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Sample records for camp-independent autocrine mechanism

  1. Autocrine and Paracrine Mechanisms Promoting Chemoresistance in Cholangiocarcinoma

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    Massimiliano Cadamuro

    2017-01-01

    Full Text Available Resistance to conventional chemotherapeutic agents, a typical feature of cholangiocarcinoma, prevents the efficacy of the therapeutic arsenal usually used to combat malignancy in humans. Mechanisms of chemoresistance by neoplastic cholangiocytes include evasion of drug-induced apoptosis mediated by autocrine and paracrine cues released in the tumor microenvironment. Here, recent evidence regarding molecular mechanisms of chemoresistance is reviewed, as well as associations between well-developed chemoresistance and activation of the cancer stem cell compartment. It is concluded that improved understanding of the complex interplay between apoptosis signaling and the promotion of cell survival represent potentially productive areas for active investigation, with the ultimate aim of encouraging future studies to unveil new, effective strategies able to overcome current limitations on treatment.

  2. Cyclic mechanical deformation stimulates human lung fibroblast proliferation and autocrine growth factor activity.

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    Bishop, J E; Mitchell, J J; Absher, P M; Baldor, L; Geller, H A; Woodcock-Mitchell, J; Hamblin, M J; Vacek, P; Low, R B

    1993-08-01

    Cellular hypertrophy and hyperplasia and increased extracellular matrix deposition are features of tissue hypertrophy resulting from increased work load. It is known, for example, that mechanical forces play a critical role in lung development, cardiovascular remodeling following pressure overload, and skeletal muscle growth. The mechanisms involved in these processes, however, remain unclear. Here we examined the effect of mechanical deformation on fibroblast function in vitro. IMR-90 human fetal lung fibroblasts grown on collagen-coated silastic membranes were subjected to cyclical mechanical deformation (10% increase in culture surface area; 1 Hz) for up to 5 days. Cell number was increased by 39% after 2 days of deformation (1.43 +/- .01 x 10(5) cells/membrane compared with control, 1.03 +/- 0.02 x 10(5) cells; mean +/- SEM; P < 0.02) increasing to 163% above control by 4 days (2.16 +/- 0.16 x 10(5) cells compared with 0.82 +/- 0.03 x 10(5) cells; P < 0.001). The medium from mechanically deformed cells was mitogenic for IMR-90 cells, with maximal activity in the medium from cells mechanically deformed for 2 days (stimulating cell replication by 35% compared with media control; P < 0.002). These data suggest that mechanical deformation stimulates human lung fibroblast replication and that this effect is mediated by the release of autocrine growth factors.

  3. Ace inhibitors and cardiovascular regulation : the importance of autocrine and paracrine mechanisms

    NARCIS (Netherlands)

    Wijngaarden, Jan van

    1992-01-01

    As demonstrated in a large number of clinical studies, angiotensin converting enzyme (ACE) inhibitors are of great value for the treatment of cardiovascular disorders. Although the clinical merits of these drugs are now well recognized, their mechanism of action is not yet completely understood. The

  4. 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

  5. TNF-α Induced by Hepatitis C Virus via TLR7 and TLR8 in Hepatocytes Supports Interferon Signaling via an Autocrine Mechanism

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    Lee, Jiyoung; Tian, Yongjun; Chan, Stephanie Tze; Kim, Ja Yeon; Cho, Cecilia; Ou, Jing-hsiung James

    2015-01-01

    Invasion by infectious pathogens can elicit a range of cytokine responses from host cells. These cytokines provide the initial host defense mechanism. In this report, we demonstrate that TNF-α, a pro-inflammatory cytokine, can be induced by hepatitis C virus (HCV) in its host cells in a biphasic manner. The initial induction of TNF-α by HCV was prompt and could be blocked by the antibody directed against the HCV E2 envelope protein and by chemicals that inhibit endocytosis, indicating the specificity of endocytic uptake of HCV in this induction. Further studies indicated that the induction of TNF-α was dependent on toll-like receptors 7 and 8 (TLR7/8) but not on other intracellular pattern recognition receptors. Consistently, siRNA-mediated gene silencing of the downstream effectors in the TLR7/8 signaling pathway including MyD88, IRAK1, TRAF6, TAK1 and p65 NF-κB suppressed the expression of TNF-α. The role of p65 NF-κB in the induction of TNF-α via transcriptional up-regulation was further confirmed by the chromatin immunoprecipitation assay. TNF-α induced by HCV could activate its own receptor TNFR1 on hepatocytes to suppress HCV replication. This suppressive effect of TNF-α on HCV was due to its role in supporting interferon signaling, as the suppression of its expression led to the loss of IFNAR2 and impaired interferon signaling and the induction of interferon-stimulated genes. In conclusion, our results indicate that hepatocytes can sense HCV infection via TLR7/8 to induce the expression of TNF-α, which inhibits HCV replication via an autocrine mechanism to support interferon signaling. PMID:26023919

  6. Aberrant, ectopic expression of VEGF and VEGF receptors 1 and 2 in malignant colonic epithelial cells. Implications for these cells growth via an autocrine mechanism

    International Nuclear Information System (INIS)

    Ahluwalia, Amrita; Jones, Michael K.; Szabo, Sandor; Tarnawski, Andrzej S.

    2013-01-01

    Highlights: •Malignant colonic epithelial cells express VEGF and its receptors. •Cultured colon cancer cells secrete VEGF into the medium. •Inhibition of VEGF receptor significantly decreases colon cancer cell proliferation. •VEGF is critical for colon cancer cell growth. -- Abstract: Vascular endothelial growth factor A (referred to as VEGF) is implicated in colon cancer growth. Currently, the main accepted mechanism by which VEGF promotes colon cancer growth is via the stimulation of angiogenesis, which was originally postulated by late Judah Folkman. However, the cellular source of VEGF in colon cancer tissue; and, the expression of VEGF and its receptors VEGF-R1 and VEGF-R2 in colon cancer cells are not fully known and are subjects of controversy. Material and methods: We examined and quantified expression of VEGF, VEGF-R1 and VEGF-R2 in three different human colonic tissue arrays containing sections of adenocarcinoma (n = 43) and normal mucosa (n = 41). In human colon cancer cell lines HCT116 and HT29 and normal colon cell lines NCM356 and NCM460, we examined expression of VEGF, VEGF-R1 and VEGF-R2 mRNA and protein, VEGF production and secretion into the culture medium; and, the effect of a potent, selective inhibitor of VEGF receptors, AL-993, on cell proliferation. Results: Human colorectal cancer specimens had strong expression of VEGF in cancer cells and also expressed VEGF-R1 and VEGF-R2.In vitro studies showed that human colon cancer cell lines, HCT116 and HT29, but not normal colonic cell lines, express VEGF, VEGF-R1 and VEGF-R2 and secrete VEGF into the medium up to a concentration 2000 pg/ml within 48 h. Furthermore, we showed that inhibition of VEGF receptors using a specific VEGF-R inhibitor significantly reduced proliferation (by >50%) of cultured colon cancer cell lines. Conclusions: Our findings support the contention that VEGF generated by colon cancer cells stimulates their growth directly through an autocrine mechanism that is

  7. Autocrine prolactin: an emerging market for homegrown (prolactin) despite the imports

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    Muthuswamy, Senthil K.

    2012-01-01

    Prolactin (PRL) is a peptide hormone that is produced by the pituitary gland and is known to regulate lactogenic differentiation. There is a significant body of evidence that points to autocrine production of prolactin and activation of an autocrine/paracrine signaling pathway to regulate cell proliferation and migration and inhibition of cell death. This perspective highlights the recent study in the October 1, 2012, issue of Genes & Development by Chen and colleagues (pp. 2154–2168) that describes a mechanism for autocrine prolactin production and places the finding in the context of a role for prolactin in breast development and cancer. PMID:23070811

  8. Distinguishing autocrine and paracrine signals in hematopoietic stem cell culture using a biofunctional microcavity platform

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    Müller, Eike; Wang, Weijia; Qiao, Wenlian; Bornhäuser, Martin; Zandstra, Peter W.; Werner, Carsten; Pompe, Tilo

    2016-08-01

    Homeostasis of hematopoietic stem cells (HSC) in the mammalian bone marrow stem cell niche is regulated by signals of the local microenvironment. Besides juxtacrine, endocrine and metabolic cues, paracrine and autocrine signals are involved in controlling quiescence, proliferation and differentiation of HSC with strong implications on expansion and differentiation ex vivo as well as in vivo transplantation. Towards this aim, a cell culture analysis on a polymer microcavity carrier platform was combined with a partial least square analysis of a mechanistic model of cell proliferation. We could demonstrate the discrimination of specific autocrine and paracrine signals from soluble factors as stimulating and inhibitory effectors in hematopoietic stem and progenitor cell culture. From that we hypothesize autocrine signals to be predominantly involved in maintaining the quiescent state of HSC in single-cell niches and advocate our analysis platform as an unprecedented option for untangling convoluted signaling mechanisms in complex cell systems being it of juxtacrine, paracrine or autocrine origin.

  9. DNMT3A and DNMT3B mediate autocrine hGH repression of plakoglobin gene transcription and consequent phenotypic conversion of mammary carcinoma cells.

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    Shafiei, F; Rahnama, F; Pawella, L; Mitchell, M D; Gluckman, P D; Lobie, P E

    2008-04-17

    Directed by microarray analyses, we report that autocrine human growth hormone (hGH) increased the mRNA and protein expression of DNA methyltransferase 1 (DNMT1), DNMT3A and DNMT3B in mammary carcinoma cells. Autocrine hGH stimulation of DNMT3A and DNMT3B expression was mediated by JAK2 and Src kinases, and treatment of mammary carcinoma cells with the DNMT inhibitor, 5'-aza-2'-deoxycytidine (AZA), abrogated autocrine hGH-stimulated cellular proliferation, apoptosis and anchorage-independent growth. AZA reversed the epitheliomesenchymal transition of mammary carcinoma cells induced by autocrine hGH, to an epithelioid morphology and abrogated cell migration stimulated by autocrine hGH. Autocrine hGH-stimulated hypermethylation of the first exon of the PLAKOGLOBIN gene and AZA abrogated the ability of autocrine hGH to repress plakoglobin gene transcription. Small interfering RNA (siRNA)-mediated depletion of the individual DNMT molecules did not release autocrine hGH repression of PLAKOGLOBIN promoter activity nor did individual DNMT depletion affect autocrine hGH-stimulated migration. However, concomitant siRNA-mediated depletion of both DNMT3A and DNMT3B abrogated hypermethylation of the PLAKOGLOBIN gene stimulated by autocrine hGH and subsequent repression of plakoglobin gene transcription and increased cell migration. Thus, the autocrine hGH-stimulated increases in DNMT3A and DNMT3B expression mediate repression of plakoglobin gene transcription by direct hypermethylation of its promoter and consequent phenotypic conversion of mammary carcinoma cells. Autocrine hGH, therefore, utilizes DNA methylation as a mechanism to exert its oncogenic effects in mammary carcinoma cells.

  10. Loss of autocrine endothelial-derived VEGF significantly reduces hemangiosarcoma development in conditional p53-deficient mice.

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    Farhang Ghahremani, Morvarid; Radaelli, Enrico; Haigh, Katharina; Bartunkova, Sonia; Haenebalcke, Lieven; Marine, Jean-Christophe; Goossens, Steven; Haigh, Jody J

    2014-01-01

    Malignant transformation of the endothelium is rare, and hemangiosarcomas comprise only 1% of all sarcomas. For this reason and due to the lack of appropriate mouse models, the genetic mechanisms of malignant endothelial transformation are poorly understood. Here, we describe a hemangiosarcoma mouse model generated by deleting p53 specifically in the endothelial and hematopoietic lineages. This strategy led to a high incidence of hemangiosarcoma, with an average latency of 25 weeks. To study the in vivo roles of autocrine or endothelial cell autonomous VEGF signaling in the initiation and/or progression of hemangiosarcomas, we genetically deleted autocrine endothelial sources of VEGF in this mouse model. We found that loss of even a single conditional VEGF allele results in substantial rescue from endothelial cell transformation. These findings highlight the important role of threshold levels of autocrine VEGF signaling in endothelial malignancies and suggest a new approach for hemangiosarcoma treatment using targeted autocrine VEGF inhibition.

  11. Network dynamics determine the autocrine and paracrine signaling functions of TNF

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    Caldwell, Andrew B.; Cheng, Zhang; Vargas, Jesse D.; Birnbaum, Harry A.

    2014-01-01

    A hallmark of the inflammatory response to pathogen exposure is the production of tumor necrosis factor (TNF) that coordinates innate and adaptive immune responses by functioning in an autocrine or paracrine manner. Numerous molecular mechanisms contributing to TNF production have been identified, but how they function together in macrophages remains unclear. Here, we pursued an iterative systems biology approach to develop a quantitative understanding of the regulatory modules that control TNF mRNA synthesis and processing, mRNA half-life and translation, and protein processing and secretion. By linking the resulting model of TNF production to models of the TLR-, the TNFR-, and the NFκB signaling modules, we were able to study TNF’s functions during the inflammatory response to diverse TLR agonists. Contrary to expectation, we predicted and then experimentally confirmed that in response to lipopolysaccaride, TNF does not have an autocrine function in amplifying the NFκB response, although it plays a potent paracrine role in neighboring cells. However, in response to CpG DNA, autocrine TNF extends the duration of NFκB activity and shapes CpG-induced gene expression programs. Our systems biology approach revealed that network dynamics of MyD88 and TRIF signaling and of cytokine production and response govern the stimulus-specific autocrine and paracrine functions of TNF. PMID:25274725

  12. Autocrine VEGF and IL-8 Promote Migration via Src/Vav2/Rac1/PAK1 Signaling in Human Umbilical Vein Endothelial Cells.

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    Ju, Li; Zhou, Zhiwen; Jiang, Bo; Lou, Yue; Guo, Xirong

    2017-01-01

    Pro-angiogenic factors VEGF and IL-8 play a major role in modulating the migratory potential of endothelial cells. The goal of this study was to investigate the effect of autocrine VEGF and IL-8 in the form of self-conditioned medium (CM) on human umbilical vein endothelial cells (HUVECs). Enzyme-linked immunosorbent assay (ELISA) examined the automatic secretion of VEGF and IL-8 protein by HUVECs. Western blot, small interfering RNA (siRNA), pulldown and Transwell assays were used to explore the role and the mechanism of autocrine VEGF and IL-8 in migration of HUVECs. Neutralizing VEGF and IL-8 in CM significantly abrogated CM-induced migration of HUVECs. Autocrine VEGF and IL-8 increased Src phosphorylation, Rac1 activity and PAK1 phosphorylation in a time dependent manner. Additionally, blocking Rac1 activity with Rac1 siRNA largely abolished autocrine VEGF and IL-8-induced cell migration. Vav2 siRNA suppressed autocrine VEGF and IL-8-induced Rac1 activation and cell migration. Furthermore, blocking Src signaling with PP2, a specific inhibitor for Src, markedly prevented autocrine VEGF and IL-8-induced Vav2 and Rac1 activation as well as consequently cell migration. PAK1 siRNA also significantly abolished autocrine VEGF and IL-8-induced cell migration. We demonstrated for the first time that autocrine VEGF and IL-8 promoted endothelial cell migration via the Src/Vav2/Rac1/PAK1 signaling pathway. This finding reveals the molecular mechanism in the increase of endothelial cell migration induced by autocrine growth factors and cytokines, which is expected to provide a novel therapeutic target in vascular diseases. © 2017 The Author(s)Published by S. Karger AG, Basel.

  13. Autocrine Effects of Tumor-Derived Complement

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    Min Soon Cho

    2014-03-01

    Full Text Available We describe a role for the complement system in enhancing cancer growth. Cancer cells secrete complement proteins that stimulate tumor growth upon activation. Complement promotes tumor growth via a direct autocrine effect that is partially independent of tumor-infiltrating cytotoxic T cells. Activated C5aR and C3aR signal through the PI3K/AKT pathway in cancer cells, and silencing the PI3K or AKT gene in cancer cells eliminates the progrowth effects of C5aR and C3aR stimulation. In patients with ovarian or lung cancer, higher tumoral C3 or C5aR mRNA levels were associated with decreased overall survival. These data identify a role for tumor-derived complement proteins in promoting tumor growth, and they therefore have substantial clinical and therapeutic implications.

  14. Autocrine-paracrine regulation of the mammary gland.

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    Weaver, S R; Hernandez, L L

    2016-01-01

    The mammary gland has a remarkable capacity for regulation at a local level, particularly with respect to its main function: milk secretion. Regulation of milk synthesis has significant effects on animal and human health, at the level of both the mother and the neonate. Control by the mammary gland of its essential function, milk synthesis, is an evolutionary necessity and is therefore tightly regulated at a local level. For at least the last 60 yr, researchers have been interested in elucidating the mechanisms underpinning the mammary gland's ability to self-regulate, largely without the influence from systemic hormones or signals. By the 1960s, scientists realized the importance of milk removal in the capacity of the gland to produce milk and that the dynamics of this removal, including emptying of the alveolar spaces and frequency of milking, were controlled locally as opposed to traditional systemic hormonal regulation. Using both in vitro systems and various mammalian species, including goats, marsupials, humans, and dairy cows, it has been demonstrated that the mammary gland is largely self-regulating in its capacity to support the young, which is the evolutionary basis for milk production. Local control occurs at the level of the mammary epithelial cell through pressure and stretching negative-feedback mechanisms, and also in an autocrine fashion through bioactive factors within the milk which act as inhibitors, regulating milk secretion within the alveoli themselves. It is only within the last 20 to 30 yr that potential candidates for these bioactive factors have been examined at a molecular level. Several, including parathyroid hormone-related protein, growth factors (transforming growth factor, insulin-like growth factor, epidermal growth factor), and serotonin, are synthesized within and act upon the gland and possess dynamic receptor activity resulting in diverse effects on growth, calcium homeostasis, and milk composition. This review will focus on the

  15. Autocrine signal transmission with extracellular ligand degradation

    International Nuclear Information System (INIS)

    Muratov, C B; Posta, F; Shvartsman, S Y

    2009-01-01

    Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand–receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers

  16. Autocrine Human Growth Hormone Stimulates Oncogenicity of Endometrial Carcinoma Cells

    OpenAIRE

    Pandey, Vijay; Perry, Jo K.; Mohankumar, Kumarasamypet M.; Kong, Xiang-Jun; Liu, Shu-Min; Wu, Zheng-Sheng; Mitchell, Murray D.; Zhu, Tao; Lobie, Peter E.

    2008-01-01

    Recent published data have demonstrated elevated levels of human GH (hGH) in endometriosis and endometrial adenocarcinoma. Herein, we demonstrate that autocrine production of hGH can enhance the in vitro and in vivo oncogenic potential of endometrial carcinoma cells. Forced expression of hGH in endometrial carcinoma cell lines RL95-2 and AN3 resulted in an increased total cell number through enhanced cell cycle progression and decreased apoptotic cell death. In addition, autocrine hGH express...

  17. Endocrine, paracrine, and autocrine placental mediators in labor.

    Science.gov (United States)

    Iliodromiti, Zoe; Antonakopoulos, Nikolaos; Sifakis, Stavros; Tsikouras, Panagiotis; Daniilidis, Angelos; Dafopoulos, Kostantinos; Botsis, Dimitrios; Vrachnis, Nikolaos

    2012-01-01

    Considering that preterm birth accounts for about 6-10% of all births in Western countries and of more than 65% of all perinatal deaths, elucidation of the particularly complicated mechanisms of labor is essential for determination of appropriate and effective therapeutic interventions. Labor in humans results from a complex interplay of fetal and maternal factors, which act upon the uterus to trigger pathways leading gradually to a coordinated cervical ripening and myometrial contractility. Although the exact mechanism of labor still remains uncertain, several components have been identified and described in detail. Based on the major role played by the human placenta in pregnancy and the cascade of labor processes activated via placental mediators exerting endocrine, paracrine, and autocrine actions, this review article has aimed at presenting the role of these mediators in term and preterm labor and the molecular pathways of their actions. Some of the aforementioned mediators are involved in myometrial activation and preparation and others in myometrial stimulation leading to delivery. In the early stages of pregnancy, myometrial molecules, like progesterone, nitric oxide, and relaxin, contribute to the retention of pregnancy. At late stages of gestation, fetal hypothalamus maturation signals act on the placenta causing the production of hormones, including CRH, in an endocrine manner; the signals then enhance paracrinically the production of more hormones, such as estrogens and neuropeptides, that contribute to cervical ripening and uterine contractility. These molecules act directly on the myometrium through specific receptors, while cytokines and multiple growth factors are also produced, additionally contributing to labor. In situations leading to preterm labor, as in maternal stress and fetal infection, cytokines trigger placental signaling sooner, thus leading to preterm birth.

  18. Active CREB1 promotes a malignant TGFβ2 autocrine loop in glioblastoma.

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    Rodón, Laura; Gonzàlez-Juncà, Alba; Inda, María del Mar; Sala-Hojman, Ada; Martínez-Sáez, Elena; Seoane, Joan

    2014-10-01

    In advanced cancer, including glioblastoma, the TGFβ pathway acts as an oncogenic factor. Some tumors exhibit aberrantly high TGFβ activity, and the mechanisms underlying this phenomenon are not well understood. We have observed that TGFβ can induce TGFβ2, generating an autocrine loop leading to aberrantly high levels of TGFβ2. We identified cAMP-responsive element-binding protein 1 (CREB1) as the critical mediator of the induction of TGFβ2 by TGFβ. CREB1 binds to the TGFB2 gene promoter in cooperation with SMAD3 and is required for TGFβ to activate transcription. Moreover, the PI3K-AKT and RSK pathways regulate the TGFβ2 autocrine loop through CREB1. The levels of CREB1 and active phosphorylated CREB1 correlate with TGFβ2 in glioblastoma. In addition, using patient-derived in vivo models of glioblastoma, we found that CREB1 levels determine the expression of TGFβ2. Our results show that CREB1 can be considered a biomarker to stratify patients for anti-TGFβ treatments and a therapeutic target in glioblastoma. TGFβ is considered a promising therapeutic target, and several clinical trials using TGFβ inhibitors are generating encouraging results. Here, we discerned the molecular mechanisms responsible for the aberrantly high levels of TGFβ2 found in certain tumors, and we propose biomarkers to predict the clinical response to anti-TGFβ therapies. ©2014 American Association for Cancer Research.

  19. Probing Embryonic Stem Cell Autocrine and Paracrine Signaling Using Microfluidics

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    Przybyla, Laralynne; Voldman, Joel

    2012-07-01

    Although stem cell fate is traditionally manipulated by exogenously altering the cells' extracellular signaling environment, the endogenous autocrine and paracrine signals produced by the cells also contribute to their two essential processes: self-renewal and differentiation. Autocrine and/or paracrine signals are fundamental to both embryonic stem cell self-renewal and early embryonic development, but the nature and contributions of these signals are often difficult to fully define using conventional methods. Microfluidic techniques have been used to explore the effects of cell-secreted signals by controlling cell organization or by providing precise control over the spatial and temporal cellular microenvironment. Here we review how such techniques have begun to be adapted for use with embryonic stem cells, and we illustrate how many remaining questions in embryonic stem cell biology could be addressed using microfluidic technologies.

  20. SDF-1 is an Autocrine Insulin-Desensitizing Factor in Adipocytes.

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    Shin, Jihoon; Fukuhara, Atsunori; Onodera, Toshiharu; Kita, Shunbun; Yokoyama, Chieko; Otsuki, Michio; Shimomura, Iichiro

    2018-03-26

    Insulin desensitization occurs not only under obese diabetic condition, but also in the fasting state. However, little is known about the common secretory factor(s) that are regulated under these two insulin-desensitized conditions. Here, using database analysis, in vitro , and in vivo experiments, we identified SDF-1 as an insulin-desensitizing factor in adipocytes, overexpressed in both fasting and obese adipose tissues. Exogenously added SDF-1 induced ERK signal, which phosphorylated and degraded IRS-1 protein in adipocytes, decreasing insulin-mediated signaling and glucose uptake. In contrast, knockdown of endogenous SDF-1 or inhibition of its receptor in adipocytes markedly increased IRS-1 protein levels and enhanced insulin sensitivity, indicating the autocrine action of SDF-1. In agreement with these findings, adipocyte-specific ablation of SDF-1 enhanced insulin sensitivity in adipose tissues and whole body. These results point to a novel regulatory mechanism of insulin sensitivity mediated by adipose autocrine SDF-1 action, and provide a new insight into the process of insulin desensitization in adipocytes. © 2018 by the American Diabetes Association.

  1. Autocrine human growth hormone (hGH) regulation of human mammary carcinoma cell gene expression. Identification of CHOP as a mediator of hGH-stimulated human mammary carcinoma cell survival.

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    Mertani, H C; Zhu, T; Goh, E L; Lee, K O; Morel, G; Lobie, P E

    2001-06-15

    By use of cDNA array technology we have screened 588 genes to determine the effect of autocrine production of human growth hormone (hGH) on gene expression in human mammary carcinoma cells. We have used a previously described cellular model to study autocrine hGH function in which the hGH gene or a translation-deficient hGH gene was stably transfected into MCF-7 cells. Fifty two of the screened genes were regulated, either positively () or negatively (), by autocrine production of hGH. We have now characterized the role of one of the up-regulated genes, chop (gadd153), in the effect of autocrine production of hGH on mammary carcinoma cell number. The effect of autocrine production of hGH on the level of CHOP mRNA was exerted at the transcriptional level as autocrine hGH increased chloramphenicol acetyltransferase production from a reporter plasmid containing a 1-kilobase pair fragment of the chop promoter. The autocrine hGH-stimulated increase in CHOP mRNA also resulted in an increase in CHOP protein. As a consequence, autocrine hGH stimulation of CHOP-mediated transcriptional activation was increased. Stable transfection of human CHOP cDNA into mammary carcinoma cells demonstrated that CHOP functioned not as a mediator of hGH-stimulated mitogenesis but rather enhanced the protection from apoptosis afforded by hGH in a p38 MAPK-dependent manner. Thus transcriptional up-regulation of chop is one mechanism by which hGH regulates mammary carcinoma cell number.

  2. Autocrine VEGF isoforms differentially regulate endothelial cell behavior

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    Hideki Yamamoto

    2016-09-01

    Full Text Available Vascular endothelial growth factor A (VEGF is involved in all the essential biology of endothelial cells, from proliferation to vessel function, by mediating intercellular interactions and monolayer integrity. It is expressed as three major alternative spliced variants. In mice, these are VEGF120, VEGF164, and VEGF188, each with different affinities for extracellular matrices and cell surfaces, depending on the inclusion of heparin-binding sites, encoded by exons 6 and 7. To determine the role of each VEGF isoform in endothelial homeostasis, we compared phenotypes of primary endothelial cells isolated from lungs of mice expressing single VEGF isoforms in normoxic and hypoxic conditions. The differential expression and distribution of VEGF isoforms affect endothelial cell functions, such as proliferation, adhesion, migration and integrity, which are dependent on the stability of and affinity to VEGF receptor 2 (VEGFR2. We found a correlation between autocrine VEGF164 and VEGFR2 stability, which is also associated with increased expression of proteins involved in cell adhesion. Endothelial cells expressing only VEGF188, which localizes to extracellular matrices or cell surfaces, presented a mesenchymal morphology and weakened monolayer integrity. Cells expressing only VEGF120 lacked stable VEGFR2 and dysfunctional downstream processes, rendering the cells unviable. Endothelial cells expressing these different isoforms in isolation also had differing rates of apoptosis, proliferation, and signaling via nitric oxide (NO synthesis. These data indicate that autocrine signaling of each VEGF isoform has unique functions on endothelial homeostasis and response to hypoxia, due to both distinct VEGF distribution and VEGFR2 stability, which appears to be, at least partly, affected by differential NO production. This study demonstrates that each autocrine VEGF isoform has a distinct effect on downstream functions, namely VEGFR2-regulated endothelial cell

  3. Autocrine/Paracrine Human Growth Hormone-stimulated MicroRNA 96-182-183 Cluster Promotes Epithelial-Mesenchymal Transition and Invasion in Breast Cancer*

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    Zhang, Weijie; Qian, Pengxu; Zhang, Xiao; Zhang, Min; Wang, Hong; Wu, Mingming; Kong, Xiangjun; Tan, Sheng; Ding, Keshuo; Perry, Jo K.; Wu, Zhengsheng; Cao, Yuan; Lobie, Peter E.; Zhu, Tao

    2015-01-01

    Human growth hormone (hGH) plays critical roles in pubertal mammary gland growth, development, and sexual maturation. Accumulated studies have reported that autocrine/paracrine hGH is an orthotopically expressed oncoprotein that promotes normal mammary epithelial cell oncogenic transformation. Autocrine/paracrine hGH has also been reported to promote mammary epithelial cell epithelial-mesenchymal transition (EMT) and invasion. However, the underlying mechanism remains largely obscure. MicroRNAs (miRNAs) are reported to be involved in regulation of multiple cellular functions of cancer. To determine whether autocrine/paracrine hGH promotes EMT and invasion through modulation of miRNA expression, we performed microarray profiling using MCF-7 cells stably expressing wild type or a translation-deficient hGH gene and identified miR-96-182-183 as an autocrine/paracrine hGH-regulated miRNA cluster. Forced expression of miR-96-182-183 conferred on epithelioid MCF-7 cells a mesenchymal phenotype and promoted invasive behavior in vitro and dissemination in vivo. Moreover, we observed that miR-96-182-183 promoted EMT and invasion by directly and simultaneously suppressing BRMS1L (breast cancer metastasis suppressor 1-like) gene expression. miR-96 and miR-182 also targeted GHR, providing a potential negative feedback loop in the hGH-GHR signaling pathway. We further demonstrated that autocrine/paracrine hGH stimulated miR-96-182-183 expression and facilitated EMT and invasion via STAT3 and STAT5 signaling. Consistent with elevated expression of autocrine/paracrine hGH in metastatic breast cancer tissue, miR-96-182-183 expression was also remarkably enhanced. Hence, we delineate the roles of the miRNA-96-182-183 cluster and elucidate a novel hGH-GHR-STAT3/STAT5-miR-96-182-183-BRMS1L-ZEB1/E47-EMT/invasion axis, which provides further understanding of the mechanism of autocrine/paracrine hGH-stimulated EMT and invasion in breast cancer. PMID:25873390

  4. Autocrine signaling is a key regulatory element during osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Paul Kopesky

    2014-07-01

    Full Text Available Osteoclasts are responsible for bone destruction in degenerative, inflammatory and metastatic bone disorders. Although osteoclastogenesis has been well-characterized in mouse models, many questions remain regarding the regulation of osteoclast formation in human diseases. We examined the regulation of human precursors induced to differentiate and fuse into multinucleated osteoclasts by receptor activator of nuclear factor kappa-B ligand (RANKL. High-content single cell microscopy enabled the time-resolved quantification of both the population of monocytic precursors and the emerging osteoclasts. We observed that prior to induction of osteoclast fusion, RANKL stimulated precursor proliferation, acting in part through an autocrine mediator. Cytokines secreted during osteoclastogenesis were resolved using multiplexed quantification combined with a Partial Least Squares Regression model to identify the relative importance of specific cytokines for the osteoclastogenesis outcome. Interleukin 8 (IL-8 was identified as one of RANKL-induced cytokines and validated for its role in osteoclast formation using inhibitors of the IL-8 cognate receptors CXCR1 and CXCR2 or an IL-8 blocking antibody. These insights demonstrate that autocrine signaling induced by RANKL represents a key regulatory component of human osteoclastogenesis.

  5. XIAP gene expression and function is regulated by autocrine and paracrine TGF-β signaling

    Directory of Open Access Journals (Sweden)

    Van Themsche Céline

    2010-08-01

    Full Text Available Abstract Background X-linked inhibitor of apoptosis protein (XIAP is often overexpressed in cancer cells, where it plays a key role in survival and also promotes invasiveness. To date however, the extracellular signals and intracellular pathways regulating its expression and activity remain incompletely understood. We have previously showed that exposure to each of the three TGF-β (transforming growth factor beta isoforms upregulates XIAP protein content in endometrial carcinoma cells in vitro. In the present study, we have investigated the clinical relevance of TGF-β isoforms in endometrial tumours and the mechanisms through which TGF-β isoforms regulate XIAP content in uterine cancer cells. Methods TGF-β isoforms immunoreactivity in clinical samples from endometrial tumours was assessed using immunofluorescence. Two model cancer cell lines (KLE endometrial carcinoma cells and HeLa cervical cancer cells and pharmacological inhibitors were used to investigate the signalling pathways regulating XIAP expression and activity in response to autocrine and paracrine TGF-β in cancer cell. Results We have found immunoreactivity for each TGF-β isoform in clinical samples from endometrial tumours, localizing to both stromal and epithelial/cancer cells. Blockade of autocrine TGF-β signaling in KLE endometrial carcinoma cells and HeLa cervical cancer cells reduced endogenous XIAP mRNA and protein levels. In addition, each TGF-β isoform upregulated XIAP gene expression when given exogenously, in a Smad/NF-κB dependent manner. This resulted in increased polyubiquitination of PTEN (phosphatase and tensin homolog on chromosome ten, a newly identified substrate for XIAP E3 ligase activity, and in a XIAP-dependent decrease of PTEN protein levels. Although each TGF-β isoform decreased PTEN content in a XIAP- and a Smad-dependent manner, decrease of PTEN levels in response to only one isoform, TGF-β3, was blocked by PI3-K inhibitor LY294002. Conclusions

  6. Acetylcholine release by human colon cancer cells mediates autocrine stimulation of cell proliferation.

    Science.gov (United States)

    Cheng, Kunrong; Samimi, Roxana; Xie, Guofeng; Shant, Jasleen; Drachenberg, Cinthia; Wade, Mark; Davis, Richard J; Nomikos, George; Raufman, Jean-Pierre

    2008-09-01

    Most colon cancers overexpress M3 muscarinic receptors (M3R), and post-M3R signaling stimulates human colon cancer cell proliferation. Acetylcholine (ACh), a muscarinic receptor ligand traditionally regarded as a neurotransmitter, may be produced by nonneuronal cells. We hypothesized that ACh release by human colon cancer cells results in autocrine stimulation of proliferation. H508 human colon cancer cells, which have robust M3R expression, were used to examine effects of muscarinic receptor antagonists, acetylcholinesterase inhibitors, and choline transport inhibitors on cell proliferation. A nonselective muscarinic receptor antagonist (atropine), a selective M3R antagonist (p-fluorohexahydro-sila-difenidol hydrochloride), and a choline transport inhibitor (hemicholinum-3) all inhibited unstimulated H508 colon cancer cell proliferation by approximately 40% (P<0.005). In contrast, two acetylcholinesterase inhibitors (eserine-hemisulfate and bis-9-amino-1,2,3,4-tetrahydroacridine) increased proliferation by 2.5- and 2-fold, respectively (P<0.005). By using quantitative real-time PCR, expression of choline acetyltransferase (ChAT), a critical enzyme for ACh synthesis, was identified in H508, WiDr, and Caco-2 colon cancer cells. By using high-performance liquid chromatography-electrochemical detection, released ACh was detected in H508 and Caco-2 cell culture media. Immunohistochemistry in surgical specimens revealed weak or no cytoplasmic staining for ChAT in normal colon enterocytes (n=25) whereas half of colon cancer specimens (n=24) exhibited moderate to strong staining (P<0.005). We conclude that ACh is an autocrine growth factor in colon cancer. Mechanisms that regulate colon epithelial cell production and release of ACh warrant further investigation.

  7. Interleukin 6 promotes endometrial cancer growth through an autocrine feedback loop involving ERK–NF-κB signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Che, Qi; Liu, Bin-Ya; Wang, Fang-Yuan; He, Yin-Yan; Lu, Wen; Liao, Yun [Department of Obstetrics and Gynecology, Shanghai First People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai (China); Gu, Wei, E-mail: krisgu70@163.com [Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai (China); Wan, Xiao-Ping, E-mail: wanxp@sjtu.edu.cn [Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital Affiliated to Tong Ji University, Shanghai (China)

    2014-03-28

    Highlights: • IL-6 could promote endometrial cancer cells proliferation. • IL-6 promotes its own production through an autocrine feedback loop. • ERK and NF-κB pathway inhibitors inhibit IL-6 production and tumor growth. • IL-6 secretion relies on the activation of ERK–NF-κB pathway axis. • An orthotopic nude endometrial carcinoma model confirms the effect of IL-6. - Abstract: Interleukin (IL)-6 as an inflammation factor, has been proved to promote cancer proliferation in several human cancers. However, its role in endometrial cancer has not been studied clearly. Previously, we demonstrated that IL-6 promoted endometrial cancer progression through local estrogen biosynthesis. In this study, we proved that IL-6 could directly stimulate endometrial cancer cells proliferation and an autocrine feedback loop increased its production even after the withdrawal of IL-6 from the medium. Next, we analyzed the mechanism underlying IL-6 production in the feedback loop and found that its production and IL-6-stimulated cell proliferation were effectively blocked by pharmacologic inhibitors of nuclear factor-kappa B (NF-κB) and extra-cellular signal-regulated kinase (ERK). Importantly, activation of ERK was upstream of the NF-κB pathways, revealing the hierarchy of this event. Finally, we used an orthotopic nude endometrial carcinoma model to confirm the effects of IL-6 on the tumor progression. Taken together, these data indicate that IL-6 promotes endometrial carcinoma growth through an expanded autocrine regulatory loop and implicate the ERK–NF-κB pathway as a critical mediator of IL-6 production, implying IL-6 to be an important therapeutic target in endometrial carcinoma.

  8. Tumor necrosis factor α functions in an autocrine manner in the induction of human immunodeficiency virus expression

    International Nuclear Information System (INIS)

    Poli, G.; Kinter, A.; Justement, J.S.; Kehrl, J.H.; Bressler, P.; Stanley, S.; Fauci, A.S.

    1990-01-01

    Tumor necrosis factor α (TNF-α) is an immunoregulatory cytokine capable of inducing viral expression in cells chronically infected with the human immunodeficiency virus (HIV), such as the promonocytic line U1 and the T-lymphocytic line ACH-2. In the present study, the authors demonstrate an autocrine mechanism of TNF-α-mediated HIV induction. Stimulation of U1 and ACH-2 cells with phorbol 12-myristate 13-acetate (PMA) resulted in the induction of TNF-α mRNA and the secretion of TNF-α. Of note is the fact that anti-TNF-α antibodies significantly suppressed the expression of HIV in PMA-stimulated U1 and ACH-2 cells. Furthermore, anti-TNF-α antibodies also suppressed both the constitutive and inducible levels of viral expression in the chronically infected promonocytic clone U33.3. This study illustrates the interrelationship between the regulation of HIV expression and normal immunoregulatory mechanisms in that virus expression, both constitutive and induced, can be modulated by an autocrine pathway involving TNF-α, a cytokine involved in the complex network of regulation of the normal human immune response

  9. BDNF, produced by a TPO-stimulated megakaryocytic cell line, regulates autocrine proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Shogo [Graduate School of Health Sciences, Hokkaido University, Sapporo (Japan); Research Fellow of the Japan Society for the Promotion of Science, Tokyo (Japan); Nagasawa, Ayumi; Masuda, Yuya; Tsunematsu, Tetsuya [Graduate School of Health Sciences, Hokkaido University, Sapporo (Japan); Hayasaka, Koji; Matsuno, Kazuhiko; Shimizu, Chikara [Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo (Japan); Ozaki, Yukio [Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi (Japan); Moriyama, Takanori, E-mail: moriyama@hs.hokuda.ac.jp [Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Sapporo (Japan)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer It has been thought that BDNF is not produced in the megakaryocytic lineage. Black-Right-Pointing-Pointer MEG-01 produces BDNF upon TPO stimulation and regulates its proliferation. Black-Right-Pointing-Pointer BDNF accelerates proliferation of MEG-01 in an autocrine manner. Black-Right-Pointing-Pointer BDNF may be an autocrine MEG-CSF, which regulates megakaryopoiesis. -- Abstract: While human platelets release endogenous brain-derived neurotrophic factor (BDNF) upon activation, a previous report on MEG-01, a megakaryocytic cell line, found no trace of BDNF production, and the pathophysiological function of platelet BDNF has remained elusive. In the present study, we demonstrate that MEG-01 produces BDNF in the presence of TPO and that this serves to potentiate cell proliferation. Our in vitro findings suggest that BDNF regulates MEG-01 proliferation in an autocrine manner, and we suggest that BDNF may be a physiological autocrine regulator of megakaryocyte progenitors.

  10. Toxoplasma gondii exposes phosphatidylserine inducing a TGF-β1 autocrine effect orchestrating macrophage evasion

    International Nuclear Information System (INIS)

    Seabra, Sergio H.; Souza, Wanderley de; Matta, Renato A. da

    2004-01-01

    Toxoplasmosis is a worldwide disease caused by Toxoplasma gondii. Activated macrophages control T. gondii growth by nitric oxide (NO) production. However, T. gondii active invasion inhibits NO production, allowing parasite persistence. Here we show that the mechanism used by T. gondii to inhibit NO production persisting in activated macrophages depends on phosphatidylserine (PS) exposure. Masking PS with annexin-V on parasites or activated macrophages abolished NO production inhibition and parasite persistence. NO production inhibition depended on a transforming growth factor-β 1 (TGF-β 1 ) autocrine effect confirmed by the expression of Smad 2 and 3 in infected macrophages. TGF-β 1 led to inducible nitric oxide synthase (iNOS) degradation, actin filament (F-actin) depolymerization, and lack of nuclear factor-κB (NF-κB) in the nucleus. All these features were reverted by TGF-β 1 neutralizing antibody treatment. Thus, T. gondii mimics the evasion mechanism used by Leishmania amazonensis and also the anti-inflammatory response evoked by apoptotic cells

  11. Positive feedback loop of autocrine BDNF from microglia causes prolonged microglia activation.

    Science.gov (United States)

    Zhang, Xin; Zeng, Lulu; Yu, Tingting; Xu, Yongming; Pu, Shaofeng; Du, Dongping; Jiang, Wei

    2014-01-01

    Microglia, which represent the immune cells of the central nervous system (CNS), have long been a subject of study in CNS disease research. Substantial evidence indicates that microglial activation functions as a strong neuro-inflammatory response in neuropathic pain, promoting the release of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α. In addition, activated microglia release brain-derived neurotrophic factor (BDNF), which acts as a powerful cytokine. In this study, we performed a series of in vitro experiments to examine whether a positive autocrine feedback loop existed between microglia-derived BDNF and subsequent microglial activation as well as the mechanisms underlying this positive feedback loop. Because ATP is a classic inducer of microglial activation, firstly, we examined ATP-activated microglia in the present study. Secondly, we used TrkB/Fc, the BDNF sequester, to eliminate the effects of endogenous BDNF. ATP-stimulated microglia without BDNF was examined. Finally, we used exogenous BDNF to further determine whether BDNF could directly activate BV2 microglia. In all experiments, to quantify BV2 microglia activation, the protein levels of CD11b, a microglial activation marker, were measured by western blot. A Transwell migration assay was used to examine microglial migration. To assess the synthesis and release of proinflammatory cytokines, western blot was used to measure BDNF synthesis, and ELISA was used to quantify TNF-α release. In our present research, we have observed that ATP dramatically activates microglia, enhancing microglial migration, increasing the synthesis of BDNF and up-regulating the release of TNF-α. Microglial activation is inhibited following the sequestration of endogenous BDNF, resulting in impaired microglial migration and decreased TNF-α release. Furthermore, exogenous BDNF can also activate microglia to subsequently enhance migration and increase TNF-α release. Therefore, we suggest that microglial

  12. Autocrine release of angiopoietin-2 mediates cerebrovascular disintegration in Moyamoya disease.

    Science.gov (United States)

    Blecharz, Kinga G; Frey, Dietmar; Schenkel, Tobias; Prinz, Vincent; Bedini, Gloria; Krug, Susanne M; Czabanka, Marcus; Wagner, Josephin; Fromm, Michael; Bersano, Anna; Vajkoczy, Peter

    2017-04-01

    Moyamoya disease is a rare steno-occlusive cerebrovascular disorder often resulting in hemorrhagic and ischemic strokes. Although sharing the same ischemic stimulus with atherosclerotic cerebrovascular disease, Moyamoya disease is characterized by a highly instable cerebrovascular system which is prone to rupture due to pathological neovascularization. To understand the molecular mechanisms underlying this instability, angiopoietin-2 gene expression was analyzed in middle cerebral artery lesions obtained from Moyamoya disease and atherosclerotic cerebrovascular disease patients. Angiopoietin-2 was significantly up-regulated in Moyamoya vessels, while serum concentrations of soluble angiopoietins were not changed. For further evaluations, cerebral endothelial cells incubated with serum from these patients in vitro were applied. In contrast to atherosclerotic cerebrovascular disease serum, Moyamoya disease serum induced an angiopoietin-2 overexpression and secretion, accompanied by loss of endothelial integrity. These effects were absent or inverse in endothelial cells of non-brain origin suggesting brain endothelium specificity. The destabilizing effects on brain endothelial cells to Moyamoya disease serum were partially suppressed by the inhibition of angiopoietin-2. Our findings define brain endothelial cells as the potential source of vessel-destabilizing factors inducing the high plasticity state and disintegration in Moyamoya disease in an autocrine manner. We also provide new insights into Moyamoya disease pathophysiology that may be helpful for preventive treatment strategies in future.

  13. HER2 overexpression elicits a proinflammatory IL-6 autocrine signaling loop that is critical for tumorigenesis.

    Science.gov (United States)

    Hartman, Zachary C; Yang, Xiao-Yi; Glass, Oliver; Lei, Gangjun; Osada, Takuya; Dave, Sandeep S; Morse, Michael A; Clay, Timothy M; Lyerly, Herbert K

    2011-07-01

    HER2 overexpression occurs in approximately 25% of breast cancers, where it correlates with poor prognosis. Likewise, systemic inflammation in breast cancer correlates with poor prognosis, although the process is not understood. In this study, we explored the relationship between HER2 and inflammation, comparing the effects of overexpressing wild-type or mutated inactive forms of HER2 in primary human breast cells. Wild-type HER2 elicited a profound transcriptional inflammatory profile, including marked elevation of interleukin-6 (IL-6) expression, which we established to be a critical determinant of HER2 oncogenesis. Mechanistic investigations revealed that IL-6 secretion induced by HER2 overexpression activated Stat3 and altered gene expression, enforcing an autocrine loop of IL-6/Stat3 expression. Both mouse and human in vivo models of HER2-amplified breast carcinoma relied critically on this HER2-IL-6-Stat3 signaling pathway. Our studies offer the first direct evidence linking HER2 to a systemic inflammatory mechanism that orchestrates HER2-mediated tumor growth. We suggest that the HER2-IL-6-STAT3 signaling axis we have defined in breast cancer could prompt new therapeutic or prevention strategies for treatment of HER2-amplified cancers. ©2011 AACR.

  14. Reactive Oxygen Species Alter Autocrine and Paracrine Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Zangar, Richard C.; Bollinger, Nikki; Weber, Thomas J.; Tan, Ruimin; Markillie, Lye Meng; Karin, Norman J.

    2011-12-01

    Cytochrome P450 (P450) 3A4 (CYP3A4) is the most abundant P450 protein in human liver and intestine and is highly inducible by a variety of drugs and other compounds. The P450 catalytic cycle is known to uncouple and release reactive oxygen species (ROS), but the effects of ROS from P450 and other enzymes in the endo-plasmic reticulum have been poorly studied from the perspective of effects on cell biology. In this study, we expressed low levels of CYP3A4 in HepG2 cells, a human hepatocarcinoma cell line, and examined effects on intracellular levels of ROS and on the secretion of a variety of growth factors that are important in extracellular communication. Using the redox-sensitive dye RedoxSensor red, we demonstrate that CYP3A4 expression increases levels of ROS in viable cells. A customELISA microarray platform was employed to demonstrate that expression of CYP3A4 increased secretion of amphiregulin, intracellular adhesion molecule 1, matrix metalloprotease 2, platelet-derived growth factor (PDGF), and vascular endothelial growth factor, but suppressed secretion of CD14. The antioxidant N-acetylcysteine suppressed all P450-dependent changes in protein secretion except for CD14. Quantitative RT-PCR demonstrated that changes in protein secretion were consistently associated with corresponding changes in gene expression. Inhibition of the NF-{kappa}B pathway blocked P450 effects on PDGF secretion. CYP3A4 expression also altered protein secretion in human mammary epithelial cells and C10 mouse lung cells. Overall, these results suggest that increased ROS production in the endoplasmic reticulum alters the secretion of proteins that have key roles in paracrine and autocrine signaling.

  15. Type I Interferons Function as Autocrine and Paracrine Factors to Induce Autotaxin in Response to TLR Activation

    Science.gov (United States)

    Song, Jianwen; Guan, Ming; Zhao, Zhenwen; Zhang, Junjie

    2015-01-01

    Lysophosphatidic acid (LPA) is an important phospholipid mediator in inflammation and immunity. However, the mechanism of LPA regulation during inflammatory response is largely unknown. Autotaxin (ATX) is the key enzyme to produce extracellular LPA from lysophosphatidylcholine (LPC). In this study, we found that ATX was induced in monocytic THP-1 cells by TLR4 ligand lipopolysaccharide (LPS), TLR9 ligand CpG oligonucleotide, and TLR3 ligand poly(I:C), respectively. The ATX induction by TLR ligand was abolished by the neutralizing antibody against IFN-β or the knockdown of IFNAR1, indicating that type I IFN autocrine loop is responsible for the ATX induction upon TLR activation. Both IFN-β and IFN-α were able to induce ATX expression via the JAK-STAT and PI3K-AKT pathways but with different time-dependent manners. The ATX induction by IFN-β was dramatically enhanced by IFN-γ, which had no significant effect on ATX expression alone, suggesting a synergy effect between type I and type II IFNs in ATX induction. Extracellular LPA levels were significantly increased when THP-1 cells were treated with IFN-α/β or TLR ligands. In addition, the type I IFN-mediated ATX induction was identified in human monocyte-derived dendritic cells (moDCs) stimulated with LPS or poly(I:C), and IFN-α/β could induce ATX expression in human peripheral blood mononuclear cells (PBMCs) and monocytes isolated form blood samples. These results suggest that, in response to TLR activation, ATX is induced through a type I INF autocrine-paracrine loop to enhance LPA generation. PMID:26313906

  16. Type I Interferons Function as Autocrine and Paracrine Factors to Induce Autotaxin in Response to TLR Activation.

    Directory of Open Access Journals (Sweden)

    Jianwen Song

    Full Text Available Lysophosphatidic acid (LPA is an important phospholipid mediator in inflammation and immunity. However, the mechanism of LPA regulation during inflammatory response is largely unknown. Autotaxin (ATX is the key enzyme to produce extracellular LPA from lysophosphatidylcholine (LPC. In this study, we found that ATX was induced in monocytic THP-1 cells by TLR4 ligand lipopolysaccharide (LPS, TLR9 ligand CpG oligonucleotide, and TLR3 ligand poly(I:C, respectively. The ATX induction by TLR ligand was abolished by the neutralizing antibody against IFN-β or the knockdown of IFNAR1, indicating that type I IFN autocrine loop is responsible for the ATX induction upon TLR activation. Both IFN-β and IFN-α were able to induce ATX expression via the JAK-STAT and PI3K-AKT pathways but with different time-dependent manners. The ATX induction by IFN-β was dramatically enhanced by IFN-γ, which had no significant effect on ATX expression alone, suggesting a synergy effect between type I and type II IFNs in ATX induction. Extracellular LPA levels were significantly increased when THP-1 cells were treated with IFN-α/β or TLR ligands. In addition, the type I IFN-mediated ATX induction was identified in human monocyte-derived dendritic cells (moDCs stimulated with LPS or poly(I:C, and IFN-α/β could induce ATX expression in human peripheral blood mononuclear cells (PBMCs and monocytes isolated form blood samples. These results suggest that, in response to TLR activation, ATX is induced through a type I INF autocrine-paracrine loop to enhance LPA generation.

  17. Chemokine CXCL3 mediates prostate cancer cells proliferation, migration and gene expression changes in an autocrine/paracrine fashion.

    Science.gov (United States)

    Xin, Hua; Cao, Yu; Shao, Ming-Liang; Zhang, Wei; Zhang, Chun-Bin; Wang, Jing-Tao; Liang, Li-Chun; Shao, Wen-Wu; Qi, Ya-Ling; Li, Yue; Zhang, Ze-Yu; Yang, Zhe; Sun, Yu-Hong; Zhang, Peng-Xia; Jia, Lin-Lin; Wang, Wei-Qun

    2018-03-09

    We have previously indicated that CXCL3 was upregulated in the tissues of prostate cancer, and exogenous administration of CXCL3 played a predominant role in the tumorigenicity of prostate cancer cells. In the present study, we further explored the role and the underlying mechanism of CXCL3 overexpression in the oncogenic potential of prostate cancer in an autocrine/paracrine fashion. CXCL3-overexpressing prostate cancer cell line PC-3 and immortalized prostate stromal cell line WPMY-1 were established by gene transfection. CCK-8, transwell assays and growth of tumor xenografts were conducted to characterize the effects of CXCL3 on PC-3 cells' proliferation and migration. Western blotting was conducted to test whether CXCL3 could affect the expression of tumorigenesis-associated genes. The results showed that CXCL3 overexpression in PC-3 cells and the PC-3 cells treated with the supernatants of CXCL3-transfected WPMY-1 cells stimulated the proliferation and migration of PC-3 cells in vitro and in a nude mouse xenograft model. Western blotting revealed higher levels of p-ERK, Akt and Bcl-2 and lower levels of Bax in the tumor xenografts transplanted with CXCL3-transfected PC-3 cells. Moreover, the tumor xenografts derived from the PC-3 cells treated with supernatants of CXCL3-transfected WPMY-1 cells showed higher expression of ERK, Akt and Bcl-2 and lower expression of Bax. These findings suggest that CXCL3 autocrine/paracrine pathways are involved in the development of prostate cancer by regulating the expression of the target genes that are related to the progression of malignancies.

  18. Reevaluation of the proposed autocrine proliferative function of prolactin in breast cancer

    DEFF Research Database (Denmark)

    Nitze, Louise Maymann; Galsgaard, Elisabeth Douglas; Din, Nanni

    2013-01-01

    The pituitary hormone prolactin (PRL) has been implicated in tumourigenesis. Expression of PRL and its receptor (PRLR) was reported in human breast epithelium and breast cancer cells. It was suggested that PRL may act as an autocrine/paracrine growth factor. Here, we addressed the role of locally...

  19. Plant Reproduction: Autocrine Machinery for the Long Journey of the Pollen Tube.

    Science.gov (United States)

    Higashiyama, Tetsuya

    2018-03-19

    Many receptor-like kinases localized at the pollen tube tip precisely control tube functions in flowering plants. Two recent reports have identified autocrine peptide ligands and receptor systems, providing insight into the molecular machinery that controls pollen tube growth and termination. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Endothelium-derived fibronectin regulates neonatal vascular morphogenesis in an autocrine fashion.

    Science.gov (United States)

    Turner, Christopher J; Badu-Nkansah, Kwabena; Hynes, Richard O

    2017-11-01

    Fibronectin containing alternatively spliced EIIIA and EIIIB domains is largely absent from mature quiescent vessels in adults, but is highly expressed around blood vessels during developmental and pathological angiogenesis. The precise functions of fibronectin and its splice variants during developmental angiogenesis however remain unclear due to the presence of cardiac, somitic, mesodermal and neural defects in existing global fibronectin KO mouse models. Using a rare family of surviving EIIIA EIIIB double KO mice, as well as inducible endothelial-specific fibronectin-deficient mutant mice, we show that vascular development in the neonatal retina is regulated in an autocrine manner by endothelium-derived fibronectin, and requires both EIIIA and EIIIB domains and the RGD-binding α5 and αv integrins for its function. Exogenous sources of fibronectin do not fully substitute for the autocrine function of endothelial fibronectin, demonstrating that fibronectins from different sources contribute differentially to specific aspects of angiogenesis.

  1. Autocrine effects of transgenic resistin reduce palmitate and glucose oxidation in brown adipose tissue

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Mlejnek, Petr; Zídek, Václav; Landa, Vladimír; Šimáková, Miroslava; Šilhavý, Jan; Strnad, Hynek; Eigner, Sebastian; Eigner-Henke, Kateřina; Škop, V.; Malínská, H.; Trnovská, J.; Kazdová, L.; Drahota, Zdeněk; Mráček, Tomáš; Houštěk, Josef

    2016-01-01

    Roč. 48, č. 6 (2016), s. 420-427 ISSN 1094-8341 R&D Projects: GA MŠk(CZ) LL1204; GA ČR(CZ) GB14-36804G; GA MZd(CZ) NT14325 Institutional support: RVO:67985823 ; RVO:68378050 ; RVO:61389005 Keywords : brown adipose tissue * autocrine * transgenic * spontaneously hypertensive rat Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.044, year: 2016

  2. Differential effects of exogenous and autocrine growth hormone on LNCaP prostate cancer cell proliferation and survival.

    Science.gov (United States)

    Nakonechnaya, Alona O; Jefferson, Holly S; Chen, Xiaofei; Shewchuk, Brian M

    2013-06-01

    The prostate gland is regulated by multiple hormones and growth factors that may also affect prostate tumorigenesis. Growth hormone (GH) contributes to prostate development and function, but the direct effects of GH on prostate cancer cells are not well understood. The expression of endogenous GH in prostate cancer cell lines has also been observed, suggesting the potential for an effect of autocrine GH. In the present study, we measure the levels of GH and GH receptor (GHR) mRNA in multiple prostate cancer and normal prostate-derived cell lines, and compare the effects of exogenous and autocrine GH on LNCaP prostate cancer cell proliferation and apoptosis, and the associated signal transduction pathways. We found that GHR and GH expression were higher in the prostate cancer cell lines, and that exogenous GH increased LNCaP cell proliferation, but had no effect on apoptosis. In contrast, autocrine GH overexpression reduced LNCaP cell proliferation and increased apoptosis. The distinct actions of exogenous and autocrine GH were accompanied by differences in the involvement of GHR-associated signal transduction pathways, and were paralleled by an alteration in the subcellular localization of GHR, in which autocrine GH appeared to sequester GHR in the Golgi and endoplasmic reticulum. This alteration of GHR trafficking may underlie a distinct mode of GH-mediated signaling associated with the effect of autocrine GH. These findings clarify the potential effects of GH on prostate cancer cell function, and indicate that the activity of autocrine GH may be distinct from that of endocrine GH in prostate cancer cells. Copyright © 2012 Wiley Periodicals, Inc.

  3. HER2 overexpression elicits a pro-inflammatory IL-6 autocrine signaling loop that is critical for tumorigenesis

    Science.gov (United States)

    Hartman, Zachary C.; Yang, Xiao-Yi; Glass, Oliver; Lei, Gangjun; Osada, Takuya; Dave, Sandeep S.; Morse, Michael A.; Clay, Timothy M.; Lyerly, Herbert Kim

    2011-01-01

    HER2 overexpression occurs in ~25% of breast cancers where it correlates with poor prognosis. Likewise, systemic inflammation in breast cancer correlates with poor prognosis although the process is not understood. In this study, we explored the relationship between HER2 and inflammation, comparing the effects of overexpressing wild-type or mutated inactive forms of HER2 in primary human breast cells. Wild-type HER2 elicited a profound transcriptional inflammatory profile, including marked elevation of IL-6 expression, which we established to be a critical determinant of HER2 oncogenesis. Mechanistic investigations revealed that IL-6 secretion induced by HER2 overexpression activated Stat3 and altered gene expression, enforcing an autocrine loop of IL-6/Stat3 expression. Both mouse and human in vivo models of HER2 amplified breast carcinoma relied critically on this HER2-IL-6-Stat3 signaling pathway. Our studies offer the first direct evidence linking HER2 to a systemic inflammatory mechanism that orchestrates HER2-mediated tumor growth. We suggest that the HER2-IL6-STAT3 signaling axis we have defined in breast cancer could prompt new therapeutic or prevention strategies for treatment of HER2-amplified cancers. PMID:21518778

  4. Autocrine role of vascular IL-15 in intimal thickening

    International Nuclear Information System (INIS)

    Cercek, Miha; Matsumoto, Michiaki; Li, Hongyan; Chyu, K.-Y.; Peter, Ashok; Shah, Prediman K.; Dimayuga, Paul C.

    2006-01-01

    Interleukin 15 (IL-15) is a pro-inflammatory cytokine that modulates T cell recruitment and activation, independent of antigen. It has been detected in human atherosclerotic plaques and atherosclerotic plaques of apoE-/- mice. IL-15 regulates fractalkine (FKN)-CX3CR1 chemokine signaling which is involved in atherogenesis and promotes SMC proliferation. We investigated the role of IL-15 in intimal thickening after arterial injury. Treatment of serum-stimulated SMC with IL-15 in vitro attenuated proliferation and suppressed CX3CR1 and FKN mRNA expression. The role of endogenous IL-15 in vivo was investigated in injured carotid arteries of mice. Periadventitial arterial injury resulted in increased IL-15 expression in the media and neointima, paralleled by increased IL-15 receptor α expression. Blockade of endogenous IL-15 increased intimal thickening. FKN and CX3CR1 expression increased after injury and were further augmented after IL-15 blockade. These data suggest that endogenous IL-15 attenuated intimal thickening after arterial injury. The potential mechanism of action is suppression of CX3CR1 signaling

  5. Dictyostelium cells bind a secreted autocrine factor that represses cell proliferation

    OpenAIRE

    Choe, Jonathan M; Bakthavatsalam, Deenadayalan; Phillips, Jonathan E; Gomer, Richard H

    2009-01-01

    Abstract Background Dictyostelium cells secrete the proteins AprA and CfaD. Cells lacking either AprA or CfaD proliferate faster than wild type, while AprA or CfaD overexpressor cells proliferate slowly, indicating that AprA and CfaD are autocrine factors that repress proliferation. CfaD interacts with AprA and requires the presence of AprA to slow proliferation. To determine if CfaD is necessary for the ability of AprA to slow proliferation, whether AprA binds to cells, and if so whether the...

  6. Autocrine/paracrine erythropoietin regulates migration and invasion potential and the stemness of human breast cancer cells

    Science.gov (United States)

    Liang, Ke; Qiu, Songbo; Lu, Yang; Fan, Zhen

    2014-01-01

    Recent studies suggest that erythropoietin (EPO) has pleiotropic effects in several cell types in addition to hematopoietic cells; however, the role of EPO-mediated cell signaling in nonhematopoietic cells, including in cancer cells, remains controversial. Here, we report our findings of autocrine/paracrine production of EPO by breast cancer cells and its functional significance. We detected a significant level of autocrine/paracrine EPO in the conditioned medium from the culture of SKBR3 breast cancer cells, particularly when the cells were cultured in hypoxia. Through knockdown of EPO and EPO receptor expression and experimental elevation of EPO receptor expression in SKBR3 breast cancer cells, we demonstrated novel roles of autocrine/paracrine EPO-mediated cell signaling in regulating migration and invasion potential and stemness-like properties of breast cancer cells. PMID:24100272

  7. Cell wall trapping of autocrine peptides for human G-protein-coupled receptors on the yeast cell surface.

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    Jun Ishii

    Full Text Available G-protein-coupled receptors (GPCRs regulate a wide variety of physiological processes and are important pharmaceutical targets for drug discovery. Here, we describe a unique concept based on yeast cell-surface display technology to selectively track eligible peptides with agonistic activity for human GPCRs (Cell Wall Trapping of Autocrine Peptides (CWTrAP strategy. In our strategy, individual recombinant yeast cells are able to report autocrine-positive activity for human GPCRs by expressing a candidate peptide fused to an anchoring motif. Following expression and activation, yeast cells trap autocrine peptides onto their cell walls. Because captured peptides are incapable of diffusion, they have no impact on surrounding yeast cells that express the target human GPCR and non-signaling peptides. Therefore, individual yeast cells can assemble the autonomous signaling complex and allow single-cell screening of a yeast population. Our strategy may be applied to identify eligible peptides with agonistic activity for target human GPCRs.

  8. Interferon beta 1, an intermediate in the tumor necrosis factor alpha- induced increased MHC class I expression and an autocrine regulator of the constitutive MHC class I expression

    OpenAIRE

    1987-01-01

    In conclusion, our observations indicate that the constitutive MHC class I expression is regulated by autocrine production of IFN-beta 1. TNF-alpha acts as an enhancer of the autocrine production of IFN-beta 1, and consequently as an enhancer of the MHC class I expression and viral protection.

  9. Collagen and Stretch Modulate Autocrine Secretion of Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Proteins from Differentiated Skeletal Muscle Cells

    Science.gov (United States)

    Perrone, Carmen E.; Fenwick-Smith, Daniela; Vandenburgh, Herman H.

    1995-01-01

    Stretch-induced skeletal muscle growth may involve increased autocrine secretion of insulin-like growth factor-1 (IGF-1) since IGF-1 is a potent growth factor for skeletal muscle hypertrophy, and stretch elevates IGF-1 mRNA levels in vivo. In tissue cultures of differentiated avian pectoralis skeletal muscle cells, nanomolar concentrations of exogenous IGF-1 stimulated growth in mechanically stretched but not static cultures. These cultures released up to 100 pg of endogenously produced IGF-1/micro-g of protein/day, as well as three major IGF binding proteins of 31, 36, and 43 kilodaltons (kDa). IGF-1 was secreted from both myofibers and fibroblasts coexisting in the muscle cultures. Repetitive stretch/relaxation of the differentiated skeletal muscle cells stimulated the acute release of IGF-1 during the first 4 h after initiating mechanical activity, but caused no increase in the long-term secretion over 24-72 h of IGF-1, or its binding proteins. Varying the intensity and frequency of stretch had no effect on the long-term efflux of IGF-1. In contrast to stretch, embedding the differentiated muscle cells in a three-dimensional collagen (Type I) matrix resulted in a 2-5-fold increase in long-term IGF-1 efflux over 24-72 h. Collagen also caused a 2-5-fold increase in the release of the IGF binding proteins. Thus, both the extracellular matrix protein type I collagen and stretch stimulate the autocrine secretion of IGF-1, but with different time kinetics. This endogenously produced growth factor may be important for the growth response of skeletal myofibers to both types of external stimuli.

  10. Autocrine abscisic acid mediates the UV-B-induced inflammatory response in human granulocytes and keratinocytes.

    Science.gov (United States)

    Bruzzone, Santina; Basile, Giovanna; Mannino, Elena; Sturla, Laura; Magnone, Mirko; Grozio, Alessia; Salis, Annalisa; Fresia, Chiara; Vigliarolo, Tiziana; Guida, Lucrezia; De Flora, Antonio; Tossi, Vanesa; Cassia, Raul; Lamattina, Lorenzo; Zocchi, Elena

    2012-06-01

    UV-B is an abiotic environmental stress in both plants and animals. Abscisic acid (ABA) is a phytohormone regulating fundamental physiological functions in plants, including response to abiotic stress. We previously demonstrated that ABA is an endogenous stress hormone also in animal cells. Here, we investigated whether autocrine ABA regulates the response to UV-B of human granulocytes and keratinocytes, the cells involved in UV-triggered skin inflammation. The intracellular ABA concentration increased in UV-B-exposed granulocytes and keratinocytes and ABA was released into the supernatant. The UV-B-induced production of NO and of reactive oxygen species (ROS), phagocytosis, and cell migration were strongly inhibited in granulocytes irradiated in the presence of a monoclonal antibody against ABA. Moreover, presence of the same antibody strongly inhibited release of NO, prostaglandin E2 (PGE(2)), and tumor necrosis factor-α (TNF-α) by UV-B irradiated keratinocytes. Lanthionine synthetase C-like protein 2 (LANCL2) is required for the activation of the ABA signaling pathway in human granulocytes. Silencing of LANCL2 in human keratinocytes by siRNA was accompanied by abrogation of the UV-B-triggered release of PGE(2), TNF-α, and NO and ROS production. These results indicate that UV-B irradiation induces ABA release from human granulocytes and keratinocytes and that autocrine ABA stimulates cell functions involved in skin inflammation. Copyright © 2011 Wiley Periodicals, Inc.

  11. Endothelin as an autocrine factor in the regulation of parathyroid cells

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Yoshio; Moreira, J.E.; Aurbach, G.D.; Sakaguchi, K. (National Inst. of Health, Bethesda, MD (United States)); Orlando, C.; Maggi, M.; Brandi, M.L. (Univ. of Florence (Italy))

    1991-05-15

    Endothelin, originally purified from porcine aortic endothelial cells, is widely distributed in tissues and is recognized as a product of epithelial cells, glial cells and neurons in addition to endothelial cells. The authors found evidence by mRNA content and immunoreactivity that this peptide is synthesized in rat parathyroid epithelial cells (PT-r cells) and bovine parathyroid chief cells. The peptide synthesized by PT-r cells comigrated with synthetic endothelin 1 in reverse-phase HPLC and was diluted out in radioimmunoassay in parallel with the synthetic peptide. Bovine parathyroid endothelial cells (BPE-1 cells) did by PT-r cells and endothelin 1 peptide production were regulated by calcium. Shifts in extracellular calcium either from high to low concentrations or vice versa elicited similar evanescent increases in expression of mRNA with a peak at 1 h. Synthesis of the peptide in the medium appears to be continuously degraded or taken up by cells because its concentration in the medium showed a time course similar to that of mRNA expression. PT-r cells also bear a single class of receptors highly specific for endothelin 1, suggesting an autocrine regulation by endothelin 1 of the parathyroid. The facile regulation of endothelin concentrations in the medium by shifts in extracellular calcium concentration and possible autocrine regulation by endothelin 1 suggest that this peptide may mediate, at least in part, effects of calcium on the parathyroid system.

  12. The Cholinergic and Adrenergic Autocrine Signaling Pathway Mediates Immunomodulation in Oyster Crassostrea gigas

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    Zhaoqun Liu

    2018-02-01

    Full Text Available It is becoming increasingly clear that neurotransmitters impose direct influence on regulation of the immune process. Recently, a simple but sophisticated neuroendocrine–immune (NEI system was identified in oyster, which modulated neural immune response via a “nervous-hemocyte”-mediated neuroendocrine immunomodulatory axis (NIA-like pathway. In the present study, the de novo synthesis of neurotransmitters and their immunomodulation in the hemocytes of oyster Crassostrea gigas were investigated to understand the autocrine/paracrine pathway independent of the nervous system. After hemocytes were exposed to lipopolysaccharide (LPS stimulation, acetylcholine (ACh, and norepinephrine (NE in the cell supernatants, both increased to a significantly higher level (2.71- and 2.40-fold, p < 0.05 comparing with that in the control group. The mRNA expression levels and protein activities of choline O-acetyltransferase and dopamine β-hydroxylase in hemocytes which were involved in the synthesis of ACh and NE were significantly elevated at 1 h after LPS stimulation, while the activities of acetylcholinesterase and monoamine oxidase, two enzymes essential in the metabolic inactivation of ACh and NE, were inhibited. These results demonstrated the existence of the sophisticated intracellular machinery for the generation, release and inactivation of ACh and NE in oyster hemocytes. Moreover, the hemocyte-derived neurotransmitters could in turn regulate the mRNA expressions of tumor necrosis factor (TNF genes, the activities of superoxide dismutase, catalase and lysosome, and hemocyte phagocytosis. The phagocytic activities of hemocytes, the mRNA expressions of TNF and the activities of key immune-related enzymes were significantly changed after the block of ACh and NE receptors with different kinds of antagonists, suggesting that autocrine/paracrine self-regulation was mediated by transmembrane receptors on hemocyte. The present study proved that

  13. Proinflammatory Effect of High Glucose Concentrations on HMrSV5 Cells via the Autocrine Effect of HMGB1

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    Yuening Chu

    2017-09-01

    Full Text Available Background: Peritoneal fibrosis, in which inflammation and apoptosis play crucial pathogenic roles, is a severe complication associated with the treatment of kidney failure with peritoneal dialysis (PD using a glucose-based dialysate. Mesothelial cells (MCs take part in the inflammatory processes by producing various cytokines and chemokines, such as monocyte chemoattractant protein 1 (MCP-1 and interleukin 8 (IL-8. The apoptosis of MCs induced by high glucose levels also contributes to complications of PD. High mobility group protein B1 (HMGB1 is an inflammatory factor that has repeatedly been proven to be related to the occurrence of peritoneal dysfunction.Aim: In this study, we aimed to explore the effect and underlying mechanism of endogenous HMGB1 in high-glucose-induced MC injury.Methods: The human peritoneal MC line, HMrSV5 was cultured in high-glucose medium and incubated with recombinant HMGB1. Cellular expression of HMGB1 was blocked using HMGB1 small interfering RNA (siRNA. Apoptosis and production of inflammatory factors as well as the potential intermediary signaling pathways were examined.Results: The major findings of these analyses were: (1 MCs secreted HMGB1 from the nucleus during exposure to high glucose levels; HMGB1 acted in an autocrine fashion on the MCs to promote the production of MCP-1 and IL-8; (2 HMGB1 had little effect on high-glucose-induced apoptosis of the MCs; and (3 HMGB1-mediated MCP-1 and IL-8 production depended on the activation of MAPK signaling pathways. In conclusion, endogenous HMGB1 plays an important role in the inflammatory reaction induced by high glucose on MCs via mitogen-activated protein kinase (MAPK signaling pathways, but it seems to have little effect on high-glucose-induced apoptosis.

  14. Autocrine production of beta-chemokines protects CMV-Specific CD4 T cells from HIV infection.

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    Joseph P Casazza

    2009-10-01

    Full Text Available Induction of a functional subset of HIV-specific CD4+ T cells that is resistant to HIV infection could enhance immune protection and decrease the rate of HIV disease progression. CMV-specific CD4+ T cells, which are less frequently infected than HIV-specific CD4+ T cells, are a model for such an effect. To determine the mechanism of this protection, we compared the functional response of HIV gag-specific and CMV pp65-specific CD4+ T cells in individuals co-infected with CMV and HIV. We found that CMV-specific CD4+ T cells rapidly up-regulated production of MIP-1alpha and MIP-1beta mRNA, resulting in a rapid increase in production of MIP-1alpha and MIP-1beta after cognate antigen stimulation. Production of beta-chemokines was associated with maturational phenotype and was rarely seen in HIV-specific CD4+ T cells. To test whether production of beta-chemokines by CD4+ T cells lowers their susceptibility to HIV infection, we measured cell-associated Gag DNA to assess the in vivo infection history of CMV-specific CD4+ T cells. We found that CMV-specific CD4+ T cells which produced MIP-1beta contained 10 times less Gag DNA than did those which failed to produce MIP-1beta. These data suggest that CD4+ T cells which produce MIP-1alpha and MIP-1beta bind these chemokines in an autocrine fashion which decreases the risk of in vivo HIV infection.

  15. Identification and targeting of a TACE-dependent autocrine loopwhich predicts poor prognosis in breast cancer

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    Kenny, Paraic A.; Bissell, Mina J.

    2005-06-15

    The ability to proliferate independently of signals from other cell types is a fundamental characteristic of tumor cells. Using a 3D culture model of human breast cancer progression, we have delineated a protease-dependent autocrine loop which provides an oncogenic stimulus in the absence of proto-oncogene mutation. Inhibition of this protease, TACE/ADAM17, reverts the malignant phenotype by preventing mobilization of two crucial growth factors, Amphiregulin and TGF{alpha}. We show further that the efficacy of EGFR inhibitors is overcome by physiological levels of growth factors and that successful EGFR inhibition is dependent on reducing ligand bioavailability. Using existing patient outcome data, we demonstrate a strong correlation between TACE and TGF{alpha} expression in human breast cancers that is predictive of poor prognosis.

  16. Arsenite evokes IL-6 secretion, autocrine regulation of STAT3 signaling, and miR-21 expression, processes involved in the EMT and malignant transformation of human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Luo, Fei; Xu, Yuan; Ling, Min; Zhao, Yue; Xu, Wenchao; Liang, Xiao; Jiang, Rongrong; Wang, Bairu; Bian, Qian; Liu, Qizhan

    2013-01-01

    Arsenite is an established human carcinogen, and arsenite-induced inflammation contributes to malignant transformation of cells, but the molecular mechanisms by which cancers are produced remain to be established. The present results showed that, evoked by arsenite, secretion of interleukin-6 (IL-6), a pro-inflammatory cytokine, led to the activation of STAT3, a transcription activator, and to increased levels of a microRNA, miR-21. Blocking IL-6 with anti-IL-6 antibody and inhibiting STAT3 activation reduced miR-21 expression. For human bronchial epithelial cells, cultured in the presence of anti-IL-6 antibody for 3 days, the arsenite-induced EMT and malignant transformation were reversed. Thus, IL-6, acting on STAT3 signaling, which up-regulates miR-21in an autocrine manner, contributes to the EMT induced by arsenite. These data define a link from inflammation to EMT in the arsenite-induced malignant transformation of HBE cells. This link, mediated through miRNAs, establishes a mechanism for arsenite-induced lung carcinogenesis. - Highlights: • Arsenite evokes IL-6 secretion. • IL-6 autocrine mediates STAT3 signaling and up-regulates miR-21expression. • Inflammation is involved in arsenite-induced EMT

  17. Raft-dependent endocytosis of autocrine motility factor/phosphoglucose isomerase: a potential drug delivery route for tumor cells.

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    Liliana D Kojic

    Full Text Available Autocrine motility factor/phosphoglucose isomerase (AMF/PGI is the extracellular ligand for the gp78/AMFR receptor overexpressed in a variety of human cancers. We showed previously that raft-dependent internalization of AMF/PGI is elevated in metastatic MDA-435 cells, but not metastatic, caveolin-1-expressing MDA-231 cells, relative to non-metastatic MCF7 and dysplastic MCF10A cells suggesting that it might represent a tumor cell-specific endocytic pathway.Similarly, using flow cytometry, we demonstrate that raft-dependent endocytosis of AMF/PGI is increased in metastatic HT29 cancer cells expressing low levels of caveolin-1 relative to metastatic, caveolin-1-expressing, HCT116 colon cells and non-metastatic Caco-2 cells. Therefore, we exploited the raft-dependent internalization of AMF/PGI as a potential tumor-cell specific targeting mechanism. We synthesized an AMF/PGI-paclitaxel conjugate and found it to be as efficient as free paclitaxel in inducing cytotoxicity and apoptosis in tumor cells that readily internalize AMF/PGI compared to tumor cells that poorly internalize AMF/PGI. Murine K1735-M1 and B16-F1 melanoma cells internalize FITC-conjugated AMF/PGI and are acutely sensitive to AMF/PGI-paclitaxel mediated cytotoxicity in vitro. Moreover, following in vivo intratumoral injection, FITC-conjugated AMF/PGI is internalized in K1735-M1 tumors. Intratumoral injection of AMF/PGI-paclitaxel induced significantly higher tumor regression compared to free paclitaxel, even in B16-F1 cells, known to be resistant to taxol treatment. Treatment with AMF/PGI-paclitaxel significantly prolonged the median survival time of tumor bearing mice. Free AMF/PGI exhibited a pro-survival role, reducing the cytotoxic effect of both AMF/PGI-paclitaxel and free paclitaxel suggesting that AMF/PGI-paclitaxel targets a pathway associated with resistance to chemotherapeutic agents. AMF/PGI-FITC uptake by normal murine spleen and thymus cells was negligible both in vitro

  18. MCP-1 expressed by osteoclasts stimulates osteoclastogenesis in an autocrine/paracrine manner

    International Nuclear Information System (INIS)

    Miyamoto, Kana; Ninomiya, Ken; Sonoda, Koh-Hei; Miyauchi, Yoshiteru; Hoshi, Hiroko; Iwasaki, Ryotaro; Miyamoto, Hiroya

    2009-01-01

    Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that plays a critical role in the recruitment and activation of leukocytes. Here, we describe that multinuclear osteoclast formation was significantly inhibited in cells derived from MCP-1-deficient mice. MCP-1 has been implicated in the regulation of osteoclast cell-cell fusion; however defects of multinuclear osteoclast formation in the cells from mice deficient in DC-STAMP, a seven transmembrane receptor essential for osteoclast cell-cell fusion, was not rescued by recombinant MCP-1. The lack of MCP-1 in osteoclasts resulted in a down-regulation of DC-STAMP, NFATc1, and cathepsin K, all of which were highly expressed in normal osteoclasts, suggesting that osteoclast differentiation was inhibited in MCP-1-deficient cells. MCP-1 alone did not induce osteoclastogenesis, however, the inhibition of osteoclastogenesis in MCP-1-deficient cells was restored by addition of recombinant MCP-1, indicating that osteoclastogenesis was regulated in an autocrine/paracrine manner by MCP-1 under the stimulation of RANKL in osteoclasts.

  19. Inhibition of KRAS-driven tumorigenicity by interruption of an autocrine cytokine circuit.

    Science.gov (United States)

    Zhu, Zehua; Aref, Amir R; Cohoon, Travis J; Barbie, Thanh U; Imamura, Yu; Yang, Shenghong; Moody, Susan E; Shen, Rhine R; Schinzel, Anna C; Thai, Tran C; Reibel, Jacob B; Tamayo, Pablo; Godfrey, Jason T; Qian, Zhi Rong; Page, Asher N; Maciag, Karolina; Chan, Edmond M; Silkworth, Whitney; Labowsky, Mary T; Rozhansky, Lior; Mesirov, Jill P; Gillanders, William E; Ogino, Shuji; Hacohen, Nir; Gaudet, Suzanne; Eck, Michael J; Engelman, Jeffrey A; Corcoran, Ryan B; Wong, Kwok-Kin; Hahn, William C; Barbie, David A

    2014-04-01

    Although the roles of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling in KRAS-driven tumorigenesis are well established, KRAS activates additional pathways required for tumor maintenance, the inhibition of which are likely to be necessary for effective KRAS-directed therapy. Here, we show that the IκB kinase (IKK)-related kinases Tank-binding kinase-1 (TBK1) and IKKε promote KRAS-driven tumorigenesis by regulating autocrine CCL5 and interleukin (IL)-6 and identify CYT387 as a potent JAK/TBK1/IKKε inhibitor. CYT387 treatment ablates RAS-associated cytokine signaling and impairs Kras-driven murine lung cancer growth. Combined CYT387 treatment and MAPK pathway inhibition induces regression of aggressive murine lung adenocarcinomas driven by Kras mutation and p53 loss. These observations reveal that TBK1/IKKε promote tumor survival by activating CCL5 and IL-6 and identify concurrent inhibition of TBK1/IKKε, Janus-activated kinase (JAK), and MEK signaling as an effective approach to inhibit the actions of oncogenic KRAS.

  20. An autocrine Wnt5a-Ror signaling loop mediates sympathetic target innervation.

    Science.gov (United States)

    Ryu, Yun Kyoung; Collins, Sarah Ellen; Ho, Hsin-Yi Henry; Zhao, Haiqing; Kuruvilla, Rejji

    2013-05-01

    During nervous system development, axon branching at nerve terminals is an essential step in the formation of functional connections between neurons and target cells. It is known that target tissues exert control of terminal arborization through secretion of trophic factors. However, whether the in-growing axons themselves produce diffusible cues to instruct target innervation remains unclear. Here, we use conditional mutant mice to show that Wnt5a derived from sympathetic neurons is required for their target innervation in vivo. Conditional deletion of Wnt5a resulted in specific deficits in the extension and arborization of sympathetic fibers in their final target fields, while no defects were observed in the overall tissue patterning, proliferation, migration or differentiation of neuronal progenitors. Using compartmentalized neuronal cultures, we further demonstrate that the Ror receptor tyrosine kinases are required locally in sympathetic axons to mediate Wnt5a-dependent branching. Thus, our study suggests an autocrine Wnt5a-Ror signaling pathway that directs sympathetic axon branching during target innervation. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Dendritic cells activated by double-stranded RNA induce arthritis via autocrine type I IFN signaling.

    Science.gov (United States)

    Narendra, Sudeep Chenna; Chalise, Jaya Prakash; Höök, Nina; Magnusson, Mattias

    2014-04-01

    Viral dsRNA can be found at the site of inflammation in RA patients, and intra-articular injection of dsRNA induces arthritis by activating type I IFN signaling in mice. Further, DCs, a major source of IFN-α, can be found in the synovium of RA patients. We therefore determined the occurrence of DCs in dsRNA-induced arthritis and their ability to induce arthritis. Here, we show, by immunohistochemistry, that cells expressing the pan-DC marker CD11c and the pDC marker 120G8 are present in the inflamed synovium in dsRNA-induced arthritis. Flt3L-generated and splenic DCs preactivated with dsRNA before intra-articular injection, but not mock-stimulated cells, clearly induced arthritis. Induction of arthritis was dependent on type I IFN signaling in the donor DCs, whereas IFNAR expression in the recipient was not required. Sorting of the Flt3L-DC population into cDCs (CD11c(+), PDCA-1(-)) and pDCs (CD11c(+), PDCA-1(+)) revealed that both subtypes were arthritogenic and produced type I IFN if treated with dsRNA. Taken together, these results demonstrate that viral nucleic acids can elicit arthritis by activating type I IFN signaling in DCs. Once triggered, autocrine type I IFN signaling in dsRNA-activated DCs is sufficient to propagate arthritis.

  2. Autocrine abscisic acid plays a key role in quartz-induced macrophage activation.

    Science.gov (United States)

    Magnone, Mirko; Sturla, Laura; Jacchetti, Emanuela; Scarfì, Sonia; Bruzzone, Santina; Usai, Cesare; Guida, Lucrezia; Salis, Annalisa; Damonte, Gianluca; De Flora, Antonio; Zocchi, Elena

    2012-03-01

    Inhalation of quartz induces silicosis, a lung disease where alveolar macrophages release inflammatory mediators, including prostaglandin-E(2) (PGE(2)) and tumor necrosis factor α (TNF-α). Here we report the pivotal role of abscisic acid (ABA), a recently discovered human inflammatory hormone, in silica-induced activation of murine RAW264.7 macrophages and of rat alveolar macrophages (AMs). Stimulation of both RAW264.7 cells and AMs with quartz induced a significant increase of ABA release (5- and 10-fold, respectively), compared to untreated cells. In RAW264.7 cells, autocrine ABA released after quartz stimulation sequentially activates the plasma membrane receptor LANCL2 and NADPH oxidase, generating a Ca(2+) influx resulting in NFκ B nuclear translocation and PGE(2) and TNF-α release (3-, 2-, and 3.5-fold increase, respectively, compared to control, unstimulated cells). Quartz-stimulated RAW264.7 cells silenced for LANCL2 or preincubated with a monoclonal antibody against ABA show an almost complete inhibition of NFκ B nuclear translocation and PGE(2) and TNF-α release compared to controls electroporated with a scramble oligonucleotide or preincubated with an unrelated antibody. AMs showed similar early and late ABA-induced responses as RAW264.7 cells. These findings identify ABA and LANCL2 as key mediators in quartz-induced inflammation, providing possible new targets for antisilicotic therapy.

  3. Interleukin-19 acts as a negative autocrine regulator of activated microglia.

    Directory of Open Access Journals (Sweden)

    Hiroshi Horiuchi

    Full Text Available Activated microglia can exert either neurotoxic or neuroprotective effects, and they play pivotal roles in the pathogenesis and progression of various neurological diseases. In this study, we used cDNA microarrays to show that interleukin-19 (IL-19, an IL-10 family cytokine, is markedly upregulated in activated microglia. Furthermore, we found that microglia are the only cells in the nervous system that express the IL-19 receptor, a heterodimer of the IL-20Rα and IL-20Rβ subunits. IL-19 deficiency increased the production of such pro-inflammatory cytokines as IL-6 and tumor necrosis factor-α in activated microglia, and IL-19 treatment suppressed this effect. Moreover, in a mouse model of Alzheimer's disease, we observed upregulation of IL-19 in affected areas in association with disease progression. Our findings demonstrate that IL-19 is an anti-inflammatory cytokine, produced by activated microglia, that acts negatively on microglia in an autocrine manner. Thus, microglia may self-limit their inflammatory response by producing the negative regulator IL-19.

  4. Autocrine regulation of cell proliferation by estrogen receptor-alpha in estrogen receptor-alpha-positive breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Pan Zhongzong

    2009-01-01

    Full Text Available Abstract Background Estrogen receptor-α (ERα is essential for mammary gland development and is a major oncogene in breast cancer. Since ERα is not colocalized with the cell proliferation marker Ki-67 in the normal mammary glands and the majority of primary breast tumors, it is generally believed that paracrine regulation is involved in ERα mediated cell proliferation. In the paracrine model, ERα-positive cells don't proliferate but will release some paracrine growth factors to stimulate the neighboring cells to proliferate. In a subpopulation of cancer cells in some primary breast tumors, however, ERα does colocalize with the cell proliferation marker Ki-67, suggesting an autocrine regulation by ERα in some primary breast tumors. Methods Colocalization of ERα with Ki-67 in ERα-positive breast cancer cell lines (MCF-7, T47D, and ZR75-1 was evaluated by immunofluorescent staining. Cell cycle phase dependent expression of ERα was determined by co-immunofluorescent staining of ERα and the major cyclins (D, E, A, B, and by flow cytometry analysis of ERαhigh cells. To further confirm the autocrine action of ERα, MCF-7 cells were growth arrested by ICI182780 treatment, followed by treatment with EGFR inhibitor, before estrogen stimulation and analyses for colocalization of Ki-67 and ERα and cell cycle progression. Results Colocalization of ERα with Ki-67 was present in all three ERα-positive breast cancer cell lines. Unlike that in the normal mammary glands and the majority of primary breast tumors, ERα is highly expressed throughout the cell cycle in MCF-7 cells. Without E2 stimulation, MCF-7 cells released from ICI182780 treatment remain at G1 phase. E2 stimulation of ICI182780 treated cells, however, promotes the expression and colocalization of ERα and Ki-67 as well as the cell cycle progressing through the S and G2/M phases. Inhibition of EGFR signaling does not inhibit the autocrine action of ERα. Conclusion Our data indicate

  5. Autocrine hGH stimulates oncogenicity, epithelial-mesenchymal transition and cancer stem cell-like behavior in human colorectal carcinoma.

    Science.gov (United States)

    Wang, Jing-Jing; Chong, Qing-Yun; Sun, Xin-Bao; You, Ming-Liang; Pandey, Vijay; Chen, Yi-Jun; Zhuang, Qiu-Shi; Liu, Dong-Xu; Ma, Lan; Wu, Zheng-Sheng; Zhu, Tao; Lobie, Peter E

    2017-11-28

    Tumor derived human growth hormone (hGH) has been implicated in cancer development and progression. However, the specific functional role of autocrine/paracrine hGH in colorectal cancer (CRC) remains largely to be determined. Herein, we demonstrated a crucial oncogenic role of autocrine hGH in CRC progression. Elevated hGH expression was detected in CRC compared to normal colorectal tissue, and hGH expression in CRC was positively associated with tumor size and lymph node metastasis. Forced expression of hGH stimulated cell proliferation, survival, oncogenicity and epithelial to mesenchymal transition (EMT) of CRC cells, and promoted xenograft growth and local invasion in vivo . Autocrine hGH expression in CRC cells stimulated the activation of the ERK1/2 pathway, which in turn resulted in increased transcription of the mesenchymal marker FIBRONECTIN 1 and transcriptional repression of the epithelial marker E-CADHERIN. The autocrine hGH-stimulated increase in CRC cell proliferation, cell survival and EMT was abrogated upon ERK1/2 inhibition. Furthermore, autocrine hGH-stimulated CRC cell migration and invasion was dependent on the ERK1/2-mediated increase in FIBRONECTIN 1 expression and decrease in E-CADHERIN expression. Forced expression of hGH also enhanced CSC-like behavior of CRC cells, as characterized by increased colonosphere formation, ALDH-positive population and CSC marker expression. Autocrine hGH-enhanced cancer stem cell (CSC)-like behavior in CRC cells was also observed to be E-CADHERIN-dependent. Thus, autocrine hGH plays a critical role in CRC progression, and inhibition of hGH could be a promising targeted therapeutic approach to limit disease progression in metastatic CRC patients.

  6. The effects of autocrine human growth hormone (hGH) on human mammary carcinoma cell behavior are mediated via the hGH receptor.

    Science.gov (United States)

    Kaulsay, K K; Zhu, T; Bennett, W; Lee, K O; Lobie, P E

    2001-02-01

    The human GH (hGH) antagonist B2036 combines a single amino acid substitution impairing receptor binding site 2 (G120K) with eight additional amino acid substitutions that improve binding site 1 affinity. B2036 does not bind, activate, or antagonize the human PRL receptor and therefore is suitable to determine cellular effects mediated specifically through the hGH receptor. We have used this hGH receptor specific antagonist in MCF-7 cells stably transfected with either the hGH gene (MCF-hGH) or a translation deficient hGH gene (MCF-MUT) to determine whether the effects of autocrine hGH on mammary carcinoma cell behavior are mediated via the hGH receptor. Enhanced JAK2 tyrosine phosphorylation observed in MCF-hGH cells compared with MCF-MUT cells is abrogated by B2036 as is the autocrine hGH stimulated increase in total cell number and DNA synthesis. Interestingly, autocrine hGH functions as a potent inhibitor of apoptosis induced by serum withdrawal compared with exogenously added hGH, and the protection against apoptosis afforded by autocrine hGH is abrogated by B2036. B2036 also inhibited autocrine hGH stimulated transcriptional activation mediated by either STAT5, CHOP (p38 MAP kinase specific) or Elk-1 (p44/42 MAP kinase specific). Finally, B2036 inhibited the autocrine hGH-dependent enhancement of the rate of mammary carcinoma cell spreading on a collagen matrix. Thus, the effects of autocrine hGH on human mammary carcinoma cell behavior are mediated via the hGH receptor.

  7. Dictyostelium cells bind a secreted autocrine factor that represses cell proliferation

    Directory of Open Access Journals (Sweden)

    Phillips Jonathan E

    2009-02-01

    Full Text Available Abstract Background Dictyostelium cells secrete the proteins AprA and CfaD. Cells lacking either AprA or CfaD proliferate faster than wild type, while AprA or CfaD overexpressor cells proliferate slowly, indicating that AprA and CfaD are autocrine factors that repress proliferation. CfaD interacts with AprA and requires the presence of AprA to slow proliferation. To determine if CfaD is necessary for the ability of AprA to slow proliferation, whether AprA binds to cells, and if so whether the binding requires the presence of CfaD, we examined the binding and effect on proliferation of recombinant AprA. Results We find that the extracellular accumulation of AprA increases with cell density and reaches a concentration of 0.3 μg/ml near a stationary cell density. When added to wild-type or aprA- cells, recombinant AprA (rAprA significantly slows proliferation at 0.1 μg/ml and higher concentrations. From 4 to 64 μg/ml, the effect of rAprA is at a plateau, slowing but not stopping proliferation. The proliferation-inhibiting activity of rAprA is roughly the same as that of native AprA in conditioned growth medium. Proliferating aprA- cells show saturable binding of rAprA to 92,000 ± 11,000 cell-surface receptors with a KD of 0.03 ± 0.02 μg/ml. There appears to be one class of binding site, and no apparent cooperativity. Native AprA inhibits the binding of rAprA to aprA- cells with a Ki of 0.03 μg/ml, suggesting that the binding kinetics of rAprA are similar to those of native AprA. The proliferation of cells lacking CrlA, a cAMP receptor-like protein, or cells lacking CfaD are not affected by rAprA. Surprisingly, both cell types still bind rAprA. Conclusion Together, the data suggest that AprA functions as an autocrine proliferation-inhibiting factor by binding to cell surface receptors. Although AprA requires CfaD for activity, it does not require CfaD to bind to cells, suggesting the possibility that cells have an AprA receptor and a Cfa

  8. Dictyostelium cells bind a secreted autocrine factor that represses cell proliferation.

    Science.gov (United States)

    Choe, Jonathan M; Bakthavatsalam, Deenadayalan; Phillips, Jonathan E; Gomer, Richard H

    2009-02-02

    Dictyostelium cells secrete the proteins AprA and CfaD. Cells lacking either AprA or CfaD proliferate faster than wild type, while AprA or CfaD overexpressor cells proliferate slowly, indicating that AprA and CfaD are autocrine factors that repress proliferation. CfaD interacts with AprA and requires the presence of AprA to slow proliferation. To determine if CfaD is necessary for the ability of AprA to slow proliferation, whether AprA binds to cells, and if so whether the binding requires the presence of CfaD, we examined the binding and effect on proliferation of recombinant AprA. We find that the extracellular accumulation of AprA increases with cell density and reaches a concentration of 0.3 microg/ml near a stationary cell density. When added to wild-type or aprA- cells, recombinant AprA (rAprA) significantly slows proliferation at 0.1 microg/ml and higher concentrations. From 4 to 64 microg/ml, the effect of rAprA is at a plateau, slowing but not stopping proliferation. The proliferation-inhibiting activity of rAprA is roughly the same as that of native AprA in conditioned growth medium. Proliferating aprA- cells show saturable binding of rAprA to 92,000 +/- 11,000 cell-surface receptors with a KD of 0.03 +/- 0.02 microg/ml. There appears to be one class of binding site, and no apparent cooperativity. Native AprA inhibits the binding of rAprA to aprA- cells with a Ki of 0.03 mug/ml, suggesting that the binding kinetics of rAprA are similar to those of native AprA. The proliferation of cells lacking CrlA, a cAMP receptor-like protein, or cells lacking CfaD are not affected by rAprA. Surprisingly, both cell types still bind rAprA. Together, the data suggest that AprA functions as an autocrine proliferation-inhibiting factor by binding to cell surface receptors. Although AprA requires CfaD for activity, it does not require CfaD to bind to cells, suggesting the possibility that cells have an AprA receptor and a CfaD receptor, and activation of both receptors is

  9. Brain-midgut cross-talk and autocrine metabolastat via the sNPF/CCAP negative feed-back loop in the American cockroach, Periplaneta americana.

    Science.gov (United States)

    Mikani, Azam; Watari, Yasuhiko; Takeda, Makio

    2015-12-01

    Immunohistochemical reactivities against short neuropeptide F (sNPF-ir) and crustacean cardioactive peptide (CCAP-ir) were detected in both the brain-subesophageal ganglion (Br-SOG) and midgut epithelial cells of the male American cockroach, Periplaneta americana. Four weeks of starvation increased the number of sNPF-ir cells and decreased the CCAP-ir cells in the Br-SOG, whereas refeeding reversed these effects. The contents of sNPF in the Br-SOG, midgut and hemolymph titer decreased in response to an injection of CCAP into the hemocoel of normally fed male cockroaches, while CCAP titers/contents decreased in response to an injection of sNPF. The results of a double-labeling experiment demonstrated that sNPF-ir co-existed in CCAP-ir cells in the pars intercerebralis (PI), dorsolateral region of protocerebrum (DL), deutocerebrum (De) and SOG. sNPF-ir and CCAP-ir were also colocalized in the midgut. sNPF and CCAP are neuropeptides and midgut factors that interact with each other. Since the two peptides are known to be secreted by identical cells that affect each other, this constitutes autocrine negative feedback regulation for a quick response to food accessibility/inaccessibility. These peptides not only constitute the switch in the digestive mechanism but also couple digestive adaptation with behavior. A CCAP injection suppressed locomotor activity when cockroaches were starved, whereas sNPF activated it when they were fed.

  10. Autocrine production of TGF-β confers resistance to apoptosis after an epithelial-mesenchymal transition process in hepatocytes: Role of EGF receptor ligands

    International Nuclear Information System (INIS)

    Castillo, Gaelle del; Murillo, Miguel M.; Alvarez-Barrientos, Alberto; Bertran, Esther; Fernandez, Margarita; Sanchez, Aranzazu; Fabregat, Isabel

    2006-01-01

    Transforming growth factor-beta (TGF-β) induces apoptosis in fetal rat hepatocytes. However, a subpopulation of these cells survives, concomitant with changes in phenotype, reminiscent of an epithelial-mesenchymal transition (EMT). We have previously suggested that EMT might confer cell resistance to apoptosis (Valdes et al., Mol. Cancer Res., 1: 68-78, 2002). However, the molecular mechanisms responsible for this resistance are not explored yet. In this work, we have isolated and subcultured the population of hepatocytes that suffered the EMT process and are resistant to apoptosis (TGF-β-treated fetal hepatocytes: TβT-FH). We prove that they secrete mitogenic and survival factors, as analyzed by the proliferative and survival capacity of conditioned medium. Inhibition of the epidermal growth factor receptor (EGFR) sensitizes TβT-FH to die after serum withdrawal. TβT-FH expresses high levels of transforming growth factor-alpha (TGF-α) and heparin-binding EGF-like growth factor (HB-EGF) and shows constitutive activation of the EGFR pathway. A blocking anti-TGF-α antibody restores the capacity of cells to die. TGF-β, which is expressed by TβT-FH, mediates up-regulation of TGF-α and HB-EGF expression in those cells. In summary, results suggest that an autocrine loop of TGF-β confers resistance to apoptosis after an EMT process in hepatocytes, through the increase in the expression of EGFR ligands

  11. Lipopolysaccharide (LPS)-mediated Angiopoietin-2-dependent Autocrine Angiogenesis Is Regulated by NADPH Oxidase 2 (Nox2) in Human Pulmonary Microvascular Endothelial Cells*

    Science.gov (United States)

    Menden, Heather; Welak, Scott; Cossette, Stephanie; Ramchandran, Ramani; Sampath, Venkatesh

    2015-01-01

    Sepsis-mediated endothelial Angiopoeitin-2 (Ang2) signaling may contribute to microvascular remodeling in the developing lung. The mechanisms by which bacterial cell wall components such as LPS mediate Ang2 signaling in human pulmonary microvascular endothelial cells (HPMECs) remain understudied. In HPMEC, LPS-induced Ang2, Tie2, and VEGF-A protein expression was preceded by increased superoxide formation. NADPH oxidase 2 (Nox2) inhibition, but not Nox4 or Nox1 inhibition, attenuated LPS-induced superoxide formation and Ang2, Tie2, and VEGF-A expression. Nox2 silencing, but not Nox4 or Nox1 silencing, inhibited LPS-mediated inhibitor of κ-B kinase β (IKKβ) and p38 phosphorylation and nuclear translocation of NF-κB and AP-1. In HPMECs, LPS increased the number of angiogenic tube and network formations in Matrigel by >3-fold. Conditioned media from LPS-treated cells also induced angiogenic tube and network formation in the presence of Toll-like receptor 4 blockade but not in the presence of Ang2 and VEGF blockade. Nox2 inhibition or conditioned media from Nox2-silenced cells attenuated LPS-induced tube and network formation. Ang2 and VEGF-A treatment rescued angiogenesis in Nox2-silenced cells. We propose that Nox2 regulates LPS-mediated Ang2-dependent autocrine angiogenesis in HPMECs through the IKKβ/NF-κB and MAPK/AP-1 pathways. PMID:25568324

  12. The putative bZIP transcription factor BzpN slows proliferation and functions in the regulation of cell density by autocrine signals in Dictyostelium.

    Directory of Open Access Journals (Sweden)

    Jonathan E Phillips

    Full Text Available The secreted proteins AprA and CfaD function as autocrine signals that inhibit cell proliferation in Dictyostelium discoideum, thereby regulating cell numbers by a negative feedback mechanism. We report here that the putative basic leucine zipper transcription factor BzpN plays a role in the inhibition of proliferation by AprA and CfaD. Cells lacking BzpN proliferate more rapidly than wild-type cells but do not reach a higher stationary density. Recombinant AprA inhibits wild-type cell proliferation but does not inhibit the proliferation of cells lacking BzpN. Recombinant CfaD also inhibits wild-type cell proliferation, but promotes the proliferation of cells lacking BzpN. Overexpression of BzpN results in a reduced cell density at stationary phase, and this phenotype requires AprA, CfaD, and the kinase QkgA. Conditioned media from high-density cells stops the proliferation of wild-type but not bzpN(- cells and induces a nuclear localization of a BzpN-GFP fusion protein, though this localization does not require AprA or CfaD. Together, the data suggest that BzpN is necessary for some but not all of the effects of AprA and CfaD, and that BzpN may function downstream of AprA and CfaD in a signal transduction pathway that inhibits proliferation.

  13. The Putative bZIP Transcripton Factor BzpN Slows Proliferation and Functions in the Regulation of Cell Density by Autocrine Signals in Dictyostelium

    Science.gov (United States)

    Phillips, Jonathan E.; Huang, Eryong; Shaulsky, Gad; Gomer, Richard H.

    2011-01-01

    The secreted proteins AprA and CfaD function as autocrine signals that inhibit cell proliferation in Dictyostelium discoideum, thereby regulating cell numbers by a negative feedback mechanism. We report here that the putative basic leucine zipper transcription factor BzpN plays a role in the inhibition of proliferation by AprA and CfaD. Cells lacking BzpN proliferate more rapidly than wild-type cells but do not reach a higher stationary density. Recombinant AprA inhibits wild-type cell proliferation but does not inhibit the proliferation of cells lacking BzpN. Recombinant CfaD also inhibits wild-type cell proliferation, but promotes the proliferation of cells lacking BzpN. Overexpression of BzpN results in a reduced cell density at stationary phase, and this phenotype requires AprA, CfaD, and the kinase QkgA. Conditioned media from high-density cells stops the proliferation of wild-type but not bzpN− cells and induces a nuclear localization of a BzpN-GFP fusion protein, though this localization does not require AprA or CfaD. Together, the data suggest that BzpN is necessary for some but not all of the effects of AprA and CfaD, and that BzpN may function downstream of AprA and CfaD in a signal transduction pathway that inhibits proliferation. PMID:21760904

  14. The putative bZIP transcription factor BzpN slows proliferation and functions in the regulation of cell density by autocrine signals in Dictyostelium.

    Science.gov (United States)

    Phillips, Jonathan E; Huang, Eryong; Shaulsky, Gad; Gomer, Richard H

    2011-01-01

    The secreted proteins AprA and CfaD function as autocrine signals that inhibit cell proliferation in Dictyostelium discoideum, thereby regulating cell numbers by a negative feedback mechanism. We report here that the putative basic leucine zipper transcription factor BzpN plays a role in the inhibition of proliferation by AprA and CfaD. Cells lacking BzpN proliferate more rapidly than wild-type cells but do not reach a higher stationary density. Recombinant AprA inhibits wild-type cell proliferation but does not inhibit the proliferation of cells lacking BzpN. Recombinant CfaD also inhibits wild-type cell proliferation, but promotes the proliferation of cells lacking BzpN. Overexpression of BzpN results in a reduced cell density at stationary phase, and this phenotype requires AprA, CfaD, and the kinase QkgA. Conditioned media from high-density cells stops the proliferation of wild-type but not bzpN(-) cells and induces a nuclear localization of a BzpN-GFP fusion protein, though this localization does not require AprA or CfaD. Together, the data suggest that BzpN is necessary for some but not all of the effects of AprA and CfaD, and that BzpN may function downstream of AprA and CfaD in a signal transduction pathway that inhibits proliferation.

  15. Mitogenic effects of a mesothelial cell growth factor: evidence for a potential autocrine regulation of normal and malignant mesothelial cell proliferation.

    Science.gov (United States)

    Donna, A.; Betta, P. G.; Ribotta, M.; Maran, E.; Mazzucco, G.; Mollo, F.; Bellingeri, D.; Libener, R.

    1992-01-01

    We have investigated the growth-factor-like activity of a approximately 200-kDa, IP 8.3, cytoplasmic glycoprotein, the expression of which appears to be restricted to normal and malignant human mesothelium. This substance stimulated the growth of human mesothelioma cell cultures at greater rates than did foetal calf serum, but it failed to induce proliferation of lung carcinoma cell cultures. In addition, we have tried to trace the biosynthetic pathway of this mitogenic factor in normal human mesothelial cells by means of immuno-electron microscopy with a polyclonal antibody directed against this molecule. Positive immunogold labelling was found in the lumina of the cisternae of the endoplasmic reticulum, to a lesser extent on the outer surface of the plasma membrane, and also in structures corresponding to the coated pits. These ultrastructural findings are consistent with the hypothesis of the glycosylation of the newly synthesized protein in the endoplasmic reticulum and the subsequent uptake of the secreted molecule, which accumulates in the coated pits before internalization. The results suggest that this mitogenic glycoprotein could play a role in an autocrine growth control mechanism influencing mesothelial cell proliferation. Images Fig. 1 Fig. 2 Fig. 3 PMID:1571279

  16. Stimulated human mast cells secrete mitochondrial components that have autocrine and paracrine inflammatory actions.

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    Bodi Zhang

    Full Text Available Mast cells are hematopoietically-derived tissue immune cells that participate in acquired and innate immunity, as well as in inflammation through release of many chemokines and cytokines, especially in response to the pro-inflammatory peptide substance P (SP. Inflammation is critical in the pathogenesis of many diseases, but the trigger(s is often unknown. We investigated if mast cell stimulation leads to secretion of mitochondrial components and whether these could elicit autocrine and/or paracrine inflammatory effects. Here we show that human LAD2 mast cells stimulated by IgE/anti-IgE or by the SP led to secretion of mitochondrial particles, mitochondrial (mt mtDNA and ATP without cell death. Mitochondria purified from LAD2 cells and, when mitochondria added to mast cells trigger degranulation and release of histamine, PGD(2, IL-8, TNF, and IL-1β. This stimulatory effect is partially inhibited by an ATP receptor antagonist and by DNAse. These results suggest that the mitochondrial protein fraction may also contribute. Purified mitochondria also stimulate IL-8 and vascular endothelial growth factor (VEGF release from cultured human keratinocytes, and VEGF release from primary human microvascular endothelial cells. In order to investigate if mitochondrial components could be secreted in vivo, we injected rats intraperiotoneally (ip with compound 48/80, which mimicks the action of SP. Peritoneal mast cells degranulated and mitochondrial particles were documented by transimission electron microscopy outside the cells. We also wished to investigate if mitochondrial components secreted locally could reach the systemic circulation. Administration ip of mtDNA isolated from LAD2 cells in rats was detected in their serum within 4 hr, indicating that extravascular mtDNA could enter the systemic circulation. Secretion of mitochondrial components from stimulated live mast cells may act as "autopathogens" contributing to the pathogenesis of inflammatory

  17. Autocrine prostaglandin E2 signaling promotes tumor cell survival and proliferation in childhood neuroblastoma.

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    Agnes Rasmuson

    Full Text Available BACKGROUND: Prostaglandin E(2 (PGE(2 is an important mediator in tumor-promoting inflammation. High expression of cyclooxygenase-2 (COX-2 has been detected in the embryonic childhood tumor neuroblastoma, and treatment with COX inhibitors significantly reduces tumor growth. Here, we have investigated the significance of a high COX-2 expression in neuroblastoma by analysis of PGE(2 production, the expression pattern and localization of PGE(2 receptors and intracellular signal transduction pathways activated by PGE(2. PRINCIPAL FINDINGS: A high expression of the PGE(2 receptors, EP1, EP2, EP3 and EP4 in primary neuroblastomas, independent of biological and clinical characteristics, was detected using immunohistochemistry. In addition, mRNA and protein corresponding to each of the receptors were detected in neuroblastoma cell lines. Immunofluorescent staining revealed localization of the receptors to the cellular membrane, in the cytoplasm, and in the nuclear compartment. Neuroblastoma cells produced PGE(2 and stimulation of serum-starved neuroblastoma cells with PGE(2 increased the intracellular concentration of calcium and cyclic AMP with subsequent phosphorylation of Akt. Addition of 16,16-dimethyl PGE(2 (dmPGE(2 increased cell viability in a time, dose- and cell line-dependent manner. Treatment of neuroblastoma cells with a COX-2 inhibitor resulted in a diminished cell growth and viability that was reversed by the addition of dmPGE(2. Similarly, PGE(2 receptor antagonists caused a decrease in neuroblastoma cell viability in a dose-dependent manner. CONCLUSIONS: These findings demonstrate that PGE(2 acts as an autocrine and/or paracrine survival factor for neuroblastoma cells. Hence, specific targeting of PGE(2 signaling provides a novel strategy for the treatment of childhood neuroblastoma through the inhibition of important mediators of tumor-promoting inflammation.

  18. The ROCO Kinase QkgA Is Necessary for Proliferation Inhibition by Autocrine Signals in Dictyostelium discoideum▿

    OpenAIRE

    Phillips, Jonathan E.; Gomer, Richard H.

    2010-01-01

    AprA and CfaD are secreted proteins that function as autocrine signals to inhibit cell proliferation in Dictyostelium discoideum. Cells lacking AprA or CfaD proliferate rapidly, and adding AprA or CfaD to cells slows proliferation. Cells lacking the ROCO kinase QkgA proliferate rapidly, with a doubling time 83% of that of the wild type, and overexpression of a QkgA-green fluorescent protein (GFP) fusion protein slows cell proliferation. We found that qkgA− cells accumulate normal levels of ex...

  19. An Autocrine Proliferation Repressor Regulates Dictyostelium discoideum Proliferation and Chemorepulsion Using the G Protein-Coupled Receptor GrlH

    OpenAIRE

    Yu Tang; Yuantai Wu; Sarah E. Herlihy; Francisco J. Brito-Aleman; Jose H. Ting; Chris Janetopoulos; Richard H. Gomer; Scott D. Emr

    2018-01-01

    In eukaryotic microbes, little is known about signals that inhibit the proliferation of the cells that secrete the signal, and little is known about signals (chemorepellents) that cause cells to move away from the source of the signal. Autocrine proliferation repressor protein A (AprA) is a protein secreted by the eukaryotic microbe Dictyostelium discoideum. AprA is a chemorepellent for and inhibits the proliferation of D. discoideum. We previously found that cells sense AprA using G proteins...

  20. Age-related autocrine diabetogenic effects of transgenic resistin in spontaneously hypertensive rats: gene expression profile analysis

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Zídek, Václav; Landa, Vladimír; Šimáková, Miroslava; Mlejnek, Petr; Šilhavý, J.; Maxová, M.; Kazdová, L.; Seidman, J. G.; Seidman, Ch. E.; Eminaga, S.; Gorham, J.; Wang, J.; Kurtz, T. W.

    2011-01-01

    Roč. 43, č. 7 (2011), s. 372-379 ISSN 1094-8341 R&D Projects: GA MŠk(CZ) ME08006; GA MŠk(CZ) 1M0510; GA AV ČR(CZ) IAA500110805; GA MZd(CZ) NS9759 Grant - others:Fondation Leducq(FR) 06CVD03 Institutional research plan: CEZ:AV0Z50110509 Keywords : transgenic rat * adipose tissue * insulin resistance * autocrine effects Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.735, year: 2011

  1. Autocrine prolactin induced by the Pten–Akt pathway is required for lactation initiation and provides a direct link between the Akt and Stat5 pathways

    Science.gov (United States)

    Chen, Chien-Chung; Stairs, Douglas B.; Boxer, Robert B.; Belka, George K.; Horseman, Nelson D.; Alvarez, James V.; Chodosh, Lewis A.

    2012-01-01

    Extrapituitary prolactin (Prl) is produced in humans and rodents; however, little is known about its in vivo regulation or physiological function. We now report that autocrine prolactin is required for terminal mammary epithelial differentiation during pregnancy and that its production is regulated by the Pten–PI3K–Akt pathway. Conditional activation of the PI3K–Akt pathway in the mammary glands of virgin mice by either Akt1 expression or Pten deletion rapidly induced terminal mammary epithelial differentiation accompanied by the synthesis of milk despite the absence of lobuloalveolar development. Surprisingly, we found that mammary differentiation was due to the PI3K–Akt-dependent synthesis and secretion of autocrine prolactin and downstream activation of the prolactin receptor (Prlr)–Jak–Stat5 pathway. Consistent with this, Akt-induced mammary differentiation was abrogated in Prl−/−, Prlr−/−, and Stat5−/− mice. Furthermore, cells treated with conditioned medium from mammary glands in which Akt had been activated underwent rapid Stat5 phosphorylation in a manner that was blocked by inhibition of Jak2, treatment with an anti-Prl antibody, or deletion of the prolactin gene. Demonstrating a physiological requirement for autocrine prolactin, mammary glands from lactation-defective Akt1−/−;Akt2+/− mice failed to express autocrine prolactin or activate Stat5 during late pregnancy despite normal levels of circulating serum prolactin and pituitary prolactin production. Our findings reveal that PI3K–Akt pathway activation is necessary and sufficient to induce autocrine prolactin production in the mammary gland, Stat5 activation, and terminal mammary epithelial differentiation, even in the absence of the normal developmental program that prepares the mammary gland for lactation. Together, these findings identify a function for autocrine prolactin during normal development and demonstrate its endogenous regulation by the PI3K–Akt pathway

  2. Role of prostaglandin E receptor subtypes EP2 and EP4 in autocrine and paracrine functions of vascular endothelial growth factor in the inner ear

    Directory of Open Access Journals (Sweden)

    Hamaguchi Kiyomi

    2010-03-01

    Full Text Available Abstract Background The physiological effects of prostaglandin E1 (PGE1 and prostaglandin E2 (PGE2 are mediated by the prostaglandin E receptor subtypes EP1, EP2, EP3, and EP4, and the respective agonists have been purified. PGE1 and PGE2 can increase the production of vascular endothelial growth factor (VEGF, particularly through EP2 and EP4. The biological effects of VEGF are mediated by the phosphotyrosine kinase receptors fms-related tyrosine kinase-1 (Flt-1 and fetal liver kinase-1 (Flk-1. Here we examined the effects of EP2 and EP4 agonists on the production of VEGF proteins and VEGF messenger RNAs (mRNAs in the inner ear, using an enzyme-linked immunosorbent assay and the real-time quantitative reverse transcription-polymerase chain reaction, respectively. We also examined the localization of EP2, VEGF, Flt-1, and Flk-1 in the cochlea by immunohistochemistry. Results The expression of EP2 occurred in the cochlea, and the local application of an EP2 or EP4 agonist increased VEGF protein and VEGF mRNA levels in the inner ear. Furthermore, the intensity of the VEGF immunoreactivity in the spiral ganglion appeared to be increased by the local EP2 or EP4 agonist treatment. Immunoreactivity for Flt-1, and Flk-1 was found in the cochlear sensory epithelium, spiral ganglion, spiral ligament, and stria vascularis. Conclusions These findings demonstrate that EP2 and EP4 agonists stimulate VEGF production in the inner ear, particularly in the spiral ganglions. Moreover, the Flt-1 and Flk-1 expression observed in the present study suggests that VEGF has autocrine and paracrine actions in the cochlea. Thus, EP2 and EP4 might be involved in the mechanisms underlying the therapeutic effects of PGE1 on acute sensorineural hearing loss via VEGF production.

  3. Role of prostaglandin E receptor subtypes EP2 and EP4 in autocrine and paracrine functions of vascular endothelial growth factor in the inner ear.

    Science.gov (United States)

    Hori, Ryusuke; Nakagawa, Takayuki; Yamamoto, Norio; Hamaguchi, Kiyomi; Ito, Juichi

    2010-03-11

    The physiological effects of prostaglandin E1 (PGE1) and prostaglandin E2 (PGE2) are mediated by the prostaglandin E receptor subtypes EP1, EP2, EP3, and EP4, and the respective agonists have been purified. PGE1 and PGE2 can increase the production of vascular endothelial growth factor (VEGF), particularly through EP2 and EP4. The biological effects of VEGF are mediated by the phosphotyrosine kinase receptors fms-related tyrosine kinase-1 (Flt-1) and fetal liver kinase-1 (Flk-1). Here we examined the effects of EP2 and EP4 agonists on the production of VEGF proteins and VEGF messenger RNAs (mRNAs) in the inner ear, using an enzyme-linked immunosorbent assay and the real-time quantitative reverse transcription-polymerase chain reaction, respectively. We also examined the localization of EP2, VEGF, Flt-1, and Flk-1 in the cochlea by immunohistochemistry. The expression of EP2 occurred in the cochlea, and the local application of an EP2 or EP4 agonist increased VEGF protein and VEGF mRNA levels in the inner ear. Furthermore, the intensity of the VEGF immunoreactivity in the spiral ganglion appeared to be increased by the local EP2 or EP4 agonist treatment. Immunoreactivity for Flt-1, and Flk-1 was found in the cochlear sensory epithelium, spiral ganglion, spiral ligament, and stria vascularis. These findings demonstrate that EP2 and EP4 agonists stimulate VEGF production in the inner ear, particularly in the spiral ganglions. Moreover, the Flt-1 and Flk-1 expression observed in the present study suggests that VEGF has autocrine and paracrine actions in the cochlea. Thus, EP2 and EP4 might be involved in the mechanisms underlying the therapeutic effects of PGE1 on acute sensorineural hearing loss via VEGF production.

  4. Autocrine activation of human monocyte/macrophages by monocyte-derived microparticles and modulation by PPARγ ligands.

    Science.gov (United States)

    Bardelli, C; Amoruso, A; Federici Canova, D; Fresu, Lg; Balbo, P; Neri, T; Celi, A; Brunelleschi, S

    2012-02-01

    Microparticles (MPs), small membrane-bound particles originating from different cell types during activation or apoptosis, mediate intercellular communication, exert pro-coagulant activity and affect inflammation and other pathophysiological conditions. Monocyte-derived MPs have undergone little investigation and, to our knowledge, have never been evaluated for their possible autocrine effects. Therefore, we assessed the ability of monocyte-derived MPs to stimulate human monocytes and monocyte-derived macrophages (MDM). MPs were generated from supernatants of human monocytes stimulated by the calcium ionophore A23187 (12 µM), and then characterized. Human monocytes and MDM of healthy donors were isolated by standard procedures. Cells were challenged by MPs or phorbol 12-myristate 13-acetate (PMA, used as standard stimulus), in the absence or presence of PPARγ agonists and antagonists. Superoxide anion production (measured spectrophotometrically), cytokine release (elisa), PPARγ protein expression (immunoblotting) and NF-κB activation (EMSA assay) were evaluated. Monocyte-derived MPs induced, in a concentration-dependent manner, oxygen radical production, cytokine release and NF-κB activation in human monocytes and macrophages, with lower effects than PMA. In both cell types, the PPARγ agonists rosiglitazone and 15-deoxy-Δ(12,14) -prostaglandin J(2) (15d-PGJ(2) ) inhibited MPs-induced stimulation and this inhibition was reversed by a PPARγ antagonist. In human monocyte/macrophages, MPs as well as rosiglitazone and 15d-PGJ(2) induced PPARγ protein expression. In human monocyte/macrophages, monocyte-derived MPs exert an autocrine activation that was modulated by PPARγ ligands, inducing both pro-inflammatory (superoxide anion production, cytokine release and NF-κB activation) and anti-inflammatory (PPARγ expression) effects. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  5. Autocrine activation of human monocyte/macrophages by monocyte-derived microparticles and modulation by PPARγ ligands

    Science.gov (United States)

    Bardelli, C; Amoruso, A; Federici Canova, D; Fresu, LG; Balbo, P; Neri, T; Celi, A; Brunelleschi, S

    2012-01-01

    BACKGROUND AND PURPOSE Microparticles (MPs), small membrane-bound particles originating from different cell types during activation or apoptosis, mediate intercellular communication, exert pro-coagulant activity and affect inflammation and other pathophysiological conditions. Monocyte-derived MPs have undergone little investigation and, to our knowledge, have never been evaluated for their possible autocrine effects. Therefore, we assessed the ability of monocyte-derived MPs to stimulate human monocytes and monocyte-derived macrophages (MDM). EXPERIMENTAL APPROACH MPs were generated from supernatants of human monocytes stimulated by the calcium ionophore A23187 (12 µM), and then characterized. Human monocytes and MDM of healthy donors were isolated by standard procedures. Cells were challenged by MPs or phorbol 12-myristate 13-acetate (PMA, used as standard stimulus), in the absence or presence of PPARγ agonists and antagonists. Superoxide anion production (measured spectrophotometrically), cytokine release (elisa), PPARγ protein expression (immunoblotting) and NF-κB activation (EMSA assay) were evaluated. KEY RESULTS Monocyte-derived MPs induced, in a concentration-dependent manner, oxygen radical production, cytokine release and NF-κB activation in human monocytes and macrophages, with lower effects than PMA. In both cell types, the PPARγ agonists rosiglitazone and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) inhibited MPs-induced stimulation and this inhibition was reversed by a PPARγ antagonist. In human monocyte/macrophages, MPs as well as rosiglitazone and 15d-PGJ2 induced PPARγ protein expression. CONCLUSION AND IMPLICATIONS In human monocyte/macrophages, monocyte-derived MPs exert an autocrine activation that was modulated by PPARγ ligands, inducing both pro-inflammatory (superoxide anion production, cytokine release and NF-κB activation) and anti-inflammatory (PPARγ expression) effects. PMID:21745193

  6. Characterization of the autocrine/paracrine function of vitamin D in human gingival fibroblasts and periodontal ligament cells.

    Directory of Open Access Journals (Sweden)

    Kaining Liu

    Full Text Available BACKGROUND: We previously demonstrated that 25-hydroxyvitamin D(3, the precursor of 1α,25-dihydroxyvitamin D(3, is abundant around periodontal soft tissues. Here we investigate whether 25-hydroxyvitamin D(3 is converted to 1α,25-dihydroxyvitamin D(3 in periodontal soft tissue cells and explore the possibility of an autocrine/paracrine function of 1α,25-dihydroxyvitamin D(3 in periodontal soft tissue cells. METHODOLOGY/PRINCIPAL FINDINGS: We established primary cultures of human gingival fibroblasts and human periodontal ligament cells from 5 individual donors. We demonstrated that 1α-hydroxylase was expressed in human gingival fibroblasts and periodontal ligament cells, as was cubilin. After incubation with the 1α-hydroxylase substrate 25-hydroxyvitamin D(3, human gingival fibroblasts and periodontal ligament cells generated detectable 1α,25-dihydroxyvitamin D(3 that resulted in an up-regulation of CYP24A1 and RANKL mRNA. A specific knockdown of 1α-hydroxylase in human gingival fibroblasts and periodontal ligament cells using siRNA resulted in a significant reduction in both 1α,25-dihydroxyvitamin D(3 production and mRNA expression of CYP24A1 and RANKL. The classical renal regulators of 1α-hydroxylase (parathyroid hormone, calcium and 1α,25-dihydroxyvitamin D(3 and Porphyromonas gingivalis lipopolysaccharide did not influence 1α-hydroxylase expression significantly, however, interleukin-1β and sodium butyrate strongly induced 1α-hydroxylase expression in human gingival fibroblasts and periodontal ligament cells. CONCLUSIONS/SIGNIFICANCE: In this study, the expression, activity and functionality of 1α-hydroxylase were detected in human gingival fibroblasts and periodontal ligament cells, raising the possibility that vitamin D acts in an autocrine/paracrine manner in these cells.

  7. Effects of Cholecalciferol on Key Components of Vitamin D-Endo/Para/Autocrine System in Experimental Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Anna Mazanova

    2018-01-01

    Full Text Available Objectives. Recent prospective studies have found the associations between type 1 diabetes (T1D and vitamin D deficiency. We investigated the role of vitamin D in the regulation of 25OHD-1α-hydroxylase (CYP27B1 and VDR expression in different tissues of T1D rats. Design. T1D was induced in male Wistar rats by streptozotocin (55 mg/k b.w.. After 2 weeks of T1D, the animals were treated orally with or without vitamin D3 (cholecalciferol; 100 IU/rat, 30 days. Methods. Serum 25-hydroxyvitamin D (25OHD was detected by ELISA. CYP27A1, CYP2R1, CYP27B1, and VDR were assayed by RT-qPCR and Western blotting or visualized by immunofluorescence staining. Results. We demonstrated that T1D led to a decrease in blood 25OHD, which is probably due to the established downregulation of CYP27A1 and CYP2R1 expression. Vitamin D deficiency was accompanied by elevated synthesis of renal CYP27B1 and VDR. Conversely, CYP27B1 and VDR expression decreased in the liver, bone tissue, and bone marrow. Cholecalciferol administration countered the impairments of the vitamin D-endo/para/autocrine system in the kidneys and extrarenal tissues of diabetic rats. Conclusions. T1D-induced vitamin D deficiency is associated with impairments of renal and extrarenal CYP27B1 and VDR expression. Cholecalciferol can be effective in the amelioration of diabetes-associated abnormalities in the vitamin D-endo/para/autocrine system.

  8. Overexpressing the novel autocrine/endocrine adipokine WISP2 induces hyperplasia of the heart, white and brown adipose tissues and prevents insulin resistance

    DEFF Research Database (Denmark)

    Grünberg, John R; Hoffmann, Jenny M; Hedjazifar, Shahram

    2017-01-01

    WISP2 is a novel adipokine, most highly expressed in the adipose tissue and primarily in undifferentiated mesenchymal cells. As a secreted protein, it is an autocrine/paracrine activator of canonical WNT signaling and, as an intracellular protein, it helps to maintain precursor cells undifferenti......WISP2 is a novel adipokine, most highly expressed in the adipose tissue and primarily in undifferentiated mesenchymal cells. As a secreted protein, it is an autocrine/paracrine activator of canonical WNT signaling and, as an intracellular protein, it helps to maintain precursor cells...... WNT ligands, WISP2 expression was inhibited by BMP4 thereby allowing normal induction of adipogenesis. WISP2 is a novel secreted regulator of mesenchymal tissue cellularity....

  9. Interleukin-8 (IL-8) over-production and autocrine cell activation are key factors in monomethylarsonous acid [MMA(III)]-induced malignant transformation of urothelial cells.

    Science.gov (United States)

    Escudero-Lourdes, C; Wu, T; Camarillo, J M; Gandolfi, A J

    2012-01-01

    The association between chronic human exposure to arsenicals and bladder cancer development is well recognized; however, the underlying molecular mechanisms have not been fully determined. We propose that inflammatory responses can play a pathogenic role in arsenic-related bladder carcinogenesis. In previous studies, it was demonstrated that chronic exposure to 50 nM monomethylarsenous acid [MMA(III)] leads to malignant transformation of an immortalized model of urothelial cells (UROtsa), with only 3 mo of exposure necessary to trigger the transformation-related changes. In the three-month window of exposure, the cells over-expressed pro-inflammatory cytokines (IL-1β, IL-6 and IL-8), consistent with the sustained activation of NFKβ and AP1/c-jun, ERK2, and STAT3. IL-8 was over-expressed within hours after exposure to MMA(III), and sustained over-expression was observed during chronic exposure. In this study, we profiled IL-8 expression in UROtsa cells exposed to 50 nM MMA(III) for 1 to 5 mo. IL-8 expression was increased mainly in cells after 3 mo MMA(III) exposure, and its production was also found increased in tumors derived from these cells after heterotransplantation in SCID mice. UROtsa cells do express both receptors, CXCR1 and CXCR2, suggesting that autocrine cell activation could be important in cell transformation. Supporting this observation and consistent with IL-8 over-expression, CXCR1 internalization was significantly increased after three months of exposure to MMA(III). The expression of MMP-9, cyclin D1, bcl-2, and VGEF was significantly increased in cells exposed to MMA(III) for 3 mo, but these mitogen-activated kinases were significantly decreased after IL-8 gene silencing, together with a decrease in cell proliferation rate and in anchorage-independent colony formation. These results suggest a relevant role of IL-8 in MMA(III)-induced UROtsa cell transformation. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Expression of autocrine motility factor mRNA is a poor prognostic factor in high-grade astrocytoma.

    Science.gov (United States)

    Tanizaki, Yoshinori; Sato, Yuichi; Oka, Hidehiro; Utsuki, Satoshi; Kondo, Koji; Miyajima, Yoshiteru; Nagashio, Ryo; Fujii, Kiyotaka

    2006-09-01

    It has been reported that tumor infiltration is correlated with the expression of autocrine motility factor (AMF) and its receptor 78 kDa glycoprotein (gp78). The purpose of the present study was to detect AMF and gp78 mRNA expression levels and their localization in high-grade astrocytomas (glioblastoma and anaplastic astrocytoma) and to determine whether AMF and gp78 are important prognostic factors. A total of 32 formalin-fixed and paraffin-embedded glioblastomas and 23 formalin-fixed and paraffin-embedded anaplastic astrocytomas was used. The expressions of AMF and gp78 mRNA were detected using the highly sensitive in situ hybridization method. The expression of AMF mRNA was detected in 27 of 32 glioblastomas (84.4%) and 11 of 23 anaplastic astrocytomas (47.8%). The positivity of AMF mRNA was significantly higher in glioblastomas than in anaplastic astrocytomas (P = 0.0094), but gp78 mRNA was detected in most cases and no statistical significance was observed. The overall survival of patients with AMF expression was significantly shorter than patients without AMF expression (P = 0.0175). In anaplastic astrocytomas, the overall survival of patients with AMF expression was also significantly shorter than in patients without AMF expression (P = 0.0058). This study demonstrated that AMF is a poor prognostic factor in high-grade astrocytomas.

  11. Activation of Vitamin D Regulates Response of Human Bronchial Epithelial Cells to Aspergillus fumigatus in an Autocrine Fashion

    Directory of Open Access Journals (Sweden)

    Pei Li

    2015-01-01

    Full Text Available Aspergillus fumigatus (A. fumigatus is one of the most common fungi to cause diseases in humans. Recent evidence has demonstrated that airway epithelial cells play an important role in combating A. fumigatus through inflammatory responses. Human airway epithelial cells have been proven to synthesize the active vitamin D, which plays a key role in regulating inflammation. The present study was conducted to investigate the impact of A. fumigatus infection on the activation of vitamin D and the role of vitamin D activation in A. fumigatus-elicited antifungal immunity in normal human airway epithelial cells. We found that A. fumigatus swollen conidia (SC induced the expression of 1α-hydroxylase, the enzyme catalyzing the synthesis of active vitamin D, and vitamin D receptor (VDR in 16HBE cells and led to increased local generation of active vitamin D. Locally activated vitamin D amplified SC-induced expression of antimicrobial peptides in 16HBE cells but attenuated SC-induced production of cytokines in an autocrine fashion. Furthermore, we identified β-glucan, the major A. fumigatus cell wall component, as the causative agent for upregulation of 1α-hydroxylase and VDR in 16HBE cells. Therefore, activation of vitamin D is inducible and provides a bidirectional regulation of the responses to A. fumigatus in 16HBE cells.

  12. An Autocrine Proliferation Repressor Regulates Dictyostelium discoideum Proliferation and Chemorepulsion Using the G Protein-Coupled Receptor GrlH

    Directory of Open Access Journals (Sweden)

    Yu Tang

    2018-02-01

    Full Text Available In eukaryotic microbes, little is known about signals that inhibit the proliferation of the cells that secrete the signal, and little is known about signals (chemorepellents that cause cells to move away from the source of the signal. Autocrine proliferation repressor protein A (AprA is a protein secreted by the eukaryotic microbe Dictyostelium discoideum. AprA is a chemorepellent for and inhibits the proliferation of D. discoideum. We previously found that cells sense AprA using G proteins, suggesting the existence of a G protein-coupled AprA receptor. To identify the AprA receptor, we screened mutants lacking putative G protein-coupled receptors. We found that, compared to the wild-type strain, cells lacking putative receptor GrlH (grlH{macron} cells show rapid proliferation, do not have large numbers of cells moving away from the edges of colonies, are insensitive to AprA-induced proliferation inhibition and chemorepulsion, and have decreased AprA binding. Expression of GrlH in grlH{macron} cells (grlH{macron}/grlHOE rescues the phenotypes described above. These data indicate that AprA signaling may be mediated by GrlH in D. discoideum.

  13. Autocrine IL-10 activation of the STAT3 pathway is required for pathological macrophage differentiation in polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Jacqueline D. Peda

    2016-09-01

    Full Text Available Polycystic kidney disease (PKD is characterized by slow expansion of fluid-filled cysts derived from tubules within the kidney. Cystic expansion results in injury to surrounding parenchyma and leads to inflammation, scarring and ultimately loss of renal function. Macrophages are a key element in this process, promoting cyst epithelial cell proliferation, cyst expansion and disease progression. Previously, we have shown that the microenvironment established by cystic epithelial cells can ‘program’ macrophages, inducing M2-like macrophage polarization that is characterized by expression of markers that include Arg1 and Il10. Here, we functionally characterize these macrophages, demonstrating that their differentiation enhances their ability to promote cyst cell proliferation. This observation indicates a model of reciprocal pathological interactions between cysts and the innate immune system: cyst epithelial cells promote macrophage polarization to a phenotype that, in turn, is especially efficient in promoting cyst cell proliferation and cyst growth. To better understand the genesis of this macrophage phenotype, we examined the role of IL-10, a regulatory cytokine shown to be important for macrophage-stimulated tissue repair in other settings. Herein, we show that the acquisition of the pathological macrophage phenotype requires IL-10 secretion by the macrophages. Further, we demonstrate a requirement for IL-10-dependent autocrine activation of the STAT3 pathway. These data suggest that the IL-10 pathway in macrophages plays an essential role in the pathological relationship between cysts and the innate immune system in PKD, and thus could be a potential therapeutic target.

  14. Thrombin induces epithelial-mesenchymal transition and collagen production by retinal pigment epithelial cells via autocrine PDGF-receptor signaling.

    Science.gov (United States)

    Bastiaans, Jeroen; van Meurs, Jan C; van Holten-Neelen, Conny; Nagtzaam, Nicole M A; van Hagen, P Martin; Chambers, Rachel C; Hooijkaas, Herbert; Dik, Willem A

    2013-12-19

    De-differentiation of RPE cells into mesenchymal cells (epithelial-mesenchymal transition; EMT) and associated collagen production contributes to development of proliferative vitreoretinopathy (PVR). In patients with PVR, intraocular coagulation cascade activation occurs and may play an important initiating role. Therefore, we examined the effect of the coagulation proteins factor Xa and thrombin on EMT and collagen production by RPE cells. Retinal pigment epithelial cells were stimulated with factor Xa or thrombin and the effect on zonula occludens (ZO)-1, α-smooth muscle actin (α-SMA), collagen, and platelet-derived growth factor (PDGF)-B were determined by real-time quantitative-polymerase chain reaction (RQ-PCR), immunofluorescence microscopy, and HPLC and ELISA for collagen and PDGF-BB in culture supernatants, respectively. PDGF-receptor activation was determined by phosphorylation analysis and inhibition studies using the PDGF-receptor tyrosine kinase inhibitor AG1296. Thrombin reduced ZO-1 gene expression (P production of α-SMA and collagen increased. In contrast to thrombin, factor Xa hardly stimulated EMT by RPE. Thrombin clearly induced PDGF-BB production and PDGF-Rβ chain phosphorylation in RPE. Moreover, AG1296 significantly blocked the effect of thrombin on EMT and collagen production. Our findings demonstrate that thrombin is a potent inducer of EMT by RPE via autocrine activation of PDGF-receptor signaling. Coagulation cascade-induced EMT of RPE may thus contribute to the formation of fibrotic retinal membranes in PVR and should be considered as treatment target in PVR.

  15. Mechanism

    Directory of Open Access Journals (Sweden)

    Yao Yu

    2010-01-01

    Full Text Available The kinematics analysis method of a novel 3-DOF wind tunnel mechanism based on cable-driven parallel mechanism is provided. Rodrigues' parameters are applied to express the transformation matrix of the wire-driven mechanism in the paper. The analytical forward kinematics model is described as three quadratic equations using three Rodridgues' parameters based on the fundamental theory of parallel mechanism. Elimination method is used to remove two of the variables, so that an eighth-order polynomial with one variable is derived. From the equation, the eight sets of Rodridgues' parameters and corresponding Euler angles for the forward kinematical problem can be obtained. In the end, numerical example of both forward and inverse kinematics is included to demonstrate the presented forward-kinematics solution method. The numerical results show that the method for the position analysis of this mechanism is effective.

  16. Promotion of human early embryonic development and blastocyst outgrowth in vitro using autocrine/paracrine growth factors.

    Science.gov (United States)

    Kawamura, Kazuhiro; Chen, Yuan; Shu, Yimin; Cheng, Yuan; Qiao, Jie; Behr, Barry; Pera, Renee A Reijo; Hsueh, Aaron J W

    2012-01-01

    Studies using animal models demonstrated the importance of autocrine/paracrine factors secreted by preimplantation embryos and reproductive tracts for embryonic development and implantation. Although in vitro fertilization-embryo transfer (IVF-ET) is an established procedure, there is no evidence that present culture conditions are optimal for human early embryonic development. In this study, key polypeptide ligands known to be important for early embryonic development in animal models were tested for their ability to improve human early embryo development and blastocyst outgrowth in vitro. We confirmed the expression of key ligand/receptor pairs in cleavage embryos derived from discarded human tri-pronuclear zygotes and in human endometrium. Combined treatment with key embryonic growth factors (brain-derived neurotrophic factor, colony-stimulating factor, epidermal growth factor, granulocyte macrophage colony-stimulating factor, insulin-like growth factor-1, glial cell-line derived neurotrophic factor, and artemin) in serum-free media promoted >2.5-fold the development of tri-pronuclear zygotes to blastocysts. For normally fertilized embryos, day 3 surplus embryos cultured individually with the key growth factors showed >3-fold increases in the development of 6-8 cell stage embryos to blastocysts and >7-fold increase in the proportion of high quality blastocysts based on Gardner's criteria. Growth factor treatment also led to a 2-fold promotion of blastocyst outgrowth in vitro when day 7 surplus hatching blastocysts were used. When failed-to-be-fertilized oocytes were used to perform somatic cell nuclear transfer (SCNT) using fibroblasts as donor karyoplasts, inclusion of growth factors increased the progression of reconstructed SCNT embryos to >4-cell stage embryos. Growth factor supplementation of serum-free cultures could promote optimal early embryonic development and implantation in IVF-ET and SCNT procedures. This approach is valuable for infertility

  17. An Autocrine Proliferation Repressor Regulates Dictyostelium discoideum Proliferation and Chemorepulsion Using the G Protein-Coupled Receptor GrlH.

    Science.gov (United States)

    Tang, Yu; Wu, Yuantai; Herlihy, Sarah E; Brito-Aleman, Francisco J; Ting, Jose H; Janetopoulos, Chris; Gomer, Richard H

    2018-02-13

    In eukaryotic microbes, little is known about signals that inhibit the proliferation of the cells that secrete the signal, and little is known about signals (chemorepellents) that cause cells to move away from the source of the signal. Autocrine proliferation repressor protein A (AprA) is a protein secreted by the eukaryotic microbe Dictyostelium discoideum AprA is a chemorepellent for and inhibits the proliferation of D. discoideum We previously found that cells sense AprA using G proteins, suggesting the existence of a G protein-coupled AprA receptor. To identify the AprA receptor, we screened mutants lacking putative G protein-coupled receptors. We found that, compared to the wild-type strain, cells lacking putative receptor GrlH ( grlH¯ cells) show rapid proliferation, do not have large numbers of cells moving away from the edges of colonies, are insensitive to AprA-induced proliferation inhibition and chemorepulsion, and have decreased AprA binding. Expression of GrlH in grlH¯ cells ( grlH¯/grlH OE ) rescues the phenotypes described above. These data indicate that AprA signaling may be mediated by GrlH in D. discoideum IMPORTANCE Little is known about how eukaryotic cells can count themselves and thus regulate the size of a tissue or density of cells. In addition, little is known about how eukaryotic cells can sense a repellant signal and move away from the source of the repellant, for instance, to organize the movement of cells in a developing embryo or to move immune cells out of a tissue. In this study, we found that a eukaryotic microbe uses G protein-coupled receptors to mediate both cell density sensing and chemorepulsion. Copyright © 2018 Tang et al.

  18. The ROCO kinase QkgA is necessary for proliferation inhibition by autocrine signals in Dictyostelium discoideum.

    Science.gov (United States)

    Phillips, Jonathan E; Gomer, Richard H

    2010-10-01

    AprA and CfaD are secreted proteins that function as autocrine signals to inhibit cell proliferation in Dictyostelium discoideum. Cells lacking AprA or CfaD proliferate rapidly, and adding AprA or CfaD to cells slows proliferation. Cells lacking the ROCO kinase QkgA proliferate rapidly, with a doubling time 83% of that of the wild type, and overexpression of a QkgA-green fluorescent protein (GFP) fusion protein slows cell proliferation. We found that qkgA(-) cells accumulate normal levels of extracellular AprA and CfaD. Exogenous AprA or CfaD does not slow the proliferation of cells lacking qkgA, and expression of QkgA-GFP in qkgA(-) cells rescues this insensitivity. Like cells lacking AprA or CfaD, cells lacking QkgA tend to be multinucleate, accumulate nuclei rapidly, and show a mass and protein accumulation per nucleus like those of the wild type, suggesting that QkgA negatively regulates proliferation but not growth. Despite their rapid proliferation, cells lacking AprA, CfaD, or QkgA expand as a colony on bacteria less rapidly than the wild type. Unlike AprA and CfaD, QkgA does not affect spore viability following multicellular development. Together, these results indicate that QkgA is necessary for proliferation inhibition by AprA and CfaD, that QkgA mediates some but not all of the effects of AprA and CfaD, and that QkgA may function downstream of these proteins in a signal transduction pathway regulating proliferation.

  19. Hypertonic stress induces VEGF production in human colon cancer cell line Caco-2: inhibitory role of autocrine PGE₂.

    Directory of Open Access Journals (Sweden)

    Luciana B Gentile

    Full Text Available Vascular Endothelial Growth Factor (VEGF is a major regulator of angiogenesis. VEGF expression is up regulated in response to micro-environmental cues related to poor blood supply such as hypoxia. However, regulation of VEGF expression in cancer cells is not limited to the stress response due to increased volume of the tumor mass. Lipid mediators in particular arachidonic acid-derived prostaglandin (PGE₂ are regulators of VEGF expression and angiogenesis in colon cancer. In addition, increased osmolarity that is generated during colonic water absorption and feces consolidation seems to activate colon cancer cells and promote PGE₂ generation. Such physiological stimulation may provide signaling for cancer promotion. Here we investigated the effect of exposure to a hypertonic medium, to emulate colonic environment, on VEGF production by colon cancer cells. The role of concomitant PGE₂ generation and MAPK activation was addressed by specific pharmacological inhibition. Human colon cancer cell line Caco-2 exposed to a hypertonic environment responded with marked VEGF and PGE₂ production. VEGF production was inhibited by selective inhibitors of ERK 1/2 and p38 MAPK pathways. To address the regulatory role of PGE₂ on VEGF production, Caco-2 cells were treated with cPLA₂ (ATK and COX-2 (NS-398 inhibitors, that completely block PGE₂ generation. The Caco-2 cells were also treated with a non selective PGE₂ receptor antagonist. Each treatment significantly increased the hypertonic stress-induced VEGF production. Moreover, addition of PGE₂ or selective EP₂ receptor agonist to activated Caco-2 cells inhibited VEGF production. The autocrine inhibitory role for PGE₂ appears to be selective to hypertonic environment since VEGF production induced by exposure to CoCl₂ was decreased by inhibition of concomitant PGE₂ generation. Our results indicated that hypertonicity stimulates VEGF production in colon cancer cell lines. Also PGE

  20. Autocrine proliferative effects of hGH are maintained in primary cultures of human mammary carcinoma cells.

    Science.gov (United States)

    Chiesa, Jean; Ferrer, Catherine; Arnould, Cécile; Vouyovitch, Cécile M; Diaz, Jean-Jacques; Gonzalez, Samia; Mares, Pierre; Morel, Gérard; Wu, Zheng-Sheng; Zhu, Tao; Lobie, Peter E; Mertani, Hichem C

    2011-09-01

    Empirical evidence suggests that autocrine human GH (hGH) may possess a proliferative and oncogenic role in human mammary carcinoma. However, this concept is largely derived from studies using cultured human mammary carcinoma cell (HMCC) lines. We investigated the expression and functionality of hGH and the hGH receptor in isolated cultures of primary HMCC. Epithelial cell adhesion molecule-positive primary HMCC were isolated from surgical biopsies of patients with mammary carcinoma and cultured in vitro. Expression of hGH and hGH receptor was determined by RT-PCR, immunofluorescence microscopy, and ELISA. The proliferative response of the cultured primary HMCC to hGH stimulation or hGH inhibition with a hGH antagonist was determined. One hundred percent of cultured primary HMCC expressed the hGH receptor, and 52% expressed hGH at the mRNA level. hGH-positive primary HMCC produced hGH protein within the cell and secreted hGH to the media. Both hGH-negative and hGH-positive HMCC responded to hGH stimulation with large increases in cell number. hGH-positive HMCC responded to inhibition of hGH by a hGH antagonist with a decrease in cell number, whereas hGH-negative HMCC did not. Primary HMCC proliferate in response to hGH, and the proliferation of hGH-positive HMCC is inhibited by hGH antagonism. Inhibition of hGH in patients with mammary carcinoma may therefore limit tumor growth.

  1. Mechanics

    CERN Document Server

    Hartog, J P Den

    1961-01-01

    First published over 40 years ago, this work has achieved the status of a classic among introductory texts on mechanics. Den Hartog is known for his lively, discursive and often witty presentations of all the fundamental material of both statics and dynamics (and considerable more advanced material) in new, original ways that provide students with insights into mechanical relationships that other books do not always succeed in conveying. On the other hand, the work is so replete with engineering applications and actual design problems that it is as valuable as a reference to the practicing e

  2. Mutant p53 regulates ovarian cancer transformed phenotypes through autocrine matrix deposition.

    Science.gov (United States)

    Iwanicki, Marcin P; Chen, Hsing-Yu; Iavarone, Claudia; Zervantonakis, Ioannis K; Muranen, Taru; Novak, Marián; Ince, Tan A; Drapkin, Ronny; Brugge, Joan S

    2016-07-07

    High-grade serous ovarian carcinoma (HGS-OvCa) harbors p53 mutations and can originate from the epithelial cell compartment of the fallopian tube fimbriae. From this site, neoplastic cells detach, survive in the peritoneal cavity, and form cellular clusters that intercalate into the mesothelium to form ovarian and peritoneal masses. To examine the contribution of mutant p53 to phenotypic alterations associated with HGS-OvCA, we developed live-cell microscopy assays that recapitulate these early events in cultured fallopian tube nonciliated epithelial (FNE) cells. Expression of stabilizing mutant variants of p53, but not depletion of endogenous wild-type p53, in FNE cells promoted survival and cell-cell aggregation under conditions of cell detachment, leading to the formation of cell clusters with mesothelium-intercalation capacity. Mutant p53 R175H -induced phenotypes were dependent on fibronectin production, α5β1 fibronectin receptor engagement, and TWIST1 expression. These results indicate that FNE cells expressing stabilizing p53 mutants acquire anchorage independence and subsequent mesothelial intercalation capacity through a mechanism involving mesenchymal transition and matrix production. These findings provide important new insights into activities of mutant p53 in the cells of origin of HGS-OvCa.

  3. Inhibition of the autocrine IL-6–JAK2–STAT3–calprotectin axis as targeted therapy for HR−/HER2+ breast cancers

    OpenAIRE

    Rodriguez-Barrueco, Ruth; Yu, Jiyang; Saucedo-Cuevas, Laura P.; Olivan, Mireia; Llobet-Navas, David; Putcha, Preeti; Castro, Veronica; Murga-Penas, Eva M.; Collazo-Lorduy, Ana; Castillo-Martin, Mireia; Alvarez, Mariano; Cordon-Cardo, Carlos; Kalinsky, Kevin; Maurer, Matthew; Califano, Andrea

    2015-01-01

    Rodriguez-Barrueco et al. found that HR−/HER2+ cells secrete high levels of IL-6, inducing the activation of STAT3, which in turn promotes a second autocrine stimulus to increase S100A8/9 complex (calprotectin) production and secretion. Inhibition of the IL-6–JAK2–STAT3–calprotectin axis with FDA-approved drugs, alone and in combination with HER2 inhibitors, reduced the tumorigenicity of HR−/HER2+ breast cancers.

  4. Mechanics

    CERN Document Server

    Chester, W

    1979-01-01

    When I began to write this book, I originally had in mind the needs of university students in their first year. May aim was to keep the mathematics simple. No advanced techniques are used and there are no complicated applications. The emphasis is on an understanding of the basic ideas and problems which require expertise but do not contribute to this understanding are not discussed. How­ ever, the presentation is more sophisticated than might be considered appropri­ ate for someone with no previous knowledge of the subject so that, although it is developed from the beginning, some previous acquaintance with the elements of the subject would be an advantage. In addition, some familiarity with element­ ary calculus is assumed but not with the elementary theory of differential equations, although knowledge of the latter would again be an advantage. It is my opinion that mechanics is best introduced through the motion of a particle, with rigid body problems left until the subject is more fully developed. Howev...

  5. Regulation of Prostate Development and Benign Prostatic Hyperplasia by Autocrine Cholinergic Signaling via Maintaining the Epithelial Progenitor Cells in Proliferating Status

    Directory of Open Access Journals (Sweden)

    Naitao Wang

    2016-05-01

    Full Text Available Regulation of prostate epithelial progenitor cells is important in prostate development and prostate diseases. Our previous study demonstrated a function of autocrine cholinergic signaling (ACS in promoting prostate cancer growth and castration resistance. However, whether or not such ACS also plays a role in prostate development is unknown. Here, we report that ACS promoted the proliferation and inhibited the differentiation of prostate epithelial progenitor cells in organotypic cultures. These results were confirmed by ex vivo lineage tracing assays and in vivo renal capsule recombination assays. Moreover, we found that M3 cholinergic receptor (CHRM3 was upregulated in a large subset of benign prostatic hyperplasia (BPH tissues compared with normal tissues. Activation of CHRM3 also promoted the proliferation of BPH cells. Together, our findings identify a role of ACS in maintaining prostate epithelial progenitor cells in the proliferating state, and blockade of ACS may have clinical implications for the management of BPH.

  6. Cervical Cancer HeLa Cell Autocrine Apoptosis Induced by Co-immobilized TNF-α plus IFN-γ Biomaterials.

    Science.gov (United States)

    Li, Jian; Zhang, Yuxiao; Chen, Liyi; Lu, Xinhua; Li, Zhibin; Xue, Yongyong; Guan, Yan-Qing

    2018-02-13

    Based on our earlier work with co-immobilized TNF-α plus IFN-γ induction of HeLa cell death, we used FRET and XRD techniques to examine the differences in the structure of co-immobilized TNF-α plus IFN-γ and free TNF-α plus IFN-γ. The expressions of both TNF-α and IFN-α increased significantly, as determined by gene microarray analysis, however, in the presence of TNF-α plus IFN-α inhibitors, TNF-α and IFN-α did not increase in HeLa cells induced by co-immobilized TNF-γ plus IFN-α. This suggests that the TNF-α and IFN-α are the results of autocrine signaling in HeLa cells, and that cell death is caused by these substances. The mortality was then measured by flow cytometry and the results demonstrate that co-immobilized TNF-α plus IFN-γ induced death is a type of autocrine-induced apoptosis in HeLa cells. In addition, we performed Elisa, RT-PCR, flow cytometry, and western blot analyses, as well as a series of analytical tests at the animal level. We demonstrated that at both the cellular and animal levels, HeLa cells induced by co-immobilized IFN-γ plus TNF-α secrete much more IFN-α and TNF-α, than these two cytokines could exert on HeLa cells alone, and that this leads to cancer cell death.

  7. The first trimester human trophoblast cell line ACH-3P: a novel tool to study autocrine/paracrine regulatory loops of human trophoblast subpopulations--TNF-alpha stimulates MMP15 expression.

    Science.gov (United States)

    Hiden, Ursula; Wadsack, Christian; Prutsch, Nicole; Gauster, Martin; Weiss, Ursula; Frank, Hans-Georg; Schmitz, Ulrike; Fast-Hirsch, Christa; Hengstschläger, Markus; Pötgens, Andy; Rüben, Angela; Knöfler, Martin; Haslinger, Peter; Huppertz, Berthold; Bilban, Martin; Kaufmann, Peter; Desoye, Gernot

    2007-12-19

    The trophoblast compartment of the placenta comprises various subpopulations with distinct functions. They interact among each other by secreted signals thus forming autocrine or paracrine regulatory loops. We established a first trimester trophoblast cell line (ACH-3P) by fusion of primary human first trimester trophoblasts (week 12 of gestation) with a human choriocarcinoma cell line (AC1-1). Expression of trophoblast markers (cytokeratin-7, integrins, matrix metalloproteinases), invasion abilities and transcriptome of ACH-3P closely resembled primary trophoblasts. Morphology, cytogenetics and doubling time was similar to the parental AC1-1 cells. The different subpopulations of trophoblasts e.g., villous and extravillous trophoblasts also exist in ACH-3P cells and can be immuno-separated by HLA-G surface expression. HLA-G positive ACH-3P display pseudopodia and a stronger expression of extravillous trophoblast markers. Higher expression of insulin-like growth factor II receptor and human chorionic gonadotropin represents the basis for the known autocrine stimulation of extravillous trophoblasts. We conclude that ACH-3P represent a tool to investigate interaction of syngeneic trophoblast subpopulations. These cells are particularly suited for studies into autocrine and paracrine regulation of various aspects of trophoblast function. As an example a novel effect of TNF-alpha on matrix metalloproteinase 15 in HLA-G positive ACH-3P and explants was found.

  8. Recently activated naive CD4 T cells can help resting B cells, and can produce sufficient autocrine IL-4 to drive differentiation to secretion of T helper 2-type cytokines.

    Science.gov (United States)

    Croft, M; Swain, S L

    1995-05-01

    and provide cognate help to B cells. They also suggest that if activated naive CD4 cells receive multiple stimulations from Ag/APC, enough endogenous IL-4 can be produced to drive differentiation into effectors secreting type 2 cytokines. The existence of such an autocrine feedback mechanism suggests that the amount and availability of Ag could influence the nature and polarization of the Th response.

  9. Melanoma cell-derived exosomes promote epithelial-mesenchymal transition in primary melanocytes through paracrine/autocrine signaling in the tumor microenvironment

    Science.gov (United States)

    Xiao, Deyi; Barry, Samantha; Kmetz, Daniel; Egger, Michael; Pan, Jianmin; Rai, Shesh N; Qu, Jifu; McMasters, Kelly M.; Hao, Hongying

    2016-01-01

    The tumor microenvironment is abundant with exosomes that are secreted by the cancer cells themselves. Exosomes are nanosized, organelle-like membranous structures that are increasingly being recognized as major contributors in the progression of malignant neoplasms. A critical element in melanoma progression is its propensity to metastasize, but little is known about how melanoma cell-derived exosomes modulate the microenvironment to optimize conditions for tumor progression and metastasis. Here, we provide evidence that melanoma cell-derived exosomes promote phenotype switching in primary melanocytes through paracrine/autocrine signaling. We found that the mitogen-activated protein kinase (MAPK) signaling pathway was activated during the exosome-mediated epithelial-to-mesenchymal transition (EMT)-resembling process, which promotes metastasis. Let-7i, an miRNA modulator of EMT, was also involved in this process. We further defined two other miRNA modulators of EMT (miR-191 and let-7a) in serum exosomes for differentiating stage I melanoma patients from non-melanoma subjects. These results provide the first strong molecular evidence that melanoma cell-derived exosomes promote the EMT-resembling process in the tumor microenvironment. Thus, novel strategies targeting EMT and modulating the tumor microenvironment may emerge as important approaches for the treatment of metastatic melanoma. PMID:27063098

  10. Autocrine growth induced by the insulin-related factor in the insulin-independent teratoma cell line 1246-3A

    International Nuclear Information System (INIS)

    Yamada, Yukio; Serrero, G.

    1988-01-01

    An insulin-independent teratoma-derived cell line, called 1246-3A, has been isolated from the adipogenic cell line 1246, which stringently requires insulin for proliferation. The 1246-3A cell line, which can proliferate in the absence of exogenous insulin, produces in its conditioned medium a growth factor similar to pancreatic insulin by its biological and immunological properties. This factor, called insulin-related factor (IRF), was purified and iodinated to study its binding to cell surface receptors. 125 I-labeled IRF binding to intact 1246-3A cells is lower than to 1246 cells. Cell surface binding can be restored by culturing the 1246-3A cells in the presence of an anti-porcine insulin monoclonal antibody of by acid prewash of the cells prior to performing the binding. Scatchard analysis of binding indicates that IRF secreted by the 1246-3A cells partially occupies high-affinity binding sites on the producer cells. Moreover, insulin monoclonal antibody inhibits the proliferation of the IRF-producing 1246-3A cells, suggesting that these cells are dependent on the secreted IRF for growth in culture. The authors conclude that the insulin-related factor secreted by the insulin-independent 1246-3A cells stimulates their proliferation in an autocrine fashion

  11. Human Umbilical Cord Perivascular Cells Exhibited Enhanced Migration Capacity towards Hepatocellular Carcinoma in Comparison with Bone Marrow Mesenchymal Stromal Cells: A Role for Autocrine Motility Factor Receptor

    Directory of Open Access Journals (Sweden)

    Juan Bayo

    2014-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the third cause of cancer-related death worldwide. Unfortunately, the incidence and mortality associated with HCC are increasing. Therefore, new therapeutic strategies are urgently needed and the use of mesenchymal stromal cells (MSCs as carrier of therapeutic genes is emerging as a promising option. Different sources of MSCs are being studied for cell therapy and bone marrow-derived cells are the most extensively explored; however, birth associated-tissues represent a very promising source. The aim of this work was to compare the in vitro and in vivo migration capacity between bone marrow MSCs (BM-MSCs and human umbilical cord perivascular cells (HUCPVCs towards HCC. We observed that HUCPVCs presented higher in vitro and in vivo migration towards factors released by HCC. The expression of autocrine motility factor (AMF receptor, genes related with the availability of the receptor on the cell surface (caveolin-1 and -2 and metalloproteinase 3, induced by the receptor activation and important for cell migration, was increased in HUCPVCs. The chemotactic response towards recombinant AMF was increased in HUCPVCs compared to BM-MSCs, and its inhibition in the conditioned medium from HCC induced higher decrease in HUCPVC migration than in BM-MSC. Our results indicate that HUCPVCs could be a useful cellular source to deliver therapeutic genes to HCC.

  12. Expression of autocrine prolactin and the short isoform of prolactin receptor are associated with inflammatory response and apoptosis in monocytes stimulated with Mycobacterium bovis proteins.

    Science.gov (United States)

    López-Rincón, Gonzalo; Mancilla, Raúl; Pereira-Suárez, Ana L; Martínez-Neri, Priscila A; Ochoa-Zarzosa, Alejandra; Muñoz-Valle, José Francisco; Estrada-Chávez, Ciro

    2015-06-01

    Increased levels of prolactin (PRL) have recently been associated with carcinogenesis and the exacerbation of autoimmune diseases, and might be involved in the progression of tuberculosis (TB). To investigate the relationship between PRL and prolactin receptor (PRLr) expression with inflammatory response and apoptosis in monocytes, we used THP-1 cells stimulated with antigens of the Mycobacterium bovis AN5 strain culture filtrate protein (CFP-M. bovis). Western blot (WB), real-time Polymerase chain reaction (PCR), and immunocytochemistry were performed to identify both PRL and PRLr molecules. PRL bioactivity and proinflammatory cytokine detection were assessed. The results showed that PRL and PRLr messenger RNA (mRNA) were synthesized in THP-1 monocytes induced with CFP-M. bovis at peaks of 176- and 404-fold, respectively. PRL forms of 60 and 80kDa and PRLr isoforms of 40, 50, and 65kDa were also identified as time-dependent, while 60-kDa PRL, as well as 40-, and 50-kDa PRLr, were found as soluble forms in culture media and later in the nucleus of THP-1 monocytes. PRL of 60kDa released by monocytes exhibited bioactivity in Nb2 cells, and both synthesized PRL and synthesized PRLr were related with nitrite and proinflammatory cytokine levels proapoptotic activity in CFP-M. bovis-induced monocytes. Our results suggest the overexpression of a full-autocrine loop of PRL and PRLr in monocytes that enhances the inflammatory response and apoptosis after priming with M. bovis antigens. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. FGF7 supports hematopoietic stem and progenitor cells and niche-dependent myeloblastoma cells via autocrine action on bone marrow stromal cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ishino, Ruri; Minami, Kaori; Tanaka, Satowa [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Nagai, Mami [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 159-8555 (Japan); Matsui, Keiji; Hasegawa, Natsumi [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Roeder, Robert G. [Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (United States); Asano, Shigetaka [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 159-8555 (Japan); Ito, Mitsuhiro, E-mail: itomi@med.kobe-u.ac.jp [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (United States); Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 159-8555 (Japan); Department of Family and Community Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 654-0142 (Japan)

    2013-10-11

    Highlights: •FGF7 is downregulated in MED1-deficient mesenchymal cells. •FGF7 produced by mesenchymal stromal cells is a novel hematopoietic niche molecule. •FGF7 supports hematopoietic progenitor cells and niche-dependent leukemia cells. •FGF7 activates FGFR2IIIb of bone marrow stromal cells in an autocrine manner. •FGF7 indirectly acts on hematopoietic cells lacking FGFR2IIIb via stromal cells. -- Abstract: FGF1 and FGF2 support hematopoietic stem and progenitor cells (HSPCs) under stress conditions. In this study, we show that fibroblast growth factor (FGF7) may be a novel niche factor for HSPC support and leukemic growth. FGF7 expression was attenuated in mouse embryonic fibroblasts (MEFs) deficient for the MED1 subunit of the Mediator transcriptional coregulator complex. When normal mouse bone marrow (BM) cells were cocultured with Med1{sup +/+} MEFs or BM stromal cells in the presence of anti-FGF7 antibody, the growth of BM cells and the number of long-time culture-initiating cells (LTC-ICs) decreased significantly. Anti-FGF7 antibody also attenuated the proliferation and cobblestone formation of MB1 stromal cell-dependent myeloblastoma cells. The addition of recombinant FGF7 to the coculture of BM cells and Med1{sup −/−} MEFs increased BM cells and LTC-ICs. FGF7 and its cognate receptor, FGFR2IIIb, were undetectable in BM cells, but MEFs and BM stromal cells expressed both. FGF7 activated downstream targets of FGFR2IIIb in Med1{sup +/+} and Med1{sup −/−} MEFs and BM stromal cells. Taken together, we propose that FGF7 supports HSPCs and leukemia-initiating cells indirectly via FGFR2IIIb expressed on stromal cells.

  14. Autocrine/paracrine prostaglandin E2 production by non-small cell lung cancer cells regulates matrix metalloproteinase-2 and CD44 in cyclooxygenase-2-dependent invasion.

    Science.gov (United States)

    Dohadwala, Mariam; Batra, Raj K; Luo, Jie; Lin, Ying; Krysan, Kostyantyn; Pold, Mehis; Sharma, Sherven; Dubinett, Steven M

    2002-12-27

    Tumor cyclooxygenase-2 (COX-2) expression is known to be associated with enhanced tumor invasiveness. In the present study, we evaluated the importance of the COX-2 product prostaglandin E2 (PGE2) and its signaling through the EP4 receptor in mediating non-small cell lung cancer (NSCLC) invasiveness. Genetic inhibition of tumor COX-2 led to diminished matrix metalloproteinase (MMP)-2, CD44, and EP4 receptor expression and invasion. Treatment of NSCLC cells with exogenous 16,16-dimethylprostaglandin E2 significantly increased EP4 receptor, CD44, and MMP-2 expression and matrigel invasion. In contrast, anti-PGE2 decreased EP4 receptor, CD44, and MMP-2 expression in NSCLC cells. EP4 receptor signaling was found to be central to this process, because antisense oligonucleotide-mediated inhibition of tumor cell EP4 receptors significantly decreased CD44 expression. In addition, agents that increased intracellular cAMP, as is typical of EP4 receptor signaling, markedly increased CD44 expression. Moreover, MMP-2-AS treatment decreased PGE2-mediated CD44 expression, and CD44-AS treatment decreased MMP-2 expression. Thus, PGE2-mediated effects through EP4 required the parallel induction of both CD44 and MMP-2 expression because genetic inhibition of either MMP-2 or CD44 expression effectively blocked PGE2-mediated invasion in NSCLC. These findings indicate that PGE2 regulates COX-2-dependent, CD44- and MMP-2-mediated invasion in NSCLC in an autocrine/paracrine manner via EP receptor signaling. Thus, blocking PGE2 production or activity by genetic or pharmacological interventions may prove to be beneficial in chemoprevention or treatment of NSCLC.

  15. Intrinsic bevacizumab resistance is associated with prolonged activation of autocrine VEGF signaling and hypoxia tolerance in colorectal cancer cells and can be overcome by nintedanib, a small molecule angiokinase inhibitor

    Science.gov (United States)

    Mésange, Paul; Poindessous, Virginie; Sabbah, Michèle; Escargueil, Alexandre E.; de Gramont, Aimery; Larsen, Annette K.

    2014-01-01

    Colorectal cancer (CRC) is a common tumor type with a high mortality rate, in part due to intrinsic drug resistance. Although bevacizumab, a VEGF-directed neutralizing antibody, is particularly active in this pathology, some patients never respond for reasons not well understood. We here wish to clarify the role of autocrine VEGF signaling in the response of CRC cells to angiogenesis inhibition. Our results show that CRC cells with intrinsic bevacizumab-resistance displayed pronounced upregulation of autocrine HIF-VEGF-VEGFR signaling in response to prolonged bevacizumab exposure whereas the same signaling pathway was downregulated in bevacizumab-sensitive xenografts. Importantly, both bevacizumab-sensitive and -resistant CRC xenografts were sensitive to nintedanib, a small molecule angiokinase inhibitor, which was associated with inhibition of mTORC1. In vitro studies revealed that bevacizumab-resistant cells displayed intrinsically higher HIF-VEGF signaling intensity and hypoxia tolerance compared to their bevacizumab-sensitive counterparts. Interestingly, although nintedanib showed comparable activity toward bevacizumab-sensitive cells under normoxia and hypoxia, the drug was three-fold more toxic to the resistant cells under hypoxia, suggesting that nintedanib attenuated the survival signaling that usually protects these cells from hypoxia-mediated cell death. In conclusion, our findings support a role for autocrine VEGF signaling in the survival of CRC cells to hypoxia and thus to angiogenesis inhibition. We further show that nintedanib, a small molecule angiokinase inhibitor, is active toward CRC models with intrinsic bevacizumab resistance supporting clinical trials of nintedanib in patients that do not respond to bevacizumab, alone or in combination with bevacizumab to increase angiogenesis inhibition. PMID:25015210

  16. Pluripotency gene expression and growth control in cultures of peripheral blood monocytes during their conversion into programmable cells of monocytic origin (PCMO: evidence for a regulatory role of autocrine activin and TGF-β.

    Directory of Open Access Journals (Sweden)

    Hendrik Ungefroren

    Full Text Available Previous studies have shown that peripheral blood monocytes can be converted in vitro to a stem cell-like cell termed PCMO as evidenced by the re-expression of pluripotency-associated genes, transient proliferation, and the ability to adopt the phenotype of hepatocytes and insulin-producing cells upon tissue-specific differentiation. However, the regulatory interactions between cultured cells governing pluripotency and mitotic activity have remained elusive. Here we asked whether activin(s and TGF-β(s, are involved in PCMO generation. De novo proliferation of PCMO was higher under adherent vs. suspended culture conditions as revealed by the appearance of a subset of Ki67-positive monocytes and correlated with down-regulation of p21WAF1 beyond day 2 of culture. Realtime-PCR analysis showed that PCMO express ActRIIA, ALK4, TβRII, ALK5 as well as TGF-β1 and the βA subunit of activin. Interestingly, expression of ActRIIA and ALK4, and activin A levels in the culture supernatants increased until day 4 of culture, while levels of total and active TGF-β1 strongly declined. PCMO responded to both growth factors in an autocrine fashion with intracellular signaling as evidenced by a rise in the levels of phospho-Smad2 and a drop in those of phospho-Smad3. Stimulation of PCMO with recombinant activins (A, B, AB and TGF-β1 induced phosphorylation of Smad2 but not Smad3. Inhibition of autocrine activin signaling by either SB431542 or follistatin reduced both Smad2 activation and Oct4A/Nanog upregulation. Inhibition of autocrine TGF-β signaling by either SB431542 or anti-TGF-β antibody reduced Smad3 activation and strongly increased the number of Ki67-positive cells. Furthermore, anti-TGF-β antibody moderately enhanced Oct4A/Nanog expression. Our data show that during PCMO generation pluripotency marker expression is controlled positively by activin/Smad2 and negatively by TGF-β/Smad3 signaling, while relief from growth inhibition is primarily the

  17. Solving the cardiac hypertrophy riddle: The angiotensin II-mechanical stress connection.

    Science.gov (United States)

    Zablocki, Daniela; Sadoshima, Junichi

    2013-11-08

    A series of studies conducted 20 years ago, documenting the cardiac hypertrophy phenotype and its underlying signaling mechanism induced by angiotensin II (Ang II) and mechanical stress, showed a remarkable similarity between the effect of the Gαq agonist and that of mechanical forces on cardiac hypertrophy. Subsequent studies confirmed the involvement of autocrine/paracrine mechanisms, including stretch-induced release of Ang II in load-induced cardiac hypertrophy. Recent studies showed that the Ang II type 1 (AT1) receptor is also directly activated by mechanical forces, suggesting that AT1 receptors play an important role in mediating load-induced cardiac hypertrophy through both ligand- and mechanical stress-dependent mechanisms.

  18. Human Scalp Hair Follicles Are Both a Target and a Source of Prolactin, which Serves as an Autocrine and/or Paracrine Promoter of Apoptosis-Driven Hair Follicle Regression

    Science.gov (United States)

    Foitzik, Kerstin; Krause, Karoline; Conrad, Franziska; Nakamura, Motonobu; Funk, Wolfang; Paus, Ralf

    2006-01-01

    The prototypic pituitary hormone prolactin (PRL) exerts a wide variety of bioregulatory effects in mammals and is also found in extrapituitary sites, including murine skin. Here, we show by reverse transcriptase-polymerase chain reaction and immunohistology that, contrary to a previous report, human skin and normal human scalp hair follicles (HFs), in particular, express both PRL and PRL receptors (PRL-R) at the mRNA and protein level. PRL and PRL-R immunoreactivity can be detected in the epithelium of human anagen VI HFs, while the HF mesenchyme is negative. During the HF transformation from growth (anagen) to apoptosis-driven regression (catagen), PRL and PRL-R immunoreactivity appear up-regulated. Treatment of organ-cultured human scalp HFs with high-dose PRL (400 ng/ml) results in a significant inhibition of hair shaft elongation and premature catagen development, along with reduced proliferation and increased apoptosis of hair bulb keratinocytes (Ki-67/terminal dUTP nick-end labeling immunohistomorphometry). This shows that PRL receptors, expressed in HFs, are functional and that human skin and human scalp HFs are both direct targets and sources of PRL. Our data suggest that PRL acts as an autocrine hair growth modulator with catagen-promoting functions and that the hair growth-inhibitory effects of PRL demonstrated here may underlie the as yet ill-understood hair loss in patients with hyperprolactinemia. PMID:16507890

  19. Human scalp hair follicles are both a target and a source of prolactin, which serves as an autocrine and/or paracrine promoter of apoptosis-driven hair follicle regression.

    Science.gov (United States)

    Foitzik, Kerstin; Krause, Karoline; Conrad, Franziska; Nakamura, Motonobu; Funk, Wolfang; Paus, Ralf

    2006-03-01

    The prototypic pituitary hormone prolactin (PRL) exerts a wide variety of bioregulatory effects in mammals and is also found in extrapituitary sites, including murine skin. Here, we show by reverse transcriptase-polymerase chain reaction and immunohistology that, contrary to a previous report, human skin and normal human scalp hair follicles (HFs), in particular, express both PRL and PRL receptors (PRL-R) at the mRNA and protein level. PRL and PRL-R immunoreactivity can be detected in the epithelium of human anagen VI HFs, while the HF mesenchyme is negative. During the HF transformation from growth (anagen) to apoptosis-driven regression (catagen), PRL and PRL-R immunoreactivity appear up-regulated. Treatment of organ-cultured human scalp HFs with high-dose PRL (400 ng/ml) results in a significant inhibition of hair shaft elongation and premature catagen development, along with reduced proliferation and increased apoptosis of hair bulb keratinocytes (Ki-67/terminal dUTP nick-end labeling immunohistomorphometry). This shows that PRL receptors, expressed in HFs, are functional and that human skin and human scalp HFs are both direct targets and sources of PRL. Our data suggest that PRL acts as an autocrine hair growth modulator with catagen-promoting functions and that the hair growth-inhibitory effects of PRL demonstrated here may underlie the as yet ill-understood hair loss in patients with hyper-prolactinemia.

  20. The predominant mechanism of intercellular calcium wave propagation changes during long-term culture of human osteoblast-like cells

    DEFF Research Database (Denmark)

    Henriksen, Zanne; Hiken, Jeffrey F; Steinberg, Thomas H

    2006-01-01

    Intercellular calcium waves (ICW) are calcium transients that spread from cell to cell in response to different stimuli. We previously demonstrated that human osteoblast-like cells in culture propagate ICW in response to mechanical stimulation by two mechanisms. One mechanism involves autocrine...... activation of P2Y receptors, and the other requires gap junctional communication. In the current work we ask whether long-term culture of osteoblast-like cells affects the propagation of ICW by these two mechanisms. Human osteoblast-like cells were isolated from bone marrow. Mechanically induced ICW were...... assessed by video imaging of Fura-2 loaded cells after 1, 2 and 4 months culture. The P2Y2 receptor and the gap junction protein Cx43 were assessed by Western blot and real-time PCR. In resting conditions, P2Y mediated ICW prevailed and spread rapidly to about 13 cells. P2Y receptor desensitization by ATP...

  1. The Vasopressin Type-2 Receptor and Prostaglandin Receptors EP2 and EP4 can Increase Aquaporin-2 Plasma Membrane Targeting Through a cAMP Independent Pathway

    DEFF Research Database (Denmark)

    Olesen, Emma Tina Bisgaard; Moeller, Hanne Bjerregaard; Assentoft, Mette

    2016-01-01

    Apical membrane targeting of the collecting duct water channel aquaporin-2 (AQP2) is essential for body water balance. As this event is regulated by Gs coupled 7-transmembrane receptors such as the vasopressin type 2 receptor (V2R) and the prostanoid receptors EP2 and EP4, it is believed to be c...

  2. Autocrine Acetylcholine, Induced by IL-17A via NFκB and ERK1/2 Pathway Activation, Promotes MUC5AC and IL-8 Synthesis in Bronchial Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Angela Marina Montalbano

    2016-01-01

    Full Text Available IL-17A is overexpressed in the lung during acute neutrophilic inflammation. Acetylcholine (ACh increases IL-8 and Muc5AC production in airway epithelial cells. We aimed to characterize the involvement of nonneuronal components of cholinergic system on IL-8 and Muc5AC production in bronchial epithelial cells stimulated with IL-17A. Bronchial epithelial cells were stimulated with recombinant human IL-17A (rhIL-17A to evaluate the ChAT expression, the ACh binding and production, the IL-8 release, and the Muc5AC production. Furthermore, the effectiveness of PD098,059 (inhibitor of MAPKK activation, Bay11-7082 (inhibitor of IkBα phosphorylation, Hemicholinium-3 (HCh-3 (choline uptake blocker, and Tiotropium bromide (Spiriva® (anticholinergic drug was tested in our in vitro model. We showed that rhIL-17A increased the expression of ChAT, the levels of ACh binding and production, and the IL-8 and Muc5AC production in stimulated bronchial epithelial cells compared with untreated cells. The pretreatment of the cells with PD098,059 and Bay11-7082 decreased the ChAT expression and the ACh production/binding, while HCh-3 and Tiotropium decreased the IL-8 and Muc5AC synthesis in bronchial epithelial cells stimulated with rhIL-17A. IL-17A is involved in the IL-8 and Muc5AC production promoting, via NFκB and ERK1/2 pathway activation, the synthesis of ChAT, and the related activity of autocrine ACh in bronchial epithelial cells.

  3. A Lys49-PLA2 myotoxin of Bothrops asper triggers a rapid death of macrophages that involves autocrine purinergic receptor signaling.

    Science.gov (United States)

    Tonello, F; Simonato, M; Aita, A; Pizzo, P; Fernández, J; Lomonte, B; Gutiérrez, J M; Montecucco, C

    2012-07-05

    Lys49-PLA(2) myotoxins, an important component of various viperid snake venoms, are a class of PLA(2)-homolog proteins deprived of catalytic activity. Similar to enzymatically active PLA(2) (Asp49) and to other classes of myotoxins, they cause severe myonecrosis. Moreover, these toxins are used as tools to study skeletal muscle repair and regeneration, a process that can be very limited after snakebites. In this work, the cytotoxic effect of different myotoxins, Bothrops asper Lys49 and Asp49-PLA(2), Notechis scutatus notexin and Naja mossambica cardiotoxin, was evaluated on macrophages, cells that have a key role in muscle regeneration. Only the Lys49-myotoxin was found to trigger a rapid asynchronous death of mouse peritoneal macrophages and macrophagic cell lines through a process that involves ATP release, ATP-induced ATP release and that is inhibited by various purinergic receptor antagonists. ATP leakage is induced also at sublytical doses of the Lys49-myotoxin, it involves Ca(2+) release from intracellular stores, and is reduced by inhibitors of VSOR and the maxi-anion channel. The toxin-induced cell death is different from that caused by high concentration of ATP and appears to be linked to localized purinergic signaling. Based on present findings, a mechanism of cell death is proposed that can be extended to other cytolytic proteins and peptides.

  4. Autocrine parathyroid hormone-like hormone promotes intrahepatic cholangiocarcinoma cell proliferation via increased ERK/JNK-ATF2-cyclinD1 signaling

    Directory of Open Access Journals (Sweden)

    Jing Tang

    2017-11-01

    Full Text Available Abstract Background and aims Intrahepatic cholangiocarcinoma (ICC is an aggressive tumor with a high fatality rate. It was recently found that parathyroid hormone-like hormone (PTHLH was frequently overexpressed in ICC compared with non-tumor tissue. This study aimed to elucidate the underlying mechanisms of PTHLH in ICC development. Methods The CCK-8 assay, colony formation assays, flow cytometry and a xenograft model were used to examine the role of PTHLH in ICC cells proliferation. Immunohistochemistry (IHC and western blot assays were used to detect target proteins. Luciferase reporter, chromatin immunoprecipitation (ChIP and DNA pull-down assays were used to verify the transcription regulation of activating transcription factor-2 (ATF2. Results PTHLH was significantly upregulated in ICC compared with adjacent and normal tissues. Upregulation of PTHLH indicated a poor pathological differentiation and intrahepatic metastasis. Functional study demonstrated that PTHLH silencing markedly suppressed ICC cells growth, while specific overexpression of PTHLH has the opposite effect. Mechanistically, secreted PTHLH could promote ICC cell growth by activating extracellular signal-related kinase (ERK and c-Jun N-terminal kinase (JNK signaling pathways, and subsequently upregulated ATF2 and cyclinD1 expression. Further study found that the promoter activity of PTHLH were negatively regulated by ATF2, indicating that a negative feedback loop exists. Conclusions Our findings demonstrated that the ICC-secreted PTHLH plays a characteristic growth-promoting role through activating the canonical ERK/JNK-ATF2-cyclinD1 signaling pathways in ICC development. We identified a negative feedback loop formed by ATF2 and PTHLH. In this study, we explored the therapeutic implication for ICC patients.

  5. Autocrine Human Growth Hormone Promotes Invasive and Cancer Stem Cell-Like Behavior of Hepatocellular Carcinoma Cells by STAT3 Dependent Inhibition of CLAUDIN-1 Expression

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    Yi-Jun Chen

    2017-06-01

    Full Text Available Despite progress in diagnosis and treatment of hepatocellular carcinoma (HCC, the clinical outcome is still unsatisfactory. Increased expression of human growth hormone (hGH in HCC has been reported and is associated with poor survival outcome in HCC patients. Herein, we investigated the mechanism of the oncogenic effects of hGH in HCC cell lines. In vitro functional assays demonstrated that forced expression of hGH in these HCC cell lines promoted cell proliferation, cell survival, anchorage-independent growth, cell migration, and invasion, as previously reported. In addition, forced expression of hGH promoted cancer stem cell (CSC-like properties of HCC cells. The increased invasive and CSC-like properties of HCC cells with forced expression of hGH were mediated by inhibition of the expression of the tight junction component CLAUDIN-1. Consistently, depletion of CLAUDIN-1 expression increased the invasive and CSC-like properties of HCC cell lines. Moreover, forced expression of CLAUDIN-1 abrogated the acquired invasive and CSC-like properties of HCC cell lines with forced expression of hGH. We further demonstrated that forced expression of hGH inhibited CLAUDIN-1 expression in HCC cell lines via signal transducer and activator of transcription 3 (STAT3 mediated inhibition of CLAUDIN-1 transcription. Hence, we have elucidated a novel hGH-STAT3-CLAUDIN-1 axis responsible for invasive and CSC-like properties in HCC. Inhibition of hGH should be considered as a therapeutic option to hinder progression and relapse of HCC.

  6. Autocrine Human Growth Hormone Promotes Invasive and Cancer Stem Cell-Like Behavior of Hepatocellular Carcinoma Cells by STAT3 Dependent Inhibition of CLAUDIN-1 Expression.

    Science.gov (United States)

    Chen, Yi-Jun; You, Ming-Liang; Chong, Qing-Yun; Pandey, Vijay; Zhuang, Qiu-Shi; Liu, Dong-Xu; Ma, Lan; Zhu, Tao; Lobie, Peter E

    2017-06-15

    Despite progress in diagnosis and treatment of hepatocellular carcinoma (HCC), the clinical outcome is still unsatisfactory. Increased expression of human growth hormone (hGH) in HCC has been reported and is associated with poor survival outcome in HCC patients. Herein, we investigated the mechanism of the oncogenic effects of hGH in HCC cell lines. In vitro functional assays demonstrated that forced expression of hGH in these HCC cell lines promoted cell proliferation, cell survival, anchorage-independent growth, cell migration, and invasion, as previously reported. In addition, forced expression of hGH promoted cancer stem cell (CSC)-like properties of HCC cells. The increased invasive and CSC-like properties of HCC cells with forced expression of hGH were mediated by inhibition of the expression of the tight junction component CLAUDIN-1. Consistently, depletion of CLAUDIN-1 expression increased the invasive and CSC-like properties of HCC cell lines. Moreover, forced expression of CLAUDIN-1 abrogated the acquired invasive and CSC-like properties of HCC cell lines with forced expression of hGH. We further demonstrated that forced expression of hGH inhibited CLAUDIN-1 expression in HCC cell lines via signal transducer and activator of transcription 3 (STAT3) mediated inhibition of CLAUDIN-1 transcription. Hence, we have elucidated a novel hGH-STAT3-CLAUDIN-1 axis responsible for invasive and CSC-like properties in HCC. Inhibition of hGH should be considered as a therapeutic option to hinder progression and relapse of HCC.

  7. Pathophysiological mechanisms of death resistance in colorectal carcinoma.

    Science.gov (United States)

    Huang, Ching-Ying; Yu, Linda Chia-Hui

    2015-11-07

    Colon cancers develop adaptive mechanisms to survive under extreme conditions and display hallmarks of unlimited proliferation and resistance to cell death. The deregulation of cell death is a key factor that contributes to chemoresistance in tumors. In a physiological context, balance between cell proliferation and death, and protection against cell damage are fundamental processes for maintaining gut epithelial homeostasis. The mechanisms underlying anti-death cytoprotection and tumor resistance often bear common pathways, and although distinguishing them would be a challenge, it would also provide an opportunity to develop advanced anti-cancer therapeutics. This review will outline cell death pathways (i.e., apoptosis, necrosis, and necroptosis), and discuss cytoprotective strategies in normal intestinal epithelium and death resistance mechanisms of colon tumor. In colorectal cancers, the intracellular mechanisms of death resistance include the direct alteration of apoptotic and necroptotic machinery and the upstream events modulating death effectors such as tumor suppressor gene inactivation and pro-survival signaling pathways. The autocrine, paracrine and exogenous factors within a tumor microenvironment can also instigate resistance against apoptotic and necroptotic cell death in colon cancers through changes in receptor signaling or transporter uptake. The roles of cyclooxygenase-2/prostaglandin E2, growth factors, glucose, and bacterial lipopolysaccharides in colorectal cancer will be highlighted. Targeting anti-death pathways in the colon cancer tissue might be a promising approach outside of anti-proliferation and anti-angiogenesis strategies for developing novel drugs to treat refractory tumors.

  8. BMP2 and mechanical loading cooperatively regulate immediate early signalling events in the BMP pathway.

    Science.gov (United States)

    Kopf, Jessica; Petersen, Ansgar; Duda, Georg N; Knaus, Petra

    2012-04-30

    Efficient osteogenic differentiation is highly dependent on coordinated signals arising from growth factor signalling and mechanical forces. Bone morphogenetic proteins (BMPs) are secreted proteins that trigger Smad and non-Smad pathways and thereby influence transcriptional and non-transcriptional differentiation cues. Crosstalk at multiple levels allows for promotion or attenuation of signalling intensity and specificity. Similar to BMPs, mechanical stimulation enhances bone formation. However, the molecular mechanism by which mechanical forces crosstalk to biochemical signals is still unclear. Here, we use a three-dimensional bioreactor system to describe how mechanical forces are integrated into the BMP pathway. Time-dependent phosphorylation of Smad, mitogen-activated protein kinases and Akt in human fetal osteoblasts was investigated under loading and/or BMP2 stimulation conditions. The phosphorylation of R-Smads is increased both in intensity and duration under BMP2 stimulation with concurrent mechanical loading. Interestingly, the synergistic effect of both stimuli on immediate early Smad phosphorylation is reflected in the transcription of only a subset of BMP target genes, while others are differently affected. Together this results in a cooperative regulation of osteogenesis that is guided by both signalling pathways. Mechanical signals are integrated into the BMP signalling pathway by enhancing immediate early steps within the Smad pathway, independent of autocrine ligand secretion. This suggests a direct crosstalk of both mechanotransduction and BMP signalling, most likely at the level of the cell surface receptors. Furthermore, the crosstalk of both pathways over longer time periods might occur on several signalling levels.

  9. Fracture Mechanics

    International Nuclear Information System (INIS)

    Jang, Dong Il; Jeong, Gyeong Seop; Han, Min Gu

    1992-08-01

    This book introduces basic theory and analytical solution of fracture mechanics, linear fracture mechanics, non-linear fracture mechanics, dynamic fracture mechanics, environmental fracture and fatigue fracture, application on design fracture mechanics, application on analysis of structural safety, engineering approach method on fracture mechanics, stochastic fracture mechanics, numerical analysis code and fracture toughness test and fracture toughness data. It gives descriptions of fracture mechanics to theory and analysis from application of engineering.

  10. Puzzling Mechanisms

    Science.gov (United States)

    van Deventer, M. Oskar

    2009-01-01

    The basis of a good mechanical puzzle is often a puzzling mechanism. This article will introduce some new puzzling mechanisms, like two knots that engage like gears, a chain whose links can be interchanged, and flat gears that do not come apart. It illustrates how puzzling mechanisms can be transformed into real mechanical puzzles, e.g., by…

  11. Quantum mechanics

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    The book is on quantum mechanics. The emphasis is on the basic concepts and the methodology. The chapters include: Breakdown of classical concepts; Quantum mechanical concepts; Basic postulates of quantum mechanics; solution of problems in quantum mechanics; Simple harmonic oscillator; and Angular Momentum

  12. Mechanical impedance

    OpenAIRE

    Couroussé, Damien

    2007-01-01

    International audience; Mechanical impedance is a transposition to mechanics of the term impedance that is used and defined in circuit theory. The theory of circuit (theory of Kirchhoff networks) is basically applicable to electric networks but can be considered more generally as a unifying simplified theory of physics available in several domains like mechanics, electromagnetism, aero-acoustics and fluids mechanics.

  13. Continuum mechanics

    CERN Document Server

    Spencer, A J M

    2004-01-01

    The mechanics of fluids and the mechanics of solids represent the two major areas of physics and applied mathematics that meet in continuum mechanics, a field that forms the foundation of civil and mechanical engineering. This unified approach to the teaching of fluid and solid mechanics focuses on the general mechanical principles that apply to all materials. Students who have familiarized themselves with the basic principles can go on to specialize in any of the different branches of continuum mechanics. This text opens with introductory chapters on matrix algebra, vectors and Cartesian ten

  14. Mechanical Ventilation

    Science.gov (United States)

    ... ventilation is a life support treatment. A mechanical ventilator is a machine that helps people breathe when ... to breathe enough on their own. The mechanical ventilator is also called a ventilator , respirator, or breathing ...

  15. Mechanisms Design

    DEFF Research Database (Denmark)

    Restrepo-Giraldo, John Dairo

    2006-01-01

    , freudenstein’s equation for three point function generation, synthesis of mechanisms for specific applications. At the end of this module you will be able to apply systematic procedures and use different methods to find a suitable configuration for a mechanism that complies with motion, trajectory and...... such mechanisms. This is a horizontal subject, which means you will be asked to make use of your knowledge in different disciplines, specially statics and dynamics, but also material selection, general product development, etc. At the end of this course you will be able to: • Generate alternative configurations...... using criteria such as size, performance parameters, operation environment, etc. Content: Understanding Mechanisms Design (2 weeks) Definitions, mechanisms representations, kinematic diagrams, the four bar linkage, mobility, applications of mechanisms, types of mechanisms, special mechanisms, the design...

  16. Mechanical design

    CERN Document Server

    Risitano, Antonino

    2011-01-01

    METHODOLOGICAL STATEMENT OF ENGINEERING DESIGNApproaches to product design and developmentMechanical design and environmental requirementsPROPERTIES OF ENGINEERING MATERIALSMaterials for mechanical designCharacterization of metalsStress conditionsFatigue of materialsOptimum material selection in mechanical designDESIGN OF MECHANICAL COMPONENTS AND SYSTEMSFailure theoriesHertz theoryLubrificationShafts and bearingsSplines and keysSpringsFlexible machine elementsSpur gearsPress and shrink fitsPressure tubesCouplingsClutchesBrakes

  17. Mechanical Kinesiology.

    Science.gov (United States)

    Barham, Jerry N.

    Mechanical kinesiology is defined as a study of the mechanical factors affecting human movement, i.e., applying the physical laws of mechanics to the study of human motor behavior. This textbook on the subject is divided into thirty lessons. Each lesson is organized into three parts: a part on the text proper; a part entitled "study…

  18. Discrete mechanics

    International Nuclear Information System (INIS)

    Lee, T.D.

    1985-01-01

    This paper reviews the role of time throughout all phases of mechanics: classical mechanics, non-relativistic quantum mechanics, and relativistic quantum theory. As an example of the relativistic quantum field theory, the case of a massless scalar field interacting with an arbitrary external current is discussed. The comparison between the new discrete theory and the usual continuum formalism is presented. An example is given of a two-dimensional random lattice and its duel. The author notes that there is no evidence that the discrete mechanics is more appropriate than the usual continuum mechanics

  19. Discrete mechanics

    CERN Document Server

    Caltagirone, Jean-Paul

    2014-01-01

    This book presents the fundamental principles of mechanics to re-establish the equations of Discrete Mechanics. It introduces physics and thermodynamics associated to the physical modeling.  The development and the complementarity of sciences lead to review today the old concepts that were the basis for the development of continuum mechanics. The differential geometry is used to review the conservation laws of mechanics. For instance, this formalism requires a different location of vector and scalar quantities in space. The equations of Discrete Mechanics form a system of equations where the H

  20. Regenerating medicine related to the stem-cells and its mechanisms of action from adults cells

    International Nuclear Information System (INIS)

    Hernandez Ramirez, Porfirio

    2009-01-01

    Regenerating medicine is a branch of Medicine very developed in past years. Advances in this field have been closely linked with the new knowledge achieved on stem-cells and its ability to become in cells of different tissues. This type of medicine is based on the behaviors adopted by organism to substitute those damaged cells by the healthy ones by different processes in specific tissues. Therapeutic measures used may include the stem-cell transplantation, the use of soluble molecules, genic therapy and tissues engineering. Nowadays, the more used method is the adult stem-cells. However, is not well known the mechanisms by which the transplanted cells could to improve or to promote the tissue regeneration. To explain these mechanisms some hypotheses has been proposed including the cellular trans-differentiation, cells fusion, and the effects secondaries to cells release by cells of different soluble molecules with specific actions; in addition to the autocrine and paracrine effects that may have these soluble factors, it is suggested too the existence of a telecrine action. It is probable that more than one of these mechanisms be executed

  1. Classical mechanics

    CERN Document Server

    Benacquista, Matthew J

    2018-01-01

    This textbook provides an introduction to classical mechanics at a level intermediate between the typical undergraduate and advanced graduate level. This text describes the background and tools for use in the fields of modern physics, such as quantum mechanics, astrophysics, particle physics, and relativity. Students who have had basic undergraduate classical mechanics or who have a good understanding of the mathematical methods of physics will benefit from this book.

  2. Mechanical science

    CERN Document Server

    Bolton, W C

    2013-01-01

    This book gives comprehensive coverage of mechanical science for HNC/HND students taking mechanical engineering courses, including all topics likely to be covered in both years of such courses, as well as for first year undergraduate courses in mechanical engineering. It features 500 problems with answers and 200 worked examples. The third edition includes a new section on power transmission and an appendix on mathematics to help students with the basic notation of calculus and solution of differential equations.

  3. Geometric mechanics

    CERN Document Server

    Muniz Oliva, Waldyr

    2002-01-01

    Geometric Mechanics here means mechanics on a pseudo-riemannian manifold and the main goal is the study of some mechanical models and concepts, with emphasis on the intrinsic and geometric aspects arising in classical problems. The first seven chapters are written in the spirit of Newtonian Mechanics while the last two ones as well as two of the four appendices describe the foundations and some aspects of Special and General Relativity. All the material has a coordinate free presentation but, for the sake of motivation, many examples and exercises are included in order to exhibit the desirable flavor of physical applications.

  4. Automotive Mechanics.

    Science.gov (United States)

    Linder, Ralph C.; And Others

    This curriculum guide, which was validated by vocational teachers and mechanics in the field, describes the competencies needed by entry-level automotive mechanics. This guide lists 15 competencies; for each competency, various tasks with their performance objective, student learning experiences, suggested instructional techniques, instructional…

  5. College mechanics

    CERN Document Server

    Şengül, Caner

    2016-01-01

    College Mechanics QueBank has been designed to be different, enthusiastic, interesting and helpful to you. Therefore, it is not just a test bank about mechanics but also it is like a compass in order to find your way in mechanics Each chapter in this book is put in an order to follow a hierarchy of the mechanics topics; from vectors to simple harmonic motion. Throughout the book there are many multiple choice and long answer questions for you to solve. They have been created for YGS, LYS, SAT, IB or other standardized exams in the world because mechanics has no boundaries and so Physics has no country. Learn the main principle of each chapter and explore the daily life applications. Then you can start to solve the questions by planning a problem solving method carefully. Finally, enjoy solving the questions and discover the meachanics of the universe once more.

  6. Fracture Mechanics

    CERN Document Server

    Zehnder, Alan T

    2012-01-01

    Fracture mechanics is a vast and growing field. This book develops the basic elements needed for both fracture research and engineering practice. The emphasis is on continuum mechanics models for energy flows and crack-tip stress- and deformation fields in elastic and elastic-plastic materials. In addition to a brief discussion of computational fracture methods, the text includes practical sections on fracture criteria, fracture toughness testing, and methods for measuring stress intensity factors and energy release rates. Class-tested at Cornell, this book is designed for students, researchers and practitioners interested in understanding and contributing to a diverse and vital field of knowledge. Alan Zehnder joined the faculty at Cornell University in 1988. Since then he has served in a number of leadership roles including Chair of the Department of Theoretical and Applied Mechanics, and Director of the Sibley School of Mechanical and Aerospace Engineering.  He teaches applied mechanics and his research t...

  7. Respiratory mechanics

    CERN Document Server

    Wilson, Theodore A

    2016-01-01

    This book thoroughly covers each subfield of respiratory mechanics: pulmonary mechanics, the respiratory pump, and flow. It presents the current understanding of the field and serves as a guide to the scientific literature from the golden age of respiratory mechanics, 1960 - 2010. Specific topics covered include the contributions of surface tension and tissue forces to lung recoil, the gravitational deformation of the lung, and the interdependence forces that act on pulmonary airways and blood vessels. The geometry and kinematics of the ribs is also covered in detail, as well as the respiratory action of the external and internal intercostal muscles, the mechanics of the diaphragm, and the quantitative compartmental models of the chest wall is also described. Additionally, flow in the airways is covered thoroughly, including the wave-speed and viscous expiratory flow-limiting mechanisms; convection, diffusion and the stationary front; and the distribution of ventilation. This is an ideal book for respiratory ...

  8. Quantum mechanics

    CERN Document Server

    Rae, Alastair I M

    2016-01-01

    A Thorough Update of One of the Most Highly Regarded Textbooks on Quantum Mechanics Continuing to offer an exceptionally clear, up-to-date treatment of the subject, Quantum Mechanics, Sixth Edition explains the concepts of quantum mechanics for undergraduate students in physics and related disciplines and provides the foundation necessary for other specialized courses. This sixth edition builds on its highly praised predecessors to make the text even more accessible to a wider audience. It is now divided into five parts that separately cover broad topics suitable for any general course on quantum mechanics. New to the Sixth Edition * Three chapters that review prerequisite physics and mathematics, laying out the notation, formalism, and physical basis necessary for the rest of the book * Short descriptions of numerous applications relevant to the physics discussed, giving students a brief look at what quantum mechanics has made possible industrially and scientifically * Additional end-of-chapter problems with...

  9. Cytoskeletal Mechanics

    Science.gov (United States)

    Mofrad, Mohammad R. K.; Kamm, Roger D.

    2011-08-01

    1. Introduction and the biological basis for cell mechanics Mohammad R. K. Mofrad and Roger Kamm; 2. Experimental measurements of intracellular mechanics Paul Janmey and Christoph Schmidt; 3. The cytoskeleton as a soft glassy material Jeffrey Fredberg and Ben Fabry; 4. Continuum elastic or viscoelastic models for the cell Mohammad R. K. Mofrad, Helene Karcher and Roger Kamm; 5. Multiphasic models of cell mechanics Farshid Guuilak, Mansoor A. Haider, Lori A. Setton, Tod A. Laursen and Frank P. T. Baaijens; 6. Models of cytoskeletal mechanics based on tensegrity Dimitrije Stamenovic; 7. Cells, gels and mechanics Gerald H. Pollack; 8. Polymer-based models of cytoskeletal networks F. C. MacKintosh; 9. Cell dynamics and the actin cytoskeleton James L. McGrath and C. Forbes Dewey, Jr; 10. Active cellular motion: continuum theories and models Marc Herant and Micah Dembo; 11. Summary Mohammad R. K. Mofrad and Roger Kamm.

  10. Quantum mechanics

    CERN Document Server

    Powell, John L

    2015-01-01

    Suitable for advanced undergraduates, this thorough text focuses on the role of symmetry operations and the essentially algebraic structure of quantum-mechanical theory. Based on courses in quantum mechanics taught by the authors, the treatment provides numerous problems that require applications of theory and serve to supplement the textual material.Starting with a historical introduction to the origins of quantum theory, the book advances to discussions of the foundations of wave mechanics, wave packets and the uncertainty principle, and an examination of the Schrödinger equation that includ

  11. Indexing mechanisms

    International Nuclear Information System (INIS)

    Wood, A.G.; Parker, G.E.; Berry, R.

    1976-01-01

    It is stated that the indexing mechanism described can be used in a nuclear reactor fuel element inspection rig. It comprises a tubular body adapted to house a canister containing a number of fuel elements located longtitudinally, and has two chucks spaced apart for displacing the fuel elements longitudinally in a stepwise manner, together with a plunger mechanism for displacing them successively into the chucks. A measuring unit is located between the chucks for measuring the diameter of the fuel elements at intervals about their circumferences, and a secondary indexing mechanism is provided for rotating the measuring unit in a stepwise manner. (U.K.)

  12. Quantum mechanics

    International Nuclear Information System (INIS)

    Rae, A.I.M.

    1981-01-01

    This book, based on a thirty lecture course given to students at the beginning of their second year, covers the quantum mechanics required by physics undergraduates. Early chapters deal with wave mechanics, including a discussion of the energy states of the hydrogen atom. These are followed by a more formal development of the theory, leading to a discussion of some advanced applications and an introduction to the conceptual problems associated with quantum measurement theory. Emphasis is placed on the fundamentals of quantum mechanics. Problems are included at the end of each chapter. (U.K.)

  13. Robot Mechanisms

    CERN Document Server

    Lenarcic, Jadran; Stanišić, Michael M

    2013-01-01

    This book provides a comprehensive introduction to the area of robot mechanisms, primarily considering industrial manipulators and humanoid arms. The book is intended for both teaching and self-study. Emphasis is given to the fundamentals of kinematic analysis and the design of robot mechanisms. The coverage of topics is untypical. The focus is on robot kinematics. The book creates a balance between theoretical and practical aspects in the development and application of robot mechanisms, and includes the latest achievements and trends in robot science and technology.

  14. BMP2 and mechanical loading cooperatively regulate immediate early signalling events in the BMP pathway

    Directory of Open Access Journals (Sweden)

    Kopf Jessica

    2012-04-01

    Full Text Available Abstract Background Efficient osteogenic differentiation is highly dependent on coordinated signals arising from growth factor signalling and mechanical forces. Bone morphogenetic proteins (BMPs are secreted proteins that trigger Smad and non-Smad pathways and thereby influence transcriptional and non-transcriptional differentiation cues. Crosstalk at multiple levels allows for promotion or attenuation of signalling intensity and specificity. Similar to BMPs, mechanical stimulation enhances bone formation. However, the molecular mechanism by which mechanical forces crosstalk to biochemical signals is still unclear. Results Here, we use a three-dimensional bioreactor system to describe how mechanical forces are integrated into the BMP pathway. Time-dependent phosphorylation of Smad, mitogen-activated protein kinases and Akt in human fetal osteoblasts was investigated under loading and/or BMP2 stimulation conditions. The phosphorylation of R-Smads is increased both in intensity and duration under BMP2 stimulation with concurrent mechanical loading. Interestingly, the synergistic effect of both stimuli on immediate early Smad phosphorylation is reflected in the transcription of only a subset of BMP target genes, while others are differently affected. Together this results in a cooperative regulation of osteogenesis that is guided by both signalling pathways. Conclusions Mechanical signals are integrated into the BMP signalling pathway by enhancing immediate early steps within the Smad pathway, independent of autocrine ligand secretion. This suggests a direct crosstalk of both mechanotransduction and BMP signalling, most likely at the level of the cell surface receptors. Furthermore, the crosstalk of both pathways over longer time periods might occur on several signalling levels.

  15. Fracture mechanics

    CERN Document Server

    Perez, Nestor

    2017-01-01

    The second edition of this textbook includes a refined presentation of concepts in each chapter, additional examples; new problems and sections, such as conformal mapping and mechanical behavior of wood; while retaining all the features of the original book. The material included in this book is based upon the development of analytical and numerical procedures pertinent to particular fields of linear elastic fracture mechanics (LEFM) and plastic fracture mechanics (PFM), including mixed-mode-loading interaction. The mathematical approach undertaken herein is coupled with a brief review of several fracture theories available in cited references, along with many color images and figures. Dynamic fracture mechanics is included through the field of fatigue and Charpy impact testing. Explains computational and engineering approaches for solving crack-related problems using straightforward mathematics that facilitate comprehension of the physical meaning of crack growth processes; Expands computational understandin...

  16. Quantum Mechanics

    CERN Document Server

    Schwabl, Franz

    2007-01-01

    This represents the introductory course which would precede and so complements the author's book on Advanced Quantum Mechanics. The new edition has been up-dated and thoroughly revised throughout and now includes many new or newly drawn figures which will facilitate an easier understanding of subtle topics. The book meets students' needs in providing detailed mathematical steps along the way, with worked examples and applications throughout the text, and many problems for the reader at the end of each chapter. It contains nonrelativistic quantum mechanics and a short treatment of the quantization of the radiation field. In addition to the essentials, topics such as the theory of measurement, the Bell inequality, decoherence, entanglement and supersymmetric quantum mechanics are discussed. "Any student wishing to develop mathematical skills and deepen their understanding of the technical side of quantum theory will find Schwabl's Quantum Mechanics very helpful". Contemporary Physics

  17. Engineering mechanics

    CERN Document Server

    Gross, Dietmar; Schröder, Jörg; Wall, Wolfgang A; Rajapakse, Nimal

    Statics is the first volume of a three-volume textbook on Engineering Mechanics. The authors, using a time-honoured straightforward and flexible approach, present the basic concepts and principles of mechanics in the clearest and simplest form possible to advanced undergraduate engineering students of various disciplines and different educational backgrounds. An important objective of this book is to develop problem solving skills in a systematic manner. Another aim of this volume is to provide engineering students as well as practising engineers with a solid foundation to help them bridge the gap between undergraduate studies on the one hand and advanced courses on mechanics and/or practical engineering problems on the other. The book contains numerous examples, along with their complete solutions. Emphasis is placed upon student participation in problem solving. The contents of the book correspond to the topics normally covered in courses on basic engineering mechanics at universities and colleges. Now in i...

  18. Supersymmetric mechanics

    International Nuclear Information System (INIS)

    Stelle, Kellogg S

    2007-01-01

    With the development of the electronic archives in high-energy physics, there has been increasing questioning of the role of traditional publishing styles, particularly in the production of conference books. One aspect of traditional publishing that still receives wide appreciation, however, is in the production of well-focussed pedagogical material. The present two-volume edition, 'Supersymmetric Mechanics-Vol 1', edited by S Bellucci and 'Supersymmetric Mechanics-Vol 2', edited by S Bellucci, S Ferrara and A Marrani, is a good example of the kind of well-digested presentation that should still find its way into university libraries. This two-volume set presents the material of a set of pedagogical lectures presented at the INFN National Laboratory in Frascati over a two-year period on the subject of supersymmetric mechanics. The articles include the results of discussions with the attending students after the lectures. Overall, this makes for a useful compilation of material on a subject that underlies much of the current effort in supersymmetric approaches to cosmology and the unification programme. The first volume comprises articles on 'A journey through garden algebras' by S Bellucci, S J Gates Jr and E Orazi on linear supermultiplet realizations in supersymmetric mechanics,'Supersymmetric mechanics in superspace' by S Bellucci and S Krivonos, 'Noncommutative mechanics, Landau levels, twistors and Yang-Mills amplitudes' by V P Nair, 'Elements of (super) Hamiltonian formalism' by A Nersessian and 'Matrix mechanics' by C Sochichiu. The second volume consists entirely of a masterful presentation on 'The attractor mechanism and space time singularities' by S Ferrara. This presents a comprehensive and detailed overview of the structure of supersymmetric black hole solutions in supergravity, critical point structure in the scalar field moduli space and the thermodynamic consequences. This second volume alone makes the set a worthwhile addition to the research

  19. Quantum Mechanics

    Science.gov (United States)

    Mandl, F.

    1992-07-01

    The Manchester Physics Series General Editors: D. J. Sandiford; F. Mandl; A. C. Phillips Department of Physics and Astronomy, University of Manchester Properties of Matter B. H. Flowers and E. Mendoza Optics Second Edition F. G. Smith and J. H. Thomson Statistical Physics Second Edition F. Mandl Electromagnetism Second Edition I. S. Grant and W. R. Phillips Statistics R. J. Barlow Solid State Physics Second Edition J. R. Hook and H. E. Hall Quantum Mechanics F. Mandl Particle Physics Second Edition B. R. Martin and G. Shaw The Physics of Stars Second Edition A. C. Phillips Computing for Scientists R. J. Barlow and A. R. Barnett Quantum Mechanics aims to teach those parts of the subject which every physicist should know. The object is to display the inherent structure of quantum mechanics, concentrating on general principles and on methods of wide applicability without taking them to their full generality. This book will equip students to follow quantum-mechanical arguments in books and scientific papers, and to cope with simple cases. To bring the subject to life, the theory is applied to the all-important field of atomic physics. No prior knowledge of quantum mechanics is assumed. However, it would help most readers to have met some elementary wave mechanics before. Primarily written for students, it should also be of interest to experimental research workers who require a good grasp of quantum mechanics without the full formalism needed by the professional theorist. Quantum Mechanics features: A flow diagram allowing topics to be studied in different orders or omitted altogether. Optional "starred" and highlighted sections containing more advanced and specialized material for the more ambitious reader. Sets of problems at the end of each chapter to help student understanding. Hints and solutions to the problems are given at the end of the book.

  20. Mechanical Graphene

    OpenAIRE

    Socolar, Joshua E. S.; Lubensky, Tom C.; Kane, Charles L.

    2016-01-01

    We present a model of a mechanical system with a vibrational mode spectrum identical to the spectrum of electronic excitations in a tight-binding model of graphene. The model consists of point masses connected by elastic couplings, called "tri-bonds," that implement certain three-body interactions, which can be tuned by varying parameters that correspond to the relative hopping amplitudes on the different bond directions in graphene. In the mechanical model, this is accomplished by varying th...

  1. Leaching mechanisms

    International Nuclear Information System (INIS)

    Dougherty, D.R.; Colombo, P.

    1984-01-01

    Sufficient data are lacking to provide a basis for adequately assessing the long term leaching behavior of solidified low level radioactive waste forms in their disposal environment. Although the release of radioactivity from a waste form to an aqueous environment is recognized to be due to one or more mechanisms such as diffusion, dissolution, corrosion or ion exchange, the leaching mechanisms and the factors which control the leaching behavior of waste forms are not fully understood. This study will determine the prevailing mechanisms for a variety of selected LLW solidification agents which are being considered for use by defense and commercial generators and which will cover the broadest possible number of mechanisms. The investigation will proceed by the postulation of mathematical models representative of the prevailing mechanism(s) and the use of statistically designed experiments to test the actual leaching behavior of laborattory samples against the postulated representations. Maximum use of existing leach data in the literature will be made by incorporating literature results into a computerized data base along with the experimental results generated in this task

  2. Computational mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Goudreau, G.L.

    1993-03-01

    The Computational Mechanics thrust area sponsors research into the underlying solid, structural and fluid mechanics and heat transfer necessary for the development of state-of-the-art general purpose computational software. The scale of computational capability spans office workstations, departmental computer servers, and Cray-class supercomputers. The DYNA, NIKE, and TOPAZ codes have achieved world fame through our broad collaborators program, in addition to their strong support of on-going Lawrence Livermore National Laboratory (LLNL) programs. Several technology transfer initiatives have been based on these established codes, teaming LLNL analysts and researchers with counterparts in industry, extending code capability to specific industrial interests of casting, metalforming, and automobile crash dynamics. The next-generation solid/structural mechanics code, ParaDyn, is targeted toward massively parallel computers, which will extend performance from gigaflop to teraflop power. Our work for FY-92 is described in the following eight articles: (1) Solution Strategies: New Approaches for Strongly Nonlinear Quasistatic Problems Using DYNA3D; (2) Enhanced Enforcement of Mechanical Contact: The Method of Augmented Lagrangians; (3) ParaDyn: New Generation Solid/Structural Mechanics Codes for Massively Parallel Processors; (4) Composite Damage Modeling; (5) HYDRA: A Parallel/Vector Flow Solver for Three-Dimensional, Transient, Incompressible Viscous How; (6) Development and Testing of the TRIM3D Radiation Heat Transfer Code; (7) A Methodology for Calculating the Seismic Response of Critical Structures; and (8) Reinforced Concrete Damage Modeling.

  3. Fluid Mechanics

    Science.gov (United States)

    Pnueli, David; Gutfinger, Chaim

    1997-01-01

    This text is intended for the study of fluid mechanics at an intermediate level. The presentation starts with basic concepts, in order to form a sound conceptual structure that can support engineering applications and encourage further learning. The presentation is exact, incorporating both the mathematics involved and the physics needed to understand the various phenomena in fluid mechanics. Where a didactical choice must be made between the two, the physics prevails. Throughout the book the authors have tried to reach a balance between exact presentation, intuitive grasp of new ideas, and creative applications of concepts. This approach is reflected in the examples presented in the text and in the exercises given at the end of each chapter. Subjects treated are hydrostatics, viscous flow, similitude and order of magnitude, creeping flow, potential flow, boundary layer flow, turbulent flow, compressible flow, and non-Newtonian flows. This book is ideal for advanced undergraduate students in mechanical, chemical, aerospace, and civil engineering. Solutions manual available.

  4. Quantum mechanics

    CERN Document Server

    Ghosh, P K

    2014-01-01

    Quantum mechanics, designed for advanced undergraduate and graduate students of physics, mathematics and chemistry, provides a concise yet self-contained introduction to the formal framework of quantum mechanics, its application to physical problems and the interpretation of the theory. Starting with a review of some of the necessary mathematics, the basic concepts are carefully developed in the text. After building a general formalism, detailed treatment of the standard material - the harmonic oscillator, the hydrogen atom, angular momentum theory, symmetry transformations, approximation methods, identical particle and many-particle systems, and scattering theory - is presented. The concluding chapter discusses the interpretation of quantum mechanics. Some of the important topics discussed in the book are the rigged Hilbert space, deformation quantization, path integrals, coherent states, geometric phases, decoherene, etc. This book is characterized by clarity and coherence of presentation.

  5. Analytical mechanics

    CERN Document Server

    Helrich, Carl S

    2017-01-01

    This advanced undergraduate textbook begins with the Lagrangian formulation of Analytical Mechanics and then passes directly to the Hamiltonian formulation and the canonical equations, with constraints incorporated through Lagrange multipliers. Hamilton's Principle and the canonical equations remain the basis of the remainder of the text. Topics considered for applications include small oscillations, motion in electric and magnetic fields, and rigid body dynamics. The Hamilton-Jacobi approach is developed with special attention to the canonical transformation in order to provide a smooth and logical transition into the study of complex and chaotic systems. Finally the text has a careful treatment of relativistic mechanics and the requirement of Lorentz invariance. The text is enriched with an outline of the history of mechanics, which particularly outlines the importance of the work of Euler, Lagrange, Hamilton and Jacobi. Numerous exercises with solutions support the exceptionally clear and concise treatment...

  6. Statistical mechanics

    CERN Document Server

    Davidson, Norman

    2003-01-01

    Clear and readable, this fine text assists students in achieving a grasp of the techniques and limitations of statistical mechanics. The treatment follows a logical progression from elementary to advanced theories, with careful attention to detail and mathematical development, and is sufficiently rigorous for introductory or intermediate graduate courses.Beginning with a study of the statistical mechanics of ideal gases and other systems of non-interacting particles, the text develops the theory in detail and applies it to the study of chemical equilibrium and the calculation of the thermody

  7. Mechanical seals

    CERN Document Server

    Mayer, E

    1977-01-01

    Mechanical Seals, Third Edition is a source of practical information on the design and use of mechanical seals. Topics range from design fundamentals and test rigs to leakage, wear, friction and power, reliability, and special designs. This text is comprised of nine chapters; the first of which gives a general overview of seals, including various types of seals and their applications. Attention then turns to the fundamentals of seal design, with emphasis on six requirements that must be considered: sealing effectiveness, length of life, reliability, power consumption, space requirements, and c

  8. Quantum mechanics

    CERN Document Server

    Chowdhury, Sujaul

    2014-01-01

    This book presents comprehensive account of the course for undergraduate students with thorough and complete calculations. The book has been written with the notion that a wave is associated with a material particle i.e. wave and particle coexist. Heisenberg's uncertainty principle has been described in light of this. A chapter is dedicated to mathematical structure of Quantum Mechanics followed by applications to one-dimensional (1D) problems. Orbital and general angular momentum are treated in two separate chapters, the latter also treats addition of angular momentum. Quantum theory of scattering, matrix formulation of Quantum Mechanics variational method and WKB approximation method have also been discussed.

  9. Mechanism of Ursolic Acid-Mediated Inhibition of Proliferation in ...

    African Journals Online (AJOL)

    endothelial growth factor/Flt1 autocrine loop interacts with hypoxia-inducible factor-1α through mitogen-activated protein kinase/extracellular signal-regulated kinase1/2 pathway in neuroblastoma. Cancer Res 2005; 65: 7267-7275. 3. Wang T, Song HY, Zhao DM. Experimental study for Fu- an-te injection on transplantable ...

  10. Acceleration Mechanisms

    OpenAIRE

    Melrose, D. B.

    2009-01-01

    Glossary I. Background and context of the subject II. Stochastic acceleration III. Resonant scattering IV. Diffusive shock acceleration V. DSA at multiple shocks VI. Applications of DSA VII. Acceleration by parallel electric fields VIII. Other acceleration mechanisms IX. Future directions X. Appendix: Quasilinear equations XI. Bibliography

  11. Fluid Mechanics.

    Science.gov (United States)

    Drazin, Philip

    1987-01-01

    Outlines the contents of Volume II of "Principia" by Sir Isaac Newton. Reviews the contributions of subsequent scientists to the physics of fluid dynamics. Discusses the treatment of fluid mechanics in physics curricula. Highlights a few of the problems of modern research in fluid dynamics. Shows that problems still remain. (CW)

  12. Mechanical allodynia

    NARCIS (Netherlands)

    Lolignier, Stéphane; Eijkelkamp, N; Wood, John N

    Mechanical allodynia (other pain) is a painful sensation caused by innocuous stimuli like light touch. Unlike inflammatory hyperalgesia that has a protective role, allodynia has no obvious biological utility. Allodynia is associated with nerve damage in conditions such as diabetes, and is likely to

  13. Soil Mechanics

    DEFF Research Database (Denmark)

    Gottlieb, Sara Wisbech Jacobsen; Hededal, Ole; Foged, Niels Nielsen

    It is widely accepted that there is a connection between the undrained shear strength and the strain rate. Thixotropy and creep behaviour are connected to the mechanical properties of clay. Thixotropy is the ability of clay to recover its shear strength over time when the shear stress is released...

  14. Statistical mechanics

    CERN Document Server

    Schwabl, Franz

    2006-01-01

    The completely revised new edition of the classical book on Statistical Mechanics covers the basic concepts of equilibrium and non-equilibrium statistical physics. In addition to a deductive approach to equilibrium statistics and thermodynamics based on a single hypothesis - the form of the microcanonical density matrix - this book treats the most important elements of non-equilibrium phenomena. Intermediate calculations are presented in complete detail. Problems at the end of each chapter help students to consolidate their understanding of the material. Beyond the fundamentals, this text demonstrates the breadth of the field and its great variety of applications. Modern areas such as renormalization group theory, percolation, stochastic equations of motion and their applications to critical dynamics, kinetic theories, as well as fundamental considerations of irreversibility, are discussed. The text will be useful for advanced students of physics and other natural sciences; a basic knowledge of quantum mechan...

  15. Statistical mechanics

    CERN Document Server

    Jana, Madhusudan

    2015-01-01

    Statistical mechanics is self sufficient, written in a lucid manner, keeping in mind the exam system of the universities. Need of study this subject and its relation to Thermodynamics is discussed in detail. Starting from Liouville theorem gradually, the Statistical Mechanics is developed thoroughly. All three types of Statistical distribution functions are derived separately with their periphery of applications and limitations. Non-interacting ideal Bose gas and Fermi gas are discussed thoroughly. Properties of Liquid He-II and the corresponding models have been depicted. White dwarfs and condensed matter physics, transport phenomenon - thermal and electrical conductivity, Hall effect, Magneto resistance, viscosity, diffusion, etc. are discussed. Basic understanding of Ising model is given to explain the phase transition. The book ends with a detailed coverage to the method of ensembles (namely Microcanonical, canonical and grand canonical) and their applications. Various numerical and conceptual problems ar...

  16. Mechanical clutch

    Science.gov (United States)

    Withey, Michael M. (Inventor); Lucas-Dean, Rob G. (Inventor)

    1995-01-01

    The present invention is directed to a mechanical clutch which limits transmission of torque to a desired, predetermined maximum torque from a first clutch plate to a second clutch plate. More specifically, the mechanical clutch includes at least one stepper member, preferably three or more evenly spaced stepper members, which transmit the torque from a first clutch plate to a second clutch plate providing a desired maximum torque is not exceeded. However, if the desired maximum torque is exceeded, the stepper member will rotate and move between the clutch plates so that the torque to the second clutch plate does not exceed the desired maximum torque. The desired maximum torque is set by the axial force compressing the stepper member between the clutch plates and when the applied torque to the first clutch plate exceeds the desired torque, the stepper member will rotate between the clutch plates rather than transmit that torque to the second clutch plate.

  17. Mechanical engineering

    International Nuclear Information System (INIS)

    1988-01-01

    The Mechanical Engineering Division provides the other NAC divisions with design and construction services. Items of special mechanical significance are discussed here. The projects which received major design attention during the past year were: a coupling capacitor for SPC2; a bending magnet and solenoid for ECR ion source; a scanner for outer orbits of the SSC; a scattering chamber for an experimental beamline; a beam swinger; a rotary target magazine for isotope production; a robot arm for isotope production; an isotope transport system and a target cooling system for isotope production. The major projects that were under construction are: a magnetic spectrometer; a second injector cyclotron (SPC2) and extensions to the high-energy beamlines. 4 figs

  18. Mechanical engineering

    CERN Document Server

    Darbyshire, Alan

    2010-01-01

    Alan Darbyshire's best-selling text book provides five-star high quality content to a potential audience of 13,000 engineering students. It explains the most popular specialist units of the Mechanical Engineering, Manufacturing Engineering and Operations & Maintenance Engineering pathways of the new 2010 BTEC National Engineering syllabus. This challenging textbook also features contributions from specialist lecturers, ensuring that no stone is left unturned.

  19. Mesoscopic Mechanics

    OpenAIRE

    Sowa, Artur

    2003-01-01

    This article is concerned with the existence, status and description of the so-called emergent phenomena believed to occur in certain principally planar electronic systems. In fact, two distinctly different if inseparable tasks are accomplished. First, a rigorous mathematical model is proposed of emergent character, which is conceptually bonded with Quantum Mechanics while apparently non-derivable from the many-body Schr\\"{o}dinger equation. I call the resulting conceptual framework the Mesos...

  20. Mechanical resonator

    OpenAIRE

    Padowitz, David; Matsiev, L; Kolosov, Oleg

    2004-01-01

    A sensor and methods for making and using the same in which a mechanical resonator is employed, comprising a resonator portion for resonating in a fluid without the substantial generation of acoustic waves; and an electrical connection between the resonator portion for oscillating and a source of an input signal; wherein the portion for resonating, the electrical connection or both includes a base material and a performance-tuning material that is different from the base material.

  1. Mechanical allodynia

    OpenAIRE

    Lolignier, Stéphane; Eijkelkamp, N; Wood, John N

    2015-01-01

    Mechanical allodynia (other pain) is a painful sensation caused by innocuous stimuli like light touch. Unlike inflammatory hyperalgesia that has a protective role, allodynia has no obvious biological utility. Allodynia is associated with nerve damage in conditions such as diabetes, and is likely to become an increasing clinical problem. Unfortunately, the mechanistic basis of this enhanced sensitivity is incompletely understood. In this review, we describe evidence for the involvement of cand...

  2. Analysis of trophic responses in lesioned brain: focus on basic fibroblast growth factor mechanisms

    Directory of Open Access Journals (Sweden)

    Chadi G.

    1998-01-01

    Full Text Available The actions of fibroblast growth factors (FGFs, particularly the basic form (bFGF, have been described in a large number of cells and include mitogenicity, angiogenicity and wound repair. The present review discusses the presence of the bFGF protein and messenger RNA as well as the presence of the FGF receptor messenger RNA in the rodent brain by means of semiquantitative radioactive in situ hybridization in combination with immunohistochemistry. Chemical and mechanical injuries to the brain trigger a reduction in neurotransmitter synthesis and neuronal death which are accompanied by astroglial reaction. The altered synthesis of bFGF following brain lesions or stimulation was analyzed. Lesions of the central nervous system trigger bFGF gene expression by neurons and/or activated astrocytes, depending on the type of lesion and time post-manipulation. The changes in bFGF messenger RNA are frequently accompanied by a subsequent increase of bFGF immunoreactivity in astrocytes in the lesioned pathway. The reactive astrocytes and injured neurons synthesize increased amount of bFGF, which may act as a paracrine/autocrine factor, protecting neurons from death and also stimulating neuronal plasticity and tissue repair

  3. Quantum mechanics

    CERN Document Server

    Rae, Alastair I M

    2007-01-01

    PREFACESINTRODUCTION The Photoelectric Effect The Compton Effect Line Spectra and Atomic Structure De Broglie Waves Wave-Particle Duality The Rest of This Book THE ONE-DIMENSIONAL SCHRÖDINGER EQUATIONS The Time-Dependent Schrödinger Equation The Time-Independent Schrödinger Equation Boundary ConditionsThe Infinite Square Well The Finite Square Well Quantum Mechanical Tunneling The Harmonic Oscillator THE THREE-DIMENSIONAL SCHRÖDINGER EQUATIONS The Wave Equations Separation in Cartesian Coordinates Separation in Spherical Polar Coordinates The Hydrogenic Atom THE BASIC POSTULATES OF QUANTUM MEC

  4. Quantum mechanics

    CERN Document Server

    Zagoskin, Alexandre

    2015-01-01

    Written by Dr Alexandre Zagoskin, who is a Reader at Loughborough University, Quantum Mechanics: A Complete Introduction is designed to give you everything you need to succeed, all in one place. It covers the key areas that students are expected to be confident in, outlining the basics in clear jargon-free English, and then providing added-value features like summaries of key ideas, and even lists of questions you might be asked in your exam. The book uses a structure that is designed to make quantum physics as accessible as possible - by starting with its similarities to Newtonian physics, ra

  5. Quantum mechanics

    International Nuclear Information System (INIS)

    Basdevant, J.L.; Dalibard, J.; Joffre, M.

    2008-01-01

    All physics is quantum from elementary particles to stars and to the big-bang via semi-conductors and chemistry. This theory is very subtle and we are not able to explain it without the help of mathematic tools. This book presents the principles of quantum mechanics and describes its mathematical formalism (wave function, Schroedinger equation, quantum operators, spin, Hamiltonians, collisions,..). We find numerous applications in the fields of new technologies (maser, quantum computer, cryptography,..) and in astrophysics. A series of about 90 exercises with their answers is included. This book is based on a physics course at a graduate level. (A.C.)

  6. Reaction mechanisms

    International Nuclear Information System (INIS)

    Nguyen Trong Anh

    1988-01-01

    The 1988 progress report of the Reaction Mechanisms laboratory (Polytechnic School, France), is presented. The research topics are: the valence bond methods, the radical chemistry, the modelling of the transition states by applying geometric constraints, the long range interactions (ion - molecule) in gaseous phase, the reaction sites in gaseous phase and the mass spectroscopy applications. The points of convergence between the investigations of the mass spectroscopy and the theoretical chemistry teams, as well as the purposes guiding the research programs, are discussed. The published papers, the conferences, the congress communications and the thesis, are also reported [fr

  7. Statistical mechanics

    CERN Document Server

    Sheffield, Scott

    2009-01-01

    In recent years, statistical mechanics has been increasingly recognized as a central domain of mathematics. Major developments include the Schramm-Loewner evolution, which describes two-dimensional phase transitions, random matrix theory, renormalization group theory and the fluctuations of random surfaces described by dimers. The lectures contained in this volume present an introduction to recent mathematical progress in these fields. They are designed for graduate students in mathematics with a strong background in analysis and probability. This book will be of particular interest to graduate students and researchers interested in modern aspects of probability, conformal field theory, percolation, random matrices and stochastic differential equations.

  8. Quantum mechanics

    International Nuclear Information System (INIS)

    Bethge, K.; Gruber, G.

    1978-01-01

    This book is addressed to students of science being in the first terms. Starting from the present knowledge on the structure of atoms the ideas are introduced which are necessary to give a microscopic description of the nature and which are quite different from the classical determinism. The book originates from lectures held for many years at the universities of Heidelberg and Frankfurt. Individual topics are: (1) Atoms, (2) electrons and photons, (3) wave mechanics, (4) the hydrogen atom, (5) multi-electron atoms, (6) the periodic system, (7) atoms in external fields, and (8) di-atomic molecules. (KBE)

  9. Fluid mechanics

    International Nuclear Information System (INIS)

    Paraschivoiu, I.; Prud'homme, M.; Robillard, L.; Vasseur, P.

    2003-01-01

    This book constitutes at the same time theoretical and practical base relating to the phenomena associated with fluid mechanics. The concept of continuum is at the base of the approach developed in this work. The general advance proceeds of simple balances of forces as into hydrostatic to more complex situations or inertias, the internal stresses and the constraints of Reynolds are taken into account. This advance is not only theoretical but contains many applications in the form of solved problems, each chapter ending in a series of suggested problems. The major part of the applications relates to the incompressible flows

  10. Adjustment mechanism

    International Nuclear Information System (INIS)

    1978-01-01

    Mechanism for the variation of the underlying support of a pick-up with a measuring crystal in particular for the application to an X-ray spectrometer, whereby the crystal is placed on a rotatable axle and the pick-up is placed on an arm of a circular track around the axis of the crystal, whereby the crystal axis and the pick-up arm are coupled so that the rotation of the crystal axis and the pickup arm are coupled so that the rotation of the crystal axis over an angle theta is paired with the rotation of the pick-up arm of an angle two-theta, characterised in that around the crystal axis is fixed a first disc with a radius r and wherein a second disc with a radius 2r is superimposed, whereby a mechanism further comprises two guide rollers over each of which a tape or wire is laid whereby each of the tapes is fixed at one end of the first disc and at the other end to the second disc. (G.C.)

  11. Pathogenic mechanisms of pancreatitis

    Science.gov (United States)

    Manohar, Murli; Verma, Alok Kumar; Venkateshaiah, Sathisha Upparahalli; Sanders, Nathan L; Mishra, Anil

    2017-01-01

    Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in promoting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways (i.e., Transforming growth factor-β/SMAD, mitogen-activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8 IL-10, IL-18, IL-33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for

  12. Combined effects of proinflammatory cytokines and intermittent cyclic mechanical strain in inhibiting osteogenicity in human periodontal ligament cells.

    Science.gov (United States)

    Sun, Chaofan; Chen, Lijiao; Shi, Xinlian; Cao, Zhensheng; Hu, Bibo; Yu, Wenbin; Ren, Manman; Hu, Rongdang; Deng, Hui

    2016-09-01

    Mechanical strain plays an important role in bone formation and resorption during orthodontic tooth movement. The mechanism has not been fully studied, and the process becomes complex with increased amounts of periodontal patients seeking orthodontic care. Our aims were to elucidate the combined effects of proinflammatory cytokines and intermittent cyclic strain (ICS) on the osteogenic capacity of human periodontal ligament cells. Cultured human periodontal ligament cells were exposed to proinflammatory cytokines (interleukin-1β 5 ng/mL and tumor necrosis factor-α 10 ng/mL) for 1 and 5 days, and ICS (0.5 Hz, 12% elongation) was applied for 4 h per day. The autocrine of inflammatory cytokines was measured by enzyme-linked immunosorbent assay. The expression of osteoblast markers runt-related transcription factor 2 and rabbit collagen type I was determined using real-time polymerase chain reaction and Western blot. The osteogenic capacity was also detected by alkaline phosphatase (ALP) staining, ALP activity, and alizarin red staining. We demonstrated that ICS impaired the osteogenic capacity of human periodontal ligament cells when incubated with proinflammatory cytokines, as evidenced by the low expression of ALP staining, low ALP activity, reduced alizarin red staining, and reduced osteoblast markers. These data, for the first time, suggest that ICS has a negative effect on the inductive inhibition of osteogenicity in human PDL cells mediated by proinflammatory cytokines. © 2016 International Federation for Cell Biology.

  13. Umbilical mechanism

    Science.gov (United States)

    Barron, Daniel R. (Inventor); Jasulaitis, Vytas (Inventor); Morrill, Brion F. (Inventor)

    1995-01-01

    Apparatus is described for automatically mating a pair of connectors and protecting them prior to mating, which minimizes weight and uses relatively simple and reliable mechanisms. Lower and upper connectors (24, 26) are held in lower and upper parts (14, 16) of a housing, with the upper connector mounted on a carrier (32) that is motor driven to move down and mate the connectors. A pair of movable members (36, 38) serve as shields, as coarse alignment aids, and as force transmitters. The movable members are pivotally mounted at the bottom of the upper housing, and as the carrier moves down it pivots the members out of the way. The movable members have socket elements (116) that closely receive pin elements (120) on the lower housing part, to coarsely align the connectors and to react mating and unmating forces between the housings. The carrier has a pair of plate portions (60, 62) with slots (64), and the movable members have cam followers engaged with the slot walls, to move the members with precision. The carrier plate-like portions engage follower members (82) that pivot open lower shield parts (44, 46) covering the lower connector, which is mounted on four stacks of Belleville washers (142).

  14. Mechanisms of realization of THz-waves of nitrogen oxide occurrence physiological effects

    Directory of Open Access Journals (Sweden)

    Vyacheslav F. Kirichuk

    2013-11-01

    Full Text Available In this review, there is generalized material of many experimental researches in interaction of THz-waves molecular emission and absorption spectrum (MEAS of nitrogen oxide occurrence with bioobjects. Thrombocytes and experimental animals were used as bioobjects. The experiments let indicate changes caused by THz-waves: at the cellular, tissular, system, organismic levels. There are all data of changes in physiological mechanisms of reglations at all levels: autocrine, paracrine, endocrine and nervous. There is a complex overview of experimental material firstly performed in the article. There had been shown that the effect of THz-waves of the given occurrence is realized by the changed activity of nitroxidergic system. It had been proved that THz-waves of nitrogen oxide occurrence can stimulate nitrogen oxide producing in organs and tissues in condition of its low concentration. Possible mechanisms of antiaggregative effect of the given waves had been described. There had been shown the possibility of regulating of vascular tone and system hemodynamics with the help of the studying these frequencies. The represented data of lipid peroxidation and enzymatic and nonenzymatic components of organism system under the influence of THz-waves of nitrogen oxide occurrence in stress conditions. Besides, there were shown changes of stress-regulating system activity and in concentration of important mediators - catecholamines and glucocorticosteroids. These data let characterize mechanism of realization of THz-waves basic effects. The research had shown the possibility of THz-waves of nitrogen oxide occurrence usage as a method of natural physiological noninvasive regulation of significant organism functions.

  15. Autocrine effects of visfatin on hepatocyte sensitivity to insulin action

    Czech Academy of Sciences Publication Activity Database

    Škop, V.; Kontrová, K.; Zídek, Václav; Pravenec, Michal; Kazdová, L.; Mikulík, Karel; Sajdok, J.; Zídková, J.

    2010-01-01

    Roč. 59, č. 4 (2010), s. 615-618 ISSN 0862-8408 R&D Projects: GA AV ČR(CZ) IAA500110805; GA MŠk(CZ) ME08006; GA MZd(CZ) NR9387; GA MZd(CZ) NR9359 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z50200510 Keywords : Visfatin * RNA interference * insulin mimetic effects Subject RIV: FB - Endocrinology, Diabetology, Metabolism , Nutrition Impact factor: 1.646, year: 2010

  16. Neuronal, neurohormonal, and autocrine control of Xenopus melanotrope cell activity

    NARCIS (Netherlands)

    Roubos, E.W.; Scheenen, W.J.J.M.; Jenks, B.G.

    2005-01-01

    Amphibian pituitary melanotropes are used to investigate principles of neuroendocrine translation of neural input into hormonal output. Here, the steps in this translation process are outlined for the melanotrope cell of Xenopus laevis, with attention to external stimuli, neurochemical messengers,

  17. Autocrine regulation of human sperm motility by tachykinins

    Directory of Open Access Journals (Sweden)

    Pinto Francisco M

    2010-08-01

    Full Text Available Abstract Background We examined the presence and function of tachykinins and the tachykinin-degrading enzymes neprilysin (NEP and neprilysin-2 (NEP2 in human spermatozoa. Methods Freshly ejaculated semen was collected from forty-eight normozoospermic human donors. We analyzed the expression of substance P, neurokinin A, neurokinin B, hemokinin-1, NEP and NEP2 in sperm cells by reverse-transcriptase polymerase chain reaction (RT-PCR, western blot and immunocytochemistry assays and evaluated the effects of the neprilysin and neprilysin-2 inhibitor phosphoramidon on sperm motility in the absence and presence of tachykinin receptor-selective antagonists. Sperm motility was measured using WHO procedures or computer-assisted sperm analysis (CASA. Results The mRNAs of the genes that encode substance P/neurokinin A (TAC1, neurokinin B (TAC3, hemokinin-1 (TAC4, neprilysin (MME and neprilysin-2 (MMEL1 were expressed in human sperm. Immunocytochemistry studies revealed that tachykinin and neprilysin proteins were present in spermatozoa and show specific and differential distributions. Phosphoramidon increased sperm progressive motility and its effects were reduced in the presence of the tachykinin receptor antagonists SR140333 (NK1 receptor-selective and SR48968 (NK2 receptor-selective but unmodified in the presence of SR142801 (NK3 receptor-selective. Conclusion These data show that tachykinins are present in human spermatozoa and participate in the regulation of sperm motility. Tachykinin activity is regulated, at least in part, by neprilysins.

  18. Autocrine regulation of human sperm motility by tachykinins.

    Science.gov (United States)

    Pinto, Francisco M; Ravina, Cristina G; Subiran, Nerea; Cejudo-Román, Antonio; Fernández-Sánchez, Manuel; Irazusta, Jon; Garrido, Nicolas; Candenas, Luz

    2010-08-26

    We examined the presence and function of tachykinins and the tachykinin-degrading enzymes neprilysin (NEP) and neprilysin-2 (NEP2) in human spermatozoa. Freshly ejaculated semen was collected from forty-eight normozoospermic human donors. We analyzed the expression of substance P, neurokinin A, neurokinin B, hemokinin-1, NEP and NEP2 in sperm cells by reverse-transcriptase polymerase chain reaction (RT-PCR), western blot and immunocytochemistry assays and evaluated the effects of the neprilysin and neprilysin-2 inhibitor phosphoramidon on sperm motility in the absence and presence of tachykinin receptor-selective antagonists. Sperm motility was measured using WHO procedures or computer-assisted sperm analysis (CASA). The mRNAs of the genes that encode substance P/neurokinin A (TAC1), neurokinin B (TAC3), hemokinin-1 (TAC4), neprilysin (MME) and neprilysin-2 (MMEL1) were expressed in human sperm. Immunocytochemistry studies revealed that tachykinin and neprilysin proteins were present in spermatozoa and show specific and differential distributions. Phosphoramidon increased sperm progressive motility and its effects were reduced in the presence of the tachykinin receptor antagonists SR140333 (NK1 receptor-selective) and SR48968 (NK2 receptor-selective) but unmodified in the presence of SR142801 (NK3 receptor-selective). These data show that tachykinins are present in human spermatozoa and participate in the regulation of sperm motility. Tachykinin activity is regulated, at least in part, by neprilysins.

  19. Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant JAK2 activation.

    Science.gov (United States)

    Gupta, Mamta; Han, Jing Jing; Stenson, Mary; Maurer, Matthew; Wellik, Linda; Hu, Guangzhen; Ziesmer, Steve; Dogan, Ahmet; Witzig, Thomas E

    2012-03-22

    Cytokines are deregulated in cancers and can contribute to tumor growth. In patients with diffuse large-cell lymphoma (DLBCL), we observed higher levels of JAK/STAT pathway-related serum cytokines (ie, IL-6, IL-10, epidermal growth factor, and IL-2) compared with controls. Of these, only IL-10 activated the JAK2 pathway in lymphoma cells in vitro. Patients with high serum IL-10 had shorter event-free survival (EFS) than patients with low levels (P > .01) and high IL-10 was correlated with high lactase dehydrogenase (P = .0085) and higher International Prognostic Index scores (P = .01). To explore the mechanism by which IL-10 may contribute to an inferior EFS, we investigated the effect of IL-10 on the JAK2 pathway and found that the IL-10/IL-10 receptor complex up-regulated JAK2 signaling. Neutralizing Ab to IL-10 inhibited constitutive and IL-10-induced JAK2/STAT3 phosphorylation. JAK2 inhibition dephosphorylated JAK2 and STAT3 and caused an inhibitory effect on phospho-JAK2-positive DLBCL cells; there was a minimal effect on phospho-JAK2-negative cells. Apoptosis induced by JAK2 inhibition was dependent on inhibition of autocrine IL-10 and c-myc expression and independent of Bcl-2 family expression. These results provide the rationale for testing JAK2 inhibitors in DLBCL patients, and indicate that serum IL-10 may be a biomarker to identify patients more likely to respond to JAK2-targeted therapy.

  20. Chitosan/β-1,3-glucan/hydroxyapatite bone scaffold enhances osteogenic differentiation through TNF-α-mediated mechanism.

    Science.gov (United States)

    Przekora, Agata; Ginalska, Grazyna

    2017-04-01

    The role of TNF-α in bone healing process is still unclear and controversial. Although it is commonly believed that TNF-α inhibits osteogenic differentiation, there are few reports that identified a crucial role of TNF-α in enhancing bone regeneration process. The aim of this study was to prove that novel chitosan/β-1,3-glucan/HA scaffold (chit/glu/HA) may promote osteogenic differentiation via TNF-α-mediated mechanism and an autocrine stimulation of osteoblasts. It was demonstrated that normal human fetal osteoblasts (hFOB 1.19) maintained in conditioned medium containing increased level of TNF-α and harvested from hFOB 1.19 cells cultured on the chit/glu/HA scaffold (CM-chit/glu/HA) were in more advanced phase of osteogenic differentiation compared to the osteoblasts cultured in non-conditioned osteogenic medium and conditioned medium harvested from hFOB 1.19 cells cultured on the polystyrene plate. Cells cultured in CM-chit/glu/HA produced significantly more Col I protein, revealed 2-fold higher bALP activity, deposited 3-fold more calcium phosphate, and formed mineralized nodules. Thus, it was demonstrated that novel chit/glu/HA scaffold is promising material for bone regeneration applications to stimulate accelerated new bone formation as it enhances osteogenic differentiation via increasing TNF-α production by osteoblasts. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Effects of every-other-day feeding on prolactin regulatory mechanism in transgenic human growth hormone mice.

    Science.gov (United States)

    Jiménez-Ortega, Vanesa; Masternak, Michal M; Panici, Jacob A; Wang, Zhihui; Bartke, Andrzej; Esquifino, Ana I

    2008-04-01

    Transgenic mice overexpressing human growth hormone (hGH) exhibit accelerated aging with functional hyperprolactinemia and greatly depressed endogenous prolactin. Calorie restriction (CR) is widely recognized as the most effective experimental intervention to delay aging. The aim of the present work was to analyze the effects of lifelong overexpression of hGH on prolactin-gene expression as well as the dopamine production at the pituitary level and discern whether this mechanism changes as a function of feeding patterns. Ten-month-old mice fed every other day (EOD) were killed after one day of fasting. The results confirmed typical phenotypic features of these transgenic mice: an increase in body weight, very high hGH plasma concentrations, and hyperinsulinemia. There was a marked inhibition of the expression of the prolactin gene, together with an increased tyrosine hydroxylase (TH) and the long isoform of dopamine receptor type 2 (D2LR) gene expression at the pituitary level. These parameters were not affected by the EOD feeding pattern. These data may suggest an autocrine or paracrine effect of dopamine at the hypophyseal level on prolactin secretion that is independent of the feeding pattern.

  2. Investigation of Nonholonomic Mechanics, Vakonomic Mechanics ...

    African Journals Online (AJOL)

    In this article, methods of modeling dynamic systems namely, Nonholonomic mechanics, Vakonomic mechanics and Chetaev methods for constrained dynamic system are investigated. The fact that Vakonomic mechanics gives a different motion equation to the other methods is verified using a particular example. It is shown ...

  3. The Mechanics of Mechanical Watches and Clocks

    CERN Document Server

    Du, Ruxu

    2013-01-01

    "The Mechanics of Mechanical Watches and Clocks" presents historical views and mathematical models of mechanical watches and clocks. Although now over six hundred years old, mechanical watches and clocks are still popular luxury items that fascinate many people around the world. However few have examined the theory of how they work as presented in this book. The illustrations and computer animations are unique and have never been published before. It will be of significant interest to researchers in mechanical engineering, watchmakers and clockmakers, as well as people who have an engineering background and are interested in mechanical watches and clocks. It will also inspire people in other fields of science and technology, such as mechanical engineering and electronics engineering, to advance their designs. Professor Ruxu Du works at the Chinese University of Hong Kong, China. Assistant Professor Longhan Xie works at the South China University of Technology, China.

  4. Advances in Applied Mechanics

    OpenAIRE

    2013-01-01

    Advances in Applied Mechanics draws together recent significant advances in various topics in applied mechanics. Published since 1948, Advances in Applied Mechanics aims to provide authoritative review articles on topics in the mechanical sciences, primarily of interest to scientists and engineers working in the various branches of mechanics, but also of interest to the many who use the results of investigations in mechanics in various application areas, such as aerospace, chemical, civil, en...

  5. Tokamak engineering mechanics

    CERN Document Server

    Song, Yuntao; Du, Shijun

    2013-01-01

    Tokamak Engineering Mechanics offers concise and thorough coverage of engineering mechanics theory and application for tokamaks, and the material is reinforced by numerous examples. Chapter topics include general principles, static mechanics, dynamic mechanics, thermal fluid mechanics and multiphysics structural mechanics of tokamak structure analysis. The theoretical principle of the design and the methods of the analysis for various components and load conditions are presented, while the latest engineering technologies are also introduced. The book will provide readers involved in the study

  6. Mechanical engineer's handbook

    CERN Document Server

    Marghitu, Dan B

    2001-01-01

    The Mechanical Engineer's Handbook was developed and written specifically to fill a need for mechanical engineers and mechanical engineering students throughout the world. With over 1000 pages, 550 illustrations, and 26 tables the Mechanical Engineer's Handbook is very comprehensive, yet affordable, compact, and durable. The Handbook covers all major areas of mechanical engineering with succinct coverage of the definitions, formulas, examples, theory, proofs, and explanations of all principle subject areas. The Handbook is an essential, practical companion for all mechanic

  7. Mechanical engineering education

    CERN Document Server

    Davim, J Paulo

    2012-01-01

    Mechanical Engineering is defined nowadays as a discipline "which involves the application of principles of physics, design, manufacturing and maintenance of mechanical systems". Recently, mechanical engineering has also focused on some cutting-edge subjects such as nanomechanics and nanotechnology, mechatronics and robotics, computational mechanics, biomechanics, alternative energies, as well as aspects related to sustainable mechanical engineering.This book covers mechanical engineering higher education with a particular emphasis on quality assurance and the improvement of academic

  8. Mechanics of machinery

    CERN Document Server

    Mostafa, Mahmoud A

    2012-01-01

    MechanismsDefinitions Degrees of Freedom of Planar Mechanisms Four-Revolute-Pairs Chains Single-Slider Chain Double-Slider Mechanisms Mechanisms with Higher Pairs Compound Mechanisms Special Mechanisms Analytical Position Analysis of Mechanisms Velocities and AccelerationsAbsolute Plane Motion of a Particle Relative Motion Applications to Common Links Analysis of Mechanisms: Graphical Method Method of Instantaneous Centers for Determining the VelocitiesAnalytical Analysis CamsIntroduction Types of Cams Modes of Input/Output Motion Follower Configurations Classes of Cams Spur GearsIntroduction

  9. Compliant Space Mechanisms

    Data.gov (United States)

    National Aeronautics and Space Administration — OBJECTIVES The proposed research will combine the areas of compliant mechanisms and space technology. Compliant mechanisms perform their function through the elastic...

  10. Analytical mechanics for relativity and quantum mechanics

    CERN Document Server

    Johns, Oliver Davis

    2011-01-01

    Analytical Mechanics for Relativity and Quantum Mechanics is an innovative and mathematically sound treatment of the foundations of analytical mechanics and the relation of classical mechanics to relativity and quantum theory. It is intended for use at the introductory graduate level. A distinguishing feature of the book is its integration of special relativity into teaching of classical mechanics. After a thorough review of the traditional theory, Part II of the book introduces extended Lagrangian and Hamiltonian methods that treat time as a transformable coordinate rather than the fixed parameter of Newtonian physics. Advanced topics such as covariant Langrangians and Hamiltonians, canonical transformations, and Hamilton-Jacobi methods are simplified by the use of this extended theory. And the definition of canonical transformation no longer excludes the Lorenz transformation of special relativity. This is also a book for those who study analytical mechanics to prepare for a critical exploration of quantum...

  11. Classical Mechanics as Nonlinear Quantum Mechanics

    International Nuclear Information System (INIS)

    Nikolic, Hrvoje

    2007-01-01

    All measurable predictions of classical mechanics can be reproduced from a quantum-like interpretation of a nonlinear Schroedinger equation. The key observation leading to classical physics is the fact that a wave function that satisfies a linear equation is real and positive, rather than complex. This has profound implications on the role of the Bohmian classical-like interpretation of linear quantum mechanics, as well as on the possibilities to find a consistent interpretation of arbitrary nonlinear generalizations of quantum mechanics

  12. Robust Design of Sounds in Mechanical Mechanisms

    DEFF Research Database (Denmark)

    Boegedal Jensen, Annemette; Munch, Natasja; Howard, Thomas J.

    2015-01-01

    Current practices for creating a desired sound by a mechanical mechanism are irrelative design-build-test processes. It seems that very little guidance is available relating design to the sound output. The focus of this study was to identify, which parameters that affect the sound output of a click...... mechanism consisting of a toothed rack and a click arm. First several geometries of the teeth and the click arm’s head were investigated to identify the most robust and repeatable design. It was found that a flat surface in the valleys between the teeth is very beneficial in relation to repeatability...... mechanisms....

  13. Fuzzy clustering of mechanisms

    Indian Academy of Sciences (India)

    type synthesis phase of mechanical design. To the best of the authors' knowledge, this type of clustering of mechanisms has not been attempted before. Thus, this is the first attempt to cluster the mechanisms based on some quantitative measures. It may help the engineers to carry out type synthesis of the mechanisms.

  14. Defense Mechanisms: A Bibliography.

    Science.gov (United States)

    Pedrini, D. T.; Pedrini, Bonnie C.

    This bibliography includes studies of defense mechanisms, in general, and studies of multiple mechanisms. Defense mechanisms, briefly and simply defined, are the unconscious ego defendants against unpleasure, threat, or anxiety. Sigmund Freud deserves the clinical credit for studying many mechanisms and introducing them in professional literature.…

  15. Molecular mechanisms of cancer

    National Research Council Canada - National Science Library

    Weber, Georg F

    2007-01-01

    ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Section I. General Mechanisms of Transformation 1. Theories of Carcinogenesis...

  16. Current Solid Mechanics Research

    DEFF Research Database (Denmark)

    Tvergaard, Viggo

    2016-01-01

    About thirty years ago James Lighthill wrote an essay on “What is Mechanics?” With that he also included some examples of the applications of mechanics. While his emphasis was on fluid mechanics, his own research area, he also included examples from research activities in solid mechanics....

  17. Characterising the mechanism of airway smooth muscle β2 adrenoceptor desensitization by rhinovirus infected bronchial epithelial cells.

    Directory of Open Access Journals (Sweden)

    David Van Ly

    Full Text Available Rhinovirus (RV infections account for approximately two thirds of all virus-induced asthma exacerbations and often result in an impaired response to β2 agonist therapy. Using an in vitro model of RV infection, we investigated the mechanisms underlying RV-induced β2 adrenoceptor desensitization in primary human airway smooth muscle cells (ASMC. RV infection of primary human bronchial epithelial cells (HBEC for 24 hours produced conditioned medium that caused β2 adrenoceptor desensitization on ASMCs without an effect on ASMCs viability. Less than 3 kDa size fractionation together with trypsin digestion of RV-induced conditioned medium did not prevent β2 adrenoceptor desensitization, suggesting it could potentially be mediated by a small peptide or lipid. RV infection of BECs, ASMCs and fibroblasts produced prostaglandins, of which PGE2, PGF2α and PGI2 had the ability to cause β2 adrenoceptor desensitization on ASMCs. RV-induced conditioned medium from HBECs depleted of PGE2 did not prevent ASMC β2 adrenoceptor desensitization; however this medium induced PGE2 from ASMCs, suggesting that autocrine prostaglandin production may be responsible. Using inhibitors of cyclooxygenase and prostaglandin receptor antagonists, we found that β2 adrenoceptor desensitization was mediated through ASMC derived COX-2 induced prostaglandins. Since ASMC prostaglandin production is unlikely to be caused by RV-induced epithelial derived proteins or lipids we next investigated activation of toll-like receptors (TLR by viral RNA. The combination of TLR agonists poly I:C and imiquimod induced PGE2 and β2 adrenoceptor desensitization on ASMC as did the RNA extracted from RV-induced conditioned medium. Viral RNA but not epithelial RNA caused β2 adrenoceptor desensitization confirming that viral RNA and not endogenous human RNA was responsible. It was deduced that the mechanism by which β2 adrenoceptor desensitization occurs was by pattern recognition receptor

  18. Handbook of compliant mechanisms

    CERN Document Server

    Howell, Larry L; Olsen, Brian M

    2013-01-01

    A fully illustrated reference book giving an easy-to-understand introduction to compliant mechanisms A broad compilation of compliant mechanisms to give inspiration and guidance to those interested in using compliant mechanisms in their designs, the Handbook of Compliant Mechanisms includes graphics and descriptions of many compliant mechanisms. It comprises an extensive categorization of devices that can be used to help readers identify compliant mechanisms related to their application. It also provides chapters on the basic background in compliant mechanisms, the categories o

  19. Mechanics and Physics of Precise Vacuum Mechanisms

    CERN Document Server

    Deulin, E. A; Panfilov, Yu V; Nevshupa, R. A

    2010-01-01

    In this book the Russian expertise in the field of the design of precise vacuum mechanics is summarized. A wide range of physical applications of mechanism design in electronic, optical-electronic, chemical, and aerospace industries is presented in a comprehensible way. Topics treated include the method of microparticles flow regulation and its determination in vacuum equipment and mechanisms of electronics; precise mechanisms of nanoscale precision based on magnetic and electric rheology; precise harmonic rotary and not-coaxial nut-screw linear motion vacuum feedthroughs with technical parameters considered the best in the world; elastically deformed vacuum motion feedthroughs without friction couples usage; the computer system of vacuum mechanisms failure predicting. This English edition incorporates a number of features which should improve its usefulness as a textbook without changing the basic organization or the general philosophy of presentation of the subject matter of the original Russian work. Exper...

  20. Tokamak engineering mechanics

    International Nuclear Information System (INIS)

    Song, Yuntao; Wu, Weiyue; Du, Shijun

    2014-01-01

    Provides a systematic introduction to tokamaks in engineering mechanics. Includes design guides based on full mechanical analysis, which makes it possible to accurately predict load capacity and temperature increases. Presents comprehensive information on important design factors involving materials. Covers the latest advances in and up-to-date references on tokamak devices. Numerous examples reinforce the understanding of concepts and provide procedures for design. Tokamak Engineering Mechanics offers concise and thorough coverage of engineering mechanics theory and application for tokamaks, and the material is reinforced by numerous examples. Chapter topics include general principles, static mechanics, dynamic mechanics, thermal fluid mechanics and multiphysics structural mechanics of tokamak structure analysis. The theoretical principle of the design and the methods of the analysis for various components and load conditions are presented, while the latest engineering technologies are also introduced. The book will provide readers involved in the study of mechanical/fusion engineering with a general understanding of tokamak engineering mechanics.

  1. Mechanical engineers' handbook, materials and engineering mechanics

    CERN Document Server

    Kutz, Myer

    2015-01-01

    Full coverage of materials and mechanical design inengineering Mechanical Engineers' Handbook, Fourth Edition provides aquick guide to specialized areas you may encounter in your work,giving you access to the basics of each and pointing you towardtrusted resources for further reading, if needed. The accessibleinformation inside offers discussions, examples, and analyses ofthe topics covered. This first volume covers materials and mechanical design, givingyou accessible and in-depth access to the most common topics you'llencounter in the discipline: carbon and alloy steels, stainlesssteels, a

  2. 507 mechanical movements mechanisms and devices

    CERN Document Server

    Brown, Henry T

    2005-01-01

    Epicyclic trains, oblique rollers, trip hammers, and lazy-tongs are among the ingenious mechanisms defined and illustrated in this intriguing collection. Spanning the first century of the Industrial Revolution, this 1868 compilation features simplified, concise illustrations of the mechanisms used in hydraulics, steam engines, pneumatics, presses, horologes, and scores of other machines.The movements of each of the 507 mechanisms are depicted in drawings on the left-hand page, and the facing page presents a brief description of the item's use and operation. Ranging from simple to intricately c

  3. Foundations of mechanics

    International Nuclear Information System (INIS)

    Zorski, Henryk; Bazanski, Stanislaw; Gutowski, Roman; Slawianowski, Jan; Wilmanski, Krysztof; Wozniak, Czeslaw

    1992-01-01

    In the last 3 decades the field of mechanics has seen spectacular progress due to the demand for applications in problems of cosmology, thermonuclear fusion, metallurgy, etc. This book provides a broad and thorough overview on the foundations of mechanics. It discusses theoretical mechanics and continuum mechanics, as well as phenomenological thermodynamics, quantum mechanics and relativistic mechanics. Each chapter presents the basic physical facts of interest without going into details and derivations and without using advanced mathematical formalism. The first part constitutes a classical exposition of Lagrange's and Hamiltonian's analytical mechanics on which most of the continuum theory is based. The section on continuum mechanics focuses mainly on the axiomatic foundations, with many pointers for further research in this area. Special attention is given to modern continuum thermodynamics, both for the foundations and applications. A section on quantum mechanics is also included, since the phenomenological description of various quantum phenomena is becoming of increasing importance. refs.; figs.; tabs

  4. Verifiably Truthful Mechanisms

    DEFF Research Database (Denmark)

    Branzei, Simina; Procaccia, Ariel D.

    2015-01-01

    It is typically expected that if a mechanism is truthful, then the agents would, indeed, truthfully report their private information. But why would an agent believe that the mechanism is truthful? We wish to design truthful mechanisms, whose truthfulness can be verified efficiently (in...... the computational sense). Our approach involves three steps: (i) specifying the structure of mechanisms, (ii) constructing a verification algorithm, and (iii) measuring the quality of verifiably truthful mechanisms. We demonstrate this approach using a case study: approximate mechanism design without money...

  5. Mechanics of Failure Mechanisms in Structures

    CERN Document Server

    Carlson, R L; Craig, J I

    2012-01-01

    This book focuses on the mechanisms and underlying mechanics of failure in various classes of materials such as metallic, ceramic, polymeric, composite and bio-material.  Topics include tensile and compressive fracture, crack initiation and growth, fatigue and creep rupture in metallic materials, matrix cracking and delamination and environmental degradation in polymeric composites, failure of bio-materials such as prosthetic heart valves and prosthetic hip joints, failure of ceramics and ceramic matrix composites, failure of metallic matrix composites, static and dynamic buckling failure, dynamic excitations and creep buckling failure in structural systems. Chapters are devoted to failure mechanisms that are characteristic of each of the materials.  The work also provides the basic elements of fracture mechanics and studies in detail several niche topics such as the effects of toughness gradients, variable amplitude loading effects in fatigue, small fatigue cracks, and creep induced brittleness. Furthe...

  6. Environmental Compliance Mechanisms

    NARCIS (Netherlands)

    Merkouris, Panagiotis; Fitzmaurice, Malgosia

    2017-01-01

    Compliance mechanisms can be found in treaties regulating such diverse issues as human rights, disarmament law, and environmental law. In this bibliography, the focus will be on compliance mechanisms of multilateral environmental agreements (MEAs). Compliance with norms of international

  7. STRUCTURE OF ECONOMIC MECHANISM

    Directory of Open Access Journals (Sweden)

    L. I. Podderegina

    2006-01-01

    Full Text Available The paper considers and analyzes scientific approaches of economists to the essence and contents of the economic mechanism. Proposals for methodological formation of economic mechanism structure are substantiated in the paper.

  8. Mechanical restraint in psychiatry

    DEFF Research Database (Denmark)

    Bak, Jesper; Zoffmann, Vibeke; Sestoft, Dorte Maria

    2014-01-01

    PURPOSE: To examine how potential mechanical restraint preventive factors in hospitals are associated with the frequency of mechanical restraint episodes. DESIGN AND METHODS: This study employed a retrospective association design, and linear regression was used to assess the associations. FINDINGS...

  9. Design of mechanical joints

    CERN Document Server

    Blake, Alexander

    2018-01-01

    A cornerstone publication that covers the basic principles and practical considerations of design methodology for joints held by rivets, bolts, weld seams, and adhesive materials, Design of Mechanical Joints gives engineers the practical results and formulas they need for the preliminary design of mechanical joints, combining the essential topics of joint mechanics...strength of materials...and fracture control to provide a complete treatment of problems pertinent to the field of mechanical connections.

  10. Project mechanisms challenges

    International Nuclear Information System (INIS)

    Perthuis, Ch. de

    2005-06-01

    The project mechanism complete the quotas systems concerning the carbon dioxide emissions market. The author explains and discusses these mechanisms and provides a panorama of the existing and developing projects. More specially she brings information on the mechanism of clean developments and renewable energies, the coordinated mechanisms, the agricultural projects, the financing of the projects and the exchange systeme of the New south Wales. (A.L.B.)

  11. Methods of celestial mechanics

    CERN Document Server

    Brouwer, Dirk

    2013-01-01

    Methods of Celestial Mechanics provides a comprehensive background of celestial mechanics for practical applications. Celestial mechanics is the branch of astronomy that is devoted to the motions of celestial bodies. This book is composed of 17 chapters, and begins with the concept of elliptic motion and its expansion. The subsequent chapters are devoted to other aspects of celestial mechanics, including gravity, numerical integration of orbit, stellar aberration, lunar theory, and celestial coordinates. Considerable chapters explore the principles and application of various mathematical metho

  12. Fuzzy clustering of mechanisms

    Indian Academy of Sciences (India)

    During the course of development of Mechanical Engineering, a large number of mechanisms (that is, linkages to perform various types of tasks) have been conceived and developed. Quite a few atlases and catalogues were prepared by the designers of machines and mechanical systems. However, often it is felt that a ...

  13. Defining Game Mechanics

    DEFF Research Database (Denmark)

    Sicart (Vila), Miguel Angel

    2008-01-01

    This article defins game mechanics in relation to rules and challenges. Game mechanics are methods invoked by agents for interacting with the game world. I apply this definition to a comparative analysis of the games Rez, Every Extend Extra and Shadow of the Colossus that will show the relevance...... of a formal definition of game mechanics. Udgivelsesdato: Dec 2008...

  14. Fundamental Fluid Mechanics

    Indian Academy of Sciences (India)

    BOOK I REVIEW. Fundamental Fluid. Mechanics. Good Text Book Material. V H Arakeri. Fluid Mechanics for Engineers. P N Chatterjee. MacMillan India Limited. Vol. 1, pp. 367. RS.143. Vo1.2, pp.306. RS.130. Fluid Mechanics for Engineers in two vol- umes by P N Chatterjee contains standard material for a first level ...

  15. Fuzzy clustering of mechanisms

    Indian Academy of Sciences (India)

    two clustering techniques, the mechanisms have been classified in the present work and in future, it may be extended to develop an expert system, which can automate type synthesis phase of mechanical design. To the best of the authors' knowledge, this type of clustering of mechanisms has not been attempted before.

  16. Randomness in Classical Mechanics and Quantum Mechanics

    Science.gov (United States)

    Volovich, Igor V.

    2011-03-01

    The Copenhagen interpretation of quantum mechanics assumes the existence of the classical deterministic Newtonian world. We argue that in fact the Newton determinism in classical world does not hold and in the classical mechanics there is fundamental and irreducible randomness. The classical Newtonian trajectory does not have a direct physical meaning since arbitrary real numbers are not observable. There are classical uncertainty relations: Δ q>0 and Δ p>0, i.e. the uncertainty (errors of observation) in the determination of coordinate and momentum is always positive (non zero). A "functional" formulation of classical mechanics was suggested. The fundamental equation of the microscopic dynamics in the functional approach is not the Newton equation but the Liouville equation for the distribution function of the single particle. Solutions of the Liouville equation have the property of delocalization which accounts for irreversibility. The Newton equation in this approach appears as an approximate equation describing the dynamics of the average values of the position and momenta for not too long time intervals. Corrections to the Newton trajectories are computed. An interpretation of quantum mechanics is attempted in which both classical and quantum mechanics contain fundamental randomness. Instead of an ensemble of events one introduces an ensemble of observers.

  17. Respiratory mechanics in mechanically ventilated patients.

    Science.gov (United States)

    Hess, Dean R

    2014-11-01

    Respiratory mechanics refers to the expression of lung function through measures of pressure and flow. From these measurements, a variety of derived indices can be determined, such as volume, compliance, resistance, and work of breathing. Plateau pressure is a measure of end-inspiratory distending pressure. It has become increasingly appreciated that end-inspiratory transpulmonary pressure (stress) might be a better indicator of the potential for lung injury than plateau pressure alone. This has resulted in a resurgence of interest in the use of esophageal manometry in mechanically ventilated patients. End-expiratory transpulmonary pressure might also be useful to guide the setting of PEEP to counterbalance the collapsing effects of the chest wall. The shape of the pressure-time curve might also be useful to guide the setting of PEEP (stress index). This has focused interest in the roles of stress and strain to assess the potential for lung injury during mechanical ventilation. This paper covers both basic and advanced respiratory mechanics during mechanical ventilation. Copyright © 2014 by Daedalus Enterprises.

  18. Mechanics of microelectromechanical systems

    CERN Document Server

    Lobontiu, Nicolae

    2005-01-01

    This book offers a comprehensive coverage to the mechanics of microelectromechanical systems (MEMS), which are analyzed from a mechanical engineer's viewpoint as devices that transform an input form of energy into output mechanical motion (in the case of actuation) or that can operate with the reversed functionality (as in sensors) and convert an external stimulus, such as mechanical motion, into (generally) electric energy. The impetus of this proposal stems from the perception that such an approach might contribute to a more solid understanding of the principles governing the mechanics of ME

  19. Sectoral Market Mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-07-01

    This paper first reviews proposals for the design of sectoral and related market mechanisms currently debated, both in the UNFCCC negotiations, and in different domestic legislative contexts. Secondly, it addresses the possible principles and technical requirements that Parties may wish to consider as the foundations for further elaboration of the mechanisms. The third issue explored herein is domestic implementation of sectoral market mechanisms by host countries, incentives to move to new market mechanisms, as well as how the transition between current and future mechanisms could be managed.

  20. Mechanisms, Transmissions and Applications

    CERN Document Server

    Corves, Burkhard

    2012-01-01

    The first Workshop on Mechanisms, Transmissions and Applications -- MeTrApp-2011 was organized by the Mechatronics Department at the Mechanical Engineering Faculty, “Politehnica” University of Timisoara, Romania, under the patronage of the IFToMM Technical Committees Linkages and Mechanical Controls and Micromachines. The workshop brought together researchers and students who work in disciplines associated with mechanisms science and offered a great opportunity for scientists from all over the world to present their achievements, exchange innovative ideas and create solid international links, setting the trend for future developments in this important and creative field. The topics treated in this volume are mechanisms and machine design, mechanical transmissions, mechatronic and biomechanic applications, computational and experimental methods, history of mechanism and machine science and teaching methods.

  1. Mechanical Seal Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Kotlyar, Oleg M.

    1999-06-18

    An improved mechanical seal assembly is provided for sealing rotating shafts with respect to their shaft housings, wherein the rotating shafts are subject to substantial axial vibrations. The mechanical seal assembly generally includes a rotating sealing ring fixed to the shaft, a non-rotating sealing ring adjacent to and in close contact with the rotating sealing ring for forming an annular seal about the shaft, and a mechanical diode element that applies a biasing force to the non-rotating sealing ring by means of hemispherical joint. The alignment of the mechanical diode with respect to the sealing rings is maintained by a series of linear bearings positioned axially along a desired length of the mechanical diode. Alternative embodiments include mechanical or hydraulic amplification components for amplifying axial displacement of the non-rotating sealing ring and transferring it to the mechanical diode.

  2. Mechanical seal assembly

    Science.gov (United States)

    Kotlyar, Oleg M.

    2001-01-01

    An improved mechanical seal assembly is provided for sealing rotating shafts with respect to their shaft housings, wherein the rotating shafts are subject to substantial axial vibrations. The mechanical seal assembly generally includes a rotating sealing ring fixed to the shaft, a non-rotating sealing ring adjacent to and in close contact with the rotating sealing ring for forming an annular seal about the shaft, and a mechanical diode element that applies a biasing force to the non-rotating sealing ring by means of hemispherical joint. The alignment of the mechanical diode with respect to the sealing rings is maintained by a series of linear bearings positioned axially along a desired length of the mechanical diode. Alternative embodiments include mechanical or hydraulic amplification components for amplifying axial displacement of the non-rotating sealing ring and transferring it to the mechanical diode.

  3. Mechanical Systems, Classical Models

    CERN Document Server

    Teodorescu, Petre P

    2007-01-01

    All phenomena in nature are characterized by motion; this is an essential property of matter, having infinitely many aspects. Motion can be mechanical, physical, chemical or biological, leading to various sciences of nature, mechanics being one of them. Mechanics deals with the objective laws of mechanical motion of bodies, the simplest form of motion. In the study of a science of nature mathematics plays an important role. Mechanics is the first science of nature which was expressed in terms of mathematics by considering various mathematical models, associated to phenomena of the surrounding nature. Thus, its development was influenced by the use of a strong mathematical tool; on the other hand, we must observe that mechanics also influenced the introduction and the development of many mathematical notions. In this respect, the guideline of the present book is precisely the mathematical model of mechanics. A special accent is put on the solving methodology as well as on the mathematical tools used; vectors, ...

  4. The Antikythera mechanism and the mechanical universe

    Science.gov (United States)

    Edmunds, M. G.

    2014-10-01

    How did our view of the Universe develop? By the mid-eighteenth century, a world view had developed of a system constrained by physical laws. These laws, if not entirely understood, showed regularity and could be handled mathematically to provide both explanation and prediction of celestial phenomena. Most of us have at least some hazy idea of the fundamental shift that came through the work of Copernicus, Kepler, Galileo and Newton. The idea of a 'Mechanical Universe' running rather like a clock tends to be associated with these sixteenth- and seventeenth-century pioneers. It remains a useful - and perhaps comforting - analogy. Yet, recent investigations based around the Antikythera Mechanism, an artefact from ancient Greece, reinforce a view that the 'Mechanical' conception has been around for a much longer time - indeed certainly as far back as the third century BC. The extent of mechanical design expertise existing around 100 BC as witnessed by the Antikythera Mechanism comes as a great surprise to most people. It is certainly a very ingenious device, often referred to as 'The World's First Computer' although it is really a sophisticated mechanical astronomical calculator with its functions pre-determined rather than programmable. In this review, the structure and functions of the Antikythera Mechanism are described. The astronomy, cosmology and technology inherent in the machine fit surprisingly well into the context of its contemporary Classical world. A strong claim will be made for the influence of such mechanisms on the development of astronomical and philosophical views, based on literary reference. There is evidence that the technology persisted until its spectacular and rather sudden re-appearance in Western Europe around 1300 AD. From then on it is not hard to chart a path through the astronomical clocks of the sixteenth century to Kepler's aim (expressed in a 1605 letter) to 'show that the heavenly machine is not a kind of divine, live being, but a

  5. Understanding the mechanisms of lung mechanical stress

    Directory of Open Access Journals (Sweden)

    C.S.N.B. Garcia

    2006-06-01

    Full Text Available Physical forces affect both the function and phenotype of cells in the lung. Bronchial, alveolar, and other parenchymal cells, as well as fibroblasts and macrophages, are normally subjected to a variety of passive and active mechanical forces associated with lung inflation and vascular perfusion as a result of the dynamic nature of lung function. These forces include changes in stress (force per unit area or strain (any forced change in length in relation to the initial length and shear stress (the stress component parallel to a given surface. The responses of cells to mechanical forces are the result of the cell's ability to sense and transduce these stimuli into intracellular signaling pathways able to communicate the information to its interior. This review will focus on the modulation of intracellular pathways by lung mechanical forces and the intercellular signaling. A better understanding of the mechanisms by which lung cells transduce physical forces into biochemical and biological signals is of key importance for identifying targets for the treatment and prevention of physical force-related disorders.

  6. Thermomechanical fatigue–Damage mechanisms and mechanism ...

    Indian Academy of Sciences (India)

    An existing extensive database on the isothermal and thermomechanical fatigue behaviour of high-temperature titanium alloy IMI 834 and dispersoidstrengthened aluminum alloy X8019 in SiC particle-reinforced as well as unreinforced conditions was used to evaluate both the adaptability of fracture mechanics approaches ...

  7. Auto Mechanics: Auto Mechanic Service Specialist (Lubrication).

    Science.gov (United States)

    Hoover, Virgil

    The unit of individualized learning activities is designed to provide training in the job skill, lubrication, for the prospective auto mechanic service specialist. The materials in the unit are divided into two sections. The developmental, or preliminary phase, for use by the instructor, includes brief descriptions of the job and of the student…

  8. Cell mechanics: a dialogue

    Science.gov (United States)

    Tao, Jiaxiang; Li, Yizeng; Vig, Dhruv K.; Sun, Sean X.

    2017-03-01

    Under the microscope, eukaryotic animal cells can adopt a variety of different shapes and sizes. These cells also move and deform, and the physical mechanisms driving these movements and shape changes are important in fundamental cell biology, tissue mechanics, as well as disease biology. This article reviews some of the basic mechanical concepts in cells, emphasizing continuum mechanics description of cytoskeletal networks and hydrodynamic flows across the cell membrane. We discuss how cells can generate movement and shape changes by controlling mass fluxes at the cell boundary. These mass fluxes can come from polymerization/depolymerization of actin cytoskeleton, as well as osmotic and hydraulic pressure-driven flow of water across the cell membrane. By combining hydraulic pressure control with force balance conditions at the cell surface, we discuss a quantitative mechanism of cell shape and volume control. The broad consequences of this model on cell mechanosensation and tissue mechanics are outlined.

  9. Nonholonomic mechanics and control

    CERN Document Server

    Murray, RM

    2015-01-01

    This book explores some of the connections between control theory and geometric mechanics; that is, control theory is linked with a geometric view of classical mechanics in both its Lagrangian and Hamiltonian formulations and in particular with the theory of mechanical systems subject to motion constraints. The synthesis of the topic is appropriate as there is a particularly rich connection between mechanics and nonlinear control theory. The book provides a unified treatment of nonlinear control theory and constrained mechanical systems and illustrates the elegant mathematics behind many simple, interesting, and useful mechanical examples. It is intended for graduate students who wish to learn this subject and researchers in the area who want to enhance their techniques. The book contains sections focusing on physical examples and elementary terms, as well as theoretical sections that use sophisticated analysis and geometry. The first four chapters offer preliminaries and background information, while the...

  10. Mechanical meta-materials

    OpenAIRE

    Zadpoor, A.A.

    2016-01-01

    The emerging concept of mechanical meta-materials has received increasing attention during the last few years partially due to the advances in additive manufacturing techniques that have enabled fabricating materials with arbitrarily complex micro/nano-architectures. The rationally designed micro/nano-architecture of mechanical meta-materials gives rise to unprecedented or rare mechanical properties that could be exploited to create advanced materials with novel functionalities. This paper pr...

  11. Problems in quantum mechanics

    CERN Document Server

    Constantinescu, Florin; Spiers, JA

    1971-01-01

    International Series in Natural Philosophy, Volume 30: Problems in Quantum Mechanics focuses on the processes, principles, reactions, and methodologies involved in quantum mechanics. The publication first elaborates on the mathematical formalism of quantum mechanics, simple quantum systems, and mean values and uncertainty relations. Discussions focus on mean values of dynamical variables, uncertainty relations, eigenfunctions and the energy spectrum, motion in a central field, matrix representation of vectors and operators, Hubert spaces, and operators in Hilbert space. The text then takes a l

  12. Equilibrium statistical mechanics

    CERN Document Server

    Jackson, E Atlee

    2000-01-01

    Ideal as an elementary introduction to equilibrium statistical mechanics, this volume covers both classical and quantum methodology for open and closed systems. Introductory chapters familiarize readers with probability and microscopic models of systems, while additional chapters describe the general derivation of the fundamental statistical mechanics relationships. The final chapter contains 16 sections, each dealing with a different application, ordered according to complexity, from classical through degenerate quantum statistical mechanics. Key features include an elementary introduction t

  13. Quantum mechanics in chemistry

    CERN Document Server

    Schatz, George C

    2002-01-01

    Intended for graduate and advanced undergraduate students, this text explores quantum mechanical techniques from the viewpoint of chemistry and materials science. Dynamics, symmetry, and formalism are emphasized. An initial review of basic concepts from introductory quantum mechanics is followed by chapters examining symmetry, rotations, and angular momentum addition. Chapter 4 introduces the basic formalism of time-dependent quantum mechanics, emphasizing time-dependent perturbation theory and Fermi's golden rule. Chapter 5 sees this formalism applied to the interaction of radiation and matt

  14. Equilibrium statistical mechanics

    CERN Document Server

    Mayer, J E

    1968-01-01

    The International Encyclopedia of Physical Chemistry and Chemical Physics, Volume 1: Equilibrium Statistical Mechanics covers the fundamental principles and the development of theoretical aspects of equilibrium statistical mechanics. Statistical mechanical is the study of the connection between the macroscopic behavior of bulk matter and the microscopic properties of its constituent atoms and molecules. This book contains eight chapters, and begins with a presentation of the master equation used for the calculation of the fundamental thermodynamic functions. The succeeding chapters highlight t

  15. Testing Nonassociative Quantum Mechanics.

    Science.gov (United States)

    Bojowald, Martin; Brahma, Suddhasattwa; Büyükçam, Umut

    2015-11-27

    The familiar concepts of state vectors and operators in quantum mechanics rely on associative products of observables. However, these notions do not apply to some exotic systems such as magnetic monopoles, which have long been known to lead to nonassociative algebras. Their quantum physics has remained obscure. This Letter presents the first derivation of potentially testable physical results in nonassociative quantum mechanics, based on effective potentials. They imply new effects which cannot be mimicked in usual quantum mechanics with standard magnetic fields.

  16. Extended quantum mechanics

    International Nuclear Information System (INIS)

    Pavel Bona

    2000-01-01

    The work can be considered as an essay on mathematical and conceptual structure of nonrelativistic quantum mechanics which is related here to some other (more general, but also to more special and 'approximative') theories. Quantum mechanics is here primarily reformulated in an equivalent form of a Poisson system on the phase space consisting of density matrices, where the 'observables', as well as 'symmetry generators' are represented by a specific type of real valued (densely defined) functions, namely the usual quantum expectations of corresponding selfjoint operators. It is shown in this paper that inclusion of additional ('nonlinear') symmetry generators (i. e. 'Hamiltonians') into this reformulation of (linear) quantum mechanics leads to a considerable extension of the theory: two kinds of quantum 'mixed states' should be distinguished, and operator - valued functions of density matrices should be used in the role of 'nonlinear observables'. A general framework for physical theories is obtained in this way: By different choices of the sets of 'nonlinear observables' we obtain, as special cases, e.g. classical mechanics on homogeneous spaces of kinematical symmetry groups, standard (linear) quantum mechanics, or nonlinear extensions of quantum mechanics; also various 'quasiclassical approximations' to quantum mechanics are all sub theories of the presented extension of quantum mechanics - a version of the extended quantum mechanics. A general interpretation scheme of extended quantum mechanics extending the usual statistical interpretation of quantum mechanics is also proposed. Eventually, extended quantum mechanics is shown to be (included into) a C * -algebraic (hence linear) quantum theory. Mathematical formulation of these theories is presented. The presentation includes an analysis of problems connected with differentiation on infinite-dimensional manifolds, as well as a solution of some problems connected with the work with only densely defined unbounded

  17. Mechanical spectral shift reactor

    International Nuclear Information System (INIS)

    Wilson, J.F.; Sherwood, D.G.

    1982-01-01

    A mechanical spectral shift reactor comprises a reactive core having fuel assemblies accommodating both water displacer elements and neutron absorbing control rods for selectively changing the volume of water-moderator in the core. The fuel assemblies with displacer and control rods are arranged in alternating fashion so that one displacer element drive mechanism may move displacer elements in more than one fuel assembly without interfering with the movement of control rods of a corresponding control rod drive mechanisms. (author)

  18. Bacterial Cell Mechanics.

    Science.gov (United States)

    Auer, George K; Weibel, Douglas B

    2017-07-25

    Cellular mechanical properties play an integral role in bacterial survival and adaptation. Historically, the bacterial cell wall and, in particular, the layer of polymeric material called the peptidoglycan were the elements to which cell mechanics could be primarily attributed. Disrupting the biochemical machinery that assembles the peptidoglycan (e.g., using the β-lactam family of antibiotics) alters the structure of this material, leads to mechanical defects, and results in cell lysis. Decades after the discovery of peptidoglycan-synthesizing enzymes, the mechanisms that underlie their positioning and regulation are still not entirely understood. In addition, recent evidence suggests a diverse group of other biochemical elements influence bacterial cell mechanics, may be regulated by new cellular mechanisms, and may be triggered in different environmental contexts to enable cell adaptation and survival. This review summarizes the contributions that different biomolecular components of the cell wall (e.g., lipopolysaccharides, wall and lipoteichoic acids, lipid bilayers, peptidoglycan, and proteins) make to Gram-negative and Gram-positive bacterial cell mechanics. We discuss the contribution of individual proteins and macromolecular complexes in cell mechanics and the tools that make it possible to quantitatively decipher the biochemical machinery that contributes to bacterial cell mechanics. Advances in this area may provide insight into new biology and influence the development of antibacterial chemotherapies.

  19. Mechanisms of galanin-induced contraction in the rat myometrium

    Science.gov (United States)

    Niiro, Naohisa; Nishimura, Junji; Hirano, Katsuya; Nakano, Hitoo; Kanaide, Hideo

    1998-01-01

    A neuropeptide, galanin, regulates the reproductive process and directly induces myometrial contraction. The aim of this study was to determine the mechanism of galanin-induced myometrial contraction. For this purpose, we simultaneously measured intracellular Ca2+ concentration ([Ca2+]i) and tension using fura-PE3-fluorometry and the rat longitudinal myometrium. The effect of galanin on the Ca2+ sensitivity of the contractile apparatus was examined in β-escin permeabilized strips. The expression of galanin and the galanin receptors mRNAs in the rat myometrium were determined by reverse transcription polymerase chain reaction (RT-PCR). Galanin (10–300 nM) induced phasic contraction with or without oscillation in the pregnant rat myometrium in a concentration-dependent manner. The maximal response was obtained at 100 nM. There was no significant difference either in the maximal responses or EC50 values for galanin-induced myometrial contractions among myometriums from non-pregnant and pregnant (day 4, day 11, day 20, day 22) rats. In the day 20 and 22 pregnant myometriums, assigning the levels of [Ca2+]i and tension at 40 mM K+-depolarization to be 100%, galanin increased the [Ca2+]i and tension to 126.9±2.9% and 116.3±2.7%, respectively. Diltiazem (10 μM) inhibited the galanin-induced elevation of [Ca2+]i and tension to 71.9±2.4% and 16.2±0.7%, respectively. Ni2+, by itself, decreased the basal [Ca2+]i to −50.2±3.9% without affecting resting tension. After Ni2+ treatment, galanin-induced increases in [Ca2+]i and tension were −19.6±3.4% and 0.9±0.1%, respectively. In myometrium treated with diltiazem, no oscillation in [Ca2+]i and tension was observed. In Ca2+-free solution with 0.1 mM EGTA, galanin increased [Ca2+]i from −40.2±2.7% to −18.0±2.6% and induced transient contraction (3.6±0.8%). In β-escin permeabilized myometrium, galanin enhanced the contraction induced by 0.3 μM Ca2+ in the presence of GTP. In the presence of GDP

  20. Contact Hamiltonian mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Bravetti, Alessandro, E-mail: alessandro.bravetti@iimas.unam.mx [Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad Nacional Autónoma de México, A. P. 70543, México, DF 04510 (Mexico); Cruz, Hans, E-mail: hans@ciencias.unam.mx [Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, A. P. 70543, México, DF 04510 (Mexico); Tapias, Diego, E-mail: diego.tapias@nucleares.unam.mx [Facultad de Ciencias, Universidad Nacional Autónoma de México, A.P. 70543, México, DF 04510 (Mexico)

    2017-01-15

    In this work we introduce contact Hamiltonian mechanics, an extension of symplectic Hamiltonian mechanics, and show that it is a natural candidate for a geometric description of non-dissipative and dissipative systems. For this purpose we review in detail the major features of standard symplectic Hamiltonian dynamics and show that all of them can be generalized to the contact case.

  1. Infection and inflammatory mechanisms

    NARCIS (Netherlands)

    Van Dyke, Thomas E.; van Winkelhoff, Arie Jan

    This introductory article examines the potential mechanisms that may play a role in the associations between periodontitis and the systemic conditions being considered in the EFP/AAP Workshop in Segovia, Spain. Three basic mechanisms have been postulated to play a role in these interactions;

  2. Shooting mechanisms in nature

    NARCIS (Netherlands)

    Sakes, Aimée; Wiel, van der Marleen; Henselmans, Paul W.J.; Leeuwen, van Johan L.; Dodou, Dimitra; Breedveld, Paul

    2016-01-01

    Background In nature, shooting mechanisms are used for a variety of purposes, including prey capture, defense, and reproduction. This review offers insight into the working principles of shooting mechanisms in fungi, plants, and animals in the light of the specific functional demands that these

  3. Problems in quantum mechanics

    CERN Document Server

    Goldman, Iosif Ilich; Geilikman, B T

    2006-01-01

    This challenging book contains a comprehensive collection of problems in nonrelativistic quantum mechanics of varying degrees of difficulty. It features answers and completely worked-out solutions to each problem. Geared toward advanced undergraduates and graduate students, it provides an ideal adjunct to any textbook in quantum mechanics.

  4. Advances in applied mechanics

    CERN Document Server

    Wu, Theodore Y; Wu, Theodore Y

    2000-01-01

    This highly acclaimed series provides survey articles on the present state and future direction of research in important branches of applied solid and fluid mechanics. Mechanics is defined as a branch of physics that focuses on motion and on the reaction of physical systems to internal and external forces.

  5. Fracture Mechanics of Concrete

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    This special issue of S¯adhan¯a is rightly dedicated to the fracture mechanics of concrete. In particular, the size effect is highlighted. As appropriately pointed out in the first inter- national conference on fracture mechanics of concrete structures, FraMCos-I, organized by Z P Ba˘zant, at Breckenridge, Colorado in 1992, ...

  6. Working group inciting mechanisms

    International Nuclear Information System (INIS)

    Bureau, D.

    2001-01-01

    This document deals with the inciting mechanisms under consideration in the framework of the greenhouse effect fight. The advantages and disadvantages, the coherence of these mechanisms and their articulation with the taxation, have been specified. A whole evaluation of the various scenario, taking into account the implementing problems and the evolution in an international context, is proposed. (A.L.B.)

  7. SOFC Cathode Mechanisms

    DEFF Research Database (Denmark)

    Jacobsen, Torben; Zachau-Christiansen, Birgit; Bay, Lasse

    1996-01-01

    litterature. It is argued that this kind of mechanism can only partly explain the experimental observations. The capacitive part of the low frequency response at anodic potentials is shown to be due to gas enclosures at the lectrode-electrolyte interface. As to the inductive activation mechanism...

  8. Why quantum mechanics?

    International Nuclear Information System (INIS)

    Landsberg, P.T.

    1988-01-01

    It is suggested that an oversight occurred in classical mechanics when time-derivatives of observables were treated on the same footing as the undifferentiated observables. Removal of this oversight points in the direction of quantum mechanics. Additional light is thrown on uncertainty relations and on quantum mechanics, as a possible form of a subtle statistical mechanics, by the formulation of a classical uncertainty relation for a very simple model. The existence of universal motion, i.e., of zero-point energy, is lastly made plausible in terms of a gravitational constant which is time-dependent. By these three considerations an attempt is made to link classical and quantum mechanics together more firmly, thus giving a better understanding of the latter

  9. Radiopharmaceutical cellular uptake mechanisms

    International Nuclear Information System (INIS)

    Stefanescu, Cipriana; Rusu, V.

    1996-01-01

    Cellular radiopharmaceutical specificity depends mainly of the uptake mechanisms. Usually, this can be one of the classical membrane transport type (a passive or active transport, a receptor mediated one or a combination of them). It can also be an electrochemical gradient dependent membrane transport in relation with Nernst equation, as in case of 99m Tc MIBI, the representative molecule of a widely studied family tracers, with applications in cardiac and oncological scintigraphy. Another mechanism can be an ATP dependent active transport, that results in the most important 201 Tl inflow. 201 Tl inflow is also an example of multiple mechanisms involved in cellular ionic inflow. Over 30% of 201 Tl transport imply other ways, like Na + - K + - Cl - co-transport. For a given tracer, the mechanism may depend also on the cell type. In conclusion, knowledge of the radiotracer uptake mechanisms allows finding the 'ideal' radiotracer with high specificity for the tissue to be visualized. (authors)

  10. Engineering quantum mechanics

    CERN Document Server

    Ahn, Doyeol

    2011-01-01

    A clear introduction to quantum mechanics concepts Quantum mechanics has become an essential tool for modern engineering, particularly due to the recent developments in quantum computing as well as the rapid progress in optoelectronic devices. Engineering Quantum Mechanics explains the fundamentals of this exciting field, providing broad coverage of both traditional areas such as semiconductor and laser physics as well as relatively new yet fast-growing areas such as quantum computation and quantum information technology. The book begins with basic quantum mechanics, reviewing measurements and probability, Dirac formulation, the uncertainty principle, harmonic oscillator, angular momentum eigenstates, and perturbation theory. Then, quantum statistical mechanics is explored, from second quantization and density operators to coherent and squeezed states, coherent interactions between atoms and fields, and the Jaynes-Cummings model. From there, the book moves into elementary and modern applications, discussing s...

  11. Membrane quantum mechanics

    Directory of Open Access Journals (Sweden)

    Tadashi Okazaki

    2015-01-01

    Full Text Available We consider the multiple M2-branes wrapped on a compact Riemann surface and study the arising quantum mechanics by taking the limit where the size of the Riemann surface goes to zero. The IR quantum mechanical models resulting from the BLG-model and the ABJM-model compactified on a torus are N=16 and N=12 superconformal gauged quantum mechanics. After integrating out the auxiliary gauge fields we find OSp(16|2 and SU(1,1|6 quantum mechanics from the reduced systems. The curved Riemann surface is taken as a holomorphic curve in a Calabi–Yau space to preserve supersymmetry and we present a prescription of the topological twisting. We find the N=8 superconformal gauged quantum mechanics that may describe the motion of two wrapped M2-branes in a K3 surface.

  12. Quantum mechanics for pedestrians

    CERN Document Server

    Pade, Jochen

    2014-01-01

    This book provides an introduction into the fundamentals of non-relativistic quantum mechanics. In Part 1, the essential principles are developed. Applications and extensions of the formalism can be found in Part 2. The book includes not only material that is presented in traditional textbooks on quantum mechanics, but also discusses in detail current issues such as interaction-free quantum measurements, neutrino oscillations, various topics in the field of quantum information as well as fundamental problems and epistemological questions, such as the measurement problem, entanglement, Bell's inequality, decoherence, and the realism debate. A chapter on current interpretations of quantum mechanics concludes the book. To develop quickly and clearly the main principles of quantum mechanics and its mathematical formulation, there is a systematic change between wave mechanics and algebraic representation in the first chapters. The required mathematical tools are introduced step by step. Moreover, the appendix coll...

  13. Mechanical Testing of MLCCs

    Science.gov (United States)

    Teverovsky, Alexander A.

    2016-01-01

    Cracking of multilayer ceramic capacitors, MLCCs, remains a serious problem for space systems. This problem increases substantially for large size capacitors and in cases when manual soldering is involved or the system experiences mechanical shock or vibration. In any case, a fracture occurs when the sum of external and internal mechanical stresses exceeds the strength of the part. To reduce the probability of cracking, the level of stress should be reduced, e.g. by optimizing the assembly workmanship and rules for board design, and the strength of the parts increased by selecting the most mechanically robust capacitors. The latter might possibly be achieved by selecting MLCCs based on the in-situ measurements of mechanical characteristics using four types of tests: flexural strength, hardness, fracture toughness, and flex bend testing. Note that military specifications MIL-PRF-123 and MIL-PRF-55681 do not have requirements for mechanical testing of the parts. However, specifications for automotive industry components employ two types of mechanical tests: beam load (break strength) test per AEC-Q200-003 and board flex test per AEC-Q200-005. A recent military specification for thin dielectric capacitors, MIL-PRF-32535, has one mechanical test, board flex testing, that is similar to AEC-Q200-005. The purpose of this report was assessment of the efficiency of different mechanical tests for selection robust capacitors and comparison of mechanical characteristics of Base Metal Electrode (BME) and Precious Metal Electrode (PME) capacitors. The report has three parts related to the first three mechanical tests mentioned above.

  14. The orbital mechanics of flight mechanics

    Science.gov (United States)

    Dunning, R. S.

    1973-01-01

    A reference handbook on modern dynamic orbit theory is presented. Starting from the most basic inverse-square law, the law of gravity for a sphere is developed, and the motion of point masses under the influence of a sphere is considered. The reentry theory and the orbital theory are discussed along with the relative motion between two bodies in orbit about the same planet. Relative-motion equations, rectangular coordinates, and the mechanics of simple rigid bodies under the influence of a gravity gradient field are also discussed.

  15. Mechanisms in environmental control

    International Nuclear Information System (INIS)

    Lindeneg, K.

    1994-01-01

    The theory of implementation provides methods for decentralization of decisions in societies. By using mechanisms (game forms) it is possible (in theory) to implement attractive states in different economic environments. As an example the market mechanisms can implement Pareto-efficient and individual rational allocations in an Arrow-Debreu economic environment without market failures. And even when there exists externalities the market mechanism sometime can be used if it is possible to make a market for the goods not allocated on a market already - examples are marketable emission permits, and deposit refund systems. But environmental problems can often be explained by the existence of other market failures (e.g. asymmetric information), and then the market mechanism do not work properly. And instead of using regulation or traditional economic instruments (subsidies, charges, fees, liability insurance, marketable emission permits, or deposit refund systems) to correct the problems caused by market failures, some other methods can be used to deal with these problems. This paper contains a survey of mechanisms that can be used in environmental control when the problems are caused by the existence of public goods, externalities, asymmetric information, and indivisible goods in the economy. By examples it will be demonstrated how the Clarke-Groves mechanism, the Cournot-Lindahl mechanism, and other mechanisms can be used to solve specific environmental problems. This is only theory and examples, but a recent field study have used the Cournot-Lindahl mechanism to solve the problem of lake liming in Sweden. So this subject may be of some interests for environmental policy in the future. (au) 23 refs

  16. Statistical mechanics in JINR

    International Nuclear Information System (INIS)

    Tonchev, N.; Shumovskij, A.S.

    1986-01-01

    The history of investigations, conducted at the JINR in the field of statistical mechanics, beginning with the fundamental works by Bogolyubov N.N. on superconductivity microscopic theory is presented. Ideas, introduced in these works and methods developed in them, have largely determined the ways for developing statistical mechanics in the JINR and Hartree-Fock-Bogolyubov variational principle has become an important method of the modern nucleus theory. A brief review of the main achievements, connected with the development of statistical mechanics methods and their application in different fields of physical science is given

  17. Rotary mechanical latch

    Science.gov (United States)

    Spletzer, Barry L.; Martinez, Michael A.; Marron, Lisa C.

    2012-11-13

    A rotary mechanical latch for positive latching and unlatching of a rotary device with a latchable rotating assembly having a latching gear that can be driven to latched and unlatched states by a drive mechanism such as an electric motor. A cam arm affixed to the latching gear interfaces with leading and trailing latch cams affixed to a flange within the drive mechanism. The interaction of the cam arm with leading and trailing latch cams prevents rotation of the rotating assembly by external forces such as those due to vibration or tampering.

  18. Notes on continuum mechanics

    CERN Document Server

    Chaves, Eduardo W V

    2013-01-01

    This publication is aimed at students, teachers, and researchers of Continuum Mechanics and focused extensively on stating and developing Initial Boundary Value equations used to solve physical problems. With respect to notation, the tensorial, indicial and Voigt notations have been used indiscriminately.   The book is divided into twelve chapters with the following topics: Tensors, Continuum Kinematics, Stress, The Objectivity of Tensors, The Fundamental Equations of Continuum Mechanics, An Introduction to Constitutive Equations, Linear Elasticity, Hyperelasticity, Plasticity (small and large deformations), Thermoelasticity (small and large deformations), Damage Mechanics (small and large deformations), and An Introduction to Fluids. Moreover, the text is supplemented with over 280 figures, over 100 solved problems, and 130 references.

  19. Fluid and particle mechanics

    CERN Document Server

    Michell, S J

    2013-01-01

    Fluid and Particle Mechanics provides information pertinent to hydraulics or fluid mechanics. This book discusses the properties and behavior of liquids and gases in motion and at rest. Organized into nine chapters, this book begins with an overview of the science of fluid mechanics that is subdivided accordingly into two main branches, namely, fluid statics and fluid dynamics. This text then examines the flowmeter devices used for the measurement of flow of liquids and gases. Other chapters consider the principle of resistance in open channel flow, which is based on improper application of th

  20. Mechanisms of hypoxemia

    Directory of Open Access Journals (Sweden)

    Malay Sarkar

    2017-01-01

    Full Text Available Oxygen is an essential element for life and without oxygen humans can survive for few minutes only. There should be a balance between oxygen demand and delivery in order to maintain homeostasis within the body. The two main organ systems responsible for oxygen delivery in the body and maintaining homeostasis are respiratory and cardiovascular system. Abnormal function of any of these two would lead to the development of hypoxemia and its detrimental consequences. There are various mechanisms of hypoxemia but ventilation/perfusion mismatch is the most common underlying mechanism of hypoxemia. The present review will focus on definition, various causes, mechanisms, and approach of hypoxemia in human.

  1. Mechanical engineers data handbook

    CERN Document Server

    Carvill, James

    1994-01-01

    This text provides the student and professional mechanical engineer with a reference text of an essentially practical nature. It is uncluttered by text, and extensive use of illustrations and tables provide quick and clear access to information. It alsoincludes examples of detailed calculations on many of the applications of technology used by mechanical and production engineers, draughtsmen and engineering designers.Although mainly intended for those studying and practising mechanical engineering, a glance at the contents will show that it is also useful to those in related br

  2. Mechanics, Waves and Thermodynamics

    Science.gov (United States)

    Ranjan Jain, Sudhir

    2016-05-01

    Figures; Preface; Acknowledgement; 1. Energy, mass, momentum; 2. Kinematics, Newton's laws of motion; 3. Circular motion; 4. The principle of least action; 5. Work and energy; 6. Mechanics of a system of particles; 7. Friction; 8. Impulse and collisions; 9. Central forces; 10. Dimensional analysis; 11. Oscillations; 12. Waves; 13. Sound of music; 14. Fluid mechanics; 15. Water waves; 16. The kinetic theory of gases; 17. Concepts and laws of thermodynamics; 18. Some applications of thermodynamics; 19. Basic ideas of statistical mechanics; Bibliography; Index.

  3. Mechanical design engineering handbook

    CERN Document Server

    Childs, Peter R N

    2013-01-01

    Mechanical Design Engineering Handbook is a straight-talking and forward-thinking reference covering the design, specification, selection, use and integration of machine elements fundamental to a wide range of engineering applications. Develop or refresh your mechanical design skills in the areas of bearings, shafts, gears, seals, belts and chains, clutches and brakes, springs, fasteners, pneumatics and hydraulics, amongst other core mechanical elements, and dip in for principles, data and calculations as needed to inform and evaluate your on-the-job decisions. Covering the full spectrum

  4. Supersymmetry in quantum mechanics

    CERN Document Server

    Cooper, Fred; Sukhatme, Uday

    2001-01-01

    This invaluable book provides an elementary description of supersymmetric quantum mechanics which complements the traditional coverage found in the existing quantum mechanics textbooks. It gives physicists a fresh outlook and new ways of handling quantum-mechanical problems, and also leads to improved approximation techniques for dealing with potentials of interest in all branches of physics. The algebraic approach to obtaining eigenstates is elegant and important, and all physicists should become familiar with this. The book has been written in such a way that it can be easily appreciated by

  5. Introduction to quantum mechanics

    CERN Document Server

    Phillips, A C

    2003-01-01

    Introduction to Quantum Mechanics is an introduction to the power and elegance of quantum mechanics. Assuming little in the way of prior knowledge, quantum concepts are carefully and precisely presented, and explored through numerous applications and problems. Some of the more challenging aspects that are essential for a modern appreciation of the subject have been included, but are introduced and developed in the simplest way possible.Undergraduates taking a first course on quantum mechanics will find this text an invaluable introduction to the field and help prepare them for more adv

  6. Abstractions for Mechanical Systems

    DEFF Research Database (Denmark)

    Sloth, Christoffer; Wisniewski, Rafael

    2012-01-01

    This paper proposes a method for discretizing the state space of mechanical systems. This is a first attempt in using reduction techniques for mechanical systems in the partitioning of the state space. The method relies on a combination of transversal and tangential manifolds for the conservative...... mechanical system. The tangential manifolds are generated using constants of motion, which can be derived from Noether's theorem. The transversal manifolds are subsequently generated on a reduced space, given by the Routhian, via action-angle coordinates. The method fully applies for integrable systems. We...

  7. Interpretations of Quantum Mechanics

    Directory of Open Access Journals (Sweden)

    Pickl Peter

    2014-04-01

    Full Text Available The problems of modern physics are man made. The Copenhagen version of quantum mechanics is formulated in a vague prosaic way, inconsistencies and paradoxes are the price. New interpretations try to solve the problem, however a reformulation rather than an interpretation is needed. In this manuscript I will point out, where the Copenhagen formulation of quantum mechanics is flawed and how one can make sense out of it. Then I will show, that it is possible to give a precise formulation of quantum mechanics without losing its compelling ability in describing experiments.

  8. Interpretations of Quantum Mechanics

    Science.gov (United States)

    Pickl, Peter

    2014-04-01

    The problems of modern physics are man made. The Copenhagen version of quantum mechanics is formulated in a vague prosaic way, inconsistencies and paradoxes are the price. New interpretations try to solve the problem, however a reformulation rather than an interpretation is needed. In this manuscript I will point out, where the Copenhagen formulation of quantum mechanics is flawed and how one can make sense out of it. Then I will show, that it is possible to give a precise formulation of quantum mechanics without losing its compelling ability in describing experiments.

  9. Analytical elements of mechanics

    CERN Document Server

    Kane, Thomas R

    2013-01-01

    Analytical Elements of Mechanics, Volume 1, is the first of two volumes intended for use in courses in classical mechanics. The books aim to provide students and teachers with a text consistent in content and format with the author's ideas regarding the subject matter and teaching of mechanics, and to disseminate these ideas. The book opens with a detailed exposition of vector algebra, and no prior knowledge of this subject is required. This is followed by a chapter on the topic of mass centers, which is presented as a logical extension of concepts introduced in connection with centroids. A

  10. Mechanics of Generalized Continua

    CERN Document Server

    Maugin, Gerard A

    2010-01-01

    In their 1909 publication "Theorie des corps deformables", Eugene and Francois Cosserat made a historic contribution to materials science by establishing the fundamental principles of the mechanics of generalized continua. The chapters collected in this volume showcase the many areas of continuum mechanics that grew out of the foundational work of the Cosserat brothers. The included contributions provide a detailed survey of the most recent theoretical developments in the field of generalized continuum mechanics. The diverse topics covered include: the properties of Cosserat media, m

  11. Epigenetic Mechanisms in Asthma.

    Science.gov (United States)

    DeVries, Avery; Vercelli, Donata

    2016-03-01

    Asthma and allergic diseases are among the most prevalent chronic noncommunicable diseases of childhood, but the underlying pathogenetic mechanisms are poorly understood. Because epigenetic mechanisms link gene regulation to environmental cues and developmental trajectories, their contribution to asthma and allergy pathogenesis is under active investigation. DNA methylation signatures associated with concurrent disease and with the development of asthma during childhood asthma have been identified, but their significance is not easily interpretable. On the other hand, the characterization of early epigenetic predictors of asthma points to a potential role of epigenetic mechanisms in regulating the inception of, and the susceptibility to, this disease.

  12. Applications in solid mechanics

    DEFF Research Database (Denmark)

    Ølgaard, Kristian Breum; Wells, Garth N.

    2012-01-01

    Problems in solid mechanics constitute perhaps the largest field of application of finite element methods. The vast majority of solid mechanics problems involve the standard momentum balance equation, posed in a Lagrangian setting, with different models distinguished by the choice of nonlinear...... or linearized kinematics, and the constitutive model for determining the stress. For some common models, the constitutive relationships are rather complex. This chapter addresses a number of canonical solid mechanics models in the context of automated modeling, and focuses on some pertinent issues that arise...

  13. Miniature Release Mechanism Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The objective is to design, build and functionally test a miniature release mechanism for CubeSats and other small satellites. The WFF 6U satellite structure will be...

  14. Mechanical chest compressions.

    Science.gov (United States)

    Pomeroy, Matthew

    2012-09-13

    The authors of this study state that there is a lack of evidence about the efficiency of mechanical devices in producing chest compressions as an adjunct to resuscitation during cardiorespiratory arrest.

  15. Mechanical ventilator - infants

    Science.gov (United States)

    Ventilator - infants; Respirator - infants ... WHY IS A MECHANICAL VENTILATOR USED? A ventilator is used to provide breathing support for ill or immature babies. Sick or premature babies are often ...

  16. Toward broadband mechanical spectroscopy

    DEFF Research Database (Denmark)

    Hecksher, Tina; Torchinsky, Darius; Klieber, Christoph

    2017-01-01

    Diverse material classes exhibit qualitatively similar behavior when made viscous upon cooling toward the glass transition, suggesting a common theoretical basis. We used seven different measurement methods to determine the mechanical relaxation kinetics of a prototype molecular glass former over...

  17. Lectures on fluid mechanics

    CERN Document Server

    Shinbrot, Marvin

    2012-01-01

    Readable and user-friendly, this high-level introduction explores the derivation of the equations of fluid motion from statistical mechanics, classical theory, and a portion of the modern mathematical theory of viscous, incompressible fluids. 1973 edition.

  18. Molecular Mechanisms of Preeclampsia

    OpenAIRE

    N. Vitoratos; D. Hassiakos; C. Iavazzo

    2012-01-01

    Preeclampsia is one of the leading causes of maternal morbidity/mortality. The pathogenesis of preeclampsia is still under investigation. The aim of this paper is to present the molecular mechanisms implicating in the pathway leading to preeclampsia.

  19. Physics: quantum mechanics

    International Nuclear Information System (INIS)

    Basdevant, J.L.

    1983-01-01

    This book is the second part of the physic lectures on quantum mechanics from Ecole Polytechnique. It contains some physic complements a little more thoroughly studied, mathematical complements to which refer, and an exercise and problem collection [fr

  20. Applied mechanics of solids

    CERN Document Server

    Bower, Allan F

    2009-01-01

    Modern computer simulations make stress analysis easy. As they continue to replace classical mathematical methods of analysis, these software programs require users to have a solid understanding of the fundamental principles on which they are based. Develop Intuitive Ability to Identify and Avoid Physically Meaningless Predictions Applied Mechanics of Solids is a powerful tool for understanding how to take advantage of these revolutionary computer advances in the field of solid mechanics. Beginning with a description of the physical and mathematical laws that govern deformation in solids, the text presents modern constitutive equations, as well as analytical and computational methods of stress analysis and fracture mechanics. It also addresses the nonlinear theory of deformable rods, membranes, plates, and shells, and solutions to important boundary and initial value problems in solid mechanics. The author uses the step-by-step manner of a blackboard lecture to explain problem solving methods, often providing...

  1. Beyond conventional quantum mechanics

    International Nuclear Information System (INIS)

    Ghirardi, C.

    1991-10-01

    The author reviews some recent attempts to overcome the conceptual difficulties encountered by trying to interpret quantum mechanics as giving a complete, objective and unified description of natural phenomena. 38 refs

  2. Statistical mechanics of superconductivity

    CERN Document Server

    Kita, Takafumi

    2015-01-01

    This book provides a theoretical, step-by-step comprehensive explanation of superconductivity for undergraduate and graduate students who have completed elementary courses on thermodynamics and quantum mechanics. To this end, it adopts the unique approach of starting with the statistical mechanics of quantum ideal gases and successively adding and clarifying elements and techniques indispensible for understanding it. They include the spin-statistics theorem, second quantization, density matrices, the Bloch–De Dominicis theorem, the variational principle in statistical mechanics, attractive interaction, and bound states. Ample examples of their usage are also provided in terms of topics from advanced statistical mechanics such as two-particle correlations of quantum ideal gases, derivation of the Hartree–Fock equations, and Landau’s Fermi-liquid theory, among others. With these preliminaries, the fundamental mean-field equations of superconductivity are derived with maximum mathematical clarity based on ...

  3. Computational Continuum Mechanics

    CERN Document Server

    Shabana, Ahmed A

    2011-01-01

    This text presents the theory of continuum mechanics using computational methods. Ideal for students and researchers, the second edition features a new chapter on computational geometry and finite element analysis.

  4. Mechanics and thermodynamics

    CERN Document Server

    Demtröder, Wolfgang

    2017-01-01

    This introduction to classical mechanics and thermodynamics provides an accessible and clear treatment of the fundamentals. Starting with particle mechanics and an early introduction to special relativity this textbooks enables the reader to understand the basics in mechanics. The text is written from the experimental physics point of view, giving numerous real life examples and applications of classical mechanics in technology. This highly motivating presentation deepens the knowledge in a very accessible way. The second part of the text gives a concise introduction to rotational motion, an expansion to rigid bodies, fluids and gases. Finally, an extensive chapter on thermodynamics and a short introduction to nonlinear dynamics with some instructive examples intensify the knowledge of more advanced topics. Numerous problems with detailed solutions are perfect for self study.

  5. Variable mechanical ventilation.

    Science.gov (United States)

    Fontela, Paula Caitano; Prestes, Renata Bernardy; Forgiarini, Luiz Alberto; Friedman, Gilberto

    2017-01-01

    To review the literature on the use of variable mechanical ventilation and the main outcomes of this technique. Search, selection, and analysis of all original articles on variable ventilation, without restriction on the period of publication and language, available in the electronic databases LILACS, MEDLINE®, and PubMed, by searching the terms "variable ventilation" OR "noisy ventilation" OR "biologically variable ventilation". A total of 36 studies were selected. Of these, 24 were original studies, including 21 experimental studies and three clinical studies. Several experimental studies reported the beneficial effects of distinct variable ventilation strategies on lung function using different models of lung injury and healthy lungs. Variable ventilation seems to be a viable strategy for improving gas exchange and respiratory mechanics and preventing lung injury associated with mechanical ventilation. However, further clinical studies are necessary to assess the potential of variable ventilation strategies for the clinical improvement of patients undergoing mechanical ventilation.

  6. Mechanical vaccum pumps

    CERN Document Server

    Chew, A D

    2007-01-01

    This presentation gives an overview of the technology of contemporary primary and secondary mechanical vacuum pumps. For reference a brief history of vacuum and a summary of important and basic vacuum concepts are first presented.

  7. The Mechanisms of Involuntary Attention

    Science.gov (United States)

    Prinzmetal, William; Ha, Ruby; Khani, Aniss

    2010-01-01

    We tested 3 mechanisms of involuntary attention: (1) a perceptual enhancement mechanism, (2) a response-decision mechanism, and (3) a serial-search mechanism. Experiment 1 used a response deadline technique to compare the perceptual enhancement and the decision mechanisms and found evidence consistent with the decision mechanism. Experiment 2 used…

  8. Phase Field Fracture Mechanics.

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, Brett Anthony [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-11-01

    For this assignment, a newer technique of fracture mechanics using a phase field approach, will be examined and compared with experimental data for a bend test and a tension test. The software being used is Sierra Solid Mechanics, an implicit/explicit finite element code developed at Sandia National Labs in Albuquerque, New Mexico. The bend test experimental data was also obtained at Sandia Labs while the tension test data was found in a report online from Purdue University.

  9. Cloud security mechanisms

    OpenAIRE

    2014-01-01

    Cloud computing has brought great benefits in cost and flexibility for provisioning services. The greatest challenge of cloud computing remains however the question of security. The current standard tools in access control mechanisms and cryptography can only partly solve the security challenges of cloud infrastructures. In the recent years of research in security and cryptography, novel mechanisms, protocols and algorithms have emerged that offer new ways to create secure services atop cloud...

  10. MECHANISMS IN ENDOCRINOLOGY

    DEFF Research Database (Denmark)

    Allin, Kristine H.; Nielsen, Trine; Pedersen, Oluf.

    2015-01-01

    Perturbations of the composition and function of the gut microbiota have been associated with metabolic disorders including obesity, insulin resistance and type 2 diabetes. Studies on mice have demonstrated several underlying mechanisms including host signalling through bacterial lipopolysacchari......Perturbations of the composition and function of the gut microbiota have been associated with metabolic disorders including obesity, insulin resistance and type 2 diabetes. Studies on mice have demonstrated several underlying mechanisms including host signalling through bacterial...

  11. Cavity opto-mechanics

    OpenAIRE

    Kippenberg, T. J.; Vahala, K. J.

    2007-01-01

    The coupling of mechanical and optical degrees of freedom via radiation pressure has been a subject of early research in the context of gravitational wave detection. Recent experimental advances have allowed studying for the first time the modifications of mechanical dynamics provided by radiation pressure. This paper reviews the consequences of back-action of light confined in whispering-gallery dielectric microcavities, and presents a unified treatment of its two manifestations: notably the...

  12. Statistical mechanics rigorous results

    CERN Document Server

    Ruelle, David

    1999-01-01

    This classic book marks the beginning of an era of vigorous mathematical progress in equilibrium statistical mechanics. Its treatment of the infinite system limit has not been superseded, and the discussion of thermodynamic functions and states remains basic for more recent work. The conceptual foundation provided by the Rigorous Results remains invaluable for the study of the spectacular developments of statistical mechanics in the second half of the 20th century.

  13. Mechanics of deformable bodies

    CERN Document Server

    Sommerfeld, Arnold Johannes Wilhelm

    1950-01-01

    Mechanics of Deformable Bodies: Lectures on Theoretical Physics, Volume II covers topics on the mechanics of deformable bodies. The book discusses the kinematics, statics, and dynamics of deformable bodies; the vortex theory; as well as the theory of waves. The text also describes the flow with given boundaries. Supplementary notes on selected hydrodynamic problems and supplements to the theory of elasticity are provided. Physicists, mathematicians, and students taking related courses will find the book useful.

  14. Molecular mechanisms in gliomagenesis

    DEFF Research Database (Denmark)

    Hulleman, Esther; Helin, Kristian

    2005-01-01

    , in order to design novel therapies and treatments for GBM, research has recently intensified to identify the cellular and molecular mechanisms leading to GBM formation. Modeling of astrocytomas by genetic manipulation of mice suggests that deregulation of the pathways that control gliogenesis during normal......-scale genomics and proteomics in combination with relevant mouse models will most likely provide novel insights into the molecular mechanisms underlying glioma formation and will hopefully lead to development of treatment modalities for GBM....

  15. Generalized classical mechanics

    International Nuclear Information System (INIS)

    De Leon, M.; Rodrigues, P.R.

    1985-01-01

    The geometrical study of Classical Mechanics shows that the Hamiltonian (respectively, Lagrangian) formalism may be characterized by intrinsical structures canonically defined on the cotangent (respectively, tangent) bundle of a differentiable manifold. A generalized formalism for higher order Lagrangians is developed. Then the Hamiltonian form of the theory is developed. Finally, the Poisson brackets are defined and the conditions under which a mapping is a canonical transformation are studied. The Hamilton-Jacobi equation for this type of mechanics is established. (Auth.)

  16. Theoretical physics. Quantum mechanics

    International Nuclear Information System (INIS)

    Rebhan, Eckhard

    2008-01-01

    From the first in two comprehensive volumes appeared Theoretical Physics of the author by this after Mechanics and Electrodynamics also Quantum mechanics appears as thinner single volume. First the illustrative approach via wave mechanics is reproduced. The more abstract Hilbert-space formulation introduces the author later by postulates, which are because of the preceding wave mechanics sufficiently plausible. All concepts of quantum mechanics, which contradict often to the intuitive understanding formed by macroscopic experiences, are extensively discussed and made by means of many examples as well as problems - in the largest part provided with solutions - understandable. To the interpretation of quantum mechanics an extensive special chapter is dedicated. this book arose from courses on theoretical physics, which the author has held at the Heinrich-Heine University in Duesseldorf, and was in numerous repetitions fitted to the requirement of the studyings. it is so designed that it is also after the study suited as reference book or for the renewing. All problems are very thoroughly and such extensively studied that each step is separately reproducible. About motivation and good understandability is cared much

  17. Nuclear Mechanics in Cancer

    Science.gov (United States)

    Denais, Celine; Lammerding, Jan

    2015-01-01

    Despite decades of research, cancer metastasis remains an incompletely understood process that is as complex as it is devastating. In recent years, there has been an increasing push to investigate the biomechanical aspects of tumorigenesis, complementing the research on genetic and biochemical changes. In contrast to the high genetic variability encountered in cancer cells, almost all metastatic cells are subject to the same physical constraints as they leave the primary tumor, invade surrounding tissues, transit through the circulatory system, and finally infiltrate new tissues. Advances in live cell imaging and other biophysical techniques, including measurements of subcellular mechanics, have yielded stunning new insights into the physics of cancer cells. While much of this research has been focused on the mechanics of the cytoskeleton and the cellular microenvironment, it is now emerging that the mechanical properties of the cell nucleus and its connection to the cytoskeleton may play a major role in cancer metastasis, as deformation of the large and stiff nucleus presents a substantial obstacle during the passage through the dense interstitial space and narrow capillaries. Here, we present an overview of the molecular components that govern the mechanical properties of the nucleus and we discuss how changes in nuclear structure and composition observed in many cancers can modulate nuclear mechanics and promote metastatic processes. Improved insights into this interplay between nuclear mechanics and metastatic progression may have powerful implications in cancer diagnostics and therapy and may reveal novel therapeutic targets for pharmacological inhibition of cancer cell invasion. PMID:24563360

  18. Clean Development Mechanism: Core of Kyoto Mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myung Kyun [United Nations Environment Programme (Denmark)

    2000-06-01

    Kyoto protocol is a foundation for achieving an ultimate goal of UNFCCC, which is to stabilizing greenhouse gas concentration in the air. The clean development system is a core element for successful implementation of Kyoto protocol with other Kyoto mechanisms. While UNFCCC requires a new paradigm changing to sustainable development considering demand and future environment from the past supply-oriented resource consumption, the clean development system will be used as a means of successful establishment of a new paradigm in 21st century. As environmental problem is integrated with economic problem and each country is thriving for securing its own economic benefit in the issue of environmental conservation, Korea should do its best to have both of global environmental conservation and economic benefit for its own. 1 tab.

  19. Noncanonical Hamiltonian mechanics

    International Nuclear Information System (INIS)

    Litteljohn, R.G.

    1986-01-01

    Noncanonical variables in Hamiltonian mechanics were first used by Lagrange in 1808. In spite of this, most work in Hamiltonian mechanics has been carried out in canonical variables, up to this day. One reason for this is that noncanonical coordinates are seldom needed for mechanical problems based on Lagrangians of the form L = T - V, where T is the kinetic energy and V is the potential energy. Of course, such Lagrangians arise naturally in celestial mechanics, and as a result they form the paradigms of nineteenth-century mechanics and have become enshrined in all the mechanics textbooks. Certain features of modern problems, however, lead to the use of noncanonical coordinates. Among these are issues of gauge invariance and singular Lagrange a Poisson structures. In addition, certain problems, like the flow of magnetic-field lines in physical space, are naturally formulated in terms of noncanonical coordinates. None of these features is present in the nineteenth-century paradigms of mechanics, but they do arise in problems involving particle motion in the presence of magnetic fields. For example, the motion of a particle in an electromagnetic wave is an important one in plasma physics, but the usual Hamiltonian formulation is gauge dependent. For this problem, noncanonical approaches based on Lagrangians in phase space lead to powerful computational techniques which are gauge invariant. In the limit of strong magnetic fields, particle motion becomes 'guiding-center motion'. Guiding-center motion is also best understood in terms of noncanonical coordinates. Finally the flow of magnetic-field lines through physical space is a Hamiltonian system which is best understood with noncanonical coordinates. No doubt many more systems will arise in the future for which these noncanonical techniques can be applied. (author)

  20. Advanced mechanics of solids

    CERN Document Server

    Bruhns, Otto T

    2003-01-01

    Mechanics, and in particular, the mechanics of solids, forms the basis of all engi­ neering sciences. It provides the essential foundations for understanding the action of forces on bodies, and the effects of these forces on the straining of the body on the one hand, and on the deformation and motion of the body on the other. Thus, it provides the solutions of many problems with which the would-be engineer is going to be confronted with on a daily basis. In addition, in engineering studies, mechanics has a more vital importance, which many students appreciate only much later. Because of its clear, and analyt­ ical setup, it aids the student to a great extent in acquiring the necessary degree of abstraction ability, and logical thinking, skills without which no engineer in the practice today would succeed. Many graduates have confirmed to me that learning mechanics is generally per­ ceived as difficult. On the other hand, they always also declared that the preoccu­ pation with mechanics made an essential c...

  1. Theory of Parallel Mechanisms

    CERN Document Server

    Huang, Zhen; Ding, Huafeng

    2013-01-01

    This book contains mechanism analysis and synthesis. In mechanism analysis, a mobility methodology is first systematically presented. This methodology, based on the author's screw theory, proposed in 1997, of which the generality and validity was only proved recently,  is a very complex issue, researched by various scientists over the last 150 years. The principle of kinematic influence coefficient and its latest developments are described. This principle is suitable for kinematic analysis of various 6-DOF and lower-mobility parallel manipulators. The singularities are classified by a new point of view, and progress in position-singularity and orientation-singularity is stated. In addition, the concept of over-determinate input is proposed and a new method of force analysis based on screw theory is presented. In mechanism synthesis, the synthesis for spatial parallel mechanisms is discussed, and the synthesis method of difficult 4-DOF and 5-DOF symmetric mechanisms, which was first put forward by the a...

  2. Fundamentals of Quantum Mechanics

    Science.gov (United States)

    Tang, C. L.

    2005-06-01

    Quantum mechanics has evolved from a subject of study in pure physics to one with a wide range of applications in many diverse fields. The basic concepts of quantum mechanics are explained in this book in a concise and easy-to-read manner emphasising applications in solid state electronics and modern optics. Following a logical sequence, the book is focused on the key ideas and is conceptually and mathematically self-contained. The fundamental principles of quantum mechanics are illustrated by showing their application to systems such as the hydrogen atom, multi-electron ions and atoms, the formation of simple organic molecules and crystalline solids of practical importance. It leads on from these basic concepts to discuss some of the most important applications in modern semiconductor electronics and optics. Containing many homework problems and worked examples, the book is suitable for senior-level undergraduate and graduate level students in electrical engineering, materials science and applied physics. Clear exposition of quantum mechanics written in a concise and accessible style Precise physical interpretation of the mathematical foundations of quantum mechanics Illustrates the important concepts and results by reference to real-world examples in electronics and optoelectronics Contains homeworks and worked examples, with solutions available for instructors

  3. Mathematical physics classical mechanics

    CERN Document Server

    Knauf, Andreas

    2018-01-01

    As a limit theory of quantum mechanics, classical dynamics comprises a large variety of phenomena, from computable (integrable) to chaotic (mixing) behavior. This book presents the KAM (Kolmogorov-Arnold-Moser) theory and asymptotic completeness in classical scattering. Including a wealth of fascinating examples in physics, it offers not only an excellent selection of basic topics, but also an introduction to a number of current areas of research in the field of classical mechanics. Thanks to the didactic structure and concise appendices, the presentation is self-contained and requires only knowledge of the basic courses in mathematics. The book addresses the needs of graduate and senior undergraduate students in mathematics and physics, and of researchers interested in approaching classical mechanics from a modern point of view.

  4. Fundamentals of quantum mechanics

    CERN Document Server

    House, J E

    2017-01-01

    Fundamentals of Quantum Mechanics, Third Edition is a clear and detailed introduction to quantum mechanics and its applications in chemistry and physics. All required math is clearly explained, including intermediate steps in derivations, and concise review of the math is included in the text at appropriate points. Most of the elementary quantum mechanical models-including particles in boxes, rigid rotor, harmonic oscillator, barrier penetration, hydrogen atom-are clearly and completely presented. Applications of these models to selected “real world” topics are also included. This new edition includes many new topics such as band theory and heat capacity of solids, spectroscopy of molecules and complexes (including applications to ligand field theory), and small molecules of astrophysical interest.

  5. Candida albicans pathogenicity mechanisms.

    Science.gov (United States)

    Mayer, François L; Wilson, Duncan; Hube, Bernhard

    2013-02-15

    The polymorphic fungus Candida albicans is a member of the normal human microbiome. In most individuals, C. albicans resides as a lifelong, harmless commensal. Under certain circumstances, however, C. albicans can cause infections that range from superficial infections of the skin to life-threatening systemic infections. Several factors and activities have been identified which contribute to the pathogenic potential of this fungus. Among them are molecules which mediate adhesion to and invasion into host cells, the secretion of hydrolases, the yeast-to-hypha transition, contact sensing and thigmotropism, biofilm formation, phenotypic switching and a range of fitness attributes. Our understanding of when and how these mechanisms and factors contribute to infection has significantly increased during the last years. In addition, novel virulence mechanisms have recently been discovered. In this review we present an update on our current understanding of the pathogenicity mechanisms of this important human pathogen.

  6. Crude oil burning mechanisms

    DEFF Research Database (Denmark)

    van Gelderen, Laurens; Malmquist, L.M.V.; Jomaas, Grunde

    2015-01-01

    In order to improve predictions for the burning efficiency and the residue composition of in-situ burning of crude oil, the burning mechanism of crude oil was studied in relation to the composition of its hydrocarbon mixture, before, during and after the burning. The surface temperature, flame...... to the predictions of four conceptual models that describe the burning mechanism of multicomponent fuels. Based on the comparisons, hydrocarbon liquids were found to be best described by the Equilibrium Flash Vaporization model, showing a constant gas composition and gasification rate. The multicomponent fuels...... followed the diffusion-limited gasification model, showing a change in the hydrocarbon composition of the fuel and its evaporating gases, as well as a decreasing gasification rate, as the burning progressed. This burning mechanism implies that the residue composition and burning efficiency mainly depend...

  7. Relativistic quantum mechanics

    International Nuclear Information System (INIS)

    Wolschin, Georg

    2016-01-01

    This course is a concise introduction to the foundations of relativistic quantum mechanics. It is concipated as one-semester, two-hour arrangement for bachelor and master students; some of the advanced parts can be also of interest or promovings. Primary adressates are studyings from the fourth semester upwards, which have already worked out the basic course of quantum mechanics and want beyond to get to know relativistic wave equations. In the introduction I draw first the development, the result of which was the establishment of Lorentz-invariant relativistic wave equations by Schroedinger, Klein, Gordon, and Dirac. After a chapter about the connection to the Galilei-invariant nonrelativistic quantum mechanics follow the presentations of the Klein-Gordon and Dirac and the study of the Dirac theory in view of invariances concerning parity, charge conjugation, ant time-reversal transformation. A short introduction to the principles of quantum field theory, especially quantum electrodynamics, follows.

  8. Mechanical Biological Treatment

    DEFF Research Database (Denmark)

    Bilitewski, B-; Oros, Christiane; Christensen, Thomas Højlund

    2011-01-01

    The basic processes and technologies of composting and anaerobic digestion, as described in the previous chapters, are usually used for specific or source-separated organic waste flows. However, in the 1990s mechanical biological waste treatment technologies (MBT) were developed for unsorted...... or residual waste (after some recyclables removed at the source). The concept was originally to reduce the amount of waste going to landfill, but MBT technologies are today also seen as plants recovering fuel as well as material fractions. As the name suggests the technology combines mechanical treatment...... technologies (screens, sieves, magnets, etc.) with biological technologies (composting, anaerobic digestion). Two main technologies are available: Mechanical biological pretreatment (MBP), which first removes an RDF fraction and then biologically treats the remaining waste before most of it is landfilled...

  9. Mechanical Properties of Transcription

    Science.gov (United States)

    Sevier, Stuart A.; Levine, Herbert

    2017-06-01

    The mechanical properties of transcription have recently been shown to play a central role in gene expression. However, a full physical characterization of this central biological process is lacking. In this Letter, we introduce a simple description of the basic physical elements of transcription where RNA elongation, RNA polymerase rotation, and DNA supercoiling are coupled. The resulting framework describes the relative amount of RNA polymerase rotation and DNA supercoiling that occurs during RNA elongation. Asymptotic behavior is derived and can be used to experimentally extract unknown mechanical parameters of transcription. Mechanical limits to transcription are incorporated through the addition of a DNA supercoiling-dependent RNA polymerase velocity. This addition can lead to transcriptional stalling and resulting implications for gene expression, chromatin structure and genome organization are discussed.

  10. Lectures on quantum mechanics

    CERN Document Server

    Weinberg, Steven

    2013-01-01

    Nobel Laureate Steven Weinberg combines his exceptional physical insight with his gift for clear exposition to provide a concise introduction to modern quantum mechanics. Ideally suited to a one-year graduate course, this textbook is also a useful reference for researchers. Readers are introduced to the subject through a review of the history of quantum mechanics and an account of classic solutions of the Schrödinger equation, before quantum mechanics is developed in a modern Hilbert space approach. The textbook covers many topics not often found in other books on the subject, including alternatives to the Copenhagen interpretation, Bloch waves and band structure, the Wigner–Eckart theorem, magic numbers, isospin symmetry, the Dirac theory of constrained canonical systems, general scattering theory, the optical theorem, the 'in-in' formalism, the Berry phase, Landau levels, entanglement and quantum computing. Problems are included at the ends of chapters, with solutions available for instructors at www.cam...

  11. Understanding Defense Mechanisms.

    Science.gov (United States)

    Cramer, Phebe

    2015-12-01

    Understanding defense mechanisms is an important part of psychotherapy. In this article, we trace the history of the concept of defense, from its origin with Freud to current views. The issue of defense as an unconscious mechanism is examined. The question of whether defenses are pathological, as well as their relation to pathology, is discussed. The effect of psychotherapy on the use of defenses, and their relation to a therapeutic alliance is explored. A series of empirical research studies that demonstrate the functioning of defense mechanisms and that support the theory is presented. Research also shows that as part of normal development, different defenses emerge at different developmental periods, and that gender differences in defense use occur.

  12. Concepts in quantum mechanics

    CERN Document Server

    Mathur, Vishnu S

    2008-01-01

    NEED FOR QUANTUM MECHANICS AND ITS PHYSICAL BASIS Inadequacy of Classical Description for Small Systems Basis of Quantum Mechanics Representation of States Dual Vectors: Bra and Ket Vectors Linear Operators Adjoint of a Linear Operator Eigenvalues and Eigenvectors of a Linear Operator Physical Interpretation Observables and Completeness Criterion Commutativity and Compatibility of Observables Position and Momentum Commutation Relations Commutation Relation and the Uncertainty ProductAppendix: Basic Concepts in Classical MechanicsREPRESENTATION THEORY Meaning of Representation How to Set up a Representation Representatives of a Linear Operator Change of Representation Coordinate Representation Replacement of Momentum Observable p by -ih d/dqIntegral Representation of Dirac Bracket A2|F|A1> The Momentum Representation Dirac Delta FunctionRelation between the Coordinate and Momentum RepresentationsEQUATIONS OF MOTIONSchrödinger Equation of Motion Schrödinger Equation in the Coordinate Representation Equation o...

  13. Classical mechanics an introduction

    CERN Document Server

    Strauch, D

    2008-01-01

    This upper-level undergraduate and beginning graduate textbook primarily covers the theory and application of Newtonian and Lagrangian, but also of Hamiltonian mechanics. In addition, included are elements of continuum mechanics and the accompanying classical field theory, wherein four-vector notation is introduced without explicit reference to special relativity. The author's writing style attempts to ease students through the primary and secondary results, thus building a solid foundation for understanding applications. So the text is thus structured around developments of the main ideas, explicit proofs, and numerous clarifications, comments and applications. Numerous examples illustrate the material and often present alternative approaches to the final results. Frequent references are made linking mechanics to other fields of physics. These lecture notes have been used frequently by students to prepare for written and/or oral examinations. Summaries and problems conclude chapters and appendices supply nee...

  14. Mechanisms of epigenetic memory.

    Science.gov (United States)

    D'Urso, Agustina; Brickner, Jason H

    2014-06-01

    Although genetics has an essential role in defining the development, morphology, and physiology of an organism, epigenetic mechanisms have an essential role in modulating these properties by regulating gene expression. During development, epigenetic mechanisms establish stable gene expression patterns to ensure proper differentiation. Such mechanisms also allow organisms to adapt to environmental changes and previous experiences can impact the future responsiveness of an organism to a stimulus over long timescales and even over generations. Here, we discuss the concept of epigenetic memory, defined as the stable propagation of a change in gene expression or potential induced by developmental or environmental stimuli. We highlight three distinct paradigms of epigenetic memory that operate on different timescales. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Mechanics of ultrasound elastography

    Science.gov (United States)

    Li, Guo-Yang

    2017-01-01

    Ultrasound elastography enables in vivo measurement of the mechanical properties of living soft tissues in a non-destructive and non-invasive manner and has attracted considerable interest for clinical use in recent years. Continuum mechanics plays an essential role in understanding and improving ultrasound-based elastography methods and is the main focus of this review. In particular, the mechanics theories involved in both static and dynamic elastography methods are surveyed. They may help understand the challenges in and opportunities for the practical applications of various ultrasound elastography methods to characterize the linear elastic, viscoelastic, anisotropic elastic and hyperelastic properties of both bulk and thin-walled soft materials, especially the in vivo characterization of biological soft tissues. PMID:28413350

  16. Candida albicans pathogenicity mechanisms

    Science.gov (United States)

    Mayer, François L.; Wilson, Duncan; Hube, Bernhard

    2013-01-01

    The polymorphic fungus Candida albicans is a member of the normal human microbiome. In most individuals, C. albicans resides as a lifelong, harmless commensal. Under certain circumstances, however, C. albicans can cause infections that range from superficial infections of the skin to life-threatening systemic infections. Several factors and activities have been identified which contribute to the pathogenic potential of this fungus. Among them are molecules which mediate adhesion to and invasion into host cells, the secretion of hydrolases, the yeast-to-hypha transition, contact sensing and thigmotropism, biofilm formation, phenotypic switching and a range of fitness attributes. Our understanding of when and how these mechanisms and factors contribute to infection has significantly increased during the last years. In addition, novel virulence mechanisms have recently been discovered. In this review we present an update on our current understanding of the pathogenicity mechanisms of this important human pathogen. PMID:23302789

  17. Relativistic wave mechanics

    CERN Document Server

    Corinaldesi, Ernesto

    1963-01-01

    Geared toward advanced undergraduate and graduate students of physics, this text provides readers with a background in relativistic wave mechanics and prepares them for the study of field theory. The treatment originated as a series of lectures from a course on advanced quantum mechanics that has been further amplified by student contributions.An introductory section related to particles and wave functions precedes the three-part treatment. An examination of particles of spin zero follows, addressing wave equation, Lagrangian formalism, physical quantities as mean values, translation and rotat

  18. Educational Mechanisms of Dioramas

    DEFF Research Database (Denmark)

    May, Michael; Achiam, Marianne

    2018-01-01

    The diorama remains one of the most popular exhibit types in museums, and it has proven its educational potential time and time again. In spite of this, the specific mechanisms behind that educational potential remain unclear. In other words, museum practitioners and museum researchers know...... that dioramas work, we just don’t know how they work. In the following, we use visual perception theory as well as cognitive linguistics to explain the perceptual and meaning-making mechanisms that give dioramas their unique potential. Specifically, we construct a framework to understand how museum visitors can...

  19. Synthesis of Mechanisms

    DEFF Research Database (Denmark)

    Hansen, John Michael

    1999-01-01

    These notes describe an automated procedure for analysis and synthesis of mechanisms. The analysis method is based on the body coordinate formulation, and the synthesis is based on applying optimization methods, used to minimize the difference between an actual and a desired behaviour......These notes describe an automated procedure for analysis and synthesis of mechanisms. The analysis method is based on the body coordinate formulation, and the synthesis is based on applying optimization methods, used to minimize the difference between an actual and a desired behaviour...

  20. The switchboard mechanism

    DEFF Research Database (Denmark)

    Albris, Kristoffer

    2018-01-01

    , several Facebook groups emerged as a primary means for citizens to gather and share information about the emergency. These networks enabled the emergence of what is here called the “switchboard mechanism,” whereby citizens in need of help could be connected to those offering it. Moreover, the online...... activity into on-the-ground emergency response by citizens. The switchboard mechanism is thus an attempt to add to a conceptual apparatus for research into the ways that such online–offline translations occur during disasters....

  1. Problems in quantum mechanics

    CERN Document Server

    Kogan, V.I; Gersch, Harold

    1963-01-01

    Written by a pair of distinguished Soviet mathematicians, this compilation presents 160 lucidly expressed problems in nonrelativistic quantum mechanics plus completely worked-out solutions. Some were drawn from the authors' courses at the Moscow Institute of Engineering, but most were prepared especially for this book. A high-level supplement rather than a primary text, it constitutes a masterful complement to advanced undergraduate and graduate texts and courses in quantum mechanics.The mathematics employed in the proofs of the problems-asymptotic expansions of functions, Green's functions, u

  2. Elastic plastic fracture mechanics

    International Nuclear Information System (INIS)

    Simpson, L.A.

    1978-07-01

    The application of linear elastic fracture mechanics (LEFM) to crack stability in brittle structures is now well understood and widely applied. However, in many structural materials, crack propagation is accompanied by considerable crack-tip plasticity which invalidates the use of LEFM. Thus, present day research in fracture mechanics is aimed at developing parameters for predicting crack propagation under elastic-plastic conditions. These include critical crack-opening-displacement methods, the J integral and R-curve techniques. This report provides an introduction to these concepts and gives some examples of their applications. (author)

  3. Classical mechanics with Maxima

    CERN Document Server

    Timberlake, Todd Keene

    2016-01-01

    This book guides undergraduate students in the use of Maxima—a computer algebra system—in solving problems in classical mechanics. It functions well as a supplement to a typical classical mechanics textbook. When it comes to problems that are too difficult to solve by hand, computer algebra systems that can perform symbolic mathematical manipulations are a valuable tool. Maxima is particularly attractive in that it is open-source, multiple-platform software that students can download and install free of charge. Lessons learned and capabilities developed using Maxima are easily transferred to other, proprietary software.

  4. Mechanism of artificial heart

    CERN Document Server

    Yamane, Takashi

    2016-01-01

    This book first describes medical devices in relation to regenerative medicine before turning to a more specific topic: artificial heart technologies. Not only the pump mechanisms but also the bearing, motor mechanisms, and materials are described, including expert information. Design methods are described to enhance hemocompatibility: main concerns are reduction of blood cell damage and protein break, as well as prevention of blood clotting. Regulatory science from R&D to clinical trials is also discussed to verify the safety and efficacy of the devices.

  5. Solid state mechanics

    International Nuclear Information System (INIS)

    Habib, P.

    1988-01-01

    The 1988 progress report of the Solid State Mechanics laboratory (Polytechnic School, France) is presented. The research program domains are the following: investigations concerning the stability and bifurcation of the reversible or irreversible mechanical systems, the problems related to the theoretical and experimental determination of the materials rheological properties, the fatigue crack formation and propagation in multiple-axial stress conditions, the expert systems, and the software applied in the reinforced earth structures dimensioning. Moreover, the published papers, the books, the congress communications, the thesis, and the patents are listed [fr

  6. Combinatorial Mechanical Metamaterials

    Science.gov (United States)

    van Hecke, Martin

    The structure of most mechanical metamaterials is periodic so that their design space is that of the unit cell. Here we introduce a combinatorial strategy to create a vast number of distinct mechanical metamaterials, each with a unique spatial texture and response. These are aperiodic stackings of anisotropic building blocks, and their functionality rests on both the block design and their stacking configuration which is governed by a tiling problem. We realize such metamaterials by 3D printing, and show that they act as soft machines, capable of pattern recognition and pattern analysis.

  7. Fundamentals of continuum mechanics

    CERN Document Server

    Rudnicki, John W

    2014-01-01

    A concise introductory course text on continuum mechanics Fundamentals of Continuum Mechanics focuses on the fundamentals of the subject and provides the background for formulation of numerical methods for large deformations and a wide range of material behaviours. It aims to provide the foundations for further study, not just of these subjects, but also the formulations for much more complex material behaviour and their implementation computationally.  This book is divided into 5 parts, covering mathematical preliminaries, stress, motion and deformation, balance of mass, momentum and energ

  8. Mechanical engineer's reference book

    CERN Document Server

    Parrish, A

    1973-01-01

    Mechanical Engineer's Reference Book: 11th Edition presents a comprehensive examination of the use of Systéme International d' Unités (SI) metrication. It discusses the effectiveness of such a system when used in the field of engineering. It addresses the basic concepts involved in thermodynamics and heat transfer. Some of the topics covered in the book are the metallurgy of iron and steel; screw threads and fasteners; hole basis and shaft basis fits; an introduction to geometrical tolerancing; mechanical working of steel; high strength alloy steels; advantages of making components as castings

  9. Mechanics of soft materials

    CERN Document Server

    Volokh, Konstantin

    2016-01-01

    This book provides a concise introduction to soft matter modelling. It offers an up-to-date review of continuum mechanical description of soft and biological materials from the basics to the latest scientific materials. It includes multi-physics descriptions, such as chemo-, thermo-, electro- mechanical coupling. It derives from a graduate course at Technion that has been established in recent years. It presents original explanations for some standard materials and features elaborated examples on all topics throughout the text. PowerPoint lecture notes can be provided to instructors. .

  10. Physics: quantum mechanics

    International Nuclear Information System (INIS)

    Basdevant, J.L.

    1983-01-01

    From important experiment descriptions (sometimes, intentionally simplified), the essential concepts in Quantum Mechanics are first introduced. Wave function notion is described, Schroedinger equation is established, and, after applications rich in physical signification, quantum state and Hilbert space formalism are introduced, which will help to understand many essential phenomena. Then the quantum mechanic general formulation is written and some important consequences are deduced. This formalism is applied to a simple physical problem series (angular momentum, hydrogen atom, etc.) aiming at assimilating the theory operation and its application [fr

  11. Mechanisms of Defibrillation

    Science.gov (United States)

    Dosdall, Derek J.; Fast, Vladimir G.; Ideker, Raymond E.

    2014-01-01

    Electrical shock has been the one effective treatment for ventricular fibrillation for several decades. With the advancement of electrical and optical mapping techniques, histology, and computer modeling, the mechanisms responsible for defibrillation are now coming to light. In this review, we discuss recent work that demonstrates the various mechanisms responsible for defibrillation. On the cellular level, membrane depolarization and electroporation affect defibrillation outcome. Cell bundles and collagenous septae are secondary sources and cause virtual electrodes at sites far from shocking electrodes. On the whole-heart level, shock field gradient and critical points determine whether a shock is successful or whether reentry causes initiation and continuation of fibrillation. PMID:20450352

  12. Probabilistic approach to mechanisms

    CERN Document Server

    Sandler, BZ

    1984-01-01

    This book discusses the application of probabilistics to the investigation of mechanical systems. The book shows, for example, how random function theory can be applied directly to the investigation of random processes in the deflection of cam profiles, pitch or gear teeth, pressure in pipes, etc. The author also deals with some other technical applications of probabilistic theory, including, amongst others, those relating to pneumatic and hydraulic mechanisms and roller bearings. Many of the aspects are illustrated by examples of applications of the techniques under discussion.

  13. Elementary quantum mechanics

    CERN Document Server

    Saxon, David S

    2012-01-01

    Based on lectures for an undergraduate UCLA course in quantum mechanics, this volume focuses on the formulas of quantum mechanics rather than applications. Widely used in both upper-level undergraduate and graduate courses, it offers a broad self-contained survey rather than in-depth treatments.Topics include the dual nature of matter and radiation, state functions and their interpretation, linear momentum, the motion of a free particle, Schrödinger's equation, approximation methods, angular momentum, and many other subjects. In the interests of keeping the mathematics as simple as possible, m

  14. Introduction to continuum mechanics

    CERN Document Server

    Lai, W Michael; Rubin, David

    1996-01-01

    Introduction to Continuum Mechanics is a recently updated and revised text which is perfect for either introductory courses in an undergraduate engineering curriculum or for a beginning graduate course.Continuum Mechanics studies the response of materials to different loading conditions. The concept of tensors is introduced through the idea of linear transformation in a self-contained chapter, and the interrelation of direct notation, indicial notation, and matrix operations is clearly presented. A wide range of idealized materials are considered through simple static and dynamic problems, a

  15. Mechanics of fluid flow

    CERN Document Server

    Basniev, Kaplan S; Chilingar, George V 0

    2012-01-01

    The mechanics of fluid flow is a fundamental engineering discipline explaining both natural phenomena and human-induced processes, and a thorough understanding of it is central to the operations of the oil and gas industry.  This book, written by some of the world's best-known and respected petroleum engineers, covers the concepts, theories, and applications of the mechanics of fluid flow for the veteran engineer working in the field and the student, alike.  It is a must-have for any engineer working in the oil and gas industry.

  16. Adventures in Celestial Mechanics

    CERN Document Server

    Szebehely, Victor G

    1998-01-01

    A fascinating introduction to the basic principles of orbital mechanics. It has been three hundred years since Isaac Newton first formulated laws to explain the orbits of the Moon and the planets of our solar system. In so doing he laid the groundwork for modern science's understanding of the workings of the cosmos and helped pave the way to the age of space exploration. Adventures in Celestial Mechanics offers students an enjoyable way to become acquainted with the basic principles involved in the motions of natural and human-made bodies in space. Packed with examples in which these principle

  17. Computational statistical mechanics

    CERN Document Server

    Hoover, WG

    1991-01-01

    Computational Statistical Mechanics describes the use of fast computers to simulate the equilibrium and nonequilibrium properties of gases, liquids, and solids at, and away from equilibrium. The underlying theory is developed from basic principles and illustrated by applying it to the simplest possible examples. Thermodynamics, based on the ideal gas thermometer, is related to Gibb's statistical mechanics through the use of Nosé-Hoover heat reservoirs. These reservoirs use integral feedback to control temperature. The same approach is carried through to the simulation and anal

  18. Primer of quantum mechanics

    CERN Document Server

    Chester, Marvin

    2003-01-01

    Introductory text examines the classical quantum bead on a track: its state and representations; operator eigenvalues; harmonic oscillator and bound bead in a symmetric force field; and bead in a spherical shell. Also, spin, matrices and structure of quantum mechanics; simplest atom; indistinguishable particles; and stationary-state perturbation theory.

  19. MOOC and mechanized grading

    OpenAIRE

    Queinnec, Christian

    2013-01-01

    4 pages; As many others, we too are developping a Massive Online Open Course or MOOC. This MOOC will teach recursive programming for beginnners and makes an heavy use of an already existing infrastructure for mechanical grading. This paper presents some ideas on how to combine these two components along with some (untested) incentives in order to increase students' involvement.

  20. Pigmi mechanical fabrication

    International Nuclear Information System (INIS)

    Hart, V.E.

    1976-01-01

    A prime goal of the mechanical design effort associated with the PIGMI (Pion Generator for Medical Irradiations) program is to investigate new materials and fabrication techniques in an effort to obtain increased machine efficiency and reliability at a reasonable cost. A discussion is given dealing with the modeling program that LASL is pursuing for 450-MHz and 1350-MHz PIGMI development

  1. PIGMI mechanical fabrication

    International Nuclear Information System (INIS)

    Hart, V.E.

    1976-01-01

    A prime goal of the mechanical design effort associated with the PIGMI (Pion Generator for Medical Irradiations) program is to investigate new materials and fabrication techniques in an effort to obtain increased machine efficiency and reliability at a reasonable cost. The following discussion deals with the modeling program that LASL is pursuing for 450-MHz and 1350-MHz PIGMI development. (author)

  2. Basic Retention Mechanisms

    DEFF Research Database (Denmark)

    Jensen, Bror Skytte; Jensen, H.

    1986-01-01

    . The data for kaolinite were similarly interpreted as adsorption of hydroxylated complexes of the polyvalent cations, a mechanism which has previously been suggested for the adsorption of heavy metals onto muds, sludges and organic debris. In the case of kaolinite, indications of additional reactions like...

  3. Residential Mechanical Precooling

    Energy Technology Data Exchange (ETDEWEB)

    German, a. [Alliance for Residential Building Innovation (ARBI), Davis, CA (United States); Hoeschele, M. [Alliance for Residential Building Innovation (ARBI), Davis, CA (United States)

    2014-12-01

    This research conducted by the Alliance for Residential Building Innovation team evaluated mechanical air conditioner pre-cooling strategies in homes throughout the United States. EnergyPlus modeling evaluated two homes with different performance characteristics in seven climates. Results are applicable to new construction homes and most existing homes built in the last 10 years, as well as fairly efficient retrofitted homes.

  4. Fundamental Fluid Mechanics

    Indian Academy of Sciences (India)

    umes by P N Chatterjee contains standard material for a first level course in fluid me- chanics for Civil, Mechanical, Aeronautical and Chemical Engineering students. It is however not suitable for Applied Science students like those majoring in Physics or. Mathematics and is not a good reference book for practising ...

  5. Mechanisms of Coronal Heating

    Indian Academy of Sciences (India)

    The Sun is a mysterious star. The high temperature of the chromosphere and corona present one of the most puzzling problems of solar physics. Observations show that the solar coronal heating problem is highly complex with many different facts. It is likely that different heating mechanisms are at work in solar corona.

  6. Mechanisms of neuroblastoma regression

    Science.gov (United States)

    Brodeur, Garrett M.; Bagatell, Rochelle

    2014-01-01

    Recent genomic and biological studies of neuroblastoma have shed light on the dramatic heterogeneity in the clinical behaviour of this disease, which spans from spontaneous regression or differentiation in some patients, to relentless disease progression in others, despite intensive multimodality therapy. This evidence also suggests several possible mechanisms to explain the phenomena of spontaneous regression in neuroblastomas, including neurotrophin deprivation, humoral or cellular immunity, loss of telomerase activity and alterations in epigenetic regulation. A better understanding of the mechanisms of spontaneous regression might help to identify optimal therapeutic approaches for patients with these tumours. Currently, the most druggable mechanism is the delayed activation of developmentally programmed cell death regulated by the tropomyosin receptor kinase A pathway. Indeed, targeted therapy aimed at inhibiting neurotrophin receptors might be used in lieu of conventional chemotherapy or radiation in infants with biologically favourable tumours that require treatment. Alternative approaches consist of breaking immune tolerance to tumour antigens or activating neurotrophin receptor pathways to induce neuronal differentiation. These approaches are likely to be most effective against biologically favourable tumours, but they might also provide insights into treatment of biologically unfavourable tumours. We describe the different mechanisms of spontaneous neuroblastoma regression and the consequent therapeutic approaches. PMID:25331179

  7. Lagrange and Classical Mechanics

    Indian Academy of Sciences (India)

    always refers to any specific theory or system by speaking of its Lagrangian. Thus one speaks of the Lagrangian for conservative multi particle systems, for the Maxwell electromagnetic field, for particle mechanics in special relativity, for general relativity, etc. It works for both discrete particle systems and for continuous fields.

  8. Principles of Mechanical Excavation

    Energy Technology Data Exchange (ETDEWEB)

    Lislerud, A. [Tamrock Corp., Tampere (Finland)

    1997-12-01

    Mechanical excavation of rock today includes several methods such as tunnel boring, raiseboring, roadheading and various continuous mining systems. Of these raiseboring is one potential technique for excavating shafts in the repository for spent nuclear fuel and dry blind boring is promising technique for excavation of deposition holes, as demonstrated in the Research Tunnel at Olkiluoto. In addition, there is potential for use of other mechanical excavation techniques in different parts of the repository. One of the main objectives of this study was to analyze the factors which affect the feasibility of mechanical rock excavation in hard rock conditions and to enhance the understanding of factors which affect rock cutting so as to provide an improved basis for excavator performance prediction modeling. The study included the following four main topics: (a) phenomenological model based on similarity analysis for roller disk cutting, (b) rock mass properties which affect rock cuttability and tool life, (c) principles for linear and field cutting tests and performance prediction modeling and (d) cutter head lacing design procedures and principles. As a conclusion of this study, a test rig was constructed, field tests were planned and started up. The results of the study can be used to improve the performance prediction models used to assess the feasibility of different mechanical excavation techniques at various repository investigation sites. (orig.). 21 refs.

  9. Fracture mechanics and parapsychology

    Science.gov (United States)

    Cherepanov, G. P.

    2010-08-01

    The problem of postcritical deformation of materials beyond the ultimate strength is considered a division of fracture mechanics. A simple example is used to show the relationship between this problem and parapsychology, which studies phenomena and processes where the causality principle fails. It is shown that the concept of postcritical deformation leads to problems with no solution

  10. Memory Mechanisms in Grasping

    Science.gov (United States)

    Hesse, Constanze; Franz, Volker H.

    2009-01-01

    The availability of visual information influences the execution of goal-directed movements. This is very prominent in memory conditions, where a delay is introduced between stimulus presentation and execution of the movement. The corresponding effects could be due to a decay of the visual information or to different processing mechanisms used for…

  11. Flight Mechanics Symposium 1997

    Science.gov (United States)

    Walls, Donna M. (Editor)

    1997-01-01

    This conference publication includes papers and abstracts presented at the Flight Mechanics Symposium. This symposium featured technical papers on a wide range of issues related to orbit-attitude prediction, determination, and control; attitude sensor calibration; attitude determination error analysis; attitude dynamics; and orbit decay and maneuver strategy. Government, industry, and the academic community participated in the preparation and presentation of these papers.

  12. Mechanisms of multidrug transporters

    NARCIS (Netherlands)

    Bolhuis, H; van Veen, H.W.; Poolman, B.; Driessen, A.J.M.; Konings, W.N

    Drug resistance, mediated by various mechanisms, plays a crucial role in the failure of the drug-based treatment of various infectious diseases. As a result, these infectious diseases re-emerge rapidly and cause many victims every year. Another serious threat is imposed by the development of

  13. Fracture mechanics and microstructures

    International Nuclear Information System (INIS)

    Gee, M.G.; Morrell, R.

    1986-01-01

    The influence of microstructure on defects in ceramics, and the consequences of their presence for the application of fracture mechanics theories are reviewed. The complexities of microstructures, especially the multiphase nature, the crystallographic anisotropy and the resultant anisotropic physical properties, and the variation of microstructure and surface finish from point to point in real components, all lead to considerable uncertainties in the actual performance of any particular component. It is concluded that although the concepts of fracture mechanics have been and will continue to be most useful for the qualitative explanation of fracture phenomena, the usefulness as a predictive tool with respect to most existing types of material is limited by the interrelation between material microstructure and mechanical properties. At present, the only method of eliminating components with unsatisfactory mechanical properties is to proof-test them, despite the fact that proof-testing itself is limited in ability to cope with changes to the component in service. The aim of the manufacturer must be to improve quality and consistency within individual components, from component to component, and from batch to batch. The aim of the fracture specialist must be to study longer-term properties to improve the accuracy of behaviour predictions with a stronger data base. Materials development needs to concentrate on obtaining defect-free materials that can be translated into more-reliable products, using our present understanding of the influence of microstructure on strength and toughness

  14. Mechanical integrity of canisters

    International Nuclear Information System (INIS)

    Nilsson, Fred

    1992-12-01

    This document constitutes the final report from 'SKBs reference group for mechanical integrity of canisters for spent nuclear fuel'. A complete list of all reports initiated by the reference group can be found in the summary report in this document. The main task of the reference group has been to advice SKB regarding the choice (ranking of alternatives) of canister type for different types of storage. The choice should be based on requirements of impermeability for a given time period and identification of possible limiting mechanisms. The main conclusions from the work were: From mechanical point of view, low phosphorous oxygen free copper (Cu-OFP) is a preferred canisters material. It exhibits satisfactory ductility both during tensile and creep testing. The residual stresses in the canisters are of such a magnitude that the estimated time to creep rupture with the data obtained for the Cu-OFP material is essentially infinite. Based on the present knowledge of stress corrosion cracking of copper there appears to be a small risk for such to occur in the projected environment. This risk need some further study. Rock shear movements of the size of 10 cm should pose no direct threat to the integrity of the canisters. Considering mechanical integrity, the composite copper/steel canister is an advantageous alternative. The recommendations for further research included continued studies of the creep properties of copper and of stress corrosion cracking. However, the studies should focus more directly on the design and fabrication aspect of the canister

  15. Turboprop Propulsion Mechanic.

    Science.gov (United States)

    Chanute AFB Technical Training Center, IL.

    This instructional package consists of a plan of instruction, glossary, and student handouts and exercises for use in training Air Force personnel to become turboprop propulsion mechanics. Addressed in the individual lessons of the course are the following: common hand tools, hardware, measuring devices, and safety wiring; aircraft and engine…

  16. Supersymmetric quantum mechanics

    International Nuclear Information System (INIS)

    Crombrugghe, M. de; Rittenberg, V.

    1982-12-01

    We give a general construction for supersymmetric Hamiltonians in quantum mechanics. We find that N-extended supersymmetry imposes very strong constraints, and for N > 4 the Hamiltonian is integrable. We give a variety of examples, for one-particle and for many-particle systems, in different numbers of dimensions. (orig.)

  17. Structured Mechanical Collage.

    Science.gov (United States)

    Huang, Zhe; Wang, Jiang; Fu, Hongbo; Lau, Rynson W H

    2014-07-01

    We present a method to build 3D structured mechanical collages consisting of numerous elements from the database given artist-designed proxy models. The construction is guided by some graphic design principles, namely unity, variety and contrast. Our results are visually more pleasing than previous works as confirmed by a user study.

  18. Motorcycle Mechanic. Teacher Edition.

    Science.gov (United States)

    Baugus, Mickey; Fulkerson, Dan, Ed.

    These teacher's materials are for a 19-unit competency-based course on entry-level motorcycle mechanics at the secondary and postsecondary levels. The 19 units are: (1) introduction to motorcycle repair; (2) general safety; (3) tools and equipment; (4) metric measurements; (5) fasteners; (6) service department operations; (7) motorcycle engines;…

  19. Fault-Mechanism Simulator

    Science.gov (United States)

    Guyton, J. W.

    1972-01-01

    An inexpensive, simple mechanical model of a fault can be produced to simulate the effects leading to an earthquake. This model has been used successfully with students from elementary to college levels and can be demonstrated to classes as large as thirty students. (DF)

  20. ORGANIC REACTION MECHANISM CONTROVERSY ...

    African Journals Online (AJOL)

    Preferred Customer

    However, there are so many chemical reactions notably in organic chemistry where reactions may not directly lead to products. ... There are concepts that support these ideas but can they be proven to the ... Reaction mechanism is one such issue in organic chemistry that has attracted a lot of controversial comments from ...

  1. Principles of Mechanical Excavation

    International Nuclear Information System (INIS)

    Lislerud, A.

    1997-12-01

    Mechanical excavation of rock today includes several methods such as tunnel boring, raiseboring, roadheading and various continuous mining systems. Of these raiseboring is one potential technique for excavating shafts in the repository for spent nuclear fuel and dry blind boring is promising technique for excavation of deposition holes, as demonstrated in the Research Tunnel at Olkiluoto. In addition, there is potential for use of other mechanical excavation techniques in different parts of the repository. One of the main objectives of this study was to analyze the factors which affect the feasibility of mechanical rock excavation in hard rock conditions and to enhance the understanding of factors which affect rock cutting so as to provide an improved basis for excavator performance prediction modeling. The study included the following four main topics: (a) phenomenological model based on similarity analysis for roller disk cutting, (b) rock mass properties which affect rock cuttability and tool life, (c) principles for linear and field cutting tests and performance prediction modeling and (d) cutter head lacing design procedures and principles. As a conclusion of this study, a test rig was constructed, field tests were planned and started up. The results of the study can be used to improve the performance prediction models used to assess the feasibility of different mechanical excavation techniques at various repository investigation sites. (orig.)

  2. Mechanical meta-materials

    NARCIS (Netherlands)

    Zadpoor, A.A.

    2016-01-01

    The emerging concept of mechanical meta-materials has received increasing attention during the last few years partially due to the advances in additive manufacturing techniques that have enabled fabricating materials with arbitrarily complex micro/nano-architectures. The rationally designed

  3. Mechanical Measurements Laboratory

    CERN Multimedia

    Maximilien Brice

    2007-01-01

    The CERN mechanical measurements team check the sensors on one of the ATLAS inner detector end-caps using high precision measurement equipment. Remote checks like this must be made on these sensitive detector components before they can be transported to make sure that all systems are working correctly.

  4. Social mechanisms and social causation

    OpenAIRE

    Friedel Weinert

    2014-01-01

    The aim of this paper is to examine the notion of social mechanisms by comparison with the notions of evolutionary and physical mechanisms. It is argued that social mechanisms are based on trends, and not lawlike regularities, so that social mechanisms are different from mechanisms in the natural sciences. Taking as an example of social causation the abolition of the slave trade, this paper argues that social mechanisms should be incorporated in Weber’s wider ...

  5. Mechanism for salt scaling

    Science.gov (United States)

    Valenza, John J., II

    Salt scaling is superficial damage caused by freezing a saline solution on the surface of a cementitious body. The damage consists of the removal of small chips or flakes of binder. The discovery of this phenomenon in the early 1950's prompted hundreds of experimental studies, which clearly elucidated the characteristics of this damage. In particular it was shown that a pessimum salt concentration exists, where a moderate salt concentration (˜3%) results in the most damage. Despite the numerous studies, the mechanism responsible for salt scaling has not been identified. In this work it is shown that salt scaling is a result of the large thermal expansion mismatch between ice and the cementitious body, and that the mechanism responsible for damage is analogous to glue-spalling. When ice forms on a cementitious body a bi-material composite is formed. The thermal expansion coefficient of the ice is ˜5 times that of the underlying body, so when the temperature of the composite is lowered below the melting point, the ice goes into tension. Once this stress exceeds the strength of the ice, cracks initiate in the ice and propagate into the surface of the cementitious body, removing a flake of material. The glue-spall mechanism accounts for all of the characteristics of salt scaling. In particular, a theoretical analysis is presented which shows that the pessimum concentration is a consequence of the effect of brine pockets on the mechanical properties of ice, and that the damage morphology is accounted for by fracture mechanics. Finally, empirical evidence is presented that proves that the glue-small mechanism is the primary cause of salt scaling. The primary experimental tool used in this study is a novel warping experiment, where a pool of liquid is formed on top of a thin (˜3 mm) plate of cement paste. Stresses in the plate, including thermal expansion mismatch, result in warping of the plate, which is easily detected. This technique revealed the existence of

  6. Crude oil burning mechanisms

    DEFF Research Database (Denmark)

    van Gelderen, Laurens; Malmquist, Linus Mattias Valdemar; Jomaas, Grunde

    2015-01-01

    In order to improve predictions for the burning efficiency and the residue composition of in-situ burning of crude oil, the burning mechanism of crude oil was studied in relation to the composition of its hydrocarbon mixture, before, during and after the burning. The surface temperature, flame...... height, mass loss rate and residues of three hydrocarbon liquids (n-octane, dodecane and hexadecane), two crude oils (DUC and REBCO) and one hydrocarbon liquid mixture of the aforementioned hydrocarbon liquids were studied using the Crude Oil Flammability Apparatus. The experimental results were compared...... on the highest achievable oil slick temperature. Based on this mechanism, predictions can then be made depending on the hydrocarbon composition of the fuel and the measured surface temperature....

  7. Imaging the Antikythera Mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Malzbender, Thomas

    2012-02-10

    In 1900, a party of sponge divers chanced on the wreck of a Roman merchant vessel between Crete and mainland Greece. It was found to contain numerous ancient Greek treasures, among them a mysterious lump of clay that split open to reveal ‘mathematical gears’ as it dried out. This object is now known as the Antikythera Mechanism, one of the most enlightening artifacts in terms of revealing the advanced nature of ancient Greek science and technology. In 2005 we travelled to the National Archeological Museum in Athens to apply our Reflectance Imaging methods to the mechanism in the hopes of revealing ancient writing on the device. We were successful, and along with the results of Microfocus CT imaging, epigraphers were able to decipher 3000 characters.

  8. Mechanisms of embodiment

    Directory of Open Access Journals (Sweden)

    Katinka eDijkstra

    2015-10-01

    Full Text Available This paper is a critical review of recent studies demonstrating the mechanism of sensorimotor simulation in different cognitive domains. Empirical studies that specify conditions under which embodiment occurs in different domains will be discussed and evaluated. Examples of relevant domains are language comprehension (Tucker & Ellis, 2004, autobiographical memory (Dijkstra, Kaschak, & Zwaan, 2007, gestures (Alibali, Boncoddo, & Hostetter, 2014, facial mimicry (Stel & Vonk, 2010, and problem solving (Wiemers, Bekkering, & Lindemann, 2014. The focus of the review is on supporting claims regarding sensorimotor simulation as well as on factors that modulate dynamic relationships between sensorimotor components in action and cognitive domains, such as expertise (Boschker, Bakker, & Michaels, 2002. This discussion takes place within the context of currently debated issues, specifically the need to specify the underlying mechanisms of embodied representations (Zwaan, 2014; Körner, Topolinski, & Strack, 2015.

  9. Mechanically reinforced glass beams

    DEFF Research Database (Denmark)

    Nielsen, Jens Henrik; Olesen, John Forbes

    2007-01-01

    The use of glass as a load carrying material in structural elements is rarely seen even though glass is a popular material for many architects. This is owed to the unreliable and low tensile strength, which is due to surface flaws and high brittleness of the material. These properties lead...... to breakage without any warning or ductility, which can be catastrophic if no precautions are taken. One aspect of this issue is treated here by looking at the possibility of mechanically reinforcing glass beams in order to obtain ductile failure for such a structural component. A mechanically reinforced...... presented. The experiments show that it is possible to obtain a very ductile structural behavior using the right amount of reinforcement. A Finite Element Model including - in a simple manner - the effects of cracking of glass is presented. Based on a comparison between experimental and model results...

  10. Airway protective mechanisms.

    Science.gov (United States)

    Pitts, Teresa

    2014-02-01

    Cough and swallow are highly coordinated reflex behaviors whose common purpose is to protect the airway. The pharynx is the common tube for air and food/liquid movement from the mouth into the thorax, has been largely overlooked, and is potentially seen as just a passive space. The thyropharyngeus muscle responds to cough inducing stimuli to prepare a transient holding area for material that has been removed from the subglottic airway. The cricopharyngeus muscle participates with the larynx to ensure regulation of pressure when a bolus/air is moving from the upper airway through to the thorax (i.e., inspiration or swallow) or the reverse (i.e., expiration reflex or vomiting). These vital mechanisms have not been evaluated in clinical conditions but could be impaired in many neurodegenerative diseases, leading to aspiration pneumonia. These newly described airway protective mechanisms need further study, especially in healthy and pathologic human populations.

  11. PARALLEL MOVING MECHANICAL SYSTEMS

    Directory of Open Access Journals (Sweden)

    Florian Ion Tiberius Petrescu

    2014-09-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Moving mechanical systems parallel structures are solid, fast, and accurate. Between parallel systems it is to be noticed Stewart platforms, as the oldest systems, fast, solid and precise. The work outlines a few main elements of Stewart platforms. Begin with the geometry platform, kinematic elements of it, and presented then and a few items of dynamics. Dynamic primary element on it means the determination mechanism kinetic energy of the entire Stewart platforms. It is then in a record tail cinematic mobile by a method dot matrix of rotation. If a structural mottoelement consists of two moving elements which translates relative, drive train and especially dynamic it is more convenient to represent the mottoelement as a single moving components. We have thus seven moving parts (the six motoelements or feet to which is added mobile platform 7 and one fixed.

  12. Mechanisms of embodiment.

    Science.gov (United States)

    Dijkstra, Katinka; Post, Lysanne

    2015-01-01

    This paper is a critical review of recent studies demonstrating the mechanism of sensorimotor simulation in different cognitive domains. Empirical studies that specify conditions under which embodiment occurs in different domains will be discussed and evaluated. Examples of relevant domains are language comprehension (Tucker and Ellis, 1998), autobiographical memory (Dijkstra et al., 2007), gestures (Alibali et al., 2014), facial mimicry (Stel and Vonk, 2010), and problem solving (Wiemers et al., 2014). The focus of the review is on supporting claims regarding sensorimotor simulation as well as on factors that modulate dynamic relationships between sensorimotor components in action and cognitive domains, such as expertise (Boschker et al., 2002). This discussion takes place within the context of currently debated issues, specifically the need to specify the underlying mechanisms of embodied representations (Zwaan, 2014; Körner et al., 2015).

  13. Mechanics of active surfaces

    Science.gov (United States)

    Salbreux, Guillaume; Jülicher, Frank

    2017-09-01

    We derive a fully covariant theory of the mechanics of active surfaces. This theory provides a framework for the study of active biological or chemical processes at surfaces, such as the cell cortex, the mechanics of epithelial tissues, or reconstituted active systems on surfaces. We introduce forces and torques acting on a surface, and derive the associated force balance conditions. We show that surfaces with in-plane rotational symmetry can have broken up-down, chiral, or planar-chiral symmetry. We discuss the rate of entropy production in the surface and write linear constitutive relations that satisfy the Onsager relations. We show that the bending modulus, the spontaneous curvature, and the surface tension of a passive surface are renormalized by active terms. Finally, we identify active terms which are not found in a passive theory and discuss examples of shape instabilities that are related to active processes in the surface.

  14. Epigenetic mechanisms in schizophrenia.

    Science.gov (United States)

    Akbarian, Schahram

    2014-09-01

    Schizophrenia is a major psychiatric disorder that lacks a unifying neuropathology, while currently available pharmacological treatments provide only limited benefits to many patients. This review will discuss how the field of neuroepigenetics could contribute to advancements of the existing knowledge on the neurobiology and treatment of psychosis. Genome-scale mapping of DMA methylation, histone modifications and variants, and chromosomal loopings for promoter-enhancer interactions and other epigenetic determinants of genome organization and function are likely to provide important clues about mechanisms contributing to dysregulated expression of synaptic and metabolic genes in schizophrenia brain, including the potential links to the underlying genetic risk architecture and environmental exposures. In addition, studies in animal models are providing a rapidly increasing list of chromatin-regulatory mechanisms with significant effects on cognition and complex behaviors, thereby pointing to the therapeutic potential of epigenetic drug targets in the nervous system.

  15. High pressure mechanical seal

    Science.gov (United States)

    Babel, Henry W. (Inventor); Anderson, Raymond H. (Inventor)

    1996-01-01

    A relatively impervious mechanical seal is formed between the outer surface of a tube and the inside surface of a mechanical fitting of a high pressure fluid or hydraulic system by applying a very thin soft metal layer onto the outer surface of the hard metal tube and/or inner surface of the hard metal fitting. The thickness of such thin metal layer is independent of the size of the tube and/or fittings. Many metals and alloys of those metals exhibit the requisite softness, including silver, gold, tin, platinum, indium, rhodium and cadmium. Suitably, the coating is about 0.0025 millimeters (0.10 mils) in thickness. After compression, the tube and fitting combination exhibits very low leak rates on the order or 10.sup.-8 cubic centimeters per second or less as measured using the Helium leak test.

  16. Time in quantum mechanics

    CERN Document Server

    Mayato, R; Egusquiza, I

    2002-01-01

    The treatment of time in quantum mechanics is still an important and challenging open question in the foundation of the theory. This book describes the problems, and the attempts and achievements in defining, formalizing and measuring different time quantities in quantum theory, such as the parametric (clock) time, tunneling times, decay times, dwell times, delay times, arrival times or jump times. This multiauthored book, written as an introductory guide for the non-initiated as well as a useful source of information for the expert, covers many of the open questions. A brief historical overview is to be found in the introduction. It is followed by 12 chapters devoted to conceptual and theoretical investigations as well as experimental issues in quantum-mechanical time measurements. This unique monograph should attract physicists as well as philosophers of science working in the foundations of quantum physics.

  17. Mechanics of Wood Machining

    CERN Document Server

    Csanády, Etele

    2013-01-01

    Wood is one of the most valuable materials for mankind, and since our earliest days wood materials have been widely used. Today we have modern woodworking machine and tools; however, the raw wood materials available are continuously declining. Therefore we are forced to use this precious material more economically, reducing waste wherever possible. This new textbook on the “Mechanics of Wood Machining” combines the quantitative, mathematical analysis of the mechanisms of wood processing with practical recommendations and solutions. Bringing together materials from many sources, the book contains new theoretical and experimental approaches and offers a clear and systematic overview of the theory of wood cutting, thermal loading in wood-cutting tools, dynamic behaviour of tool and work piece, optimum choice of operational parameters and energy consumption, the wear process of the tools, and the general regularities of wood surface roughness. Diagrams are provided for the quick estimation of various process ...

  18. Branched organs: mechanics of morphogenesis by multiple mechanisms.

    Science.gov (United States)

    Lubkin, Sharon R

    2008-01-01

    Branching morphogenesis is ubiquitous and important in creating bulk transport systems. Branched ducts can be generated by several different mechanisms including growth, cell rearrangements, contractility, adhesion changes, and other mechanisms. We have developed several models of the mechanics of cleft formation, which we review. We discuss the implications of several candidate mechanisms and review what has been found in models and in experiments.

  19. Quantum Mechanics As A Limiting Case of Classical Mechanics

    OpenAIRE

    Ghose, Partha

    2000-01-01

    In spite of its popularity, it has not been possible to vindicate the conventional wisdom that classical mechanics is a limiting case of quantum mechanics. The purpose of the present paper is to offer an alternative point of view in which quantum mechanics emerges as a limiting case of classical mechanics in which the classical system is decoupled from its environment.

  20. Child abuse: underlying mechanisms

    OpenAIRE

    Martínez, Gladys S.

    2009-01-01

    Exposure to traumatic stress during childhood, in the form of abuse or neglect, is related to an increased vulnerability resulting in the development of several pathologies, this relation has been confi rmed by epidemiological studies; however, the neural mechanisms underlying such abnormalities are still unknown. Most of the research done has focused on the effects in the infant, and only recently it has begun to focus on the neurobiological changes in the abusive parents. In this article, I...

  1. Principles of fluid mechanics

    International Nuclear Information System (INIS)

    Kreider, J.F.

    1985-01-01

    This book is an introduction on fluid mechanics incorporating computer applications. Topics covered are as follows: brief history; what is a fluid; two classes of fluids: liquids and gases; the continuum model of a fluid; methods of analyzing fluid flows; important characteristics of fluids; fundamentals and equations of motion; fluid statics; dimensional analysis and the similarity principle; laminar internal flows; ideal flow; external laminar and channel flows; turbulent flow; compressible flow; fluid flow measurements

  2. Acoustic Mechanical Feedthroughs

    Science.gov (United States)

    Sherrit, Stewart; Walkemeyer, Phillip; Bao, Xiaoqi; Bar-Cohen, Yoseph; Badescu, Mircea

    2013-01-01

    Electromagnetic motors can have problems when operating in extreme environments. In addition, if one needs to do mechanical work outside a structure, electrical feedthroughs are required to transport the electric power to drive the motor. In this paper, we present designs for driving rotary and linear motors by pumping stress waves across a structure or barrier. We accomplish this by designing a piezoelectric actuator on one side of the structure and a resonance structure that is matched to the piezoelectric resonance of the actuator on the other side. Typically, piezoelectric motors can be designed with high torques and lower speeds without the need for gears. One can also use other actuation materials such as electrostrictive, or magnetostrictive materials in a benign environment and transmit the power in acoustic form as a stress wave and actuate mechanisms that are external to the benign environment. This technology removes the need to perforate a structure and allows work to be done directly on the other side of a structure without the use of electrical feedthroughs, which can weaken the structure, pipe, or vessel. Acoustic energy is pumped as a stress wave at a set frequency or range of frequencies to produce rotary or linear motion in a structure. This method of transferring useful mechanical work across solid barriers by pumping acoustic energy through a resonant structure features the ability to transfer work (rotary or linear motion) across pressure or thermal barriers, or in a sterile environment, without generating contaminants. Reflectors in the wall of barriers can be designed to enhance the efficiency of the energy/power transmission. The method features the ability to produce a bi-directional driving mechanism using higher-mode resonances. There are a variety of applications where the presence of a motor is complicated by thermal or chemical environments that would be hostile to the motor components and reduce life and, in some instances, not be

  3. Control mechanisms during interaction

    OpenAIRE

    Ooi, Can-Seng

    2010-01-01

    In using the Bakhtinian dialogic approach, this paper examines the microscopic interaction of three artists, two art buyers and one gallery sales executive in Singapore. The importance of galleries, as go-betweens for artists and art buyers is acknowledged in art world research. This paper however looks at the interactional levels and identifies social mechanisms that shape art buying and selling behavior. Despite the possibility of skipping galleries in acquiring art, the c...

  4. Radiation Bystander Effects Mechanism

    Directory of Open Access Journals (Sweden)

    Shokohzaman Soleymanifard

    2009-06-01

    Full Text Available Introduction: Radiation Induced Bystander Effect (RIBE which cause radiation effects in non-irradiated cells, has challenged the principle according to which radiation traversal through the nucleus of a cell is necessary for producing biological responses. What is the mechanism of this phenomenon? To have a better understanding of this rather ambiguous concept substantial number of original and reviewed article were carefully examined. Results: Irradiated cells release molecules which can propagate in cell environment and/or transmit through gap junction intercellular communication. These molecules can reach to non-irradiated cells and transmit bystander signals. In many investigations, it has been confirmed that these molecules are growth factors, cytokines, nitric oxide and free radicals like reactive oxygen species (ROS. Transmission of by stander signal to neighboring cells persuades them to produce secondary growth factors which in their turn cause further cell injuries. Some investigators suggest, organelles other than nucleus (mitochondria and cell membrane are the origin of these signals.  There is another opinion which suggests double strand breaks (DSB are not directly generated in bystander cells, rather they are due to smaller damage like single strand breaks which accumulate and end up to DSB. Although bystander mechanisms have not been exactly known, it can be confirmed that multiple mechanisms and various pathways are responsible for this effect. Cell type, radiation type, experimental conditions and end points identify the dominant mechanism. Conclusion: Molecules and pathways which are responsible for RIBE, also cause systemic responses to other non-irradiation stresses. So RIBE is a kind of systemic stress or innate immune responses, which are performed by cell microenvironment. Irradiated cells and their signals are components of microenvironment for creating bystander effects.

  5. Mechanical properties of wood

    Science.gov (United States)

    David W. Green; Jerrold E. Winandy; David E. Kretschmann

    1999-01-01

    The mechanical properties presented in this chapter were obtained from tests of small pieces of wood termed “clear” and “straight grained” because they did not contain characteristics such as knots, cross grain, checks, and splits. These test pieces did have anatomical characteristics such as growth rings that occurred in consistent patterns within each piece. Clear...

  6. Symmetry and quantum mechanics

    CERN Document Server

    Corry, Scott

    2016-01-01

    This book offers an introduction to quantum mechanics for professionals, students, and others in the field of mathematics who have a minimal background in physics with an understanding of linear algebra and group theory. It covers such topics as Lie groups, algebras and their representations, and analysis (Hilbert space, distributions, the spectral Theorem, and the Stone-Von Neumann Theorem). The book emphasizes the role of symmetry and is useful to physicists as it provides a mathematical introduction to the topic.

  7. MECHANISMS OF BACTERIAL POLYHOSTALITY

    Directory of Open Access Journals (Sweden)

    Markova Yu.A.

    2007-12-01

    Full Text Available In the review data about factors of pathogenicity of the bacteria, capable to amaze both animals, and a plant are collected. Such properties of microorganisms as adhesion, secretion of some enzymes, mobility, a phenomenon of cooperative sensitivity - play an essential role at defeat of different organisms. They are used for many universal offensive strategy overcoming protection of an organism, irrespective of its evolutionary origin. Studying of these mechanisms, will allow to provide new approaches to monitoring illnesses.

  8. Quantum mechanics and computation

    International Nuclear Information System (INIS)

    Cirac Sasturain, J. I.

    2000-01-01

    We review how some of the basic principles of Quantum Mechanics can be used in the field of computation. In particular, we explain why a quantum computer can perform certain tasks in a much more efficient way than the computers we have available nowadays. We give the requirements for a quantum system to be able to implement a quantum computer and illustrate these requirements in some particular physical situations. (Author) 16 refs

  9. Discrete variational Hamiltonian mechanics

    International Nuclear Information System (INIS)

    Lall, S; West, M

    2006-01-01

    The main contribution of this paper is to present a canonical choice of a Hamiltonian theory corresponding to the theory of discrete Lagrangian mechanics. We make use of Lagrange duality and follow a path parallel to that used for construction of the Pontryagin principle in optimal control theory. We use duality results regarding sensitivity and separability to show the relationship between generating functions and symplectic integrators. We also discuss connections to optimal control theory and numerical algorithms

  10. Mechanical beam isolator

    International Nuclear Information System (INIS)

    Post, R.F.; Vann, C.S.

    1996-10-01

    Back-reflections from a target, lenses, etc. can gain energy passing backwards through a laser just like the main beam gains energy passing forwards. Unless something blocks these back-reflections early in their path, they can seriously damage the laser. A Mechanical Beam Isolator is a device that blocks back-reflections early, relatively inexpensively, and without introducing aberrations to the laser beam

  11. 1999 Flight Mechanics Symposium

    Science.gov (United States)

    Lynch, John P. (Editor)

    1999-01-01

    This conference publication includes papers and abstracts presented at the Flight Mechanics Symposium held on May 18-20, 1999. Sponsored by the Guidance, Navigation and Control Center of Goddard Space Flight Center, this symposium featured technical papers on a wide range of issues related to orbit-attitude prediction, determination, and control; attitude sensor calibration; attitude determination error analysis; attitude dynamics; and orbit decay and maneuver strategy. Government, industry, and the academic community participated in the preparation and presentation of these papers.

  12. Probability in quantum mechanics

    Directory of Open Access Journals (Sweden)

    J. G. Gilson

    1982-01-01

    Full Text Available By using a fluid theory which is an alternative to quantum theory but from which the latter can be deduced exactly, the long-standing problem of how quantum mechanics is related to stochastic processes is studied. It can be seen how the Schrödinger probability density has a relationship to time spent on small sections of an orbit, just as the probability density has in some classical contexts.

  13. Classical fracture mechanics methods

    International Nuclear Information System (INIS)

    Schwalbe, K.H.; Heerens, J.; Landes, J.D.

    2007-01-01

    Comprehensive Structural Integrity is a reference work which covers all activities involved in the assurance of structural integrity. It provides engineers and scientists with an unparalleled depth of knowledge in the disciplines involved. The new online Volume 11 is dedicated to the mechanical characteristics of materials. This paper contains the chapter 11.02 of this volume and is structured as follows: Test techniques; Analysis; Fracture behavior; Fracture toughness tests for nonmetals

  14. Mechanical seal program

    International Nuclear Information System (INIS)

    Lowery, G.B.

    1983-01-01

    The experimental plans and timing for completion of the mechanical seal program for both the slurry and transfer pumps are given. The slurry pump seal program will be completed by April 1984 with turnover of two seals in pumps to SRP Tank 15H. Transfer pump seal design will be released for plant use by May 1984. Also included are various other pump and seal related tests

  15. Relational quantum mechanics

    International Nuclear Information System (INIS)

    Rovelli, C.

    1996-01-01

    I suggest that the common unease with taking quantum mechanics as a fundamental description of nature (the open-quotes measurement problemclose quotes) could derive from the use of an incorrect notion, as the unease with the Lorentz transformations before Einstein derived from the notion of observer-independent time. I suggest that this incorrect notion that generates the unease with quantum mechanics is the notion of open-quotes observer-independent stateclose quotes of a system, or open-quotes observer-independent values of physical quantities.close quotes I reformulate the problem of the open-quotes interpretation of quantum mechanicsclose quotes as the problem of deriving the formalism from a set of simple physical postulates. I consider a reformulation of quantum mechanics in terms of information theory. All systems are assumed to be equivalent, there is no observer-observed distinction, and the theory describes only the information that systems have about each other; nevertheless, the theory is complete

  16. Relativistic viscoelastic fluid mechanics.

    Science.gov (United States)

    Fukuma, Masafumi; Sakatani, Yuho

    2011-08-01

    A detailed study is carried out for the relativistic theory of viscoelasticity which was recently constructed on the basis of Onsager's linear nonequilibrium thermodynamics. After rederiving the theory using a local argument with the entropy current, we show that this theory universally reduces to the standard relativistic Navier-Stokes fluid mechanics in the long time limit. Since effects of elasticity are taken into account, the dynamics at short time scales is modified from that given by the Navier-Stokes equations, so that acausal problems intrinsic to relativistic Navier-Stokes fluids are significantly remedied. We in particular show that the wave equations for the propagation of disturbance around a hydrostatic equilibrium in Minkowski space-time become symmetric hyperbolic for some range of parameters, so that the model is free of acausality problems. This observation suggests that the relativistic viscoelastic model with such parameters can be regarded as a causal completion of relativistic Navier-Stokes fluid mechanics. By adjusting parameters to various values, this theory can treat a wide variety of materials including elastic materials, Maxwell materials, Kelvin-Voigt materials, and (a nonlinearly generalized version of) simplified Israel-Stewart fluids, and thus we expect the theory to be the most universal description of single-component relativistic continuum materials. We also show that the presence of strains and the corresponding change in temperature are naturally unified through the Tolman law in a generally covariant description of continuum mechanics.

  17. Mechanical Design of Spacecraft

    Science.gov (United States)

    1962-01-01

    In the spring of 1962, engineers from the Engineering Mechanics Division of the Jet Propulsion Laboratory gave a series of lectures on spacecraft design at the Engineering Design seminars conducted at the California Institute of Technology. Several of these lectures were subsequently given at Stanford University as part of the Space Technology seminar series sponsored by the Department of Aeronautics and Astronautics. Presented here are notes taken from these lectures. The lectures were conceived with the intent of providing the audience with a glimpse of the activities of a few mechanical engineers who are involved in designing, building, and testing spacecraft. Engineering courses generally consist of heavily idealized problems in order to allow the more efficient teaching of mathematical technique. Students, therefore, receive a somewhat limited exposure to actual engineering problems, which are typified by more unknowns than equations. For this reason it was considered valuable to demonstrate some of the problems faced by spacecraft designers, the processes used to arrive at solutions, and the interactions between the engineer and the remainder of the organization in which he is constrained to operate. These lecture notes are not so much a compilation of sophisticated techniques of analysis as they are a collection of examples of spacecraft hardware and associated problems. They will be of interest not so much to the experienced spacecraft designer as to those who wonder what part the mechanical engineer plays in an effort such as the exploration of space.

  18. Relativistic viscoelastic fluid mechanics

    International Nuclear Information System (INIS)

    Fukuma, Masafumi; Sakatani, Yuho

    2011-01-01

    A detailed study is carried out for the relativistic theory of viscoelasticity which was recently constructed on the basis of Onsager's linear nonequilibrium thermodynamics. After rederiving the theory using a local argument with the entropy current, we show that this theory universally reduces to the standard relativistic Navier-Stokes fluid mechanics in the long time limit. Since effects of elasticity are taken into account, the dynamics at short time scales is modified from that given by the Navier-Stokes equations, so that acausal problems intrinsic to relativistic Navier-Stokes fluids are significantly remedied. We in particular show that the wave equations for the propagation of disturbance around a hydrostatic equilibrium in Minkowski space-time become symmetric hyperbolic for some range of parameters, so that the model is free of acausality problems. This observation suggests that the relativistic viscoelastic model with such parameters can be regarded as a causal completion of relativistic Navier-Stokes fluid mechanics. By adjusting parameters to various values, this theory can treat a wide variety of materials including elastic materials, Maxwell materials, Kelvin-Voigt materials, and (a nonlinearly generalized version of) simplified Israel-Stewart fluids, and thus we expect the theory to be the most universal description of single-component relativistic continuum materials. We also show that the presence of strains and the corresponding change in temperature are naturally unified through the Tolman law in a generally covariant description of continuum mechanics.

  19. Control rod driving mechanisms

    International Nuclear Information System (INIS)

    Maejima, Yoshinori.

    1986-01-01

    Purpose: To conduct reactor scram by an external signal and, also by a signal for the abnormal temperature from a temperature detector in the nuclear reactor. Constitution: Control rod driving mechanisms magnetically coupling the extension pipe with the elevating mechanism above the reactor core and the holding magnet, and retains a control rod to the lower portion of the extension pipe by way of a latch mechanism. The temperature detector is immersed in reactor coolants. If the temperature of the coolants rises abnormally, bimetal contacts of the temperature detector are opened to interrupt the current supply to the holding electromagnet. Then, the extension pipe released from the magnetic coupling is lowered and the control rod free from latch is rapidly dropped and inserted into the reactor core. Since this procedure is carried out for all of the control rods, the reactor scram can be attained. The feature of this invention resides in that the reactor scram can be attained also by the signal of the reactor core itself even if the signal system for the external signals should be failed. (Horiuchi, T.)

  20. Copenhagen quantum mechanics

    Science.gov (United States)

    Hollowood, Timothy J.

    2016-07-01

    In our quantum mechanics courses, measurement is usually taught in passing, as an ad-hoc procedure involving the ugly collapse of the wave function. No wonder we search for more satisfying alternatives to the Copenhagen interpretation. But this overlooks the fact that the approach fits very well with modern measurement theory with its notions of the conditioned state and quantum trajectory. In addition, what we know of as the Copenhagen interpretation is a later 1950s development and some of the earlier pioneers like Bohr did not talk of wave function collapse. In fact, if one takes these earlier ideas and mixes them with later insights of decoherence, a much more satisfying version of Copenhagen quantum mechanics emerges, one for which the collapse of the wave function is seen to be a harmless book keeping device. Along the way, we explain why chaotic systems lead to wave functions that spread out quickly on macroscopic scales implying that Schrödinger cat states are the norm rather than curiosities generated in physicists' laboratories. We then describe how the conditioned state of a quantum system depends crucially on how the system is monitored illustrating this with the example of a decaying atom monitored with a time of arrival photon detector, leading to Bohr's quantum jumps. On the other hand, other kinds of detection lead to much smoother behaviour, providing yet another example of complementarity. Finally we explain how classical behaviour emerges, including classical mechanics but also thermodynamics.

  1. Mechanical Properties of Materials

    CERN Document Server

    Pelleg, Joshua

    2013-01-01

    The subject of mechanical behavior has been in the front line of basic studies in engineering curricula for many years.  This textbook was written for engineering students with the aim of presenting, in a relatively simple manner, the basic concepts of mechanical behavior in solid materials. A second aim of the book is to guide students in their laboratory experiments by helping them to understand their observations in parallel with the lectures of their various courses; therefore the first chapter of the book is devoted to mechanical testing. Another aim of the book is to provide practicing engineers with basic help to bridge the gap of time that has passed from their graduation up to their actual involvement in engineering work. The book also serves as the basis for more advanced studies and seminars when pursuing courses on a graduate level. The content of this textbook and the topics discussed correspond to courses that are usually taught in universities and colleges all over the world, but with a differ...

  2. [Mechanisms of tooth eruption].

    Science.gov (United States)

    Maltha, J C

    2014-04-01

    Tooth eruption is of the utmost importance for the normal development of the dentition and the face. Since the 1980s, it has been known that the tooth germ itself is not essential for facilitating the processes that make tooth eruption possible. For that reason, recent research on the regulatory mechanisms of tooth eruption has focused mainly on the enamel organ and the dental follicle. Different regulatory mechanisms act on the occlusal and the apical sides of an erupting tooth. On the occlusal side osteoclast differentiation is stimulated. This leads to the development of an eruption canal, a process in which macrophages and matrix metalloproteases also play an important role. On the apical side the most important factors are the transcription factor RUNX2 and the bone morphogenic protein 2. They are responsible for the deposition of trabecular bone in that area. Many regulatory mechanisms which are involved in tooth eruption are also active in other developmental processes. This explains that certain syndromes can also have an effect on the tooth eruption process.

  3. The physio-mechanical

    Directory of Open Access Journals (Sweden)

    C.U. Atuanya

    2014-01-01

    Full Text Available This work presents a systematic approach to evaluate the physio-mechanical properties of bean pod ash particles (BPAp reinforced recycled polyethylene (RLDPE polymer based composites. The bean pod ash particles of 75 μm with a weight percentage of 0, 5, 10, 15, 20, 25, 30 (wt% and recycled polyethylene (RLDPE were prepared. The surface morphology, physical and the mechanical properties of the composites were examined. The results showed that the fair distribution of the bean pod ash particles in the microstructure of the polymer composites is the major factor responsible for the improvement in the mechanical properties. The bean pod ash particles added to the RLDPE polymer increased the percentage of water absorption and improved its rigidity, modulus and hardness values of the composites. The tensile and flexural strengths increased to a maximum of 20.1 and 39.0 N/mm2 at 20 wt% BPAp respectively. Based on the results obtained in this study, it is recommended that the composites can be used in the production of indoor and outdoor applications.

  4. Nonlinear crack mechanics

    International Nuclear Information System (INIS)

    Khoroshun, L.P.

    1995-01-01

    The characteristic features of the deformation and failure of actual materials in the vicinity of a crack tip are due to their physical nonlinearity in the stress-concentration zone, which is a result of plasticity, microfailure, or a nonlinear dependence of the interatomic forces on the distance. Therefore, adequate models of the failure mechanics must be nonlinear, in principle, although linear failure mechanics is applicable if the zone of nonlinear deformation is small in comparison with the crack length. Models of crack mechanics are based on analytical solutions of the problem of the stress-strain state in the vicinity of the crack. On account of the complexity of the problem, nonlinear models are bason on approximate schematic solutions. In the Leonov-Panasyuk-Dugdale nonlinear model, one of the best known, the actual two-dimensional plastic zone (the nonlinearity zone) is replaced by a narrow one-dimensional zone, which is then modeled by extending the crack with a specified normal load equal to the yield point. The condition of finite stress is applied here, and hence the length of the plastic zone is determined. As a result of this approximation, the displacement in the plastic zone at the abscissa is nonzero

  5. Time Asymmetric Quantum Mechanics

    Directory of Open Access Journals (Sweden)

    Arno R. Bohm

    2011-09-01

    Full Text Available The meaning of time asymmetry in quantum physics is discussed. On the basis of a mathematical theorem, the Stone-von Neumann theorem, the solutions of the dynamical equations, the Schrödinger equation (1 for states or the Heisenberg equation (6a for observables are given by a unitary group. Dirac kets require the concept of a RHS (rigged Hilbert space of Schwartz functions; for this kind of RHS a mathematical theorem also leads to time symmetric group evolution. Scattering theory suggests to distinguish mathematically between states (defined by a preparation apparatus and observables (defined by a registration apparatus (detector. If one requires that scattering resonances of width Γ and exponentially decaying states of lifetime τ=h/Γ should be the same physical entities (for which there is sufficient evidence one is led to a pair of RHS's of Hardy functions and connected with it, to a semigroup time evolution t_0≤t<∞, with the puzzling result that there is a quantum mechanical beginning of time, just like the big bang time for the universe, when it was a quantum system. The decay of quasi-stable particles is used to illustrate this quantum mechanical time asymmetry. From the analysis of these processes, we show that the properties of rigged Hilbert spaces of Hardy functions are suitable for a formulation of time asymmetry in quantum mechanics.

  6. Mechanical stop mechanism for overcoming MEMS fabrication tolerances

    International Nuclear Information System (INIS)

    Hussein, Hussein; Bourbon, Gilles; Le Moal, Patrice; Lutz, Philippe; Haddab, Yassine

    2017-01-01

    A mechanical stop mechanism is developed in order to compensate MEMS fabrication tolerances in discrete positioning. The mechanical stop mechanism is designed to be implemented on SOI wafers using a common DRIE etching process. The various fabrication tolerances obtained due to the etching process are presented and discussed in the paper. The principle and design of the mechanism are then presented. Finally, experiments on microfabricated positioning prototypes show accurate steps unaffected by the fabrication tolerances. (technical note)

  7. Game mechanics : advanced game design

    NARCIS (Netherlands)

    Adams, Ernest; Dormans, Joris

    2012-01-01

    Game Mechanics is aimed at game design students and industry professionals who want to improve their understanding of how to design, build, and test the mechanics of a game. Game Mechanics will show you how to design, test, and tune the core mechanics of a game—any game, from a huge role-playing

  8. Understanding Bohmian mechanics: A dialogue

    OpenAIRE

    Tumulka, Roderich

    2004-01-01

    This paper is an introduction to the ideas of Bohmian mechanics, an interpretation of quantum mechanics in which the observer plays no fundamental role. Bohmian mechanics describes, instead of probabilities of measurement results, objective microscopic events. In recent years, Bohmian mechanics has attracted increasing attention by researchers. The form of a dialogue allows me to address questions about the Bohmian view that often arise.

  9. Bistable Mechanisms for Space Applications.

    Science.gov (United States)

    Zirbel, Shannon A; Tolman, Kyler A; Trease, Brian P; Howell, Larry L

    2016-01-01

    Compliant bistable mechanisms are monolithic devices with two stable equilibrium positions separated by an unstable equilibrium position. They show promise in space applications as nonexplosive release mechanisms in deployment systems, thereby eliminating friction and improving the reliability and precision of those mechanical devices. This paper presents both analytical and numerical models that are used to predict bistable behavior and can be used to create bistable mechanisms in materials not previously feasible for compliant mechanisms. Materials compatible with space applications are evaluated for use as bistable mechanisms and prototypes are fabricated in three different materials. Pin-puller and cutter release mechanisms are proposed as potential space applications.

  10. Bistable Mechanisms for Space Applications

    Science.gov (United States)

    Zirbel, Shannon A.; Tolman, Kyler A.; Trease, Brian P.

    2016-01-01

    Compliant bistable mechanisms are monolithic devices with two stable equilibrium positions separated by an unstable equilibrium position. They show promise in space applications as nonexplosive release mechanisms in deployment systems, thereby eliminating friction and improving the reliability and precision of those mechanical devices. This paper presents both analytical and numerical models that are used to predict bistable behavior and can be used to create bistable mechanisms in materials not previously feasible for compliant mechanisms. Materials compatible with space applications are evaluated for use as bistable mechanisms and prototypes are fabricated in three different materials. Pin-puller and cutter release mechanisms are proposed as potential space applications. PMID:28030588

  11. Epigenetic mechanisms in neurogenesis

    Science.gov (United States)

    Yao, Bing; Christian, Kimberly M.; He, Chuan; Jin, Peng; Ming, Guo-li; Song, Hongjun

    2017-01-01

    In the embryonic and adult brain, neural stem cells proliferate and give rise to neurons and glia through highly regulated processes. Epigenetic mechanisms — including DNA and histone modifications, as well as regulation by non-coding RNAs — have pivotal roles in different stages of neurogenesis. Aberrant epigenetic regulation also contributes to the pathogenesis of various brain disorders. Here, we review recent advances in our understanding of epigenetic regulation in neurogenesis and its dysregulation in brain disorders, including discussion of newly identified DNA cytosine modifications. We also briefly cover the emerging field of epitranscriptomics, which involves modifications of mRNAs and long non-coding RNAs. PMID:27334043

  12. Sediment transport mechanics

    Science.gov (United States)

    Ballio, Francesco; Tait, Simon

    2012-12-01

    The Editor of Acta Geophysica and the Guest Editors wish to dedicate this Topical Issue on Sediment Transport Mechanics to the memory of Stephen Coleman, who died recently. During his career, Stephen had made an outstanding scientific contribution to the topic of Sediment Transport. The level of his contribution is demonstrated in the paper by Aberle, Coleman, and Nikora included in this issue, on which he started working before becoming aware of the illness that led to his untimely death. For scholars and colleagues Stephen remains an example of intellectual honesty and scientific insight.

  13. Advances in computational mechanics

    International Nuclear Information System (INIS)

    Donea, J.; Belytschko, T.

    1992-01-01

    Some of the major issues which have been addressed in finite element research are reviewed, including some issues which remain unresolved. The focus is on topics related to problems of constrained media and fluid dynamics by finite elements. Two examples of constrained media are considered: isoparametric element approaches to incompressible materials and beam and shell elements. Pertinent issues include locking, spurious singular modes, and stress oscillations. In fluid mechanics, the central themes are stable treatments of the convection or transport terms and arbitrary Lagrangian-Eulerian meshes. (orig.)

  14. Statistical mechanics of learning

    CERN Document Server

    Engel, Andreas

    2001-01-01

    The effort to build machines that are able to learn and undertake tasks such as datamining, image processing and pattern recognition has led to the development of artificial neural networks in which learning from examples may be described and understood. The contribution to this subject made over the past decade by researchers applying the techniques of statistical mechanics is the subject of this book. The authors provide a coherent account of various important concepts and techniques that are currently only found scattered in papers, supplement this with background material in mathematics and physics, and include many examples and exercises.

  15. Mechanics of Generalized Continua

    CERN Document Server

    Altenbach, Holm; Erofeev, Vladimir

    2011-01-01

    This collection on auMechanics of Generalized Continua - from Micromechanical Basics to Engineering Applications" brings together leading scientists in this field from France, Russian Federation, and Germany. The attention in this publication is be focussed on the most recent research items, i.e., - new models, - application of well-known models to new problems, - micro-macro aspects, - computational effort, - possibilities to identify the constitutive equations, and - old problems with incorrect or non-satisfying solutions based on the classical continua assumptions.

  16. Unwaving quantum mechanics

    International Nuclear Information System (INIS)

    Torre, A.C. de la; Mirabella, D.; Izus, G.

    1990-01-01

    The so called diffraction experiments are explained making no reference to any wave whatsoever. It is proposed that these waves are a mere mathematical artifact without any physical reality. If propensities and transmission between them are accepted as a physical reality, then the wave concept can be set aside along with duality and complementarity, thus eliminating controversy on the interpretation of quantum mechanics. An outline is made of the formulation of the theory based on the preparation of the system according to propensities and the transmission between them. (Author). 19 refs., 1 fig

  17. Mechanically Invisible Polymer Coatings

    DEFF Research Database (Denmark)

    2014-01-01

    phase comprises particles, said particles comprising a filler material and an encapsulating coating of a second polymeric material, wherein the backbones of the first and second polymeric materials are the same. The composition may be used in electroactive polymers (EAPs) in order to obtain mechanically......The present invention relates to a composition comprising encapsulated particles in a polymeric material. The composition comprises a continuous phase and a discontinuous phase incorporated therein, wherein the continuous phase comprises a first polymeric material and wherein the discontinuous...... invisible polymer coatings....

  18. 2001 Flight Mechanics Symposium

    Science.gov (United States)

    Lynch, John P. (Editor)

    2001-01-01

    This conference publication includes papers and abstracts presented at the Flight Mechanics Symposium held on June 19-21, 2001. Sponsored by the Guidance, Navigation and Control Center of Goddard Space Flight Center, this symposium featured technical papers on a wide range of issues related to attitude/orbit determination, prediction and control; attitude simulation; attitude sensor calibration; theoretical foundation of attitude computation; dynamics model improvements; autonomous navigation; constellation design and formation flying; estimation theory and computational techniques; Earth environment mission analysis and design; and, spacecraft re-entry mission design and operations.

  19. Quantum mechanical resonances

    International Nuclear Information System (INIS)

    Cisneros S, A.; McIntosh, H.V.

    1982-01-01

    A discussion of the nature of quantum mechanical resonances is presented from the point of view of the spectral theory of operators. In the case of Bohr-Feshbach resonances, graphs are presented to illustrate the theory showing the decay of a doubly excited metastable state and the excitation of the resonance by an incident particle with proper energy. A characterization of resonances is given as well as a procedure to determine widths using the spectral density function. A sufficient condition is given for the validity of the Breit-Wigner formula for Bohr-Feshbach resonances. (author)

  20. Mechanical engineering principles

    CERN Document Server

    Bird, John

    2014-01-01

    A student-friendly introduction to core engineering topicsThis book introduces mechanical principles and technology through examples and applications, enabling students to develop a sound understanding of both engineering principles and their use in practice. These theoretical concepts are supported by 400 fully worked problems, 700 further problems with answers, and 300 multiple-choice questions, all of which add up to give the reader a firm grounding on each topic.The new edition is up to date with the latest BTEC National specifications and can also be used on undergraduate courses in mecha

  1. Nanoantenna using mechanical resonance

    KAUST Repository

    Chang Hwa Lee,

    2010-11-01

    Nanoantenna using mechanical resonance vibration is made from an indium tin oxide (ITO) coated vertically aligned nanorod array. Only this structure works as a radio with demodulator without any electrical circuit using field emission phenomenon. A top-down fabrication method of an ITO coated nanorod array is proposed using a modified UV lithography. The received radio frequency and the resonance frequency of nanoantenna can be controlled by the fabrication condition through the height of a nanorod array. The modulated signals are received successfully with the transmission carrier wave frequency (248MHz) and the proposed nanoantenna is expected to be used in communication system for ultra small scale sensor. ©2010 IEEE.

  2. Molecular mechanisms in gliomagenesis

    DEFF Research Database (Denmark)

    Hulleman, Esther; Helin, Kristian

    2005-01-01

    , in order to design novel therapies and treatments for GBM, research has recently intensified to identify the cellular and molecular mechanisms leading to GBM formation. Modeling of astrocytomas by genetic manipulation of mice suggests that deregulation of the pathways that control gliogenesis during normal...... brain development, such as the differentiation of neural stem cells (NSCs) into astrocytes, might contribute to GBM formation. These pathways include growth factor-induced signal transduction routes and processes that control cell cycle progression, such as the p16-CDK4-RB and the ARF-MDM2-p53 pathways...

  3. Chaos in Structural Mechanics

    CERN Document Server

    Awrejcewicz, Jan

    2008-01-01

    This volume introduces and reviews novel theoretical approaches to modeling strongly nonlinear behaviour of either individual or interacting structural mechanical units such as beams, plates and shells or composite systems thereof. The approach draws upon the well-established fields of bifurcation theory and chaos and emphasizes the notion of control and stability of objects and systems the evolution of which is governed by nonlinear ordinary and partial differential equations. Computational methods, in particular the Bubnov-Galerkin method, are thus described in detail.

  4. Introduction to continuum mechanics

    CERN Document Server

    Rubin, David; Lai, W Michael

    1994-01-01

    Continuum mechanics studies the response of materials to different loading conditions. The concept of tensors is introduced through the idea of linear transformation in a self-contained chapter, and the interrelation of direct notation, indicial notation and matrix operations is clearly presented. A wide range of idealized materials are considered through simple static and dynamic problems, and the book contains an abundance of illustrative examples and problems, many with solutions. Through the addition of more advanced material (solution of classical elasticity problems, constitutive e

  5. Turbulent current drive mechanisms

    Science.gov (United States)

    McDevitt, Christopher J.; Tang, Xian-Zhu; Guo, Zehua

    2017-08-01

    Mechanisms through which plasma microturbulence can drive a mean electron plasma current are derived. The efficiency through which these turbulent contributions can drive deviations from neoclassical predictions of the electron current profile is computed by employing a linearized Coulomb collision operator. It is found that a non-diffusive contribution to the electron momentum flux as well as an anomalous electron-ion momentum exchange term provide the most efficient means through which turbulence can modify the mean electron current for the cases considered. Such turbulent contributions appear as an effective EMF within Ohm's law and hence provide an ideal means for driving deviations from neoclassical predictions.

  6. Mechanics of materials model

    Science.gov (United States)

    Meister, Jeffrey P.

    1987-01-01

    The Mechanics of Materials Model (MOMM) is a three-dimensional inelastic structural analysis code for use as an early design stage tool for hot section components. MOMM is a stiffness method finite element code that uses a network of beams to characterize component behavior. The MOMM contains three material models to account for inelastic material behavior. These include the simplified material model, which assumes a bilinear stress-strain response; the state-of-the-art model, which utilizes the classical elastic-plastic-creep strain decomposition; and Walker's viscoplastic model, which accounts for the interaction between creep and plasticity that occurs under cyclic loading conditions.

  7. Mechanisms of Cardiac Regeneration

    Science.gov (United States)

    Uygur, Aysu; Lee, Richard T.

    2016-01-01

    Adult humans fail to regenerate their hearts following injury, and this failure to regenerate myocardium is a leading cause of heart failure and death worldwide. Although all adult mammals appear to lack significant cardiac regeneration potential, some vertebrates can regenerate myocardium throughout life. In addition, new studies indicate that mammals have cardiac regeneration potential during development and very soon after birth. The mechanisms of heart regeneration among model organisms, including neonatal mice, appear remarkably similar. Orchestrated waves of inflammation, matrix deposition and remodeling, and cardiomyocyte proliferation are commonly seen in heart regeneration models. Understanding why adult mammals develop extensive scarring instead of regeneration is a crucial goal for regenerative biology. PMID:26906733

  8. 15. Amygdala pain mechanisms

    Science.gov (United States)

    Neugebauer, Volker

    2015-01-01

    A limbic brain area the amygdala plays a key role in emotional responses and affective states and disorders such as learned fear, anxiety and depression. The amygdala has also emerged as an important brain center for the emotional-affective dimension of pain and for pain modulation. Hyperactivity in the laterocapsular division of the central nucleus of the amygdala (CeLC, also termed the “nociceptive amygdala”) accounts for pain-related emotional responses and anxiety-like behavior. Abnormally enhanced output from the CeLC is the consequence of an imbalance between excitatory and inhibitory mechanisms. Impaired inhibitory control mediated by a cluster of GABAergic interneurons in the intercalated cell masses (ITC) allows the development of glutamate- and neuropeptide-driven synaptic plasticity of excitatory inputs from the brainstem (parabrachial area) and from the lateral-basolateral amygdala network (LA-BLA, site of integration of polymodal sensory information). BLA hyperactivity also generates abnormally enhanced feedforward inhibition of principal cells in the medial prefrontal cortex (mPFC), a limbic cortical area that is strongly interconnected with the amygdala. Pain-related mPFC deactivation results in cognitive deficits and failure to engage cortically driven ITC-mediated inhibitory control of amygdala processing. Impaired cortical control allows the uncontrolled persistence of amygdala pain mechanisms. PMID:25846623

  9. Residential Mechanical Precooling

    Energy Technology Data Exchange (ETDEWEB)

    German, Alea [Davis Energy Group, Davis, CA (United States). Alliance for Residential Building Innovation (ARBI); Hoeschele, Marc [Davis Energy Group, Davis, CA (United States). Alliance for Residential Building Innovation (ARBI)

    2014-12-01

    Residential air conditioning (AC) represents a challenging load for many electric utilities with poor load factors. Mechanical precooling improves the load factor by shifting cooling operation from on-peak to off-peak hours. This provides benefits to utilities and the electricity grid, as well as to occupants who can take advantage of time-of-use (TOU) electricity rates. Performance benefits stem from reduced compressor cycling, and shifting condensing unit operation to earlier periods of the day when outdoor temperatures are more favorable to operational efficiency. Finding solutions that save energy and reduce demand on the electricity grid is an important national objective and supports key Building America goals. The Alliance for Residential Building Innovation team evaluated mechanical AC precooling strategies in homes throughout the United States. EnergyPlus modeling was used to evaluate two homes with different performance characteristics in seven climates. Results are applicable to new construction homes and most existing homes built in the last 10 years, as well as fairly efficient retrofitted homes. A successful off-peak AC strategy offers the potential for increased efficiency and improved occupant comfort, and promotes a more reliable and robust electricity grid. Demand response capabilities and further integration with photovoltaic TOU generation patterns provide additional opportunities to flatten loads and optimize grid impacts.

  10. Mechanisms of Plasma Therapeutics

    Science.gov (United States)

    Graves, David

    2015-09-01

    In this talk, I address research directed towards biomedical applications of atmospheric pressure plasma such as sterilization, surgery, wound healing and anti-cancer therapy. The field has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that plasmas readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. It is postulated that cold atmospheric plasma (CAP) can trigger a therapeutic shielding response in tissue in part by creating a time- and space-localized, burst-like form of oxy-nitrosative stress on near-surface exposed cells through the flux of plasma-generated RONS. RONS-exposed surface layers of cells communicate to the deeper levels of tissue via a form of the ``bystander effect,'' similar to responses to other forms of cell stress. In this proposed model of CAP therapeutics, the plasma stimulates a cellular survival mechanism through which aerobic organisms shield themselves from infection and other challenges.

  11. Lectures on Quantum Mechanics

    CERN Document Server

    Basdevant, Jean-Louis

    2007-01-01

    Beautifully illustrated and engagingly written, Lectures on Quantum Mechanics presents theoretical physics with a breathtaking array of examples and anecdotes. Basdevant's style is clear and stimulating, in the manner of a brisk classroom lecture that students can follow with ease and enjoyment. Here is a sample of the book's style, from the opening of Chapter 1: "If one were to ask a passer-by to quote a great formula of physics, chances are that the answer would be 'E = mc2'. Nevertheless, the formula 'E=hV' which was written in the same year 1905 by the same Albert Einstein, and which started quantum theory, concerns their daily life considerably more. In fact, of the three watershed years for physics toward the beginning of the 20th century - 1905: the Special Relativity of Einstein, Lorentz and Poincaré; 1915: the General Relativity of Einstein, with its extraordinary reflections on gravitation, space and time; and 1925: the full development of Quantum Mechanics - it is surely the last which has the mos...

  12. Clonus: definition, mechanism, treatment

    Directory of Open Access Journals (Sweden)

    Ismail Boyraz

    2015-02-01

    Full Text Available Clonus is involuntary and rhythmic muscle contractions caused by a permanent lesion in descending motor neurons. Clonus may be found at the ankle, patella, triceps surae, wrist, jaw, biceps brachii. In general, clonus may occur in any muscle with a frequency of 5-8 Hz and the average period of oscillations of the ankle clonus is approximately 160–200 ms. Plantar flexion (PF comprises 45% of the period, dorsifleksion (DF comprises 55% of the period. The first beat is always longer, with the time shortening in continuing beats and becoming stable in the 4th or 5th period. The exact mechanism of clonus remains unclear. Two different hypotheses have been asserted regarding the development of clonus. The most widely accepted explanation is that hyperactive stretch reflexes in clonus are caused by self-excitation. Another alternative explanation for clonus is central generator activity that arises as a consequence of appropriate peripheral events and produces rhythmic stimulation of the lower motor neurons. The durations of clonus burst were found longer than the durations of Soleus medium-latency reflex (MLR. There is a similarity in their nature, although the speed and cause of the stretch of triceps surae differ in the MLR and the clonus, and there is a sufficient period of time for group II afferents and for other spinal mechanisms to be involved in the clonus, together with Ia afferents. Clonus can be treated by using baclofen, applying cold, botox or phenol injections.

  13. Decomposition mechanisms of tertiarybutylarsine

    Science.gov (United States)

    Larsen, C. A.; Buchan, N. I.; Li, S. H.; Stringfellow, G. B.

    1989-03-01

    As a new source compound to replace AsH 3 for organometallic vapor phase epitaxy (OMVPE) of III/V semiconductors, tertiarybutylarsine (TBAs) has the advantages of low decomposition temperatures, lower safety hazards, and low carbon contamination in OMVPE grown GaAs layers. The vapor pressure of TBAs was measured, and is given by log 10P( Torr) = 7.500 - 1562.3/ T( K). The decomposition mechanisms of TBAs were studied in a D 2 ambient using a time-of-flight mass spectrometer to analyze the gaseous products. Although a free radical mechanisms would seem the most likely, it is not the dominant route for decomposition. Instead, unimolecular processes are the preferred pathway. Two such reactions are proposed. The major step is intramolecular coupling yielding AsH and isobutane. At higher temperatures β-elimination becomes important, producing AsH 3 and isobutene. The reactions are catalyzed by GaAs surfaces, but not by silica. The temperature dependence of the reaction rates was studied, and Arrhenius parameters for the rate constants are given.

  14. Peripheral Auditory Mechanisms

    CERN Document Server

    Hall, J; Hubbard, A; Neely, S; Tubis, A

    1986-01-01

    How weIl can we model experimental observations of the peripheral auditory system'? What theoretical predictions can we make that might be tested'? It was with these questions in mind that we organized the 1985 Mechanics of Hearing Workshop, to bring together auditory researchers to compare models with experimental observations. Tbe workshop forum was inspired by the very successful 1983 Mechanics of Hearing Workshop in Delft [1]. Boston University was chosen as the site of our meeting because of the Boston area's role as a center for hearing research in this country. We made a special effort at this meeting to attract students from around the world, because without students this field will not progress. Financial support for the workshop was provided in part by grant BNS- 8412878 from the National Science Foundation. Modeling is a traditional strategy in science and plays an important role in the scientific method. Models are the bridge between theory and experiment. Tbey test the assumptions made in experim...

  15. The French capacity mechanism

    International Nuclear Information System (INIS)

    2014-01-01

    The French capacity mechanism has been design to ensure security of supply in the context of the energy transition. This energy transition challenges the electricity market design with several features: peak load growth, the development of renewables, demand response,... To ensure security of supply in this context, a capacity mechanism is being implemented in France. It is a market wide capacity obligation on electricity suppliers, based on market principles. Suppliers are responsible for forecasting their obligation, which corresponds to their contribution to winter peak load, and must procure enough capacity certificates to meet their obligations. Capacity certificates are granted to capacities through a certification process, which assesses their contribution to security of supply on the basis of availability commitments. This certification process is technology neutral and performance based, associated with controls and penalties in case of non compliance. Demand Side is fully integrated in the market, either through the reduction of suppliers' capacity obligation or direct participation after certification. In addition to the expected benefits in terms of security of supply, the French capacity market will foster the development of demand response. The participation of foreign capacities will require adaptations which are scheduled in a road-map, and could pave the way for further European integration of energy policies. (authors)

  16. Immune Mechanisms in Epileptogenesis

    Directory of Open Access Journals (Sweden)

    Dan eXu

    2013-11-01

    Full Text Available Epilepsy is a chronic brain disorder that affects one percent of the human population worldwide. Immune responses are implicated in seizure induction and the development of epilepsy. Pre-clinical and clinical evidence have accumulated to suggest a positive feedback cycle between brain inflammation and epileptogenesis. Prolonged or recurrent seizures and brain injuries lead to upregulation of proinflammatory cytokines and activated immune responses to further increase seizure susceptibility, promote neuronal excitability, and induce blood-brain barrier (BBB breakdown. This review focuses on the potential role of innate and adaptive immune responses in the pathogenesis of epilepsy. Both human studies and animal models that help delineate the contributions of brain inflammation in epileptogenesis will be discussed. We highlight the critical role of brain-resident immune mediators and emphasize the contribution of brain-infiltrating peripheral leukocytes. Additionally, we propose possible immune mechanisms that underlie epileptogenesis. Several proinflammatory pathways are discussed, including the interleukin-1 receptor/ toll-like receptor signaling cascade, the pathways activated by danger-associated molecular patterns, and the cyclooxygenase-2 / prostaglandin pathway. Finally, development of better therapies that target the key constituents and processes identified in these mechanisms are considered, for instance, engineering antagonizing agents that effectively block these pathways in an antigen-specific manner.

  17. Rod drive and latching mechanism

    International Nuclear Information System (INIS)

    Veronesi, L.; Sherwood, D.G.

    1982-01-01

    Hydraulic drive and latching mechanisms for driving reactivity control mechanisms in nuclear reactors are described. Preferably, the pressurized reactor coolant is utilized to raise the drive rod into contact with and to pivot the latching mechanism so as to allow the drive rod to pass the latching mechanism. The pressure in the housing may then be equalized which allows the drive rod to move downwardly into contact with the latching mechanism but to hold the shaft in a raised position with respect to the reactor core. Once again, the reactor coolant pressure may be utilized to raise the drive rod and thus pivot the latching mechanism so that the drive rod passes above the latching mechanism. Again, the mechanism pressure can be equalized which allows the drive rod to fall and pass by the latching mechanism so that the drive rod approaches the reactor core. (author)

  18. 1st National Mechanics Congress

    CERN Document Server

    Nieuwstadt, F

    1990-01-01

    The Department of Applied Mechanics of the Royal Institution of Engineers in the Netherlands (Koninklijk Instituut van Ingenieurs) organised on April 2-4, 1990 the first National Applied Mechanics Congress about the theme: "Integration of Theory and Applications in Applied Mechanics" The idea behind this initiative was to bring together the Applied Mechanics communities in The Netherlands and Belgium and to create an environment in which new developments in the field could be discussed and in which connections to other disciplines could be established. Among an extensive list of possible subjects the following were selected as congress topics: - non-linear material behaviour, - chaos, - mechatronics, - liquid-solid interactions, - mathematics and applied mechanics, - integration of Applied Mechanics and other disciplines. Applied Mechanics comprises both solid mechanics and fluid mechanics. These can be subdivided further into: rheology, plasticity, theory of plates and shells, theory of elasticity, multibody...

  19. Hydro-mechanical processes

    Energy Technology Data Exchange (ETDEWEB)

    Laouafa, F.; Kazmierczak, J.B. [Institut National de l' Environnement Industriel et des Risques (INERIS), Parc Technologique ALATA, 60 - Verneuil en Halatte (France); Armand, G. [Agence Nationale pour la Gestion des Dechets Radioactifs, Lab. de Souterrain de Meuse/Haute-Marne, 55 - Bure (France); Vaunat, J. [Catalonia UPC- Technical Univ., Barcelona (Spain); Jobmann, M.; Polster, M. [DBETEC- DBE Technology GmbH, Peine (Germany); Su, K.; Lebon, P.; Plas, F.; Armand, G.; Abou-Chakra Guery, A.; Cormery, F.; Shao, J.F.; Kondo, D. [ANDRA - Agence Nationale pour la Gestion des Dechets Radioactifs, 92 - Chatenay Malabry (France); Souley, M. [Institut National de l' Environnement Industriel et des Risques (INERIS), 54 - Nancy (France); Coll, C.; Charlier, R.; Collin, F.; Gerard, P. [Liege Univ., Dept. ArGEnCo (Belgium); Xiang Ling, Li [ESV EURIDICE, SCK.CEN, Belgian Nuclear Research Centre, Mol (Belgium); Collin, F. [Liege Univ., Charge de Recherches FNRS (Belgium); Pellet, F.L.; Fabre, G. [University Joseph Fourier, Laboratory 3S-R, 38 - Grenoble (France); Garcia-Sineriz, J.L.; Rey, M. [AITEMIN - Asociacion para la Investigacion y Desarrollo Industrial de los Recursos Naturales, Madrid (Spain); Mayor, J.C. [ENRESA - Empresa Nacional des Residuos Radioactivos, Madrid (Spain); Castellanos, E.; Romero, E.; Lloret, A.; Gens, A. [Catalunya Univ. Politecnica, UPC (Spain); Villar, M.V. [CIEMAT - Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas, Madrid (Spain); Chambon, R. [Laboratoire 3S, UJF-INPG-CNRS, 38 - Grenoble (France); Czaikowski, O.; Lux, K.H. [Clausthal Univ. of Technology, Professorship for Waste Disposal and Geomechanics, Clausthal-Zellerfeld (Germany); Van Geet, M.; Bastiaens, W.; Volckaert, G.; Weetjens, E.; Sillen, X. [SCK-CEN, Waste and Disposal dept., Mol (Belgium); ONDRAF/NIRAS, Brussel (Belgium); Imbert, Ch. [CEA Saclay, Dept. de Physico-Chimie (DPC/SCCME/LECBA), 91 - Gif sur Yvette (France)] [and others

    2007-07-01

    This session gathers 13 articles dealing with: three-dimensional and time stepping modelling of the whole Meuse/Haute-Marne ANDRA URL (F. Laouafa, J.B. Kazmierczak, G. Armand, J. Vaunat, M. Jobmann, M. Polster); a constitutive model for a deep argillaceous rock using Hoek-Brown criteria (K. Su, C. Chavant, M. Souley); the long term behaviour of the Boom clay: influence of viscosity on the pore pressure distribution (C. Coll, R. Charlier, X.L. Li, F. Collin); the microstructural changes induced by viscoplastic deformations in argillaceous rocks (F.L. Pellet, G. Fabre, K. Su, P. Lebon); the engineered barrier experiment at Mont Terri rock laboratory (J.L. Garcia-Sineriz, M. Rey, J.C. Mayor); the chemical influence on the Hydro-Mechanical behaviour of high-density FEBEX bentonite (E. Castellanos, M.V. Villar, E. Romero, A. Lloret, A. Gens); the influence of water exchanges on the gallery convergence (P. Gerard, R. Charlier, R. Chambon, F. Collin); a new method for ageing resistant storage of argillaceous rock samples to achieve reproducible experimental results even after long intermediate storage times (O. Czaikowski, K.H. Lux); the installation and evaluation of a large-scale in-situ shaft seal experiment in Boom clay the RESEAL project M. Van Geet, W. Bastiaens, G. Volckaert, E. Weetjens, X. Sillen, A. Gens, M.V. Villar, Ch. Imbert, M. Filippi, F. Plas); the hydro-Mechanical response of the Callovo-Oxfordian mud-stone around a deep vertical drift (J. Vaunat, B. Garitte, A. Gens, K. Su, G. Armand); the sensitivity of total stress to changes in externally applied water pressure in KBS-3 buffer bentonite (J.F. Harrington, D.J. Birchall, P. Sellin); the comparison of the poro-elastic behavior of Meuse/Haute Marne and Tournemire argillites: effect of loading and saturation states (E. Bemer, A. Noiret, F. Homand, A. Rejeb); and the multi-scale modelling of the argillites mechanical behaviour (A. Abou-Chakra Guery, F. Cormery, K. Su, J.F. Shao, D. Kondo)

  20. Cellular mechanics and motility

    Science.gov (United States)

    Hénon, Sylvie; Sykes, Cécile

    2015-10-01

    The term motility defines the movement of a living organism. One widely known example is the motility of sperm cells, or the one of flagellar bacteria. The propulsive element of such organisms is a cilium(or flagellum) that beats. Although cells in our tissues do not have a flagellum in general, they are still able to move, as we will discover in this chapter. In fact, in both cases of movement, with or without a flagellum, cell motility is due to a dynamic re-arrangement of polymers inside the cell. Let us first have a closer look at the propulsion mechanism in the case of a flagellum or a cilium, which is the best known, but also the simplest, and which will help us to define the hydrodynamic general conditions of cell movement. A flagellum is sustained by cellular polymers arranged in semi-flexible bundles and flagellar beating generates cell displacement. These polymers or filaments are part of the cellular skeleton, or "cytoskeleton", which is, in this case, external to the cellular main body of the organism. In fact, bacteria move in a hydrodynamic regime in which viscosity dominates over inertia. The system is thus in a hydrodynamic regime of low Reynolds number (Box 5.1), which is nearly exclusively the case in all cell movements. Bacteria and their propulsion mode by flagella beating are our unicellular ancestors 3.5 billion years ago. Since then, we have evolved to form pluricellular organisms. However, to keep the ability of displacement, to heal our wounds for example, our cells lost their flagellum, since it was not optimal in a dense cell environment: cells are too close to each other to leave enough space for the flagella to accomplish propulsion. The cytoskeleton thus developed inside the cell body to ensure cell shape changes and movement, and also mechanical strength within a tissue. The cytoskeleton of our cells, like the polymers or filaments that sustain the flagellum, is also composed of semi-flexible filaments arranged in bundles, and also in

  1. Computational mechanics research at ONR

    International Nuclear Information System (INIS)

    Kushner, A.S.

    1986-01-01

    Computational mechanics is not an identified program at the Office of Naval Research (ONR), but rather plays a key role in the Solid Mechanics, Fluid Mechanics, Energy Conversion, and Materials Science programs. The basic philosophy of the Mechanics Division at ONR is to support fundamental research which expands the basis for understanding, predicting, and controlling the behavior of solid and fluid materials and systems at the physical and geometric scales appropriate to the phenomena of interest. It is shown in this paper that a strong commonalty of computational mechanics drivers exists for the forefront research areas in both solid and fluid mechanics

  2. Principles of discrete time mechanics

    CERN Document Server

    Jaroszkiewicz, George

    2014-01-01

    Could time be discrete on some unimaginably small scale? Exploring the idea in depth, this unique introduction to discrete time mechanics systematically builds the theory up from scratch, beginning with the historical, physical and mathematical background to the chronon hypothesis. Covering classical and quantum discrete time mechanics, this book presents all the tools needed to formulate and develop applications of discrete time mechanics in a number of areas, including spreadsheet mechanics, classical and quantum register mechanics, and classical and quantum mechanics and field theories. A consistent emphasis on contextuality and the observer-system relationship is maintained throughout.

  3. Stochastic mechanics and quantum theory

    International Nuclear Information System (INIS)

    Goldstein, S.

    1987-01-01

    Stochastic mechanics may be regarded as both generalizing classical mechanics to processes with intrinsic randomness, as well as providing the sort of detailed description of microscopic events declared impossible under the traditional interpretation of quantum mechanics. It avoids the many conceptual difficulties which arise from the assumption that quantum mechanics, i.e., the wave function, provides a complete description of (microscopic) physical reality. Stochastic mechanics presents a unified treatment of the microscopic and macroscopic domains, in which the process of measurement plays no special physical role and which reduces to Newtonian mechanics in the macroscopic limit

  4. Mechanics of moving materials

    CERN Document Server

    Banichuk, Nikolay; Neittaanmäki, Pekka; Saksa, Tytti; Tuovinen, Tero

    2014-01-01

    This book deals with theoretical aspects of modelling the mechanical behaviour of manufacturing, processing, transportation or other systems in which the processed or supporting material is travelling through the system. Examples of such applications include paper making, transmission cables, band saws, printing presses, manufacturing of plastic films and sheets, and extrusion of aluminium foil, textiles and other materials.   The work focuses on out-of-plane dynamics and stability analysis for isotropic and orthotropic travelling elastic and viscoelastic materials, with and without fluid-structure interaction, using analytical and semi-analytical approaches.  Also topics such as fracturing and fatigue are discussed in the context of moving materials. The last part of the book deals with optimization problems involving physical constraints arising from the stability and fatigue analyses, including uncertainties in the parameters.   The book is intended for researchers and specialists in the field, providin...

  5. Payload Launch Lock Mechanism

    Science.gov (United States)

    Young, Ken (Inventor); Hindle, Timothy (Inventor)

    2014-01-01

    A payload launch lock mechanism includes a base, a preload clamp, a fastener, and a shape memory alloy (SMA) actuator. The preload clamp is configured to releasibly restrain a payload. The fastener extends, along an axis, through the preload clamp and into the base, and supplies a force to the preload clamp sufficient to restrain the payload. The SMA actuator is disposed between the base and the clamp. The SMA actuator is adapted to receive electrical current and is configured, upon receipt of the electrical current, to supply a force that causes the fastener to elongate without fracturing. The preload clamp, in response to the fastener elongation, either rotates or pivots to thereby release the payload.

  6. Incretin secretion: direct mechanisms

    DEFF Research Database (Denmark)

    Balk-Møller, Emilie; Holst, Jens Juul; Kuhre, Rune Ehrenreich

    2014-01-01

    enzyme responsible for incretin degradation (dipeptidyl peptidase-4) is inhibited (drugs are already on the market) while the secretion of endogenous GLP-1 secretion is stimulated at the same time may prove particularly rewarding. In this section we review current knowledge on the mechanisms for direct......The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are secreted from gastro-intestinal K- and L-cells, respectively, and play an important role in post-prandial blood glucose regulation. They do this by direct stimulation of the pancreatic β....... This suggests that the therapeutic potential of GIP for the treatment for T2D is limited, whereas GLP-1 based treatments have been on the market since 2005. Research is now pursuing novel approaches to utilize the effects of GLP-1 for T2D treatment. A combinatorial approach by which the activity of the major...

  7. Molecular Mechanisms of Parturition

    Directory of Open Access Journals (Sweden)

    F. Ferré

    1997-01-01

    Full Text Available The initial signal for triggering human parturition might be fetal but of trophoblastic origin. Concomitantly, this placental signal would have as its target not only the uterus but also the fetus by activating its hypothalamo-pituitary-adrenocortical axis. The latter would represent a second fetal signal which, at the fetomaternal interface, would amplify and define in time the mechanisms responsible for the onset of labor, implying changes in the myometrial and cervical extracellular matrix associated with the accession of the contractile phenotype for myometrial cells. At each phase of these processes in the utero-feto-placental system, the nature of these signals remains to be identified. Is there a single substance, or rather, and more likely, a combination of several?

  8. Mechanical relaxation in glasses

    International Nuclear Information System (INIS)

    Hiki, Y.

    2004-01-01

    The basic properties of glasses and the characteristics of mechanical relaxation in glasses were briefly reviewed, and then our studies concerned were presented. Experimental methods adopted were viscosity, internal friction, ultrasonic attenuation, and Brillouin scattering measurements. The specimens used were several kinds of inorganic, organic, and metallic glasses. The measurements were mainly carried out from the room temperature up to the glass transition temperature, and the relaxation time was determined as a function of temperature. The 'double relaxation' composed of two Arrhenius-type relaxations was observed in many materials. In both relaxations, the 'compensation effect' showing a correlation of the pre-exponential factor and the activation energy was observed. These results were explained by considering the 'complex relaxation' due to cooperative motions of atoms or group of atoms. Values of activation energy near the glass transition determined by the various experimental methods were compared with each other

  9. Mechanics of slide dams

    International Nuclear Information System (INIS)

    Young, G.A.

    1970-01-01

    Studies which promote the use of nuclear energy for peaceful projects in engineering are sponsored by the Atomic Energy Commission under the Plowshare program. Specific projects being considered include the construction of harbors, canals, and dams. Of these projects, perhaps the most difficult to accomplish will be the latter. This paper which is in two parts considers the problems which are associated with the construction of slide dams with nuclear explosives. It examines first the characteristics of conventional earth and rock-fill dams which are based upon proven techniques developed after many years of experience. The characteristics of natural landslide dams are also briefly considered to identify potential problems that must be overcome by slide dam construction techniques. Second, the mechanics of slide dams as determined from small-scale laboratory studies are presented. It is concluded that slide dams can be constructed and that small-scale field tests and additional laboratory studies are justified. (author)

  10. Continuous damage mechanics

    International Nuclear Information System (INIS)

    Chaboche, J.L.

    1981-01-01

    The classical structural life predictions are based on stabilized stress-strain analysis and some parametric relations with the number of cycles to failure. During the last ten years a different approach, initiated by the works of Kachanov and Rabotnov for creep rupture, has been developed by different laboratories. This continuous Damage Mechanics, treating the damaged material as a macroscopically homogeneous one, leads to the possibility of globally modelling the nucleation and the propagation of microdefects including their effect on the stress-strain behaviour. This paper presents the general theory and several applications to a turbine blade refractory alloy. It includes the description of sequence effects and creep-fatigue interaction. The generalization for three-dimensional conditions, where anisotropic damage effects are possible, is discussed and some new proposals are given for the determination of simple anisotropic damage equations. (orig.)

  11. Mechanisms of Phosphine Toxicity

    Directory of Open Access Journals (Sweden)

    Nisa S. Nath

    2011-01-01

    Full Text Available Fumigation with phosphine gas is by far the most widely used treatment for the protection of stored grain against insect pests. The development of high-level resistance in insects now threatens its continued use. As there is no suitable chemical to replace phosphine, it is essential to understand the mechanisms of phosphine toxicity to increase the effectiveness of resistance management. Because phosphine is such a simple molecule (PH3, the chemistry of phosphorus is central to its toxicity. The elements above and below phosphorus in the periodic table are nitrogen (N and arsenic (As, which also produce toxic hydrides, namely, NH3 and AsH3. The three hydrides cause related symptoms and similar changes to cellular and organismal physiology, including disruption of the sympathetic nervous system, suppressed energy metabolism and toxic changes to the redox state of the cell. We propose that these three effects are interdependent contributors to phosphine toxicity.

  12. Incretin secretion: direct mechanisms

    DEFF Research Database (Denmark)

    Balk-Møller, Emilie; Holst, Jens Juul; Kuhre, Rune Ehrenreich

    2014-01-01

    The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are secreted from gastro-intestinal K- and L-cells, respectively, and play an important role in post-prandial blood glucose regulation. They do this by direct stimulation of the pancreatic β......-cell, accounting for some 25-70% of postprandial insulin secretion in healthy subjects. In patients with type 2 diabetes (T2D, however, this effect is greatly reduced or lost due to a combination of severely impaired or eliminated insulinotrophic effect of GIP and reduced meal stimulated GLP-1 secretion...... enzyme responsible for incretin degradation (dipeptidyl peptidase-4) is inhibited (drugs are already on the market) while the secretion of endogenous GLP-1 secretion is stimulated at the same time may prove particularly rewarding. In this section we review current knowledge on the mechanisms for direct...

  13. Continuum mechanics for engineers

    CERN Document Server

    Mase, G Thomas; Mase, George E

    2009-01-01

    Continuum TheoryContinuum MechanicsStarting OverNotationEssential MathematicsScalars, Vectors and Cartesian TensorsTensor Algebra in Symbolic Notation - Summation ConventionIndicial NotationMatrices and DeterminantsTransformations of Cartesian TensorsPrincipal Values and Principal DirectionsTensor Fields, Tensor CalculusIntegral Theorems of Gauss and StokesStress PrinciplesBody and Surface Forces, Mass DensityCauchy Stress PrincipleThe Stress TensorForce and Moment Equilibrium; Stress Tensor SymmetryStress Transformation LawsPrincipal Stresses; Principal Stress DirectionsMaximum and Minimum Stress ValuesMohr's Circles For Stress Plane StressDeviator and Spherical Stress StatesOctahedral Shear StressKinematics of Deformation and MotionParticles, Configurations, Deformations and MotionMaterial and Spatial CoordinatesLangrangian and Eulerian DescriptionsThe Displacement FieldThe Material DerivativeDeformation Gradients, Finite Strain TensorsInfinitesimal Deformation TheoryCompatibility EquationsStretch RatiosRot...

  14. Advanced quantum mechanics

    CERN Document Server

    Dyson, Freeman John

    2007-01-01

    Renowned physicist and mathematician Freeman Dyson is famous for his work in quantum mechanics, nuclear weapons policy and bold visions for the future of humanity. In the 1940s, he was responsible for demonstrating the equivalence of the two formulations of quantum electrodynamics Richard Feynman's diagrammatic path integral formulation and the variational methods developed by Julian Schwinger and Sin-Itiro Tomonoga showing the mathematical consistency of QED. This invaluable volume comprises the legendary, never-before-published, lectures on quantum electrodynamics first given by Dyson at Cornell University in 1951. The late theorist Edwin Thompson Jaynes once remarked "For a generation of physicists they were the happy medium: clearer and motivated than Feynman, and getting to the point faster than Schwinger . Future generations of physicists are bound to read these lectures with pleasure, benefiting from the lucid style that is so characteristic of Dyson's exposition.

  15. Nuclear Mechanics in Disease

    Science.gov (United States)

    Zwerger, Monika; Ho, Chin Yee; Lammerding, Jan

    2015-01-01

    Over the past two decades, the biomechanical properties of cells have emerged as key players in a broad range of cellular functions, including migration, proliferation, and differentiation. Although much of the attention has focused on the cytoskeletal networks and the cell’s microenvironment, relatively little is known about the contribution of the cell nucleus. Here, we present an overview of the structural elements that determine the physical properties of the nucleus and discuss how changes in the expression of nuclear components or mutations in nuclear proteins can affect not only nuclear mechanics but also modulate cytoskeletal organization and diverse cellular functions. These findings illustrate that the nucleus is tightly integrated into the surrounding cellular structure. Consequently, changes in nuclear structure and composition are highly relevant to normal development and physiology and can contribute to many human diseases, such as muscular dystrophy, dilated cardiomyopathy, (premature) aging, and cancer. PMID:21756143

  16. Quantum mechanics and electrodynamics

    CERN Document Server

    Zamastil, Jaroslav

    2017-01-01

    This book highlights the power and elegance of algebraic methods of solving problems in quantum mechanics. It shows that symmetries not only provide elegant solutions to problems that can be solved exactly, but also substantially simplify problems that must be solved approximately. Furthermore, the book provides an elementary exposition of quantum electrodynamics and its application to low-energy physics, along with a thorough analysis of the role of relativistic, magnetic, and quantum electrodynamic effects in atomic spectroscopy. Included are essential derivations made clear through detailed, transparent calculations. The book’s commitment to deriving advanced results with elementary techniques, as well as its inclusion of exercises will enamor it to advanced undergraduate and graduate students.

  17. Postulates of quantum mechanics

    International Nuclear Information System (INIS)

    Cohen-Tannoudji, Claude; Diu, Bernard; Laloe, Franck.

    1977-01-01

    Postulates of quantum mechanics and physical interpretation on observables and their measurement are presented. The physical content of Schroedinger equation, the superposition principle and the physical forecastings are also exposed. In complement are also presented: physical study of a particle in a infinite potential well; study of probability current; mean deviations of two conjugate observables; measurements on a part only of a physical system; density operator; evolution operator; Heisenberg and Schoredinger pictures; gauge invariance; propagator of the Schroedinger equation; unsteady levels lifetime; bound states of a particle in a potential well of any shape; non-bound states of a particle in a well or a potential barrier of some shape; quantum properties of a particle in a one-dimensional periodic structure [fr

  18. Quantum mechanics with applications

    CERN Document Server

    Beard, David B

    2014-01-01

    This introductory text emphasizes Feynman's development of path integrals and its application to wave theory for particles. Suitable for undergraduate and graduate students of physics, the well-written, clear, and rigorous text was written by two of the nation's leading authorities on quantum physics. A solid foundation in quantum mechanics and atomic physics is assumed. Early chapters provide background in the mathematical treatment and particular properties of ordinary wave motion that also apply to particle motion. The close relation of quantum theory to physical optics is stressed. Subsequent sections emphasize the physical consequences of a wave theory of material properties, and they offer extensive applications in atomic physics, nuclear physics, solid state physics, and diatomic molecules. Four helpful Appendixes supplement the text.

  19. Mechanical strainer unit

    International Nuclear Information System (INIS)

    Kraeling, J.B.; Netkowicz, R.J.; Schnall, I.H.

    1983-01-01

    The mechanical strainer unit is connected to a flanged conduit which originates in and extends out of a suppression chamber in a nuclear reactor. The strainer includes a plurality of centrally apertured plates positioned along a common central axis and in parallel and spaced relationship. The plates have a plurality of bores radially spaced about the central axis. Spacer means such as washers are positioned between adjacent plates to maintain the plates is spaced relationship and form communicating passages of a predetermined size to the central apertures. Connecting means such as bolts or studs extend through the aligned bores to maintain the unit in assembled relationship and secure the unit to the pipe. By employing perforated plates and blocking off certain of the communicating passages, a dual straining effect can be achieved

  20. Quo Vadis Quantum Mechanics?

    CERN Document Server

    Dolev, S; Kolenda, N

    2005-01-01

    For more than a century, quantum mechanics has served as a very powerful theory that has expanded physics and technology far beyond their classical limits, yet it has also produced some of the most difficult paradoxes known to the human mind. This book represents the combined efforts of sixteen of today's most eminent theoretical physicists to lay out future directions for quantum physics. The authors include Yakir Aharonov, Anton Zeilinger; the Nobel laureates Anthony Leggett and Geradus 't Hooft; Basil Hiley, Lee Smolin and Henry Stapp. Following a foreword by Roger Penrose, the individual chapters address questions such as quantum non-locality, the measurement problem, quantum insights into relativity, cosmology and thermodynamics, and the possible bearing of quantum phenomena on biology and consciousness.

  1. Fundamentals of quantum mechanics

    CERN Document Server

    Erkoc, Sakir

    2006-01-01

    HISTORICAL EXPERIMENTS AND THEORIESDates of Important Discoveries and Events Blackbody RadiationPhotoelectrice Effect Quantum Theory of Spectra TheComptone Effect Matterwaves, the de Broglie HypothesisThe Davisson -Germer Experiment Heisenberg's Uncertainity PrincipleDifference Between Particles and Waves Interpretation of the Wavefunction AXIOMATIC STRUCTURE OF QUANTUM MECHANICSThe Necessity of Quantum TheoryFunction Spaces Postulates of Quantum Mechanics The Kronecker Delta and the Dirac Delta Function Dirac Notation OBSERVABLES AND SUPERPOSITIONFree Particle Particle In A Box Ensemble Average Hilbert -Space Interpretation The Initial Square Wave Particle Beam Superposition and Uncertainty Degeneracy of States Commutators and Uncertainty TIME DEVELOPMENT AND CONSERVATION THEOREMSTime Development of State Functions, The Discrete Case The Continuous Case, Wave Packets Particle Beam Gaussian Wave Packet Free Particle Propagator The Limiting Cases of the Gaussian Wave Packets Time Development of Expectation Val...

  2. Mechanisms of cascade collapse

    International Nuclear Information System (INIS)

    Diaz de la Rubia, T.; Smalinskas, K.; Averback, R.S.; Robertson, I.M.; Hseih, H.; Benedek, R.

    1988-12-01

    The spontaneous collapse of energetic displacement cascades in metals into vacancy dislocation loops has been investigated by molecular dynamics (MD) computer simulation and transmission electron microscopy (TEM). Simulations of 5 keV recoil events in Cu and Ni provide the following scenario of cascade collapse: atoms are ejected from the central region of the cascade by replacement collision sequences; the central region subsequently melts; vacancies are driven to the center of the cascade during resolidification where they may collapse into loops. Whether or not collapse occurs depends critically on the melting temperature of the metal and the energy density and total energy in the cascade. Results of TEM are presented in support of this mechanism. 14 refs., 4 figs., 1 tab

  3. Gastrointestinal defense mechanisms.

    Science.gov (United States)

    Said, Hyder; Kaunitz, Jonathan D

    2016-11-01

    To summarize and illuminate the recent findings regarding gastroduodenal mucosal defense mechanisms and the specific biomolecules involved in regulating this process, such as glucagon-like peptides (GLPs). There has been a growing interest in luminal nutrient chemosensing and its physiological effects throughout the digestive system. From the ingestion of food in the oral cavity to the processing and absorption of nutrients in the intestines, nutrient chemosensing receptors signal the production and release of numerous bioactive peptides from enteroendocrine cells, such as the proglucagon-derived peptides. There has been a major emphasis on two proglucagon-derived peptides, namely GLP-1 and GLP-2, due to their apparent beneficial effect on gut structure, function, and on metabolic processes. As an incretin, GLP-1 not only enhances the effect and release of insulin on pancreatic βcells but also has been implicated in having trophic effects on the intestinal epithelium. In addition, GLP-2, the other major proglucagon-derived peptide, has potent intestinotrophic effects, such as increasing the rate of mucosal stem cell proliferation, mucosal blood flow, and fluid absorption, as well as augmenting the rate of duodenal bicarbonate secretion to improve gastric mucosal health and longevity. Understanding the mechanisms underlying nutrient chemosensing and how it relates to GLP release can further elucidate how the gut functions in response to cellular changes and disturbances. Furthermore, a more in-depth comprehension of GLP release and its tissue-specific effects will help improve the utility of GLP-1 and GLP-2 receptor agonists in clinical settings. This, in turn, should help patients suffering from intestinal failure, malabsorption, and mucosal injury.

  4. Mechanisms of oxygen evolution

    Energy Technology Data Exchange (ETDEWEB)

    Radmer, R; Cheniae, G

    1976-08-01

    The production of O/sub 2/ from water requires the collaboration of four oxidizing equivalents. When dark-adapted O/sub 2/ evolving photosynthetic material is illuminated by a sequence of short (less than 2 ..mu..sec) saturating flashes, the amount of O/sub 2/ evolved per flash oscillates with a period of four. This indicates that a charge-collector, operating with its own reaction center, successively collects and stores four oxidizing equivalents, which are used in a concerted oxidation of two water molecules. Luminescence, fluorescence, and pH changes also reflect this cycle of four. The O/sub 2/ precursor states are quite stable; under some conditions they can have a lifetime of several minutes. The O/sub 2/-yielding reactions and reactions associated with trap recovery are fast relative to the rate-limiting step of photosynthesis. The molecular identity of the charge-collector is unknown, but correlative evidence suggests that a manganese containing catalyst (approximately 4 Mn/charge collector) participates, possibly directly. Formation of the active Mn-containing catalyst occurs via a multi-quantum process occurring within the System II reaction center. The photoactivated catalyst, located on the inner face of the thylakoid membrane, remains permanently active and essentially inaccessible to chemicals other than analogs of H/sub 2/O (e.g., NH/sub 3/, NH/sub 2/OH). This O/sub 2/ evolving catalyst can be deactivated by a variety of treatments that do not alter the system II reaction center. Anions such as chloride seem to participate rather directly in the O/sub 2/ evolution process via unknown mechanism(s).

  5. Bladder activation: afferent mechanisms.

    Science.gov (United States)

    Andersson, Karl-Erik

    2002-05-01

    The major function of the lower urinary tract is to store and periodically evacuate urine from the bladder. This requires coordination of the smooth muscles of the bladder and urethra, and of the striated muscles of the outflow region and pelvic floor by a complex neural control system. Lumbosacral afferent fibers (pelvic afferents), but also afferents in the hypogastric and pudendal nerves, are of major importance for the regulation of the mechanisms for continence and micturition. In the bladder, afferent nerves have been identified suburothelially as well as in the detrusor muscle. Suburothelially, they form a plexus that lies immediately beneath the epithelial lining. This plexus is particularly dense in the bladder neck and the trigone. The most important afferents for the micturition process are myelinated Adelta-fibers and unmyelinated C-fibers. Immunocytochemical and tracing studies have revealed that numerous peptides, including substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, enkephalins, and cholecystokinin are localized either alone, or in combination, in afferent pathways of the bladder and urethra. The receptors on these nerves include: vanilloid receptors, purinoceptors, tachykinin, and prostanoid receptors. Extracellular adenosine triphosphate (ATP) has been found to mediate excitation of small-diameter sensory neurons via P2X3 receptors, and it has been proposed that in the bladder, distention causes release of ATP from the urothelium. ATP, in turn, can activate P2X3 receptors on suburothelial afferent nerve terminals to evoke a neural discharge. However, it is most likely that a cascade of inhibitory and stimulatory transmitters/mediators, as well as ATP, are involved in the transduction mechanisms underlying the activation of afferent fibers during bladder filling.

  6. Teaching Continuum Mechanics in a Mechanical Engineering Program

    Science.gov (United States)

    Liu, Yucheng

    2011-01-01

    This paper introduces a graduate course, continuum mechanics, which is designed for and taught to graduate students in a Mechanical Engineering (ME) program. The significance of continuum mechanics in engineering education is demonstrated and the course structure is described. Methods used in teaching this course such as topics, class…

  7. On Galilean covariant quantum mechanics

    International Nuclear Information System (INIS)

    Horzela, A.; Kapuscik, E.; Kempczynski, J.; Joint Inst. for Nuclear Research, Dubna

    1991-08-01

    Formalism exhibiting the Galilean covariance of wave mechanics is proposed. A new notion of quantum mechanical forces is introduced. The formalism is illustrated on the example of the harmonic oscillator. (author)

  8. Vibrating Wingstroke Mechanism, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This proposed work will develop a new method and mechanism for generating wing stroke motion of any shape and orientation. The mechanism will provide power, lift and...

  9. TREND MECHANISMS IN CONTEMPORARY FASHION

    DEFF Research Database (Denmark)

    Mackinney-Valentin, Maria

    2013-01-01

    Explores a spatial approach to trend mechanisms that is argued to be more contemporary than the traditional temporal appraoch.......Explores a spatial approach to trend mechanisms that is argued to be more contemporary than the traditional temporal appraoch....

  10. New Physical Mechanism for Lightning

    Science.gov (United States)

    Artekha, Sergey N.; Belyan, Andrey V.

    2018-02-01

    The article is devoted to electromagnetic phenomena in the atmosphere. The set of experimental data on the thunderstorm activity is analyzed. It helps to identify a possible physical mechanism of lightning flashes. This mechanism can involve the formation of metallic bonds in thunderclouds. The analysis of the problem is performed at a microphysical level within the framework of quantum mechanics. The mechanism of appearance of metallic conductivity includes the resonant tunneling of electrons along resonance-percolation trajectories. Such bonds allow the charges from the vast cloud charged subsystems concentrate quickly in lightning channel. The formation of metal bonds in the thunderstorm cloudiness is described as the second-order phase transition. A successive mechanism for the process of formation and development of the lightning channel is suggested. This mechanism is associated with the change in the orientation of crystals in growing electric field. Possible consequences of the quantum-mechanical mechanism under discussion are compared with the results of observations.

  11. Martensite and bainite in steels: transformation mechanism and mechanical properties

    International Nuclear Information System (INIS)

    Bhadeshia, H.K.D.H.

    1997-01-01

    Many essential properties of iron alloys depend on what actually happens when one allotropic form gives way to another, i.e. on the mechanism of phase change. The dependence of the mechanical properties on the atomic mechanism by which bainite and martensite grow is the focus of this paper. The discussion is illustrated in the context of some common engineering design parameters, and with a brief example of the inverse problem in which the mechanism may be a function of the mechanical properties. (orig.)

  12. MECHANISM TO DRAW MACLAURIN TRISECTRIX

    Directory of Open Access Journals (Sweden)

    Mirela CHERCIU

    2013-05-01

    Full Text Available It is used a geometrical method for generating Maclaurin trisectrix and based on it , thesynthesis of a mechanism that can draw it, is made. The structure of the found mechanism is R-RTRTtype, having two driving elements with correlated movements. This mechanism is analysedand the desired curve is obtained just for certain dimensions of the mechanism. The mechanism’smovement is studied based on some diagrams and different outputs are obtained for certain initialdimensions of the mechanism’s.

  13. Trace of Korean mechanical industry

    International Nuclear Information System (INIS)

    1996-12-01

    This book reports 50 years of Korean mechanical engineers, which includes birth and history, remembrance and future of Korean society of mechanical engineers, current situation and development of mechanical industry such as national industry and 50 years of mechanical industry, track, airline industry, ship and marine engine, a precision instrument, cutting work, casting, welding, plastic working freeze and air handling nuclear power and textile machinery.

  14. Statistical mechanics of nonequilibrium liquids

    CERN Document Server

    Evans, Denis J; Craig, D P; McWeeny, R

    1990-01-01

    Statistical Mechanics of Nonequilibrium Liquids deals with theoretical rheology. The book discusses nonlinear response of systems and outlines the statistical mechanical theory. In discussing the framework of nonequilibrium statistical mechanics, the book explains the derivation of a nonequilibrium analogue of the Gibbsian basis for equilibrium statistical mechanics. The book reviews the linear irreversible thermodynamics, the Liouville equation, and the Irving-Kirkwood procedure. The text then explains the Green-Kubo relations used in linear transport coefficients, the linear response theory,

  15. Mechanism of cytotoxicity of paraquat

    OpenAIRE

    Fukushima, Tetsuhito; Tanaka, Keiko; Lim, Heejin; Moriyama, Masaki

    2002-01-01

    Acute paraquat poisoning seems to be very complex because many possible mechanisms of paraquat cytotoxicity have been reported. Some may not be the cause of paraquat poisoning but the result or an accompanying phenomenon of paraquat action. The mechanism critical for cell damage is still unknown. Paraquat poisoning is probably a combination of several paraquat actions. Arguing which mechanism is more critical may not be important, and these clarified mechanisms should be connected and utilize...

  16. Quantum mechanics. 2. printing (paperback).

    International Nuclear Information System (INIS)

    Lipkin, H.J.

    1986-01-01

    Intended for a first year graduate course in quantum mechanics, this collection of topics can also be considered as a set of self-contained 'monographs for pedestrians' on the Moessbauer effect, many-body quantum mechanics, kaon physics, scattering theory, Feynman diagrams, symmetries and relativistic quantum mechanics. (Auth.)

  17. p-Adic quantum mechanics

    International Nuclear Information System (INIS)

    Vladimirov, V.S.; Volovich, I.V.

    1988-01-01

    Quantum mechanics above the field of p-adic numbers is constructed. Three formulations of p-adic quantum mechanics are considered: 1) quantum mechanics with complex-valued wave functions and p-adic coordinates and pulses; an approach based on Weyl representation is suggested; 2) the probability (Euclidean) formulation; 3) the secondary quantization representation (Fock representation) with p-adic wave functions

  18. Collected papers on wave mechanics

    CERN Document Server

    Schrödinger, Erwin

    1929-01-01

    Quantisation as a problem of proper values ; the continuous transition from micro- to macro-mechanics ; on the relation between the quantum mechanics of Heisenberg, Born, and Jordan, and that of Schrödinger ; the Compton effect ; the energy-momentum theorem for material waves ; the exchange of energy according to wave mechanics

  19. Mechanisms of Antibiotic Resistance

    Science.gov (United States)

    Munita, Jose M.; Arias, Cesar A.

    2015-01-01

    Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice providing specific examples in relevant bacterial pathogens. PMID:27227291

  20. Mechanisms of ouabain resistance

    International Nuclear Information System (INIS)

    Schulz, J.T. III.

    1987-01-01

    Experiments were designed to investigate the mechanism of ouabain resistance in two distinct types of transfected cells derived from ouabain-sensitive CV-1 cell parents. The first type of transfectant is the recipient of a gene encoding the alpha subunit of the rodent renal Na,K-ATPase (R-alphal gene); the second type of transfectant is the recipient of the mouse ouabain resistance gene. Measurements of 86 Rb + uptake and Na,K=ATPase activity in R-alphal gene transfectant cells and CV-1 parent cells indicate that the ouabain-resistant phenotype of the transfectants is due to expression of a relatively ouabain-insensitive Na,K=ATPase. CV-1 parent cells express one component of ouabain sensitive 86 Rb + uptake and one component of ouabain-sensitive Na, K-ATPase activity. R-alpha 1 gene transfectants express the parental forms of ouabain-sensitive 86 Rb + uptake and Na,K-ATPase activity, but in addition express new,relatively ouabain-insensitive forms of 86 Rb + uptake activity and Na,K-ATPase activity