the second part, we present an investigation of the static and dynamic behavior of a fully clamped microplate. We investigate the effect of different non-dimensional design parameters on the static response. The forced-vibration response of the plate is then investigated when the plate is excited by a harmonic AC load superimposed to a DC load. The dynamic behavior is examined near the primary and secondary (superharmonic and subharmonic) resonances. The microplate shows a strong hardening behavior due to the cubic nonlinearity of midplane stretching. However, the behavior switches to softening as the DC load is increased. Next, near-square plates are studied to understand the effect of geometric imperfections of microplates. In the final part of the dissertation, we investigate the mechanical behavior of

  16. Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism

    Directory of Open Access Journals (Sweden)

    Nguyen Quoc Vuong Tran

    2017-01-01

    Full Text Available The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD and attention deficit hyperactivity disorder (ADHD, calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates, persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment.

  17. MECHANICAL BEHAVIOR OF PRESTRESSED VISCOELASTIC ADHESIVE AREAS UNDER COMBINING LOADINGS

    Directory of Open Access Journals (Sweden)

    Halil Murat Enginsoy

    2017-12-01

    Full Text Available In this article, mechanical behaviors of adhesive tape VHB 4950 elastomeric material, which is an element of acrylic polymer group and which is in viscoelastic behavior, under different pre-stress conditions and complex forces of different geometric parameters created by combining loadings have been experimentally and numerically investigated. In experimental studies, loading-unloading cyclic tests, one of the different standardized tests for the mechanical characterization of viscoelastic material, have been applied which give the most suitable convergent optimization parameters for the finite element model. Different material models were also investigated by using the data obtained from loading-unloading test results in all numerical models. According to the experimental results, the most suitable material parameters were determined with the Abaqus Parallel Rheological Framework Model (PRF for 4 Yeoh Networks with Bergstrom-Boyce Flow model created in the Mcalibration software for finite element analysis. Subsequently, using these material parameters, finite element analysis was performed as three dimension non-linear viscoelastic with a commercial finite element software Abaqus. The finite element analysis results showed good correlation to the Force (N-Displacement (mm experimental data for maximum load-carrying capacity of structural specimens.

  18. Using Drosophila to discover mechanisms underlying type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Ronald W. Alfa

    2016-04-01

    Full Text Available Mechanisms of glucose homeostasis are remarkably well conserved between the fruit fly Drosophila melanogaster and mammals. From the initial characterization of insulin signaling in the fly came the identification of downstream metabolic pathways for nutrient storage and utilization. Defects in these pathways lead to phenotypes that are analogous to diabetic states in mammals. These discoveries have stimulated interest in leveraging the fly to better understand the genetics of type 2 diabetes mellitus in humans. Type 2 diabetes results from insulin insufficiency in the context of ongoing insulin resistance. Although genetic susceptibility is thought to govern the propensity of individuals to develop type 2 diabetes mellitus under appropriate environmental conditions, many of the human genes associated with the disease in genome-wide association studies have not been functionally studied. Recent advances in the phenotyping of metabolic defects have positioned Drosophila as an excellent model for the functional characterization of large numbers of genes associated with type 2 diabetes mellitus. Here, we examine results from studies modeling metabolic disease in the fruit fly and compare findings to proposed mechanisms for diabetic phenotypes in mammals. We provide a systematic framework for assessing the contribution of gene candidates to insulin-secretion or insulin-resistance pathways relevant to diabetes pathogenesis.

  19. Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism

    Science.gov (United States)

    2017-01-01

    The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD), calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD) hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates), persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment. PMID:28567415

  20. Mechanisms underlying the social enhancement of vocal learning in songbirds.

    Science.gov (United States)

    Chen, Yining; Matheson, Laura E; Sakata, Jon T

    2016-06-14

    Social processes profoundly influence speech and language acquisition. Despite the importance of social influences, little is known about how social interactions modulate vocal learning. Like humans, songbirds learn their vocalizations during development, and they provide an excellent opportunity to reveal mechanisms of social influences on vocal learning. Using yoked experimental designs, we demonstrate that social interactions with adult tutors for as little as 1 d significantly enhanced vocal learning. Social influences on attention to song seemed central to the social enhancement of learning because socially tutored birds were more attentive to the tutor's songs than passively tutored birds, and because variation in attentiveness and in the social modulation of attention significantly predicted variation in vocal learning. Attention to song was influenced by both the nature and amount of tutor song: Pupils paid more attention to songs that tutors directed at them and to tutors that produced fewer songs. Tutors altered their song structure when directing songs at pupils in a manner that resembled how humans alter their vocalizations when speaking to infants, that was distinct from how tutors changed their songs when singing to females, and that could influence attention and learning. Furthermore, social interactions that rapidly enhanced learning increased the activity of noradrenergic and dopaminergic midbrain neurons. These data highlight striking parallels between humans and songbirds in the social modulation of vocal learning and suggest that social influences on attention and midbrain circuitry could represent shared mechanisms underlying the social modulation of vocal learning.

  1. Thermal stability of nafion membranes under mechanical stress

    Energy Technology Data Exchange (ETDEWEB)

    Quintilii, M; Struis, R [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1997-06-01

    The feasibility of adequately modified fluoro-ionomer membranes (NAFION{sup R}) is demonstrated for the selective separation of methanol synthesis products from the raw reactor gas at temperatures around 200{sup o}C. For an economically relevant application of this concept on a technical scale the Nafion membranes should be thin ({approx_equal}10 {mu}m) and thermally stable over a long period of time (1-2 years). In cooperation with industry (Methanol Casale SA, Lugano (CH)), we test the thermal stability of Nafion hollow fibers and supported Nafion thin sheet membranes at temperatures between 160 and 200{sup o}C under mechanical stress by applying a gas pressure difference over the membrane surface ({Delta}P{<=} 40 bar). Tests with the hollow fibers revealed that Nafion has visco-elastic properties. Tests with 50 {mu}m thin Nafion sheets supported by a porous metal carrier at 200{sup o}C and {Delta}P=39 bar showed no mechanical defects over a period of 92 days. (author) 5 figs., 4 refs.

  2. Different neurophysiological mechanisms underlying word and rule extraction from speech.

    Directory of Open Access Journals (Sweden)

    Ruth De Diego Balaguer

    Full Text Available The initial process of identifying words from spoken language and the detection of more subtle regularities underlying their structure are mandatory processes for language acquisition. Little is known about the cognitive mechanisms that allow us to extract these two types of information and their specific time-course of acquisition following initial contact with a new language. We report time-related electrophysiological changes that occurred while participants learned an artificial language. These changes strongly correlated with the discovery of the structural rules embedded in the words. These changes were clearly different from those related to word learning and occurred during the first minutes of exposition. There is a functional distinction in the nature of the electrophysiological signals during acquisition: an increase in negativity (N400 in the central electrodes is related to word-learning and development of a frontal positivity (P2 is related to rule-learning. In addition, the results of an online implicit and a post-learning test indicate that, once the rules of the language have been acquired, new words following the rule are processed as words of the language. By contrast, new words violating the rule induce syntax-related electrophysiological responses when inserted online in the stream (an early frontal negativity followed by a late posterior positivity and clear lexical effects when presented in isolation (N400 modulation. The present study provides direct evidence suggesting that the mechanisms to extract words and structural dependencies from continuous speech are functionally segregated. When these mechanisms are engaged, the electrophysiological marker associated with rule-learning appears very quickly, during the earliest phases of exposition to a new language.

  3. Understanding and imitating unfamiliar actions: distinct underlying mechanisms.

    Directory of Open Access Journals (Sweden)

    Joana C Carmo

    Full Text Available The human "mirror neuron system" has been proposed to be the neural substrate that underlies understanding and, possibly, imitating actions. However, since the brain activity with mirror properties seems insufficient to provide a good description for imitation of actions outside one's own repertoire, the existence of supplementary processes has been proposed. Moreover, it is unclear whether action observation requires the same neural mechanisms as the explicit access to their meaning. The aim of this study was two-fold as we investigated whether action observation requires different processes depending on 1 whether the ultimate goal is to imitate or understand the presented actions and 2 whether the to-be-imitated actions are familiar or unfamiliar to the subject. Participants were presented with both meaningful familiar actions and meaningless unfamiliar actions that they had to either imitate or discriminate later. Event-related Potentials were used as differences in brain activity could have been masked by the use of other techniques with lower temporal resolution. In the imitation task, a sustained left frontal negativity was more pronounced for meaningless actions than for meaningful ones, starting from an early time-window. Conversely, observing unfamiliar versus familiar actions with the intention of discriminating them led to marked differences over right centro-posterior scalp regions, in both middle and latest time-windows. These findings suggest that action imitation and action understanding may be sustained by dissociable mechanisms: while imitation of unfamiliar actions activates left frontal processes, that are likely to be related to learning mechanisms, action understanding involves dedicated operations which probably require right posterior regions, consistent with their involvement in social interactions.

  4. Vacuum-assisted breast biopsy under ultrasonographic guidance: analysis of a 10 year experience

    International Nuclear Information System (INIS)

    Lee, Seung Hyun; KIm, Eun Kyung; Kim, Min Jung; Moon, Hee Jung; Yoon, Jung Hyun

    2014-01-01

    To determine the indications and the diagnostic accuracy of vacuum-assisted breast biopsy (Vb) under ultrasonographic (US) guidance based on a 10-year period of clinical use. This was a retrospective analysis of 2,920 breast lesions in 2,477 consecutive patients who underwent US-guided Vb between February 2002 and December 2011. The proportions of each indication for Vb were analyzed as well as the trend of its use over divided time periods. Histopathological diagnosis and the malignancy rate of the lesions with Vb were analyzed. A comparison of the pathological diagnosis of Vb and the gold standard diagnosis revealed the false negative rate, the underestimation rate, and the agreement rate. Palpable lesions (44.4%), low-suspicion lesions (15.7%), high-risk lesions (12.4%), and calcifications (10.3%) were the most common indications for US-guided Vb. The malignancy rate of lesions submitted to Vb was 5.4%. The false negative rate was only 0.1%, while the underestimation rate of high-risk lesions and ductal carcinoma in situ was 3.1% and 13.8%, respectively, with a 98.7% agreement rate. Among 1,512 therapeutic Vb cases, 84.9% showed no residual or recurrent lesions on long term follow-up US for more than a year. Complications occurred in 1% of the patients without need for surgical intervention. US-guided Vb is an accurate and safe method that can help decision-making in the diagnostic process and can be an alternative for excision al surgery in some therapeutic circumstances.

  5. The effects and mechanisms of SLC34A2 on maintaining stem cell-like phenotypes in CD147+ breast cancer stem cells.

    Science.gov (United States)

    Lv, Yonggang; Wang, Ting; Fan, Jing; Zhang, Zhenzhen; Zhang, Juliang; Xu, Cheng; Li, Yongping; Zhao, Ge; He, Chenyang; Meng, Huimin; Yang, Hua; Wang, Zhen; Liu, Jiayun; Chen, Jianghao; Wang, Ling

    2017-04-01

    The cancer stem cell (CSC) hypothesis has gained significant recognition in describing tumorigenesis. Identification of the factors critical to development of breast cancer stem cells (BCSCs) may provide insight into the improvement of effective therapies against breast cancer. In this study, we aim to investigate the biological function of SLC34A2 in affecting the stem cell-like phenotypes in BCSCs and its underlying mechanisms. We demonstrated that CD147 + cells from breast cancer tissue samples and cell lines possessed BCSC-like features, including the ability of self-renewal in vitro, differentiation, and tumorigenic potential in vivo. Flow cytometry analysis showed the presence of a variable fraction of CD147 + cells in 9 of 10 tumor samples. Significantly, SLC34A2 expression in CD147 + BCSCs was enhanced compared with that in differentiated adherent progeny of CD147 + BCSCs and adherently cultured cell line cells. In breast cancer patient cohorts, SLC34A2 expression was found increased in 9 of 10 tumor samples. By using lentiviral-based approach, si-SLC34A2-transduced CD147 + BCSCs showed decreased ability of sphere formation, cell viability in vitro, and tumorigenicity in vivo, which suggested the essential role of SLC34A2 in CD147 + BCSCs. Furthermore, PI3K/AKT pathway and SOX2 were found necessary to maintain the stemness of CD147 + BCSCs by using LY294002 or lentiviral-si-SOX2. Finally, we indicated that SLC34A2 could regulate SOX2 to maintain the stem cell-like features in CD147 + BCSCs through PI3K/AKT pathway. Therefore, our report identifies a novel role of SLC34A2 in BCSCs' state regulation and establishes a rationale for targeting the SLC34A2/PI3K/AKT/SOX2 signaling pathway for breast cancer therapy.

  6. Microcracking in composite laminates under thermal and mechanical loading. Thesis

    Science.gov (United States)

    Maddocks, Jason R.

    1995-01-01

    Composites used in space structures are exposed to both extremes in temperature and applied mechanical loads. Cracks in the matrix form, changing the laminate thermoelastic properties. The goal of the present investigation is to develop a predictive methodology to quantify microcracking in general composite laminates under both thermal and mechanical loading. This objective is successfully met through a combination of analytical modeling and experimental investigation. In the analysis, the stress and displacement distributions in the vicinity of a crack are determined using a shear lag model. These are incorporated into an energy based cracking criterion to determine the favorability of crack formation. A progressive damage algorithm allows the inclusion of material softening effects and temperature-dependent material properties. The analysis is implemented by a computer code which gives predicted crack density and degraded laminate properties as functions of any thermomechanical load history. Extensive experimentation provides verification of the analysis. AS4/3501-6 graphite/epoxy laminates are manufactured with three different layups to investigate ply thickness and orientation effects. Thermal specimens are cooled to progressively lower temperatures down to -184 C. After conditioning the specimens to each temperature, cracks are counted on their edges using optical microscopy and in their interiors by sanding to incremental depths. Tensile coupons are loaded monotonically to progressively higher loads until failure. Cracks are counted on the coupon edges after each loading. A data fit to all available results provides input parameters for the analysis and shows them to be material properties, independent of geometry and loading. Correlation between experiment and analysis is generally very good under both thermal and mechanical loading, showing the methodology to be a powerful, unified tool. Delayed crack initiation observed in a few cases is attributed to a

  7. Mechanism of Akt1 inhibition of breast cancer cell invasionreveals a protumorigenic role for TSC2

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Hong; Radisky, Derek C.; Nelson, Celeste M.; Zhang, Hui; Fata, Jimmie; Roth, Richard A.; Bissell, Mina J.

    2006-02-07

    Akt1 is frequently upregulated in human tumors, and has been shown to accelerate cell proliferation and to suppress programmed cell death; consequently, inhibiting the activity of Akt1 has been seen as an attractive target for therapeutic intervention. Paradoxically, hyperactivation of the Akt1 oncogene can also prevent the invasive behavior that underlies progression to metastasis. Here we show that overexpression of activated myr-Akt1 in human breast cancer cells phosphorylates and thereby targets the tumor suppressor tuberous sclerosis complex 2 (TSC2) for degradation, leading to reduced Rho-GTPase activity, decreased actin stress fibers and focal adhesions, and reduced motility and invasion. Overexpression of TSC2 rescues the migration phenotype of myr-Akt1-expressing tumor cells, and high levels of TSC2 in breast cancer patients correlate with increased metastasis and reduced survival. These data indicate that the functional properties of genes designated as oncogenes or tumor suppressor genes depends on the context of the cell type and the tissues studied, and suggest the need for caution in designing therapies targeting the function of individual genes in epithelial tissues.

  8. Paclitaxel Induces Apoptosis in Breast Cancer Cells through Different Calcium—Regulating Mechanisms Depending on External Calcium Conditions

    Science.gov (United States)

    Pan, Zhi; Avila, Andrew; Gollahon, Lauren

    2014-01-01

    Previously, we reported that endoplasmic reticulum calcium stores were a direct target for paclitaxel initiation of apoptosis. Furthermore, the actions of paclitaxel attenuated Bcl-2 resistance to apoptosis through endoplasmic reticulum-mediated calcium release. To better understand the calcium-regulated mechanisms of paclitaxel-induced apoptosis in breast cancer cells, we investigated the role of extracellular calcium, specifically; whether influx of extracellular calcium contributed to and/or was necessary for paclitaxel-induced apoptosis. Our results demonstrated that paclitaxel induced extracellular calcium influx. This mobilization of extracellular calcium contributed to subsequent cytosolic calcium elevation differently, depending on dosage. Under normal extracellular calcium conditions, high dose paclitaxel induced apoptosis-promoting calcium influx, which did not occur in calcium-free conditions. In the absence of extracellular calcium an “Enhanced Calcium Efflux” mechanism in which high dose paclitaxel stimulated calcium efflux immediately, leading to dramatic cytosolic calcium decrease, was observed. In the absence of extracellular calcium, high dose paclitaxel’s stimulatory effects on capacitative calcium entry and apoptosis could not be completely restored. Thus, normal extracellular calcium concentrations are critical for high dose paclitaxel-induced apoptosis. In contrast, low dose paclitaxel mirrored controls, indicating that it occurs independent of extracellular calcium. Thus, extracellular calcium conditions only affect efficacy of high dose paclitaxel-induced apoptosis. PMID:24549172

  9. Mechanisms of Resistance to Endocrine Therapy in Breast Cancer: Focus on Signaling Pathways, miRNAs and Genetically Based Resistance

    Science.gov (United States)

    García-Becerra, Rocío; Santos, Nancy; Díaz, Lorenza; Camacho, Javier

    2013-01-01

    Breast cancer is the most frequent malignancy diagnosed in women. Approximately 70% of breast tumors express the estrogen receptor (ER). Tamoxifen and aromatase inhibitors (AIs) are the most common and effective therapies for patients with ERα-positive breast cancer. Alone or combined with chemotherapy, tamoxifen significantly reduces disease progression and is associated with more favorable impact on survival in patients. Unfortunately, endocrine resistance occurs, either de novo or acquired during the course of the treatment. The mechanisms that contribute to hormonal resistance include loss or modification in the ERα expression, regulation of signal transduction pathways, altered expression of specific microRNAs, balance of co-regulatory proteins, and genetic polymorphisms involved in tamoxifen metabolic activity. Because of the clinical consequences of endocrine resistance, new treatment strategies are arising to make the cells sensitive to tamoxifen. Here, we will review the current knowledge on mechanisms of endocrine resistance in breast cancer cells. In addition, we will discuss novel therapeutic strategies to overcome such resistance. Undoubtedly, circumventing endocrine resistance should help to improve therapy for the benefit of breast cancer patients. PMID:23344024

  10. Mechanical Modeling of a WIPP Drum Under Pressure

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Jeffrey A. [Sandia National Laboratories, Albuquerque, NM (United States)

    2014-11-25

    Mechanical modeling was undertaken to support the Waste Isolation Pilot Plant (WIPP) technical assessment team (TAT) investigating the February 14th 2014 event where there was a radiological release at the WIPP. The initial goal of the modeling was to examine if a mechanical model could inform the team about the event. The intention was to have a model that could test scenarios with respect to the rate of pressurization. It was expected that the deformation and failure (inability of the drum to contain any pressure) would vary according to the pressurization rate. As the work progressed there was also interest in using the mechanical analysis of the drum to investigate what would happen if a drum pressurized when it was located under a standard waste package. Specifically, would the deformation be detectable from camera views within the room. A finite element model of a WIPP 55-gallon drum was developed that used all hex elements. Analyses were conducted using the explicit transient dynamics module of Sierra/SM to explore potential pressurization scenarios of the drum. Theses analysis show similar deformation patterns to documented pressurization tests of drums in the literature. The calculated failure pressures from previous tests documented in the literature vary from as little as 16 psi to 320 psi. In addition, previous testing documented in the literature shows drums bulging but not failing at pressures ranging from 69 to 138 psi. The analyses performed for this study found the drums failing at pressures ranging from 35 psi to 75 psi. When the drums are pressurized quickly (in 0.01 seconds) there is significant deformation to the lid. At lower pressurization rates the deformation of the lid is considerably less, yet the lids will still open from the pressure. The analyses demonstrate the influence of pressurization rate on deformation and opening pressure of the drums. Analyses conducted with a substantial mass on top of the closed drum demonstrate that the

  11. [Mechanism research on the lupeol treatment on MCF-7 breast cancer cells based on cell metabonomics].

    Science.gov (United States)

    Shi, Dongdong; Kuang, Yuanyuan; Wang, Guiming; Peng, Zhangxiao; Wang, Yan; Yan, Chao

    2014-03-01

    The objective of this research is to investigate the suppressive effects of lupeol on MCF-7 breast cancer cells, and explore its mechanism on inhibiting the proliferation of MCF-7 cells based on cell metabonomics and cell cycle. Gas chromatography-mass spectrometry (GC-MS) was used in the cell metabonomics assay to identify metabolites of MCF-7 cells and MCF-7 cells treated with lupeol. Then, orthogonal partial least squares discriminant analysis (OPLS-DA) was used to process the metabolic data and model parameters of OPLS-DA were as follows: R2Ycum = 0.988, Q2Ycum = 0.964, which indicated that these two groups could be distinguished clearly. The metabolites (VIP (variable importance in the projection) > 1) were analyzed by t-test, and finally, metabolites (t metabonomics.

  12. Breast Gangrene

    Directory of Open Access Journals (Sweden)

    Husasin Irfan

    2011-08-01

    Full Text Available Abstract Background Breast gangrene is rare in surgical practice. Gangrene of breast can be idiopathic or secondary to some causative factor. Antibiotics and debridement are used for management. Acute inflammatory infiltrate, severe necrosis of breast tissue, necrotizing arteritis, and venous thrombosis is observed on histopathology. The aim of was to study patients who had breast gangrene. Methods A prospective study of 10 patients who had breast gangrene over a period of 6 years were analyzed Results All the patients in the study group were female. Total of 10 patients were encountered who had breast gangrene. Six patients presented with breast gangrene on the right breast whereas four had on left breast. Out of 10 patients, three had breast abscess after teeth bite followed by gangrene, one had iatrogenic trauma by needle aspiration of erythematous area of breast under septic conditions. Four had history of application of belladonna on cutaneous breast abscess and had then gangrene. All were lactating female. Amongst the rest two were elderly, one of which was a diabetic who had gangrene of breast and had no application of belladonna. All except one had debridement under cover of broad spectrum antibiotics. Three patients had grafting to cover the raw area. Conclusion Breast gangrene occurs rarely. Etiology is variable and mutifactorial. Teeth bite while lactation and the iatrogenic trauma by needle aspiration of breast abscess under unsterlised conditions could be causative. Uncontrolled diabetes can be one more causative factor for the breast gangrene. Belladonna application as a topical agent could be inciting factor. Sometimes gangrene of breast can be idiopathic. Treatment is antibiotics and debridement.

  13. Molecular Mechanisms Underlying Genomic Instability in Brca-Deficient Cells

    Science.gov (United States)

    2014-03-01

    repair defects asso- ciated with downstream mediators of the HR reaction (e.g., XRCC2, BRCA2, or PALB2) (Bouwman et al., 2010; Bowman- Colin et al., 2013...and BRCA-mutated breast cancers. Nat. Struct. Mol. Biol. 17, 688–695. Bowman- Colin , C., Xia, B., Bunting, S., Klijn, C., Drost, R., Bouwman, P., Fine...chromosomes. It is thus surprising that cells use ‘quick and dirty ’ repair by NHEJ rather than the slower, more accurate repair by homologous recombination

  14. The behavior of the planetary rings under the Kozai Mechanism

    Science.gov (United States)

    Sucerquia, M. A.; Ramírez, C. V.; Zuluaga, J. I.

    2017-07-01

    Rings are one of the main feature of almost all giant planets in the Solar System. Even though thousands of exoplanets have been discovered to date, no evidence of exoplanetary rings have been found despite the effort made in the development and enhancing of techniques and methods for direct or indirect detection. In the transit of a ringed planet, the dynamic of the ring itself could play a meaningful role due to the so called Kozai Mechanism (KM) acting on each particle of it. When some specific initial conditions of the ring are fulfilled (as a ring inclination greater than ˜ 39°), KM generates short periodic changes in the inclination and eccentricity of each particle, leading to a meaningful characteristic collective behavior of the ring: it changes its width, inclination and optical depth. These changes induce periodic variations on the eclipsed area of the parent star, generating slight changes in the observed transit signal. Under this mechanism, light curves depths and shapes oscillate according to the fluctuations of the ring. To show this effect we have performed numerical simulations of the dynamic of a system of particles to asses the ring inclination and width variations over time. We have calculated the expected variations in the transit depth and finally, we have estimated the effect on the light curve of a hypothetical ringed exoplanet affected by the KM. The detection of this effect could be used as an alternative method to detect/confirm exoplanetary rings, and also it could be considered as a way to explain anomalous light curves patterns of exoplanets, as the case of KIC 8462852 star.

  15. Mechanisms underlying recovery of zooplankton in Lake Orta after liming

    Directory of Open Access Journals (Sweden)

    Roberta Piscia

    2016-04-01

    Full Text Available The goal of this study was to improve the understanding of the large-scale mechanisms underlying the recovery of the zooplankton of Lake Orta from historical contamination, following reduced input of ammonia and metals and the subsequent 1989/90 liming intervention. The industrial pollution had been severe and long-lasting (1929-1990. Zooplankton biodiversity has improved, but most of the new taxa appearing in our counts are rotifers, while many calanoids and the large cladoceran predators (Bythotrephes and Leptodora that are common in the nearby Lake Maggiore, were still absent from Lake Orta 17 years after liming. To aid understanding of the large-scale mechanisms controlling changes in annual richness, we assessed the annual persistence (P of Crustacea and Rotifera taxa as an estimator of whether propagules that survived introduction, as result of the natural recolonization process, also thrived. We found that the rate of introduction of zooplankton colonists and their persistence in the water column of Lake Orta changed from 1971 to 2007. New rotifer taxa appeared in the lake after the mid-1980s, when discharge of toxic substances decreased, but their annual persistence was low (P<0.5 until the turn of the century. The numerical values of rotifer and crustacean persistence in Lake Orta were unexpectedly high in 2001 and 2007 (0.55 and 0.72 for rotifers, 0.85 and 0.86 for crustacean, respectively, much higher than in limed lakes in Sudbury, Canada, and in adjacent Lake Maggiore. We hypothesize this could be related to the lack of Cladoceran predators and zooplanktivorous fish in the pelagic waters of Lake Orta.

  16. Mechanisms underlying stage-1 TRPL channel translocation in Drosophila photoreceptors.

    Directory of Open Access Journals (Sweden)

    Minh-Ha Lieu

    Full Text Available TRP channels function as key mediators of sensory transduction and other cellular signaling pathways. In Drosophila, TRP and TRPL are the light-activated channels in photoreceptors. While TRP is statically localized in the signaling compartment of the cell (the rhabdomere, TRPL localization is regulated by light. TRPL channels translocate out of the rhabdomere in two distinct stages, returning to the rhabdomere with dark-incubation. Translocation of TRPL channels regulates their availability, and thereby the gain of the signal. Little, however, is known about the mechanisms underlying this trafficking of TRPL channels.We first examine the involvement of de novo protein synthesis in TRPL translocation. We feed flies cycloheximide, verify inhibition of protein synthesis, and test for TRPL translocation in photoreceptors. We find that protein synthesis is not involved in either stage of TRPL translocation out of the rhabdomere, but that re-localization to the rhabdomere from stage-1, but not stage-2, depends on protein synthesis. We also characterize an ex vivo eye preparation that is amenable to biochemical and genetic manipulation. We use this preparation to examine mechanisms of stage-1 TRPL translocation. We find that stage-1 translocation is: induced with ATP depletion, unaltered with perturbation of the actin cytoskeleton or inhibition of endocytosis, and slowed with increased membrane sterol content.Our results indicate that translocation of TRPL out of the rhabdomere is likely due to protein transport, and not degradation/re-synthesis. Re-localization from each stage to the rhabdomere likely involves different strategies. Since TRPL channels can translocate to stage-1 in the absence of ATP, with no major requirement of the cytoskeleton, we suggest that stage-1 translocation involves simple diffusion through the apical membrane, which may be regulated by release of a light-dependent anchor in the rhabdomere.

  17. Underlying Mechanisms of Tinnitus: Review and Clinical Implications

    Science.gov (United States)

    Henry, James A.; Roberts, Larry E.; Caspary, Donald M.; Theodoroff, Sarah M.; Salvi, Richard J.

    2016-01-01

    Background The study of tinnitus mechanisms has increased tenfold in the last decade. The common denominator for all of these studies is the goal of elucidating the underlying neural mechanisms of tinnitus with the ultimate purpose of finding a cure. While these basic science findings may not be immediately applicable to the clinician who works directly with patients to assist them in managing their reactions to tinnitus, a clear understanding of these findings is needed to develop the most effective procedures for alleviating tinnitus. Purpose The goal of this review is to provide audiologists and other health-care professionals with a basic understanding of the neurophysiological changes in the auditory system likely to be responsible for tinnitus. Results It is increasingly clear that tinnitus is a pathology involving neuroplastic changes in central auditory structures that take place when the brain is deprived of its normal input by pathology in the cochlea. Cochlear pathology is not always expressed in the audiogram but may be detected by more sensitive measures. Neural changes can occur at the level of synapses between inner hair cells and the auditory nerve and within multiple levels of the central auditory pathway. Long-term maintenance of tinnitus is likely a function of a complex network of structures involving central auditory and nonauditory systems. Conclusions Patients often have expectations that a treatment exists to cure their tinnitus. They should be made aware that research is increasing to discover such a cure and that their reactions to tinnitus can be mitigated through the use of evidence-based behavioral interventions. PMID:24622858

  18. Rules and mechanisms governing octahedral tilts in perovskites under pressure

    Science.gov (United States)

    Xiang, H. J.; Guennou, Mael; Íñiguez, Jorge; Kreisel, Jens; Bellaiche, L.

    2017-08-01

    The rotation of octahedra (octahedral tilting) is common in A B O3 perovskites and relevant to many physical phenomena, ranging from electronic and magnetic properties, metal-insulator transitions to improper ferroelectricity. Hydrostatic pressure is an efficient way to tune and control octahedral tiltings. However, the pressure behavior of such tiltings can dramatically differ from one material to another, with the origins of such differences remaining controversial. In this paper, we discover several new mechanisms and formulate a set of simple rules that allow us to understand how pressure affects oxygen octahedral tiltings via the use and analysis of first-principles results for a variety of compounds. Besides the known A -O interactions, we reveal that the interactions between specific B ions and oxygen ions contribute to the tilting instability. We explain the previously reported trend that the derivative of the oxygen octahedral tilting with respect to pressure (dR /dP ) usually decreases with both the tolerance factor and the ionization state of the A ion by illustrating the key role of A -O interactions and their change under pressure. Furthermore, three new mechanisms/rules are discovered, namely that (i) the octahedral rotations in A B O3 perovskites with empty low-lying d states on the B site are greatly enhanced by pressure, in order to lower the electronic kinetic energy; (ii) dR /dP is enhanced when the system possesses weak tilt instabilities, and (iii) for the most common phase exhibited by perovskites—the orthorhombic Pbnm state—the in-phase and antiphase octahedral rotations are not automatically both suppressed or both enhanced by the application of pressure because of a trilinear coupling between these two rotation types and an antipolar mode involving the A ions. We further predict that the polarization associated with the so-called hybrid improper ferroelectricity could be manipulated by hydrostatic pressure by indirectly controlling the

  19. The Mechanical Behaviors of Various Dental Implant Materials under Fatigue

    Directory of Open Access Journals (Sweden)

    Fatma Bayata

    2018-01-01

    Full Text Available The selection of materials has a considerable role on long-term stability of implants. The materials having high resistance to fatigue are required for dental implant applications since these implants are subjected to cyclic loads during chewing. This study evaluates the performance of different types of materials (AISI 316L stainless steel, alumina and its porous state, CoCr alloys, yttrium-stabilized zirconia (YSZ, zirconia-toughened alumina (ZTA, and cp Ti with the nanotubular TiO2 surface by finite element analysis (FEA under real cyclic biting loads and researches the optimum material for implant applications. For the analysis, the implant design generated by our group was utilized. The mechanical behavior and the life of the implant under biting loads were estimated based on the material and surface properties. According to the condition based on ISO 14801, the FEA results showed that the equivalent von Mises stress values were in the range of 226.95 MPa and 239.05 MPa. The penetration analysis was also performed, and the calculated penetration of the models onto the bone structure ranged between 0.0037389 mm and 0.013626 mm. L-605 CoCr alloy-assigned implant model showed the least penetration, while cp Ti with the nanotubular TiO2 surface led to the most one. However, the difference was about 0.01 mm, and it may not be evaluated as a distinct difference. As the final numerical evaluation item, the fatigue life was executed, and the results were achieved in the range of 4 × 105 and 1 × 109 cycles. These results indicated that different materials showed good performance for each evaluation component, but considering the overall mechanical performance and the treatment process (implant adsorption by means of surface properties, cp Ti with the nanotubular TiO2 surface material was evaluated as the suitable one, and it may also be implied that it displayed enough performance in the designed dental implant model.

  20. On the mechanical properties of tooth enamel under spherical indentation.

    Science.gov (United States)

    Chai, Herzl

    2014-11-01

    The mechanical properties of tooth enamel generally exhibit large variations, which reflect its structural and material complexity. Some key properties were evaluated under localized contact, simulating actual functioning conditions. Prominent cusps of extracted human molar teeth were polished down ~0.7 mm below the cusp tip and indented by tungsten carbide balls. The internal damage was assessed after unloading from longitudinal or transverse sections. The ultimate tensile stress (UTS) was determined using a novel bilayer specimen. The damage is characterized by penny-like radial cracks driven by hoop stresses and cylindrical cracks driven along protein-rich interrod materials by shear stresses. Shallow cone cracks typical of homogeneous materials which may cause rapid tooth wear under repeat contact are thus avoided. The mean stress vs. indentation strain curve is highly nonlinear, attributable to plastic shearing of protein between and within enamel rods. This curve is also affected by damage, especially radial cracks, the onset of which depends on ball radius. Several material properties were extracted from the tests, including shear strain at the onset of ring cracks γ(F) (=0.14), UTS (=119 MPa), toughness K(C) (=0.94 MPa m(1/2)), a crack propagation law and a constitutive response determined by trial and error with the aid of a finite-element analysis. These quantities, which are only slightly sensitive to anatomical location within the enamel region tested, facilitate a quantitative assessment of crown failure. Causes for variations in published UTS and K(C) values are discussed. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  1. Failure mechanisms of aluminium foams under compressive loads

    Directory of Open Access Journals (Sweden)

    Sáenz, E.

    2000-08-01

    Full Text Available The purpose of this paper is the investigation of the major failure mechanisms of aluminium foams, which were obtained by powder metallurgy route, under compressive loads. The study was focused on two commonly aluminium alloys AlMg1Si or A 6061 and AlSi12. Due to the fact that the failure mechanisms strongly depend on the density and the macrostructural properties of the material, the mechanical properties always have to be correlated to the structural properties. Therefore, macrostructural investigations were used as a basis to establish the correlation between structural and mechanical properties. This was done with a commercially available image analysis system. The average cell size, the cell size distribution and the cell density (number of cells/area were obtained. In order to evaluate the influence of foaming direction on the cell morphology, some cross sections parallel to the foaming direction were prepared. For the characterization of the mechanical compression properties the compressive or upper yield strength (UYS, the densification strain (eD, the energy absorption (Ea and the efficiency (Eff were obtained. Furthermore, the failure behavior of the samples was in-situ observed with a digital video camera and continuously recorded during the test.

    El objetivo de este estudio es investigar los principales mecanismos de fallo de espumas de aluminio sometidas a cargas de compresión. Las espumas metálicas fueron obtenidas mediante el proceso pulvimetalúrgico, utilizándose como materia prima dos aleaciones comerciales AlMg1Si o A 6061 y AlSi12. Debido a que los mecanismos de fallo en este tipo de materiales depende fuertemente de la densidad y las características macroestructurales del material, en este estudio se busca correlacionar las propiedades mecánicas con estas características. La macroestructura se caracterizó mediante análisis de imagen. El tamaño de celda promedio, la distribución de tamaño y la densidad de

  2. PBX1 Genomic Pioneer Function Drives ERα Signaling Underlying Progression in Breast Cancer

    Science.gov (United States)

    Magnani, Luca; Ballantyne, Elizabeth B.; Zhang, Xiaoyang; Lupien, Mathieu

    2011-01-01

    Altered transcriptional programs are a hallmark of diseases, yet how these are established is still ill-defined. PBX1 is a TALE homeodomain protein involved in the development of different types of cancers. The estrogen receptor alpha (ERα) is central to the development of two-thirds of all breast cancers. Here we demonstrate that PBX1 acts as a pioneer factor and is essential for the ERα-mediated transcriptional response driving aggressive tumors in breast cancer. Indeed, PBX1 expression correlates with ERα in primary breast tumors, and breast cancer cells depleted of PBX1 no longer proliferate following estrogen stimulation. Profiling PBX1 recruitment and chromatin accessibility across the genome of breast cancer cells through ChIP-seq and FAIRE-seq reveals that PBX1 is loaded and promotes chromatin openness at specific genomic locations through its capacity to read specific epigenetic signatures. Accordingly, PBX1 guides ERα recruitment to a specific subset of sites. Expression profiling studies demonstrate that PBX1 controls over 70% of the estrogen response. More importantly, the PBX1-dependent transcriptional program is associated with poor-outcome in breast cancer patients. Correspondingly, PBX1 expression alone can discriminate a priori the outcome in ERα-positive breast cancer patients. These features are markedly different from the previously characterized ERα-associated pioneer factor FoxA1. Indeed, PBX1 is the only pioneer factor identified to date that discriminates outcome such as metastasis in ERα-positive breast cancer patients. Together our results reveal that PBX1 is a novel pioneer factor defining aggressive ERα-positive breast tumors, as it guides ERα genomic activity to unique genomic regions promoting a transcriptional program favorable to breast cancer progression. PMID:22125492

  3. Mechanisms Underlying HIV-Associated Noninfectious Lung Disease.

    Science.gov (United States)

    Presti, Rachel M; Flores, Sonia C; Palmer, Brent E; Atkinson, Jeffrey J; Lesko, Catherine R; Lau, Bryan; Fontenot, Andrew P; Roman, Jesse; McDyer, John F; Twigg, Homer L

    2017-11-01

    Pulmonary disease remains a primary source of morbidity and mortality in persons living with HIV (PLWH), although the advent of potent combination antiretroviral therapy has resulted in a shift from predominantly infectious to noninfectious pulmonary complications. PLWH are at high risk for COPD, pulmonary hypertension, and lung cancer even in the era of combination antiretroviral therapy. The underlying mechanisms of this are incompletely understood, but recent research in both human and animal models suggests that oxidative stress, expression of matrix metalloproteinases, and genetic instability may result in lung damage, which predisposes PLWH to these conditions. Some of the factors that drive these processes include tobacco and other substance use, direct HIV infection and expression of specific HIV proteins, inflammation, and shifts in the microbiome toward pathogenic and opportunistic organisms. Further studies are needed to understand the relative importance of these factors to the development of lung disease in PLWH. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  4. [Underlying Mechanisms and Management of Refractory Gastroesophageal Reflux Disease].

    Science.gov (United States)

    Lee, Kwang Jae

    2015-08-01

    The prevalence of gastroesophageal reflux disease (GERD) in South Korea has increased over the past 10 years. Patients with erosive reflux disease (ERD) shows better response to proton pump inhibitors (PPIs) than those with non-erosive reflux disease (NERD). NERD is a heterogeneous condition, showing pathological gastroesophageal reflux or esophageal hypersensitivity to reflux contents. NERD patients with pathological gastroesophageal reflux or hypersensitivity to acid may respond to PPIs. However, many patients with esophageal hypersensitivity to nonacid or functional heartburn do not respond to PPIs. Therefore, careful history and investigations are required when managing patients with refractory GERD who show poor response to conventional dose PPIs. Combined pH-impedance studies and a PPI diagnostic trial are recommended to reveal underlying mechanisms of refractory symptoms. For those with ongoing reflux-related symptoms, split dose administration, change to long-acting PPIs or PPIs less influenced by CYP2C19 genotypes, increasing dose of PPIs, and the addition of alginate preparations, prokinetics, selective serotonin reuptake inhibitors, or tricyclic antidepressants can be considered. Pain modulators, selective serotonin reuptake inhibitors, or tricyclic antidepressants are more likely to be effective for those with reflux-unrelated symptoms. Surgery or endoscopic per oral fundoplication may be effective in selected patients.

  5. Enabling optimal energy options under the Clean Development Mechanism

    International Nuclear Information System (INIS)

    Gilau, Asmerom M.; Van Buskirk, Robert; Small, Mitchell J.

    2007-01-01

    This paper addresses the cost effectiveness of renewable energy technologies in achieving low abatement costs and promoting sustainable developments under the Clean Development Mechanism (CDM). According to the results of our optimal energy option's analysis, at project scale, compared with a diesel-only energy option, photovoltaic (PV)-diesel (PVDB), wind-diesel (WDB) and PV-wind-diesel (PVWDB) hybrids are very cost-effective energy options. Moreover, energy options with high levels of renewable energy, including 100% renewables, have the lowest net present cost and they are already cost effective without CDM. On the other hand, while the removal of about 87% carbon dioxide emissions could be achieved at negative cost, initial investment could increase by a factor of 40, which is one of the primary barriers hindering wider renewable energy applications in developing countries, among others. Thus, in order to increase developing countries' participation in the carbon market, CDM policy should shift from a purely market-oriented approach to investigating how to facilitate renewable energy projects through barrier removal. Thus, we recommend that further research should focus on how to efficiently remove renewable energy implementation barriers as a means to improve developing countries' participation in meaningful emission reduction while at the same time meeting the needs of sustainable economic development

  6. Neural mechanisms underlying the induction and relief of perceptual curiosity

    Directory of Open Access Journals (Sweden)

    Marieke eJepma

    2012-02-01

    Full Text Available Curiosity is one of the most basic biological drives in both animals and humans, and has been identified as a key motive for learning and discovery. Despite the importance of curiosity and related behaviors, the topic has been largely neglected in human neuroscience; hence little is known about the neurobiological mechanisms underlying curiosity. We used functional magnetic resonance imaging (fMRI to investigate what happens in our brain during the induction and subsequent relief of perceptual curiosity. Our core findings were that (i the induction of perceptual curiosity, through the presentation of ambiguous visual input, activated the anterior insula and anterior cingulate cortex, brain regions sensitive to conflict and arousal; (ii the relief of perceptual curiosity, through visual disambiguation, activated regions of the striatum that have been related to reward processing; and (iii the relief of perceptual curiosity was associated with hippocampal activation and enhanced incidental memory. These findings provide the first demonstration of the neural basis of human perceptual curiosity. Our results provide neurobiological support for a classic psychological theory of curiosity, which holds that curiosity is an aversive condition of increased arousal whose termination is rewarding and facilitates memory.

  7. Underlying mechanisms and the evolving influence of diet

    DEFF Research Database (Denmark)

    Larsen, Lesli Hingstrup

    2012-01-01

    Obesity is determined by both genetic and environmental factors. Since 2007, 52 genes have been associated with obesity and obesity-related measurements in genome-wide association studies (GWAS), among these the fat and obesity-associated gene (FTO). Despite the success in identifying genes predi...... and the microbiome that can be modified by diet, and by genotype, adding to the complexity of determining the contributors to obesity....... has been shown to attenuate the effect of FTO on obesity. Several studies have examined gene-diet interactions in relation to obesity, but only a few suggestive interactions have been identified. This is most probably due to small effect sizes of the interactions and thereby a demand for large samples...... to increased risk of developing obesity. Recently, the intestinal microbiome, the collected genome of the bacteria, also has been associated with obesity and with specific dietary profiles. The underlying mechanisms determining the susceptibility to obesity do not only include the genome but also the epigenome...

  8. Deciphering Molecular Mechanism Underlying Hypolipidemic Activity of Echinocystic Acid

    Directory of Open Access Journals (Sweden)

    Li Han

    2014-01-01

    Full Text Available Our previous study showed that a triterpene mixture, consisting of echinocystic acid (EA and oleanolic acid (OA at a ratio of 4 : 1, dose-dependently ameliorated the hyperlipidemia and atherosclerosis in rabbits fed with high fat/high cholesterol diets. This study was aimed at exploring the mechanisms underlying antihyperlipidemic effect of EA. Molecular docking simulation of EA was performed using Molegro Virtual Docker (version: 4.3.0 to investigate the potential targets related to lipid metabolism. Based on the molecular docking information, isotope labeling method or spectrophotometry was applied to examine the effect of EA on the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase, acyl-CoA:cholesterol acyltransferase (ACAT, and diacylglycerol acyltransferase (DGAT in rat liver microsomes. Our results revealed a strong affinity of EA towards ACAT and DGAT in molecular docking analysis, while low binding affinity existed between EA and HMG-CoA reductase as well as between EA and cholesteryl ester transfer protein. Consistent with the results of molecular docking, in vitro enzyme activity assays showed that EA inhibited ACAT and DGAT, with IC50 values of 103 and 139 μM, respectively, and exhibited no significant effect on HMG-CoA reductase activity. The present findings suggest that EA may exert hypolipidemic effect by inhibiting the activity of ACAT and DGAT.

  9. Potential mechanisms of diet therapy for fibrocystic breast conditions show inadequate evidence of effectiveness.

    Science.gov (United States)

    Horner, N K; Lampe, J W

    2000-11-01

    Fibrocystic breast conditions, formerly referred to as fibrocystic breast disease, affect about half of all women and typically present as any combination of breast nodularity, swelling, and pain. We reviewed the literature to evaluate evidence supporting nutrition interventions commonly recommended for fibrocystic breast conditions by health care providers. Randomized, controlled studies of the effectiveness of caffeine restriction fail to support any benefit in fibrocystic breast conditions. Similarly, evidence supporting evening primrose oil, vitamin E, or pyridoxine as treatments for the discomforts of fibrocystic breast conditions is insufficient to draw conclusions about effectiveness. Dietary alterations that influence the intermediate markers for fibrocystic breast conditions include low-fat (15% to 20% energy), high-fiber (30 g/day), and soy isoflavone regimens. However, our findings provide no solid evidence for secondary prevention or treatment of fibrocystic breast conditions through a dietary approach. Health care providers should limit recommendations to proven diet therapies supported by randomized, placebo-controlled trials, given the instability inherent in fibrocystic breast conditions and the near 20% placebo effect associated with intervention. Because excessive estrogen or altered sensitivity to estrogen is the dominant theory of etiology, interventions that may modulate endogenous steroid hormones warrant further investigation as potential treatments for symptomatic fibrocystic breast conditions.

  10. Mechanism of crack initiation and crack growth under thermal and mechanical fatigue loading

    International Nuclear Information System (INIS)

    Utz, S.; Soppa, E.; Silcher, H.; Kohler, C.

    2013-01-01

    The present contribution is focused on the experimental investigations and numerical simulations of the deformation behaviour and crack development in the austenitic stainless steel X6CrNiNb18-10 under thermal and mechanical cyclic loading in HCF and LCF regimes. The main objective of this research is the understanding of the basic mechanisms of fatigue damage and the development of simulation methods, which can be applied further in safety evaluations of nuclear power plant components. In this context the modelling of crack initiation and crack growth inside the material structure induced by varying thermal or mechanical loads are of particular interest. The mechanisms of crack initiation depend among other things on the type of loading, microstructure, material properties and temperature. The Nb-stabilized austenitic stainless steel in the solution-annealed condition was chosen for the investigations. Experiments with two kinds of cyclic loading - pure thermal and pure mechanical - were carried out and simulated. The fatigue behaviour of the steel X6CrNiNb18-10 under thermal loading was studied within the framework of the joint research project [4]. Interrupted thermal cyclic tests in the temperature range of 150 C to 300 C combined with non-destructive residual stress measurements (XRD) and various microscopic investigations, e.g. in SEM (Scanning Electron Microscope), were used to study the effects of thermal cyclic loading on the material. This thermal cyclic loading leads to thermal induced stresses and strains. As a result intrusions and extrusions appear inside the grains (at the surface), at which microcracks arise and evolve to a dominant crack. Finally, these microcracks cause a continuous and significant decrease of residual stresses. The fatigue behaviour of the steel X6CrNiNb18-10 under mechanical loading at room temperature was studied within the framework of the research project [5], [8]. With a combination of interrupted LCF tests and EBSD

  11. Mechanism of crack initiation and crack growth under thermal and mechanical fatigue loading

    Energy Technology Data Exchange (ETDEWEB)

    Utz, S.; Soppa, E.; Silcher, H.; Kohler, C. [Stuttgart Univ. (Germany). Materials Testing Inst.

    2013-07-01

    The present contribution is focused on the experimental investigations and numerical simulations of the deformation behaviour and crack development in the austenitic stainless steel X6CrNiNb18-10 under thermal and mechanical cyclic loading in HCF and LCF regimes. The main objective of this research is the understanding of the basic mechanisms of fatigue damage and the development of simulation methods, which can be applied further in safety evaluations of nuclear power plant components. In this context the modelling of crack initiation and crack growth inside the material structure induced by varying thermal or mechanical loads are of particular interest. The mechanisms of crack initiation depend among other things on the type of loading, microstructure, material properties and temperature. The Nb-stabilized austenitic stainless steel in the solution-annealed condition was chosen for the investigations. Experiments with two kinds of cyclic loading - pure thermal and pure mechanical - were carried out and simulated. The fatigue behaviour of the steel X6CrNiNb18-10 under thermal loading was studied within the framework of the joint research project [4]. Interrupted thermal cyclic tests in the temperature range of 150 C to 300 C combined with non-destructive residual stress measurements (XRD) and various microscopic investigations, e.g. in SEM (Scanning Electron Microscope), were used to study the effects of thermal cyclic loading on the material. This thermal cyclic loading leads to thermal induced stresses and strains. As a result intrusions and extrusions appear inside the grains (at the surface), at which microcracks arise and evolve to a dominant crack. Finally, these microcracks cause a continuous and significant decrease of residual stresses. The fatigue behaviour of the steel X6CrNiNb18-10 under mechanical loading at room temperature was studied within the framework of the research project [5], [8]. With a combination of interrupted LCF tests and EBSD

  12. Antioxidant Property of Jobelyn as the Possible Mechanism Underlying

    Directory of Open Access Journals (Sweden)

    Solomon Umukoro

    2013-01-01

    Full Text Available   Introduction: Amnesia or loss of memory is the cardinal hallmark of Alzheimer’s disease (AD, a progressive neurodegenerative disorder associated with ageing process. Although, AD had been discovered over a century ago, drugs which could cure or halt the progression of the disease are yet to see the light of the day. However, there has been a growing interest in the use of phytomedicines with multipronged mechanisms of action that could target various aspects of the pathologies of AD. Jobelyn (JB is a potent antioxidant African polyherbal formulation with active components that have been acclaimed to show neuroprotection. T his investigation was carried out to evaluate whether JB has anti-amnesic and antioxidant activities.   Methods: The alteration of alternation behavior in the Y-maze paradigm was utilized as the test for memory function in mice. The effect of JB on a cetylcholinesterase (AChE activity, malondialdehyde (MDA level and the concentrations of glutathione (GSH in the frontal cortex and hippocampus were assessed in rats as means of providing insight into the mechanism underlying its anti-amnesic activity. The animals were given JB (1, 2.5 or 5mg/kg, i.p. daily for 7 days before the biochemical assays or test for memory functions were carried out.   Results: JB was found to produce a significant increase in the level of alternation behavior compared with the control, suggesting anti-amnesic activity. Also, JB reversed the memory impairment induced by scopolamine, which further indicates anti-amnesic property. Furthermore, JB demonstrated a significant inhibition of MDA formation in the frontal cortex and hippocampus of rats, indicating antioxidant property. In addition, it increased the defense armory of the brain tissues, as it significantly increased the concentrations of GSH in the frontal cortex and hippocampus of rats. However, JB did not demonstrate any inhibitory effect against AChE activity in the frontal cortex and

  13. Mechanisms underlying the antihypertensive properties of Urtica dioica.

    Science.gov (United States)

    Qayyum, Rahila; Qamar, Hafiz Misbah-Ud-Din; Khan, Shamim; Salma, Umme; Khan, Taous; Shah, Abdul Jabbar

    2016-09-01

    Urtica dioica has traditionally been used in the management of cardiovascular disorders especially hypertension. The aim of this study was to explore pharmacological base of its use in hypertension. Crude methanolic extract of U. dioica (Ud.Cr) and its fractions (Ud.EtAc, Ud.nHex, Ud.Chl and Ud.Aq) were tested in vivo on normotensive and hypertensive rats under anesthesia for blood pressure lowering effect. In-vitro experiments on rat and rabbit aortae were employed to probe the vasorelaxation mechanism(s). The responses were measured using pressure and force transducers connected to PowerLab Data Acquisition System. Ud.Cr and fractions were found more effective antihypertensive in hypertensive rats than normotensive with remarkable potency exhibited by the ethyl acetate fraction. The effect was same in the presence of atropine. In isolated rat aortic rings, Ud.Cr and all its fractions exhibited L-NAME sensitive endothelium-dependent vasodilator effect and also inhibit K(+) (80 mM)-induced pre-contractions. In isolated rabbit thoracic aortic rings Ud.Cr and its fractions induced relaxation with more potency against K(+) (80 mM) than phenylephrine (1 µM) like verapamil, showing Ud.EtAc fraction the most potent one. Pre-incubation of aortic rings with Ud.Cr and its fractions exhibited Ca(2+) channel blocking activity comparable with verapamil by shifting Ca(2+) concentration response curves to the right. Ud.Cr and its fractions also ablated the intracellular Ca(2+) release by suppressing PE peak formation in Ca(2+) free medium. When tested on basal tension, the crude extract and all fractions were devoid of any vasoconstrictor effect. These data indicate that crude methanolic extract and its fractions possess antihypertensive effect. Identification of NO-mediated vasorelaxation and calcium channel blocking effects explain the antihypertensive potential of U. dioica and provide a potential pharmacological base to its medicinal use in the management of hypertension.

  14. Mechanisms of microstructure formation under the influence of ultrasonic vibrations

    Science.gov (United States)

    Rakita, Milan

    Positive effects of ultrasound on crystallization have been known for almost 90 years. Application of ultrasound has been very successful in many industries, most notably in chemistry, creating a new branch of science - sonochemistry. However, ultrasonication has not found wide commercial application in the solidification processing. The reason for that is the complexity of underlying phenomena and the lack of predicting models which correlate processing parameters with the properties of a product. The purpose of this study is to give some contribution toward better understanding of mechanisms that lead to changes in the solidifying microstructure. It has been found that, under experimental conditions used in this work, cavitation-induced nucleation is the major contributor to the grain refinement. Ultrasonication at minimal supercoolings is expected to give maximal grain refinement. Dendrite fragmentation has not shown to be a significant contributor to the grain refinement. Dendrite fragmentation is maximal if done by bubbles that come in contact with the solidifying phase, or that are created there. Alloys/solutions with long solidification interval, or wide mushy zone, are expected to exhibit more dendrite fragmentation. Bubbles are recognized as a crucial feature in ultrasonication. Their size distribution in the liquid phase prior to ultrasonication dictates the cavitation threshold and intensity of cavitation. For the first time, radiation pressure has been recognized as potentially significant factor in grain refinement. In the experimental setup used in this study, acoustic pressure at the main (driving) frequency is not substantial to cause significant fragmentation, and only dendrites close to the sonotrode were fragmented. However, application of ultrasound with frequencies that are several times higher than the current industrial practice could substantially increase dendrite fragmentation. Appearance of fractional harmonics has also been recognized

  15. Polymer Composite Rebars under Moisture and Mechanical Loading

    Science.gov (United States)

    Adam, Mohamed Ibrahim

    structural GFRP composites will, through their design life, be exposed to a range of hygrothermal and other environmental conditions. This study aims to investigate the durability of glass fiber reinforced vinyl ester rebars exposed to moisture at different temperatures and under mechanical loading. Rebars of 10 mm, 13 mm, and 16 mm diameter were immersed in deionized water until saturation for 220 days at three different temperatures 30°C, 70°C, and 100°C. The rebars were examined as-received and following exposure to moisture by scanning electron microscopy and CT scan for possible microvoids and for modes of failures after being tested in both compression as well as non-tested specimens. Diffusion parameters were calculated and the accelerated hygrothermal effect on the compressive strength, modulus, and porosity was investigated. Significant decrease in compressive modulus and a much less degree of degradation in strength was observed. Three modes of failure were noted: splitting, fiber microbuckling, and fiber kinking. Presence of microvoids on both as-received and exposed to moisture specimens was evident. Despite this degradation due to hygrothermal exposure, GFRP rebars were able to maintain their strength. This can be regarded as an edge in their performance compared to steel. However this advantage may not hold with prolonged exposure. It was also noted that the specimens exposed to moisture and temperature exhibited an increase in microvoids of approximately 33% and new distribution of microvoids sizes was recorded. The degradation of the mechanical properties of the GFRP rebars was attributed to the hygrothermal effect that was facilitated by the presence of microvoids which allow moisture to diffuse. Presence and growth of Microvoids due to exposure to moisture and temperature was deemed the primary reason causing the degradation of GFRP rebars. Presence of microvoids needs to be addressed in order to enhance the durability and performance of GFRP rebar.

  16. Mechanisms underlying reduced fertility in anovular dairy cows.

    Science.gov (United States)

    Santos, J E P; Bisinotto, R S; Ribeiro, E S

    2016-07-01

    Resumption of ovulation after parturition is a coordinated process that involves recoupling of the GH/insulin-like growth factor 1 axis in the liver, increase in follicular development and steroidogenesis, and removal of negative feedback from estradiol in the hypothalamus. Infectious diseases and metabolic disorders associated with extensive negative energy balance during early lactation disrupt this pathway and delay first ovulation postpartum. Extended periods of anovulation postpartum exert long-lasting effects on fertility in dairy cows including the lack of spontaneous estrus, reduced pregnancy per artificial insemination (P/AI), and increased risk of pregnancy loss. Concentrations of progesterone in anovular cows subjected to synchronized programs for AI are insufficient to optimize follicular maturation, oocyte competence, and subsequent fertility to AI. Ovulation of first wave follicles, which develop under low concentrations of progesterone, reduces embryo quality in the first week after fertilization and P/AI in dairy cows. Although the specific mechanisms by which anovulation and low concentrations of progesterone impair oocyte quality have not been defined, studies with persistent follicles support the involvement of premature resumption of meiosis and degradation of maternal RNA. Suboptimal concentrations of progesterone before ovulation also increase the synthesis of PGF2α in response to oxytocin during the subsequent estrous cycle, which explains the greater incidence of short luteal phases after the first AI postpartum in anovular cows compared with estrous cyclic herd mates. It is suggested that increased spontaneous luteolysis early in the estrous cycle is one of the mechanisms that contributes to early embryonic losses in anovular cows. Anovulation also leads to major shifts in gene expression in elongated conceptuses during preimplantation stages of pregnancy. Transcripts involved with control of energy metabolism and DNA repair were

  17. Knowledge Regarding Symptoms and Risk Factors and Screening of Breast Cancer in Women Under 30 Years and Their Practice Relative to Self-Examination

    Directory of Open Access Journals (Sweden)

    F. Jafari

    2013-08-01

    Full Text Available Background: Breast cancer is the most common malignancy among women worldwide. In Iran, breast cancer ranks first among cancers diagnosed in women. Nevertheless, many of women haven’t enough knowledge about breast cancer risk factors and symptoms. The main reason for this escalating mortality is lack of awareness and late diagnosis of disease. The aim of present study assessed the knowledge about risk factors and symptoms of breast cancer, also the screening method and practice (Breast self examination about it. Methods: This is a descriptive and cross-sectional study. In this study 340 red crescent volunteer women participated in a national congress were selected with convenience sampling method. The data collection instrument consisted of a three part questionnaire which included demographic factors, Knowledge level about risk factors, symptoms and screening methods of breast cancer and questions concerning practice about breast self examination (BSE.The study tool was a researcher-designed questionnaire which could evaluated a number of variables. After data collection, analysis was carried out with descriptive tests by SPSS.16 software. Results: The mean age of subjects was 23±2.1yrs. Knowledge about breast cancer risk factors was very poor, the most widely known risk factor and lowest among the participants was family history of breast cancer (30.6 % and early menarche (under 12 years (0.3% respectively. Only 47.9% respondents correctly recognized breast lump and 11.2% breast discharge as the most common symptoms of breast cancer.30% of subjects were aware of BSE. However, a lesser proportion (9.4% was done BSE regular monthly every few months. Conclusion: Regarding the low level of the women’s knowledge about breast cancer especially in young educated women, screening and interventional programs to improve awareness and practice is essential.

  18. Alteration mechanisms of UOX spent fuel under water

    International Nuclear Information System (INIS)

    Muzeau, B.

    2008-06-01

    The mechanisms of spent fuel alteration in aqueous media need to be understood on the assumption of a direct disposal of the assemblies in a geological formation or for long duration storage in pool. This work is a contribution to the study of the effects of the alpha and/or beta/gamma radiolysis of water on the oxidation and the dissolution of the UO 2 matrix of UOX spent fuel. The effects of the alpha radiolysis, predominant in geological disposal conditions, were quantified by using samples of UO 2 doped with plutonium. The leaching experiments highlighted two types of control for the matrix alteration according to the alpha activity. The first is based on the radiolytic oxidation of the surface and leads to a continuous release of uranium in solution whereas the second is based on a control by the solubility of uranium. An activity threshold, between 18 MBq.g -1 and 33 MBq.g -1 , was defined in a carbonated water. The value of this threshold is dependent on the experimental conditions and the presence or not of electro-active species such as hydrogen in the system. The effects of the alpha/beta/gamma radiolysis in relation with the storage conditions were also quantified. The experimental data obtained on spent fuel indicate that the alteration rate of the matrix based on the behaviour of tracer elements (caesium and strontium) reached a maximum value of some mg.m -2 .d -1 , even under very oxidizing conditions. The solubility of uranium and the nature of the secondary phases depend however on the extent of the oxidizing conditions. (author)

  19. Memories of paternal relations are associated with coping and defense mechanisms in breast cancer patients: an observational study

    Directory of Open Access Journals (Sweden)

    Chiara Renzi

    2017-11-01

    Full Text Available Abstract Background Breast cancer diagnosis and treatment represent stressful events that demand emotional adjustment, thus recruiting coping strategies and defense mechanisms. As parental relations were shown to influence emotion regulation patterns and adaptive processes in adulthood, the present study investigated whether they are specifically associated to coping and defense mechanisms in patients with breast cancer. Methods One hundred and ten women hospitalized for breast cancer surgery were administered questionnaires assessing coping with cancer, defense mechanisms, and memories of parental bonding in childhood. Results High levels of paternal overprotection were associated with less mature defenses, withdrawal and fantasy and less adaptive coping mechanisms, such as hopelessness/helplessness. Low levels of paternal care were associated with a greater use of repression. No association was found between maternal care, overprotection, coping and defense mechanisms. Immature defenses correlated positively with less adaptive coping styles, while mature defenses were positively associated to a fighting spirit and to fatalism, and inversely related to less adaptive coping styles. Conclusions These data suggest that paternal relations in childhood are associated with emotional, cognitive, and behavioral regulation in adjusting to cancer immediately after surgery. Early experiences of bonding may constitute a relevant index for adaptation to cancer, indicating which patients are at risk and should be considered for psychological interventions.

  20. Plant-insect interactions under bacterial influence: ecological implications and underlying mechanisms.

    Science.gov (United States)

    Sugio, Akiko; Dubreuil, Géraldine; Giron, David; Simon, Jean-Christophe

    2015-02-01

    Plants and insects have been co-existing for more than 400 million years, leading to intimate and complex relationships. Throughout their own evolutionary history, plants and insects have also established intricate and very diverse relationships with microbial associates. Studies in recent years have revealed plant- or insect-associated microbes to be instrumental in plant-insect interactions, with important implications for plant defences and plant utilization by insects. Microbial communities associated with plants are rich in diversity, and their structure greatly differs between below- and above-ground levels. Microbial communities associated with insect herbivores generally present a lower diversity and can reside in different body parts of their hosts including bacteriocytes, haemolymph, gut, and salivary glands. Acquisition of microbial communities by vertical or horizontal transmission and possible genetic exchanges through lateral transfer could strongly impact on the host insect or plant fitness by conferring adaptations to new habitats. Recent developments in sequencing technologies and molecular tools have dramatically enhanced opportunities to characterize the microbial diversity associated with plants and insects and have unveiled some of the mechanisms by which symbionts modulate plant-insect interactions. Here, we focus on the diversity and ecological consequences of bacterial communities associated with plants and herbivorous insects. We also highlight the known mechanisms by which these microbes interfere with plant-insect interactions. Revealing such mechanisms in model systems under controlled environments but also in more natural ecological settings will help us to understand the evolution of complex multitrophic interactions in which plants, herbivorous insects, and micro-organisms are inserted. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions

  1. A comprehensive sensitivity analysis of microarray breast cancer classification under feature variability

    NARCIS (Netherlands)

    Sontrop, H.M.J.; Moerland, P.D.; Van den Ham, R.; Reinders, M.J.T.; Verhaegh, W.F.J.

    2009-01-01

    Background: Large discrepancies in signature composition and outcome concordance have been observed between different microarray breast cancer expression profiling studies. This is often ascribed to differences in array platform as well as biological variability. We conjecture that other reasons for

  2. A comprehensive sensitivity analysis of microarray breast cancer classification under feature variability

    NARCIS (Netherlands)

    Sontrop, Herman M. J.; Moerland, Perry D.; van den Ham, René; Reinders, Marcel J. T.; Verhaegh, Wim F. J.

    2009-01-01

    Large discrepancies in signature composition and outcome concordance have been observed between different microarray breast cancer expression profiling studies. This is often ascribed to differences in array platform as well as biological variability. We conjecture that other reasons for the

  3. Long-term exposure to estrogen enhances chemotherapeutic efficacy potentially through epigenetic mechanism in human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Yu-Wei Chang

    Full Text Available Chemotherapy is the most common clinical option for treatment of breast cancer. However, the efficacy of chemotherapy depends on the age of breast cancer patients. Breast tissues are estrogen responsive and the levels of ovarian estrogen vary among the breast cancer patients primarily between pre- and post-menopausal age. Whether this age-dependent variation in estrogen levels influences the chemotherapeutic efficacy in breast cancer patients is not known. Therefore, the objective of this study was to evaluate the effects of natural estrogen 17 beta-estradiol (E2 on the efficacy of chemotherapeutic drugs in breast cancer cells. Estrogen responsive MCF-7 and T47D breast cancer cells were long-term exposed to 100 pg/ml estrogen, and using these cells the efficacy of chemotherapeutic drugs doxorubicin and cisplatin were determined. The result of cell viability and cell cycle analysis revealed increased sensitivities of doxorubicin and cisplatin in estrogen-exposed MCF-7 and T47D cells as compared to their respective control cells. Gene expression analysis of cell cycle, anti-apoptosis, DNA repair, and drug transporter genes further confirmed the increased efficacy of chemotherapeutic drugs in estrogen-exposed cells at molecular level. To further understand the role of epigenetic mechanism in enhanced chemotherapeutic efficacy by estrogen, cells were pre-treated with epigenetic drugs, 5-aza-2-deoxycytidine and Trichostatin A prior to doxorubicin and cisplatin treatments. The 5-aza-2 deoxycytidine pre-treatment significantly decreased the estrogen-induced efficacy of doxorubicin and cisplatin, suggesting the role of estrogen-induced hypermethylation in enhanced sensitivity of these drugs in estrogen-exposed cells. In summary, the results of this study revealed that sensitivity to chemotherapy depends on the levels of estrogen in breast cancer cells. Findings of this study will have clinical implications in selecting the chemotherapy strategies for

  4. Effectiveness of a Brief Health Education Intervention for Breast Cancer Prevention in Greece Under Economic Crisis

    Directory of Open Access Journals (Sweden)

    Kyriakoula Merakou

    2013-01-01

    Full Text Available Background: Prevalence rates in breast cancer have now reached epidemic levels. One of the main reasons behind onset of breast cancer is poor preventive beliefs and behavior of women towards cancer prevention. We examined the effectiveness of health education intervention in two communities of South Greece.Objective: The study investigates the effectiveness of a brief health education intervention on women’s beliefs and behaviour changes concerning breast cancer prevention.Methodology: A 90-minute, one-off encounter, health education study was designed for 300 women from Peloponissos, South Greece. A Health Belief Model questionnaire, was used before the intervention, immediately after and 6-months after the intervention.Results: Despite certain perception-related barriers (embarrassment, anxiety, ect women’s overall beliefs towards breast cancer prevention (perceived susceptibility, perceived benefits and perceived barriers changed positively after the health education intervention and this change was sustained at 6-month follow up. However, specific barriers (embarrassment, fear of pain, anxiety when anticipating tests’ results were not maintained at the same level of post-intervention during the same follow up. During the follow up period, women performed breast self-examination every month (73% and 55.10% had breast examination by a clinician and underwent a mammography.Conclusions: Short, low cost, health education interventions for breast cancer prevention to women can be effective in changing beliefs and behaviour. Tailored interventions are necessary to overcome relapsing of specific barriers. Emphasis should be given on the importance of doctor/nurse role in breast screening.

  5. Versican G3 domain modulates breast cancer cell apoptosis: a mechanism for breast cancer cell response to chemotherapy and EGFR therapy.

    Directory of Open Access Journals (Sweden)

    William Weidong Du

    Full Text Available Overexpression of EGFR and versican has been reported in association with breast cancers. Considered oncogenic, these molecules may be attractive therapeutic targets. Possessing anti-apoptotic and drug resistant properties, overexpression of these molecules is accompanied by selective sensitization to the process of apoptosis. In this study, we exogenously expressed a versican G3 construct in breast cancer cell lines and analyzed the effects of G3 on cell viability in fetal bovine serum free conditioned media and evaluated the effects of apoptotic agent C2-ceramide, and chemotherapeutic agents including Docetaxel, Doxorubicin, and Epirubicin. Versican G3 domain enhanced tumor cell resistance to apoptosis when cultured in serum free medium, Doxorubicin, or Epirubicin by up-regulating pERK and GSK-3β (S9P. However, it could be prevented by selective EGFR inhibitor AG 1478 and selective MEK inhibitor PD 98059. Both AG 1478 and PD 98059 enhanced expression of pSAPK/JNK, while selective JNK inhibitor SP 600125 enhanced expression of GSK-3β (S9P. Versican G3 promoted cell apoptosis induced by C2-ceramide or Docetaxel by enhancing expression of pSAPK/JNK and decreasing expression of GSK-3β (S9P, an observation blocked by AG 1478 or SP 6000125. Inhibition of endogenous versican expression by siRNA or reduction of versican G3's expression by linking G3 with 3'UTR prevented G3 modulated cell apoptosis. The dual roles of G3 in modulating breast cancer cell resistance to chemotherapeutic agents may in part explain a potential mechanism for breast cancer cell resistance to chemotherapy and EGFR therapy. The apoptotic effects of chemotherapeutics depend upon the activation and balance of down stream signals in the EGFR pathway. GSK-3β (S9P appears to function as a key checkpoint in this balance of apoptosis and anti-apoptosis. Investigation and potential consideration of targeting GSK-3β (S9P merits further study.

  6. Versican G3 domain modulates breast cancer cell apoptosis: a mechanism for breast cancer cell response to chemotherapy and EGFR therapy.

    Science.gov (United States)

    Du, William Weidong; Yang, Burton B; Yang, Bing L; Deng, Zhaoqun; Fang, Ling; Shan, Sze Wan; Jeyapalan, Zina; Zhang, Yaou; Seth, Arun; Yee, Albert J

    2011-01-01

    Overexpression of EGFR and versican has been reported in association with breast cancers. Considered oncogenic, these molecules may be attractive therapeutic targets. Possessing anti-apoptotic and drug resistant properties, overexpression of these molecules is accompanied by selective sensitization to the process of apoptosis. In this study, we exogenously expressed a versican G3 construct in breast cancer cell lines and analyzed the effects of G3 on cell viability in fetal bovine serum free conditioned media and evaluated the effects of apoptotic agent C2-ceramide, and chemotherapeutic agents including Docetaxel, Doxorubicin, and Epirubicin. Versican G3 domain enhanced tumor cell resistance to apoptosis when cultured in serum free medium, Doxorubicin, or Epirubicin by up-regulating pERK and GSK-3β (S9P). However, it could be prevented by selective EGFR inhibitor AG 1478 and selective MEK inhibitor PD 98059. Both AG 1478 and PD 98059 enhanced expression of pSAPK/JNK, while selective JNK inhibitor SP 600125 enhanced expression of GSK-3β (S9P). Versican G3 promoted cell apoptosis induced by C2-ceramide or Docetaxel by enhancing expression of pSAPK/JNK and decreasing expression of GSK-3β (S9P), an observation blocked by AG 1478 or SP 6000125. Inhibition of endogenous versican expression by siRNA or reduction of versican G3's expression by linking G3 with 3'UTR prevented G3 modulated cell apoptosis. The dual roles of G3 in modulating breast cancer cell resistance to chemotherapeutic agents may in part explain a potential mechanism for breast cancer cell resistance to chemotherapy and EGFR therapy. The apoptotic effects of chemotherapeutics depend upon the activation and balance of down stream signals in the EGFR pathway. GSK-3β (S9P) appears to function as a key checkpoint in this balance of apoptosis and anti-apoptosis. Investigation and potential consideration of targeting GSK-3β (S9P) merits further study.

  7. Effect of different probiotics on breast quality characteristics of broilers under Salmonella challenge

    Directory of Open Access Journals (Sweden)

    Abdullah N. Al-Owaimer

    2014-07-01

    Full Text Available The current study was performed to investigate the influence of probiotics or antibiotic on breast quality characteristics of broiler chickens that were subjected to Salmonella challenge. Two hundred, one-day-old Cobb 500 chicks were allocated in five experimental treatments for 42 d. Ten cages of birds received one of the following treatments: T1=positive control (+CONT, unsupplemented, unchallenged; T2=negative control (-CONT, unsupplemented, challenged; T3=supplemented with antibiotic neoxyval (NEOX, challenged; T4=supplemented with probiotic Toyocerin (TOYO, challenged; and T5=supplemented with probiotic CloSTATTM (CLOS, challenged. Birds in treatments T2 to T5 were challenged with 3×109 CFU/mL of Salmonella enterica subsp. typhimurium on day 16. Nine birds per treatment were sampled at the end of the trial for breast characteristics. Overall, pH and temperature values of the breast muscle were similar among all groups tested. Cooking loss results indicated that breasts from T3 birds had the highest degree of shrinkage upon cooking while those of the probiotic group had similar control values (P<0.0001. Probiotic supplementation reduced the extent of destruction of myofibrils caused by homogenisation (P<0.0001. Warner-Bratzler shear test and texture profile analysis showed that neither treatments nor Salmonella challenge had any negative impact on texture or sensory attributes of chicken breast. In conclusion, results show that breast characteristics were better when probiotics were supplemented in the diets.

  8. [Neural mechanism underlying autistic savant and acquired savant syndrome].

    Science.gov (United States)

    Takahata, Keisuke; Kato, Motoichiro

    2008-07-01

    , especially that of the prefrontal cortex and the posterior regions of the brain. (3) Autistic models, including those based on weak central coherence theory (Frith, 1989), that focus on how savant skills emerge from an autistic brain. Based on recent neuroimaging studies of ASD, Just et al. (2004) suggested the underconnectivity theory, which emphasizes the disruption of long-range connectivity and the relative intact or even more enhanced local connectivity in the autistic brain. All the models listed above have certain advantages and shortcomings. At the end of this review, we propose another integrative model of savant syndrome. In this model, we predict an altered balance of local/global connectivity patterns that contribute to an altered functional segregation/integration ratio. In particular, we emphasize the crucial role played by the disruption of global connectivity in a parallel distributed cortical network, which might result in impairment in integrated cognitive processing, such as impairment in executive function and social cognition. On the other hand, the reduced inter-regional collaboration could lead to a disinhibitory enhancement of neural activity and connectivity in local cortical regions. In addition, enhanced connectivity in the local brain regions is partly due to the abnormal organization of the cortical network as a result of developmental and pathological states. This enhanced local connectivity results in the specialization and facilitation of low-level cognitive processing. The disruption of connectivity between the prefrontal cortex and other regions is considered to be a particularly important factor because the prefrontal region shows the most influential inhibitory control on other cortical areas. We propose that these neural mechanisms as the underlying causes for the emergence of savant ability in ASD and FTD patients.

  9. Neural Mechanisms Underlying Cross-Modal Phonetic Encoding.

    Science.gov (United States)

    Shahin, Antoine J; Backer, Kristina C; Rosenblum, Lawrence D; Kerlin, Jess R

    2018-02-14

    Audiovisual (AV) integration is essential for speech comprehension, especially in adverse listening situations. Divergent, but not mutually exclusive, theories have been proposed to explain the neural mechanisms underlying AV integration. One theory advocates that this process occurs via interactions between the auditory and visual cortices, as opposed to fusion of AV percepts in a multisensory integrator. Building upon this idea, we proposed that AV integration in spoken language reflects visually induced weighting of phonetic representations at the auditory cortex. EEG was recorded while male and female human subjects watched and listened to videos of a speaker uttering consonant vowel (CV) syllables /ba/ and /fa/, presented in Auditory-only, AV congruent or incongruent contexts. Subjects reported whether they heard /ba/ or /fa/. We hypothesized that vision alters phonetic encoding by dynamically weighting which phonetic representation in the auditory cortex is strengthened or weakened. That is, when subjects are presented with visual /fa/ and acoustic /ba/ and hear /fa/ ( illusion-fa ), the visual input strengthens the weighting of the phone /f/ representation. When subjects are presented with visual /ba/ and acoustic /fa/ and hear /ba/ ( illusion-ba ), the visual input weakens the weighting of the phone /f/ representation. Indeed, we found an enlarged N1 auditory evoked potential when subjects perceived illusion-ba , and a reduced N1 when they perceived illusion-fa , mirroring the N1 behavior for /ba/ and /fa/ in Auditory-only settings. These effects were especially pronounced in individuals with more robust illusory perception. These findings provide evidence that visual speech modifies phonetic encoding at the auditory cortex. SIGNIFICANCE STATEMENT The current study presents evidence that audiovisual integration in spoken language occurs when one modality (vision) acts on representations of a second modality (audition). Using the McGurk illusion, we show

  10. Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response.

    Science.gov (United States)

    Shahin, Mohamed H; Johnson, Julie A

    2016-04-01

    Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response. Copyright © 2016. Published by Elsevier Ltd.

  11. Mechanical response of collagen molecule under hydrostatic compression

    International Nuclear Information System (INIS)

    Saini, Karanvir; Kumar, Navin

    2015-01-01

    Proteins like collagen are the basic building blocks of various body tissues (soft and hard). Collagen molecules find their presence in the skeletal system of the body where they bear mechanical loads from different directions, either individually or along with hydroxy-apatite crystals. Therefore, it is very important to understand the mechanical behavior of the collagen molecule which is subjected to multi-axial state of loading. The estimation of strains of collagen molecule along different directions resulting from the changes in hydrostatic pressure magnitude, can provide us new insights into its mechanical behavior. In the present work, full atomistic simulations have been used to study global (volumetric) as well as local (along different directions) mechanical properties of the hydrated collagen molecule which is subjected to different hydrostatic pressure magnitudes. To estimate the local mechanical properties, the strains of collagen molecule along its longitudinal and transverse directions have been acquired at different hydrostatic pressure magnitudes. In spite of non-homogeneous distribution of atoms within the collagen molecule, the calculated values of local mechanical properties have been found to carry the same order of magnitude along the longitudinal and transverse directions. It has been demonstrated that the values of global mechanical properties like compressibility, bulk modulus, etc. as well as local mechanical properties like linear compressibility, linear elastic modulus, etc. are functions of magnitudes of applied hydrostatic pressures. The mechanical characteristics of collagen molecule based on the atomistic model have also been compared with that of the continuum model in the present work. The comparison showed up orthotropic material behavior for the collagen molecule. The information on collagen molecule provided in the present study can be very helpful in designing the future bio-materials.

  12. Mechanical response of collagen molecule under hydrostatic compression.

    Science.gov (United States)

    Saini, Karanvir; Kumar, Navin

    2015-04-01

    Proteins like collagen are the basic building blocks of various body tissues (soft and hard). Collagen molecules find their presence in the skeletal system of the body where they bear mechanical loads from different directions, either individually or along with hydroxy-apatite crystals. Therefore, it is very important to understand the mechanical behavior of the collagen molecule which is subjected to multi-axial state of loading. The estimation of strains of collagen molecule along different directions resulting from the changes in hydrostatic pressure magnitude, can provide us new insights into its mechanical behavior. In the present work, full atomistic simulations have been used to study global (volumetric) as well as local (along different directions) mechanical properties of the hydrated collagen molecule which is subjected to different hydrostatic pressure magnitudes. To estimate the local mechanical properties, the strains of collagen molecule along its longitudinal and transverse directions have been acquired at different hydrostatic pressure magnitudes. In spite of non-homogeneous distribution of atoms within the collagen molecule, the calculated values of local mechanical properties have been found to carry the same order of magnitude along the longitudinal and transverse directions. It has been demonstrated that the values of global mechanical properties like compressibility, bulk modulus, etc. as well as local mechanical properties like linear compressibility, linear elastic modulus, etc. are functions of magnitudes of applied hydrostatic pressures. The mechanical characteristics of collagen molecule based on the atomistic model have also been compared with that of the continuum model in the present work. The comparison showed up orthotropic material behavior for the collagen molecule. The information on collagen molecule provided in the present study can be very helpful in designing the future bio-materials. Copyright © 2015 Elsevier B.V. All rights

  13. Mechanical response of collagen molecule under hydrostatic compression

    Energy Technology Data Exchange (ETDEWEB)

    Saini, Karanvir, E-mail: karans@iitrpr.ac.in; Kumar, Navin

    2015-04-01

    Proteins like collagen are the basic building blocks of various body tissues (soft and hard). Collagen molecules find their presence in the skeletal system of the body where they bear mechanical loads from different directions, either individually or along with hydroxy-apatite crystals. Therefore, it is very important to understand the mechanical behavior of the collagen molecule which is subjected to multi-axial state of loading. The estimation of strains of collagen molecule along different directions resulting from the changes in hydrostatic pressure magnitude, can provide us new insights into its mechanical behavior. In the present work, full atomistic simulations have been used to study global (volumetric) as well as local (along different directions) mechanical properties of the hydrated collagen molecule which is subjected to different hydrostatic pressure magnitudes. To estimate the local mechanical properties, the strains of collagen molecule along its longitudinal and transverse directions have been acquired at different hydrostatic pressure magnitudes. In spite of non-homogeneous distribution of atoms within the collagen molecule, the calculated values of local mechanical properties have been found to carry the same order of magnitude along the longitudinal and transverse directions. It has been demonstrated that the values of global mechanical properties like compressibility, bulk modulus, etc. as well as local mechanical properties like linear compressibility, linear elastic modulus, etc. are functions of magnitudes of applied hydrostatic pressures. The mechanical characteristics of collagen molecule based on the atomistic model have also been compared with that of the continuum model in the present work. The comparison showed up orthotropic material behavior for the collagen molecule. The information on collagen molecule provided in the present study can be very helpful in designing the future bio-materials.

  14. The use of ultrasonography and digital mammography in women under 40 years with symptomatic breast cancer: a 7-year Irish experience.

    Science.gov (United States)

    Redmond, C E; Healy, G M; Murphy, C F; O'Doherty, A; Foster, A

    2017-02-01

    Breast cancer in women under 40 years of age is rare and typically presents symptomatically. The optimal imaging modality for this patient group is controversial. Most women undergo ultrasonography with/without mammography. Young women typically have dense breasts, which can obscure the features of malignancy on film mammography, however, initial studies have suggested that digital mammography may have a more accurate diagnostic performance in younger women. Ultrasound generally performs well in this age group, although it is poor at detecting carcinoma in situ (DCIS). To evaluate the comparative diagnostic performance of ultrasonography and digital mammography in the initial diagnostic evaluation of women under 40 years of age with symptomatic breast cancer. Retrospective review of all women under the age of 40 years managed at our symptomatic breast cancer unit from January 2009 to December 2015. There were 120 patients that met the inclusion criteria for this study. The sensitivity of ultrasonography and digital mammography for breast cancer in this patient group was 95.8 and 87.5 %, respectively. The patients with a false negative mammographic examination were more likely to have dense breasts (p breast cancer in women under the age of 40 years, however, the results show that digital mammography has an important complimentary role in the comprehensive assessment of these patients, particularly in the diagnosis of DCIS.

  15. Poroelastic Mechanical Effects of Hemicelluloses on Cellulosic Hydrogels under Compression

    Science.gov (United States)

    Lopez-Sanchez, Patricia; Cersosimo, Julie; Wang, Dongjie; Flanagan, Bernadine; Stokes, Jason R.; Gidley, Michael J.

    2015-01-01

    Hemicelluloses exhibit a range of interactions with cellulose, the mechanical consequences of which in plant cell walls are incompletely understood. We report the mechanical properties of cell wall analogues based on cellulose hydrogels to elucidate the contribution of xyloglucan or arabinoxylan as examples of two hemicelluloses displaying different interactions with cellulose. We subjected the hydrogels to mechanical pressures to emulate the compressive stresses experienced by cell walls in planta. Our results revealed that the presence of either hemicellulose increased the resistance to compression at fast strain rates. However, at slow strain rates, only xyloglucan increased composite strength. This behaviour could be explained considering the microstructure and the flow of water through the composites confirming their poroelastic nature. In contrast, small deformation oscillatory rheology showed that only xyloglucan decreased the elastic moduli. These results provide evidence for contrasting roles of different hemicelluloses in plant cell wall mechanics and man-made cellulose-based composite materials. PMID:25794048

  16. An Analysis of the Dispute Settlement Mechanism under the

    African Journals Online (AJOL)

    user

    This article examines and evaluates the consumer redress mechanism, .... 23 The behaviour or conduct must be prohibited in terms of the Competition Act ...... appropriate orders and provide "sufficient" remedies to avoid the involvement of the.

  17. New Insights on Neurobiological Mechanisms underlying Alcohol Addiction

    Science.gov (United States)

    Cui, Changhai; Noronha, Antonio; Morikawa, Hitoshi; Alvarez, Veronica A.; Stuber, Garret D.; Szumlinski, Karen K.; Kash, Thomas L.; Roberto, Marisa; Wilcox, Mark V.

    2012-01-01

    Alcohol dependence/addiction is mediated by complex neural mechanisms that involve multiple brain circuits and neuroadaptive changes in a variety of neurotransmitter and neuropeptide systems. Although recent studies have provided substantial information on the neurobiological mechanisms that drive alcohol drinking behavior, significant challenges remain in understanding how alcohol-induced neuroadaptations occur and how different neurocircuits and pathways cross-talk. This review article highlights recent progress in understanding neural mechanisms of alcohol addiction from the perspectives of the development and maintenance of alcohol dependence. It provides insights on cross talks of different mechanisms and reviews the latest studies on metaplasticity, structural plasticity, interface of reward and stress pathways, and cross-talk of different neural signaling systems involved in binge-like drinking and alcohol dependence. PMID:23159531

  18. Fracture behavior and deformation mechanisms under fast neutron irradiation

    International Nuclear Information System (INIS)

    Boutard, J.L.; Dupouy, J.M.

    1980-09-01

    We have established the out-of-pile and in-pile deformation mechanism maps of a 316 stainless steel irradiated in a fast reactor. The knowledge of the dominating deformation mechanism either in post irradiation creep experiments or during the in-pile steady state operating conditions allows to rationalize the apparent discrepancy between the very low out-of-pile ductility and the rather high plastic diametral strains which are obtained in the fast reactor environment without fracture

  19. Features wear nodes mechanization wing aircraft operating under dynamic loads

    Directory of Open Access Journals (Sweden)

    А.М. Хімко

    2009-03-01

    Full Text Available  The conducted researches of titanic alloy ВТ-22 at dynamic loading with cycled sliding and dynamic loading in conditions of rolling with slipping. It is established that roller jamming in the carriage increases wear of rod of mechanization of a wing to twenty times. The optimum covering for strengthening wearied sites and restoration of working surfaces of wing’s mechanization rod is defined.

  20. Potentiation of radiosensitivity by tetrandrine in human breast cancer cells and its mechanism

    International Nuclear Information System (INIS)

    Sun Xinchen; Zhen Yongsu; Shao Rongguang; Wang Junjie

    2003-01-01

    Objective: To investigate the potentiation of radiosensitivity and mechanism by tetrandrine (Tet) in human breast cancer p53-mutant MCF-7/ADR and p53-wt MCF-7 cells. Methods: Clonogenic assay, flow cytometry, Western blotting were preformed in this experiment. Results: The data of clonogenic assay showed that Tet markedly sensitized MCF-7/ADR cell to X-rays, and the sensitization enhancement ratio (SER) of Tet was 1.51. Flow cytometry assay showed that exposure of MCF-7/ADR cells to X-rays caused cells to arrest in G 2 phase, whereas Tet was able to lower the number of cells arrested in G 2 phase. However, in MCF-7 cells, the potentiation effect of Tet was lower, and its SER was 1.10. MCF-7 cells were induced to arrest in G 1 and G 2 phases by X-rays, and the number of cells arrested in G 2 phase abrogated by Tet was less than that in MCF-7/ADR cells. Furthermore, the results showed that the levels of Cyclin B1 and Cdc2 expression decreased after X-irradiation, and the mitotic index was lower too. Tet could reverse this decrease and induce X-ray-irradiated cells to enter mitosis. Conclusion: Tet is a potent G 2 checkpoint abrogator and markedly enhances the cytotoxicity of X irradiation in the p53-mutant cancer cells

  1. Mechanisms of dihydrotestosterone action on resveratrol-induced anti-proliferation in breast cancer cells with different ERα status.

    Science.gov (United States)

    Chin, Yu-Tang; Yang, Sheng-Huei; Chang, Tung-Cheng; Changou, Chun A; Lai, Hsuan-Yu; Fu, Earl; HuangFu, Wei-Chun; Davis, Paul J; Lin, Hung-Yun; Liu, Leroy F

    2015-11-03

    Dihydrotestosterone (DHT) has been shown to promote breast cancer growth via different mechanisms. In addition to binding to ERα, the DHT membrane receptor exists on integrin αvβ3. Resveratrol induces p53-dependent apoptosis via plasma membrane integrin αvβ3. Resveratrol and DHT signals are both transduced by activated ERK1/2; however, DHT promotes cell proliferation in cancer cells, whereas resveratrol is pro-apoptotic. In this study, we examined the mechanism by which DHT inhibits resveratrol-induced apoptosis in human ERα positive (MCF-7) and negative (MDA-MB-231) breast cancer cells. DHT inhibited resveratrol-stimulated phosphorylation of Ser-15 of p53 in a concentration-dependent manner. These effects of DHT on resveratrol action were blocked by an ERα antagonist, ICI 182,780, in MCF-7 breast cancer cells. DHT inhibited resveratrol-induced nuclear complex of p53-COX-2 formation which is required p53-dependent apoptosis. ChIP studies of COX-2/p53 binding to DNA and expression of p53-responsive genes indicated that DHT inhibited resveratrol-induced p53-directed transcriptional activity. In addition, DHT did inhibit resveratrol-induced COX-2/p53-dependent gene expression. These results suggest that DHT inhibits p53-dependent apoptosis in breast cancer cells by interfering with nuclear COX-2 accumulation which is essential for stimulation of apoptotic pathways. Thus, the surface receptor sites for resveratrol and DHT are discrete and activate ERK1/2-dependent downstream effects on apoptosis that are distinctive. These studies provide new insights into the antagonizing effects of resveratrol versus DHT, an important step toward better understanding and eventually treating breast cancer. It also indicates the complex pathways by which apoptosis is induced by resveratrol in DHT-depleted and -repleted environments.

  2. Synthetic oligorotaxanes exert high forces when folding under mechanical load

    Science.gov (United States)

    Sluysmans, Damien; Hubert, Sandrine; Bruns, Carson J.; Zhu, Zhixue; Stoddart, J. Fraser; Duwez, Anne-Sophie

    2018-01-01

    Folding is a ubiquitous process that nature uses to control the conformations of its molecular machines, allowing them to perform chemical and mechanical tasks. Over the years, chemists have synthesized foldamers that adopt well-defined and stable folded architectures, mimicking the control expressed by natural systems1,2. Mechanically interlocked molecules, such as rotaxanes and catenanes, are prototypical molecular machines that enable the controlled movement and positioning of their component parts3-5. Recently, combining the exquisite complexity of these two classes of molecules, donor-acceptor oligorotaxane foldamers have been synthesized, in which interactions between the mechanically interlocked component parts dictate the single-molecule assembly into a folded secondary structure6-8. Here we report on the mechanochemical properties of these molecules. We use atomic force microscopy-based single-molecule force spectroscopy to mechanically unfold oligorotaxanes, made of oligomeric dumbbells incorporating 1,5-dioxynaphthalene units encircled by cyclobis(paraquat-p-phenylene) rings. Real-time capture of fluctuations between unfolded and folded states reveals that the molecules exert forces of up to 50 pN against a mechanical load of up to 150 pN, and displays transition times of less than 10 μs. While the folding is at least as fast as that observed in proteins, it is remarkably more robust, thanks to the mechanically interlocked structure. Our results show that synthetic oligorotaxanes have the potential to exceed the performance of natural folding proteins.

  3. The Benefits of Goal Adjustment Capacities for Well-Being Among Women With Breast Cancer: Potential Mechanisms of Action.

    Science.gov (United States)

    Mens, Maria G; Scheier, Michael F

    2016-12-01

    Breast cancer can seriously disrupt a person's important life goals. As such, the ability to adjust one's goals may be critical for well-being. The present study investigated the relationships between disengagement/reengagement capacity and well-being among women with breast cancer, as well as several potential mechanisms (intrusive thoughts, life purpose, and physical activity) that could explain these relationships. The sample consisted of 230 women with early-stage (n = 172) or late-stage (n = 58) breast cancer, who were followed prospectively for 8 months. Well-being measures consisted of global mental health, perceived physical health, positive/negative affect, and sleep efficiency. Disengagement capacity did not predict any outcome variable. In contrast, reengagement capacity prospectively predicted changes in global mental health, positive affect, negative affect, sleep efficiency, life purpose, and physical activity. Life purpose mediated the prospective relationship between reengagement capacity and multiple aspects of well-being. The relationships between purpose and positive/negative affect were reciprocal over time. Results also suggested that physical activity is not a mediator, but is in fact a result of the effect of reengagement capacity on well-being. The results demonstrate that reengagement capacity is important for well-being among women with breast cancer. © 2015 Wiley Periodicals, Inc.

  4. The Role of Ovarian Sex Steroids in Metabolic Homeostasis, Obesity, and Postmenopausal Breast Cancer: Molecular Mechanisms and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Viroj Boonyaratanakornkit

    2015-01-01

    Full Text Available Obese postmenopausal women have an increased risk of breast cancer and are likely to have a worse prognosis than nonobese postmenopausal women. The cessation of ovarian function after menopause results in withdrawal of ovarian sex steroid hormones, estrogen, and progesterone. Accumulating evidence suggests that the withdrawal of estrogen and progesterone causes homeostasis imbalances, including decreases in insulin sensitivity and leptin secretion and changes in glucose and lipid metabolism, resulting in a total reduction in energy expenditure. Together with a decrease in physical activity and consumption of a high fat diet, these factors significantly contribute to obesity in postmenopausal women. Obesity may contribute to breast cancer development through several mechanisms. Obesity causes localized inflammation, an increase in local estrogen production, and changes in cellular metabolism. In addition, obese women have a higher risk of insulin insensitivity, and an increase in insulin and other growth factor secretion. In this review, we describe our current understanding of the molecular actions of estrogen and progesterone and their contributions to cellular metabolism, obesity, inflammation, and postmenopausal breast cancer. We also discuss how modifications of estrogen and progesterone actions might be used as a therapeutic approach for obesity and postmenopausal breast cancer.

  5. n-3 Polyunsaturated Fatty Acids and Mechanisms to Mitigate Inflammatory Paracrine Signaling in Obesity-Associated Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jennifer M. Monk

    2014-10-01

    Full Text Available Globally, the prevalence of obesity is increasing which subsequently increases the risk of the development of obesity-related chronic diseases. Low-grade chronic inflammation and dysregulated adipose tissue inflammatory mediator/adipokine secretion are well-established in obesity, and these factors increase the risk of developing inflammation-associated cancer. Breast cancer is of particular interest given that increased inflammation within the subcutaneous mammary adipose tissue depot can alter the local tissue inflammatory microenvironment such that it resembles that of obese visceral adipose tissue. Therefore, in obese women with breast cancer, increased inflammatory mediators both locally and systemically can perpetuate inflammation-associated pro-carcinogenic signaling pathways, thereby increasing disease severity. Herein, we discuss some of these inflammation-associated pro-carcinogenic mechanisms of the combined obese breast cancer phenotype and offer evidence that dietary long chain n-3 polyunsaturated fatty acids (PUFA may have utility in mitigating the severity of obesity-associated inflammation and breast cancer.

  6. Mechanism and kinetics of mineral weathering under acid conditions

    NARCIS (Netherlands)

    Anbeek, C.

    1994-01-01

    This study deals with the relationships between crystal structure, grain diameter, surface morphology and dissolution kinetics for feldspar and quartz under acid conditions.

    Intensively ground samples from large, naturally weathered mineral fragments are frequently used in

  7. Advanced waterflooding in chalk reservoirs: Understanding of underlying mechanisms

    DEFF Research Database (Denmark)

    Zahid, Adeel; Sandersen, Sara Bülow; Stenby, Erling Halfdan

    2011-01-01

    Over the last decade, a number of studies have shown SO42−, Ca2+ and Mg2+ to be potential determining ions, which may be added to the injected brine for improving oil recovery during waterflooding in chalk reservoirs. However the understanding of the mechanism leading to an increase in oil recove...... of a microemulsion phase could be the possible reasons for the observed increase in oil recovery with sulfate ions at high temperature in chalk reservoirs besides the mechanism of the rock wettability alteration, which has been reported in most previous studies.......Over the last decade, a number of studies have shown SO42−, Ca2+ and Mg2+ to be potential determining ions, which may be added to the injected brine for improving oil recovery during waterflooding in chalk reservoirs. However the understanding of the mechanism leading to an increase in oil recovery...

  8. Performance of multifilamentary Nb3Sn under mechanical load

    International Nuclear Information System (INIS)

    Easton, D.S.; Schwall, R.E.

    1976-01-01

    The critical current of a commercial multifilamentary Nb 3 Sn conductor has been measured under the application of uniaxial tension at 4.2 K and following bending at room temperature. Significant reductions in J/subc/ are observed under uniaxial loading. Results are presented for a monolithic conductor manufactured by the bronze diffusion technique and for cable conductors formed by the tin-dip technique

  9. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast–ovarian cancer susceptibility locus

    Science.gov (United States)

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J.; Li, Qiyuan; Delgado, Melissa K.; Lee, Janet M.; Aittomäki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K.; Arver, Brita; Bandera, Elisa V.; Barile, Monica; Barkardottir, Rosa B.; Barrowdale, Daniel; Beckmann, Matthias W.; Benitez, Javier; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Blot, William; Bogdanova, Natalia; Bojesen, Anders; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Bruinsma, Fiona; Brunet, Joan; Buhari, Shaik Ahmad; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S.; Cai, Qiuyin; Caldes, Trinidad; Campbell, Ian; Canniotto, Rikki; Chang-Claude, Jenny; Chiquette, Jocelyne; Choi, Ji-Yeob; Claes, Kathleen B. M.; Collonge-Rame, Marie- Agnès; Damette, Alexandre; Barouk-Simonet, Emmanuelle; Bonnet, Françoise; Bubien, Virginie; Sevenet, Nicolas; Longy, Michel; Berthet, Pascaline; Vaur, Dominique; Castera, Laurent; Ferrer, Sandra Fert; Bignon, Yves-Jean; Uhrhammer, Nancy; Coron, Fanny; Faivre, Laurence; Baurand, Amandine; Jacquot, Caroline; Bertolone, Geoffrey; Lizard, Sarab; Leroux, Dominique; Dreyfus, Hélène; Rebischung, Christine; Peysselon, Magalie; Peyrat, Jean-Philippe; Fournier, Joëlle; Révillion, Françoise; Adenis, Claude; Vénat-Bouvet, Laurence; Léone, Mélanie; Boutry-Kryza, Nadia; Calender, Alain; Giraud, Sophie; Verny-Pierre, Carole; Lasset, Christine; Bonadona, Valérie; Barjhoux, Laure; Sobol, Hagay; Bourdon, Violaine; Noguchi, Tetsuro; Remenieras, Audrey; Coupier, Isabelle; Pujol, Pascal; Sokolowska, Johanna; Bronner, Myriam; Delnatte, Capucine; Bézieau, Stéphane; Mari, Véronique; Gauthier-Villars, Marion; Buecher, Bruno; Rouleau, Etienne; Golmard, Lisa; Moncoutier, Virginie; Belotti, Muriel; de Pauw, Antoine; Elan, Camille; Fourme, Emmanuelle; Birot, Anne-Marie; Saule, Claire; Laurent, Maïté; Houdayer, Claude; Lesueur, Fabienne; Mebirouk, Noura; Coulet, Florence; Colas, Chrystelle; Soubrier, Florent; Warcoin, Mathilde; Prieur, Fabienne; Lebrun, Marine; Kientz, Caroline; Muller, Danièle; Fricker, Jean-Pierre; Toulas, Christine; Guimbaud, Rosine; Gladieff, Laurence; Feillel, Viviane; Mortemousque, Isabelle; Bressac-de-Paillerets, Brigitte; Caron, Olivier; Guillaud-Bataille, Marine; Cook, Linda S.; Cox, Angela; Cramer, Daniel W.; Cross, Simon S.; Cybulski, Cezary; Czene, Kamila; Daly, Mary B.; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Diez, Orland; Doherty, Jennifer A.; Domchek, Susan M.; Dorfling, Cecilia M.; Dörk, Thilo; Dumont, Martine; Ehrencrona, Hans; Ejlertsen, Bent; Ellis, Steve; Gregory, Helen; Miedzybrodzka, Zosia; Morrison, Patrick J.; Donaldson, Alan; Rogers, Mark T.; Kennedy, M. John; Porteous, Mary E.; Brady, Angela; Barwell, Julian; Foo, Claire; Lalloo, Fiona; Side, Lucy E.; Eason, Jacqueline; Henderson, Alex; Walker, Lisa; Cook, Jackie; Snape, Katie; Murray, Alex; McCann, Emma; Engel, Christoph; Lee, Eunjung; Evans, D. Gareth; Fasching, Peter A.; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Foretova, Lenka; Fostira, Florentia; Foulkes, William D.; Fridley, Brooke L.; Friedman, Eitan; Frost, Debra; Gambino, Gaetana; Ganz, Patricia A.; Garber, Judy; García-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Ghoussaini, Maya; Giles, Graham G.; Glasspool, Rosalind; Godwin, Andrew K.; Goldberg, Mark S.; Goldgar, David E.; González-Neira, Anna; Goode, Ellen L.; Goodman, Marc T.; Greene, Mark H.; Gronwald, Jacek; Guénel, Pascal; Haiman, Christopher A.; Hall, Per; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V. O.; Harrington, Patricia A.; Hartman, Mikael; Hassan, Norhashimah; Healey, Sue; Rookus, M. A.; van Leeuwen, F. E.; van der Kolk, L. E.; Schmidt, M. K.; Russell, N. S.; de Lange, J. L.; Wijnands, R.; Collée, J. M.; Hooning, M. J.; Seynaeve, C.; van Deurzen, C. H. M.; Obdeijn, I. M.; van Asperen, C. J.; Tollenaar, R. A. E. M.; van Cronenburg, T. C. T. E. F.; Kets, C. M.; Ausems, M. G. E. M.; van der Pol, C. C.; van Os, T. A. M.; Waisfisz, Q.; Meijers-Heijboer, H. E. J.; Gómez-Garcia, E. B.; Oosterwijk, J. C.; Mourits, M. J.; de Bock, G. H.; Vasen, H. F.; Siesling, S.; Verloop, J.; Overbeek, L. I. H.; Heitz, Florian; Herzog, Josef; Høgdall, Estrid; Høgdall, Claus K.; Hogervorst, Frans B. L.; Hollestelle, Antoinette; Hopper, John L.; Hulick, Peter J.; Huzarski, Tomasz; Imyanitov, Evgeny N.; Fox, Stephen; Kirk, Judy; Lindeman, Geoff; Price, Melanie; Bowtell, David; deFazio, Anna; Webb, Penny; Isaacs, Claudine; Ito, Hidemi; Jakubowska, Anna; Janavicius, Ramunas; Jensen, Allan; John, Esther M.; Johnson, Nichola; Kabisch, Maria; Kang, Daehee; Kapuscinski, Miroslav; Karlan, Beth Y.; Khan, Sofia; Kiemeney, Lambertus A.; Kjaer, Susanne Kruger; Knight, Julia A.; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kupryjanczyk, Jolanta; Kwong, Ava; de la Hoya, Miguel; Laitman, Yael; Lambrechts, Diether; Le, Nhu; De Leeneer, Kim; Lester, Jenny; Levine, Douglas A.; Li, Jingmei; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Loud, Jennifer T.; Lu, Karen; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Le Marchand, Loic; Margolin, Sara; Marme, Frederik; Massuger, Leon F. A. G.; Matsuo, Keitaro; Mazoyer, Sylvie; McGuffog, Lesley; McLean, Catriona; McNeish, Iain; Meindl, Alfons; Menon, Usha; Mensenkamp, Arjen R.; Milne, Roger L.; Montagna, Marco; Moysich, Kirsten B.; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L.; Ness, Roberta B.; Neuhausen, Susan L.; Nevanlinna, Heli; Nord, Silje; Nussbaum, Robert L.; Odunsi, Kunle; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I.; Olson, Janet E.; Olswold, Curtis; O'Malley, David; Orlow, Irene; Orr, Nick; Osorio, Ana; Park, Sue Kyung; Pearce, Celeste L.; Pejovic, Tanja; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M.; Poole, Elizabeth M.; Pylkäs, Katri; Radice, Paolo; Rantala, Johanna; Rashid, Muhammad Usman; Rennert, Gad; Rhenius, Valerie; Rhiem, Kerstin; Risch, Harvey A.; Rodriguez, Gus; Rossing, Mary Anne; Rudolph, Anja; Salvesen, Helga B.; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schildkraut, Joellen M.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Sellers, Thomas A.; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Sieh, Weiva; Singer, Christian F.; Sinilnikova, Olga M.; Slager, Susan; Song, Honglin; Soucy, Penny; Southey, Melissa C.; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Sutter, Christian; Swerdlow, Anthony; Tchatchou, Sandrine; Teixeira, Manuel R.; Teo, Soo H.; Terry, Kathryn L.; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; Toland, Amanda Ewart; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Tseng, Chiu-chen; Tung, Nadine; Tworoger, Shelley S.; Vachon, Celine; van den Ouweland, Ans M. W.; van Doorn, Helena C.; van Rensburg, Elizabeth J.; Van't Veer, Laura J.; Vanderstichele, Adriaan; Vergote, Ignace; Vijai, Joseph; Wang, Qin; Wang-Gohrke, Shan; Weitzel, Jeffrey N.; Wentzensen, Nicolas; Whittemore, Alice S.; Wildiers, Hans; Winqvist, Robert; Wu, Anna H.; Yannoukakos, Drakoulis; Yoon, Sook-Yee; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Khanna, Kum Kum; Simard, Jacques; Monteiro, Alvaro N.; French, Juliet D.; Couch, Fergus J.; Freedman, Matthew L.; Easton, Douglas F.; Dunning, Alison M.; Pharoah, Paul D.; Edwards, Stacey L.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Gayther, Simon A.

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10−3) and ABHD8 (P<2 × 10−3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk. PMID:27601076

  10. A review of mechanisms underlying anticarcinogenicity by brassica vegetables

    NARCIS (Netherlands)

    Verhoeven, D.T.H.; Verhagen, H.; Goldbohm, R.A.; Brandt, P.A. van den; Poppel, G. van

    1997-01-01

    The mechanisms by which brassica vegetables might decrease the risk of cancer are reviewed in this paper. Brassicas, including all types of cabbages, broccoli, cauliflower and Brussels sprouts, may be protective against cancer due to their relatively high glucosinolate content. Glucosinolates are

  11. Mechanical behaviour of adhesive joint under tensile and shear loading

    NARCIS (Netherlands)

    Jiang, X.; Kolstein, M.H.; Bijlaard, F.S.K.

    2013-01-01

    Due to various advantages of Fibre-Reinforced Polymer (FRP) decks, the FRP to steel composite bridge system is being increasingly used in new bridge structures as well as rehabilitation projects for old bridges. This paper focuses on the mechanical behaviours and failure modes of the

  12. Wire bond degradation under thermo- and pure mechanical loading

    DEFF Research Database (Denmark)

    Pedersen, Kristian Bonderup; Nielsen, Dennis Achton; Czerny, Bernhard

    2017-01-01

    This paper presents a fundamental study on degradation of heavy Al bond wires typically used in high power modules. Customized samples are designed to only consist of Al bond wires on standard Si diodes. These samples are subjected to pure mechanical and passive thermal cycling to investigate...

  13. Transcriptome profiling reveals regulatory mechanisms underlying Corolla Senescence in Petunia

    Science.gov (United States)

    Genetic regulatory mechanisms that govern petal natural senescence in petunia is complicated and unclear. To identify key genes and pathways that regulate the process, we initiated a transcriptome analysis in petunia petals at four developmental time points, including petal opening without anthesis ...

  14. Survival under stress: molecular mechanisms of metabolic rate ...

    African Journals Online (AJOL)

    Studies in my laboratory are analysing the molecular mechanisms and regulatory events that underlie transitions to and from hypometabolic states In systems including anoxia-tolerant turtles and molluscs, estivating snails and toads, hibernating small mammals, and freeze tolerant frogs and insects. Our newest research ...

  15. Underlying mechanisms of transient luminous events: a review

    Directory of Open Access Journals (Sweden)

    V. V. Surkov

    2012-08-01

    Full Text Available Transient luminous events (TLEs occasionally observed above a strong thunderstorm system have been the subject of a great deal of research during recent years. The main goal of this review is to introduce readers to recent theories of electrodynamics processes associated with TLEs. We examine the simplest versions of these theories in order to make their physics as transparent as possible. The study is begun with the conventional mechanism for air breakdown at stratospheric and mesospheric altitudes. An electron impact ionization and dissociative attachment to neutrals are discussed. A streamer size and mobility of electrons as a function of altitude in the atmosphere are estimated on the basis of similarity law. An alternative mechanism of air breakdown, runaway electron mechanism, is discussed. In this section we focus on a runaway breakdown field, characteristic length to increase avalanche of runaway electrons and on the role played by fast seed electrons in generation of the runaway breakdown. An effect of thunderclouds charge distribution on initiation of blue jets and gigantic jets is examined. A model in which the blue jet is treated as upward-propagating positive leader with a streamer zone/corona on the top is discussed. Sprite models based on streamer-like mechanism of air breakdown in the presence of atmospheric conductivity are reviewed. To analyze conditions for sprite generation, thunderstorm electric field arising just after positive cloud-to-ground stroke is compared with the thresholds for propagation of positively/negatively charged streamers and with runway breakdown. Our own estimate of tendril's length at the bottom of sprite is obtained to demonstrate that the runaway breakdown can trigger the streamer formation. In conclusion we discuss physical mechanisms of VLF (very low frequency and ELF (extremely low frequency phenomena associated with sprites.

  16. Breast hamartoma: A report of 14 cases of an under-recognized and under-reported entity

    Directory of Open Access Journals (Sweden)

    R.A. Amir

    2016-01-01

    Results: A total of 14 cases with diagnosis of breast hamartoma were identified in our institute. Histologically the lesion is mostly sharply demarcated showing a mixture of varying proportions of fibrous, adipose, and glandular tissue. 13 cases were seen in females (93% and only one rare occurrence in a male patient (7%. The age ranges quite vastly from 18 to 51 years (mean 33 years. Two-third of these lesions were seen involving the right breast (9 cases/64.3% and only one-third in the left side (5 cases/35.7%. 13 out of 14 patients had a well circumscribed lesion (92.9% while only 1 case showed irregular borders (7.1%. The size varied from 1.4 to 9.5 cm. Three cases (21.4% showed evidence of myoid differentiation, a histopathologic variance which is important to identify however has no clinical significance. 3 cases had associated epithelial ductal hyperplasia of the usual type varying from mild (2 cases to moderate (1 case; with two of these cases exhibiting additional features of fibrocystic mastopathy including adenosis, apocrine metaplasia, and cyst formation. None of our cases showed any malignancy or pseudoangiomatous stroma hyperplasia (PASH.

  17. Mechanisms of Bone Metastasis from Breast Cancer Using a Clinically Relevant Model

    National Research Council Canada - National Science Library

    Anderson, Robin

    2001-01-01

    .... We have developed a murine model of breast cancer that actively mimics the human disease. After implantation of tumor cells into the mammary gland, a primary tumour develops and subsequently metastasises to the lymph nodes, lung and bone...

  18. Studies on Molecular Mechanisms Underlying Spinocerebellar Ataxia Type 3

    DEFF Research Database (Denmark)

    Kristensen, Line Vildbrad

    . Even though a range of mechanisms contributing to polyQ diseases have been uncovered, there is still no treatment available. One of the more common polyQ diseases is SCA3, which is caused by a polyQ expansion in the ataxin-3 protein that normally functions as a deubiquitinating enzyme involved...... in protein quality control. In SCA3 patients polyQ expanded ataxin-3 forms intranuclear inclusions in various brain areas, but why the polyQ expansion of ataxin-3 leads to neuronal dysfunction is still not well understood. This thesis describes molecular biological investigations of ataxin-3 biology, aimed...... at furthering our understanding of SCA3 disease mechanisms. In manuscript I, we investigated if post-translational modifications of ataxin-3 were changed by the polyQ expansion. The ubiquitin chain topology and ubiquitination pattern of ataxin-3 were unaltered by the polyQ expansion. In contrast...

  19. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwen Xiao

    2014-01-01

    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

  20. Peer influence: neural mechanisms underlying in-group conformity.

    Science.gov (United States)

    Stallen, Mirre; Smidts, Ale; Sanfey, Alan G

    2013-01-01

    People often conform to the behavior of others with whom they identify. However, it is unclear what fundamental mechanisms underlie this type of conformity. Here, we investigate the processes mediating in-group conformity by using functional magnetic resonance imaging (fMRI). Participants completed a perceptual decision-making task while undergoing fMRI, during which they were exposed to the judgments of both in-group and out-group members. Our data suggest that conformity to the in-group is mediated by both positive affect as well as the cognitive capacity of perspective taking. Examining the processes that drive in-group conformity by utilizing a basic decision-making paradigm combined with neuroimaging methods provides important insights into the potential mechanisms of conformity. These results may provide an integral step in developing more effective campaigns using group conformity as a tool for behavioral change.

  1. Pore closure in zeolitic imidazolate frameworks under mechanical pressure.

    Science.gov (United States)

    Henke, Sebastian; Wharmby, Michael T; Kieslich, Gregor; Hante, Inke; Schneemann, Andreas; Wu, Yue; Daisenberger, Dominik; Cheetham, Anthony K

    2018-02-14

    We investigate the pressure-dependent mechanical behaviour of the zeolitic imidazolate framework ZIF-4 (M(im) 2 ; M 2+ = Co 2+ or Zn 2+ , im - = imidazolate) with high pressure, synchrotron powder X-ray diffraction and mercury intrusion measurements. A displacive phase transition from a highly compressible open pore ( op ) phase with continuous porosity (space group Pbca , bulk modulus ∼1.4 GPa) to a closed pore ( cp ) phase with inaccessible porosity (space group P 2 1 / c , bulk modulus ∼3.3-4.9 GPa) is triggered by the application of mechanical pressure. Over the course of the transitions, both ZIF-4 materials contract by about 20% in volume. However, the threshold pressure, the reversibility and the immediate repeatability of the phase transition depend on the metal cation. ZIF-4(Zn) undergoes the op-cp phase transition at a hydrostatic mechanical pressure of only 28 MPa, while ZIF-4(Co) requires about 50 MPa to initiate the transition. Interestingly, ZIF-4(Co) fully returns to the op phase after decompression, whereas ZIF-4(Zn) remains in the cp phase after pressure release and requires subsequent heating to switch back to the op phase. These variations in high pressure behaviour can be rationalised on the basis of the different electron configurations of the respective M 2+ ions (3d 10 for Zn 2+ and 3d 7 for Co 2+ ). Our results present the first examples of op-cp phase transitions ( i.e. breathing transitions) of ZIFs driven by mechanical pressure and suggest potential applications of these functional materials as shock absorbers, nanodampers, or in mechanocalorics.

  2. Underlying mechanisms of transient luminous events: a review

    OpenAIRE

    V. V. Surkov; M. Hayakawa

    2012-01-01

    Transient luminous events (TLEs) occasionally observed above a strong thunderstorm system have been the subject of a great deal of research during recent years. The main goal of this review is to introduce readers to recent theories of electrodynamics processes associated with TLEs. We examine the simplest versions of these theories in order to make their physics as transparent as possible. The study is begun with the conventional mechanism for air breakdown at stratospheric...

  3. Mechanical Characterization of Femoral Cartilage Under Unicompartimental Osteoarthritis

    OpenAIRE

    Vidal-Lesso, A.; Ledesma-Orozco, E.; Daza-Benítez, L.; Lesso-Arroyo, R.

    2014-01-01

    The aim of this study was to determine the mechanical properties and thickness of articular cartilage in the unaffected femoral regions in cases of unicompartimental osteoarthritis on the knees. The specimens were tested using a 3mm plane-ended cylindrical indenter and a displacement of 0.5mm was applied at specific points in seven femoral knee cartilages with unicompartimental osteoarthritis. The thickness, stiffness, elastic modulus, shear modulus and bulk modulus were obtained. These prope...

  4. Chronic and Recurrent Subareolar Abscess of the Breast from Underlying Causes

    International Nuclear Information System (INIS)

    An, Jin Kyung; Kang, Jae Hee; Kim, Eun Kyung; Hong, Young Ok

    2012-01-01

    A subareolar abscess is the most common non-puerperal abscess of the breast. The main cause of a subareolar abscess is squamous metaplasia, which obstructs the lactiferous ducts and leads to the stasis of secretions and rupture of the ducts. However, there are other causes of subareolar abscess formation

  5. Chronic and Recurrent Subareolar Abscess of the Breast from Underlying Causes

    Energy Technology Data Exchange (ETDEWEB)

    An, Jin Kyung; Kang, Jae Hee; Kim, Eun Kyung; Hong, Young Ok [Eulji University, Eulji Hospital, Daejeon (Korea, Republic of)

    2012-03-15

    A subareolar abscess is the most common non-puerperal abscess of the breast. The main cause of a subareolar abscess is squamous metaplasia, which obstructs the lactiferous ducts and leads to the stasis of secretions and rupture of the ducts. However, there are other causes of subareolar abscess formation

  6. Short-term displacement and reproducibility of the breast and nodal targets under active breathing control

    NARCIS (Netherlands)

    Moran, Jean M.; Balter, James M.; Ben-David, Merav A.; Marsh, Robin B.; van Herk, Marcel; Pierce, Lori J.

    2007-01-01

    PURPOSE: The short-term displacement and reproducibility of the breast or chest wall, and the internal mammary (IM), infraclavicular (ICV), and supraclavicular (SCV) nodal regions have been assessed as a function of breath-hold state using an active breathing control (ABC) device for patients

  7. Passive and active response of bacteria under mechanical compression

    Science.gov (United States)

    Garces, Renata; Miller, Samantha; Schmidt, Christoph F.; Byophysics Team; Institute of Medical Sciences Collaboration

    Bacteria display simple but fascinating cellular structures and geometries. Their shapes are the result of the interplay between osmotic pressure and cell wall construction. Typically, bacteria maintain a high difference of osmotic pressure (on the order of 1 atm) to the environment. This pressure difference (turgor pressure) is supported by the cell envelope, a composite of lipid membranes and a rigid cell wall. The response of the cell envelope to mechanical perturbations such as geometrical confinements is important for the cells survival. Another key property of bacteria is the ability to regulate turgor pressure after abrupt changes of external osmotic conditions. This response relies on the activity of mechanosensitive (MS) channels: membrane proteins that release solutes in response to excessive stress in the cell envelope. We here present experimental data on the mechanical response of the cell envelope and on turgor regulation of bacteria subjected to compressive forces. We indent living cells with micron-sized beads attached to the cantilever of an atomic force microscope (AFM). This approach ensures global deformation of the cell. We show that such mechanical loading is sufficient to gate mechanosensitive channels in isosmotic conditions.

  8. The Survival Advantage: Underlying Mechanisms and Extant Limitations

    Directory of Open Access Journals (Sweden)

    Stephanie A. Kazanas

    2015-04-01

    Full Text Available Recently, researchers have begun to investigate the function of memory in our evolutionary history. According to Nairne and colleagues (e.g., Nairne, Pandeirada, and Thompson, 2008; Nairne, Thompson, and Pandeirada, 2007, the best mnemonic strategy for learning lists of unrelated words may be one that addresses the same problems that our Pleistocene ancestors faced: fitness-relevant problems including securing food and water, as well as protecting themselves from predators. Survival processing has been shown to promote better recall and recognition memory than many well-known mnemonic strategies (e.g., pleasantness ratings, imagery, generation, etc.. However, the survival advantage does not extend to all types of stimuli and tasks. The current review presents research that has replicated Nairne et al.'s (2007 original findings, in addition to the research designs that fail to replicate the survival advantage. In other words, there are specific manipulations in which survival processing does not appear to benefit memory any more than other strategies. Potential mechanisms for the survival advantage are described, with an emphasis on those that are the most plausible. These proximate mechanisms outline the memory processes that may contribute to the advantage, although the ultimate mechanism may be the congruity between the survival scenario and Pleistocene problem-solving.

  9. Expected utility violations evolve under status-based selection mechanisms.

    Science.gov (United States)

    Dickson, Eric S

    2008-10-07

    The expected utility theory of decision making under uncertainty, a cornerstone of modern economics, assumes that humans linearly weight "utilities" for different possible outcomes by the probabilities with which these outcomes occur. Despite the theory's intuitive appeal, both from normative and from evolutionary perspectives, many experiments demonstrate systematic, though poorly understood, patterns of deviation from EU predictions. This paper offers a novel theoretical account of such patterns of deviation by demonstrating that EU violations can emerge from evolutionary selection when individual "status" affects inclusive fitness. In humans, battles for resources and social standing involve high-stakes decision making, and assortative mating ensures that status matters for fitness outcomes. The paper therefore proposes grounding the study of decision making under uncertainty in an evolutionary game-theoretic framework.

  10. Phosphorene under strain:electronic, mechanical and piezoelectric responses

    Science.gov (United States)

    Drissi, L. B.; Sadki, S.; Sadki, K.

    2018-01-01

    Structural, electronic, elastic and piezoelectric properties of pure phosphorene under in-plane strain are investigated using first-principles calculations based on density functional theory. The two critical yielding points are determined along armchair and zigzag directions. It is shown that the buckling, the band gap and the charge transfer can be controlled under strains. A semiconductor to metallic transition is observed in metastable region. Polar plots of Young's modulus, Poisson ratio, sound velocities and Debye temperature exhibit evident anisotropic feature of phosphorene and indicate auxetic behavior for some angles θ. Our calculations show also that phosphorene has both in-plane and out-of-plane piezoelectric responses comparable to known 2D materials. The findings of this work reveal the great potential of pure phosphorene in nanomechanical applications.

  11. Corrosion mechanisms of spent fuel under oxidizing conditions

    International Nuclear Information System (INIS)

    Finn, P.A.; Finch, R.; Buck, E.; Bates, J.

    1997-01-01

    The release of 99 Tc can be used as a reliable marker for the extent of spent oxide fuel reaction under unsaturated high-drip-rate conditions at 90 degrees C. Evidence from leachate data and from scanning and transmission electron microscopy (SEM and TEM) examination of reacted fuel samples is presented for radionuclide release, potential reaction pathways, and the formation of alteration products. In the ATM-103 fuel, 0.03 of the total inventory of 99 Tc is released in 3.7 years under unsaturated and oxidizing conditions. Two reaction pathways that have been identified from SEM are (1) through-grain dissolution with subsequent formation of uranyl alteration products, and (2) grain-boundary dissolution. The major alteration product identified by x-ray diffraction (XRD) and SEM, is Na-boltwoodite, Na[(UO 2 )(SiO 3 OH)]lg-bullet H 2 O, which is formed from sodium and silicon in the water leachant

  12. Performance of multifilamentary Nb3Sn under mechanical load

    International Nuclear Information System (INIS)

    Easton, D.S.; Schwall, R.E.

    1976-11-01

    The critical current density of commercial multifilamentary Nb 3 Sn conductor has been measured during the application of uniaxial tension at 4.2 0 K and after bending at room temperature. Significant reductions in the critical current density J/sub c/ occurred under uniaxial loading. Results are presented for a monolithic conductor manufactured by the bronze diffusion technique and for cable conductors formed by the tin-dip technique

  13. Electronic, mechanical and dielectric properties of silicane under tensile strain

    International Nuclear Information System (INIS)

    Jamdagni, Pooja; Sharma, Munish; Ahluwalia, P. K.; Kumar, Ashok; Thakur, Anil

    2015-01-01

    The electronic, mechanical and dielectric properties of fully hydrogenated silicene i.e. silicane in stable configuration are studied by means of density functional theory based calculations. The band gap of silicane monolayer can be flexibly reduced to zero when subjected to bi-axial tensile strain, leading to semi-conducting to metallic transition, whereas the static dielectric constant for in-plane polarization increases monotonically with increasing strain. Also the EEL function show the red shift in resonance peak with tensile strain. Our results offer useful insight for the application of silicane monolayer in nano-optical and electronics devices

  14. Self-DNA inhibitory effects: Underlying mechanisms and ecological implications.

    Science.gov (United States)

    Cartenì, Fabrizio; Bonanomi, Giuliano; Giannino, Francesco; Incerti, Guido; Vincenot, Christian Ernest; Chiusano, Maria Luisa; Mazzoleni, Stefano

    2016-01-01

    DNA is usually known as the molecule that carries the instructions necessary for cell functioning and genetic inheritance. A recent discovery reported a new functional role for extracellular DNA. After fragmentation, either by natural or artificial decomposition, small DNA molecules (between ∼50 and ∼2000 bp) exert a species specific inhibitory effect on individuals of the same species. Evidence shows that such effect occurs for a wide range of organisms, suggesting a general biological process. In this paper we explore the possible molecular mechanisms behind those findings and discuss the ecological implications, specifically those related to plant species coexistence.

  15. Ethanol Neurotoxicity in the Developing Cerebellum: Underlying Mechanisms and Implications

    Directory of Open Access Journals (Sweden)

    Ambrish Kumar

    2013-06-01

    Full Text Available Ethanol is the main constituent of alcoholic beverages that exerts toxicity to neuronal development. Ethanol affects synaptogenesis and prevents proper brain development. In humans, synaptogenesis takes place during the third trimester of pregnancy, and in rodents this period corresponds to the initial few weeks of postnatal development. In this period neuronal maturation and differentiation begin and neuronal cells start migrating to their ultimate destinations. Although the neuronal development of all areas of the brain is affected, the cerebellum and cerebellar neurons are more susceptible to the damaging effects of ethanol. Ethanol’s harmful effects include neuronal cell death, impaired differentiation, reduction of neuronal numbers, and weakening of neuronal plasticity. Neuronal development requires many hormones and growth factors such as retinoic acid, nerve growth factors, and cytokines. These factors regulate development and differentiation of neurons by acting through various receptors and their signaling pathways. Ethanol exposure during development impairs neuronal signaling mechanisms mediated by the N-methyl-d-aspartate (NMDA receptors, the retinoic acid receptors, and by growth factors such as brain-derived neurotrophic factor (BDNF, insulin-like growth factor 1 (IGF-I, and basic fibroblast growth factor (bFGF. In combination, these ethanol effects disrupt cellular homeostasis, reduce the survival and migration of neurons, and lead to various developmental defects in the brain. Here we review the signaling mechanisms that are required for proper neuronal development, and how these processes are impaired by ethanol resulting in harmful consequences to brain development.

  16. Parametric study of control mechanism of cortical bone remodeling under mechanical stimulus

    Science.gov (United States)

    Wang, Yanan; Qin, Qing-Hua

    2010-03-01

    The control mechanism of mechanical bone remodeling at cellular level was investigated by means of an extensive parametric study on a theoretical model described in this paper. From a perspective of control mechanism, it was found that there are several control mechanisms working simultaneously in bone remodeling which is a complex process. Typically, an extensive parametric study was carried out for investigating model parameter space related to cell differentiation and apoptosis which can describe the fundamental cell lineage behaviors. After analyzing all the combinations of 728 permutations in six model parameters, we have identified a small number of parameter combinations that can lead to physiologically realistic responses which are similar to theoretically idealized physiological responses. The results presented in the work enhanced our understanding on mechanical bone remodeling and the identified control mechanisms can help researchers to develop combined pharmacological-mechanical therapies to treat bone loss diseases such as osteoporosis.

  17. Mechanical Alterations Associated with Repeated Treadmill Sprinting under Heat Stress.

    Directory of Open Access Journals (Sweden)

    Olivier Girard

    Full Text Available Examine the mechanical alterations associated with repeated treadmill sprinting performed in HOT (38°C and CON (25°C conditions.Eleven recreationally active males performed a 30-min warm-up followed by three sets of five 5-s sprints with 25-s recovery and 3-min between sets in each environment. Constant-velocity running for 1-min at 10 and 20 km.h-1 was also performed prior to and following sprinting.Mean skin (37.2±0.7 vs. 32.7±0.8°C; P<0.001 and core (38.9±0.2 vs. 38.8±0.3°C; P<0.05 temperatures, together with thermal comfort (P<0.001 were higher following repeated sprinting in HOT vs. CON. Step frequency and vertical stiffness were lower (-2.6±1.6% and -5.5±5.5%; both P<0.001 and contact time (+3.2±2.4%; P<0.01 higher in HOT for the mean of sets 1-3 compared to CON. Running distance per sprint decreased from set 1 to 3 (-7.0±6.4%; P<0.001, with a tendency for shorter distance covered in HOT vs. CON (-2.7±3.4%; P = 0.06. Mean vertical (-2.6±5.5%; P<0.01, horizontal (-9.1±4.4%; P<0.001 and resultant ground reaction forces (-3.0±2.8%; P<0.01 along with vertical stiffness (-12.9±2.3%; P<0.001 and leg stiffness (-8.4±2.7%; P<0.01 decreased from set 1 to 3, independently of conditions. Propulsive power decreased from set 1 to 3 (-16.9±2.4%; P<0.001, with lower propulsive power values in set 2 (-6.6%; P<0.05 in HOT vs. CON. No changes in constant-velocity running patterns occurred between conditions, or from pre-to-post repeated-sprint exercise.Thermal strain alters step frequency and vertical stiffness during repeated sprinting; however without exacerbating mechanical alterations. The absence of changes in constant-velocity running patterns suggests a strong link between fatigue-induced velocity decrements during sprinting and mechanical alterations.

  18. Mechanical Alterations Associated with Repeated Treadmill Sprinting under Heat Stress

    Science.gov (United States)

    Brocherie, Franck; Morin, Jean-Benoit; Racinais, Sébastien; Millet, Grégoire P.; Périard, Julien D.

    2017-01-01

    Purpose Examine the mechanical alterations associated with repeated treadmill sprinting performed in HOT (38°C) and CON (25°C) conditions. Methods Eleven recreationally active males performed a 30-min warm-up followed by three sets of five 5-s sprints with 25-s recovery and 3-min between sets in each environment. Constant-velocity running for 1-min at 10 and 20 km.h-1 was also performed prior to and following sprinting. Results Mean skin (37.2±0.7 vs. 32.7±0.8°C; P<0.001) and core (38.9±0.2 vs. 38.8±0.3°C; P<0.05) temperatures, together with thermal comfort (P<0.001) were higher following repeated sprinting in HOT vs. CON. Step frequency and vertical stiffness were lower (-2.6±1.6% and -5.5±5.5%; both P<0.001) and contact time (+3.2±2.4%; P<0.01) higher in HOT for the mean of sets 1–3 compared to CON. Running distance per sprint decreased from set 1 to 3 (-7.0±6.4%; P<0.001), with a tendency for shorter distance covered in HOT vs. CON (-2.7±3.4%; P = 0.06). Mean vertical (-2.6±5.5%; P<0.01), horizontal (-9.1±4.4%; P<0.001) and resultant ground reaction forces (-3.0±2.8%; P<0.01) along with vertical stiffness (-12.9±2.3%; P<0.001) and leg stiffness (-8.4±2.7%; P<0.01) decreased from set 1 to 3, independently of conditions. Propulsive power decreased from set 1 to 3 (-16.9±2.4%; P<0.001), with lower propulsive power values in set 2 (-6.6%; P<0.05) in HOT vs. CON. No changes in constant-velocity running patterns occurred between conditions, or from pre-to-post repeated-sprint exercise. Conclusions Thermal strain alters step frequency and vertical stiffness during repeated sprinting; however without exacerbating mechanical alterations. The absence of changes in constant-velocity running patterns suggests a strong link between fatigue-induced velocity decrements during sprinting and mechanical alterations. PMID:28146582

  19. Functional methods underlying classical mechanics, relativity and quantum theory

    International Nuclear Information System (INIS)

    Kryukov, A

    2013-01-01

    The paper investigates the physical content of a recently proposed mathematical framework that unifies the standard formalisms of classical mechanics, relativity and quantum theory. In the framework states of a classical particle are identified with Dirac delta functions. The classical space is ''made'' of these functions and becomes a submanifold in a Hilbert space of states of the particle. The resulting embedding of the classical space into the space of states is highly non-trivial and accounts for numerous deep relations between classical and quantum physics and relativity. One of the most striking results is the proof that the normal probability distribution of position of a macroscopic particle (equivalently, position of the corresponding delta state within the classical space submanifold) yields the Born rule for transitions between arbitrary quantum states.

  20. Mechanisms underlying rapid aldosterone effects in the kidney.

    LENUS (Irish Health Repository)

    Thomas, Warren

    2012-02-01

    The steroid hormone aldosterone is a key regulator of electrolyte transport in the kidney and contributes to both homeostatic whole-body electrolyte balance and the development of renal and cardiovascular pathologies. Aldosterone exerts its action principally through the mineralocorticoid receptor (MR), which acts as a ligand-dependent transcription factor in target tissues. Aldosterone also stimulates the activation of protein kinases and secondary messenger signaling cascades that act independently on specific molecular targets in the cell membrane and also modulate the transcriptional action of aldosterone through MR. This review describes current knowledge regarding the mechanisms and targets of rapid aldosterone action in the nephron and how aldosterone integrates these responses into the regulation of renal physiology.

  1. Mechanisms underlying rapid aldosterone effects in the kidney.

    LENUS (Irish Health Repository)

    Thomas, Warren

    2011-03-17

    The steroid hormone aldosterone is a key regulator of electrolyte transport in the kidney and contributes to both homeostatic whole-body electrolyte balance and the development of renal and cardiovascular pathologies. Aldosterone exerts its action principally through the mineralocorticoid receptor (MR), which acts as a ligand-dependent transcription factor in target tissues. Aldosterone also stimulates the activation of protein kinases and secondary messenger signaling cascades that act independently on specific molecular targets in the cell membrane and also modulate the transcriptional action of aldosterone through MR. This review describes current knowledge regarding the mechanisms and targets of rapid aldosterone action in the nephron and how aldosterone integrates these responses into the regulation of renal physiology.

  2. Ecological mechanisms underlying arthropod species diversity in grasslands.

    Science.gov (United States)

    Joern, Anthony; Laws, Angela N

    2013-01-01

    Arthropods are an important component of grassland systems, contributing significantly to biodiversity and ecosystem structure and function. Climate, fire, and grazing by large herbivores are important drivers in grasslands worldwide. Arthropod responses to these drivers are highly variable and clear patterns are difficult to find, but responses are largely indirect with respect to changes in resources, species interactions, habitat structure, and habitat heterogeneity resulting from interactions among fire, grazing, and climate. Here, we review these ecological mechanisms influencing grassland arthropod diversity. We summarize hypotheses describing species diversity at local and regional scales and then discuss specific factors that may affect arthropod diversity in grassland systems. These factors include direct and indirect effects of grazing, fire, and climate, species interactions, above- and belowground interactions, and landscape-level effects.

  3. Uranium dioxide sintering Kinetics and mechanisms under controlled oxygen potentials

    International Nuclear Information System (INIS)

    Freitas, C.T. de.

    1980-06-01

    The initial, intermediate, and final sintering stages of uranium dioxide were investigated as a function of stoichiometry and temperature by following the kinetics of the sintering reaction. Stoichiometry was controlled by means of the oxygen potential of the sintering atmosphere, which was measured continuously by solid-state oxygen sensors. Included in the kinetic study were microspheres originated from UO 2 gels and UO 2 pellets produced by isostatic pressing ceramic grade powders. The microspheres sintering behavior was examined using hot-stage microscopy and a specially designed high-temperature, controlled atmosphere furnace. This same furnace was employed as part of an optical dilatometer, which was utilized in the UO 2 pellet sintering investigations. For controlling the deviations from stoichiometry during heat treatment, the oxygen partial pressure in the sintering atmosphere was varied by passing the gas through a Cu-Ti-Cu oxygen trap. The trap temperature determined the oxygen partial pressure of the outflowing mixture. Dry hydrogen was also used in some of the UO sub(2+x) sintering experiments. The determination of diametrial shrinkages and sintering indices was made utilizing high-speed microcinematography and ultra-microbalance techniques. It was observed that the oxygen potential has a substantial influence on the kinetics of the three sintering stages. The control of the sintering atmosphere oxygen partial pressure led to very fast densification of UO sub(2+x). Values in the interval 95.0 to 99.5% of theoretical density were reached in less than one minute. Uranium volume diffusion is the dominant mechanism in the initial and intermediate sintering stages. For the final stage, uranium grain boundary diffusion was found to be the main sintering mechanism. (Author) [pt

  4. Mechanisms underlying probucol-induced hERG-channel deficiency

    Directory of Open Access Journals (Sweden)

    Shi YQ

    2015-07-01

    Full Text Available Yuan-Qi Shi,1,* Cai-Chuan Yan,1,* Xiao Zhang,1 Meng Yan,1 Li-Rong Liu,1 Huai-Ze Geng,1 Lin Lv,1 Bao-Xin Li1,21Department of Pharmacology, Harbin Medical University, 2State-Province Key Laboratory of Biopharmaceutical Engineering, Harbin, Heilongjiang, People’s Republic of China*These authors contributed equally to this workAbstract: The hERG gene encodes the pore-forming α-subunit of the rapidly activating delayed rectifier potassium channel (IKr, which is important for cardiac repolarization. Reduction of IhERG due to genetic mutations or drug interferences causes long QT syndrome, leading to life-threatening cardiac arrhythmias (torsades de pointes or sudden death. Probucol is a cholesterol-lowering drug that could reduce hERG current by decreasing plasma membrane hERG protein expression and eventually cause long QT syndrome. Here, we investigated the mechanisms of probucol effects on IhERG and hERG-channel expression. Our data demonstrated that probucol reduces SGK1 expression, known as SGK isoform, in a concentration-dependent manner, resulting in downregulation of phosphorylated E3 ubiquitin ligase Nedd4-2 expression, but not the total level of Nedd4-2. As a result, the hERG protein reduces, due to the enhanced ubiquitination level. On the contrary, carbachol could enhance the phosphorylation level of Nedd4-2 as an alternative to SGK1, and thus rescue the ubiquitin-mediated degradation of hERG channels caused by probucol. These discoveries provide a novel mechanism of probucol-induced hERG-channel deficiency, and imply that carbachol or its analog may serve as potential therapeutic compounds for the handling of probucol cardiotoxicity.Keywords: long QT, hERG potassium channels, probucol, SGK1, Nedd4-2

  5. Pathological mechanisms underlying single large‐scale mitochondrial DNA deletions

    Science.gov (United States)

    Rocha, Mariana C.; Rosa, Hannah S.; Grady, John P.; Blakely, Emma L.; He, Langping; Romain, Nadine; Haller, Ronald G.; Newman, Jane; McFarland, Robert; Ng, Yi Shiau; Gorman, Grainne S.; Schaefer, Andrew M.; Tuppen, Helen A.; Taylor, Robert W.

    2018-01-01

    Objective Single, large‐scale deletions in mitochondrial DNA (mtDNA) are a common cause of mitochondrial disease. This study aimed to investigate the relationship between the genetic defect and molecular phenotype to improve understanding of pathogenic mechanisms associated with single, large‐scale mtDNA deletions in skeletal muscle. Methods We investigated 23 muscle biopsies taken from adult patients (6 males/17 females with a mean age of 43 years) with characterized single, large‐scale mtDNA deletions. Mitochondrial respiratory chain deficiency in skeletal muscle biopsies was quantified by immunoreactivity levels for complex I and complex IV proteins. Single muscle fibers with varying degrees of deficiency were selected from 6 patient biopsies for determination of mtDNA deletion level and copy number by quantitative polymerase chain reaction. Results We have defined 3 “classes” of single, large‐scale deletion with distinct patterns of mitochondrial deficiency, determined by the size and location of the deletion. Single fiber analyses showed that fibers with greater respiratory chain deficiency harbored higher levels of mtDNA deletion with an increase in total mtDNA copy number. For the first time, we have demonstrated that threshold levels for complex I and complex IV deficiency differ based on deletion class. Interpretation Combining genetic and immunofluorescent assays, we conclude that thresholds for complex I and complex IV deficiency are modulated by the deletion of complex‐specific protein‐encoding genes. Furthermore, removal of mt‐tRNA genes impacts specific complexes only at high deletion levels, when complex‐specific protein‐encoding genes remain. These novel findings provide valuable insight into the pathogenic mechanisms associated with these mutations. Ann Neurol 2018;83:115–130 PMID:29283441

  6. Mechanism and kinetics of parathion degradation under ultrasonic irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Yao Juanjuan, E-mail: yao_juanjuan@yahoo.cn [State Key laboratory of Pollution Control and Resources Reuse, Tongji University, Shanghai, 200092 (China); Gao Naiyun; Li Cong; Li Lei; Xu Bin [State Key laboratory of Pollution Control and Resources Reuse, Tongji University, Shanghai, 200092 (China)

    2010-03-15

    The parathion degradation under ultrasonic irradiation in aqueous solution was investigated. The results indicate that at the conditions in question, degradation rate of parathion decreased with increasing initial concentration and decreasing power. The optimal frequency for parathion degradation was 600 kHz. The free radical reactions predominate in the sonochemical degradation of parathion and the reaction zones are predominately at the bubble interface and, to a much lesser extent, in bulk solution. The gas/liquid interfacial regions are the real effective reaction sites for sonochemical degradation of parathion. The reaction can be well described as a gas/liquid heterogeneous reaction which obeys a kinetic model based on Langmuir-Hinshelwood model. The main pathways of parathion degradation by ultrasonic irradiation were also proposed by qualitative and quantitative analysis of organic and inorganic byproducts. It is indicated that the N{sub 2} in air takes part in the parathion degradation through the formation of {center_dot}NO{sub 2} under ultrasonic irradiation. Parathion is decomposed into paraoxon and 4-nitrophenol in the first step via two different pathways, respectively, which is in agreement with the theoretical molecular orbital (MO) calculations.

  7. Mechanisms Underlying Mammalian Hybrid Sterility in Two Feline Interspecies Models.

    Science.gov (United States)

    Davis, Brian W; Seabury, Christopher M; Brashear, Wesley A; Li, Gang; Roelke-Parker, Melody; Murphy, William J

    2015-10-01

    The phenomenon of male sterility in interspecies hybrids has been observed for over a century, however, few genes influencing this recurrent phenotype have been identified. Genetic investigations have been primarily limited to a small number of model organisms, thus limiting our understanding of the underlying molecular basis of this well-documented "rule of speciation." We utilized two interspecies hybrid cat breeds in a genome-wide association study employing the Illumina 63 K single-nucleotide polymorphism array. Collectively, we identified eight autosomal genes/gene regions underlying associations with hybrid male sterility (HMS) involved in the function of the blood-testis barrier, gamete structural development, and transcriptional regulation. We also identified several candidate hybrid sterility regions on the X chromosome, with most residing in close proximity to complex duplicated regions. Differential gene expression analyses revealed significant chromosome-wide upregulation of X chromosome transcripts in testes of sterile hybrids, which were enriched for genes involved in chromatin regulation of gene expression. Our expression results parallel those reported in Mus hybrids, supporting the "Large X-Effect" in mammalian HMS and the potential epigenetic basis for this phenomenon. These results support the value of the interspecies feline model as a powerful tool for comparison to rodent models of HMS, demonstrating unique aspects and potential commonalities that underpin mammalian reproductive isolation. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Protein metabolism in marine animals: the underlying mechanism of growth.

    Science.gov (United States)

    Fraser, Keiron P P; Rogers, Alex D

    2007-01-01

    Growth is a fundamental process within all marine organisms. In soft tissues, growth is primarily achieved by the synthesis and retention of proteins as protein growth. The protein pool (all the protein within the organism) is highly dynamic, with proteins constantly entering the pool via protein synthesis or being removed from the pool via protein degradation. Any net change in the size of the protein pool, positive or negative, is termed protein growth. The three inter-related processes of protein synthesis, degradation and growth are together termed protein metabolism. Measurement of protein metabolism is vital in helping us understand how biotic and abiotic factors affect growth and growth efficiency in marine animals. Recently, the developing fields of transcriptomics and proteomics have started to offer us a means of greatly increasing our knowledge of the underlying molecular control of protein metabolism. Transcriptomics may also allow us to detect subtle changes in gene expression associated with protein synthesis and degradation, which cannot be detected using classical methods. A large literature exists on protein metabolism in animals; however, this chapter concentrates on what we know of marine ectotherms; data from non-marine ectotherms and endotherms are only discussed when the data are of particular relevance. We first consider the techniques available to measure protein metabolism, their problems and what validation is required. Protein metabolism in marine organisms is highly sensitive to a wide variety of factors, including temperature, pollution, seasonality, nutrition, developmental stage, genetics, sexual maturation and moulting. We examine how these abiotic and biotic factors affect protein metabolism at the level of whole-animal (adult and larval), tissue and cellular protein metabolism. Available gene expression data, which help us understand the underlying control of protein metabolism, are also discussed. As protein metabolism appears to

  9. A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer.

    Science.gov (United States)

    Polak, Paz; Kim, Jaegil; Braunstein, Lior Z; Karlic, Rosa; Haradhavala, Nicholas J; Tiao, Grace; Rosebrock, Daniel; Livitz, Dimitri; Kübler, Kirsten; Mouw, Kent W; Kamburov, Atanas; Maruvka, Yosef E; Leshchiner, Ignaty; Lander, Eric S; Golub, Todd R; Zick, Aviad; Orthwein, Alexandre; Lawrence, Michael S; Batra, Rajbir N; Caldas, Carlos; Haber, Daniel A; Laird, Peter W; Shen, Hui; Ellisen, Leif W; D'Andrea, Alan D; Chanock, Stephen J; Foulkes, William D; Getz, Gad

    2017-10-01

    Biallelic inactivation of BRCA1 or BRCA2 is associated with a pattern of genome-wide mutations known as signature 3. By analyzing ∼1,000 breast cancer samples, we confirmed this association and established that germline nonsense and frameshift variants in PALB2, but not in ATM or CHEK2, can also give rise to the same signature. We were able to accurately classify missense BRCA1 or BRCA2 variants known to impair homologous recombination (HR) on the basis of this signature. Finally, we show that epigenetic silencing of RAD51C and BRCA1 by promoter methylation is strongly associated with signature 3 and, in our data set, was highly enriched in basal-like breast cancers in young individuals of African descent.

  10. Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy.

    Science.gov (United States)

    Haricharan, Svasti; Dong, Jie; Hein, Sarah; Reddy, Jay P; Du, Zhijun; Toneff, Michael; Holloway, Kimberly; Hilsenbeck, Susan G; Huang, Shixia; Atkinson, Rachel; Woodward, Wendy; Jindal, Sonali; Borges, Virginia F; Gutierrez, Carolina; Zhang, Hong; Schedin, Pepper J; Osborne, C Kent; Tweardy, David J; Li, Yi

    2013-12-31

    While a first pregnancy before age 22 lowers breast cancer risk, a pregnancy after age 35 significantly increases life-long breast cancer risk. Pregnancy causes several changes to the normal breast that raise barriers to transformation, but how pregnancy can also increase cancer risk remains unclear. We show in mice that pregnancy has different effects on the few early lesions that have already developed in the otherwise normal breast-it causes apoptosis evasion and accelerated progression to cancer. The apoptosis evasion is due to the normally tightly controlled STAT5 signaling going astray-these precancerous cells activate STAT5 in response to pregnancy/lactation hormones and maintain STAT5 activation even during involution, thus preventing the apoptosis normally initiated by oncoprotein and involution. Short-term anti-STAT5 treatment of lactation-completed mice bearing early lesions eliminates the increased risk after a pregnancy. This chemoprevention strategy has important implications for preventing increased human breast cancer risk caused by pregnancy. DOI: http://dx.doi.org/10.7554/eLife.00996.001.

  11. Algorithmic mechanisms for reliable crowdsourcing computation under collusion.

    Science.gov (United States)

    Fernández Anta, Antonio; Georgiou, Chryssis; Mosteiro, Miguel A; Pareja, Daniel

    2015-01-01

    We consider a computing system where a master processor assigns a task for execution to worker processors that may collude. We model the workers' decision of whether to comply (compute the task) or not (return a bogus result to save the computation cost) as a game among workers. That is, we assume that workers are rational in a game-theoretic sense. We identify analytically the parameter conditions for a unique Nash Equilibrium where the master obtains the correct result. We also evaluate experimentally mixed equilibria aiming to attain better reliability-profit trade-offs. For a wide range of parameter values that may be used in practice, our simulations show that, in fact, both master and workers are better off using a pure equilibrium where no worker cheats, even under collusion, and even for colluding behaviors that involve deviating from the game.

  12. Mechanisms of microstructural changes of fuel under irradiation

    International Nuclear Information System (INIS)

    Garcia, P.; Carlot, G.; Dorado, B.; Maillard, S.; Sabathier, C.; Martin, G.; Oh, J.Y.; Welland, M.J.

    2015-01-01

    Nuclear fuels are subjected to high levels of radiation damage mainly due to the slowing of fission fragments, which results in substantial modifications of the initial fuel microstructure. Microstructure changes alter practically all engineering fuel properties such as atomic transport or thermomechanical properties so understanding these changes is essential to predicting the performance of fuel elements. Also, with increasing burn-up, the fuel drifts away from its initial composition as the fission process produces new chemical elements. Because nuclear fuels operate at high temperature and usually under high-temperature gradients, damage annealing, foreign atom or defect clustering and migration occur on multiple time and length scales, which make long-term predictions difficult. The end result is a fuel microstructure which may show extensive differences on the scale of a single fuel pellet. The main challenge we are faced with is, therefore, to identify the phenomena occurring on the atom scale that are liable to have macroscopic effects that will determine the microstructure changes and ultimately the life-span of a fuel element. One step towards meeting this challenge is to develop and apply experimental or modelling methods capable of connecting events that occur over very short length and timescales to changes in the fuel microstructure over engineering length and timescales. In the first part of this chapter, we provide an overview of some of the more important microstructure modifications observed in nuclear fuels. The emphasis is placed on oxide fuels because of the extensive amount of data available in relation to these materials under neutron or ion irradiation. When possible and relevant, the specifics of other types of fuels such as metallic or carbide fuels are alluded to. Throughout this chapter but more specifically in the latter part, we attempt to give examples of how modelling and experimentation at various scales can provide us with

  13. Neural mechanisms underlying melodic perception and memory for pitch.

    Science.gov (United States)

    Zatorre, R J; Evans, A C; Meyer, E

    1994-04-01

    The neural correlates of music perception were studied by measuring cerebral blood flow (CBF) changes with positron emission tomography (PET). Twelve volunteers were scanned using the bolus water method under four separate conditions: (1) listening to a sequence of noise bursts, (2) listening to unfamiliar tonal melodies, (3) comparing the pitch of the first two notes of the same set of melodies, and (4) comparing the pitch of the first and last notes of the melodies. The latter two conditions were designed to investigate short-term pitch retention under low or high memory load, respectively. Subtraction of the obtained PET images, superimposed on matched MRI scans, provides anatomical localization of CBF changes associated with specific cognitive functions. Listening to melodies, relative to acoustically matched noise sequences, resulted in CBF increases in the right superior temporal and right occipital cortices. Pitch judgments of the first two notes of each melody, relative to passive listening to the same stimuli, resulted in right frontal-lobe activation. Analysis of the high memory load condition relative to passive listening revealed the participation of a number of cortical and subcortical regions, notably in the right frontal and right temporal lobes, as well as in parietal and insular cortex. Both pitch judgment conditions also revealed CBF decreases within the left primary auditory cortex. We conclude that specialized neural systems in the right superior temporal cortex participate in perceptual analysis of melodies; pitch comparisons are effected via a neural network that includes right prefrontal cortex, but active retention of pitch involves the interaction of right temporal and frontal cortices.

  14. Neural Mechanisms of Updating under Reducible and Irreducible Uncertainty.

    Science.gov (United States)

    Kobayashi, Kenji; Hsu, Ming

    2017-07-19

    Adaptive decision making depends on an agent's ability to use environmental signals to reduce uncertainty. However, because of multiple types of uncertainty, agents must take into account not only the extent to which signals violate prior expectations but also whether uncertainty can be reduced in the first place. Here we studied how human brains of both sexes respond to signals under conditions of reducible and irreducible uncertainty. We show behaviorally that subjects' value updating was sensitive to the reducibility of uncertainty, and could be quantitatively characterized by a Bayesian model where agents ignore expectancy violations that do not update beliefs or values. Using fMRI, we found that neural processes underlying belief and value updating were separable from responses to expectancy violation, and that reducibility of uncertainty in value modulated connections from belief-updating regions to value-updating regions. Together, these results provide insights into how agents use knowledge about uncertainty to make better decisions while ignoring mere expectancy violation. SIGNIFICANCE STATEMENT To make good decisions, a person must observe the environment carefully, and use these observations to reduce uncertainty about consequences of actions. Importantly, uncertainty should not be reduced purely based on how surprising the observations are, particularly because in some cases uncertainty is not reducible. Here we show that the human brain indeed reduces uncertainty adaptively by taking into account the nature of uncertainty and ignoring mere surprise. Behaviorally, we show that human subjects reduce uncertainty in a quasioptimal Bayesian manner. Using fMRI, we characterize brain regions that may be involved in uncertainty reduction, as well as the network they constitute, and dissociate them from brain regions that respond to mere surprise. Copyright © 2017 the authors 0270-6474/17/376972-11$15.00/0.

  15. Chemotherapy in Old Women with Breast Cancer: Is Age Still a Predictor for Under Treatment?

    Science.gov (United States)

    Meresse, Mégane; Bouhnik, Anne-Déborah; Bendiane, Marc-Karim; Retornaz, Frédérique; Rousseau, Frédérique; Rey, Dominique; Giorgi, Roch

    2017-05-01

    Breast cancer affects mostly older women but there are no guidelines especially devoted to adjuvant chemotherapy for this population. In this context, this study was carried out in a population-based cohort of French elderly women with breast cancer, to check adherence to the existing national guidelines according to the women's age, taking into account the evolution of the situation over time for women requiring chemotherapy. Between October 2006 and December 2008, all consecutive women included in the French Health registry for a biopsy-proven primary nonmetastatic breast cancer, aged 65-80 years at diagnosis, and living in South Eastern France, were asked to participate in a cohort study. Medical information was collected from physicians. The study population was restricted to the 223 women who were recommended adjuvant chemotherapy according to national guidelines. Those who received chemotherapy were compared to those who did not receive this treatment. Among these 223 women 55% had received chemotherapy. Only three women refused the treatment. Less than 8% have had a geriatric assessment before treatment decision and only two were proposed to participate in a clinical trial. After adjustment for comorbidity score, tumor characteristics, socio-demographic characteristics, and year of diagnosis, increasing patient age was independently associated with decreased guideline concordance for adjuvant chemotherapy. Women aged 75-80 years received chemotherapy more than four times less often than women aged 65-74 years. However, the percentage of women who received chemotherapy increased from 33% to 58% between 2006 and 2008, in parallel with the setting up of Onco-Geriatric Coordination Units in the area. In France, chronological age remains a barrier to receive chemotherapy for older breast cancer women but the establishment of a formal collaboration between oncologists and geriatricians seems to be an effective way to improve care delivery in this population.

  16. Thin circular cylinder under axisymmetrical thermal and mechanical loading

    International Nuclear Information System (INIS)

    Arnaudeau, F.; Zarka, J.; Gerij, J.

    1977-01-01

    A special purpose computer code (Ratch) was developed to analyse a thin circular cylinder subjected to axisymmetrical mechanical and thermal loadings. The Mendelson's approach of this problem is followed. Classical Kirchoff-Love hypothesis of thin shells is used and a state of plane stress is assumed. Space integrations are performed by Gaussian quadrature in the axial direction and by Simpson's one third rule throughout the thickness. Thermoelastic-plastic constitutive equations are solved with an implicit scheme (Nguyen). Thermovisco-plastic constitutive equations are solved with an explicit time integration scheme (Treanor's algorithm especially fitted). A Bree type diagram is obtained for an axial step of temperature which varies cyclically and a sustained constant axial load. The material behavior is assumed perfectly plastic and creep effect is not considered. Results show that the domain where ratchetting occurs is reduced when compared with the domain predicted by the Bree diagram. To investigate the effect of material hardening the authors verify Halphen's Theorem which states that a structure made of material with kinematic hardening behavior and constant properties with temperature will always shake down to a periodic behavior. (Auth.)

  17. The neural sociometer: brain mechanisms underlying state self-esteem.

    Science.gov (United States)

    Eisenberger, Naomi I; Inagaki, Tristen K; Muscatell, Keely A; Byrne Haltom, Kate E; Leary, Mark R

    2011-11-01

    On the basis of the importance of social connection for survival, humans may have evolved a "sociometer"-a mechanism that translates perceptions of rejection or acceptance into state self-esteem. Here, we explored the neural underpinnings of the sociometer by examining whether neural regions responsive to rejection or acceptance were associated with state self-esteem. Participants underwent fMRI while viewing feedback words ("interesting," "boring") ostensibly chosen by another individual (confederate) to describe the participant's previously recorded interview. Participants rated their state self-esteem in response to each feedback word. Results demonstrated that greater activity in rejection-related neural regions (dorsal ACC, anterior insula) and mentalizing regions was associated with lower-state self-esteem. Additionally, participants whose self-esteem decreased from prescan to postscan versus those whose self-esteem did not showed greater medial prefrontal cortical activity, previously associated with self-referential processing, in response to negative feedback. Together, the results inform our understanding of the origin and nature of our feelings about ourselves.

  18. Raynaud's Phenomenon: a Brief Review of the Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Manal Fardoun

    2016-11-01

    Full Text Available Raynaud's phenomenon (RP is characterized by exaggerated cold-induced vasoconstriction. This augmented vasoconstriction occurs by virtue of a reflex response to cooling via the sympathetic nervous system as well as by local activation of α2C adrenoceptors (α2C-AR. In a cold-initiated, mitochondrion-mediated mechanism involving reactive oxygen species and the Rho/ROCK pathway, cytoskeletal rearrangement in vascular smooth muscle cells (VSMCs orchestrates the translocation of α2C-AR to the cell membrane, where this receptor readily interacts with its ligand. Different parameters are involved in this spatial and functional rescue of α2C-AR. Of notable relevance is the female hormone, 17β-estradiol, or estrogen. This is consistent with the high prevalence of RP in pre-menopausal women compared to age-matched males. In addition to dissecting the role of these various players, the contribution of pollution as well as genetic background to the onset and prevalence of RP are also discussed. Different therapeutic approaches employed as treatment modalities for this disease are also highlighted and analyzed. The lack of an appropriate animal model for RP mandates that more efforts be undertaken in order to better understand and eventually treat this disease. Although several lines of treatment are utilized, it is important to note that precaution is often effective in reducing severity or frequency of RP attacks.

  19. Neurobiological mechanisms underlying the blocking effect in aversive learning.

    Science.gov (United States)

    Eippert, Falk; Gamer, Matthias; Büchel, Christian

    2012-09-19

    Current theories of classical conditioning assume that learning depends on the predictive relationship between events, not just on their temporal contiguity. Here we employ the classic experiment substantiating this reasoning-the blocking paradigm-in combination with functional magnetic resonance imaging (fMRI) to investigate whether human amygdala responses in aversive learning conform to these assumptions. In accordance with blocking, we demonstrate that significantly stronger behavioral and amygdala responses are evoked by conditioned stimuli that are predictive of the unconditioned stimulus than by conditioned stimuli that have received the same pairing with the unconditioned stimulus, yet have no predictive value. When studying the development of this effect, we not only observed that it was related to the strength of previous conditioned responses, but also that predictive compared with nonpredictive conditioned stimuli received more overt attention, as measured by fMRI-concurrent eye tracking, and that this went along with enhanced amygdala responses. We furthermore observed that prefrontal regions play a role in the development of the blocking effect: ventromedial prefrontal cortex (subgenual anterior cingulate) only exhibited responses when conditioned stimuli had to be established as nonpredictive for an outcome, whereas dorsolateral prefrontal cortex also showed responses when conditioned stimuli had to be established as predictive. Most importantly, dorsolateral prefrontal cortex connectivity to amygdala flexibly switched between positive and negative coupling, depending on the requirements posed by predictive relationships. Together, our findings highlight the role of predictive value in explaining amygdala responses and identify mechanisms that shape these responses in human fear conditioning.

  20. Linking Pesticide Exposure with Pediatric Leukemia: Potential Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Antonio F. Hernández

    2016-03-01

    Full Text Available Leukemia is the most common cancer in children, representing 30% of all childhood cancers. The disease arises from recurrent genetic insults that block differentiation of hematopoietic stem and/or progenitor cells (HSPCs and drives uncontrolled proliferation and survival of the differentiation-blocked clone. Pediatric leukemia is phenotypically and genetically heterogeneous with an obscure etiology. The interaction between genetic factors and environmental agents represents a potential etiological driver. Although information is limited, the principal toxic mechanisms of potential leukemogenic agents (e.g., etoposide, benzene metabolites, bioflavonoids and some pesticides include topoisomerase II inhibition and/or excessive generation of free radicals, which may induce DNA single- and double-strand breaks (DNA-DSBs in early HSPCs. Chromosomal rearrangements (duplications, deletions and translocations may occur if these lesions are not properly repaired. The initiating hit usually occurs in utero and commonly leads to the expression of oncogenic fusion proteins. Subsequent cooperating hits define the disease latency and occur after birth and may be of a genetic, epigenetic or immune nature (i.e., delayed infection-mediated immune deregulation. Here, we review the available experimental and epidemiological evidence linking pesticide exposure to infant and childhood leukemia and provide a mechanistic basis to support the association, focusing on early initiating molecular events.

  1. Coordination of frontline defense mechanisms under severe oxidative stress.

    Science.gov (United States)

    Kaur, Amardeep; Van, Phu T; Busch, Courtney R; Robinson, Courtney K; Pan, Min; Pang, Wyming Lee; Reiss, David J; DiRuggiero, Jocelyne; Baliga, Nitin S

    2010-07-01

    Complexity of cellular response to oxidative stress (OS) stems from its wide-ranging damage to nucleic acids, proteins, carbohydrates, and lipids. We have constructed a systems model of OS response (OSR) for Halobacterium salinarum NRC-1 in an attempt to understand the architecture of its regulatory network that coordinates this complex response. This has revealed a multi-tiered OS-management program to transcriptionally coordinate three peroxidase/catalase enzymes, two superoxide dismutases, production of rhodopsins, carotenoids and gas vesicles, metal trafficking, and various other aspects of metabolism. Through experimental validation of interactions within the OSR regulatory network, we show that despite their inability to directly sense reactive oxygen species, general transcription factors have an important function in coordinating this response. Remarkably, a significant fraction of this OSR was accurately recapitulated by a model that was earlier constructed from cellular responses to diverse environmental perturbations--this constitutes the general stress response component. Notwithstanding this observation, comparison of the two models has identified the coordination of frontline defense and repair systems by regulatory mechanisms that are triggered uniquely by severe OS and not by other environmental stressors, including sub-inhibitory levels of redox-active metals, extreme changes in oxygen tension, and a sub-lethal dose of gamma rays.

  2. Comparative analysis reveals the underlying mechanism of vertebrate seasonal reproduction.

    Science.gov (United States)

    Ikegami, Keisuke; Yoshimura, Takashi

    2016-02-01

    Animals utilize photoperiodic changes as a calendar to regulate seasonal reproduction. Birds have highly sophisticated photoperiodic mechanisms and functional genomics analysis in quail uncovered the signal transduction pathway regulating avian seasonal reproduction. Birds detect light with deep brain photoreceptors. Long day (LD) stimulus induces secretion of thyroid-stimulating hormone (TSH) from the pars tuberalis (PT) of the pituitary gland. PT-derived TSH locally activates thyroid hormone (TH) in the hypothalamus, which induces gonadotropin-releasing hormone (GnRH) and hence gonadotropin secretion. However, during winter, low temperatures increase serum TH for adaptive thermogenesis, which accelerates germ cell apoptosis by activating the genes involved in metamorphosis. Therefore, TH has a dual role in the regulation of seasonal reproduction. Studies using TSH receptor knockout mice confirmed the involvement of PT-derived TSH in mammalian seasonal reproduction. In addition, studies in mice revealed that the tissue-specific glycosylation of TSH diversifies its function in the circulation to avoid crosstalk. In contrast to birds and mammals, one of the molecular machineries necessary for the seasonal reproduction of fish are localized in the saccus vasculosus from the photoreceptor to the neuroendocrine output. Thus, comparative analysis is a powerful tool to uncover the universality and diversity of fundamental properties in various organisms. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Neural mechanisms underlying social conformity in an ultimatum game

    Directory of Open Access Journals (Sweden)

    Zhenyu eWei

    2013-12-01

    Full Text Available When individuals’ actions are incongruent with those of the group they belong to, they may change their initial behavior in order to conform to the group norm. This phenomenon is known as social conformity. In the present study, we used event-related functional magnetic resonance imaging (fMRI to investigate brain activity in response to group opinion during an ultimatum game. Results showed that participants changed their choices when these choices conflicted with the normative opinion of the group they were members of, especially in conditions of unfair treatment. The fMRI data revealed that a conflict with group norms activated the brain regions involved in norm violations and behavioral adjustment. Furthermore, in the reject-unfair condition, we observed that a conflict with group norms activated the medial frontal gyrus. These findings contribute to recent research examining neural mechanisms involved in detecting violations of social norms, and provide information regarding the neural representation of conformity behavior in an economic game.

  4. Adhesive wear mechanism under combined electric diamond grinding

    Directory of Open Access Journals (Sweden)

    Popov Vyacheslav

    2017-01-01

    Full Text Available The article provides a scientific substantiation of loading of metal-bond diamond grinding wheels and describes the mechanism of contact interaction (interlocking of wheels with tool steel as well as its general properties having an influence on combined electric diamond grinding efficiency. The study concluded that a loaded layer can be formed in a few stages different by nature. It is known, that one of the causes of grinding degradation is a continuous loading of active grits (abrasive grinding tool by workpiece chips. It all affects the diamond grinding wheels efficiency and grinding ability with a result in increase of tool pressure, contact temperature and wheels specific removal rate. Science has partially identified some various methods to minimize grinding wheel loading, however, as to loading of metal-bond diamond grinding wheels the search is still in progress. Therefore, research people have to state, that in spite of the fact that the wheels made of cubic boron nitride are of little use as applied to ceramic, ultrahard, hard-alloyed hard-to-machine and nano-materials of the time, but manufactures have to apply cubic boron nitride wheels wherein diamond ones preferable.

  5. RISK FACTORS FOR PANCREATIC CANCER: UNDERLYING MECHANISMS AND POTENTIAL TARGETS

    Directory of Open Access Journals (Sweden)

    Thomas eKolodecik

    2014-01-01

    Full Text Available Purpose of the review:Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer.Recent Findings:Intracellular activation of both pancreatic enzymes and the transcription factor NF-kB are important mechanisms that induce acute pancreatitis. Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogneic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16 can ultimately lead to development of pancreatic cancer. Summary:Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions.

  6. Thin circular cylinder under axisymmetrical thermal and mechanical loading

    International Nuclear Information System (INIS)

    Arnaudeau, F.; Zarka, J.; Gerij, J.

    1977-01-01

    To assess structural integrity of components subjected to cyclic thermal loadings one must look at thermal ratchetting as a possible failure mode. Considering a thin circular cylinder subjected to constant internal pressure and cyclically varying thermal gradient through the thickness Bree, J. Strain Analysis 2 (1967) No.3, obtained a diagram that serves as a foundation for many design rules (e.g.: ASME code). The upper part of the french LMFBR main vessel is subjected to an axisymmetrical axial thermal loading and an axial load (own weight). Operation of the reactor leads to cyclic variations of the axial thermal loading. The question that arises is whether or not the Bree diagram is realistic for such loading conditions. A special purpose computer code (Ratch) was developed to analyse a thin circular cylinder subjected to axisymmetrical mechanical and thermal loadings. The Mendelson's approach of this problem is followed. Classical Kirchoff-Love hypothesis of thin shells is used and a state of plane stress is assumed. Space integrations are performed by Gaussian quadrature in the axial direction and by Simpson's one third rule throughout the thickness. Thermoelastic-plastic constitutive equations are solved with an implicit scheme (Nguyen). Thermovisco-plastic constitutive equations are solved with an explicit time integration scheme (Treanor's algorithm especially fitted). A Bree type diagram is obtained for an axial step of temperature which varies cyclically and a sustained constant axial load. The material behavior is assumed perfectly plastic and creep effect is not considered. Results show that the domain where no ratchetting occurs is reduced when compared with the domain predicted by the Bree diagram

  7. Compression under a mechanical counter pressure space suit glove

    Science.gov (United States)

    Waldie, James M A.; Tanaka, Kunihiko; Tourbier, Dietmar; Webb, Paul; Jarvis, Christine W.; Hargens, Alan R.

    2002-01-01

    Background: Current gas-pressurized space suits are bulky stiff shells severely limiting astronaut function and capability. A mechanical counter pressure (MCP) space suit in the form of a tight elastic garment could dramatically improve extravehicular activity (EVA) dexterity, but also be advantageous in safety, cost, mass and volume. The purpose of this study was to verify that a prototype MCP glove exerts the design compression of 200 mmHg, a pressure similar to the current NASA EVA suit. Methods: Seven male subjects donned a pressure measurement array and MCP glove on the right hand, which was placed into a partial vacuum chamber. Average compression was recorded on the palm, the bottom of the middle finger, the top of the middle finger and the dorsum of the hand at pressures of 760 (ambient), 660 and 580 mmHg. The vacuum chamber was used to simulate the pressure difference between the low breathing pressure of the current NASA space suits (approximately 200 mmHg) and an unprotected hand in space. Results: At ambient conditions, the MCP glove compressed the dorsum of the hand at 203.5 +/- 22.7 mmHg, the bottom of the middle finger at 179.4 +/- 16.0 mmHg, and the top of the middle finger at 183.8 +/- 22.6 mmHg. The palm compression was significantly lower (59.6 +/- 18.8 mmHg, pglove compression with the chamber pressure reductions. Conclusions: The MCP glove compressed the dorsum of the hand and middle finger at the design pressure.

  8. Enhancement of sleep slow waves: underlying mechanisms and practical consequences.

    Directory of Open Access Journals (Sweden)

    Michele eBellesi

    2014-10-01

    Full Text Available Even modest sleep restriction, especially the loss of sleep slow wave activity, is invariably associated with slower EEG activity during wake, the occurrence of local sleep in an otherwise awake brain, and impaired performance due to cognitive and memory deficits. Recent studies not only confirm the beneficial role of sleep in memory consolidation, but also point to a specific role for sleep slow waves. Thus, the implementation of methods to enhance sleep slow waves without unwanted arousals or lightening of sleep could have significant practical implications. Here we first review the evidence that it is possible to enhance sleep slow waves in humans using transcranial direct-current stimulation and transcranial magnetic stimulation. Since these methods are currently impractical and their safety is questionable, especially for chronic long-term exposure, we then discuss novel data suggesting that it is possible to enhance slow waves using sensory stimuli. We consider the physiology of the K-complex, a peripheral evoked slow wave, and show that, among different sensory modalities, acoustic stimulation is the most effective in increasing the magnitude of slow waves, likely through the activation of non-lemniscal ascending pathways to the thalamo-cortical system. In addition, we discuss how intensity and frequency of the acoustic stimuli, as well as exact timing and pattern of stimulation, affect sleep enhancement. Finally, we discuss automated algorithms that read the EEG and, in real-time, adjust the stimulation parameters in a closed-loop manner to obtain an increase in sleep slow waves and avoid undesirable arousals. In conclusion, while discussing the mechanisms that underlie the generation of sleep slow waves, we review the converging evidence showing that acoustic stimulation is safe and represents an ideal tool for slow wave sleep enhancement.

  9. Mechanical Model for Dynamic Behavior of Concrete Under Impact Loading

    Science.gov (United States)

    Sun, Yuanxiang

    Concrete is a geo-material which is used substantively in the civil building and military safeguard. One coupled model of damage and plasticity to describe the complex behavior of concrete subjected to impact loading is proposed in this research work. The concrete is assumed as homogeneous continuum with pre-existing micro-cracks and micro-voids. Damage to concrete is caused due to micro-crack nucleation, growth and coalescence, and defined as the probability of fracture at a given crack density. It induces a decrease of strength and stiffness of concrete. Compaction of concrete is physically a collapse of the material voids. It produces the plastic strain in the concrete and, at the same time, an increase of the bulk modulus. In terms of crack growth model, micro-cracks are activated, and begin to propagate gradually. When crack density reaches a critical value, concrete takes place the smashing destroy. The model parameters for mortar are determined using plate impact experiment with uni-axial strain state. Comparison with the test results shows that the proposed model can give consistent prediction of the impact behavior of concrete. The proposed model may be used to design and analysis of concrete structures under impact and shock loading. This work is supported by State Key Laboratory of Explosion science and Technology, Beijing Institute of Technology (YBKT14-02).

  10. Neural mechanism underlying autobiographical memory modulated by remoteness and emotion

    Science.gov (United States)

    Ge, Ruiyang; Fu, Yan; Wang, DaHua; Yao, Li; Long, Zhiying

    2012-03-01

    Autobiographical memory is the ability to recollect past events from one's own life. Both emotional tone and memory remoteness can influence autobiographical memory retrieval along the time axis of one's life. Although numerous studies have been performed to investigate brain regions involved in retrieving processes of autobiographical memory, the effect of emotional tone and memory age on autobiographical memory retrieval remains to be clarified. Moreover, whether the involvement of hippocampus in consolidation of autobiographical events is time dependent or independent has been controversial. In this study, we investigated the effect of memory remoteness (factor1: recent and remote) and emotional valence (factor2: positive and negative) on neural correlates underlying autobiographical memory by using functional magnetic resonance imaging (fMRI) technique. Although all four conditions activated some common regions known as "core" regions in autobiographical memory retrieval, there are some other regions showing significantly different activation for recent versus remote and positive versus negative memories. In particular, we found that bilateral hippocampal regions were activated in the four conditions regardless of memory remoteness and emotional valence. Thus, our study confirmed some findings of previous studies and provided further evidence to support the multi-trace theory which believes that the role of hippocampus involved in autobiographical memory retrieval is time-independent and permanent in memory consolidation.

  11. The effects of divided attention on encoding processes under incidental and intentional learning instructions: underlying mechanisms?

    Science.gov (United States)

    Naveh-Benjamin, Moshe; Guez, Jonathan; Hara, Yoko; Brubaker, Matthew S; Lowenschuss-Erlich, Iris

    2014-01-01

    Divided attention (DA) at encoding has been shown to significantly disrupt later memory for the studied information. However, what type of processing gets disrupted during DA remains unresolved. In this study, we assessed the degree to which strategic effortful processes are affected under DA by comparing the effects of DA at encoding under intentional and pure incidental learning instructions. In three experiments, participants studied list of words or word pairs under either full or divided attention. Results of three experiments, which used different methodologies, converged to show that the effects of DA at encoding reduce memory performance to the same degree under incidental and intentional learning. Secondary task performance indicated that encoding under intentional learning instructions was more effortful than under incidental learning instructions. In addition, the results indicated enhanced attention to the initial appearance of the words under both types of learning instructions. Results are interpreted to imply that other processes, rather than only strategic effortful ones, might be affected by DA at encoding.

  12. The Neural Mechanisms Underlying Internally and Externally Guided Task Selection

    Science.gov (United States)

    Orr, Joseph M.; Banich, Marie T.

    2013-01-01

    While some prior work suggests that medial prefrontal cortex (MFC) regions mediate freely chosen actions, other work suggests that the lateral frontal pole (LFP) is responsible for control of abstract, internal goals. The present study uses fMRI to determine whether the voluntary selection of a task in pursuit of an overall goal relies on MFC regions or the LFP. To do so, we used a modified voluntary task switching (VTS) paradigm, in which participants choose an individual task to perform on each trial (i.e., a subgoal), under instructions to perform the tasks equally often and in a random order (i.e. the overall goal). In conjunction, we examined patterns of activation in the face of irrelevant, but task-related external stimuli that might nonetheless influence task selection. While there was some evidence that the MFC was involved in voluntary task selection, we found that the LFP and anterior insula (AI) were crucial to task selection in the pursuit of an overall goal. In addition, activation of the LFP and AI increased in the face of environmental stimuli that might serve as an interfering or conflicting external bias on voluntary task choice. These findings suggest that the LFP supports task selection according to abstract, internal goals, and leaves open the possibility that MFC may guide action selection in situations lacking in such top-down biases. As such, the current study represents a critical step towards understanding the neural underpinnings of how tasks are selected voluntarily to enable an overarching goal. PMID:23994316

  13. Particle behavior and char burnout mechanisms under pressurized combustion conditions

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, C.M.; Spliethoff, H.; Hein, K.R.G.

    1999-07-01

    Combined cycle systems with coal-fired gas turbines promise highest cycle efficiencies for this fuel. Pressurized pulverized coal combustion, in particular, yields high cycle efficiencies due to the high flue gas temperatures possible. The main problem, however, is to ensure a flue gas clean enough to meet the high gas turbine standards with a dirty fuel like coal. On the one hand, a profound knowledge of the basic chemical and physical processes during fuel conversion under elevated pressures is required whereas on the other hand suitable hot gas cleaning systems need to be developed. The objective of this work was to provide experimental data to enable a detailed description of pressurized coal combustion processes. A series of experiments were performed with two German hvb coals, Ensdorf and Goettelborn, and one German brown coal, Garzweiler, using a semi-technical scale pressurized entrained flow reactor. The parameters varied in the experiments were pressure, gas temperature and bulk gas oxygen concentration. A two-color pyrometer was used for in-situ determination of particle surface temperatures and particle sizes. Flue gas composition was measured and solid residue samples taken and subsequently analyzed. The char burnout reaction rates were determinated varying the parameters pressure, gas temperature and initial oxygen concentration. Variation of residence time was achieved by taking the samples at different points along the reaction zone. The most influential parameters on char burnout reaction rates were found to be oxygen partial pressure and fuel volatile content. With increasing pressure the burn-out reactions are accelerated and are mostly controlled by product desorption and pore diffusion being the limiting processes. The char burnout process is enhanced by a higher fuel volatile content.

  14. Design principles and developmental mechanisms underlying retinal mosaics.

    Science.gov (United States)

    Reese, Benjamin E; Keeley, Patrick W

    2015-08-01

    Most structures within the central nervous system (CNS) are composed of different types of neuron that vary in both number and morphology, but relatively little is known about the interplay between these two features, i.e. about the population dynamics of a given cell type. How such arrays of neurons are distributed within a structure, and how they differentiate their dendrites relative to each other, are issues that have recently drawn attention in the invertebrate nervous system, where the genetic and molecular underpinnings of these organizing principles are being revealed in exquisite detail. The retina is one of the few locations where these principles have been extensively studied in the vertebrate CNS, indeed, where the design principles of 'mosaic regularity' and 'uniformity of coverage' were first explicitly defined, quantified, and related to each other. Recent studies have revealed a number of genes that influence the formation of these histotypical features in the retina, including homologues of those invertebrate genes, although close inspection reveals that they do not always mediate comparable developmental processes nor elucidate fundamental design principles. The present review considers just how pervasive these features of 'mosaic regularity' and 'uniform dendritic coverage' are within the mammalian retina, discussing the means by which such features can be assessed in the mature and developing nervous system and examining the limitations associated with those assessments. We then address the extent to which these two design principles co-exist within different populations of neurons, and how they are achieved during development. Finally, we consider the neural phenotypes obtained in mutant nervous systems, to address whether a prospective gene of interest underlies those very design principles. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

  15. Mechanism underlying the development of unilateral spatial neglect

    International Nuclear Information System (INIS)

    Nishikiori, Etsuko

    1992-01-01

    To test the hypothesis that functional disturbance of the neural network involving the inferior parietal lobule (IPL), anterior cingulate gyrus (ACG), dorsolateral frontal lobe (DLF), and thalamus (TH) as components of the right hemisphere underlies the development of unilateral spatial neglect (USN), cerebral perfusion was measured by 123 I-IMP SPECT in 32 patients with cerebrovascular right brain damage, 20 of whom had USN and 12 of whom did not. In analyzing the SPECT data, RI uptake in the four component regions and cerebellum (serving as a control) were estimated by symmetrically placing 'regions of interest' from both hemispheres on SPECT slices, most suitable for each region. The 'regional to cerebellar ratio' (R/CE ratio) for each component region was calculated and the values were compared. In the USN group, R/CE ratio values for each component region in the right hemisphere were significantly lower than those in the left, whereas in the non-USN group there was no right-left difference. When R/CE ratio values for each component region in the right hemisphere were compared between the USN and non-USN group, those for the IPL, ACG and TH were significantly lower in the USN group; the value for the DLF was also lower in the USN group, although the difference was not significant. Significantly lower values of R/CE for each component region in the right hemisphere were noticed when the regions showed apparent involvement on X-ray CT/MRI. Furthermore, in seven of the USN patients where lesions revealed by CT/MRI did not involve network components, the R/CE ratio values for the components in the right hemisphere were lower than those in the left; the difference was significant for the IPL, ACG and TH, but not for the DLF. It is suggested that functional disturbance of the neural network involving the IPL, ACG, DLF and TH in the right hemisphere might underlie the development of USN. (author)

  16. Corticonic models of brain mechanisms underlying cognition and intelligence

    Science.gov (United States)

    Farhat, Nabil H.

    underlying intelligence and other higher level brain functions.

  17. Mechanisms of Breast Cancer in Shift Workers: DNA Methylation in Five Core Circadian Genes in Nurses Working Night Shifts.

    Science.gov (United States)

    Samulin Erdem, Johanna; Skare, Øivind; Petersen-Øverleir, Marte; Notø, Heidi Ødegaard; Lie, Jenny-Anne S; Reszka, Edyta; Pepłońska, Beata; Zienolddiny, Shanbeh

    2017-01-01

    Shift work has been suggested to be associated with breast cancer risk, and circadian disruption in shift workers is hypothesized as one of the mechanisms of increased cancer risk. There is, however, insufficient molecular evidence supporting this hypothesis. Using the quantitative methodology of pyrosequencing, epigenetic changes in 5-methyl cytosine (5mC) in five circadian genes CLOCK , BMAL1 , CRY1, PER1 and PER2 in female nurses working night shift work (278 breast cancer cases, 280 controls) were analyzed. In breast cancer cases, a medium exposure to night work was associated with increased methylation levels of the CLOCK (p=0.050), BMAL1 (p=0.001) and CRY1 (p=0.040) genes, compared with controls. Within the cases, analysis of the effects of shift work on the methylation patterns showed that methylation of CRY1 was lower in those who had worked night shift and had a high exposure (p=0.006) compared with cases that had worked only days. For cases with a medium exposure to night work, an increase in BMAL1 (p=0.003) and PER1 (p=0.035) methylation was observed compared with day working (unexposed) cases. The methylation levels of the five core circadian genes were also analyzed in relation to the estrogen and progesterone receptors status of the tumors in the cases, and no correlations were observed. Furthermore, nineteen polymorphisms in the five circadian genes were assessed for their effects on the methylation levels of the respective genes, but no associations were found. In summary, our data suggest that epigenetic regulation of CLOCK , BMAL1, CRY1 and PER1 may contribute to breast cancer in shift workers.

  18. Quality Characteristics of Marinated Chicken Breast as Influenced by the Methods of Mechanical Processing

    Science.gov (United States)

    Kim, Hack-Youn; Kim, Kon-Joong; Lee, Jong-Wan; Kim, Gye-Woong; Choe, Ju-Hui; Kim, Hyun-Wook; Yoon, Yohan; Kim, Cheon-Jei

    2015-01-01

    The aim of this study was to investigate the effects of various marination processes on the quality characteristics of chicken breast prepared with chicken feet gelatin and wheat fiber. The chicken feet gelatin was swollen with hydrochloric solution (0.1 N HCl, pH 1.31±0.02) and dehydrated by freeze-drying. The composition (w/w) of the marinade was water (10%), soy sauce (12%), phosphate (0.3%), wheat fiber (1.5%), and chicken feet gelatin (1.5%). Three samples of chicken breast were manufactured with Tumbler (only tumbler), Tenderizer (tenderizer and tumbler), and Injector (injector and tumbler). The water content of the Injector sample was significantly higher than those of the Tumbler and Tenderizer samples (pchicken breasts increased and the redness decreased. The tumbling and cooking yield of the Injector sample were significantly higher than those of the Tumbler and Tenderizer samples (pchicken breast, considering the types of final products. PMID:26761806

  19. Loss of PEDF: A Novel Mechanism of Antihormone Resistance in Breast Cancer

    Science.gov (United States)

    2015-10-01

    Lewis-Wambi JS, Slifker MJ, Willis AL, Ramos P, Tapia C, Kim HR, Yerrum S, Sharma CG, Nicolas E, Balagurunathan Y, Ross EA, Jordan VC: Estrogen...J, Tan LP, Platteel I, Sluis T, Huitema S, et al. Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in

  20. Modification of BRCA1 Breast Cancer Risk by Coffee Consumption: Potential Mechanisms for Biologic Effect

    National Research Council Canada - National Science Library

    Holt, Jeffrey

    2007-01-01

    The purpose of this study was to investigate the role of coffee and caffeine in the function of the DNA repair protein BRCA1 and to determine whether or not coffee and/or caffeine prevent BRCA1 hereditary breast cancer...

  1. Role of Aspirin in Breast Cancer Survival.

    Science.gov (United States)

    Chen, Wendy Y; Holmes, Michelle D

    2017-07-01

    Chemotherapy and hormonal therapy have significantly decreased breast cancer mortality, although with considerable side effects and financial costs. In the USA, over three million women are living after a breast cancer diagnosis and are eager for new treatments that are low in toxicity and cost. Multiple observational studies have reported improved breast cancer survival with regular aspirin use. Furthermore, pooled data from five large randomized trials of aspirin for cardiovascular disease showed that subjects on aspirin had decreased risk of cancer mortality and decreased risk of metastatic cancer. Although the potential mechanism for aspirin preventing breast cancer is not known, possible pathways may involve platelets, inflammation, cyclooxygenase (COX) 2, hormones, or PI3 kinase. This review article summarizes the current epidemiologic and clinical trial evidence as well as possible underlying mechanisms that justify current phase III randomized trials of aspirin to improve breast cancer survival.

  2. Luminal and basal-like breast cancer cells show increased migration induced by hypoxia, mediated by an autocrine mechanism

    International Nuclear Information System (INIS)

    Voss, Melanie J; Möller, Mischa F; Powe, Desmond G; Niggemann, Bernd; Zänker, Kurt S; Entschladen, Frank

    2011-01-01

    Some breast cancer patients receiving anti-angiogenic treatment show increased metastases, possibly as a result of induced hypoxia. The effect of hypoxia on tumor cell migration was assessed in selected luminal, post-EMT and basal-like breast carcinoma cell lines. Migration was assessed in luminal (MCF-7), post-EMT (MDA-MB-231, MDA-MB-435S), and basal-like (MDA-MB-468) human breast carcinoma cell lines under normal and oxygen-deprived conditions, using a collagen-based assay. Cell proliferation was determined, secreted cytokine and chemokine levels were measured using flow-cytometry and a bead-based immunoassay, and the hypoxic genes HIF-1α and CA IX were assessed using PCR. The functional effect of tumor-cell conditioned medium on the migration of neutrophil granulocytes (NG) was tested. Hypoxia caused increased migratory activity but not proliferation in all tumor cell lines, involving the release and autocrine action of soluble mediators. Conditioned medium (CM) from hypoxic cells induced migration in normoxic cells. Hypoxia changed the profile of released inflammatory mediators according to cell type. Interleukin-8 was produced only by post-EMT and basal-like cell lines, regardless of hypoxia. MCP-1 was produced by MDA-MB-435 and -468 cells, whereas IL-6 was present only in MDA-MB-231. IL-2, TNF-α, and NGF production was stimulated by hypoxia in MCF-7 cells. CM from normoxic and hypoxic MDA-MB-231 and MDA-MB-435S cells and hypoxic MCF-7 cells, but not MDA-MB-468, induced NG migration. Hypoxia increases migration by the autocrine action of released signal substances in selected luminal and basal-like breast carcinoma cell lines which might explain why anti-angiogenic treatment can worsen clinical outcome in some patients

  3. Fracture mechanics in new designed power module under thermo-mechanical loads

    Directory of Open Access Journals (Sweden)

    Durand Camille

    2014-06-01

    Full Text Available Thermo-mechanically induced failure is a major reliability issue in the microelectronic industry. On this account, a new type of Assembly Interconnected Technology used to connect MOSFETs in power modules has been developed. The reliability is increased by using a copper clip soldered on the top side of the chip, avoiding the use of aluminium wire bonds, often responsible for the failure of the device. Thus the new designed MOSFET package does not follow the same failure mechanisms as standard modules. Thermal and power cycling tests were performed on these new packages and resulting failures were analyzed. Thermo-mechanical simulations including cracks in the aluminium metallization and intermetallics (IMC were performed using Finite Element Analysis in order to better understand crack propagation and module behaviour.

  4. Handy-type gamma probe-guided sentinel lymph node biopsy for breast cancer under ambulatory local anesthesia

    International Nuclear Information System (INIS)

    Fujiwara, Ikuya; Nagata, Hiroaki; Takaki, Wataru

    2016-01-01

    Prior to surgery for clinically node-negative breast cancer, we diagnosed metastases on the basis of permanent sections and sentinel lymph node biopsy (SNB) using the combined radio isotope (RI)/blue dye method with a hand-type gamma probe under ambulatory local anesthesia. SNB was performed for 99 patients with 103 lesions, including 4 patients with bilateral breast cancer. We achieved an identification rate of 100%, in which the identification pattern included detection by RI and blue-dye in 65 patients (63.1%), detection by RI alone in 37 patients (35.9%), and blue-dye alone in one patient (1.0%). Sentinel lymph node metastasis was macrometastasis in 21 patients (20.4%), micrometastasis in 8 patients (7.8%), and isolated tumor cells in patients (4.9%). In the 80 patients who did not undergo post-SNB axillary lymph node dissection, the median observation period was 33 months and there were no recurrences in the axillary lymph nodes observed. Although the present procedure requires two surgeries, it is a useful method that enables metastasis detection and highly accurate SNB. (author)

  5. Efficacy and mechanism of action of the tyrosine kinase inhibitors gefitinib, lapatinib and neratinib in the treatment of HER2-positive breast cancer: preclinical and clinical evidence.

    Science.gov (United States)

    Segovia-Mendoza, Mariana; González-González, María E; Barrera, David; Díaz, Lorenza; García-Becerra, Rocío

    2015-01-01

    An increasing number of tumors, including breast cancer, overexpress proteins of the epidermal growth factor receptor (EGFR) family. The interaction between family members activates signaling pathways that promote tumor progression and resistance to treatment. Human epidermal growth factor receptor type II (HER2) positive breast cancer represents a clinical challenge for current therapy. It has motivated the development of novel and more effective therapeutic EGFR family target drugs, such as tyrosine kinase inhibitors (TKIs). This review focuses on the effects of three TKIs mostly studied in HER2- positive breast cancer, lapatinib, gefitinib and neratinib. Herein, we discuss the mechanism of action, therapeutic advantages and clinical applications of these TKIs. To date, TKIs seem to be promising therapeutic agents for the treatment of HER2-overexpressing breast tumors, either as monotherapy or combined with other pharmacological agents.

  6. Fibrin glue instillation under skin flaps to prevent seroma-related morbidity following breast and axillary surgery.

    Science.gov (United States)

    Sajid, Muhammad S; Hutson, Kristian H; Rapisarda, Ignazio F; Bonomi, Riccardo

    2013-05-31

    Fibrin glue (FG) combines fibrinogen and thrombin, under the presence of factor XIII and calcium chloride, and produces a 'fibrin clot' as would occur through the natural clotting cascade. FG is thought to close over any small vessels including lymphatics that are too small for conventional surgical closure, thereby reducing seroma formation, seroma incidence and related comorbidities. To assess the evidence on the effectiveness of FG in people undergoing breast and axillary surgery and to establish whether FG is an efficient modality to prevent postoperative seroma and seroma-related outcomes. We searched the Cochrane Breast Cancer Group's (CBCG) Specialised Register (9 December 2011), the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1 2012), MEDLINE (9 December 2011), EMBASE (9 December 2011), LILACS (22 October 2012), SCI-E (22 October 2012), the World Health Organization's International Clinical Trial Registry (9 December 2011) and ClinicalTrials.gov (22 October 2012). Randomised controlled trials (RCTs) comparing the effectiveness of FG in terms of reducing the postoperative seroma incidence and related comorbidities in people undergoing breast and axillary surgery. At least two review authors independently scrutinised search results, selected eligible studies and extracted the data. The pooled analysis of the extracted data was achieved by the statistical analysis on Review Manager software. The quality of studies was assessed using The Cochrane Collaboration's 'Risk of bias' tool. The search of four standard electronic databases yielded 119 potentially relevant studies but only 18 RCTs involving 1252 people were found suitable for statistical analysis. There was significant heterogeneity among trials and the majority of trials were of poor quality. The use of FG under skin flaps following breast and axillary surgery failed to reduce the incidence of postoperative seroma (risk ratio (RR) 1.02; 95% Confidence Interval (CI) 0.90 to 1.16, P

  7. Interactivity effects in social media marketing on brand engagement: an investigation of underlying mechanisms

    NARCIS (Netherlands)

    Antheunis, M.L.; van Noort, G.; Eisend, M.; Langner, T.

    2011-01-01

    Although, SNS advertising spending increases, research on SNS campaigning is still underexposed. First, this study aims to investigate the effect of SNS campaign interactivity on the receivers brand engagement, taking four underlying mechanisms into account (brand identification, campaign

  8. Imitation in Newborn Infants: Exploring the Range of Gestures Imitated and the Underlying Mechanisms.

    Science.gov (United States)

    Meltzoff, Andrew N.; Moore, M. Keith

    1989-01-01

    Evaluated psychological mechanisms underlying imitation of facial actions in 40 newborn infants. Results showed imitation of head movement and a tongue-protrusion gesture. Subjects imitated from memory after displays had stopped. (RJC)

  9. Mechanisms underlying the effects of prenatal psychosocial stress on child outcomes: beyond the HPA axis

    NARCIS (Netherlands)

    Beijers, R.; Buitelaar, J.K.; Weerth, C. de

    2014-01-01

    Accumulating evidence from preclinical and clinical studies indicates that maternal psychosocial stress and anxiety during pregnancy adversely affect child outcomes. However, knowledge on the possible mechanisms underlying these relations is limited. In the present paper, we review the most often

  10. Elucidating the molecular mechanisms underlying cellular response to biophysical cues using synthetic biology approaches

    NARCIS (Netherlands)

    Denning, Denise; Roos, Wouter H

    2016-01-01

    The use of synthetic surfaces and materials to influence and study cell behavior has vastly progressed our understanding of the underlying molecular mechanisms involved in cellular response to physicochemical and biophysical cues. Reconstituting cytoskeletal proteins and interfacing them with a

  11. micro-mechanical experimental investigation and modelling of strain and damage of argillaceous rocks under combined hydric and mechanical loads

    International Nuclear Information System (INIS)

    Wang, L.

    2012-01-01

    The hydro-mechanical behavior of argillaceous rocks, which are possible host rocks for underground radioactive nuclear waste storage, is investigated by means of micro-mechanical experimental investigations and modellings. Strain fields at the micrometric scale of the composite structure of this rock, are measured by the combination of environmental scanning electron microscopy, in situ testing and digital image correlation technique. The evolution of argillaceous rocks under pure hydric loading is first investigated. The strain field is strongly heterogeneous and manifests anisotropy. The observed nonlinear deformation at high relative humidity (RH) is related not only to damage, but also to the nonlinear swelling of the clay mineral itself, controlled by different local mechanisms depending on RH. Irreversible deformations are observed during hydric cycles, as well as a network of microcracks located in the bulk of the clay matrix and/or at the inclusion-matrix interface. Second, the local deformation field of the material under combined hydric and mechanical loadings is quantified. Three types of deformation bands are evidenced under mechanical loading, either normal to stress direction (compaction), parallel (microcracking) or inclined (shear). Moreover, they are strongly controlled by the water content of the material: shear bands are in particular prone to appear at high RH states. In view of understanding the mechanical interactions a local scale, the material is modeled as a composite made of non-swelling elastic inclusions embedded in an elastic swelling clay matrix. The internal stress field induced by swelling strain incompatibilities between inclusions and matrix, as well as the overall deformation, is numerically computed at equilibrium but also during the transient stage associated with a moisture gradient. An analytical micro-mechanical model based on Eshelby's solution is proposed. In addition, 2D finite element computations are performed. Results

  12. Mechanisms Underlying Stress Fracture and the Influence of Sex and Race/Ethnicity

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0652 TITLE: Mechanisms Underlying Stress Fracture and the Influence of Sex and Race/Ethnicity PRINCIPAL INVESTIGATOR...5a. CONTRACT NUMBER W81XWH-16-1-0652 Mechanisms Underlying Stress Fracture and the Influence of Sex and Race/Ethnicity 5b. GRANT NUMBER W81XWH...to stress fracture risk. In particular, in Study 1, we will perform advanced skeletal imaging along with gait-assessments in subjects with history of

  13. Cognitive mechanisms underlying disorganization of thought in a genetic syndrome (47,XXY)

    NARCIS (Netherlands)

    Van Rijn, Sophie; Aleman, Andre; De Sonneville, Leo; Swaab, Hanna

    Because of the risk for development of psychopathology such as psychotic symptoms, it has been suggested that studying men with the XXY karyotype may help in the search for underlying cognitive, neural and genetic mechanisms. The aim of this study was to identify cognitive mechanisms that may

  14. Mechanisms for closing bores and releasably securing articles within the bores under longitudinal load

    International Nuclear Information System (INIS)

    Klahn, F.C.; Nolan, J.H.; Wills, C.

    1979-01-01

    This invention relates to mechanisms for closing bores of tubular passages and for releasably securing articles within the bores under longitudinal load. The system includes an axially movable latch, an actuator and locking devices. Embodiments of the invention can be used as closure mechanisms for tubular irradiation surveillance specimen assembly holders used in nuclear reactors. (UK)

  15. Mechanisms for closing bores and releasably securing articles within the bores under longitudinal load

    International Nuclear Information System (INIS)

    Kalen, D.D.; Mitchem, J.W.

    1979-01-01

    This invention relates to mechanisms for closing bores of tubular passages and for releasably securing articles within the bores under longitudinal load. The system includes an axially movable actuator and a latch which engages the tubular opening. Embodiments of the invention can be used as closure mechanisms for tubular irradiation surveillance specimen assembly holders used in nuclear reactors. (UK)

  16. Molecular Mechanisms Underlying the Epileptogenesis and Seizure Progression in Tuberous Sclerosis Complex 1 Deficient Mouse Models

    Science.gov (United States)

    2016-10-01

    dysregulation in epileptogenesis in the developing brain? 2) What are the molecular mechanisms downstream of mTOR hyperactivation that trigger epileptogenesis...underlying epilepsy. Hopefully, a knowledge of these mechanisms will aid in a rational development of therapies. KEYWORDS Tuberous Sclerosis, Epilepsy

  17. Friction Stir Weld Failure Mechanisms in Aluminum-Armor Structures Under Ballistic Impact Loading Conditions

    Science.gov (United States)

    2013-01-01

    REPORT Friction Stir Weld Failure Mechanisms in Aluminum-Armor Structures Under Ballistic Impact Loading Conditions 14. ABSTRACT 16. SECURITY...properties and of the attendant ballistic-impact failure mechanisms in prototypical friction stir welding (FSW) joints found in armor structures made of high...mechanisms, friction stir welding M. Grujicic, B. Pandurangan, A. Arakere, C-F. Yen, B. A. Cheeseman Clemson University Office of Sponsored Programs 300

  18. Microenvironment-Mediated Mechanisms of Resistance to HER2 Inhibitors Differ between HER2+ Breast Cancer Subtypes.

    Science.gov (United States)

    Watson, Spencer S; Dane, Mark; Chin, Koei; Tatarova, Zuzana; Liu, Moqing; Liby, Tiera; Thompson, Wallace; Smith, Rebecca; Nederlof, Michel; Bucher, Elmar; Kilburn, David; Whitman, Matthew; Sudar, Damir; Mills, Gordon B; Heiser, Laura M; Jonas, Oliver; Gray, Joe W; Korkola, James E

    2018-03-28

    Extrinsic signals are implicated in breast cancer resistance to HER2-targeted tyrosine kinase inhibitors (TKIs). To examine how microenvironmental signals influence resistance, we monitored TKI-treated breast cancer cell lines grown on microenvironment microarrays composed of printed extracellular matrix proteins supplemented with soluble proteins. We tested ∼2,500 combinations of 56 soluble and 46 matrix microenvironmental proteins on basal-like HER2+ (HER2E) or luminal-like HER2+ (L-HER2+) cells treated with the TKIs lapatinib or neratinib. In HER2E cells, hepatocyte growth factor, a ligand for MET, induced resistance that could be reversed with crizotinib, an inhibitor of MET. In L-HER2+ cells, neuregulin1-β1 (NRG1β), a ligand for HER3, induced resistance that could be reversed with pertuzumab, an inhibitor of HER2-HER3 heterodimerization. The subtype-specific responses were also observed in 3D cultures and murine xenografts. These results, along with bioinformatic pathway analysis and siRNA knockdown experiments, suggest different mechanisms of resistance specific to each HER2+ subtype: MET signaling for HER2E and HER2-HER3 heterodimerization for L-HER2+ cells. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Quantum mechanical/molecular mechanical and docking study of the novel analogues based on hybridization of common pharmacophores as potential anti-breast cancer agents.

    Science.gov (United States)

    Asadi, Parvin; Khodarahmi, Ghadamali; Farrokhpour, Hossein; Hassanzadeh, Farshid; Saghaei, Lotfollah

    2017-06-01

    In an attempt to identify some new potential leads as anti-breast cancer agents, novel hybrid compounds were designed by molecular hybridization approach. These derivatives were structurally derived from hybrid benzofuran-imidazole and quinazolinone derivatives, which had shown good cytotoxicity against the breast cancer cell line (MCF-7). Since aromatase enzyme (CYP19) is highly expressed in the MCF-7 cell line, the binding of these novel hybrid compounds to aromatase was investigated using the docking method. In this study, due to the positive charge on the imidazole ring of the designed ligands and also, the presence of heme iron in the active site of the enzyme, it was decided to optimize the ligand inside the protein to obtain more realistic atomic charges for it. Quantum mechanical/molecular mechanical (QM/MM) method was used to obtain more accurate atomic charges of ligand for docking calculations by considering the polarization effects of CYP19 on ligands. It was observed that the refitted charge improved the binding energy of the docked compounds. Also, the results showed that these novel hybrid compounds were adopted properly within the aromatase binding site, thereby suggesting that they could be potential inhibitors of aromatase. The main binding modes in these complexes were through hydrophobic and H bond interactions showing agreement with the basic physicochemical features of known anti aromatase compounds. Finally, the complex structures obtained from the docking study were used for single point QM/MM calculations to obtain more accurate electronic interaction energy, considering the electronic polarization of the ligand by its protein environment.

  20. Mechanical and tribological behaviour of molten salt processed self-lubricated aluminium composite under different treatments

    Science.gov (United States)

    Kannan, C.; Ramanujam, R.

    2018-05-01

    The aim of this research work is to evaluate the mechanical and tribological behaviour of Al 7075 based self-lubricated hybrid nanocomposite under different treated conditions viz. as-cast, T6 and deep cryo treated. In order to overcome the drawbacks associated with conventional stir casting, a combinational approach that consists of molten salt processing, ultrasonic assistance and optimized mechanical stirring is adopted in this study to fabricate the nanocomposite. The mechanical characterisation tests carried out on this nanocomposite reveals an improvement of about 39% in hardness and 22% in ultimate tensile strength possible under T6 condition. Under specific conditions, the wear rate can be reduced to the extent of about 63% through the usage of self-lubricated hybrid nanocomposite under T6 condition.

  1. Behavioral Symptoms after Breast Cancer Treatment: A Biobehavioral Approach

    Directory of Open Access Journals (Sweden)

    Christopher Fagundes

    2015-08-01

    Full Text Available Being diagnosed and treated for breast cancer is emotionally and physically challenging. Breast cancer is the most commonly diagnosed cancer and the second leading cause of death for women in the United States. Accordingly, women with a breast cancer history are the largest group of female cancer survivors. Psychological stress substantially augments adverse autonomic, endocrine, and immune discharge, including enhanced production of proinflammatory cytokines. Importantly, inflammation is a key biological mechanism underlying the symptom cluster of pain, depression, fatigue, and sleep disturbances; there is also good evidence that inflammation contributes to breast cancer recurrence. Stress may exert direct effects on psychological and physiological risk processes. In this review, we take a biobehavioral approach to understanding predictors and mechanisms underlying somatic symptoms in breast cancer survivors.

  2. Induction of PTEN-p53 crosstalk in mammary epithelial cells: A novel mechanism of breast cancer prevention by the dietary factor genistein

    Science.gov (United States)

    Consumption of soy foods either at an early age or for lifetime has been associated with reduced risk for developing breast cancer in humans and in animal models. However, this association continues to be controversial, and the precise mechanisms for protection remain elusive. Among the soy products...

  3. On the dynamic mechanical property and deformation mechanism of as-extruded Mg-Sn-Ca alloys under tension

    International Nuclear Information System (INIS)

    Huang, Qiuyan; Pan, Hucheng; Tang, Aitao; Ren, Yuping; Song, Bo; Qin, Gaowu; Zhang, Mingxing; Pan, Fusheng

    2016-01-01

    To further understand the deformation mechanism of magnesium alloys and expand their applications under dynamic conditions, the newly developed Mg-2Sn-1Ca alloy (TX21) is selected as the representative sample and tested under wide loading rate ranging from quasi-static to dynamic level (10"−"3–500/s). Both ultimate tensile strength and elongation of the as-extruded TX21 alloys increase with strain rate. Although twinning is accompanied due to the enhanced activity at higher strain rate, the preferential activation of dislocations is readily clarified and confirmed as the dominant deformation modes. Active interactions of pyramidal dislocations result in the higher strain hardening ability and could be correlated to the obviously positive strain-rate sensitivity for mechanical properties. Moreover, it is observed that the larger grain size and higher content of solute atoms dissolved in matrix would lead to the more active dislocations and twinning formations. The present results would provide insight into further understanding the deformation mechanism under dynamic rate loading and designing Mg alloy suitable for impact conditions.

  4. On the dynamic mechanical property and deformation mechanism of as-extruded Mg-Sn-Ca alloys under tension

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Qiuyan [National Engineering Research Center for Magnesium Alloys, Chongqing University, Chongqing 400044 (China); Pan, Hucheng [Key Laboratory for Anisotropy and Texture of Materials (Ministry of Education), Northeastern University, Shenyang 110819 (China); Tang, Aitao, E-mail: tat@cqu.edu.cn [National Engineering Research Center for Magnesium Alloys, Chongqing University, Chongqing 400044 (China); Ren, Yuping [Key Laboratory for Anisotropy and Texture of Materials (Ministry of Education), Northeastern University, Shenyang 110819 (China); Song, Bo [Faculty of Materials and Energy, Southwest University, Chongqing 400715 (China); Qin, Gaowu, E-mail: qingw@smm.neu.edu.cn [Key Laboratory for Anisotropy and Texture of Materials (Ministry of Education), Northeastern University, Shenyang 110819 (China); Zhang, Mingxing [School of Mechanical and Mining Engineering, University of Queensland, St Lucia, QLD 4072 (Australia); Pan, Fusheng [National Engineering Research Center for Magnesium Alloys, Chongqing University, Chongqing 400044 (China)

    2016-05-10

    To further understand the deformation mechanism of magnesium alloys and expand their applications under dynamic conditions, the newly developed Mg-2Sn-1Ca alloy (TX21) is selected as the representative sample and tested under wide loading rate ranging from quasi-static to dynamic level (10{sup −3}–500/s). Both ultimate tensile strength and elongation of the as-extruded TX21 alloys increase with strain rate. Although twinning is accompanied due to the enhanced activity at higher strain rate, the preferential activation of dislocations is readily clarified and confirmed as the dominant deformation modes. Active interactions of pyramidal dislocations result in the higher strain hardening ability and could be correlated to the obviously positive strain-rate sensitivity for mechanical properties. Moreover, it is observed that the larger grain size and higher content of solute atoms dissolved in matrix would lead to the more active dislocations and twinning formations. The present results would provide insight into further understanding the deformation mechanism under dynamic rate loading and designing Mg alloy suitable for impact conditions.

  5. Trends in incidence of breast cancer among women under 40 in seven European countries: a GRELL cooperative study.

    Science.gov (United States)

    Leclère, Brice; Molinié, Florence; Trétarre, Brigitte; Stracci, Fabrizio; Daubisse-Marliac, Laetitia; Colonna, Marc

    2013-10-01

    Young women are not usually screened for breast cancer (BC). The trends in incidence in this population may better reflect changes in risk factors. However, studies on this subject are scarce and heterogeneous. The aim of this study was to describe the trends in incidence of BC in women under 40 from 1990 to 2008, using pooled European data. Thirty-seven European population-based cancer registries from Belgium, Bulgaria, France, Italy, Portugal, Spain and Switzerland participated in this study. World age-standardized incidence rates were first analyzed graphically and then using a Poisson regression model, in order to estimate average annual percent changes (AAPCs). The overall incidence rate of BC in the area covered increased linearly during the study period by 1.19% (0.93; 1.46) on average per year. This increase varied between countries from 0.20% (-0.53; 0.64) in Bulgaria to 2.68% (1.97; 3.40) in Portugal. In Italy, after a significant rise of 2.33% (1.14; 3.54) per year, BC incidence began decreasing in 2002 by -2.30% (-4.07; -0.50) yearly. The rise in incidence was greater for women under 35 and for ductal carcinomas. This increase can be due to a rise in risk factors and/or changes in diagnosis and surveillance practices, but we could not clearly distinguish between these two non-exclusive explanations. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Intrinsic mechanism of estradiol-induced apoptosis in breast cancer cells resistant to estrogen deprivation.

    Science.gov (United States)

    Lewis, Joan S; Meeke, Kathleen; Osipo, Clodia; Ross, Eric A; Kidawi, Noman; Li, Tianyu; Bell, Eric; Chandel, Navdeep S; Jordan, V Craig

    2005-12-07

    We previously developed an estrogen receptor (ER)-positive breast cancer cell line (MCF-7:5C) that is resistant to long-term estrogen deprivation and undergoes rapid and complete apoptosis in the presence of physiologic concentrations of 17beta-estradiol. Here, we investigated the role of the mitochondrial apoptotic pathway in this process. Apoptosis in MCF-7:5C cells treated with estradiol, fulvestrant, or vehicle (control) was investigated by annexin V-propidium iodide double staining and 4',6-diamidino-2-phenylindole (DAPI) staining. Apoptosis was also analyzed in MCF-7:5C cells transiently transfected with small interfering RNAs (siRNAs) to apoptotic pathway components. Expression of apoptotic pathway intermediates was measured by western blot analysis. Mitochondrial transmembrane potential (psim) was determined by rhodamine-123 retention assay. Mitochondrial pathway activity was determined by cytochrome c release and cleavage of poly(ADP-ribose) polymerase (PARP) protein. Tumorigenesis was studied in ovariectomized athymic mice that were injected with MCF-7:5C cells. Differences between the treatment groups and control group were determined by two-sample t test or one-factor analysis of variance. All statistical tests were two-sided. MCF-7:5C cells treated with estradiol underwent apoptosis and showed increased expression of proapoptotic proteins, decreased psim, enhanced cytochrome c release, and PARP cleavage compared with cells treated with fulvestrant or vehicle. Blockade of Bax, Bim, and p53 mRNA expression by siRNA reduced estradiol-induced apoptosis relative to control by 76% [95% confidence interval (CI) = 73% to 79%, P estradiol-induced apoptosis in long-term estrogen-deprived breast cancer cells. Physiologic concentrations of estradiol could potentially be used to induce apoptosis and tumor regression in tumors that have developed resistance to aromatase inhibitors.

  7. Unraveling the Molecular Mechanism(s) Underlying Er+/PR-Breast Tumorigenesis Using a Novel Genetically Engineered Mouse Model

    Science.gov (United States)

    2011-11-01

    and subjected to silver stain, immunoblot, or LC-MS/MS spec- tral analyses (The MSU Proteomics Facility, Michigan State University). Mouse Hepatocyte... flotation gradient essentially as described [29]. Briefly, cells were incubated with 10 ng/ml EGF for 10 min at 37uC. After several washings, cells were

  8. An investigation of the mechanism underlying teacher aggression : Testing I3 theory and the General Aggression Model

    NARCIS (Netherlands)

    Montuoro, Paul; Mainhard, Tim

    2017-01-01

    Background: Considerable research has investigated the deleterious effects of teachers responding aggressively to students who misbehave, but the mechanism underlying this dysfunctional behaviour remains unknown. Aims: This study investigated whether the mechanism underlying teacher aggression

  9. Mechanisms underlying 3-bromopyruvate-induced cell death in colon cancer.

    Science.gov (United States)

    Sun, Yiming; Liu, Zhe; Zou, Xue; Lan, Yadong; Sun, Xiaojin; Wang, Xiu; Zhao, Surong; Jiang, Chenchen; Liu, Hao

    2015-08-01

    3-Bromopyruvate (3BP) is an energy-depleting drug that inhibits Hexokinase II activity by alkylation during glycolysis, thereby suppressing the production of ATP and inducing cell death. As such, 3BP can potentially serve as an anti-tumorigenic agent. Our previous research showed that 3BP can induce apoptosis via AKT /protein Kinase B signaling in breast cancer cells. Here we found that 3BP can also induce colon cancer cell death by necroptosis and apoptosis at the same time and concentration in the SW480 and HT29 cell lines; in the latter, autophagy was also found to be a mechanism of cell death. In HT29 cells, combined treatment with 3BP and the autophagy inhibitor 3-methyladenine (3-MA) exacerbated cell death, while viability in 3BP-treated cells was enhanced by concomitant treatment with the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (z-VAD-fmk) and the necroptosis inhibitor necrostatin (Nec)-1. Moreover, 3BP inhibited tumor growth in a SW480 xenograft mouse model. These results indicate that 3BP can suppress tumor growth and induce cell death by multiple mechanisms at the same time and concentration in different types of colon cancer cell by depleting cellular energy stores.

  10. Progressive damage analysis of carbon/epoxy laminates under couple laser and mechanical loading

    Directory of Open Access Journals (Sweden)

    Wanlei Liu

    Full Text Available A multiscale model based bridge theory is proposed for the progressive damage analysis of carbon/epoxy laminates under couple laser and mechanical loading. The ablation model is adopted to calculate ablation temperature changing and ablation surface degradation. The polynomial strengthening model of matrix is used to improve bridging model for reducing parameter input. Stiffness degradation methods of bridging model are also improved in order to analyze the stress redistribution more accurately when the damage occurs. Thermal-mechanical analyses of the composite plate are performed using the ABAQUS/Explicit program with the developed model implemented in the VUMAT. The simulation results show that this model can be used to proclaim the mesoscale damage mechanism of composite laminates under coupled loading. Keywords: Laser irradiation, Multiscale analysis, Bridge model, Thermal-mechanical

  11. How diagnostic tests help to disentangle the mechanisms underlying neuropathic pain symptoms in painful neuropathies.

    Science.gov (United States)

    Truini, Andrea; Cruccu, Giorgio

    2016-02-01

    Neuropathic pain, ie, pain arising directly from a lesion or disease affecting the somatosensory afferent pathway, manifests with various symptoms, the commonest being ongoing burning pain, electrical shock-like sensations, and dynamic mechanical allodynia. Reliable insights into the mechanisms underlying neuropathic pain symptoms come from diagnostic tests documenting and quantifying somatosensory afferent pathway damage in patients with painful neuropathies. Neurophysiological investigation and skin biopsy studies suggest that ongoing burning pain primarily reflects spontaneous activity in nociceptive-fiber pathways. Electrical shock-like sensations presumably arise from high-frequency ectopic bursts generated in demyelinated, nonnociceptive, Aβ fibers. Although the mechanisms underlying dynamic mechanical allodynia remain debatable, normally innocuous stimuli might cause pain by activating spared and sensitized nociceptive afferents. Extending the mechanistic approach to neuropathic pain symptoms might advance targeted therapy for the individual patient and improve testing for new drugs.

  12. Weight Gain in Breast Cancer Patients on Chemotheraphy: Exploring Hormonal Body Composition and Behavioral Mechanisms

    National Research Council Canada - National Science Library

    Kumar, Nagi

    1999-01-01

    Purpose: The purpose of this study is to prospectively and systematically observe the relative contribution of each viable mechanism such as nutritional intake, activity levels, body composition, hormonal...

  13. PHYSIOLOGICAL QUALITY OF SOYBEAN SEEDS UNDER MECHANICAL INJURIES CAUSED BY COMBINES

    OpenAIRE

    FÁBIO PALCZEWSKI PACHECO; LÚCIA HELENA PEREIRA NÓBREGA; GISLAINE PICOLLO DE LIMA; MÁRCIA SANTORUM; WALTER BOLLER; LORIVAN FORMIGHIERI

    2015-01-01

    The mechanical harvesting causes injuries on seeds and may affect their quality. Different threshing mechanisms and their adjustments may also affect the intensity of impacts that machines cause on seeds. So, this study aimed at diagnosing and evaluating the effect of two combines: the first one with a threshing system of axial flow and the other one with a threshing system of tangential flow, under adjustments of concave opening (10 mm, 30 mm and 10 mm for a combine with axial ...

  14. Uncovering the underlying physical mechanisms of biological systems via quantification of landscape and flux

    International Nuclear Information System (INIS)

    Xu Li; Chu Xiakun; Yan Zhiqiang; Zheng Xiliang; Zhang Kun; Zhang Feng; Yan Han; Wu Wei; Wang Jin

    2016-01-01

    In this review, we explore the physical mechanisms of biological processes such as protein folding and recognition, ligand binding, and systems biology, including cell cycle, stem cell, cancer, evolution, ecology, and neural networks. Our approach is based on the landscape and flux theory for nonequilibrium dynamical systems. This theory provides a unifying principle and foundation for investigating the underlying mechanisms and physical quantification of biological systems. (topical review)

  15. Investigation on the interaction of catalase with sodium lauryl sulfonate and the underlying mechanisms.

    Science.gov (United States)

    Wang, Jing; Jia, Rui; Wang, Jiaxi; Sun, Zhiqiang; Wu, Zitao; Liu, Rutao; Zong, Wansong

    2018-02-01

    As a classic type of anionic surfactants, sodium lauryl sulfonate (SLS) might change the structure and function of antioxidant enzyme catalase (CAT) through their direct interactions. However, the underlying molecular mechanism is still unknown. This study investigated the direct interaction of SLS with CAT molecule and the underlying mechanisms using multi-spectroscopic methods, isothermal titration calorimetry, and molecular docking studies. No obvious effects were observed on CAT structure and activity under low SLS concentration exposure. The particle size of CAT molecule decreased and CAT activity was slightly inhibited under high SLS concentration exposure. SLS prefers to bind to the interface of CAT mainly via van der Waals' forces and hydrogen bonds. Subsequently, SLS interacts with the amino acid residues around the heme groups of CAT via hydrophobic interactions and might inhibit CAT activity. © 2017 Wiley Periodicals, Inc.

  16. Role of Estrogen Receptor Signaling in Breast Cancer Metastasis

    International Nuclear Information System (INIS)

    Roy, S.S.; Vadlamudi, R.K.

    2012-01-01

    Metastatic breast cancer is a life-threatening stage of cancer and is the leading cause of death in advanced breast cancer patients. Estrogen signaling and the estrogen receptor (ER) are implicated in breast cancer progression, and the majority of the human breast cancers start out as estrogen dependent. Accumulating evidence suggests that ER signaling is complex, involving coregulatory proteins and extranuclear actions. ER-coregualtory proteins are tightly regulated under normal conditions with miss expression primarily reported in cancer. Deregulation of ER coregualtors or ER extranuclear signaling has potential to promote metastasis in ER-positive breast cancer cells. This review summarizes the emerging role of ER signaling in promoting metastasis of breast cancer cells, discusses the molecular mechanisms by which ER signaling contributes to metastasis, and explores possible therapeutic targets to block ER-driven metastasis

  17. Breast cancer lung metastasis: Molecular biology and therapeutic implications.

    Science.gov (United States)

    Jin, Liting; Han, Bingchen; Siegel, Emily; Cui, Yukun; Giuliano, Armando; Cui, Xiaojiang

    2018-03-26

    Distant metastasis accounts for the vast majority of deaths in patients with cancer. Breast cancer exhibits a distinct metastatic pattern commonly involving bone, liver, lung, and brain. Breast cancer can be divided into different subtypes based on gene expression profiles, and different breast cancer subtypes show preference to distinct organ sites of metastasis. Luminal breast tumors tend to metastasize to bone while basal-like breast cancer (BLBC) displays a lung tropism of metastasis. However, the mechanisms underlying this organ-specific pattern of metastasis still remain to be elucidated. In this review, we will summarize the recent advances regarding the molecular signaling pathways as well as the therapeutic strategies for treating breast cancer lung metastasis.

  18. CIRCADIAN REGULATION METABOLIC SIGNALING MECHANISMS OF HUMAN BREAST CANCER GROWTH BY THE NOCTURNAL MELATONIN SIGNAL AND THE CONSEQUENCES OF ITS DISRUPTION BY LIGHT AT NIGHT

    Science.gov (United States)

    Blask, David E.; Hill, Steven M.; Dauchy, Robert T.; Xiang, Shulin; Yuan, Lin; Duplessis, Tamika; Mao, Lulu; Dauchy, Erin; Sauer, Leonard A.

    2011-01-01

    This review article discusses recent work on the melatonin-mediated circadian regulation and integration of molecular, dietary and metabolic signaling mechanisms involved in human breast cancer growth and the consequences of circadian disruption by exposure to light-at-night (LAN). The antiproliferative effects of the circadian melatonin signal are mediated through a major mechanism involving the activation of MT1 melatonin receptors expressed in human breast cancer cell lines and xenografts. In estrogen receptor (ERα+) human breast cancer cells, melatonin suppresses both ERα mRNA expression and estrogen-induced transcriptional activity of the ERα via MT1-induced activation of Gαi2 signaling and reduction of cAMP levels. Melatonin also regulates the transactivation of additional members of the steroid hormone/nuclear receptor super-family, enzymes involved in estrogen metabolism, expression/activation of telomerase and the expression of core clock and clock-related genes. The anti-invasive/anti-metastatic actions of melatonin involve the blockade of p38 phosphorylation and the expression of matrix metalloproteinases. Melatonin also inhibits the growth of human breast cancer xenografts via another critical pathway involving MT1-mediated suppression of cAMP leading to blockade of linoleic acid (LA) uptake and its metabolism to the mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Down-regulation of 13-HODE reduces the activation of growth factor pathways supporting cell proliferation and survival. Experimental evidence in rats and humans indicating that LAN-induced circadian disruption of the nocturnal melatonin signal activates human breast cancer growth, metabolism and signaling provides the strongest mechanistic support, thus far, for population and ecological studies demonstrating elevated breast cancer risk in night shift workers and other individuals increasingly exposed to LAN. PMID:21605163

  19. Model test study of evaporation mechanism of sand under constant atmospheric condition

    OpenAIRE

    CUI, Yu Jun; DING, Wenqi; SONG, Weikang

    2014-01-01

    The evaporation mechanism of Fontainebleau sand using a large-scale model chamber is studied. First, the evaporation test on a layer of water above sand surface is performed under various atmospheric conditions, validating the performance of the chamber and the calculation method of actual evaporation rate by comparing the calculated and measured cumulative evaporations. Second,the evaporation test on sand without water layer is conducted under constant atmospheric condition. Both the evoluti...

  20. Crack formation and crack propagation under multiaxial mechanical and thermal stresses. Proceedings

    International Nuclear Information System (INIS)

    1993-01-01

    The 25th meeting of the DV Fracture Group was held on 16/17 February 1993 at Karlsruhe Technical University. The main topic, ''Crack formation and crack propagation under multiaxial mechanical and thermal stresses'', was discussed by five invited papers (by K.J. Miller, D. Loehe, H.A. Richard, W. Brocks, A. Brueckner-Foit) and 23 short papers. The other 21 papers were devoted to various domains of fracture mechanics, with emphasis on elastoplastic fracture mechanics. (orig./MM) [de

  1. Ultrastructural changes of cell walls under intense mechanical treatment of selective plant raw material

    International Nuclear Information System (INIS)

    Bychkov, Aleksey L.; Ryabchikova, E.I.; Korolev, K.G.; Lomovsky, O.I.

    2012-01-01

    Structural changes of cell walls under intense mechanical treatment of corn straw and oil-palm fibers were studied by electron and light microscopy. Differences in the character of destruction of plant biomass were revealed, and the dependence of destruction mechanisms on the structure of cell walls and lignin content was demonstrated. We suggest that the high reactivity of the particles of corn straw (about 18% of lignin) after intense mechanical treatment is related to disordering of cell walls and an increase of the surface area, while in the case of oil palm (10% of lignin) the major contribution into an increase in the reactivity is made by an increase of surface area. -- Highlights: ► Structure of cell walls determines the processes of plant materials' destruction. ► Ultrastructure of highly lignified materials strongly disordering by mechanical action. ► Ultrastructure of low-lignified materials is not disordering by mechanical action.

  2. Effectiveness of core biopsy for screen-detected breast lesions under 10 mm: implications for surgical management.

    Science.gov (United States)

    Farshid, Gelareh; Downey, Peter; Pieterse, Steve; Gill, P Grantley

    2017-09-01

    Technical advances have improved the detection of small mammographic lesions. In the context of mammographic screening, accurate sampling of these lesions by percutaneous biopsy is crucial in limiting diagnostic surgical biopsies, many of which show benign results. Women undergoing core biopsy between January 1997 and December 2007 for core histology, 345 women (43.0%) were immediately cleared of malignancy and 300 (37.4%) were referred for definitive cancer treatment. A further 157 women (19.6%) required diagnostic surgical biopsy because of indefinite or inadequate core results or radiological-pathological discordance, and one woman (0.1%) needed further imaging in 12 months. The open biopsies were malignant in 46 (29.3%) cases. The positive predictive value of malignant core biopsy was 100%. The negative predictive value for benign core results was 97.7%, and the false-negative rate was 2.6%. The lesion could not be visualized after core biopsy in 5.1% of women and in 4.0% of women with malignant core biopsies excision specimens did not contain residual malignancy. Excessive delays in surgery because of complications of core biopsy were not reported. Even at this small size range, core biopsy evaluation of screen-detected breast lesions is highly effective and accurate. A lesion miss rate of 3.1% and under-representation of lesions on core samples highlight the continued need for multidisciplinary collaboration and selective use of diagnostic surgical biopsy. © 2015 Royal Australasian College of Surgeons.

  3. Breast Self- Examination Contradiction

    OpenAIRE

    Ayla Akkas Gursoy

    2008-01-01

    Breast cancer is very important health problem among women in the World and Turkey. Although treatment chance is very rising and survival is getting longer thanks to early diagnosis in breast cancer. Some discussion is making related to breast self examination which is one of the early detection methods in recent years. This article consider the discussions about breast self examination under the historical development light. [TAF Prev Med Bull 2008; 7(3.000): 257-260

  4. Breast Self- Examination Contradiction

    Directory of Open Access Journals (Sweden)

    Ayla Akkas Gursoy

    2008-06-01

    Full Text Available Breast cancer is very important health problem among women in the World and Turkey. Although treatment chance is very rising and survival is getting longer thanks to early diagnosis in breast cancer. Some discussion is making related to breast self examination which is one of the early detection methods in recent years. This article consider the discussions about breast self examination under the historical development light. [TAF Prev Med Bull 2008; 7(3.000: 257-260

  5. Mechanism of c-Src Synergy with the EGFR in Breast Cancer

    National Research Council Canada - National Science Library

    Tice, David

    1997-01-01

    .... To gain further insights into the mechanism of c-Src synergy with the EGFR, stable cell lines containing various c-Src mutants and overexpressed wt EGFR were generated and examined for tumorigenic...

  6. Furanodiene Induces Extrinsic and Intrinsic Apoptosis in Doxorubicin-Resistant MCF-7 Breast Cancer Cells via NF-κB-Independent Mechanism.

    Science.gov (United States)

    Zhong, Zhang-Feng; Yu, Hai-Bing; Wang, Chun-Ming; Qiang, Wen-An; Wang, Sheng-Peng; Zhang, Jin-Ming; Yu, Hua; Cui, Liao; Wu, Tie; Li, De-Qiang; Wang, Yi-Tao

    2017-01-01

    Chemotherapy is used as a primary approach in cancer treatment after routine surgery. However, chemo-resistance tends to occur when chemotherapy is used clinically, resulting in poor prognosis and recurrence. Currently, Chinese medicine may provide insight into the design of new therapies to overcome chemo-resistance. Furanodiene, as a heat-sensitive sesquiterpene, is isolated from the essential oil of Rhizoma Curcumae . Even though mounting evidence claiming that furanodiene possesses anti-cancer activities in various types of cancers, the underlying mechanisms against chemo-resistant cancer are not fully clear. Our study found that furanodiene could display anti-cancer effects by inhibiting cell viability, inducing cell cytotoxicity, and suppressing cell proliferation in doxorubicin-resistant MCF-7 breast cancer cells. Furthermore, furanodiene preferentially causes apoptosis by interfering with intrinsic/extrinsic-dependent and NF-κB-independent pathways in doxorubicin-resistant MCF-7 cells. These observations also prompt that furanodiene may be developed as a promising natural product for multidrug-resistant cancer therapy in the future.

  7. Camel Milk Triggers Apoptotic Signaling Pathways in Human Hepatoma HepG2 and Breast Cancer MCF7 Cell Lines through Transcriptional Mechanism

    Directory of Open Access Journals (Sweden)

    Hesham M. Korashy

    2012-01-01

    Full Text Available Few published studies have reported the use of crude camel milk in the treatment of stomach infections, tuberculosis and cancer. Yet, little research was conducted on the effect of camel milk on the apoptosis and oxidative stress associated with human cancer. The present study investigated the effect and the underlying mechanisms of camel milk on the proliferation of human cancer cells using an in vitro model of human hepatoma (HepG2 and human breast (MCF7 cancer cells. Our results showed that camel milk, but not bovine milk, significantly inhibited HepG2 and MCF7 cells proliferation through the activation of caspase-3 mRNA and activity levels, and the induction of death receptors in both cell lines. In addition, Camel milk enhanced the expression of oxidative stress markers, heme oxygenase-1 and reactive oxygen species production in both cells. Mechanistically, the increase in caspase-3 mRNA levels by camel milk was completely blocked by the transcriptional inhibitor, actinomycin D; implying that camel milk increased de novo RNA synthesis. Furthermore, Inhibition of the mitogen activated protein kinases differentially modulated the camel milk-induced caspase-3 mRNA levels. Taken together, camel milk inhibited HepG2 and MCF7 cells survival and proliferation through the activation of both the extrinsic and intrinsic apoptotic pathways.

  8. Asymmetric migration of human keratinocytes under mechanical stretch and cocultured fibroblasts in a wound repair model.

    Directory of Open Access Journals (Sweden)

    Dongyuan Lü

    Full Text Available Keratinocyte migration during re-epithelization is crucial in wound healing under biochemical and biomechanical microenvironment. However, little is known about the underlying mechanisms whereby mechanical tension and cocultured fibroblasts or keratinocytes modulate the migration of keratinocytes or fibroblasts. Here we applied a tensile device together with a modified transwell assay to determine the lateral and transmembrane migration dynamics of human HaCaT keratinocytes or HF fibroblasts. A novel pattern of asymmetric migration was observed for keratinocytes when they were cocultured with non-contact fibroblasts, i.e., the accumulative distance of HaCaT cells was significantly higher when moving away from HF cells or migrating from down to up cross the membrane than that when moving close to HF cells or when migrating from up to down, whereas HF migration was symmetric. This asymmetric migration was mainly regulated by EGF derived from fibroblasts, but not transforming growth factor α or β1 production. Mechanical stretch subjected to fibroblasts fostered keratinocyte asymmetric migration by increasing EGF secretion, while no role of mechanical stretch was found for EGF secretion by keratinocytes. These results provided a new insight into understanding the regulating mechanisms of two- or three-dimensional migration of keratinocytes or fibroblasts along or across dermis and epidermis under biomechanical microenvironment.

  9. Mechanisms underlying prorenin actions on hypothalamic neurons implicated in cardiometabolic control

    Directory of Open Access Journals (Sweden)

    Soledad Pitra

    2016-10-01

    Conclusions: We identified novel neuronal targets and cellular mechanisms underlying PR/PRR actions in critical hypothalamic neurons involved in cardiometabolic regulation. This fundamental mechanistic information regarding central PR/PRR actions is essential for the development of novel RAS-based therapeutic targets for the treatment of cardiometabolic disorders in obesity and hypertension.

  10. Nonlinear Dynamic Analysis of Telescopic Mechanism for Truss Structure Bridge Inspection Vehicle Under Pedestrian Excitation

    Directory of Open Access Journals (Sweden)

    Wenwen Sui

    Full Text Available Abstract Nonlinear dynamic analysis of an axially moving telescopic mechanism for truss structure bridge inspection vehicle under pedestrian excitation is carried out. A biomechanically inspired inverted-pendulum model is utilized to simplify the pedestrian. The nonlinear equations of motion for the beam-pedestrian system are derived using the Hamilton's principle. The equations are transformed into two ordinary differential equations by applying the Galerkin's method at the first two orders. The solutions to the equations are acquired by using the Newmark-β method associated with the Newton-Raphson method. The time-dependent feature of the eigenfunctions for the two beams are taken into consideration in the solutions. Accordingly, the equations of motion for a simplified system, in which the pedestrian is regarded as moving cart, are given. In the numerical examples, dynamic responses of the telescopic mechanism in eight conditions of different beam-telescoping and pedestrian-moving directions are simulated. Comparisons between the vibrations of the beams under pedestrian excitation and corresponding moving cart are carried out to investigate the influence of the pedestrian excitation on the telescopic mechanism. The results show that the displacement of the telescopic mechanism under pedestrian excitation is smaller than that under moving cart especially when the pedestrian approaches the beams end. Additionally, compared with moving cart, the pedestrian excitation can effectively strengthen the vibration when the beam extension is small or when the pedestrian is close to the beams end.

  11. Unraveling the mechanisms underlying postural instability in Parkinson's disease using dynamic posturography

    NARCIS (Netherlands)

    Nonnekes, J.H.; Kam, D. de; Geurts, A.C.; Weerdesteijn, V.G.M.; Bloem, B.R.

    2013-01-01

    Postural instability, one of the cardinal symptoms of Parkinson's disease (PD), has devastating consequences for affected patients. Better strategies to prevent falls are needed, but this calls for an improved understanding of the complex mechanisms underlying postural instability. We must also

  12. Mechanisms underlying the associations of maternal age with adverse perinatal outcomes

    DEFF Research Database (Denmark)

    Lawlor, Debbie A; Mortensen, Laust; Andersen, Anne-Marie Nybo

    2011-01-01

    The mechanisms underlying the association between maternal age (both young and older maternal age) and adverse perinatal outcomes are unclear. Methods We examined the association of maternal age at first birth with preterm birth (<37 weeks gestation) and small for gestational age (SGA) in a cohor...

  13. The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF

    Science.gov (United States)

    Cheng, Ying; Shao, Can; Lathrop, Quinn N.

    2016-01-01

    Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable…

  14. Biological mechanisms underlying the role of physical fitness in health and resilience

    OpenAIRE

    Silverman, Marni N.; Deuster, Patricia A.

    2014-01-01

    Physical fitness, achieved through regular exercise and/or spontaneous physical activity, confers resilience by inducing positive psychological and physiological benefits, blunting stress reactivity, protecting against potentially adverse behavioural and metabolic consequences of stressful events and preventing many chronic diseases. In this review, we discuss the biological mechanisms underlying the beneficial effects of physical fitness on mental and physical health. Physical fitness appear...

  15. Second primary cancers after adjuvant radiotherapy in early breast cancer patients: A national population based study under the Danish Breast Cancer Cooperative Group (DBCG)

    International Nuclear Information System (INIS)

    Grantzau, Trine; Mellemkjær, Lene; Overgaard, Jens

    2013-01-01

    Background and purpose: To analyze the long-term risk of second primary solid non-breast cancer in a national population-based cohort of 46,176 patients treated for early breast cancer between 1982 and 2007. Patients and methods: All patients studied were treated according to the national guidelines of the Danish Breast Cancer Cooperative Group. The risk of second primary cancers was estimated by Standardised incidence ratios (SIRs) and multivariate Cox regression models were used to estimate adjusted hazard ratios (HR) among irradiated women compared to non-irradiated. All irradiated patients were treated on linear accelerators. Second cancers were a priori categorized into two groups; radiotherapy-associated- (oesophagus, lung, heart/mediastinum, pleura, bones, and connective tissue) and non-radiotherapy-associated sites (all other cancers). Results: 2358 second cancers had occurred during the follow-up. For the radiotherapy-associated sites the HR among irradiated women was 1.34 (95% CI 1.11–1.61) with significantly increased HRs for the time periods of 10–14 years (HR 1.55; 95% CI 1.08–2.24) and ⩾15 years after treatment (HR 1.79; 95% CI 1.14–2.81). There was no increased risk for the non-radiotherapy-associated sites (HR 1.04; 95% CI 0.94–1.1). The estimated attributable risk related to radiotherapy for the radiotherapy-associated sites translates into one radiation-induced second cancer in every 200 women treated with radiotherapy. Conclusions: Radiotherapy treated breast cancer patients have a small but significantly excess risk of second cancers

  16. The effect of carbon dioxide on the shelf life of ready-to-eat shredded chicken breast stored under refrigeration.

    Science.gov (United States)

    Rodriguez, M B R; Junior, C A Conte; Carneiro, C S; Franco, R M; Mano, S B

    2014-01-01

    The objective of the present study was to determine the shelf life of ready-to-eat cooked chicken breast fillets (shredded) stored in atmospheres that were modified with different concentrations of CO2 and to establish a relationship between the concentration of this gas and bacterial growth. The samples were divided into 7 groups with different packaging conditions: aerobiosis, vacuum, and 10, 30, 50, 70, and 90% CO2 (with the remaining volume filled with N2). All of the samples were stored at 4 ± 2°C for 28 d. During this period, pH tests and counts of aerobic heterotrophic mesophyll bacteria (AHMB), aerobic heterotrophic psychotropic bacteria (AHPB), Enterobacteriaceae, and lactic acid bacteria (LAB) were performed, and the gas compositions of the packaging atmospheres were verified. The pH of the aerobic packages increased during storage. However, the other treatments resulted in the opposite trend, with the CO2 concentration decreasing over the first 24 h and then remaining constant until the end of experiment. A gradual increase in the AHMB, AHPB, Enterobacteriaceae, and LAB counts was observed during storage; this increase was faster in the meat that was packed under aerobiosis conditions than in the other treatments. The treatments with a CO2 concentration above 10% exhibited lower Enterobacteriaceae growth, whereas LAB growth was discrete in all of the treatments, independent of the CO2 concentration. The shelf life of the samples packed with 90% CO2 was 28 d. Based on the AHMB and AHPB counts, the shelf life was 3 times longer than for the samples packed under aerobiosis conditions (9 d). The increased package CO2 concentration caused a reduction in the growth rate of the examined bacteria (r = 0.99), and treatment with 90% CO2 appears promising as a method with which to increase the product's shelf life.

  17. Mechanical behavior of glass/epoxy composite laminate with varying amount of MWCNTs under different loadings

    Science.gov (United States)

    Singh, K. K.; Rawat, Prashant

    2018-05-01

    This paper investigates the mechanical response of three phased (glass/MWCNTs/epoxy) composite laminate under three different loadings. Flexural strength, short beam strength and low-velocity impact (LVI) testing are performed to find an optimum doping percentage value for maximum enhancement in mechanical properties. In this work, MWCNTs were used as secondary reinforcement for three-phased composite plate. MWCNT doping was done in a range of 0–4 wt% of the thermosetting matrix system. Symmetrical design eight layered glass/epoxy laminate with zero bending extension coupling laminate was fabricated using a hybrid method i.e. hand lay-up technique followed by vacuum bagging method. Ranging analysis of MWCNT mixing highlighted the enhancement in flexural, short beam strength and improvement in damage tolerance under LVI loading. While at higher doping wt%, agglomeration of MWCNTs are observed. Results of mechanical testing proposed an optimized doping value for maximum strength and damage resistance of the laminate.

  18. Intercomparison of chemical mechanisms for air quality policy formulation and assessment under North American conditions.

    Science.gov (United States)

    Derwent, Richard

    2017-07-01

    The intercomparison of seven chemical mechanisms for their suitability for air quality policy formulation and assessment is described. Box modeling techniques were employed using 44 sets of background environmental conditions covering North America to constrain the chemical development of the longer lived species. The selected mechanisms were modified to enable an unbiased assessment of the adequacy of the parameterizations of photochemical ozone production from volatile organic compound (VOC) oxidation in the presence of NO x . Photochemical ozone production rates responded differently to 30% NO x and VOC reductions with the different mechanisms, despite the striking similarities between the base-case ozone production rates. The 30% reductions in NO x and VOCs also produced changes in OH. The responses in OH to 30% reductions in NO x and VOCs appeared to be more sensitive to mechanism choice, compared with the responses in the photochemical ozone production rates. Although 30% NO x reductions generally led to decreases in OH, 30% reductions in VOCs led to increases in OH, irrespective of mechanism choice and background environmental conditions. The different mechanisms therefore gave different OH responses to NO x and VOC reductions and so would give different responses in terms of changes in the fate and behavior of air toxics, acidification and eutrophication, and fine particle formation compared with others, in response to ozone control strategies. Policymakers need to understand that there are likely to be inherent differences in the responses to ozone control strategies between different mechanisms, depending on background environmental conditions and the extents of NO x and VOC reductions under consideration. The purpose of this paper is to compare predicted ozone responses to NO x and VOC reductions with seven chemical mechanisms under North American conditions. The good agreement found between the tested mechanisms should provide some support for their

  19. Mechanical Behavior of Shale Rock under Uniaxial Cyclic Loading and Unloading Condition

    Directory of Open Access Journals (Sweden)

    Baoyun Zhao

    2018-01-01

    Full Text Available In order to investigate the mechanical behavior of shale rock under cyclic loading and unloading condition, two kinds of incremental cyclic loading tests were conducted. Based on the result of the short-term uniaxial incremental cyclic loading test, the permanent residual strain, modulus, and damage evolution were analyzed firstly. Results showed that the relationship between the residual strains and the cycle number can be expressed by an exponential function. The deformation modulus E50 and elastic modulus ES first increased and then decreased with the peak stress under the loading condition, and both of them increased approximately linearly with the peak stress under the unloading condition. On the basis of the energy dissipation, the damage variables showed an exponential increasing with the strain at peak stress. The creep behavior of the shale rock was also analyzed. Results showed that there are obvious instantaneous strain, decay creep, and steady creep under each stress level and the specimen appears the accelerated creep stage under the 4th stress of 51.16 MPa. Based on the characteristics of the Burgers creep model, a viscoelastic-plastic creep model was proposed through viscoplastic mechanics, which agrees very well with the experimental results and can better describe the creep behavior of shale rock better than the Burgers creep model. Results can provide some mechanics reference evidence for shale gas development.

  20. Feeding Problems and Their Underlying Mechanisms in the Esophageal Atresia–Tracheoesophageal Fistula Patient

    Science.gov (United States)

    Mahoney, Lisa; Rosen, Rachel

    2017-01-01

    Feeding difficulties such as dysphagia, coughing, choking, or vomiting during meals, slow eating, oral aversion, food refusal, and stressful mealtimes are common in children with repaired esophageal atresia (EA) and the reasons for this are often multifactorial. The aim of this review is to describe the possible underlying mechanisms contributing to feeding difficulties in patients with EA and approaches to management. Underlying mechanisms for these feeding difficulties include esophageal dysphagia, oropharyngeal dysphagia and aspiration, and aversions related to prolonged gastrostomy tube feeding. The initial diagnostic evaluation for feeding difficulties in a patient with EA may involve an esophagram, videofluoroscopic imaging or fiberoptic endoscopic evaluation during swallowing, upper endoscopy with biopsies, pH-impedance testing, and/or esophageal motility studies. The main goal of management is to reduce the factors contributing to feeding difficulties and may include reducing esophageal stasis, maximizing reflux therapies, treating underlying lung disease, dilating strictures, and altering feeding methods, routes, or schedules. PMID:28620597

  1. Fumonisin B1 contamination in breast milk and its exposure in infants under 6 months of age in Rombo, Northern Tanzania.

    Science.gov (United States)

    Magoha, Happy; De Meulenaer, Bruno; Kimanya, Martin; Hipolite, Danstan; Lachat, Carl; Kolsteren, Patrick

    2014-12-01

    The carry-over of fumonisin B1 from contaminated feed into dairy milk also suggests its carry-over from contaminated food into breast milk. This study assessed fumonisin B1 contamination in breast milk and associated exposures of infants under 6 months of age. Breast milk samples were collected from 131 lactating mothers and the weight of their infants was measured during the first month of lactation. Fumonisin B1 was extracted using methanol:acetone, cleaned up with Strong Anion Exchange columns and quantified by HPLC. Fumonisin B1 exposure in each child was estimated using deterministic approach. Out of the 131 samples, 58 (44.3%) contained fumonisin B1 at levels ranging from 6.57 to 471.05 ng/ml. Of the contaminated samples, 10.3% had fumonisin B1 levels above the EU limit of 200 ppb for fumonisins in infants' food. Exposure in the infants ranged from 0.78 to 64.93 µg/kg body weight (bw) per day (median, 3 µg/kg bw/day) and exceeded the provisional maximum tolerable limit of 2 µg/kg bw/day in 29% of the infants. In conclusion, breast milk from mothers in Northern Tanzania is contaminated with fumonisins at levels that lead to unacceptable exposures in infants. Strategies to prevent lactating mothers from fumonisin exposure are urgently needed to minimise fumonisin exposure in infants. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Pro-oncogene Pokemon promotes breast cancer progression by upregulating survivin expression

    OpenAIRE

    Zu, Xuyu; Ma, Jun; Liu, Hongxia; Liu, Feng; Tan, Chunyan; Yu, Lingling; Wang, Jue; Xie, Zhenhua; Cao, Deliang; Jiang, Yuyang

    2011-01-01

    Introduction Pokemon is an oncogenic transcription factor involved in cell growth, differentiation and oncogenesis, but little is known about its role in human breast cancer. In this study, we aimed to reveal the role of Pokemon in breast cancer progression and patient survival and to understand its underlying mechanisms. Methods Tissue microarray analysis of breast cancer tissues from patients with complete clinicopathological data and more than 20 years of follow-up were used to evaluate Po...

  3. Transformational Leadership and Organizational Citizenship Behavior: A Meta-Analytic Test of Underlying Mechanisms.

    Science.gov (United States)

    Nohe, Christoph; Hertel, Guido

    2017-01-01

    Based on social exchange theory, we examined and contrasted attitudinal mediators (affective organizational commitment, job satisfaction) and relational mediators (trust in leader, leader-member exchange; LMX) of the positive relationship between transformational leadership and organizational citizenship behavior (OCB). Hypotheses were tested using meta-analytic path models with correlations from published meta-analyses (761 samples with 227,419 individuals overall). When testing single-mediator models, results supported our expectations that each of the mediators explained the relationship between transformational leadership and OCB. When testing a multi-mediator model, LMX was the strongest mediator. When testing a model with a latent attitudinal mechanism and a latent relational mechanism, the relational mechanism was the stronger mediator of the relationship between transformational leadership and OCB. Our findings help to better understand the underlying mechanisms of the relationship between transformational leadership and OCB.

  4. Effects of delaying transplanting on agronomic traits and grain yield of rice under mechanical transplantation pattern.

    Directory of Open Access Journals (Sweden)

    Qihua Liu

    Full Text Available A delay in the mechanical transplantation (MT of rice seedlings frequently occurs in Huanghuai wheat-rice rotation cropping districts of China, due to the late harvest of wheat, the poor weather conditions and the insufficiency of transplanters, missing the optimum transplanting time and causing seedlings to age. To identify how delaying transplanting rice affects the agronomic characteristics including the growth duration, photosynthetic productivity and dry matter remobilization efficiency and the grain yield under mechanical transplanting pattern, an experiment with a split-plot design was conducted over two consecutive years. The main plot includes two types of cultivation: mechanical transplanting and artificial transplanting (AT. The subplot comprises four japonica rice cultivars. The results indicate that the rice jointing, booting, heading and maturity stages were postponed under MT when using AT as a control. The tiller occurrence number, dry matter weight per tiller, accumulative dry matter for the population, leaf area index, crop growth rate, photosynthetic potential, and dry matter remobilization efficiency of the leaf under MT significantly decreased compared to those under AT. In contrast, the reduction rate of the leaf area during the heading-maturity stage was markedly enhanced under MT. The numbers of effective panicles and filled grains per panicle and the grain yield significantly decreased under MT. A significant correlation was observed between the dry matter production, remobilization and distribution characteristics and the grain yield. We infer that, as with rice from old seedlings, the decrease in the tiller occurrence, the photosynthetic productivity and the assimilate remobilization efficiency may be important agronomic traits that are responsible for the reduced grain yield under MT.

  5. [Study on mechanism of SOM stabilization of paddy soils under long-term fertilizations].

    Science.gov (United States)

    Luo, Lu; Zhou, Ping; Tong, Cheng-Li; Shi, Hui; Wu, Jin-Shui; Huang, Tie-Ping

    2013-02-01

    Fourier transform infrared spectroscopy (FTIR) was applied to study the structure of soil organic matter (SOM) of paddy soils under long-term different fertilization treatments. The aim was to clarify the different distribution of SOM between different fertilization methods and between topsoil and subsoil, and to explore the stability mechanism of SOM under different fertilization treatments. The results showed that the content of topsoil organic carbon (SOC) was the highest under organic-inorganic fertilizations, with the increment of SOC by 18.5%, 12.9% and 18.4% under high organic manure (HOM), low organic manure (LOM) and straw returning (STW) respectively compared with no fertilization treatment (CK). The long-term fertilizations also changed the chemical structure of SOM. As compared with CK, different fertilization treatments increased the functional group absorbing intensity of chemical resistance compounds (aliphatic, aromaticity), carbohydrate and organo-silicon compounds, which was the most distinctive under treatments of HOM, LOM and STW. For example, the absorbing intensity of alkyl was 0.30, 0.25 and 0.29 under HOM, LOM and STW, respectively. These values were increased by 87% , 56% and 81% as compared with that under CK treatment. The functional group absorbing intensity of SOM in the topsoil was stronger than that in the subsoil, with the most distinctive difference under HOM, LOM and STW treatments. The present research indicated that the enhanced chemical resistance of functional group of SOM may contribute to the high contents of SOC in the paddy soils under long-term organic-inorganic fertilizations, which also suggested a chemical stabilization mechanism of SOM in the paddy soils.

  6. Carbon Footprint Management of Road Freight Transport under the Carbon Emission Trading Mechanism

    Directory of Open Access Journals (Sweden)

    Jin Li

    2015-01-01

    Full Text Available Growing concern over environmental issues has considerably increased the number of regulations and legislation that aim to curb carbon emissions. Carbon emission trading mechanism, which is one of the most effective means, has been broadly adopted by several countries. This paper presents a road truck routing problem under the carbon emission trading mechanism. By introducing a calculation method of carbon emissions that considers the load and speed of the vehicle among other factors, a road truck routing optimizing model under the cap and trade mechanism based on the Travelling Salesman Problem (TSP is described. Compared with the classical TSP model that only considers the economic cost, this model suggests that the truck routing decision under the cap and trade mechanism is more effective in reducing carbon emissions. A modified tabu search algorithm is also proposed to obtain solutions within a reasonable amount of computation time. We theoretically and numerically examine the impacts of carbon trading, carbon cap, and carbon price on truck routing decision, carbon emissions, and total cost. From the results of numerical experiments, we derive interesting observations about how to control the total cost and reduce carbon emissions.

  7. Fatigue response of a PZT multilayer actuator under high-field electric cycling with mechanical preload

    Science.gov (United States)

    Wang, Hong; Wereszczak, Andrew A.; Lin, Hua-Tay

    2009-01-01

    An electric fatigue test system was developed for evaluating the reliability of piezoelectric actuators with a mechanical loading capability. Fatigue responses of a lead zirconate titanate (PZT) multilayer actuator with a platethrough electrode configuration were studied under an electric field (1.7 times that of the coercive field of PZT material) and a concurrent mechanical preload (30.0 MPa). A total of 109 cycles was carried out. Variations in charge density and mechanical strain under the high electric field and constant mechanical loads were observed during the fatigue test. The dc and the first harmonic (at 10 Hz) dielectric and piezoelectric coefficients were subsequently characterized using fast Fourier transformation. Both the dielectric and the piezoelectric coefficients exhibited a monotonic decrease prior to 2.86×108 cycles under certain preloading conditions, and then fluctuated. Both the dielectric loss tangent and the piezoelectric loss tangent also fluctuated after a decrease. The results are interpreted and discussed with respect to domain wall activities, microdefects, and other anomalies.

  8. A novel gene expression signature for bone metastasis in breast carcinomas

    NARCIS (Netherlands)

    Savci-Heijink, C. Dilara; Halfwerk, Hans; Koster, Jan; van de Vijver, Marc J.

    2016-01-01

    Metastatic cancer remains the leading cause of death for patients with breast cancer. To understand the mechanisms underlying the development of distant metastases to specific sites is therefore important and of potential clinical value. From 157 primary breast tumours of the patients with known

  9. Inspection Mechanism and Experimental Study of Prestressed Reverse Tension Method under PC Beam Bridge Anchorage

    Science.gov (United States)

    Peng, Zhang

    2018-03-01

    the prestress under anchorage is directly related to the structural security and performance of PC beam bridge. The reverse tension method is a kind of inspection which confirms the prestress by exerting reversed tension load on the exposed prestressing tendon of beam bridge anchoring system. The thesis elaborately expounds the inspection mechanism and mechanical effect of reverse tension method, theoretically analyzes the influential elements of inspection like tool anchorage deformation, compression of conjuncture, device glide, friction of anchorage loop mouth and elastic compression of concrete, and then presents the following formula to calculate prestress under anchorage. On the basis of model experiment, the thesis systematically studies some key issues during the reverse tension process of PC beam bridge anchorage system like the formation of stress-elongation curve, influential factors, judgment method of prestress under anchorage, variation trend and compensation scale, verifies the accuracy of mechanism analysis and demonstrates: the prestress under anchorage is less than or equal to 75% of the ultimate strength of prestressing tendon, the error of inspect result is less than 1%, which can meet with the demands of construction. The research result has provided theoretical basis and technical foundation for the promotion and application of reverse tension in bridge construction.

  10. Dynamic Response and Failure Mechanism of Brittle Rocks Under Combined Compression-Shear Loading Experiments

    Science.gov (United States)

    Xu, Yuan; Dai, Feng

    2018-03-01

    A novel method is developed for characterizing the mechanical response and failure mechanism of brittle rocks under dynamic compression-shear loading: an inclined cylinder specimen using a modified split Hopkinson pressure bar (SHPB) system. With the specimen axis inclining to the loading direction of SHPB, a shear component can be introduced into the specimen. Both static and dynamic experiments are conducted on sandstone specimens. Given carefully pulse shaping, the dynamic equilibrium of the inclined specimens can be satisfied, and thus the quasi-static data reduction is employed. The normal and shear stress-strain relationships of specimens are subsequently established. The progressive failure process of the specimen illustrated via high-speed photographs manifests a mixed failure mode accommodating both the shear-dominated failure and the localized tensile damage. The elastic and shear moduli exhibit certain loading-path dependence under quasi-static loading but loading-path insensitivity under high loading rates. Loading rate dependence is evidently demonstrated through the failure characteristics involving fragmentation, compression and shear strength and failure surfaces based on Drucker-Prager criterion. Our proposed method is convenient and reliable to study the dynamic response and failure mechanism of rocks under combined compression-shear loading.

  11. Molecular mechanisms underlying the emergence of bacterial pathogens: an ecological perspective.

    Science.gov (United States)

    Bartoli, Claudia; Roux, Fabrice; Lamichhane, Jay Ram

    2016-02-01

    The rapid emergence of new bacterial diseases negatively affects both human health and agricultural productivity. Although the molecular mechanisms underlying these disease emergences are shared between human- and plant-pathogenic bacteria, not much effort has been made to date to understand disease emergences caused by plant-pathogenic bacteria. In particular, there is a paucity of information in the literature on the role of environmental habitats in which plant-pathogenic bacteria evolve and on the stress factors to which these microbes are unceasingly exposed. In this microreview, we focus on three molecular mechanisms underlying pathogenicity in bacteria, namely mutations, genomic rearrangements and the acquisition of new DNA sequences through horizontal gene transfer (HGT). We briefly discuss the role of these mechanisms in bacterial disease emergence and elucidate how the environment can influence the occurrence and regulation of these molecular mechanisms by directly impacting disease emergence. The understanding of such molecular evolutionary mechanisms and their environmental drivers will represent an important step towards predicting bacterial disease emergence and developing sustainable management strategies for crops. © 2015 BSPP AND JOHN WILEY & SONS LTD.

  12. An analytical model of the mechanical properties of bulk coal under confined stress

    Science.gov (United States)

    Wang, G.X.; Wang, Z.T.; Rudolph, V.; Massarotto, P.; Finley, R.J.

    2007-01-01

    This paper presents the development of an analytical model which can be used to relate the structural parameters of coal to its mechanical properties such as elastic modulus and Poisson's ratio under a confined stress condition. This model is developed primarily to support process modeling of coalbed methane (CBM) or CO2-enhanced CBM (ECBM) recovery from coal seam. It applied an innovative approach by which stresses acting on and strains occurring in coal are successively combined in rectangular coordinates, leading to the aggregated mechanical constants. These mechanical properties represent important information for improving CBM/ECBM simulations and incorporating within these considerations of directional permeability. The model, consisting of constitutive equations which implement a mechanically consistent stress-strains correlation, can be used as a generalized tool to study the mechanical and fluid behaviors of coal composites. An example using the model to predict the stress-strain correlation of coal under triaxial confined stress by accounting for the elastic and brittle (non-elastic) deformations is discussed. The result shows a good agreement between the prediction and the experimental measurement. ?? 2007 Elsevier Ltd. All rights reserved.

  13. Mechanical and electronic properties of monolayer and bilayer phosphorene under uniaxial and isotropic strains.

    Science.gov (United States)

    Hu, Ting; Han, Yang; Dong, Jinming

    2014-11-14

    The mechanical and electronic properties of both the monolayer and bilayer phosphorenes under either isotropic or uniaxial strain have been systematically investigated using first-principles calculations. It is interesting to find that: 1) Under a large enough isotropic tensile strain, the monolayer phosphorene would lose its pucker structure and transform into a flat hexagonal plane, while two inner sublayers of the bilayer phosphorene could be bonded due to its interlayer distance contraction. 2) Under the uniaxial tensile strain along a zigzag direction, the pucker distance of each layer in the bilayer phosphorene can exhibit a specific negative Poisson's ratio. 3) The electronic properties of both the monolayer and bilayer phosphorenes are sensitive to the magnitude and direction of the applied strains. Their band gaps decrease more rapidly under isotropic compressive strain than under uniaxial strain. Also, their direct-indirect band gap transitions happen at the larger isotropic tensile strains compared with that under uniaxial strain. 4) Under the isotropic compressive strain, the bilayer phosphorene exhibits a transition from a direct-gap semiconductor to a metal. In contrast, the monolayer phosphorene initially has the direct-indirect transition and then transitions to a metal. However, under isotropic tensile strain, both the bilayer and monolayer phosphorene show the direct-indirect transition and, finally, the transition to a metal. Our numerical results may open new potential applications of phosphorene in nanoelectronics and nanomechanical devices by external isotropic strain or uniaxial strain along different directions.

  14. Mechanical failure of zigzag graphene nanoribbons under tensile strain induced by edge reconstruction

    KAUST Repository

    Cheng, Yingchun

    2012-10-01

    The structural and mechanical properties of graphene nanoribbons (GNRs) under uniaxial tensile strain are studied by density functional theory. The ideal strength of a zigzag GNR (120 GPa) is close to that of pristine graphene. However, for a GNR with both edges reconstructed to pentagon–heptagon pairs (from hexagon–hexagon pairs) it decreases to 94 GPa and the maximum tensile strain is reduced to 15%. Our results constitute a comprehensive picture of the edge structure effect on the mechanical properties of GNRs.

  15. Study of the changes in the magnetic properties of stainless steels under mechanical treatment

    Energy Technology Data Exchange (ETDEWEB)

    Iankov, R.; Rusanov, V., E-mail: rusanov@phys.uni-sofia.bg [Magna Powertrain Ltd., Industrial Zone Rakowski (Bulgaria); Paneva, D.; Mitov, I. [Institute of Catalysis, Bulgarian Academy of Sciences (Bulgaria); Trautwein, A. X. [Institut für Physik, Universität zu Lübeck (Germany)

    2016-12-15

    Six types of stainless steels (SS) were studied for changes in its structure and magnetic properties under mechanical treatment. Depending on intensity and duration of the process of plastic deformation and the SS type the paramagnetic austenite structure transforms partially to completely into ferrite structure with ferromagnetic behaviour. Some of the SS tested were found slightly modified yet in the process of its manufacturing. Only one SS type with high Ni content preserved its structure and paramagnetic properties even after very intense mechanical treatment.

  16. The underlying mechanism of action for various medicinal properties of Piper betle (betel).

    Science.gov (United States)

    Haslan, H; Suhaimi, F H; Thent, Zar Chi; Das, S

    2015-01-01

    Piper betle (betel) plant belongs to the Piperaceae family. Piper. betle is widely known for its potent medicinal properties. Various active compounds are present in Piper. betle such as allylpyrocatechol, hydroxychavicol, piperbetol, ethylpiperbetol, piperol A, piperol B, chavibetol, and alkaloids which account for these beneficial medicinal properties. In the present narrative review, we looked into the various active compounds present in the Piper betle and attempted to understand their underlying mechanism of action. Proper understanding of the molecular biology involving the mechanism of action may help in better drug formulation and provide better therapeutic actions in the field of alternative and complementary medicine.

  17. Oxidative Stress and Mitochondrial Activation as the Main Mechanisms Underlying Graphene Toxicity against Human Cancer Cells

    Directory of Open Access Journals (Sweden)

    Anna Jarosz

    2016-01-01

    Full Text Available Due to the development of nanotechnology graphene and graphene-based nanomaterials have attracted the most attention owing to their unique physical, chemical, and mechanical properties. Graphene can be applied in many fields among which biomedical applications especially diagnostics, cancer therapy, and drug delivery have been arousing a lot of interest. Therefore it is essential to understand better the graphene-cell interactions, especially toxicity and underlying mechanisms for proper use and development. This review presents the recent knowledge concerning graphene cytotoxicity and influence on different cancer cell lines.

  18. Push-and-stick mechanism for charged and excited small cluster emission under ion bombardment

    International Nuclear Information System (INIS)

    Bitensky, I.S.; Parilis, E.S.; Wojciechowski, I.A.

    1992-01-01

    The mechanism for the formation, excitation and ionization of small clusters emitted under ion bombardment is discussed. It is shown that the increased degree of ionization for the transition metal dimers, trimers and tetramers can be explained by the existence of an additional effective channel for their formation, namely the associative ionization process. A simple estimate shows that the sticking together of a fast cascade atom and the pushed out surface atom is 30-40 times more effective for dimer formation, than the recombination of two fast atoms. This push-and-stick mechanism of cluster formation could also be effective for the formation of trimers and tetramers. (orig.)

  19. Mechanical failure of zigzag graphene nanoribbons under tensile strain induced by edge reconstruction

    KAUST Repository

    Cheng, Yingchun; Schwingenschlö gl, Udo; Zhu, Zhiyong

    2012-01-01

    The structural and mechanical properties of graphene nanoribbons (GNRs) under uniaxial tensile strain are studied by density functional theory. The ideal strength of a zigzag GNR (120 GPa) is close to that of pristine graphene. However, for a GNR with both edges reconstructed to pentagon–heptagon pairs (from hexagon–hexagon pairs) it decreases to 94 GPa and the maximum tensile strain is reduced to 15%. Our results constitute a comprehensive picture of the edge structure effect on the mechanical properties of GNRs.

  20. [Regulatory effect and mechanism of RNA binding motif protein 38 on the expression of progesterone receptor in human breast cancer ZR-75-1 cells].

    Science.gov (United States)

    Lou, P P; Li, C L; Xia, T S; Shi, L; Wu, J; Zhou, X J; Wang, Y; Ding, Q

    2016-06-23

    To investigate the regulatory mechanism of RNA binding motif protein 38 (RNPC1) on the expression of progesterone receptor (PR) in breast cancer cell line ZR-75-1. Lentiviral vector was used to induce overexpression of RNPC1 in ZR-75-1 cells. qRT-PCR and Western blot were used to assess the regulatory effect of RNPC1 on PR expression. Actinomycin was used to detect the regulatory mechanism involved. Immunohistochemical (IHC) staining was used to determine the protein expression of RNPC1 and PR in 80 breast cancer tissues. IHC staining showed that the expression of RNPC1 was significantly higher in the PR positive breast cancer tissues than that in the PR negative breast cancer tissues (P<0.05). The qRT-PCR results showed that overexpression of RNPC1 in ZR-75-1 cells significantly upregulated the mRNA level of PR (1.764±0.028 vs. 1.001±0.037, P<0.01), whereas knockdown of RNPC1 did the opposite (0.579± 0.007 vs. 1.000±0.002, P<0.01). The Western blot results also showed that overexpression of RNPC1 up-regulated PR levels, while knockdown of RNPC1 resulted in down-regulation of PR levels in the ZR-75-1 cells.The actinomycin assay showed that overexpression of RNPC1 increased the mRNA stability of PR. The half-life of PR mRNA was increased from 4.0 h to 6.5 h. Knockdown of RNPC1 decreased the mRNA stability of PR and the half-life of PR transcript was decreased from 4.1 h to 3.0 h. RNPC1 plays a crucial role in regulating the expression of PR in breast cancer ZR-75-1 cells.

  1. Role and Mechanism of Structural Variation in Progression of Breast Cancer

    Science.gov (United States)

    2013-09-01

    of 87 (11%) neuro- blastomas showed chromothripsis ( Molenaar et al. 2012). Further clouding the issue, prostate cancer genome sequencing has re...mutation data ( Molenaar et al. 2012). The human genetics and cancer fields have converged with the description of chromothripsis events in the germline...al. 2011; Stephens et al. 2011; Molenaar et al. 2012; Rausch et al. 2012). Replication-based mechanisms such as MMBIR can in theory generate an

  2. Loss of PEDF: A Novel Mechanism of Antihormone Resistance in Breast Cancer

    Science.gov (United States)

    2014-08-01

    transcriptionally silent , and that DNA methylation gradually accumulates upon long-term gene silencing and are associated with human malignancies. 5-Aza-2...in various neoplasms of the thyroid , where specific mutations lead to defined tumor types [60-62]. The RET protein spans the cell membrane, so that one...BM: Mechanisms of disease: cancer targeting and the impact of oncogenic RET for medullary thyroid carcinoma therapy. Nat Clin Pract Oncol 2006, 3:564

  3. Assessing the underlying breast cancer risk of Chinese females contributed by dietary intake of residual DDT from agricultural soils.

    Science.gov (United States)

    Tang, Mengling; Zhao, Meirong; Zhou, Shanshan; Chen, Kun; Zhang, Chunlong; Liu, Weiping

    2014-12-01

    The greatest concern over DDT exposure in China arose since the early 1990s for the rising breast cancer incidence, and the cause still remains to be elucidated. An extensive survey of DDT background in agricultural soils, covered the entire region of China, was conducted. DDT at concentrations greater than 100 ng/g (the China's Farmland Environmental Quality Evaluation Standards for Edible Agricultural Products) was found to impact 42.3 million Chinese population. Considering the geographical differences with diverse DDT contributions and different diet products and habits, the average daily dietary intake was modeled and estimated to be 0.34 μg/kg p,p'-DDE (the main bioactive constituent in DDT). Population attributable fraction derived from a case-control study from 78 women with breast cancer and 72 controls was used to assess the DDT exposure risk to breast cancer. Based on the estimated population attributable fraction with a median value of 0.6% (IQR 0.23-2.11%), the excess annual breast cancer incidence rate attributable to p,p'-DDE exposure averaged 0.06×10(-5) with significant spatial variations varying from 0.00021×10(-5) to 11.05×10(-5) in Chinese females. Exposure to DDT is a contributor to breast cancer, but the overall limited relative risk and population attributable fraction imply confounding factors for breast cancer in Chinese females. Exposure risk in a regional scale helps understand the cause and prevention of breast cancer. Our mapping and modeling method could be used to assess other environmental carcinogens and related cancer diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. A novel mechanism of regulating breast cancer cell migration via palmitoylation-dependent alterations in the lipid raft affiliation of CD44.

    Science.gov (United States)

    Babina, Irina S; McSherry, Elaine A; Donatello, Simona; Hill, Arnold D K; Hopkins, Ann M

    2014-02-10

    , the relevance of these findings is underscored by the fact that levels of palmitoylated CD44 were lower in primary cultures from invasive ductal carcinomas relative to non-tumour tissue, while CD44 co-localisation with a lipid raft marker was less in invasive ductal carcinoma relative to ductal carcinoma in situ cultures. Our results support a novel mechanism whereby CD44 palmitoylation and consequent lipid raft affiliation inversely regulate breast cancer cell migration, and may act as a new therapeutic target in breast cancer metastasis.

  5. Reliability-based optimization of maintenance scheduling of mechanical components under fatigue

    Science.gov (United States)

    Beaurepaire, P.; Valdebenito, M.A.; Schuëller, G.I.; Jensen, H.A.

    2012-01-01

    This study presents the optimization of the maintenance scheduling of mechanical components under fatigue loading. The cracks of damaged structures may be detected during non-destructive inspection and subsequently repaired. Fatigue crack initiation and growth show inherent variability, and as well the outcome of inspection activities. The problem is addressed under the framework of reliability based optimization. The initiation and propagation of fatigue cracks are efficiently modeled using cohesive zone elements. The applicability of the method is demonstrated by a numerical example, which involves a plate with two holes subject to alternating stress. PMID:23564979

  6. Estimation of mechanical properties of gelatin using a microbubble under acoustic radiation force

    International Nuclear Information System (INIS)

    Shirota, Eriko; Ando, Keita

    2015-01-01

    This paper is concerned with observations of the translation of a microbubble (80 μm or 137 μm in radius) in a viscoelastic medium (3 w% gelatin), which is induced by acoustic radiation force originating from 1 MHz focused ultrasound. An optical system using a high-speed camera was designed to visualize the bubble translation and deformation. If the bubble remains its spherical shape under the sonication, the bubble translation we observed can be described by theory based on the Voigt model for linear viscoelastic solids; mechanical properties of the gelatin are calculated from measurements of the terminal displacement under the sonication. (paper)

  7. CISM course on mechanical behaviour of soils under environmentally induced cyclic loads

    CERN Document Server

    Wood, David; Mechanical Behaviour of Soils Under Environmentally Induced Cyclic Loads

    2012-01-01

    The book gives a comprehensive description of the mechanical response of soils (granular and cohesive materials) under cyclic loading. It provides the geotechnical engineer with the theoretical and analytical tools necessary for the evaluation of settlements developng with time under cyclic, einvironmentally idncued loads (such as wave motion, wind actions, water table level variation) and their consequences for the serviceability and durability of structures such as the shallow or deep foundations used in offshore engineering, caisson beakwaters, ballast and airport pavements and also to interpret monitoring data, obtained from both natural and artificial slopes and earth embankments, for the purposes of risk assessment and mitigation.

  8. Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action

    International Nuclear Information System (INIS)

    Tsujita-Kyutoku, Miki; Ogawa, Yutaka; Tsubura, Airo; Yuri, Takashi; Danbara, Naoyuki; Senzaki, Hideto; Kiyozuka, Yasuhiko; Uehara, Norihisa; Takada, Hideho; Hada, Takahiko; Miyazawa, Teruo

    2004-01-01

    The present study was conducted to examine the effect of conjugated docosahexaenoic acid (CDHA) on cell growth, cell cycle progression, mode of cell death, and expression of cell cycle regulatory and/or apoptosis-related proteins in KPL-1 human breast cancer cell line. This effect of CDHA was compared with that of docosahexaenoic acid (DHA). KPL-1 cell growth was assessed by colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; cell cycle progression and mode of cell death were examined by flow cytometry; and levels of expression of p53, p21 Cip1/Waf1 , cyclin D 1 , Bax, and Bcl-2 proteins were examined by Western blotting analysis. In vivo tumor growth was examined by injecting KPL-1 cells subcutaneously into the area of the right thoracic mammary fat pad of female athymic mice fed a CDHA diet. CDHA inhibited KPL-1 cells more effectively than did DHA (50% inhibitory concentration for 72 hours: 97 μmol/l and 270 μmol/l, respectively). With both CDHA and DHA growth inhibition was due to apoptosis, as indicated by the appearance of a sub-G 1 fraction. The apoptosis cascade involved downregulation of Bcl-2 protein; Bax expression was unchanged. Cell cycle progression was due to G 0 /G 1 arrest, which involved increased expression of p53 and p21 Cip1/Waf1 , and decreased expression of cyclin D 1 . CDHA modulated cell cycle regulatory proteins and apoptosis-related proteins in a manner similar to that of parent DHA. In the athymic mouse system 1.0% dietary CDHA, but not 0.2%, significantly suppressed growth of KPL-1 tumor cells; CDHA tended to decrease regional lymph node metastasis in a dose dependent manner. CDHA inhibited growth of KPL-1 human breast cancer cells in vitro more effectively than did DHA. The mechanisms of action involved modulation of apoptosis cascade and cell cycle progression. Dietary CDHA at 1.0% suppressed KPL-1 cell growth in the athymic mouse system

  9. Scientific conception on mechanisms of calcium homeostasis disorders under low dose effect of ionizing radiation

    International Nuclear Information System (INIS)

    Abylaev, Zh.A.; Dospolova, Zh.G.

    1997-01-01

    Scientific conception of probable consequences of calcium homeostasis disorders in personals, exposed to low dose effect of ionizing radiation has been developed. Principle positions of the conception is that pathologic processes development have different ways of conducting. During predominance of low doses of external gamma-radiation there is leading pathologic mechanism (mechanism 1) of disorder neuroendocrine regulation of both the calcium and the phosphor. In this case sicks have disorders of both the vegetative tonus and the endocrine status. Under internal irradiation (mechanism 2) there is disfunction of organs and systems (bore changes and disorders of hormone status). These changes are considered as consequence of negative action on organism of incorporated long-living radionuclides. Radio-toxic factors action (mechanism 3) provokes the excess of hormones, which acting on bone tissue and could be cause of steroid osteoporosis. Influence of chronic stress factor (mechanism 4) enlarges and burden action on organism of low radiation doses. It is emphasized, that decisive role in development of pathologic processes has mechanism of disturbance of neuroendocrine regulation of calcium exchange

  10. From Sound to Significance: Exploring the Mechanisms Underlying Emotional Reactions to Music.

    Science.gov (United States)

    Juslin, Patrik N; Barradas, Gonçalo; Eerola, Tuomas

    2015-01-01

    A common approach to studying emotional reactions to music is to attempt to obtain direct links between musical surface features such as tempo and a listener's responses. However, such an analysis ultimately fails to explain why emotions are aroused in the listener. In this article we explore an alternative approach, which aims to account for musical emotions in terms of a set of psychological mechanisms that are activated by different types of information in a musical event. This approach was tested in 4 experiments that manipulated 4 mechanisms (brain stem reflex, contagion, episodic memory, musical expectancy) by selecting existing musical pieces that featured information relevant for each mechanism. The excerpts were played to 60 listeners, who were asked to rate their felt emotions on 15 scales. Skin conductance levels and facial expressions were measured, and listeners reported subjective impressions of relevance to specific mechanisms. Results indicated that the target mechanism conditions evoked emotions largely as predicted by a multimechanism framework and that mostly similar effects occurred across the experiments that included different pieces of music. We conclude that a satisfactory account of musical emotions requires consideration of how musical features and responses are mediated by a range of underlying mechanisms.

  11. Contact force and mechanical loss of multistage cable under tension and bending

    Science.gov (United States)

    Ru, Yanyun; Yong, Huadong; Zhou, Youhe

    2016-10-01

    A theoretical model for calculating the stress and strain states of cabling structures with different loadings has been developed in this paper. We solve the problem for the first- and second-stage cable with tensile or bending strain. The contact and friction forces between the strands are presented by two-dimensional contact model. Several theoretical models have been proposed to verify the results when the triplet subjected to the tensile strain, including contact force, contact stresses, and mechanical loss. It is found that loadings will affect the friction force and the mechanical loss of the triplet. The results show that the contact force and mechanical loss are dependent on the twist pitch. A shorter twist pitch can lead to higher contact force, while the trend of mechanical loss with twist pitch is complicated. The mechanical loss may be reduced by adjusting the twist pitch reasonably. The present model provides a simple analysis method to investigate the mechanical behaviors in multistage-structures under different loads.

  12. Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action

    International Nuclear Information System (INIS)

    Kampa, Marilena; Boskou, Dimitrios; Gravanis, Achille; Castanas, Elias; Alexaki, Vassilia-Ismini; Notas, George; Nifli, Artemissia-Phoebe; Nistikaki, Anastassia; Hatzoglou, Anastassia; Bakogeorgou, Efstathia; Kouimtzoglou, Elena; Blekas, George

    2004-01-01

    The oncoprotective role of food-derived polyphenol antioxidants has been described but the implicated mechanisms are not yet clear. In addition to polyphenols, phenolic acids, found at high concentrations in a number of plants, possess antioxidant action. The main phenolic acids found in foods are derivatives of 4-hydroxybenzoic acid and 4-hydroxycinnamic acid. This work concentrates on the antiproliferative action of caffeic acid, syringic acid, sinapic acid, protocatechuic acid, ferulic acid and 3,4-dihydroxy-phenylacetic acid (PAA) on T47D human breast cancer cells, testing their antioxidant activity and a number of possible mechanisms involved (interaction with membrane and intracellular receptors, nitric oxide production). The tested compounds showed a time-dependent and dose-dependent inhibitory effect on cell growth with the following potency: caffeic acid > ferulic acid = protocatechuic acid = PAA > sinapic acid = syringic acid. Caffeic acid and PAA were chosen for further analysis. The antioxidative activity of these phenolic acids in T47D cells does not coincide with their inhibitory effect on tumoral proliferation. No interaction was found with steroid and adrenergic receptors. PAA induced an inhibition of nitric oxide synthase, while caffeic acid competes for binding and results in an inhibition of aryl hydrocarbon receptor-induced CYP1A1 enzyme. Both agents induce apoptosis via the Fas/FasL system. Phenolic acids exert a direct antiproliferative action, evident at low concentrations, comparable with those found in biological fluids after ingestion of foods rich in phenolic acids. Furthermore, the direct interaction with the aryl hydrocarbon receptor, the nitric oxide synthase inhibition and their pro-apoptotic effect provide some insights into their biological mode of action

  13. Damage evolution of TBC system under in-phase thermo-mechanical tests

    International Nuclear Information System (INIS)

    Kitazawa, R.; Tanaka, M.; Kagawa, Y.; Liu, Y.F.

    2010-01-01

    In-phase thermo-mechanical tests (TMF) of EB-PVD Y 2 O 3 -ZrO 2 thermal barrier coating (TBC) system (8 wt% Y 2 O 3 -ZrO 2 /CoNiCrAlY/IN-738 substrate) were done under a through-the-thick-direction thermal gradient from TBC surface temperature at 1150 deg. C to substrate temperature at 1000 deg. C. Deformation and failure behaviors of the TBC system were observed at the macroscopic and microscopic scales and damage evolution of the system under in-phase thermo-mechanical test was discussed. Special attention was paid to TBC layer cracking, thermally grown oxide (TGO) layer formation and void formation in bond coat and substrate. Effect of TMF conditions on the damage evolution behaviors was also discussed.

  14. Behavioral Effects of Upper Respiratory Tract Illnesses: A Consideration of Possible Underlying Cognitive Mechanisms

    Directory of Open Access Journals (Sweden)

    Andrew P. Smith

    2012-03-01

    Full Text Available Previous research has shown that both experimentally induced upper respiratory tract illnesses (URTIs and naturally occurring URTIs influence mood and performance. The present study investigated possible cognitive mechanisms underlying the URTI-performance changes. Those who developed a cold (N = 47 had significantly faster, but less accurate, performance than those who remained healthy (N = 54. Illness had no effect on manipulations designed to influence encoding, response organisation (stimulus-response compatilibility or response preparation. Similarly, there was no evidence that different components of working memory were impaired. Overall, the present research confirms that URTIs can have an effect on performance efficiency. Further research is required to identify the physiological and behavioral mechanisms underlying these effects.

  15. Damage evolution of TBC system under in-phase thermo-mechanical tests

    Energy Technology Data Exchange (ETDEWEB)

    Kitazawa, R.; Tanaka, M.; Kagawa, Y. [Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904 (Japan); Liu, Y.F., E-mail: yfliu@hyper.rcast.u-tokyo.ac.jp [Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904 (Japan)

    2010-10-15

    In-phase thermo-mechanical tests (TMF) of EB-PVD Y{sub 2}O{sub 3}-ZrO{sub 2} thermal barrier coating (TBC) system (8 wt% Y{sub 2}O{sub 3}-ZrO{sub 2}/CoNiCrAlY/IN-738 substrate) were done under a through-the-thick-direction thermal gradient from TBC surface temperature at 1150 deg. C to substrate temperature at 1000 deg. C. Deformation and failure behaviors of the TBC system were observed at the macroscopic and microscopic scales and damage evolution of the system under in-phase thermo-mechanical test was discussed. Special attention was paid to TBC layer cracking, thermally grown oxide (TGO) layer formation and void formation in bond coat and substrate. Effect of TMF conditions on the damage evolution behaviors was also discussed.

  16. Exact solution for stresses/displacements in a multilayered hollow cylinder under thermo-mechanical loading

    International Nuclear Information System (INIS)

    Yeo, W.H.; Purbolaksono, J.; Aliabadi, M.H.; Ramesh, S.; Liew, H.L.

    2017-01-01

    In this study, a new analytical solution by the recursive method for evaluating stresses/displacements in multilayered hollow cylinder under thermo-mechanical loading was developed. The results for temperature distribution, displacements and stresses obtained by using the proposed solution were shown to be in good agreement with the FEM results. The proposed analytical solution was also found to produce more accurate results than those by the analytical solution reported in literature. - Highlights: • A new analytical solution for evaluating stresses in multilayered hollow cylinder under thermo-mechanical loading. • A simple computational procedure using a recursive method. • A promising technique for evaluating the operating axial and hoop stresses in pressurized composite vessels.

  17. Mechanical strength of an ITER coil insulation system under static and dynamic load after reactor irradiation

    International Nuclear Information System (INIS)

    Bittner-Rohrhofer, K.; Humer, K.; Weber, H.W.; Hamada, K.; Sugimoto, M.; Okuno, K.

    2002-01-01

    The insulation system proposed by the Japanese Home Team for the ITER Toroidal Field coil (TF coil) is a T-glass-fiber/Kapton reinforced epoxy prepreg system. In order to assess the material performance under the actual operating conditions of the coils, the insulation system was irradiated in the TRIGA reactor (Vienna) to a fast neutron fluence of 2x10 22 m -2 (E>0.1 MeV). After measurements of swelling, all mechanical tests were carried out at 77 K. Tensile and short-beam-shear (SBS) tests were performed under static loading conditions. In addition, tension-tension fatigue experiments up to about 10 6 cycles were made. The laminate swells in the through-thickness direction by 0.86% at the highest dose level. The fatigue tests as well as the static tests do not show significant influences of the irradiation on the mechanical behavior of this composite

  18. Mechanical strength of an ITER coil insulation system under static and dynamic load after reactor irradiation

    Science.gov (United States)

    Bittner-Rohrhofer, K.; Humer, K.; Weber, H. W.; Hamada, K.; Sugimoto, M.; Okuno, K.

    2002-12-01

    The insulation system proposed by the Japanese Home Team for the ITER Toroidal Field coil (TF coil) is a T-glass-fiber/Kapton reinforced epoxy prepreg system. In order to assess the material performance under the actual operating conditions of the coils, the insulation system was irradiated in the TRIGA reactor (Vienna) to a fast neutron fluence of 2×10 22 m -2 ( E>0.1 MeV). After measurements of swelling, all mechanical tests were carried out at 77 K. Tensile and short-beam-shear (SBS) tests were performed under static loading conditions. In addition, tension-tension fatigue experiments up to about 10 6 cycles were made. The laminate swells in the through-thickness direction by 0.86% at the highest dose level. The fatigue tests as well as the static tests do not show significant influences of the irradiation on the mechanical behavior of this composite.

  19. Music and Memory in Alzheimer's Disease and The Potential Underlying Mechanisms.

    Science.gov (United States)

    Peck, Katlyn J; Girard, Todd A; Russo, Frank A; Fiocco, Alexandra J

    2016-01-01

    With population aging and a projected exponential expansion of persons diagnosed with Alzheimer's disease (AD), the development of treatment and prevention programs has become a fervent area of research and discovery. A growing body of evidence suggests that music exposure can enhance memory and emotional function in persons with AD. However, there is a paucity of research that aims to identify specific underlying neural mechanisms associated with music's beneficial effects in this particular population. As such, this paper reviews existing anecdotal and empirical evidence related to the enhancing effects of music exposure on cognitive function and further provides a discussion on the potential underlying mechanisms that may explain music's beneficial effect. Specifically, this paper will outline the potential role of the dopaminergic system, the autonomic nervous system, and the default network in explaining how music may enhance memory function in persons with AD.

  20. Sevoflurane suppresses proliferation by upregulating microRNA-203 in breast cancer cells.

    Science.gov (United States)

    Liu, Jiaying; Yang, Longqiu; Guo, Xia; Jin, Guangli; Wang, Qimin; Lv, Dongdong; Liu, Junli; Chen, Qiu; Song, Qiong; Li, Baolin

    2018-05-03

    Rapid proliferation is one of the critical characteristics of breast cancer. However, the underlying regulatory mechanism of breast cancer cell proliferation is largely unclear. The present study indicated that sevoflurane, one of inhalational anesthetics, could significantly suppress breast cancer cell proliferation by arresting cell cycle at G1 phase. Notably, the rescue experiment indicated that miR-203 was upregulated by sevoflurane and mediated the function of sevoflurane on suppressing the breast cancer cell proliferation. The present study indicated the function of the sevoflurane/miR-203 signaling pathway on regulating breast cancer cell proliferation. These results provide mechanistic insight into how the sevoflurane/miR-203 signaling pathway supresses proliferation of breast cancer cells, suggesting the sevoflurane/miR-203 pathway may be a potential target in the treatment of breast cancer.

  1. Detecting method for crude oil price fluctuation mechanism under different periodic time series

    International Nuclear Information System (INIS)

    Gao, Xiangyun; Fang, Wei; An, Feng; Wang, Yue

    2017-01-01

    Highlights: • We proposed the concept of autoregressive modes to indicate the fluctuation patterns. • We constructed transmission networks for studying the fluctuation mechanism. • There are different fluctuation mechanism under different periodic time series. • Only a few types of autoregressive modes control the fluctuations in crude oil price. • There are cluster effects during the fluctuation mechanism of autoregressive modes. - Abstract: Current existing literatures can characterize the long-term fluctuation of crude oil price time series, however, it is difficult to detect the fluctuation mechanism specifically under short term. Because each fluctuation pattern for one short period contained in a long-term crude oil price time series have dynamic characteristics of diversity; in other words, there exhibit various fluctuation patterns in different short periods and transmit to each other, which reflects the reputedly complicate and chaotic oil market. Thus, we proposed an incorporated method to detect the fluctuation mechanism, which is the evolution of the different fluctuation patterns over time from the complex network perspective. We divided crude oil price time series into segments using sliding time windows, and defined autoregressive modes based on regression models to indicate the fluctuation patterns of each segment. Hence, the transmissions between different types of autoregressive modes over time form a transmission network that contains rich dynamic information. We then capture transmission characteristics of autoregressive modes under different periodic time series through the structure features of the transmission networks. The results indicate that there are various autoregressive modes with significantly different statistical characteristics under different periodic time series. However, only a few types of autoregressive modes and transmission patterns play a major role in the fluctuation mechanism of the crude oil price, and these

  2. A fracture mechanics study of tungsten failure under high heat flux loads

    International Nuclear Information System (INIS)

    Li, Muyuan

    2015-01-01

    The performance of fusion devices is highly dependent on plasma-facing components. Tungsten is the most promising candidate material for armors in plasma-facing components in ITER and DEMO. However, the brittleness of tungsten below the ductile-to-brittle transition temperature is very critical to the reliability of plasma-facing components. In this work, thermo-mechanical and fracture behaviors of tungsten are predicted numerically under fusion relevant thermal loadings.

  3. Stress State Analysis and Failure Mechanisms of Masonry Columns Reinforced with FRP under Concentric Compressive Load

    OpenAIRE

    Jiří Witzany; Radek Zigler

    2016-01-01

    The strengthening and stabilization of damaged compressed masonry columns with composites based on fabrics of high-strength fibers and epoxy resin, or polymer-modified cement mixtures, belongs to novel, partially non-invasive and reversible progressive methods. The stabilizing and reinforcing effect of these fabrics significantly applies to masonry structures under concentric compressive loading whose failure mechanism is characterized by the appearance and development of vertical tensile cra...

  4. The Dynamic Evolution of Firms’ Pollution Control Strategy under Graded Reward-Penalty Mechanism

    OpenAIRE

    Li Ming Chen; Wen Ping Wang

    2016-01-01

    The externality of pollution problem makes firms lack enough incentive to reduce pollution emission. Therefore, it is necessary to design a reasonable environmental regulation mechanism so as to effectively urge firms to control pollution. In order to inspire firms to control pollution, we divide firms into different grades according to their pollution level and construct an evolutionary game model to analyze the interaction between government’s regulation and firms’ pollution control under g...

  5. Modulating Conscious Movement Intention by Noninvasive Brain Stimulation and the Underlying Neural Mechanisms

    OpenAIRE

    Douglas, Zachary H.; Maniscalco, Brian; Hallett, Mark; Wassermann, Eric M.; He, Biyu J.

    2015-01-01

    Conscious intention is a fundamental aspect of the human experience. Despite long-standing interest in the basis and implications of intention, its underlying neurobiological mechanisms remain poorly understood. Using high-definition transcranial DC stimulation (tDCS), we observed that enhancing spontaneous neuronal excitability in both the angular gyrus and the primary motor cortex caused the reported time of conscious movement intention to be ∼60–70 ms earlier. Slow brain waves recorded ∼2–...

  6. MECHANICAL BEHAVIOR OF COLD BITUMINOUS MIXTURE UNDER EFFECTS OF STATIC AND REPEATED LOADS1

    OpenAIRE

    Tamyres Karla da Silva; Carlos Alexandre Braz de Carvalho; Geraldo Luciano de Oliveira Marques; Dario Cardoso de Lima; Taciano Oliveira da Silva; Carlos Cardoso Machado

    2017-01-01

    Abstract This paper presents the results of an experimental research aimed at analyzing the mechanical behavior of a cold bituminous mixture under effects of static and repeated loads. Initially, a Marshall mixture design was performed to determine the mixture design contents according to standard DNER (1994a). After obtaining the mixture design contents, nine bituminous specimens were molded and subjected to the following tests: resilient modulus, tensile strength by diametral compression, a...

  7. Vitamin D and Breast Cancer

    OpenAIRE

    Shao, Theresa; Klein, Paula; Grossbard, Michael L.

    2012-01-01

    Vitamin D metabolism and its mechanism of action, the current evidence on the relationship between vitamin D and breast cancer, and the optimal dosing of vitamin D for breast cancer prevention are summarized.

  8. Different intra- and interspecific facilitation mechanisms between two Mediterranean trees under a climate change scenario.

    Science.gov (United States)

    Gimeno, Teresa E; Escudero, Adrián; Valladares, Fernando

    2015-01-01

    In harsh environments facilitation alleviates biotic and abiotic constraints on tree recruitment. Under ongoing drier climate change, we expect facilitation to increase as a driver of coexistence. However, this might not hold under extreme abiotic stress and when the outcome depends on the interaction with other drivers such as altered herbivore pressure due to land use change. We performed a field water-manipulation experiment to quantify the importance of facilitation in two coexisting Mediterranean trees (dominant Juniperus thurifera and coexisting Quercus ilex subsp. ballota) under a climate change scenario. Shifts in canopy dominance favouring Q. ilex could be based on the extension of heterospecific facilitation to the detriment of conspecific alleviation. We found that saplings of both species transplanted under the canopy of nurse trees had greater survival probability, growth and photochemical efficiency. Intra- and interspecific facilitation mechanisms differed: alleviation of abiotic stress benefited both species during summer and J. thurifera during winter, whereas browsing protection was relevant only for Q. ilex. Facilitation was greater under the dry treatment only for Q. ilex, which partially agreed with the predictions of the stress gradient hypothesis. We conclude that present rainfall availability limits neither J. thurifera nor Q. ilex establishment. Nevertheless, under current global change scenarios, imposing increasing abiotic stress together with altered herbivore browsing, nurse trees could differentially facilitate the establishment of Q. ilex due to species-specific traits, i.e. palatability; drought, heat and cold tolerance, underlying species differences in the facilitation mechanisms and eventually triggering a change from pure juniper woodlands to mixed formations.

  9. Contraction and elongation: Mechanics underlying cell boundary deformations in epithelial tissue.

    Science.gov (United States)

    Hara, Yusuke

    2017-06-01

    The cell-cell boundaries of epithelial cells form cellular frameworks at the apical side of tissues. Deformations in these boundaries, for example, boundary contraction and elongation, and the associated forces form the mechanical basis of epithelial tissue morphogenesis. In this review, using data from recent Drosophila studies on cell boundary contraction and elongation, I provide an overview of the mechanism underlying the bi-directional deformations in the epithelial cell boundary, that are sustained by biased accumulations of junctional and apico-medial non-muscle myosin II. Moreover, how the junctional tensions exist on cell boundaries in different boundary dynamics and morphologies are discussed. Finally, some future perspectives on how recent knowledge about single cell boundary-level mechanics will contribute to our understanding of epithelial tissue morphogenesis are discussed. © 2017 Japanese Society of Developmental Biologists.

  10. Experimental Investigation on Shock Mechanical Properties of Red Sandstone under Preloaded 3D Static Stresses

    Directory of Open Access Journals (Sweden)

    Niu Yong

    2015-11-01

    Full Text Available Triaxial impact mechanical performance experiment was performed to study the mechanical properties of red sandstone subjected to three-dimensional (3D coupled static and dynamic loads, i.e., three confining pressures (0, 5, and 10 MPa and three axial pressures (11, 27, and 43 MPa. A modified 3D split Hopkinson pressure bar testing system was used. The change trend in the deformation of red sandstone and the strength and failure modes under axial pressures and confining pressures were analyzed. Results show that, when the confining pressure is constant, the compressive strength, secant modulus, and energy absorbed per unit volume of red sandstone initially increases and subsequently decreases, whereas the average strain rate exhibits an opposite trend. When the axial pressure is constant, both the compressive strength and secant modulus of red sandstone are enhanced, but the average strain rate is decreased with increasing confining pressure. The energy absorbed per unit volume is initially increased and subsequently decreased as the confining pressure increases. Red sandstone exhibits a cone-shaped compression–shear failure mode under the 3D coupled static and dynamic loads. The conclusions serve as theoretical basis on the mechanical properties of deep medium-strength rock under a high ground stress and external load disturbance condition

  11. Cavitation behavior observed in three monoleaflet mechanical heart valves under accelerated testing conditions.

    Science.gov (United States)

    Lo, Chi-Wen; Liu, Jia-Shing; Li, Chi-Pei; Lu, Po-Chien; Hwang, Ned H

    2008-01-01

    Accelerated testing provides a substantial amount of data on mechanical heart valve durability in a short period of time, but such conditions may not accurately reflect in vivo performance. Cavitation, which occurs during mechanical heart valve closure when local flow field pressure decreases below vapor pressure, is thought to play a role in valve damage under accelerated conditions. The underlying flow dynamics and mechanisms behind cavitation bubble formation are poorly understood. Under physiologic conditions, random perivalvular cavitation is difficult to capture. We applied accelerated testing at a pulse rate of 600 bpm and transvalvular pressure of 120 mm Hg, with synchronized videographs and high-frequency pressure measurements, to study cavitation of the Medtronic Hall Standard (MHS), Medtronic Hall D-16 (MHD), and Omni Carbon (OC) valves. Results showed cavitation bubbles between 340 and 360 micros after leaflet/housing impact of the MHS, MHD, and OC valves, intensified by significant leaflet rebound. Squeeze flow, Venturi, and water hammer effects each contributed to cavitation, depending on valve design.

  12. Kinetic theory approach to modeling of cellular repair mechanisms under genome stress.

    Directory of Open Access Journals (Sweden)

    Jinpeng Qi

    Full Text Available Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR by using mathematical framework of kinetic theory of active particles (KTAP. Firstly, we focus on illustrating the profile of Cellular Repair System (CRS instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs and Repair Protein (RP generating, DSB-protein complexes (DSBCs synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances.

  13. Kinetic theory approach to modeling of cellular repair mechanisms under genome stress.

    Science.gov (United States)

    Qi, Jinpeng; Ding, Yongsheng; Zhu, Ying; Wu, Yizhi

    2011-01-01

    Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR) by using mathematical framework of kinetic theory of active particles (KTAP). Firstly, we focus on illustrating the profile of Cellular Repair System (CRS) instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs) and Repair Protein (RP) generating, DSB-protein complexes (DSBCs) synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances.

  14. Design options for cooperation mechanisms under the new European renewable energy directive

    International Nuclear Information System (INIS)

    Klessmann, Corinna; Lamers, Patrick; Ragwitz, Mario; Resch, Gustav

    2010-01-01

    In June 2009, a new EU directive on the promotion of renewable energy sources (RES) entered into effect. The directive 2009/28/EC, provides for three cooperation mechanisms that will allow member states to achieve their national RES target in cooperation with other member states: statistical transfer, joint projects, and joint support schemes. This article analyses the pros and cons of the three mechanisms and explores design options for their implementation through strategic and economic questions: How to counterbalance the major drawbacks of each mechanism? How to reflect a balance of costs and benefits between the involved member states? The analysis identifies a number of design options that respond to these questions, e.g. long term contracts to ensure sufficient flexibility for statistical transfers, a coordinated, standardised joint project approach to increase transparency in the European market, and a stepwise harmonisation of joint support schemes that is based on a cost-effective accounting approach. One conclusion is that the three cooperation mechanisms are closely interlinked. One can consider their relation to be a gradual transition from member state cooperation under fully closed national support systems in case of statistical transfers, to cooperation under fully open national support systems in a joint support scheme.

  15. Simulation of fatigue damage in ferroelectric polycrystals under mechanical/electrical loading

    Science.gov (United States)

    Kozinov, S.; Kuna, M.

    2018-07-01

    The reliability of smart-structures made of ferroelectric ceramics is essentially reduced by the formation of cracks under the action of external electrical and/or mechanical loading. In the current research a numerical model for low-cycle fatigue in ferroelectric mesostructures is proposed. In the finite element simulations a combination of two user element routines is utilized. The first one is used to model a micromechanical ferroelectric domain switching behavior inside the grains. The second one is used to simulate fatigue damage of grain boundaries by a cohesive zone model (EMCCZM) based on an electromechanical cyclic traction-separation law (TSL). For numerical simulations a scanning electron microscope image of the ceramic's grain structure was digitalized and meshed. The response of this mesostructure to cyclic electrical or mechanical loading is systematically analyzed. As a result of the simulations, the distribution of electric potential, field, displacement and polarization as well as mechanical stresses and deformations inside the grains are obtained. At the grain boundaries, the formation and evolution of damage are analyzed until final failure and induced degradation of electric permittivity. It is found that the proposed model correctly mimics polycrystalline behavior during poling processes and progressive damage under cyclic electromechanical loading. To the authors' knowledge, it is the first model and numerical analysis of ferroelectric polycrystals taking into account both domain reorientation and cohesive modeling of intergranular fracture. It can help to understand failure mechanisms taking place in ferroelectrics during fatigue processes.

  16. A mechanical deformation model of metallic fuel pin under steady state conditions

    International Nuclear Information System (INIS)

    Lee, D. W.; Lee, B. W.; Kim, Y. I.; Han, D. H.

    2004-01-01

    As a mechanical deformation model of the MACSIS code predicts the cladding deformation due to the simple thin shell theory, it is impossible to predict the FCMI(Fuel-Cladding Mechanical Interaction). Therefore, a mechanical deformation model used the generalized plane strain is developed. The DEFORM is a mechanical deformation routine which is used to analyze the stresses and strains in the fuel and cladding of a metallic fuel pin of LMRs. The accuracy of the program is demonstrated by comparison of the DEFORM predictions with the result of another code calculations or experimental results in literature. The stress/strain distributions of elastic part under free thermal expansion condition are completely matched with the results of ANSYS code. The swelling and creep solutions are reasonably well agreed with the simulations of ALFUS and LIFE-M codes, respectively. The predicted cladding strains are under estimated than experimental data at the range of high burnup. Therefore, it is recommended that the fine tuning of the DEFORM based on various range of experimental data

  17. Breast Pain

    Science.gov (United States)

    ... result in the development of breast cysts. Breast trauma, prior breast surgery or other factors localized to the breast can lead to breast pain. Breast pain may also start outside the breast — in the chest wall, muscles, joints or heart, for example — and ...

  18. Mechanical behavior of confined self-compacting reinforced concrete circular columns under concentric axial loading

    Directory of Open Access Journals (Sweden)

    Fouad Khairallah

    2013-12-01

    Full Text Available While there is abundant research information on ordinary confined concrete, there are little data on the behavior of Self-Compacting Concrete (SCC under such condition. Due to higher shrinkage and lower coarse aggregate content of SCC compared to that of Normal Concrete (NC, its composite performance under confined conditions needs more investigation. This paper has been devoted to investigate and compare the mechanical behavior of confined concrete circular columns cast with SCC and NC under concentric axial loading. The parameters affecting are including concrete compressive strength and confinement configuration. Twenty column specimens were casted and confined using four confinement techniques, CFRP wrap, FRP tube, GFRP wrap, and spiral steel hoops. The performance of the tested column specimens is evaluated based on mode of failure, load–displacement curve, stress–strain characteristics, ultimate strength, ductility, and degree of confinement.

  19. Reactive Molecular Dynamics Simulations to Understand Mechanical Response of Thaumasite under Temperature and Strain Rate Effects.

    Science.gov (United States)

    Hajilar, Shahin; Shafei, Behrouz; Cheng, Tao; Jaramillo-Botero, Andres

    2017-06-22

    Understanding the structural, thermal, and mechanical properties of thaumasite is of great interest to the cement industry, mainly because it is the phase responsible for the aging and deterioration of civil infrastructures made of cementitious materials attacked by external sources of sulfate. Despite the importance, effects of temperature and strain rate on the mechanical response of thaumasite had remained unexplored prior to the current study, in which the mechanical properties of thaumasite are fully characterized using the reactive molecular dynamics (RMD) method. With employing a first-principles based reactive force field, the RMD simulations enable the description of bond dissociation and formation under realistic conditions. From the stress-strain curves of thaumasite generated in the x, y, and z directions, the tensile strength, Young's modulus, and fracture strain are determined for the three orthogonal directions. During the course of each simulation, the chemical bonds undergoing tensile deformations are monitored to reveal the bonds responsible for the mechanical strength of thaumasite. The temperature increase is found to accelerate the bond breaking rate and consequently the degradation of mechanical properties of thaumasite, while the strain rate only leads to a slight enhancement of them for the ranges considered in this study.

  20. New developments on the neurobiological and pharmaco-genetic mechanisms underlying internet and videogame addiction.

    Science.gov (United States)

    Weinstein, Aviv; Lejoyeux, Michel

    2015-03-01

    There is emerging evidence that the psychobiological mechanisms underlying behavioral addictions such as internet and videogame addiction resemble those of addiction for substances of abuse. Review of brain imaging, treatment and genetic studies on videogame and internet addiction. Literature search of published articles between 2009 and 2013 in Pubmed using "internet addiction" and "videogame addiction" as the search word. Twenty-nine studies have been selected and evaluated under the criteria of brain imaging, treatment, and genetics. Brain imaging studies of the resting state have shown that long-term internet game playing affected brain regions responsible for reward, impulse control and sensory-motor coordination. Brain activation studies have shown that videogame playing involved changes in reward and loss of control and that gaming pictures have activated regions similarly to those activated by cue-exposure to drugs. Structural studies have shown alterations in the volume of the ventral striatum possible as result of changes in reward. Furthermore, videogame playing was associated with dopamine release similar in magnitude to those of drugs of abuse and that there were faulty inhibitory control and reward mechanisms videogame addicted individuals. Finally, treatment studies using fMRI have shown reduction in craving for videogames and reduced associated brain activity. Videogame playing may be supported by similar neural mechanisms underlying drug abuse. Similar to drug and alcohol abuse, internet addiction results in sub-sensitivity of dopamine reward mechanisms. Given the fact that this research is in its early stage it is premature to conclude that internet addiction is equivalent to substance addictions. © American Academy of Addiction Psychiatry.

  1. Steroid induction of therapy-resistant cytokeratin-5-positive cells in estrogen receptor-positive breast cancer through a BCL6-dependent mechanism

    Science.gov (United States)

    Goodman, C R; Sato, T; Peck, A R; Girondo, M A; Yang, N; Liu, C; Yanac, A F; Kovatich, A J; Hooke, J A; Shriver, C D; Mitchell, E P; Hyslop, T; Rui, H

    2016-01-01

    Therapy resistance remains a major problem in estrogen receptor-α (ERα)-positive breast cancer. A subgroup of ERα-positive breast cancer is characterized by mosaic presence of a minor population of ERα-negative cancer cells expressing the basal cytokeratin-5 (CK5). These CK5-positive cells are therapy resistant and have increased tumor-initiating potential. Although a series of reports document induction of the CK5-positive cells by progestins, it is unknown if other 3-ketosteroids share this ability. We now report that glucocorticoids and mineralocorticoids effectively expand the CK5-positive cell population. CK5-positive cells induced by 3-ketosteroids lacked ERα and progesterone receptors, expressed stem cell marker, CD44, and displayed increased clonogenicity in soft agar and broad drug-resistance in vitro and in vivo. Upregulation of CK5-positive cells by 3-ketosteroids required induction of the transcriptional repressor BCL6 based on suppression of BCL6 by two independent BCL6 small hairpin RNAs or by prolactin. Prolactin also suppressed 3-ketosteroid induction of CK5+ cells in T47D xenografts in vivo. Survival analysis with recursive partitioning in node-negative ERα-positive breast cancer using quantitative CK5 and BCL6 mRNA or protein expression data identified patients at high or low risk for tumor recurrence in two independent patient cohorts. The data provide a mechanism by which common pathophysiological or pharmacologic elevations in glucocorticoids or other 3-ketosteroids may adversely affect patients with mixed ERα+/CK5+ breast cancer. The observations further suggest a cooperative diagnostic utility of CK5 and BCL6 expression levels and justify exploring efficacy of inhibitors of BCL6 and 3-ketosteroid receptors for a subset of ERα-positive breast cancers. PMID:26096934

  2. Microscale experimental investigation of deformation and damage of argillaceous rocks under cyclic hydric and mechanical loads

    International Nuclear Information System (INIS)

    Wang, Linlin; Yang, Diansen; Heripre, Eva; Chanchole, Serge; Bornert, Michel; Pouya, Ahmad; Halphen, Bernard

    2012-01-01

    Document available in abstract form only. Argillaceous rocks are possible host rocks for underground nuclear waste repositories. They exhibit complex coupled thermo-hydro-chemo-mechanical behavior, the description of which would strongly benefit from an improved experimental insight on their deformation and damage mechanisms at microscale. We present some recent observations of the evolution of these rocks at the scale of their composite microstructure, essentially made of a clay matrix with embedded carbonates and quartz particles with sizes ranging from a few to several tens of micrometers, when they are subjected to cyclic variations of relative humidity and mechanical loading. They are based on the combination of high definition and high resolution imaging in an environmental scanning electron microscope (ESEM), in situ hydro-mechanical loading of the samples, and digital image correlation techniques. Samples, several millimeters in diameter, are held at a constant temperature of 2 deg. Celsius while the vapor pressure in the ESEM chamber is varied from a few to several hundreds of Pascals, generating a relative humidity ranging from about 10% up to 90%. Results show a strongly heterogeneous deformation field at microscale, which is the result of complex hydro-mechanical interactions. In particular, it can be shown that local swelling incompatibilities can generate irreversible deformations in the clay matrix, even if the overall hydric deformations seem reversible. In addition, local damage can be generated, in the form of a network of microcracks, located in the bulk of the clay matrix and/or at the interface between clay and other mineral particles. The morphology of this network, described in terms of crack length, orientation and preferred location, has been observed to be dependent on the speed of the variation of the relative humidity, and is different in a saturation or desaturation process. Besides studying the deformation and damage under hydric

  3. Genome-Wide Progesterone Receptor Binding: Cell Type-Specific and Shared Mechanisms in T47D Breast Cancer Cells and Primary Leiomyoma Cells

    Science.gov (United States)

    Huang, Lei; Owen, Jonas K.; Xie, Anna; Navarro, Antonia; Monsivais, Diana; Coon V, John S.; Kim, J. Julie; Dai, Yang; Bulun, Serdar E.

    2012-01-01

    Background Progesterone, via its nuclear receptor (PR), exerts an overall tumorigenic effect on both uterine fibroid (leiomyoma) and breast cancer tissues, whereas the antiprogestin RU486 inhibits growth of these tissues through an unknown mechanism. Here, we determined the interaction between common or cell-specific genome-wide binding sites of PR and mRNA expression in RU486-treated uterine leiomyoma and breast cancer cells. Principal Findings ChIP-sequencing revealed 31,457 and 7,034 PR-binding sites in breast cancer and uterine leiomyoma cells, respectively; 1,035 sites overlapped in both cell types. Based on the chromatin-PR interaction in both cell types, we statistically refined the consensus progesterone response element to G•ACA• • •TGT•C. We identified two striking differences between uterine leiomyoma and breast cancer cells. First, the cis-regulatory elements for HSF, TEF-1, and C/EBPα and β were statistically enriched at genomic RU486/PR-targets in uterine leiomyoma, whereas E2F, FOXO1, FOXA1, and FOXF sites were preferentially enriched in breast cancer cells. Second, 51.5% of RU486-regulated genes in breast cancer cells but only 6.6% of RU486-regulated genes in uterine leiomyoma cells contained a PR-binding site within 5 kb from their transcription start sites (TSSs), whereas 75.4% of RU486-regulated genes contained a PR-binding site farther than 50 kb from their TSSs in uterine leiomyoma cells. RU486 regulated only seven mRNAs in both cell types. Among these, adipophilin (PLIN2), a pro-differentiation gene, was induced via RU486 and PR via the same regulatory region in both cell types. Conclusions Our studies have identified molecular components in a RU486/PR-controlled gene network involved in the regulation of cell growth, cell migration, and extracellular matrix function. Tissue-specific and common patterns of genome-wide PR binding and gene regulation may determine the therapeutic effects of antiprogestins in uterine fibroids and

  4. Corporate debts ad credit performance under the new mechanism of reorganization of the Russian banks

    Directory of Open Access Journals (Sweden)

    Sergey A. Andryushin

    2017-09-01

    Full Text Available Objective to explore the dynamics and factors of formation of corporate debts the characteristics of low credit activity of the Russian banks and regulation of liquidity deficit of enterprises under the new reorganization mechanism in the Russian banking sector. Methods systematic approach to the cognition of economic phenomena which allows to study them in their dynamic development taking into account the influence of various environmental factors. The systematic approach determined selection of specific research methods empirical logical comparative and statistical. Results the article is devoted to the problems of declining credit activity of commercial banks under the conditions of economic activity revival as well as to assessing the impact of the new reorganization mechanism on this process. It is shown that in the recent years the nonfinancial sector faces the trend of optimizing the corporate debts and the liquidity deficit which reduced the demand for loans and as a consequence decreased the banksrsquo credit activity. To analyze the dynamics of deficitsurplus of liquidity in the corporate sector a new classification of liquidity deficitsurplus levels was introduced. Based on the proposed classification the risk factors were identified that influenced the dynamics of indebtedness in the corporate sector. The article also analyses the modern monetary mechanism of money supply in the economy and its transformation. It was determined that the main limitation of credit issuance by commercial banks is their capital not the reserve multiplier. The new mechanism of credit institutionsrsquo financial recovery and its impact on the banksrsquo credit activity was estimated. The conditions of liquidity deficiency reduction in the Russian companies were analyzed in the medium term. Scientific novelty for the first time on the basis of system analysis methods the growth factors of the corporate debt load were identified the peculiarities of low

  5. Mechanism Underlying the Spatial Pattern Formation of Dominant Tree Species in a Natural Secondary Forest.

    Directory of Open Access Journals (Sweden)

    Guodong Jia

    Full Text Available Studying the spatial pattern of plant species may provide significant insights into processes and mechanisms that maintain stand stability. To better understand the dynamics of naturally regenerated secondary forests, univariate and bivariate Ripley's L(r functions were employed to evaluate intra-/interspecific relationships of four dominant tree species (Populus davidiana, Betula platyphylla, Larix gmelinii and Acer mono and to distinguish the underlying mechanism of spatial distribution. The results showed that the distribution of soil, water and nutrients was not fragmented but presented clear gradients. An overall aggregated distribution existed at most distances. No correlation was found between the spatial pattern of soil conditions and that of trees. Both positive and negative intra- and interspecific relationships were found between different DBH classes at various distances. Large trees did not show systematic inhibition of the saplings. By contrast, the inhibition intensified as the height differences increased between the compared pairs. Except for Larix, universal inhibition of saplings by upper layer trees occurred among other species, and this reflected the vertical competition for light. Therefore, we believe that competition for light rather than soil nutrients underlies the mechanism driving the formation of stand spatial pattern in the rocky mountainous areas examined.

  6. An investigation of the mechanical behavior of initially curved microplates under electrostatic actuation

    KAUST Repository

    Saghir, Shahid

    2018-03-28

    In this article, we investigate the mechanical behavior of initially curved microplates under electrostatic actuation. Microplates are essential components of many Micro-Electro-Mechanical System devices; however, they commonly undergo an initial curvature imperfection, due to the microfabrication process. Initial curvature imperfection significantly affects the mechanical behavior of microplates. In this work, we derive a dynamic analogue of the von Kármán governing equation for such plates. These equations are then used to develop a reduced order model based on the Galerkin procedure to simulate the static and dynamic behavior of the microplate. Two profiles of initial curvature commonly encountered in microfabricated structures are considered, where one assumes a variation in shape along one dimension of the plate only (cylindrical bending shape) while the other assumes a variation in shape along both dimensions of the plate. Their effects on both the static and dynamic responses of the microplates are examined and compared. We validate the reduced order model by comparing the calculated static behavior and the fundamental natural frequency with those computed by a finite element model over a range of the initial plate rise. The static behavior of the microplate is investigated when varying the DC voltage. Then, the dynamic behavior of the microplate is examined under the application of a harmonic AC voltage superimposed to a DC voltage.

  7. Morphological and molecular variations induce mitochondrial dysfunction as a possible underlying mechanism of athletic amenorrhea.

    Science.gov (United States)

    Xiong, Ruo-Hong; Wen, Shi-Lei; Wang, Qiang; Zhou, Hong-Ying; Feng, Shi

    2018-01-01

    Female athletes may experience difficulties in achieving pregnancy due to athletic amenorrhea (AA); however, the underlying mechanisms of AA remain unknown. The present study focuses on the mitochondrial alteration and its function in detecting the possible mechanism of AA. An AA rat model was established by excessive swimming. Hematoxylin and eosin staining, and transmission electron microscopic methods were performed to evaluate the morphological changes of the ovary, immunohistochemical examinations and radioimmunoassays were used to detect the reproductive hormones and corresponding receptors. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to test the mtDNA copy number. PCR and western blot analysis were used to test the expression of ND2. The change of morphological features of the rat ovaries revealed evident abnormalities. Particularly, the features of the mitochondria were markedly altered. In addition, reproductive hormones in the serum and tissues of AA rats were also detected to evaluate the function of the ovaries, and the levels of these hormones were significantly decreased. Furthermore, the mitochondrial DNA copy number (mtDNA) and expression of NADH dehydrogenase subunit 2 (ND2) were quantitated by qPCR or western blot analysis. Accordingly, the mtDNA copy number and expression of ND2 expression were markedly reduced in the AA rats. In conclusion, mitochondrial dysfunction in AA may affect the cellular energy supply and, therefore, result in dysfunction of the ovary. Thus, mitochondrial dysfunction may be considered as a possible underlying mechanism for the occurrence of AA.

  8. Neural mechanisms underlying cognitive control of men with lifelong antisocial behavior.

    Science.gov (United States)

    Schiffer, Boris; Pawliczek, Christina; Mu Ller, Bernhard; Forsting, Michael; Gizewski, Elke; Leygraf, Norbert; Hodgins, Sheilagh

    2014-04-30

    Results of meta-analyses suggested subtle deficits in cognitive control among antisocial individuals. Because almost all studies focused on children with conduct problems or adult psychopaths, however, little is known about cognitive control mechanisms among the majority of persistent violent offenders who present an antisocial personality disorder (ASPD). The present study aimed to determine whether offenders with ASPD, relative to non-offenders, display dysfunction in the neural mechanisms underlying cognitive control and to assess the extent to which these dysfunctions are associated with psychopathic traits and trait impulsivity. Participants comprised 21 violent offenders and 23 non-offenders who underwent event-related functional magnetic resonance imaging while performing a non-verbal Stroop task. The offenders, relative to the non-offenders, exhibited reduced response time interference and a different pattern of conflict- and error-related activity in brain areas involved in cognitive control, attention, language, and emotion processing, that is, the anterior cingulate, dorsolateral prefrontal, superior temporal and postcentral cortices, putamen, thalamus, and amygdala. Moreover, between-group differences in behavioural and neural responses revealed associations with core features of psychopathy and attentional impulsivity. Thus, the results of the present study confirmed the hypothesis that offenders with ASPD display alterations in the neural mechanisms underlying cognitive control and that those alterations relate, at least in part, to personality characteristics. Copyright © 2014. Published by Elsevier Ireland Ltd.

  9. Linear Analytical Solutions of Mechanical Sensitivity in Large Deflection of Unsymmetrically Layered Piezoelectric Plate under Pretension

    Directory of Open Access Journals (Sweden)

    Chun-Fu Chen

    2014-03-01

    Full Text Available Linear analytical study on the mechanical sensitivity in large deflection of unsymmetrically layered and laterally loaded piezoelectric plate under pretension is conducted. von Karman plate theory for large deflection is utilized but extended to the case of an unsymmetrically layered plate embedded with a piezoelectric layer. The governing equations thus obtained are simplified by omitting the arising nonlinear terms, yielding a Bessel or modified Bessel equation for the lateral slope. Depending on the relative magnitude of the piezoelectric effect, for both cases, analytical solutions of various geometrical responses are developed and formulated via Bessel and modified Bessel functions. The associated ultimate radial stresses are further derived following lamina constitutive law to evaluate the mechanical sensitivity of the considered plate. For a nearly monolithic plate under a very low applied voltage, the results are in good agreement with those for a single-layered case due to pure mechanical load available in literature, and thus the present approach is checked. For a two-layered unsymmetric plate made of typical silicon-based materials, a sound piezoelectric effect is illustrated particularly in a low pretension condition.

  10. Theoretical modeling of mechanical homeostasis of a mammalian cell under gravity-directed vector.

    Science.gov (United States)

    Zhou, Lüwen; Zhang, Chen; Zhang, Fan; Lü, Shouqin; Sun, Shujin; Lü, Dongyuan; Long, Mian

    2018-02-01

    Translocation of dense nucleus along gravity vector initiates mechanical remodeling of a eukaryotic cell. In our previous experiments, we quantified the impact of gravity vector on cell remodeling by placing an MC3T3-E1 cell onto upward (U)-, downward (D)-, or edge-on (E)- orientated substrate. Our experimental data demonstrate that orientation dependence of nucleus longitudinal translocation is positively correlated with cytoskeletal (CSK) remodeling of their expressions and structures and also is associated with rearrangement of focal adhesion complex (FAC). However, the underlying mechanism how CSK network and FACs are reorganized in a mammalian cell remains unclear. In this paper, we developed a theoretical biomechanical model to integrate the mechanosensing of nucleus translocation with CSK remodeling and FAC reorganization induced by a gravity vector. The cell was simplified as a nucleated tensegrity structure in the model. The cell and CSK filaments were considered to be symmetrical. All elements of CSK filaments and cytomembrane that support the nucleus were simplified as springs. FACs were simplified as an adhesion cluster of parallel bonds with shared force. Our model proposed that gravity vector-directed translocation of the cell nucleus is mechanically balanced by CSK remodeling and FAC reorganization induced by a gravitational force. Under gravity, dense nucleus tends to translocate and exert additional compressive or stretching force on the cytoskeleton. Finally, changes of the tension force acting on talin by microfilament alter the size of FACs. Results from our model are in qualitative agreement with those from experiments.

  11. The pathologic mechanisms underlying lumbar distraction spinal cord injury in rabbits.

    Science.gov (United States)

    Wu, Di; Zheng, Chao; Wu, Ji; Xue, Jing; Huang, Rongrong; Wu, Di; Song, Yueming

    2017-11-01

    A reliable experimental rabbit model of distraction spinal cord injury (SCI) was established to successfully simulate gradable and replicable distraction SCI. However, further research is needed to elucidate the pathologic mechanisms underlying distraction SCI. The aim of this study was to investigate the pathologic mechanisms underlying lumbar distraction SCI in rabbits. This is an animal laboratory study. Using a self-designed spine distractor, the experimental animals were divided into a control group and 10%, 20%, and 30% distraction groups. Pathologic changes to the spinal cord microvessels in the early stage of distraction SCI were identified by perfusion of the spinal cord vasculature with ink, production of transparent specimens, observation by light microscopy, and observation of corrosion casts of the spinal cord microvascular architecture by scanning electron microscopy. Malondialdehyde (MDA) and superoxide dismutase (SOD) concentrations in the injured spinal cord tissue were measured after 8 hours. With an increasing degree and duration of distraction, the spinal cord microvessels were only partially filled and had the appearance of spasm until rupture and hemorrhage were observed. The MDA concentration increased and the SOD concentration decreased in the spinal cord tissue. Changes to the internal and external spinal cord vessels led to spinal cord ischemia, which is a primary pathologic mechanism of distraction SCI. Lipid peroxidation mediated by free radicals took part in secondary pathologic damage of distraction SCI. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. The Immunomodulatory Effects of Macrolides—A Systematic Review of the Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Petra Zimmermann

    2018-03-01

    Full Text Available BackgroundThe mechanisms underlying the non-antimicrobial immunomodulatory properties of macrolides are not well understood.ObjectivesTo systematically review the evidence for the immunomodulatory properties of macrolides in humans and to describe the underlying mechanism and extent of their influence on the innate and adaptive immune system.MethodsA systematic literature search was done in MEDLINE using the OVID interface from 1946 to December 2016 according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA. Original articles investigating the influence of four macrolides (azithromycin, clarithromycin, erythromycin, and roxithromycin on immunological markers in humans were included.ResultsWe identified 22 randomized, controlled trials, 16 prospective cohort studies, and 8 case–control studies investigating 47 different immunological markers (186 measurements in 1,834 participants. The most frequently reported outcomes were a decrease in the number of neutrophils, and the concentrations of neutrophil elastase, interleukin (IL-8, IL-6, IL-1beta, tumor necrosis factor (TNF-alpha, eosinophilic cationic protein, and matrix metalloproteinase 9. Inhibition of neutrophil function was reported more frequently than eosinophil function. A decrease in T helper (Th 2 cells cytokines (IL-4, IL-5, IL-6 was reported more frequently than a decrease in Th1 cytokines (IL-2, INF-gamma.ConclusionMacrolides influence a broad range of immunological mechanisms resulting in immunomodulatory effects. To optimize the treatment of chronic inflammatory diseases by macrolides, further studies are necessary, particularly comparing different macrolides and dose effect relationships.

  13. Magnesium alloys as body implants: fracture mechanism under dynamic and static loadings in a physiological environment.

    Science.gov (United States)

    Choudhary, Lokesh; Raman, R K Singh

    2012-02-01

    It is essential that a metallic implant material possesses adequate resistance to cracking/fracture under the synergistic action of a corrosive physiological environment and mechanical loading (i.e. stress corrosion cracking (SCC)), before the implant can be put to actual use. This paper presents a critique of the fundamental issues with an assessment of SCC of a rapidly corroding material such as magnesium alloys, and describes an investigation into the mechanism of SCC of a magnesium alloy in a physiological environment. The SCC susceptibility of the alloy in a simulated human body fluid was established by slow strain rate tensile (SSRT) testing using smooth specimens under different electrochemical conditions for understanding the mechanism of SCC. However, to assess the life of the implant devices that often possess fine micro-cracks, SCC susceptibility of notched specimens was investigated by circumferential notch tensile (CNT) testing. CNT tests also produced important design data, i.e. threshold stress intensity for SCC (KISCC) and SCC crack growth rate. Fractographic features of SCC were examined using scanning electron microscopy. The SSRT and CNT results, together with fractographic evidence, confirmed the SCC susceptibility of both smooth and notched specimens of a magnesium alloy in the physiological environment. Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  14. Mechanical characteristics under monotonic and cyclic simple shear of spark plasma sintered ultrafine-grained nickel

    International Nuclear Information System (INIS)

    Dirras, G.; Bouvier, S.; Gubicza, J.; Hasni, B.; Szilagyi, T.

    2009-01-01

    The present work focuses on understanding the mechanical behavior of bulk ultrafine-grained nickel specimens processed by spark plasma sintering of high purity nickel nanopowder and subsequently deformed under large amplitude monotonic simple shear tests and strain-controlled cyclic simple shear tests at room temperature. During cyclic tests, the samples were deformed up to an accumulated von Mises strain of about ε VM = 0.75 (the flow stress was in the 650-700 MPa range), which is extremely high in comparison with the low tensile/compression ductility of this class of materials at quasi-static conditions. The underlying physical mechanisms were investigated by electron microscopy and X-ray diffraction profile analysis. Lattice dislocation-based plasticity leading to cell formation and dislocation interactions with twin boundaries contributed to the work-hardening of these materials. The large amount of plastic strain that has been reached during the shear tests highlights intrinsic mechanical characteristics of the ultrafine-grained nickel studied here.

  15. Mechanical characteristics under monotonic and cyclic simple shear of spark plasma sintered ultrafine-grained nickel

    Energy Technology Data Exchange (ETDEWEB)

    Dirras, G., E-mail: dirras@univ-paris13.fr [LPMTM - CNRS, Institut Galilee, Universite Paris 13, 99 Avenue J.B. Clement, 93430 Villetaneuse (France); Bouvier, S. [LPMTM - CNRS, Institut Galilee, Universite Paris 13, 99 Avenue J.B. Clement, 93430 Villetaneuse (France); Gubicza, J. [Department of Materials Physics, Eoetvoes Lorand University, P.O.B. 32, Budapest H-1518 (Hungary); Hasni, B. [LPMTM - CNRS, Institut Galilee, Universite Paris 13, 99 Avenue J.B. Clement, 93430 Villetaneuse (France); Szilagyi, T. [Department of Materials Physics, Eoetvoes Lorand University, P.O.B. 32, Budapest H-1518 (Hungary)

    2009-11-25

    The present work focuses on understanding the mechanical behavior of bulk ultrafine-grained nickel specimens processed by spark plasma sintering of high purity nickel nanopowder and subsequently deformed under large amplitude monotonic simple shear tests and strain-controlled cyclic simple shear tests at room temperature. During cyclic tests, the samples were deformed up to an accumulated von Mises strain of about {epsilon}{sub VM} = 0.75 (the flow stress was in the 650-700 MPa range), which is extremely high in comparison with the low tensile/compression ductility of this class of materials at quasi-static conditions. The underlying physical mechanisms were investigated by electron microscopy and X-ray diffraction profile analysis. Lattice dislocation-based plasticity leading to cell formation and dislocation interactions with twin boundaries contributed to the work-hardening of these materials. The large amount of plastic strain that has been reached during the shear tests highlights intrinsic mechanical characteristics of the ultrafine-grained nickel studied here.

  16. Failure mechanism of monolayer graphene under hypervelocity impact of spherical projectile

    Science.gov (United States)

    Xia, Kang; Zhan, Haifei; Hu, De'An; Gu, Yuantong

    2016-09-01

    The excellent mechanical properties of graphene have enabled it as appealing candidate in the field of impact protection or protective shield. By considering a monolayer graphene membrane, in this work, we assessed its deformation mechanisms under hypervelocity impact (from 2 to 6 km/s), based on a serial of in silico studies. It is found that the cracks are formed preferentially in the zigzag directions which are consistent with that observed from tensile deformation. Specifically, the boundary condition is found to exert an obvious influence on the stress distribution and transmission during the impact process, which eventually influences the penetration energy and crack growth. For similar sample size, the circular shape graphene possesses the best impact resistance, followed by hexagonal graphene membrane. Moreover, it is found the failure shape of graphene membrane has a strong relationship with the initial kinetic energy of the projectile. The higher kinetic energy, the more number the cracks. This study provides a fundamental understanding of the deformation mechanisms of monolayer graphene under impact, which is crucial in order to facilitate their emerging future applications for impact protection, such as protective shield from orbital debris for spacecraft.

  17. Causes of breast lumps (image)

    Science.gov (United States)

    ... breast lumps are benign (non-cancerous), as in fibroadenoma, a condition that mostly affects women under age ... with the menstrual cycle, whereas a lump from fibroadenoma does not. While most breast lumps are benign, ...

  18. Organ-specific proteomics analysis for identification of response mechanism in soybean seedlings under flooding stress.

    Science.gov (United States)

    Khatoon, Amana; Rehman, Shafiq; Hiraga, Susumu; Makino, Takahiro; Komatsu, Setsuko

    2012-10-22

    Flooding is one of the severe environmental factors which impair growth and yield in soybean plant. To investigate the organ specific response mechanism of soybean under flooding stress, changes in protein species were analyzed using a proteomics approach. Two-day-old soybeans were subjected to flooding for 5 days. Proteins were extracted from root, hypocotyl and leaf, and separated by two-dimensional polyacrylamide gel electrophoresis. In root, hypocotyl and leaf, 51, 66 and 51 protein species were significantly changed, respectively, under flooding stress. In root, metabolism related proteins were increased; however these proteins were decreased in hypocotyl and leaf. In all 3 organs, cytoplasm localized proteins were decreased, and leaf chloroplastic proteins were also decreased. Isoflavone reductase was commonly decreased at protein level in all 3 organs; however, mRNA of isoflavone reductase gene was up-regulated in leaf under flooding stress. Biophoton emission was increased in all 3 organs under flooding stress. The up-regulation of isoflavone reductase gene at transcript level; while decreased abundance at protein level indicated that flooding stress affected the mRNA translation to proteins. These results suggest that concurrence in expression of isoflavone reductase gene at mRNA and protein level along with imbalance in other disease/defense and metabolism related proteins might lead to impaired growth of root, hypocotyl and leaf of soybean seedlings under flooding stress. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Ablation characteristics and reaction mechanism of insulation materials under slag deposition condition

    Science.gov (United States)

    Guan, Yiwen; Li, Jiang; Liu, Yang

    2017-07-01

    Current understanding of the physical and chemical processes involved in the ablation of insulation materials by highly aluminized solid propellants is limited. The study on the heat transfer and ablation principle of ethylene propylene diene monomer (EPDM) materials under slag deposition condition is essential for future design or modification of large solid rocket motors (SRMs) for launch application. In this paper, the alumina liquid flow pattern and the deposition principle in full-scale SRM engines are discussed. The interaction mechanism between the alumina droplets and the wall are analyzed. Then, an experimental method was developed to simulate the insulation material ablation under slag deposition condition. Experimental study was conducted based on a laboratory-scale device. Meanwhile, from the analysis of the cross-sectional morphology and chemical composition of the charring layer after ablation, the reaction mechanism of the charring layer under deposition condition was discussed, and the main reaction equation was derived. The numerical simulation and experimental results show the following. (i) The alumina droplet flow in the deposition section of the laboratory-scale device is similar to that of a full-scale SRM. (ii) The charring layer of the EPDM insulator displays a porous tight/loose structure under high-temperature slag deposition condition. (iii) A seven-step carbothermal reduction in the alumina is derived and established under high-pressure and high-temperature environment in the SRM combustion chamber. (iv) The analysis using thermodynamic software indicates that the reaction of the alumina and charring layer initially forms Al4C3 during the operation. Then, Al element and Al2OC compound are subsequently produced with the reduction in the release of gas CO as well with continuous environmental heating.

  20. Mechanical properties of cellulose electro-active paper under different environmental conditions

    International Nuclear Information System (INIS)

    Kim, Heung Soo; Kim, Jaehwan; Jung, Woochul; Ampofo, Joshua; Craft, William; Sankar, Jagannathan

    2008-01-01

    The mechanical properties of cellulose-based electro-active paper (EAPap) are investigated under various environmental conditions. Cellulose EAPap has been discovered as a smart material that can be used as both sensor and actuator. Its advantages include low voltage operation, light weight, low power consumption, biodegradability and low cost. EAPap is made with cellulose paper coated with thin electrodes. EAPap shows a reversible and reproducible bending movement as well as longitudinal displacement under an electric field. However, EAPap is a complex anisotropic material which has not been fully characterized. This study investigates the mechanical properties of cellulose-based EAPap, including Young's modulus, yield strength, ultimate strength and creep, along with orientation directions, humidity and temperature levels. To test the materials in different humidity and temperature levels, a special material testing system was made that can control the testing environmental conditions. The initial Young's modulus of EAPap is in the range of 4–9 GPa, which was higher than that of other polymer materials. Also, the Young's modulus is orientation dependent, which may be associated with the piezoelectricity of EAPap materials. The elastic strength and stiffness gradually decreased when the humidity and temperature were increased. Creep and relaxation were observed under constant stress and strain, respectively. Through scanning electron microscopy, EAPap is shown to exhibit both layered and oriented cellulose macromolecular structures that impact both the elastic and plastic behavior

  1. Handedness is related to neural mechanisms underlying hemispheric lateralization of face processing

    Science.gov (United States)

    Frässle, Stefan; Krach, Sören; Paulus, Frieder Michel; Jansen, Andreas

    2016-06-01

    While the right-hemispheric lateralization of the face perception network is well established, recent evidence suggests that handedness affects the cerebral lateralization of face processing at the hierarchical level of the fusiform face area (FFA). However, the neural mechanisms underlying differential hemispheric lateralization of face perception in right- and left-handers are largely unknown. Using dynamic causal modeling (DCM) for fMRI, we aimed to unravel the putative processes that mediate handedness-related differences by investigating the effective connectivity in the bilateral core face perception network. Our results reveal an enhanced recruitment of the left FFA in left-handers compared to right-handers, as evidenced by more pronounced face-specific modulatory influences on both intra- and interhemispheric connections. As structural and physiological correlates of handedness-related differences in face processing, right- and left-handers varied with regard to their gray matter volume in the left fusiform gyrus and their pupil responses to face stimuli. Overall, these results describe how handedness is related to the lateralization of the core face perception network, and point to different neural mechanisms underlying face processing in right- and left-handers. In a wider context, this demonstrates the entanglement of structurally and functionally remote brain networks, suggesting a broader underlying process regulating brain lateralization.

  2. Experimental Investigation into Corrosion Effect on Mechanical Properties of High Strength Steel Bars under Dynamic Loadings

    Directory of Open Access Journals (Sweden)

    Hui Chen

    2018-01-01

    Full Text Available The tensile behaviors of corroded steel bars are important in the capacity evaluation of corroded reinforced concrete structures. The present paper studies the mechanical behavior of the corroded high strength reinforcing steel bars under static and dynamic loading. High strength reinforcing steel bars were corroded by using accelerated corrosion methods and the tensile tests were carried out under different strain rates. The results showed that the mechanical properties of corroded high strength steel bars were strain rate dependent, and the strain rate effect decreased with the increase of corrosion degree. The decreased nominal yield and ultimate strengths were mainly caused by the reduction of cross-sectional areas, and the decreased ultimate deformation and the shortened yield plateau resulted from the intensified stress concentration at the nonuniform reduction. Based on the test results, reduction factors were proposed to relate the tensile behaviors with the corrosion degree and strain rate for corroded bars. A modified Johnson-Cook strength model of corroded high strength steel bars under dynamic loading was proposed by taking into account the influence of corrosion degree. Comparison between the model and test results showed that proposed model properly describes the dynamic response of the corroded high strength rebars.

  3. Does the insertion of a gel-based marker at stereotactic breast biopsy allow subsequent wire localizations to be carried out under ultrasound guidance?

    International Nuclear Information System (INIS)

    McMahon, M.A.; James, J.J.; Cornford, E.J.; Hamilton, L.J.; Burrell, H.C.

    2011-01-01

    Aim: To investigate whether the insertion of a gel-based marker at the time of stereotactic breast biopsy allows subsequent preoperative localization to be performed under ultrasound guidance. Materials and methods: One hundred consecutive women who underwent either a 10 G stereotactic vacuum-assisted breast biopsy or 14 G stereotactic core biopsy with marker placement, followed by wire localization and surgical excision were identified. All had mammographic abnormalities not initially visible with ultrasound. The method of preoperative localization was recorded and its success judged with reference to the wire position on the post-procedure films relative to the mammographic abnormality and the marker. Histopathology data were reviewed to ensure the lesion had been adequately excised. Results: Eighty-three women (83%) had a successful ultrasound-guided wire localization. Successful ultrasound-guided localization was more likely after stereotactic vacuum biopsy (86%) compared to stereotactic core biopsy (68%), although this did not quite reach statistical significance (p = 0.06). Conclusion: The routine placement of a gel-based marker after stereotactic breast biopsy facilitates preoperative ultrasound-guided localization.

  4. Thêta-Cream versus Bepanthol lotion in breast cancer patients under radiotherapy. A new prophylactic agent in skin care?

    Science.gov (United States)

    Röper, Barbara; Kaisig, Danielle; Auer, Florian; Mergen, Ertan; Molls, Michael

    2004-05-01

    In radiotherapy of the breast following breast-conserving surgery, the adverse reaction predominantly found is confined to the skin. After phase II studies, Thêta-Cream, containing CM Glucan, Hydroxyprolisilan C und Matrixyl as active substances, was said to have prophylactic properties of preventing acute radiation side effects in skin tissue. In a prospective randomized study, Thêta-cream was compared with standard skin care using Bepanthol lotion. 20 breast cancer patients were randomly assigned to use Thêta-Cream or Bepanthol lotion during radiotherapy. At 0, 30, and 50 Gy, acute skin toxicity was scored with a modified RTOG scoring system. The patients' content with the skin care and the technical assistants' content with the skin marks were recorded. For single aspects of toxicity and their sums in defined skin areas, no differences in median and range between study groups were found. The maximal toxicity anywhere in the breast averaged in a moderate erythema, mild elevation of skin temperature, no desquamation in both groups. Mild itchiness and sporadic efflorescences were more frequently seen with Thêta-Cream. According to a ranking of anonymized breast photos at 50 Gy by independent investigators, side effects were equal. Patients' content was high with both skin care regimens (1.25 on a scale from 0 to 10). With Thêta-Cream a trend toward worse skin marks was noted. Adverse events exclusively occurred in Thêta-Cream users: suspected allergic reaction once, and the necessity for resimulation twice. In direct comparison with dexpanthenol-containing lotion, no advantage for Thêta-Cream was found. Higher costs and problems with skin marks prevent a general recommendation.

  5. Fatigue behaviour of the austenitic steel 1.4550 under mechanical and thermal cyclic loading

    Energy Technology Data Exchange (ETDEWEB)

    Siegele, D.; Fingerhuth, J.; Varfolomeev, I.; Moroz, S. [Fraunhofer Institute for Mechanics of Materials (IWM), Freiburg (Germany)

    2014-07-01

    Fatigue behaviour of the austenitic steel 1.4550 (X6CrNiNb18-10) under low-cycle fatigue and high-cycle thermal fatigue was investigated with in two research projects supported by the Federal Ministry of Economic Affairs and Energy and the Ministry of Education and Research. The objectives of the projects were the gain of deep understanding of the damage mechanisms under mechanical and thermal cyclic loading and the development of material models and simulation procedures for an improved lifetime assessment. In comparison to the advanced mechanism based material models engineering computational procedures were proven with respect to their applicability and conservatisms. For thermal cyclic loading, test equipment and technique were developed which allow for cyclic thermal loading with temperature ranges between 1 00 C and 300 C and frequencies between 0.1 and 1 Hz. As a result, tests with a temperature range of 150 C and lower showed no crack formation up to 300,000 cycles. For temperature ranges of 200 C and higher multiple crack patterns were observed with the deepest crack of about 1.3 mm after 1,000,000 cycles, whereas the difference in crack depth between 300,000 and 1,000,000 cycles was negligibly small. To model the fatigue lifetime, the D{sub TMF} damage parameter was applied to the low-cycle fatigue and the thermal, high frequent fatigue tests. For thermal fatigue, the analyses predicted in agreement with the tests crack initiation followed by crack propagation, subsequent retardation and arrest. This behaviour can be explained qualitatively and quantitatively using the methods of linear-elastic fracture mechanics, whereas the consideration of the interaction of multiple cracks is essential to describe the experimentally observed crack retardation. The results for thermal fatigue are in the scatterband of the mechanical p and thermo-mechanical fatigue results and the cycles to failure are 10 times higher than those estimated according to the KTA fatigue

  6. Peripheral afferent mechanisms underlying acupuncture inhibition of cocaine behavioral effects in rats.

    Directory of Open Access Journals (Sweden)

    Seol Ah Kim

    Full Text Available Administration of cocaine increases locomotor activity by enhancing dopamine transmission. To explore the peripheral mechanisms underlying acupuncture treatment for drug addiction, we developed a novel mechanical acupuncture instrument (MAI for objective mechanical stimulation. The aim of this study was to evaluate whether acupuncture inhibition of cocaine-induced locomotor activity is mediated through specific peripheral nerves, the afferents from superficial or deep tissues, or specific groups of nerve fibers. Mechanical stimulation of acupuncture point HT7 with MAI suppressed cocaine-induced locomotor activity in a stimulus time-dependent manner, which was blocked by severing the ulnar nerve or by local anesthesia. Suppression of cocaine-induced locomotor activity was elicited after HT7 stimulation at frequencies of either 50 (for Meissner corpuscles or 200 (for Pacinian corpuscles Hz and was not affected by block of C/Aδ-fibers in the ulnar nerve with resiniferatoxin, nor generated by direct stimulation of C/Aδ-fiber afferents with capsaicin. These findings suggest that HT7 inhibition of cocaine-induced locomotor activity is mediated by A-fiber activation of ulnar nerve that originates in superficial and deep tissue.

  7. An easily reversible structural change underlies mechanisms enabling desert crust cyanobacteria to survive desiccation.

    Science.gov (United States)

    Bar-Eyal, Leeat; Eisenberg, Ido; Faust, Adam; Raanan, Hagai; Nevo, Reinat; Rappaport, Fabrice; Krieger-Liszkay, Anja; Sétif, Pierre; Thurotte, Adrien; Reich, Ziv; Kaplan, Aaron; Ohad, Itzhak; Paltiel, Yossi; Keren, Nir

    2015-10-01

    Biological desert sand crusts are the foundation of desert ecosystems, stabilizing the sands and allowing colonization by higher order organisms. The first colonizers of the desert sands are cyanobacteria. Facing the harsh conditions of the desert, these organisms must withstand frequent desiccation-hydration cycles, combined with high light intensities. Here, we characterize structural and functional modifications to the photosynthetic apparatus that enable a cyanobacterium, Leptolyngbya sp., to thrive under these conditions. Using multiple in vivo spectroscopic and imaging techniques, we identified two complementary mechanisms for dissipating absorbed energy in the desiccated state. The first mechanism involves the reorganization of the phycobilisome antenna system, increasing excitonic coupling between antenna components. This provides better energy dissipation in the antenna rather than directed exciton transfer to the reaction center. The second mechanism is driven by constriction of the thylakoid lumen which limits diffusion of plastocyanin to P700. The accumulation of P700(+) not only prevents light-induced charge separation but also efficiently quenches excitation energy. These protection mechanisms employ existing components of the photosynthetic apparatus, forming two distinct functional modes. Small changes in the structure of the thylakoid membranes are sufficient for quenching of all absorbed energy in the desiccated state, protecting the photosynthetic apparatus from photoinhibitory damage. These changes can be easily reversed upon rehydration, returning the system to its high photosynthetic quantum efficiency. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Kidney branching morphogenesis under the control of a ligand–receptor-based Turing mechanism

    International Nuclear Information System (INIS)

    Menshykau, Denis; Iber, Dagmar

    2013-01-01

    The main signalling proteins that control early kidney branching have been defined. Yet the underlying mechanism is still elusive. We have previously shown that a Schnakenberg-type Turing mechanism can recapitulate the branching and protein expression patterns in wild-type and mutant lungs, but it is unclear whether this mechanism would extend to other branched organs that are regulated by other proteins. Here, we show that the glial cell line-derived neurotrophic factor–RET regulatory interaction gives rise to a Schnakenberg-type Turing model that reproduces the observed budding of the ureteric bud from the Wolffian duct, its invasion into the mesenchyme and the observed branching pattern. The model also recapitulates all relevant protein expression patterns in wild-type and mutant mice. The lung and kidney models are both based on a particular receptor–ligand interaction and require (1) cooperative binding of ligand and receptor, (2) a lower diffusion coefficient for the receptor than for the ligand and (3) an increase in the receptor concentration in response to receptor–ligand binding (by enhanced transcription, more recycling or similar). These conditions are met also by other receptor–ligand systems. We propose that ligand–receptor-based Turing patterns represent a general mechanism to control branching morphogenesis and other developmental processes. (paper)

  9. Numerical and experimental characterization of ceramic pebble beds under cycling mechanical loading

    Energy Technology Data Exchange (ETDEWEB)

    Pupeschi, S., E-mail: pupeschi.simone@hotmail.it [Institute for Applied Materials, Karlsruhe Institute of Technology (KIT) (Germany); Knitter, R.; Kamlah, M. [Institute for Applied Materials, Karlsruhe Institute of Technology (KIT) (Germany); Gan, Y. [School of Civil Engineering, The University of Sydney, Sydney, NSW, 2006 (Australia)

    2016-11-15

    Highlights: • The effect of cyclic loading on the mechanical response of pebble beds was assessed. • Numerical simulations were performed with KIT-DEM code. • The numerical simulations were compared with the experimental outcomes. • A good qualitative agreement between experimental and simulation results was found. • The pebble size distribution affects the mechanical response of the assemblies. - Abstract: All solid breeder concepts considered to be tested in ITER (International Thermonuclear Experimental Reactor), make use of lithium-based ceramics in the form of pebble-packed beds as tritium breeder. A thorough understanding of the thermal and mechanical properties of the ceramic pebble beds under fusion relevant conditions is essential for the design of the breeder blanket modules of future fusion reactors. In this study, the effect of cyclic loading on the mechanical behaviour of pebble bed assemblies was investigated using a Discrete Element Method (DEM) code. The numerical simulations were compared with the experimental outcomes. The results of numerical simulations show that the pebble size distribution affects noticeably the stress-strain behaviour of the assemblies. A good qualitative agreement between experimental and simulation results was found in terms of difference between residual strains of consecutive cycles. An increase of the oedometric modulus with the compressive load was observed for all investigated compositions in both experimental and DEM simulations. The numerical results show an increase of the oedometric modulus (E) with progressive compaction of the assemblies due to the cycling loading, while no significant influence of the pebbles size distribution was observed.

  10. Mechanical properties and fracture behaviour of defective phosphorene nanotubes under uniaxial tension

    Science.gov (United States)

    Liu, Ping; Pei, Qing-Xiang; Huang, Wei; Zhang, Yong-Wei

    2017-12-01

    The easy formation of vacancy defects and the asymmetry in the two sublayers of phosphorene nanotubes (PNTs) may result in brand new mechanical properties and failure behaviour. Herein, we investigate the mechanical properties and fracture behaviour of defective PNTs under uniaxial tension using molecular dynamics simulations. Our simulation results show that atomic vacancies cause local stress concentration and thus significantly reduce the fracture strength and fracture strain of PNTs. More specifically, a 1% defect concentration is able to reduce the fracture strength and fracture strain by as much as 50% and 66%, respectively. Interestingly, the reduction in the mechanical properties is found to depend on the defect location: a defect located in the outer sublayer has a stronger effect than one located in the inner layer, especially for PNTs with a small diameter. Temperature is also found to strongly influence the mechanical properties of both defect-free and defective PNTs. When the temperature is increased from 0 K to 400 K, the fracture strength and fracture strain of defective PNTs with a defect concentration of 1% are reduced further by 71% and 61%, respectively. These findings are of great importance for the structural design of PNTs as building blocks in nanodevices.

  11. Mechanical properties of novel forms of graphyne under strain: A density functional theory study

    Science.gov (United States)

    Majidi, Roya

    2017-06-01

    The mechanical properties of two forms of graphyne sheets named α-graphyne and α2-graphyne under uniaxial and biaxial strains were studied. In-plane stiffness, bulk modulus, and shear modulus were calculated based on density functional theory. The in-plane stiffness, bulk modulus, and shear modulus of α2-graphyne were found to be larger than that of α-graphyne. The maximum values of supported uniaxial and biaxial strains before failure were determined. The α-graphyne was entered into the plastic region with the higher magnitude of tension in comparison to α2-graphyne. The mechanical properties of α-graphyne family revealed that these forms of graphyne are proper materials for use in nanomechanical applications.

  12. Fatigue responses of lead zirconate titanate stacks under semibipolar electric cycling with mechanical preload

    Science.gov (United States)

    Wang, Hong; Cooper, Thomas A.; Lin, Hua-Tay; Wereszczak, Andrew A.

    2010-10-01

    Lead zirconate titanate (PZT) stacks that had an interdigital internal electrode configuration were tested to more than 108 cycles. A 100 Hz semibipolar sine wave with a field range of +4.5/-0.9 kV/mm was used in cycling with a concurrently-applied 20 MPa preload. Significant reductions in piezoelectric and dielectric responses were observed during the cycling depending on the measuring condition. Extensive partial discharges were also observed. These surface events resulted in the erosion of external electrode and the exposure of internal electrodes. Sections prepared by sequential polishing technique revealed a variety of damage mechanisms including delaminations, pores, and etch grooves. The scale of damage was correlated with the degree of fatigue-induced reduction in piezoelectric and dielectric responses. The results from this study demonstrate the feasibility of using a semibipolar mode to drive a PZT stack under a mechanical preload and illustrate the potential fatigue and damages of the stack in service.

  13. Investigation of sheet steel St 37.2 under mechanical impact

    International Nuclear Information System (INIS)

    Berg, H.P.; Brennecke, P.; Koester, R.; Friehmelt, V.

    1990-01-01

    Special waste originating, e.g. from chemical industry and radioactive wastes are emplaced in disposal mines. Slinger stowing is an approved technique to fill up residual voids in emplacement rooms. If it should be applied, possible mechanical loads on the integrity of sheet steel containers have to be considered. By theoretical calculations and by experiments under variation of different parameters using test specimen and backfill material from the Konrad mine using the container type V as an example it has been shown that sheet steel St 37.2 with a wall thickness of 3 mm will withstand mechanical impact imposed by backfill particles having a speed of 24 m/s. (orig.) [de

  14. Mechanisms Underlying the Anti-Aging and Anti-Tumor Effects of Lithocholic Bile Acid

    Directory of Open Access Journals (Sweden)

    Anthony Arlia-Ciommo

    2014-09-01

    Full Text Available Bile acids are cholesterol-derived bioactive lipids that play essential roles in the maintenance of a heathy lifespan. These amphipathic molecules with detergent-like properties display numerous beneficial effects on various longevity- and healthspan-promoting processes in evolutionarily distant organisms. Recent studies revealed that lithocholic bile acid not only causes a considerable lifespan extension in yeast, but also exhibits a substantial cytotoxic effect in cultured cancer cells derived from different tissues and organisms. The molecular and cellular mechanisms underlying the robust anti-aging and anti-tumor effects of lithocholic acid have emerged. This review summarizes the current knowledge of these mechanisms, outlines the most important unanswered questions and suggests directions for future research.

  15. Laboratory studies of the corrosion and mechanical properties of titanium grade-12 under WIPP repository conditions

    International Nuclear Information System (INIS)

    Sorensen, N.R.

    1990-01-01

    The author reviews laboratory work done at the Sandia Laboratories on the properties of titanium grade 12. The effect of gamma radiation on corrosion and mechanical properties has been investigated; no real effect has been detected on corrosion rate, Charpy impact energy, or tensile properties at 90 degrees and 10 4 rad/h. No structural changes are evident under examination by SEM or TEM. There is also no evidence of crevice corrosion after five years of exposure. The effect of radiation on hydrogen uptake was also investigated. Radiation appears to reduce the extent of uptake. The microstructure of titanium-12 changes with the addition of hydrogen to a structure with alternating layers of alpha and beta phase. A decrease in mechanical properties is associated with this change

  16. Atrial Arrhythmias in Obstructive Sleep Apnea: Underlying Mechanisms and Implications in the Clinical Setting

    Directory of Open Access Journals (Sweden)

    David Filgueiras-Rama

    2013-01-01

    Full Text Available Obstructive sleep apnea (OSA is a common disorder characterized by repetitive interruption of ventilation during sleep caused by recurrent upper airway collapse, which leads to intermittent hypoxia. The disorder is commonly undiagnosed despite its relationship with substantial cardiovascular morbidity and mortality. Moreover, the effects of the disorder appear to be particularly dangerous in young subjects. In the last decade, substantial clinical evidence has identified OSA as independent risk factor for both bradyarrhythmias and tachyarrhythmias. To date the mechanisms leading to such arrhythmias have not been completely understood. However, recent data from animal models and new molecular analyses have increased our knowledge of the field, which might lead to future improvement in current therapeutic strategies mainly based on continuous positive airway pressure. This paper aims at providing readers a brief and specific revision of current knowledge about the mechanisms underlying atrial arrhythmias in OSA and their clinical and therapeutic implications.

  17. Pluripotent Stem Cell Studies Elucidate the Underlying Mechanisms of Early Embryonic Development

    Directory of Open Access Journals (Sweden)

    Lingyu Li

    2011-03-01

    Full Text Available Early embryonic development is a multi-step process that is intensively regulated by various signaling pathways. Because of the complexity of the embryo and the interactions between the germ layers, it is very difficult to fully understand how these signals regulate embryo patterning. Recently, pluripotent stem cell lines derived from different developmental stages have provided an in vitro system for investigating molecular mechanisms regulating cell fate decisions. In this review, we summarize the major functions of the BMP, FGF, Nodal and Wnt signaling pathways, which have well-established roles in vertebrate embryogenesis. Then, we highlight recent studies in pluripotent stem cells that have revealed the stage-specific roles of BMP,FGF and Nodal pathways during neural differentiation. These findings enhance our understanding of the stepwise regulation of embryo patterning by particular signaling pathways and provide new insight into the mechanisms underlying early embryonic development.

  18. The Dynamic Evolution of Firms’ Pollution Control Strategy under Graded Reward-Penalty Mechanism

    Directory of Open Access Journals (Sweden)

    Li Ming Chen

    2016-01-01

    Full Text Available The externality of pollution problem makes firms lack enough incentive to reduce pollution emission. Therefore, it is necessary to design a reasonable environmental regulation mechanism so as to effectively urge firms to control pollution. In order to inspire firms to control pollution, we divide firms into different grades according to their pollution level and construct an evolutionary game model to analyze the interaction between government’s regulation and firms’ pollution control under graded reward-penalty mechanism. Then, we discuss stability of firms’ pollution control strategy and derive the condition of inspiring firms to control pollution. Our findings indicate that firms tend to control pollution after long-term repeated games if government’s excitation level and monitoring frequency meet some conditions. Otherwise, firms tend to discharge pollution that exceeds the stipulated standards. As a result, in order to effectively control pollution, a government should adjust its excitation level and monitoring frequency reasonably.

  19. Molecular and Microbial Mechanisms Increasing Soil C Storage Under Future Rates of Anthropogenic N Deposition

    Energy Technology Data Exchange (ETDEWEB)

    Zak, Donald R. [Univ. of Michigan, Ann Arbor, MI (United States)

    2017-11-17

    A growing body of evidence reveals that anthropogenic N deposition can reduce the microbial decay of plant detritus and increase soil C storage across a wide range of terrestrial ecosystems. This aspect of global change has the potential to constrain the accumulation of anthropogenic CO2 in the Earth’s atmosphere, and hence slow the pace of climate warming. The molecular and microbial mechanisms underlying this biogeochemical response are not understood, and they are not a component of any coupled climate-biogeochemical model estimating ecosystem C storage, and hence, the future climate of an N-enriched Earth. Here, we report the use of genomic-enabled approaches to identify the molecular underpinnings of the microbial mechanisms leading to greater soil C storage in response to anthropogenic N deposition, thereby enabling us to better anticipate changes in soil C storage.

  20. A hypothesis regarding the molecular mechanism underlying dietary soy-induced effects on seizure propensity.

    Directory of Open Access Journals (Sweden)

    Cara Jean Westmark

    2014-09-01

    Full Text Available Numerous neurological disorders including fragile X syndrome, Down syndrome, autism and Alzheimer’s disease are comorbid with epilepsy. We have observed elevated seizure propensity in mouse models of these disorders dependent on diet. Specifically, soy-based diets exacerbate audiogenic-induced seizures in juvenile mice. We have also found potential associations between the consumption of soy-based infant formula and seizure incidence, epilepsy comorbidity and autism diagnostic scores in autistic children by retrospective analyses of medical record data. In total, these data suggest that consumption of high levels of soy protein during postnatal development may affect neuronal excitability. Herein, we present our theory regarding the molecular mechanism underlying soy-induced effects on seizure propensity. We hypothesize that soy phytoestrogens interfere with metabotropic glutamate receptor signaling through an estrogen receptor-dependent mechanism, which results in elevated production of key synaptic proteins and decreased seizure threshold.

  1. Curcumin-mediated regulation of intestinal barrier function: The mechanism underlying its beneficial effects.

    Science.gov (United States)

    Ghosh, Siddhartha S; He, Hongliang; Wang, Jing; Gehr, Todd W; Ghosh, Shobha

    2018-01-02

    Curcumin has anti-inflammatory, anti-oxidant and anti-proliferative properties established largely by in vitro studies. Accordingly, oral administration of curcumin beneficially modulates many diseases including diabetes, fatty-liver disease, atherosclerosis, arthritis, cancer and neurological disorders such as depression, Alzheimer's or Parkinson's disease. However, limited bioavailability and inability to detect curcumin in circulation or target tissues has hindered the validation of a causal role. We established curcumin-mediated decrease in the release of gut bacteria-derived lipopolysaccharide (LPS) into circulation by maintaining the integrity of the intestinal barrier function as the mechanism underlying the attenuation of metabolic diseases (diabetes, atherosclerosis, kidney disease) by curcumin supplementation precluding the need for curcumin absorption. In view of the causative role of circulating LPS and resulting chronic inflammation in the development of diseases listed above, this review summarizes the mechanism by which curcumin affects the several layers of the intestinal barrier and, despite negligible absorption, can beneficially modulate these diseases.

  2. Modeling of the mechanical behavior of austenitic stainless steels under pure fatigue and fatigue relaxation loadings

    International Nuclear Information System (INIS)

    Hajjaji-Rachdi, Fatima

    2015-01-01

    Austenitic stainless steels are potential candidates for structural components of sodium-cooled fast neutron reactors. Many of these components will be subjected to cyclic loadings including long hold times (1 month) under creep or relaxation at high temperature. These hold times are unattainable experimentally. The aim of the present study is to propose mechanical models which take into account the involved mechanisms and their interactions during such complex loadings. First, an experimental study of the pure fatigue and fatigue-relaxation behavior of 316L(N) at 500 C has been carried out with very long hold times (10 h and 50 h) compared with the ones studied in literature. Tensile tests at 600 C with different applied strain rates have been undertaken in order to study the dynamic strain ageing phenomenon. Before focusing on more complex loadings, the mean field homogenization approach has been used to predict the mechanical behavior of different FCC metals and alloys under low cycle fatigue at room temperature. Both Hill-Hutchinson and Kroener models have been used. Next, a physically-based model based on dislocation densities has been developed and its parameters measured. The model allows predictions in a qualitative agreement with experimental data for tensile loadings. Finally, this model has been enriched to take into account visco-plasticity, dislocation climb and interaction between dislocations and solute atoms, which are influent during creep-fatigue or fatigue relaxation at high temperature. The proposed model uses three adjustable parameters only and allows rather accurate prediction of the behavior of 316L(N) steel under tensile loading and relaxation. (author) [fr

  3. Mechanical properties of the human spinal cord under the compressive loading.

    Science.gov (United States)

    Karimi, Alireza; Shojaei, Ahmad; Tehrani, Pedram

    2017-12-01

    The spinal cord as the most complex and critical part of the human body is responsible for the transmission of both motor and sensory impulses between the body and the brain. Due to its pivotal role any types of physical injury in that disrupts its function following by shortfalls, including the minor motor and sensory malfunctions as well as complicate quadriplegia and lifelong ventilator dependency. In order to shed light on the injuries to the spinal cord, the application of the computational models to simulate the trauma impact loading to that are deemed required. Nonetheless, it has not been fulfilled since there is a paucity of knowledge about the mechanical properties of the spinal cord, especially the cervical one, under the compressive loading on the grounds of the difficulty in obtaining this tissue from the human body. This study was aimed at experimentally measuring the mechanical properties of the human cervical spinal cord of 24 isolated fresh samples under the unconfined compressive loading at a relatively low strain rate. The stress-strain data revealed the elastic modulus and maximum/failure stress of 40.12±6.90 and 62.26±5.02kPa, respectively. Owing to the nonlinear response of the spinal cord, the Yeoh, Ogden, and Mooney-Rivlin hyperelastic material models have also been employed. The results may have implications not only for understanding the linear elastic and nonlinear hyperelastic mechanical properties of the cervical spinal cord under the compressive loading, but also for providing a raw data for investigating the injury as a result of the trauma thru the numerical simulations. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Dynamic tensile behaviour and deformational mechanism of C5191 phosphor bronze under high strain rates deformation

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Dao-chun [College of Mechanical and Electrical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 210016 (China); College of Mechanical and Electrical Engineering, Taizhou Vocational & Technical College, Taizhou 318000 (China); Chen, Ming-he, E-mail: meemhchen@nuaa.edu.cn [College of Mechanical and Electrical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 210016 (China); Wang, Lei; Cheng, Hu [College of Mechanical Engineering, Taizhou University, Taizhou 318000 (China)

    2016-01-01

    High speed stamping process is used to high strength and high electrical conductivity phosphor bronze with extremely high strain rates more than 10{sup 3} s{sup −1}. This study on the dynamic tensile behaviour and deformational mechanism is to optimise the high speed stamping processes and improve geometrical precision in finished products. Thus, the tensile properties and deformation behaviour of C5191 phosphor bronze under quasi-static tensile condition at a strain rate of 0.001 s{sup −1} by electronic universal testing machine, and dynamic tensile condition at strain rate of 500, 1000 and 1500 s{sup −1} by split Hopkinson tensile bar (SHTB) apparatus were studied. The effects of strain rate and the deformation mechanism were investigated by means of SEM and TEM. The results showed that the yield strength and tensile strength of C5191 phosphor bronze under high strain rates deformation increased by 32.77% and 11.07% respectively compared with quasi-static condition, the strain hardening index increases from 0.075 to 0.251, and the strength of the material strain rates sensitivity index change from 0.005 to 0.022, which presented a clear sensitive to strain rates. Therefore, it is claimed that the dominant deformation mechanism was changed by the dislocation motion under different strain rates, and the ability of plastic deformation of C5191 phosphor bronze increased due to the number of movable dislocations increased significantly, started multi-line slip, and the soft effect of adiabatic temperature rise at the strain rate ranging from 500 to 1500 s{sup −1}.

  5. Mechanisms of astrocytic K(+) clearance and swelling under high extracellular K(+) concentrations.

    Science.gov (United States)

    Murakami, Shingo; Kurachi, Yoshihisa

    2016-03-01

    In response to the elevation of extracellular K(+) concentration ([K(+)]out), astrocytes clear excessive K(+) to maintain conditions necessary for neural activity. K(+) clearance in astrocytes occurs via two processes: K(+) uptake and K(+) spatial buffering. High [K(+)]out also induces swelling in astrocytes, leading to edema and cell death in the brain. Despite the importance of astrocytic K(+) clearance and swelling, the underlying mechanisms remain unclear. Here, we report results from a simulation analysis of astrocytic K(+) clearance and swelling. Astrocyte models were constructed by incorporating various mechanisms such as intra/extracellular ion concentrations of Na(+), K(+), and Cl(-), cell volume, and models of Na,K-ATPase, Na-K-Cl cotransporter (NKCC), K-Cl cotransporter, inwardly-rectifying K(+) (KIR) channel, passive Cl(-) current, and aquaporin channel. The simulated response of astrocyte models under the uniform distribution of high [K(+)]out revealed significant contributions of NKCC and Na,K-ATPase to increases of intracellular K(+) and Cl(-) concentrations, and swelling. Moreover, we found that, under the non-uniform distribution of high [K(+)]out, KIR channels localized at synaptic clefts absorbed excess K(+) by depolarizing the equivalent potential of K(+) (E K) above membrane potential, while K(+) released through perivascular KIR channels was enhanced by hyperpolarizing E K and depolarizing membrane potential. Further analysis of simulated drug effects revealed that astrocyte swelling was modulated by blocking each of the ion channels and transporters. Our simulation analysis revealed controversial mechanisms of astrocytic K(+) clearance and swelling resulting from complex interactions among ion channels and transporters.

  6. Pontomedullary lacerations and concomitant head and neck injuries: their underlying mechanism. A prospective autopsy study.

    Science.gov (United States)

    Živković, Vladimir; Nikolić, Slobodan; Strajina, Veljko; Babić, Dragan; Djonić, Danijela; Djurić, Marija

    2012-09-01

    It is a well-documented fact that pontomedullary lacerations (PML) occur as a result of severe craniocervical injury, but their underlying mechanism has yet to be fully clarified. The aim of this prospective study has been to give greater insight into the underlying mechanism of PML through determining the site of blunt head-impact, as well as the presence of concomitant head and neck injuries in cases of brainstem PML. A total of 56 cases with partial PML have been analysed for this study. The case group was composed of 40 men and 16 women, averaging in age 44.2 ± 19.2 years and consisting of 7 motorcyclists, 4 bicyclists, 18 car occupants, 16 pedestrians, and 10 victims of falls from a height, as well as 1 victim of a fall from standing height. The presented study has shown that there are several possible mechanisms of PML. Impact to the chin, with or without a skull base fracture, most often leads to this fatal injury, due to the impact force transmission either through the jawbone or vertebral column; most likely in combination with a fronto-posterior hyperextension of the head. Additionally, lateral head-impacts with subsequent hinge fractures and PML may also be a possible mechanism. The jawbone and other facial bones are able to act as shock absorbers, and their fracture may diminish the energy transfer towards the skull and protect the brain and brainstem from injury. The upper cervical spine can act as damper and energy absorber as well, and may prevent any occurrence of fracture to the base of the skull.

  7. Structural integrity and failure mechanisms of a smart piezoelectric actuator under a cyclic bending mode

    International Nuclear Information System (INIS)

    Woo, Sung-Choong; Goo, Nam Seo

    2008-01-01

    Information on the onset and evolution of damage within materials is essential for guaranteeing the integrity of actuator systems. The authors have evaluated the structural integrity and the failure mechanisms of smart composite actuators with a PZT ceramic plate under electric cyclic loading. For this, two kinds of actuators, actuator 1 and actuator 2, were manufactured. Prior to the main testing, performance testing was performed on the actuators to determine their resonant frequencies. Electric cyclic tests were conducted up to twenty million cycles. An acoustic emission technique was used for monitoring the damage evolution in real time. We observed the extent of the damage after testing using scanning electron microscopy and reflected optical microscopy to support characteristics in the acoustic emission behavior that corresponded to specific types of damage mechanisms. It was shown that the initial damage mechanism of the smart composite actuator under electric cyclic loading originated from the transgranular micro-fatigue damage in the PZT ceramic layer. With increasing cycles, a local intergranular crack initiated and developed onto the surface of the PZT ceramic layer or propagated into the internal layer. Finally, short-circuiting led to the electric breakdown of the actuator. These results were different depending on the drive frequencies and the configuration of the actuators. Moreover, we differentiated between the aforementioned damage mechanisms via AE signal pattern analyses based on the primary frequency and the waveform. From our results, we conclude that the drive frequency and the existence of a protecting layer are dominant factors in the structural integrity of the smart composite actuator

  8. Evaluation of Possible Proximate Mechanisms Underlying the Kinship Theory of Intragenomic Conflict in Social Insects.

    Science.gov (United States)

    Galbraith, David A; Yi, Soojin V; Grozinger, Christina M

    2016-12-01

    Kinship theory provides a universal framework in which to understand the evolution of altruism, but there are many molecular and genetic mechanisms that can generate altruistic behaviors. Interestingly, kinship theory specifically predicts intragenomic conflict between maternally-derived alleles (matrigenes) and paternally-derived alleles (patrigenes) over the generation of altruistic behavior in cases where the interests of the matrigenes and patrigenes are not aligned. Under these conditions, individual differences in selfish versus altruistic behavior are predicted to arise from differential expression of the matrigenes and patrigenes (parent-specific gene expression or PSGE) that regulate selfish versus altruistic behaviors. As one of the leading theories to describe PSGE and genomic imprinting, kinship theory has been used to generate predictions to describe the reproductive division of labor in social insect colonies, which represents an excellent model system to test the hypotheses of kinship theory and examine the underlying mechanisms driving it. Recent studies have confirmed the predicted differences in the influence of matrigenes and patrigenes on reproductive division of labor in social insects, and demonstrated that these differences are associated with differences in PSGE of key genes involved in regulating reproductive physiology, providing further support for kinship theory. However, the mechanisms mediating PSGE in social insects, and how PSGE leads to differences in selfish versus altruistic behavior, remain to be determined. Here, we review the available supporting evidence for three possible epigenetic mechanisms (DNA methylation, piRNAs, and histone modification) that may generate PSGE in social insects, and discuss how these may lead to variation in social behavior. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email

  9. Experimental study of the anisotropic properties of argillite under moisture and mechanical loads

    International Nuclear Information System (INIS)

    Yang, D.S.; Chanchole, S.; Wang, L.L.; Bornert, M.; Gatmiri, B.

    2012-01-01

    Document available in extended abstract form only. Due to various factors, such as sedimentation, layered morphology of clay mineral, in-situ stress, etc., the behavior of argillite rocks is often anisotropic. In order to study the anisotropy of the Callovo-Oxfordian (COx) argillite considered as a possible host rock for high-level radioactive nuclear waste repository in France, a series of tests including uniaxial compression and dehydration and hydration at different constant applied stress levels, are carried out using a specific setup combining mechanical and moisture loading devices. During these hydro-mechanical tests, this specific setup can also continuously capture images of the sample surfaces to be subsequently analyzed using Digital Image Correlation techniques (DIC) in order to determine full-field strains. In this study, three sampling directions are used with the angle θ between the bedding plane and the cylindrical sample axis equal to 45 deg., 60 deg. and 90 deg.. To investigate the mechanical anisotropy, uniaxial compressive tests with mechanical loading and unloading cycles are performed on several different samples at the same moisture level. The results show that the mechanical parameters (apparent modulus, failure stress) depend on loading orientation relative to the stratification plane. For a given water content, the failure stress reaches maximum values for θ =90 deg. and minimum values for θ =45 deg.. To study the hydric anisotropy, dehydration and hydration tests under stress-free conditions are performed on two cylindrical samples (θ=90 deg. and θ=60 deg.). Three cycles of hydration and dehydration are carried out by varying the relative humidity between 40% and 95%. The sample weight, the deformation measured by strain gages and the relative humidity are continuously recorded during the test by means of another specific setup described in [Pham et al., 2007]. Fig.1a illustrates the evolution of the strains of the sample EST28030-No

  10. Acoustic and Vibration Control for an Underwater Structure under Mechanical Excitation

    Directory of Open Access Journals (Sweden)

    Shi-Jian Zhu

    2014-01-01

    Full Text Available Acoustic and vibration control for an underwater structure under mechanical excitation has been investigated by using negative feedback control algorithm. The underwater structure is modeled with cylindrical shells, conical shells, and circular bulkheads, of which the motion equations are built with the variational approach, respectively. Acoustic property is analyzed by the Helmholtz integration formulation with boundary element method. Based on negative feedback control algorithm, a control loop with a coupling use of piezoelectric sensor and actuator is built, and accordingly some numerical examples are carried out on active control of structural vibration and acoustic response. Effects of geometrical and material parameters on acoustic and vibration properties are investigated and discussed.

  11. Concurrent material-fabrication optimization of metal-matrix laminates under thermo-mechanical loading

    Science.gov (United States)

    Saravanos, D. A.; Morel, M. R.; Chamis, C. C.

    1991-01-01

    A methodology is developed to tailor fabrication and material parameters of metal-matrix laminates for maximum loading capacity under thermomechanical loads. The stresses during the thermomechanical response are minimized subject to failure constrains and bounds on the laminate properties. The thermomechanical response of the laminate is simulated using nonlinear composite mechanics. Evaluations of the method on a graphite/copper symmetric cross-ply laminate were performed. The cross-ply laminate required different optimum fabrication procedures than a unidirectional composite. Also, the consideration of the thermomechanical cycle had a significant effect on the predicted optimal process.

  12. Radiation pneumonitis and fibrosis: Mechanisms underlying its pathogenesis and implications for future research

    International Nuclear Information System (INIS)

    Tsoutsou, Pelagia G.; Koukourakis, Michael I.

    2006-01-01

    Radiation pneumonitis and subsequent radiation pulmonary fibrosis are the two main dose-limiting factors when irradiating the thorax that can have severe implications for patients' quality of life. In this article, the current concepts about the pathogenetic mechanisms underlying radiation pneumonitis and fibrosis are presented. The clinical course of fibrosis, a postulated acute inflammatory stage, and a late fibrotic and irreversible stage are discussed. The interplay of cells and the wide variety of molecules orchestrating the immunologic response to radiation, their interactions with specific receptors, and the cascade of events they trigger are elucidated. Finally, the implications of this knowledge with respect to the therapeutic interventions are critically presented

  13. Neuro-cognitive mechanisms underlying the emotional modulation of word reading

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A novel neural model for emotional modulation of word reading is proposed. This model has four principal hypotheses: the dominant activation region hypothesis, the emotional modulation hypothesis, the attentional level hypothesis, and the interaction hypothesis. Four lines of research were reviewed to provide evidence for these hypotheses: (1) neuro-cognitive studies on the mechanisms of word reading (i.e., neural networks for reading); (2) studies on the influence of words' emotional valence on word reading; (3) studies of the effect of attention on word reading; and (4) studies on emotional modulation of word reading under different attentional levels.

  14. Mechanical properties of pure and doped InP single crystals under concentrated loading

    International Nuclear Information System (INIS)

    Boyarskaya, Yu.S.; Grabko, D.Z.; Medinskaya, M.I.; Palistrant, N.A.

    1997-01-01

    The mechanical properties of pure and doped (Fe, Zn, Sn) InP single crystals were investigated in the temperature interval from 293 to 600 K. It was shown that impurity hardening (the microhardness increase) was more pronounced at elevated temperatures than at 293 K. This is conditioned by braking of the moving dislocations with impurities which is more observed in the the high temperature region. The obvious anisotropy of the scratch hardness was revealed at room temperature for the (001) face of crystals under investigation. This anisotropy decreased sharply in increasing the temperature from 293 to 600 K

  15. Mechanical behavior of irradiated fuel-pin cladding evaluated under transient heating and pressure conditions

    International Nuclear Information System (INIS)

    Hamilton, M.L.; Johnson, G.D.; Hunter, C.W.; Duncan, D.R.

    1982-11-01

    Fast breeder fuel-pin cladding has been tested under experimental conditions simulating the temperature and pressure history characteristic of anticipated transient events. Irradiation induces severe reductions in both strength and ductility. Ductility losses are independent of the rate of temperature increase and saturate by a fluence of approx. 2 x 10 22 n/cm 2 (E > 0.1 MeV). Losses in strength are dependent on the rate of temperature increase but saturate at a fluence of approx.5 x 10 22 n/cm 2 . Evidence is presented to show that fission products are probably responsible for the degradation in mechanical properties

  16. An Investigation of the Mechanism Underlying Teacher Aggression: Testing I[superscript 3] Theory and the General Aggression Model

    Science.gov (United States)

    Montuoro, Paul; Mainhard, Tim

    2017-01-01

    Background: Considerable research has investigated the deleterious effects of teachers responding aggressively to students who misbehave, but the mechanism underlying this dysfunctional behaviour remains unknown. Aims: This study investigated whether the mechanism underlying teacher aggression follows I[superscript 3] theory or General Aggression…

  17. Experimental Investigation of Mechanical Properties of PVC Polymer under Different Heating and Cooling Conditions

    Directory of Open Access Journals (Sweden)

    Sarkawt Rostam

    2016-01-01

    Full Text Available Due to a widely increasing usage of polymers in various industrial applications, there should be a continuous need in doing research investigations for better understanding of their properties. These applications require the usage of the polymer in different working environments subjecting the material to various temperature ranges. In this paper, an experimental investigation of mechanical properties of polyvinyl chloride (PVC polymer under heating and cooling conditions is presented. For this purpose standard samples are prepared and tested in laboratory using universal material testing apparatus. The samples are tested under different conditions including the room temperature environment, cooling in a refrigerator, and heating at different heating temperatures. It is observed that the strength of the tested samples decreases with the increasing of heating temperature and accordingly the material becomes softer. Meanwhile the cooling environments give a clear increasing to the strength of the material.

  18. A numerical study of crack interactions under thermo-mechanical load using EFGM

    International Nuclear Information System (INIS)

    Pant, Mohit; Singh, I. V.; Mishra, B. K.

    2011-01-01

    In this work, element free Galerkin method (EFGM) has been used to obtain the solution of various edge crack problems under thermo-mechanical loads as it provides a versatile technique to model stationary as well as moving crack problems without re-meshing. Standard diffraction criterion has been modified with multiple crack weight technique to characterize the presence of various cracks in the domain of influence of a particular node. The effect of crack inclination has been studied for single as well as two edge cracks, whereas the cracks interaction has been studied for two edge cracks lying on same as well as opposite edges under plane stress conditions. The values of mode-I and mode-II stress intensity factors have been evaluated by the interaction integral approach

  19. Macrocrack propagation in concrete specimens under sustained loading: Study of the physical mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Rossi, Pierre, E-mail: pierre.rossi@lcpc.fr; Boulay, Claude; Tailhan, Jean-Louis; Martin, Eric; Desnoyers, Dominic

    2014-09-15

    This study presents a series of 4-point bending tests performed to describe the delayed behavior of unreinforced pre-cracked beams under low, moderate and high sustained loading levels. The deflection creep rate, the failure time and the load level were assessed. A linear relation, in a semi-log scale, was found for the deflection creep rate at high load levels. In addition, a linear relation, in a log–log scale, between the secondary deflection creep rate and failure time was observed. Besides, it was shown that the secondary creep deflection rate increases with the sustained loading level and the macrocrack propagation rate when macrocrack propagation occurs during the sustained loading. Physical mechanisms are proposed to explain these results and may be summarized as follows: the delayed behavior of an unreinforced cracked concrete specimen under sustained loading is mainly due to the cracking evolution, thus the creation of microcracks and/or the propagation of a macrocrack.

  20. Numerical Analysis on Failure Modes and Mechanisms of Mine Pillars under Shear Loading

    Directory of Open Access Journals (Sweden)

    Tianhui Ma

    2016-01-01

    Full Text Available Severe damage occurs frequently in mine pillars subjected to shear stresses. The empirical design charts or formulas for mine pillars are not applicable to orebodies under shear. In this paper, the failure process of pillars under shear stresses was investigated by numerical simulations using the rock failure process analysis (RFPA 2D software. The numerical simulation results indicate that the strength of mine pillars and the corresponding failure mode vary with different width-to-height ratios and dip angles. With increasing dip angle, stress concentration first occurs at the intersection between the pillar and the roof, leading to formation of microcracks. Damage gradually develops from the surface to the core of the pillar. The damage process is tracked with acoustic emission monitoring. The study in this paper can provide an effective means for understanding the failure mechanism, planning, and design of mine pillars.

  1. Macrocrack propagation in concrete specimens under sustained loading: Study of the physical mechanisms

    International Nuclear Information System (INIS)

    Rossi, Pierre; Boulay, Claude; Tailhan, Jean-Louis; Martin, Eric; Desnoyers, Dominic

    2014-01-01

    This study presents a series of 4-point bending tests performed to describe the delayed behavior of unreinforced pre-cracked beams under low, moderate and high sustained loading levels. The deflection creep rate, the failure time and the load level were assessed. A linear relation, in a semi-log scale, was found for the deflection creep rate at high load levels. In addition, a linear relation, in a log–log scale, between the secondary deflection creep rate and failure time was observed. Besides, it was shown that the secondary creep deflection rate increases with the sustained loading level and the macrocrack propagation rate when macrocrack propagation occurs during the sustained loading. Physical mechanisms are proposed to explain these results and may be summarized as follows: the delayed behavior of an unreinforced cracked concrete specimen under sustained loading is mainly due to the cracking evolution, thus the creation of microcracks and/or the propagation of a macrocrack

  2. Optimal Contract Design for Cooperative Relay Incentive Mechanism under Moral Hazard

    Directory of Open Access Journals (Sweden)

    Nan Zhao

    2015-01-01

    Full Text Available Cooperative relay can effectively improve spectrum efficiency by exploiting the spatial diversity in the wireless networks. However, wireless nodes may acquire different network information with various users’ location and mobility, channels’ conditions, and other factors, which results in asymmetric information between the source and the relay nodes (RNs. In this paper, the relay incentive mechanism between relay nodes and the source is investigated under the asymmetric information. By modelling multiuser cooperative relay as a labour market, a contract model with moral hazard for relay incentive is proposed. To effectively incentivize the potential RNs to participate in cooperative relay, the optimization problems are formulated to maximize the source’s utility while meeting the feasible conditions under both symmetric and asymmetric information scenarios. Numerical simulation results demonstrate the effectiveness of the proposed contract design scheme for cooperative relay.

  3. ALK and TGF-Beta Resistance in Breast Cancer

    Science.gov (United States)

    2017-10-01

    Award Number: W81XWH‐15‐1‐0650 TITLE: ALK