Science.gov

Sample records for protein-2 drives apoptosis

  1. Amphiregulin impairs apoptosis-stimulating protein 2 of p53 overexpression-induced apoptosis in hepatoma cells.

    PubMed

    Liu, Kai; Lin, Dongdong; Ouyang, Yabo; Pang, Lijun; Guo, Xianghua; Wang, Shanshan; Zang, Yunjin; Chen, Dexi

    2017-03-01

    Overexpression of apoptosis-stimulating protein 2 of p53 (ASPP2) induces apoptotic cell death in hepatoma cells (e.g. HepG2 cells) by enhancing the transactivation activity of p53, but long-term ASPP2 overexpression fails to induce more apoptosis since activation of the epidermal growth factor/epidermal growth factor receptor/SOS1 pathway impairs the pro-apoptotic role of ASPP2. In this study, in recombinant adenovirus-ASPP2-infected HepG2 cells, ASPP2 overexpression induces amphiregulin expression in a p53-dependent manner. Although amphiregulin initially contributes to ASPP2-induced apoptosis, it eventually impairs the pro-apoptotic function of ASPP2 by activating the epidermal growth factor/epidermal growth factor receptor/SOS1 pathway, leading to apoptosis resistance. Moreover, blocking soluble amphiregulin with a neutralizing antibody also significantly increased apoptotic cell death of HepG2 cells due to treatment with methyl methanesulfonate, cisplatin, or a recombinant p53 adenovirus, suggesting that the function of amphiregulin involved in inhibiting apoptosis may be a common mechanism by which hepatoma cells escape from stimulus-induced apoptosis. Thus, our data elucidate an apoptosis-evasion mechanism in hepatocellular carcinoma and have potential implications for hepatocellular carcinoma therapy.

  2. Calpain-mediated cleavage of collapsin response mediator protein-2 drives acute axonal degeneration

    PubMed Central

    Zhang, Jian-Nan; Michel, Uwe; Lenz, Christof; Friedel, Caroline C.; Köster, Sarah; d’Hedouville, Zara; Tönges, Lars; Urlaub, Henning; Bähr, Mathias; Lingor, Paul; Koch, Jan C.

    2016-01-01

    Axonal degeneration is a key initiating event in many neurological diseases. Focal lesions to axons result in a rapid disintegration of the perilesional axon by acute axonal degeneration (AAD) within several hours. However, the underlying molecular mechanisms of AAD are only incompletely understood. Here, we studied AAD in vivo through live-imaging of the rat optic nerve and in vitro in primary rat cortical neurons in microfluidic chambers. We found that calpain is activated early during AAD of the optic nerve and that calpain inhibition completely inhibits axonal fragmentation on the proximal side of the crush while it attenuates AAD on the distal side. A screening of calpain targets revealed that collapsin response mediator protein-2 (CRMP2) is a main downstream target of calpain activation in AAD. CRMP2-overexpression delayed bulb formation and rescued impairment of axonal mitochondrial transport after axotomy in vitro. In vivo, CRMP2-overexpression effectively protected the proximal axon from fragmentation within 6 hours after crush. Finally, a proteomic analysis of the optic nerve was performed at 6 hours after crush, which identified further proteins regulated during AAD, including several interactors of CRMP2. These findings reveal CRMP2 as an important mediator of AAD and define it as a putative therapeutic target. PMID:27845394

  3. mTORC1-dependent translation of collapsin response mediator protein-2 drives neuroadaptations underlying excessive alcohol-drinking behaviors

    PubMed Central

    Liu, F; Laguesse, S; Legastelois, R; Morisot, N; Ben Hamida, S; Ron, D

    2017-01-01

    Mammalian target of rapamycin complex 1 (mTORC1) has an essential role in dendritic mRNA translation and participates in mechanisms underlying alcohol-drinking and reconsolidation of alcohol-related memories. Here, we report that excessive alcohol consumption increases the translation of downstream targets of mTORC1, including collapsin response mediator protein-2 (CRMP-2), in the nucleus accumbens (NAc) of rodents. We show that alcohol-mediated induction of CRMP-2 translation is mTORC1-dependent, leading to increased CRMP-2 protein levels. Furthermore, we demonstrate that alcohol intake also blocks glycogen synthase kinase-3β (GSK-3β)-phosphorylation of CRMP-2, which results in elevated binding of CRMP-2 to microtubules and a concomitant increase in microtubule content. Finally, we show that systemic administration of the CRMP-2 inhibitor lacosamide, or knockdown of CRMP-2 in the NAc decreases excessive alcohol intake. These results suggest that CRMP-2 in the NAc is a convergent point that receives inputs from two signaling pathways, mTORC1 and GSK-3β, that in turn drives excessive alcohol-drinking behaviors. PMID:26952865

  4. The interaction between HIV-1 Nef and adaptor protein-2 reduces Nef-mediated CD4(+) T cell apoptosis.

    PubMed

    Jacob, Rajesh Abraham; Johnson, Aaron L; Pawlak, Emily N; Dirk, Brennan S; Van Nynatten, Logan R; Haeryfar, S M Mansour; Dikeakos, Jimmy D

    2017-09-01

    Acquired Immune Deficiency Syndrome is characterized by a decline in CD4(+) T cells. Here, we elucidated the mechanism underlying apoptosis in Human Immunodeficiency Virus-1 (HIV-1) infection by examining host apoptotic pathways hijacked by the HIV-1 Nef protein in the CD4(+) T-cell line Sup-T1. Using a panel of Nef mutants unable to bind specific host proteins we uncovered that Nef generates pro- and anti-apoptotic signals. Apoptosis increased upon mutating the motifs involved in the interaction of Nef:AP-1 (NefM20A or NefEEEE62-65AAAA) or Nef:AP-2 (NefLL164/165AA), implying these interactions limit Nef-mediated apoptosis. In contrast, disrupting the Nef:PAK2 interaction motifs (NefH89A or NefF191A) reduced apoptosis. To validate further, apoptosis was measured after short-hairpin RNA knock-down of AP-1, AP-2 and PAK2. AP-2α depletion enhanced apoptosis, demonstrating that disrupting the Nef:AP-2α interaction limits Nef-mediated apoptosis. Collectively, we describe a mechanism by which HIV-1 regulates cell survival and demonstrate the consequence of interfering with Nef:host protein interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Caspase signalling in the absence of apoptosis drives Jnk-dependent invasion

    PubMed Central

    Rudrapatna, Vivek A; Bangi, Erdem; Cagan, Ross L

    2013-01-01

    Tumours evolve several mechanisms to evade apoptosis, yet many resected carcinomas show significantly elevated caspase activity. Moreover, caspase activity is positively correlated with tumour aggression and adverse patient outcome. These observations indicate that caspases might have a functional role in promoting tumour invasion and metastasis. Using a Drosophila model of invasion, we show that precise effector caspase activity drives cell invasion without initiating apoptosis. Affected cells express the matrix metalloprotinase Mmp1 and invade by activating Jnk. Our results link Jnk and effector caspase signalling during the invasive process and suggest that tumours under apoptotic stresses from treatment, immune surveillance or intrinsic signals might be induced further along the metastatic cascade. PMID:23306653

  6. 5-Hydroxytryptamine drives apoptosis in biopsylike Burkitt lymphoma cells: reversal by selective serotonin reuptake inhibitors.

    PubMed

    Serafeim, Adamantios; Grafton, Gillian; Chamba, Anita; Gregory, Christopher D; Blakely, Randy D; Bowery, Norman G; Barnes, Nicholas M; Gordon, John

    2002-04-01

    Serotonin (5-HT), a well-known neurotransmitter of the central nervous system, has been implicated in diverse aspects of immune regulation. Here we show that 5-HT can efficiently drive programmed cell death in established Burkitt lymphoma (BL) lines that remain faithful to the original biopsy phenotype (group 1). Group 1 BL cells cultured in the presence of 5-HT exhibited marked suppression of DNA synthesis that was accompanied by extensive apoptosis-serotonin-driven apoptosis was complete within 24 hours, was preceded by early caspase activation, and was accompanied by a decline in mitochondrial membrane potential. BL cells that had drifted to a lymphoblastic group 3 phenotype were relatively resistant to these actions of serotonin, and the forced ectopic expression of either bcl-2 or bcl-x(L) provided substantial protection from 5-HT-induced apoptosis. 5-HT receptor antagonists (SDZ205-557, granisetron, methysergide) failed to inhibit serotonin-induced apoptosis, whereas the selective serotonin reuptake inhibitors (SSRI)-fluoxetine (Prozac), paroxetine (Paxil), and citalopram (Celexa)-substantially blocked the monoamine actions. Western blot analysis showed that BL cells expressed protein for the 5-HT transporter, and transport assays confirmed active uptake of serotonin by the cells. Unlike what was suggested for neuronal cells, there was no evidence that intracellular oxidative metabolites were responsible for the 5-HT-induced programmed death of BL cells. These data indicate that serotonin drives apoptosis in biopsylike BL cells after its entry through an active transport mechanism, and they suggest a novel therapeutic modality for Burkitt lymphoma.

  7. Killers creating new life: caspases drive apoptosis-induced proliferation in tissue repair and disease

    PubMed Central

    Fogarty, Caitlin E; Bergmann, Andreas

    2017-01-01

    Apoptosis is a carefully orchestrated and tightly controlled form of cell death, conserved across metazoans. As the executioners of apoptotic cell death, cysteine-dependent aspartate-directed proteases (caspases) are critical drivers of this cellular disassembly. Early studies of genetically programmed cell death demonstrated that the selective activation of caspases induces apoptosis and the precise elimination of excess cells, thereby sculpting structures and refining tissues. However, over the past decade there has been a fundamental shift in our understanding of the roles of caspases during cell death—a shift precipitated by the revelation that apoptotic cells actively engage with their surrounding environment throughout the death process, and caspases can trigger a myriad of signals, some of which drive concurrent cell proliferation regenerating damaged structures and building up lost tissues. This caspase-driven compensatory proliferation is referred to as apoptosis-induced proliferation (AiP). Diverse mechanisms of AiP have been found across species, ranging from planaria to mammals. In this review, we summarize the current knowledge of AiP and we highlight recent advances in the field including the involvement of reactive oxygen species and macrophage-like immune cells in one form of AiP, novel regulatory mechanisms affecting caspases during AiP, and emerging clinical data demonstrating the critical importance of AiP in cancer. PMID:28362431

  8. The microRNA-302b-inhibited insulin-like growth factor-binding protein 2 signaling pathway induces glioma cell apoptosis by targeting nuclear factor IA

    PubMed Central

    Lee, Chin-Cheng; Chen, Peng-Hsu; Ho, Kuo-Hao; Shih, Chwen-Ming; Cheng, Chia-Hsiung; Lin, Cheng-Wei; Cheng, Kur-Ta; Liu, Ann-Jeng

    2017-01-01

    MicroRNAs are small noncoding RNAs that post-transcriptionally control the expression of genes involved in glioblastoma multiforme (GBM) development. Although miR-302b functions as a tumor suppressor, its role in GBM is still unclear. Therefore, this study comprehensively explored the roles of miR-302b-mediated gene networks in GBM cell death. We found that miR-302b levels were significantly higher in primary astrocytes than in GBM cell lines. miR-302b overexpression dose dependently reduced U87-MG cell viability and induced apoptosis through caspase-3 activation and poly(ADP ribose) polymerase degradation. A transcriptome microarray revealed 150 downregulated genes and 380 upregulated genes in miR-302b-overexpressing cells. Nuclear factor IA (NFIA), higher levels of which were significantly related to poor survival, was identified as a direct target gene of miR-302b and was involved in miR-302b-induced glioma cell death. Higher NFIA levels were observed in GBM cell lines and human tumor sections compared with astrocytes and non-tumor tissues, respectively. NFIA knockdown significantly enhanced apoptosis. We found high levels of insulin-like growth factor-binding protein 2 (IGFBP2), another miR-302b-downregulated gene, in patients with poor survival. We verified that NFIA binds to the IGFBP2 promoter and transcriptionally enhances IGFBP2 expression levels. We identified that NFIA-mediated IGFBP2 signaling pathways are involved in miR-302b-induced glioma cell death. The identification of a regulatory loop whereby miR-302b inhibits NFIA, leading to a decrease in expression of IGFBP-2, may provide novel directions for developing therapies to target glioblastoma tumorigenesis. PMID:28323865

  9. Extracellular Reactive Oxygen Species drive Apoptosis-induced Proliferation via Drosophila Macrophages

    PubMed Central

    Fogarty, Caitlin E.; Diwanji, Neha; Lindblad, Jillian L.; Tare, Meghana; Amcheslavsky, Alla; Makhijani, Kalpana; Brückner, Katja; Fan, Yun; Bergmann, Andreas

    2016-01-01

    Summary Apoptosis-induced proliferation (AiP) is a compensatory mechanism to maintain tissue size and morphology following unexpected cell loss during normal development, and may also be a contributing factor to cancer and drug resistance. In apoptotic cells, caspase-initiated signaling cascades lead to the downstream production of mitogenic factors and the proliferation of neighbouring surviving cells. In epithelial cells of Drosophila imaginal discs, the Caspase-9 ortholog Dronc drives AiP via activation of Jun N-terminal kinase (JNK); however, the specific mechanisms of JNK activation remain unknown. Here, we show that caspase-induced activation of JNK during AiP depends on an inflammatory response. This is mediated by extracellular reactive oxygen species (ROS) generated by the NADPH oxidase Duox in epithelial disc cells. Extracellular ROS activate Drosophila macrophages (hemocytes), which in turn trigger JNK activity in epithelial cells by signaling through the TNF ortholog Eiger. We propose that in an immortalized (‘undead’) model of AiP, signaling back and forth between epithelial disc cells and hemocytes by extracellular ROS and TNF/Eiger drives overgrowth of the disc epithelium. These data illustrate a bidirectional cell/cell communication pathway with implication for tissue repair, regeneration and cancer. PMID:26898463

  10. Extracellular Reactive Oxygen Species Drive Apoptosis-Induced Proliferation via Drosophila Macrophages.

    PubMed

    Fogarty, Caitlin E; Diwanji, Neha; Lindblad, Jillian L; Tare, Meghana; Amcheslavsky, Alla; Makhijani, Kalpana; Brückner, Katja; Fan, Yun; Bergmann, Andreas

    2016-03-07

    Apoptosis-induced proliferation (AiP) is a compensatory mechanism to maintain tissue size and morphology following unexpected cell loss during normal development, and may also be a contributing factor to cancer and drug resistance. In apoptotic cells, caspase-initiated signaling cascades lead to the downstream production of mitogenic factors and the proliferation of neighboring surviving cells. In epithelial cells of Drosophila imaginal discs, the Caspase-9 ortholog Dronc drives AiP via activation of Jun N-terminal kinase (JNK); however, the specific mechanisms of JNK activation remain unknown. Here we show that caspase-induced activation of JNK during AiP depends on an inflammatory response. This is mediated by extracellular reactive oxygen species (ROSs) generated by the NADPH oxidase Duox in epithelial disc cells. Extracellular ROSs activate Drosophila macrophages (hemocytes), which in turn trigger JNK activity in epithelial cells by signaling through the tumor necrosis factor (TNF) ortholog Eiger. We propose that in an immortalized ("undead") model of AiP, signaling back and forth between epithelial disc cells and hemocytes by extracellular ROSs and TNF/Eiger drives overgrowth of the disc epithelium. These data illustrate a bidirectional cell-cell communication pathway with implication for tissue repair, regeneration, and cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Poly (C)-binding protein 2 (PCBP2) promotes the progression of esophageal squamous cell carcinoma (ESCC) through regulating cellular proliferation and apoptosis.

    PubMed

    Ye, Jinjun; Zhou, Guoren; Zhang, Zhi; Sun, Lei; He, Xia; Zhou, Jianwei

    2016-08-01

    PCBP2 (Poly(C)-binding protein 2) is a member of PCBP family, which has many functions including mRNA stabilization, translational silence and translational enhancement performed by their poly(C)-binding ability. The abnormal expression of PCBP2 was correlated with various carcinomas. However, the significance and mechanism of PCBP2 in esophageal squamous cell carcinoma (ESCC) progression remain unclear. In this study, Western Blot and immunohistochemistry (IHC) analysis revealed that PCBP2 was overexpressed in ESCC tissues and cell lines. Statistical results also indicated that PCBP2 expression level was significantly positively correlated with ESCC clinicopathological parameters such as tumor grade and tumor size. Furthermore, PCBP2 expression level could also be recognized as an independent prognostic factor for ESCC patients' overall survival. Serum starvation and refeeding assay along with PCBP2-shRNA transfection demonstrated that PCBP2 expression promoted proliferation of ESCC cells. The results above are partly due to growth arrest of cell cycle at G1/S phase. We also found that reduced PCBP2 expression might induce ESCC cell apoptosis with increased cleaved caspase3 expression. Overall, our findings indicated that PCBP2 might be involved in the ESCC progression and be considered as a new treatment target in ESCC.

  12. Combinations of PARP Inhibitors with Temozolomide Drive PARP1 Trapping and Apoptosis in Ewing's Sarcoma.

    PubMed

    Gill, Sonja J; Travers, Jon; Pshenichnaya, Irina; Kogera, Fiona A; Barthorpe, Syd; Mironenko, Tatiana; Richardson, Laura; Benes, Cyril H; Stratton, Michael R; McDermott, Ultan; Jackson, Stephen P; Garnett, Mathew J

    2015-01-01

    Ewing's sarcoma is a malignant pediatric bone tumor with a poor prognosis for patients with metastatic or recurrent disease. Ewing's sarcoma cells are acutely hypersensitive to poly (ADP-ribose) polymerase (PARP) inhibition and this is being evaluated in clinical trials, although the mechanism of hypersensitivity has not been directly addressed. PARP inhibitors have efficacy in tumors with BRCA1/2 mutations, which confer deficiency in DNA double-strand break (DSB) repair by homologous recombination (HR). This drives dependence on PARP1/2 due to their function in DNA single-strand break (SSB) repair. PARP inhibitors are also cytotoxic through inhibiting PARP1/2 auto-PARylation, blocking PARP1/2 release from substrate DNA. Here, we show that PARP inhibitor sensitivity in Ewing's sarcoma cells is not through an apparent defect in DNA repair by HR, but through hypersensitivity to trapped PARP1-DNA complexes. This drives accumulation of DNA damage during replication, ultimately leading to apoptosis. We also show that the activity of PARP inhibitors is potentiated by temozolomide in Ewing's sarcoma cells and is associated with enhanced trapping of PARP1-DNA complexes. Furthermore, through mining of large-scale drug sensitivity datasets, we identify a subset of glioma, neuroblastoma and melanoma cell lines as hypersensitive to the combination of temozolomide and PARP inhibition, potentially identifying new avenues for therapeutic intervention. These data provide insights into the anti-cancer activity of PARP inhibitors with implications for the design of treatment for Ewing's sarcoma patients with PARP inhibitors.

  13. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein-induced lysosomal translocation of proapoptotic effectors is mediated by phosphofurin acidic cluster sorting protein-2 (PACS-2).

    PubMed

    Werneburg, Nathan W; Bronk, Steve F; Guicciardi, Maria Eugenia; Thomas, Laurel; Dikeakos, Jimmy D; Thomas, Gary; Gores, Gregory J

    2012-07-13

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of liver cancer cell lines requires death receptor-5 (DR5)-dependent permeabilization of lysosomal membranes. Ligated DR5 triggers recruitment of the proapoptotic proteins Bim and Bax to lysosomes, releasing cathepsin B into the cytosol where it mediates mitochondria membrane permeabilization and activation of executioner caspases. Despite the requirement for lysosome membrane permeabilization during TRAIL-induced apoptosis, little is known about the mechanism that controls recruitment of Bim and Bax to lysosomal membranes. Here we report that TRAIL induces recruitment of the multifunctional sorting protein phosphofurin acidic cluster sorting protein-2 (PACS-2) to DR5-positive endosomes in Huh-7 cells where it forms an immunoprecipitatable complex with Bim and Bax on lysosomal membranes. shRNA-targeted knockdown of PACS-2 prevents recruitment of Bim or Bax to lysosomes, blunting the TRAIL-induced lysosome membrane permeabilization. Consistent with the reduced lysosome membrane permeabilization, shRNA knockdown of PACS-2 in Huh-7 cells reduced TRAIL-induced apoptosis and increased clonogenic cell survival. The determination that recombinant PACS-2 bound Bim but not Bax in vitro and that shRNA knockdown of Bim blocked Bax recruitment to lysosomes suggests that TRAIL/DR5 triggers endosomal PACS-2 to recruit Bim and Bax to lysosomes to release cathepsin B and induce apoptosis. Together, these findings provide insight into the lysosomal pathway of apoptosis.

  14. PUMA promotes apoptosis of hematopoietic progenitors driving leukemic progression in a mouse model of myelodysplasia.

    PubMed

    Guirguis, A A; Slape, C I; Failla, L M; Saw, J; Tremblay, C S; Powell, D R; Rossello, F; Wei, A; Strasser, A; Curtis, D J

    2016-06-01

    Myelodysplastic syndrome (MDS) is characterized by ineffective hematopoiesis with resultant cytopenias. Increased apoptosis and aberrantly functioning progenitors are thought to contribute to this phenotype. As is the case for other malignancies, overcoming apoptosis is believed to be important in progression toward acute myeloid leukemia (AML). Using the NUP98-HOXD13 (NHD13) transgenic mouse model of MDS, we previously reported that overexpression of the anti-apoptotic protein BCL2, blocked apoptosis and improved cytopenias, paradoxically, delaying leukemic progression. To further understand this surprising result, we examined the role of p53 and its pro-apoptotic effectors, PUMA and NOXA in NHD13 mice. The absence of p53 or PUMA but not NOXA reduced apoptosis and expanded the numbers of MDS-repopulating cells. Despite a similar effect on apoptosis and cell numbers, the absence of p53 and PUMA had diametrically opposed effects on progression to AML: absence of p53 accelerated leukemic progression, while absence of PUMA significantly delayed progression. This may be explained in part by differences in cellular responses to DNA damage. The absence of p53 led to higher levels of γ-H2AX (indicative of persistent DNA lesions) while PUMA-deficient NHD13 progenitors resolved DNA lesions in a manner comparable to wild-type cells. These results suggest that targeting PUMA may improve the cytopenias of MDS without a detrimental effect on leukemic progression thus warranting further investigation.

  15. Lutzomyia longipalpis saliva drives apoptosis and enhances parasite burden in neutrophils.

    PubMed

    Prates, Deboraci Brito; Araújo-Santos, Théo; Luz, Nívea Farias; Andrade, Bruno B; França-Costa, Jaqueline; Afonso, Lilian; Clarêncio, Jorge; Miranda, José Carlos; Bozza, Patrícia T; Dosreis, George A; Brodskyn, Cláudia; Barral-Netto, Manoel; Borges, Valéria Matos; Borges, Valéria de Matos; Barral, Aldina

    2011-09-01

    Neutrophils are considered the host's first line of defense against infections and have been implicated in the immunopathogenesis of Leishmaniasis. Leishmania parasites are inoculated alongside vectors' saliva, which is a rich source of pharmacologically active substances that interfere with host immune response. In the present study, we tested the hypothesis that salivary components from Lutzomyia longipalpis, an important vector of visceral Leishmaniasis, enhance neutrophil apoptosis. Murine inflammatory peritoneal neutrophils cultured in the presence of SGS presented increased surface expression of FasL and underwent caspase-dependent and FasL-mediated apoptosis. This proapoptosis effect of SGS on neutrophils was abrogated by pretreatment with protease as well as preincubation with antisaliva antibodies. Furthermore, in the presence of Leishmania chagasi, SGS also increased apoptosis on neutrophils and increased PGE(2) release and decreased ROS production by neutrophils, while enhancing parasite viability inside these cells. The increased parasite burden was abrogated by treatment with z-VAD, a pan caspase inhibitor, and NS-398, a COX-2 inhibitor. In the presence of SGS, Leishmania-infected neutrophils produced higher levels of MCP-1 and attracted a high number of macrophages by chemotaxis in vitro assays. Both of these events were abrogated by pretreatment of neutrophils with bindarit, an inhibitor of CCL2/MCP-1 expression. Taken together, our data support the hypothesis that vector salivary proteins trigger caspase-dependent and FasL-mediated apoptosis, thereby favoring Leishmania survival inside neutrophils, which may represent an important mechanism for the establishment of Leishmania infection.

  16. On How Fas Apoptosis-Independent Pathways Drive T Cell Hyperproliferation and Lymphadenopathy in lpr Mice

    PubMed Central

    Balomenos, Dimitrios; Shokri, Rahman; Daszkiewicz, Lidia; Vázquez-Mateo, Cristina; Martínez-A, Carlos

    2017-01-01

    Fas induces massive apoptosis in T cells after repeated in vitro T cell receptor (TCR) stimulation and is critical for lymphocyte homeostasis in Fas-deficient (lpr) mice. Although the in vitro Fas apoptotic mechanism has been defined, there is a large conceptual gap between this in vitro phenomenon and the pathway that leads to in vivo development of lymphadenopathy and autoimmunity. A striking abnormality in lpr mice is the excessive proliferation of CD4+ and CD8+ T cells, and more so of the double-negative TCR+CD4−CD8−B220+ T cells. The basis of lpr T cell hyperproliferation remains elusive, as it cannot be explained by Fas-deficient apoptosis. T cell-directed p21 overexpression reduces hyperactivation/hyperproliferation of all lpr T cell subtypes and lymphadenopathy in lpr mice. p21 controls expansion of repeatedly stimulated T cells without affecting apoptosis. These results confirm a direct link between hyperactivation/hyperproliferation, autoreactivity, and lymphadenopathy in lpr mice and, with earlier studies, suggest that Fas apoptosis-independent pathways control lpr T cell hyperproliferation. lpr T cell hyperproliferation could be an indirect result of the defective apoptosis of repeatedly stimulated lpr T cells. Nonetheless, in this perspective, we argue for an alternative setting, in which lack of Fas would directly cause lpr T cell hyperactivation/hyperproliferation in vivo. We propose that Fas/Fas ligand (FasL) acts as an activation inhibitor of recurrently stimulated T cells, and that its disruption causes overexpansion of T cells in lpr mice. Research to define the underlying mechanism of this Fas/FasL effect could resolve the phenotype of lpr mice and lead to therapeutics for related human syndromes. PMID:28344578

  17. On How Fas Apoptosis-Independent Pathways Drive T Cell Hyperproliferation and Lymphadenopathy in lpr Mice.

    PubMed

    Balomenos, Dimitrios; Shokri, Rahman; Daszkiewicz, Lidia; Vázquez-Mateo, Cristina; Martínez-A, Carlos

    2017-01-01

    Fas induces massive apoptosis in T cells after repeated in vitro T cell receptor (TCR) stimulation and is critical for lymphocyte homeostasis in Fas-deficient (lpr) mice. Although the in vitro Fas apoptotic mechanism has been defined, there is a large conceptual gap between this in vitro phenomenon and the pathway that leads to in vivo development of lymphadenopathy and autoimmunity. A striking abnormality in lpr mice is the excessive proliferation of CD4(+) and CD8(+) T cells, and more so of the double-negative TCR(+)CD4(-)CD8(-)B220(+) T cells. The basis of lpr T cell hyperproliferation remains elusive, as it cannot be explained by Fas-deficient apoptosis. T cell-directed p21 overexpression reduces hyperactivation/hyperproliferation of all lpr T cell subtypes and lymphadenopathy in lpr mice. p21 controls expansion of repeatedly stimulated T cells without affecting apoptosis. These results confirm a direct link between hyperactivation/hyperproliferation, autoreactivity, and lymphadenopathy in lpr mice and, with earlier studies, suggest that Fas apoptosis-independent pathways control lpr T cell hyperproliferation. lpr T cell hyperproliferation could be an indirect result of the defective apoptosis of repeatedly stimulated lpr T cells. Nonetheless, in this perspective, we argue for an alternative setting, in which lack of Fas would directly cause lpr T cell hyperactivation/hyperproliferation in vivo. We propose that Fas/Fas ligand (FasL) acts as an activation inhibitor of recurrently stimulated T cells, and that its disruption causes overexpansion of T cells in lpr mice. Research to define the underlying mechanism of this Fas/FasL effect could resolve the phenotype of lpr mice and lead to therapeutics for related human syndromes.

  18. Apigenin induces apoptosis via downregulation of S-phase kinase-associated protein 2-mediated induction of p27Kip1 in primary effusion lymphoma cells.

    PubMed

    Hussain, A R; Khan, A S; Ahmed, S O; Ahmed, M; Platanias, L C; Al-Kuraya, K S; Uddin, S

    2010-04-01

    The mechanisms that regulate mitogenic and antiapoptotic signals in primary effusion lymphoma (PEL) are not well known. In efforts to identify novel approaches to block the proliferation of PEL cells, we assessed the effect of apigenin (4',5,7-trihydroxyflavone), a flavonoid on a panel of PEL cell lines. We studied the effect of apigenin on four PEL cell lines. Apoptosis was measured by annexin V/PI dual staining and DNA laddering. Protein expression was measured by immunoblotting. Apigenin induced apoptosis in PEL cell lines in a dose dependent manner. Such effects of apigenin appeared to result from suppression of constitutively active kinase AKT resulting in down-regulation of SKP2, hypo-phosphorylation of Rb and accumulation of p27Kip1. Apigenin treatment of PEL cells caused dephosphorylation of p-Bad protein leading to down regulation of the anti-apoptotic protein, Bcl-2 and an increase in Bax/Bcl2 ratio. Apigenin treatment also triggered Bax conformational change and subsequently translocation from cytosole to mitochondria causing loss of mitochondrial membrane potential with subsequent release of cytochrome c. Released cytochrome c onto the cytosole activated caspase-9 and caspase-3, followed by polyadenosin-5'-diphosphate-ribose polymerase (PARP) cleavage. Finally, treatment of PEL cells with apigenin down-regulated the expression of inhibitor of apoptosis protein (IAPs). Altogether, these data suggest a novel function for apigenin, acting as a suppressor of AKT/PKB pathway in PEL cells, and raise the possibility that this agent may have a future therapeutic role in PEL and possibly other malignancies with constitutive activation of the AKT/PKB pathway.

  19. Coagulation factor Xa drives tumor cells into apoptosis through BH3-only protein Bim up-regulation

    SciTech Connect

    Borensztajn, Keren S. . E-mail: K.S.Borensztajn@amc.uva.nl; Bijlsma, Maarten F.; Groot, Angelique P.; Brueggemann, Lois W.; Versteeg, Henri H.; Reitsma, Pieter H.; Peppelenbosch, Maikel P.; Spek, C. Arnold

    2007-07-15

    Coagulation Factor (F)Xa is a serine protease that plays a crucial role during blood coagulation by converting prothrombin into active thrombin. Recently, however, it emerged that besides this role in coagulation, FXa induces intracellular signaling leading to different cellular effects. Here, we show that coagulation factor (F)Xa drives tumor cells of epithelial origin, but not endothelial cells or monocytes, into apoptosis, whereas it even enhances fibroblast survival. FXa signals through the protease activated receptor (PAR)-1 to activate extracellular-signal regulated kinase (ERK) 1/2 and p38. This activation is associated with phosphorylation of the transcription factor CREB, and in tumor cells with up-regulation of the BH3-only pro-apoptotic protein Bim, leading to caspase-3 cleavage, the main hallmark of apoptosis. Transfection of tumor cells with dominant negative forms of CREB or siRNA for either PAR-1, Bim, ERK1 and/or p38 inhibited the pro-apoptotic effect of FXa. In fibroblasts, FXa-induced PAR-1 activation leads to down-regulation of Bim and pre-treatment with PAR-1 or Bim siRNA abolishes proliferation. We thus provide evidence that beyond its role in blood coagulation, FXa plays a key role in cellular processes in which Bim is the central player in determining cell survival.

  20. Estrogen Receptor β Modulates Apoptosis Complexes and the Inflammasome to Drive the Pathogenesis of Endometriosis

    PubMed Central

    Han, Sang Jun; Jung, Sung Yun; Wu, San-Pin; Hawkins, Shannon M.; Park, Mi Jin; Kyo, Satoru; Qin, Jun; Lydon, John P.; Tsai, Sophia Y.; Tsai, Ming-Jer; DeMayo, Francesco J.; O’Malley, Bert W.

    2015-01-01

    Summary Alterations in estrogen-mediated cellular signaling play an essential role in the pathogenesis of endometriosis. In addition to higher estrogen receptor (ER)β levels, enhanced ERβ activity was detected in endometriotic tissues, and the inhibition of enhanced ERβ activity by an ERβ-selective antagonist suppressed mouse ectopic lesion growth. Notably, gain of ERβ function stimulated the progression of endometriosis. As a mechanism to evade endogenous immune surveillance for cell survival, ERβ interacts with cellular apoptotic machinery in the cytoplasm to inhibit TNFα-induced apoptosis. ERβ also interacts with components of the cytoplasmic inflammasome to increase interleukin-1β and thus enhance its cellular adhesion and proliferation properties. Furthermore, this gain of ERβ function enhances epithelial-mesenchymal transition signaling, thereby increasing the invasion activity of endometriotic tissues for establishment of ectopic lesions. Collectively, we reveal how endometrial tissue generated by retrograde menstruation can escape immune surveillance and develop into sustained ectopic lesions via gain of ERβ function. PMID:26544941

  1. The Alternative Splicing of Cytoplasmic Polyadenylation Element Binding Protein 2 Drives Anoikis Resistance and the Metastasis of Triple Negative Breast Cancer.

    PubMed

    Johnson, Ryan M; Vu, Ngoc T; Griffin, Brian P; Gentry, Amanda E; Archer, Kellie J; Chalfant, Charles E; Park, Margaret A

    2015-10-16

    Triple negative breast cancer (TNBC) represents an anomalous subset of breast cancer with a greatly reduced (30%) 5-year survival rate. The enhanced mortality and morbidity of TNBC arises from the high metastatic rate, which requires the acquisition of AnR, a process whereby anchorage-dependent cells become resistant to cell death induced by detachment. In this study TNBC cell lines were selected for AnR, and these cell lines demonstrated dramatic enhancement in the formation of lung metastases as compared with parental cells. Genetic analysis of the AnR subclones versus parental cells via next generation sequencing and analysis of global alternative RNA splicing identified that the mRNA splicing of cytoplasmic polyadenylation element binding 2 (CPEB2), a translational regulator, was altered in AnR TNBC cells. Specifically, increased inclusion of exon 4 into the mature mRNA to produce the CPEB2B isoform was observed in AnR cell lines. Molecular manipulations of CPEB2 splice variants demonstrated a key role for this RNA splicing event in the resistance of cells to anoikis. Specifically, down-regulation of the CPEB2B isoform using siRNA re-sensitized the AnR cell lines to detachment-induced cell death. The ectopic expression of CPEB2B in parental TNBC cell lines induced AnR and dramatically increased metastatic potential. Importantly, alterations in the alternative splicing of CPEB2 were also observed in human TNBC and additional subtypes of human breast cancer tumors linked to a high metastatic rate. Our findings demonstrate that the regulation of CPEB2 mRNA splicing is a key mechanism in AnR and a driving force in TNBC metastasis.

  2. Hyaluronic acid-fabricated nanogold delivery of the inhibitor of apoptosis protein-2 siRNAs inhibits benzo[a]pyrene-induced oncogenic properties of lung cancer A549 cells

    NASA Astrophysics Data System (ADS)

    Lin, Chung-Ming; Kao, Wei-Chien; Yeh, Chun-An; Chen, Hui-Jye; Lin, Shinn-Zong; Hsieh, Hsien-Hsu; Sun, Wei-Shen; Chang, Chih-Hsuan; Hung, Huey-Shan

    2015-03-01

    Benzo[a]pyrene (BaP), a component of cooking oil fumes (COF), promotes lung cancer cell proliferation and survival via the induction of inhibitor of apoptosis protein-2 (IAP-2) proteins. Thus knockdown of IAP-2 would be a promising way to battle against lung cancer caused by COF. Functionalized gold nanoparticle (AuNP) is an effective delivery system for bio-active materials. Here, biocompatible hyaluronic acid (HA) was fabricated into nanoparticles to increase the target specificity by binding to CD44-over-expressed cancer cells. IAP-2-specific small-interfering RNA (siRNAs) or fluorescein isothiocyanate (FITC) were then incorporated into AuNP-HA. Conjugation of IAP-2 siRNA into AuNPs-HA was verified by the UV-vis spectrometer and Fourier transform infrared spectrometer. Further studies showed that AuNP-HA/FITC were effectively taken up by A549 cells through CD44-mediated endocytosis. Incubation of BaP-challenged cells with AuNP-HA-IAP-2 siRNAs silenced the expression of IAP-2, decreased cell proliferation and triggered pronounced cell apoptosis by the decrease in Bcl-2 protein and the increase in Bax protein as well as the active form of caspases-3. The BaP-elicited cell migration and enzymatic activity of the secreted matrix metalloproteinase-2 were also substantially suppressed by treatment with AuNP-HA-IAP-2 siRNAs. These results indicated that IAP-2 siRNAs can be efficiently delivered into A549 cells by functionalized AuNP-HA to repress the IAP-2 expression and BaP-induced oncogenic events, suggesting the potential therapeutic application of IAP-2 siRNA or other siRNA-conjugated AuNP-HA composites to COF-induced lung cancer and other gene-caused diseases in the future.

  3. Cyclin-dependent kinases 7 and 9 specifically regulate neutrophil transcription and their inhibition drives apoptosis to promote resolution of inflammation

    PubMed Central

    Leitch, A E; Lucas, C D; Marwick, J A; Duffin, R; Haslett, C; Rossi, A G

    2012-01-01

    Terminally differentiated neutrophils are short-lived but the key effector cells of the innate immune response, and have a prominent role in the pathogenesis and propagation of many inflammatory diseases. Delayed apoptosis, which is responsible for their extended longevity, is critically dependent on a balance of intracellular survival versus pro-apoptotic proteins. Here, we elucidate the mechanism by which the cyclin-dependent kinase (CDK) inhibitor drugs such as R-roscovitine and DRB (5,6-dichloro-1-beta-𝒟-ribofuranosylbenzimidazole) mediate neutrophil apoptosis. We demonstrate (by a combination of microarray, confocal microscopy, apoptosis assays and western blotting) that the phosphorylation of RNA polymerase II by CDKs 7 and 9 is inhibited by R-roscovitine and that specific effects on neutrophil transcriptional capacity are responsible for neutrophil apoptosis. Finally, we show that specific CDK7 and 9 inhibition with DRB drives resolution of neutrophil-dominant inflammation. Thus, we highlight a novel mechanism that controls both primary human neutrophil transcription and apoptosis that could be targeted by selective CDK inhibitor drugs to resolve established inflammation. PMID:22743999

  4. Endotoxin Tolerance Inhibits Degradation of Tumor Necrosis Factor Receptor-Associated Factor 3 by Suppressing Pellino 1 Expression and the K48 Ubiquitin Ligase Activity of Cellular Inhibitor of Apoptosis Protein 2.

    PubMed

    Li, Peizhi; Liu, Hongxiang; Zhang, Yiyin; Liao, Rui; He, Kun; Ruan, Xiongzhong; Gong, Jianping

    2016-09-15

    Pellino 1 positively regulates Toll-like receptor 4 signaling by regulating tumor necrosis factor receptor-associated factor 3 (TRAF3) degradation and is suppressed with the induction of endotoxin tolerance. However, the role of TRAF3 in endotoxin tolerance is largely unknown. In this study, we found that lipopolysaccharide (LPS) stimulation decreased TARF3 protein expression in mouse Kupffer cells (KCs) and liver tissues, whereas endotoxin tolerization abrogated this effect. Degradative TRAF3 K48-linked ubiquitination and the cytoplasmic translocation of the MYD88-associated multiprotein complex were significantly inhibited in tolerized KCs, which led to markedly impaired activation of MYD88-dependent JNK and p38 and downregulation of inflammatory cytokines. TRAF3 ablation failed to induce a fully endotoxin-tolerant state in RAW264.7 cells. Pellino 1 knockdown in Raw264.7 cells did not impair induction of cIAP2 in response to LPS but inhibited the K63-linked ubiquitination of cellular inhibitor of apoptosis protein 2 (cIAP2) and K48-linked ubiquitination of TRAF3 protein. We also found upregulation of Pellino 1 and downregulation of TRAF3 in liver tissues of patients with cholangitis. Our findings reveal a novel mechanism that endotoxin tolerance reprograms mitogen-activated protein kinase signaling by suppressing Pellino 1-mediated K63-linked ubiquitination of cIAP2, K48-linked ubiquitination, and degradation of TRAF3. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  5. Hypoxia drives apoptosis independently of p53 and metallothionein transcript levels in hemocytes of the whiteleg shrimp Litopenaeus vannamei.

    PubMed

    Felix-Portillo, Monserrath; Martínez-Quintana, José A; Arenas-Padilla, Marina; Mata-Haro, Verónica; Gómez-Jiménez, Silvia; Yepiz-Plascencia, Gloria

    2016-10-01

    The cellular mechanisms used by the shrimp Litopenaeus vannamei to respond to hypoxia have been studied from the energetic metabolism and antioxidant angles. We herein investigated the participation of p53 and metallothionein (MT) in the apoptotic process in response to hypoxia in shrimp hemocytes. The Lvp53 or LvMT genes were efficiently silenced by injection of double stranded RNA for p53 or MT. The effects of silencing on apoptosis were measured as caspase-3 activity and flow cytometry in hemocytes after 24 and 48 h of hypoxia (1.5 mg DO L(-1)). Hemocytes from unsilenced animals had significantly higher apoptosis levels upon both times of hypoxia. The apoptotic levels were diminished but not suppressed in dsp53-silenced but not dsMT-silenced hemocytes after 24 h of hypoxia, indicating a contribution of Lvp53 to apoptosis. Apoptosis in normoxia was significantly higher in dsp53-and dsMT-silenced animals compared to the unsilenced controls, pointing to a possible cytoprotective role of LvMT and Lvp53 during the basal apoptotic program in normoxia. Overall, these results indicate that hypoxia augments apoptosis in shrimp hemocytes and high mRNA levels of Lvp53 and LvMT are not necessary for this response.

  6. Genetic and pharmacological inhibition of CDK9 drives neutrophil apoptosis to resolve inflammation in zebrafish in vivo

    PubMed Central

    Hoodless, Laura J.; Lucas, Christopher D.; Duffin, Rodger; Denvir, Martin A.; Haslett, Christopher; Tucker, Carl S.; Rossi, Adriano G.

    2016-01-01

    Neutrophilic inflammation is tightly regulated and subsequently resolves to limit tissue damage and promote repair. When the timely resolution of inflammation is dysregulated, tissue damage and disease results. One key control mechanism is neutrophil apoptosis, followed by apoptotic cell clearance by phagocytes such as macrophages. Cyclin-dependent kinase (CDK) inhibitor drugs induce neutrophil apoptosis in vitro and promote resolution of inflammation in rodent models. Here we present the first in vivo evidence, using pharmacological and genetic approaches, that CDK9 is involved in the resolution of neutrophil-dependent inflammation. Using live cell imaging in zebrafish with labelled neutrophils and macrophages, we show that pharmacological inhibition, morpholino-mediated knockdown and CRISPR/cas9-mediated knockout of CDK9 enhances inflammation resolution by reducing neutrophil numbers via induction of apoptosis after tailfin injury. Importantly, knockdown of the negative regulator La-related protein 7 (LaRP7) increased neutrophilic inflammation. Our data show that CDK9 is a possible target for controlling resolution of inflammation. PMID:27833165

  7. Inhibition of the intrinsic but not the extrinsic apoptosis pathway accelerates and drives MYC-driven tumorigenesis towards acute myeloid leukemia.

    PubMed

    Högstrand, Kari; Hejll, Eduar; Sander, Birgitta; Rozell, Björn; Larsson, Lars-Gunnar; Grandien, Alf

    2012-01-01

    Myc plays an important role in tumor development, including acute myeloid leukemia (AML). However, MYC is also a powerful inducer of apoptosis, which is one of the major failsafe programs to prevent cancer development. To clarify the relative importance of the extrinsic (death receptor-mediated) versus the intrinsic (mitochondrial) pathway of apoptosis in MYC-driven AML, we coexpressed MYC together with anti-apoptotic proteins of relevance for AML; BCL-X(L)/BCL-2 (inhibiting the intrinsic pathway) or FLIP(L) (inhibiting the extrinsic pathway), in hematopoietic stems cells (HSCs). Transplantation of HSCs expressing MYC into syngeneic recipient mice resulted in development of AML and T-cell lymphomas within 7-9 weeks as expected. Importantly, coexpression of MYC together with BCL-X(L)/BCL-2 resulted in strongly accelerated kinetics and favored tumor development towards aggressive AML. In contrast, coexpression of MYC and FLIP(L) did neither accelerate tumorigenesis nor change the ratio of AML versus T-cell lymphoma. However, a change in distribution of immature CD4(+)CD8(+) versus mature CD4(+) T-cell lymphoma was observed in MYC/FLIP(L) mice, possibly as a result of increased survival of the CD4+ population, but this did not significantly affect the outcome of the disease. In conclusion, our findings provide direct evidence that BCL-X(L) and BCL-2 but not FLIP(L) acts in synergy with MYC to drive AML development.

  8. The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in neurons.

    PubMed

    Chen, Y; McPhie, D L; Hirschberg, J; Neve, R L

    2000-03-24

    APP-BP1 binds to the amyloid precursor protein (APP) carboxyl-terminal domain. Recent work suggests that APP-BP1 participates in a novel ubiquitinylation-related pathway involving the ubiquitin-like molecule NEDD8. We show here that, in vivo in mammalian cells, APP-BP1 interacts with hUba3, its presumptive partner in the NEDD8 activation pathway, and that the APP-BP1 binding site for hUba3 is within amino acids 443-479. We also provide evidence that the human APP-BP1 molecule can rescue the ts41 mutation in Chinese hamster cells. This mutation previously has been shown to lead to successive S phases of the cell cycle without intervening G(2), M, and G(1), suggesting that the product of this gene negatively regulates entry into the S phase and positively regulates entry into mitosis. We show that expression of APP-BP1 in ts41 cells drives the cell cycle through the S-M checkpoint and that this function requires both hUba3 and hUbc12. Overexpression of APP-BP1 in primary neurons causes apoptosis via the same pathway. A specific caspase-6 inhibitor blocks this apoptosis. These findings are discussed in the context of abnormalities in the cell cycle that have been observed in Alzheimer's disease.

  9. Biomechanics drive histological wall remodeling of neoaortic root: A mathematical model to study the expression levels of ki 67, metalloprotease, and apoptosis transition.

    PubMed

    Nappi, Francesco; Fraldi, Massimiliano; Spadaccio, Cristiano; Carotenuto, Angelo Rosario; Montagnani, Stefania; Castaldo, Clotilde; Chachques, Juan Carlos; Acar, Christophe

    2016-11-01

    The pulmonary artery autograft (PA) is the ideal substitute for aortic valve disease in children and young adult. However, it is harnessed by the issue of long-term dilation and regurgitation, often requiring surgery. PA implanted in aortic position during the growth phase in children undergoes a process of mechanical remodeling. We previously developed a semiresorbable armored prosthesis able to mechanically sustain the neoaorta preventing dilation and to gradually integrate with the PA wall inducing a progressive arterial-like tissue positive remodeling. We also described the mechanisms of growth, remodeling and stress shielding of the reinforced PA through a mathematical model. We sought to demonstrate the biological counterpart and the potential molecular mechanisms underlying this histological and mechanical remodeling. A specific mathematical model was developed to describe mechanical behavior of the PA. Mallory trichrome red staining and immunohistochemistry for MMP-9 were performed to elucidate extracellular matrix remodeling phenomena. Apoptosis and cell proliferation were determined by TUNEL assay and immunohistochemistry for Ki67, respectively. An histological remodeling phenomenon sustained by increased level of MMP-9, augmented cell proliferation and reduced apoptosis in the reinforced PA was demonstrated. The mathematical model predicted the biomechanical behavior subtended by the histological changes of the PA in these settings. Changes in metalloproteinases (MMP-9), cell proliferation and apoptosis are the main actors in the remodeling process occurring after transposition of the PA into systemic regimens. Use of semiresorbable reinforcements might induce a positive remodeling of the PA in the context of Ross operation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2785-2793, 2016.

  10. Coexpression of hyperactivated AKT1 with additional genes activated in leukemia drives hematopoietic progenitor cells to cell cycle block and apoptosis.

    PubMed

    Tang, Yanjuan; Halvarsson, Camilla; Nordigården, Amanda; Kumar, Komal; Åhsberg, Josefine; Rörby, Emma; Wong, Wan Man; Jönsson, Jan-Ingvar

    2015-07-01

    The phosphatidylinositol 3-kinase/AKT pathway is an integral component of signaling involved in the development of many cancers, including myeloid leukemias such as chronic myeloid leukemia and acute myeloid leukemia (AML). Increased AKT1 activity is frequently seen in AML patients, providing leukemic cells with growth and survival promoting signals. An important aspect of AKT1 function is its involvement in cellular metabolism and energy production. Under some circumstances, strong activation of AKT1 increases oxidative stress, which can cause apoptosis when cells progressively build up excess free radicals. This has been described in hematopoietic cells overexpressing activated AKT1; however, whether this is true in cells coexpressing other genetic events involved in leukemia is not known. This prompted us to investigate the effect of constitutively active AKT1 (myristoylated AKT1) in hematopoietic progenitor cells expressing constitutively active signal transducer and activator of transcription 5, Fms-related tyrosine kinase 3-internal tandem duplication, or antiapoptotic B-cell lymphoma 2. Surprisingly, myristoylated AKT1 was incompatible with proliferation driven by both signal transducer and activator of transcription 5 and Fms-related tyrosine kinase 3-internal tandem duplication, which triggered cell cycle block and apoptosis. Moreover, transplantable cells of B-cell lymphoma 2-transgenic mice were impaired in their engraftment ability to recipient mice when expressing hyperactivated AKT1. This was linked to AKT1-mediated proapoptotic functions and not to impairment in homing to the bone marrow. Although cells expressing hyperactivated AKT1 displayed higher levels of reactive oxygen species both in vitro and in vivo, the addition of the antioxidant N-acetyl-L-cysteine significantly reduced apoptosis. Taken together, the results indicate that constitutive AKT1 activity is incompatible with growth- and survival-promoting ability of other activated genes in

  11. Perturbation of neddylation-dependent NF-κB responses in the intestinal epithelium drives apoptosis and inhibits resolution of mucosal inflammation

    PubMed Central

    Ehrentraut, Stefan F.; Curtis, Valerie F.; Wang, Ruth X.; Saeedi, Bejan J.; Ehrentraut, Heidi; Onyiah, Joseph C.; Kelly, Caleb J.; Campbell, Eric L.; Glover, Louise E.; Kominsky, Douglas J.; Colgan, Sean P.

    2016-01-01

    Recent work has revealed a central role for neddylation (the conjugation of a Nedd8 moiety to Cullin proteins) in the fine-tuning of the NF-κB response (via Cullin-1). In the present study, we investigated the contribution of Cullin-1 neddylation and NF-κB signaling to mucosal inflammatory responses in vitro and in vivo. Initial in vitro studies using cultured intestinal epithelial cells revealed that the neddylation inhibitor MLN4924 prominently induces the deneddylation of Cullin-1. Parallel Western blot, luciferase reporter, and gene target assays identified MLN4924 as a potent inhibitor of intestinal epithelial NF-κB. Subsequent studies revealed that MLN4924 potently induces epithelial apoptosis but only in the presence of additional inflammatory stimuli. In vivo administration of MLN4924 (3 mg/kg per day) in a TNBS-induced colitis model significantly accentuated disease severity. Indeed, MLN4924 resulted in worsened clinical scores and increased mortality early in the inflammatory response. Histologic analysis of the colon revealed that neddylation inhibition results in increased tissue damage and significantly increased mucosal apoptosis as determined by TUNEL and cleaved caspase-3 staining, which was particularly prominent within the epithelium. Extensions of these studies revealed that ongoing inflammation is associated with significant loss of deneddylase-1 (SENP8) expression. These studies reveal that intact Cullin-1 neddylation is central to resolution of acute inflammation. PMID:27682585

  12. Perturbation of neddylation-dependent NF-κB responses in the intestinal epithelium drives apoptosis and inhibits resolution of mucosal inflammation.

    PubMed

    Ehrentraut, Stefan F; Curtis, Valerie F; Wang, Ruth X; Saeedi, Bejan J; Ehrentraut, Heidi; Onyiah, Joseph C; Kelly, Caleb J; Campbell, Eric L; Glover, Louise E; Kominsky, Douglas J; Colgan, Sean P

    2016-09-28

    Recent work has revealed a central role for neddylation (the conjugation of a Nedd8-moiety to Cullin proteins) in the fine tuning of the NF-κB response (via Cullin-1). In the present study, we investigated the contribution of Cullin-1 neddylation and NF-κB signaling to mucosal inflammatory responses in vitro and in vivo. Initial in vitro studies using cultured intestinal epithelial cells revealed that the neddylation inhibitor MLN4924 prominently induces the deneddylation of Cullin-1. Parallel western blot, luciferase reporter and gene target assays identified MLN4924 as a potent inhibitor of intestinal epithelial NF-κB. Subsequent studies revealed that MLN4924 potently induces epithelial apoptosis but only in the presence of additional inflammatory stimuli. In vivo administration of MLN4924 (3 mg/kg/d) in a TNBS-induce colitis model significantly accentuated disease severity. Indeed, MLN4924 resulted in worsened clinical scores and increased mortality early in the inflammatory response. Histologic analysis of the colon revealed that neddylation inhibition results in increased tissue damage and significantly increased mucosal apoptosis as determined by TUNEL and cleaved caspase-3 staining, particularly prominent within the epithelium. Extensions of these studies revealed that ongoing inflammation is associated with significant loss of deneddylase-1 (SENP8) expresssion. These studies reveal that intact Cullin-1 neddylation is central to resolution of acute inflammation.

  13. Cell-free methemoglobin drives platelets to apoptosis via mitochondrial ROS-mediated activation of JNK and p38 MAP kinase.

    PubMed

    NaveenKumar, Somanathapura K; Hemshekhar, Mahadevappa; Sundaram, Mahalingam S; Kemparaju, Kempaiah; Girish, Kesturu S

    2017-09-09

    Cell-free hemoglobin (Hb), a well-known marker of intravascular hemolysis, is eventually oxidized to methemoglobin (MtHb). Elevated levels of MtHb have been noted, alongside depleted levels of platelets, in several hemolytic diseases. The current study aims to probe the possible role of MtHb in platelet death, based on the facts that it is a pro-inflammatory and pro-apoptotic agent, as well as the sensitive nature of platelets and their tendency to undergo apoptosis under oxidative stress. An attempt is made to establish the link between hemolysis and thrombocytopenia, by deciphering the underlying molecular signaling pathways. The results of this study demonstrate that MtHb, not Hb exerts oxidative stress on platelets, which triggers their death via ROS-mediated mitochondrial apoptotic pathway. It was further established that the MtHb-induced platelet apoptotic events mediate through JNK and p38 MAPK activation. Thus, the study presents a mechanistic insight into the previous studies that reported the incidence of thrombocytopenia in hemolytic diseases. This study highlights the fate of platelets in intravascular hemolytic conditions, which demands the need for a specific treatment strategy considering the risks associated with thrombocytopenia during severe hemolytic diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Bromelain inhibits nuclear factor kappa-B translocation, driving human epidermoid carcinoma A431 and melanoma A375 cells through G(2)/M arrest to apoptosis.

    PubMed

    Bhui, Kulpreet; Tyagi, Shilpa; Srivastava, Amit Kumar; Singh, Madhulika; Roy, Preeti; Singh, Richa; Shukla, Yogeshwer

    2012-03-01

    Bromelain, obtained from pineapple, is already in use clinically as adjunct in chemotherapy. Our objective was to test its ability to act as a sole anti-cancer agent. Therefore, we describe its anti-proliferative, anti-inflammatory and subsequent anti-cancer effects in vitro, against human epidermoid carcinoma-A431 and melanoma-A375 cells. Bromelain exhibited reduction in proliferation of both these cell-lines and suppressed their potential for anchorage-independent growth. Further, suppression of inflammatory signaling by bromelain was evident by inhibition of Akt regulated-nuclear factor-kappaB activation via suppression of inhibitory-kappaBα phosphorylation and concomitant reduction in cyclooxygenase-2. Since, the inflammatory cascade is well-known to be closely allied to cancer; we studied the effect of bromelain on events/molecules central to it. Bromelain caused depletion of intracellular glutathione and generation of reactive oxygen-species followed by mitochondrial membrane depolarization. This led to bromelain-induced cell-cycle arrest at G(2)/M phase which was mediated by modulation of cyclin B1, phospho-cdc25C, Plk1, phospho-cdc2, and myt1. This was subsequently followed by induction of apoptosis, indicated by membrane-blebbing, modulation of Bax-Bcl-2 ratio, Apaf-1, caspase-9, and caspase-3; chromatin-condensation, increase in caspase-activity and DNA-fragmentation. Bromelain afforded substantial anti-cancer potential in these settings; hence we suggest it as a potential prospect for anti-cancer agent besides only an additive in chemotherapy.

  15. Maternal and Fetal Mechanisms of B Cell Regulation during Pregnancy: Human Chorionic Gonadotropin Stimulates B Cells to Produce IL-10 While Alpha-Fetoprotein Drives Them into Apoptosis

    PubMed Central

    Fettke, Franziska; Schumacher, Anne; Canellada, Andrea; Toledo, Natalia; Bekeredjian-Ding, Isabelle; Bondt, Albert; Wuhrer, Manfred; Costa, Serban-Dan; Zenclussen, Ana Claudia

    2016-01-01

    Maternal immune tolerance toward the fetus is an essential requisite for pregnancy. While T cell functions are well documented, little is known about the participation of B cells. We have previously suggested that IL-10-producing B cells are involved in pregnancy tolerance in mice and humans. By employing murine and human systems, we report now that fetal trophoblasts positively regulate the generation of IL-10-producing B cells. We next studied the participation of hormones produced by the placenta as well as the fetal protein alpha-fetoprotein (AFP) in B cell modulation. Human chorionic gonadotropin (hCG), but not progesterone, estrogen, or a combination of both, was able to promote changes in B cell phenotype and boost their IL-10 production, which was abolished after blocking hCG. The hCG-induced B cell phenotype was not associated with augmented galactosylation, sialylation, or fucosylation of IgG subclasses in their Fc. In vitro, hCG induced the synthesis of asymmetrically glycosylated antibodies in their Fab region. Interestingly, AFP had dual effects depending on the concentration. At concentrations corresponding to maternal serum levels, it did not modify the phenotype or IL-10 secretion of B cells. At fetal concentrations, however, AFP was able to drive B cells into apoptosis, which may indicate a protective mechanism to avoid maternal B cells to reach the fetus. Our data suggest that the fetus secrete factors that promote a pregnancy-friendly B cell phenotype, unraveling interesting aspects of B cell function, and modulation by pregnancy hormones and fetal proteins. PMID:28008329

  16. iDriving (Intelligent Driving)

    SciTech Connect

    Malikopoulos, Andreas

    2012-09-17

    iDriving identifies the driving style factors that have a major impact on fuel economy. An optimization framework is used with the aim of optimizing a driving style with respect to these driving factors. A set of polynomial metamodels is constructed to reflect the responses produced in fuel economy by changing the driving factors. The optimization framework is used to develop a real-time feedback system, including visual instructions, to enable drivers to alter their driving styles in responses to actual driving conditions to improve fuel efficiency.

  17. A hallmark of immunoreceptor, the tyrosine-based inhibitory motif ITIM, is present in the G protein-coupled receptor OX1R for orexins and drives apoptosis: a novel mechanism.

    PubMed

    Voisin, Thierry; El Firar, Aadil; Rouyer-Fessard, Christiane; Gratio, Valérie; Laburthe, Marc

    2008-06-01

    Orexins acting at the G protein-coupled receptor (GPCR) OX1R have recently been shown to promote dramatic apoptosis in cancer cells. We report here that orexin-induced apoptosis is driven by an immunoreceptor tyrosine-based inhibitory motif (ITIM) (IIY(358)NFL) present in the OX1R. This effect is mediated by SHP-2 phosphatase recruitment via a mechanism that requires Gq protein but is independent of phospholipase C activation. This is based on the following observations: 1) mutation of Y(358) into F abolished orexin-induced tyrosine phosphorylation in ITIM, orexin-induced apoptosis, and uncoupled OX1R from Gq protein in transfected Chinese hamster ovary (CHO) cells; 2) orexin-induced apoptosis in CHO cells expressing recombinant OX1R and in colon cancer cells expressing the native receptor was abolished by treatment with the tyrosine phosphatase inhibitor PAO and by transfection with a dominant-negative mutant of SHP-2; 3) orexins were unable to promote apoptosis in fibroblast cells invalidated for the G alpha q subunit and transfected with OX1R cDNA, whereas they promoted apoptosis in cells equipped with G alpha q and OX1R; and 4) the phospholipase C inhibitor U-73122 blocked orexin-stimulated inositol phosphate formation, whereas it had no effect on orexin-induced apoptosis in CHO cells expressing OX1R. These data unravel a novel mechanism, whereby ITIM-expressing GPCRs may trigger apoptosis.

  18. Impaired Driving

    MedlinePlus

    Impaired driving is dangerous. It's the cause of more than half of all car crashes. It means operating a ... texting Having a medical condition which affects your driving For your safety and the safety of others, ...

  19. Pile Driving

    NASA Technical Reports Server (NTRS)

    1987-01-01

    Machine-oriented structural engineering firm TERA, Inc. is engaged in a project to evaluate the reliability of offshore pile driving prediction methods to eventually predict the best pile driving technique for each new offshore oil platform. Phase I Pile driving records of 48 offshore platforms including such information as blow counts, soil composition and pertinent construction details were digitized. In Phase II, pile driving records were statistically compared with current methods of prediction. Result was development of modular software, the CRIPS80 Software Design Analyzer System, that companies can use to evaluate other prediction procedures or other data bases.

  20. OSTEOCYTE APOPTOSIS

    PubMed Central

    Jilka, Robert L.; Noble, Brendon; Weinstein, Robert S.

    2012-01-01

    Apoptotic death of osteocytes was recognized over 15 years ago, but its significance for bone homeostasis has remained elusive. A new paradigm has emerged that invokes osteocyte apoptosis as a critical event in the recruitment of osteoclasts to a specific site in response to skeletal unloading, fatigue damage, estrogen deficiency and perhaps in other states where bone must be removed. This is accomplished by yet to be defined signals emanating from dying osteocytes, which stimulate neighboring viable osteocytes to produce osteoclastogenic cytokines. The osteocyte apoptosis caused by chronic glucocorticoid administration does not increase osteoclasts; however, it does negatively impact maintenance of bone hydration, vascularity, and strength. PMID:23238124

  1. Impaired Driving

    MedlinePlus

    ... people were killed in alcohol-impaired driving crashes, accounting for nearly one-third (31%) of all traffic- ... promotion efforts into practice that influence economic, organizational, policy, and school/community action. 13,14 Using community- ...

  2. Distracted Driving

    MedlinePlus

    ... other distractions. 3 At 55 mph, the average text takes your eyes off the road long enough ... risk behaviors among high school students, including sending texts while driving. 6,7 In 2013, more than ...

  3. Pile driving

    SciTech Connect

    Merjan, S.

    1988-02-16

    Process for producing in the ground a driven composite pile is described having (a) a lower pipe stem having an upper part having a top, the lower pipe stem being capable of withstanding pile driving blows applied to the top and (b) an upper corrugated shell stem incapable of withstanding pile driving blows, the corrugated shell stem having a lower end, which process comprises driving the lower pipe stem into the ground fitting to the top of the lower pipe stem a splicer. The splicer comprises a plate having a top face and a bottom face, an integral body portion depending from the plate and surrounding the upper part of the pipe stem and, welded to the top face of the plate, an upwardly extending corrugated shell stub up to about three feet long, screwing the lower end of the upper corrugated shell stem to the shell stub after driving the lower pipe stem into the ground, placing a non-expanding pipe mandrel into the shell stem with the bottom of the mandrel resting on the plate, striking pile-driving blows on the top of the mandrel to drive the composite pile into the ground, and filling the shell stem and pipe stem with concrete from above.

  4. Disk Drives

    NASA Technical Reports Server (NTRS)

    1994-01-01

    A new material known as AlBeMet, developed by Brush Wellman for research applications in the National Aero-Space Plane (NASP) program, is now used for high performance disk drives. AlBeMet is a compression of aluminum, beryllium metal matrix composite. It reduces system weight and its high thermal conductivity can effectively remove heat and increase an electrical system's lifetime. The lighter, stiffer AlBeMet (AlBeMet 160) used in the disk drive means heads can be moved faster, improving disk performance.

  5. Effect of Immortalization-Upregulated Protein-2 (IMUP-2) on Cell Death of Trophoblast

    PubMed Central

    Jung, Ran; Choi, Jong Ho; Lee, Hyun Jung; Kim, Jin Kyeoung; Kim, Gi Jin

    2013-01-01

    Trophoblasts, in the placenta, play a role for placental development as well as implantation in the early pregnancy. The characteristics and functions of trophoblast are identified by their localization and potency for proliferation, differentiation, and invasion. Thus, inadequate trophoblast cell death induces trophoblast dysfunction resulting in abnormal placental development and several gynecological diseases. Recently, it was reported that increased immortalization-upregulated protein-2 (IMUP-2) by hypoxia influences trophoblast apoptosis. However, IMUP-2 function on autophagy, which is type II programmed cell death remains unclear. In this study, we analyzed IMUP-2 expression in trophoblast cells (HTR8-SVneo) and compared IMUP-2 effects on cell death including apoptosis and autophagy in trophoblast regardless of IMUP-2 expression. Increased IMUP-2 in trophoblast by IMUP-2 gene transfection induces cell death, especially, apoptosis increases more than autophagy (p<0.05). However, the decreased IMUP-2 in trophoblasts after siRNA treatment decreased apoptosis with the decreased activities of caspase 3 and 7. The expressions of LC3 and MDC as an autophagosome makers and phosphorylated mTOR, which is a negative regulator for autophagy, increased. In addition, the S phase of cell cycle increased in trophoblasts when IMUP-2 expression decreased. Taken together, the alteration of IMUP-2 can control the balance between apoptosis and autophagy of trophoblasts resulting in functional involvement in placental development and in gynecological diseases by regulating the function of trophoblasts. PMID:25949126

  6. Uncoupling protein-2 regulates lifespan in mice

    PubMed Central

    Andrews, Zane B.; Horvath, Tamas L.

    2009-01-01

    The long-term effects of uncoupled mitochondrial respiration by uncoupling protein-2 (UCP2) in mammalian physiology remain controversial. Here we show that increased mitochondrial uncoupling activity of different tissues predicts longer lifespan of rats compared with mice. UCP2 reduces reactive oxygen species (ROS) production and oxidative stress throughout the aging process in different tissues in mice. The absence of UCP2 shortens lifespan in wild-type mice, and the level of UCP2 positively correlates with the postnatal survival of superoxide dismutase-2 mutant animals. Thus UCP2 has a beneficial influence on cell and tissue function leading to increased lifespan. PMID:19141680

  7. Cl(-) channels in apoptosis.

    PubMed

    Wanitchakool, Podchanart; Ousingsawat, Jiraporn; Sirianant, Lalida; MacAulay, Nanna; Schreiber, Rainer; Kunzelmann, Karl

    2016-10-01

    A remarkable feature of apoptosis is the initial massive cell shrinkage, which requires opening of ion channels to allow release of K(+), Cl(-), and organic osmolytes to drive osmotic water movement and cell shrinkage. This article focuses on the role of the Cl(-) channels LRRC8, TMEM16/anoctamin, and cystic fibrosis transmembrane conductance regulator (CFTR) in cellular apoptosis. LRRC8A-E has been identified as a volume-regulated anion channel expressed in many cell types. It was shown to be required for regulatory and apoptotic volume decrease (RVD, AVD) in cultured cell lines. Its presence also determines sensitivity towards cytostatic drugs such as cisplatin. Recent data point to a molecular and functional relationship of LRRC8A and anoctamins (ANOs). ANO6, 9, and 10 (TMEM16F, J, and K) augment apoptotic Cl(-) currents and AVD, but it remains unclear whether these anoctamins operate as Cl(-) channels or as regulators of other apoptotic Cl(-) channels, such as LRRC8. CFTR has been known for its proapoptotic effects for some time, and this effect may be based on glutathione release from the cell and increase in cytosolic reactive oxygen species (ROS). Although we find that CFTR is activated by cell swelling, it is possible that CFTR serves RVD/AVD through accumulation of ROS and activation of independent membrane channels such as ANO6. Thus activation of ANO6 will support cell shrinkage and induce additional apoptotic events, such as membrane phospholipid scrambling.

  8. Is X-linked methyl-CpG binding protein 2 a new target for the treatment of Parkinson's disease

    PubMed Central

    Xie, Teng; Zhang, Jie; Yuan, Xianhou; Yang, Jing; Ding, Wei; Huang, Xin; Wu, Yong

    2013-01-01

    X-linked methyl-CpG binding protein 2 mutations can induce symptoms similar to those of Parkinson's disease and dopamine metabolism disorders, but the specific role of X-linked methyl-CpG binding protein 2 in the pathogenesis of Parkinson's disease remains unknown. In the present study, we used 6-hydroxydopamine-induced human neuroblastoma cell (SH-SY5Y cells) injury as a cell model of Parkinson's disease. The 6-hydroxydopamine (50 μmol/L) treatment decreased protein levels for both X-linked methyl-CpG binding protein 2 and tyrosine hydroxylase in these cells, and led to cell death. However, overexpression of X-linked methyl-CpG binding protein 2 was able to ameliorate the effects of 6-hydroxydopamine, it reduced 6-hydroxydopamine-induced apoptosis, and increased the levels of tyrosine hydroxylase in SH-SY5Y cells. These findings suggesting that X-linked methyl-CpG binding protein 2 may be a potential therapeutic target for the treatment of Parkinson's disease. PMID:25206503

  9. Mechanism of Hepatocyte Apoptosis

    PubMed Central

    Cao, Lei; Quan, Xi-Bing; Zeng, Wen-Jiao; Yang, Xiao-Ou; Wang, Ming-Jie

    2016-01-01

    Hepatocyte apoptosis plays important roles in both the removal of external microorganisms and the occurrence and development of liver diseases. Different conditions, such as virus infection, fatty liver disease, hepatic ischemia reperfusion, and drug-induced liver injury, are accompanied by hepatocyte apoptosis. This review summarizes recent research on the mechanism of hepatocyte apoptosis involving the classical extrinsic and intrinsic apoptotic pathways, endoplasmic reticulum stress, and oxidative stress-induced apoptosis. We emphasized the major causes of apoptosis according to the characteristics of different liver diseases. Several concerns regarding future research and clinical application are also raised. PMID:28058033

  10. Coaxial Redundant Drives

    NASA Technical Reports Server (NTRS)

    Brissette, R.

    1983-01-01

    Harmonic drives allow redundancy and high out put torque in small package. If main drive fails, standby drive takes over and produces torque along same axis as main drive. Uses include power units in robot for internal pipeline inspection, manipulators in deep submersible probes or other applications in which redundancy protects against costly failures.

  11. [Apoptosis in allergic disease].

    PubMed

    Rojas Ramos, E; Martínez Jiménez, N E; Martínez Aguilar, N E; Garfias Becerra, J

    2000-01-01

    Apoptosis (cell programmed death) it is a mechanism that implicate a physiological suicide, to keep the cellular homeostasis in big amount of tissues. Fas (APO-1; CD95) system is one of the most important cellular responsible via to induce apoptosis on different tissues. Eosinophillia on peripheral blood and tissues are the main characteristics on allergic like asthma. Eosinophil apoptosis is upper regulated in those diseases by IL-5 y GM-CSF. Corticoids, teophyllin and some macrolids have been used like apoptosis inductors on eosinophills, these could be a novel mechanism to promote a better solution on inflammatory allergic diseases.

  12. Uncoupling Protein 2 Increases Susceptibility to Lipopolysaccharide-Induced Acute Lung Injury in Mice

    PubMed Central

    Wang, Qin; Wang, Jianchun; Hu, Mingdong; Yang, Yu; Guo, Liang; Xu, Jing; Lei, Chuanjiang; Jiao, Yan; Xu, JianCheng

    2016-01-01

    Uncoupling protein 2 (UCP2) is upregulated in patients with systemic inflammation and infection, but its functional role is unclear. We up- or downregulated UCP2 expression using UCP2 recombinant adenovirus or the UCP2 inhibitor, genipin, in lungs of mice, and investigated the mechanisms of UCP2 in ALI. UCP2 overexpression in mouse lungs increased LPS-induced pathological changes, lung permeability, lung inflammation, and lowered survival rates. Furthermore, ATP levels and mitochondrial membrane potential were decreased, while reactive oxygen species production was increased. Additionally, mitogen-activated protein kinases (MAPKs) activity was elevated, which increased the sensitivity to LPS-induced apoptosis and inflammation. LPS-induced apoptosis and release of inflammatory factors were alleviated by pretreatment of the Jun N-terminal kinase (JNK) inhibitor SP600125 or the p38 MAPK inhibitor SB203580, but not by the extracellular signal-regulated kinase (ERK) inhibitor PD98059 in UCP2-overexpressing mice. On the other hand, LPS-induced alveolar epithelial cell death and inflammation were attenuated by genipin. In conclusion, UCP2 increased susceptibility to LPS-induced cell death and pulmonary inflammation, most likely via ATP depletion and activation of MAPK signaling following ALI in mice. PMID:27057102

  13. Power semiconductor controlled drives

    NASA Astrophysics Data System (ADS)

    Dubey, Gopal K.

    This book presents power semiconductor controlled drives employing dc motors, induction motors, and synchronous motors. The dynamics of motor and load systems are covered. Open-loop and closed-loop drives are considered, and thyristor, power transistor, and GTO converters are discussed. In-depth coverage is given to ac drives, particularly those fed by voltage and current source inverters and cycloconverters. Full coverage is given to brushless and commutatorless dc drives, including load-commuted synchronous motor drives. Rectifier-controlled dc drives are presented in detail.

  14. Lung endothelial monocyte-activating protein 2 is a mediator of cigarette smoke-induced emphysema in mice.

    PubMed

    Clauss, Matthias; Voswinckel, Robert; Rajashekhar, Gangaraju; Sigua, Ninotchka L; Fehrenbach, Heinz; Rush, Natalia I; Schweitzer, Kelly S; Yildirim, Ali Ö; Kamocki, Krzysztof; Fisher, Amanda J; Gu, Yuan; Safadi, Bilal; Nikam, Sandeep; Hubbard, Walter C; Tuder, Rubin M; Twigg, Homer L; Presson, Robert G; Sethi, Sanjay; Petrache, Irina

    2011-06-01

    Pulmonary emphysema is a disease characterized by alveolar cellular loss and inflammation. Recently, excessive apoptosis of structural alveolar cells has emerged as a major mechanism in the development of emphysema. Here, we investigated the proapoptotic and monocyte chemoattractant cytokine endothelial monocyte-activating protein 2 (EMAPII). Lung-specific overexpression of EMAPII in mice caused simplification of alveolar structures, apoptosis, and macrophage accumulation, compared with that in control transgenic mice. Additionally, in a mouse model of cigarette smoke-induced (CS-induced) emphysema, EMAPII levels were significantly increased in murine lungs. This upregulation was necessary for emphysema development, as neutralizing antibodies to EMAPII resulted in reduced alveolar cell apoptosis, inflammation, and emphysema-associated structural changes in alveoli and small airways and improved lung function. The mechanism of EMAPII upregulation involved an apoptosis-dependent feed-forward loop, since caspase-3 instillation in the lung markedly increased EMAPII expression, while caspase inhibition decreased its production, even in transgenic EMAPII mice. These findings may have clinical significance, as both current smokers and ex-smoker chronic obstructive pulmonary disease (COPD) patients had increased levels of secreted EMAPII in the bronchoalveolar lavage fluid compared with that of nonsmokers. In conclusion, we suggest that EMAPII perpetuates the mechanism of CS-induced lung emphysema in mice and, given its secretory nature, is a suitable target for neutralization antibody therapy.

  15. Lung endothelial monocyte-activating protein 2 is a mediator of cigarette smoke–induced emphysema in mice

    PubMed Central

    Clauss, Matthias; Voswinckel, Robert; Rajashekhar, Gangaraju; Sigua, Ninotchka L.; Fehrenbach, Heinz; Rush, Natalia I.; Schweitzer, Kelly S.; Yildirim, Ali Ö.; Kamocki, Krzysztof; Fisher, Amanda J.; Gu, Yuan; Safadi, Bilal; Nikam, Sandeep; Hubbard, Walter C.; Tuder, Rubin M.; Twigg, Homer L.; Presson, Robert G.; Sethi, Sanjay; Petrache, Irina

    2011-01-01

    Pulmonary emphysema is a disease characterized by alveolar cellular loss and inflammation. Recently, excessive apoptosis of structural alveolar cells has emerged as a major mechanism in the development of emphysema. Here, we investigated the proapoptotic and monocyte chemoattractant cytokine endothelial monocyte-activating protein 2 (EMAPII). Lung-specific overexpression of EMAPII in mice caused simplification of alveolar structures, apoptosis, and macrophage accumulation, compared with that in control transgenic mice. Additionally, in a mouse model of cigarette smoke–induced (CS-induced) emphysema, EMAPII levels were significantly increased in murine lungs. This upregulation was necessary for emphysema development, as neutralizing antibodies to EMAPII resulted in reduced alveolar cell apoptosis, inflammation, and emphysema-associated structural changes in alveoli and small airways and improved lung function. The mechanism of EMAPII upregulation involved an apoptosis-dependent feed-forward loop, since caspase-3 instillation in the lung markedly increased EMAPII expression, while caspase inhibition decreased its production, even in transgenic EMAPII mice. These findings may have clinical significance, as both current smokers and ex-smoker chronic obstructive pulmonary disease (COPD) patients had increased levels of secreted EMAPII in the bronchoalveolar lavage fluid compared with that of nonsmokers. In conclusion, we suggest that EMAPII perpetuates the mechanism of CS-induced lung emphysema in mice and, given its secretory nature, is a suitable target for neutralization antibody therapy. PMID:21576822

  16. Dementia and driving

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000028.htm Dementia and driving To use the sharing features on this page, ... their independence is being taken away. Signs That Driving May No Longer be Safe People with signs ...

  17. Ocular disease and driving.

    PubMed

    Wood, Joanne M; Black, Alex A

    2016-09-01

    As the driving population ages, the number of drivers with visual impairment resulting from ocular disease will increase given the age-related prevalence of ocular disease. The increase in visual impairment in the driving population has a number of implications for driving outcomes. This review summarises current research regarding the impact of common ocular diseases on driving ability and safety, with particular focus on cataract, glaucoma, age-related macular degeneration, hemianopia and diabetic retinopathy. The evidence considered includes self-reported driving outcomes, driving performance (on-road and simulator-based) and various motor vehicle crash indices. Collectively, this review demonstrates that driving ability and safety are negatively affected by ocular disease; however, further research is needed in this area. Older drivers with ocular disease need to be aware of the negative consequences of their ocular condition and in the case where treatment options are available, encouraged to seek these earlier for optimum driving safety and quality of life benefits.

  18. Impaired Driving - Multiple Languages

    MedlinePlus

    ... Are Here: Home → Multiple Languages → All Health Topics → Impaired Driving URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Impaired Driving - Multiple Languages To use the sharing features on ...

  19. Gear bearing drive

    NASA Technical Reports Server (NTRS)

    Weinberg, Brian (Inventor); Mavroidis, Constantinos (Inventor); Vranish, John M. (Inventor)

    2011-01-01

    A gear bearing drive provides a compact mechanism that operates as an actuator providing torque and as a joint providing support. The drive includes a gear arrangement integrating an external rotor DC motor within a sun gear. Locking surfaces maintain the components of the drive in alignment and provide support for axial loads and moments. The gear bearing drive has a variety of applications, including as a joint in robotic arms and prosthetic limbs.

  20. Grieving while Driving

    ERIC Educational Resources Information Center

    Rosenblatt, Paul C.

    2004-01-01

    Secondary analysis of data from 84 people in 2 interview studies shows that some bereaved people grieve actively while driving. The grief can be intense, even years after a death. Grief while driving may erupt spontaneously or be set off by a wide range of reminders. Some bereaved people seem to save their grieving for times when they drive,…

  1. Sequential Dependencies in Driving

    ERIC Educational Resources Information Center

    Doshi, Anup; Tran, Cuong; Wilder, Matthew H.; Mozer, Michael C.; Trivedi, Mohan M.

    2012-01-01

    The effect of recent experience on current behavior has been studied extensively in simple laboratory tasks. We explore the nature of sequential effects in the more naturalistic setting of automobile driving. Driving is a safety-critical task in which delayed response times may have severe consequences. Using a realistic driving simulator, we find…

  2. Sequential Dependencies in Driving

    ERIC Educational Resources Information Center

    Doshi, Anup; Tran, Cuong; Wilder, Matthew H.; Mozer, Michael C.; Trivedi, Mohan M.

    2012-01-01

    The effect of recent experience on current behavior has been studied extensively in simple laboratory tasks. We explore the nature of sequential effects in the more naturalistic setting of automobile driving. Driving is a safety-critical task in which delayed response times may have severe consequences. Using a realistic driving simulator, we find…

  3. Magnetic drive coupling

    NASA Technical Reports Server (NTRS)

    Carter, Edward L. (Inventor)

    1987-01-01

    The driving and driven members of a magnetic drive are separated by en enlarged gap to provide clearance for a conduit or other member. Flux pins in the gap maintain the torque transmitting capability of the drive. The spacing between two of the flux pins is increased to provide space for the conduit.

  4. Syncope and Driving.

    PubMed

    Guzman, Juan C; Morillo, Carlos A

    2015-08-01

    The occurrence of syncope while driving has obvious implications for personal and public safety. Neurally mediated syncope is the most common type of syncope in general and, thereby, also while driving. The presence of structural heart disease (reduced ejection fraction, previous myocardial infarction, significant congenital heart disease) potentially leads to high risk and should determine driving restrictions pending clarification of underlying heart disease and etiology of syncope. The clinical approach to syncope evaluation and recommendations for driving should not differ, whether or not the syncopal spell occurred while driving.

  5. Apoptosis and cancer mechanisms.

    PubMed

    Pan, H; Yin, C; Van Dyke, T

    1997-01-01

    For nearly two decades, studies in the cancer research field focussed on identifying genes that act as positive and negative regulators of cell growth. Only relatively recently was it recognized that the regulation of cell death (apoptosis) is also an important modulator of tumorigenesis. At least two genes linked to human cancers, BCL2 and TP53, have been shown to regulate apoptosis. The correlation between apoptosis modulating genes and human tumours raises an important question as to how dysregulation of apoptosis contributes to neoplastic transformation and malignant cell growth. Cell culture studies have clearly demonstrated that TP53 can induce and BCL2 can suppress apoptosis in response to various stimuli. Studies of mammalian viruses, which possess mechanisms for both inducing and evading apoptosis, have also extended our understanding of this process. On the basis of such findings, several animal models have been developed which begin to address the role of apoptosis regulation in tumorigenesis. This chapter discusses those animal models, focussing on bcl-2 (and its relatives) and p53.

  6. Reconfigurable Drive Current System

    NASA Technical Reports Server (NTRS)

    Alhorn, Dean C. (Inventor); Dutton, Kenneth R. (Inventor); Howard, David E. (Inventor); Smith, Dennis A. (Inventor)

    2017-01-01

    A reconfigurable drive current system includes drive stages, each of which includes a high-side transistor and a low-side transistor in a totem pole configuration. A current monitor is coupled to an output of each drive stage. Input channels are provided to receive input signals. A processor is coupled to the input channels and to each current monitor for generating at least one drive signal using at least one of the input signals and current measured by at least one of the current monitors. A pulse width modulation generator is coupled to the processor and each drive stage for varying the drive signals as a function of time prior to being supplied to at least one of the drive stages.

  7. Lysosomes in apoptosis.

    PubMed

    Ivanova, Saska; Repnik, Urska; Bojic, Lea; Petelin, Ana; Turk, Vito; Turk, Boris

    2008-01-01

    Lysosomes are specialized organelles for protein recycling and as such are involved in the terminal steps of autophagy. However, it has become evident that lysosomes also play an important role in the progression of apoptosis. This latter function seems to be dependent on lysosomal proteases, which need to be released into the cytosol for apoptosis to be efficient. Among the lysosomal proteases, the most abundant are the cysteine cathepsins and the aspartic protease cathepsin D, which seem to be the major apoptosis mediators. This chapter reviews the methods used to study lysosomes and lysosomal proteases.

  8. Drill drive mechanism

    DOEpatents

    Dressel, Michael O.

    1979-01-01

    A drill drive mechanism is especially adapted to provide both rotational drive and axial feed for a drill of substantial diameter such as may be used for drilling holes for roof bolts in mine shafts. The drill shaft is made with a helical pattern of scroll-like projections on its surface for removal of cuttings. The drill drive mechanism includes a plurality of sprockets carrying two chains of drive links which are arranged to interlock around the drill shaft with each drive link having depressions which mate with the scroll-like projections. As the chain links move upwardly or downwardly the surfaces of the depressions in the links mate with the scroll projections to move the shaft axially. Tangs on the drive links mate with notch surfaces between scroll projections to provide a means for rotating the shaft. Projections on the drive links mate together at the center to hold the drive links tightly around the drill shaft. The entire chain drive mechanism is rotated around the drill shaft axis by means of a hydraulic motor and gear drive to cause rotation of the drill shaft. This gear drive also connects with a differential gearset which is interconnected with a second gear. A second motor is connected to the spider shaft of the differential gearset to produce differential movement (speeds) at the output gears of the differential gearset. This differential in speed is utilized to drive said second gear at a speed different from the speed of said gear drive, this speed differential being utilized to drive said sprockets for axial movement of said drill shaft.

  9. Apoptosis in pneumovirus infection.

    PubMed

    van den Berg, Elske; van Woensel, Job B M; Bem, Reinout A

    2013-01-23

    Pneumovirus infections cause a wide spectrum of respiratory disease in humans and animals. The airway epithelium is the major site of pneumovirus replication. Apoptosis or regulated cell death, may contribute to the host anti-viral response by limiting viral replication. However, apoptosis of lung epithelial cells may also exacerbate lung injury, depending on the extent, the timing and specific location in the lungs. Differential apoptotic responses of epithelial cells versus innate immune cells (e.g., neutrophils, macrophages) during pneumovirus infection can further contribute to the complex and delicate balance between host defense and disease pathogenesis. The purpose of this manuscript is to give an overview of the role of apoptosis in pneumovirus infection. We will examine clinical and experimental data concerning the various pro-apoptotic stimuli and the roles of apoptotic epithelial and innate immune cells during pneumovirus disease. Finally, we will discuss potential therapeutic interventions targeting apoptosis in the lungs.

  10. Apoptosis in Pneumovirus Infection

    PubMed Central

    van den Berg, Elske; van Woensel, Job B.M.; Bem, Reinout A.

    2013-01-01

    Pneumovirus infections cause a wide spectrum of respiratory disease in humans and animals. The airway epithelium is the major site of pneumovirus replication. Apoptosis or regulated cell death, may contribute to the host anti-viral response by limiting viral replication. However, apoptosis of lung epithelial cells may also exacerbate lung injury, depending on the extent, the timing and specific location in the lungs. Differential apoptotic responses of epithelial cells versus innate immune cells (e.g., neutrophils, macrophages) during pneumovirus infection can further contribute to the complex and delicate balance between host defense and disease pathogenesis. The purpose of this manuscript is to give an overview of the role of apoptosis in pneumovirus infection. We will examine clinical and experimental data concerning the various pro-apoptotic stimuli and the roles of apoptotic epithelial and innate immune cells during pneumovirus disease. Finally, we will discuss potential therapeutic interventions targeting apoptosis in the lungs. PMID:23344499

  11. Neurofibromin and Neuronal Apoptosis

    DTIC Science & Technology

    2006-07-01

    role of familial pheochromocytoma genes, including succinate dehydrogenase (SDH) and Nf1, in modulating neuronal apoptosis following neurotrophin...gene products, in Nf1-/- sensory and sympathetic neurons; this work will also have relevance to the biology of familial pheochromocytoma . "So what...Schlisio, S. (2005). Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial pheochromocytoma genes: Developmental culling and cancer. Cancer

  12. Hybrid drive arrangement

    SciTech Connect

    Oetting, H.; Heidemeyer, P.

    1985-02-19

    The invention concerns a hybrid drive arrangement for vehicles, with an engine drive and with a flywheel storage drive, which includes a storage flywheel supported concentrically relative to the crankshaft for storing kinetic energy during such operations as braking operations of the vehicle. Both drives can be connected with the driving wheels of the vehicle by means of a common, preferably continuously variable, transmission. In order to obtain a faster response of the engine drive on suddenly occurring power demands and in order to achieve a more favorable design of the storage flywheel, there is to be provided in accordance with the invention, in addition to a storage flywheel, an engine flywheel associated with the reciprocating-piston internal combustion engine, which compensates for torque irregularities of the engine. The engine flywheel can be connected with a crankshaft by means of a first clutch and with the storage flywheel by means of at least one further clutch.

  13. Marihuana and driving.

    PubMed

    Moskowitz, H

    1985-08-01

    A review was performed of the marihuana and driving literature, both epidemiological and experimental. It was noted that epidemiological studies face considerable difficulties in obtaining estimates of risks involved for drivers utilizing marihuana due to the rapid decline in blood levels of tetrahydrocannabinol. On the other hand, experimental studies examining the relationship between administered marihuana dose and performance have identified many driving-related areas as exhibiting impairment. Areas impaired include coordination, tracking, perception, vigilance and performance in both driving simulators and on the road. Other behavioral areas of lesser importance for driving also exhibited evidence of impairment by marihuana. Areas for further research are suggested.

  14. Vehicle drive system

    SciTech Connect

    Kurata, N.

    1986-08-19

    A vehicle is described having driving wheels both on the left and right sides of the chassis frame thereof comprising: a power unit including an engine and a transmission system for transmitting the power from an output shaft of the engine to the driving wheels independently. The power unit has a casing constructed as a rigid member for supporting the driving wheels and pivotally connected through a pivot shaft to the chassis frame so as to permit vertical movement of the driving wheels, the transmission system including a differential gear means having a case connected through speed reduction gears to the output shaft. The differential gear means include left and right side output gears, the transmission system including left and right input drive shafts extending laterally from the left and right side output gears of the differential gear means. The transmission system includes left and right output sections to which the input drive shafts are drivingly connected and output shafts connected to the respective driving wheels, and the output section including V-belt type automatic transmissions connected between the input drive shafts and the output shafts.

  15. Poliovirus protein 2BC increases cytosolic free calcium concentrations.

    PubMed Central

    Aldabe, R; Irurzun, A; Carrasco, L

    1997-01-01

    Poliovirus-infected cells undergo an increase in cytoplasmic calcium concentrations from the 4th h postinfection. The protein responsible for this effect was identified by the expression of different poliovirus nonstructural proteins in HeLa cells by using a recombinant vaccinia virus system. Synthesis of protein 2BC enhances cytoplasmic calcium concentrations in a manner similar to that observed in poliovirus-infected cells. To identify the regions in 2BC involved in modifying cytoplasmic calcium levels, several 2BC variants were generated. Regions present in both 2B and 2C are necessary to augment cellular free calcium levels. Therefore, in addition to inducing proliferation of membranous vesicles, poliovirus protein 2BC also alters cellular calcium homeostasis. PMID:9223520

  16. Morphine enhances macrophage apoptosis.

    PubMed

    Singhal, P C; Sharma, P; Kapasi, A A; Reddy, K; Franki, N; Gibbons, N

    1998-02-15

    Laboratory data indicate that morphine decreases the numbier of peritoneal and alveolar macrophages (Mphi) and compromises their phagocytic capability for immune complexes and bacteria. We hypothesize that morphine decreases the number of, as well as compromises the phagocytic capability of, Mphi by programming their death. We studied the effect of morphine on Mphi apoptosis in vivo as well as in vitro. Peritoneal Mphi harvested from morphine-treated rats showed DNA fragmentation. Morphine enhanced murine Mphi (J 774.16) apoptosis in a dose-dependent manner. Human monocytes treated with morphine showed a classic ladder pattern in gel electrophoretic and end-labeling studies. Morphine promoted nitric oxide (NO) production both under basal and LPS-activated states. N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-monomethyl-L-arginine monoacetate (L-NMMA), inhibitors of NO synthase, attenuated the morphine-induced generation of NO by Mphi. Morphine also enhanced Mphi mRNA expression of inducible NO synthase (iNOS). Since morphine-induced Mphi apoptosis was inhibited by L-NAME and L-NMMA, it appears that morphine-induced Mphi apoptosis may be mediated through the generation of NO. Morphine promoted the synthesis of Bax and p53 proteins by Mphi. Moreover, IL-converting enzyme (ICE)-1 inhibitor attenuated morphine-induced Mphi apoptosis. These studies suggest that morphine activates the induction phase of the apoptotic pathway through accumulation of p53. The effector phase of morphine-induced apoptosis appears to proceed through the accumulation of Bax and activation of ICE-1. The present study provides a basis for a hypothesis that morphine may be directly compromising immune function by promoting Mphi apoptosis in patients with opiate addiction.

  17. Reading Text While Driving

    PubMed Central

    Horrey, William J.; Hoffman, Joshua D.

    2015-01-01

    Objective In this study, we investigated how drivers adapt secondary-task initiation and time-sharing behavior when faced with fluctuating driving demands. Background Reading text while driving is particularly detrimental; however, in real-world driving, drivers actively decide when to perform the task. Method In a test track experiment, participants were free to decide when to read messages while driving along a straight road consisting of an area with increased driving demands (demand zone) followed by an area with low demands. A message was made available shortly before the vehicle entered the demand zone. We manipulated the type of driving demands (baseline, narrow lane, pace clock, combined), message format (no message, paragraph, parsed), and the distance from the demand zone when the message was available (near, far). Results In all conditions, drivers started reading messages (drivers’ first glance to the display) before entering or before leaving the demand zone but tended to wait longer when faced with increased driving demands. While reading messages, drivers looked more or less off road, depending on types of driving demands. Conclusions For task initiation, drivers avoid transitions from low to high demands; however, they are not discouraged when driving demands are already elevated. Drivers adjust time-sharing behavior according to driving demands while performing secondary tasks. Nonetheless, such adjustment may be less effective when total demands are high. Application This study helps us to understand a driver’s role as an active controller in the context of distracted driving and provides insights for developing distraction interventions. PMID:25850162

  18. Dendroaspis natriuretic peptide induces the apoptosis of cardiac muscle cells.

    PubMed

    Ha, Ki-Chan; Chae, Han-Jung; Piao, Cheng-Shi; Kim, Suhn-Hee; Kim, Hyung-Ryong; Chae, Soo-Wan

    2005-01-01

    Early heart failure is characterized by elevated plasma Dendroaspis natriuretic peptide-like immunoreactivity (DNP-LI). However, the direct effects of DNP on heart or the heart-associated cell system are not well known. Therefore, we investigated whether DNP induces the apoptosis of H9c2 cardiac muscle cells. H9c2 cardiac muscle cells and rat neonatal cardiomyocytes were treated with various concentrations of DNP. Cell viability and nuclear morphology change were determined by trypan blue staining and Hoechst 33258 staining, respectively. Caspase-3-like activity was measured using specific fluorogenic substrates. Pro-and antiapoptotic proteins were assayed by Western blotting. DNP induced the apoptosis of H9c2 cardiac muscle cells in a dose-dependent manner. Maximum effects occurred at 100 nM concentration of DNP, with a 7-8-fold increase in apoptotic cells, to reach a maximum apoptotic index of 17%. We also identified that H9c2 cardiac muscle cells expressed Natriuretic peptide reactor -A and -B, which respond to DNP to generate cGMP. The treatment with DNP also markedly reduced levels of Bcl-2, inhibitor of apoptosis protein-1, and inhibitor of apoptosis protein-2 and increased the level of Bax and cytochrome c release into cytoplasm and subsequent caspase-3 activation, which co-occurred with increased apoptosis. DNP-induced apoptosis was mediated by cyclic GMP, and this effect was mimicked by dibutylyl-cGMP (30 microM), a membrane permeable analog of cGMP. Furthermore, DNP-induced apoptosis was observed in rat neonatal cardiomyocytes. These results suggest that DNP induces the apoptosis of H9c2 cardiac muscle cells and of cardiomyocytes via cGMP and demonstrate that the operative mechanism includes the regulation of Bcl-2 family proteins.

  19. Apoptosis in metanephric development

    PubMed Central

    1992-01-01

    During metanephric development, non-polarized mesenchymal cells are induced to form the epithelial structures of the nephron following interaction with extracellular matrix proteins and factors produced by the inducing tissue, ureteric bud. This induction can occur in a transfilter organ culture system where it can also be produced by heterologous cells such as the embryonic spinal cord. We found that when embryonic mesenchyme was induced in vitro and in vivo, many of the cells surrounding the new epithelium showed morphological evidence of programmed cell death (apoptosis) such as condensed nuclei, fragmented cytoplasm, and cell shrinking. A biochemical correlate of apoptosis is the transcriptional activation of a calcium-sensitive endonuclease. Indeed, DNA isolated from uninduced mesenchyme showed progressive degradation, a process that was prevented by treatment with actinomycin- D or cycloheximide and by buffering intracellular calcium. These results demonstrate that the metanephric mesenchyme is programmed for apoptosis. Incubation of mesenchyme with a heterologous inducer, embryonic spinal cord prevented this DNA degradation. To investigate the mechanism by which inducers prevented apoptosis we tested the effects of protein kinase C modulators on this process. Phorbol esters mimicked the effects of the inducer and staurosporine, an inhibitor of this protein kinase, prevented the effect of the inducer. EGF also prevented DNA degradation but did not lead to differentiation. These results demonstrate that conversion of mesenchyme to epithelial requires at least two steps, rescue of the mesenchyme from apoptosis and induction of differentiation. PMID:1447305

  20. Piezoelectric drive circuit

    DOEpatents

    Treu, Jr., Charles A.

    1999-08-31

    A piezoelectric motor drive circuit is provided which utilizes the piezoelectric elements as oscillators and a Meacham half-bridge approach to develop feedback from the motor ground circuit to produce a signal to drive amplifiers to power the motor. The circuit automatically compensates for shifts in harmonic frequency of the piezoelectric elements due to pressure and temperature changes.

  1. Piezoelectric drive circuit

    DOEpatents

    Treu, C.A. Jr.

    1999-08-31

    A piezoelectric motor drive circuit is provided which utilizes the piezoelectric elements as oscillators and a Meacham half-bridge approach to develop feedback from the motor ground circuit to produce a signal to drive amplifiers to power the motor. The circuit automatically compensates for shifts in harmonic frequency of the piezoelectric elements due to pressure and temperature changes. 7 figs.

  2. Electric vehicles: Driving range

    NASA Astrophysics Data System (ADS)

    Kempton, Willett

    2016-09-01

    For uptake of electric vehicles to increase, consumers' driving-range needs must be fulfilled. Analysis of the driving patterns of personal vehicles in the US now shows that today's electric vehicles can meet all travel needs on almost 90% of days from a single overnight charge.

  3. Spaceflight Associated Apoptosis

    NASA Technical Reports Server (NTRS)

    Ichiki, Albert T.; Gibson, Linda A.; Allebban, Zuhair

    1996-01-01

    Lymphoid tissues have been shown to atrophy in rats flown on Russian spaceflights. Histological examination indicated evidence for cell degradation. Lymphoid tissues from rats flown on Spacelab Life Sciences-2 mission were analyzed for apoptosis by evidence of fragmented lymphocytes, which could be engulfed by macrophages, or DNA strand breaks using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Apoptosis was not detected in the thymus and spleen collected inflight or from the synchronous ground rats but was detected in the thymus, spleen and inguinal lymph node of the flight animals on recovery. These results indicate that the apoptosis observed in the lymphatic tissues of the rats on recovery could have been induced by the gravitational stress of reentry, corroborating the findings from the early space-flight observations.

  4. Glutathione and apoptosis

    PubMed Central

    Circu, Magdalena L.; Yee Aw, Tak

    2011-01-01

    Apoptosis or programmed cell death represents a physiologically conserved mechanism of cell death that is pivotal in normal development and tissue homeostasis in all organisms. As a key modulator of cell functions, the most abundant non-protein thiol, glutathione (GSH), has important roles in cellular defense against oxidant aggression, redox regulation of proteins thiols and maintaining redox homeostasis that is critical for proper function of cellular processes, including apoptosis. Thus, a shift in the cellular GSH-to-GSSG redox balance in favour of the oxidized species, GSSG, constitutes an important signal that could decide the fate of a cell. The current review will focus on three main areas: (1) general description of cellular apoptotic pathways, (2) cellular compartmentation of GSH and the contribution of mitochondrial GSH and redox proteins to apoptotic signalling and (3) role of redox mechanisms in the initiation and execution phases of apoptosis. PMID:18671159

  5. The biochemistry of apoptosis.

    PubMed

    Hengartner, M O

    2000-10-12

    Apoptosis--the regulated destruction of a cell--is a complicated process. The decision to die cannot be taken lightly, and the activity of many genes influence a cell's likelihood of activating its self-destruction programme. Once the decision is taken, proper execution of the apoptotic programme requires the coordinated activation and execution of multiple subprogrammes. Here I review the basic components of the death machinery, describe how they interact to regulate apoptosis in a coordinated manner, and discuss the main pathways that are used to activate cell death.

  6. Epstein-Barr virus latent membrane protein 2A contributes to anoikis resistance through ERK activation.

    PubMed

    Iwakiri, Dai; Minamitani, Takeharu; Samanta, Mrinal

    2013-07-01

    Epstein-Barr virus (EBV) is associated with various malignancies, including epithelial cancers. In this study, we analyzed the effect of EBV infection on epithelial cells by using EBV-converted epithelial cells. In EBV-positive cells, the extracellular signal-regulated kinase (ERK) pathway is constitutively activated. Inhibition of ERK activity leads to reduced anoikis resistance; therefore, EBV-positive cells are more resistant to anoikis, a type of apoptosis induced by cell detachment, than are EBV-negative cells. Among the viral genes expressed in EBV-positive cells, the latent membrane protein 2A (LMP2A) is responsible for induction of ERK-mediated anoikis resistance, although the expression level of LMP2A is much lower in EBV-positive cells than in EBV-transformed B cells. Further analysis demonstrated that LMP2A downregulation of the proanoikis mediator Bim through proteasomal degradation is dependent on the immunoreceptor tyrosine-based activation motif (ITAM). These findings suggest that LMP2A-mediated ERK activation is involved in the generation of EBV-associated epithelial malignancies.

  7. Insulin growth factor binding protein 2 mediates the progression of lymphangioleiomyomatosis

    PubMed Central

    Zhang, Linda; Li, Chenggang; Zhang, Erik; Ma, Wang; Fan, Qingxia; Yu, Jane J.

    2017-01-01

    Lymphangioleiomyomatosis (LAM) is a progressive pulmonary disease that almost exclusively affects women. LAM cells migrate to the lungs, where they cause cystic destruction of lung parenchyma. Mutations in TSC1 or TSC2 lead to the activation of the mammalian target of rapamycin complex-1, a kinase that regulates growth factor-dependent protein translation, cell growth, and metabolism. Insulin-like growth factor binding protein 2 (IGFBP2) binds insulin, IGF1 and IGF2 in circulation, thereby modulating cell survival, migration, and invasion in neoplasms. In this study, we identified that IGFBP2 primarily localized in the nucleus of TSC2-null LAM patient-derived cells in vitro and in vivo. We also showed that nuclear accumulation of IGFBP2 is closely associated with estrogen receptor alpha (ERa) expression. Furthermore, estrogen treatment induced IGFBP2 nuclear translocation in TSC2-null LAM patient-derived cells. Importantly, depletion of IGFBP2 by siRNA reduced cell proliferation, enhanced apoptosis, and decreased migration and invasion of TSC2-null LAM patient-derived cells. More interestingly, depletion of IGFBP2 markedly decreased the phosphorylation of MAPK in LAM patient-derived TSC2-null cells. Collectively, these results suggest that IGFBP2 plays an important role in promoting tumorigenesis, through estrogen and ERalpha signaling pathway. Thus, targeting IGFBP2 may serve as a potential therapeutic strategy for women with LAM and other female gender specific neoplasms. PMID:28410230

  8. Driving and dementia

    PubMed Central

    Lee, Linda; Molnar, Frank

    2017-01-01

    Abstract Objective To provide primary care physicians with an approach to driving safety concerns when older persons present with memory difficulties. Sources of information The approach is based on an accredited memory clinic training program developed by the Centre for Family Medicine Primary Care Collaborative Memory Clinic. Main message One of the most challenging aspects of dementia care is the assessment of driving safety. Drivers with dementia are at higher risk of motor vehicle collisions, yet many drivers with mild dementia might be safely able to continue driving for several years. Because safe driving is dependent on multiple cognitive and functional skills, clinicians should carefully consider many factors when determining if cognitive concerns affect driving safety. Specific findings on corroborated history and office-based cognitive testing might aid in the physician’s decisions to refer for comprehensive on-road driving evaluation and whether to notify transportation authorities in accordance with provincial reporting requirements. Sensitive communication and a person-centred approach are essential. Conclusion Primary care physicians must consider many factors when determining if cognitive concerns might affect driving safety in older drivers. PMID:28115437

  9. Role of nuclear bodies in apoptosis signalling.

    PubMed

    Krieghoff-Henning, Eva; Hofmann, Thomas G

    2008-11-01

    Promyelocytic leukemia nuclear bodies (PML NBs) are dynamic macromolecular multiprotein complexes that recruit and release a plethora of proteins. A considerable number of PML NB components play vital roles in apoptosis, senescence regulation and tumour suppression. The molecular basis by which PML NBs control these cellular responses is still just beginning to be understood. In addition to PML itself, numerous further tumour suppressors including transcriptional regulator p53, acetyl transferase CBP (CREB binding protein) and protein kinase HIPK2 (homeodomain interacting protein kinase 2) are recruited to PML NBs in response to genotoxic stress or oncogenic transformation and drive the senescence and apoptosis response by regulating p53 activity. Moreover, in response to death-receptor activation, PML NBs may act as nuclear depots that release apoptotic factors, such as the FLASH (FLICE-associated huge) protein, to amplify the death signal. PML NBs are also associated with other nuclear domains including Cajal bodies and nucleoli and share apoptotic regulators with these domains, implying crosstalk between NBs in apoptosis regulation. In conclusion, PML NBs appear to regulate cell death decisions through different, pathway-specific molecular mechanisms.

  10. Vision and Driving

    PubMed Central

    Owsley, Cynthia; McGwin, Gerald

    2010-01-01

    Driving is the primary means of personal travel in many countries and is relies heavily on vision for its successful execution. Research over the past few decades has addressed the role of vision in driver safety (motor vehicle collision involvement) and in driver performance (both on-road and using interactive simulators in the laboratory). Here we critically review what is currently known about the role of various aspects of visual function in driving. We also discuss translational research issues on vision screening for licensure and re-licensure and rehabilitation of visually impaired persons who want to drive. PMID:20580907

  11. The Test Drive

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This image taken at NASA's Jet Propulsion Laboratory shows engineers rehearsing the sol 133 (June 8, 2004) drive into 'Endurance' crater by NASA's Mars Exploration Rover Opportunity. Engineers and scientists have recreated the martian surface and slope the rover will encounter using a combination of bare and thinly sand-coated rocks, simulated martian 'blueberries' and a platform tilted at a 25-degree angle. The results of this test convinced engineers that the rover was capable of driving up and down a straight slope before it attempted the actual drive on Mars.

  12. The Test Drive

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This image taken at NASA's Jet Propulsion Laboratory shows engineers rehearsing the sol 133 (June 8, 2004) drive into 'Endurance' crater by NASA's Mars Exploration Rover Opportunity. Engineers and scientists have recreated the martian surface and slope the rover will encounter using a combination of bare and thinly sand-coated rocks, simulated martian 'blueberries' and a platform tilted at a 25-degree angle. The results of this test convinced engineers that the rover was capable of driving up and down a straight slope before it attempted the actual drive on Mars.

  13. Fast wave current drive

    SciTech Connect

    Goree, J.; Ono, M.; Colestock, P.; Horton, R.; McNeill, D.; Park, H.

    1985-07-01

    Fast wave current drive is demonstrated in the Princeton ACT-I toroidal device. The fast Alfven wave, in the range of high ion-cyclotron harmonics, produced 40 A of current from 1 kW of rf power coupled into the plasma by fast wave loop antenna. This wave excites a steady current by damping on the energetic tail of the electron distribution function in the same way as lower-hybrid current drive, except that fast wave current drive is appropriate for higher plasma densities.

  14. Drive System Research

    NASA Technical Reports Server (NTRS)

    Handschuh, Robert F.

    2007-01-01

    An overview of the NASA Glenn Research Center Drive Systems Research will be presented. The primary purpose of this research is to improve performance, reliability, and integrity of aerospace drive systems and space mechanisms. The research is conducted through a combination of in-house, academia, and through contractors. Research is conducted through computer code development and validated through component and system testing. The drive system activity currently has four major thrust areas including: thermal behavior of high speed gearing, health and usage monitoring, advanced components, and space mechanisms.

  15. Polar Direct Drive

    NASA Astrophysics Data System (ADS)

    Skupsky, S.

    2003-10-01

    Direct drive offers the potential of higher target gain on the National Ignition Facility (NIF) than x-ray drive: The initial direct-drive target design had a 1-D gain of 45 and consisted primarily of a pure cryogenic DT shell. Using the expected levels of target and laser nonuniformities for the NIF, two-dimensional (2-D) hydrodynamic simulations predicted target gains around 30.(P.W. McKenty et al.), Phys. Plasmas 8, 2315 (2001). More-recent designs have shown that higher target gains could be obtained by replacing a portion of the DT shell with ``wetted'' CH foam and by using adiabat shaping: (1) Higher-Z material (C) in the foam increases laser absorption by about 40% (from 60% absorption to 85%).(S. Skupsky et al.), in Inertial Fusion Sciences and Applications 2001, edited by K. Tanaka et al. (Elsevier, Paris, 2002), p. 240. (2) Adiabat shaping allows the main portion of the fuel to be placed on a lower adiabat without compromising target stability.(V.N. Goncharov et al.), Phys. Plasmas 10, 1906 (2003). These direct-drive concepts can be tested on the NIF, long before that facility is converted to a direct-drive (spherically symmetric) irradiation configuration. Using the NIF x-ray-drive beam configuration, some of the near-polar beams could be pointed to better illuminate the target's equator. These more-oblique, equatorial beams will have lower absorption and reduced drive efficiency than the polar beams. One strategy to compensate for the difference in polar and equatorial drive is to reduce the irradiation at the poles and employ different pulse shapes to accommodate the time-dependent variations in drive and absorption. This concept of polar direct drive (PDD) has been studied using the 2-D hydrocode DRACO to determine the requirements for achieving ignition and moderate target gain for the NIF. Experiments on the OMEGA laser will examine the effects of oblique irradiation on target drive. Results of simulations for different direct-drive target designs

  16. Turbulent current drive mechanisms

    NASA Astrophysics Data System (ADS)

    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.

  17. Role of Daxx in Apoptosis

    DTIC Science & Technology

    2002-07-01

    protection against cancer . We previously identified a pro-apoptotic protein Daxx (1). Daxx can be found in large amount in the promyelocytic leukemia protein...Words) Control of the activation of apoptosis is important in protection against cancer . PML oncogenic domains (PODs) are subnuclear macromolecular...apoptosis, and may help identify new approaches to modulate apoptosis for cancer therapy. 14. SUBJECT TERMS 15. NUMBER OF PAGES apoptosis, cancer , PML

  18. [Driving and Alzheimer's disease].

    PubMed

    Roche, Jean

    2005-09-01

    Although most aged people remain safe drivers, a greater risk for crashes due to medical conditions is observed in the elderly. Impairment of important functions for safe driving such as visuospatial skills, attention, memory and judgement are observed in dementia, particularly in Alzheimer's disease. The accident rate increases from 9.4 accidents per million vehicle kilometers traveled for 80 to 85 year-old drivers, but raises to 163.6 for drivers with moderate AD. Patients and their families should be informed that patients with mild dementia related to Alzheimer's disease (stage 1 on the Clinical Dementia Rating, CDR), have a substantially increased rate of traffic accidents and therefore should not drive. But subjects in the pre-dementia phase (stage 0.5 at the CDR, mild cognitive impairment) also pose significant driving safety problems. In most States of the USA, and many European countries, but not in France, law requires regular investigating of driving performance in the elderly.

  19. Assessment: A Driving Force.

    ERIC Educational Resources Information Center

    Rakow, Steven J.

    1992-01-01

    Asserts that educational assessment drives the curriculum. Thus, assessment is very important in contemplating reform in science education. Assessment should be an integral part of the instructional process, utilizing diagnostic testing, monitoring, and summative evaluations. (PR)

  20. Drive program documentation

    NASA Technical Reports Server (NTRS)

    Graham, S.

    1979-01-01

    The program description and user's guide for the Downlist Requirement Integrated Verification and Evaluation (DRIVE) program is provided. The program is used to compare existing telemetry downlist files with updated downlist requirements.

  1. Safe driving for teens

    MedlinePlus

    ... drivers. Do not use cell phones for talking, texting, or email when you are driving. Mobile phones ... pull off of the road before answering or texting. Other tips include: Avoid putting on makeup while ...

  2. RoboSimian Driving

    NASA Image and Video Library

    2015-06-09

    JPL's RoboSimian drives a four-wheeled vehicle through a slalom course at the DARPA Robotics Challenge Finals in Pomona, California. This image was taken on June 6, 2015. http://photojournal.jpl.nasa.gov/catalog/PIA19325

  3. Control rod drive

    SciTech Connect

    Hawke, Basil C.

    1986-01-01

    A control rod drive uses gravitational forces to insert one or more control rods upwardly into a reactor core from beneath the reactor core under emergency conditions. The preferred control rod drive includes a vertically movable weight and a mechanism operatively associating the weight with the control rod so that downward movement of the weight is translated into upward movement of the control rod. The preferred control rod drive further includes an electric motor for driving the control rods under normal conditions, an electrically actuated clutch which automatically disengages the motor during a power failure and a decelerator for bringing the control rod to a controlled stop when it is inserted under emergency conditions into a reactor core.

  4. [Driving and aging].

    PubMed

    Cantón-Cortés, David; Durán Segura, Mercedes; Castro Ramírez, Cándida

    2010-01-01

    The number of older people who continue to drive is constantly increasing. However, whether older people have more traffic accidents than other age groups is unclear. This age group has certain risk factors due to decreased motor, sensory and cognitive functions and also has greater frailty and vulnerability to injury. However, older drivers are aware of their heightened crash risk and employ certain compensatory actions, avoiding traveling under threatening conditions (dense traffic, bad weather or night driving), traveling by well-known routes and driving carefully. In view of these apparent contradictions, the present study attempts to discern the real crash risk and the driving and crash patterns characteristic of this population, which is continually increasing in industrialized countries.

  5. Direct drive wind turbine

    DOEpatents

    Bywaters, Garrett; Danforth, William; Bevington, Christopher; Jesse, Stowell; Costin, Daniel

    2006-10-10

    A wind turbine is provided that minimizes the size of the drive train and nacelle while maintaining the power electronics and transformer at the top of the tower. The turbine includes a direct drive generator having an integrated disk brake positioned radially inside the stator while minimizing the potential for contamination. The turbine further includes a means for mounting a transformer below the nacelle within the tower.

  6. Direct drive wind turbine

    DOEpatents

    Bywaters, Garrett; Danforth, William; Bevington, Christopher; Jesse, Stowell; Costin, Daniel

    2007-02-27

    A wind turbine is provided that minimizes the size of the drive train and nacelle while maintaining the power electronics and transformer at the top of the tower. The turbine includes a direct drive generator having an integrated disk brake positioned radially inside the stator while minimizing the potential for contamination. The turbine further includes a means for mounting a transformer below the nacelle within the tower.

  7. Direct drive wind turbine

    DOEpatents

    Bywaters, Garrett; Danforth, William; Bevington, Christopher; Stowell, Jesse; Costin, Daniel

    2006-07-11

    A wind turbine is provided that minimizes the size of the drive train and nacelle while maintaining the power electronics and transformer at the top of the tower. The turbine includes a direct drive generator having an integrated disk brake positioned radially inside the stator while minimizing the potential for contamination. The turbine further includes a means for mounting a transformer below the nacelle within the tower.

  8. Direct drive wind turbine

    DOEpatents

    Bywaters, Garrett Lee; Danforth, William; Bevington, Christopher; Stowell, Jesse; Costin, Daniel

    2006-09-19

    A wind turbine is provided that minimizes the size of the drive train and nacelle while maintaining the power electronics and transformer at the top of the tower. The turbine includes a direct drive generator having an integrated disk brake positioned radially inside the stator while minimizing the potential for contamination. The turbine further includes a means for mounting a transformer below the nacelle within the tower.

  9. CONTROL ROD DRIVE

    DOEpatents

    Chapellier, R.A.

    1960-05-24

    BS>A drive mechanism was invented for the control rod of a nuclear reactor. Power is provided by an electric motor and an outside source of fluid pressure is utilized in conjunction with the fluid pressure within the reactor to balance the loadings on the motor. The force exerted on the drive mechanism in the direction of scramming the rod is derived from the reactor fluid pressure so that failure of the outside pressure source will cause prompt scramming of the rod.

  10. Telescopic lenses and driving.

    PubMed

    Keller, J T; Eskridge, J B

    1976-11-01

    In some states, persons with significantly reduced visual acuity are being licensed to drive while wearing telescopic spectacle lenses (TSL). In order to evaluate possible visual field limitations present with these devices, the peripheral visual fields of a group of normally sighted subjects were measured while they wore TSL. Severely restricted central fields and sizeable ring scotomas were present with all units tested. These result indicate that driving with TSL should be discouraged.

  11. [Monophthalmia and automobile driving].

    PubMed

    Fodor, F

    1993-01-01

    The estimation of the visual abilities of monophtalmic patients must be done individually and the driving licence must be released only after careful consideration of all the anatomo-functional aspects of the eye in connection with the functional state of the nervous system. For releasing the driving licence to monophthalmic patients are proposed to be done: the determination of the kinetical visual acuity, the exam of the stereoscopic vision and the effectuation of some psychological tests by the ophthalmologist.

  12. Common drive unit

    NASA Technical Reports Server (NTRS)

    Ellis, R. C.; Fink, R. A.; Moore, E. A.

    1987-01-01

    The Common Drive Unit (CDU) is a high reliability rotary actuator with many versatile applications in mechanism designs. The CDU incorporates a set of redundant motor-brake assemblies driving a single output shaft through differential. Tachometers provide speed information in the AC version. Operation of both motors, as compared to the operation of one motor, will yield the same output torque with twice the output speed.

  13. Electric Drive Study

    DTIC Science & Technology

    1987-03-01

    Track-Laying Combat Vehicles , and (3) Parametric Study of Electric Drive Component Technologies. The technology survey results are given in a separate...and projections of future electric drive system improvements relative to combat vehicle applications. Unclassified SECURITY CLASSIFICATION OF THIS...273 5.7.2.3.1 DC Homopolar Drum Machine, Design and Performance 5-278 APPENDIX A 19.5 TON AND 40.0 TON VEHICLE SPECIFICATION APPENDIX B ELECTRIC

  14. Dementia and driving.

    PubMed

    O'Neill, D; Neubauer, K; Boyle, M; Gerrard, J; Surmon, D; Wilcock, G K

    1992-04-01

    Many European countries test cars, but not their drivers, as they age. There is evidence to suggest that human factors are more important than vehicular factors as causes of motor crashes. The elderly also are involved in more accidents per distance travelled than middle-aged drivers. As the UK relies on self-certification of health by drivers over the age of 70 years, we examined the driving practices of patients with dementia attending a Memory Clinic. Nearly one-fifth of 329 patients with documented dementia continued to drive after the onset of dementia, and impaired driving ability was noted in two-thirds of these. Their families experienced great difficulty in persuading patients to stop driving, and had to invoke outside help in many cases. Neuropsychological tests did not help to identify those who drove badly while activity of daily living scores were related to driving ability. These findings suggest that many patients with dementia drive in an unsafe fashion after the onset of the illness. The present system of self-certification of health by the elderly for driver-licensing purposes needs to be reassessed.

  15. Self-driving carsickness.

    PubMed

    Diels, Cyriel; Bos, Jelte E

    2016-03-01

    This paper discusses the predicted increase in the occurrence and severity of motion sickness in self-driving cars. Self-driving cars have the potential to lead to significant benefits. From the driver's perspective, the direct benefits of this technology are considered increased comfort and productivity. However, we here show that the envisaged scenarios all lead to an increased risk of motion sickness. As such, the benefits this technology is assumed to bring may not be capitalised on, in particular by those already susceptible to motion sickness. This can negatively affect user acceptance and uptake and, in turn, limit the potential socioeconomic benefits that this emerging technology may provide. Following a discussion on the causes of motion sickness in the context of self-driving cars, we present guidelines to steer the design and development of automated vehicle technologies. The aim is to limit or avoid the impact of motion sickness and ultimately promote the uptake of self-driving cars. Attention is also given to less well known consequences of motion sickness, in particular negative aftereffects such as postural instability, and detrimental effects on task performance and how this may impact the use and design of self-driving cars. We conclude that basic perceptual mechanisms need to be considered in the design process whereby self-driving cars cannot simply be thought of as living rooms, offices, or entertainment venues on wheels. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  16. Dangers of Texting While Driving

    MedlinePlus

    ... Dangers of Distracted Driving Español The popularity of mobile devices has had some unintended and sometimes deadly consequences. ... linked to driving while distracted, including use of mobile devices while driving, resulting in injury and loss of ...

  17. Hydraulic drive system prevents backlash

    NASA Technical Reports Server (NTRS)

    Acord, J. D.

    1965-01-01

    Hydraulic drive system uses a second drive motor operating at reduced torque. This exerts a relative braking action which eliminates the normal gear train backlash that is intolerable when driving certain heavy loads.

  18. The Oscar-worthy role of Myc in apoptosis.

    PubMed

    Meyer, Natalie; Kim, Sam S; Penn, Linda Z

    2006-08-01

    The discovery that the Myc oncoprotein could drive cells to undergo apoptosis in addition to its well-established role in cellular proliferation came in the early 1990s, at the beginning of a period of explosive research on cell death. Experimental evidence revealed that Myc sensitises cells to a wide range of death stimuli and abrogating this biological activity plays a profound role in tumorigenesis. Our understanding of the molecular mechanism and genetic programme of Myc-induced apoptosis remains shrouded in mystery and the focus of much attention. In this review, we will discuss established data, recent advances and future objectives regarding the regulatory processes and the functional cooperators that effect and abrogate apoptosis induced by Myc.

  19. Mental workload and driving

    PubMed Central

    Paxion, Julie; Galy, Edith; Berthelon, Catherine

    2014-01-01

    The aim of this review is to identify the most representative measures of subjective and objective mental workload in driving, and to understand how the subjective and objective levels of mental workload influence the performance as a function of situation complexity and driving experience, i.e., to verify whether the increase of situation complexity and the lack of experience increase the subjective and physiological levels of mental workload and lead to driving performance impairments. This review will be useful to both researchers designing an experimental study of mental workload and to designers of drivers’ training content. In the first part, we will broach the theoretical approach with two factors of mental workload and performance, i.e., situation complexity and driving experience. Indeed, a low complex situation (e.g., highways), or conversely a high complex situation (e.g., town) can provoke an overload. Additionally, performing the driving tasks implies producing a high effort for novice drivers who have not totally automated the driving activity. In the second part, we will focus on subjective measures of mental workload. A comparison of questionnaires usually used in driving will allow identifying the most appropriate ones as a function of different criteria. Moreover, we will review the empirical studies to verify if the subjective level of mental workload is high in simple and very complex situations, especially for novice drivers compared to the experienced ones. In the third part, we will focus on physiological measures. A comparison of physiological indicators will be realized in order to identify the most correlated to mental workload. An empirical review will also take the effect of situation complexity and experience on these physiological indicators into consideration. Finally, a more nuanced comparison between subjective and physiological measures will be established from the impact on situation complexity and experience. PMID:25520678

  20. DNA DAMAGE BINDING PROTEIN2 Shapes the DNA Methylation Landscape

    PubMed Central

    Schalk, Catherine; Kramdi, Amira; Ahmed, Ikhlak; Cognat, Valérie; Graindorge, Stéfanie; Bergdoll, Marc; Baumberger, Nicolas; Heintz, Dimitri; Bowler, Chris; Genschik, Pascal; Barneche, Fredy; Molinier, Jean

    2016-01-01

    In eukaryotes, DNA repair pathways help to maintain genome integrity and epigenomic patterns. However, the factors at the nexus of DNA repair and chromatin modification/remodeling remain poorly characterized. Here, we uncover a previously unrecognized interplay between the DNA repair factor DNA DAMAGE BINDING PROTEIN2 (DDB2) and the DNA methylation machinery in Arabidopsis thaliana. Loss-of-function mutation in DDB2 leads to genome-wide DNA methylation alterations. Genetic and biochemical evidence indicate that at many repeat loci, DDB2 influences de novo DNA methylation by interacting with ARGONAUTE4 and by controlling the local abundance of 24-nucleotide short interfering RNAs (siRNAs). We also show that DDB2 regulates active DNA demethylation mediated by REPRESSOR OF SILENCING1 and DEMETER LIKE3. Together, these findings reveal a role for the DNA repair factor DDB2 in shaping the Arabidopsis DNA methylation landscape in the absence of applied genotoxic stress. PMID:27531226

  1. DEDRICK DRIVE, LOOKING NORTH FROM SOUTH END OF DEDRICK DRIVE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DEDRICK DRIVE, LOOKING NORTH FROM SOUTH END OF DEDRICK DRIVE NEAR BUILDING 80 - Pacific Coast Torpedo Station, Keyport Industrial District, Both sides of Second Street, between Dedrick Drive and Liberty Bay and one building west of Dedrick Drive and south of Second Street, Keyport, Kitsap County, WA

  2. Driving Anger and Driving Behavior in Adults with ADHD

    ERIC Educational Resources Information Center

    Richards, Tracy L.; Deffenbacher, Jerry L.; Rosen, Lee A.; Barkley, Russell A.; Rodricks, Trisha

    2006-01-01

    Objective: This study assesses whether anger in the context of driving is associated with the negative driving outcomes experienced by individuals with ADHD. Method: ADHD adults (n = 56) complete measures of driving anger, driving anger expression, angry thoughts behind the wheel, and aggressive, risky, and crash-related behavior. Results are…

  3. Driving Anger and Driving Behavior in Adults with ADHD

    ERIC Educational Resources Information Center

    Richards, Tracy L.; Deffenbacher, Jerry L.; Rosen, Lee A.; Barkley, Russell A.; Rodricks, Trisha

    2006-01-01

    Objective: This study assesses whether anger in the context of driving is associated with the negative driving outcomes experienced by individuals with ADHD. Method: ADHD adults (n = 56) complete measures of driving anger, driving anger expression, angry thoughts behind the wheel, and aggressive, risky, and crash-related behavior. Results are…

  4. Gadolinium induces macrophage apoptosis.

    PubMed

    Mizgerd, J P; Molina, R M; Stearns, R C; Brain, J D; Warner, A E

    1996-02-01

    Gadolinium (Gd) suppresses reticuloendothelial functions in vivo by unknown mechanisms. In vitro exposure of rat alveolar macrophages to GdCl3.6H20 caused cell death, as measured by trypan blue permeability, in both dose- and time-dependent fashions. Even a 10-min exposure to Gd caused significant cell death by 24 h. The morphology of Gd-treated cells, pyknosis and karyorrhexis prior to loss of membrane integrity, suggested apoptosis. Upon flow cytometric examination, Gd-treated propidium iodide-excluding cells demonstrated light scatter changes characteristic of apoptotic cells (decreased forward and increased right angle scatter). Gel electrophoresis of DNA from Gd-treated macrophages clearly showed the ladder pattern unique to apoptotic cells. Electron-dense structures containing Gd were observed via electron spectroscopic imaging within phagosomes and also within nuclei (associated with condensed chromatin). Gadolinium, endocytosed by macrophages and distributed to nuclei, causes apoptosis of macrophages in vitro.

  5. Genetic conflict and apoptosis.

    PubMed

    LeGrand, E K

    2001-01-01

    The benefits of apoptosis in the removal of unnecessary, damaged, or dangerous cells are dependent on the altruism resulting from the absence of genetic conflict between genes in cells. However, this altruism can be exploited by self-promoting or ultra-selfish genes. These self-promoting genes can be endogenous, as with neoplasia or germ cell mutations, or exogenous, as with cellular pathogens. The fundamental flaw of apoptosis is that its development and maintenance as a system is constantly opposed by the emergence of self-promoting genes. Since apoptotically impaired cells cannot be relied on to kill themselves, apoptotic input from other cells is required for controlling self-promoting genes. Certain unique features of germ cell development, such as linkage by cytoplasmic bridges and the requirement for granulosa or Sertoli cells, appear to serve this requirement for control of self-promoting genes.

  6. Mortalin, Apoptosis, and Neurodegeneration

    PubMed Central

    Londono, Carolina; Osorio, Cristina; Gama, Vivian; Alzate, Oscar

    2012-01-01

    Mortalin is a highly conserved heat-shock chaperone usually found in multiple subcellular locations. It has several binding partners and has been implicated in various functions ranging from stress response, control of cell proliferation, and inhibition/prevention of apoptosis. The activity of this protein involves different structural and functional mechanisms, and minor alterations in its expression level may lead to serious biological consequences, including neurodegeneration. In this article we review the most current data associated with mortalin’s binding partners and how these protein-protein interactions may be implicated in apoptosis and neurodegeneration. A complete understanding of the molecular pathways in which mortalin is involved is important for the development of therapeutic strategies for cancer and neurodegenerative diseases. PMID:24970131

  7. Evading apoptosis in cancer.

    PubMed

    Fernald, Kaleigh; Kurokawa, Manabu

    2013-12-01

    Carcinogenesis is a mechanistically complex and variable process with a plethora of underlying genetic causes. Cancer development comprises a multitude of steps that occur progressively starting with initial driver mutations leading to tumorigenesis and, ultimately, metastasis. During these transitions, cancer cells accumulate a series of genetic alterations that confer on the cells an unwarranted survival and proliferative advantage. During the course of development, however, cancer cells also encounter a physiologically ubiquitous cellular program that aims to eliminate damaged or abnormal cells: apoptosis. Thus, it is essential that cancer cells acquire instruments to circumvent programmed cell death. Here we discuss emerging evidence indicating how cancer cells adopt various strategies to override apoptosis, including amplifying the antiapoptotic machinery, downregulating the proapoptotic program, or both. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Evading apoptosis in cancer

    PubMed Central

    Fernald, Kaleigh

    2013-01-01

    Carcinogenesis is a mechanistically complex and variable process with a plethora of underlying genetic causes. Cancer development consists of a multitude of steps that occur progressively starting with initial driver mutation(s), to tumorigenesis, and ultimately metastasis. During these transitions, cancer cells accumulate a series of genetic alterations that confer upon the cells an unwarranted survival and proliferative advantage. During the course of development, however, cancer cells also encounter a physiologically ubiquitous cellular program that aims to eliminate damaged or abnormal cells: Apoptosis. Thus, it is essential that cancer cells acquire instruments to circumvent programmed cell death. Here we discuss emerging evidence indicating how cancer cells adopt various strategies to override apoptosis including amplifying the anti-apoptotic machinery, downregulating the pro-apoptotic program, or both. PMID:23958396

  9. [Drug use and driving].

    PubMed

    Lemaire-Hurtel, Anne-Sophie; Goullé, Jean-Pierre; Alvarez, Jean-Claude; Mura, Patrick; Verstraete, Alain G

    2015-10-01

    Some drugs are known to impair driving because they can change the vision or hearing, and/or disrupt the intellectual or motor abilities: impaired vigilance, sedation, disinhibition effect, the coordination of movement disorders and the balance. The doctor during prescribing and the pharmacist during deliverance of drug treatment should inform their patients of the potential risks of drugs on driving or operating machinery. The driver has direct responsibility, who hired him and him alone, to follow the medical advice received. The pictograms on the outer packaging of medicinal products intended to classify substances according to their risk driving: The driver can whether to observe simple precautions (level one "be prudent"), or follow the advice of a health professional (level two "be very careful"), or if it is totally not drive (level three "danger caution: do not drive"). This classification only evaluates the intrinsic danger of drugs but not the individual variability. Medicines should be taken into account also the conditions for which the medication is prescribed. It is important to inform the patient on several points. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  10. Driving anger in Malaysia.

    PubMed

    Sullman, Mark J M; Stephens, Amanda N; Yong, Michelle

    2014-10-01

    The present study examined the types of situations that cause Malaysian drivers to become angry. The 33-item version of the driver anger scale (Deffenbacher et al., 1994) was used to investigate driver anger amongst a sample of 339 drivers. Confirmatory factor analysis showed that the fit of the original six-factor model (discourtesy, traffic obstructions, hostile gestures, slow driving, illegal driving and police presence), after removing one item and allowing three error pairs to covary, was satisfactory. Female drivers reported more anger, than males, caused by traffic obstruction and hostile gestures. Age was also negatively related to five (discourtesy, traffic obstructions, hostile gestures, slow driving and police presence) of the six factors and also to the total DAS score. Furthermore, although they were not directly related to crash involvement, several of the six forms of driving anger were significantly related to the crash-related conditions of: near misses, loss of concentration, having lost control of a vehicle and being ticketed. Overall the pattern of findings made in the present research were broadly similar to those from Western countries, indicating that the DAS is a valid measure of driving anger even among non-European based cultures.

  11. Apoptosis in canine distemper.

    PubMed

    Moro, L; de Sousa Martins, A; de Moraes Alves, C; de Araújo Santos, F G; dos Santos Nunes, J E; Carneiro, R A; Carvalho, R; Vasconcelos, A C

    2003-01-01

    Canine distemper is a systemic viral disease characterized by immunosuppression followed by secondary infections. Apoptosis is observed in several immunosuppressive diseases and its occurrence on canine distemper in vivo has not been published. In this study, the occurrence of apoptosis was determined in lymphoid tissues of thirteen naturally infected dogs and nine experimentally inoculated puppies. Healthy dogs were used as negative controls. Samples of lymph nodes, thymus, spleen and brain were collected for histopathological purposes. Sections, 5 microm thick, of retropharingeal lymph nodes were stained by HE, Shorr, Methyl Green-Pyronin and TUNEL reaction. Shorr stained sections were further evaluated by morphometry. Canine distemper virus nucleoprotein was detected by immunohistochemistry. Retropharingeal lymph nodes of naturally and experimentally infected dogs had more apoptotic cells per field than controls. In addition, DNA from thymus of infected dogs were more fragmented than controls. Therefore, apoptosis is increased in lymphoid depletion induced by canine distemper virus and consequently play a role in the immunosuppression seen in this disease.

  12. Apoptosis, fibrosis and senescence.

    PubMed

    Portilla, Didier

    2014-01-01

    Fibrosis is a major hallmark of progressive kidney disease. The cellular mechanisms that lead to kidney tissue fibrosis are complex and include, for example, increased inflammation, increased oxidative stress, and proximal tubule cell death in the form of apoptosis or senescence. Recent studies have identified TWEAK, a tumor necrosis factor-like weak inducer of apoptosis, as a novel cytokine that mediates kidney inflammation in models of renal fibrosis. Inhibition of apoptosis via TWEAK inhibition has been shown to reduce kidney fibrosis. Recent studies using lineage tracing suggest that interstitial pericytes/perivascular fibroblasts differentiate into myofibroblasts and undergo proliferative expansion during fibrosis. Furthermore, increased expression of nuclear peroxisome proliferator-activated receptor-α in proximal tubules can directly reduce increased expression of transforming growth factor-β1 and interstitial inflammation in models of renal fibrosis, which suggests preservation of proximal tubule cell metabolism and integrity represents an important new therapeutic target. In this review, the current evidence and potential molecular mechanisms involved in the development of kidney fibrosis are discussed. 2014 S. Karger AG, Basel.

  13. Current drive, anticurrent drive, and balanced injection

    SciTech Connect

    von Goeler, S.; Stevens, J.; Beiersdorfer, P.; Bell, R.; Bernabei, S.; Bitter, M.; Cavallo, A.; Chu, T.K.; Fishman, H.; Hill, K.

    1987-08-01

    In lower hybrid (LH) discharges, the number of suprathermal electrons is limited by the upper bound on the current density from the q = 1 condition, which is caused by the onset of the m = 1 MHD instability. The stored energy of suprathermal electrons, measured in terms of a poloidal beta, scales with plasma current as I/sub p//sup -1/. Potentially, these bounds represent very restrictive conditions for heating in larger machines. Consequently, it seems necessary to perform experiments where the electrons are driven in both directions, parallel and antiparallel to the magnetic field, i.e., bidirectional scenarios like anticurrent drive or balanced injection. Data from PLT relevant to these ideas are discussed. 6 refs., 4 figs.

  14. Ceramic vane drive joint

    DOEpatents

    Smale, Charles H.

    1981-01-01

    A variable geometry gas turbine has an array of ceramic composition vanes positioned by an actuating ring coupled through a plurality of circumferentially spaced turbine vane levers to the outer end of a metallic vane drive shaft at each of the ceramic vanes. Each of the ceramic vanes has an end slot of bow tie configuration including flared end segments and a center slot therebetween. Each of the vane drive shafts has a cross head with ends thereof spaced with respect to the sides of the end slot to define clearance for free expansion of the cross head with respect to the vane and the cross head being configured to uniformly distribute drive loads across bearing surfaces of the vane slot.

  15. U.S. DRIVE

    SciTech Connect

    2012-03-16

    U.S. DRIVE, which stands for United States Driving Research and Innovation for Vehicle efficiency and Energy sustainability, is an expanded government-industry partnership among the U.S. Department of Energy; USCAR, representing Chrysler Group LLC, Ford Motor Company and General Motors; Tesla Motors; five energy companies – BP America, Chevron Corporation, ConocoPhillips, ExxonMobil Corporation, and Shell Oil Products US; two utilities – Southern California Edison and Michigan-based DTE Energy; and the Electric Power Research Institute (EPRI). The U.S. DRIVE mission is to accelerate the development of pre-competitive and innovative technologies to enable a full range of affordable and clean advanced light-duty vehicles, as well as related energy infrastructure.

  16. Turbulent current drive mechanisms

    DOE PAGES

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

    2017-07-01

    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 deviationsmore » from neoclassical predictions.« less

  17. Sequential dependencies in driving.

    PubMed

    Doshi, Anup; Tran, Cuong; Wilder, Matthew H; Mozer, Michael C; Trivedi, Mohan M

    2012-07-01

    The effect of recent experience on current behavior has been studied extensively in simple laboratory tasks. We explore the nature of sequential effects in the more naturalistic setting of automobile driving. Driving is a safety-critical task in which delayed response times may have severe consequences. Using a realistic driving simulator, we find significant sequential effects in pedal-press response times that depend on the history of recent stimuli and responses. Response times are slowed up to 100 ms in particular cases, a delay that has dangerous practical consequences. Further, we observe a significant number of history-related pedal misapplications, which have recently been noted as a cause for concern in the automotive safety community. By anticipating these consequences of sequential context, driver assistance systems could mitigate the effects of performance degradations and thus critically improve driver safety. Copyright © 2012 Cognitive Science Society, Inc.

  18. CONTROL ROD DRIVE

    DOEpatents

    Chapellier, R.A.; Rogers, I.

    1961-06-27

    Accurate and controlled drive for the control rod is from an electric motor. A hydraulic arrangement is provided to balance a piston against which a control rod is urged by the application of fluid pressure. The electric motor drive of the control rod for normal operation is made through the aforementioned piston. In the event scramming is required, the fluid pressure urging the control rod against the piston is relieved and an opposite fluid pressure is applied. The lack of mechanical connection between the electric motor and control rod facilitates the scramming operation.

  19. Microlinear piezo drive experiments

    NASA Astrophysics Data System (ADS)

    Azin, A. V.; Bogdanov, E. P.; Rikkonen, S. V.; Ponomarev, S. V.; Khramtsov, A. M.

    2017-02-01

    The article embraces the experimental description of the micro linear piezo drive intended for the peripheral cord tensioner in the reflecting surface shape regulator system for large-sized transformable spacecraft antenna reflectors. The research target is the experimental investigation of the micro linear piezo drive to determine the stable oscillatory system operating modes which would include improved energy conversion parameters. The following points are briefly presented: test stand construction-design of the peripheral cord tensioner; the determined frequency characteristics and the identified resonant and actual frequencies of an oscillatory system under inertia load. A series of experiments has been conducted for both different preliminary voltages and inertia mass values.

  20. Stromal cell-derived factor-1 potentiates bone morphogenetic protein-2 induced bone formation.

    PubMed

    Higashino, Kosaku; Viggeswarapu, Manjula; Bargouti, Maggie; Liu, Hui; Titus, Louisa; Boden, Scott D

    2011-02-01

    The mechanisms driving bone marrow stem cell mobilization are poorly understood. A recent murine study found that circulating bone marrow-derived osteoprogenitor cells (MOPCs) were recruited to the site of recombinant human bone morphogenetic protein-2 (BMP-2)-induced bone formation. Stromal cell-derived factor-1α (SDF-1α) and its cellular receptor CXCR4 have been shown to mediate the homing of stem cells to injured tissues. We hypothesized that chemokines, such as SDF-1, are also involved with mobilization of bone marrow cells. The CD45(-) fraction is a major source of MOPCs. In this report we determined that the addition of BMP-2 or SDF-1 to collagen implants increased the number of MOPCs in the peripheral blood. BMP-2-induced mobilization was blocked by CXCR4 antibody, confirming the role of SDF-1 in mobilization. We determined for the first time that addition of SDF-1 to implants containing BMP-2 enhances mobilization, homing of MOPCs to the implant, and ectopic bone formation induced by suboptimal BMP-2 doses. These results suggest that SDF-1 increases the number of osteoprogenitor cells that are mobilized from the bone marrow and then home to the implant. Thus, addition of SDF-1 to BMP-2 may improve the efficiency of BMPs in vivo, making their routine use for orthopaedic applications more affordable and available to more patients.

  1. Broad targeting of resistance to apoptosis in cancer

    PubMed Central

    Mohammad, Ramzi M.; Muqbil, Irfana; Lowe, Leroy; Yedjou, Clement; Hsu, Hsue-Yin; Lin, Liang-Tzung; Siegelin, Markus David; Fimognari, Carmela; Kumar, Nagi B.; Dou, Q. Ping; Yang, Huanjie; Samadi, Abbas K.; Russo, Gian Luigi; Spagnuolo, Carmela; Ray, Swapan K.; Chakrabarti, Mrinmay; Morre, James D.; Coley, Helen M.; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Amedei, Amedeo; Niccolai, Elena; Amin, Amr; Ashraf, S. Salman; Helferich, William G.; Yang, Xujuan; Boosani, Chandra S.; Guha, Gunjan; Bhakta, Dipita; Ciriolo, Maria Rosa; Aquilano, Katia; Chen, Sophie; Mohammed, Sulma I.; Keith, W. Nicol; Bilsland, Alan; Halicka, Dorota; Nowsheen, Somaira; Azmi, Asfar S.

    2015-01-01

    Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer. PMID:25936818

  2. Sal-like protein 2 upregulates p16 expression through a proximal promoter element

    PubMed Central

    Wu, Zhenghua; Cheng, Kebin; Shi, Lidan; Li, Zheqi; Negi, Hema; Gao, Guangwei; Kamle, Suchitra; Li, Dawei

    2015-01-01

    Sal-like protein 2 (Sall2), a homeotic transcription factor, is a putative tumor suppressor. We have previously shown that Sall2 activates the transcription of tumor suppressor gene p21 and suppresses tumorigenesis through cell cycle inhibition and induction of apoptosis. To investigate additional Sall2-regulated downstream genes, we analyzed the differences in mRNA expression profiles with and without exogenously expressed Sall2. We identified 1616 Sall2-responsive genes through gene expression arrays. Promoter-reporter assays of p16INK4A and several other tumor-related genes indicated that the Sall2 regulation of these promoters was not significantly different between the two major forms of Sall2 with alternative exon 1 or exon 1A. Additional analysis showed that Sall2-induced p16 promoter activation was Sall2 dose-dependent. Deletion and site-directed mutagenesis of the p16 promoter identified a consensus Sall2 binding site (GGGTGGG) proximal to the p16 transcription start site and was critical for p16 promoter activation. Finally, to confirm the significance of Sall2-activated p16 expression in cell cycle regulation, we co-transfected the SKOV3 cells with a Sall2 expression construct and a p16 minigene and also co-transfected the ES-2 cells with a Sall2 expression construct and the siRNA against p16 for flow cytometry analysis. Our results showed that Sall2 enhanced the p16 minigene blocking of cell cycle progression and p16 knockdown with siRNA abolished most of the Sall2 inhibition of cell cycle progression. These findings indicate that Sall2 targets multiple cell cycle regulators, including p16, through their promoters, adding knowledge to the understanding of Sall2 and p16 gene regulation, and how Sall2 deregulation may promote cancer formation. PMID:25580951

  3. Mitochondrial uncoupling protein 2 induces cell cycle arrest and necrotic cell death.

    PubMed

    Palanisamy, Arun P; Cheng, Gang; Sutter, Alton G; Evans, Zachary P; Polito, Carmen C; Jin, Lan; Liu, John; Schmidt, Michael G; Chavin, Kenneth D

    2014-03-01

    Uncoupling protein 2 (UCP2) is a mitochondrial membrane protein that regulates energy metabolism and reactive oxygen species (ROS) production. We generated mouse carboxy- and amino-terminal green fluorescent protein (GFP)-tagged UCP2 constructs to investigate the effect of UCP2 expression on cell proliferation and viability. UCP2-transfected Hepa 1-6 cells did not show reduced cellular adenosine triphosphate (ATP) but showed increased levels of glutathione. Flow cytometry analysis indicated that transfected cells were less proliferative than nontransfected controls, with most cells blocked at the G1 phase. The effect of UCP2 on cell cycle arrest could not be reversed by providing exogenous ATP or oxidant supply, and was not affected by the chemical uncoupler carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP). However, this effect of UCP2 was augmented by treatment with genistein, a tyrosine kinase inhibitor, which by itself did not affect cell proliferation on control hepatocytes. Western blotting analysis revealed decreased expression levels of CDK6 but not CDK2 and D-type cyclins. Examination of cell viability in UCP2-transfected cells with Trypan Blue and Annexin-V staining revealed that UCP2 transfection led to significantly increased cell death. However, characteristics of apoptosis were absent in UCP2-transfected Hepa 1-6 cells, including lack of oligonucleosomal fragmentation (laddering) of chromosomal DNA, release of cytochrome c from mitochondria, and cleavage of caspase-3. In conclusion, our results indicate that UCP2 induces cell cycle arrest at G1 phase and causes nonapoptotic cell death, suggesting that UCP2 may act as a powerful influence on hepatic regeneration and cell death in the steatotic liver.

  4. Skeletal muscle apoptosis, sarcopenia and frailty at old age.

    PubMed

    Marzetti, Emanuele; Leeuwenburgh, Christiaan

    2006-12-01

    The loss of muscle mass and strength with aging, also referred to as sarcopenia of aging, is a highly prevalent condition among older adults and predicts several adverse outcomes, including disability, institutionalization and mortality. Although the exact mechanisms underlying sarcopenia are far to be unveiled, accumulating preclinical evidence suggests that an age-related acceleration of myocytes loss via apoptosis might represent a key mechanism driving the onset and progression of muscle loss. Furthermore, increased levels of apoptosis have also been reported in old rats undergoing acute muscle atrophy subsequent to muscle unloading, a condition that mimics the muscle loss observed during prolonged bed rest. Notably, preliminary evidence seems to confirm a causative role for apoptosis in age-related muscle loss in human subjects. Several signaling pathways of skeletal muscle apoptosis are currently under intense investigation, with a particular focus on the role played by mitochondria. Here, we will review the most recent evidence regarding various pathways of muscle apoptosis and their modulation by several interventions (caloric restriction, physical exercise, muscle unloading).

  5. Flywheel sickle drive mechanism

    SciTech Connect

    Guinn, R.K.

    1989-03-21

    A releasable, eccentric drive mechanism is described, comprising: a first shaft extending along a central axis and presenting a generally cylindrical portion; a second shaft extending along a reference axis substantially parallel to the central axis in offset relation to the latter and having a generally cylindrical portion; a drive member having structure defining an opening including a first, generally cylindrical region receiving over one half of the circumference of the first shaft portion and a second, generally cylindrical region receiving over one half of the circumference of the second shaft portion, the second region being in side-by-side relationship to the first region and in open communication with the latter, the first shaft portion and the second shaft portion each including a substantially flat wall section extending in a plane substantially perpendicular to a reference plane passing through the central axis and the reference axis, each of the wall sections being inclined relative to the central axis in complemental, flat engagement with each other; and means coupled to one of the drive member and the second shaft for urging the first shaft in a longitudinal direction generally toward the second shaft in order to bring the wall section of the first shaft into a position of flat, wedging contact with the wall section of the second shaft and in contact with the structure defining the opening in order to securely interconnect the first shaft, the second shaft and the drive member.

  6. Who's driving the centromere?

    PubMed Central

    Copenhaver, Gregory P

    2004-01-01

    Centromere function is remarkably conserved between species, yet the satellite sequences that make up centromeric DNA are highly divergent. Proteins that bind these sequences appear to be evolving under positive selection, supporting a model wherein the interplay between centromeric repeats and the proteins that bind them creates an opportunity for an intriguing phenomenon known as centromere-based meiotic drive. PMID:15485584

  7. Who's driving the centromere?

    PubMed

    Copenhaver, Gregory P

    2004-01-01

    Centromere function is remarkably conserved between species, yet the satellite sequences that make up centromeric DNA are highly divergent. Proteins that bind these sequences appear to be evolving under positive selection, supporting a model wherein the interplay between centromeric repeats and the proteins that bind them creates an opportunity for an intriguing phenomenon known as centromere-based meiotic drive.

  8. Drive-Through Training

    ERIC Educational Resources Information Center

    Carter, Margie

    2010-01-01

    In this article, the author discusses how the early childhood field's approach to staff training reflects the drive-through, fast-food culture. Year after year directors send their teachers to workshops to get some quick refresher techniques. The author suggests that rather than focusing professional development on topics, focus on observing…

  9. Drive-Through Training

    ERIC Educational Resources Information Center

    Carter, Margie

    2010-01-01

    In this article, the author discusses how the early childhood field's approach to staff training reflects the drive-through, fast-food culture. Year after year directors send their teachers to workshops to get some quick refresher techniques. The author suggests that rather than focusing professional development on topics, focus on observing…

  10. Magnetized drive fluids

    SciTech Connect

    Rosensweig, R.E.; Zahn, M.

    1986-04-01

    A process is described for recovering a first fluid from a porous subterranean formation which comprises injecting a displacement fluid in an effective amount to displace the first fluid, injecting a ferrofluid, applying a magnetic field containing a gradient of field intensity within the formation, driving the displacement fluid through the formation with the ferrofluid and recovering first fluid.

  11. DrivePy

    SciTech Connect

    King, Ryan; Guo, Yi

    2014-08-30

    DrivePy is physics-based drivetrain model that sizes drivetrain components based on aerodynamic and operational loads for use in a systems engineering model. It also calculates costs based on empirical data collected by NREL's National Wind Technology Center.

  12. Teachers with Drive

    ERIC Educational Resources Information Center

    Coggins, Celine; Diffenbaugh, P. K.

    2013-01-01

    For students in U.S. classrooms today, the odds of being assigned to an inexperienced teacher are higher than they have ever been because so many teachers, some in the top 20 percent of effectiveness are leaving the classroom in their first five years. Coggins and Diffenbaugh turn to Daniel Pink's work on drive to determine how to motivate…

  13. Teachers with Drive

    ERIC Educational Resources Information Center

    Coggins, Celine; Diffenbaugh, P. K.

    2013-01-01

    For students in U.S. classrooms today, the odds of being assigned to an inexperienced teacher are higher than they have ever been because so many teachers, some in the top 20 percent of effectiveness are leaving the classroom in their first five years. Coggins and Diffenbaugh turn to Daniel Pink's work on drive to determine how to motivate…

  14. The Drive to Influence

    ERIC Educational Resources Information Center

    Rodriguez, Diego

    2017-01-01

    At the heart of the educational vocation is a drive to influence, to meaningfully affect the learning and development of others. For adult educators working in higher education, daily activities--from teaching classes to supervising student research to attending faculty meetings to sitting on advisory boards--are full of opportunities to…

  15. Driving While Intoxicated.

    ERIC Educational Resources Information Center

    Brick, John

    Alcohol intoxication increases the risk of highway accidents, the relative risk of crash probability increasing as a function of blood alcohol content (BAC). Because alcohol use is more prevalent than use of other drugs, more is known about the relationship between alcohol use and driving. Most states presume a BAC of .10% to be evidence of drunk…

  16. CSI: Hard Drive

    ERIC Educational Resources Information Center

    Sturgeon, Julie

    2008-01-01

    Acting on information from students who reported seeing a classmate looking at inappropriate material on a school computer, school officials used forensics software to plunge the depths of the PC's hard drive, searching for evidence of improper activity. Images were found in a deleted Internet Explorer cache as well as deleted file space.…

  17. Enhanced apoptosis in post-liver transplant hepatitis C: Effects of virus and immunosuppressants

    PubMed Central

    Lim, Eu Jin; Chin, Ruth; Angus, Peter W; Torresi, Joseph

    2012-01-01

    Hepatitis C (HCV)-infected patients have a poorer survival post-liver transplantation compared to patients transplanted for other indications, since HCV recurrence post-transplant is universal and commonly follows an aggressive course. There is increasing evidence that in the non-transplant setting, induction of hepatocyte apoptosis is one of the main mechanisms by which HCV drives liver inflammation and fibrosis, and that HCV proteins directly promote apoptosis. Recent studies have shown that post-liver transplant, there is a link between high levels of HCV replication, enhanced hepatocyte apoptosis and the subsequent development of rapidly progressive liver fibrosis. Although the responsible mechanisms remain unclear, it is likely that immunosuppressive drugs play an important role. It is well known that immunosuppressants impair immune control of HCV, thereby allowing increased viral replication. However there is also evidence that immunosuppressants may directly induce apoptosis and this may be facilitated by the presence of high levels of HCV replication. Thus HCV and immunosuppressants may synergistically interact to further enhance apoptosis and drive more rapid fibrosis. These findings suggest that modulation of apoptosis within the liver either by changing immunosuppressive therapy or the use of apoptosis inhibitors may help prevent fibrosis progression in patients with post-transplant HCV disease. PMID:22611309

  18. A structural appraisal of sterol carrier protein 2.

    PubMed

    Burgardt, Noelia I; Gianotti, Alejo R; Ferreyra, Raúl G; Ermácora, Mario R

    2017-05-01

    Sterol Carrier Protein 2 (SCP2) has been associated with lipid binding and transfer activities. However, genomic, proteomic, and structural studies revealed that it is an ubiquitous domain of complex proteins with a variety functions in all forms of life. High-resolution structures of representative SCP2 domains are available, encouraging a comprehensive review of the structural basis for its success. Most SCP2 domains pertain to three major families and are frequently found as stand-alone or at the C-termini of lipid related peroxisomal enzymes, acetyltransferases causing bacterial resistance, and bacterial environmentally important sulfatases. We (1) analyzed the structural basis of the fold and the classification of SCP2 domains; (2) identified structure-determined sequence features; (3) compared the lipid binding cavity of SCP2 and other lipid binding proteins; (4) surveyed proposed mechanisms of SCP2 mediated lipid transfer between membranes; and (5) uncovered a possible new function of the SCP2 domain as a protein-protein recognition device.

  19. [Human bone morphogenetic protein-2: recombinant expression in E. coli].

    PubMed

    Ma, Q; Dang, G; Ma, D

    1998-04-01

    To explore the way of producing human bone morphogenetic protein-2(hBMP-2) for bone healing by using the gene engeneering techniques. hBMP-2 cDNA fragment, which consists of 3' end partial propeptide and mature peptide sequence, was inserted into the multiple cloning site of expression vector pkpL-3a via ligation. The recombinant plasmid pkpL-3a/hBMP-2 was transformed into E. coli pOp2136. By the method of restriction map, the positive expression clone was selected. SDS-PAGE analysis showed a new foreign protein band near 27,000 after induction. The yield of induced hBMP-2 accouned for 10% of the total bacterial proteins. The partial purified recombinant hBMP-2 was implanted into Wistar rat thigh. After 4 weeks, histological analysis showed that it induced the proliferation of mesenchymal type cells and formation of new cartilage and bone in the implantation area. The hBMP-2 produced by gene engeneering techniques has the biologic capacity of ectopic bone formation.

  20. The effect of bone morphogenetic protein-2 on osteosarcoma metastasis

    PubMed Central

    Gill, Jonathan; Connolly, Patrick; Roth, Michael; Chung, So Hak; Zhang, Wendong; Piperdi, Sajida; Hoang, Bang; Yang, Rui; Guzik, Hillary; Gorlick, Richard; Geller, David S.

    2017-01-01

    Purpose Bone Morphogenetic Protein-2 (BMP-2) may offer the potential to enhance allograft-host osseous union in limb-salvage surgery following osteosarcoma resection. However, there is concern regarding the effect of locally applied BMP-2 on tumor recurrence and metastasis. The purpose of this project was to evaluate the effect of exogenous BMP-2 on osteosarcoma migration and invasion across a panel of tumor cell lines in vitro and to characterize the effect of BMP-2 on pulmonary osteosarcoma metastasis within a xenograft model. Experimental design The effect of BMP-2 on in vitro tumor growth and development was assessed across multiple standard and patient-derived xenograft osteosarcoma cell lines. Tumor migration capacity, invasion, and cell proliferation were characterized. In addition, the effect on metastasis was measured using a xenograft model following tail-vein injection. The effect of exogenous BMP-2 on the development of metastases was measured following both single and multiple BMP-2 administrations. Results There was no significant difference in migration capacity, invasion, or cell proliferation between the BMP-2 treated and the untreated osteosarcoma cell lines. There was no significant difference in pulmonary metastases between either the single-dose or multi-dose BMP-2 treated animals and the untreated control animals. Conclusions In the model systems tested, the addition of BMP-2 does not increase osteosarcoma proliferation, migration, invasion, or metastasis to the lungs. PMID:28264040

  1. Interaction of Approved Drugs with Synaptic Vesicle Protein 2A.

    PubMed

    Danish, Azeem; Namasivayam, Vigneshwaran; Schiedel, Anke C; Müller, Christa E

    2017-04-01

    Levetiracetam (LEV) and its recently approved derivative brivaracetam are anti-epileptic drugs with a unique mechanism of action. The synaptic vesicle protein 2A (SV2A) was previously identified as their main target. In the current study, we tested a collection of 500 approved drugs for interaction with the human SV2A protein expressed in Chinese hamster ovary cells. Competition binding studies were performed using cell lysates with high SV2A expression and [(3) H]brivaracetam as a radioligand. A hit rate of 3% was obtained, defined as compounds that inhibited radioligand binding by more than 90% at a screening concentration of 20 μM. Subsequent concentration-inhibition curves revealed the antihistaminic prodrug loratadine (Ki  = 1.16 μM) and the antimalarial drug quinine (Ki  = 2.03 μM) to be the most potent SV2A protein ligands of the investigated drug library. Both compounds were similarly potent as LEV (Ki  = 1.74 μM), providing structurally novel scaffolds for SV2A ligands. A pharmacophore model was established, which indicated steric and electronic conformities of brivaracetam with the new SV2A ligands, and preliminary structure-activity relationships were determined. The anti-convulsive effects of the natural product quinine may - at least in part - be explained by interaction with SV2A. Loratadine and quinine represent new lead structures for anti-epileptic drug development.

  2. The effect of bone morphogenetic protein-2 on osteosarcoma metastasis.

    PubMed

    Gill, Jonathan; Connolly, Patrick; Roth, Michael; Chung, So Hak; Zhang, Wendong; Piperdi, Sajida; Hoang, Bang; Yang, Rui; Guzik, Hillary; Morris, Jonathan; Gorlick, Richard; Geller, David S

    2017-01-01

    Bone Morphogenetic Protein-2 (BMP-2) may offer the potential to enhance allograft-host osseous union in limb-salvage surgery following osteosarcoma resection. However, there is concern regarding the effect of locally applied BMP-2 on tumor recurrence and metastasis. The purpose of this project was to evaluate the effect of exogenous BMP-2 on osteosarcoma migration and invasion across a panel of tumor cell lines in vitro and to characterize the effect of BMP-2 on pulmonary osteosarcoma metastasis within a xenograft model. The effect of BMP-2 on in vitro tumor growth and development was assessed across multiple standard and patient-derived xenograft osteosarcoma cell lines. Tumor migration capacity, invasion, and cell proliferation were characterized. In addition, the effect on metastasis was measured using a xenograft model following tail-vein injection. The effect of exogenous BMP-2 on the development of metastases was measured following both single and multiple BMP-2 administrations. There was no significant difference in migration capacity, invasion, or cell proliferation between the BMP-2 treated and the untreated osteosarcoma cell lines. There was no significant difference in pulmonary metastases between either the single-dose or multi-dose BMP-2 treated animals and the untreated control animals. In the model systems tested, the addition of BMP-2 does not increase osteosarcoma proliferation, migration, invasion, or metastasis to the lungs.

  3. Cysteine-rich protein 2 accelerates actin filament cluster formation

    PubMed Central

    Shinohara, Satoko; Takaoka, Shunpei; Miyake, Jun

    2017-01-01

    Filamentous actin (F-actin) forms many types of structures and dynamically regulates cell morphology and movement, and plays a mechanosensory role for extracellular stimuli. In this study, we determined that the smooth muscle-related transcription factor, cysteine-rich protein 2 (CRP2), regulates the supramolecular networks of F-actin. The structures of CRP2 and F-actin in solution were analyzed by small-angle X-ray solution scattering (SAXS). The general shape of CRP2 was partially unfolded and relatively ellipsoidal in structure, and the apparent cross sectional radius of gyration (Rc) was about 15.8 Å. The predicted shape, derived by ab initio modeling, consisted of roughly four tandem clusters: LIM domains were likely at both ends with the middle clusters being an unfolded linker region. From the SAXS analysis, the Rc of F-actin was about 26.7 Å, and it was independent of CRP2 addition. On the other hand, in the low angle region of the CRP2-bound F-actin scattering, the intensities showed upward curvature with the addition of CRP2, which indicates increasing branching of F-actin following CRP2 binding. From biochemical analysis, the actin filaments were augmented and clustered by the addition of CRP2. This F-actin clustering activity of CRP2 was cooperative with α-actinin. Thus, binding of CRP2 to F-actin accelerates actin polymerization and F-actin cluster formation. PMID:28813482

  4. Pathophysiological Significance of Hepatic Apoptosis

    PubMed Central

    Wang, Kewei; Lin, Bingliang

    2013-01-01

    Apoptosis is a classical pathological feature in liver diseases caused by various etiological factors such as drugs, viruses, alcohol, and cholestasis. Hepatic apoptosis and its deleterious effects exacerbate liver function as well as involvement in fibrosis/cirrhosis and carcinogenesis. An imbalance between apoptotic and antiapoptotic capabilities is a prominent characteristic of liver injury. The regulation of apoptosis and antiapoptosis can be a pivotal step in the treatment of liver diseases. PMID:27335822

  5. Uncoupling protein 2 gene polymorphisms are associated with obesity

    PubMed Central

    2012-01-01

    Background Uncoupling protein 2 (UCP2) gene polymorphisms have been reported as genetic risk factors for obesity and type 2 diabetes mellitus (T2DM). We examined the association of commonly observed UCP2 G(−866)A (rs659366) and Ala55Val (C > T) (rs660339) single nucleotide polymorphisms (SNPs) with obesity, high fasting plasma glucose, and serum lipids in a Balinese population. Methods A total of 603 participants (278 urban and 325 rural subjects) were recruited from Bali Island, Indonesia. Fasting plasma glucose (FPG), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were measured. Obesity was determined based on WHO classifications for adult Asians. Participants were genotyped for G(−866)A and Ala55Val polymorphisms of the UCP2 gene. Results Obesity prevalence was higher in urban subjects (51%) as compared to rural subjects (23%). The genotype, minor allele (MAF), and heterozygosity frequencies were similar between urban and rural subjects for both SNPs. All genotype frequencies were in Hardy-Weinberg equilibrium. A combined analysis of genotypes and environment revealed that the urban subjects carrying the A/A genotype of the G(−866)A SNP have higher BMI than the rural subjects with the same genotype. Since the two SNPs showed strong linkage disequilibrium (D’ = 0.946, r2 = 0.657), a haplotype analysis was performed. We found that the AT haplotype was associated with high BMI only when the urban environment was taken into account. Conclusions We have demonstrated the importance of environmental settings in studying the influence of the common UCP2 gene polymorphisms in the development of obesity in a Balinese population. PMID:22533685

  6. Sterol Carrier Protein-2: Binding Protein for Endocannabinoids

    PubMed Central

    Liedhegner, Elizabeth Sabens; Vogt, Caleb D.; Sem, Daniel S.; Cunningham, Christopher W.

    2015-01-01

    The endocannabinoid (eCB) system, consisting of eCB ligands and the type 1 cannabinoid receptor (CB1R), subserves retrograde, activity-dependent synaptic plasticity in the brain. eCB signaling occurs “on-demand,” thus the processes regulating synthesis, mobilization and degradation of eCBs are also primary mechanisms for the regulation of CB1R activity. The eCBs, N-arachidonylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), are poorly soluble in water. We hypothesize that their aqueous solubility, and, therefore, their intracellular and transcellular distribution, are facilitated by protein binding. Using in silico docking studies, we have identified the nonspecific lipid binding protein, sterol carrier protein 2 (SCP-2), as a potential AEA binding protein. The docking studies predict that AEA and AM404 associate with SCP-2 at a putative cholesterol binding pocket with ΔG values of −3.6 and −4.6 kcal/mol, respectively. These values are considerably higher than cholesterol (−6.62 kcal/mol) but consistent with a favorable binding interaction. In support of the docking studies, SCP-2-mediated transfer of cholesterol in vitro is inhibited by micromolar concentrations of AEA; and heterologous expression of SCP-2 in HEK 293 cells increases time-related accumulation of AEA in a temperature-dependent fashion. These results suggest that SCP-2 facilitates cellular uptake of AEA. However, there is no effect of SCP-2 transfection on the cellular accumulation of AEA determined at equilibrium or the IC50 values for AEA, AM404 or 2-AG to inhibit steady state accumulation of radiolabelled AEA. We conclude that SCP-2 is a low affinity binding protein for AEA that can facilitate its cellular uptake but does not contribute significantly to intracellular sequestration of AEA. PMID:24510313

  7. Apoptosis Resistance in Endometriosis

    PubMed Central

    Salmassi, Ali; Acar-Perk, Bengi; Schmutzler, Andreas G.; Koch, Kerstin; Püngel, Frank; Jonat, Walter; Mettler, Liselotte

    2011-01-01

    Introduction In a cytological analysis of endometriotic lesions neither granulocytes nor cytotoxic T-cells appear in an appreciable number. Based on this observation we aimed to know, whether programmed cell death plays an essential role in the destruction of dystopic endometrium. Disturbances of the physiological mechanisms of apoptosis, a persistence of endometrial tissue could explain the disease. Another aspect of this consideration is the proliferation competence of the dystopic mucous membrane. Methods Endometriotic lesions of 15 patients were examined through a combined measurement of apoptosis activity with the TUNEL technique (terminal deoxyribosyltransferase mediated dUTP Nick End Labeling) and the proliferation activity (with the help of the Ki-67-Antigens using the monoclonal antibody Ki-S5). Results Twelve out of 15 women studied showed a positive apoptotic activity of 3-47% with a proliferation activity of 2-25% of epithelial cells. Therefore we concluded that the persistence of dystopic endometrium requires proliferative epithelial cells from middle to lower endometrial layers. Conclusion A dystopia misalignment of the epithelia of the upper layers of the functionalism can be rapidly eliminated by apoptotic procedures. PMID:23678417

  8. Lovastatin induces platelet apoptosis.

    PubMed

    Zhao, Qing; Li, Ming; Chen, Mengxing; Zhou, Ling; Zhao, Lili; Hu, Renping; Yan, Rong; Dai, Kesheng

    2016-03-01

    Statins are widely used in the prevention of atherosclerosis and treatment of coronary artery disease because of pleiotropic effects on thrombosis. Thrombocytopenia and hemorrhage occurred in some statin-treated patients, but the reason remains unclear. In the current study, we show that lovastatin dose-dependently induces depolarization of mitochondrial inner transmembrane potential, leading to up-regulation of Bak, down-regulation of Bcl-XL, and activation of caspase-3/8/9. Lovastatin treatment did not increase the surface expression of P-selectin or PAC-1 binding but led to strongly reduced collagen- and thrombin-induced platelet aggregation. The integrin αIIbβ3 antagonist, RGDS, inhibited lovastatin-induced apoptosis in both human platelets and Chinese hamster ovary (CHO) cells stably expressing integrin αIIbβ3. The number of circulating platelets in mice was significantly reduced after intraperitoneal injections with lovastatin. Taken together, these data indicate that lovastatin induced caspase-dependent platelet apoptosis. Lovastatin does not incur platelet activation, whereas impairs platelet function and reduces circulating platelets in vivo, suggesting the possible pathogenesis of thrombocytopenia and hemorrhage in patients treated with statins. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. [Driving ability with multiple sclerosis].

    PubMed

    Küst, J; Dettmers, C

    2014-07-01

    Driving is an important issue for young patients, especially for those whose walking capacity is impaired. Driving might support the patient's social and vocational participation. The question as to whether a patient with multiple sclerosis (MS) is restricted in the ability to drive a car depends on neurological and neuropsychological deficits, self-awareness, insight into deficits and ability to compensate for loss of function. Because of the enormous variability of symptoms in MS the question is highly individualized. A practical driving test under supervision of a driving instructor (possibly accompanied by a neuropsychologist) might be helpful in providing both patient and relatives adequate feedback on driving abilities.

  10. Forces Driving Chaperone Action

    PubMed Central

    Koldewey, Philipp; Stull, Frederick; Horowitz, Scott; Martin, Raoul; Bardwell, James C. A.

    2016-01-01

    SUMMARY It is still unclear what molecular forces drive chaperone-mediated protein folding. Here, we obtain a detailed mechanistic understanding of the forces that dictate the four key steps of chaperone-client interaction: initial binding, complex stabilization, folding, and release. Contrary to the common belief that chaperones recognize unfolding intermediates by their hydrophobic nature, we discover that the model chaperone Spy uses long-range electrostatic interactions to rapidly bind to its unfolded client protein Im7. Short-range hydrophobic interactions follow, which serve to stabilize the complex. Hydrophobic collapse of the client protein then drives its folding. By burying hydrophobic residues in its core, the client’s affinity to Spy decreases, which causes client release. By allowing the client to fold itself, Spy circumvents the need for client-specific folding instructions. This mechanism might help explain how chaperones can facilitate the folding of various unrelated proteins. PMID:27293188

  11. Advanced Motor Drives Studies

    NASA Technical Reports Server (NTRS)

    Ehsani, M.; Tchamdjou, A.

    1997-01-01

    This report presents an evaluation of advanced motor drive systems as a replacement for the hydrazine fueled APU units. The replacement technology must meet several requirements which are particular to the space applications and the Orbiter in general. Some of these requirements are high efficiency, small size, high power density. In the first part of the study several motors are compared, based on their characteristics and in light of the Orbiter requirements. The best candidate, the brushless DC is chosen because of its particularly good performance with regards to efficiency. Several power electronics drive technologies including the conventional three-phase hard switched and several soft-switched inverters are then presented. In the last part of the study, a soft-switched inverter is analyzed and compared to its conventional hard-switched counterpart. Optimal efficiency is a basic requirement for space applications and the soft-switched technology represents an unavoidable trend for the future.

  12. [Cannabis affects driving skills].

    PubMed

    Khiabani, Hassan Z; Christophersen, Asbjørg S; Mørland, Jørg

    2007-03-01

    Delta (9)-tetrahydrocannabinol (THC), the most important psychoactive substance in cannabis, is frequently detected in blood from apprehended drivers suspected for drugged driving. Both experimental and epidemiological studies have demonstrated the negative effects of THC upon cognitive functions and psychomotor skills. These effects could last longer than a measurable concentration of THC in blood. Culpability studies have recently demonstrated an increased risk of becoming responsible in fatal or injurious traffic accidents, even with low blood concentrations of THC. It has also been demonstrated that there is a correlation between the degree of impairment, the drug dose and the THC blood concentration. It is very important to focus on the negative effect of cannabis on fitness to drive in order to prevent injuries and loss of human life and to avoid large economic consequences to the society.

  13. A driving commitment.

    PubMed

    McGuire, S

    1995-01-01

    Italy's statistics institute, ISTAT, has announced in its annual report that the number of AIDS deaths is threatening to pass the number of deaths from traffic accidents. According to ISTAT, 4,370 Italians died from AIDS in 1994, while some 6,000 died on the country's roads. The report states that AIDS is the second leading cause of death after road accidents for young males, aged 18 to 29. Three years ago, Americans made a commitment to safer automobile engineering, better highway design, and increased penalties for drunken driving; consequently reducing both the total numbers and the per-capita incidence of traffic deaths, in spite of much more driving. A similar commitment to prevention and treatment efforts could have an equally dramatic impact on the incidence of AIDS and HIV transmission in the United States. However, that commitment will not likely emerge anytime soon given Congress's current plans for the budget.

  14. Magnetostrictive direct drive motors

    NASA Technical Reports Server (NTRS)

    Naik, Dipak; Dehoff, P. H.

    1990-01-01

    Developing magnetostrictive direct drive research motors to power robot joints is discussed. These type motors are expected to produce extraordinary torque density, to be able to perform microradian incremental steps and to be self-braking and safe with the power off. Several types of motor designs have been attempted using magnetostrictive materials. One of the candidate approaches (the magnetostrictive roller drive) is described. The method in which the design will function is described as is the reason why this approach is inherently superior to the other approaches. Following this, the design will be modelled and its expected performance predicted. This particular candidate design is currently undergoing detailed engineering with prototype construction and testing scheduled for mid 1991.

  15. Variable speed drive

    NASA Technical Reports Server (NTRS)

    Obler, H. D. (Inventor)

    1983-01-01

    A variable speed drive wherein a first embodiment is comprised of a pivotally mounted prime mover coupled to a rotary fluid output device, such as a fan or pump, through a variable and fixed pulley drive arrangement is described. The pivotal position of the prime mover and accordingly the pitch diameter of variable pulley means is controlled in accordance with fluid motor means coupled to the prime mover. This is actuated in response to a fluid feedback control signal derived from a sensed output of the rotary fluid output device. The pivotal motion of the prime mover imparts an arcuate motion to the variable pulley means which effects a speed variation of the rotary fluid output device in accordance with the variation of the pitch diameter ratio of opposing variable and fixed pulley means.

  16. Sex Chromosome Drive

    PubMed Central

    Helleu, Quentin; Gérard, Pierre R.; Montchamp-Moreau, Catherine

    2015-01-01

    Sex chromosome drivers are selfish elements that subvert Mendel's first law of segregation and therefore are overrepresented among the products of meiosis. The sex-biased progeny produced then fuels an extended genetic conflict between the driver and the rest of the genome. Many examples of sex chromosome drive are known, but the occurrence of this phenomenon is probably largely underestimated because of the difficulty to detect it. Remarkably, nearly all sex chromosome drivers are found in two clades, Rodentia and Diptera. Although very little is known about the molecular and cellular mechanisms of drive, epigenetic processes such as chromatin regulation could be involved in many instances. Yet, its evolutionary consequences are far-reaching, from the evolution of mating systems and sex determination to the emergence of new species. PMID:25524548

  17. Drive transmission means

    SciTech Connect

    Marsh, M. R.

    1985-01-15

    This invention provides apparatus for use in a drive transmission system comprising a pump adapted to perform work on a medium and means repetitively and automatically to unload the pump. When connected with a flywheel driven by a prime mover an embodiment alternately performs work and then is unloaded to permit acceleration of the flywheel. In use in a driven transmission system there is provided a flywheel driven by an engine, a pump driven by the flywheel, powered by the pump, and means repetitively to unload the pump permitting the engine to accelerate the flywheel and compensation means to power the hydraulic motor while the pump is unloaded. The pump is preferably a rotary positive displacement pump having relief galleries eliminating the seal between pumping elements driving each cycle.

  18. Gear Drive Testing

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Philadelphia Gear Corporation used two COSMIC computer programs; one dealing with shrink fit analysis and the other with rotor dynamics problems in computerized design and test work. The programs were used to verify existing in-house programs to insure design accuracy by checking its company-developed computer methods against procedures developed by other organizations. Its specialty is in custom units for unique applications, such as Coast Guard ice breaking ships, steel mill drives, coal crusher, sewage treatment equipment and electricity.

  19. Variable reluctance drive system

    SciTech Connect

    Lipo, T.A.; Liang, F.

    1995-10-17

    A variable reluctance drive system including a motor and corresponding converter for improved current commutation is described. The motor incorporates a salient pole rotor and a salient pole stator having one or more full pitch windings which operate by mutual inductance to transfer the current from the active short pitch winding following phase alignment. This increases output torque and/or speed and permits a number of simple and economical converter circuits. 17 figs.

  20. Butalbital and driving impairment.

    PubMed

    Yeakel, Jillian K; Logan, Barry K

    2013-07-01

    Butalbital (Fiorinal(®)), used in the treatment of migraines and muscle pain, is the most commonly encountered barbiturate in impaired driving cases. It has central nervous system (CNS) depressant properties, including sedation, drowsiness, and feelings of intoxication, which can contribute to driving impairment. Twenty-six driving under the influence cases are reviewed including results from field sobriety tests and toxicology testing. Blood samples were screened using enzyme multiplied immunoassay technique immunoassay, and the presence of butalbital was confirmed and quantified using gas chromatography/mass spectrometry, gas chromatography with flame ionization detection, or gas chromatography nitrogen/phosphorus detection. Butalbital concentrations ranged from 1.0 to 30.2 mg/L, with a mean and median of 16.0 mg/L. General impairment indicators in these cases included horizontal and vertical nystagmus, lack of convergence, poor motor coordination, and balance and speech problems, which are common to CNS depressant intoxication, similar to that associated with alcohol. These findings indicate the importance of toxicological testing for butalbital in cases where CNS depressants are indicated. © 2013 American Academy of Forensic Sciences.

  1. [Automobile driving capacity in dementia].

    PubMed

    Seeger, Rolf

    2015-04-01

    Dementia influences at an early stage the driving aptitude of motor vehicle steering persons. Every year in Switzerland, around 16'000 driving permit holders suffer newly from dementia; therefore the driving aptitude is questioned, especially because of possibly limited executive functions. Individuals with early-stage dementia often may show a dangerous driving stile. However, a mild dementia does not a priori exclude the driving aptitude, and less than half of these drivers can continue driving for another 1 - 3 years. In contrast, there is no further driving aptitude in presence of moderate dementia. In the assessment of driving aptitude, the underlying cause of dementia is always taken into account. Cognitive short tests such as the Mini-Mental Status Exam, Clock Drawing Test and Trail-Making Test are not suitable to make reliable statements about the aptitude to drive, but these tests are very important for the initial diagnosis of dementia in primary care practice and can lead the way for further examination concerning driving aptitude. The legally prescribed regular check-up for motorists aged over 70 years in Switzerland provides an ideal opportunity for early detection of incipient dementia. The practical procedure for the assessment of aptitude to drive in the primary care practice is presented. The physician-guided on-road driving test represents a meaningful, practical and relatively cost-effective tool for the evaluation of driving aptitude in cases of doubt.

  2. BARC: A Novel Apoptosis Regulator

    DTIC Science & Technology

    2004-07-01

    turnover is normally achieved through programmed cell death , also known as apoptosis. Effects in apoptosis occur in breast cancers and other types of...malignancies, making tumor cells difficult to kill by chemotherapy, hormonal therapy, and radiation. Restoring function of cell death pathways is a strategy...These findings provide new insights into cell death regulation in breast cancer.

  3. Apoptosis and the Airway Epithelium

    PubMed Central

    White, Steven R.

    2011-01-01

    The airway epithelium functions as a barrier and front line of host defense in the lung. Apoptosis or programmed cell death can be elicited in the epithelium as a response to viral infection, exposure to allergen or to environmental toxins, or to drugs. While apoptosis can be induced via activation of death receptors on the cell surface or by disruption of mitochondrial polarity, epithelial cells compared to inflammatory cells are more resistant to apoptotic stimuli. This paper focuses on the response of airway epithelium to apoptosis in the normal state, apoptosis as a potential regulator of the number and types of epithelial cells in the airway, and the contribution of epithelial cell apoptosis in important airways diseases. PMID:22203854

  4. Apoptosis Evaluation by Electrochemical Techniques.

    PubMed

    Yin, Jian; Miao, Peng

    2016-03-04

    Apoptosis has close relevance to pathology, pharmacology, and toxicology. Accurate and convenient detection of apoptosis would be beneficial for biological study, clinical diagnosis, and drug development. Based on distinct features of apoptotic cells, a diversity of analytical techniques have been exploited for sensitive analysis of apoptosis, such as surface plasmon resonance, electrochemical methods, flow cytometry, and some imaging assays. Among them, the features of simplicity, easy operation, low cost, and high sensitivity make electrochemical techniques powerful tools to investigate electron-transfer processes of in vitro biological systems. In this contribution, a general overview of current knowledge on various technical approaches for apoptosis evaluation is provided. Furthermore, recently developed electrochemical biosensors for detecting apoptotic cells and their advantages over traditional methods are summarized. One of the main considerations focuses on designing the recognition elements based on various biochemical events during apoptosis.

  5. Solution structure of murine macrophage inflammatory protein-2.

    PubMed

    Shao, W; Jerva, L F; West, J; Lolis, E; Schweitzer, B I

    1998-06-09

    The solution structure of murine macrophage inflammatory protein-2 (MIP-2), a heparin-binding chemokine that is secreted in response to inflammatory stimuli, has been determined using two-dimensional homonuclear and heteronuclear NMR spectroscopy. Structure calculations were carried out by means of torsion-angle molecular dynamics using the program X-PLOR. The structure is based on a total of 2390 experimental restraints, comprising 2246 NOE-derived distance restraints, 44 distance restraints for 22 hydrogen bonds, and 100 torsion angle restraints. The structure is well-defined, with the backbone (N, Calpha, C) and heavy atom atomic rms distribution about the mean coordinates for residues 9-69 of the dimer being 0.57 +/- 0.16 A and 0.96 +/- 0.12 A, respectively. The N- and C-terminal residues (1-8 and 70-73, respectively) are disordered. The overall structure of the MIP-2 dimer is similar to that reported previously for the NMR structures of MGSA and IL-8 and consists of a six-stranded antiparallel beta-sheet (residue 25-29, 39-44, and 48-52) packed against two C-terminal antiparallel alpha-helices. A best fit superposition of the NMR structure of MIP-2 on the structures of MGSA, NAP-2, and the NMR and X-ray structures of IL-8 are 1.11, 1.02, 1.27, and 1.19 A, respectively, for the monomers, and 1.28, 1.10, 1.55, and 1.36 A, respectively, for the dimers (IL-8 residues 7-14 and 16-67, NAP-2 residues 25-84). At the tertiary level, the main differences between the MIP-2 solution structure and the IL-8, MGSA, and NAP-2 structures involve the N-terminal loop between residues 9-23 and the loops formed by residues 30-38 and residues 53-58. At the quaternary level, the difference between MIP-2 and IL-8, MGSA, or NAP-2 results from differing interhelical angles and separations.

  6. Fas ligand-expressing lymphocytes enhance alveolar macrophage apoptosis in the resolution of acute pulmonary inflammation

    PubMed Central

    Barthel, Lea; Bednarek, Joseph M.; Yunt, Zulma X.; Henson, Peter M.; Janssen, William J.

    2014-01-01

    Apoptosis of alveolar macrophages and their subsequent clearance by neighboring phagocytes are necessary steps in the resolution of acute pulmonary inflammation. We have recently identified that activation of the Fas death receptor on the cell surface of macrophages drives macrophage apoptosis. However, the source of the cognate ligand for Fas (FasL) responsible for induction of alveolar macrophage apoptosis is not defined. Given their known role in the resolution of inflammation and ability to induce macrophage apoptosis ex vivo, we hypothesized that T lymphocytes represented a critical source of FasL. To address this hypothesis, C57BL/6J and lymphocyte-deficient (Rag-1−/−) mice were exposed to intratracheal lipopolysaccharide to induce pulmonary inflammation. Furthermore, utilizing mice expressing nonfunctional FasL, we adoptively transferred donor lymphocytes into inflamed lymphocyte-deficient mice to characterize the effect of lymphocyte-derived FasL on alveolar macrophage apoptosis in the resolution of inflammation. Herein, evidence is presented that lymphocytes expressing FasL enhance alveolar macrophage apoptosis during the resolution of LPS-induced inflammation. Moreover, lymphocyte induction of alveolar macrophage apoptosis results in contraction of the alveolar macrophage pool, which occurs in a FasL-dependent manner. Specifically, FasL-expressing CD8+ T lymphocytes potently induce alveolar macrophage apoptosis and contraction of the alveolar macrophage pool. Together, these studies identify a novel role for CD8+ T lymphocytes in the resolution of acute pulmonary inflammation. PMID:24838751

  7. Drive system failure control for distributed drive electric vehicles

    NASA Astrophysics Data System (ADS)

    Liu, Tao; Tang, Yuan; Wang, Jianfeng; Li, Yaou; Yang, Na; Liu, Yiqun

    2017-09-01

    Aiming at the failure problem of distributed electric drive vehicle, the conventional control strategy of drive system failure is designed according to the characteristics of each wheel torque independent control and the redundant configuration of the power unit. On this basis, combined with the traditional body stability control technology, the direct yaw moment control method is used. The simulation results show that the conventional control method designed of the drive system failure can effectively improve the driving condition of the vehicle. The driving stability of the vehicle is further improved after the direct yaw torque control is applied.

  8. Apoptosis in Primary Hyperparathyroidism.

    PubMed

    Segiet, Oliwia Anna; Mielańczyk, Łukasz; Piecuch, Adam; Michalski, Marek; Tyczyński, Szczepan; Brzozowa-Zasada, Marlena; Deska, Mariusz; Wojnicz, Romuald

    2017-03-31

    Primary hyperparathyroidism (PHPT) is defined by inappropriate elevation of parathormone, caused by parathyroid hyperplasia, also known as multi-gland disease (MGD), parathyroid adenoma (PA), or parathyroid carcinoma (PC). Although several studies have already been conducted, there is a lack of a definite diagnostic marker, which could unambiguously distinguish MGD from PA or PC. The accurate and prompt diagnosis has the key meaning for effective treatment and follow-up. This review paper presents the role of apoptosis in PHPT. The comparison of the expression of Fas, TRAIL, BCL-2 family members, p53 in MGD, PA, and PC, among others, was described. The expression of described factors varies among proliferative lesions of parathyroid gland; therefore, these could serve as additional markers to assist in the diagnosis.

  9. Drive alignment pays maintenance dividends

    SciTech Connect

    Fedder, R.

    2008-12-15

    Proper alignment of the motor and gear drive on conveying and processing equipment will result in longer bearing and coupling life, along with lower maintenance costs. Selecting an alignment free drive package instead of a traditional foot mounted drive and motor is a major advancement toward these goals. 4 photos.

  10. Drive Diagnostic Filter Wheel Control

    SciTech Connect

    Uhlich, D.

    2007-07-17

    DrD Filter Wheel Control is National Instrument's Labview software that drives a Drive Diagnostic filter wheel. The software can drive the filter wheel between each end limit, detect the positive and negative limit and each home position and post the stepper motot values to an Excel spreadsheet. The software can also be used to cycle the assembly between the end limits.

  11. Offset Compound Gear Drive

    NASA Technical Reports Server (NTRS)

    Stevens, Mark A.; Handschuh, Robert F.; Lewicki, David G.

    2010-01-01

    The Offset Compound Gear Drive is an in-line, discrete, two-speed device utilizing a special offset compound gear that has both an internal tooth configuration on the input end and external tooth configuration on the output end, thus allowing it to mesh in series, simultaneously, with both a smaller external tooth input gear and a larger internal tooth output gear. This unique geometry and offset axis permits the compound gear to mesh with the smaller diameter input gear and the larger diameter output gear, both of which are on the same central, or primary, centerline. This configuration results in a compact in-line reduction gear set consisting of fewer gears and bearings than a conventional planetary gear train. Switching between the two output ratios is accomplished through a main control clutch and sprag. Power flow to the above is transmitted through concentric power paths. Low-speed operation is accomplished in two meshes. For the purpose of illustrating the low-speed output operation, the following example pitch diameters are given. A 5.0 pitch diameter (PD) input gear to 7.50 PD (internal tooth) intermediate gear (0.667 reduction mesh), and a 7.50 PD (external tooth) intermediate gear to a 10.00 PD output gear (0.750 reduction mesh). Note that it is not required that the intermediate gears on the offset axis be of the same diameter. For this example, the resultant low-speed ratio is 2:1 (output speed = 0.500; product of stage one 0.667 reduction and stage two 0.750 stage reduction). The design is not restricted to the example pitch diameters, or output ratio. From the output gear, power is transmitted through a hollow drive shaft, which, in turn, drives a sprag during which time the main clutch is disengaged.

  12. Modular droplet actuator drive

    NASA Technical Reports Server (NTRS)

    Pollack, Michael G. (Inventor); Paik, Philip (Inventor)

    2011-01-01

    A droplet actuator drive including a detection apparatus for sensing a property of a droplet on a droplet actuator; circuitry for controlling the detection apparatus electronically coupled to the detection apparatus; a droplet actuator cartridge connector arranged so that when a droplet actuator cartridge electronically is coupled thereto: the droplet actuator cartridge is aligned with the detection apparatus; and the detection apparatus can sense the property of the droplet on a droplet actuator; circuitry for controlling a droplet actuator coupled to the droplet actuator connector; and the droplet actuator circuitry may be coupled to a processor.

  13. Engine valve driving apparatus

    SciTech Connect

    Masuda, S.; Uesugi, T.; Oda, H.

    1989-01-03

    An engine valve driving apparatus for an internal combustion engine having a cam driven engine valve is described. It consists of a camshaft rotatable in synchronism with rotation of a crankshaft of an engine and a movable cam member supported by the camshaft for axial movement and prevented from turning relative to the camshaft. The movable cam member can be axially shifted between an operative position wherein the cam member is cooperative with a member of the engine valve so as to cause an operation of the engine valve and an inoperative position wherein the cam member is out of cooperation with the member.

  14. Generative design drives manufacturing

    NASA Astrophysics Data System (ADS)

    Logan, Frank A.

    1989-04-01

    This paper reviews the collaboration that is being forced on Engineering and Manufacturing as they move from the manual translation of Engineering drawings toward automatic decoding of Product Data Definitions (PDDs), a pre-requisite to integrated manufacture. Based on case studies and implementation experience gained over the last decade, it defines the step-by-step evolution of a generative design capability that will drive manufacturing logic. It reviews the changing relationship of Engineering to Manufacturing and Industrial Engineering and the challenge this presents to manufacturing management in its struggle to remain competitive in both domestic and international markets.

  15. Base drive circuit

    DOEpatents

    Lange, Arnold C.

    1995-01-01

    An improved base drive circuit (10) having a level shifter (24) for providing bistable input signals to a pair of non-linear delays (30, 32). The non-linear delays (30, 32) provide gate control to a corresponding pair of field effect transistors (100, 106) through a corresponding pair of buffer components (88, 94). The non-linear delays (30, 32) provide delayed turn-on for each of the field effect transistors (100, 106) while an associated pair of transistors (72, 80) shunt the non-linear delays (30, 32) during turn-off of the associated field effect transistor (100, 106).

  16. Base drive circuit

    DOEpatents

    Lange, A.C.

    1995-04-04

    An improved base drive circuit having a level shifter for providing bistable input signals to a pair of non-linear delays. The non-linear delays provide gate control to a corresponding pair of field effect transistors through a corresponding pair of buffer components. The non-linear delays provide delayed turn-on for each of the field effect transistors while an associated pair of transistors shunt the non-linear delays during turn-off of the associated field effect transistor. 2 figures.

  17. Advances in traction drive technology

    NASA Technical Reports Server (NTRS)

    Loewenthal, S. H.; Anderson, N. E.; Rohn, D. A.

    1983-01-01

    Traction drives are traced from early uses as main transmissions in automobiles at the turn of the century to modern, high-powered traction drives capable of transmitting hundreds of horsepower. Recent advances in technology are described which enable today's traction drive to be a serious candidate for off-highway vehicles and helicopter applications. Improvements in materials, traction fluids, design techniques, power loss and life prediction methods will be highlighted. Performance characteristics of the Nasvytis fixed-ratio drive are given. Promising future drive applications, such as helicopter main transmissions and servo-control positioning mechanisms are also addressed.

  18. Apoptosis in Gingival Overgrowth Tissues

    PubMed Central

    Kantarci, A.; Augustin, P.; Firatli, E.; Sheff, M.C.; Hasturk, H.; Graves, D.T.; Trackman, P.C.

    2010-01-01

    Variations in the balance between cell proliferation and apoptosis could contribute to the etiology of gingival overgrowth. The aim of this study was to test the hypothesis that, in fibrotic gingival lesions, fibroblast proliferation is stimulated and apoptosis is decreased. Apoptotic index, caspase 3 expression, the proliferative index, FOXO1 expression, and histological inflammation were measured in situ. Analysis of data showed that apoptosis decreased in all forms of gingival overgrowth examined (p < 0.05), and inflammation caused a small but significant increase compared with non-inflamed tissues (p < 0.05). The greatest decrease of apoptosis occurred in the most fibrotic tissues. Cell proliferation was elevated in all forms of gingival overgrowth tested, independent of inflammation (p < 0.05). To identify potential mechanisms of transcriptional regulation of apoptosis, we assessed FOXO1 and caspase 3 expression levels and found them to correlate well with diminished apoptosis. Analysis of data suggests that increased fibroblast proliferation and a simultaneous decrease in apoptosis contribute to gingival overgrowth. PMID:17720861

  19. Text messaging during simulated driving.

    PubMed

    Drews, Frank A; Yazdani, Hina; Godfrey, Celeste N; Cooper, Joel M; Strayer, David L

    2009-10-01

    This research aims to identify the impact of text messaging on simulated driving performance. In the past decade, a number of on-road, epidemiological, and simulator-based studies reported the negative impact of talking on a cell phone on driving behavior. However, the impact of text messaging on simulated driving performance is still not fully understood. Forty participants engaged in both a single task (driving) and a dual task (driving and text messaging) in a high-fidelity driving simulator. Analysis of driving performance revealed that participants in the dual-task condition responded more slowly to the onset of braking lights and showed impairments in forward and lateral control compared with a driving-only condition. Moreover, text-messaging drivers were involved in more crashes than drivers not engaged in text messaging. Text messaging while driving has a negative impact on simulated driving performance. This negative impact appears to exceed the impact of conversing on a cell phone while driving. The results increase our understanding of driver distraction and have potential implications for public safety and device development.

  20. Regulation of Apoptosis by Inhibitors of Apoptosis (IAPs)

    PubMed Central

    Berthelet, Jean; Dubrez, Laurence

    2013-01-01

    Abstract Inhibitors of Apoptosis (IAPs) are a family of proteins with various biological functions including regulation of innate immunity and inflammation, cell proliferation, cell migration and apoptosis. They are characterized by the presence of at least one N-terminal baculoviral IAP repeat (BIR) domain involved in protein-protein interaction. Most of them also contain a C-terminal RING domain conferring an E3-ubiquitin ligase activity. In drosophila, IAPs are essential to ensure cell survival, preventing the uncontrolled activation of the apoptotic protease caspases. In mammals, IAPs can also regulate apoptosis through controlling caspase activity and caspase-activating platform formation. Mammalian IAPs, mainly X-linked IAP (XIAP) and cellular IAPs (cIAPs) appeared to be important determinants of the response of cells to endogenous or exogenous cellular injuries, able to convert the survival signal into a cell death-inducing signal. This review highlights the role of IAP in regulating apoptosis in Drosophila and Mammals. PMID:24709650

  1. Fast wave current drive

    NASA Astrophysics Data System (ADS)

    Goree, J.; Ono, M.; Colestock, P.; Horton, R.; McNeill, D.; Park, H.

    1985-07-01

    Experiments on the fast wave in the range of high ion cyclotron harmonics in the ACT-1 device show that current drive is possible with the fast wave just as it is for the lower hybrid wave, except that it is suitable for higher plasma densities. A 140° loop antenna launched the high ion cyclotron harmonic fast wave [ω/Ω=O(10)] into a He+ plasma with ne≂4×1012 cm-3 and B=4.5 kG. Probe and magnetic loop diagnostics and FIR laser scattering confirmed the presence of the fast wave, and the Rogowski loop indicated that the circulating plasma current increased by up to 40A with 1 kW of coupled power, which is comparable to lower hybrid current drive in the same device with the same unidirectional fast electron beam used as the target for the rf. A phased antenna array would be used for FWCD in a tokamak without the E-beam.

  2. Sunscreen use while driving.

    PubMed

    Kim, Dennis P; Chabra, Indy; Chabra, Pawan; Jones, Evan C

    2013-06-01

    Data regarding patient perceptions and behaviors about sun-protection measures while driving are lacking. This study evaluates patients' awareness of the importance of sun protection while in an automobile, and assesses perceptions about and compliance with sun protection. A secondary objective was to detect any significant laterality in melanoma and nonmelanoma skin cancers. We performed a retrospective survey of patients seen at a Mohs micrographic surgery clinic. Significantly fewer patients reported wearing sunscreen while in an automobile when compared with general daily sunscreen use (52% vs 27%, P < .05). Most respondents did not think they needed to use sunscreen while driving, especially if the windows were closed. Those who believed they were protected from sun damage while in a car were much less likely to use sunscreen (12% vs 46%, P < .05). There was a significant left-sided predominance of nonmelanoma skin cancers, except in patients who used automobiles with tinted windows. This retrospective survey study design is not as ideal as a randomized controlled trial. Additional limitations of this study include small sample size, selection bias, and recall bias. Our results reveal poor patient awareness of and compliance with sun-protection measures while in an automobile. Skin cancer prevention efforts should be modified to specifically address automobile-related sun exposure. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  3. Turbulent current drive

    NASA Astrophysics Data System (ADS)

    Garbet, X.; Esteve, D.; Sarazin, Y.; Dif-Pradalier, G.; Ghendrih, P.; Grandgirard, V.; Latu, G.; Smolyakov, A.

    2014-11-01

    The Ohm's law is modified when turbulent processes are accounted for. Besides an hyper-resistivity, already well known, pinch terms appear in the electron momentum flux. Moreover it appears that turbulence is responsible for a source term in the Ohm's law, called here turbulent current drive. Two terms contribute to this source. The first term is a residual stress in the momentum flux, while the second contribution is an electro-motive force. A non zero average parallel wave number is needed to get a finite source term. Hence a symmetry breaking mechanism must be invoked, as for ion momentum transport. E × B shear flows and turbulence intensity gradients are shown to provide similar contributions. Moreover this source term has to compete with the collision friction term (resistivity). The effect is found to be significant for a large scale turbulence in spite of an unfavorable scaling with the ratio of the electron to ion mass. Turbulent current drive appears to be a weak effect in the plasma core, but could be substantial in the plasma edge where it may produce up to 10 % of the local current density.

  4. Driving on ice: impaired driving skills in current methamphetamine users.

    PubMed

    Bosanquet, David; Macdougall, Hamish G; Rogers, Stephen J; Starmer, Graham A; McKetin, Rebecca; Blaszczynski, Alexander; McGregor, Iain S

    2013-01-01

    Previous research indicates a complex link between methamphetamine (METH) and driving performance. Acute dosing with amphetamines has improved driving-related performance in some laboratory studies, while epidemiological studies suggest an association between METH use, impaired driving, and accident culpability. Current METH users were compared to a control group of nonusers on driving simulator performance. Groups were matched for age, gender, and driving experience. Subjects were assessed for current drug use, drug dependence, and drug levels in saliva/blood as well as personality variables, sleepiness, and driving performance. METH users, most of whom met the criteria for METH dependence, were significantly more likely to speed and to weave from side to side when driving. They also left less distance between their vehicle and oncoming vehicles when making a right-hand turn. This risky driving was not associated with current blood levels of METH or its principal metabolite, amphetamine, which varied widely within the METH group. Other drugs were detected (principally low levels of THC or MDMA) in some METH users, but at levels that were unlikely to impair driving performance. There were higher levels of impulsivity and antisocial personality disorder in the METH-using cohort. These findings confirm indications from epidemiological studies of an association between METH use and impaired driving ability and provide a platform for future research to further explore the factors contributing to increased accident risk in this population.

  5. Glaucoma and Driving: On-Road Driving Characteristics

    PubMed Central

    Wood, Joanne M.; Black, Alex A.; Mallon, Kerry; Thomas, Ravi; Owsley, Cynthia

    2016-01-01

    Purpose To comprehensively investigate the types of driving errors and locations that are most problematic for older drivers with glaucoma compared to those without glaucoma using a standardized on-road assessment. Methods Participants included 75 drivers with glaucoma (mean = 73.2±6.0 years) with mild to moderate field loss (better-eye MD = -1.21 dB; worse-eye MD = -7.75 dB) and 70 age-matched controls without glaucoma (mean = 72.6 ± 5.0 years). On-road driving performance was assessed in a dual-brake vehicle by an occupational therapist using a standardized scoring system which assessed the types of driving errors and the locations where they were made and the number of critical errors that required an instructor intervention. Driving safety was rated on a 10-point scale. Self-reported driving ability and difficulties were recorded using the Driving Habits Questionnaire. Results Drivers with glaucoma were rated as significantly less safe, made more driving errors, and had almost double the rate of critical errors than those without glaucoma. Driving errors involved lane positioning and planning/approach, and were significantly more likely to occur at traffic lights and yield/give-way intersections. There were few between group differences in self-reported driving ability. Conclusions Older drivers with glaucoma with even mild to moderate field loss exhibit impairments in driving ability, particularly during complex driving situations that involve tactical problems with lane-position, planning ahead and observation. These results, together with the fact that these drivers self-report their driving to be relatively good, reinforce the need for evidence-based on-road assessments for evaluating driving fitness. PMID:27472221

  6. Parkinson's disease and driving ability

    PubMed Central

    Singh, Rajiv; Pentland, Brian; Hunter, John; Provan, Frances

    2007-01-01

    Objectives To explore the driving problems associated with Parkinson's disease (PD) and to ascertain whether any clinical features or tests predict driver safety. Methods The driving ability of 154 individuals with PD referred to a driving assessment centre was determined by a combination of clinical tests, reaction times on a test rig and an in‐car driving test. Results The majority of cases (104, 66%) were able to continue driving although 46 individuals required an automatic transmission and 10 others needed car modifications. Ability to drive was predicted by the severity of physical disease, age, presence of other associated medical conditions, particularly dementia, duration of disease, brake reaction, time on a test rig and score on a driving test (all p<0.001). The level of drug treatment and the length of driving history were not correlated. Discriminant analysis revealed that the most important features in distinguishing safety to drive were severe physical disease (Hoehn and Yahr stage 3), reaction time, moderate disease associated with another medical condition and high score on car testing. Conclusions Most individuals with PD are safe to drive, although many benefit from car modifications or from using an automatic transmission. A combination of clinical tests and in‐car driving assessment will establish safety to drive, and a number of clinical correlates can be shown to predict the likely outcome and may assist in the decision process. This is the largest series of consecutive patients seen at a driving assessment centre reported to date, and the first to devise a scoring system for on‐road driving assessment. PMID:17178820

  7. Marked over expression of uncoupling protein-2 in beta cells exerts minor effects on mitochondrial metabolism

    SciTech Connect

    Hals, Ingrid K.; Ogata, Hirotaka; Pettersen, Elin; Ma, Zuheng; Bjoerklund, Anneli; Skorpen, Frank; Egeberg, Kjartan Wollo; Grill, Valdemar

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer The impact of UCP-2 over expression on mitochondrial function is controversial. Black-Right-Pointing-Pointer We tested mitochondrial functions at defined levels of overexpression. Black-Right-Pointing-Pointer We find minor increases of fatty acid oxidation and uncoupling. Black-Right-Pointing-Pointer Effects were seen only at high level (fourfold) of over expression. Black-Right-Pointing-Pointer Hence it is doubtful whether these effects are of importance in diabetes. -- Abstract: Evidence is conflicting as to the impact of elevated levels of uncoupling protein-2 (UCP-2) on insulin-producing beta cells. Here we investigated effects of a fourfold induction of UCP-2 protein primarily on mitochondrial parameters and tested for replication of positive findings at a lower level of induction. We transfected INS-1 cells to obtain a tet-on inducible cell line. A 48 h exposure to 1 {mu}g/ml of doxycycline (dox) induced UCP-2 fourfold (424 {+-} 113%, mean {+-} SEM) and 0.1 {mu}g/ml twofold (178 {+-} 29%, n = 3). Fourfold induced cells displayed normal viability (MTT, apoptosis), normal cellular insulin contents and, glucose-induced insulin secretion (+27 {+-} 11%) as well as D-[U-{sup 14}C]-glucose oxidation (+5 {+-} 9% at 11 mM glucose). Oxidation of [1-{sup 14}C]-oleate was increased from 4088 to 5797 fmol/{mu}g prot/2 h at 3.3 mM glucose, p < 0.03. Oxidation of L-[{sup 14}C(U)]-glutamine was unaffected. Induction of UCP-2 did not significantly affect measures of mitochondrial membrane potential (Rhodamine 123) or mitochondrial mass (Mitotracker Green) and did not affect ATP levels. Oligomycin-inhibited oxygen consumption (a measure of mitochondrial uncoupling) was marginally increased, the effect being significant in comparison with dox-only treated cells, p < 0.05. Oxygen radicals, assessed by dichlorofluorescin diacetate, were decreased by 30%, p < 0.025. Testing for the lower level of UCP-2 induction did not reproduce any of the

  8. S-phase kinase-associated protein 2 knockdown blocks colorectal cancer growth via regulation of both p27 and p16 expression.

    PubMed

    Xu, S-Y; Wang, F; Wei, G; Wang, B; Yang, J-Y; Huang, Y-Z; Zhang, L; Zheng, F; Guo, L-Y; Wang, J-N; Tang, J-M

    2013-12-01

    The objective of this study was to determine the role and mechanism of S-phase kinase-associated protein 2 (Skp2) in colorectal cancer cell proliferation and survival both in vitro and in vivo. Adenoviral vector expressing Skp2 short hairpin RNA was transduced into SW480 cells. The effects of Skp2 on cell cycle and survival were assessed by Flow Cytometry. Cell proliferation was analyzed by MTT assay. The expression of cell cycle regulators p16 and p27 were measured by western blot. In vivo, human colorectal cancer was produced by xenograft of cancer cells in nude mouse. Tumor growth inhibitory rate was calculated to generate growth curve. Tumor growth was monitored by examining proliferating cell nuclear antigen expression, whereas tumor cell apoptosis was detected by TdT-mediated dUTP nick-end labeling (TUNEL) staining. Knockdown of Skp2 blocked SW480 tumor cell growth and induced cell apoptosis. Skp2 appeared to be very important for the progression of cell cycle at G1/S phase. In vivo, blockade of Skp2 expression inhibited tumor growth and induced tumor apoptosis. Mechanistically, Skp2 regulated the expression of both p27 and p16 both in vitro and in vivo. The conclusion that we derive from this study is that Skp2 regulates colorectal cancer cell growth by inhibiting the expression of cell cycle regulator p27 and p16.

  9. Vascular calcification in chronic kidney disease is induced by bone morphogenetic protein-2 via a mechanism involving the Wnt/β-catenin pathway.

    PubMed

    Rong, Shu; Zhao, Xuezhi; Jin, Xiucai; Zhang, Zheng; Chen, Lei; Zhu, Yuxian; Yuan, Weijie

    2014-01-01

    Vascular calcification (VC), in which vascular smooth muscle cells (VSMCs) undergo a phenotypic transformation into osteoblast-like cells, is one of the emergent risk factors for the accelerated atherosclerosis process characteristic of chronic kidney disease (CKD). Phosphate is an important regulator of VC. The expression of different smooth muscle cell or osteogenesis markers in response to high concentrations of phosphate or exogenous bone morphogenetic protein 2 (BMP-2) was examined by qRT-PCR and western blotting in rat VSMCs. Osteocalcin secretion was measured by radioimmunoassay. Differentiation and calcification of VSMCs were examined by alkaline phosphatase (ALP) activity assay and Alizarin staining. Short hairpin RNA-mediated silencing of β-catenin was performed to examine the involvement of Wnt/β-catenin signaling in VSMC calcification and osteoblastic differentiation induced by high phosphate or BMP-2. Apoptosis was determined by TUNEL assay and immunofluorescence imaging. BMP-2 serum levels were significantly higher in CKD patients than in controls. High phosphate concentrations and BMP-2 induced VSMC apoptosis and upregulated the expression of β-catenin, Msx2, Runx2 and the phosphate cotransporter Pit1, whereas a BMP-2 neutralization antibody reversed these effects. Knockdown of β-catenin abolished the effect of high phosphate and BMP-2 on VSMC apoptosis and calcification. BMP-2 plays a crucial role in calcium deposition in VSMCs and VC in CKD patients via a mechanism involving the Wnt/β-catenin pathway.

  10. ASC directs NF-kappaB activation by regulating receptor interacting protein-2 (RIP2) caspase-1 interactions.

    PubMed

    Sarkar, Anasuya; Duncan, Michelle; Hart, Judy; Hertlein, Erin; Guttridge, Denis C; Wewers, Mark D

    2006-04-15

    Receptor interacting protein-2 (RIP2) is a caspase recruitment domain (CARD)-containing kinase that interacts with caspase-1 and plays an important role in NF-kappaB activation. Apoptosis-associated speck-like protein containing a CARD (ASC) is a PYRIN and CARD-containing molecule, important in the induction of apoptosis and caspase-1 activation. Although RIP2 has also been linked to caspase-1 activation, RIP2 knockout animals fail to show a defect in caspase-1-mediated processing of proIL-1beta to its active form. Therefore, RIP2 function in binding to caspase-1 remains poorly understood. We hypothesized that caspase-1 may serve as a scaffolding molecule that promotes RIP2 interaction with IkappaB kinase-gamma thus inducing NF-kappaB activation. We further hypothesized that ASC, which also interacts with caspase-1 via its CARD, may interfere with the caspase-1 RIP2 interaction. In HEK293 cells, ASC induced prominent activation of caspase-1 and proIL-1beta processing. RIP2 transient transfection induced transcription of an NF-kappaB reporter gene. This RIP2-induced NF-kappaB activity and caspase-1 binding was inhibited in a dose-dependent fashion by ASC. Consistent with a role for caspase-1 as a scaffold for RIP2, caspase-1 knockout macrophages were suppressed in their ability to activate NF-kappaB, and septic caspase-1 knockout animals produced less IL-6, a functional marker of NF-kappaB activity. Lastly, THP-1 cells treated with small interfering RNA for ASC decreased their caspase-1 activity while enhancing their NF-kappaB signal. These data suggest that ASC may direct caspase-1 away from RIP2-mediated NF-kappaB activation, toward caspase-1-mediated processing of proIL-1beta by interfering with the RIP2 caspase-1 interaction.

  11. Learning to drive: learners' self-reported cognitive failure level predicts driving instructor's observation rating of driving performance.

    PubMed

    Elfering, Achim; Ruppen, Veronique; Grebner, Simone

    2013-01-01

    Evidence increases that cognitive failure may be used to screen for drivers at risk. Until now, most studies have relied on driving learners. This exploratory pilot study examines self-report of cognitive failure in driving beginners and error during real driving as observed by driving instructors. Forty-two driving learners of 14 driving instructors filled out a work-related cognitive failure questionnaire. Driving instructors observed driving errors during the next driving lesson. In multiple linear regression analysis, driving errors were regressed on cognitive failure with the number of driving lessons as an estimator of driving experience controlled. Higher cognitive failure predicted more driving errors (p < .01) when age, gender and driving experience were controlled in analysis. Cognitive failure was significantly associated with observed driving errors. Systematic research on cognitive failure in driving beginners is recommended.

  12. Flavones induce neutrophil apoptosis by down-regulation of Mcl-1 via a proteasomal-dependent pathway.

    PubMed

    Lucas, Christopher D; Allen, Keith C; Dorward, David A; Hoodless, Laura J; Melrose, Lauren A; Marwick, John A; Tucker, Carl S; Haslett, Christopher; Duffin, Rodger; Rossi, Adriano G

    2013-03-01

    Neutrophil apoptosis and subsequent nonphlogistic clearance by surrounding phagocytes are key to the successful resolution of neutrophilic inflammation, with dysregulated apoptosis reported in multiple human inflammatory diseases. Enhancing neutrophil apoptosis has proresolution and anti-inflammatory effects in preclinical models of inflammation. Here we investigate the ability of the flavones apigenin, luteolin, and wogonin to induce neutrophil apoptosis in vitro and resolve neutrophilic inflammation in vivo. Human neutrophil apoptosis was assessed morphologically and by flow cytometry following incubation with apigenin, luteolin, and wogonin. All three flavones induced time- and concentration-dependent neutrophil apoptosis (apigenin, EC=12.2 μM; luteolin, EC=14.6 μM; and wogonin, EC=28.9 μM). Induction of apoptosis was caspase dependent, as it was blocked by the broad-spectrum caspase inhibitor Q-VD-OPh and was associated with both caspase-3 and caspase-9 activation. Flavone-induced apoptosis was preceded by down-regulation of the prosurvival protein Mcl-1, with proteasomal inhibition preventing flavone-induced Mcl-1 down-regulation and apoptosis. The flavones abrogated the survival effects of mediators that prolong neutrophil life span, including lipoteichoic acid, peptidoglycan, dexamethasone, and granulocyte-macrophage colony stimulating factor, by driving apoptosis. Furthermore, wogonin enhanced resolution of established neutrophilic inflammation in a zebrafish model of sterile tissue injury. Wogonin-induced resolution was dependent on apoptosis in vivo as it was blocked by caspase inhibition. Our data show that the flavones induce neutrophil apoptosis and have potential as neutrophil apoptosis-inducing anti-inflammatory, proresolution agents.

  13. Hyperactive children as young adults: driving abilities, safe driving behavior, and adverse driving outcomes.

    PubMed

    Fischer, Mariellen; Barkley, Russell A; Smallish, Lori; Fletcher, Kenneth

    2007-01-01

    ADHD has been linked to poorer driving abilities and greater adverse outcomes (crashes, citations) in clinic-referred cases of teens and adults with ADHD. No study, however, has focused systematically on ADHD children followed into adulthood. The present paper does so while measuring driving-related cognitive abilities, driving behavior, and history of adverse driving outcomes. A multi-method, multi-source battery of driving measures was collected at the young adult follow-up on hyperactive (H; N=147; mean age=21.1) and community control children (CC; N=71; mean age=20.5) followed for more than 13 years. More of the H than CC groups had been ticketed for reckless driving, driving without a license, hit-and-run crashes, and had their licenses suspended or revoked. Official driving records found more of the H group having received traffic citations and a greater frequency of license suspensions. The cost of damage in their initial crashes was also significantly greater in the H than CC group. Both self-report and other ratings of actual driving behavior revealed less safe driving practices being used by the H group. Observations by driving instructors during a behind-the-wheel road test indicated significantly more impulsive errors. Performance on a simulator further revealed slower and more variable reaction times, greater errors of impulsiveness (false alarms, poor rule following), more steering variability, and more scrapes and crashes of the simulated vehicle against road boundaries in the H than in the CC group. These findings suggest that children growing up with ADHD may either have fewer driving risks or possibly under-report those risks relative to clinic-referred adults with this disorder. Deficits in simulator performance and safe driving behavior, however, are consistent with clinic-referred adults with ADHD suggesting ongoing risks for such adverse driving outcomes in children growing up with ADHD.

  14. QUICK RELEASABLE DRIVE

    DOEpatents

    Dickson, J.J.

    1958-07-01

    A quick releasable mechanical drive system suitable for use in a nuclear reactor is described. A small reversible motor positions a control rod by means of a worm and gear speed reducer, a magnetic torque clutch, and a bell crank. As the control rod is raised to the operating position, a heavy coil spring is compressed. In the event of an emergency indicated by either a''scram'' signal or a power failure, the current to the magnetic clutch is cut off, thereby freeing the coil spring and the bell crank positioner from the motor and speed reduction gearing. The coil spring will immediately act upon the bell crank to cause the insertion of the control rod. This arrangement will allow the slow, accurate positioning of the control rod during reactor operation, while providing an independent force to rapidly insert the rod in the event of an emergency.

  15. Magnetostrictive direct drive motors

    NASA Technical Reports Server (NTRS)

    Naik, Dipak; Dehoff, P. H.

    1992-01-01

    A new rare earth alloy, Terfenol-D, combines low frequency operation and extremely high energy density with high magnetostriction. Its material properties make it suitable as a drive element for actuators requiring high output torque. The high strains, the high forces and the high controllability of Terfenol alloys provide a powerful and challenging basis for new ways to generate motion in actuators. Two prototypes of motors using Terfenol-D rods were developed at NASA Goddard. The basic principles of operation are provided of the motor along with other relevant details. A conceptual design of a torque limiting safety clutch/brake under development is illustrated. Also, preliminary design drawings of a linear actuator using Terfenol-D is shown.

  16. What Drives Blend Miscibility?

    NASA Astrophysics Data System (ADS)

    White, Ronald; Lipson, Jane

    2014-03-01

    With no mixture data available, can one predict phase behavior in polymeric systems based on pure component information only? Due to the very weak entropic drive for large molecules to mix, predicting and understanding miscibility behavior is indeed very difficult. However, while not perfect, some a priori insight is attainable when pure component properties are analyzed within the framework of a theoretical model. A theory provides a platform, allowing one to define quantities and other measures that may not always be directly measurable, but, are physically appealing and insightful none-the-less. Are there properties that can explain for example, why a polymer like polyisobutylene (PIB) exhibits such different phase behavior compared to other polyolefins? Applying our simple lattice-based equation of state, we have recently analyzed a large number of different polymers. In this talk we will present insights from trends and patterns we have observed. Work supported by the National Science Foundation.

  17. [Car driving and psychiatry].

    PubMed

    Jonas, Carol

    2015-10-01

    Among the specialties involved in the order of 31 August 2010, psychiatry is in Chapter IV alongside addictive behavior and drug use may impair the ability of the driver. As well as for personal vehicles for professional vehicles the incompatibility of health with driving exists when clinical factors can interfere with the skills required of the driver. There would simply absolute incompatibility for psychoses in active phase. In the other phases of psychosis is at the discretion of specialist as for illiteracy or social maladjustment. The role of the authorized psychiatrist is therefore always subjective. This article also makes room for attention-deficit disorder with hyperactivity (ADHD), not listed, but the subject of numerous articles in the English literature.

  18. Rotary drive mechanism

    DOEpatents

    Kenderdine, Eugene W.

    1991-01-01

    A rotary drive mechanism includes a rotary solenoid having a stator and multi-poled rotor. A moving member rotates with the rotor and is biased by a biasing device. The biasing device causes a further rotational movement after rotation by the rotary solenoid. Thus, energization of the rotary solenoid moves the member in one direction to one position and biases the biasing device against the member. Subsequently, de-energization of the rotary solenoid causes the biasing device to move the member in the same direction to another position from where the moving member is again movable by energization and de-energization of the rotary solenoid. Preferably, the moving member is a multi-lobed cam having the same number of lobes as the rotor has poles. An anti-overdrive device is also preferably provided for preventing overdrive in the forward direction or a reverse rotation of the moving member and for precisely aligning the moving member.

  19. Methylselenium and Prostate Cancer Apoptosis

    DTIC Science & Technology

    2005-02-01

    15. NUMBER OF PAGES Selenium, methylselenol , prostate cancer chemoprevention, apoptosis 15 16. PRICE CODE 17. SECURITY CLASSIFICATION 18. SECURITY...that Methylselenol has been implicated as an active metabolite inhibit one or more steps in the natural history of prostate for the anticancer effect of...in PCa chemoprevention and therapy activity) for their apoptosis responses to the methylselenol by selenium compounds (8). Methylselenol has been impli

  20. [Apoptosis: cellular and clinical aspects].

    PubMed

    Løvschall, H; Mosekilde, L

    1997-04-01

    Removal of damaged cells is essential for the maintenance of life in multicellular organisms. The process of self destruction, apoptosis, eliminates surplus or damaged cells as part of the pathophysiological defence system. Apoptosis is essential in structural and functional organogenesis during embryological development. The physiological regulation of tissue kinetics is a product of both cell proliferation and cell death. Internal and external regulatory stimuli regulate the balance between apoptosis and mitosis by genetic interaction. Apoptosis is characterized by condensation of chromatine as a result of DNA degradation, formation of blebs in the plasma and nuclear membranes, condensation of cytoplasma, formation of vesicular apoptotic bodies, and phagocytosis by neighbouring cells without inflammatory response. A number of observations indicate that programmed cell death plays an important role in the regulation of cytofunctional homeostasis and defense against accumulation of damaged cells, eg with DNA alterations. Dysregulation of the apoptotic gene program, eg by mutations, may not only lead to loss or degeneration of tissue, but also to hyperproliferative and tumorigenic disorders. New evidence indicates that apoptosis regulation is important both in aging processes and diseases such as: neuropathies, immunopathies, viral infections, cancer, etc. Pharmacological intervention designed to modulate apoptosis seems to raise new possibilities in the treatment of disease.

  1. Electric Drive Study. Volume 1

    DTIC Science & Technology

    1987-12-21

    necessary and identify by block number) FIELD j GROUP SUB-GROUP IElectric Drives, Motors , Homopolar Motors , Induction Motof’s, I-u I ’Propulsion Systems...Planetary Final Drive (19.5 Ton) ( Homopolar ) . . . 80 5-32. Integrated Motor /Final Drive ....... ............ 82 5-33. Configuration II, 19.5 Ton...98 5-43. Homopolar Motor System Efficiency Map .... ......... 101 5-44. Potential Rotary Field Exciter Configuratio ......... 104 5-45

  2. Sequenced drive for rotary valves

    DOEpatents

    Mittell, Larry C.

    1981-01-01

    A sequenced drive for rotary valves which provides the benefits of applying rotary and linear motions to the movable sealing element of the valve. The sequenced drive provides a close approximation of linear motion while engaging or disengaging the movable element with the seat minimizing wear and damage due to scrubbing action. The rotary motion of the drive swings the movable element out of the flowpath thus eliminating obstruction to flow through the valve.

  3. Driving anger in Ukraine: Appraisals, not trait driving anger, predict anger intensity while driving.

    PubMed

    Stephens, A N; Hill, T; Sullman, M J M

    2016-03-01

    Trait driving anger is often, but not always, found to predict both the intensity of anger while driving and subsequent crash-related behaviours. However, a number of studies have not found support for a direct relationship between one's tendency to become angry and anger reported while driving, suggesting that other factors may mediate this relationship. The present self-report study investigated whether, in anger provoking driving situations, the appraisals made by drivers influence the relationship between trait and state anger. A sample of 339 drivers from Ukraine completed the 33-item version of the Driver Anger Scale (DAS; Deffenbacher et al., 1994) and eight questions about their most recent experience of driving anger. A structural equation model found that the intensity of anger experienced was predicted by the negative evaluations of the situation, which was in turn predicted by trait driving anger. However, trait driving anger itself did not predict anger intensity; supporting the hypothesis that evaluations of the driving situation mediate the relationship between trait and state anger. Further, the unique structure of the DAS required to fit the data from the Ukrainian sample, may indicate that the anger inducing situations in Ukraine are different to those of a more developed country. Future research is needed to investigate driving anger in Ukraine in a broader sample and also to confirm the role of the appraisal process in the development of driving anger in both developed and undeveloped countries.

  4. The drive-wise project: driving simulator training increases real driving performance in healthy older drivers

    PubMed Central

    Casutt, Gianclaudio; Theill, Nathan; Martin, Mike; Keller, Martin; Jäncke, Lutz

    2014-01-01

    Background: Age-related cognitive decline is often associated with unsafe driving behavior. We hypothesized that 10 active training sessions in a driving simulator increase cognitive and on-road driving performance. In addition, driving simulator training should outperform cognitive training. Methods: Ninety-one healthy active drivers (62–87 years) were randomly assigned to one of three groups: (1) a driving simulator training group, (2) an attention training group (vigilance and selective attention), or (3) a control group. The main outcome variables were on-road driving and cognitive performance. Seventy-seven participants (85%) completed the training and were included in the analyses. Training gains were analyzed using a multiple regression analysis with planned orthogonal comparisons. Results: The driving simulator-training group showed an improvement in on-road driving performance compared to the attention-training group. In addition, both training groups increased cognitive performance compared to the control group. Conclusion: Driving simulator training offers the potential to enhance driving skills in older drivers. Compared to the attention training, the simulator training seems to be a more powerful program for increasing older drivers' safety on the road. PMID:24860497

  5. Noninductive current drive in tokamaks

    SciTech Connect

    Uckan, N.A.

    1985-01-01

    Various current drive mechanisms may be grouped into four classes: (1) injection of energetic particle beams; (2) launching of rf waves; (3) hybrid schemes, which are combinations of various rf schemes (rf plus beams, rf and/or beam plus ohmic heating, etc.); and (4) other schemes, some of which are specific to reactor plasma conditions requiring the presence of alpha particle or intense synchrotron radiation. Particle injection schemes include current drive by neutral beams and relativistic electron beams. The rf schemes include current drive by the lower hybrid (LH) waves, the electron waves, the waves in the ion cyclotron range of frequencies, etc. Only a few of these approaches, however, have been tested experimentally, with the broadest data base available for LH waves. Included in this report are (1) efficiency criteria for current drive, (2) current drive by neutral beam injection, (3) LH current drive, (4) electron cyclotron current drive, (5) current drive by ion cyclotron waves - minority species heating, and (6) current drive by other schemes (such as hybrids and low frequency waves).

  6. Pecanex functions as a competitive endogenous RNA of S-phase kinase associated protein 2 in lung cancer.

    PubMed

    Li, Jingqiu; Tian, Haihua; Pan, Jinchang; Jiang, Nan; Yang, Jie; Zhou, Chengwei; Xu, Dazhi; Meng, Xiaodan; Gong, Zhaohui

    2017-10-10

    Investigating the RNA-RNA interactions involving in the initiation and progression of non-small cell lung cancer (NSCLC) may provide promising diagnostic and targeted therapeutic strategies. Here, we showed that pecanex (PCNX) positively regulates the mRNA and protein expressions of S-phase kinase associated protein 2 (Skp2) in miRNA- and 3' UTR-dependent manners. And miR-26, miR-182, miR-340 and miR-506 were verified as the common miRNAs shared by Skp2 and PCNX. Intriguingly, we initially uncovered that PCNX-3' UTR promotes cell growth, proliferation and cell cycle progression, and suppresses apoptosis of lung cancer cells, which is consistent with the oncogenic activity of Skp2-3' UTR. Consequently, PCNX was identified as a competitive endogenous RNA (ceRNA) of Skp2. Moreover, knockdown of PCNX inhibits EGF-induced Akt phosphorylation, which can be reversed by the silencing of Dicer. Finally, we further discovered that Skp2 and PCNX are coordinately upregulated in lung cancer tissues compared with the adjacent non-tumor tissues. Our study establishes for the first time the oncogenic property of PCNX-3' UTR and Skp2-3' UTR, and the PCNX-miRNA-Skp2 regulatory pattern, which may offer a molecular basis for the diagnosis and targeted therapy in NSCLC. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Rottlerin exhibits anti-cancer effect through inactivation of S phase kinase-associated protein 2 in pancreatic cancer cells

    PubMed Central

    Su, Jingna; Wang, Lixia; Yin, Xuyuan; Zhao, Zhe; Hou, Yingying; Ye, Xiantao; Zhou, Xiuxia; Wang, Zhiwei

    2016-01-01

    Rottlerin, a natural product isolated from Mallotus philippinensis, has been characterized as an effective chemoprevention agent in inhibiting tumor cell growth. Although multiple studies have revealed the role of rottlerin in tumorigenesis, the molecular mechanism of rottlerin-mediated anti-tumor activity has not been fully elucidated. It has been reported that Skp2 (S-phase kinase associated protein 2) plays an oncogenic role in human malignancies, indicating that inactivation of Skp2 could be a promising approach for the treatment of cancers. Therefore, in this study, we aim to investigate whether rottlerin exhibits its anti-tumor activities via targeting Skp2 pathway in pancreatic cancer. We found that rottlerin inhibited cell growth, induced apoptosis, arrested cell cycle, and retarded cell invasion and migration. Notably, we observed that the expression of Skp2 was significantly decreased in rottlerin-treated pancreatic cancer cells. Importantly, overexpression of Skp2 abrogated the anti-tumor function induced by rottlerin in pancreatic cancer cells. Consistently, depletion of Skp2 promoted rottlerin-mediated inhibition of cell growth and invasion. Collectively, our study demonstrated that rottlerin could suppress Skp2 expression and subsequently exert its tumor suppressive function in pancreatic cancer cells, suggesting that rottlerin might be a potential therapeutic compound for treating pancreatic cancer. PMID:27822410

  8. Vesicle-associated membrane protein 2 mediates trafficking of {alpha}5{beta}1 integrin to the plasma membrane

    SciTech Connect

    Hasan, Nazarul; Hu, Chuan

    2010-01-01

    Integrins are major receptors for cell adhesion to the extracellular matrix (ECM). As transmembrane proteins, the levels of integrins at the plasma membrane or the cell surface are ultimately determined by the balance between two vesicle trafficking events: endocytosis of integrins at the plasma membrane and exocytosis of the vesicles that transport integrins. Here, we report that vesicle-associated membrane protein 2 (VAMP2), a SNARE protein that mediates vesicle fusion with the plasma membrane, is involved in the trafficking of {alpha}5{beta}1 integrin. VAMP2 was present on vesicles containing endocytosed {beta}1 integrin. Small interfering RNA (siRNA) silencing of VAMP2 markedly reduced cell surface {alpha}5{beta}1 and inhibited cell adhesion and chemotactic migration to fibronectin, the ECM ligand of {alpha}5{beta}1, without altering cell surface expression of {alpha}2{beta}1 integrin or {alpha}3{beta}1 integrin. By contrast, silencing of VAMP8, another SNARE protein, had no effect on cell surface expression of the integrins or cell adhesion to fibronectin. In addition, VAMP2-mediated trafficking is involved in cell adhesion to collagen but not to laminin. Consistent with disruption of integrin functions in cell proliferation and survival, VAMP2 silencing diminished proliferation and triggered apoptosis. Collectively, these data indicate that VAMP2 mediates the trafficking of {alpha}5{beta}1 integrin to the plasma membrane and VAMP2-dependent integrin trafficking is critical in cell adhesion, migration and survival.

  9. VIEW OF BEND IN CEDAR DRIVE WITH 603 CEDAR DRIVE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF BEND IN CEDAR DRIVE WITH 603 CEDAR DRIVE ON RIGHT. VIEW FACING NORTHEAST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Intersection of Acacia Road and Brich Circle, Pearl City, Honolulu County, HI

  10. 26. CAN CONVEYOR DRIVE MECHANISM Empty can conveyor driving mechanism, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    26. CAN CONVEYOR DRIVE MECHANISM Empty can conveyor driving mechanism, second floor above canning area. The belt has been removed from the conveyor, but sections of can conveyor tracks are visible on the floor. - Hovden Cannery, 886 Cannery Row, Monterey, Monterey County, CA

  11. Driving for All Seasons and Reasons. Book Four. Project Drive.

    ERIC Educational Resources Information Center

    Zook, Doris; And Others

    This Project Drive booklet titled Driving for All Seasons and Reasons is one of eight booklets designed for intermediate-level English-as-a-second-language students and low-level adult basic education/basic reading students. The goal of the booklet is to aid the student in developing the oral and sight vocabulary necessary for a basic driver…

  12. To Drive or Not to Drive: Assessment Dilemmas for GPs

    PubMed Central

    Sims, J.; Rouse-Watson, S.; Schattner, P.; Beveridge, A.; Jones, K. M.

    2012-01-01

    Introduction. Most Australians are dependent on their cars for mobility, thus relinquishing driving licences for medical reasons poses challenges. Aims. To investigate how general practitioners (GPs) recognise and manage patients' fitness to drive, GPs' attitudes and beliefs about their role as assessors, and GPs' experiences in assessing and reporting to driving authorities and identify GPs' educational needs. Methods. Mixed methods: questionnaire mailed to GPs from three rural and two metropolitan Divisons of General Practice in Victoria, Australia. Results. 217/1028 completed questionnaires were returned: 85% recognised a patients' fitness to drive, 54% felt confident in their assessment ability, 21% felt the GP should have primary responsibility for declaring patients' fitness to drive, 79% felt that reporting a patient would negatively impact on the doctor-patient relationship, 74% expressed concern about legal liability, and 74% favoured further education. Discussion. This study provides considerable information including recommendations about GP education, the assessment forms, and legal clarification. PMID:22295200

  13. The "genetics" of driving behavior: parents' driving style predicts their children's driving style.

    PubMed

    Bianchi, Alessandra; Summala, Heikki

    2004-07-01

    It can be hypothesized that children inherit their parents' driving habits both through genetic disposition and model learning. A few studies have shown indeed that parents' and their children's traffic convictions and accidents correlate which, however, may be due to life style and other exposure factors. This study aimed at investigating the relationships between parents' and their children's self-reported driving behavior. The subjects were 174 parent-child pairs who independently completed a questionnaire. Driving behavior-driving style-was evaluated by means of Manchester driver behavior questionnaire (DBQ), while data about driving exposure, life style, accidents, and traffic tickets were also collected. A series of regression models indicated that parents' self-reported driving behavior explains their children's respective self-reported behavior, even when exposure and demographic and life-style factors are controlled.

  14. Drive-By Pharming

    NASA Astrophysics Data System (ADS)

    Stamm, Sid; Ramzan, Zulfikar; Jakobsson, Markus

    This paper describes an attack concept termed Drive-by Pharming where an attacker sets up a web page that, when simply viewed by the victim (on a JavaScript-enabled browser), attempts to change the DNS server settings on the victim's home broadband router. As a result, future DNS queries are resolved by a DNS server of the attacker's choice. The attacker can direct the victim's Internet traffic and point the victim to the attacker's own web sites regardless of what domain the victim thinks he is actually going to, potentially leading to the compromise of the victim's credentials. The same attack methodology can be used to make other changes to the router, like replacing its firmware. Routers could then host malicious web pages or engage in click fraud. Since the attack is mounted through viewing a web page, it does not require the attacker to have any physical proximity to the victim nor does it require the explicit download of traditional malicious software. The attack works under the reasonable assumption that the victim has not changed the default management password on their broadband router.

  15. Handbook for Driving Knowledge Testing.

    ERIC Educational Resources Information Center

    Pollock, William T.; McDole, Thomas L.

    Materials intended for driving knowledge test development for use by operational licensing and education agencies are presented. A pool of 1,313 multiple choice test items is included, consisting of sets of specially developed and tested items covering principles of safe driving, legal regulations, and traffic control device knowledge pertinent to…

  16. Handbook for Driving Knowledge Testing.

    ERIC Educational Resources Information Center

    Pollock, William T.; McDole, Thomas L.

    Materials intended for driving knowledge test development for use by operational licensing and education agencies are presented. A pool of 1,313 multiple choice test items is included, consisting of sets of specially developed and tested items covering principles of safe driving, legal regulations, and traffic control device knowledge pertinent to…

  17. Low Sex Drive in Women

    MedlinePlus

    Diseases and Conditions Low sex drive in women By Mayo Clinic Staff A woman's sexual desire naturally fluctuates over the years. Highs and lows commonly ... and anti-seizure medications also can cause low sex drive in women. If you have a persistent ...

  18. Parental Role in Teenage Driving.

    ERIC Educational Resources Information Center

    Preusser, David F.; And Others

    1985-01-01

    This study examined the role of parents in students' early driving experiences and travel as passengers and its effects on students' crash and injury rates. Over 50,000 high school students responded to a questionnaire covering obtaining a license, learning to drive, vehicle access, parental rules, and student attitudes on parental role. (BS)

  19. Bidirectional drive and brake mechanism

    NASA Technical Reports Server (NTRS)

    Swan, Scott A. (Inventor)

    1991-01-01

    A space transport vehicle is disclosed as including a body which is arranged to be movably mounted on an elongated guide member disposed in outer space and driven therealong. A drive wheel is mounted on a drive shaft and arranged to be positioned in rolling engagement with the elongated guide carrying the vehicle. A brake member is arranged on the drive shaft for movement into and out of engagement with an adjacent surface of the drive wheel. An actuator is mounted on the body to be manually moved back and forth between spaced positions in an arc of movement. A ratchet-and-pawl mechanism is arranged to operate upon movements of the actuator in one direction between first and second positions for coupling the actuator to the drive wheel to incrementally rotate the wheel in one rotational direction and to operate upon movements of the actuator in the opposite direction for uncoupling the actuator from the wheel. The brake member is threadedly coupled to the drive shaft in order that the brake member will be operated only when the actuator is moved on beyond its first and second positions for shifting the brake member along the drive shaft and into frictional engagement with the adjacent surface on the drive wheel.

  20. Hydraulic drive system for platen

    SciTech Connect

    Kubik, P.A.

    1988-06-21

    A hydraulic drive system for driving a platen in a forward and return reciprocatory stroke cycle is described comprising a rigid platen, means for guiding the platen for forward and return movement along a fixed linear path between a rest position and an extended position, a crank arm mounted for rotation about a fixed axis normal to the linear path, link means coupling the crank arm to the platen for driving the platen from the rest position to the extended position upon rotation of the crank about the axis through 180 degrees in a first direction from a start position wherein the crank extends from the axis parallel to the linear path and for returning the platen from the extended position to the rest position upon rotation of the crank in the opposite direction from the finish position to the start position. First reversible hydraulic motor means for driving the crank in rotation about the axis, second motor means connected to the platen for driving the platen between the rest position and the extending position, variable speed hydraulic pump means for generating a variable flow of fluid under pressure to drive the first and second motor means, reversing valve means hydraulically connected across the pump means, and conduit means hydraulically connecting the first and second motor means in parallel with each other to the reversing valve means to enable the pump means to drive both the motor means in unison to cooperatively drive the platen in forward or return movement.

  1. Driving difficulties in Parkinson's disease

    PubMed Central

    Rizzo, Matthew; Uc, Ergun Y; Dawson, Jeffrey; Anderson, Steven; Rodnitzky, Robert

    2011-01-01

    Safe driving requires the coordination of attention, perception, memory, motor and executive functions (including decision-making) and self-awareness. PD and other disorders may impair these abilities. Because age or medical diagnosis alone is often an unreliable criterion for licensure, decisions on fitness to drive should be based on empirical observations of performance. Linkages between cognitive abilities measured by neuropsychological tasks, and driving behavior assessed using driving simulators, and natural and naturalistic observations in instrumented vehicles, can help standardize the assessment of fitness-to-drive. By understanding the patterns of driver safety errors that cause crashes, it may be possible to design interventions to reduce these errors and injuries and increase mobility. This includes driver performance monitoring devices, collision alerting and warning systems, road design, and graded licensure strategies. PMID:20187237

  2. Quantum gates by periodic driving

    PubMed Central

    Shi, Z. C.; Wang, W.; Yi, X. X.

    2016-01-01

    Topological quantum computation has been extensively studied in the past decades due to its robustness against decoherence. One way to realize the topological quantum computation is by adiabatic evolutions—it requires relatively long time to complete a gate, so the speed of quantum computation slows down. In this work, we present a method to realize single qubit quantum gates by periodic driving. Compared to adiabatic evolution, the single qubit gates can be realized at a fixed time much shorter than that by adiabatic evolution. The driving fields can be sinusoidal or square-well field. With the sinusoidal driving field, we derive an expression for the total operation time in the high-frequency limit, and an exact analytical expression for the evolution operator without any approximations is given for the square well driving. This study suggests that the period driving could provide us with a new direction in regulations of the operation time in topological quantum computation. PMID:26911900

  3. Driving the Landscape

    NASA Astrophysics Data System (ADS)

    Haff, P. K.

    2012-12-01

    Technological modification of the earth's surface (e.g., agriculture, urbanization) is an old story in human history, but what about the future? The future of landscape in an accelerating technological world, beyond a relatively short time horizon, lies hidden behind an impenetrable veil of complexity. Sufficiently complex dynamics generates not only the trajectory of a variable of interest (e.g., vegetation cover) but also the environment in which that variable evolves (e.g., background climate). There is no way to anticipate what variables will define that environment—the dynamics creates its own variables. We are always open to surprise by a change of conditions we thought or assumed were fixed or by the appearance of new phenomena of whose possible existence we had been unaware or thought unlikely. This is especially true under the influence of technology, where novelty is the rule. Lack of direct long-term predictability of landscape change does not, however, mean we cannot say anything about its future. The presence of persistence (finite time scales) in a system means that prediction by a calibrated numerical model should be good for a limited period of time barring bad luck or faulty implementation. Short-term prediction, despite its limitations, provides an option for dealing with the longer-term future. If a computer-controlled car tries to drive itself from New York to Los Angeles, no conceivable (or possible) stand-alone software can be constructed to predict a priori the space-time trajectory of the vehicle. Yet the drive is normally completed easily by most drivers. The trip is successfully completed because each in a series of very short (linear) steps can be "corrected" on the fly by the driver, who takes her cues from the environment to keep the car on the road and headed toward its destination. This metaphor differs in a fundamental way from the usual notion of predicting geomorphic change, because it involves a goal—to reach a desired

  4. Electric vehicle drive systems

    NASA Astrophysics Data System (ADS)

    Appleyard, M.

    1992-01-01

    New legislation in the State of California requires that 2% of vehicles sold there from 1998 will be 'zero-emitting'. This provides a unique market opportunity for developers of electric vehicles but substantial improvements in the technology are probably required if it is to be successfully exploited. There are around a dozen types of battery that are potentially relevant to road vehicles but, at the present, lead/acid and sodium—sulphur come closest to combining acceptable performance, life and cost. To develop an efficient, lightweight electric motor system requires up-to-date techniques of magnetics design, and the latest power-electronic and microprocessor control methods. Brushless machines, coupled with solid-state inverters, offer the most economical solution for mass production, even though their development costs are higher than for direct-current commutator machines. Fitted to a small car, even the highest energy-density batteries will only provide around 200 km average range before recharging. Therefore, some form of supplementary on-board power generation will probably be needed to secure widespread acceptance by the driving public. Engine-driven generators of quite low power can achieve useful increases in urban range but will fail to qualify as 'zero-emitting'. On the other hand, if the same function could be economically performed by a small fuel-cell using hydrogen derived from a methanol reformer, then most of the flexibility provided by conventional vehicles would be retained. The market prospects for electric cars would then be greatly enhanced and their dependence on very advanced battery technology would be reduced.

  5. Placental apoptosis in recurrent miscarriage.

    PubMed

    Atia, Tarek A

    2017-09-01

    Apoptosis is an interactive and dynamic biological process involved in all phases of embryogenesis. We aimed to study the effect of placental apoptosis on recurrent miscarriage (RM). Placental tissue samples were collected from 40 women with RM (study group) and 30 women with sporadic spontaneous abortion (control group). Samples were prepared and stained immunohistochemically with markers for both the apoptotic protein (p53) and anti-apoptotic Bcl-2 antibodies. Our results showed that expression of the apoptotic (p53) protein was significantly increased in the placental tissues of the RM group (p = 0.003). By contrast, the expression of anti-apoptotic (Bcl-2) antibodies was significantly increased in the placental tissues of the control group (p = 0.025). We concluded that placental apoptosis plays a crucial role in pregnancy continuation. However, increased p53 expression in placental tissue in early pregnancy could negatively affect pregnancy continuation. Copyright © 2017. Published by Elsevier Taiwan.

  6. Linear Back-Drive Differentials

    NASA Technical Reports Server (NTRS)

    Waydo, Peter

    2003-01-01

    Linear back-drive differentials have been proposed as alternatives to conventional gear differentials for applications in which there is only limited rotational motion (e.g., oscillation). The finite nature of the rotation makes it possible to optimize a linear back-drive differential in ways that would not be possible for gear differentials or other differentials that are required to be capable of unlimited rotation. As a result, relative to gear differentials, linear back-drive differentials could be more compact and less massive, could contain fewer complex parts, and could be less sensitive to variations in the viscosities of lubricants. Linear back-drive differentials would operate according to established principles of power ball screws and linear-motion drives, but would utilize these principles in an innovative way. One major characteristic of such mechanisms that would be exploited in linear back-drive differentials is the possibility of designing them to drive or back-drive with similar efficiency and energy input: in other words, such a mechanism can be designed so that a rotating screw can drive a nut linearly or the linear motion of the nut can cause the screw to rotate. A linear back-drive differential (see figure) would include two collinear shafts connected to two parts that are intended to engage in limited opposing rotations. The linear back-drive differential would also include a nut that would be free to translate along its axis but not to rotate. The inner surface of the nut would be right-hand threaded at one end and left-hand threaded at the opposite end to engage corresponding right- and left-handed threads on the shafts. A rotation and torque introduced into the system via one shaft would drive the nut in linear motion. The nut, in turn, would back-drive the other shaft, creating a reaction torque. Balls would reduce friction, making it possible for the shaft/nut coupling on each side to operate with 90 percent efficiency.

  7. Secreted Frizzled-Related Protein 2 and Inflammation-Induced Skeletal Muscle Atrophy.

    PubMed

    Zhu, Xiaoxi; Kny, Melanie; Schmidt, Franziska; Hahn, Alexander; Wollersheim, Tobias; Kleber, Christian; Weber-Carstens, Steffen; Fielitz, Jens

    2017-02-01

    In sepsis, the disease course of critically ill patients is often complicated by muscle failure leading to ICU-acquired weakness. The myokine transforming growth factor-β1 increases during inflammation and mediates muscle atrophy in vivo. We observed that the transforming growth factor-β1 inhibitor, secreted frizzled-related protein 2, was down-regulated in skeletal muscle of ICU-acquired weakness patients. We hypothesized that secreted frizzled-related protein 2 reduction enhances transforming growth factor-β1-mediated effects and investigated the interrelationship between transforming growth factor-β1 and secreted frizzled-related protein 2 in inflammation-induced atrophy. Observational study and prospective animal trial. Two ICUs and research laboratory. Twenty-six critically ill patients with Sequential Organ Failure Assessment scores greater than or equal to 8 underwent a skeletal muscle biopsy from the vastus lateralis at median day 5 in ICU. Four patients undergoing elective orthopedic surgery served as controls. To search for signaling pathways enriched in muscle of ICU-acquired weakness patients, a gene set enrichment analysis of our recently published gene expression profiles was performed. Quantitative reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry were used to analyze secreted frizzled-related protein 2 expression and protein content. A mouse model of inflammation-induced skeletal muscle atrophy due to polymicrobial sepsis and cultured myocytes were used for mechanistic analyses. None. Gene set enrichment analysis uncovered transforming growth factor-β1 signaling activation in vastus lateralis from ICU-acquired weakness patients. Muscular secreted frizzled-related protein 2 expression was reduced after 5 days in ICU. Likewise, muscular secreted frizzled-related protein 2 expression was decreased early and continuously in mice with inflammation-induced atrophy. In muscle, secreted frizzled-related protein 2

  8. Abscisic-acid-induced cellular apoptosis and differentiation in glioma via the retinoid acid signaling pathway.

    PubMed

    Zhou, Nan; Yao, Yu; Ye, Hongxing; Zhu, Wei; Chen, Liang; Mao, Ying

    2016-04-15

    Retinoid acid (RA) plays critical roles in regulating differentiation and apoptosis in a variety of cancer cells. Abscisic acid (ABA) and RA are direct derivatives of carotenoids and share structural similarities. Here we proposed that ABA may also play a role in cellular differentiation and apoptosis by sharing a similar signaling pathway with RA that may be involved in glioma pathogenesis. We reported for the first time that the ABA levels were twofold higher in low-grade gliomas compared with high-grade gliomas. In glioma tissues, there was a positive correlation between the ABA levels and the transcription of cellular retinoic acid-binding protein 2 (CRABP2) and a negative correlation between the ABA levels and transcription of fatty acid-binding protein 5 (FABP5). ABA treatment induced a significant increase in the expression of CRABP2 and a decrease in the expression of peroxisome proliferator-activated receptor (PPAR) in glioblastoma cells. Remarkably, both cellular apoptosis and differentiation were increased in the glioblastoma cells after ABA treatment. ABA-induced cellular apoptosis and differentiation were significantly reduced by selectively silencing RAR-α, while RAR-α overexpression exaggerated the ABA-induced effects. These results suggest that ABA may play a role in the pathogenesis of glioma by promoting cellular apoptosis and differentiation through the RA signaling pathway. © 2015 UICC.

  9. Epigenetic inactivation of secreted frizzled-related protein 2 in esophageal squamous cell carcinoma

    PubMed Central

    Hao, Xiao-Wen; Zhu, Sheng-Tao; He, Yuan-Long; Li, Peng; Wang, Yong-Jun; Zhang, Shu-Tian

    2012-01-01

    AIM: To investigate the expression and methylation status of the secreted frizzled-related protein 2 (SFRP2) in esophageal squamous cell carcinoma (ESCC) and explore its role in ESCC carcinogenesis. METHODS: Seven ESCC cell lines (KYSE 30, KYSE150, KYSE410, KYSE510, EC109, EC9706 and TE-1) and one immortalized human esophageal epithelial cell line (Het-1A), 20 ESCC tissue samples and 20 paired adjacent non-tumor esophageal epithelial tissues were analyzed in this study. Reverse-transcription polymerase chain reaction (RT-PCR) was employed to investigate the expression of SFRP2 in cell lines, primary ESCC tumor tissue, and paired adjacent normal tissue. Methylation status was evaluated by methylation-specific PCR and bisulfite sequencing. The correlation between expression and promoter methylation of the SFRP2 gene was confirmed with treatment of 5-aza-2’-deoxycytidine. To assess the potential role of SFRP2 in ESCC, we established stable SFRP2-transfected cells and examined them with regard to cell proliferation, colony formation, apoptosis and cell cycle in vivo and in vitro. RESULTS: SFRP2 mRNA was expressed in the immortalized normal esophageal epithelial cell line but not in seven ESCC cell lines. By methylation-specific PCR, complete methylation was detected in three cell lines with silenced SFRP2 expression, and extensive methylation was observed in the other four ESCC cell lines. 5-aza-2’-deoxycytidine could restore the expression of SFRP2 mRNA in the three ESCC cell lines lacking SFRP2 expression. SFRP2 mRNA expression was obviously lower in primary ESCC tissue than in adjacent normal tissue (0.939 ± 0.398 vs 1.51 ± 0.399, P < 0.01). SFRP2 methylation was higher in tumor tissue than in paired normal tissue (95% vs 65%, P < 0.05). The DNA methylation status of the SFRP2 correlated inversely with the SFRP2 expression. To assess the potential role of SFRP2 in ESCC, we established stable SFRP2 transfectants and control counterparts by introducing pcDNA3

  10. Driving Performance Under Alcohol in Simulated Representative Driving Tasks

    PubMed Central

    Kenntner-Mabiala, Ramona; Kaussner, Yvonne; Jagiellowicz-Kaufmann, Monika; Hoffmann, Sonja; Krüger, Hans-Peter

    2015-01-01

    Abstract Comparing drug-induced driving impairments with the effects of benchmark blood alcohol concentrations (BACs) is an approved approach to determine the clinical relevance of findings for traffic safety. The present study aimed to collect alcohol calibration data to validate findings of clinical trials that were derived from a representative test course in a dynamic driving simulator. The driving performance of 24 healthy volunteers under placebo and with 0.05% and 0.08% BACs was measured in a double-blind, randomized, crossover design. Trained investigators assessed the subjects’ driving performance and registered their driving errors. Various driving parameters that were recorded during the simulation were also analyzed. Generally, the participants performed worse on the test course (P < 0.05 for the investigators’ assessment) under the influence of alcohol. Consistent with the relevant literature, lane-keeping performance parameters were sensitive to the investigated BACs. There were significant differences between the alcohol and placebo conditions in most of the parameters analyzed. However, the total number of errors was the only parameter discriminating significantly between all three BAC conditions. In conclusion, data show that the present experimental setup is suitable for future psychopharmacological research. Thereby, for each drug to be investigated, we recommend to assess a profile of various parameters that address different levels of driving. On the basis of this performance profile, the total number of driving errors is recommended as the primary endpoint. However, this overall endpoint should be completed by a specifically sensitive parameter that is chosen depending on the effect known to be induced by the tested drug. PMID:25689289

  11. Magnetic compression laser driving circuit

    DOEpatents

    Ball, Don G.; Birx, Dan; Cook, Edward G.

    1993-01-01

    A magnetic compression laser driving circuit is disclosed. The magnetic compression laser driving circuit compresses voltage pulses in the range of 1.5 microseconds at 20 Kilovolts of amplitude to pulses in the range of 40 nanoseconds and 60 Kilovolts of amplitude. The magnetic compression laser driving circuit includes a multi-stage magnetic switch where the last stage includes a switch having at least two turns which has larger saturated inductance with less core material so that the efficiency of the circuit and hence the laser is increased.

  12. Magnetic compression laser driving circuit

    DOEpatents

    Ball, D.G.; Birx, D.; Cook, E.G.

    1993-01-05

    A magnetic compression laser driving circuit is disclosed. The magnetic compression laser driving circuit compresses voltage pulses in the range of 1.5 microseconds at 20 kilovolts of amplitude to pulses in the range of 40 nanoseconds and 60 kilovolts of amplitude. The magnetic compression laser driving circuit includes a multi-stage magnetic switch where the last stage includes a switch having at least two turns which has larger saturated inductance with less core material so that the efficiency of the circuit and hence the laser is increased.

  13. How to maintain chain drives

    SciTech Connect

    Wright, J.L. )

    1992-06-18

    Properly selected and maintained chain drives can be expected to give thousands of hours of reliable service. Selection is usually done just once. This paper reports on good maintenance which must be done regularly to keep the drive operating. An effective maintenance program for roller chain should include correct type and adequate amounts of lubrication, replacement of worn chains and sprockets, and elimination of drive interferences. It is important to set u a lubrication and inspection/correction schedule to ensure that all required maintenance is carried out.

  14. The mechanism of PDT-induced apoptosis

    NASA Astrophysics Data System (ADS)

    Cai, Xiongwei; Liu, Timon C.; Ding, Xin-Min; Gu, Ying; Liu, Fan-Guang; Liu, Song-Hao

    2003-12-01

    Photodynamic therapy (PDT) can induce apoptosis in many cancer cells in vitro and in tumors in vivo. Cells become more oxidation with PDT, and maintain differentiation and proliferation, go apoptosis and necrosis with the increase of reactive oxygen species (ROS) concentration. ROS can induce apoptosis through mitochondria by inhibiting respiration chain or oxidative phosphorylation or damaging mitochondrial membrane. ROS can initiate apoptosis through endoplamic reticulum(ER) by opening Ca2+ channel or starting unfold protein response (UPR). ROS can also induce apoptosis through Golgi by producing ganglioside GD3 by use of ceramide, which induces apoptosis by activating caspase-3, JNK and p38 MAPK. It can also induce apoptosis by activating Bip (mitochondria-dependant) or preocaspase-12 (mitochondria- independent) or inhibiting protein synthesizing. There are so complicated cross-talking among different signal pathways or organnells that we think PDT-induced apoptosis is mediated by multiplex pathways and excessive levels in a refined network.

  15. Phoning while driving II: a review of driving conditions influence.

    PubMed

    Collet, C; Guillot, A; Petit, C

    2010-05-01

    The first paper examined how the variables related to driving performance were impacted by the management of holding a phone conversation. However, the conditions under which this dual task is carried out are dependent upon a set of factors that may particularly influence the risk of crash. These conditions are defined by several independent variables, classified into five main categories: i) legislation; ii) phone type (hands-free or hand-held); iii) drivers' features regarding age, gender, personal individual profile and driving experience; iv) conversation content (casual or professional) and its context (held with passengers or with a cell (mobile) phone); v) driving conditions (actual or simulated driving, road type, traffic density and weather). These independent variables determine the general conditions. The way in which these factors are combined and interact one with another thus determines the risk that drivers undergo when a cell phone is used while driving. Finally, this review defined the general conditions of driving for which managing a phone conversation is likely to elicit a high risk of car crash or, conversely, may provide a situation of lower risk, with sufficient acceptance to ensure safety.

  16. APOPTOSIS IN WHOLE MOUSE OVARIES

    EPA Science Inventory

    Apoptosis in Whole Mouse Ovaries
    Robert M. Zucker Susan C. Jeffay and Sally D. Perreault
    Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, 27711.

  17. Methylselenium and Prostate Cancer Apoptosis

    DTIC Science & Technology

    2003-02-01

    dependent apoptosis execution in PCa cells. We have in the reporting period refined a methylselenol generation system based on methioninase with... methylselenol , methylselenium 16. PRICE CODE 17. SECURITY CLASSIFICATION 18. SECURITY CLASSIFICATION 19. SECURITY CLASSIFICATION 20. LIMITATION OF... methylselenol generation system based on methioninase with selenomethionine as substrate (Wang et al, Mol. Carcinogenesis, 2002, appendix 1) and

  18. Methylselenium and Prostate Cancer Apoptosis

    DTIC Science & Technology

    2008-02-01

    methylselenol , prostate cancer chemoprevention, apoptosis 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF...considered an immediate precursor to the in vivo active anticancer selenium metabolite methylselenol , greatly sensitized HRPCa cells to undergo

  19. Methylselenium and Prostate Cancer Apoptosis

    DTIC Science & Technology

    2006-02-01

    will lay ground work for future validation studies in vivo and translation from the bench to the bedside. 15. SUBJECT TERMS Selenium, methylselenol ...Results: The methylselenol precursor methylseleninic acid (MSeA) increased the apoptosis potency of SN38, etoposide or paclitaxel by several folds

  20. Pancreatic carcinogenesis: apoptosis and angiogenesis.

    PubMed

    Onizuka, Shinya; Kawakami, Shunsuke; Taniguchi, Ken; Fujioka, Hikaru; Miyashita, Kosei

    2004-04-01

    Apoptosis and angiogenesis are critical biologic processes that are altered during carcinogenesis. Both apoptosis and angiogenesis may play an important role in pancreatic carcinogenesis. Despite numerous advances in the diagnosis and treatment of pancreatic cancer, its prognosis remains dismal and a new therapeutic approach is much needed. Recent research has revealed that apoptosis and angiogenesis are closely interrelated. Several reports show that a tumor suppresser gene that is expressed in pancreatic carcinoma and related to malignant potential can induce apoptosis and also inhibit angiogenesis. At present, it is generally accepted that tumor growth in cancers, including pancreatic cancer, depends on angiogenesis. We have identified 2 new angiogenesis inhibitors from a conditioned medium of human pancreatic carcinoma cell line (BxPC-3): antiangiogenic antithrombin III (aaAT-III) and vitamin D binding protein-macrophage activating factor (DBP-maf). These molecules were able to regress tumors in severe combined immunodeficiency disease (SCID) mice, demonstrating potent inhibition of endothelial cell proliferation. Moreover, the angiogenesis inhibitors induced tumor dormancy in the animal model. These results suggest that antiangiogenic therapy using angiogenesis inhibitors may become a new strategy for treatment of pancreatic cancer in the near future.

  1. [Apoptosis in chronic lymphocytic leukemia].

    PubMed

    Giordano, M

    2000-01-01

    Chronic lymphocytic leukemia of B cells (B-CLL) is the most prevalent leukemia in the Occidental Hemisphere. It is characterized by a progressive accumulation of monoclonal CD5+ B lymphocytes, with low amounts of surface Ig. Most B-CLL cells are arrested in the G0 phase of the cell cycle; therefore their accumulation in vivo appears to result from the inhibition of apoptosis which has been attributed to over-expression of the anti-apoptotic protein Bcl-2. When cultured in vitro, spontaneous apoptosis occurs, suggesting the existence in vivo of survival-promoting factors. We here show that non-malignant leukocytes, particularly monocytes and NK cells, are able to inhibit B-CLL cells apoptosis, at least in part, through the release of soluble factors. Neutralizing antibodies directed to interferon-gamma or IL-4 only partially abolish the protecting effects of accessory cells suggesting that they are not the main cytokines involved. Increased apoptosis of B-CLL cells is not associated with modifications in the expression of Bcl-2, Fas or Fas ligand. Considering that B-CLL is associated to autoimmune phenomena and recurrent infections due to hypogammaglobulinemia, it should be interesting to correlate the activation of immune responses with disease progression.

  2. APOPTOSIS IN WHOLE MOUSE OVARIES

    EPA Science Inventory

    Apoptosis in Whole Mouse Ovaries
    Robert M. Zucker Susan C. Jeffay and Sally D. Perreault
    Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, 27711.

  3. Methods for determining Myc-induced apoptosis.

    PubMed

    Lu, Dan; Littlewood, Trevor D

    2013-01-01

    Although many oncoproteins promote cell growth and proliferation, some also possess the potential to induce cell death by apoptosis. Deregulated expression of the myc oncogene promotes apoptosis in both cultured cells and in some tissues in vivo. Here we describe techniques to detect Myc-induced apoptosis in vitro using flow cytometry and microscopy and in vivo using immunohistochemical staining.

  4. Driving Speed vs Fuel Efficiency.

    ERIC Educational Resources Information Center

    Vest, Floyd

    1980-01-01

    A mathematical treatment of the relationship between driving speed and fuel efficiency is presented. The material involves applications of exponentials, logarithms, and elementary calculus, and is intended to be enrichment material for secondary and lower college mathematics classes. (MP)

  5. Power requirements for current drive

    NASA Astrophysics Data System (ADS)

    Boozer, Allen H.

    1988-03-01

    General formulas for the efficiency of current drive in toroidal plasmas are derived using entropy arguments. The highest possible efficiency for current drive in which a high-energy electron tail is formed is shown to be p=Erj, with p and j the power and current densities and Er≊0.09n14 V/m with n14 the electron density in units of 1014/cm.3 The electric field required to maintain the current in a runaway discharge is also shown to equal Er. If the plasma current is carried by near-Maxwellian electrons, waves that have a low phase velocity, compared to the energy of the electrons with which they interact, can drive a current with Ohmic efficiency, p=ηj2. Such waves were first discussed in the context of current drive by Fisch [Rev. Mod. Phys. 59, 175 (1987)].

  6. Quantum effects in warp drives

    NASA Astrophysics Data System (ADS)

    Finazzi, Stefano

    2013-09-01

    Warp drives are interesting configurations that, at least theoretically, provide a way to travel at superluminal speed. Unfortunately, several issues seem to forbid their realization. First, a huge amount of exotic matter is required to build them. Second, the presence of quantum fields propagating in superluminal warp-drive geometries makes them semiclassically unstable. Indeed, a Hawking-like high-temperature flux of particles is generated inside the warp-drive bubble, which causes an exponential growth of the energy density measured at the front wall of the bubble by freely falling observers. Moreover, superluminal warp drives remain unstable even if the Lorentz symmetry is broken by the introduction of regulating higher order terms in the Lagrangian of the quantum field. If the dispersion relation of the quantum field is subluminal, a black-hole laser phenomenon yields an exponential amplification of the emitted flux. If it is superluminal, infrared effects cause a linear growth of this flux.

  7. Alzheimer's: When to Stop Driving

    MedlinePlus

    Healthy Lifestyle Caregivers If your loved one has Alzheimer's, he or she may not be safe on ... for safe driving tends to decline with age, Alzheimer's disease accelerates this process dramatically. If you're ...

  8. Apparatus for forming drive belts

    NASA Technical Reports Server (NTRS)

    Topits, A., Jr. (Inventor)

    1974-01-01

    An apparatus for manufacturing belts, such as seamless belts, is provided, the apparatus has relatively movable rollers that are mounted in an oven. A belt blank, for example, of a thin polyester film, is rotated on the rollers as heat is applied. Four rollers, each mounted on a separate roller assembly, are movable along appropriate tracks while a fifth centrally located roller is stationary. A pair of dc motors are operatively connected to a speed reduction gear assembly to provide a pair of rotating drive shafts that extend into the oven. One rotating shaft drives all of the rollers through a rotational gear assembly while the other drive shaft is capable of positioning the movable rollers through respective rotating threaded shafts. Control devices are provided for controlling the motors while measuring devices are operatively connected to the positional drive shaft to indicate the position of the rollers.

  9. PTEN induces apoptosis and cavitation via HIF-2-dependent Bnip3 upregulation during epithelial lumen formation

    PubMed Central

    Qi, Y; Liu, J; Saadat, S; Tian, X; Han, Y; Fong, G-H; Pandolfi, P P; Lee, L Y; Li, S

    2015-01-01

    The tumor suppressor phosphatase and tensin homolog (PTEN) dephosphorylates PIP3 and antagonizes the prosurvival PI3K-Akt pathway. Targeted deletion of PTEN in mice led to early embryonic lethality. To elucidate its role in embryonic epithelial morphogenesis and the underlying mechanisms, we used embryonic stem cell-derived embryoid body (EB), an epithelial cyst structurally similar to the periimplantation embryo. PTEN is upregulated during EB morphogenesis in parallel with apoptosis of core cells, which mediates EB cavitation. Genetic ablation of PTEN causes Akt overactivation, apoptosis resistance and cavitation blockade. However, rescue experiments using mutant PTEN and pharmacological inhibition of Akt suggest that the phosphatase activity of PTEN and Akt are not involved in apoptosis-mediated cavitation. Instead, hypoxia-induced upregulation of Bnip3, a proapoptotic BH3-only protein, mediates PTEN-dependent apoptosis and cavitation. PTEN inactivation inhibits hypoxia- and reactive oxygen species-induced Bnip3 elevation. Overexpression of Bnip3 in PTEN-null EBs rescues apoptosis of the core cells. Mechanistically, suppression of Bnip3 following PTEN loss is likely due to reduction of hypoxia-inducible factor-2α (HIF-2α) because forced expression of an oxygen-stable HIF-2α mutant rescues Bnip3 expression and apoptosis. Lastly, we show that HIF-2α is upregulated by PTEN at both transcriptional and posttranscriptional levels. Ablation of prolyl hydroxylase domain-containing protein 2 (PHD2) in normal EBs or inhibition of PHD activities in PTEN-null EBs stabilizes HIF-2α and induces Bnip3 and caspase-3 activation. Altogether, these results suggest that PTEN is required for apoptosis-mediated cavitation during epithelial morphogenesis by regulating the expression of HIF-2α and Bnip3. PMID:25394489

  10. cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in rat hepatocytes.

    PubMed

    Bhattacharjee, Rajesh; Xiang, Wenpei; Wang, Yinna; Zhang, Xiaoying; Billiar, Timothy R

    2012-06-22

    Tumor necrosis factor α (TNF) is a pleiotropic proinflammatory cytokine that plays a role in immunity and the control of cell proliferation, cell differentiation, and apoptosis. The pleiotropic nature of TNF is due to the formation of different signaling complexes upon the binding of TNF to its receptor, TNF receptor type 1 (TNFR1). TNF induces apoptosis in various mammalian cells when the cells are co-treated with a transcription inhibitor like actinomycin D (ActD). When TNFR1 is activated, it recruits an adaptor protein, TNF receptor-associated protein with death domain (TRADD), through its cytoplasmic death effector domain (DED). TRADD, in turn, recruits other signaling proteins, including TNF receptor-associated protein 2 (TRAF2) and receptor-associated protein kinase (RIPK) 1, to form a complex. Subsequently, this complex combines with FADD and procaspase-8, converts into a death-inducing signaling complex (DISC) to induce apoptosis. Cyclic AMP (cAMP) is a second messenger that regulates various cellular processes such as cell proliferation, gene expression, and apoptosis. cAMP analogues are reported to act as anti-apoptotic agents in various cell types, including hepatocytes. We found that a cAMP analogue, dibutyryl cAMP (db-cAMP), inhibits TNF+ActD-induced apoptosis in rat hepatocytes. The protein kinase A (PKA) inhibitor KT-5720 reverses this inhibitory effect of cAMP on apoptosis. Cytoprotection by cAMP involves down-regulation of various apoptotic signal regulators like TRADD and FADD and inhibition of caspase-8 and caspase-3 cleavage. We also found that cAMP exerts its affect at the proximal level of TNF signaling by inhibiting the formation of the DISC complex upon the binding of TNF to TNFR1. In conclusion, our study shows that cAMP prevents TNF+ActD-induced apoptosis in rat hepatocytes by inhibiting DISC complex formation.

  11. [Vision and car driving ability].

    PubMed

    Wilhelm, Helmut

    2011-05-01

    Visual functions relevant for car driving are: Visual acuity, contrast and twilight vision, visual field, ocular motility and alignment and colour vision. Generally accepted and standardized tests are available for visual acuity and visual field. Maximum permissible values have been defined arbitrarily and are hardly supported by studies. European standards have been published comprising also contrast and twilight vision. When examining driving ability progressive and treatable ocular disorders such as cataract and glaucoma have to be considered.

  12. Direct drive field actuator motors

    DOEpatents

    Grahn, A.R.

    1998-03-10

    A positive-drive field actuator motor is described which includes a stator carrying at least one field actuator which changes in dimension responsive to application of an energy field, and at least one drive shoe movable by the dimensional changes of the field actuator to contact and move a rotor element with respect to the stator. Various embodiments of the motor are disclosed, and the rotor element may be moved linearly or arcuately. 62 figs.

  13. Direct drive field actuator motors

    SciTech Connect

    Grahn, Allen R.

    1998-01-01

    A positive-drive field actuator motor including a stator carrying at least one field actuator which changes in dimension responsive to application of an energy field, and at least one drive shoe movable by the dimensional changes of the field actuator to contact and move a rotor element with respect to the stator. Various embodiments of the motor are disclosed, and the rotor element may be moved linearly or arcuately.

  14. Mechanical drive for blood pump

    DOEpatents

    Bifano, N.J.; Pouchot, W.D.

    1975-07-29

    This patent relates to a highly efficient blood pump to be used as a replacement for a ventricle of the human heart to restore people disabled by heart disease. The mechanical drive of the present invention is designed to operate in conjunction with a thermoelectric converter power source. The mechanical drive system essentially converts the output of a rotary power into pulsatile motion so that the power demand from the thermoelectric converter remains essentially constant while the blood pump output is pulsed. (auth)

  15. Chemokines, macrophage inflammatory protein-2 and stromal cell-derived factor-1{alpha}, suppress amyloid {beta}-induced neurotoxicity

    SciTech Connect

    Raman, Dayanidhi; Milatovic, Snjezana-Zaja; Milatovic, Dejan; Fan, Guo-Huang; Richmond, Ann

    2011-11-15

    Alzheimer's disease (AD) is characterized by a progressive cognitive decline and accumulation of neurotoxic oligomeric peptides amyloid-{beta} (A{beta}). Although the molecular events are not entirely known, it has become evident that inflammation, environmental and other risk factors may play a causal, disruptive and/or protective role in the development of AD. The present study investigated the ability of the chemokines, macrophage inflammatory protein-2 (MIP-2) and stromal cell-derived factor-1{alpha} (SDF-1{alpha}), the respective ligands for chemokine receptors CXCR2 and CXCR4, to suppress A{beta}-induced neurotoxicity in vitro and in vivo. Pretreatment with MIP-2 or SDF-1{alpha} significantly protected neurons from A{beta}-induced dendritic regression and apoptosis in vitro through activation of Akt, ERK1/2 and maintenance of metalloproteinase ADAM17 especially with SDF-1{alpha}. Intra-cerebroventricular (ICV) injection of A{beta} led to reduction in dendritic length and spine density of pyramidal neurons in the CA1 area of the hippocampus and increased oxidative damage 24 h following the exposure. The A{beta}-induced morphometric changes of neurons and increase in biomarkers of oxidative damage, F{sub 2}-isoprostanes, were significantly inhibited by pretreatment with the chemokines MIP-2 or SDF-1{alpha}. Additionally, MIP-2 or SDF-1{alpha} was able to suppress the aberrant mislocalization of p21-activated kinase (PAK), one of the proteins involved in the maintenance of dendritic spines. Furthermore, MIP-2 also protected neurons against A{beta} neurotoxicity in CXCR2-/- mice, potentially through observed up regulation of CXCR1 mRNA. Understanding the neuroprotective potential of chemokines is crucial in defining the role for their employment during the early stages of neurodegeneration. -- Research highlights: Black-Right-Pointing-Pointer Neuroprotective ability of the chemokines MIP2 and CXCL12 against A{beta} toxicity. Black-Right-Pointing-Pointer MIP-2 or

  16. Low backlash direct drive actuator

    DOEpatents

    Kuklo, Thomas C.

    1994-01-01

    A low backlash direct drive actuator is described which comprises a motor such as a stepper motor having at least 200 steps per revolution; a two part hub assembly comprising a drive hub coaxially attached to the shaft of the motor and having a plurality of drive pins; a driven hub having a plurality of bores in one end thereof in alignment with the drive pins in the drive hub and a threaded shaft coaxially mounted in an opposite end of the driven hub; and a housing having a central bore therein into which are fitted the drive hub and driven hub, the housing having a motor mount on one end thereof to which is mounted the stepper motor, and a closed end portion with a threaded opening therein coaxial with the central bore in the housing and receiving therein the threaded shaft attached to the driven hub. Limit switches mounted to the housing cooperate with an enlarged lip on the driven hub to limit the lateral travel of the driven hub in the housing, which also acts to limit the lateral travel of the threaded shaft which functions as a lead screw.

  17. Low backlash direct drive actuator

    DOEpatents

    Kuklo, T.C.

    1994-10-25

    A low backlash direct drive actuator is described which comprises a motor such as a stepper motor having at least 200 steps per revolution; a two part hub assembly comprising a drive hub coaxially attached to the shaft of the motor and having a plurality of drive pins; a driven hub having a plurality of bores in one end thereof in alignment with the drive pins in the drive hub and a threaded shaft coaxially mounted in an opposite end of the driven hub; and a housing having a central bore therein into which are fitted the drive hub and driven hub, the housing having a motor mount on one end thereof to which is mounted the stepper motor, and a closed end portion with a threaded opening therein coaxial with the central bore in the housing and receiving therein the threaded shaft attached to the driven hub. Limit switches mounted to the housing cooperate with an enlarged lip on the driven hub to limit the lateral travel of the driven hub in the housing, which also acts to limit the lateral travel of the threaded shaft which functions as a lead screw. 10 figs.

  18. The Hydroxyl at Position C1 of Genipin Is the Active Inhibitory Group that Affects Mitochondrial Uncoupling Protein 2 in Panc-1 Cells

    PubMed Central

    Hou, Jianwei; Ding, Yue; Zhang, Tong; Zhang, Yong; Wang, Jianying; Shi, Chenchen; Fu, Wenwei; Cai, Zhenzhen

    2016-01-01

    Genipin (GNP) effectively inhibits uncoupling protein 2 (UCP2), which regulates the leakage of protons across the inner mitochondrial membrane. UCP2 inhibition may induce pancreatic adenocarcinoma cell death by increasing reactive oxygen species (ROS) levels. In this study, the hydroxyls at positions C10 (10-OH) and C1 (1-OH) of GNP were hypothesized to be the active groups that cause these inhibitory effects. Four GNP derivatives in which the hydroxyl at position C10 or C1 was replaced with other chemical groups were synthesized and isolated. Differences in the inhibitory effects of GNP and its four derivatives on pancreatic carcinoma cell (Panc-1) proliferation were assessed. The effects of GNP and its derivatives on apoptosis, UCP2 inhibition and ROS production were also studied to explore the relationship between GNP’s activity and its structure. The derivatives with 1-OH substitutions, geniposide (1-GNP1) and 1-ethyl-genipin (1-GNP2) lacked cytotoxic effects, while the other derivatives that retained 1-OH, 10-piv-genipin (10-GNP1) and 10-acetic acid-genipin (10-GNP2) exerted biological effects similar to those of GNP, even in the absence of 10-OH. Thus, 1-OH is the key functional group in the structure of GNP that is responsible for GNP’s apoptotic effects. These cytotoxic effects involve the induction of Panc-1 cell apoptosis through UCP2 inhibition and subsequent ROS production. PMID:26771380

  19. Control of Pathological Cardiac Hypertrophy by Transcriptional Corepressor IRF2BP2 (Interferon Regulatory Factor-2 Binding Protein 2).

    PubMed

    Fang, Jing; Li, Tianyu; Zhu, Xuehai; Deng, Ke-Qiong; Ji, Yan-Xiao; Fang, Chun; Zhang, Xiao-Jing; Guo, Jun-Hong; Zhang, Peng; Li, Hongliang; Wei, Xiang

    2017-09-01

    The transcription factor NFAT1 (nuclear factor of activated T-cells 1), with the aid of transcriptional coactivators, has been recognized for its necessity and sufficiency to drive pathological cardiac hypertrophy. However, how the transcriptional activity of NFAT1 in terms of cardiac hypertrophy is controlled at the transcriptional level has not been well defined. Herein, we showed that a cardiac-enriched protein IRF2BP2 (interferon regulatory factor-2 binding protein 2) was further upregulated in both human and mouse hypertrophied myocardium and negatively regulated cardiomyocyte hypertrophic response in vitro. By generating cardiomyocyte-specific Irf2bp2 knockout and Irf2bp2-transgenic mouse strains, our in vivo experiments showed that, whereas IRF2BP2 loss-of-function exacerbated both aortic banding- and angiotensin II infusion-induced cardiac hypertrophic response, IRF2BP2 overexpression exerted a strong protective effect against these maladaptive processes. Particularly, IRF2BP2 directly interacted with the C-terminal transactivation domain of NFAT1 by competing with myocyte enhancer factor-2C and disturbing their transcriptional synergism, thereby impeding NFAT1-transactivated hypertrophic transcriptome. As a result, the devastating effect of Irf2bp2 deficiency on cardiac hypertrophy was largely rescued by NFAT1 blockage. Our study, thus, defined IRF2BP2 as a novel negative regulator in controlling pathological cardiac hypertrophy at the transcriptional level. © 2017 American Heart Association, Inc.

  20. Actin-Related Protein 2 (ARP2) and Virus-Induced Filopodia Facilitate Human Respiratory Syncytial Virus Spread

    PubMed Central

    McCarty, Thomas; Martin, Scott E.; Le Nouën, Cyril; Buehler, Eugen; Chen, Yu-Chi; Smelkinson, Margery; Ganesan, Sundar; Fischer, Elizabeth R.; Brock, Linda G.; Liang, Bo; Munir, Shirin; Collins, Peter L.; Buchholz, Ursula J.

    2016-01-01

    Human respiratory syncytial virus (RSV) is an enveloped RNA virus that is the most important viral cause of acute pediatric lower respiratory tract illness worldwide, and lacks a vaccine or effective antiviral drug. The involvement of host factors in the RSV replicative cycle remains poorly characterized. A genome-wide siRNA screen in human lung epithelial A549 cells identified actin-related protein 2 (ARP2) as a host factor involved in RSV infection. ARP2 knockdown did not reduce RSV entry, and did not markedly reduce gene expression during the first 24 hr of infection, but decreased viral gene expression thereafter, an effect that appeared to be due to inhibition of viral spread to neighboring cells. Consistent with reduced spread, there was a 10-fold reduction in the release of infectious progeny virions in ARP2-depleted cells at 72 hr post-infection. In addition, we found that RSV infection induced filopodia formation and increased cell motility in A549 cells and that this phenotype was ARP2 dependent. Filopodia appeared to shuttle RSV to nearby uninfected cells, facilitating virus spread. Expression of the RSV F protein alone from a plasmid or heterologous viral vector in A549 cells induced filopodia, indicating a new role for the RSV F protein, driving filopodia induction and virus spread. Thus, this study identified roles for ARP2 and filopodia in RSV-induced cell motility, RSV production, and RSV cell-to-cell spread. PMID:27926942

  1. Efficient Driving of Piezoelectric Transducers Using a Biaxial Driving Technique

    PubMed Central

    2015-01-01

    Efficient driving of piezoelectric materials is desirable when operating transducers for biomedical applications such as high intensity focused ultrasound (HIFU) or ultrasound imaging. More efficient operation reduces the electric power required to produce the desired bioeffect or contrast. Our preliminary work [Cole et al. Journal of Physics: Condensed Matter. 2014;26(13):135901.] suggested that driving transducers by applying orthogonal electric fields can significantly reduce the coercivity that opposes ferroelectric switching. We present here the experimental validation of this biaxial driving technique using piezoelectric ceramics typically used in HIFU. A set of narrow-band transducers was fabricated with two sets of electrodes placed in an orthogonal configuration (following the propagation and the lateral mode). The geometry of the ceramic was chosen to have a resonance frequency similar for the propagation and the lateral mode. The average (± s.d.) resonance frequency of the samples was 465.1 (± 1.5) kHz. Experiments were conducted in which each pair of electrodes was driven independently and measurements of effective acoustic power were obtained using the radiation force method. The efficiency (acoustic/electric power) of the biaxial driving method was compared to the results obtained when driving the ceramic using electrodes placed only in the pole direction. Our results indicate that the biaxial method increases efficiency from 50% to 125% relative to the using a single electric field. PMID:26418550

  2. Efficient Driving of Piezoelectric Transducers Using a Biaxial Driving Technique.

    PubMed

    Pichardo, Samuel; Silva, Rafael R C; Rubel, Oleg; Curiel, Laura

    2015-01-01

    Efficient driving of piezoelectric materials is desirable when operating transducers for biomedical applications such as high intensity focused ultrasound (HIFU) or ultrasound imaging. More efficient operation reduces the electric power required to produce the desired bioeffect or contrast. Our preliminary work [Cole et al. Journal of Physics: Condensed Matter. 2014;26(13):135901.] suggested that driving transducers by applying orthogonal electric fields can significantly reduce the coercivity that opposes ferroelectric switching. We present here the experimental validation of this biaxial driving technique using piezoelectric ceramics typically used in HIFU. A set of narrow-band transducers was fabricated with two sets of electrodes placed in an orthogonal configuration (following the propagation and the lateral mode). The geometry of the ceramic was chosen to have a resonance frequency similar for the propagation and the lateral mode. The average (± s.d.) resonance frequency of the samples was 465.1 (± 1.5) kHz. Experiments were conducted in which each pair of electrodes was driven independently and measurements of effective acoustic power were obtained using the radiation force method. The efficiency (acoustic/electric power) of the biaxial driving method was compared to the results obtained when driving the ceramic using electrodes placed only in the pole direction. Our results indicate that the biaxial method increases efficiency from 50% to 125% relative to the using a single electric field.

  3. A tumor suppressor role of the Bub3 spindle checkpoint protein after apoptosis inhibition

    PubMed Central

    Moutinho-Santos, Tatiana

    2013-01-01

    Most solid tumors contain aneuploid cells, indicating that the mitotic checkpoint is permissive to the proliferation of chromosomally aberrant cells. However, mutated or altered expression of mitotic checkpoint genes accounts for a minor proportion of human tumors. We describe a Drosophila melanogaster tumorigenesis model derived from knocking down spindle assembly checkpoint (SAC) genes and preventing apoptosis in wing imaginal discs. Bub3-deficient tumors that were also deficient in apoptosis displayed neoplastic growth, chromosomal aneuploidy, and high proliferative potential after transplantation into adult flies. Inducing aneuploidy by knocking down CENP-E and preventing apoptosis does not induce tumorigenesis, indicating that aneuploidy is not sufficient for hyperplasia. In this system, the aneuploidy caused by a deficient SAC is not driving tumorigenesis because preventing Bub3 from binding to the kinetochore does not cause hyperproliferation. Our data suggest that Bub3 has a nonkinetochore-dependent function that is consistent with its role as a tumor suppressor. PMID:23609535

  4. Identification of potential molecular associations between chikungunya virus non-structural protein 2 and human host proteins.

    PubMed

    Rana, J; Gulati, S; Rajasekharan, S; Gupta, A; Chaudhary, V; Gupta, S

    2017-01-01

    Chikungunya virus (CHIKV) non-structural protein 2 (nsP2) is considered to be the master regulator of viral RNA replication and host responses generated during viral infection. This protein has two main functional domains: an N-terminal domain which exhibits NTPase, RNA triphosphatase and helicase activities and a C-terminal protease domain. Understanding how CHIKV nsP2 interacts with its host proteins is essential for elucidating all the required processes for viral replication and pathogenesis along with the identification of potential targets for antiviral therapy. In current study yeast two-hybrid (Y2H) screening of a human fetal brain cDNA library was performed using nsP2 protein as bait. The analysis identified seven host proteins (CCDC130, CPNE6, POLR2C, MAPK9, EIF4A2, EEF1A1 and EIF3I) as putative interactors of CHIKV nsP2 which were selected for further analysis based on their roles in host cellular machinery. The gene ontology analysis indicates that these proteins are mainly involved in apoptosis, transcription and translational mechanism of host cell. Domain mapping of nsP2 revealed that these associations are not random connections but instead they have functional significance. Further studies to identify the amino acid residues and their chemical interactions that may help in opening new possibilities for preventing these interactions, thus reducing chances of chikungunya infection were performed. This study expands the understanding of CHIKV-host interactions and is important for rational approaches of discovering new antiviral agents.

  5. Special AT-rich Binding Protein-2 (SATB2) Differentially Affects Disease-causing p63 Mutant Proteins*

    PubMed Central

    Chung, Jacky; Grant, R. Ian; Kaplan, David R.; Irwin, Meredith S.

    2011-01-01

    p63, a p53 family member, is critical for proper skin and limb development and directly regulates gene expression in the ectoderm. Mice lacking p63 exhibit skin and craniofacial defects including cleft palate. In humans p63 mutations are associated with several distinct developmental syndromes. p63 sterile-α-motif domain, AEC (ankyloblepharon-ectodermal dysplasia-clefting)-associated mutations are associated with a high prevalence of orofacial clefting disorders, which are less common in EEC (ectrodactyly-ectodermal dysplasia-clefting) patients with DNA binding domain p63 mutations. However, the mechanisms by which these mutations differentially influence p63 function remain unclear, and interactions with other proteins implicated in craniofacial development have not been identified. Here, we show that AEC p63 mutations affect the ability of the p63 protein to interact with special AT-rich binding protein-2 (SATB2), which has recently also been implicated in the development of cleft palate. p63 and SATB2 are co-expressed early in development in the ectoderm of the first and second branchial arches, two essential sites where signaling is required for craniofacial patterning. SATB2 attenuates p63-mediated gene expression of perp (p53 apoptosis effector related to PMP-22), a critical downstream target gene during development, and specifically decreases p63 perp promoter binding. Interestingly, AEC but not EEC p63 mutations affect the ability of p63 to interact with SATB2 and the inhibitory effects of SATB2 on p63 transactivation of perp are most pronounced for AEC-associated p63 mutations. Our findings reveal a novel gain-of-function property of AEC-causing p63 mutations and identify SATB2 as the first p63 binding partner that differentially influences AEC and EEC p63 mutant proteins. PMID:21965674

  6. PTEN-induction in U251 glioma cells decreases the expression of insulin-like growth factor binding protein-2

    SciTech Connect

    Levitt, Randy J.; Georgescu, Maria-Magdalena; Pollak, Michael . E-mail: michael.pollak@mcgill.ca

    2005-11-04

    PTEN is a tumor suppressor gene whose loss of function is observed in {approx}40-50% of human cancers. Although insulin-like growth factor binding protein-2 (IGFBP-2) was classically described as a growth inhibitor, multiple recent reports have shown an association of overexpression and/or high serum levels of IGFBP-2 with poor prognosis of several malignancies, including gliomas. Using an inducible PTEN expression system in the PTEN-null glioma cell line U251, we demonstrate that PTEN-induction is associated with reduced proliferation, increased apoptosis, and a substantial reduction of the high levels of IGFBP-2 expression. The PTEN-induced decrease in IGFBP-2 expression could be mimicked with the PI3-kinase inhibitor LY294002, indicating that the lipid phosphatase activity of PTEN is responsible for the observed effect. However, the rapamycin analog CCI-779 did not affect IGFBP-2 expression, suggesting that the PTEN-induced decrease in IGFBP-2 expression is not attributable to decreased mTOR signalling. Recombinant human IGFBP-2 was unable to rescue U251-PTEN cells from the antiproliferative effects of PTEN, and IGFBP-2 siRNA did not affect the IGF-dependent or -independent growth of this cell line. These results suggest that the clinical data linking IGFBP-2 expression to poor prognosis may arise, at least in part, because high levels of IGFBP-2 expression correlate with loss of function of PTEN, which is well known to lead to aggressive behavior of gliomas. Our results motivate translational research regarding the relationship between IGFBP-2 expression and loss of function of PTEN.

  7. Driving performance and driver discomfort in an elevated and standard driving position during a driving simulation.

    PubMed

    Smith, Jordan; Mansfield, Neil; Gyi, Diane; Pagett, Mark; Bateman, Bob

    2015-07-01

    The primary purposes of a vehicle driver's seat, is to allow them to complete the driving task comfortably and safely. Within each class of vehicle (e.g. passenger, commercial, industrial, agricultural), there is an expected driving position to which a vehicle cabin is designed. This paper reports a study that compares two driving positions, in relation to Light Commercial Vehicles (LCVs), in terms of driver performance and driver discomfort. In the 'elevated' driving position, the seat is higher than usually used in road vehicles; this is compared to a standard driving position replicating the layout for a commercially available vehicle. It is shown that for a sample of 12 drivers, the elevated position did not, in general, show more discomfort than the standard position over a 60 min driving simulation, although discomfort increased with duration. There were no adverse effects shown for emergency stop reaction time or for driver headway for the elevated posture compared to the standard posture. The only body part that showed greater discomfort for the elevated posture compared to the standard posture was the right ankle. A second experiment confirmed that for 12 subjects, a higher pedal stiffness eliminated the ankle discomfort problem.

  8. Apoptosis in virus infection dynamics models

    PubMed Central

    Fan, Ruili; Dong, Yueping; Huang, Gang; Takeuchi, Yasuhiro

    2014-01-01

    In this paper, on the basis of the simplified two-dimensional virus infection dynamics model, we propose two extended models that aim at incorporating the influence of activation-induced apoptosis which directly affects the population of uninfected cells. The theoretical analysis shows that increasing apoptosis plays a positive role in control of virus infection. However, after being included the third population of cytotoxic T lymphocytes immune response in HIV-infected patients, it shows that depending on intensity of the apoptosis of healthy cells, the apoptosis can either promote or comfort the long-term evolution of HIV infection. Further, the discrete-time delay of apoptosis is incorporated into the pervious model. Stability switching occurs as the time delay in apoptosis increases. Numerical simulations are performed to illustrate the theoretical results and display the different impacts of a delay in apoptosis. PMID:24963975

  9. Relationships between driving simulator performance and driving test results.

    PubMed

    de Winter, J C F; de Groot, S; Mulder, M; Wieringa, P A; Dankelman, J; Mulder, J A

    2009-02-01

    This article is considered relevant because: 1) car driving is an everyday and safety-critical task; 2) simulators are used to an increasing extent for driver training (related topics: training, virtual reality, human-machine interaction); 3) the article addresses relationships between performance in the simulator and driving test results--a relevant topic for those involved in driver training and the virtual reality industries; 4) this article provides new insights about individual differences in young drivers' behaviour. Simulators are being used to an increasing extent for driver training, allowing for the possibility of collecting objective data on driver proficiency under standardised conditions. However, relatively little is known about how learner drivers' simulator measures relate to on-road driving. This study proposes a theoretical framework that quantifies driver proficiency in terms of speed of task execution, violations and errors. This study investigated the relationships between these three measures of learner drivers' (n=804) proficiency during initial simulation-based training and the result of the driving test on the road, occurring an average of 6 months later. A higher chance of passing the driving test the first time was associated with making fewer steering errors on the simulator and could be predicted in regression analysis with a correlation of 0.18. Additionally, in accordance with the theoretical framework, a shorter duration of on-road training corresponded with faster task execution, fewer violations and fewer steering errors (predictive correlation 0.45). It is recommended that researchers conduct more large-scale studies into the reliability and validity of simulator measures and on-road driving tests.

  10. Driving performance at lateral system limits during partially automated driving.

    PubMed

    Naujoks, Frederik; Purucker, Christian; Wiedemann, Katharina; Neukum, Alexandra; Wolter, Stefan; Steiger, Reid

    2017-11-01

    This study investigated driver performance during system limits of partially automated driving. Using a motion-based driving simulator, drivers encountered different situations in which a partially automated vehicle could no longer safely keep the lateral guidance. Drivers were distracted by a non-driving related task on a touch display or driving without an additional secondary task. While driving in partially automated mode drivers could either take their hands off the steering wheel for only a short period of time (10s, so-called 'Hands-on' variant) or for an extended period of time (120s, so-called 'Hands-off' variant). When the system limit was reached (e.g., when entering a work zone with temporary lines), the lateral vehicle control by the automation was suddenly discontinued and a take-over request was issued to the drivers. Regardless of the hands-off interval and the availability of a secondary task, all drivers managed the transition to manual driving safely. No lane exceedances were observed and the situations were rated as 'harmless' by the drivers. The lack of difference between the hands-off intervals can be partly attributed to the fact that most of the drivers kept contact to the steering wheel, even in the hands-off condition. Although all drivers were able to control the system limits, most of them could not explain why exactly the take-over request was issued. The average helpfulness of the take-over request was rated on an intermediate level. Consequently, providing drivers with information about the reason for a system limit can be recommended. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. [Apoptosis modulation by human papillomavirus].

    PubMed

    Jave-Suárez, Luis Felipe; Ratkovich-González, Sarah; Olimón-Andalón, Vicente; Aguilar-Lemarroy, Adriana

    2015-01-01

    One of the most important processes to keep the homeostasis in organisms is the apoptosis, also called programmed cell death. This mechanism works through two pathways: The intrinsic or mitochondrial, which responds to DNA damage and extern agents like UV radiation; and the extrinsic or receptor-mediated, which binds to their ligands to initiate the apoptotic trail. The evasion of apoptosis is one of the main causes of cellular transformation to malignity. Many viruses had shown capacity to modify the apoptotic process; among them is the human papillomavirus, which, by means of its oncoproteins, interferes in pathways, reacting with the receptors and molecules and participating in the death mechanism. This creates ideal conditions for cancer development.

  12. Hydrodynamic drive of tubular centrifuges

    SciTech Connect

    Tsybul'nik, A.P.

    1986-07-01

    A drive has been developed for a tubular centrifuge having a 10 kW ASTs-10-504 high-frequency electric motor with a synchronous rotation speed of 15,000 rpm. Despite a few demerits, the drive met the basic production requirements; simplicity and reliability of design, admissable rotation speed, and explosion resistance. However, this drive for tubular centrifuges had to be abandoned because experimental prototypes of high-frequency motors were used for the industrial tests and lot production of such motors is not probable in the near future. Industrial tests of a new hydrodynamic drive were performed, and the schematic diagram is shown. The hydrodrive was tested during centrifuge operation with polyester lac. It was found that the hydodynamic drive is distinguished by operational reliability and easy serviceability, holds promise for increased centrifuge speed, ensures smooth start of the centrifuge and satisfactory stability of the rotor rotation speed in the steady regime, reliably protects the motor from overloading and is fully explosion-proof.

  13. Studies on the expression of outer membrane protein 2 in escherichia coli.

    PubMed

    Fralick, J A; Diedrich, D L

    1982-01-01

    The relative level of protein 2 expressed in the outer membrane of strains of Escherichia coli K-12 lysogenized with bacteriophage PA-2 was found to be influenced by both the growth temperature and lc+ gene dosage. An increase in either of these parameters was accompanied by an increase in the level of protein 2 up to an apparent saturation level. Any increase in the amount of protein 2 was accompanied by a concomittant decrease in the amount of OmpF and OmpC porins. This inverse relationship led to the maintenance of an approximately constant protein mass per unit of peptidoglycan. Our results are discussed in light of recent genetic studies on the regulation of the OmpF and OmpC porins and can be explained through the competition of these three matrix proteins for a common export or insertion site.

  14. Apoptosis in Cryopreserved Eukaryotic Cells.

    PubMed

    Savitskaya, M A; Onishchenko, G E

    2016-05-01

    This review considers apoptosis mechanisms that have been revealed in cryopreserved cells and which can be controlled using different chemical agents, thereby improving the viability of cells after their return to normal conditions. The role of oxidative stress as of the most significant damaging factor is discussed, as well as the reasonability of including antioxidants into cryopreservation/thawing protocols as independent agents or in combination with other compounds.

  15. Apoptosis in human retinal degenerations.

    PubMed

    Xu, G Z; Li, W W; Tso, M O

    1996-01-01

    This paper examined the role of apoptosis in human retinal degenerations including pathologic myopia, age-related macular degeneration, serous retinal detachment, retinal lattice, and paving stone degenerations. Thirty-seven enucleated human eyes with 1 of the above-mentioned retinal degenerations were studied by histopathology and by TdT-mediated biotin-dUTP nicked-end labelling (TUNEL) technique. Tunnel labelling characteristic DNA fragmentation of apoptosis was observed in photoreceptor cells in 2 of the 4 eyes with pathologic myopia and in 4 of 16 eyes with age-related macular degeneration, 2 of which were exudative and 2 of which were atrophic. However, only a few scattered photoreceptor cells were labelled in 4 of 8 eyes with serous retinal detachment secondary to malignant melanoma of the choroid. Moreover, none of the photoreceptors cells in the 4 eyes with retinal lattice degeneration and 6 eyes with retinal paving stone degeneration were labelled. Apoptosis is 1 of the important pathways of photoreceptor cell degeneration in pathologic myopia and age-related macular degeneration.

  16. Enterovirus 71 2B Induces Cell Apoptosis by Directly Inducing the Conformational Activation of the Proapoptotic Protein Bax.

    PubMed

    Cong, Haolong; Du, Ning; Yang, Yang; Song, Lei; Zhang, Wenliang; Tien, Po

    2016-11-01

    To survive and replicate within a host, many viruses have evolved strategies that target crucial components within the apoptotic cascade, leading to either inhibition or induction of cell apoptosis. Enterovirus 71 (EV71) infections have been demonstrated to impact the mitochondrial apoptotic pathway and induce apoptosis in many cell lines. However, the detailed mechanism of EV71-induced apoptosis remains to be elucidated. In this study, we report that EV71 2B protein (2B) localized to the mitochondria and induced cell apoptosis by interacting directly with and activating the proapoptotic protein Bax. 2B recruited Bax to the mitochondria and induced Bax conformational activation. In addition, mitochondria isolated from 2B-expressing cells that were treated with a recombinant Bax showed increased Bax interaction and cytochrome c (Cyt c) release. Importantly, apoptosis in cells with either EV71 infection or 2B expression was dramatically reduced in Bax knockdown cells but not in Bak knockdown cells, suggesting that Bax played a pivotal role in EV71- or 2B-induced apoptosis. Further studies indicate that a hydrophobic region of 18 amino acids (aa) in the C-terminal region of 2B (aa 63 to 80) was responsible for the location of 2B in the mitochondria. A hydrophilic region of 14 aa in the N-terminal region of 2B was functional in Bax interaction and its subsequent activation. Moreover, overexpression of the antiapoptotic protein Bcl-XL abrogates 2B-induced release of Cyt c and caspase activation. Therefore, this study provides direct evidence that EV71 2B induces cell apoptosis and impacts the mitochondrial apoptotic pathway by directly modulating the redistribution and activation of proapoptotic protein Bax. EV71 infections are usually accompanied by severe neurological complications. It has also been postulated that the induction of cell apoptosis resulting from tissue damage is a possible process of EV71-related pathogenesis. In this study, we report that EV71 2B

  17. Enterovirus 71 2B Induces Cell Apoptosis by Directly Inducing the Conformational Activation of the Proapoptotic Protein Bax

    PubMed Central

    Cong, Haolong; Du, Ning; Yang, Yang; Song, Lei; Zhang, Wenliang

    2016-01-01

    ABSTRACT To survive and replicate within a host, many viruses have evolved strategies that target crucial components within the apoptotic cascade, leading to either inhibition or induction of cell apoptosis. Enterovirus 71 (EV71) infections have been demonstrated to impact the mitochondrial apoptotic pathway and induce apoptosis in many cell lines. However, the detailed mechanism of EV71-induced apoptosis remains to be elucidated. In this study, we report that EV71 2B protein (2B) localized to the mitochondria and induced cell apoptosis by interacting directly with and activating the proapoptotic protein Bax. 2B recruited Bax to the mitochondria and induced Bax conformational activation. In addition, mitochondria isolated from 2B-expressing cells that were treated with a recombinant Bax showed increased Bax interaction and cytochrome c (Cyt c) release. Importantly, apoptosis in cells with either EV71 infection or 2B expression was dramatically reduced in Bax knockdown cells but not in Bak knockdown cells, suggesting that Bax played a pivotal role in EV71- or 2B-induced apoptosis. Further studies indicate that a hydrophobic region of 18 amino acids (aa) in the C-terminal region of 2B (aa 63 to 80) was responsible for the location of 2B in the mitochondria. A hydrophilic region of 14 aa in the N-terminal region of 2B was functional in Bax interaction and its subsequent activation. Moreover, overexpression of the antiapoptotic protein Bcl-XL abrogates 2B-induced release of Cyt c and caspase activation. Therefore, this study provides direct evidence that EV71 2B induces cell apoptosis and impacts the mitochondrial apoptotic pathway by directly modulating the redistribution and activation of proapoptotic protein Bax. IMPORTANCE EV71 infections are usually accompanied by severe neurological complications. It has also been postulated that the induction of cell apoptosis resulting from tissue damage is a possible process of EV71-related pathogenesis. In this study, we

  18. Virtual Rover Drives Toward Rock

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This image shows a screenshot from the software used by engineers to test and drive the Mars Exploration Rover Spirit. The software simulates the rover's movements across the martian terrain, helping to plot a safe course. Here, engineers simulated Spirit's first post-egress drive on Mars Sunday. The 3-meter (10-foot) drive totaled approximately 30 minutes, including time to stop and take images. The rover drove toward its first rock target, a mountain-shaped rock called Adirondack. The blue line denotes the path of the rover's 'belly button,' as engineers like to call it, as the rover drove toward Adirondack. The virtual 3-D world around the rover was built from images taken by Spirit's stereo navigation cameras. Regions for which the rover has not yet acquired 3-D data are represented in beige.

  19. Multi-propeller drive system

    NASA Astrophysics Data System (ADS)

    Belenger, Robert V.

    1995-05-01

    A multipropeller drive system having a single input shaft for connection to an engine system, a differential gear assembly for dividing the driving force from the input drive shaft between a pair of output shafts, and a pair of laterally spaced propellers driven by the output shafts of the differential gear assembly is disclosed. The differential gear assembly operates in a manner wherein one output shaft, if required, is permitted to revolve at a different rate than the other output shaft. A pair of brake mechanisms acting on the output shafts of the differential gear assembly enable an operator to control the rotational speed of the respective propellers without modifying the engine speed or transmission settings.

  20. Drive: Theory and Construct Validation

    PubMed Central

    Petrides, K. V.

    2016-01-01

    This article explicates the theory of drive and describes the development and validation of two measures. A representative set of drive facets was derived from an extensive corpus of human attributes (Study 1). Operationalised using an International Personality Item Pool version (the Drive:IPIP), a three-factor model was extracted from the facets in two samples and confirmed on a third sample (Study 2). The multi-item IPIP measure showed congruence with a short form, based on single-item ratings of the facets, and both demonstrated cross-informant reliability. Evidence also supported the measures’ convergent, discriminant, concurrent, and incremental validity (Study 3). Based on very promising findings, the authors hope to initiate a stream of research in what is argued to be a rather neglected niche of individual differences and non-cognitive assessment. PMID:27409773

  1. MULTIPLE DIFFERENTIAL ROTARY MECHANICAL DRIVE

    DOEpatents

    Smits, R.G.

    1964-01-28

    This patent relates to a mechanism suitable for such applications as driving two spaced-apart spools which carry a roll film strip under conditions where the film movement must be rapidly started, stopped, and reversed while maintaining a constant tension on the film. The basic drive is provided by a variable speed, reversible rnotor coupled to both spools through a first differential mechanism and driving both spools in the same direction. A second motor, providing a constant torque, is connected to the two spools through a second differential mechanism and is coupled to impart torque to one spool in a first direction anid to the other spool in the reverse direction thus applying a constant tension to the film passing over the two spools irrespective of the speed or direction of rotation thereof. (AEC)

  2. Rover Takes a Sunday Drive

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This animation, made with images from the Mars Exploration Rover Spirit hazard-identification camera, shows the rover's perspective of its first post-egress drive on Mars Sunday. Engineers drove Spirit approximately 3 meters (10 feet) toward its first rock target, a football-sized, mountain-shaped rock called Adirondack. The drive took approximately 30 minutes to complete, including time stopped to take images. Spirit first made a series of arcing turns totaling approximately 1 meter (3 feet). It then turned in place and made a series of short, straightforward movements totaling approximately 2 meters (6.5 feet).

  3. Future hard disk drive systems

    NASA Astrophysics Data System (ADS)

    Wood, Roger

    2009-03-01

    This paper briefly reviews the evolution of today's hard disk drive with the additional intention of orienting the reader to the overall mechanical and electrical architecture. The modern hard disk drive is a miracle of storage capacity and function together with remarkable economy of design. This paper presents a personal view of future customer requirements and the anticipated design evolution of the components. There are critical decisions and great challenges ahead for the key technologies of heads, media, head-disk interface, mechanics, and electronics.

  4. 32 CFR 634.43 - Driving records.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Driving records. 634.43 Section 634.43 National... INVESTIGATIONS MOTOR VEHICLE TRAFFIC SUPERVISION Driving Records and the Traffic Point System § 634.43 Driving... suspension or revocation actions. Table 5-1 of Part 634 Suspension/Revocation of Driving Privileges...

  5. 32 CFR 634.43 - Driving records.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 4 2014-07-01 2013-07-01 true Driving records. 634.43 Section 634.43 National... INVESTIGATIONS MOTOR VEHICLE TRAFFIC SUPERVISION Driving Records and the Traffic Point System § 634.43 Driving... suspension or revocation actions. Table 5-1 of Part 634 Suspension/Revocation of Driving Privileges...

  6. 32 CFR 634.43 - Driving records.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 4 2013-07-01 2013-07-01 false Driving records. 634.43 Section 634.43 National... INVESTIGATIONS MOTOR VEHICLE TRAFFIC SUPERVISION Driving Records and the Traffic Point System § 634.43 Driving... suspension or revocation actions. Table 5-1 of Part 634 Suspension/Revocation of Driving Privileges...

  7. 32 CFR 634.43 - Driving records.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 4 2012-07-01 2011-07-01 true Driving records. 634.43 Section 634.43 National... INVESTIGATIONS MOTOR VEHICLE TRAFFIC SUPERVISION Driving Records and the Traffic Point System § 634.43 Driving... suspension or revocation actions. Table 5-1 of Part 634 Suspension/Revocation of Driving Privileges...

  8. Driving and Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

  9. Driving and Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

  10. Basic principles of variable speed drives

    NASA Technical Reports Server (NTRS)

    Loewenthal, S. H.

    1973-01-01

    An understanding of the principles which govern variable speed drive operation is discussed for successful drive application. The fundamental factors of torque, speed ratio, and power as they relate to drive selection are discussed. The basic types of variable speed drives, their operating characteristics and their applications are also presented.

  11. Type I interferons induce apoptosis by balancing cFLIP and caspase-8 independent of death ligands.

    PubMed

    Apelbaum, Amir; Yarden, Ganit; Warszawski, Shira; Harari, Daniel; Schreiber, Gideon

    2013-02-01

    Interferons induce a pleiotropy of responses through binding the same cell surface receptor. Here we investigated the molecular mechanism driving interferon-induced apoptosis. Using a nonbiased small interfering RNA (siRNA) screen, we show that silencing genes whose products are directly engaged in the initiation of interferon signaling completely abrogate the interferon antiproliferative response. Apoptosis-related genes such as the caspase-8, cFLIP, and DR5 genes specifically interfere with interferon-induced apoptosis, which we found to be independent of the activity of death ligands. The one gene for which silencing resulted in the strongest proapoptotic effect upon interferon signaling is the cFLIP gene, where silencing shortened the time of initiation of apoptosis from days to hours and increased dramatically the population of apoptotic cells. Thus, cFLIP serves as a regulator for interferon-induced apoptosis. A shift over time in the balance between cFLIP and caspase-8 results in downstream caspase activation and apoptosis. While gamma interferon (IFN-γ) also causes caspase-8 upregulation, we suggest that it follows a different path to apoptosis.

  12. Roller/Gear Drives For Robotic Manipulators

    NASA Technical Reports Server (NTRS)

    Anderson, William J.; Shipitalo, William

    1995-01-01

    Pitch/yaw roller/gear drive and wrist-roll roller/gear drive designed to incorporate several features desirable in robotic-joint actuators. Includes zero backlash, high efficiency, smooth motion (little ripple in torque and in speed ratio), and high degree of back-drivability. Pitch/yaw drive is novel two-axis drive containing combination of gears, rollers, and springs acting together eliminating backlash and cogging. Wrist-roll drive more-conventional single-axis drive offering advantages like those of pitch/yaw drive.

  13. Drive reconfiguration mechanism for tracked robotic vehicle

    DOEpatents

    Willis, W. David

    2000-01-01

    Drive reconfiguration apparatus for changing the configuration of a drive unit with respect to a vehicle body may comprise a guide system associated with the vehicle body and the drive unit which allows the drive unit to rotate about a center of rotation that is located at about a point where the drive unit contacts the surface being traversed. An actuator mounted to the vehicle body and connected to the drive unit rotates the drive unit about the center of rotation between a first position and a second position.

  14. Electronic 4-wheel drive control device

    NASA Technical Reports Server (NTRS)

    Hayato, S.; Takanori, S.; Shigeru, H.; Tatsunori, S.

    1984-01-01

    The internal rotation torque generated during operation of a 4-wheel drive vehicle is reduced using a control device whose clutch is attached to one part of the rear-wheel drive shaft. One torque sensor senses the drive torque associated with the rear wheel drive shaft. A second sensor senses the drive torque associated with the front wheel drive shaft. Revolution count sensors sense the revolutions of each drive shaft. By means of a microcomputer, the engagement of the clutch is changed to insure that the ratio of the torque sensors remains constant.

  15. Role of the tumor microenvironment in regulating apoptosis and cancer progression.

    PubMed

    Yaacoub, Katherine; Pedeux, Remy; Tarte, Karin; Guillaudeux, Thierry

    2016-08-10

    Apoptosis is a gene-directed program that is engaged to efficiently eliminate dysfunctional cells. Evasion of apoptosis may be an important gate to tumor initiation and therapy resistance. Like any other developmental program, apoptosis can be disrupted by several genetic aberrations driving malignant cells into an uncontrolled progression and survival. For its sustained growth, cancer develops in a complex environment, which provides survival signals and rescues malignant cells from apoptosis. Recent studies have clearly shown a wide interaction between tumor cells and their microenvironment, confirming the influence of the surrounding cells on tumor expansion and invasion. These non-malignant cells not only intensify tumor cells growth but also upgrade the process of metastasis. The strong crosstalk between malignant cells and a reactive microenvironment is mediated by soluble chemokines and cytokines, which act on tumor cells through surface receptors. Disturbing the microenvironment signaling might be an encouraging approach for patient's treatment. Therefore, the ultimate knowledge of "tumor-microenvironment" interactions facilitates the identification of novel therapeutic procedures that mobilize cancer cells from their supportive cells. This review focuses on cancer progression mediated by the dysfunction of apoptosis and by the fundamental relationship between tumor and reactive cells. New insights and valuable targets for cancer prevention and therapy are also presented. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Imbalance between apoptosis and cell proliferation during early stages of mammary gland carcinogenesis in ACI rats.

    PubMed

    Kutanzi, Kristy R; Koturbash, Igor; Bronson, Roderick T; Pogribny, Igor P; Kovalchuk, Olga

    2010-12-10

    Estrogen and ionizing radiation are well-documented human breast carcinogens, yet the exact mechanisms of their deleterious effects on mammary gland remain to be discerned. Here we analyze the balance between cellular proliferation and apoptosis in the mammary glands of rats exposed to estrogen and X-ray radiation and the combined action of these carcinogenic agents. For the first time, we show that combined exposure to estrogen and radiation has a synergistic effect on cell proliferation in the mammary glands of ACI rats, as evidenced by a substantially greater magnitude of cell proliferation, especially after 12 and 18 weeks of treatment, when compared to mammary glands of rats exposed to estrogen or radiation alone. We also demonstrate that an imbalance between cell proliferation and apoptosis, rather than enhanced cell proliferation or apoptosis suppression alone, may be a driving force for carcinogenesis. Our studies further suggest that compromised functional activity of p53 may be one of the mechanisms responsible for the proliferation/apoptosis imbalance. In sum, the results of our study indicate that evaluation of the extent of cell proliferation and apoptosis before the onset of preneoplastic lesions may be a potential biomarker of breast cancer risk after exposure to breast carcinogens.

  17. Inhibition of human neutrophil apoptosis by Paracoccidioides brasiliensis: role of interleukin-8.

    PubMed

    Acorci, M J; Dias-Melicio, L A; Golim, M A; Bordon-Graciani, A P; Peraçoli, M T S; Soares, A M V C

    2009-02-01

    Paracoccidioidomycosis (PCM) is a systemic mycosis caused by Paracoccidiodes brasiliensis that presents a wide spectrum of clinical manifestations. Because of the great number of neutrophils polymorphonuclear neutrophils (PMN) found in the P. brasiliensis granuloma, studies have been done to evaluate the role of these cells during the development of the infection. This fungus is found intracellularly in PMN and monocytes/macrophages, suggesting that it is capable of evading damage and surviving inside these cells. Thus, in the present study, we investigated whether P. brasiliensis can prolong the lifetime of PMN, and if this process would be related with IL-8 levels. PMN apoptosis and intracellular levels of IL-8 were analysed by flow cytometry and culture supernatants IL-8 levels were evaluated by enzyme-linked immunosorbent assay. We found that coincubation with P. brasiliensis yeast cells results in an inhibition of PMN apoptosis, which was associated with increase in IL-8 production by these cells. Cocultures treatment with monoclonal antibody anti-IL-8 reversed the inhibitory effect of P. brasiliensis on PMN apoptosis, besides to increase spontaneous apoptosis of these cells. These data show that, in contrast to other microbial pathogens that drive phagocytes into apoptosis to escape killing, P. brasiliensis can extend the lifetime of normal human PMN by inducing autocrine IL-8 production.

  18. OXIDATIVE STRESS ACTIVATES ANION EXCHANGE PROTEIN 2 AND AP-1 IN AIRWAY EPITHELIAL CELLS

    EPA Science Inventory

    Anion exchange protein 2 (AE2) is a membrane-bound protein that mediates chloride-bicarbonate exchange. In addition to regulating intracellular pH and cell volume, AE2 exports superoxide (O.) to the extracellular matrix in an HCO-dependent process. Given this ability to export O....

  19. OXIDATIVE STRESS ACTIVATES ANION EXCHANGE PROTEIN 2 AND AP-1 IN AIRWAY EPITHELIAL CELLS

    EPA Science Inventory

    Anion exchange protein 2 (AE2) is a membrane-bound protein that mediates chloride-bicarbonate exchange. In addition to regulating intracellular pH and cell volume, AE2 exports superoxide (O.) to the extracellular matrix in an HCO-dependent process. Given this ability to export O....

  20. Mouse fat storage-inducing transmembrane protein 2 (FIT2) promotes lipid droplet accumulation in plants

    USDA-ARS?s Scientific Manuscript database

    Fat Storage-Inducing Transmembrane protein 2 (FIT2) is an endoplasmic reticulum (ER)-localized protein that plays an important role in lipid droplet (LD) formation in animal cells. However, no obvious homologue of FIT2 is found in plants. Here, we tested the function of FIT2 in plant cells by ectopi...

  1. Virtual Rewards for Driving Green

    ERIC Educational Resources Information Center

    Pritchard, Josh

    2010-01-01

    Carbon dioxide from automobiles is a major contributor to global climate change. In "Virtual Rewards for Driving Green," Josh Pritchard proposes a computer application that will enable fuel-efficient drivers to earn "green" dollars with which to buy digital merchandise on the Web. Can getting items that exist only in cyberspace actually change a…

  2. Torque-Splitting Gear Drive

    NASA Technical Reports Server (NTRS)

    Kish, J.

    1991-01-01

    Geared drive train transmits torque from input shaft in equal parts along two paths in parallel, then combines torques in single output shaft. Scheme reduces load on teeth of meshing gears while furnishing redundancy to protect against failures. Such splitting and recombination of torques common in design of turbine engines.

  3. Promising Electric Aircraft Drive Systems

    NASA Technical Reports Server (NTRS)

    Dudley, Michael R.

    2010-01-01

    An overview of electric aircraft propulsion technology performance thresholds for key power system components is presented. A weight comparison of electric drive systems with equivalent total delivered energy is made to help identify component performance requirements, and promising research and development opportunities.

  4. Hydromechanical transmission with hydrodynamic drive

    DOEpatents

    Orshansky, Jr., deceased, Elias; Weseloh, William E.

    1979-01-01

    This transmission has a first planetary gear assembly having first input means connected to an input shaft, first output means, and first reaction means, and a second planetary gear assembly having second input means connected to the first input means, second output means, and second reaction means connected directly to the first reaction means by a reaction shaft. First clutch means, when engaged, connect the first output means to an output shaft in a high driving range. A hydrodynamic drive is used; for example, a torque converter, which may or may not have a stationary case, has a pump connected to the second output means, a stator grounded by an overrunning clutch to the case, and a turbine connected to an output member, and may be used in a starting phase. Alternatively, a fluid coupling or other type of hydrodynamic drive may be used. Second clutch means, when engaged, for connecting the output member to the output shaft in a low driving range. A variable-displacement hydraulic unit is mechanically connected to the input shaft, and a fixed-displacement hydraulic unit is mechanically connected to the reaction shaft. The hydraulic units are hydraulically connected together so that when one operates as a pump the other acts as a motor, and vice versa. Both clutch means are connected to the output shaft through a forward-reverse shift arrangement. It is possible to lock out the torque converter after the starting phase is over.

  5. Test-Driving Their Passions

    ERIC Educational Resources Information Center

    Davis, Noah

    2007-01-01

    This article describes how the Watson fellowships give recipients an opportunity to test-drive their passions and see if they could lead to a career path. Over the last 40 years, the Thomas J. Watson Foundation has awarded $29 million in fellowships to seniors graduating from 50 mostly top-tier colleges with fewer than 3,000 students. In 2007, 50…

  6. Test-Driving Their Passions

    ERIC Educational Resources Information Center

    Davis, Noah

    2007-01-01

    This article describes how the Watson fellowships give recipients an opportunity to test-drive their passions and see if they could lead to a career path. Over the last 40 years, the Thomas J. Watson Foundation has awarded $29 million in fellowships to seniors graduating from 50 mostly top-tier colleges with fewer than 3,000 students. In 2007, 50…

  7. Virtual Rewards for Driving Green

    ERIC Educational Resources Information Center

    Pritchard, Josh

    2010-01-01

    Carbon dioxide from automobiles is a major contributor to global climate change. In "Virtual Rewards for Driving Green," Josh Pritchard proposes a computer application that will enable fuel-efficient drivers to earn "green" dollars with which to buy digital merchandise on the Web. Can getting items that exist only in cyberspace actually change a…

  8. Drive axle for electric vehicle

    SciTech Connect

    Travis, J.M.

    1981-06-02

    An electric powered vehicle drive axle is disclosed. The axle of the present invention comprises a ring gear; a first pinion gear for rotating the ring gear; a differential carried by the ring gear; a pair of axle shafts driven by the differential for rotatably driving a pair of drive wheels; the device supported and enclosed by a housing. A second pinion gear is employed which rotatably engages the ring gear. A first electric motor rotatably connected to the first pinion gear is connected to a power source for rotatably driving the vehicle. A second electric motor/generator is connected to the second pinion gear and electrically connected to the power source. The second electric motor/generator selectively powers the differential or derives power from the differential to recharge the power source as dictated by the power needs of the electric vehicle. A plurality of bevel gears are deployed along the length of the axles. Each bevel gear is rotatably connected to a pair of opposed bevel gears, each opposed bevel gear is rotatably connected to an electric motor/generator. By selectively and electrically causing the plurality of motors/generators to either power the axle or be powered by the axle optimum efficiency and recharging of the battery over a range of vehicle operating conditions is obtained.

  9. Driving and working with syncope.

    PubMed

    Barbic, Franca; Casazza, Giovanni; Zamunér, Antonio Roberto; Costantino, Giorgio; Orlandi, Mauro; Dipaola, Franca; Capitanio, Chiara; Achenza, Sara; Sheldon, Robert; Furlan, Raffaello

    2014-09-01

    Syncope is usually addressed in the Emergency Department (ED) by the doctor in charge of the clinical picture, i.e. the patient's risk is stratified, a diagnostic work-up is done and a prognosis is set. Patients are ultimately admitted to hospital or discharged. However, other aspects related to syncope may deeply affect their daily lives. These include how and when to return to work and to driving, the feelings about a recent loss of consciousness, and the potential relapse of syncope. This is particularly significant if the work setting is intrinsically hazardous. These patients need adequate clinical and psychological support. For patients with syncope, two main parameters should be considered regarding returning to work and to driving. The first is to evaluate the risk of syncope recurrence and the second is to consider the expected harm if syncope does indeed occur during these activities. In the present paper we detail the problem of driving (including professional driving) and work after syncope. We propose a new quantitative model that will guide the physician in stratifying the risk for patients who have had a previous syncope event. The new model considers the syncope recurrence risk, the job task duration, and features that facilitate a syncope during work. On the basis of these variables, the global risk index for a worker is calculated. Following appropriate validation, this method might help ED and occupational physicians in their decision-making process with the goal of safely readmitting syncope patients to the workplace.

  10. Mechanical planetary compensating drive system

    NASA Technical Reports Server (NTRS)

    Zeiger, R. J.; Gerdts, J. C., Jr.

    1973-01-01

    Drive enables two concentric output shafts to be controlled independently or rotated as a unit. Possible uses are pointing and tracking devices, rotary camera shutters with variable light control, gimbal systems with yaw and pitch movement, spectrometer mirror scanning devices, etc.

  11. Anomalous-viscosity current drive

    DOEpatents

    Stix, T.H.; Ono, M.

    1986-04-25

    The present invention relates to a method and apparatus for maintaining a steady-state current for magnetically confining the plasma in a toroidal magnetic confinement device using anomalous viscosity current drive. A second aspect of this invention relates to an apparatus and method for the start-up of a magnetically confined toroidal plasma.

  12. Human papillomavirus oncoproteins and apoptosis (Review)

    PubMed Central

    JIANG, PEIYUE; YUE, YING

    2014-01-01

    The aim of this study was to review the literature and identify the association between human papillomavirus (HPV) oncoproteins and apoptosis. HPV-associated apoptosis may be primarily blocked by a number of oncoproteins, including E5, E6 and E7. E5 protein protects cells from tumor necrosis factor-associated apoptosis; the oncoprotein E6 predominantly inhibits apoptosis through the p53 pathway; and oncoprotein E7 is involved in apoptosis activation and inhibition. In addition, HPV oncoproteins are involved in activating or repressing the transcription of E6/E7. In conclusion, HPV oncoproteins, including E5, E6 and E7 protein, may interfere with apoptosis via certain regulatory principles. PMID:24348754

  13. Cannabis Effects on Driving Skills

    PubMed Central

    Hartman, Rebecca L.; Huestis, Marilyn A.

    2013-01-01

    BACKGROUND Cannabis is the most prevalent illicit drug identified in impaired drivers. The effects of cannabis on driving continue to be debated, making prosecution and legislation difficult. Historically, delays in sample collection, evaluating the inactive Δ9-tetrahydrocannabinol (THC) metabolite 11-nor-9-carboxy-THC, and polydrug use have complicated epidemiologic evaluations of driver impairment after cannabis use. CONTENT We review and evaluate the current literature on cannabis’ effects on driving, highlighting the epidemiologic and experimental data. Epidemiologic data show that the risk of involvement in a motor vehicle accident (MVA) increases approximately 2-fold after cannabis smoking. The adjusted risk of driver culpability also increases substantially, particularly with increased blood THC concentrations. Studies that have used urine as the biological matrix have not shown an association between cannabis and crash risk. Experimental data show that drivers attempt to compensate by driving more slowly after smoking cannabis, but control deteriorates with increasing task complexity. Cannabis smoking increases lane weaving and impaired cognitive function. Critical-tracking tests, reaction times, divided-attention tasks, and lane-position variability all show cannabis-induced impairment. Despite purported tolerance in frequent smokers, complex tasks still show impairment. Combining cannabis with alcohol enhances impairment, especially lane weaving. SUMMARY Differences in study designs frequently account for inconsistencies in results between studies. Participant-selection bias and confounding factors attenuate ostensible cannabis effects, but the association with MVA often retains significance. Evidence suggests recent smoking and/or blood THC concentrations 2–5 ng/mL are associated with substantial driving impairment, particularly in occasional smokers. Future cannabis-and-driving research should emphasize challenging tasks, such as divided attention

  14. Autophagy and apoptosis in planarians.

    PubMed

    González-Estévez, Cristina; Saló, Emili

    2010-03-01

    Adult planarians are capable of undergoing regeneration and body remodelling in order to adapt to physical damage or extreme environmental conditions. Moreover, most planarians can tolerate long periods of starvation and during this time, they shrink from an adult size to, and sometimes beyond, the initial size at hatching. Indeed, these properties have made them a classic model to study stem cells and regeneration. Under such stressful conditions, food reserves from the gastrodermis and parenchyma are first used up and later the testes, copulatory organs and ovaries are digested. More surprisingly, when food is again made available to shrunken individuals, they grow back to adult size and all their reproductive structures reappear. These cycles of growth and shrinkage may occur over long periods without any apparent impairment to the individual, or to its future maturation and breeding capacities. This plasticity resides in a mesoderm tissue known as the parenchyma, which is formed by several differentiated non-proliferating cell types and only one mitotically active cell type, the neoblasts, which represent approximately 20-30% of the cells in the parenchyma. Neoblasts are generally thought to be somatic stem-cells that participate in the normal continuous turnover of all cell types in planarians. Hence, planarians are organisms that continuously adapt their bodies (morphallaxis) to different environmental stresses (i.e.: injury or starvation). This adaptation involves a variety of processes including proliferation, differentiation, apoptosis and autophagy, all of which are perfectly orchestrated and tightly regulated to remodel or restore the body pattern. While neoblast biology and body re-patterning are currently the subject of intense research, apoptosis and autophagy remain much less studied. In this review we will summarize our current understanding and hypotheses regarding where and when apoptosis and autophagy occur and fulfil an essential role in

  15. Mycobacterium tuberculosis effectors interfering host apoptosis signaling.

    PubMed

    Liu, Minqiang; Li, Wu; Xiang, Xiaohong; Xie, Jianping

    2015-07-01

    Tuberculosis remains a serious human public health concern. The coevolution between its pathogen Mycobacterium tuberculosis and human host complicated the way to prevent and cure TB. Apoptosis plays subtle role in this interaction. The pathogen endeavors to manipulate the apoptosis via diverse effectors targeting key signaling nodes. In this paper, we summarized the effectors pathogen used to subvert the apoptosis, such as LpqH, ESAT-6/CFP-10, LAMs. The interplay between different forms of cell deaths, such as apoptosis, autophagy, necrosis, is also discussed with a focus on the modes of action of effectors, and implications for better TB control.

  16. Apoptosis and Molecular Targeting Therapy in Cancer

    PubMed Central

    Hassan, Mohamed; Watari, Hidemichi; AbuAlmaaty, Ali; Ohba, Yusuke; Sakuragi, Noriaki

    2014-01-01

    Apoptosis is the programmed cell death which maintains the healthy survival/death balance in metazoan cells. Defect in apoptosis can cause cancer or autoimmunity, while enhanced apoptosis may cause degenerative diseases. The apoptotic signals contribute into safeguarding the genomic integrity while defective apoptosis may promote carcinogenesis. The apoptotic signals are complicated and they are regulated at several levels. The signals of carcinogenesis modulate the central control points of the apoptotic pathways, including inhibitor of apoptosis (IAP) proteins and FLICE-inhibitory protein (c-FLIP). The tumor cells may use some of several molecular mechanisms to suppress apoptosis and acquire resistance to apoptotic agents, for example, by the expression of antiapoptotic proteins such as Bcl-2 or by the downregulation or mutation of proapoptotic proteins such as BAX. In this review, we provide the main regulatory molecules that govern the main basic mechanisms, extrinsic and intrinsic, of apoptosis in normal cells. We discuss how carcinogenesis could be developed via defective apoptotic pathways or their convergence. We listed some molecules which could be targeted to stimulate apoptosis in different cancers. Together, we briefly discuss the development of some promising cancer treatment strategies which target apoptotic inhibitors including Bcl-2 family proteins, IAPs, and c-FLIP for apoptosis induction. PMID:25013758

  17. Apoptosis in cancer: from pathogenesis to treatment

    PubMed Central

    2011-01-01

    Apoptosis is an ordered and orchestrated cellular process that occurs in physiological and pathological conditions. It is also one of the most studied topics among cell biologists. An understanding of the underlying mechanism of apoptosis is important as it plays a pivotal role in the pathogenesis of many diseases. In some, the problem is due to too much apoptosis, such as in the case of degenerative diseases while in others, too little apoptosis is the culprit. Cancer is one of the scenarios where too little apoptosis occurs, resulting in malignant cells that will not die. The mechanism of apoptosis is complex and involves many pathways. Defects can occur at any point along these pathways, leading to malignant transformation of the affected cells, tumour metastasis and resistance to anticancer drugs. Despite being the cause of problem, apoptosis plays an important role in the treatment of cancer as it is a popular target of many treatment strategies. The abundance of literature suggests that targeting apoptosis in cancer is feasible. However, many troubling questions arise with the use of new drugs or treatment strategies that are designed to enhance apoptosis and critical tests must be passed before they can be used safely in human subjects. PMID:21943236

  18. Apoptosis-Dependent and Apoptosis-Independent Functions Bim in Prostate Cancer Cells

    DTIC Science & Technology

    2004-03-01

    AD_ Award Number: DAMD17-03-1-0146 TITLE: Apoptosis-Dependent and Apoptosis-Independent Functions of Bim in Prostate Cancer Cells PRINCIPAL...FUNDING NUMBERS Apoptosis-Dependent and Apoptosis-Independent Functions of DAMD17-03-1-0146 Bim in Prostate Cancer Cells 6. A UTHORs) Junwei Liu, M.D...extended cell survival have been implicated in prostate cancer (PCa) development and progression. We recently found that Bim , a BH3-only pro

  19. Driving with Hemianopia, I: Detection Performance in a Driving Simulator

    PubMed Central

    Bowers, Alex R.; Mandel, Aaron J.; Goldstein, Robert B.; Peli, Eli

    2009-01-01

    Purpose This study was designed to examine the effect of homonymous hemianopia (HH) on detection of pedestrian figures in multiple realistic and hazardous situations within the controlled environment of a driving simulator. Methods Twelve people with complete HH and without visual neglect or cognitive decline and 12 matched (age, sex, and years of driving experience) normally sighted (NV) drivers participated. They drove predetermined city and rural highway routes (total, 120 minutes) during which pedestrian figures appeared at random intervals along the roadway (R-Peds; n = 144) and at intersections (I-Peds; n = 10). Detection rates and response times were derived from participant horn presses. Results Drivers with HH exhibited significantly (P < 0.001) lower R-Ped detection rates on the blind side than did NV drivers (range, 6%–100%). Detection of I-Peds on the blind side was also poor (8%–55%). Age and blind-side detection rates correlated negatively (Spearman r = −0.71, P = 0.009). Although blind-side response times of drivers with HH were significantly (P < 0.001) longer than those of NV drivers, most were within a commonly used 2.5-second guideline. Conclusions Most participants with HH had blind-side detection rates that seem incompatible with safe driving; however, the relationship of our simulator detection performance measures to on-road performance has yet to be established. In determining fitness to drive for people with HH, the results underscore the importance of individualized assessments including evaluations of blind-side hazard detection. PMID:19608541

  20. Stability and skill in driving.

    PubMed

    Treffner, Paul; Barrett, Rod; Petersen, Andrew

    2002-12-01

    Two experiments addressed the relation between postural stability, perceptual sensitivity, and stability of driving performance. A vehicle was fitted with differential GPS for measuring position and speed, position sensors for measuring brake and accelerator depression, force transducers for measuring door, console and footrest bracing forces, and an accelerometer for measuring the 3D accelerations of the vehicle. In Experiment 1, we investigated whether the initiation of deceleration and the control of braking might be due to sensitivity to the perceptual variable tau, which specifies time-to-contact (TTC), and in particular, whether its first derivative, tau-dot, is used to maintain a constant deceleration profile. Using both untrained experienced drivers (EDs) and trained driving instructors from the Holden Performance Driving Centre (HPDC), results confirmed that, regardless of skill level, tau-dot was maintained at a value close to 0.5 and, as predicted by Lee [Perception 5 (1976) 437], braking was initiated when TTC approximately 5 s. In Experiment 2, we wished to quantify the purported differences in driving behaviour between EDs and HPDC instructors during a variety of everyday manoeuvres. Results indicated that instructors utilised a different cornering trajectory, a different emergency braking strategy, and were able to perform a high-speed swerve and recovery task more effectively than the EDs. In general, the instructors applied greater bracing forces using the door and console compared with EDs. The instructors also applied greater footrest forces during emergency braking than did the EDs. The greater use of bracing by instructor drivers to resist g-forces represents a strategy of active stabilisation that enhances both postural stability, as well as overall stability and consistency of driving performance. Results are discussed with regard to the dynamics of perceptual-motor coordination, and how increased stability might improve sensitivity to

  1. Apoptosis in oral lichen planus.

    PubMed

    Neppelberg, E; Johannessen, A C; Jonsson, R

    2001-10-01

    Apoptotic cell death may be a contributory cause of basal cell destruction in oral lichen planus (OLP). Therefore. the purpose of this study was to investigate the rate of apoptosis in OLP and the expression of two proteins (FasR and FasL) regulating this process. Biopsies from 18 patients with histologically diagnosed OLP were investigated, with comparison to normal oral mucosa of healthy persons. For visualisation of DNA fragmentation, the TUNEL method was used. In order to characterise the infiltrating cell population (CD3. CD4, CD8) and expression of FasR and FasL, we used an immunohistochemical technique. The results showed that T cells dominated in the subepithelial cell infiltrate. Within the epithelium the apoptotic cells were confined to the basal cell layer, and more apoptotic cells were seen in areas with basal cell degeneration and atrophic epithelium. There was a prominent expression of FasR/FasL in OLP. with a rather uniform distribution throughout the inflammatory cell infiltrate. In the epithelium, the FasR/FasL expression was more abundant in the basal cell area compared to the suprabasal cell layer. In conclusion, apoptosis within the epithelium is significantly increased in situ in OLP compared to normal oral mucosa, and seems to be related to the epithelial thickness.

  2. Differentiation and apoptosis in pilomatrixoma.

    PubMed

    Ishige, Toshiyuki; Kikuchi, Kentaro; Miyazaki, Yuji; Hara, Hiroyuki; Yoshino, Atsuo; Terui, Tadashi; Katayama, Yoichi; Kusama, Kaoru; Nemoto, Norimichi

    2011-02-01

    We carried out a histopathologic study of pilomatrixoma, a benign skin tumor, and also examined apoptosis and hair differentiation with the aim to understand the presence of amorphous debris and cyst formation in the tumor. Among 16 cases of pilomatrixoma examined, 11 were at the early regressive stage and 5 were at the late regressive stage according to the classification by Kaddu et al. In the former cases, tumor nests were basically composed of basophilic, transitional, and shadow cells. Cyst formation was evident in all cases and squamoid epithelium was observed in 4 cases at the early regressive stage. Amorphous debris was found in all cases including those at the late regressive stage. Immunohistochemical analysis revealed positive reaction products for β-catenin and Lef-1 in basophilic and transitional cells, although their distribution differed. Immunoreactivity for β-catenin was observed in the lower transitional cells, whereas immunoreactivity for Lef-1 was also evident in the upper transitional cells. Positive reactions for hair keratins were found in the cytoplasm of transitional and shadow cells, but not in the amorphous debris. Examination by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method revealed positive reactions in transitional and some shadow cells. These results suggest that in pilomatrixoma, production of hair keratin and induction of apoptosis may occur at the same time, and that unlike the normal hair follicle irregular expression of β-catenin and Lef-1 results in the appearance of amorphous debris and cyst formation.

  3. Magnetically Coupled Adjustable Speed Drive Systems

    SciTech Connect

    Chvala, William D.; Winiarski, David W.

    2002-08-18

    Adjustable speed drive (ASD) technologies have the ability to precisely control motor sytems output and produce a numbr of benefits including energy and demand savings. This report examines the performance and cost effectiveness of a specific class of ASDs called magnetically-coupled adjustable speed drives (MC-ASD) which use the strength of a magnetic field to control the amount of torque transferred between motor and drive shaft. The MagnaDrive Adjustable Speed Coupling System uses fixed rare-earth magnets and varies the distance between rotating plates in the assembly. the PAYBACK Variable Speed Drive uses an electromagnet to control the speed of the drive

  4. Conditional dynamics driving financial markets

    NASA Astrophysics Data System (ADS)

    Boguñá, M.; Masoliver, J.

    2004-08-01

    We revisit the problem of daily correlations in speculative prices and report empirical evidences on the existence of what we term a conditional or dual dynamics driving the evolution of financial assets. This dynamics is detected in several markets around the world and for different historical periods. In particular, we have analyzed the DJIA database from 1900 to 2002 as well as 65 companies trading in the LIFFE market of futures and 12 of the major European and American treasury bonds. In all cases, we find a twofold dynamics driving the financial evolution depending on whether the previous price went up or down. We conjecture that this effect is universal and intrinsic to all markets.

  5. Sensory drive in cichlid speciation.

    PubMed

    Maan, Martine E; Hofker, Kees D; van Alphen, Jacques J M; Seehausen, Ole

    2006-06-01

    The role of selection in speciation is a central yet poorly understood problem in evolutionary biology. The rapid radiations of extremely colorful cichlid fish in African lakes have fueled the hypothesis that sexual selection can drive species divergence without geographical isolation. Here we present experimental evidence for a mechanism by which sexual selection becomes divergent: in two sibling species from Lake Victoria, female mating preferences for red and blue male nuptial coloration coincide with their context-independent sensitivities to red and blue light, which in turn correspond to a difference in ambient light in the natural habitat of the species. These results suggest that natural selection on visual performance, favoring different visual properties in different spectral environments, may lead to divergent sexual selection on male nuptial coloration. This interplay of ecological and sexual selection along a light gradient may provide a mechanism of rapid speciation through divergent sensory drive.

  6. Warp Drive - A New Approach

    NASA Astrophysics Data System (ADS)

    Obousy, R. K.; Cleaver, G.

    Certain classes of higher dimensional models suggest that the Casimir Effect is a candidate for the cosmological constant. In this paper we demonstrate that a sufficiently advanced civilization could, in principal, manipulate the radius of the extra dimension to locally adjust the value of the cosmological constant. This adjustment could be tuned to generate an expansion/ contraction of spacetime around a spacecraft creating an exotic form of field-propulsion. Due to the fact that spacetime expansion itself is not restricted by relativity, a faster-than-light `warp drive' could be created. Calculations of the energy requirements of such a drive are performed and an `ultimate' speed limit, based on the Planckian limits on the size of the extra dimensions is found.

  7. Adjustable frequency drives save energy

    SciTech Connect

    Lambeth, J. ); Houston, J. )

    1991-05-01

    This article describes the use of an adjustable frequency drive for a water pump in a waste water treatment plant. In addition to reducing energy consumption, maintenance costs were reduced and the efficiency of the plant and the primary clarifier was increased. Variations in water level are reduced by improved control of the pump speed, rather than an on/off response to water level.

  8. Low frequency rf current drive

    SciTech Connect

    Hershkowitz, N.

    1992-01-01

    An unshielded antenna for rf heating has been developed and tested during this report period. In addition to design specifications being given, some experimental results are presented utilizing: (1) an unprotected Faraday shield, (2) insulating guard limiters, (3) unshielded antenna experiments, (4) method for detecting small rf driven currents, (5) rf fast wave current drive experiments, (6) alfven wave interactions with electrons, and (7) machine conditioning, impurity generation and density control.

  9. Electric vehicle drive train components

    SciTech Connect

    Silver, F.

    1994-12-31

    Power Control Systems has developed a family of electric vehicle drive systems that range from 65 horsepower through 300 horse power. These propulsion systems support vehicle applications ranging from light cars and pickups to buses and trucks weighing as much as 40,000 lbs (18,400 kg). These robust systems are designed specifically for automotive applications including safety, electromagnetic emissions, and environment ruggedness. Dolphin Drive Systems are very flexible. Their inverter controllers are programmable and can be provided as stand alone components matched to customer specified motors. A selection of pre-calibrated systems including motor and inverter/controller can be provided. Accessory tools are also available for customer self programming. Dolphin Drive Systems provide precision control of AC induction motors providing excellent torque-speed performance usually eliminating the need for multistage transmissions. In addition, they are very efficient over a wide speed/torque range. This provides for excellent power management over a variety of continuous speed and stop and go applications.

  10. Non-differential drive axle

    SciTech Connect

    Hardt, J.G.; Shea, D.W.

    1987-02-17

    This patent describes a drive axle for a vehicle, the vehicle having a set of wheels spaced along a first axis of rotation of the wheels, the drive axle comprising: a housing adapted to extend generally along the first axis between the two wheels, the housing first and second axially spaced ends, a gear support rotatably journalled in the housing adjacent the first end of the housing, an intermediate shaft drivingly connected to the gear support and rotatably journalled in the housing adjacent the second end of the housing, a first output shaft rotatably journalled in the first end of the housing and the gear support, a second output shaft rotatably journalled in the second end of the housing and the intermediate shaft, and a first bi-directional overrunning clutch positioned adjacent the first end of the housing and operable to connect the first output shaft with the gear support for conjoint rotation. The first overrunning clutch includes a first non-circular surface on the gear support, a first drum connected to the first output shaft and overlying the first non-circular surface, and rollers disposed between the first drum and the first non-circular surface actuatable to connect the first drum and the first non-circular surface for conjoint rotation.

  11. Apoptosis in mammalian oocytes: a review.

    PubMed

    Tiwari, Meenakshi; Prasad, Shilpa; Tripathi, Anima; Pandey, Ashutosh N; Ali, Irfan; Singh, Arvind K; Shrivastav, Tulsidas G; Chaube, Shail K

    2015-08-01

    Apoptosis causes elimination of more than 99% of germ cells from cohort of ovary through follicular atresia. Less than 1% of germ cells, which are culminated in oocytes further undergo apoptosis during last phases of oogenesis and depletes ovarian reserve in most of the mammalian species including human. There are several players that induce apoptosis directly or indirectly in oocytes at various stages of meiotic cell cycle. Premature removal of encircling granulosa cells from immature oocytes, reduced levels of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate, increased levels of calcium (Ca(2+)) and oxidants, sustained reduced level of maturation promoting factor, depletion of survival factors, nutrients and cell cycle proteins, reduced meiotic competency, increased levels of proapoptotic as well as apoptotic factors lead to oocyte apoptosis. The BH3-only proteins also act as key regulators of apoptosis in oocyte within the ovary. Both intrinsic (mitochondria-mediated) as well as extrinsic (cell surface death receptor-mediated) pathways are involved in oocyte apoptosis. BID, a BH3-only protein act as a bridge between both apoptotic pathways and its cleavage activates cell death machinery of both the pathways inside the follicular microenvironment. Oocyte apoptosis leads to the depletion of ovarian reserve that directly affects reproductive outcome of various mammals including human. In this review article, we highlight some of the important players and describe the pathways involved during oocyte apoptosis in mammals.

  12. Apoptosis in chronic tonsillitis and tonsillar hypertrophy.

    PubMed

    Önal, Merih; Yılmaz, Taner; Bilgiç, Elif; Müftüoğlu, Sevda Fatma; Kuşçu, Oğuz; Günaydın, Rıza Önder

    2015-02-01

    Chronic tonsillitis is the persistent inflammation of the tonsillar tissue that occurs due to recurrent, acute or subclinical infection. The recurrent and chronic inflammation of palatine tonsils sometimes results in hypertrophy. Apoptosis provides an important balance between lymphocytes in tonsillar lymphoid tissue. The aim of this study is to investigate the apoptosis in tonsillar diseases. 43 patients with chronic tonsilitis and tonsillar hypertrophy underwent tonsillectomy. The specimens were examined immunohistochemically for apoptosis. Tonsils were assembled into groups according to their size. Specimens were compared for their apoptotic cell count. The apoptosis difference between the tonsil size groups is not statistically significant (p>0.05). However, when the study group was divided into two at age 6, the difference was not statistically significant for patients at and below 6 years of age; but, the difference was statistically significant for patients above 6 years of age (p<0.05). The comparison of apoptosis in microcompartments of tonsil tissue (intrafollicular, interfollicular, subepithelial and intraepithelial) between tonsil size stages and between chronic tonsillitis and tonsillar hypertrophy groups revealed no statistical significance (p>0.05). There was a statistically significant positive correlation between intrafollicular and interfollicular, interfollicular and intraepithelial & subepithelial and intraepithelial areas (p<0.05). In the light of these findings, it was concluded that apoptosis played a role in the tonsillar hypertrophy and atrophy. Apoptosis functioned to balance lymphocyte proliferation in tonsil tissue. The association of apoptosis with tonsillar hypertrophy seemed to be age-dependent. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Apoptosis in immune-mediated diseases

    PubMed Central

    Sankari, S. Leena; Babu, N. Aravindha; Rajesh, E.; Kasthuri, M.

    2015-01-01

    Apoptosis plays a significant role in both the physiological and pathological process. A dysfunctional apoptotic system can lead to either excessive removal or prolonged survival of cells. Therefore, dysregulation is involved in the pathogenesis of a variety of immunological diseases. The present review aims to provide an overview regarding role of apoptosis in immune-mediated disease. PMID:26015710

  14. Proteases in Fas-mediated apoptosis.

    PubMed

    Zhivotovsky, B; Burgess, D H; Schlegel, J; Pörn, M I; Vanags, D; Orrenius, S

    1997-01-01

    Involvement of a unique family of cysteine proteases in the multistep apoptotic process has been documented. Cloning of several mammalian genes identifies some components of this cellular response. However, it is currently unclear which protease plays a role as a signal and/or effector of apoptosis. We summarize contributions to the data concerning proteases in Fas-mediated apoptosis.

  15. THE ROLE OF APOPTOSIS IN NEUROTOXICOLOGY.

    EPA Science Inventory

    The role of apoptosis in neurodegeneration in developing animals and in adults has become increasingly apparent in the past ten years. Normal apoptosis occurs in the CNS from the embryonic stage through senescence, with different cells in each region of the nervous system having ...

  16. Local anesthetics induce human renal cell apoptosis.

    PubMed

    Lee, H Thomas; Xu, Hua; Siegel, Cory D; Krichevsky, Igor E

    2003-01-01

    Renal cell apoptosis contributes significantly to the pathogenesis of acute renal failure. Local anesthetics induce apoptosis in neuronal and lymphocytic cell lines. We examined the effects of chronic (48 h) local anesthetic treatment (lidocaine, bupivacaine and tetracaine) on human proximal tubular (HK-2) cells. Apoptosis induction was assessed by detecting poly(ADP)-ribose polymerase fragmentation, caspase activation, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining, DNA laddering and by cellular morphology. Cell death was quantified by measuring neutral red dye uptake and lactate dehydrogenase released into the cell culture medium. All 3 local anesthetics caused concentration-dependent cell death, induced HK-2 cell apoptosis and potentiated TNF-alpha induced apoptosis. Local anesthetics induced HK-2 cell apoptosis by activation of caspases 3, 6, 7, 8 and 9. ZVAD-fmk, a pan-caspase inhibitor, blocked the local anesthetic induced HK-2 cell apoptosis. Local anesthetics also inhibited the activities of anti-apoptotic kinases protein kinase B (Akt) and extracellular signal regulated mitrogen-activated protein kinase. Local anesthetic's pro-apoptotic effects are independent of sodium channel inhibition as tetrodotoxin, a selective voltage-gated sodium channel blocker, failed to mimic local anesthetic-mediated induction or potentiation of HK-2 cell apoptosis. We conclude that local anesthetics induce human renal cell apoptotic signaling by caspase activation and via inhibition of pro-survival signaling pathways.

  17. Apoptosis in acquired and genetic hearing impairment

    PubMed Central

    de Beeck, Ken Op; Schacht, Jochen; Van Camp, Guy

    2012-01-01

    Apoptosis is an important physiological process. Normally, a healthy cell maintains a delicate balance between pro- and anti-apoptotic factors, allowing it to live and proliferate. It is thus not surprising that disturbance of this delicate balance may result in disease. It is a well known fact that apoptosis also contributes to several acquired forms of hearing impairment. Noise-induced hearing loss is the result of prolonged exposure to excessive noise, triggering apoptosis in terminally differentiated sensory hair cells. Moreover, hearing loss caused by the use of therapeutic drugs such as aminoglycoside antibiotics and cisplatin potentially may result in the activation of apoptosis in sensory hair cells leading to hearing loss due to the “ototoxicity” of the drugs. Finally, apoptosis is a key contributor to the development of presbycusis, age-related hearing loss. Recently, several mutations in apoptosis genes were identified as the cause of monogenic hearing impairment. These genes are TJP2, DFNA5 and MSRB3. This implies that apoptosis not only contributes to the pathology of acquired forms of hearing impairment, but also to genetic hearing impairment as well. We believe that these genes constitute a new functional class within the hearing loss field. Here, the contribution of apoptosis in the pathology of both acquired and genetic hearing impairment is reviewed. PMID:21782914

  18. THE ROLE OF APOPTOSIS IN NEUROTOXICOLOGY.

    EPA Science Inventory

    The role of apoptosis in neurodegeneration in developing animals and in adults has become increasingly apparent in the past ten years. Normal apoptosis occurs in the CNS from the embryonic stage through senescence, with different cells in each region of the nervous system having ...

  19. A Novel Transcription Complex That Selectively Modulates Apoptosis of Breast Cancer Cells through Regulation of FASTKD2 ▿

    PubMed Central

    Yeung, Kay T.; Das, Sharmistha; Zhang, Jin; Lomniczi, Alejandro; Ojeda, Sergio R.; Xu, Chong-Feng; Neubert, Thomas A.; Samuels, Herbert H.

    2011-01-01

    We previously reported that expression of NRIF3 (nuclear receptor interacting factor-3) rapidly and selectively leads to apoptosis of breast cancer cells. DIF-1 (also known as interferon regulatory factor-2 binding protein 2 [IRF-2BP2]), the cellular target of NRIF3, was identified as a transcriptional repressor, and DIF-1 knockdown leads to apoptosis of breast cancer cells but not other cell types. Here, we identify IRF-2BP1 and EAP1 (enhanced at puberty 1) as important components of the DIF-1 complex mediating both complex stability and transcriptional repression. This interaction of DIF-1, IRF-2BP1, and EAP1 occurs through the conserved C4 zinc fingers of these proteins. Microarray studies were carried out in breast cancer cell lines engineered to conditionally and rapidly increase the levels of the death domain (DD1) region of NRIF3. The DIF-1 complex was found to repress FASTKD2, a putative proapoptotic gene, in breast cancer cells and to bind to the FASTKD2 gene by chromatin immunoprecipitation. FASTKD2 knockdown prevents apoptosis of breast cancer cells from NRIF3 expression or DIF-1 knockdown, while expression of FASTKD2 leads to apoptosis of both breast and nonbreast cancer cells. Thus, regulation of FASTKD2 by NRIF3 and the DIF-1 complex acts as a novel death switch that selectively modulates apoptosis in breast cancer. PMID:21444724

  20. Regulation of apoptosis by heat shock proteins.

    PubMed

    Kennedy, Donna; Jäger, Richard; Mosser, Dick D; Samali, Afshin

    2014-05-01

    Thermotolerance, the acquired resistance of cells to stress, is a well-established phenomenon. Studies of the key mediators of this response, the heat shock proteins (HSPs), have led to the discovery of the important roles played by these proteins in the regulation of apoptotic cell death. Apoptosis is critical for normal tissue homeostasis and is involved in diverse processes including development and immune clearance. Apoptosis is tightly regulated by both proapoptotic and antiapoptotic factors, and dysregulation of apoptosis plays a significant role in the pathophysiology of many diseases. In the recent years, HSPs have been identified as key determinants of cell survival, which can modulate apoptosis by directly interacting with components of the apoptotic machinery. Therefore, manipulation of the HSPs could represent a viable strategy for the treatment of diseases. Here, we review the current knowledge with regard to the mechanisms of HSP-mediated regulation of apoptosis. © 2014 International Union of Biochemistry and Molecular Biology.

  1. Cancer Therapy Due to Apoptosis: Galectin-9

    PubMed Central

    Fujita, Koji; Iwama, Hisakazu; Oura, Kyoko; Tadokoro, Tomoko; Samukawa, Eri; Sakamoto, Teppei; Nomura, Takako; Tani, Joji; Yoneyama, Hirohito; Morishita, Asahiro; Himoto, Takashi; Hirashima, Mitsuomi; Masaki, Tsutomu

    2017-01-01

    Dysregulation of apoptosis is a major hallmark in cancer biology that might equip tumors with a higher malignant potential and chemoresistance. The anti-cancer activities of lectin, defined as a carbohydrate-binding protein that is not an enzyme or antibody, have been investigated for over a century. Recently, galectin-9, which has two distinct carbohydrate recognition domains connected by a linker peptide, was noted to induce apoptosis in thymocytes and immune cells. The apoptosis of these cells contributes to the development and regulation of acquired immunity. Furthermore, human recombinant galectin-9, hG9NC (null), which lacks an entire region of the linker peptide, was designed to resist proteolysis. The hG9NC (null) has demonstrated anti-cancer activities, including inducing apoptosis in hematological, dermatological and gastrointestinal malignancies. In this review, the molecular characteristics, history and apoptosis-inducing potential of galectin-9 are described. PMID:28045432

  2. Cancer Therapy Due to Apoptosis: Galectin-9.

    PubMed

    Fujita, Koji; Iwama, Hisakazu; Oura, Kyoko; Tadokoro, Tomoko; Samukawa, Eri; Sakamoto, Teppei; Nomura, Takako; Tani, Joji; Yoneyama, Hirohito; Morishita, Asahiro; Himoto, Takashi; Hirashima, Mitsuomi; Masaki, Tsutomu

    2017-01-01

    Dysregulation of apoptosis is a major hallmark in cancer biology that might equip tumors with a higher malignant potential and chemoresistance. The anti-cancer activities of lectin, defined as a carbohydrate-binding protein that is not an enzyme or antibody, have been investigated for over a century. Recently, galectin-9, which has two distinct carbohydrate recognition domains connected by a linker peptide, was noted to induce apoptosis in thymocytes and immune cells. The apoptosis of these cells contributes to the development and regulation of acquired immunity. Furthermore, human recombinant galectin-9, hG9NC (null), which lacks an entire region of the linker peptide, was designed to resist proteolysis. The hG9NC (null) has demonstrated anti-cancer activities, including inducing apoptosis in hematological, dermatological and gastrointestinal malignancies. In this review, the molecular characteristics, history and apoptosis-inducing potential of galectin-9 are described.

  3. Apoptosis inducers in chronic lymphocytic leukemia

    PubMed Central

    Billard, Christian

    2014-01-01

    Chronic lymphocytic leukemia (CLL) is characterized by a typical defect in apoptosis and is still an incurable disease. Numerous apoptosis inducers have been described. These synthetic compounds and natural products (mainly derived from plants) display antileukemic properties in vitro and in vivo and some have even been tested in the clinic in CLL. They act through several different mechanisms. Most of them involve proteins of the Bcl-2 family, which are the key regulators in triggering the mitochondrial pathway of caspase-dependent apoptosis. Thus, the Mcl-1/Noxa axis appeared as a target. Here I overview natural and synthetic apoptosis inducers and their mechanisms of action in CLL cells. Opportunities for developing novel, apoptosis-based therapeutics are presented. PMID:24525395

  4. 30 CFR 77.406 - Drive belts.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Mechanical Equipment § 77.406 Drive belts. (a) Drive belts shall not be shifted while in motion unless the machines are provided with mechanical shifters. (b) Belt dressing shall not be applied while belts are...

  5. 30 CFR 77.406 - Drive belts.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Mechanical Equipment § 77.406 Drive belts. (a) Drive belts shall not be shifted while in motion unless the machines are provided with mechanical shifters. (b) Belt dressing shall not be applied while belts are...

  6. Autophagy and apoptosis: where do they meet?

    PubMed

    Mukhopadhyay, Subhadip; Panda, Prashanta Kumar; Sinha, Niharika; Das, Durgesh Nandini; Bhutia, Sujit Kumar

    2014-04-01

    Autophagy and apoptosis are two important cellular processes with complex and intersecting protein networks; as such, they have been the subjects of intense investigation. Recent advances have elucidated the key players and their molecular circuitry. For instance, the discovery of Beclin-1's interacting partners has resulted in the identification of Bcl-2 as a central regulator of autophagy and apoptosis, which functions by interacting with both Beclin-1 and Bax/Bak respectively. When localized to the endoplasmic reticulum and mitochondria, Bcl-2 inhibits autophagy. Cellular stress causes the displacement of Bcl-2 from Beclin-1 and Bax, thereby triggering autophagy and apoptosis, respectively. The induction of autophagy or apoptosis results in disruption of complexes by BH3-only proteins and through post-translational modification. The mechanisms linking autophagy and apoptosis are not fully defined; however, recent discoveries have revealed that several apoptotic proteins (e.g., PUMA, Noxa, Nix, Bax, XIAP, and Bim) modulate autophagy. Moreover, autophagic proteins that control nucleation and elongation regulate intrinsic apoptosis through calpain- and caspase-mediated cleavage of autophagy-related proteins, which switches the cellular program from autophagy to apoptosis. Similarly, several autophagic proteins are implicated in extrinsic apoptosis. This highlights a dual cellular role for autophagy. On one hand, autophagy degrades damaged mitochondria and caspases, and on the other hand, it provides a membrane-based intracellular platform for caspase processing in the regulation of apoptosis. In this review, we highlight the crucial factors governing the crosstalk between autophagy and apoptosis and describe the mechanisms controlling cell survival and cell death.

  7. Hepatic encephalopathy and fitness to drive.

    PubMed

    Kircheis, Gerald; Knoche, Anja; Hilger, Norbert; Manhart, Frank; Schnitzler, Alfons; Schulze, Horst; Häussinger, Dieter

    2009-11-01

    Low-grade hepatic encephalopathy (HE) may impair fitness to drive. Driving deficits have not yet been characterized, and their relation to psychometric test results is unclear. Fifty-one cirrhotic patients and 48 age-matched controls underwent real driving in a multiple sensor and camera-equipped car, laboratory and "in-car" computer psychometry, and driving instructor's assessment. Ten cirrhotic patients had no hepatic encephalopathy (HE0); 27 and 14 patients suffered from minimal HE (mHE) and overt HE grade I (oHE), respectively. During real driving, mHE and oHE patients showed significantly more violations of in-lane keeping, reduced break use, prolonged reaction times, and diminished stress tolerance compared with control or cirrhotic HE0 patients. In a self-evaluation questionnaire, mHE and oHE, but not the HE0, patients strongly overestimated their driving abilities. According to the driving instructor's assessment, 75%, 48%, and 39% of the patients with HE0, mHE, and oHE, respectively, were fit to drive, compared with 87% in the control group. Driving deficits in oHE patients were largely due to cognitive defects and prolonged reaction times, whereas, in mHE patients, mistakes and attention deficits predominated. Computer psychometric test results worsened with HE severity and age, whereas real driving was age independent. In 25 out of 94 patients, discordant results for driving fitness were obtained (driving instructor's assessment vs computer psychometry); in mHE and oHE patients, the concordance rates were only 62% and 64%, respectively. Despite significant driving deficits, HE patients overestimate their driving abilities. The presence of mHE does not necessarily predict driving unfitness, and computer-based testings cannot reliably predict driving fitness.

  8. Calcium, a Cell Cycle Commander, Drives Colon Cancer Cell Diffpoptosis.

    PubMed

    Abd-Rabou, Ahmed A

    2017-03-01

    The story of the cell commonder, calcium, reaches into all corners of the cell and controls cell proliferation, differentiation, function, and even death. The calcium-driven eukaryotic revolution is one of the great turning points in the life history, happened about two billion years later when it was converted from a dangerous killer that had to be kept out of cell into the cell master which drives the cell. This review article will take the readers to a tour of tissues chosen to best show the calcium's many faces (proliferator, differentiator, and killer). The reader will first see calcium and its many helpers, such as the calcium-binding signaler protein calmodulin, directing the key events of the cell cycle. Then the tour will move onto the colon to show calcium driving the proliferation of progenitor cells, then the differentiation and ultimately the programmed death of their progeny. Moreover, the reader will learn of the striking disabling and bypassing of calcium-dependent control mechanisms during carcinogenesis. Finally, recommendations should be taken from the underlying mechanisms through which calcium masters the presistance, progression, and even apoptosis of colorectal cancer cells. Thus, this could be of great interest for designing of chemoprevention protocols.

  9. 77 FR 51610 - Distracted Driving Grant Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-24

    ... Driving Grant (hereinafter ``First-Year Texting-Ban Grant''). See ] Section III.C. The basis for an award... Section 405(e), as outlined below: (1) Prohibition on texting while driving. The State statute must-- (a) Prohibit drivers from texting through a personal wireless communications device while driving; (b) Make...

  10. 77 FR 61048 - Distracted Driving Grant Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-05

    ... National Highway Traffic Safety Administration Distracted Driving Grant Program AGENCY: National Highway... Transportation (DOT) announced the availability of funding authorized for distracted driving grants on August 24... grant program. DOT recently published a notice of funding availability (NOFA) for the distracted driving...

  11. Driving When You Have Parkinson's Disease

    MedlinePlus

    Driving When You Have Parkinson’s Disease DRIVEWELL You have been a safe driver for years. For you, driving means freedom and control. As you get ... mental health can affect how safely you drive. Parkinson’s disease is a disorder of the central nervous ...

  12. Basic principles of variable speed drives.

    NASA Technical Reports Server (NTRS)

    Loewenthal, S. H.

    1973-01-01

    The basic available types of variable speed drive systems are described in terms of operating characteristics and typical applications. The fundamental factors of torque, speed ratio, and power are discussed as they relate to drive selection, and the use of a systems approach is urged in the choice and development of a variable speed drive train.

  13. 30 CFR 75.1727 - Drive belts.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Drive belts. 75.1727 Section 75.1727 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Miscellaneous § 75.1727 Drive belts. (a) Drive belts shall not...

  14. 30 CFR 75.1727 - Drive belts.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Drive belts. 75.1727 Section 75.1727 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Miscellaneous § 75.1727 Drive belts. (a) Drive belts shall not...

  15. 30 CFR 75.1727 - Drive belts.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Drive belts. 75.1727 Section 75.1727 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Miscellaneous § 75.1727 Drive belts. (a) Drive belts shall not...

  16. 30 CFR 77.406 - Drive belts.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Drive belts. 77.406 Section 77.406 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY... Mechanical Equipment § 77.406 Drive belts. (a) Drive belts shall not be shifted while in motion unless...

  17. 30 CFR 77.406 - Drive belts.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Drive belts. 77.406 Section 77.406 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY... Mechanical Equipment § 77.406 Drive belts. (a) Drive belts shall not be shifted while in motion unless...

  18. 30 CFR 77.406 - Drive belts.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Drive belts. 77.406 Section 77.406 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY... Mechanical Equipment § 77.406 Drive belts. (a) Drive belts shall not be shifted while in motion unless...

  19. 30 CFR 75.1727 - Drive belts.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Drive belts. 75.1727 Section 75.1727 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Miscellaneous § 75.1727 Drive belts. (a) Drive belts shall not...

  20. 30 CFR 75.1727 - Drive belts.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Drive belts. 75.1727 Section 75.1727 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Miscellaneous § 75.1727 Drive belts. (a) Drive belts shall not...

  1. Measuring the Propensity to Drink and Drive

    ERIC Educational Resources Information Center

    Bertelli, Anthony M.; Richardson, Lilliard E., Jr.

    2007-01-01

    Laws such as 0.08 blood alcohol content, open container, and license revocation provide a policy framework for reducing drinking and driving. Drinking and driving behavior is difficult to assess; unlike property and violent crimes, where incidence statistics can approximate behavior, most drink-driving trips go undetected. The authors develop a…

  2. Assessment of driving outcomes after epilepsy surgery.

    PubMed

    Dawkins, Ross L; Omar, Nidal B; Agee, Bonita S; Walters, Beverly C; Riley, Kristen O

    2015-11-01

    Driving is an important factor contributing to good quality of life in patients with epilepsy. Little work has been undertaken to explore the details of driving experience alone in this patient population. We assessed the driving status of our patients prior to and following surgery for epilepsy. We also sought to determine what associations exist between patient characteristics and postoperative driving status. The participants were selected from those adult patients with epilepsy who have required surgical treatment at our home institution between 2006 and 2010. Each participant received a questionnaire asking about driving and seizure status before and after surgery. The surveys were distributed using a modified Dillman approach. Perioperative patient data were obtained from the electronic medical record system in addition to a previously assembled epilepsy database from the Neurology Department at our institution. Independent variables were analyzed to look for significant associations with driving outcomes. One hundred forty eligible patients were included in the survey population; 78 patients returned a questionnaire for a response rate of 55.7%. Eighty percent of patients experienced driving as a regular part of life at some point prior to surgery. At the time of the questionnaire distribution, 68% of patients had returned to regular driving. Demographic characteristics did not play a significant role in whether or not the patient had a favorable driving outcome after surgery. However, patients who had a history of driving on a regular basis prior to surgery and those who had an Engel Class I outcome after surgery had significantly higher rates of good driving outcomes. Also, patients with an unfavorable preoperative driving status were more likely to have a favorable driving outcome after surgery if they had an Engel Class I outcome. Patients in whom intracranial electroencephalography (EEG) was utilized prior to resection had worse driving outcomes. A

  3. Protein phosphorylation associated with epipodophyllotoxin-induced apoptosis of lymphoid cells: role of a serine/threonine protein kinase.

    PubMed

    Ye, X; Mody, N S; Hingley, S T; Coffman, F D; Cohen, S; Fresa, K L

    1998-11-01

    We have previously shown that apoptosis induced in thymocytes by dexamethasone or teniposide (VM-26) could be inhibited by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) and sangivamycin, both relatively specific inhibitors for protein kinase C, but not by N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004), a more specific inhibitor for cAMP-dependent protein kinases. Apoptosis in this model system was not blocked by EGTA and no increase in cytosolic Ca2+ was observed during apoptosis induced by either dexamethasone or VM-26, suggesting that this kinase was Ca2+-independent. In the present study, we demonstrate that addition of 10 microM sangivamycin to thymocyte cultures up to 2 h after addition of either inducer resulted in virtually complete inhibition of apoptosis. Addition of 10 microM sangivamycin at 3 or 4 h after addition of inducer resulted in partial inhibition of apoptosis. Computerized image analysis of two-dimensional PAGE analyses of whole-cell lysates demonstrated that treatment of mouse thymocytes with VM-26 resulted in a limited number of de novo phosphorylation events within 1 h of treatment. The most prominent phosphorylation events associated with VM-26-induced apoptosis were that two intracellular protein species (Protein 1: m.w. = 22.9 kDa, pI, 5.11; and Protein 2: m.w. = 22.9 kDa, pI, 4.98). Similar phosphorylation events were seen in cells treated with dexamethasone. Finally, Western blot analysis suggests that de novo protein phosphorylation induced by VM-26 is on serine/threonine residues. These results provide further evidence that the mechanism of VM-26-induced apoptosis of murine thymocytes involves the action of one or more serine/threonine kinases. Copyright 1998 Academic Press.

  4. Effect of Immunosuppressive Agents on Hepatocyte Apoptosis Post-Liver Transplantation.

    PubMed

    Lim, Eu Jin; Chin, Ruth; Nachbur, Ueli; Silke, John; Jia, Zhiyuan; Angus, Peter W; Torresi, Joseph

    2015-01-01

    Immunosuppressants are used ubiquitously post-liver transplantation to prevent allograft rejection. However their effects on hepatocytes are unknown. Experimental data from non-liver cells indicate that immunosuppressants may promote cell death thereby driving an inflammatory response that promotes fibrosis and raises concerns that a similar effect may occur within the liver. We evaluated apoptosis within the liver tissue of post-liver transplant patients and correlated these findings with in vitro experiments investigating the effects of immunosuppressants on apoptosis in primary hepatocytes. Hepatocyte apoptosis was assessed using immunohistochemistry for M30 CytoDEATH and cleaved PARP in human liver tissue. Primary mouse hepatocytes were treated with various combinations of cyclosporine, tacrolimus, sirolimus, or MMF. Cell viability and apoptosis were evaluated using crystal violet assays and Western immunoblots probed for cleaved PARP and cleaved caspase 3. Post-liver transplant patients had a 4.9-fold and 1.7-fold increase in M30 CytoDEATH and cleaved PARP compared to normal subjects. Cyclosporine and tacrolimus at therapeutic concentrations did not affect hepatocyte apoptosis, however when they were combined with MMF, cell death was significantly enhanced. Cell viability was reduced by 46% and 41%, cleaved PARP was increased 2.6-fold and 2.2-fold, and cleaved caspase 3 increased 2.2-fold and 1.8-fold following treatment with Cyclosporine/MMF and Tacrolimus/MMF respectively. By contrast, the sirolimus/MMF combination did not significantly reduce hepatocyte viability or promote apoptosis. Commonly used immunosuppressive drug regimens employed after liver transplantation enhance hepatocyte cell death and may thus contribute to the increased liver fibrosis that occurs in a proportion of liver transplant recipients.

  5. Effect of Immunosuppressive Agents on Hepatocyte Apoptosis Post-Liver Transplantation

    PubMed Central

    Lim, Eu Jin; Chin, Ruth; Nachbur, Ueli; Silke, John; Jia, Zhiyuan; Angus, Peter W.; Torresi, Joseph

    2015-01-01

    Introduction Immunosuppressants are used ubiquitously post-liver transplantation to prevent allograft rejection. However their effects on hepatocytes are unknown. Experimental data from non-liver cells indicate that immunosuppressants may promote cell death thereby driving an inflammatory response that promotes fibrosis and raises concerns that a similar effect may occur within the liver. We evaluated apoptosis within the liver tissue of post-liver transplant patients and correlated these findings with in vitro experiments investigating the effects of immunosuppressants on apoptosis in primary hepatocytes. Methods Hepatocyte apoptosis was assessed using immunohistochemistry for M30 CytoDEATH and cleaved PARP in human liver tissue. Primary mouse hepatocytes were treated with various combinations of cyclosporine, tacrolimus, sirolimus, or MMF. Cell viability and apoptosis were evaluated using crystal violet assays and Western immunoblots probed for cleaved PARP and cleaved caspase 3. Results Post-liver transplant patients had a 4.9-fold and 1.7-fold increase in M30 CytoDEATH and cleaved PARP compared to normal subjects. Cyclosporine and tacrolimus at therapeutic concentrations did not affect hepatocyte apoptosis, however when they were combined with MMF, cell death was significantly enhanced. Cell viability was reduced by 46% and 41%, cleaved PARP was increased 2.6-fold and 2.2-fold, and cleaved caspase 3 increased 2.2-fold and 1.8-fold following treatment with Cyclosporine/MMF and Tacrolimus/MMF respectively. By contrast, the sirolimus/MMF combination did not significantly reduce hepatocyte viability or promote apoptosis. Conclusion Commonly used immunosuppressive drug regimens employed after liver transplantation enhance hepatocyte cell death and may thus contribute to the increased liver fibrosis that occurs in a proportion of liver transplant recipients. PMID:26390404

  6. Fluid cooled vehicle drive module

    DOEpatents

    Beihoff, Bruce C.; Radosevich, Lawrence D.; Meyer, Andreas A.; Gollhardt, Neil; Kannenberg, Daniel G.

    2005-11-15

    An electric vehicle drive includes a support may receive one or more power electronic circuits. The support may aid in removing heat from the circuits through fluid circulating through the support. The support, in conjunction with other packaging features may form a shield from both external EM/RFI and from interference generated by operation of the power electronic circuits. Features may be provided to permit and enhance connection of the circuitry to external circuitry, such as improved terminal configurations. Modular units may be assembled that may be coupled to electronic circuitry via plug-in arrangements or through interface with a backplane or similar mounting and interconnecting structures.

  7. Driving trajectories in chaotic scattering.

    PubMed

    Macau, Elbert E N; Caldas, Iberê L

    2002-02-01

    In this work we introduce a general approach for targeting in chaotic scattering that can be used to find a transfer trajectory between any two points located inside the scattering region. We show that this method can be used in association with a control of chaos strategy to drive around and keep a particle inside the scattering region. As an illustration of how powerful this approach is, we use it in a case of practical interest in celestial mechanics in which it is desired to control the evolution of two satellites that evolve around a large central body.

  8. Efficient alternatives for electric drives

    SciTech Connect

    Comnes, G.A.; Barnes, R.W.

    1987-11-01

    This analysis of industrial electric motors describes the current motor stock, its energy use and operating characteristics, and innovations that could change current use patterns. It provides calculations characterizing the economic attractiveness of several existing and potential options. One attractive option given particular attention is the adjustable-speed drive which can replace throttles or valves for many pumping operations. A major conclusion is that, throughout industry, options that are both energy-saving and economically attractive appear to penetrate markets more slowly than would be socially optimal. The final section examines characteristics of industry that may contribute to slow market penetration. 29 refs., 14 figs., 14 tabs.

  9. Computer-Aided Remote Driving

    NASA Technical Reports Server (NTRS)

    Wilcox, Brian H.

    1994-01-01

    System for remote control of robotic land vehicle requires only small radio-communication bandwidth. Twin video cameras on vehicle create stereoscopic images. Operator views cross-polarized images on two cathode-ray tubes through correspondingly polarized spectacles. By use of cursor on frozen image, remote operator designates path. Vehicle proceeds to follow path, by use of limited degree of autonomous control to cope with unexpected conditions. System concept, called "computer-aided remote driving" (CARD), potentially useful in exploration of other planets, military surveillance, firefighting, and clean-up of hazardous materials.

  10. Preliminary screening of differentially expressed genes involved in methyl-CpG-binding protein 2 gene-mediated proliferation in human osteosarcoma cells.

    PubMed

    Meng, Gang; Li, Yi; Lv, YangFan; Dai, Huanzi; Zhang, Xi; Guo, Qiao-Nan

    2015-04-01

    Methyl-CpG-binding protein 2 (MeCP2) is essential in human brain development and has been linked to several cancer types and neuro-developmental disorders. This study aims to screen the MeCP2 related differentially expressed genes and discover the therapeutic targets for osteosarcoma. CCK8 assay was used to detect the proliferation and SaOS2 and U2OS cells. Apoptosis of cells was detected by flow cytometry analysis that monitored Annexin V-APC/7-DD binding and 7-ADD uptake simultaneously. Denaturing formaldehyde agarose gel electrophoresis was employed to examine the quality of total RNA 18S and 28S units. Gene chip technique was utilized to discover the differentially expressed genes correlated with MeCP2 gene. Differential gene screening criteria were used to screen the changed genes. The gene up-regulation or down-regulation more than 1.5 times was regarded as significant differential expression genes. The CCK8 results indicated that the cell proliferation of MeCP2 silencing cells (LV-MeCP2-RNAi) was significantly decreased compared to non-silenced cells (LV-MeCP2-RNAi-CN) (P < 0.05). MeCP2 silencing could also induce significant apoptosis compared to non-silenced cells (P < 0.05); 107 expression changed genes were screened from a total of 49,395 transcripts. Among the total 107 transcripts, 34 transcripts were up-regulated and 73 transcripts were down-regulated. There were five significant differentially expressed genes, including IGFBP4, HOXC8, LMO4, MDK, and CTGF, which correlated with the MeCP2 gene. The methylation frequency of CpG in IGFBP4 gene could achieve 55%. In conclusion, the differentially expressed IGFBP4, HOXC8, LMO4, MDK, and CTGF genes may be involved in MeCP2 gene-mediated proliferation and apoptosis in osteosarcoma cells.

  11. Voight variable speed drive. [for windpowered generator

    NASA Technical Reports Server (NTRS)

    Tompkin, J.

    1973-01-01

    The variable speed drive transmission is mounted within the gondola and connected with the wind turbine blades and the hub. This unit is designed for the production of ac power. The turbine turns by means of the variable speed drive and a set of synchronous three phase generators. This motion is controlled automatically by two wind rosettes in such a way that the wind turbine always opposes the wind direction. The Voight variable speed drive is a mechanical variable positive drive gear transmission. It has an unlimited power and torque transmission, a constant ratio with high degree of accuracy, a speed variation over a wide range, and a nonslip drive.

  12. Engine starter and accessory drive system

    SciTech Connect

    Stockton, T.R.

    1986-10-07

    An engine starter and accessory drive system is described which consists of: an accessory drive means; a planetary gearset having a sun gear driveably connected to the accessory drive means, a ring gear, a carrier and planet pinions rotatably mounted on the carrier, fixed to the engine crankshaft, meshing with the sun gear and with the ring gear; means for holding the ring gear against rotation; and a starter motor and first clutch means for providing a one-way driving connection between the motor and the accessory drive means.

  13. Phytosphingosine induced mitochondria-involved apoptosis.

    PubMed

    Nagahara, Yukitoshi; Shinomiya, Takahisa; Kuroda, Sachiko; Kaneko, Naoki; Nishio, Reiji; Ikekita, Masahiko

    2005-02-01

    Sphingolipids are putative intracellular signal mediators in cell differentiation, growth inhibition, and apoptosis. Sphingosine, sphinganine, and phytosphingosine are structural analogs of sphingolipids and are classified as long-chain sphingoid bases. Sphingosine and sphinganine are known to play important roles in apoptosis. In the present study, we examined the phytosphingosine-induced apoptosis mechanism, focusing on mitochondria in human T-cell lymphoma Jurkat cells. Phytosphingosine significantly induced chromatin DNA fragmentation, which is a hallmark of apoptosis. Enzymatic activity measurements of caspases revealed that caspase-3 and caspase-9 are activated in phytosphingosine-induced apoptosis, but there is little activation of caspase-8 suggesting that phytosphingosine influences mitochondrial functions. In agreement with this hypothesis, a decrease in DeltaPsi(m) and the release of cytochrome c to the cytosol were observed upon phytosphingosine treatment. Furthermore, overexpression of mitochondria-localized anti-apoptotic protein Bcl-2 prevented phytosphingosine apoptotic stimuli. Western blot assays revealed that phytosphingosine decreases phosphorylated Akt and p70S6k. Dephosphorylation of Akt was partially inhibited by protein phosphatase inhibitor OA and OA attenuated phytosphingosine-induced apoptosis. Moreover, using a cell-free system, phytosphingosine directly reduced DeltaPsi(m). These results indicate that phytosphingosine perturbs mitochondria both directly and indirectly to induce apoptosis.

  14. Posttraumatic Chondrocyte Apoptosis in the Murine Xiphoid.

    PubMed

    Davis, Christopher G; Eisner, Eric; McGlynn, Margaret; Shelton, John M; Richardson, James; Borrelli, Joseph; Chen, Christopher C T

    2013-10-01

    To demonstrate posttraumatic chondrocyte apoptosis in the murine xiphoid after a crush-type injury and to ultimately determine the pathway (i.e., intrinsic or extrinsic) by which chondrocytes undergo apoptosis in response to mechanical injury. The xiphoids of adult female wild-type mice were injured with the use of a modified Kelly clamp. Postinjury xiphoid cartilage was analyzed via 3 well-described independent means of assessing apoptosis in chondrocytes: hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and activated caspase-3 staining. Injured specimens contained many chondrocytes with evidence of apoptosis, which is characterized by cell shrinkage, chromatin condensation, nuclear fragmentation, and the liberation of apoptotic bodies. There was a statistically significant increase in the number of chondrocytes undergoing apoptosis in the injured specimens as compared with the uninjured specimens. Chondrocytes can be stimulated to undergo apoptosis as a result of mechanical injury. These experiments involving predominantly cartilaginous murine xiphoid in vivo establish a baseline for future investigations that employ the genetic and therapeutic modulation of chondrocyte apoptosis in response to mechanical injury.

  15. Semaphorins as mediators of neuronal apoptosis.

    PubMed

    Shirvan, A; Ziv, I; Fleminger, G; Shina, R; He, Z; Brudo, I; Melamed, E; Barzilai, A

    1999-09-01

    Shrinkage and collapse of the neuritic network are often observed during the process of neuronal apoptosis. However, the molecular and biochemical basis for the axonal damage associated with neuronal cell death is still unclear. We present evidence for the involvement of axon guidance molecules with repulsive cues in neuronal cell death. Using the differential display approach, an up-regulation of collapsin response mediator protein was detected in sympathetic neurons undergoing dopamine-induced apoptosis. A synchronized induction of mRNA of the secreted collapsin-1 and the intracellular collapsin response mediator protein that preceded commitment of neurons to apoptosis was detected. Antibodies directed against a conserved collapsin-derived peptide provided marked and prolonged protection of several neuronal cell types from dopamine-induced apoptosis. Moreover, neuronal apoptosis was inhibited by antibodies against neuropilin-1, a putative component of the semaphorin III/collapsin-1 receptor. Induction of neuronal apoptosis was also caused by exposure of neurons to semaphorin III-alkaline phosphatase secreted from 293EBNA cells. Anti-collapsin-1 antibodies were effective in blocking the semaphorin III-induced death process. We therefore suggest that, before their death, apoptosis-destined neurons may produce and secrete destructive axon guidance molecules that can affect their neighboring cells and thus transfer a "death signal" across specific and susceptible neuronal populations.

  16. The role of apoptosis in respiratory diseases.

    PubMed

    Pierce, Janet D; Pierce, Jana; Stremming, Stephanie; Fakhari, Mahtab; Clancy, Richard L

    2007-01-01

    The purpose of this article is to define apoptosis and describe how this cellular pathway is relevant to the pathogenesis of different respiratory diseases. This will assist clinical nurse specialists in understanding how new drugs and therapies inhibit and stimulate apoptotic pathways. Clinical nurse specialists need to expand their knowledge concerning the role of apoptosis so that they can better expand their spheres of influence. The 4 stages of apoptosis are discussed, as well as the various apoptotic pathways involved with asthma, emphysema, and acute respiratory distress syndrome that promote and inhibit apoptosis in patients. It is crucial for clinical nurse specialists to know what apoptosis is and how it relates to different pathophysiologic states. The challenge facing clinical nurse specialists is how to be kept informed and current concerning molecular and cellular mechanisms that are important in the practice setting. Strategies needed to maintain expertise include acquiring new knowledge, developing new skills, and changing attitudes about molecular biology. Apoptosis must become a significant part of any health professionals' continuing educational program because it has been recognized as the pathway to most any disease. Clinical nurse specialists who understand apoptosis and its pathways can use this knowledge to aid in the prevention and treatment of respiratory diseases.

  17. 32 CFR 634.14 - Restoration of driving privileges upon acquittal of intoxicated driving.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 4 2014-07-01 2013-07-01 true Restoration of driving privileges upon acquittal of intoxicated driving. 634.14 Section 634.14 National Defense Department of Defense (Continued... SUPERVISION Driving Privileges § 634.14 Restoration of driving privileges upon acquittal of...

  18. 32 CFR 634.14 - Restoration of driving privileges upon acquittal of intoxicated driving.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 4 2012-07-01 2011-07-01 true Restoration of driving privileges upon acquittal of intoxicated driving. 634.14 Section 634.14 National Defense Department of Defense (Continued... SUPERVISION Driving Privileges § 634.14 Restoration of driving privileges upon acquittal of...

  19. 32 CFR 634.14 - Restoration of driving privileges upon acquittal of intoxicated driving.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 4 2013-07-01 2013-07-01 false Restoration of driving privileges upon acquittal of intoxicated driving. 634.14 Section 634.14 National Defense Department of Defense (Continued... SUPERVISION Driving Privileges § 634.14 Restoration of driving privileges upon acquittal of...

  20. 32 CFR 634.14 - Restoration of driving privileges upon acquittal of intoxicated driving.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Restoration of driving privileges upon acquittal of intoxicated driving. 634.14 Section 634.14 National Defense Department of Defense (Continued... SUPERVISION Driving Privileges § 634.14 Restoration of driving privileges upon acquittal of...

  1. 32 CFR 634.14 - Restoration of driving privileges upon acquittal of intoxicated driving.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 4 2011-07-01 2011-07-01 false Restoration of driving privileges upon acquittal of intoxicated driving. 634.14 Section 634.14 National Defense Department of Defense (Continued... SUPERVISION Driving Privileges § 634.14 Restoration of driving privileges upon acquittal of...

  2. The impact of continuous driving time and rest time on commercial drivers' driving performance and recovery.

    PubMed

    Wang, Lianzhen; Pei, Yulong

    2014-09-01

    This real road driving study was conducted to investigate the effects of driving time and rest time on the driving performance and recovery of commercial coach drivers. Thirty-three commercial coach drivers participated in the study, and were divided into three groups according to driving time: (a) 2 h, (b) 3 h, and (c) 4 h. The Stanford Sleepiness Scale (SSS) was used to assess the subjective fatigue level of the drivers. One-way ANOVA was employed to analyze the variation in driving performance. The statistical analysis revealed that driving time had a significant effect on the subjective fatigue and driving performance measures among the three groups. After 2 h of driving, both the subjective fatigue and driving performance measures began to deteriorate. After 4 h of driving, all of the driving performance indicators changed significantly except for depth perception. A certain amount of rest time eliminated the negative effects of fatigue. A 15-minute rest allowed drivers to recover from a two-hour driving task. This needed to be prolonged to 30 min for driving tasks of 3 to 4 h of continuous driving. Drivers' attention, reactions, operating ability, and perceptions are all affected in turn after over 2 h of continuous driving. Drivers should take a certain amount of rest to recover from the fatigue effects before they continue driving. Copyright © 2014 National Safety Council and Elsevier Ltd. All rights reserved.

  3. Metadherin facilitates podocyte apoptosis in diabetic nephropathy

    PubMed Central

    Liu, Wen-Ting; Peng, Fen-Fen; Li, Hong-Yu; Chen, Xiao-Wen; Gong, Wang-Qiu; Chen, Wen-Jing; Chen, Yi-Hua; Li, Pei-Lin; Li, Shu-Ting; Xu, Zhao-Zhong; Long, Hai-Bo

    2016-01-01

    Apoptosis, one of the major causes of podocyte loss, has been reported to have a vital role in diabetic nephropathy (DN) pathogenesis, and understanding the mechanisms underlying the regulation of podocyte apoptosis is crucial. Metadherin (MTDH) is an important oncogene, which is overexpressed in most cancers and responsible for apoptosis, metastasis, and poor patient survival. Here we show that the expression levels of Mtdh and phosphorylated p38 mitogen-activated protein kinase (MAPK) are significantly increased, whereas those of the microRNA-30 family members (miR-30s) are considerably reduced in the glomeruli of DN rat model and in high glucose (HG)-induced conditionally immortalized mouse podocytes (MPC5). These levels are positively correlated with podocyte apoptosis rate. The inhibition of Mtdh expression, using small interfering RNA, but not Mtdh overexpression, was shown to inhibit HG-induced MPC5 apoptosis and p38 MAPK pathway, and Bax and cleaved caspase 3 expression. This was shown to be similar to the effects of p38 MAPK inhibitor (SB203580). Furthermore, luciferase assay results demonstrated that Mtdh represents the target of miR-30s. Transient transfection experiments, using miR-30 microRNA (miRNA) inhibitors, led to the increase in Mtdh expression and induced the apoptosis of MPC5, whereas the treatment with miR-30 miRNA mimics led to the reduction in Mtdh expression and apoptosis of HG-induced MPC5 cells in comparison with their respective controls. Our results demonstrate that Mtdh is a potent modulator of podocyte apoptosis, and that it represents the target of miR-30 miRNAs, facilitating podocyte apoptosis through the activation of HG-induced p38 MAPK-dependent pathway. PMID:27882943

  4. Driving induced many-body localization

    NASA Astrophysics Data System (ADS)

    Bairey, Eyal; Refael, Gil; Lindner, Netanel H.

    2017-07-01

    Subjecting a many-body localized system to a time-periodic drive generically leads to delocalization and a transition to ergodic behavior if the drive is sufficiently strong or of sufficiently low frequency. Here we show that a specific drive can have an opposite effect, taking a static delocalized system into the many-body localized phase. We demonstrate this effect using a one-dimensional system of interacting hard-core bosons subject to an oscillating linear potential. The system is weakly disordered, and is ergodic absent the driving. The time-periodic linear potential leads to a suppression of the effective static hopping amplitude, increasing the relative strengths of disorder and interactions. Using numerical simulations, we find a transition into the many-body localized phase above a critical driving frequency and in a range of driving amplitudes. Our findings highlight the potential of driving schemes exploiting the coherent destruction of tunneling for engineering long-lived Floquet phases.

  5. Asymmetric relationship between driving and safety skills.

    PubMed

    Sümer, Nebi; Ozkan, Türker; Lajunen, Timo

    2006-07-01

    We hypothesized that the combination of self reported high ratings of driving skills and low ratings of safety skills creates a serious risk for road accident involvement. This study was aimed at investigating the asymmetric interplay between driving and safety skills among Turkish drivers (N=785) using the Driving Skills Inventory [Lajunen, T., Summala, H., 1995. Driver experience, personality, and skill and safety motive dimensions in drivers' self-assessments. Pers. Indiv. Differ. 19, 307-318]. The assumed asymmetric interactions were tested on a number of outcome variables representing risky driving using moderated regression analyses. The results revealed that driving skills moderated the effects of safety skills on six out of the eight outcome variables including the number of accidents, tickets, overtaking tendencies, speed on motorways, and aggressive driving style. Results suggested that high levels of safety skills buffer the negative effect of overconfidence resulting from exaggerated ratings of self-reported driving skills.

  6. Four-wheel drive car

    SciTech Connect

    Ashikawa, N.

    1986-03-25

    A drive train in a four-wheel drive vehicle is described having an engine mounted on one end with a crankshaft oriented transverse to the direction of vehicle travel which consists of: a transmission having an output gear driven by the crankshaft and rotatable around an axis parallel to the axis of the crankshaft; a reduction gear operatively engaged with the output gear; a first differential gear having a gear and being concentrically engaged with the reduction gear to transmit the output of the reduction gear in a divided manner; a second differential gear transmitting power from one output of the differential gear to left and right wheels of the one end of the vehicle; a transmission gear meshing with the gear of the first differential gear for transmitting power from another output of the first differential gear in a direction generally perpendicular to the crankshaft through a propeller shaft to the other end of the vehicle, opposite the one end; a third differential gear receiving power from the propeller shaft for transmitting power to left and right wheels on the other end; and wherein a mesh portion where the transmission gear meshes with the gear of the first differential gear is closer to the crankshaft axis of engine than is the axis of the reduction gear.

  7. Driving Extreme Efficiency to Market

    NASA Astrophysics Data System (ADS)

    Garbesi, Karina

    2014-03-01

    The rapid development of extremely energy efficient appliances and equipment is essential to curtail catastrophic climate disruption. This will require the on-going development of products that apply all best-practices and that take advantage of the synergies of hybridization and building integration. Beyond that, it requires the development of new disruptive technologies and concepts. To facilitate these goals, in 2011 the Lawrence Berkeley National Laboratory and the U.S. Department of Energy launched the Max Tech and Beyond Design Competition for Ultra-Low-Energy-Use Appliances and Equipment. Now in its third year, the competition supports faculty-lead student design teams at U.S. universities to develop and test new technology prototypes. This talk describes what the competition and the Max Tech Program are doing to drive such rapid technology progress and to facilitate the entry to the market of successful Max Tech prototypes. The talk also initiates a discussion of physicists' unique role in driving that technology progress faster and farther. Emerging Technologies, Building Technologies Office, U.S. Department of Energy.

  8. Learning headway estimation in driving.

    PubMed

    Taieb-Maimon, Meirav

    2007-08-01

    The main purpose of the present study was to examine to what extent the ability to attain a required headway of 1 or 2 s can be improved through practical driving instruction under real traffic conditions and whether the learning is sustained after a period during which there has been no controlled training. The failure of drivers to estimate headways correctly has been demonstrated in previous studies. Two methods of training were used: time based (in seconds) and distance based (in a combination of meters and car lengths). For each method, learning curves were examined for 18 participants at speeds of 50, 80, and 100 km/hr. The results indicated that drivers were weak in estimating headway prior to training using both methods. The learning process was rapid for both methods and similar for all speeds; thus, after one trial with feedback, there was already a significant improvement. The learning was retained over time, for at least the 1 month examined in this study. Both the time and distance training of headway improved drivers' ability to attain required headways, with the learning being maintained over a retention interval. The learning process was based on perceptual cues from the driving scene and feedback from the experimenter, regardless of the formal training method. The implications of these results are that all drivers should be trained in headway estimation using an objective distance measuring device, which can be installed on driver instruction vehicles.

  9. Modeling heterogeneous responsiveness of intrinsic apoptosis pathway

    PubMed Central

    2013-01-01

    Background Apoptosis is a cell suicide mechanism that enables multicellular organisms to maintain homeostasis and to eliminate individual cells that threaten the organism’s survival. Dependent on the type of stimulus, apoptosis can be propagated by extrinsic pathway or intrinsic pathway. The comprehensive understanding of the molecular mechanism of apoptotic signaling allows for development of mathematical models, aiming to elucidate dynamical and systems properties of apoptotic signaling networks. There have been extensive efforts in modeling deterministic apoptosis network accounting for average behavior of a population of cells. Cellular networks, however, are inherently stochastic and significant cell-to-cell variability in apoptosis response has been observed at single cell level. Results To address the inevitable randomness in the intrinsic apoptosis mechanism, we develop a theoretical and computational modeling framework of intrinsic apoptosis pathway at single-cell level, accounting for both deterministic and stochastic behavior. Our deterministic model, adapted from the well-accepted Fussenegger model, shows that an additional positive feedback between the executioner caspase and the initiator caspase plays a fundamental role in yielding the desired property of bistability. We then examine the impact of intrinsic fluctuations of biochemical reactions, viewed as intrinsic noise, and natural variation of protein concentrations, viewed as extrinsic noise, on behavior of the intrinsic apoptosis network. Histograms of the steady-state output at varying input levels show that the intrinsic noise could elicit a wider region of bistability over that of the deterministic model. However, the system stochasticity due to intrinsic fluctuations, such as the noise of steady-state response and the randomness of response delay, shows that the intrinsic noise in general is insufficient to produce significant cell-to-cell variations at physiologically relevant level of

  10. [Endothelial cell apoptosis in erectile dysfunction].

    PubMed

    Jiang, Rui

    2012-10-01

    Erectile dysfunction (ED) is one of the most common male diseases, which seriously affects the patient's quality of life. The risk factors of ED include aging, diabetes, hypertension, hyperlipidemia, and unhealthy lifestyle, and its exact mechanism remains unclear. The apoptosis of endothelial cells in the corpus cavernosum penis may reduce NOS activity, block NO synthesis, and affect penile erection, and the mechanisms of their apoptosis vary with different causes of ED. This article updates the relationship between the apoptosis of endothelial cells and the development of ED.

  11. The Role of Mitochondria in Apoptosis*

    PubMed Central

    Wang, Chunxin; Youle, Richard J.

    2016-01-01

    Mitochondria play key roles in activating apoptosis in mammalian cells. Bcl-2 family members regulate the release of proteins from the space between the mitochondrial inner and outer membrane that, once in the cytosol, activate caspase proteases that dismantle cells and signal efficient phagocytosis of cell corpses. Here we review the extensive literature on proteins released from the intermembrane space and consider genetic evidence for and against their roles in apoptosis activation. We also compare and contrast apoptosis pathways in Caenorhabditis elegans, Drosophila melanogaster, and mammals that indicate major mysteries remaining to be solved. PMID:19659442

  12. Inactivation of bone morphogenetic protein 2 may predict clinical outcome and poor overall survival for renal cell carcinoma through epigenetic pathways.

    PubMed

    Mitsui, Yozo; Hirata, Hiroshi; Arichi, Naoko; Hiraki, Miho; Yasumoto, Hiroaki; Chang, Inik; Fukuhara, Shinichiro; Yamamura, Soichiro; Shahryari, Varahram; Deng, Guoren; Saini, Sharanjot; Majid, Shahana; Dahiya, Rajvir; Tanaka, Yuichiro; Shiina, Hiroaki

    2015-04-20

    We investigated whether impaired regulation of bone morphogenetic protein-2 (BMP-2) via epigenetic pathways is associated with renal cell carcinoma (RCC) pathogenesis. Expression and CpG methylation of the BMP-2 gene were analyzed using RCC cell lines, and 96 matched RCC and normal renal tissues. We also performed functional analysis using BMP-2 restored RCC cells. A significant association of BMP-2 mRNA expression was also found with advanced tumor stage and lymph node involvement, while lower BMP-2 mRNA expression was significantly associated with poor overall survival after radical nephrectomy. In RCC cells, BMP-2 restoration significantly inhibited cell proliferation, migration, invasion, and colony formation. In addition, BMP-2 overexpression induced p21(WAF1/CIP1) and p27(KIP1) expression, and cellular apoptosis in RCC cells. BMP-2 mRNA expression was significantly enhanced in RCC cells by 5-aza-2'-deoxycitidine treatment. The prevalence of BMP-2 promoter methylation was significantly greater and BMP-2 mRNA expression was significantly lower in RCC samples as compared to normal kidney samples. Furthermore, a significant correlation was found between BMP-2 promoter methylation and mRNA transcription in tumors. Aberrant BMP-2 methylation and the resultant loss of BMP-2 expression may be a useful molecular marker for designing improved diagnostic and therapeutic strategies for RCC.

  13. Inactivation of bone morphogenetic protein 2 may predict clinical outcome and poor overall survival for renal cell carcinoma through epigenetic pathways

    PubMed Central

    Mitsui, Yozo; Hirata, Hiroshi; Arichi, Naoko; Hiraki, Miho; Yasumoto, Hiroaki; Chang, Inik; Fukuhara, Shinichiro; Yamamura, Soichiro; Shahryari, Varahram; Deng, Guoren; Saini, Sharanjot; Majid, Shahana; Dahiya, Rajvir; Tanaka, Yuichiro; Shiina, Hiroaki

    2015-01-01

    We investigated whether impaired regulation of bone morphogenetic protein-2 (BMP-2) via epigenetic pathways is associated with renal cell carcinoma (RCC) pathogenesis. Expression and CpG methylation of the BMP-2 gene were analyzed using RCC cell lines, and 96 matched RCC and normal renal tissues. We also performed functional analysis using BMP-2 restored RCC cells. A significant association of BMP-2 mRNA expression was also found with advanced tumor stage and lymph node involvement, while lower BMP-2 mRNA expression was significantly associated with poor overall survival after radical nephrectomy. In RCC cells, BMP-2 restoration significantly inhibited cell proliferation, migration, invasion, and colony formation. In addition, BMP-2 overexpression induced p21WAF1/CIP1 and p27KIP1 expression, and cellular apoptosis in RCC cells. BMP-2 mRNA expression was significantly enhanced in RCC cells by 5-aza-2′-deoxycitidine treatment. The prevalence of BMP-2 promoter methylation was significantly greater and BMP-2 mRNA expression was significantly lower in RCC samples as compared to normal kidney samples. Furthermore, a significant correlation was found between BMP-2 promoter methylation and mRNA transcription in tumors. Aberrant BMP-2 methylation and the resultant loss of BMP-2 expression may be a useful molecular marker for designing improved diagnostic and therapeutic strategies for RCC. PMID:25797254

  14. DISCO interacting protein 2 determines direction of axon projection under the regulation of c-Jun N-terminal kinase in the Drosophila mushroom body.

    PubMed

    Nitta, Yohei; Sugie, Atsushi

    2017-04-08

    Precisely controlled axon guidance for complex neuronal wiring is essential for appropriate neuronal function. c-Jun N-terminal kinase (JNK) was found to play a role in axon guidance recently as well as in cell proliferation, protection and apoptosis. In spite of many genetic and molecular studies on these biological processes regulated by JNK, how JNK regulates axon guidance accurately has not been fully explained thus far. To address this question, we use the Drosophila mushroom body (MB) as a model since the α/β axons project in two distinct directions. Here we show that DISCO interacting protein 2 (DIP2) is required for the accurate direction of axonal guidance. DIP2 expression is under the regulation of Basket (Bsk), the Drosophila homologue of JNK. We additionally found that the Bsk/DIP2 pathway is independent from the AP-1 transcriptional factor complex pathway, which is directly activated by Bsk. In conclusion, our findings revealed DIP2 as a novel effector downstream of Bsk modulating the direction of axon projection.

  15. Expression, purification, crystallization and preliminary X-ray crystallographic analysis of human histidine triad nucleotide-binding protein 2 (hHINT2)

    PubMed Central

    Dolot, Rafał; Włodarczyk, Artur; Bujacz, Grzegorz D.; Nawrot, Barbara

    2013-01-01

    Histidine triad nucleotide-binding protein 2 (HINT2) is a mitochondrial adenosine phosphoramidase mainly expressed in the pancreas, liver and adrenal gland. HINT2 possibly plays a role in apoptosis, as well as being involved in steroid biosynthesis, hepatic lipid metabolism and regulation of hepatic mitochondria function. The expression level of HINT2 is significantly down-regulated in hepatocellular carcinoma patients. To date, endogenous substrates for this enzyme, as well as the three-dimensional structure of human HINT2, are unknown. In this study, human HINT2 was cloned, overexpressed in Escherichia coli and purified. Crystallization was performed at 278 K using PEG 4000 as the main precipitant; the crystals, which belonged to the tetragonal space group P41212 with unit-cell parameters a = b = 76.38, c = 133.25 Å, diffracted to 2.83 Å resolution. Assuming two molecules in the asymmetric unit, the Matthews coefficient and the solvent content were calculated to be 2.63 Å3 Da−1 and 53.27%, respectively. PMID:23832208

  16. Expression, purification, crystallization and preliminary X-ray crystallographic analysis of human histidine triad nucleotide-binding protein 2 (hHINT2).

    PubMed

    Dolot, Rafał; Włodarczyk, Artur; Bujacz, Grzegorz D; Nawrot, Barbara

    2013-07-01

    Histidine triad nucleotide-binding protein 2 (HINT2) is a mitochondrial adenosine phosphoramidase mainly expressed in the pancreas, liver and adrenal gland. HINT2 possibly plays a role in apoptosis, as well as being involved in steroid biosynthesis, hepatic lipid metabolism and regulation of hepatic mitochondria function. The expression level of HINT2 is significantly down-regulated in hepatocellular carcinoma patients. To date, endogenous substrates for this enzyme, as well as the three-dimensional structure of human HINT2, are unknown. In this study, human HINT2 was cloned, overexpressed in Escherichia coli and purified. Crystallization was performed at 278 K using PEG 4000 as the main precipitant; the crystals, which belonged to the tetragonal space group P41212 with unit-cell parameters a = b = 76.38, c = 133.25 Å, diffracted to 2.83 Å resolution. Assuming two molecules in the asymmetric unit, the Matthews coefficient and the solvent content were calculated to be 2.63 Å(3) Da(-1) and 53.27%, respectively.

  17. Anterior gradient protein 2 expression in high grade head and neck squamous cell carcinoma correlated with cancer stem cell and epithelial mesenchymal transition.

    PubMed

    Ma, Si-Rui; Wang, Wei-Ming; Huang, Cong-Fa; Zhang, Wen-Feng; Sun, Zhi-Jun

    2015-04-20

    Anterior gradient protein 2 (AGR2) is a novel biomarker with potential oncogenic role. We sought to investigate the diagnostic and prognostic role of AGR2 on head and neck squamous cell carcinoma (HNSCC) with an emphasis on its correlation of cancer stemloid cells (CSC) and epithelial mesenchymal transition (EMT). We found that AGR2 protein levels were higher in HNSCC than in normal oral mucosa. High levels of AGR2 were associated with the T category, pathological grade and lymph node metastasis of HNSCC. Expression of AGR2 increased in recurring HNSCC after radiotherapy and in post cisplatin-based chemotherapeutic tissues. In HNSCC cell lines, knock-down of AGR2 induced apoptosis, reduced sphere formation, and down-regulated Survivin, Cyclin D1, Bcl2, Bcl2l1, Slug, Snail, Nanog and Oct4. In addition, over-expressed AGR2 in transgenic mice with spontaneous HNSCC was associated with lost function of Tgfbr1 and/ or lost function of Pten. In vitro knockdown TGFBR1 in HNSCC cell lines increased AGR2 expression. These results suggest that AGR2 is involved in EMT and self-renewal of CSC and may present a potential therapeutic target (oncotarget) for HNSCC.

  18. Naturalistic drive cycle synthesis for pickup trucks.

    PubMed

    Liu, Zifan; Ivanco, Andrej; Filipi, Zoran

    2015-09-01

    Future pick-up trucks are meeting much stricter fuel economy and exhaust emission standards. Design tradeoffs will have to be carefully evaluated to satisfy consumer expectations within the regulatory and cost constraints. Boundary conditions will obviously be critical for decision making: thus, the understanding of how customers are driving in naturalistic settings is indispensable. Federal driving schedules, while critical for certification, do not capture the richness of naturalistic cycles, particularly the aggressive maneuvers that often shape consumer perception of performance. While there are databases with large number of drive cycles, applying all of them directly in the design process is impractical. Therefore, representative drive cycles that capture the essence of the naturalistic driving should be synthesized from naturalistic driving data. Naturalistic drive cycles are firstly categorized by investigating their micro-trip components, defined as driving activities between successive stops. Micro-trips are expected to characterize underlying local traffic conditions, and separate different driving patterns. Next, the transitions from one vehicle state to another vehicle state in each cycle category are captured with Transition Probability Matrix (TPM). Candidate drive cycles can subsequently be synthesized using Markov Chain based on TPMs for each category. Finally, representative synthetic drive cycles are selected through assessment of significant cycle metrics to identify the ones with smallest errors. This paper provides a framework for synthesis of representative drive cycles from naturalistic driving data, which can subsequently be used for efficient optimization of design or control of pick-up truck powertrains. Manufacturers will benefit from representative drive cycles in several aspects, including quick assessments of vehicle performance and energy consumption in simulations, component sizing and design, optimization of control strategies, and

  19. Exposure to Movie Reckless Driving in Early Adolescence Predicts Reckless, but Not Inattentive Driving.

    PubMed

    Kostermans, Evelien; Stoolmiller, Mike; de Leeuw, Rebecca N H; Engels, Rutger C M E; Sargent, James D

    2014-01-01

    We examine the association between exposure to depictions of reckless driving in movies and unsafe driving, modeling inattentive and reckless driving as separate outcomes. Data were obtained by telephone from 1,630 US adolescents aged 10 to 14 years at baseline who were drivers at a survey 6 years later. Exposure to movie reckless driving was measured based on movies seen from a randomly selected list of 50 movie titles that had been content coded for reckless driving among characters. Associations were tested with inattentive and reckless driving behaviors in the subsequent survey-controlling for baseline age, sex, socioeconomic status, parental education, school performance, extracurricular activities, daily television and video/computer game exposure, number of movies watched per week, self-regulation and sensation seeking. Exposure to movie reckless driving was common, with approximately 10% of movie characters having driven recklessly. Confirmatory factor analysis revealed a significant distinction between items tapping reckless and inattentive driving at the 6th wave. Age and exposure to movie reckless driving at baseline were directly associated with wave-6 reckless (but not inattentive) driving. Additionally, growth in sensation seeking mediated a prospective relation between the total number of movies watched per week at baseline and reckless driving, independent of exposure to movie reckless driving. Males and high sensation seekers reported lower seatbelt usage and more reckless driving, whereas lower self-regulation predicted inattentive driving. In this study, exposure to movie reckless driving during early adolescence predicted adolescents' reckless driving, suggesting a direct modeling effect. Other aspects of movies were also associated with reckless driving, with that association mediated through growth in sensation seeking. Predictors of reckless driving were different from predictors of inattentive driving, with lower self-regulation associated

  20. Exposure to Movie Reckless Driving in Early Adolescence Predicts Reckless, but Not Inattentive Driving

    PubMed Central

    Kostermans, Evelien; Stoolmiller, Mike; de Leeuw, Rebecca N. H.; Engels, Rutger C. M. E.; Sargent, James D.

    2014-01-01

    Objective We examine the association between exposure to depictions of reckless driving in movies and unsafe driving, modeling inattentive and reckless driving as separate outcomes. Methods Data were obtained by telephone from 1,630 US adolescents aged 10 to 14 years at baseline who were drivers at a survey 6 years later. Exposure to movie reckless driving was measured based on movies seen from a randomly selected list of 50 movie titles that had been content coded for reckless driving among characters. Associations were tested with inattentive and reckless driving behaviors in the subsequent survey–controlling for baseline age, sex, socioeconomic status, parental education, school performance, extracurricular activities, daily television and video/computer game exposure, number of movies watched per week, self-regulation and sensation seeking. Results Exposure to movie reckless driving was common, with approximately 10% of movie characters having driven recklessly. Confirmatory factor analysis revealed a significant distinction between items tapping reckless and inattentive driving at the 6th wave. Age and exposure to movie reckless driving at baseline were directly associated with wave-6 reckless (but not inattentive) driving. Additionally, growth in sensation seeking mediated a prospective relation between the total number of movies watched per week at baseline and reckless driving, independent of exposure to movie reckless driving. Males and high sensation seekers reported lower seatbelt usage and more reckless driving, whereas lower self-regulation predicted inattentive driving. Discussion In this study, exposure to movie reckless driving during early adolescence predicted adolescents’ reckless driving, suggesting a direct modeling effect. Other aspects of movies were also associated with reckless driving, with that association mediated through growth in sensation seeking. Predictors of reckless driving were different from predictors of inattentive driving

  1. Induction of murine cytotoxic T lymphocytes against Plasmodium falciparum sporozoite surface protein 2.

    PubMed

    Wizel, B; Rogers, W O; Houghten, R A; Lanar, D E; Tine, J A; Hoffman, S L

    1994-07-01

    Sporozoite surface protein 2 has been identified as a target of malaria vaccines designed to produce protective CD8+ cytotoxic T lymphocytes (CTL) because mice immunized with mastocytoma cells expressing a fragment of Plasmodium yoelii sporozoite surface protein 2 (PySSP2) are protected against malaria by an immune response that requires CD8+ CTL. To define CTL epitopes in the Plasmodium falciparum sporozoite surface protein 2 (PfSSP2), spleen cells (SC) from mice immunized with irradiated sporozoites (irr spz) were stimulated with synthetic peptides, and these effectors were tested for cytolytic activity against peptide-pulsed, major histocompatibility complex (MHC)-matched targets. Two peptides containing CTL epitopes, A6 (Pf SSP2 3D7 214-233) and BH1 (Pf SSP2 3D7 3-11) were identified in bulk cultures of SC from immune C57BL/6 mice, and by production of CTL lines. Immunization with recombinant vaccinia expressing the full length PfSSP2 induced antigen specific, MHC-restricted, CD8+ T cell-dependent cytolytic activity against these two peptides. Finally, CTL were induced by immunization with a bacteria-derived recombinant fragment of PfSSP2 (rPfSSP2) mixed with a liposomal formulation containing a cationic lipid (Lipofectin Reagent, LPF). Induced CTL lysed target cells pulsed with peptide A6 or with LPF/rPfSSP2, but not targets pulsed with only rPfSSP2. These studies demonstrate that CTL specific to PfSSP2 are present in C57BL/6 mice and that immunization with purified rPfSSP2 delivered with LPF induces a cytotoxic T cell response.

  2. A study on the effects of fatigue driving and drunk driving on drivers' physical characteristics.

    PubMed

    Zhang, Xingjian; Zhao, Xiaohua; Du, Hongji; Rong, Jian

    2014-01-01

    The purpose of this study was to analyze the effects of fatigue driving and drunk driving on drivers' physical characteristics; to analyze the differences in drivers' physical characteristics affected by different kinds of fatigue; and to compare the differences in the effects of the 2 driving states, fatigue driving and drunk driving. Twenty-five participants' physical characteristics were collected under 5 controlled situations: normal, tired driving, drowsy driving, drowsiness + tired driving, and drunk driving. In this article, fatigue driving refers to tiredness and drowsiness and includes 3 situations: tired driving, drowsy driving, and drowsiness + tired driving. The drivers' physical characteristics were measured in terms of 9 parameters: systolic blood pressure (SBP), heart rate (HR), eyesight, dynamic visual acuity (DVA), time for dark adaption (TDA), reaction time to sound (RTS), reaction time to light (RTL), deviation of depth perception (DDP), and time deviation of speed anticipation (TDSA). They were analyzed using analysis of variance (ANOVA) with repeated measures. Binary logistical regression analysis was used to explain the relationship between drivers' physical characteristics and the two driving states. Most of the drivers' physical characteristic parameters were found to be significantly different under the influence of different situations. Four indicators are significantly affected by fatigue driving during deep fatigue (in decreasing order of influence): HR, RTL, SBP and RTS. HR and RTL are significant in the logistical regression model of the drowsiness + tired driving situation and normal situations. Six indicators of the drivers' physical characteristics are significantly affected by drunk driving (in decreasing order of influence): SBP, RTL, DDP, eyesight, RTS, and TDSA. SBP and DDP have a significant effect in the logistical regression model of the drunk driving situation and the normal situation. Both fatigue driving and drunk driving

  3. IGF-binding protein 2 is a candidate target of therapeutic potential in cancer.

    PubMed

    Yao, Xiaofeng; Sun, Shanshan; Zhou, Xuan; Guo, Wenyu; Zhang, Lun

    2016-02-01

    Insulin-like growth factor (IGF)-binding protein 2(IGFBP2), a key member of IGF family, has been reported as a notable oncogene in most human epithelium cancers. Increasing evidences suggested that IGFBP2 might be a candidate target of therapuetic potential by regulating key cancer metastasis and invasion-associated signaling networks, but there is still confusion about the mechanism on how IGFBP2 takes part in these processes. In this review, we summarized the current points of view that IGFBP2 functions in signaling pathways during tumorigenesis and tumor progression and discussed its potential clinical applications as a therapeutic target.

  4. Improving time to optimal Staphylococcus aureus treatment using a penicillin-binding protein 2a assay.

    PubMed

    Rao, Sonia N; Wang, Sheila K; Gonzalez Zamora, Jose; Hanson, Amy P; Polisetty, Radhika S; Singh, Kamaljit

    2016-12-01

    The penicillin-binding protein 2a (PBP2a) assay is a quick, accurate and inexpensive test for determining methicillin susceptibility in Staphylococcus aureus. A pre-post-study design was conducted using a PBP2a assay with and without the impact of an antimicrobial stewardship intervention to improve time to optimal therapy for methicillin-susceptible and methicillin-resistant S. aureus isolates. Our results demonstrate significantly improved time to optimal therapy and support the use of a PBP2a assay as part of an programme for all healthcare facilities, especially those with limited resources.

  5. Crystal structure of the TLDc domain of oxidation resistance protein 2 from zebrafish.

    PubMed

    Blaise, Mickaël; Alsarraf, Husam M A B; Wong, Jaslyn E M M; Midtgaard, Søren Roi; Laroche, Fabrice; Schack, Lotte; Spaink, Herman; Stougaard, Jens; Thirup, Søren

    2012-06-01

    The oxidation resistance proteins (OXR) help to protect eukaryotes from reactive oxygen species. The sole C-terminal domain of the OXR, named TLDc is sufficient to perform this function. However, the mechanism by which oxidation resistance occurs is poorly understood. We present here the crystal structure of the TLDc domain of the oxidation resistance protein 2 from zebrafish. The structure was determined by X-ray crystallography to atomic resolution (0.97Å) and adopts an overall globular shape. Two antiparallel β-sheets form a central β-sandwich, surrounded by two helices and two one-turn helices. The fold shares low structural similarity to known structures.

  6. Penicillin-Binding Protein 2a of Methicillin-Resistant Staphylococcus aureus

    PubMed Central

    Fishovitz, Jennifer; Hermoso, Juan A.; Chang, Mayland

    2014-01-01

    Summary High-level resistance to β-lactam antibiotics in methicillin-resistant Staphylococcus aureus (MRSA) is due to expression of penicillin-binding protein 2a (PBP2a), a transpeptidase that catalyzes cell-wall crosslinking in the face of the challenge by β-lactam antibiotics. The activity of this protein is regulated by allostery at a site 60 Å distant from the active site, where crosslinking of cell wall takes place. This review discusses the state of knowledge on this important enzyme of cell-wall biosynthesis in MRSA. PMID:25044998

  7. No association of chromatin-modifying protein 2B with sporadic frontotemporal dementia.

    PubMed

    Schumacher, Axel; Friedrich, Patricia; Diehl-Schmid, Janine; Ibach, Bernd; Eisele, Tamara; Laws, Simon M; Förstl, Hans; Kurz, Alexander; Riemenschneider, Matthias

    2007-11-01

    Mutations of the chromatin modifying protein 2B gene (CHMP2B) were identified, in a Danish pedigree, to cause familial frontotemporal dementia (FTD). To explore the possible genetic contribution of common CHMP2B variants in sporadic FTD, we analyzed 14 single nucleotide polymorphisms covering the entire genomic region of CHMP2B. After adjustment for multiple testing single marker and haplotype analysis revealed no significant association with sporadic FTD. Thus, we conclude that CHMP2B can be excluded as a susceptibility gene conferring risk to sporadic forms of FTD.

  8. Maxillary anterior ridge augmentation with recombinant human bone morphogenetic protein 2.

    PubMed

    Edmunds, Ryan K; Mealey, Brian L; Mills, Michael P; Thoma, Daniel S; Schoolfield, John; Cochran, David L; Mellonig, Jim

    2014-01-01

    No human studies exist on the use of recombinant human bone morphogenetic protein 2 (rhBMP-2) on an absorbable collagen sponge (ACS) as a sole graft material for lateral ridge augmentation in large ridge defect sites. This series evaluates the treatment outcome of maxillary anterior lateral ridge augmentation with rhBMP-2/ACS. Twenty patients were treated with rhBMP-2/ACS and fixation screws for space maintenance. Cone beam volumetric tomography measurements were used to determine gain in ridge width, and a bone core biopsy was obtained. The mean horizontal ridge gain was 1.2 mm across sites, and every site gained width.

  9. MicroRNA-1 promotes apoptosis of hepatocarcinoma cells by targeting apoptosis inhibitor-5 (API-5).

    PubMed

    Li, Dong; Liu, Yu; Li, Hua; Peng, Jing-Jing; Tan, Yan; Zou, Qiang; Song, Xiao-Feng; Du, Min; Yang, Zheng-Hui; Tan, Yong; Zhou, Jin-Jun; Xu, Tao; Fu, Zeng-Qiang; Feng, Jian-Qiong; Cheng, Peng; chen, Tao; Wei, Dong; Su, Xiao-Mei; Liu, Huan-Yi; Qi, Zhong-Chun; Tang, Li-Jun; Wang, Tao; Guo, Xin; Hu, Yong-He; Zhang, Tao

    2015-01-02

    Although microRNA-1 (miR-1) is a known liver cancer suppressor, the role of miR-1 in apoptosis of hepatoma cells has remained largely unknown. Our study shows that ectopic miR-1 overexpression induced apoptosis of liver hepatocellular carcinoma (HepG2) cells. Apoptosis inhibitor 5 (API-5) was found to be a potential regulator of miR-1 induced apoptosis, using a bioinformatics approach. Furthermore, an inverse relationship between miR-1 and API-5 expression was observed in human liver cancer tissues and adjacent normal liver tissues. Negative regulation of API-5 expression by miR-1 was demonstrated to promote apoptosis of HepG2 cells. Our study provides a novel regulatory mechanism of miR-1 in the apoptosis of hepatoma cells. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  10. cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in rat hepatocytes

    SciTech Connect

    Bhattacharjee, Rajesh; Xiang, Wenpei; Wang, Yinna; Zhang, Xiaoying

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer cAMP blocks cell death induced by TNF and actinomycin D in cultured hepatocytes. Black-Right-Pointing-Pointer cAMP blocks NF-{kappa}B activation induced by TNF and actinomycin D. Black-Right-Pointing-Pointer cAMP blocks DISC formation following TNF and actinomycin D exposure. Black-Right-Pointing-Pointer cAMP blocks TNF signaling at a proximal step. -- Abstract: Tumor necrosis factor {alpha} (TNF) is a pleiotropic proinflammatory cytokine that plays a role in immunity and the control of cell proliferation, cell differentiation, and apoptosis. The pleiotropic nature of TNF is due to the formation of different signaling complexes upon the binding of TNF to its receptor, TNF receptor type 1 (TNFR1). TNF induces apoptosis in various mammalian cells when the cells are co-treated with a transcription inhibitor like actinomycin D (ActD). When TNFR1 is activated, it recruits an adaptor protein, TNF receptor-associated protein with death domain (TRADD), through its cytoplasmic death effector domain (DED). TRADD, in turn, recruits other signaling proteins, including TNF receptor-associated protein 2 (TRAF2) and receptor-associated protein kinase (RIPK) 1, to form a complex. Subsequently, this complex combines with FADD and procaspase-8, converts into a death-inducing signaling complex (DISC) to induce apoptosis. Cyclic AMP (cAMP) is a second messenger that regulates various cellular processes such as cell proliferation, gene expression, and apoptosis. cAMP analogues are reported to act as anti-apoptotic agents in various cell types, including hepatocytes. We found that a cAMP analogue, dibutyryl cAMP (db-cAMP), inhibits TNF + ActD-induced apoptosis in rat hepatocytes. The protein kinase A (PKA) inhibitor KT-5720 reverses this inhibitory effect of cAMP on apoptosis. Cytoprotection by cAMP involves down-regulation of various apoptotic signal regulators like TRADD and FADD and inhibition of caspase-8 and caspase-3 cleavage. We also found

  11. Macroautophagy inhibition maintains fragmented mitochondria to foster T cell receptor-dependent apoptosis.

    PubMed

    Corrado, Mauro; Mariotti, Francesca R; Trapani, Laura; Taraborrelli, Lucia; Nazio, Francesca; Cianfanelli, Valentina; Soriano, Maria Eugenia; Schrepfer, Emilie; Cecconi, Francesco; Scorrano, Luca; Campello, Silvia

    2016-08-15

    Mitochondrial dynamics and functionality are linked to the autophagic degradative pathway under several stress conditions. However, the interplay between mitochondria and autophagy upon cell death signalling remains unclear. The T-cell receptor pathway signals the so-called activation-induced cell death (AICD) essential for immune tolerance regulation. Here, we show that this apoptotic pathway requires the inhibition of macroautophagy. Protein kinase-A activation downstream of T-cell receptor signalling inhibits macroautophagy upon AICD induction. This leads to the accumulation of damaged mitochondria, which are fragmented, display remodelled cristae and release cytochrome c, thereby driving apoptosis. Autophagy-forced reactivation that clears the Parkin-decorated mitochondria is as effective in inhibiting apoptosis as genetic interference with cristae remodelling and cytochrome c release. Thus, upon AICD induction regulation of macroautophagy, rather than selective mitophagy, ensures apoptotic progression. © 2016 The Authors.

  12. Circuit for Driving Piezoelectric Transducers

    NASA Technical Reports Server (NTRS)

    Randall, David P.; Chapsky, Jacob

    2009-01-01

    The figure schematically depicts an oscillator circuit for driving a piezoelectric transducer to excite vibrations in a mechanical structure. The circuit was designed and built to satisfy application-specific requirements to drive a selected one of 16 such transducers at a regulated amplitude and frequency chosen to optimize the amount of work performed by the transducer and to compensate for both (1) temporal variations of the resonance frequency and damping time of each transducer and (2) initially unknown differences among the resonance frequencies and damping times of different transducers. In other words, the circuit is designed to adjust itself to optimize the performance of whichever transducer is selected at any given time. The basic design concept may be adaptable to other applications that involve the use of piezoelectric transducers in ultrasonic cleaners and other apparatuses in which high-frequency mechanical drives are utilized. This circuit includes three resistor-capacitor networks that, together with the selected piezoelectric transducer, constitute a band-pass filter having a peak response at a frequency of about 2 kHz, which is approximately the resonance frequency of the piezoelectric transducers. Gain for generating oscillations is provided by a power hybrid operational amplifier (U1). A junction field-effect transistor (Q1) in combination with a resistor (R4) is used as a voltage-variable resistor to control the magnitude of the oscillation. The voltage-variable resistor is part of a feedback control loop: Part of the output of the oscillator is rectified and filtered for use as a slow negative feedback to the gate of Q1 to keep the output amplitude constant. The response of this control loop is much slower than 2 kHz and, therefore, does not introduce significant distortion of the oscillator output, which is a fairly clean sine wave. The positive AC feedback needed to sustain oscillations is derived from sampling the current through the

  13. Myocardial apoptosis in heart disease: does the emperor have clothes?

    PubMed

    Jose Corbalan, J; Vatner, Dorothy E; Vatner, Stephen F

    2016-05-01

    Since the discovery of a novel mechanism of cell death that differs from traditional necrosis, i.e., apoptosis, there have been numerous studies concluding that increased apoptosis augments myocardial infarction and heart failure and that limiting apoptosis protects the heart. Importantly, the vast majority of cells in the heart are non-myocytes with only roughly 30 % myocytes, yet almost the entire field studying apoptosis in the heart has disregarded non-myocyte apoptosis, e.g., only 4.7 % of 423 studies on myocardial apoptosis in the past 3 years quantified non-myocyte apoptosis. Accordingly, we reviewed the history of apoptosis in the heart focusing first on myocyte apoptosis, followed by the history of non-myocyte apoptosis in myocardial infarction and heart failure. Apoptosis of several of the major non-myocyte cell types in the heart (cardiac fibroblasts, endothelial cells, vascular smooth muscle cells, macrophages and leukocytes) may actually be responsible for affecting the severity of myocardial infarction and heart failure. In summary, even though it is now known that the majority of apoptosis in the heart occurs in non-myocytes, very little work has been done to elucidate the mechanisms by which non-myocyte apoptosis might be responsible for the adverse effects of apoptosis in myocardial infarction and heart failure. The goal of this review is to provide an impetus for future work in this field on non-myocyte apoptosis that will be required for a better understanding of the role of apoptosis in the heart.

  14. Targeting apoptosis in acute tubular injury.

    PubMed

    Ortiz, Alberto; Justo, Pilar; Sanz, Ana; Lorz, Corina; Egido, Jesús

    2003-10-15

    Recent research has shown that apoptosis and its regulatory mechanisms contribute to cell number regulation in acute renal failure. Acute tubular necrosis is the most frequent form of parenchymal acute renal failure. The main causes are ischemia-reperfusion, sepsis and nephrotoxic drugs. Exogenous factors such as nephrotoxic drugs and bacterial products, and endogenous factors such as lethal cytokines promote tubular cell apoptosis. Such diverse stimuli engage intracellular death pathways that in some cases are stimulus-specific. We now review the role of apoptosis in acute renal failure, the potential molecular targets of therapeutic intervention, the therapeutic weapons to modulate the activity of these targets and the few examples of therapeutic intervention on apoptosis.

  15. Molecular mechanisms of UV-induced apoptosis.

    PubMed

    Kulms, D; Schwarz, T

    2000-10-01

    Sunburn cells, single standing cells with typical morphologic features occurring in UV-exposed skin, have been recognized as keratinocytes undergoing apoptosis following UV irradiation. Induction of apoptosis following UV exposure appears to be a protective mechanism, getting rid off severely damaged cells that bear the risk of malignant transformation. UV-mediated apoptosis is a highly complex process in which different molecular pathways are involved. These include DNA damage, activation of the tumor suppressor gene p53, triggering of cell death receptors either directly by UV or by autocrine release of death ligands, mitochondrial damage and cytochrome C release. Detailed knowledge about the interplay between these pathways will increase our understanding of photocarcinogenesis. This review briefly discusses recent findings concerning the molecular mechanisms underlying UV-induced apoptosis.

  16. Driving, brain injury and assistive technology.

    PubMed

    Lane, Amy K; Benoit, Dana

    2011-01-01

    Individuals with brain injury often present with cognitive, physical and emotional impairments which impact their ability to resume independence in activities of daily living. Of those activities, the resumption of driving privileges is cited as one of the greatest concerns by survivors of brain injury. The integration of driving fundamentals within the hierarchical model proposed by Keskinen represents the complexity of skills and behaviors necessary for driving. This paper provides a brief review of specific considerations concerning the driver with TBI and highlights current vehicle technology which has been developed by the automotive industry and by manufacturers of adaptive driving equipment that may facilitate the driving task. Adaptive equipment technology allows for compensation of a variety of operational deficits, whereas technological advances within the automotive industry provide drivers with improved safety and information systems. However, research has not yet supported the use of such intelligent transportation systems or advanced driving systems for drivers with brain injury. Although technologies are intended to improve the safety of drivers within the general population, the potential of negative consequences for drivers with brain injury must be considered. Ultimately, a comprehensive driving evaluation and training by a driving rehabilitation specialist is recommended for individuals with brain injury. An understanding of the potential impact of TBI on driving-related skills and knowledge of current adaptive equipment and technology is imperative to determine whether return-to-driving is a realistic and achievable goal for the individual with TBI.

  17. Optimizing digital 8mm drive performance

    NASA Technical Reports Server (NTRS)

    Schadegg, Gerry

    1993-01-01

    The experience of attaching over 350,000 digital 8mm drives to 85-plus system platforms has uncovered many factors which can reduce cartridge capacity or drive throughput, reduce reliability, affect cartridge archivability and actually shorten drive life. Some are unique to an installation. Others result from how the system is set up to talk to the drive. Many stem from how applications use the drive, the work load that's present, the kind of media used and, very important, the kind of cleaning program in place. Digital 8mm drives record data at densities that rival those of disk technology. Even with technology this advanced, they are extremely robust and, given proper usage, care and media, should reward the user with a long productive life. The 8mm drive will give its best performance using high-quality 'data grade' media. Even though it costs more, good 'data grade' media can sustain the reliability and rigorous needs of a data storage environment and, with proper care, give users an archival life of 30 years or more. Various factors, taken individually, may not necessarily produce performance or reliability problems. Taken in combination, their effects can compound, resulting in rapid reductions in a drive's serviceable life, cartridge capacity, or drive performance. The key to managing media is determining the importance one places upon their recorded data and, subsequently, setting media usage guidelines that can deliver data reliability. Various options one can implement to optimize digital 8mm drive performance are explored.

  18. Optimizing digital 8mm drive performance

    NASA Technical Reports Server (NTRS)

    Schadegg, Gerry

    1993-01-01

    The experience of attaching over 350,000 digital 8mm drives to 85-plus system platforms has uncovered many factors which can reduce cartridge capacity or drive throughput, reduce reliability, affect cartridge archivability and actually shorten drive life. Some are unique to an installation. Others result from how the system is set up to talk to the drive. Many stem from how applications use the drive, the work load that's present, the kind of media used and, very important, the kind of cleaning program in place. Digital 8mm drives record data at densities that rival those of disk technology. Even with technology this advanced, they are extremely robust and, given proper usage, care and media, should reward the user with a long productive life. The 8mm drive will give its best performance using high-quality 'data grade' media. Even though it costs more, good 'data grade' media can sustain the reliability and rigorous needs of a data storage environment and, with proper care, give users an archival life of 30 years or more. Various factors, taken individually, may not necessarily produce performance or reliability problems. Taken in combination, their effects can compound, resulting in rapid reductions in a drive's serviceable life, cartridge capacity, or drive performance. The key to managing media is determining the importance one places upon their recorded data and, subsequently, setting media usage guidelines that can deliver data reliability. Various options one can implement to optimize digital 8mm drive performance are explored.

  19. Driving and attention deficit hyperactivity disorder.

    PubMed

    Fuermaier, Anselm B M; Tucha, Lara; Evans, Ben Lewis; Koerts, Janneke; de Waard, Dick; Brookhuis, Karel; Aschenbrenner, Steffen; Thome, Johannes; Lange, Klaus W; Tucha, Oliver

    2017-02-01

    Adults with attention deficit hyperactivity disorder (ADHD) suffer from various impairments of cognitive, emotional and social functioning, which can have considerable consequences for many areas of daily living. One of those areas is driving a vehicle. Driving is an important activity of everyday life and requires an efficient interplay between multiple cognitive, perceptual, and motor skills. In the present study, a selective review of the literature on driving-related difficulties associated with ADHD is performed, seeking to answer whether individuals with ADHD show increased levels of unsafe driving behaviours, which cognitive (dys)functions of individuals with ADHD are related to driving difficulty, and whether pharmacological treatment significantly improves the driving behaviour of individuals with ADHD. The available research provides convincing evidence that individuals with ADHD have different and more adverse driving outcomes than individuals without the condition. However, it appears that not all individuals with ADHD are affected uniformly. Despite various cognitive functions being related with driving difficulties, these functions do not appear helpful in detecting high risk drivers with ADHD, nor in predicting driving outcomes in individuals with ADHD, since impairments in these functions are defining criteria for the diagnoses of ADHD (e.g., inattention and impulsivity). Pharmacological treatment of ADHD, in particular stimulant drug treatment, appears to be beneficial to the driving difficulties experienced by individuals with ADHD. However, additional research is needed, in particular further studies that address the numerous methodological weaknesses of many of the previous studies.

  20. Suppression of Grb2 expression improved hepatic steatosis, oxidative stress, and apoptosis induced by palmitic acid in vitro partly through insulin signaling alteration.

    PubMed

    Shan, Xiangxiang; Miao, Yufeng; Fan, Rengen; Song, Changzhi; Wu, Guangzhou; Wan, Zhengqiang; Zhu, Jian; Sun, Guan; Zha, Wenzhang; Mu, Xiangming; Zhou, Guangjun; Chen, Yan

    2013-09-01

    In this study, we aimed to study the role of growth factor receptor-bound protein 2 (Grb2) in palmitic acid-induced steatosis and other "fatty liver" symptoms in vitro. HepG2 cells, with or without stably suppressed Grb2 expression, were incubated with palmitic acid for 24 h to induce typical clinical "fatty liver" features, including steatosis, impaired glucose metabolism, oxidative stress, and apoptosis. MTT and Oil Red O assays were applied to test cell viability and fat deposition, respectively. Glucose uptake assay was used to evaluate the glucose utilization of cells. Quantitative polymerase chain reaction and Western blot were used to measure expressional changes of key markers of insulin signaling, lipid/glucose metabolism, oxidative stress, and apoptosis. After 24-h palmitic acid induction, increased fat accumulation, reduced glucose uptake, impaired insulin signaling, enhanced oxidative stress, and increased apoptosis were observed in HepG2 cells. Suppression of Grb2 in HepG2 significantly reduced fat accumulation, improved glucose metabolism, ameliorated oxidative stress, and restored the activity of insulin receptor substrate-1/Akt and MEK/ERK pathways. In addition, Grb2 deficiency attenuated hepatic apoptosis shown by reduced activation of caspase-3 and fluorescent staining. Modulation of Bcl-2 and Bak1 also contributed to reduced apoptosis. In conclusion, suppression of Grb2 expression in HepG2 cells improved hepatic steatosis, glucose metabolism, oxidative stress, and apoptosis induced by palmitic acid incubation partly though modulating the insulin signaling pathway.

  1. [Apoptosis and thymocyte development (epithelial cells as inducers of thymocyte apoptosis)].

    PubMed

    Iarilin, A A; Bulanova, E G; Sharova, N I; Budagian, V M

    1998-01-01

    Apoptosis, together with proliferation, is a main factor of selection of the clones of developing T-lymphocytes: the clones not supported by positive selection are subject to apoptosis and apoptosis accounts for discarding of potentially autoaggressive clones, i.e., for negative selection in the thymus and peripheral lymphoid tissue. Realization of apoptosis at different stages of the development of T-lymphocytes depends to a varying extent on Fas, Bcl-2, p53, and other regulators. The dendritic cells are the main cell type, the contact with determines apoptosis of T-lymphocytes. A possible role of the epithelial cells was shown in few models (on murine cells) and was not practically studied. We obtained a line of epithelial cells of the human thymus cells HTSC, cocultivation with which induces apoptosis of immature thymocytes and blood T-cells activated by mitogens. Development of apoptosis is suppressed by inhibitors of protein and RNA synthesis, chelators Ca2+, ions Zn2+, and factors destroying the cytoskeleton components. In this model, interaction of pairs of molecules CD4-HLA class II and LFA-1-ICAM-1. When in contact with the HTSC cells, the thymocytes of mice mutant for Fas-receptor (line MRL.lpr) are subject to apoptosis, but when this receptor is present, it affects the development of apoptosis.

  2. Drug addiction as drive satisfaction ("antidrive") dysfunction.

    PubMed

    Kostowski, Wojciech

    2002-01-01

    Drug addiction is a complex brain disorder, characterized by the loss of control over drug seeking and drug taking behavior, and by the risk of relapse, even after a prolonged period of abstinence. This disorder may have its source in a disturbed balance of drive-related behaviors, which control appetitive reactions aimed at seeking contact with an addictive substance. The act of consumption becomes more and more attractive, and the behavior takes on compulsive character. We suppose that drug addiction may involve a change in the mechanism of satisfaction of drives and states of satiation as well. To understand how the motivational processes are changed with the development of dependence, one must consider the mechanism of drive satisfaction and satiation states that occur in relation to the consumatory reflex. When a given drive is satisfied a state of fulfillment occurs. This state may be a result of a so-called "antidrive" mechanism (Konorski 1967). While a drive activity is characterized by general activation and tension, the drive satisfaction state ("antidrive") is characterized by relaxation and relief. When a particular drive is satisfied, the operation of other drives become possible. Therefore, we postulate that dysfunction of drive satisfaction leads to the sustained activation related to the current drug-related drive, which blocks the operation of other drives. In effect, uncontrolled compulsive appetitive behavior is released, and the operation of other drives is restrained, thus forcing the organism to focus on drug-related drive. The reason for an "antidrive" dysfunction may be related to adaptive changes which develop during a contact with an addictive substance.

  3. Subduction Drive of Plate Tectonics

    NASA Astrophysics Data System (ADS)

    Hamilton, W. B.

    2003-12-01

    Don Anderson emphasizes that plate tectonics is self-organizing and is driven by subduction, which rights the density inversion generated as oceanic lithosphere forms by cooling of asthenosphere from the top. The following synthesis owes much to many discussions with him. Hinge rollback is the key to kinematics, and, like the rest of actual plate behavior, is incompatible with bottom-up convection drive. Subduction hinges (which are under, not in front of, thin leading parts of arcs and overriding plates) roll back into subducting plates. The Pacific shrinks because bounding hinges roll back into it. Colliding arcs, increasing arc curvatures, back-arc spreading, and advance of small arcs into large plates also require rollback. Forearcs of overriding plates commonly bear basins which preclude shortening of thin plate fronts throughout periods recorded by basin strata (100 Ma for Cretaceous and Paleogene California). This requires subequal rates of advance and rollback, and control of both by subduction. Convergence rate is equal to rates of rollback and advance in many systems but is greater in others. Plate-related circulation probably is closed above 650 km. Despite the popularity of concepts of plumes from, and subduction into, lower mantle, there is no convincing evidence for, and much evidence against, penetration of the 650 in either direction. That barrier not only has a crossing-inhibiting negative Clapeyron slope but also is a compositional boundary between fractionated (not "primitive"), sluggish lower mantle and fertile, mobile upper mantle. Slabs sink more steeply than they dip. Slabs older than about 60 Ma when their subduction began sink to, and lie down on and depress, the 650-km discontinuity, and are overpassed, whereas younger slabs become neutrally buoyant in mid-upper mantle, into which they are mixed as they too are overpassed. Broadside-sinking old slabs push all upper mantle, from base of oceanic lithosphere down to the 650, back under

  4. Current Drive in Recombining Plasma

    SciTech Connect

    P.F. Schmit and N.J. Fisch

    2012-05-15

    The Langevin equations describing the average collisional dynamics of suprathermal particles in nonstationary plasma remarkably admit an exact analytical solution in the case of recombining plasma. The current density produced by arbitrary particle fluxes is derived including the effect of charge recombination. Since recombination has the effect of lowering the charge density of the plasma, thus reducing the charged particle collisional frequencies, the evolution of the current density can be modified substantially compared to plasma with fixed charge density. The current drive efficiency is derived and optimized for discrete and continuous pulses of current, leading to the discovery of a nonzero "residual" current density that persists indefinitely under certain conditions, a feature not present in stationary plasmas.

  5. Characterising exotic matter driving wormholes

    NASA Astrophysics Data System (ADS)

    Chianese, Marco; Di Grezia, Elisabetta; Manfredonia, Mattia; Miele, Gennaro

    2017-04-01

    In this paper, we develop an iterative approach to span the whole set of exotic matter models able to drive a traversable wormhole. The method, based on a Taylor expansion of metric and stress-energy tensor components in a neighbourhood of the wormhole throat, reduces the Einstein equation to an infinite set of algebraic conditions, which can be satisfied order by order. The approach easily allows the implementation of further conditions linking the stress-energy tensor components among each other, like symmetry conditions or equations of state. The method is then applied to some relevant examples of exotic matter characterised by a constant energy density and that also show an isotropic behaviour in the stress-energy tensor or obeying to a quintessence-like equation of state.

  6. Molecular Mechanisms and Apoptosis in Pdt

    NASA Astrophysics Data System (ADS)

    Krammer, Barbara; Verwanger, Thomas

    2010-04-01

    Photodynamic Therapy (PDT) is a successful new therapy for malignant and non-malignant diseases. It is based on the activation of a photosensitizing dye by visible light in the target tissue, followed by production of cytotoxic substances. The article gives a short overview on the field of PDT with main focus on molecular mechanisms and apoptosis. It includes photodynamic principles, clinical application and procedures, biological effects, molecular mechanisms of damage processing and apoptosis.

  7. Apoptosis in amphibian organs during metamorphosis

    PubMed Central

    Ishizuya-Oka, Atsuko; Hasebe, Takashi; Shi, Yun-Bo

    2012-01-01

    During amphibian metamorphosis, the larval tissues/organs rapidly degenerate to adapt from the aquatic to the terrestrial life. At the cellular level, a large quantity of apoptosis occurs in a spatiotemporally-regulated fashion in different organs to ensure timely removal of larval organs/tissues and the development of adult ones for the survival of the individuals. Thus, amphibian metamorphosis provides us a good opportunity to understand the mechanisms regulating apoptosis. To investigate this process at the molecular level, a number of thyroid hormone (TH) response genes have been isolated from several organs of Xenopus laevis tadpoles and their expression and functional analyses are now in progress using modern molecular and genetic technologies. In this review, we will first summarize when and where apoptosis occurs in typical larva-specific and larval-to-adult remodeling amphibian organs to highlight that the timing of apoptosis is different in different tissues/organs, even though all are induced by the same circulating TH. Next, to discuss how TH spatiotemporally regulates the apoptosis, we will focus on apoptosis of the X. laevis small intestine, one of the best characterized remodeling organs. Functional studies of TH response genes using transgenic frogs and culture techniques have shown that apoptosis of larval epithelial cells can be induced by TH either cell-autonomously or indirectly through interactions with extracellular matrix (ECM) components of the underlying basal lamina. Here, we propose that multiple intra- and extracellular apoptotic pathways are coordinately controlled by TH to ensure massive but well-organized apoptosis, which is essential for the proper progression of amphibian metamorphosis. PMID:20238476

  8. Modulation of apoptosis by cancer chemopreventive agents.

    PubMed

    D'Agostini, Francesco; Izzotti, Alberto; Balansky, Roumen M; Bennicelli, Carlo; De Flora, Silvio

    2005-12-11

    A review of almost 2000 studies showed that the large majority of 39 putative cancer chemopreventive agents induced "spontaneous" apoptosis. Inhibition of the programmed cell death triggered by a variety of stimuli was consistently reported only with ascorbic acid, alpha-tocopherol, and N-acetylcysteine (NAC). We performed experimental studies in rodents exposed to cigarette smoke, either mainstream (MCS) or environmental (ECS), and UV-A/B-containing light. The nonsteroidal anti-inflammatory drug sulindac did not affect the apoptotic process in the skin of light-exposed mice and in the lungs of ECS-exposed mice. Likewise, 5,6-benzoflavone, indole-3-carbinol, 1,2-dithiole-3-thione and oltipraz failed to modulate apoptosis in the respiratory tract of ECS-exposed rats. Phenethyl isothiocyanate further enhanced the frequency of apoptosis in pulmonary alveolar macrophages and bronchial epithelial cells, and upregulated several genes in the lung of ECS-exposed rats. Both individually and in combination with oltipraz, NAC inhibited apoptosis in the respiratory tract of rats exposed either to MCS or ECS. Moreover, NAC attenuated the ECS-related overexpression of proapoptotic genes and normalized the levels of proapoptotic proteins in rat lung. The transplacental administration of NAC to mice considerably attenuated gene overexpression in the liver of fetuses exposed to ECS throughout pregnancy. Inhibition of apoptosis by chemopreventive agents reflects their ability to counteract certain upstream signals, such as genotoxic damage, redox imbalances, and other forms of cellular stress that trigger apoptosis. On the other hand, enhancement of apoptosis is a double-edged sword, since it represents a protective mechanism in carcinogenesis but may contribute to the pathogenesis of other degenerative diseases. We suggest that stimulation of apoptosis by so many chemopreventive agents, as reported in the literature, may often reflect the occurrence of toxic effects at high doses.

  9. Trends in global warming and evolution of matrix protein 2 family from influenza A virus.

    PubMed

    Yan, Shao-Min; Wu, Guang

    2009-12-01

    The global warming is an important factor affecting the biological evolution, and the influenza is an important disease that threatens humans with possible epidemics or pandemics. In this study, we attempted to analyze the trends in global warming and evolution of matrix protein 2 family from influenza A virus, because this protein is a target of anti-flu drug, and its mutation would have significant effect on the resistance to anti-flu drugs. The evolution of matrix protein 2 of influenza A virus from 1959 to 2008 was defined using the unpredictable portion of amino-acid pair predictability. Then the trend in this evolution was compared with the trend in the global temperature, the temperature in north and south hemispheres, and the temperature in influenza A virus sampling site, and species carrying influenza A virus. The results showed the similar trends in global warming and in evolution of M2 proteins although we could not correlate them at this stage of study. The study suggested the potential impact of global warming on the evolution of proteins from influenza A virus.

  10. Sparse and incomplete factorial matrices to screen membrane protein 2D crystallization

    PubMed Central

    Lasala, R.; Coudray, N.; Abdine, A.; Zhang, Z.; Lopez-Redondo, M.; Kirshenbaum, R.; Alexopoulos, J.; Zolnai, Z.; Stokes, D.L.; Ubarretxena-Belandia, I.

    2014-01-01

    Electron crystallography is well suited for studying the structure of membrane proteins in their native lipid bilayer environment. This technique relies on electron cryomicroscopy of two-dimensional (2D) crystals, grown generally by reconstitution of purified membrane proteins into proteoliposomes under conditions favoring the formation of well-ordered lattices. Growing these crystals presents one of the major hurdles in the application of this technique. To identify conditions favoring crystallization a wide range of factors that can lead to a vast matrix of possible reagent combinations must be screened. However, in 2D crystallization these factors have traditionally been surveyed in a relatively limited fashion. To address this problem we carried out a detailed analysis of published 2D crystallization conditions for 12 β-barrel and 138 α-helical membrane proteins. From this analysis we identified the most successful conditions and applied them in the design of new sparse and incomplete factorial matrices to screen membrane protein 2D crystallization. Using these matrices we have run 19 crystallization screens for 16 different membrane proteins totaling over 1,300 individual crystallization conditions. Six membrane proteins have yielded diffracting 2D crystals suitable for structure determination, indicating that these new matrices show promise to accelerate the success rate of membrane protein 2D crystallization. PMID:25478971

  11. Sparse and incomplete factorial matrices to screen membrane protein 2D crystallization.

    PubMed

    Lasala, R; Coudray, N; Abdine, A; Zhang, Z; Lopez-Redondo, M; Kirshenbaum, R; Alexopoulos, J; Zolnai, Z; Stokes, D L; Ubarretxena-Belandia, I

    2015-02-01

    Electron crystallography is well suited for studying the structure of membrane proteins in their native lipid bilayer environment. This technique relies on electron cryomicroscopy of two-dimensional (2D) crystals, grown generally by reconstitution of purified membrane proteins into proteoliposomes under conditions favoring the formation of well-ordered lattices. Growing these crystals presents one of the major hurdles in the application of this technique. To identify conditions favoring crystallization a wide range of factors that can lead to a vast matrix of possible reagent combinations must be screened. However, in 2D crystallization these factors have traditionally been surveyed in a relatively limited fashion. To address this problem we carried out a detailed analysis of published 2D crystallization conditions for 12 β-barrel and 138 α-helical membrane proteins. From this analysis we identified the most successful conditions and applied them in the design of new sparse and incomplete factorial matrices to screen membrane protein 2D crystallization. Using these matrices we have run 19 crystallization screens for 16 different membrane proteins totaling over 1300 individual crystallization conditions. Six membrane proteins have yielded diffracting 2D crystals suitable for structure determination, indicating that these new matrices show promise to accelerate the success rate of membrane protein 2D crystallization. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Mitochondrial Ceramide and the Induction of Apoptosis

    PubMed Central

    Siskind, Leah J.

    2007-01-01

    In most cell types, a key event in apoptosis is the release of proapoptotic intermembrane space proteins from mitochondria to the cytoplasm. In general, it is the release of these intermembrane space proteins that is responsible for the activation of caspases and DNases that are responsible for the execution of apoptosis. The mechanism for the increased permeability of the mitochondrial outer membrane during the induction phase of apoptosis is currently unknown and highly debated. This review will focus on one such proposed mechanism, namely, the formation of ceramide channels in the mitochondrial outer membrane. Ceramides are known to play a major regulatory role in apoptosis by inducing the release of proapoptotic proteins from the mitochondria. As mitochondria are known to contain the enzymes responsible for the synthesis and hydrolysis of ceramide, there exists a mechanism for regulating the level of ceramide in mitochondria. In addition, mitochondrial ceramide levels have been shown to be elevated prior to the induction phase of apoptosis. Ceramide has been shown to form large protein permeable channels in planar phospholipid and mitochondrial outer membranes. Thus, ceramide channels are good candidates for the pathway with which proapoptotic proteins are released from mitochondria during the induction phase of apoptosis. PMID:16167171

  13. Yeast as a model to study apoptosis?

    PubMed

    Fleury, Christophe; Pampin, Mathieu; Tarze, Agathe; Mignotte, Bernard

    2002-02-01

    Programmed cell death (PCD) serves as a major mechanism for the precise regulation of cell numbers, and as a defense mechanism to remove unwanted and potentially dangerous cells. Despite the striking heterogeneity of cell death induction pathways, the execution of the death program is often associated with characteristic morphological and biochemical changes termed apoptosis. Although for a long time the absence of mitochondrial changes was considered as a hallmark of apoptosis, mitochondria appear today as the central executioner of programmed cell death. This crucial position of mitochondria in programmed cell death control is not due to a simple loss of function (deficit in energy supplying), but rather to an active process in the regulation of effector mechanisms. The large diversity of regulators of apoptosis in mammals and their numerous interactions complicate the analysis of their individual functions. Yeast, eukaryotic but unicellular organism, lack the main regulators of apoptosis (caspases, Bcl-2 family members, ...) found in mammals. This absence render them a powerful tool for heterologous expression, functional studies, and even cloning of new regulators of apoptosis. Great advances have thus been made in our understanding of the molecular mechanisms of Bcl-2 family members interactions with themselves and other cellular proteins, specially thanks to the two hybrid system and the easy manipulation of yeast (molecular biology and genetics). This review will focus on the use of yeast as a tool to identify new regulators and study function of mammalian apoptosis regulators.

  14. DPI induces mitochondrial superoxide-mediated apoptosis.

    PubMed

    Li, Nianyu; Ragheb, Kathy; Lawler, Gretchen; Sturgis, Jennie; Rajwa, Bartek; Melendez, J Andres; Robinson, J Paul

    2003-02-15

    The iodonium compounds diphenyleneiodonium (DPI) and diphenyliodonium (IDP) are well-known phagocyte NAD(P)H oxidase inhibitors. However, it has been shown that at high concentrations they can inhibit the mitochondrial respiratory chain as well. Since inhibition of the mitochondrial respiratory chain has been shown to induce superoxide production and apoptosis, we investigated the effect of iodonium compounds on mitochondria-derived superoxide and apoptosis. Mitochondrial superoxide production was measured on both cultured cells and isolated rat-heart submitochondrial particles. Mitochondria function was examined by monitoring mitochondrial membrane potential. Apoptotic pathways were studied by measuring cytochrome c release and caspase 3 activation. Apoptosis was characterized by detecting DNA fragmentation on agarose gel and measuring propidium iodide- (PI-) stained subdiploid cells using flow cytometry. Our results showed that DPI could induce mitochondrial superoxide production. The same concentration of DPI induced apoptosis by decreasing mitochondrial membrane potential and releasing cytochrome c. Addition of antioxidants or overexpression of MnSOD significantly reduced DPI-induced mitochondrial damage, cytochrome c release, caspase activation, and apoptosis. These observations suggest that DPI can induce apoptosis via induction of mitochondrial superoxide. DPI-induced mitochondrial superoxide production may prove to be a useful model to study the signaling pathways of mitochondrial superoxide.

  15. Estrogens sensitize anterior pituitary gland to apoptosis.

    PubMed

    Pisera, D; Candolfi, M; Navarra, S; Ferraris, J; Zaldivar, V; Jaita, G; Castro, M G; Seilicovich, A

    2004-10-01

    Tissue homeostasis results from a balance between cell proliferation and cell death by apoptosis. Estradiol affects proliferation as well as apoptosis in hormone-dependent tissues. In the present study, we investigated the apoptotic response of the anterior pituitary gland to lipopolysaccharide (LPS) in cycling female rats, and the influence of estradiol in this response in ovariectomized (OVX) rats. The OVX rats were chronically estrogenized with implanted Silastic capsules containing 1 mg of 17beta-estradiol (E2). Cycling or OVX and E2-treated rats were injected with LPS (250 microg/rat ip). Apoptosis was determined by the terminal deoxynucleotidyl-mediated dUTP nick-end labeling (TUNEL) method in sections of the anterior pituitary gland and spleen. Chronic estrogenization induced apoptosis in the anterior pituitary gland. Acute endotoxemia triggered apoptosis of cells in the anterior pituitary gland of E2-treated rats but not of OVX rats. No differences were observed in the apoptotic response to LPS in spleen between OVX and E2-treated rats. The apoptotic response of the anterior pituitary to LPS was variable along the estrous cycle, being higher at proestrus than at estrus or diestrus I. Approximately 75% of the apoptotic cells were identified as lactotropes by immunofluorescence. In conclusion, our results indicate that estradiol induces apoptosis and enables the proapoptotic action of LPS in the anterior pituitary gland. Also, our study suggests that estrogens may be involved in anterior pituitary cell renewal during the estrous cycle, sensitizing lactotropes to proapoptotic stimuli.

  16. Personal and situational influences on drink driving and sober driving among a cohort of young adults

    PubMed Central

    Morrison, L; Begg, D; Langley, J

    2002-01-01

    Objectives: To compare personal and situational influences on incidents involving drink driving with those involving sober driving. Methods: Information on a range of road safety practices was sought in face to face interviews conducted with 969 members of the Dunedin Multidisciplinary Health and Development Study cohort at age 26 years. A total of 750 study members reported an incident that involved the opportunity to consume alcohol and also travel by motor vehicle. Of these, 87 were classified as "drink drive incidents" and 663 as "sober drive incidents". Results: Study members who were male, of lower socioeconomic status, had no school qualifications, or were dependent on alcohol or marijuana at age 21 were significantly more likely to report a drink drive incident at age 26. Compared with the sober drive incidents, the drink drive incidents were more commonly associated with driving alone, drinking at bars, and no advanced planning. For drink drive incidents the amount of alcohol consumed was influenced by the conviviality of the occasion, whereas for sober drive incidents it was the need to drive. One quarter of those reporting drink drive incidents stated they had used marijuana and/or LSD at the event at which they drank. Conclusions: Drink drive and sober drive incidents differed, particularly with regard to decisions made before the event. Prevention efforts could usefully be targeted toward these decisions. PMID:12120828

  17. Driving Task: How Older Drivers' On-Road Driving Performance Relates to Abilities, Perceptions, and Restrictions.

    PubMed

    Koppel, Sjaan; Charlton, Judith L; Langford, Jim; Di Stefano, Marilyn; MacDonald, Wendy; Vlahodimitrakou, Zafiroula; Mazer, Barbara L; Gelinas, Isabelle; Vrkljan, Brenda; Eliasz, Kinga; Myers, Anita; Tuokko, Holly A; Marshall, Shawn C

    2016-06-01

    This study examined a cohort of 227 older drivers and investigated the relationship between performance on the electronic Driver Observation Schedule (eDOS) driving task and: (1) driver characteristics; (2) functional abilities; (3) perceptions of driving comfort and abilities; and (4) self-reported driving restrictions. Participants (male: 70%; age: M = 81.53 years, SD = 3.37 years) completed a series of functional ability measures and scales on perceived driving comfort, abilities, and driving restrictions from the Year 2 Candrive/Ozcandrive assessment protocol, along with an eDOS driving task. Observations of participants' driving behaviours during the driving task were recorded for intersection negotiation, lane-changing, merging, low-speed maneuvers, and maneuver-free driving. eDOS driving task scores were high (M = 94.74; SD = 5.70) and significantly related to participants' perceived driving abilities, reported frequency of driving in challenging situations, and number of driving restrictions. Future analyses will explore potential changes in driving task scores over time.

  18. Electric vehicle drive train with contactor protection

    DOEpatents

    Konrad, C.E.; Benson, R.A.

    1994-11-29

    A drive train for an electric vehicle includes a traction battery, a power drive circuit, a main contactor for connecting and disconnecting the traction battery and the power drive circuit, a voltage detector across contacts of the main contactor, and a controller for controlling the main contactor to prevent movement of its contacts to the closed position when the voltage across the contacts exceeds a predetermined threshold, to thereby protect the contacts of the contactor. The power drive circuit includes an electric traction motor and a DC-to-AC inverter with a capacitive input filter. The controller also inhibits the power drive circuit from driving the motor and thereby discharging the input capacitor if the contacts are inadvertently opened during motoring. A precharging contactor is controlled to charge the input filter capacitor prior to closing the main contactor to further protect the contacts of the main contactor. 3 figures.

  19. Electric vehicle drive train with contactor protection

    DOEpatents

    Konrad, Charles E.; Benson, Ralph A.

    1994-01-01

    A drive train for an electric vehicle includes a traction battery, a power drive circuit, a main contactor for connecting and disconnecting the traction battery and the power drive circuit, a voltage detector across contacts of the main contactor, and a controller for controlling the main contactor to prevent movement of its contacts to the closed position when the voltage across the contacts exceeds a predetermined threshold, to thereby protect the contacts of the contactor. The power drive circuit includes an electric traction motor and a DC-to-AC inverter with a capacitive input filter. The controller also inhibits the power drive circuit from driving the motor and thereby discharging the input capacitor if the contacts are inadvertently opened during motoring. A precharging contactor is controlled to charge the input filter capacitor prior to closing the main contactor to further protect the contacts of the main contactor.

  20. Parkinson's disease and issues related to driving.

    PubMed

    Uitti, Ryan J

    2009-12-01

    Driving a motor vehicle represents an important activity associated with personal independence and freedom. Being told that one can no longer drive is itself associated with loss of independence, depression, low self-esteem and reduced activities [1,2]. Patients with Parkinson's disease (PD), therefore, understandably wish to continue to be able to maintain their ability to drive automobiles, motorcycles, airplanes, and boats, etc. The ability to determine if and when a PD patient is no longer fit to drive a motor vehicle is important for maintaining safety for the PD patient and the public. There are numerous requirements for being able to drive a motor vehicle safely. When any of these capacities deteriorate, the ability to drive safely may be lost. This review will concentrate upon common issues that would be peculiar to patients with PD.

  1. Application of traction drives as servo mechanisms

    NASA Technical Reports Server (NTRS)

    Loewenthal, S. H.; Rohn, D. A.; Steinetz, B. M.

    1985-01-01

    The suitability of traction drives for a wide class of aerospace control mechanisms is examined. Potential applications include antenna or solar array drive positioners, robotic joints, control moment gyro (CMG) actuators and propeller pitch change mechanisms. In these and similar applications the zero backlash, high torsional stiffness, low hysteresis and torque ripple characteristics of traction drives are of particular interest, as is the ability to run without liquid lubrication in certain cases. Wear and fatigue considerations for wet and dry operation are examined along with the tribological performance of several promising self lubricating polymers for traction contracts. The speed regulation capabilities of variable ratio traction drives are reviewed. A torsional stiffness analysis described suggests that traction contacts are relatively stiff compared to gears and are significantly stiffer than the other structural elements in the prototype CMG traction drive analyzed. Discussion is also given of an advanced turboprop propeller pitch change mechanism that incorporates a traction drive.

  2. Drive mechanism for track-type vehicle

    SciTech Connect

    Aoki, H.; Hashimoto, M.

    1986-03-11

    A drive mechanism is described for a track-type vehicle having a bevel gear case which forms a mounting support, a steering clutch and brake unit including a steering clutch and brake assembly, and a final drive unit including a final drive assembly. The drive mechanism consists of: a first housing which houses the steering clutch and brake assembly and defines a first annular flange; a second housing which houses the final drive assembly and defines a second annular flange engaging with the first annular flange; a freely connectable and disconnectable connecting shaft mounted between the steering clutch and brake assembly and the final drive assembly for operatively connecting the assemblies; a connecting and disconnecting means for connecting shaft; and an annular sealing sleeve for connecting the first annular flange and the second annular flange movably disposed between the flanges.

  3. Potential driving issues in combat returnees.

    PubMed

    Lew, Henry L; Amick, Melissa M; Kraft, Malissa; Stein, Murray B; Cifu, David X

    2010-01-01

    The driving abilities of service members returning from Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) have not been well reported and are an important aspect of their return to normal life. This article reviews the unique risk factors for unsafe driving in this cohort. In particular, the cognitive and psychological symptoms of mild traumatic brain injury and postraumatic stress disorder, two of the most common diagnoses affecting these returning warriors, are specified, and their possible association with impaired driving is examined. The potential negative impact of the "battlemind driving tactics" (i.e., evasive driving skills) acquired by these service members as part of their military tours is also highlighted. The article concludes with comments about the functional consequences of impaired driving in this population, including limits to participation in rehabilitation and community reintegration, as well as recognition of the need for further research in this area.

  4. A new driving circuit for IGBT devices

    SciTech Connect

    Licitra, C.; Musumeci, S.; Raciti, A.; Galluzzo, A.U.; Letor, R.; Melito, M.

    1995-05-01

    IGBT devices are increasingly used in power electronic equipment due to their high power handling capability. This paper deals with the problems that concern the turn-on, turn-off, and short-circuit of these devices. An optimal new driving circuit is proposed which gives excellent device output performances. Experimental oscillogram traces of transient condition tests are given, which demonstrate the advantages of using the new driving circuit. The suitability of the driving circuit for integration is analyzed.

  5. Get the message: distracted driving and teens.

    PubMed

    Adeola, Ruth; Gibbons, Mallory

    2013-01-01

    Distracted driving is a growing problem in the United States. With the integration of wireless devices into everyday life, cell phone use behind the wheel is a distraction requiring increasing concern. Teen drivers are most susceptible to the dangers of distracted driving as made evident in the overrepresentation of teens in distraction-related motor vehicle crashes. This article describes the causes, consequences, and statistics related to distracted driving in teenagers and an injury prevention program for teenagers.

  6. Optimal Sector Sampling for Drive Triage

    DTIC Science & Technology

    2013-06-01

    known files, which we call target data, that could help identify a drive holding evidence such as child pornography or malware. Triage is needed to sift...we call target data, that could help identify a drive holding evidence such as child pornography or malware. Triage is needed to sift through drives...situations where the user is looking for known data.1 One example is a law enforcement officer searching for evidence of child pornography from a large num

  7. Life Analysis of Multiroller Planetary Traction Drive

    DTIC Science & Technology

    1981-04-01

    Nasvytis eUltirollcr Traction Drive. The analysis was based on the Lundberg- Palmgren method for rolling- element bearing life prediction. Life...a steel rail. There are dozens bearing life. The effect of stress, stressed volume, of traction drive designs, distinguished by the and depth to the...clene¶,t bearing materials, lubrication and traction drive concept. Cleaner steels (vacuum design were considered as well as the potentially induction

  8. Return to driving after head injury.

    PubMed

    Hawley, C A

    2001-06-01

    To determine whether patients who return to driving after head injury can be considered safe to do so and to compare the patient characteristics of those who return to driving with those who do not. In a multicentre qualitative study 10 rehabilitation units collectively registered 563 adults with traumatic brain injury during a 2.5 year period. Recruitment to the study varied from immediately after hospital admission to several years after injury. Patients and their families were interviewed around 3 to 6 months after recruitment. A total of 383 (67.5%) subjects were interviewed within 1 year of injury, of whom 270 (47.6%) were interviewed within 6 months of injury. Main outcome measures were the presence or absence of driving related problems reported by drivers and ex-drivers, and scores on driving related items of the functional independence/functional assessment measure (FIM+FAM). Of the 563 patients 381 were drivers before the injury and 139 had returned to driving at interview. Many current drivers reported problems with behaviour (anger, aggression, irritability; 67 (48.2%)), memory ( 89 (64%)), concentration and attention (39 (28.1%)), and vision (39 (28.1%)). Drivers reported most driving related problems as often as ex-drivers, main exceptions were epilepsy and community mobility. Current drivers scored significantly higher on the FIM+FAM (were more independent), than ex-drivers. The driving group had sustained less severe head injuries than ex-drivers; nevertheless, 78 (56.2%) current drivers had received a severe head injury. Few (61 (16%)) previous drivers reported receiving formal advice about driving after injury. The existence of problems which could significantly affect driving does not prevent patients returning to driving after traumatic brain injury. Patients should be assessed for both mental and physical status before returning to driving after a head injury, and systems put in place to enable clear and consistent advice to be given to

  9. The antifungal plant defensin RsAFP2 from radish induces apoptosis in a metacaspase independent way in Candida albicans.

    PubMed

    Aerts, An M; Carmona-Gutierrez, Didac; Lefevre, Sophie; Govaert, Gilmer; François, Isabelle E J A; Madeo, Frank; Santos, Renata; Cammue, Bruno P A; Thevissen, Karin

    2009-08-06

    We show that the antifungal plant defensin Raphanus sativus antifungal protein 2 (RsAFP2) from radish induces apoptosis and concomitantly triggers activation of caspases or caspase-like proteases in the human pathogen Candida albicans. Furthermore, we demonstrate that deletion of C. albicans metacaspase 1, encoding the only reported (putative) caspase in C. albicans, significantly affects caspase activation by the apoptotic stimulus acetic acid, but not by RsAFP2. To our knowledge, this is the first report on the induction of apoptosis with concomitant caspase activation by a defensin in this pathogen. Moreover, our data point to the existence of at least two different types of caspases or caspase-like proteases in C. albicans.

  10. Camshaft driving device for internal combustion engine

    SciTech Connect

    Ebesu, H.

    1988-06-14

    A camshaft driving device for use in a double overhead cam type internal combustion engine having a cylinder block, an upper deck formed at an upper portion of the cylinder block, a cylinder head disposed on the cylinder block, a driving shaft rotatably mounted at a lower portion of the cylinder block, and a pair of camshafts rotatably mounted at an upper portion of the cylinder head, is described comprising: driving force transmitting endless chain members engaging in the reduction gear means for transmitting a driving force from the driving shaft to the pair of camshaft through the reduction gear means. The camshaft driving device further including chain tensioners for tightening the chain, a nozzle means for supplying a lubricating oil to the driving force chain members on the side of the drive shaft and an oil guide wall formed immediately above the sprocket of the transmitting portion of the reduction gear means at a lower end portion of the journal boss and lapping thereover both in the radial direction and in the axial direction of the driving shaft. A mounting boss for mounting the reduction gear means thereon is formed on the upper deck of the cylinder block.

  11. Risky driving behaviors in Tehran, Iran.

    PubMed

    Shams, Mohsen; Rahimi-Movaghar, Vafa

    2009-03-01

    Iran has one of the highest fatality rates due to road traffic crashes (RTC) in the world. The disability adjusted life years (DALYs) for RTC in Iran is more than 1,300,000 years, which is more than that for any other disease such as cardiovascular or cancer. We evaluated risky driving behaviors in Tehran, the capital of Iran. A retrospective analysis was conducted based on the data obtained from the Tehran Police Safety Driving Department. Offenses and crashes were studied in different municipal districts in Tehran from March 2006 to March 2007. The inclusion criteria were risky driving behaviors fined by the police. Nonbehavioral offences were excluded. There were 3,821,798 offenses in Tehran. Not wearing a seat belt was the most common (59%) example of risky driving behavior, followed by tailgating, not wearing motorcycle helmets, talking on the cell phone while driving, overtaking from the wrong side, speeding, not driving between the lanes, weaving in and out of traffic, left deviation, and changing lanes without signals. The most common causes of RTC in Tehran are speeding, overtaking from the wrong side, and the rapid changing of driving lanes. The study factors effective in preventing risky driving behaviors in Tehran is recommended. The consideration of specific characteristics of the municipal districts is necessary to reduce risky driving behaviors.

  12. Risky driving and lifestyles in adolescence.

    PubMed

    Bina, Manuela; Graziano, Federica; Bonino, Silvia

    2006-05-01

    Several studies have shown that risky driving is especially prevalent among young drivers and recent research has pointed out that driving in adolescence should be investigated in the more general context of adolescent development. The first aim of this contribution was to analyze involvement in risky driving in a normative sample of 645 Italian adolescents, boys and girls, aged 14-17, through a self-report questionnaire. A second aim was to evaluate the association between risky driving and lifestyle, defined as involvement in other health risk behaviors and leisure activities. The main results showed that many adolescents drove cars and motorcycles without the required driving license and the most frequent offences were speeding and failure to maintain a safe braking distance. Gender and age differences were also investigated. Results concerning the association between risky driving and lifestyle showed that risky driving was not an isolated behavior. Boys who displayed risky driving practices were more likely to adopt a lifestyle characterized by high involvement in antisocial behaviors, tobacco smoking, comfort eating and time spent in non-organized activities with friends. Girls involved in risky driving were more likely to be involved in other risk-taking behaviors, antisocial behaviors and drug use.

  13. Women drive better if not stereotyped.

    PubMed

    Moè, Angelica; Cadinu, Mara; Maass, Anne

    2015-12-01

    A commonly held stereotype is that women are poor drivers. This stereotype is recognized and endorsed by women and girls very early on, long before taking their driving licence, nevertheless they are less involved in accidents and drive safer and less fast than men. In line with the stereotype threat theory, the present study tests the hypothesis that making the driving stereotype salient will lead women to underperform in a driving simulation task. In Experiment 1women in the stereotype threat condition were told that the aim of the study was to detect gender differences in driving whereas in a control condition no study aim was provided. In Experiment 2, two conditions were compared: stereotype threat (same instructions as in Experiment 1), and stereotype boost (the alleged goal was to compare driving ability of young vs. old people). As predicted, the results of both experiments showed that women under stereotype threat, as compared to either control or stereotype boost participants, doubled the number of mistakes. Nevertheless, they overall expected/self-reported to drive/have driven poorly. Importantly, their level of expectation was a significant predictor of their actual driving performance only in the stereotype threat condition. Implications of these effects of stereotype threat on women's driving performance and self-assessment are discussed.

  14. Driving Retirement in Older Adults with Dementia

    PubMed Central

    Croston, Jami; Meuser, Thomas M.; Berg-Weger, Marla; Grant, Elizabeth A.; Carr, David B.

    2010-01-01

    In order to characterize the driving and mobility status of older adults with dementia, a questionnaire was mailed to 527 informants; 119 were returned. The majority of patients were diagnosed with Dementia of the Alzheimer’s Type. Only 28% were actively driving at the time of survey. Informants rated 53% of current or recently retired drivers as potentially unsafe. Few informants reported using community/educational resources. Individuals with progressive dementia retire from driving for differing reasons, many subsequent to family recognition of impaired driving performance. Opportunities for education and supportive assistance exist but are underutilized. PMID:20161565

  15. Metal band drives in spacecraft mechanisms

    NASA Technical Reports Server (NTRS)

    Maus, Daryl

    1993-01-01

    Transmitting and changing the characteristics of force and stroke is a requirement in nearly all mechanisms. Examples include changing linear to rotary motion, providing a 90 deg change in direction, and amplifying stroke or force. Requirements for size, weight, efficiency and reliability create unique problems in spacecraft mechanisms. Flexible metal band and cam drive systems provide powerful solutions to these problems. Band drives, rack and pinion gears, and bell cranks are compared for effectiveness. Band drive issues are discussed including materials, bend radius, fabrication, attachment and reliability. Numerous mechanisms are shown which illustrate practical applications of band drives.

  16. Temporal shift in methyl-CpG binding protein 2 expression in a mouse model of Rett syndrome.

    PubMed

    Metcalf, B M; Mullaney, B C; Johnston, M V; Blue, M E

    2006-01-01

    Rett syndrome is an X-linked neurodevelopmental disorder caused by mutations in methyl-CpG binding protein 2. Females with identical mutations in the methyl-CpG binding protein 2 gene can display varying severity of symptoms, suggesting that other factors such as X-chromosome inactivation affect phenotypic expression in Rett syndrome. Although X-chromosome inactivation is random and balanced in the blood and brain of the majority of girls with classic Rett syndrome, skewing in the ratio of expression of the mutant methyl-CpG binding protein 2-X to the wildtype-X affects the severity of symptoms. In this study, the pattern of immunostaining for methyl-CpG binding protein 2 was compared with that of neuronal nuclei specific protein, a pan-neuronal marker, to assess X-chromosome inactivation in a Rett syndrome mouse model. The number of cortical neurons and cortical volume were assessed by unbiased stereological measurements in younger adult (7-9 week old) wildtype (wildtype/methyl-CpG binding protein 2+/+), female heterozygous (heterozygous/methyl-CpG binding protein 2+/-), and null (methyl-CpG binding protein 2-/y) male mice and in older adult (24-95 week old) wildtype and heterozygous mice. The results showed that the number of neuronal nuclei specific protein-positive cells and cortical volume did not differ by genotype or age. However, younger adult heterozygous mice had significantly fewer methyl-CpG binding protein 2 cells and the pattern of methyl-CpG binding protein 2 staining was less distinct than in younger adult wildtype mice. However, in older adult heterozygous mice, the number and pattern of methyl-CpG binding protein 2-expressing neurons were similar to the wildtype. The ratio of methyl-CpG binding protein 2 to neuronal nuclei specific protein-stained neurons, a potential measure of X-chromosome inactivation, was close to 50% in the younger adult heterozygous mice, but nearly 70% in the older adult heterozygous mice. These results suggest that X

  17. Modulation of apoptosis and viral latency - an axis to be well understood for successful cure of human immunodeficiency virus.

    PubMed

    Timilsina, Uddhav; Gaur, Ritu

    2016-04-01

    Human immunodeficiency virus (HIV) is the causative agent of the deadly disease AIDS, which is characterized by the progressive decline of CD4(+)T-cells. HIV-1-encoded proteins such as envelope gp120 (glycoprotein gp120), Tat (trans-activator of transcription), Nef (negative regulatory factor), Vpr (viral protein R), Vpu (viral protein unique) and protease are known to be effective in modulating host cell signalling pathways that lead to an alteration in apoptosis of both HIV-infected and uninfected bystander cells. Depending on the stage of the virus life cycle and host cell type, these viral proteins act as mediators of pro- or anti-apoptotic signals. HIV latency in viral reservoirs is a persistent phenomenon that has remained beyond the control of the human immune system. To cure HIV infections completely, it is crucial to reactivate latent HIV from cellular pools and to drive these apoptosis-resistant cells towards death. Several previous studies have reported the role of HIV-encoded proteins in apoptosis modulation, but the molecular basis for apoptosis evasion of some chronically HIV-infected cells and reactivated latently HIV-infected cells still needs to be elucidated. The current review summarizes our present understanding of apoptosis modulation in HIV-infected cells, uninfected bystander cells and latently infected cells, with a focus on highlighting strategies to activate the apoptotic pathway to kill latently infected cells.

  18. Roles and regulation of autophagy and apoptosis in the remodelling of the lepidopteran midgut epithelium during metamorphosis.

    PubMed

    Romanelli, Davide; Casartelli, Morena; Cappellozza, Silvia; de Eguileor, Magda; Tettamanti, Gianluca

    2016-09-09

    We previously showed that autophagy and apoptosis occur in the removal of the lepidopteran larval midgut during metamorphosis. However, their roles in this context and the molecular pathways underlying their activation and regulation were only hypothesized. The results of the present study better clarify the timing of the activation of these two processes: autophagic and apoptotic genes are transcribed at the beginning of metamorphosis, but apoptosis intervenes after autophagy. To investigate the mechanisms that promote the activation of autophagy and apoptosis, we designed a set of experiments based on injections of 20-hydroxyecdysone (20E). Our data demonstrate that autophagy is induced at the end of the last larval stage by the 20E commitment peak, while the onset of apoptosis occurs concomitantly with the 20E metamorphic peak. By impairing autophagic flux, the midgut epithelium degenerated faster, and higher caspase activity was observed compared to controls, whereas inhibiting caspase activation caused a severe delay in epithelial degeneration. Our data demonstrate that autophagy plays a pro-survival function in the silkworm midgut during metamorphosis, while apoptosis is the major process that drives the demise of the epithelium. The evidence collected in this study seems to exclude the occurrence of autophagic cell death in this setting.

  19. Roles and regulation of autophagy and apoptosis in the remodelling of the lepidopteran midgut epithelium during metamorphosis

    PubMed Central

    Romanelli, Davide; Casartelli, Morena; Cappellozza, Silvia; de Eguileor, Magda; Tettamanti, Gianluca

    2016-01-01

    We previously showed that autophagy and apoptosis occur in the removal of the lepidopteran larval midgut during metamorphosis. However, their roles in this context and the molecular pathways underlying their activation and regulation were only hypothesized. The results of the present study better clarify the timing of the activation of these two processes: autophagic and apoptotic genes are transcribed at the beginning of metamorphosis, but apoptosis intervenes after autophagy. To investigate the mechanisms that promote the activation of autophagy and apoptosis, we designed a set of experiments based on injections of 20-hydroxyecdysone (20E). Our data demonstrate that autophagy is induced at the end of the last larval stage by the 20E commitment peak, while the onset of apoptosis occurs concomitantly with the 20E metamorphic peak. By impairing autophagic flux, the midgut epithelium degenerated faster, and higher caspase activity was observed compared to controls, whereas inhibiting caspase activation caused a severe delay in epithelial degeneration. Our data demonstrate that autophagy plays a pro-survival function in the silkworm midgut during metamorphosis, while apoptosis is the major process that drives the demise of the epithelium. The evidence collected in this study seems to exclude the occurrence of autophagic cell death in this setting. PMID:27609527

  20. Apoptosis-Dependent and Apoptosis-Independent Functions of Bim in Prostate Cancer Cells

    DTIC Science & Technology

    2005-03-01

    Independent Functions of Bim in Prostate Cancer Cells PRINCIPAL INVESTIGATOR: Dr. Dean Tang...SUBTITLE 5a. CONTRACT NUMBER Apoptosis-Dependent and Apoptosis-Independent Functions of Bim in Prostate Cancer Cells 5b. GRANT NUMBER DAMD17-03-1...Unlimited 13. SUPPLEMENTARY NOTES Original contains colored plates: ALL DTIC reproductions will be in black and white. 14. ABSTRACT

  1. Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation.

    PubMed

    Dichtel-Danjoy, M-L; Ma, D; Dourlen, P; Chatelain, G; Napoletano, F; Robin, M; Corbet, M; Levet, C; Hafsi, H; Hainaut, P; Ryoo, H D; Bourdon, J-C; Mollereau, B

    2013-01-01

    Irradiated or injured cells enter apoptosis, and in turn, promote proliferation of surrounding unaffected cells. In Drosophila, apoptotic cells have an active role in proliferation, where the caspase Dronc and p53 induce mitogen expression and growth in the surrounding tissues. The Drosophila p53 gene structure is conserved and encodes at least two protein isoforms: a full-length isoform (Dp53) and an N-terminally truncated isoform (DΔNp53). Historically, DΔNp53 was the first p53 isoform identified and was thought to be responsible for all p53 biological activities. It was shown that DΔNp53 induces apoptosis by inducing the expression of IAP antagonists, such as Reaper. Here we investigated the roles of Dp53 and DΔNp53 in apoptosis and apoptosis-induced proliferation. We found that both isoforms were capable of activating apoptosis, but that they each induced distinct IAP antagonists. Expression of DΔNp53 induced Wingless (Wg) expression and enhanced proliferation in both 'undead cells' and in 'genuine' apoptotic cells. In contrast to DΔNp53, Dp53 did not induce Wg expression in the absence of the endogenous p53 gene. Thus, we propose that DΔNp53 is the main isoform that regulates apoptosis-induced proliferation. Understanding the roles of Drosophila p53 isoforms in apoptosis and in apoptosis-induced proliferation may shed new light on the roles of p53 isoforms in humans, with important implications in cancer biology.

  2. Toward understanding induction of oxidative stress and apoptosis by proteasome inhibitors.

    PubMed

    Paniagua Soriano, Guillem; De Bruin, Gerjan; Overkleeft, Herman S; Florea, Bogdan I

    2014-12-10

    Proteasome inhibitors (PIs) are used in the clinic for the treatment of hematopoietic malignancies. PI inhibitors induce endoplasmatic reticulum (ER) stress and oxidative stress, disruption of signaling pathways, mitochondrial dysfunction, and, eventually, cell death by apoptosis. PIs designated as clinical candidates include natural product derivatives and compounds developed by rational design and feature a wide diversity of structural elements. The vast amount of literature on this topic underscores PIs significance in driving basic research alongside therapeutic benefit. Research in recent years has brought an in-depth insight into the molecular mechanisms of PI-induced apoptosis. However, there are some paradoxes and controversies in the literature. In this review, the advances and uncertainties, in particular on the time course events that make cells commit to apoptosis, are discussed. In addition, some mechanisms of evolved PI resistance are presented, and speculations on the difference in sensitivity between cell or tumor types are brought forward. The review concludes by giving an outlook of recent methods that may be employed to describe the system biology of how PIs impact cell survival decisions. The biology of ER stress, reactive oxygen species (ROS) production, and apoptosis as induced by PIs is not well understood. Absorbed by the strong focus on PIs, one might overlook the importance of proteasome activity activators or modulators and the study of enzymatic pathways that lie up- or downstream from the proteasome function. An increased understanding of the systems biology at mRNA and protein levels and the kinetics behind the interaction between PIs and cells is imperative. The design and synthesis of subunit specific inhibitors for each of the seven known proteasome activities and for the enzymes associated to proteasomes will aid in unraveling biology of the ubiquitin-proteasome system in relation to ER stress, ROS production, and apoptosis and

  3. Apoptosis predominates in nonmyocytes in heart failure.

    PubMed

    Park, Misun; Shen, You-Tang; Gaussin, Vinciane; Heyndrickx, Guy R; Bartunek, Jozef; Resuello, Ranillo R G; Natividad, Filipinas F; Kitsis, Richard N; Vatner, Dorothy E; Vatner, Stephen F

    2009-08-01

    The goal of this investigation was to determine the distribution of myocardial apoptosis in myocytes and nonmyocytes in primates and patients with heart failure (HF). Almost all clinical cardiologists and cardiovascular investigators believe that myocyte apoptosis is considered to be a cardinal sign of HF and a major factor in its pathogenesis. However, with the knowledge that 75% of the number of cells in the heart are nonmyocytes, it is important to determine whether the apoptosis in HF is occurring in myocytes or in nonmyocytes. We studied both a nonhuman primate model of chronic HF, induced by rapid pacing 2-6 mo after myocardial infarction (MI), and biopsies from patients with ischemic cardiomyopathy. Dual labeling with a cardiac muscle marker was used to discriminate apoptosis in myocytes versus nonmyocytes. Left ventricular ejection fraction decreased following MI (from 78% to 60%) and further with HF (35%, P < 0.05). As expected, total apoptosis was increased in the myocardium following recovery from MI (0.62 cells/mm(2)) and increased further with the development of HF (1.91 cells/mm(2)). Surprisingly, the majority of apoptotic cells in MI and MI + HF, and in both the adjacent and remote areas, were nonmyocytes. This was also observed in myocardial biopsies from patients with ischemic cardiomyopathy. We found that macrophages contributed the largest fraction of apoptotic nonmyocytes (41% vs. 18% neutrophils, 16% fibroblast, and 25% endothelial and other cells). Although HF in the failing human and monkey heart is characterized by significant apoptosis, in contrast to current concepts, the apoptosis in nonmyocytes was eight- to ninefold greater than in myocytes.

  4. Apoptosis predominates in nonmyocytes in heart failure

    PubMed Central

    Park, Misun; Shen, You-Tang; Gaussin, Vinciane; Heyndrickx, Guy R.; Bartunek, Jozef; Resuello, Ranillo R. G.; Natividad, Filipinas F.; Kitsis, Richard N.; Vatner, Dorothy E.; Vatner, Stephen F.

    2009-01-01

    The goal of this investigation was to determine the distribution of myocardial apoptosis in myocytes and nonmyocytes in primates and patients with heart failure (HF). Almost all clinical cardiologists and cardiovascular investigators believe that myocyte apoptosis is considered to be a cardinal sign of HF and a major factor in its pathogenesis. However, with the knowledge that 75% of the number of cells in the heart are nonmyocytes, it is important to determine whether the apoptosis in HF is occurring in myocytes or in nonmyocytes. We studied both a nonhuman primate model of chronic HF, induced by rapid pacing 2–6 mo after myocardial infarction (MI), and biopsies from patients with ischemic cardiomyopathy. Dual labeling with a cardiac muscle marker was used to discriminate apoptosis in myocytes versus nonmyocytes. Left ventricular ejection fraction decreased following MI (from 78% to 60%) and further with HF (35%, P < 0.05). As expected, total apoptosis was increased in the myocardium following recovery from MI (0.62 cells/mm2) and increased further with the development of HF (1.91 cells/mm2). Surprisingly, the majority of apoptotic cells in MI and MI + HF, and in both the adjacent and remote areas, were nonmyocytes. This was also observed in myocardial biopsies from patients with ischemic cardiomyopathy. We found that macrophages contributed the largest fraction of apoptotic nonmyocytes (41% vs. 18% neutrophils, 16% fibroblast, and 25% endothelial and other cells). Although HF in the failing human and monkey heart is characterized by significant apoptosis, in contrast to current concepts, the apoptosis in nonmyocytes was eight- to ninefold greater than in myocytes. PMID:19465551

  5. Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis

    PubMed Central

    Hwang, Hyun Sook; Kim, Hyun Ah

    2015-01-01

    Apoptosis is a highly-regulated, active process of cell death involved in development, homeostasis and aging. Dysregulation of apoptosis leads to pathological states, such as cancer, developmental anomalies and degenerative diseases. Osteoarthritis (OA), the most common chronic joint disease in the elderly population, is characterized by progressive destruction of articular cartilage, resulting in significant disability. Because articular cartilage depends solely on its resident cells, the chondrocytes, for the maintenance of extracellular matrix, the compromising of chondrocyte function and survival would lead to the failure of the articular cartilage. The role of subchondral bone in the maintenance of proper cartilage matrix has been suggested as well, and it has been proposed that both articular cartilage and subchondral bone interact with each other in the maintenance of articular integrity and physiology. Some investigators include both articular cartilage and subchondral bone as targets for repairing joint degeneration. In late-stage OA, the cartilage becomes hypocellular, often accompanied by lacunar emptying, which has been considered as evidence that chondrocyte death is a central feature in OA progression. Apoptosis clearly occurs in osteoarthritic cartilage; however, the relative contribution of chondrocyte apoptosis in the pathogenesis of OA is difficult to evaluate, and contradictory reports exist on the rate of apoptotic chondrocytes in osteoarthritic cartilage. It is not clear whether chondrocyte apoptosis is the inducer of cartilage degeneration or a byproduct of cartilage destruction. Chondrocyte death and matrix loss may form a vicious cycle, with the progression of one aggravating the other, and the literature reveals that there is a definite correlation between the degree of cartilage damage and chondrocyte apoptosis. Because current treatments for OA act only on symptoms and do not prevent or cure OA, chondrocyte apoptosis would be a valid

  6. CASPASE CONTROL: PROTAGONISTS OF CANCER CELL APOPTOSIS

    PubMed Central

    Fiandalo, M.V.; Kyprianou, N.

    2013-01-01

    Emergence of castration-resistant metastatic prostate cancer is due to activation of survival pathways, including apoptosis suppression and anoikis resistance, and increased neovascularization. Thus targeting of apoptotic players is of critical significance in prostate cancer therapy since loss of apoptosis and resistance to anoikis are critical in aberrant malignant growth, metastasis and conferring therapeutic failure. The majority of therapeutic agents act through intrinsic mitochondrial, extrinsic death receptor pathways or endoplasmic reticulum stress pathways to induce apoptosis. Current therapeutic strategies target restoring regulatory molecules that govern the pro-survival pathways such as PTEN which regulates AKT activity. Other strategies focus on reactivating the apoptotic pathways either by down-regulating anti-apoptotic players such as BCL-2 or by up-regulating pro-apoptotic protein families, most notably, the caspases. Caspases are a family of cystine proteases which serve critical roles in apoptotic and inflammatory signaling pathways. During tumorigenesis, significant loss or inactivation of lead members in the caspase family leads to impairing apoptosis induction, causing a dramatic imbalance in the growth dynamics, ultimately resulting in aberrant growth of human cancers. Recent exploitation of apoptosis pathways towards re-instating apoptosis induction via caspase re-activation has provided new molecular platforms for the development of therapeutic strategies effective against advanced prostate cancer as well as other solid tumors. This review will discuss the current cellular landscape featuring the caspase family in tumor cells and their activation via pharmacologic intervention towards optimized anti-cancer therapeutic modalities. This article is part of a Special Issue entitled “Apoptosis: Four Decades Later”. PMID:23070001

  7. EGCG disaggregates amyloid-like fibrils formed by Plasmodium falciparum merozoite surface protein 2

    PubMed Central

    Chandrashekaran, Indu R.; Adda, Christopher G.; MacRaild, Christopher A.; Anders, Robin F.; Norton, Raymond S.

    2011-01-01

    Merozoite surface protein 2 (MSP2), one of the most abundant proteins on the surface of Plasmodium falciparum merozoites, is a promising malaria vaccine candidate. MSP2 is intrinsically unstructured and forms amyloid-like fibrils in solution. As this propensity of MSP2 to form fibrils in solution has the potential to impede its development as a vaccine candidate, finding an inhibitor that inhibits fibrillogenesis may enhance vaccine development. We have shown previously that EGCG inhibits the formation of MSP2 fibrils. Here we show that EGCG can alter the β-sheet-like structure of the fibril and disaggregate pre-formed fibrils of MSP2 into soluble oligomers. The fibril remodelling effects of EGCG and other flavonoids were characterized using Thioflavin T fluorescence assays, electron microscopy and other biophysical methods. PMID:21784057

  8. Structure and phosphorylation of microtubule-associated protein 2 (MAP 2).

    PubMed Central

    Vallee, R

    1980-01-01

    Chymotryptic fragments of microtubule-associated protein 2 (MAP 2) containing the portion of the molecule responsible for promoting microtubule assembly were identified. These assembly-promoting fragments displaced intact MAP 2, but not MAP 1, from assembled microtubules. This indicates that the association of MAP 2 with the microtubule surface is reversible. Both the assembly-promoting fragments and fragments representing the portion of the MAP 2 molecule observed as a projection on the microtubule surface were found to contain sites for endogenous cyclic AMP-dependent phosphorylation. The projection fragments were capable of endogenous phosphorylation even after their physical separation from microtubules. This suggests an intimate association of a kinase activity with the projections. Detailed analysis of the properties of the chymotryptic fragments of MAP 2 has led to a map of the molecule showing the major sites of proteolytic attack and the sites of phosphorylation. Images PMID:6251448

  9. Delivery of bone morphogenetic protein-2 and substance P using graphene oxide for bone regeneration

    PubMed Central

    La, Wan-Geun; Jin, Min; Park, Saibom; Yoon, Hee-Hun; Jeong, Gun-Jae; Bhang, Suk Ho; Park, Hoyoung; Char, Kookheon; Kim, Byung-Soo

    2014-01-01

    In this study, we demonstrate that graphene oxide (GO) can be used for the delivery of bone morphogenetic protein-2 (BMP-2) and substance P (SP), and that this delivery promotes bone formation on titanium (Ti) implants that are coated with GO. GO coating on Ti substrate enabled a sustained release of BMP-2. BMP-2 delivery using GO-coated Ti exhibited a higher alkaline phosphatase activity in bone-forming cells in vitro compared with bare Ti. SP, which is known to recruit mesenchymal stem cells (MSCs), was co-delivered using Ti or GO-coated Ti to further promote bone formation. SP induced the migration of MSCs in vitro. The dual delivery of BMP-2 and SP using GO-coated Ti showed the greatest new bone formation on Ti implanted in the mouse calvaria compared with other groups. This approach may be useful to improve osteointegration of Ti in dental or orthopedic implants. PMID:24872706

  10. Irradiated human chondrocytes expressing bone morphogenetic protein 2 promote healing of osteoporotic bone fracture in rats.

    PubMed

    Yi, Youngsuk; Choi, Kyoung Baek; Lim, Chae-Lyul; Hyun, Jong-Pil; Lee, Hyeon-Youl; Lee, Kun Bok; Yun, Lillian; Ayverdi, Asli; Hwang, Sally; Yip, Vivian; Noh, Moon Jong; Lee, Kwan Hee

    2009-10-01

    Bone morphogenetic protein 2 (BMP2) was selected as a transgene to regenerate osteoporotic bone defects after several BMPs were tested using a bone formation study in nude mice. Human chondrocytes were transduced with a BMP2-containing retroviral vector, and single clones were selected. The cells were characterized over numerous passages for growth and BMP2 expression. The single clones were irradiated and tested for viability. BMP2 expression lasted for 3 weeks before dying off completely after approximately 1 month. Irradiated and non-irradiated transduced chondrocytes successfully healed fractures in osteoporotic rats induced by ovariectomy. The osteoinducing effect of irradiated cells was better than that of their non-irradiated counterparts or a chondrocytes-only control. This study showed that delivering BMP2 from the transduced and irradiated chondrocytes could be an effective and safe method of repairing osteoporotic bone fractures.

  11. Amyloid precursor protein and amyloid precursor-like protein 2 in cancer

    PubMed Central

    Pandey, Poomy; Sliker, Bailee; Peters, Haley L.; Tuli, Amit; Herskovitz, Jonathan; Smits, Kaitlin; Purohit, Abhilasha; Singh, Rakesh K.; Dong, Jixin; Batra, Surinder K.; Coulter, Donald W.; Solheim, Joyce C.

    2016-01-01

    Amyloid precursor protein (APP) and its family members amyloid precursor-like protein 1 (APLP1) and amyloid precursor-like protein 2 (APLP2) are type 1 transmembrane glycoproteins that are highly conserved across species. The transcriptional regulation of APP and APLP2 is similar but not identical, and the cleavage of both proteins is regulated by phosphorylation. APP has been implicated in Alzheimer's disease causation, and in addition to its importance in neurology, APP is deregulated in cancer cells. APLP2 is likewise overexpressed in cancer cells, and APLP2 and APP are linked to increased tumor cell proliferation, migration, and invasion. In this present review, we discuss the unfolding account of these APP family members’ roles in cancer progression and metastasis. PMID:26840089

  12. [Cloning of human bone morphogenetic protein-2 gene and the construction of its eukaryotic expression vector].

    PubMed

    Zhou, Nuo; Huang, Xuan-ping; Liao, Ni; Wei, Shan-liang; Liang, Fei-xin; Mai, Hua-ming

    2007-10-01

    To clone human bone morphogenetic protein-2 (hBMP2) gene and construct its eukaryotic expression vector pcDNA3.1 -hBMP2. Human BMP2 gene was amplified by RT-PCR method from human osteosarcoma cells and constructed into eukaryotic expression vector pcDNA3.1-hBMP2. The gene in the vector pcDNA3.1-hBMP2 was identified by PCR amplification, enzyme digestion and DNA sequencing. The cloned DNA was confirmed to be hBMP-2 gene. In this study, hBMP2 gene is successfully cloned and its eukaryotic expression vector pcDNA3.1-hBMP2 is constructed, which provides the foundation of using BMP2 gene therapy to accelerate new bone formation in distraction osteogenesis.

  13. Axonal pruning is actively regulated by the microtubule-destabilizing protein kinesin superfamily protein 2A.

    PubMed

    Maor-Nof, Maya; Homma, Noriko; Raanan, Calanit; Nof, Aviv; Hirokawa, Nobutaka; Yaron, Avraham

    2013-04-25

    Extensive axonal pruning and neuronal cell death are critical events for the development of the nervous system. Like neuronal cell death, axonal elimination occurs in discrete steps; however, the regulators of these processes remain mostly elusive. Here, we identify the kinesin superfamily protein 2A (KIF2A) as a key executor of microtubule disassembly and axonal breakdown during axonal pruning. Knockdown of Kif2a, but not other microtubule depolymerization or severing proteins, protects axonal microtubules from disassembly upon trophic deprivation. We further confirmed and extended this result to demonstrate that the entire degeneration process is delayed in neurons from the Kif2a knockout mice. Finally, we show that the Kif2a-null mice exhibit normal sensory axon patterning early during development, but abnormal target hyperinnervation later on, as they compete for limited skin-derived trophic support. Overall, these findings reveal a central regulatory mechanism of axonal pruning during development.

  14. UNCOUPLING PROTEIN-2 MODULATES THE LIPID METABOLIC RESPONSE TO FASTING IN MICE

    PubMed Central

    Sheets, Anthony R.; Fülöp, Péter; Derdák, Zoltán; Kassai, Andrea; Sabo, Edmond; Mark, Nicholas M.; Paragh, György; Wands, Jack R.; Baffy, György

    2008-01-01

    Uncoupling protein-2 (UCP2) regulates insulin secretion by controlling ATP levels in β cells. While UCP2 deficiency improves glycemic control in mice, increased expression of UCP2 interferes with glucose-stimulated insulin secretion. These observations link UCP2 to β cell dysfunction in type 2 diabetes with a perplexing evolutionary role. We found higher residual serum insulin levels and blunted lipid metabolic responses in fasted ucp2−/− mice, supporting the concept that UCP2 evolved to suppress insulin effects and to accommodate the fuel switch to fatty acids during starvation. In the absence of UCP2, fasting initially promotes peripheral lipolysis and hepatic fat accumulation at less than expected rates, but culminates in protracted steatosis indicating diminished hepatic utilization and clearance of fatty acids. We conclude that UCP2-mediated control of insulin secretion is a physiologically relevant mechanism of the metabolic response to fasting. PMID:18292186

  15. Recombinant human bone morphogenetic protein 2 in augmentation procedures: case reports.

    PubMed

    Luiz, Jaques; Padovan, Luis Eduardo Marques; Claudino, Marcela

    2014-01-01

    To successfully rehabilitate edentulous patients using endosseous implants, there must be enough available bone. Several techniques have been proposed for augmentation of sites with insufficient bone volume. Although autogenous bone has long been considered the gold standard for such procedures, the limited availability of graft material and a high morbidity rate are potential disadvantages of this type of graft. An alternative is to use recombinant human bone morphogenetic protein 2 (rhBMP-2), which is able to support bone regeneration in the oral environment. These cases demonstrate the applicability of rhBMP-2 in maxillary sinus elevation and augmentation procedures in the maxilla to enable dental implant placement. The use of rhBMP-2 in alveolar augmentation procedures had several clinical benefits for these patients.

  16. Dynamic regulation of uncoupling protein 2 content in INS-1E insulinoma cells.

    PubMed

    Azzu, Vian; Affourtit, Charles; Breen, Eamon P; Parker, Nadeene; Brand, Martin D

    2008-10-01

    Uncoupling protein 2 (UCP2) regulates glucose-stimulated insulin secretion in pancreatic beta-cells. UCP2 content, measured by calibrated immunoblot in INS-1E insulinoma cells (a pancreatic beta-cell model) grown in RPMI medium, and INS-1E mitochondria, was 2.0 ng/million cells (7.9 ng/mg mitochondrial protein). UCP2 content was lower in cells incubated without glutamine and higher in cells incubated with 20 mM glucose, and varied from 1.0-4.4 ng/million cells (2.7-14.5 ng/mg mitochondrial protein). This dynamic response to nutrients was achieved by varied expression rates against a background of a very short UCP2 protein half-life of about 1 h.

  17. Driving patterns in older adults with glaucoma

    PubMed Central

    2013-01-01

    Background The ability to drive is important for ensuring quality of life for many older adults. Glaucoma is prevalent in this age group and may affect driving. The purpose of this study is to determine if glaucoma and glaucomatous visual field (VF) loss are associated with driving cessation, limitations, and deference to another driver in older adults. Methods Cross-sectional study. Eighty-one glaucoma subjects and 58 glaucoma suspect controls between age 60 and 80 reported if they had ceased driving, limited their driving in various ways, or preferred another to drive. Results Twenty-three percent of glaucoma subjects and 6.9% of suspects had ceased driving (p = 0.01). Glaucoma subjects also had more driving limitations than suspects (2.0 vs. 1.1, p = 0.007). In multivariable models, driving cessation was more likely for glaucoma subjects as compared to suspects (OR = 4.0; 95% CI = 1.1-14.7; p = 0.03). The odds of driving cessation doubled with each 5 decibel (dB) decrement in the better-eye VF mean deviation (MD) (OR = 2.0; 95% CI = 1.4-2.9; p < 0.001). Glaucoma subjects were also more likely than suspects to report a greater number of driving limitations (OR = 4.7; 95% CI = 1.3-16.8; p = 0.02). The likelihood of reporting more limitations increased with the VF loss severity (OR = 1.6 per 5 dB decrement in the better-eye VF MD; 95% CI = 1.1-2.4; p = 0.02). Neither glaucoma nor VF MD was associated with other driver preference (p > 0.1 for both). Conclusions Glaucoma and glaucomatous VF loss are associated with greater likelihood of driving cessation and greater limitation of driving in the elderly. Further prospective study is merited to assess when and why people with glaucoma change their driving habits, and to determine if their observed self-regulation of driving is adequate to ensure safety. PMID:23432845

  18. Analysis of cache for streaming tape drive

    NASA Technical Reports Server (NTRS)

    Chinnaswamy, V.

    1993-01-01

    A tape subsystem consists of a controller and a tape drive. Tapes are used for backup, data interchange, and software distribution. The backup operation is addressed. During a backup operation, data is read from disk, processed in CPU, and then sent to tape. The processing speeds of a disk subsystem, CPU, and a tape subsystem are likely to be different. A powerful CPU can read data from a fast disk, process it, and supply the data to the tape subsystem at a faster rate than the tape subsystem can handle. On the other hand, a slow disk drive and a slow CPU may not be able to supply data fast enough to keep a tape drive busy all the time. The backup process may supply data to tape drive in bursts. Each burst may be followed by an idle period. Depending on the nature of the file distribution in the disk, the input stream to the tape subsystem may vary significantly during backup. To compensate for these differences and optimize the utilization of a tape subsystem, a cache or buffer is introduced in the tape controller. Most of the tape drives today are streaming tape drives. A streaming tape drive goes into reposition when there is no data from the controller. Once the drive goes into reposition, the controller can receive data, but it cannot supply data to the tape drive until the drive completes its reposition. A controller can also receive data from the host and send data to the tape drive at the same time. The relationship of cache size, host transfer rate, drive transfer rate, reposition, and ramp up times for optimal performance of the tape subsystem are investigated. Formulas developed will also show the advantages of cache watermarks to increase the streaming time of the tape drive, maximum loss due to insufficient cache, tradeoffs between cache and reposition times and the effectiveness of cache on a streaming tape drive due to idle times or interruptions due in host transfers. Several mathematical formulas are developed to predict the performance of the tape

  19. Structural Basis for Host Membrane Remodeling Induced by Protein 2B of Hepatitis A Virus

    PubMed Central

    Vives-Adrián, Laia; Garriga, Damià; Buxaderas, Mònica; Fraga, Joana; Pereira, Pedro José Barbosa

    2015-01-01

    ABSTRACT The complexity of viral RNA synthesis and the numerous participating factors require a mechanism to topologically coordinate and concentrate these multiple viral and cellular components, ensuring a concerted function. Similarly to all other positive-strand RNA viruses, picornaviruses induce rearrangements of host intracellular membranes to create structures that act as functional scaffolds for genome replication. The membrane-targeting proteins 2B and 2C, their precursor 2BC, and protein 3A appear to be primarily involved in membrane remodeling. Little is known about the structure of these proteins and the mechanisms by which they induce massive membrane remodeling. Here we report the crystal structure of the soluble region of hepatitis A virus (HAV) protein 2B, consisting of two domains: a C-terminal helical bundle preceded by an N-terminally curved five-stranded antiparallel β-sheet that displays striking structural similarity to the β-barrel domain of enteroviral 2A proteins. Moreover, the helicoidal arrangement of the protein molecules in the crystal provides a model for 2B-induced host membrane remodeling during HAV infection. IMPORTANCE No structural information is currently available for the 2B protein of any picornavirus despite it being involved in a critical process in viral factory formation: the rearrangement of host intracellular membranes. Here we present the structure of the soluble domain of the 2B protein of hepatitis A virus (HAV). Its arrangement, both in crystals and in solution under physiological conditions, can help to understand its function and sheds some light on the membrane rearrangement process, a putative target of future antiviral drugs. Moreover, this first structure of a picornaviral 2B protein also unveils a closer evolutionary relationship between the hepatovirus and enterovirus genera within the Picornaviridae family. PMID:25589659

  20. [The effect of bone morphogenetic protein-2 and osteoprotegerin in trans-sutural distraction osteogenesis].

    PubMed

    Yao, Yusheng; Huang, Hua; Chang, Shimin; Wang, Chengyue; Wang, Guijun

    2012-08-01

    To determine if locally administered bone morphogenetic protein-2 (BMP-2) and osteoprotegerin (OPG) improved osteogenesis and new bone formation by trans-sutural distraction osteogenesis. Twenty four dogs were divided into three groups randomly and received new internal trans-sutural distraction osteogenesis treatment. Five days after operation, infusion apparatus with double-tube was inserted to submucosa near the distracted zone to deliver controlled release agent of recombinant human bone morphogenetic protein-2/poly (lactic-co-glycolic acid)/fibrin sealant (rhBMP-2/PLGA/FS) in group A and group C. Recombinant human osteoprotegerin/fibrin sealant (rhOPG/ FS) was injected three weeks later in group B and group C. Histology staining and bone histomorphometry were used to measure the changes of maxillary bone sutura after distraction for 1, 2, 4 and 6 weeks. New bone formation observed in distracted zone showed a significant increase in group A and C. Transmission electron microscope showed the osteoblast and osteocyte were active with dilated rough endoplasmic reticulum and a large number of chondriosomes and Golgi complex. After distraction for 6 weeks, indexes of osteoblast of group A, B, and C were 38.5 +/- 7.7, 35.7 +/- 6.5, and 41.7 +/- 11.0, indexes of osteoclast (Ioc) were 5.9 +/- 1.0, 1.2 +/- 0.3, and 2.8 +/- 0.4, bone trabecula thicknesses were (38.36 +/- 13.28), (66.20 +/- 9.16), and (51.85 +/- 9.92) microm respectively. Increased bone density and decreased Ioc were found in group B and C. The new elastic distractor is effective in inducing new bone formation. BMP-2 and OPG combination acts synergistically, and leads to significant enhancement of bone formation and remodeling.