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Sample records for bim-bh3 mimetic therapy

  1. Gefitinib-induced killing of NSCLC cell lines expressing mutant EGFR requires BIM and can be enhanced by BH3 mimetics.

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    Mark S Cragg

    2007-10-01

    Full Text Available The epidermal growth factor receptor (EGFR plays a critical role in the control of cellular proliferation, differentiation, and survival. Abnormalities in EGF-EGFR signaling, such as mutations that render the EGFR hyperactive or cause overexpression of the wild-type receptor, have been found in a broad range of cancers, including carcinomas of the lung, breast, and colon. EGFR inhibitors such as gefitinib have proven successful in the treatment of certain cancers, particularly non-small cell lung cancers (NSCLCs harboring activating mutations within the EGFR gene, but the molecular mechanisms leading to tumor regression remain unknown. Therefore, we wished to delineate these mechanisms.We performed biochemical and genetic studies to investigate the mechanisms by which inhibitors of EGFR tyrosine kinase activity, such as gefitinib, inhibit the growth of human NSCLCs. We found that gefitinib triggered intrinsic (also called "mitochondrial" apoptosis signaling, involving the activation of BAX and mitochondrial release of cytochrome c, ultimately unleashing the caspase cascade. Gefitinib caused a rapid increase in the level of the proapoptotic BH3-only protein BIM (also called BCL2-like 11 through both transcriptional and post-translational mechanisms. Experiments with pharmacological inhibitors indicated that blockade of MEK-ERK1/2 (mitogen-activated protein kinase kinase-extracellular signal-regulated protein kinase 1/2 signaling, but not blockade of PI3K (phosphatidylinositol 3-kinase, JNK (c-Jun N-terminal kinase or mitogen-activated protein kinase 8, or AKT (protein kinase B, was critical for BIM activation. Using RNA interference, we demonstrated that BIM is essential for gefitinib-induced killing of NSCLC cells. Moreover, we found that gefitinib-induced apoptosis is enhanced by addition of the BH3 mimetic ABT-737.Inhibitors of the EGFR tyrosine kinase have proven useful in the therapy of certain cancers, in particular NSCLCs possessing

  2. The BH3 α-Helical Mimic BH3-M6 Disrupts Bcl-XL, Bcl-2, and MCL-1 Protein-Protein Interactions with Bax, Bak, Bad, or Bim and Induces Apoptosis in a Bax- and Bim-dependent Manner*

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    Kazi, Aslamuzzaman; Sun, Jiazhi; Doi, Kenichiro; Sung, Shen-Shu; Takahashi, Yoshinori; Yin, Hang; Rodriguez, Johanna M.; Becerril, Jorge; Berndt, Norbert; Hamilton, Andrew D.; Wang, Hong-Gang; Sebti, Saïd M.

    2011-01-01

    A critical hallmark of cancer cell survival is evasion of apoptosis. This is commonly due to overexpression of anti-apoptotic proteins such as Bcl-2, Bcl-XL, and Mcl-1, which bind to the BH3 α-helical domain of pro-apoptotic proteins such as Bax, Bak, Bad, and Bim, and inhibit their function. We designed a BH3 α-helical mimetic BH3-M6 that binds to Bcl-XL and Mcl-1 and prevents their binding to fluorescently labeled Bak- or Bim-BH3 peptides in vitro. Using several approaches, we demonstrate that BH3-M6 is a pan-Bcl-2 antagonist that inhibits the binding of Bcl-XL, Bcl-2, and Mcl-1 to multi-domain Bax or Bak, or BH3-only Bim or Bad in cell-free systems and in intact human cancer cells, freeing up pro-apoptotic proteins to induce apoptosis. BH3-M6 disruption of these protein-protein interactions is associated with cytochrome c release from mitochondria, caspase-3 activation and PARP cleavage. Using caspase inhibitors and Bax and Bak siRNAs, we demonstrate that BH3-M6-induced apoptosis is caspase- and Bax-, but not Bak-dependent. Furthermore, BH3-M6 disrupts Bcl-XL/Bim, Bcl-2/Bim, and Mcl-1/Bim protein-protein interactions and frees up Bim to induce apoptosis in human cancer cells that depend for tumor survival on the neutralization of Bim with Bcl-XL, Bcl-2, or Mcl-1. Finally, BH3-M6 sensitizes cells to apoptosis induced by the proteasome inhibitor CEP-1612. PMID:21148306

  3. The BH3 alpha-helical mimic BH3-M6 disrupts Bcl-X(L), Bcl-2, and MCL-1 protein-protein interactions with Bax, Bak, Bad, or Bim and induces apoptosis in a Bax- and Bim-dependent manner.

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    Kazi, Aslamuzzaman; Sun, Jiazhi; Doi, Kenichiro; Sung, Shen-Shu; Takahashi, Yoshinori; Yin, Hang; Rodriguez, Johanna M; Becerril, Jorge; Berndt, Norbert; Hamilton, Andrew D; Wang, Hong-Gang; Sebti, Saïd M

    2011-03-18

    A critical hallmark of cancer cell survival is evasion of apoptosis. This is commonly due to overexpression of anti-apoptotic proteins such as Bcl-2, Bcl-X(L), and Mcl-1, which bind to the BH3 α-helical domain of pro-apoptotic proteins such as Bax, Bak, Bad, and Bim, and inhibit their function. We designed a BH3 α-helical mimetic BH3-M6 that binds to Bcl-X(L) and Mcl-1 and prevents their binding to fluorescently labeled Bak- or Bim-BH3 peptides in vitro. Using several approaches, we demonstrate that BH3-M6 is a pan-Bcl-2 antagonist that inhibits the binding of Bcl-X(L), Bcl-2, and Mcl-1 to multi-domain Bax or Bak, or BH3-only Bim or Bad in cell-free systems and in intact human cancer cells, freeing up pro-apoptotic proteins to induce apoptosis. BH3-M6 disruption of these protein-protein interactions is associated with cytochrome c release from mitochondria, caspase-3 activation and PARP cleavage. Using caspase inhibitors and Bax and Bak siRNAs, we demonstrate that BH3-M6-induced apoptosis is caspase- and Bax-, but not Bak-dependent. Furthermore, BH3-M6 disrupts Bcl-X(L)/Bim, Bcl-2/Bim, and Mcl-1/Bim protein-protein interactions and frees up Bim to induce apoptosis in human cancer cells that depend for tumor survival on the neutralization of Bim with Bcl-X(L), Bcl-2, or Mcl-1. Finally, BH3-M6 sensitizes cells to apoptosis induced by the proteasome inhibitor CEP-1612.

  4. B cell lymphoma-2 (BCL-2) homology domain 3 (BH3) mimetics demonstrate differential activities dependent upon the functional repertoire of pro- and anti-apoptotic BCL-2 family proteins.

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    Renault, Thibaud T; Elkholi, Rana; Bharti, Archana; Chipuk, Jerry E

    2014-09-19

    The B cell lymphoma-2 (BCL-2) family is the key mediator of cellular sensitivity to apoptosis during pharmacological interventions for numerous human pathologies, including cancer. There is tremendous interest to understand how the proapoptotic BCL-2 effector members (e.g. BCL-2-associated X protein, BAX) cooperate with the BCL-2 homology domain only (BH3-only) subclass (e.g. BCL-2 interacting mediator of death, BIM; BCL-2 interacting-domain death agonist, BID) to induce mitochondrial outer membrane permeabilization (MOMP) and apoptosis and whether these mechanisms may be pharmacologically exploited to enhance the killing of cancer cells. Indeed, small molecule inhibitors of the anti-apoptotic BCL-2 family members have been designed rationally. However, the success of these "BH3 mimetics" in the clinic has been limited, likely due to an incomplete understanding of how these drugs function in the presence of multiple BCL-2 family members. To increase our mechanistic understanding of how BH3 mimetics cooperate with multiple BCL-2 family members in vitro, we directly compared the activity of several BH3-mimetic compounds (i.e. ABT-263, ABT-737, GX15-070, HA14.1, TW-37) in biochemically defined large unilamellar vesicle model systems that faithfully recapitulate BAX-dependent mitochondrial outer membrane permeabilization. Our investigations revealed that the presence of BAX, BID, and BIM differentially regulated the ability of BH3 mimetics to derepress proapoptotic molecules from anti-apoptotic proteins. Using mitochondria loaded with fluorescent BH3 peptides and cells treated with inducers of cell death, these differences were supported. Together, these data suggest that although the presence of anti-apoptotic BCL-2 proteins primarily dictates cellular sensitivity to BH3 mimetics, additional specificity is conferred by proapoptotic BCL-2 proteins. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. BH3 mimetics inhibit growth of chondrosarcoma--a novel targeted-therapy for candidate models.

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    Morii, Takeshi; Ohtsuka, Kouki; Ohnishi, Hiroaki; Mochizuki, Kazuo; Yoshiyama, Akira; Aoyagi, Takayuki; Hornicek, Francis J; Ichimura, Shoichi

    2014-11-01

    Chondrosarcoma is refractory to conventional chemotherapy. BH-3 mimetics ABT-737 and ABT-263 are synthetic small-molecule inhibitors of anti-apoptotic proteins B-cell lymphoma-2 (Bcl2) and Bcl-xL, which play a critical role in survival of chondrosarcoma cells. Chondrosarcoma cell lines SW-1353 and CS-1 were used as the disease model. We used immunoblotting to assess the expression of target molecules Bcl2 and Bcl-xL, and the apoptotic inducers Bcl2-associated X (Bax) and Bcl2-antagonist/killer (Bak). In vitro growth inhibition by BH-3 mimetics was confirmed by photomicroscopic cell counting and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Apoptotic induction was confirmed by Enzyme-Linked ImmunoSorbent Assay (ELISA). In vivo growth inhibition was assessed in a non-obese diabetic/severe combined immunodeficient (NOD/SCID) mouse model. Expression of the target and effector molecules was confirmed in chondrosarcoma cell lines. BH3 mimetics significantly inhibited cell growth and induced apoptosis in vitro. Administration of ABT-263 inhibited chondrosarcoma growth and improved survival in a mouse model. BH3 mimetics represent a novel treatment modality for chondrosarcoma. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  6. Bcl-2 family of proteins as drug targets for cancer chemotherapy: the long way of BH3 mimetics from bench to bedside.

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    Vela, Laura; Marzo, Isabel

    2015-08-01

    Bcl-2 proteins are key determinants in the life-death balance. In recent years, proteins in this family have been identified as drug targets in the design of new anti-tumor therapies. Advances in the knowledge of the mechanism of action of anti-apoptotic and pro-apoptotic members of the Bcl-2 family have enabled the development of the so-called 'BH3 mimetics'. These compounds act by inhibiting anti-apoptotic proteins of the family, imitating the function of the BH3-only subset of pro-apoptotic members. Combinations of BH3-mimetics with anti-tumor drugs are being evaluated in both preclinical models and clinical trials. Recent advances in these approaches will be reviewed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics.

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    Dennie T Frederick

    Full Text Available While response rates to BRAF inhibitiors (BRAFi are high, disease progression emerges quickly. One strategy to delay the onset of resistance is to target anti-apoptotic proteins such as BCL-2, known to be associated with a poor prognosis. We analyzed BCL-2 family member expression levels of 34 samples from 17 patients collected before and 10 to 14 days after treatment initiation with either vemurafenib or dabrafenib/trametinib combination. The observed changes in mRNA and protein levels with BRAFi treatment led us to hypothesize that combining BRAFi with a BCL-2 inhibitor (the BH3-mimetic navitoclax would improve outcome. We tested this hypothesis in cell lines and in mice. Pretreatment mRNA levels of BCL-2 negatively correlated with maximal tumor regression. Early increases in mRNA levels were seen in BIM, BCL-XL, BID and BCL2-W, as were decreases in MCL-1 and BCL2A. No significant changes were observed with BCL-2. Using reverse phase protein array (RPPA, significant increases in protein levels were found in BIM and BID. No changes in mRNA or protein correlated with response. Concurrent BRAF (PLX4720 and BCL2 (navitoclax inhibition synergistically reduced viability in BRAF mutant cell lines and correlated with down-modulation of MCL-1 and BIM induction after PLX4720 treatment. In xenograft models, navitoclax enhanced the efficacy of PLX4720. The combination of a selective BRAF inhibitor with a BH3-mimetic promises to be an important therapeutic strategy capable of enhancing the clinical efficacy of BRAF inhibition in many patients that might otherwise succumb quickly to de novo resistance. Trial registrations: ClinicalTrials.gov NCT01006980; ClinicalTrials.gov NCT01107418; ClinicalTrials.gov NCT01264380; ClinicalTrials.gov NCT01248936; ClinicalTrials.gov NCT00949702; ClinicalTrials.gov NCT01072175.

  8. BH3-only protein Bim inhibits activity of antiapoptotic members of Bcl-2 family when expressed in yeast.

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    Juhásová, Barbora; Mentel, Marek; Bhatia-Kiššová, Ingrid; Zeman, Igor; Kolarov, Jordan; Forte, Michael; Polčic, Peter

    2011-09-02

    Proteins of the Bcl-2 family regulate programmed cell death in mammals by promoting the release of cytochrome c from mitochondria in response to various proapoptotic stimuli. The mechanism by which BH3-only members of the family activate multidomain proapoptotic proteins Bax and Bak to form a pore in mitochondrial membranes remains under dispute. We report that cell death promoting activity of BH3-only protein Bim can be reconstituted in yeast when both Bax and antiapoptotic protein Bcl-X(L) are present, suggesting that Bim likely activates Bax indirectly by inhibiting antiapoptotic proteins. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  9. Overcoming EMT-driven therapeutic resistance by BH3 mimetics.

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    Keitel, Ulrike; Scheel, Christina; Dobbelstein, Matthias

    2014-01-01

    Epithelial-mesenchymal transition (EMT) contributes to the progression of cancer through enhanced invasion and stem-like properties of cancer cells. Additionally, EMT confers resistance towards many chemotherapeutics. We recently described a mechanism that mediates EMT-driven chemoresistance through augmented levels of Bcl-xL, an anti-apoptotic member of the Bcl-2 family (Keitel et al., Oncotarget, in press). Here, we elaborate on how these findings pertain to cancer cells dispersed in the tumor-adjacent stroma of breast cancer tissues, and how BH3-mimetics may provide a therapeutic strategy to eliminate cancer cell populations that have passed through an EMT.

  10. Knockdown of BAG3 sensitizes bladder cancer cells to treatment with the BH3 mimetic ABT-737.

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    Mani, Jens; Antonietti, Patrick; Rakel, Stefanie; Blaheta, Roman; Bartsch, Georg; Haferkamp, Axel; Kögel, Donat

    2016-02-01

    BAG3 is overexpressed in several malignancies and mediates a non-canonical, selective form of (macro)autophagy. By stabilizing pro-survival Bcl-2 proteins in complex with HSP70, BAG3 can also exert an apoptosis-antagonizing function. ABT-737 is a high affinity Bcl-2 inhibitor that fails to target Mcl-1. This failure may confer resistance in various cancers. Urothelial cancer cells were treated with the BH3 mimetics ABT-737 and (-)-gossypol, a pan-Bcl-2 inhibitor which inhibits also Mcl-1. To clarify the importance of the core autophagy regulator ATG5 and BAG3 in ABT-737 treatment, cell lines carrying a stable lentiviral knockdown of ATG5 and BAG3 were created. The synergistic effect of ABT-737 and pharmaceutical inhibition of BAG3 with the HSF1 inhibitor KRIBB11 or sorafenib was also evaluated. Total cell death and apoptosis were quantified by FACS analysis of propidium iodide, annexin. Target protein analysis was conducted by Western blotting. Knockdown of BAG3 significantly downregulated Mcl-1 protein levels and sensitized urothelial cancer cells to apoptotic cell death induced by ABT-737, while inhibition of bulk autophagy through depletion of ATG5 had no discernible effect on cell death. Similar to knockdown of BAG3, pharmacological targeting of the BAG3/Mcl-1 pathway with KRIBB11 was capable to sensitize both cell lines to treatment with ABT-737. Our results show that BAG3, but not bulk autophagy has a major role in the response of bladder cancer cells to BH3 mimetics. They also suggest that BAG3 is a suitable target for combined therapies aimed at synergistically inducing apoptosis in bladder cancer.

  11. BH3-only proteins and BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin 1 and Bcl-2/Bcl-X(L).

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    Maiuri, Maria Chiara; Criollo, Alfredo; Tasdemir, Ezgi; Vicencio, José Miguel; Tajeddine, Nicolas; Hickman, John A; Geneste, Olivier; Kroemer, Guido

    2007-01-01

    Beclin 1 has recently been identified as novel BH3-only protein, meaning that it carries one Bcl-2-homology-3 (BH3) domain. As other BH3-only proteins, Beclin 1 interacts with anti-apoptotic multidomain proteins of the Bcl-2 family (in particular Bcl-2 and its homologue Bcl-X(L)) by virtue of its BH3 domain, an amphipathic alpha-helix that binds to the hydrophobic cleft of Bcl-2/Bcl-X(L). The BH3 domains of other BH3-only proteins such as Bad, as well as BH3-mimetic compounds such as ABT737, competitively disrupt the inhibitory interaction between Beclin 1 and Bcl-2/Bcl-X(L). This causes autophagy of mitochondria (mitophagy) but not of the endoplasmic reticulum (reticulophagy). Only ER-targeted (not mitochondrion-targeted) Bcl-2/Bcl-X(L) can inhibit autophagy induced by Beclin 1, and only Beclin 1-Bcl-2/Bcl-X(L) complexes present in the ER (but not those present on heavy membrane fractions enriched in mitochondria) are disrupted by ABT737. These findings suggest that the Beclin 1-Bcl-2/Bcl-X(L) complexes that normally inhibit autophagy are specifically located in the ER and point to an organelle-specific regulation of autophagy. Furthermore, these data suggest a spatial organization of autophagy and apoptosis control in which BH3-only proteins exert two independent functions. On the one hand, they can induce apoptosis, by (directly or indirectly) activating the mitochondrion-permeabilizing function of pro-apoptotic multidomain proteins from the Bcl-2 family. On the other hand, they can activate autophagy by liberating Beclin 1 from its inhibition by Bcl-2/Bcl-X(L) at the level of the endoplasmic reticulum.

  12. BH3-mimetics- and cisplatin-induced cell death proceeds through different pathways depending on the availability of death-related cellular components.

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    Vicente Andreu-Fernández

    Full Text Available BACKGROUND: Owing to their important function in regulating cell death, pharmacological inhibition of Bcl-2 proteins by dubbed BH3-mimetics is a promising strategy for apoptosis induction or sensitization to chemotherapy. However, the role of Apaf-1, the main protein constituent of the apoptosome, in the process has yet not been analyzed. Furthermore as new chemotherapeutics develop, the possible chemotherapy-induced toxicity to rapidly dividing normal cells, especially sensitive differentiated cells, has to be considered. Such undesirable effects would probably be ameliorated by selectively and locally inhibiting apoptosis in defined sensitive cells. METHODOLOGY AND PRINCIPAL FINDINGS: Mouse embryonic fibroblasts (MEFS from Apaf-1 knock out mouse (MEFS KO Apaf-1 and Bax/Bak double KO (MEFS KO Bax/Bak, MEFS from wild-type mouse (MEFS wt and human cervix adenocarcinoma (HeLa cells were used to comparatively investigate the signaling cell death-induced pathways of BH3-mimetics, like ABT737 and GX15-070, with DNA damage-inducing agent cisplatin (cis-diammineplatinum(II dichloride, CDDP. The study was performed in the absence or presence of apoptosis inhibitors namely, caspase inhibitors or apoptosome inhibitors. BH3-mimetic ABT737 required of Apaf-1 to exert its apoptosis-inducing effect. In contrast, BH3-mimetic GX15-070 and DNA damage-inducing CDDP induced cell death in the absence of both Bax/Bak and Apaf-1. GX15-070 induced autophagy-based cell death in all the cell lines analyzed. MEFS wt cells were protected from the cytotoxic effects of ABT737 and CDDP by chemical inhibition of the apoptosome through QM31, but not by using general caspase inhibitors. CONCLUSIONS: BH3-mimetic ABT737 not only requires Bax/Bak to exert its apoptosis-inducing effect, but also Apaf-1, while GX15-070 and CDDP induce different modalities of cell death in the absence of Bax/Bak or Apaf-1. Inclusion of specific Apaf-1 inhibitors in topical and well

  13. The BH3 Mimetic Obatoclax Accumulates in Lysosomes and Causes Their Alkalinization.

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    Stamelos, Vasileios A; Fisher, Natalie; Bamrah, Harnoor; Voisey, Carolyn; Price, Joshua C; Farrell, William E; Redman, Charles W; Richardson, Alan

    2016-01-01

    Obatoclax belongs to a class of compounds known as BH3 mimetics which function as antagonists of Bcl-2 family apoptosis regulators. It has undergone extensive preclinical and clinical evaluation as a cancer therapeutic. Despite this, it is clear that obatoclax has additional pharmacological effects that contribute to its cytotoxic activity. It has been claimed that obatoclax, either alone or in combination with other molecularly targeted therapeutics, induces an autophagic form of cell death. In addition, obatoclax has been shown to inhibit lysosomal function, but the mechanism of this has not been elucidated. We have evaluated the mechanism of action of obatoclax in eight ovarian cancer cell lines. Consistent with its function as a BH3 mimetic, obatoclax induced apoptosis in three cell lines. However, in the remaining cell lines another form of cell death was evident because caspase activation and PARP cleavage were not observed. Obatoclax also failed to show synergy with carboplatin and paclitaxel, chemotherapeutic agents which we have previously shown to be synergistic with authentic Bcl-2 family antagonists. Obatoclax induced a profound accumulation of LC-3 but knockdown of Atg-5 or beclin had only minor effects on the activity of obatoclax in cell growth assays suggesting that the inhibition of lysosomal function rather than stimulation of autophagy may play a more prominent role in these cells. To evaluate how obatoclax inhibits lysosomal function, confocal microscopy studies were conducted which demonstrated that obatoclax, which contains two basic pyrrole groups, accumulates in lysosomes. Studies using pH sensitive dyes demonstrated that obatoclax induced lysosomal alkalinization. Furthermore, obatoclax was synergistic in cell growth/survival assays with bafilomycin and chloroquine, two other drugs which cause lysosomal alkalinization. These studies explain, for the first time, how obatoclax inhibits lysosomal function and suggest that lysosomal

  14. The pro-apoptotic BH3-only protein Bim interacts with components of the translocase of the outer mitochondrial membrane (TOM.

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    Daniel O Frank

    Full Text Available The pro-apoptotic Bcl-2-family protein Bim belongs to the BH3-only proteins known as initiators of apoptosis. Recent data show that Bim is constitutively inserted in the outer mitochondrial membrane via a C-terminal transmembrane anchor from where it can activate the effector of cytochrome c-release, Bax. To identify regulators of Bim-activity, we conducted a search for proteins interacting with Bim at mitochondria. We found an interaction of Bim with Tom70, Tom20 and more weakly with Tom40, all components of the Translocase of the Outer Membrane (TOM. In vitro import assays performed on tryptically digested yeast mitochondria showed reduced Bim insertion into the outer mitochondrial membrane (OMM indicating that protein receptors may be involved in the import process. However, RNAi against components of TOM (Tom40, Tom70, Tom22 or Tom20 by siRNA, individually or in combination, did not consistently change the amount of Bim on HeLa mitochondria, either at steady state or upon de novo-induction. In support of this, the individual or combined knock-downs of TOM receptors also failed to alter the susceptibility of HeLa cells to Bim-induced apoptosis. In isolated yeast mitochondria, lack of Tom70 or the TOM-components Tom20 or Tom22 alone did not affect the import of Bim into the outer mitochondrial membrane. In yeast, expression of Bim can sensitize the cells to Bax-dependent killing. This sensitization was unaffected by the absence of Tom70 or by an experimental reduction in Tom40. Although thus the physiological role of the Bim-TOM-interaction remains unclear, TOM complex components do not seem to be essential for Bim insertion into the OMM. Nevertheless, this association should be noted and considered when the regulation of Bim in other cells and situations is investigated.

  15. The pro-apoptotic BH3-only protein Bim interacts with components of the translocase of the outer mitochondrial membrane (TOM).

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    Frank, Daniel O; Dengjel, Jörn; Wilfling, Florian; Kozjak-Pavlovic, Vera; Häcker, Georg; Weber, Arnim

    2015-01-01

    The pro-apoptotic Bcl-2-family protein Bim belongs to the BH3-only proteins known as initiators of apoptosis. Recent data show that Bim is constitutively inserted in the outer mitochondrial membrane via a C-terminal transmembrane anchor from where it can activate the effector of cytochrome c-release, Bax. To identify regulators of Bim-activity, we conducted a search for proteins interacting with Bim at mitochondria. We found an interaction of Bim with Tom70, Tom20 and more weakly with Tom40, all components of the Translocase of the Outer Membrane (TOM). In vitro import assays performed on tryptically digested yeast mitochondria showed reduced Bim insertion into the outer mitochondrial membrane (OMM) indicating that protein receptors may be involved in the import process. However, RNAi against components of TOM (Tom40, Tom70, Tom22 or Tom20) by siRNA, individually or in combination, did not consistently change the amount of Bim on HeLa mitochondria, either at steady state or upon de novo-induction. In support of this, the individual or combined knock-downs of TOM receptors also failed to alter the susceptibility of HeLa cells to Bim-induced apoptosis. In isolated yeast mitochondria, lack of Tom70 or the TOM-components Tom20 or Tom22 alone did not affect the import of Bim into the outer mitochondrial membrane. In yeast, expression of Bim can sensitize the cells to Bax-dependent killing. This sensitization was unaffected by the absence of Tom70 or by an experimental reduction in Tom40. Although thus the physiological role of the Bim-TOM-interaction remains unclear, TOM complex components do not seem to be essential for Bim insertion into the OMM. Nevertheless, this association should be noted and considered when the regulation of Bim in other cells and situations is investigated.

  16. The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized

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    van Delft, Mark F.; Wei, Andrew H.; Mason, Kylie D.; Vandenberg, Cassandra J.; Chen, Lin; Czabotar, Peter E.; Willis, Simon N.; Scott, Clare L.; Day, Catherine L.; Cory, Suzanne; Adams, Jerry M.; Roberts, Andrew W.; Huang, David C.S.

    2006-01-01

    Since apoptosis is impaired in malignant cells overexpressing pro-survival Bcl-2 proteins, drugs mimicking their natural antagonists, BH3-only proteins, might overcome chemoresistance. Of seven putative BH3 mimetics tested, only ABT-737 triggered Bax/Bak-mediated apoptosis. Despite its high affinity for Bcl-2, Bcl-xL and Bcl-w, many cell types proved refractory to ABT-737. We show that this resistance reflects its inability to target another pro-survival relative, Mcl-1. Down-regulation of Mc...

  17. BIM-Mediated Membrane Insertion of the BAK Pore Domain Is an Essential Requirement for Apoptosis

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    Kathrin Weber

    2013-10-01

    Full Text Available BAK activation represents a key step during apoptosis, but how it converts into a mitochondria-permeabilizing pore remains unclear. By further delineating the structural rearrangements involved, we reveal that BAK activation progresses through a series of independent steps: BH3-domain exposure, N-terminal change, oligomerization, and membrane insertion. Employing a “BCL-XL-addiction” model, we show that neutralization of BCL-XL by the BH3 mimetic ABT-737 resulted in death only when cells were reconstituted with BCL-XL:BAK, but not BCL-2/ BCL-XL:BIM complexes. Although this resembles the indirect model, release of BAK from BCL-XL did not result in spontaneous adoption of the pore conformation. Commitment to apoptosis required association of the direct activator BIM with oligomeric BAK promoting its conversion to a membrane-inserted pore. The sequential nature of this cascade provides multiple opportunities for other BCL-2 proteins to interfere with or promote BAK activation and unites aspects of the indirect and direct activation models.

  18. Phospho-BAD BH3 Mimicry Protects β Cells and Restores Functional β Cell Mass in Diabetes

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    Sanda Ljubicic

    2015-02-01

    Full Text Available Strategies that simultaneously enhance the survival and glucose responsiveness of insulin-producing β cells will greatly augment β cell replacement therapies in type 1 diabetes (T1D. We show that genetic and pharmacologic mimetics of the phosphorylated BCL-2 homology 3 (BH3 domain of BAD impart β-cell-autonomous protective effects in the face of stress stimuli relevant to β cell demise in T1D. Importantly, these benefits translate into improved engraftment of donor islets in transplanted diabetic mice, increased β cell viability in islet grafts, restoration of insulin release, and diabetes reversal. Survival of β cells in this setting is not merely due to the inability of phospho-BAD to suppress prosurvival BCL-2 proteins but requires its activation of the glucose-metabolizing enzyme glucokinase. Thus, BAD phospho-BH3 mimetics may prove useful in the restoration of functional β cell mass in diabetes.

  19. BH3-only protein Bim is associated with the degree of Helicobacter pylori-induced gastritis and is localized to the mitochondria of inflammatory cells in the gastric mucosa.

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    Akazawa, Yuko; Matsuda, Katsuya; Isomoto, Hajime; Matsushima, Kayoko; Kido, Yoko; Urabe, Shigetoshi; Yamaghchi, Naoyuki; Ohnita, Ken; Takeshima, Fuminao; Kondo, Hisayoshi; Tsugawa, Hitoshi; Suzuki, Hidekazu; Moss, Joel; Nakao, Kazuhiko; Nakashima, Masahiro

    2015-09-01

    BH3-only protein, Bim, is a pro-apoptotic protein that mediates mitochondria-dependent cell death. However, the role of Bim in Helicobacter pylori-associated gastritis remains unclear. This study aimed to assess the cellular localization of Bim and its possible role in H. pylori-induced gastritis. The study was conducted on biopsy specimens obtained from 80 patients who underwent upper gastrointestinal endoscopy (H. pylori-negative: n=30, positive: n=50). Association between Bim mRNA expression and severity of gastritis was evaluated and the localization of Bim was examined by immunofluorescence. Bim mRNA expression was positively correlated with the degree of gastritis, as defined by the Sydney system. Immunohistochemical analysis confirmed increased Bim expression in H. pylori-infected gastric mucosa compared with uninfected mucosa in both humans and mice. Bim localized in myeloperoxidase- and CD138-positive cells of H. pylori-infected lamina propria and submucosa of the gastric tract, indicating that this protein is predominantly expressed in neutrophils and plasma cells. In contrast, Bim did not localize in CD20-, CD3-, or CD68-positive cells. Bim was expressed in the mitochondria, where it was partially co-localized with activated Bax and cleaved-PARP. In conclusion, Bim is expressed in neutrophils and plasma cells in H. pylori-associated gastritis, where it may participate in the termination of inflammatory response by causing mitochondria-mediated apoptosis in specific leucocytes. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. Canonical Bcl-2 motifs of the Na+/K+ pump revealed by the BH3 mimetic chelerythrine: early signal transducers of apoptosis?

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    Lauf, Peter K; Heiny, Judith; Meller, Jarek; Lepera, Michael A; Koikov, Leonid; Alter, Gerald M; Brown, Thomas L; Adragna, Norma C

    2013-01-01

    Chelerythrine [CET], a protein kinase C [PKC] inhibitor, is a prop-apoptotic BH3-mimetic binding to BH1-like motifs of Bcl-2 proteins. CET action was examined on PKC phosphorylation-dependent membrane transporters (Na+/K+ pump/ATPase [NKP, NKA], Na+-K+-2Cl+ [NKCC] and K+-Cl- [KCC] cotransporters, and channel-supported K+ loss) in human lens epithelial cells [LECs]. K+ loss and K+ uptake, using Rb+ as congener, were measured by atomic absorption/emission spectrophotometry with NKP and NKCC inhibitors, and Cl- replacement by NO3ˉ to determine KCC. 3H-Ouabain binding was performed on a pig renal NKA in the presence and absence of CET. Bcl-2 protein and NKA sequences were aligned and motifs identified and mapped using PROSITE in conjunction with BLAST alignments and analysis of conservation and structural similarity based on prediction of secondary and crystal structures. CET inhibited NKP and NKCC by >90% (IC50 values ~35 and ~15 μM, respectively) without significant KCC activity change, and stimulated K+ loss by ~35% at 10-30 μM. Neither ATP levels nor phosphorylation of the NKA α1 subunit changed. 3H-ouabain was displaced from pig renal NKA only at 100 fold higher CET concentrations than the ligand. Sequence alignments of NKA with BH1- and BH3-like motifs containing pro-survival Bcl-2 and BclXl proteins showed more than one BH1-like motif within NKA for interaction with CET or with BH3 motifs. One NKA BH1-like motif (ARAAEILARDGPN) was also found in all P-type ATPases. Also, NKA possessed a second motif similar to that near the BH3 region of Bcl-2. Findings support the hypothesis that CET inhibits NKP by binding to BH1-like motifs and disrupting the α1 subunit catalytic activity through conformational changes. By interacting with Bcl-2 proteins through their complementary BH1- or BH3-like-motifs, NKP proteins may be sensors of normal and pathological cell functions, becoming important yet unrecognized signal transducers in the initial phases of apoptosis. CET

  1. Canonical Bcl-2 Motifs of the Na+/K+ Pump Revealed by the BH3 Mimetic Chelerythrine: Early Signal Transducers of Apoptosis?

    Directory of Open Access Journals (Sweden)

    Peter K. Lauf

    2013-02-01

    Full Text Available Background/Aims: Chelerythrine [CET], a protein kinase C [PKC] inhibitor, is a prop-apoptotic BH3-mimetic binding to BH1-like motifs of Bcl-2 proteins. CET action was examined on PKC phosphorylation-dependent membrane transporters (Na+/K+ pump/ATPase [NKP, NKA], Na+-K+-2Cl+ [NKCC] and K+-Cl- [KCC] cotransporters, and channel-supported K+ loss in human lens epithelial cells [LECs]. Methods: K+ loss and K+ uptake, using Rb+ as congener, were measured by atomic absorption/emission spectrophotometry with NKP and NKCC inhibitors, and Cl- replacement by NO3ˉ to determine KCC. 3H-Ouabain binding was performed on a pig renal NKA in the presence and absence of CET. Bcl-2 protein and NKA sequences were aligned and motifs identified and mapped using PROSITE in conjunction with BLAST alignments and analysis of conservation and structural similarity based on prediction of secondary and crystal structures. Results: CET inhibited NKP and NKCC by >90% (IC50 values ∼35 and ∼15 µM, respectively without significant KCC activity change, and stimulated K+ loss by ∼35% at 10-30 µM. Neither ATP levels nor phosphorylation of the NKA α1 subunit changed. 3H-ouabain was displaced from pig renal NKA only at 100 fold higher CET concentrations than the ligand. Sequence alignments of NKA with BH1- and BH3-like motifs containing pro-survival Bcl-2 and BclXl proteins showed more than one BH1-like motif within NKA for interaction with CET or with BH3 motifs. One NKA BH1-like motif (ARAAEILARDGPN was also found in all P-type ATPases. Also, NKA possessed a second motif similar to that near the BH3 region of Bcl-2. Conclusion: Findings support the hypothesis that CET inhibits NKP by binding to BH1-like motifs and disrupting the α1 subunit catalytic activity through conformational changes. By interacting with Bcl-2 proteins through their complementary BH1- or BH3-like-motifs, NKP proteins may be sensors of normal and pathological cell functions, becoming important yet

  2. Bim and Bmf synergize to induce apoptosis in Neisseria gonorrhoeae infection.

    Directory of Open Access Journals (Sweden)

    Oliver Kepp

    2009-03-01

    Full Text Available Bcl-2 family proteins including the pro-apoptotic BH3-only proteins are central regulators of apoptotic cell death. Here we show by a focused siRNA miniscreen that the synergistic action of the BH3-only proteins Bim and Bmf is required for apoptosis induced by infection with Neisseria gonorrhoeae (Ngo. While Bim and Bmf were associated with the cytoskeleton of healthy cells, they both were released upon Ngo infection. Loss of Bim and Bmf from the cytoskeleton fraction required the activation of Jun-N-terminal kinase-1 (JNK-1, which in turn depended on Rac-1. Depletion and inhibition of Rac-1, JNK-1, Bim, or Bmf prevented the activation of Bak and Bax and the subsequent activation of caspases. Apoptosis could be reconstituted in Bim-depleted and Bmf-depleted cells by additional silencing of antiapoptotic Mcl-1 and Bcl-X(L, respectively. Our data indicate a synergistic role for both cytoskeletal-associated BH3-only proteins, Bim, and Bmf, in an apoptotic pathway leading to the clearance of Ngo-infected cells.

  3. Exposure to the viral by-product dsRNA or Coxsackievirus B5 triggers pancreatic beta cell apoptosis via a Bim / Mcl-1 imbalance.

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    Maikel L Colli

    2011-09-01

    Full Text Available The rise in type 1 diabetes (T1D incidence in recent decades is probably related to modifications in environmental factors. Viruses are among the putative environmental triggers of T1D. The mechanisms regulating beta cell responses to viruses, however, remain to be defined. We have presently clarified the signaling pathways leading to beta cell apoptosis following exposure to the viral mimetic double-stranded RNA (dsRNA and a diabetogenic enterovirus (Coxsackievirus B5. Internal dsRNA induces cell death via the intrinsic mitochondrial pathway. In this process, activation of the dsRNA-dependent protein kinase (PKR promotes eIF2α phosphorylation and protein synthesis inhibition, leading to downregulation of the antiapoptotic Bcl-2 protein myeloid cell leukemia sequence 1 (Mcl-1. Mcl-1 decrease results in the release of the BH3-only protein Bim, which activates the mitochondrial pathway of apoptosis. Indeed, Bim knockdown prevented both dsRNA- and Coxsackievirus B5-induced beta cell death, and counteracted the proapoptotic effects of Mcl-1 silencing. These observations indicate that the balance between Mcl-1 and Bim is a key factor regulating beta cell survival during diabetogenic viral infections.

  4. BIM is the primary mediator of MYC-induced apoptosis in multiple solid tissues.

    Science.gov (United States)

    Muthalagu, Nathiya; Junttila, Melissa R; Wiese, Katrin E; Wolf, Elmar; Morton, Jennifer; Bauer, Barbara; Evan, Gerard I; Eilers, Martin; Murphy, Daniel J

    2014-09-11

    MYC is one of the most frequently overexpressed oncogenes in human cancer, and even modestly deregulated MYC can initiate ectopic proliferation in many postmitotic cell types in vivo. Sensitization of cells to apoptosis limits MYC's oncogenic potential. However, the mechanism through which MYC induces apoptosis is controversial. Some studies implicate p19ARF-mediated stabilization of p53, followed by induction of proapoptotic BH3 proteins NOXA and PUMA, whereas others argue for direct regulation of BH3 proteins, especially BIM. Here, we use a single experimental system to systematically evaluate the roles of p19ARF and BIM during MYC-induced apoptosis, in vitro, in vivo, and in combination with a widely used chemotherapeutic, doxorubicin. We find a common specific requirement for BIM during MYC-induced apoptosis in multiple settings, which does not extend to the p53-responsive BH3 family member PUMA, and find no evidence of a role for p19ARF during MYC-induced apoptosis in the tissues examined. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  5. BCL2-BH4 antagonist BDA-366 suppresses human myeloma growth.

    Science.gov (United States)

    Deng, Jiusheng; Park, Dongkyoo; Wang, Mengchang; Nooka, Ajay; Deng, Qiaoya; Matulis, Shannon; Kaufman, Jonathan; Lonial, Sagar; Boise, Lawrence H; Galipeau, Jacques; Deng, Xingming

    2016-05-10

    Multiple myeloma (MM) is a heterogeneous plasma cell malignancy and remains incurable. B-cell lymphoma-2 (BCL2) protein correlates with the survival and the drug resistance of myeloma cells. BH3 mimetics have been developed to disrupt the binding between BCL2 and its pro-apoptotic BCL2 family partners for the treatment of MM, but with limited therapeutic efficacy. We recently identified a small molecule BDA-366 as a BCL2 BH4 domain antagonist, converting it from an anti-apoptotic into a pro-apoptotic molecule. In this study, we demonstrated that BDA-366 induces robust apoptosis in MM cell lines and primary MM cells by inducing BCL2 conformational change. Delivery of BDA-366 substantially suppressed the growth of human MM xenografts in NOD-scid/IL2Rγnull mice, without significant cytotoxic effects on normal hematopoietic cells or body weight. Thus, BDA-366 functions as a novel BH4-based BCL2 inhibitor and offers an entirely new tool for MM therapy.

  6. Expression of Bim, Noxa, and Puma in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Sakakibara-Konishi, Jun; Oizumi, Satoshi; Kikuchi, Junko; Kikuchi, Eiki; Mizugaki, Hidenori; Kinoshita, Ichiro; Dosaka-Akita, Hirotoshi; Nishimura, Masaharu

    2012-01-01

    The BH3-only members of the Bcl-2 protein family have been proposed to play a key role in the control of apoptosis and in the initiation of the apoptotic pathways. In this study, we evaluated the expression of Bim, Noxa, and Puma in non-small cell lung cancer (NSCLC). A total of 135 surgically resected NSCLCs were immunohistochemically assessed for Bim, Noxa, and Puma expression. The immunoscores were determined, and then its correlation with either the clinicopathological variables or the survival outcomes were analyzed. Immunohistochemical reactivity for Bim, Noxa, and Puma was detected in the cytoplasm of the tumor cells. Bim expression was associated with several clinicopathological factors, including sex (p < 0.001), smoking habit (p = 0.03), pathological histology (p = 0.001), pathological T stage (p = 0.03), pathological disease stage (p = 0.02), and differentiation of tumor (p < 0.001). Multivariate logistic regression analysis showed a significant correlation between low Bim expression and squamous cell carcinoma (p = 0.04), in addition to a correlation between high Bim expression and well differentiated tumors (p = 0.02). Analysis of cellular biological expression demonstrated a link between low Bim expression and high Ki67. While Noxa expression was also shown to be correlated with both smoking habit (p = 0.02) and the pathological histology (p = 0.03), there was no strong association observed between the expression and the clinical features when they were examined by a multivariate logistic regression analysis. No correlations were noted between Puma expression and any of the variables. Our analyses also indicated that the expression levels of the BH3-only proteins were not pertinent to the survival outcome. The current analyses demonstrated that Bim expression in the NSCLCs was associated with both squamous cell carcinoma histology and tumor proliferation

  7. Concurrent acetylation of FoxO1/3a and p53 due to sirtuins inhibition elicit Bim/PUMA mediated mitochondrial dysfunction and apoptosis in berberine-treated HepG2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Shukla, Shatrunajay [Herbal Research Section, CSIR — Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow‐226001 (India); Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi ‐110062 (India); Sharma, Ankita [Herbal Research Section, CSIR — Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow‐226001 (India); Pandey, Vivek Kumar [Herbal Research Section, CSIR — Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow‐226001 (India); Academy of Scientific and Innovative Research (India); Raisuddin, Sheikh [Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi ‐110062 (India); Kakkar, Poonam, E-mail: kakkarp59@gmail.com [Herbal Research Section, CSIR — Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow‐226001 (India); Academy of Scientific and Innovative Research (India)

    2016-01-15

    Post-translational modifications i.e. phosphorylation and acetylation are pivotal requirements for proper functioning of eukaryotic proteins. The current study aimed to decode the impact of acetylation/deacetylation of non-histone targets i.e. FoxO1/3a and p53 of sirtuins (NAD{sup +} dependent enzymes with lysine deacetylase activity) in berberine treated human hepatoma cells. Berberine (100 μM) inhibited sirtuins significantly (P < 0.05) at transcriptional level as well as at translational level. Combination of nicotinamide (sirtuin inhibitor) with berberine potentiated sirtuins inhibition and increased the expression of FoxO1/3a and phosphorylation of p53 tumor suppressor protein. As sirtuins deacetylate non-histone targets including FoxO1/3a and p53, berberine increased the acetylation load of FoxO1/3a and p53 proteins. Acetylated FoxO and p53 proteins transcriptionally activate BH3-only proteins Bim and PUMA (3.89 and 3.87 fold respectively, P<0.001), which are known as direct activator of pro-apoptotic Bcl-2 family protein Bax that culminated into mitochondria mediated activation of apoptotic cascade. Bim/PUMA knock-down showed no changes in sirtuins' expression while cytotoxicity induced by berberine and nicotinamide was curtailed up to 28.3% (P < 0.001) and it restored pro/anti apoptotic protein ratio in HepG2 cells. Sirtuins inhibition was accompanied by decline in NAD{sup +}/NADH ratio, ATP generation, enhanced ROS production and decreased mitochondrial membrane potential. TEM analysis confirmed mitochondrial deterioration and cell damage. SRT-1720 (1–10 μM), a SIRT-1 activator, when pre-treated with berberine (25 μM), reversed sirtuins expression comparable to control and significantly restored the cell viability (P < 0.05). Thus, our findings suggest that berberine mediated sirtuins inhibition resulting into FoxO1/3a and p53 acetylation followed by BH3-only protein Bim/PUMA activation may in part be responsible for mitochondria

  8. JNK Promotes Epithelial Cell Anoikis by Transcriptional and Post-translational Regulation of BH3-Only Proteins

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    Nomeda Girnius

    2017-11-01

    Full Text Available Summary: Developmental morphogenesis, tissue injury, and oncogenic transformation can cause the detachment of epithelial cells. These cells are eliminated by a specialized form of apoptosis (anoikis. While the processes that contribute to this form of cell death have been studied, the underlying mechanisms remain unclear. Here, we tested the role of the cJUN NH2-terminal kinase (JNK signaling pathway using murine models with compound JNK deficiency in mammary and kidney epithelial cells. These studies demonstrated that JNK is required for efficient anoikis in vitro and in vivo. Moreover, JNK-promoted anoikis required pro-apoptotic members of the BCL2 family of proteins. We show that JNK acts through a BAK/BAX-dependent apoptotic pathway by increasing BIM expression and phosphorylating BMF, leading to death of detached epithelial cells. : Developmental morphogenesis, tissue injury, and oncogenic transformation can cause epithelial cell detachment. These cells are eliminated by a specialized form of apoptosis termed anoikis. Girnius and Davis show that anoikis is mediated by the cJUN NH2-terminal kinase (JNK, which increases BIM expression and phosphorylates BMF to engage BAK/BAX-dependent apoptosis. Keywords: apoptosis, anoikis, epithelial cell, mammary gland, JNK, BAX, BAK, BH3-only protein, BIM, BMF

  9. Hypoxic human cancer cells are sensitized to BH-3 mimetic–induced apoptosis via downregulation of the Bcl-2 protein Mcl-1

    OpenAIRE

    Harrison, Luke R.E.; Micha, Dimitra; Brandenburg, Martin; Simpson, Kathryn L.; Morrow, Christopher J.; Denneny, Olive; Hodgkinson, Cassandra; Yunus, Zaira; Dempsey, Clare; Roberts, Darren; Blackhall, Fiona; Makin, Guy; Dive, Caroline

    2011-01-01

    Solid tumors contain hypoxic regions in which cancer cells are often resistant to chemotherapy-induced apoptotic cell death. Therapeutic strategies that specifically target hypoxic cells and promote apoptosis are particularly appealing, as few normal tissues experience hypoxia. We have found that the compound ABT-737, a Bcl-2 homology domain 3 (BH-3) mimetic, promotes apoptotic cell death in human colorectal carcinoma and small cell lung cancer cell lines exposed to hypoxia. This hypoxic indu...

  10. Modalna raba slovanskega bimƄ, bychƄ, bēchƄ

    Directory of Open Access Journals (Sweden)

    Alenka Šivic

    1971-12-01

    Full Text Available V cerkveni slovanščini so pogojnost izražali opisno s posebno pogojniško spregatvijo (l. edn. bim, 2., 3. edn. bi, l. mn. bim, 2. mn. biste, 3. mn. bQ; dvojina ni ohranjena + deležnik na -lb. Nanjo je že zelo zgodaj začel vplivati aorist (npr.: 2. mn. biste namesto *bite pod vplivom 2. mn. sigm. aorista byste, 1. mn. bichomb, 3. mn. biše pod vplivom 1. mn. oz. 3. mn. aorista bychomb, byše, kasneje pa jo je v spomenikih popolnoma zamenjal. Razlika med aoristom, rabljenim v časovni in pogojni funkciji je bila le v 2., 3. edn., saj se v časovni funkciji rabi bystb, v pogojniški pa vedno by (van Wijk, Istor. staroslavj. j., 1957, str. 308. Prav zaradi tega je Vatillant. Gramm. comp. III, 1966, str. 95 d., menil, da ima bych'b itd. v pogojniški funkciji le aoristov vid, v resnici pa ni aorist. Stang, Das slav. und balt. Verbum, 1942, str. 238, pa domneva, da bi by utegnil biti le analogna tvorba po pogojniku bi, ne pa stari korenski aorist *bhūs, *bhūt.

  11. A liquid-based eutectic system: LiBH4·NH 3-nNH3BH3 with high dehydrogenation capacity at moderate temperature

    KAUST Repository

    Tan, Yingbin; Guo, Yanhui; Li, Shaofeng; Sun, Weiwei; Zhu, Yihan; Li, Qi; Yu, Xuebin

    2011-01-01

    A novel eutectic hydrogen storage system, LiBH4·NH 3-nNH3BH3, which exists in a liquid state at room temperature, was synthesized through a simple mixing of LiBH 4·NH3 and NH3BH3 (AB). In the temperature range of 90-110 °C, the eutectic system

  12. Bim is a crucial regulator of apoptosis induced by Mycobacterium tuberculosis

    Science.gov (United States)

    Aguiló, N; Uranga, S; Marinova, D; Martín, C; Pardo, J

    2014-01-01

    Mycobacterium tuberculosis, the causative agent of tuberculosis, induces apoptosis in infected macrophages in vitro and in vivo. However, the molecular mechanism controlling this process is not known. In order to study the involvement of the mitochondrial apoptotic pathway in M. tuberculosis-induced apoptosis, we analysed cell death in M. tuberculosis-infected embryonic fibroblasts (MEFs) derived from different knockout mice for genes involved in this route. We found that apoptosis induced by M. tuberculosis is abrogated in the absence of Bak and Bax, caspase 9 or the executioner caspases 3 and 7. Notably, we show that MEF deficient in the BH3-only BCL-2-interacting mediator of cell death (Bim) protein were also resistant to this process. The relevance of these results has been confirmed in the mouse macrophage cell line J774, where cell transfection with siRNA targeting Bim impaired apoptosis induced by virulent mycobacteria. Notably, only infection with a virulent strain, but not with attenuated ESX-1-defective strains, such as Bacillus Calmette-Guerin and live-attenuated M. tuberculosis vaccine strain MTBVAC, induced Bim upregulation and apoptosis, probably implicating virulence factor early secreted antigenic target 6-kDa protein in this process. Our results suggest that Bim upregulation and apoptosis is mediated by the p38MAPK-dependent pathway. Our findings show that Bim is a master regulator of apoptosis induced by M. tuberculosis. PMID:25032866

  13. A liquid-based eutectic system: LiBH4·NH 3-nNH3BH3 with high dehydrogenation capacity at moderate temperature

    KAUST Repository

    Tan, Yingbin

    2011-01-01

    A novel eutectic hydrogen storage system, LiBH4·NH 3-nNH3BH3, which exists in a liquid state at room temperature, was synthesized through a simple mixing of LiBH 4·NH3 and NH3BH3 (AB). In the temperature range of 90-110 °C, the eutectic system showed significantly improved dehydrogenation properties compared to the neat AB and LiBH 4·NH3 alone. For example, in the case of the LiBH4·NH3/AB with a mole ratio of 1:3, over 8 wt.% hydrogen could be released at 90 °C within 4 h, while only 5 wt.% hydrogen released from the neat AB at the same conditions. Through a series of experiments it has been demonstrated that the hydrogen release of the new system is resulted from an interaction of AB and the NH3 group in the LiBH4·NH3, in which LiBH4 works as a carrier of ammonia and plays a crucial role in promoting the interaction between the NH3 group and AB. The enhanced dehydrogenation of LiBH 4·NH3/AB may result from the polar liquid state reaction environments and the initially promoted formation of the diammoniate of diborane, which will facilitate the B-H⋯H-N interaction between LiBH4·NH3 and AB. Kinetics analysis revealed that the rate-controlling steps of the dehydrogenation process are three-dimensional diffusion of hydrogen at temperatures ranging from 90 to 110 °C. This journal is © The Royal Society of Chemistry.

  14. Maximal killing of lymphoma cells by DNA damage–inducing therapy requires not only the p53 targets Puma and Noxa, but also Bim

    OpenAIRE

    Happo, Lina; Cragg, Mark S.; Phipson, Belinda; Haga, Jon M.; Jansen, Elisa S.; Herold, Marco J.; Dewson, Grant; Michalak, Ewa M.; Vandenberg, Cassandra J.; Smyth, Gordon K.; Strasser, Andreas; Cory, Suzanne; Scott, Clare L.

    2010-01-01

    DNA-damaging chemotherapy is the backbone of cancer treatment, although it is not clear how such treatments kill tumor cells. In nontransformed lymphoid cells, the combined loss of 2 proapoptotic p53 target genes, Puma and Noxa, induces as much resistance to DNA damage as loss of p53 itself. In Eμ-Myc lymphomas, however, lack of both Puma and Noxa resulted in no greater drug resistance than lack of Puma alone. A third B-cell lymphoma-2 homology domain (BH)3-only gene, Bim, although not a dire...

  15. Hypoxic human cancer cells are sensitized to BH-3 mimetic–induced apoptosis via downregulation of the Bcl-2 protein Mcl-1

    Science.gov (United States)

    Harrison, Luke R.E.; Micha, Dimitra; Brandenburg, Martin; Simpson, Kathryn L.; Morrow, Christopher J.; Denneny, Olive; Hodgkinson, Cassandra; Yunus, Zaira; Dempsey, Clare; Roberts, Darren; Blackhall, Fiona; Makin, Guy; Dive, Caroline

    2011-01-01

    Solid tumors contain hypoxic regions in which cancer cells are often resistant to chemotherapy-induced apoptotic cell death. Therapeutic strategies that specifically target hypoxic cells and promote apoptosis are particularly appealing, as few normal tissues experience hypoxia. We have found that the compound ABT-737, a Bcl-2 homology domain 3 (BH-3) mimetic, promotes apoptotic cell death in human colorectal carcinoma and small cell lung cancer cell lines exposed to hypoxia. This hypoxic induction of apoptosis was mediated through downregulation of myeloid cell leukemia sequence 1 (Mcl-1), a Bcl-2 family protein that serves as a biomarker for ABT-737 resistance. Downregulation of Mcl-1 in hypoxia was independent of hypoxia-inducible factor 1 (HIF-1) activity and was consistent with decreased global protein translation. In addition, ABT-737 induced apoptosis deep within tumor spheroids, consistent with an optimal hypoxic oxygen tension being necessary to promote ABT-737–induced cell death. Tumor xenografts in ABT-737–treated mice also displayed significantly more apoptotic cells within hypoxic regions relative to normoxic regions. Synergies between ABT-737 and other cytotoxic drugs were maintained in hypoxia, suggesting that this drug may be useful in combination with chemotherapeutic agents. Taken together, these findings suggest that Mcl-1–sparing BH-3 mimetics may induce apoptosis in hypoxic tumor cells that are resistant to other chemotherapeutic agents and may have a role in combinatorial chemotherapeutic regimens for treatment of solid tumors. PMID:21393866

  16. Hydrogen generation behaviors of NaBH4-NH3BH3 composite by hydrolysis

    Science.gov (United States)

    Xu, Yanmin; Wu, Chaoling; Chen, Yungui; Huang, Zhifen; Luo, Linshan; Wu, Haiwen; Liu, Peipei

    2014-09-01

    In this work, NH3BH3 (AB) is used to induce hydrogen generation during NaBH4 (SB) hydrolysis in order to reduce the use of catalysts, simplify the preparation process, reduce the cost and improve desorption kinetics and hydrogen capacity as well. xNaBH4-yNH3BH3 composites are prepared by ball-milling in different proportions (from x:y = 1:1 to 8:1). The experimental results demonstrate that all composites can release more than 90% of hydrogen at 70 °C within 1 h, and their hydrogen yields can reach 9 wt% (taking reacted water into account). Among them, the composites in the proportion of 4:1 and 5:1, whose hydrogen yields reach no less than 10 wt%, show the best hydrogen generation properties. This is due to the impact of the following aspects: AB additive improves the dispersibility of SB particles, makes the composite more porous, hampers the generated metaborate from adhering to the surface of SB, and decreases the pH value of the composite during hydrolysis. The main solid byproduct of this hydrolysis system is NaBO2·2H2O. By hydrolytic kinetic simulation of the composites, the fitted activation energies of the complexes are between 37.2 and 45.6 kJ mol-1, which are comparable to the catalytic system with some precious metals and alloys.

  17. Statsbygg forces BIM; Statsbygg presser frem BIM

    Energy Technology Data Exchange (ETDEWEB)

    Seehusen, Joachim

    2009-07-01

    Statsbygg requires Building Information Model (BIM) of all contractors and subcontractors when two new buildings are going to be raised at the University of Stavanger. BIM is a 3-D model on a common server where all the information and coding for the building project is gathered. IFC BIM is preferred for standardization. (AG)

  18. The combination of BH3-mimetic ABT-737 with the alkylating agent temozolomide induces strong synergistic killing of melanoma cells independent of p53.

    Directory of Open Access Journals (Sweden)

    Steven N Reuland

    Full Text Available Metastatic melanoma has poor prognosis and is refractory to most conventional chemotherapies. The alkylating agent temozolomide (TMZ is commonly used in treating melanoma but has a disappointing response rate. Agents that can act cooperatively with TMZ and improve its efficacy are thus highly sought after. The BH3 mimetic ABT-737, which can induce apoptosis by targeting pro-survival Bcl-2 family members, has been found to enhance the efficacy of many conventional chemotherapeutic agents in multiple cancers. We found that combining TMZ and ABT-737 induced strong synergistic apoptosis in multiple human melanoma cell lines. When the drugs were used in combination in a mouse xenograft model, they drastically reduced tumor growth at concentrations where each individual drug had no significant effect. We found that TMZ treatment elevated p53 levels, and that the pro-apoptotic protein Noxa was elevated in TMZ/ABT-737 treated cells. Experiments with shRNA demonstrated that the synergistic effect of TMZ and ABT-737 was largely dependent on Noxa. Experiments with nutlin-3, a p53 inducer, demonstrated that p53 induction was sufficient for synergistic cell death with ABT-737 in a Noxa-dependent fashion. However, p53 was not necessary for TMZ/ABT-737 synergy as demonstrated by a p53-null line, indicating that TMZ and ABT-737 together induce Noxa in a p53-independent fashion. These results demonstrate that targeting anti-apoptotic Bcl-2 members is a promising method for treating metastatic melanoma, and that clinical trials with TMZ and Bcl-2 inhibitors are warranted.

  19. Bim nuclear translocation and inactivation by viral interferon regulatory factor.

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    Young Bong Choi

    2010-08-01

    Full Text Available Viral replication efficiency is in large part governed by the ability of viruses to counteract pro-apoptotic signals induced by infection of the host cell. Human herpesvirus 8 (HHV-8 uses several strategies to block the host's innate antiviral defenses via interference with interferon and apoptotic signaling. Contributors include the four viral interferon regulatory factors (vIRFs 1-4, which function in dominant negative fashion to block cellular IRF activities in addition to targeting IRF signaling-induced proteins such as p53 and inhibiting other inducers of apoptosis such as TGFbeta receptor-activated Smad transcription factors. Here we identify direct targeting by vIRF-1 of BH3-only pro-apoptotic Bcl-2 family member Bim, a key negative regulator of HHV-8 replication, to effect its inactivation via nuclear translocation. vIRF-1-mediated relocalization of Bim was identified in transfected cells, by both immunofluorescence assay and western analysis of fractionated cell extracts. Also, co-localization of vIRF-1 and Bim was detected in nuclei of lytically infected endothelial cells. In vitro co-precipitation assays using purified vIRF-1 and Bim revealed direct interaction between the proteins, and Bim-binding residues of vIRF-1 were mapped by deletion and point mutagenesis. Generation and experimental utilization of Bim-refractory vIRF-1 variants revealed the importance of vIRF-1:Bim interaction, specifically, in pro-replication and anti-apoptotic activity of vIRF-1. Furthermore, blocking of the interaction with cell-permeable peptide corresponding to the Bim-binding region of vIRF-1 confirmed the relevance of vIRF-1:Bim association to vIRF-1 pro-replication activity. To our knowledge, this is the first report of an IRF protein that interacts with a Bcl-2 family member and of nuclear sequestration of Bim or any other member of the family as a means of inactivation. The data presented reveal a novel mechanism utilized by a virus to control

  20. Non-Covalent Interactions in Hydrogen Storage Materials LiN(CH32BH3 and KN(CH32BH3

    Directory of Open Access Journals (Sweden)

    Filip Sagan

    2016-03-01

    Full Text Available In the present work, an in-depth, qualitative and quantitative description of non-covalent interactions in the hydrogen storage materials LiN(CH32BH3 and KN(CH32BH3 was performed by means of the charge and energy decomposition method (ETS-NOCV as well as the Interacting Quantum Atoms (IQA approach. It was determined that both crystals are stabilized by electrostatically dominated intra- and intermolecular M∙∙∙H–B interactions (M = Li, K. For LiN(CH32BH3 the intramolecular charge transfer appeared (B–H→Li to be more pronounced compared with the corresponding intermolecular contribution. We clarified for the first time, based on the ETS-NOCV and IQA methods, that homopolar BH∙∙∙HB interactions in LiN(CH32BH3 can be considered as destabilizing (due to the dominance of repulsion caused by negatively charged borane units, despite the fact that some charge delocalization within BH∙∙∙HB contacts is enforced (which explains H∙∙∙H bond critical points found from the QTAIM method. Interestingly, quite similar (to BH∙∙∙HB intermolecular homopolar dihydrogen bonds CH∙∙∙HC appared to significantly stabilize both crystals—the ETS-NOCV scheme allowed us to conclude that CH∙∙∙HC interactions are dispersion dominated, however, the electrostatic and σ/σ*(C–H charge transfer contributions are also important. These interactions appeared to be more pronounced in KN(CH32BH3 compared with LiN(CH32BH3.

  1. Acetylation of FoxO1 Activates Bim Expression to Induce Apoptosis in Response to Histone Deacetylase Inhibitor Depsipeptide Treatment

    Directory of Open Access Journals (Sweden)

    Yang Yang

    2009-04-01

    Full Text Available Histone deacetylase (HDAC inhibitors have been shown to induce cell cycle arrest and apoptosis in cancer cells. However, the mechanisms of HDAC inhibitor induced apoptosis are incompletely understood. In this study, depsipeptide, a novel HDAC inhibitor, was shown to be able to induce significant apoptotic cell death in human lung cancer cells. Further study showed that Bim, a BH3-only proapoptotic protein, was significantly upregulated by depsipeptide in cancer cells, and Bim's function in depsipeptide-induced apoptosis was confirmed by knockdown of Bim with RNAi. In addition, we found that depsipeptide-induced expression of Bim was directly dependent on acetylation of forkhead box class O1 (FoxO1 that is catalyzed by cyclic adenosine monophosphate-responsive element-binding protein-binding protein, and indirectly induced by a decreased four-and-a-half LIM-domain protein 2. Moreover, our results demonstrated that FoxO1 acetylation is required for the depsipeptide-induced activation of Bim and apoptosis, using transfection with a plasmid containing FoxO1 mutated at lysine sites and a luciferase reporter assay. These data show for the first time that an HDAC inhibitor induces apoptosis through the FoxO1 acetylation-Bim pathway.

  2. Paclitaxel-induced apoptosis is BAK-dependent, but BAX and BIM-independent in breast tumor.

    Directory of Open Access Journals (Sweden)

    Anna V Miller

    Full Text Available Paclitaxel (Taxol-induced cell death requires the intrinsic cell death pathway, but the specific participants and the precise mechanisms are poorly understood. Previous studies indicate that a BH3-only protein BIM (BCL-2 Interacting Mediator of cell death plays a role in paclitaxel-induced apoptosis. We show here that BIM is dispensable in apoptosis with paclitaxel treatment using bim(-/- MEFs (mouse embryonic fibroblasts, the bim(-/- mouse breast tumor model, and shRNA-mediated down-regulation of BIM in human breast cancer cells. In contrast, both bak (-/- MEFs and human breast cancer cells in which BAK was down-regulated by shRNA were more resistant to paclitaxel. However, paclitaxel sensitivity was not affected in bax(-/- MEFs or in human breast cancer cells in which BAX was down-regulated, suggesting that paclitaxel-induced apoptosis is BAK-dependent, but BAX-independent. In human breast cancer cells, paclitaxel treatment resulted in MCL-1 degradation which was prevented by a proteasome inhibitor, MG132. A Cdk inhibitor, roscovitine, blocked paclitaxel-induced MCL-1 degradation and apoptosis, suggesting that Cdk activation at mitotic arrest could induce subsequent MCL-1 degradation in a proteasome-dependent manner. BAK was associated with MCL-1 in untreated cells and became activated in concert with loss of MCL-1 expression and its release from the complex. Our data suggest that BAK is the mediator of paclitaxel-induced apoptosis and could be an alternative target for overcoming paclitaxel resistance.

  3. Conformations of 1,3,3,5,7,7-Hexamethyl-1,5-diazacyclooctane and Its Bis-BH(3) Adduct. Mono- and Bis-BH(3) Adducts of Di-Tertiary Amines.

    Science.gov (United States)

    Livant, P.; Majors, A. W.; Webb, T. R.

    1996-05-03

    A variable-temperature (1)H- and (13)C-NMR study revealed a conformational equilibrium for 1,3,3,5,7,7-hexamethyl-1,5-diazacyclooctane (4) having DeltaG() = 8.8 +/- 0.6 kcal/mol at 184 K. This activation barrier connects a major and a minor form of 4. Molecular mechanics calculations on 4 led to the conclusion that the major form is a set of twist-chair-chairs interconverting rapidly via the chair-chair and that the minor form is most likely a set of twist-boat-boats interconverting rapidly via the boat-boat. The proximity of the two nitrogen lone pairs in the major form of 4 made plausible the expectation that 4, as well as a related diamine with apposed nitrogens, 3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane (3), might bind a Lewis acid, namely BH(3), using both lone pairs simultaneously and equally. This proved not to be the case: for 3 only the bis-BH(3) adduct was found and for 4 the mono-BH(3) adduct utilized only one nitrogen lone pair. The structure of the bis-BH(3) adduct of 4 (12) was determined by X-ray crystallography to be a twist-boat-boat with BH(3)s cis. Molecular mechanics calculations on 12 were consistent with the solid state conformation found.

  4. Vorinostat eliminates multicellular resistance of mesothelioma 3D spheroids via restoration of Noxa expression.

    Directory of Open Access Journals (Sweden)

    Dario Barbone

    Full Text Available When grown in 3D cultures as spheroids, mesothelioma cells acquire a multicellular resistance to apoptosis that resembles that of solid tumors. We have previously found that resistance to the proteasome inhibitor bortezomib in 3D can be explained by a lack of upregulation of Noxa, the pro-apoptotic BH3 sensitizer that acts via displacement of the Bak/Bax-activator BH3-only protein, Bim. We hypothesized that the histone deacetylase inhibitor vorinostat might reverse this block to Noxa upregulation in 3D. Indeed, we found that vorinostat effectively restored upregulation of Noxa protein and message and abolished multicellular resistance to bortezomib in the 3D spheroids. The ability of vorinostat to reverse resistance was ablated by knockdown of Noxa or Bim, confirming the essential role of the Noxa/Bim axis in the response to vorinostat. Addition of vorinostat similarly increased the apoptotic response to bortezomib in another 3D model, the tumor fragment spheroid, which is grown from human mesothelioma ex vivo. In addition to its benefit when used with bortezomib, vorinostat also enhanced the response to cisplatin plus pemetrexed, as shown in both 3D models. Our results using clinically relevant 3D models show that the manipulation of the core apoptotic repertoire may improve the chemosensitivity of mesothelioma. Whereas neither vorinostat nor bortezomib alone has been clinically effective in mesothelioma, vorinostat may undermine chemoresistance to bortezomib and to other therapies thereby providing a rationale for combinatorial strategies.

  5. Vorinostat Eliminates Multicellular Resistance of Mesothelioma 3D Spheroids via Restoration of Noxa Expression

    Science.gov (United States)

    Barbone, Dario; Cheung, Priscilla; Battula, Sailaja; Busacca, Sara; Gray, Steven G.; Longley, Daniel B.; Bueno, Raphael; Sugarbaker, David J.; Fennell, Dean A.; Broaddus, V. Courtney

    2012-01-01

    When grown in 3D cultures as spheroids, mesothelioma cells acquire a multicellular resistance to apoptosis that resembles that of solid tumors. We have previously found that resistance to the proteasome inhibitor bortezomib in 3D can be explained by a lack of upregulation of Noxa, the pro-apoptotic BH3 sensitizer that acts via displacement of the Bak/Bax-activator BH3-only protein, Bim. We hypothesized that the histone deacetylase inhibitor vorinostat might reverse this block to Noxa upregulation in 3D. Indeed, we found that vorinostat effectively restored upregulation of Noxa protein and message and abolished multicellular resistance to bortezomib in the 3D spheroids. The ability of vorinostat to reverse resistance was ablated by knockdown of Noxa or Bim, confirming the essential role of the Noxa/Bim axis in the response to vorinostat. Addition of vorinostat similarly increased the apoptotic response to bortezomib in another 3D model, the tumor fragment spheroid, which is grown from human mesothelioma ex vivo. In addition to its benefit when used with bortezomib, vorinostat also enhanced the response to cisplatin plus pemetrexed, as shown in both 3D models. Our results using clinically relevant 3D models show that the manipulation of the core apoptotic repertoire may improve the chemosensitivity of mesothelioma. Whereas neither vorinostat nor bortezomib alone has been clinically effective in mesothelioma, vorinostat may undermine chemoresistance to bortezomib and to other therapies thereby providing a rationale for combinatorial strategies. PMID:23300762

  6. Targeting apoptotic machinery as approach for anticancer therapy: Smac mimetics as anticancer agents

    Directory of Open Access Journals (Sweden)

    Nevine M.Y. Elsayed

    2015-06-01

    Full Text Available Apoptosis is a chief regulator of cellular homeostasis. Impairment of apoptotic machinery is a main characteristic of several diseases such as cancer, where the evasion of apoptosis is a cardinal hallmark of cancer. Apoptosis is regulated by contribution of pro- and anti- apoptotic proteins, where caspases are the main executioners of the apoptotic machinery. IAP (inhibitors of apoptosis proteins is a family of endogenous inhibitors of apoptosis, which perform their function through interference with the function of caspases. Smac (second mitochondria-derived activator of caspases is endogenous inhibitor of IAPs, thus it is one of the major proapoptotic endogenous proteins. Thus, the development of Smac mimetics has evolved as an approach for anticancer therapy. Several Smac mimetic agents have been introduced to clinical trial such as birinapanet 12. Herein, the history of development of Smac mimetics along with the recent development in this field is briefly discussed.

  7. Association between BIM deletion polymorphism and clinical outcome of EGFR-mutated NSCLC patient with EGFR-TKI therapy: A meta-analysis.

    Science.gov (United States)

    Ma, Ji-Yong; Yan, Hai-Jun; Gu, Wei

    2015-01-01

    BIM deletion polymorphism was deemed to be associated with downregulation of BIM, resulting in a decreased apoptosis induced by epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutation-positive non-small cell lung cancer (NSCLC). However, accumulating evidences concerning the association between BIM deletion polymorphism and efficacy of EGFR-TKI and survival in EGFR-mutation-driven NSCLC patient reported contradictory results. A meta-analysis was conducted by combing six original eligible studies including 871 NSCLC patients. Our study showed that BIM deletion polymorphism was significantly associated with poor response to EGFR-TKI therapy in mutant EGFRNSCLC patients (P(h) = 0.309, P(z) = 0.001, OR = 0.39, 95% confidence interval (CI) = 0.23-0.67). Disease control rate (DCR) in mutant EGFRNSCLC patient with treatment of EGFR-TKI was significantly decreased in patients with BIM deletion polymorphism comparing to patients harbored BIM wild variant (P(h) = 0.583, P(Z) = 0.007, OR = 0.46, 95%CI = 0.25-0.85). EGFR mutation-derived NSCLC patient carrying BIM deletion polymorphism had a shorter progression-free survival (PFS; P(h) deletion polymorphism might be a cause that contributes to primary EGFR-TKI resistance, and it could be used as a genetic predictor for EGFR-TKI outcome and an independent prognostic factor of EGFR mutation-driven NSCLC patient.

  8. Molecular basis for the interplay of apoptosis and proliferation mediated by Bcl-xL:Bim interactions in pancreatic cancer cells

    International Nuclear Information System (INIS)

    Abrol, Ravinder; Edderkaoui, Mouad; Goddard, William A.; Pandol, Stephen J.

    2012-01-01

    Highlights: ► Direct role of Bcl-2 protein interactions in cell proliferation is not clear. ► Designed Bcl-xL mutants show opposite effects on apoptosis and proliferation. ► Disrupting Bcl-xL:Bim interaction increased apoptosis in pancreatic cancer. ► Disrupting Bcl-xL:Bim interaction decreased proliferation in pancreatic cancer. ► Bcl-xL:Bim interaction can control both apoptosis and proliferation. -- Abstract: A major mechanism through which cancer cells avoid apoptosis is by promoting the association of anti-apoptotic members of the pro-survival Bcl-2 protein family (like Bcl-2 and Bcl-xL) with BH 3 domain-only proteins (like Bim and Bid). Apoptosis and cell proliferation have been shown to be linked for many cancers but the molecular basis for this link is far from understood. We have identified the Bcl-xL:Bim protein–protein interface as a direct regulator of proliferation and apoptosis in pancreatic cancer cells. We were able to predict and subsequently verify experimentally the effect of various Bcl-xL single-point mutants (at the position A142) on binding to Bim by structural analysis and computational modeling of the inter-residue interactions at the Bcl-xL:Bim protein–protein interface. The mutants A142N, A142Q, and A142Y decreased binding of Bim to Bcl-xL and A142S increased this binding. The Bcl-xL mutants, with decreased affinity for Bim, caused an increase in apoptosis and a corresponding decrease in cell proliferation. However, we could prevent these effects by introducing a small interfering RNA (siRNA) targeted at Bim. These results show a novel role played by the Bcl-xL:Bim interaction in regulating proliferation of pancreatic cancer cells at the expense of apoptosis. This study presents a physiologically relevant model of the Bcl-xL:Bim interface that can be used for rational therapeutic design for the inhibition of proliferation and cancer cell resistance to apoptosis.

  9. Experiment for Integrating Dutch 3d Spatial Planning and Bim for Checking Building Permits

    Science.gov (United States)

    van Berlo, L.; Dijkmans, T.; Stoter, J.

    2013-09-01

    This paper presents a research project in The Netherlands in which several SMEs collaborated to create a 3D model of the National spatial planning information. This 2D information system described in the IMRO data standard holds implicit 3D information that can be used to generate an explicit 3D model. The project realized a proof of concept to generate a 3D spatial planning model. The team used the model to integrate it with several 3D Building Information Models (BIMs) described in the open data standard Industry Foundation Classes (IFC). Goal of the project was (1) to generate a 3D BIM model from spatial planning information to be used by the architect during the early design phase, and (2) allow 3D checking of building permits. The team used several technologies like CityGML, BIM clash detection and GeoBIM to explore the potential of this innovation. Within the project a showcase was created with a part of the spatial plan from the city of The Hague. Several BIM models were integrated in the 3D spatial plan of this area. A workflow has been described that demonstrates the benefits of collaboration between the spatial domain and the AEC industry in 3D. The research results in a showcase with conclusions and considerations for both national and international practice.

  10. Materialdokumentation inom BIM

    OpenAIRE

    Buszman, Angelica; Canel, Caroline

    2014-01-01

    Byggbranschen befinner sig mitt i ett paradigmskifte – detta i samband med att BIM kommer att ersätta de traditionella arbetsmetoderna inom byggprocessen. BIM, även kallat objektsbaserad informationshantering, används idag till 3D-projektering, visualisering och samordning. Dock utnyttjas inte BIM till sin fulla potential. Förändringar sker även beträffande miljöaspekter inom byggsektorn. Miljökrav är inte längre enbart lagstadgade, utan kommer även från fastighetsägarna själva. En anledning ...

  11. Bim Demystified

    CERN Document Server

    Race, Steve

    2012-01-01

    BIM Demystified is a short, practical introduction to Building Information Modelling (BIM). Addressing BIM from the point of view of mainstream practice as opposed to a cutting-edge technological perspective, it offers an easy-going yet thorough explanation of a subject which is often swamped by jargon and deluged with spin. Taking a wide view of BIM - encompassing business opportunity, Code of Conduct, cultural issues and the necessity for better legal arrangements too - the book's chapters range from the BIM ingredients (including objects, parametrics, and standards), to the business case for BIM and how to implement it. BIM requires a shift in attitudes if its benefits are to be obtained - and this book will allow individuals at all levels in any practice to build a firmer understanding of the merits and wider application of the subject. It aims bring together both managers and technologists within businesses throughout the AECC chain to form better and more valuable propositions for built environment inte...

  12. Modulation of NO and ROS production by AdiNOS transduced vascular cells through supplementation with L-Arg and BH4: implications for gene therapy of restenosis.

    Science.gov (United States)

    Forbes, Scott P; Alferiev, Ivan S; Chorny, Michael; Adamo, Richard F; Levy, Robert J; Fishbein, Ilia

    2013-09-01

    Gene therapy with viral vectors encoding for NOS enzymes has been recognized as a potential therapeutic approach for the prevention of restenosis. Optimal activity of iNOS is dependent on the intracellular availability of L-Arg and BH4 via prevention of NOS decoupling and subsequent ROS formation. Herein, we investigated the effects of separate and combined L-Arg and BH4 supplementation on the production of NO and ROS in cultured rat arterial smooth muscle and endothelial cells transduced with AdiNOS, and their impact on the antirestenotic effectiveness of AdiNOS delivery to balloon-injured rat carotid arteries. Supplementation of AdiNOS transduced endothelial and vascular smooth muscle cells with L-Arg (3.0 mM), BH4 (10 μM) and especially their combination resulted in a significant increase in NO production as measured by nitrite formation in media. Formation of ROS was dose-dependently increased following transduction with increasing MOIs of AdiNOS. Exposure of RASMC to AdiNOS tethered to meshes via a hydrolyzable cross-linker, modeling viral delivery from stents, resulted in increased ROS production, which was decreased by supplementation with BH4 but not L-Arg or L-Arg/BH4. Enhanced cell death, caused by AdiNOS transduction, was also preventable with BH4 supplementation. In the rat carotid model of balloon injury, intraluminal delivery of AdiNOS in BH4-, L-Arg-, and especially in BH4 and L-Arg supplemented animals was found to significantly enhance the antirestenotic effects of AdiNOS-mediated gene therapy. Fine-tuning of iNOS function by L-Arg and BH4 supplementation in the transduced vasculature augments the therapeutic potential of gene therapy with iNOS for the prevention of restenosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Molecular basis for the interplay of apoptosis and proliferation mediated by Bcl-xL:Bim interactions in pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Abrol, Ravinder, E-mail: abrol@wag.caltech.edu [Materials and Process Simulation Center, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125 (United States); Edderkaoui, Mouad [Veterans Affairs Greater Los Angeles Healthcare System and UCLA, Los Angeles, CA 90073 (United States); Goddard, William A. [Materials and Process Simulation Center, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125 (United States); Pandol, Stephen J., E-mail: stephen.pandol@va.gov [Veterans Affairs Greater Los Angeles Healthcare System and UCLA, Los Angeles, CA 90073 (United States)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer Direct role of Bcl-2 protein interactions in cell proliferation is not clear. Black-Right-Pointing-Pointer Designed Bcl-xL mutants show opposite effects on apoptosis and proliferation. Black-Right-Pointing-Pointer Disrupting Bcl-xL:Bim interaction increased apoptosis in pancreatic cancer. Black-Right-Pointing-Pointer Disrupting Bcl-xL:Bim interaction decreased proliferation in pancreatic cancer. Black-Right-Pointing-Pointer Bcl-xL:Bim interaction can control both apoptosis and proliferation. -- Abstract: A major mechanism through which cancer cells avoid apoptosis is by promoting the association of anti-apoptotic members of the pro-survival Bcl-2 protein family (like Bcl-2 and Bcl-xL) with BH{sub 3} domain-only proteins (like Bim and Bid). Apoptosis and cell proliferation have been shown to be linked for many cancers but the molecular basis for this link is far from understood. We have identified the Bcl-xL:Bim protein-protein interface as a direct regulator of proliferation and apoptosis in pancreatic cancer cells. We were able to predict and subsequently verify experimentally the effect of various Bcl-xL single-point mutants (at the position A142) on binding to Bim by structural analysis and computational modeling of the inter-residue interactions at the Bcl-xL:Bim protein-protein interface. The mutants A142N, A142Q, and A142Y decreased binding of Bim to Bcl-xL and A142S increased this binding. The Bcl-xL mutants, with decreased affinity for Bim, caused an increase in apoptosis and a corresponding decrease in cell proliferation. However, we could prevent these effects by introducing a small interfering RNA (siRNA) targeted at Bim. These results show a novel role played by the Bcl-xL:Bim interaction in regulating proliferation of pancreatic cancer cells at the expense of apoptosis. This study presents a physiologically relevant model of the Bcl-xL:Bim interface that can be used for rational therapeutic design for the

  14. BIM Software Capability and Interoperability Analysis : An analytical approach toward structural usage of BIM software (S-BIM)

    OpenAIRE

    A. Taher, Ali

    2016-01-01

    This study focused on the structuralanalysis of BIM models. Different commercial software (Autodesk products and Rhinoceros)are presented through modelling and analysis of different structures with varying complexity,section properties, geometry, and material. Beside the commercial software, differentarchitectural and different tools for structural analysis are evaluated (dynamo, grasshopper,add-on tool, direct link, indirect link via IFC). BIM and Structural BIM (S-BIM)

  15. Histone Deacetylase 3 Inhibition Overcomes BIM Deletion Polymorphism-Mediated Osimertinib Resistance in EGFR-Mutant Lung Cancer.

    Science.gov (United States)

    Tanimoto, Azusa; Takeuchi, Shinji; Arai, Sachiko; Fukuda, Koji; Yamada, Tadaaki; Roca, Xavier; Ong, S Tiong; Yano, Seiji

    2017-06-15

    Purpose: The BIM deletion polymorphism is associated with apoptosis resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI), such as gefitinib and erlotinib, in non-small cell lung cancer (NSCLC) harboring EGFR mutations. Here, we investigated whether the BIM deletion polymorphism contributes to resistance against osimertinib, a third-generation EGFR-TKI. In addition, we determined the efficacy of a histone deacetylase (HDAC) inhibitor, vorinostat, against this form of resistance and elucidated the underlying mechanism. Experimental Design: We used EGFR -mutated NSCLC cell lines, which were either heterozygous or homozygous for the BIM deletion polymorphism, to evaluate the effect of osimertinib in vitro and in vivo Protein expression was examined by Western blotting. Alternative splicing of BIM mRNA was analyzed by RT-PCR. Results: EGFR -mutated NSCLC cell lines with the BIM deletion polymorphism exhibited apoptosis resistance to osimertinib in a polymorphism dosage-dependent manner, and this resistance was overcome by combined use with vorinostat. Experiments with homozygous BIM deletion-positive cells revealed that vorinostat affected the alternative splicing of BIM mRNA in the deletion allele, increased the expression of active BIM protein, and thereby induced apoptosis in osimertinib-treated cells. These effects were mediated predominantly by HDAC3 inhibition. In xenograft models, combined use of vorinostat with osimertinib could regress tumors in EGFR -mutated NSCLC cells homozygous for the BIM deletion polymorphism. Moreover, this combination could induce apoptosis even when tumor cells acquired EGFR -T790M mutations. Conclusions: These findings indicate the importance of developing HDAC3-selective inhibitors, and their combined use with osimertinib, for treating EGFR -mutated lung cancers carrying the BIM deletion polymorphism. Clin Cancer Res; 23(12); 3139-49. ©2016 AACR . ©2016 American Association for Cancer Research.

  16. A BIM-Info delivery protocol

    Directory of Open Access Journals (Sweden)

    Martin Hooper

    2015-10-01

    Full Text Available Today, with many of the technological issues of integrated information management resolved (perhaps excluding the matter of interoperability, defining the content and status of BIM information deliveries remains both a practical and a theoretical problem. New BIM tools and new design processes and procedures have led to a certain confusion of what information is needed for particular BIM uses. This paper seeks to explore and enable a method of defining the content of model information deliverables through a review of 2 key primary specific BIM uses: 3d Design Coordination and Early Energy Appraisal through an analysis of practical application. The scope of this study is limited to a review of information flow within residential projects in a Swedish context and looks at two projects with a view to identify and establish a common definition of the key BIM objects and properties necessary for particular tasks. The key deliverable from this study is the BIM-Info Delivery Protocol (IDP which attempts to align consultant BIM-information delivery expectations and represents a tangible solution to assist consultants to manage BIM information. Concluding reflections consider the positioning of the IDP relative to the on-going development of IDMs / MVDs and highlight the key constituent parameters of an Information Delivery Specification (IDS.

  17. SHARING HIGH-RESOLUTION MODELS AND INFORMATION ON WEB: THE WEB MODULE OF BIM3DSG SYSTEM

    Directory of Open Access Journals (Sweden)

    F. Rechichi

    2016-06-01

    Full Text Available BIM3DSG system is described here. It is an ad hoc designed BIM system created for Cultural Heritage applications. It proposes some solutions to solve some issues related to the use of BIM in this field. First, it tries to resolve the problem of managing huge, complex, high resolution and heterogeneous 3D models, and then it offers a practical, easy and efficient solution for a wide sharing of data and information.

  18. Uporaba BIM pri projektiranju cestne infrastrukture

    OpenAIRE

    Svetina, Gregor

    2018-01-01

    Magistrsko delo obravnava uporabo informacijskega modeliranja gradenj (angl. Building Information Modeling, kratica BIM) v infrastrukturnih projektih. Pri tem je kot primer uporabljen projekt Druge cevi predora Karavanke, pri katerem je bil BIM dejansko uporabljen. Naredili smo modele cest, ki se bodo uporabljale za odvoz materiala na deponije. Najprej je predstavljenih nekaj osnov o BIM-u, vključno s predstavitvami lastnosti 3D, 4D, 5D in 6D modelov, ovrednotenjem BIM-a, stopnjami podrobn...

  19. BIM quickscan: benchmark of BIM performance in the Netherlands

    NARCIS (Netherlands)

    Berlo, L.A.H.M. van; Dijkmans, T.J.A.; Hendriks, H.; Spekkink, D.; Pel, W.

    2012-01-01

    In 2009 a “BIM QuickScan” for benchmarking BIM performance was created in the Netherlands (Sebastian, Berlo 2010). This instrument aims to provide insight into the current BIM performance of a company. The benchmarking instrument combines quantitative and qualitative assessments of the ‘hard’ and

  20. Association of BIM Deletion Polymorphism and BIM-γ RNA Expression in NSCLC with EGFR Mutation.

    Science.gov (United States)

    Isobe, Kazutoshi; Kakimoto, Atsushi; Mikami, Tetsuo; Kaburaki, Kyohei; Kobayashi, Hiroshi; Yoshizawa, Takahiro; Makino, Takashi; Otsuka, Hajime; Sano, G O; Sugino, Keishi; Sakamoto, Susumu; Takai, Yujiro; Tochigi, Naobumi; Iyoda, Akira; Homma, Sakae

    This pilot study assessed the association of BIM deletion polymorphism and BIM RNA isoform in patients with EGFR-positive non-small cell lung cancer (NSCLC). The study included 33 patients with EGFR-positive NSCLC treated with gefitinib. BIM deletion polymorphism and BIM RNA isoform (EL/L/S/γ) were determined by polymerase chain reaction (PCR). BIM-γ expression was significantly higher in patients with BIM deletion polymorphism than among those without BIM deletion polymorphism inside tumors (p=0.038) and around tumors (p=0.0024). Relative BIM-γ expression was significantly higher in patients with BIM deletion polymorphism than among those without BIM deletion polymorphism (p=0.0017). Patients with BIM-γ had significantly shorter progression-free survival than those without BIM-γ (median: 304 vs. 732 days; p=0.023). Expression of BIM-γ mRNA and BIM deletion polymorphism were strongly associated. BIM-γ overexpression may have a role in apoptosis related to EGFR-tyrosine kinase inhibitor. Copyright© 2016, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

  1. Open Source Cloud-Based Technologies for Bim

    Science.gov (United States)

    Logothetis, S.; Karachaliou, E.; Valari, E.; Stylianidis, E.

    2018-05-01

    This paper presents a Cloud-based open source system for storing and processing data from a 3D survey approach. More specifically, we provide an online service for viewing, storing and analysing BIM. Cloud technologies were used to develop a web interface as a BIM data centre, which can handle large BIM data using a server. The server can be accessed by many users through various electronic devices anytime and anywhere so they can view online 3D models using browsers. Nowadays, the Cloud computing is engaged progressively in facilitating BIM-based collaboration between the multiple stakeholders and disciplinary groups for complicated Architectural, Engineering and Construction (AEC) projects. Besides, the development of Open Source Software (OSS) has been rapidly growing and their use tends to be united. Although BIM and Cloud technologies are extensively known and used, there is a lack of integrated open source Cloud-based platforms able to support all stages of BIM processes. The present research aims to create an open source Cloud-based BIM system that is able to handle geospatial data. In this effort, only open source tools will be used; from the starting point of creating the 3D model with FreeCAD to its online presentation through BIMserver. Python plug-ins will be developed to link the two software which will be distributed and freely available to a large community of professional for their use. The research work will be completed by benchmarking four Cloud-based BIM systems: Autodesk BIM 360, BIMserver, Graphisoft BIMcloud and Onuma System, which present remarkable results.

  2. OPEN SOURCE CLOUD-BASED TECHNOLOGIES FOR BIM

    Directory of Open Access Journals (Sweden)

    S. Logothetis

    2018-05-01

    Full Text Available This paper presents a Cloud-based open source system for storing and processing data from a 3D survey approach. More specifically, we provide an online service for viewing, storing and analysing BIM. Cloud technologies were used to develop a web interface as a BIM data centre, which can handle large BIM data using a server. The server can be accessed by many users through various electronic devices anytime and anywhere so they can view online 3D models using browsers. Nowadays, the Cloud computing is engaged progressively in facilitating BIM-based collaboration between the multiple stakeholders and disciplinary groups for complicated Architectural, Engineering and Construction (AEC projects. Besides, the development of Open Source Software (OSS has been rapidly growing and their use tends to be united. Although BIM and Cloud technologies are extensively known and used, there is a lack of integrated open source Cloud-based platforms able to support all stages of BIM processes. The present research aims to create an open source Cloud-based BIM system that is able to handle geospatial data. In this effort, only open source tools will be used; from the starting point of creating the 3D model with FreeCAD to its online presentation through BIMserver. Python plug-ins will be developed to link the two software which will be distributed and freely available to a large community of professional for their use. The research work will be completed by benchmarking four Cloud-based BIM systems: Autodesk BIM 360, BIMserver, Graphisoft BIMcloud and Onuma System, which present remarkable results.

  3. BIM. Building Information Model. Special issue; BIM. Building Information Model. Themanummer

    Energy Technology Data Exchange (ETDEWEB)

    Van Gelder, A.L.A. [Arta and Consultancy, Lage Zwaluwe (Netherlands); Van den Eijnden, P.A.A. [Stichting Marktwerking Installatietechniek, Zoetermeer (Netherlands); Veerman, J.; Mackaij, J.; Borst, E. [Royal Haskoning DHV, Nijmegen (Netherlands); Kruijsse, P.M.D. [Wolter en Dros, Amersfoort (Netherlands); Buma, W. [Merlijn Media, Waddinxveen (Netherlands); Bomhof, F.; Willems, P.H.; Boehms, M. [TNO, Delft (Netherlands); Hofman, M.; Verkerk, M. [ISSO, Rotterdam (Netherlands); Bodeving, M. [VIAC Installatie Adviseurs, Houten (Netherlands); Van Ravenswaaij, J.; Van Hoven, H. [BAM Techniek, Bunnik (Netherlands); Boeije, I.; Schalk, E. [Stabiplan, Bodegraven (Netherlands)

    2012-11-15

    A series of 14 articles illustrates the various aspects of the Building Information Model (BIM). The essence of BIM is to capture information about the building process and the building product. [Dutch] In 14 artikelen worden diverse aspecten m.b.t. het Building Information Model (BIM) belicht. De essentie van BIM is het vastleggen van informatie over het bouwproces en het bouwproduct.

  4. Building information modelling (BIM) after ten years: Malaysian construction players’ perception of BIM

    Science.gov (United States)

    Latiffi, A. Ahmad; Brahim, J.; Fathi, M. S.

    2017-08-01

    Building Information Modelling (BIM) concept has expanded widely in many countries for more than a decade with its role of improving current practices in construction projects. However, the understanding of BIM differs among construction players, depending on how construction players utilize the concept in their projects. Therefore, this paper aims to explore the understanding of BIM concept among construction players in the Malaysian construction industry. A literature review on BIM concept and semi-structured interviews with construction players in BIM such as client, civil and structural (C&S) engineer and mechanical and electrical (M&E) engineer, quantity surveyor (QS), contractor, facilities manager and BIM consultant have been conducted in order to achieve this study’s the aim. The results show that the understanding of BIM concept among the construction players is limited to BIM as a process and technology. It is important for the construction players to improve their understanding of BIM as it can be used to enhance performance and productivity of construction projects.

  5. INTEGRATION OF GIS AND BIM FOR INDOOR GEOVISUAL ANALYTICS

    Directory of Open Access Journals (Sweden)

    B. Wu

    2016-06-01

    Full Text Available This paper presents an endeavour of integration of GIS (Geographical Information System and BIM (Building Information Modelling for indoor geovisual analytics. The merits of two types of technologies, GIS and BIM are firstly analysed in the context of indoor environment. GIS has well-developed capabilities of spatial analysis such as network analysis, while BIM has the advantages for indoor 3D modelling and dynamic simulation. This paper firstly investigates the important aspects for integrating GIS and BIM. Different data standards and formats such as the IFC (Industry Foundation Classes and GML (Geography Markup Language are discussed. Their merits and limitations in data transformation between GIS and BIM are analysed in terms of semantic and geometric information. An optimized approach for data exchange between GIS and BIM datasets is then proposed. After that, a strategy of using BIM for 3D indoor modelling, GIS for spatial analysis, and BIM again for visualization and dynamic simulation of the analysis results is presented. Based on the developments, this paper selects a typical problem, optimized indoor emergency evacuation, to demonstrate the integration of GIS and BIM for indoor geovisual analytics. The block Z of the Hong Kong Polytechnic University is selected as a test site. Detailed indoor and outdoor 3D models of the block Z are created using a BIM software Revit. The 3D models are transferred to a GIS software ArcGIS to carry out spatial analysis. Optimized evacuation plans considering dynamic constraints are generated based on network analysis in ArcGIS assuming there is a fire accident inside the building. The analysis results are then transferred back to BIM software for visualization and dynamic simulation. The developed methods and results are of significance to facilitate future development of GIS and BIM integrated solutions in various applications.

  6. Synthesis, Structure, and Li-Ion Conductivity of LiLa(BH4)3X, X = Cl, Br, I

    DEFF Research Database (Denmark)

    Payandeh GharibDoust, SeyedHosein; Brighi, Matteo; Sadikin, Yolanda

    2017-01-01

    In this work, a new type of addition reaction between La(BH4)3 and LiX, X = Cl, Br, I, is used to synthesize LiLa(BH4)3Cl and two new compounds LiLa(BH4)3X, X = Br, I. This method increases the amounts of LiLa(BH4)3X and the sample purity. The highest Li-ion conductivity is observed for LiLa(BH4)...

  7. FOXO3-mediated up-regulation of Bim contributes to rhein-induced cancer cell apoptosis.

    Science.gov (United States)

    Wang, Jiao; Liu, Shu; Yin, Yancun; Li, Mingjin; Wang, Bo; Yang, Li; Jiang, Yangfu

    2015-03-01

    The anthraquinone compound rhein is a natural agent in the traditional Chinese medicine rhubarb. Preclinical studies demonstrate that rhein has anticancer activity. Treatment of a variety of cancer cells with rhein may induce apoptosis. Here, we report that rhein induces atypical unfolded protein response in breast cancer MCF-7 cells and hepatoma HepG2 cells. Rhein induces CHOP expression, eIF2α phosphorylation and caspase cleavage, while it does not induce glucose-regulated protein 78 (GRP78) expression in both MCF-7 and HepG2 cells. Meanwhile, rhein inhibits thapsigargin-induced GRP78 expression and X box-binding protein 1 splicing. In addition, rhein inhibits Akt phosphorylation and stimulates FOXO transactivation activity. Rhein induces Bim expression in MCF-7 and HepG2 cells, which can be abrogated by FOXO3a knockdown. Knockdown of FOXO3a or Bim abrogates rhein-induced caspase cleavage and apoptosis. The chemical chaperone 4-phenylbutyrate acid antagonizes the induction of FOXO activation, Bim expression and caspase cleavage by rhein, indicating that protein misfolding may be involved in triggering these deleterious effects. We conclude that FOXO3a-mediated up-regulation of Bim is a key mechanism underlying rhein-induced cancer cells apoptosis.

  8. SHAVING BIM: ESTABLISHING A FRAMEWORK FOR FUTURE BIM RESEARCH IN NEW ZEALAND

    Directory of Open Access Journals (Sweden)

    Tran, Van

    2012-08-01

    Full Text Available This paper reviews and analyses issues relating to the uptake of BIM in the NZ construction industry. There have been few BIM applications in NZ; in particular, in post-construction phases like facilities management, there is none. The paper found that the three reasons why BIM has not been widely accepted and used in New Zealand are: the slow uptake by NZ construction companies; a lack of Kiwi-focused BIM initiatives (led by the government and industry bodies; and a lack of BIM-based building life cycle considerations. Therefore, the paper concludes that there is an urgent need for a joint research programme in NZ to develop a Kiwi-oriented knowledge base on BIM. Given the fact that all major research organisations currently have development plans in their pipelines, coupled with potential developments of the Christchurch Cit after the quake, it seems an ideal time to take a BIM-based research initiative in the country. This joint BIM- focused research programme should concentrate on construction management processes, including procurement management, contract management, information management, as well as post-construction aspects such as facility management.

  9. BIM education in Denmark

    DEFF Research Database (Denmark)

    Svidt, Kjeld

    The International Conference on Digital Construction of 2015, Vilnius, Lithuania. See the invited speak ppt. presentation here http://skaitmeninestatyba.lt/files/SKST'15%20skaidr%C4%97s/2_3_Svidt_BIM_education_i_Denmark_Skaitmenine_statyba2015.pdf......The International Conference on Digital Construction of 2015, Vilnius, Lithuania. See the invited speak ppt. presentation here http://skaitmeninestatyba.lt/files/SKST'15%20skaidr%C4%97s/2_3_Svidt_BIM_education_i_Denmark_Skaitmenine_statyba2015.pdf...

  10. Melting Behavior and Thermolysis of NaBH4−Mg(BH42 and NaBH4−Ca(BH42 Composites

    Directory of Open Access Journals (Sweden)

    Morten B. Ley

    2015-04-01

    Full Text Available The physical properties and the hydrogen release of NaBH4–Mg(BH42 and NaBH4−Ca(BH42 composites are investigated using in situ synchrotron radiation powder X-ray diffraction, thermal analysis and temperature programmed photographic analysis. The composite, xNaBH4–(1 − xMg(BH42, x = 0.4 to 0.5, shows melting/frothing between 205 and 220 °C. However, the sample does not become a transparent molten phase. This behavior is similar to other alkali-alkaline earth metal borohydride composites. In the xNaBH4–(1 − xCa(BH42 system, eutectic melting is not observed. Interestingly, eutectic melting in metal borohydrides systems leads to partial thermolysis and hydrogen release at lower temperatures and the control of sample melting may open new routes for obtaining high-capacity hydrogen storage materials.

  11. Vapor Pressure Measurements of LiBH4, NaBH 4 and Ca(BH4)2 using Knudsen Torsion Effusion Gravimetric Method

    Science.gov (United States)

    Danyan, Mohammad Masoumi

    Hydrogen storage is one of the critical technologies needed on the path towards commercialization for mobile applications. In the past few years, a range of new light weight hydrogen containing material has been discovered with good storage properties. Among them, lithium borohydride (LiBH 4) sodium borohydride (NaBH4) and calcium borohydride (Ca(BH 4)2) have shown promising results to be used as solid state hydrogen storage material. In this work, we have determined equilibrium vapor pressures of LiBH 4 NaBH4 and Ca(BH4)2 obtained by Torsion effusion thermogravimetric method. Results for all the three hydrides exhibited that a small fraction of the materials showed congruency, and sublimed as gaseous compound, but the majority of the material showed incongruent vaporization. Two Knudsen cells of 0.3 and 0.6mm orifice size was employed to measure the total vapor pressures. A Whitman-Motzfeldt method is used to extrapolate the measured vapor pressures to zero orifice size to calculate the equilibrium vapor pressures. In the case of LiBH4 we found that 2% of the material evaporated congruently (LiBH4(s) → LiBH4(g)) according to the equation: logPLiBH4/P 0 =-3263.5 +/-309/T + (1.079 +/-0.69) and rest as incongruent vaporization to LiH, B, and hydrogen gas according to the equation logPeq/P0 =(-3263.5 +/-309)/T+ (2.458 +/-0.69) with DeltaH evap.= 62.47+/-5.9 kJ/mol of H2, DeltaSevap. = 47.05+/-13 J/mol of H2.K. The NaBH4 also had somewhat similar behavior, with 9% congruent evaporation and equilibrium vapor pressure equation of logPLiBH4=-7700+/-335/ T+ (6.7+/-1.5) and 91% incongruent decomposition to Na and Boron metal, and hydrogen gas. The enthalpy of vaporization; DeltaHevap. = 147.2+/-6.4kJ/molH2 and DeltaSevap.= 142 +/-28 kJ/molH2.K (550-650K). The Ca(BH4) 2 exhibited similar vaporization behavior with congruency of 3.2%. The decomposition products are CaH2 and Boron metal with evolution of hydrogen gas varying with the pressure equation as logPeq /P0 =(-1562

  12. Effect of cAMP signaling on expression of glucocorticoid receptor, Bim and Bad in glucocorticoid-sensitive and resistant leukemic and multiple myeloma cells.

    Science.gov (United States)

    Dong, Hongli; Carlton, Michael E; Lerner, Adam; Epstein, Paul M

    2015-01-01

    Stimulation of cAMP signaling induces apoptosis in glucocorticoid-sensitive and resistant CEM leukemic and MM.1 multiple myeloma cell lines, and this effect is enhanced by dexamethasone in both glucocorticoid-sensitive cell types and in glucocorticoid-resistant CEM cells. Expression of the mRNA for the glucocorticoid receptor alpha (GR) promoters 1A3, 1B and 1C, expression of mRNA and protein for GR, and the BH3-only proapoptotic proteins, Bim and Bad, and the phosphorylation state of Bad were examined following stimulation of the cAMP and glucocorticoid signaling pathways. Expression levels of GR promoters were increased by cAMP and glucocorticoid signaling, but GR protein expression was little changed in CEM and decreased in MM.1 cells. Stimulation of these two signaling pathways induced Bim in CEM cells, induced Bad in MM.1 cells, and activated Bad, as indicated by its dephosphorylation on ser112, in both cell types. This study shows that leukemic and multiple myeloma cells, including those resistant to glucocorticoids, can be induced to undergo apoptosis by stimulating the cAMP signaling pathway, with enhancement by glucocorticoids, and the mechanism by which this occurs may be related to changes in Bim and Bad expression, and in all cases, to activation of Bad.

  13. BIM for Construction Site Logistics Management

    Directory of Open Access Journals (Sweden)

    K. Whitlock

    2018-01-01

    Full Text Available Emerging Building Information Modelling (BIM has been hailed as a revolutionary technology and information management process that facilitates collaboration and more efficient design and construction processes through innovative 3D modelling software, open access to information and multidisciplinary integration. The deadline of compliance to BIM level 2 on all public sector centrally procured construction projects has expired leaving many construction firms anxious to adopt BIM. Most common documented applications of BIM have been in the areas of architectural and structural design, quantity surveying, construction project management, and sustainability with very limited peer-reviewed studies on construction logistics management. The aim of this study is to investigate how BIM can be applied to construction logistics management. This study adopts a desk-top approach, with articles sources from renowned scientific databases such as ScienceDirect, Google Scholar and Emerald. The study culminated in the identification of benefits and barriers of adopting BIM for construction logistics management. Given only a desk-top approach has been used, the recommendation for future study is to build on this to conduct an empirical study using both qualitative and quantitative data. This will provide an in-depth understanding of the use of BIM for construction logistics management and open opportunities for further research.

  14. The BIM management handbook

    CERN Document Server

    Shepherd, David

    2016-01-01

    An authoritative and practical road map for those implementing and managing BIM workflows. With the 2016 deadline for BIM level 2 fast approaching and the growing realisation of the huge benefits BIM brings these skills are becoming industry essentials. Concentrating on the how rather than the why this will help you to adapt by clearly, and without jargon, explaining standard BIM processes, Government standards and the effective coordination of design, construction and asset information. Spanning both organisational strategy and day-to-day practical tasks it explores bottom line business reasoning as well as potential risks and challenges. Extra features include: • Case studies that demonstrate real world approaches as well as problems and solutions • Checklists for adequately resourcing BIM roles and responsibilities in relation to PAS-1192 • Self-check questions allowing you to evaluate your BIM implementation methodology This is the go-to guide for BIM Coordinators and Managers, architectural pr...

  15. Synergy of the Developed 6D BIM Framework and Conception of the nD BIM Framework and nD BIM Process Ontology

    Science.gov (United States)

    O'Keeffe, Shawn Edward

    2013-01-01

    The author developed a unified nD framework and process ontology for Building Information Modeling (BIM). The research includes a framework developed for 6D BIM, nD BIM, and nD ontology that defines the domain and sub-domain constructs for future nD BIM dimensions. The nD ontology defines the relationships of kinds within any new proposed…

  16. Synthesis, Structure, and Li-Ion Conductivity of LiLa(BH4)3X, X = Cl, Br, I

    DEFF Research Database (Denmark)

    GharibDoust, Seyed Hosein Payandeh; Brighi, Matteo; Sadikin, Yolanda

    2017-01-01

    In this work, a new type of addition reaction between La(BH4)3 and LiX, X = Cl, Br, I, is used to synthesize LiLa(BH4)3Cl and two new compounds LiLa(BH4)3X, X = Br, I. This method increases the amounts of LiLa(BH4)3X and the sample purity. The highest Li-ion conductivity is observed for LiLa(BH4...... with increasing lattice parameter, that is, increasing size of the halide ion in the structure. Thus, we conclude that the sizes of both windows are important for the lithium ion conduction in LiLa(BH4)3X compounds. The lithium ion conductivity is measured over one to three heating cycles and with different...

  17. Based on the development status of British BIM, exploring China’s BIM road

    Science.gov (United States)

    Tiangang, Chu; hui, Li; shanjun, Zhang; Ningshan, Jiang; Dan, Zhang; Yu, Zhang; Guibo, Bao

    2018-05-01

    This article mainly analyses the development and application status and development trend of BIM technology after the implementation of the British government, to explore the policies and methods that our government should carry out in the development of BIM. The article also summarizes and analyses the relevant policies and standards implemented by various provincial and municipal governments in promoting BIM technology in China and summarizes the strengths and weaknesses of each other by comparing the development status of the implementation of BIM policies in various provinces and cities. The article also analysed the obstacles encountered in the implementation of some specific projects at the current stage of BIM technology, and summarized the feasible solutions. The article mainly analyses the application prospects of BIM from the technical aspects of design, the application of technology in the construction process, and the strategic implementation and operation of the company, and provides a reference for promoting the application of BIM in the construction industry in China, especially in the western region.

  18. An Integrated Bioinformatics and Computational Biology Approach Identifies New BH3-Only Protein Candidates.

    Science.gov (United States)

    Hawley, Robert G; Chen, Yuzhong; Riz, Irene; Zeng, Chen

    2012-05-04

    In this study, we utilized an integrated bioinformatics and computational biology approach in search of new BH3-only proteins belonging to the BCL2 family of apoptotic regulators. The BH3 (BCL2 homology 3) domain mediates specific binding interactions among various BCL2 family members. It is composed of an amphipathic α-helical region of approximately 13 residues that has only a few amino acids that are highly conserved across all members. Using a generalized motif, we performed a genome-wide search for novel BH3-containing proteins in the NCBI Consensus Coding Sequence (CCDS) database. In addition to known pro-apoptotic BH3-only proteins, 197 proteins were recovered that satisfied the search criteria. These were categorized according to α-helical content and predictive binding to BCL-xL (encoded by BCL2L1) and MCL-1, two representative anti-apoptotic BCL2 family members, using position-specific scoring matrix models. Notably, the list is enriched for proteins associated with autophagy as well as a broad spectrum of cellular stress responses such as endoplasmic reticulum stress, oxidative stress, antiviral defense, and the DNA damage response. Several potential novel BH3-containing proteins are highlighted. In particular, the analysis strongly suggests that the apoptosis inhibitor and DNA damage response regulator, AVEN, which was originally isolated as a BCL-xL-interacting protein, is a functional BH3-only protein representing a distinct subclass of BCL2 family members.

  19. Epigenetic Silencing of the Proapoptotic Gene BIM in Anaplastic Large Cell Lymphoma through an MeCP2/SIN3a Deacetylating Complex

    Directory of Open Access Journals (Sweden)

    Rocco Piazza

    2013-05-01

    Full Text Available BIM is a proapoptotic member of the Bcl-2 family. Here, we investigated the epigenetic status of the BIM locus in NPM/ALK+ anaplastic large cell lymphoma (ALCL cell lines and in lymph node biopsies from NPM/ALK+ ALCL patients. We show that BIM is epigenetically silenced in cell lines and lymph node specimens and that treatment with the deacetylase inhibitor trichostatin A restores the histone acetylation, strongly upregulates BIM expression, and induces cell death. BIM silencing occurs through recruitment of MeCP2 and the SIN3a/histone deacetylase 1/2 (HDAC1/2 corepressor complex. This event requires BIM CpG methylation/demethylation with 5-azacytidine that leads to detachment of the MeCP2 corepressor complex and reacetylation of the histone tails. Treatment with the ALK inhibitor PF2341066 or with an inducible shRNA targeting NPM/ALK does not restore BIM locus reacetylation; however, enforced expression of NPM/ALK in an NPM/ALK-negative cell line significantly increases the methylation at the BIM locus. This study demonstrates that BIM is epigenetically silenced in NPM/ALK-positive cells through recruitment of the SIN3a/HDAC1/2 corepressor complex and that NPM/ALK is dispensable to maintain BIM epigenetic silencing but is able to act as an inducer of BIM methylation.

  20. An Investigation into the Possibilities of BIM and GIS Cooperation and Utilization of GIS in the BIM Process

    Directory of Open Access Journals (Sweden)

    Pavel Tobiáš

    2015-06-01

    Full Text Available In the coming years we will most probably watch a significant increase of the BIM (building information model utilization in the AEC (Architecture/Engineering/Construction sector even in the Czech Republic. Therefore, it would be reasonable to consider possible utilization of the well-established geographic information systems within the building information modelling process. This paper is based on the currently existing literature and is focused on the interrelationship between BIM and GIS. The main goal is to reveal potential fields of cooperation and to find possible utilization of GIS in BIM. To provide a theoretical framework, this article briefly introduces and defines the term of BIM and deals with the most important semantic models in AEC and 3D GIS IFC and CityGML. The paper also contains examples of specific efforts recently dealing with the BIM and GIS collaboration.

  1. Increasing Hydrogen Density with the Cation-Anion Pair BH4−-NH4+ in Perovskite-Type NH4Ca(BH43

    Directory of Open Access Journals (Sweden)

    Pascal Schouwink

    2015-08-01

    Full Text Available A novel metal borohydride ammonia-borane complex Ca(BH42·NH3BH3 is characterized as the decomposition product of the recently reported perovskite-type metal borohydride NH4Ca(BH43, suggesting that ammonium-based metal borohydrides release hydrogen gas via ammonia-borane-complexes. For the first time the concept of proton-hydride interactions to promote hydrogen release is applied to a cation-anion pair in a complex metal hydride. NH4Ca(BH43 is prepared mechanochemically from Ca(BH42 and NH4Cl as well as NH4BH4 following two different protocols, where the synthesis procedures are modified in the latter to solvent-based ball-milling using diethyl ether to maximize the phase yield in chlorine-free samples. During decomposition of NH4Ca(BH43 pure H2 is released, prior to the decomposition of the complex to its constituents. As opposed to a previously reported adduct between Ca(BH42 and NH3BH3, the present complex is described as NH3BH3-stuffed α-Ca(BH42.

  2. Melting Behavior and Thermolysis of NaBH4−Mg(BH4)2 and NaBH4−Ca(BH4)2 Composites

    OpenAIRE

    Ley, Morten; Roedern, Elsa; Thygesen, Peter; Jensen, Torben

    2015-01-01

    The physical properties and the hydrogen release of NaBH 4 –Mg(BH 4 ) 2 and NaBH 4 −Ca(BH 4 ) 2 composites are investigated using in situ synchrotron radiation powder X-ray diffraction, thermal analysis and temperature programmed photographic analysis. The composite, x NaBH 4 –(1 − x )Mg(BH 4 ) 2 , x = 0.4 to 0.5, shows melting/frothing between 205 and 220 °C. However, the sample does not become a transparent molten phase. This behavior is similar to other alkali-alkaline earth metal borohydr...

  3. Inhibition of Bcl-2 or IAP proteins does not provoke mutations in surviving cells

    Energy Technology Data Exchange (ETDEWEB)

    Shekhar, Tanmay M. [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia); Green, Maja M. [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia); Department of Anatomy & Neuroscience, The University of Melbourne, Parkville 3010 (Australia); Rayner, David M.; Miles, Mark A.; Cutts, Suzanne M. [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia); Hawkins, Christine J., E-mail: c.hawkins@latrobe.edu.au [Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083 (Australia)

    2015-07-15

    Graphical abstract: - Highlights: • Mutagenicities of anti-cancer drugs were tested using HPRT, γH2AX and comet assays. • TRAIL, doxorubicin and etoposide were more mutagenic than BH3- or Smac-mimetics. • Physiologically achievable levels of the BH3-mimetic ABT-737 were not mutagenic. • High concentrations of ABT-737 provoked mutations via an off-target mechanism. • Even very high concentrations of IAP antagonists were not mutagenic. - Abstract: Chemotherapy and radiotherapy can cause permanent damage to the genomes of surviving cells, provoking severe side effects such as second malignancies in some cancer survivors. Drugs that mimic the activity of death ligands, or antagonise pro-survival proteins of the Bcl-2 or IAP families have yielded encouraging results in animal experiments and early phase clinical trials. Because these agents directly engage apoptosis pathways, rather than damaging DNA to indirectly provoke tumour cell death, we reasoned that they may offer another important advantage over conventional therapies: minimisation or elimination of side effects such as second cancers that result from mutation of surviving normal cells. Disappointingly, however, we previously found that concentrations of death receptor agonists like TRAIL that would be present in vivo in clinical settings provoked DNA damage in surviving cells. In this study, we used cell line model systems to investigate the mutagenic capacity of drugs from two other classes of direct apoptosis-inducing agents: the BH3-mimetic ABT-737 and the IAP antagonists LCL161 and AT-406. Encouragingly, our data suggest that IAP antagonists possess negligible genotoxic activity. Doses of ABT-737 that were required to damage DNA stimulated Bax/Bak-independent signalling and exceeded concentrations detected in the plasma of animals treated with this drug. These findings provide hope that cancer patients treated by BH3-mimetics or IAP antagonists may avoid mutation-related illnesses that afflict

  4. Inhibition of Bcl-2 or IAP proteins does not provoke mutations in surviving cells

    International Nuclear Information System (INIS)

    Shekhar, Tanmay M.; Green, Maja M.; Rayner, David M.; Miles, Mark A.; Cutts, Suzanne M.; Hawkins, Christine J.

    2015-01-01

    Graphical abstract: - Highlights: • Mutagenicities of anti-cancer drugs were tested using HPRT, γH2AX and comet assays. • TRAIL, doxorubicin and etoposide were more mutagenic than BH3- or Smac-mimetics. • Physiologically achievable levels of the BH3-mimetic ABT-737 were not mutagenic. • High concentrations of ABT-737 provoked mutations via an off-target mechanism. • Even very high concentrations of IAP antagonists were not mutagenic. - Abstract: Chemotherapy and radiotherapy can cause permanent damage to the genomes of surviving cells, provoking severe side effects such as second malignancies in some cancer survivors. Drugs that mimic the activity of death ligands, or antagonise pro-survival proteins of the Bcl-2 or IAP families have yielded encouraging results in animal experiments and early phase clinical trials. Because these agents directly engage apoptosis pathways, rather than damaging DNA to indirectly provoke tumour cell death, we reasoned that they may offer another important advantage over conventional therapies: minimisation or elimination of side effects such as second cancers that result from mutation of surviving normal cells. Disappointingly, however, we previously found that concentrations of death receptor agonists like TRAIL that would be present in vivo in clinical settings provoked DNA damage in surviving cells. In this study, we used cell line model systems to investigate the mutagenic capacity of drugs from two other classes of direct apoptosis-inducing agents: the BH3-mimetic ABT-737 and the IAP antagonists LCL161 and AT-406. Encouragingly, our data suggest that IAP antagonists possess negligible genotoxic activity. Doses of ABT-737 that were required to damage DNA stimulated Bax/Bak-independent signalling and exceeded concentrations detected in the plasma of animals treated with this drug. These findings provide hope that cancer patients treated by BH3-mimetics or IAP antagonists may avoid mutation-related illnesses that afflict

  5. Enhancing knowledge sharing management using BIM technology in construction.

    Science.gov (United States)

    Ho, Shih-Ping; Tserng, Hui-Ping; Jan, Shu-Hui

    2013-01-01

    Construction knowledge can be communicated and reused among project managers and jobsite engineers to alleviate problems on a construction jobsite and reduce the time and cost of solving problems related to constructability. This paper proposes a new methodology for the sharing of construction knowledge by using Building Information Modeling (BIM) technology. The main characteristics of BIM include illustrating 3D CAD-based presentations and keeping information in a digital format and facilitation of easy updating and transfer of information in the BIM environment. Using the BIM technology, project managers and engineers can gain knowledge related to BIM and obtain feedback provided by jobsite engineers for future reference. This study addresses the application of knowledge sharing management using BIM technology and proposes a BIM-based Knowledge Sharing Management (BIMKSM) system for project managers and engineers. The BIMKSM system is then applied in a selected case study of a construction project in Taiwan to demonstrate the effectiveness of sharing knowledge in the BIM environment. The results demonstrate that the BIMKSM system can be used as a visual BIM-based knowledge sharing management platform by utilizing the BIM technology.

  6. Mimetic Learning

    Directory of Open Access Journals (Sweden)

    Christoph Wulf

    2008-03-01

    Full Text Available Mimetic learning, learning by imitation, constitutes one of the most important forms of learning. Mimetic learning does not, however, just denote mere imitation or copying: Rather, it is a process by which the act of relating to other persons and worlds in a mimetic way leads to an en-hancement of one’s own world view, action, and behaviour. Mimetic learning is productive; it is related to the body, and it establishes a connection between the individual and the world as well as other persons; it creates practical knowledge, which is what makes it constitutive of social, artistic, and practical action. Mimetic learning is cultural learning, and as such it is crucial to teaching and education (Wulf, 2004; 2005.

  7. Studies of the effects of TiCl3 in LiBH4/CaH2/TiCl3 reversible hydrogen storage system

    International Nuclear Information System (INIS)

    Liu Dongan; Yang Jun; Ni Jun; Drews, Andy

    2012-01-01

    Highlights: ► We systematically studied the effects of TiCl 3 in LiBH 4 /CaH 2 /TiCl 3 hydrogen storage system. ► It is found that adding 0.25 TiCl 3 produces fully reversible hydrogen absorption and desorption and a lower desorption temperature. ► LiCl experiences four different states, i.e. “formed-solid solution-molten solution-precipitation”, in the whole desorption process of the system. ► The incorporation of LiCl into LiBH 4 forms more viscous molten LiBH 4 ·LiCl, leading to fast kinetics. ► The precipitation and re-incorporation of LiCl into LiBH 4 lead to a fully reversible complex hydrogen storage system. - Abstract: In the present study, the effects of TiCl 3 on desorption kinetics, absorption/desorption reversibility, and related phase transformation processes in LiBH 4 /CaH 2 /TiCl 3 hydrogen storage system was studied systematically by varying its concentration (x = 0, 0.05, 0.15 and 0.25). The results show that LiCl forms during ball milling of 6LiBH 4 /CaH 2 /xTiCl 3 and that as temperature increases, o-LiBH 4 transforms into h-LiBH 4 , into which LiCl incorporates, forming solid solution of LiBH 4 ·LiCl, which melts above 280 °C. Molten LiBH 4 ·LiCl is more viscous than molten LiBH 4 , preventing the clustering of LiBH 4 and the accompanied agglomeration of CaH 2 , and thus preserving the nano-sized phase arrangement formed during ball milling. Above 350 °C, the molten solution LiBH 4 ·LiCl further reacts with CaH 2 , precipitating LiCl. The main hydrogen desorption reaction is between molten LiBH 4 ·LiCl and CaH 2 and not between molten LiBH 4 and CaH 2 . This alters the hydrogen reaction thermodynamics and lowers the hydrogen desorption temperature. In addition, the solid–liquid nano-sized phase arrangement in the nano-composites improves the hydrogen reaction kinetics. The reversible incorporation/precipitation of LiCl at the hydrogen reaction temperature and during temperature cycling makes the 6LiBH 4 /CaH 2 /0.25TiCl 3

  8. Implementation of Space Charge Forces in BimBim

    CERN Document Server

    Gottlob, Emmanuel; Oeftiger, Adrian

    An numerical algorithm is described for the implementation of linearised coherent space charge forces into BimBim, an eigenvalue solver for the coherent modes of oscillation of multibunch beams in the presence of beam coupling impedance, beam-beam, transverse feedback and now space charge effects. First results obtained with the model are described and compared to existing results where applicable.

  9. Yield-to-BIM: impacts of BIM maturity on project performance

    NARCIS (Netherlands)

    Smits, W.; van Buiten, Marinus; Hartmann, Timo

    2016-01-01

    How does organizational experience (maturity) with building information modelling (BIM) impact on the broad implementation of BIM and on company performance? A survey of Dutch architectural, engineering, construction, and operation (AECO) professionals (n = 890) is used to examine their perceptions

  10. Y(BH4)3--an old-new ternary hydrogen store aka learning from a multitude of failures.

    Science.gov (United States)

    Jaroń, Tomasz; Grochala, Wojciech

    2010-01-07

    Fourteen different synthetic approaches towards pure solvent-free Y(BH(4))(3) have been tested, thirteen of which have failed. Attempted reactions of YCl(3) or Y(OC(4)H(9))(3) with LiBH(4) in THF, those of YCl(3) with (C(4)H(9))(4)N(+) BH(4)(-), as well as between YH(x approximately 3) and R(4)NBH(3) (R = CH(3), C(2)H(5)) in the presence or absence of a solvent (n-hexane or CH(2)Cl(2)) did not lead to the expected product. The mechanochemical solid/solid reactions (MBH(4) + 3 YX(3)--> Y(BH(4))(3) + 3 LiCl, where M = Li, Na; X = F, Cl) have succeeded only for the LiBH(4) and YCl(3) reagents, but the separation of the crystalline reaction products (Y(BH(4))(3) in its Pa3 phase and LiCl) by dissolution or flotation in various solvents has not been successful. The thermal decomposition process of Y(BH(4))(3) in a mixture with LiCl has been investigated with thermogravimetric (TGA) and calorimetric analysis (DSC) combined with spectroscopic evolved gas analysis (EGA). Three major endothermic steps could be distinguished in the DSC profile at ca. 232, 282, 475 degrees C (heating rate 10 K min(-1)) corresponding to a phase transition and two steps of thermal decomposition. Solid decomposition products are amorphous except for the new cubic polymorph of Y(BH(4))(3) overlooked in previous work. The high-temperature phase forms at the onset of thermal decomposition and it may be prepared by heating of the low-temperature phase up to a narrow temperature range (194-210 degrees C) followed by rapid quenching. Y(BH(4))(3) constitutes a novel highly efficient hydrogen storage material (theor. 9.0 wt% H) but, unfortunately, the evolved H(2) is contaminated by toxic boron hydrides and products of their pyrolysis.

  11. Stimulating a Sustainable Construction through Holistic BIM Adoption: The Root Causes of Recurring Low BIM Adoption in Malaysia

    Science.gov (United States)

    Mamter, S.; Abdul-Aziz, AR; Mamat, ME

    2017-06-01

    Fostering the Building Information Modelling (BIM) implementation is one of Malaysia sustainable strategies towards greener construction. Hence, the Eleventh Malaysia plan focuses on transforming construction industry through the increase of technology adoption in order to enhance construction productivity. Therefore, there is a growing and urgent demand to provide BIM competent. However, a significant number of parties are reluctant to develop and invest in BIM due to unsolved root causes. Scholars have identified barriers relating to the infancy stage of BIM adoption in Malaysia. Unfortunately, there is a lack of study to explore deeper the root causes of recurring for the barriers anticipate the low BIM adoption. This paper attempts to delve into the initiatives of BIM stake players in fostering BIM adoption and to determine the root causes of recurring barriers due to low BIM adoption. The study adopted the semi-structured interviews which involved BIM stake players as a sample population. From the findings, authors revealed four root causes of recurring barriers; absence of BIM policy and BIM compulsion, poor holistic readiness, software integration competition strategy, and reluctant in sharing knowledge. The findings espoused here are preliminary and more results are expected to emerge as the research progresses.

  12. MESH-TO-BIM: FROM SEGMENTED MESH ELEMENTS TO BIM MODEL WITH LIMITED PARAMETERS

    Directory of Open Access Journals (Sweden)

    X. Yang

    2018-05-01

    Full Text Available Building Information Modelling (BIM technique has been widely utilized in heritage documentation and comes to a general term Historical/Heritage BIM (HBIM. The current HBIM project mostly employs the scan-to-BIM process to manually create the geometric model from the point cloud. This paper explains how it is possible to shape from the mesh geometry with reduced human involvement during the modelling process. Aiming at unbuilt heritage, two case studies are handled in this study, including a ruined Roman stone architectural and a severely damaged abbey. The pipeline consists of solid element modelling based on documentation data using Autodesk Revit, a common BIM platform, and the successive modelling from these geometric primitives using Autodesk Dynamo, a visual programming built-in plugin tool in Revit. The BIM-based reconstruction enriches the classic visual model from computer graphics approaches with measurement, semantic and additional information. Dynamo is used to develop a semi-automated function to reduce the manual process, which builds the final BIM model from segmented parametric elements directly. The level of detail (LoD of the final models is dramatically relevant with the manual involvement in the element creation. The proposed outline also presents two potential issues in the ongoing work: combining the ontology semantics with the parametric BIM model, and introducing the proposed pipeline into the as-built HBIM process.

  13. Interaction of a putative BH3 domain of clusterin with anti-apoptotic Bcl-2 family proteins as revealed by NMR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong-Hwa; Ha, Ji-Hyang [Medical Proteomics Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Kim, Yul [Department of Bio and Brain Engineering, KAIST, Daejeon 305-701 (Korea, Republic of); Bae, Kwang-Hee [Medical Proteomics Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Park, Jae-Yong [Department of Physiology, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660-751 (Korea, Republic of); Choi, Wan Sung [Department of Anatomy and Neurobiology, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660-751 (Korea, Republic of); Yoon, Ho Sup [Division of Structural and Computational Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637511 (Singapore); Park, Sung Goo; Park, Byoung Chul [Medical Proteomics Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Yi, Gwan-Su, E-mail: gsyi@kaist.ac.kr [Department of Bio and Brain Engineering, KAIST, Daejeon 305-701 (Korea, Republic of); Chi, Seung-Wook, E-mail: swchi@kribb.re.kr [Medical Proteomics Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of)

    2011-05-20

    Highlights: {yields} Identification of a conserved BH3 motif in C-terminal coiled coil region of nCLU. {yields} The nCLU BH3 domain binds to BH3 peptide-binding grooves in both Bcl-X{sub L} and Bcl-2. {yields} A conserved binding mechanism of nCLU BH3 and the other pro-apoptotic BH3 peptides with Bcl-X{sub L}. {yields} The absolutely conserved Leu323 and Asp328 of nCLU BH3 domain are critical for binding to Bcl-X{sub L.} {yields} Molecular understanding of the pro-apoptotic function of nCLU as a novel BH3-only protein. -- Abstract: Clusterin (CLU) is a multifunctional glycoprotein that is overexpressed in prostate and breast cancers. Although CLU is known to be involved in the regulation of apoptosis and cell survival, the precise molecular mechanism underlying the pro-apoptotic function of nuclear CLU (nCLU) remains unclear. In this study, we identified a conserved BH3 motif in C-terminal coiled coil (CC2) region of nCLU by sequence analysis and characterized the molecular interaction of the putative nCLU BH3 domain with anti-apoptotic Bcl-2 family proteins by nuclear magnetic resonance (NMR) spectroscopy. The chemical shift perturbation data demonstrated that the nCLU BH3 domain binds to pro-apoptotic BH3 peptide-binding grooves in both Bcl-X{sub L} and Bcl-2. A structural model of the Bcl-X{sub L}/nCLU BH3 peptide complex reveals that the binding mode is remarkably similar to those of other Bcl-X{sub L}/BH3 peptide complexes. In addition, mutational analysis confirmed that Leu323 and Asp328 of nCLU BH3 domain, absolutely conserved in the BH3 motifs of BH3-only protein family, are critical for binding to Bcl-X{sub L}. Taken altogether, our results suggest a molecular basis for the pro-apoptotic function of nCLU by elucidating the residue specific interactions of the BH3 motif in nCLU with anti-apoptotic Bcl-2 family proteins.

  14. Historic Bim: a New Repository for Structural Health Monitoring

    Science.gov (United States)

    Banfi, F.; Barazzetti, L.; Previtali, M.; Roncoroni, F.

    2017-05-01

    Recent developments in Building Information Modelling (BIM) technologies are facilitating the management of historic complex structures using new applications. This paper proposes a generative method combining the morphological and typological aspects of the historic buildings (H-BIM), with a set of monitoring information. This combination of 3D digital survey, parametric modelling and monitoring datasets allows for the development of a system for archiving and visualizing structural health monitoring (SHM) data (Fig. 1). The availability of a BIM database allows one to integrate a different kind of data stored in different ways (e.g. reports, tables, graphs, etc.) with a representation directly connected to the 3D model of the structure with appropriate levels of detail (LoD). Data can be interactively accessed by selecting specific objects of the BIM, i.e. connecting the 3D position of the sensors installed with additional digital documentation. Such innovative BIM objects, which form a new BIM family for SHM, can be then reused in other projects, facilitating data archiving and exploitation of data acquired and processed. The application of advanced modeling techniques allows for the reduction of time and costs of the generation process, and support cooperation between different disciplines using a central workspace. However, it also reveals new challenges for parametric software and exchange formats. The case study presented is the medieval bridge Azzone Visconti in Lecco (Italy), in which multi-temporal vertical movements during load testing were integrated into H-BIM.

  15. HISTORIC BIM: A NEW REPOSITORY FOR STRUCTURAL HEALTH MONITORING

    Directory of Open Access Journals (Sweden)

    F. Banfi

    2017-05-01

    Full Text Available Recent developments in Building Information Modelling (BIM technologies are facilitating the management of historic complex structures using new applications. This paper proposes a generative method combining the morphological and typological aspects of the historic buildings (H-BIM, with a set of monitoring information. This combination of 3D digital survey, parametric modelling and monitoring datasets allows for the development of a system for archiving and visualizing structural health monitoring (SHM data (Fig. 1. The availability of a BIM database allows one to integrate a different kind of data stored in different ways (e.g. reports, tables, graphs, etc. with a representation directly connected to the 3D model of the structure with appropriate levels of detail (LoD. Data can be interactively accessed by selecting specific objects of the BIM, i.e. connecting the 3D position of the sensors installed with additional digital documentation. Such innovative BIM objects, which form a new BIM family for SHM, can be then reused in other projects, facilitating data archiving and exploitation of data acquired and processed. The application of advanced modeling techniques allows for the reduction of time and costs of the generation process, and support cooperation between different disciplines using a central workspace. However, it also reveals new challenges for parametric software and exchange formats. The case study presented is the medieval bridge Azzone Visconti in Lecco (Italy, in which multi-temporal vertical movements during load testing were integrated into H-BIM.

  16. Awareness of BIM adoption in Brunei

    Science.gov (United States)

    Rahman, Md Motiar

    2017-09-01

    Building Information Modelling (BIM) is getting increased attention day-by-day due to its many benefits, including clash detection, collaboration between contract parties, visualization future structure, optimized schedule and project control, waste control, design documentation, and harmonized facilities management. As such, many countries have already adopted BIM, and many other countries are exploring the potential of adopting it. However, it is still relatively new and unknown to some other countries like Brunei. This study was therefore undertaken to generate and/or gauge the awareness of Brunei construction industry participants, targeting adoption of BIM, through a structured questionnaire survey. Responses from 90 industry participants reveal that Brunei Construction industry is not well aware of BIM, lack the required technical knowledge and application in construction, and cost involvement. They are unsure about the potential benefits and barriers to implementing BIM. However, respondents are hopeful that BIM can bring the required changes in construction, willing to adopt BIM, expects cliental support with initial investment for its adoption, and believe that BIM is the future of construction project information management. On the whole, private sector was seen to be more aware on BIM than public sector. The study outcomes are expected to provide the policy makers a first-hand information on the industry awareness on BIM, which in turn help them for further exploration / examination and to design any action plan and guidelines for BIM adoption.

  17. Cycloheximide Can Induce Bax/Bak Dependent Myeloid Cell Death Independently of Multiple BH3-Only Proteins.

    Directory of Open Access Journals (Sweden)

    Katharine J Goodall

    Full Text Available Apoptosis mediated by Bax or Bak is usually thought to be triggered by BH3-only members of the Bcl-2 protein family. BH3-only proteins can directly bind to and activate Bax or Bak, or indirectly activate them by binding to anti-apoptotic Bcl-2 family members, thereby relieving their inhibition of Bax and Bak. Here we describe a third way of activation of Bax/Bak dependent apoptosis that does not require triggering by multiple BH3-only proteins. In factor dependent myeloid (FDM cell lines, cycloheximide induced apoptosis by a Bax/Bak dependent mechanism, because Bax-/-Bak-/- lines were profoundly resistant, whereas FDM lines lacking one or more genes for BH3-only proteins remained highly sensitive. Addition of cycloheximide led to the rapid loss of Mcl-1 but did not affect the expression of other Bcl-2 family proteins. In support of these findings, similar results were observed by treating FDM cells with the CDK inhibitor, roscovitine. Roscovitine reduced Mcl-1 abundance and caused Bax/Bak dependent cell death, yet FDM lines lacking one or more genes for BH3-only proteins remained highly sensitive. Therefore Bax/Bak dependent apoptosis can be regulated by the abundance of anti-apoptotic Bcl-2 family members such as Mcl-1, independently of several known BH3-only proteins.

  18. The perceived value of using BIM for energy simulation

    Science.gov (United States)

    Lewis, Anderson M.

    Building Information Modeling (BIM) is becoming an increasingly important tool in the Architectural, Engineering & Construction (AEC) industries. Some of the benefits associated with BIM include but are not limited to cost and time savings through greater trade and design coordination, and more accurate estimating take-offs. BIM is a virtual 3D, parametric design software that allows users to store information of a model within and can be used as a communication platform between project stakeholders. Likewise, energy simulation is an integral tool for predicting and optimizing a building's performance during design. Creating energy models and running energy simulations can be a time consuming activity due to the large number of parameters and assumptions that must be addressed to achieve reasonably accurate results. However, leveraging information imbedded within Building Information Models (BIMs) has the potential to increase accuracy and reduce the amount of time required to run energy simulations and can facilitate continuous energy simulations throughout the design process, thus optimizing building performance. Although some literature exists on how design stakeholders perceive the benefits associated with leveraging BIM for energy simulation, little is known about how perceptions associated with leveraging BIM for energy simulation differ between various green design stakeholder user groups. Through an e-survey instrument, this study seeks to determine how perceptions of using BIMs to inform energy simulation differ among distinct design stakeholder groups, which include BIM-only users, energy simulation-only users and BIM and energy simulation users. Additionally, this study seeks to determine what design stakeholders perceive as the main barriers and benefits of implementing BIM-based energy simulation. Results from this study suggest that little to no correlation exists between green design stakeholders' perceptions of the value associated with using

  19. The new Federal Act for the protection against nuisances (BImSchV)

    International Nuclear Information System (INIS)

    Froeba, K.; Thomas, L.

    1977-01-01

    Text of the decree with introduction and comprehensive explanations. Furnaces (1st decree of BImSchV); Chemical purification installations (2nd decree of BImSchV); sulfur content of light fuel oil and diesel oil (3rd decree of BImSchV); installations subject to licensing (4th decree of BImSchV); persons authorized with the protection against nuisances (5th decree of BImSchV); know-how and reliability of these persons (6th decree of BImSchV); ejection limitation for wood dust (7th decree of BImSchV); limitation of noise made by lawn mowing machines (8th decree of BImSchV); principles of the licensing procedure (9th decree of BImSchV). Text of the Federal Act for the Protection Against Nuisances. (orig.) [de

  20. Working with Open BIM Standards to Source Legal Spaces for a 3D Cadastre

    Directory of Open Access Journals (Sweden)

    Jennifer Oldfield

    2017-11-01

    Full Text Available Much work has already been done on how a 3D Cadastre should best be developed. An inclusive information model, the Land Administration Model (LADM ISO 19152 has been developed to provide an international framework for how this can best be done. This conceptual model does not prescribe the technical data format. One existing source from which data could be obtained is 3D Building Information Models (BIMs, or, more specifically in this context, BIMs in the form of one of buildingSMART’s open standards: the Industry Foundation Classes (IFC. The research followed a standard BIM methodology of first defining the requirements through the use of the Information Delivery Manual (IDM ISO29481 and then translating the process described in the IDM into technical requirements using a Model View Definition (MVD, a practice to coordinate upfront the multidisciplinary stakeholders of a construction project. The proposed process model illustrated how the time it takes to register 3D spatial units in a Land Registry could substantially be reduced compared to the first 3D registration in the Netherlands. The modelling of an MVD or a subset of the IFC data model helped enable the creation and exchange of boundary representations of topological objects capable of being combined into a 3D legal space overview map.

  1. Enhanced Hydrogen Storage Properties and Reversibility of LiBH4 Confined in Two-Dimensional Ti3C2.

    Science.gov (United States)

    Zang, Lei; Sun, Weiyi; Liu, Song; Huang, Yike; Yuan, Huatang; Tao, Zhanliang; Wang, Yijing

    2018-05-30

    LiBH 4 is of particular interest as one of the most promising materials for solid-state hydrogen storage. Herein, LiBH 4 is confined into a novel two-dimensional layered Ti 3 C 2 MXene through a facile impregnation method for the first time to improve its hydrogen storage performance. The initial desorption temperature of LiBH 4 is significantly reduced, and the de-/rehydrogenation kinetics are remarkably enhanced. It is found that the initial desorption temperature of LiBH 4 @2Ti 3 C 2 hybrid decreases to 172.6 °C and releases 9.6 wt % hydrogen at 380 °C within 1 h, whereas pristine LiBH 4 only releases 3.2 wt % hydrogen under identical conditions. More importantly, the dehydrogenated products can partially rehydrogenate at 300 °C and under 95 bar H 2 . The nanoconfined effect caused by unique layered structure of Ti 3 C 2 can hinder the particles growth and agglomeration of LiBH 4 . Meanwhile, Ti 3 C 2 could possess superior effect to destabilize LiBH 4 . The synergetic effect of destabilization and nanoconfinement contributes to the remarkably lowered desorption temperature and improved de-/rehydrogenation kinetics.

  2. Open BIM in courses in engineering education

    DEFF Research Database (Denmark)

    Karlshøj, Jan; Vestergaard, Flemming

    2016-01-01

    The Technical University of Denmark has included open BIM in its BIM or BIM-related courses for bachelor, master and PhD students studying civil or architectural engineering. A majority of students are introduced to open BIM during their education, and those who are selecting courses in advanced...... BIM or building design are becoming more familiar with the concept. A number of students are including open BIM in their bachelor projects or master theses. The main reason for including open BIM in teaching is that open BIM has been a mandatory deliverable in Denmark since 2007 in state......-financed construction projects through the IFC format. From 2013 the requirements also included social housing and all public building projects. Students are exploring the capabilities of open BIM, and have been able both to identify satisfactory results as well as propose enhancements in order to compensate...

  3. Mimetic discretization methods

    CERN Document Server

    Castillo, Jose E

    2013-01-01

    To help solve physical and engineering problems, mimetic or compatible algebraic discretization methods employ discrete constructs to mimic the continuous identities and theorems found in vector calculus. Mimetic Discretization Methods focuses on the recent mimetic discretization method co-developed by the first author. Based on the Castillo-Grone operators, this simple mimetic discretization method is invariably valid for spatial dimensions no greater than three. The book also presents a numerical method for obtaining corresponding discrete operators that mimic the continuum differential and

  4. Smart-BIM (Building Information Modeling)

    NARCIS (Netherlands)

    de Vries, B.; Allameh, E.; Heidari Jozam, M.; van Bronswijk, J.E.M.H.; Maas, G.J.; van Gassel, F. J.M.

    2012-01-01

    Purpose: After a long period of international research and development, BIM has become mature. Many tools support the BIM process, or at least they claim. BIM not only offers opportunities for the Architectural Engineering and Construction industry, but also for the client. In this paper we don’t

  5. Discovery and molecular characterization of a Bcl-2-regulated cell death pathway in schistosomes.

    Science.gov (United States)

    Lee, Erinna F; Clarke, Oliver B; Evangelista, Marco; Feng, Zhiping; Speed, Terence P; Tchoubrieva, Elissaveta B; Strasser, Andreas; Kalinna, Bernd H; Colman, Peter M; Fairlie, W Douglas

    2011-04-26

    Schistosomiasis is an infectious disease caused by parasites of the phylum platyhelminthe. Here, we describe the identification and characterization of a Bcl-2-regulated apoptosis pathway in Schistosoma japonicum and S. mansoni. Genomic, biochemical, and cell-based mechanistic studies provide evidence for a tripartite pathway, similar to that in humans including BH3-only proteins that are inhibited by prosurvival Bcl-2-like molecules, and Bax/Bak-like proteins that facilitate mitochondrial outer-membrane permeabilization. Because Bcl-2 proteins have been successfully targeted with "BH3 mimetic" drugs, particularly in the treatment of cancer, we investigated whether schistosome apoptosis pathways could provide targets for future antischistosomal drug discovery efforts. Accordingly, we showed that a schistosome prosurvival protein, sjA, binds ABT-737, a well-characterized BH3 mimetic. A crystal structure of sjA bound to a BH3 peptide provides direct evidence for the feasibility of developing BH3 mimetics to target Bcl-2 prosurvival proteins in schistosomes, suggesting an alternative application for this class of drugs beyond cancer treatment.

  6. BIM-BASED SCHEDULING OF CONSTRUCTION

    DEFF Research Database (Denmark)

    Andersson, Niclas; Büchmann-Slorup, Rolf

    2010-01-01

    The potential of BIM is generally recognized in the construction industry, but the practical application of BIM for management purposes is, however, still limited among contractors. The objective of this study is to review the current scheduling process of construction in light of BIM...... and communicate. Scheduling on the detailed level, on the other hand, follows a stipulated approach to scheduling, i.e. the Last Planner System (LPS), which is characterized by involvement of all actors in the construction phase. Thus, the major challenge when implementing BIM-based scheduling is to improve...

  7. Unmet Medical Needs in Non-Small-Cell Lung Cancer Treatment: How to Design Pre-Emptive Combination Therapies

    Directory of Open Access Journals (Sweden)

    Niki Karachaliou

    2014-11-01

    Full Text Available The rapidly expanding catalogue of human oncogenic mutations, coupled with difficulties in identifying the cellular targets of active compounds in phenotypic screens, has refocused drug discovery efforts on inhibitors of specific cellular proteins. This new ‘target-based’ approach has enjoyed some spectacular successes in several types of tumours, including non-small-cell lung cancer (NSCLC. Epidermal growth factor receptor (EGFR mutations occur in 17% of NSCLC patients, with notable response to single agent therapy. Unfortunately, all patients eventually develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs, while complete remission rate to EGFR TKIs monotherapy is low. Priming BIM, a proapoptotic signalling BH3-only protein, induces sensitivity to erlotinib [Tarceva®] in EGFR-mutant cell lines. Synthetic lethal approaches and pre-emptive therapies based on the initial expression of BIM may significantly improve treatment outcomes. EGFR mutations result in transient pro-death imbalance of survival and apoptotic signalling in response to EGFR inhibition. Src homology 2 domain-containing phosphatase 2 is essential to the balance between extracellular signal-regulated kinase, phosphoinositide- 3-kinase/protein kinase B and signal transducer and activator of transcription 3 activity. Furthermore, stromal hepatocyte growth factor confers EGFR TKI resistance and induces inter-receptor crosstalk with Ephrin Type-A receptor 2, CDCP1, AXL, and JAK1. A better understanding of the complex cancer molecular biology of EGFR mutant lung cancer is crucial for development of effective treatment and design of successful future clinical studies.

  8. Bim Automation: Advanced Modeling Generative Process for Complex Structures

    Science.gov (United States)

    Banfi, F.; Fai, S.; Brumana, R.

    2017-08-01

    The new paradigm of the complexity of modern and historic structures, which are characterised by complex forms, morphological and typological variables, is one of the greatest challenges for building information modelling (BIM). Generation of complex parametric models needs new scientific knowledge concerning new digital technologies. These elements are helpful to store a vast quantity of information during the life cycle of buildings (LCB). The latest developments of parametric applications do not provide advanced tools, resulting in time-consuming work for the generation of models. This paper presents a method capable of processing and creating complex parametric Building Information Models (BIM) with Non-Uniform to NURBS) with multiple levels of details (Mixed and ReverseLoD) based on accurate 3D photogrammetric and laser scanning surveys. Complex 3D elements are converted into parametric BIM software and finite element applications (BIM to FEA) using specific exchange formats and new modelling tools. The proposed approach has been applied to different case studies: the BIM of modern structure for the courtyard of West Block on Parliament Hill in Ottawa (Ontario) and the BIM of Masegra Castel in Sondrio (Italy), encouraging the dissemination and interaction of scientific results without losing information during the generative process.

  9. Development of Al2O3 carrier-Ru composite catalyst for hydrogen generation from alkaline NaBH4 hydrolysis

    International Nuclear Information System (INIS)

    Huang, Yao-Hui; Su, Chia-Chi; Wang, Shu-Ling; Lu, Ming-Chun

    2012-01-01

    A recyclable and reusable Ru/Al 2 O 3 catalyst is prepared for hydrogen generation from the hydrolysis process of alkaline sodium borohydride (NaBH 4 ) solution. The hydrogen generation rate by the hydrolysis and methanolysis of alkaline NaBH 4 was explored as a function of NaOH concentration. Meantime, the byproducts derived from the spent alkaline NaBH 4 solution were characterized by X-ray diffraction (XRD), scanning electro microscope/energy dispersive spectrometer (SEM/EDS) and NMR (Nuclear Magnetic Resonance). The effect of NaOH concentration on the hydrogen generation from the hydrolysis of NaBH 4 significantly depends on the type of catalysts. With increasing NaOH concentration, the hydrogen generation rates decrease when using ruthenium (Ru) composite as a catalyst. The hydrogen generation rate of the methanolysis of NaBH 4 is significantly inhibited in the presence of NaOH as compared with the hydrolysis of NaBH 4 . The durability test of the Ru/Al 2 O 3 catalyst shows that the hydrogen generation rate decreases with recycling and reuse. The XRD and NMR analysis results show that the borate hydrate (NaBO 2 H 2 O) was derived from the hydrolysis of 20 wt% and 30 wt% NaBH 4 . -- Highlights: ► A recyclable Ru/Al 2 O 3 catalyst was synthesized for hydrogen generation. ► Ru/Al 2 O 3 significantly promotes the hydrogen generation rate from alkaline NaBH 4 solution. ► The prepared Ru/Al 2 O 3 catalyst can easily collect from the spent alkaline NaBH 4 solution.

  10. Screening for potential targets for therapy in mesenchymal, clear cell, and dedifferentiated chondrosarcoma reveals Bcl-2 family members and TGFβ as potential targets

    DEFF Research Database (Denmark)

    van Oosterwijk, Jolieke G; Meijer, Danielle; van Ruler, Maayke A J H

    2013-01-01

    . As in conventional chondrosarcoma, antiapoptotic proteins (Bcl-2, and/or Bcl-xl) were highly expressed in all subtypes. Inhibition with the BH-3 mimetic ABT-737 rendered dedifferentiated chondrosarcoma cell lines sensitive to doxorubicin or cisplatin. Our data indicate that antiapoptotic proteins may play...

  11. Building renovations in BIM systems

    Directory of Open Access Journals (Sweden)

    Smutný Marian

    2018-01-01

    Full Text Available Renovation of buildings is a demanding challenge for computer systems. Nowadays, complex 3D models of historic buildings can be scanned and modelled, including sculptural filigrees and stucco decorations with possibility to generate different projections, cross-sections and elevations according to descriptive geometry rules. However, all of this falls within the field of “3D Modelling”. BIM systems work with elements that have to be classified according to their purpose, or according to the way they are realized. The system is then able to sort, filter or group them. Also, it is able to compute their bill of quantity and quality based on their attributes. Last but not least, it has to be able to schematically display civil engineering drawings on the basis of classification of the elements which differ considerably from the display of descriptive geometry. In regular constructions, repeatability and predictability of the links between the elements suit computer systems. Thus, the issue of building renovations in BIM systems is to find a balance between modelling irregular constructions and irregular space arrangements, while maintaining the ability to interact with other BIM elements.

  12. Unimodular-mimetic cosmology

    International Nuclear Information System (INIS)

    Nojiri, S; Odintsov, S D; Oikonomou, V K

    2016-01-01

    We combine the unimodular gravity and mimetic gravity theories into a unified theoretical framework, which is proposed to provide a suggestive proposal for a framework that may assist in the discussion and search for a solution to the cosmological constant problem and the dark matter issue. After providing the formulation of the unimodular mimetic gravity and investigating all the new features that the vacuum unimodular gravity implies, by using the underlying reconstruction method, we realize some well known cosmological evolutions, with some of these being exotic for the ordinary Einstein–Hilbert gravity. Specifically we provide the vacuum unimodular mimetic gravity description of the de Sitter cosmology and of the perfect fluid with constant equation of state cosmology. As we demonstrate, these cosmologies can be realized by vacuum mimetic unimodular gravity, without the existence of any matter fluid source. Moreover, we investigate how cosmologically viable cosmologies, which are compatible with the recent observational data, can be realized by the vacuum unimodular mimetic gravity. Since in some cases, a graceful exit from inflation problem might exist, we provide a qualitative description of the mechanism that can potentially generate the graceful exit from inflation in these theories, by searching for the unstable de Sitter solutions in the context of unimodular mimetic theories of gravity. (paper)

  13. Benefit Evaluation of Implementing BIM in Construction Projects

    Science.gov (United States)

    Chou, Hui-Yu; Chen, Pei-Yu

    2017-10-01

    Since 2014, public construction projects in Taiwan have progressively undertaken steps to promote the use of Building Information Modelling (BIM) technology, the use of BIM has therefore become a necessity for contractors. However, issues such as the high upfront costs relating to software and hardware setup and BIM user training, combined with the difficulties of incorporating BIM into existing workflow operations and management systems, remain a challenge to contractors. Consequently, the benefits stemming from the BIM implementation in turn will affect the activeness and enthusiasm of contractors to implement BIM. While there have been previous studies abroad where the benefits relating to BIM implementation had been calculated and quantified numerically, a benefit evaluation index would require considerations for regional industry practices and characteristics. This study established a benefit evaluation index and method for the implementation of BIM suitable for contractors in Taiwan. The three main principal indexes are: (1) RCR means the effects of reducing costs associated with rework; (2) SDR & DPR mean the effects of mitigating delays that occur due to construction interface coordination or rework, as well as the effects of reducing the penalty costs associated with overdue delivery; (3) AQE means the effects of improving the ability to estimate the amounts of building materials and resources. This study also performed a benefit evaluation calculation of a real world case study construction project using the first two established indexes. The results showed a 0.16% reduction in rework costs, a 6.49% reduction in delays that occur from construction interface coordination or rework, and a 5.0% reduction in penalty costs associated with overdue deliveries. The results demonstrated the applicability of the benefit evaluation index established in this study for real world construction projects.

  14. Open BIM in course on advanced building design

    DEFF Research Database (Denmark)

    Karlshøj, Jan

    2016-01-01

    shall hand in BIM models in open BIM, specifically in IFC-format. The paper describes how the course and use of BIM is evaluated by the students, and the finding correcting the delivered BIM models in IFC-format. Use of model servers and BCF are briefly described. Issues regarding challenges...... in coordination, teamwork building and mutual dependencies were registered from students’ evaluation of the course. Overall, the students reported becoming familiar with open BIM and experienced the freedom to choose their preferred BIM tool for each specific job to see if it was possible to coordinate a building...... design project using open BIM. Graduate students working in the building construction industry expressed satisfaction with the course....

  15. Building information modelling (BIM)

    CSIR Research Space (South Africa)

    Conradie, Dirk CU

    2009-02-01

    Full Text Available The concept of a Building Information Model (BIM) also known as a Building Product Model (BPM) is nothing new. A short article on BIM will never cover the entire filed, because it is a particularly complex filed that is recently beginning to receive...

  16. Theoretical investigation of structure and stability of molecules of borohydrides B2H6, AlBH6 and ScBH6

    International Nuclear Information System (INIS)

    Musaev, D.G.; Zyubin, A.S.; Charkin, O.P.; Bonakkorsi, R.; Tomazi, Ya.

    1988-01-01

    Geometry of alternative structures of M 3+ BH 6 molecules are optimized on the two-exponent bases; their energies are refined with a fuller basis DEHD taking into account electron correlation within the frames of the MP3 method. The tendencies in the change of relative energies of the structures and their stability to decomposition are analyzed. It is noted that AlBH 6 and ScBH 6 molecules are not rigid to migration of M 3+ H 2 + ''cation'' round BH 4 - anion, as well ScBH 6 molecules are flexible to rotation of H 2 Sc group round the Sc-B axis. The data are compared with the results of previous similar calculations of borohydrides of elements in the first two groups (Li-Cu and Be-Zn)

  17. Combination of erlotinib and EGCG induces apoptosis of head and neck cancers through posttranscriptional regulation of Bim and Bcl-2.

    Science.gov (United States)

    Haque, Abedul; Rahman, Mohammad Aminur; Chen, Zhuo Georgia; Saba, Nabil F; Khuri, Fadlo R; Shin, Dong M; Ruhul Amin, A R M

    2015-07-01

    Combinatorial approaches using two or more compounds are gaining increasing attention for cancer therapy. We have previously reported that the combination of the EGFR-TKI erlotinib and epigallocatechin-3-gallate (EGCG) exhibited synergistic chemopreventive effects in head and neck cancers by inducing the expression of Bim, p21, p27, and by inhibiting the phosphorylation of ERK and AKT and expression of Bcl-2. In the current study, we further investigated the mechanism of regulation of Bim, Bcl-2, p21 and p27, and their role in apoptosis. shRNA-mediated silencing of Bim significantly inhibited apoptosis induced by the combination of erlotinib and EGCG (p = 0.005). On the other hand, overexpression of Bcl-2 markedly protected cells from apoptosis (p = 0.003), whereas overexpression of constitutively active AKT only minimally protected cells from apoptosis induced by the combination of the two compounds. Analysis of mRNA expression by RT-PCR revealed that erlotinib, EGCG and their combination had no significant effects on the mRNA expression of Bim, p21, p27 or Bcl-2 suggesting the post-transcriptional regulation of these molecules. Furthermore, we found that erlotinib or the combination of EGCG and erlotinib inhibited the phosphorylation of Bim and stabilized Bim after inhibition of protein translation by cycloheximide. Taken together, our results strongly suggest that the combination of erlotinib and EGCG induces apoptosis of SCCHN cells by regulating Bim and Bcl-2 at the posttranscriptional level.

  18. Studies of the effects of TiCl{sub 3} in LiBH{sub 4}/CaH{sub 2}/TiCl{sub 3} reversible hydrogen storage system

    Energy Technology Data Exchange (ETDEWEB)

    Liu Dongan [Ford Motor Company, Research and Advanced Engineering, MD 1170/RIC, Dearborn, MI 48121 (United States); Department of Mechanical Engineering, University of Michigan, 1023 H. H. Dow Building 2350 Hayward Street, Ann Arbor, MI 48109-2125 (United States); Yang Jun, E-mail: jyang27@ford.com [Ford Motor Company, Research and Advanced Engineering, MD 1170/RIC, Dearborn, MI 48121 (United States); Ni Jun [Department of Mechanical Engineering, University of Michigan, 1023 H. H. Dow Building 2350 Hayward Street, Ann Arbor, MI 48109-2125 (United States); Drews, Andy [Ford Motor Company, Research and Advanced Engineering, MD 1170/RIC, Dearborn, MI 48121 (United States)

    2012-02-15

    Highlights: Black-Right-Pointing-Pointer We systematically studied the effects of TiCl{sub 3} in LiBH{sub 4}/CaH{sub 2}/TiCl{sub 3} hydrogen storage system. Black-Right-Pointing-Pointer It is found that adding 0.25 TiCl{sub 3} produces fully reversible hydrogen absorption and desorption and a lower desorption temperature. Black-Right-Pointing-Pointer LiCl experiences four different states, i.e. 'formed-solid solution-molten solution-precipitation', in the whole desorption process of the system. Black-Right-Pointing-Pointer The incorporation of LiCl into LiBH{sub 4} forms more viscous molten LiBH{sub 4}{center_dot}LiCl, leading to fast kinetics. Black-Right-Pointing-Pointer The precipitation and re-incorporation of LiCl into LiBH{sub 4} lead to a fully reversible complex hydrogen storage system. - Abstract: In the present study, the effects of TiCl{sub 3} on desorption kinetics, absorption/desorption reversibility, and related phase transformation processes in LiBH{sub 4}/CaH{sub 2}/TiCl{sub 3} hydrogen storage system was studied systematically by varying its concentration (x = 0, 0.05, 0.15 and 0.25). The results show that LiCl forms during ball milling of 6LiBH{sub 4}/CaH{sub 2}/xTiCl{sub 3} and that as temperature increases, o-LiBH{sub 4} transforms into h-LiBH{sub 4}, into which LiCl incorporates, forming solid solution of LiBH{sub 4}{center_dot}LiCl, which melts above 280 Degree-Sign C. Molten LiBH{sub 4}{center_dot}LiCl is more viscous than molten LiBH{sub 4}, preventing the clustering of LiBH{sub 4} and the accompanied agglomeration of CaH{sub 2}, and thus preserving the nano-sized phase arrangement formed during ball milling. Above 350 Degree-Sign C, the molten solution LiBH{sub 4}{center_dot}LiCl further reacts with CaH{sub 2}, precipitating LiCl. The main hydrogen desorption reaction is between molten LiBH{sub 4}{center_dot}LiCl and CaH{sub 2} and not between molten LiBH{sub 4} and CaH{sub 2}. This alters the hydrogen reaction thermodynamics and

  19. Involvement of the JNK/FOXO3a/Bim Pathway in Neuronal Apoptosis after Hypoxic-Ischemic Brain Damage in Neonatal Rats.

    Directory of Open Access Journals (Sweden)

    Deyuan Li

    Full Text Available c-Jun N-terminal kinase (JNK plays a key role in the regulation of neuronal apoptosis. Previous studies have revealed that forkhead transcription factor (FOXO3a is a critical effector of JNK-mediated tumor suppression. However, it is not clear whether the JNK/FOXO3a pathway is involved in neuronal apoptosis in the developing rat brain after hypoxia-ischemia (HI. In this study, we generated an HI model using postnatal day 7 rats. Fluorescence immunolabeling and Western blot assays were used to detect the distribution and expression of total and phosphorylated JNK and FOXO3a and the pro-apoptotic proteins Bim and CC3. We found that JNK phosphorylation was accompanied by FOXO3a dephosphorylation, which induced FOXO3a translocation into the nucleus, resulting in the upregulation of levels of Bim and CC3 proteins. Furthermore, we found that JNK inhibition by AS601245, a specific JNK inhibitor, significantly increased FOXO3a phosphorylation, which attenuated FOXO3a translocation into the nucleus after HI. Moreover, JNK inhibition downregulated levels of Bim and CC3 proteins, attenuated neuronal apoptosis and reduced brain infarct volume in the developing rat brain. Our findings suggest that the JNK/FOXO3a/Bim pathway is involved in neuronal apoptosis in the developing rat brain after HI. Agents targeting JNK may offer promise for rescuing neurons from HI-induced damage.

  20. Eliminating Legionella by inhibiting BCL-XL to induce macrophage apoptosis.

    Science.gov (United States)

    Speir, Mary; Lawlor, Kate E; Glaser, Stefan P; Abraham, Gilu; Chow, Seong; Vogrin, Adam; Schulze, Keith E; Schuelein, Ralf; O'Reilly, Lorraine A; Mason, Kylie; Hartland, Elizabeth L; Lithgow, Trevor; Strasser, Andreas; Lessene, Guillaume; Huang, David C S; Vince, James E; Naderer, Thomas

    2016-02-24

    Human pathogenic Legionella replicate in alveolar macrophages and cause a potentially lethal form of pneumonia known as Legionnaires' disease(1). Here, we have identified a host-directed therapeutic approach to eliminate intracellular Legionella infections. We demonstrate that the genetic deletion, or pharmacological inhibition, of the host cell pro-survival protein BCL-XL induces intrinsic apoptosis of macrophages infected with virulent Legionella strains, thereby abrogating Legionella replication. BCL-XL is essential for the survival of Legionella-infected macrophages due to bacterial inhibition of host-cell protein synthesis, resulting in reduced levels of the short-lived, related BCL-2 pro-survival family member, MCL-1. Consequently, a single dose of a BCL-XL-targeted BH3-mimetic therapy, or myeloid cell-restricted deletion of BCL-XL, limits Legionella replication and prevents lethal lung infections in mice. These results indicate that repurposing BH3-mimetic compounds, originally developed to induce cancer cell apoptosis, may have efficacy in treating Legionnaires' and other diseases caused by intracellular microbes.

  1. BIM 08-11

    DEFF Research Database (Denmark)

    2011-01-01

    During the last 10 years Building Information Modelling (BIM) has become an increasingly used tool in architectural design practice. The ideal that the architectural drawing evolves into a model that can contain information about its site, material and use, has presented architects with a new set....... The publication aims to outline and discuss our research findings, communicate our results and develop a perspective for future research projects into BIM and complex information modelling....

  2. Application of 6D Building Information Model (6D BIM) for Business-storage Building in Slovenia

    Science.gov (United States)

    Pučko, Zoran; Vincek, Dražen; Štrukelj, Andrej; Šuman, Nataša

    2017-10-01

    The aim of this paper is to present an application of 6D building information modelling (6D BIM) on a real business-storage building in Slovenia. First, features of building maintenance in general are described according to the current Slovenian legislation, and also a general principle of BIM is given. After that, step-by-step activities for modelling 6D BIM are exposed, namely from Element list for maintenance, determination of their lifetime and service measures, cost analysing and time analysing to 6D BIM modelling. The presented 6D BIM model is designed in a unique way in which cost analysis is performed as 5D BIM model with linked data to use BIM Construction Project Management Software (Vico Office), integrated with 3D BIM model, whereas time analysis as 4D BIM model is carried out as non-linked data with the help of Excel (without connection to 3D BIM model). The paper is intended to serve as a guide to the building owners to prepare 6D BIM and to provide an insight into the relevant dynamic information about intervals and costs for execution of maintenance works in the whole building lifecycle.

  3. From BIM to GIS at the Smithsonian Institution

    Science.gov (United States)

    Günther-Diringer, Detlef

    2018-05-01

    BIM-files (Building Information Models) are in modern architecture and building management a basic prerequisite for successful creation of construction engineering projects. At the facilities department of the Smithsonian Institution more than six hundred buildings were maintained. All facilities were digital available in an ESRI ArcGIS-environment with connection to the database information about single rooms with the usage and further maintenance information. These data are organization wide available by an intranet viewer, but only in a two-dimensional representation. Goal of the carried out project was the development of a workflow from available BIM-models to the given GIS-structure. The test-environment were the BIM-models of the buildings of the Smithsonian museums along the Washington Mall. Based on new software editions of Autodesk Revit, FME and ArcGIS Pro the workflow from BIM to the GIS-data structure of the Smithsonian was successfully developed and may be applied for the setup of the future 3D intranet viewer.

  4. Beyond Antibodies as Binding Partners: The Role of Antibody Mimetics in Bioanalysis.

    Science.gov (United States)

    Yu, Xiaowen; Yang, Yu-Ping; Dikici, Emre; Deo, Sapna K; Daunert, Sylvia

    2017-06-12

    The emergence of novel binding proteins or antibody mimetics capable of binding to ligand analytes in a manner analogous to that of the antigen-antibody interaction has spurred increased interest in the biotechnology and bioanalytical communities. The goal is to produce antibody mimetics designed to outperform antibodies with regard to binding affinities, cellular and tumor penetration, large-scale production, and temperature and pH stability. The generation of antibody mimetics with tailored characteristics involves the identification of a naturally occurring protein scaffold as a template that binds to a desired ligand. This scaffold is then engineered to create a superior binder by first creating a library that is then subjected to a series of selection steps. Antibody mimetics have been successfully used in the development of binding assays for the detection of analytes in biological samples, as well as in separation methods, cancer therapy, targeted drug delivery, and in vivo imaging. This review describes recent advances in the field of antibody mimetics and their applications in bioanalytical chemistry, specifically in diagnostics and other analytical methods.

  5. Web-based topology queries on a BIM model

    DEFF Research Database (Denmark)

    Rasmussen, Mads Holten; Hviid, Christian Anker; Karlshøj, Jan

    Building Information Modeling (BIM) is in the industry often confused with 3D-modeling regardless that the potential of modeling information goes way beyond performing clash detections on geometrical objects occupying the same physical space. Lately, several research projects have tried to change...... that by extending BIM with information using linked data technologies. However, when showing information alone the strong communication benefits of 3D are neglected, and a practical way of connecting the two worlds is currently missing. In this paper, we present a prototype of a visual query interface running...... is to establish a baseline for discussion of the general design choices that have been considered, and the developed application further serves as a proof of concept for combining BIM model data with a knowledge graph and potentially other sources of Linked Open Data, in a simple web interface....

  6. Alpha-helical destabilization of the Bcl-2-BH4-domain peptide abolishes its ability to inhibit the IP3 receptor.

    Directory of Open Access Journals (Sweden)

    Giovanni Monaco

    Full Text Available The anti-apoptotic Bcl-2 protein is the founding member and namesake of the Bcl-2-protein family. It has recently been demonstrated that Bcl-2, apart from its anti-apoptotic role at mitochondrial membranes, can also directly interact with the inositol 1,4,5-trisphosphate receptor (IP3R, the primary Ca(2+-release channel in the endoplasmic reticulum (ER. Bcl-2 can thereby reduce pro-apoptotic IP3R-mediated Ca(2+ release from the ER. Moreover, the Bcl-2 homology domain 4 (Bcl-2-BH4 has been identified as essential and sufficient for this IP3R-mediated anti-apoptotic activity. In the present study, we investigated whether the reported inhibitory effect of a Bcl-2-BH4 peptide on the IP 3R1 was related to the distinctive α-helical conformation of the BH4 domain peptide. We therefore designed a peptide with two glycine "hinges" replacing residues I14 and V15, of the wild-type Bcl-2-BH4 domain (Bcl-2-BH4-IV/GG. By comparing the structural and functional properties of the Bcl-2-BH4-IV/GG peptide with its native counterpart, we found that the variant contained reduced α-helicity, neither bound nor inhibited the IP 3R1 channel, and in turn lost its anti-apoptotic effect. Similar results were obtained with other substitutions in Bcl-2-BH4 that destabilized the α-helix with concomitant loss of IP3R inhibition. These results provide new insights for the further development of Bcl-2-BH4-derived peptides as specific inhibitors of the IP3R with significant pharmacological implications.

  7. Building information modelling (BIM: now and beyond

    Directory of Open Access Journals (Sweden)

    Salman Azhar

    2015-10-01

    Full Text Available Building Information Modeling (BIM, also called n-D Modeling or Virtual Prototyping Technology, is a revolutionary development that is quickly reshaping the Architecture-Engineering-Construction (AEC industry. BIM is both a technology and a process. The technology component of BIM helps project stakeholders to visualize what is to be built in a simulated environment to identify any potential design, construction or operational issues. The process component enables close collaboration and encourages integration of the roles of all stakeholders on a project. The paper presents an overview of BIM with focus on its core concepts, applications in the project life cycle and benefits for project stakeholders with the help of case studies. The paper also elaborates risks and barriers to BIM implementation and future trends.

  8. Building information modelling (BIM: now and beyond

    Directory of Open Access Journals (Sweden)

    Salman Azhar

    2012-12-01

    Full Text Available Building Information Modeling (BIM, also called n-D Modeling or Virtual Prototyping Technology, is a revolutionary development that is quickly reshaping the Architecture-Engineering-Construction (AEC industry. BIM is both a technology and a process. The technology component of BIM helps project stakeholders to visualize what is to be built in a simulated environment to identify any potential design, construction or operational issues. The process component enables close collaboration and encourages integration of the roles of all stakeholders on a project. The paper presents an overview of BIM with focus on its core concepts, applications in the project life cycle and benefits for project stakeholders with the help of case studies. The paper also elaborates risks and barriers to BIM implementation and future trends.

  9. Synthesis and evaluation of di- and trimeric hydroxylamine-based β-(1→3)-glucan mimetics.

    Science.gov (United States)

    Ferry, Angélique; Malik, Gaëlle; Guinchard, Xavier; Vĕtvička, Václav; Crich, David

    2014-10-22

    Di- and trimeric hydroxylamine-based mimetics of β-(1→3)-glucans have been accessed by an asymmetric synthesis route featuring an iterative double ring-closing reductive amination reaction. These oligomeric hydroxylamines are demonstrated to inhibit the staining of human neutrophils and of mouse macrophages by fluorescent anti-CR3 and anti-dectin-1 antibodies, respectively, and to stimulate phagocytosis, all in a linkage-dependent manner suggestive of binding to the lectin domains of complement receptor 3 (CR3) and dectin-1. The ability of these relatively short mimetics to bind to CR3 and dectin-1, as compared to the greater degree of polymerization required in β-(1→3)-glucans, is discussed in terms of the increased hydrophobicity of the α-face on replacement of the glycosidic bond by the hydroxylamine linkage.

  10. A Brief Introduction to Building Information Modeling (BIM and its interoperability with TRNSYS

    Directory of Open Access Journals (Sweden)

    Abdelaziz Naamane

    2015-08-01

    Full Text Available Abstract:Hand-drafted print, sketching and hand modeling were the standard  for building designs before the advent of computer aided design (CAD systems . Nowadays CAD systems are better understood, their adoption increased until the 2D, 3D CAD system  and the virtual reality became the norm. Their natural evolution has given rise to a new and more complex generation of building design tools known as building information modeling, or BIM. There is insufficient clarity about what BIM is, although this is improving, and there is much shared understanding. There is agreement that BIM is not just software. BIM is not just CAD, or geometric data. BIM is a collaboratively generated and maintained, data rich, information source for the life of the design process and beyond. In this paper , we present briefly the greatest value derived from BIM in the use and maintenance of buildings and the use of TRNSYS with BIM.

  11. Using BIM Technology to Optimize the Traditional Interior Design Work Mode

    Science.gov (United States)

    Zhu, Ning Ke

    2018-06-01

    the development of BIM technology and application in the field of architecture design has produced results, but BIM technology and application in the field of interior design is still immaturity because of construction and decoration engineering separation. The article analyzes the problems that BIM technology lead to the interior design work mode optimization, from the 3D visualization work environment, real-time collaborative design mode, physical analysis design mode, information integration design mode state the application in interior design.

  12. A Project-Based Quantification of BIM Benefits

    Directory of Open Access Journals (Sweden)

    Jian Li

    2014-08-01

    Full Text Available In the construction industry, research is being carried out to look for feasible methods and technologies to cut down project costs and waste. Building Information Modelling (BIM is certainly currently a promising technology/method that can achieve this. The output of the construction industry has a considerable scale; however, the concentration of the industry and the level of informatization are still not high. There is still a large gap in terms of productivity between the construction industry and other industries. Due to the lack of first-hand data regarding how much of an effect can be genuinely had by BIM in real cases, it is unrealistic for construction stakeholders to take the risk of widely adopting BIM. This paper focuses on the methodological quantification (through a case study approach of BIM's benefits in building construction resource management and real-time costs control, in contrast to traditional non-BIM technologies. Through the use of BIM technology for the dynamic querying and statistical analysis of construction schedules, engineering, resources and costs, the three implementations considered demonstrate how BIM can facilitate the comprehensive grasp of a project's implementation and progress, identify and solve the contradictions and conflicts between construction resources and costs controls, reduce project over-spends and protect the supply of resources.

  13. Implementation of BIM in Spanish construction industry = Implementación BIM en la industria española de la construcción

    Directory of Open Access Journals (Sweden)

    Silvia Andrés

    2017-04-01

    La directiva UE 2014/24 invita a los Estados miembros a que fomenten, especifiquen y requieran el uso de Building Information Modeling (BIM en los proyectos de construcción financiados con fondos públicos de la UE a partir de 2016. El Proyecto QBIMInvest (financiado por la Universidad Europea de Madrid ha llevado a cabo una encuesta para conocer el uso de BIM en el sector AEC español. Las 548 respuestas, obtenidas de una muestra de profesionales españoles del sector, muestran que las herramientas BIM actualmente solamente están siendo utilizadas en la etapa de diseño de edificios residenciales. Hay pocos casos en los que se aplica en las etapas de construcción, operación y mantenimiento o en otros tipos de proyectos. Por otro lado, los profesionales piensan que van a necesitar por lo menos de 3 a 5 años para completar la integración de BIM en los proyectos.

  14. Application of Cloud Storage on BIM Life-Cycle Management

    Directory of Open Access Journals (Sweden)

    Lieyun Ding

    2014-08-01

    Full Text Available Because of its high information intensity, strong consistency and convenient visualization features, building information modelling (BIM has received widespread attention in the fields of construction and project management. However, due to large amounts of information, high integration, the need for resource sharing between various departments, the long time-span of the BIM application, challenges relating to data interoperability, security and cost all slow down the adoption of BIM. This paper constructs a BIM cloud storage concept system using cloud storage, an advanced computer technology, to solve the problem of mass data processing, information security, and cost problems in the existing application of BIM to full life-cycle management. This system takes full advantage of the cloud storage technique. Achievements are reached in four areas of BIM information management, involving security and licensing management, file management, work process management and collaborative management. The system expands the time and space scales, improves the level of participation, and reduces the cost of BIM. The construction of the BIM cloud storage system is one of the most important directions of the development of BIM, which benefits the promotion and further development of BIM to better serve construction and engineering project management.

  15. BIM TEACHING: CURRENT INTERNATIONAL TRENDS

    Directory of Open Access Journals (Sweden)

    Maria Bernardete Barison

    2012-02-01

    Full Text Available Existem hoje muitas companhias no mundo todo que estão desenvolvendo projetos utilizando processos BIM. Estas companhias estão procurando profissionais que possam efetivamente trabalhar em projetos BIM. Para atender a esta demanda muitas universidades têm implementado uma variedade de cursos para expor os alunos a esse novo paradigma. Contudo, essas experiências acadêmicas são relativamente novas e baseadas em pedagogias ainda não consolidadas. Com base em revisão da literatura internacional focando experiências didáticas sobre BIM, o presente estudo resume as tendências observadas. São apresentados os principais obstáculos enfrentados no ensino de BIM, exemplos de como superá-los e estratégias de implementação. As estratégias são apresentadas para os níveis: introdutório, intermediário e avançado. Sugere-se o estabelecimento de parcerias entre academia e indústria.

  16. BIM IMPLEMENTATION IN A NEW ZEALAND CONSULTING QUANTITY SURVEYING PRACTICE

    Directory of Open Access Journals (Sweden)

    Curtis Harrison

    2015-07-01

    Full Text Available 5D BIM – generating cost data via the building information modelling (BIM process- has the potential to be used by quantity surveyors (QSs to streamline their workflows and increase their provision of quality service. Consultant QSs experienced in the use 5D BIM, from the New Zealand office of one large global practice, were interviewed on their perceptions of the benefits of, and barriers to, 5D BIM implementation within their firm. Findings suggest that 5D BIM has numerous benefits over traditional methods, chiefly through the increased efficiency and visualization that BIM provides, along with the rapid identification of design changes. However, realization of these perceived benefits limited to date, due to several barriers hindering 5D BIM implementation: incomplete design and insufficient model object data in the BIM model; a lack of standards to facilitate electronic measurement; legal issues, and a lack of government support. However, participants perceived that 5D BIM implementation will achieve these benefits to a far greater extent in the future. Further research is recommended to identify the BIM skills which QSs will need in the future to reach the full potential of 5D BIM

  17. Developing Mobile- and BIM-Based Integrated Visual Facility Maintenance Management System

    Directory of Open Access Journals (Sweden)

    Yu-Cheng Lin

    2013-01-01

    Full Text Available Facility maintenance management (FMM has become an important topic for research on the operation phase of the construction life cycle. Managing FMM effectively is extremely difficult owing to various factors and environments. One of the difficulties is the performance of 2D graphics when depicting maintenance service. Building information modeling (BIM uses precise geometry and relevant data to support the maintenance service of facilities depicted in 3D object-oriented CAD. This paper proposes a new and practical methodology with application to FMM using BIM technology. Using BIM technology, this study proposes a BIM-based facility maintenance management (BIMFMM system for maintenance staff in the operation and maintenance phase. The BIMFMM system is then applied in selected case study of a commercial building project in Taiwan to verify the proposed methodology and demonstrate its effectiveness in FMM practice. Using the BIMFMM system, maintenance staff can access and review 3D BIM models for updating related maintenance records in a digital format. Moreover, this study presents a generic system architecture and its implementation. The combined results demonstrate that a BIMFMM-like system can be an effective visual FMM tool.

  18. BIM adoption within Australian Small and Medium-sized Enterprises (SMEs: an innovation diffusion model

    Directory of Open Access Journals (Sweden)

    M. Reza Hosseini

    2016-09-01

    Full Text Available Despite the envisaged benefits of BIM adoption for SMEs, BIM in SMEs has remained an underrepresented area within the available academic literature. This study proposes and draws upon a framework grounded on innovation diffusion theory (IDT to provide an illuminating insight into the current state of BIM and the main barriers to BIM adoption within Australian SMEs. Based on analyses of 135 questionnaires completed by SMEs through partial least squares structural equation modelling (PLS-SEM and grounded on the proposed framework, the current state of BIM adoption and barriers to BIM adoption for SMEs are discussed. The findings show that currently around 42% of Australian SMEs use BIM in Level 1 and Level 2 with only around 5% have tried Level 3. It comes to light that lack of knowledge within SMEs and across the construction supply chain is not a major barrier for Australian SMEs. In essence, the main barriers stem from the risks associated with an uncertain return on investment (ROI for BIM as perceived by key players in SMEs. The findings also show the validity of the framework proposed for explaining BIM adoption in Australian SMEs.

  19. Mimetic finite difference method

    Science.gov (United States)

    Lipnikov, Konstantin; Manzini, Gianmarco; Shashkov, Mikhail

    2014-01-01

    The mimetic finite difference (MFD) method mimics fundamental properties of mathematical and physical systems including conservation laws, symmetry and positivity of solutions, duality and self-adjointness of differential operators, and exact mathematical identities of the vector and tensor calculus. This article is the first comprehensive review of the 50-year long history of the mimetic methodology and describes in a systematic way the major mimetic ideas and their relevance to academic and real-life problems. The supporting applications include diffusion, electromagnetics, fluid flow, and Lagrangian hydrodynamics problems. The article provides enough details to build various discrete operators on unstructured polygonal and polyhedral meshes and summarizes the major convergence results for the mimetic approximations. Most of these theoretical results, which are presented here as lemmas, propositions and theorems, are either original or an extension of existing results to a more general formulation using polyhedral meshes. Finally, flexibility and extensibility of the mimetic methodology are shown by deriving higher-order approximations, enforcing discrete maximum principles for diffusion problems, and ensuring the numerical stability for saddle-point systems.

  20. Multi-agent chemotherapy overcomes glucocorticoid resistance conferred by a BIM deletion polymorphism in pediatric acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Sheila Xinxuan Soh

    Full Text Available A broad range of anti-cancer agents, including glucocorticoids (GCs and tyrosine kinase inhibitors (TKIs, kill cells by upregulating the pro-apoptotic BCL2 family member, BIM. A common germline deletion in the BIM gene was recently shown to favor the production of non-apoptotic BIM isoforms, and to predict inferior responses in TKI-treated chronic myeloid leukemia (CML and EGFR-driven lung cancer patients. Given that both in vitro and in vivo GC resistance are predictive of adverse outcomes in acute lymphoblastic leukemia (ALL, we hypothesized that this polymorphism would mediate GC resistance, and serve as a biomarker of poor response in ALL. Accordingly, we used zinc finger nucleases to generate ALL cell lines with the BIM deletion, and confirmed the ability of the deletion to mediate GC resistance in vitro. In contrast to CML and lung cancer, the BIM deletion did not predict for poorer clinical outcome in a retrospective analysis of 411 pediatric ALL patients who were uniformly treated with GCs and chemotherapy. Underlying the lack of prognostic significance, we found that the chemotherapy agents used in our cohort (vincristine, L-asparaginase, and methotrexate were each able to induce ALL cell death in a BIM-independent fashion, and resensitize BIM deletion-containing cells to GCs. Together, our work demonstrates how effective therapy can overcome intrinsic resistance in ALL patients, and suggests the potential of using combinations of drugs that work via divergent mechanisms of cell killing to surmount BIM deletion-mediated drug resistance in other cancers.

  1. Perspectives on Modelling BIM-enabled Estimating Practices

    Directory of Open Access Journals (Sweden)

    Willy Sher

    2014-12-01

    Full Text Available BIM-enabled estimating processes do not replace or provide a substitute for the traditional approaches used in the architecture, engineering and construction industries. This paper explores the impact of BIM on these traditional processes.  It identifies differences between the approaches used with BIM and other conventional methods, and between the various construction professionals that prepare estimates. We interviewed 17 construction professionals from client organizations, contracting organizations, consulting practices and specialist-project firms. Our analyses highlight several logical relationships between estimating processes and BIM attributes. Estimators need to respond to the challenges BIM poses to traditional estimating practices. BIM-enabled estimating circumvents long-established conventions and traditional approaches, and focuses on data management.  Consideration needs to be given to the model data required for estimating, to the means by which these data may be harnessed when exported, to the means by which the integrity of model data are protected, to the creation and management of tools that work effectively and efficiently in multi-disciplinary settings, and to approaches that narrow the gap between virtual reality and actual reality.  Areas for future research are also identified in the paper.

  2. Architectural Competition and BIM

    DEFF Research Database (Denmark)

    Sørensen, Nils Lykke; Frandsen, Anne Kathrine; Øien, Turid Borgestrand

    2015-01-01

    on architecturalcompetitions, a series of interviews was conducted with building clients as well as architects, focusing on the impact of the above-mentioned changes within the building sector on architectural competitions as an institution. In the interviews, ICT and notleast BIM was a recurring theme that both parties saw...... as having a positive impact on competitions. But when looking closely into the answers, these revealed diverse understandings of how and why the impact of BIM on competitions could be said to be positive. The paper sheds light on the interaction between the actors (building clients, architects and client...... consultants) and the applied technologies (competition forms, ICT tools, directives) in architectural competitions in a theoretical actor-network perspective. The diverging understandings of the role of BIM are demonstrating one of many negotiations in progress in the network of architectural competitions...

  3. Dehydrogenation of Surface-Oxidized Mixtures of 2LiBH4 + Al/Additives (TiF3 or CeO2

    Directory of Open Access Journals (Sweden)

    Juan Luis Carrillo-Bucio

    2017-11-01

    Full Text Available Research for suitable hydrogen storage materials is an important ongoing subject. LiBH4–Al mixtures could be attractive; however, several issues must be solved. Here, the dehydrogenation reactions of surface-oxidized 2LiBH4 + Al mixtures plus an additive (TiF3 or CeO2 at two different pressures are presented. The mixtures were produced by mechanical milling and handled under welding-grade argon. The dehydrogenation reactions were studied by means of temperature programmed desorption (TPD at 400 °C and at 3 or 5 bar initial hydrogen pressure. The milled and dehydrogenated materials were characterized by scanning electron microscopy (SEM, X-ray diffraction (XRD, and Fourier transformed infrared spectroscopy (FT-IR The additives and the surface oxidation, promoted by the impurities in the welding-grade argon, induced a reduction in the dehydrogenation temperature and an increase in the reaction kinetics, as compared to pure (reported LiBH4. The dehydrogenation reactions were observed to take place in two main steps, with onsets at 100 °C and 200–300 °C. The maximum released hydrogen was 9.3 wt % in the 2LiBH4 + Al/TiF3 material, and 7.9 wt % in the 2LiBH4 + Al/CeO2 material. Formation of CeB6 after dehydrogenation of 2LiBH4 + Al/CeO2 was confirmed.

  4. Transformation of Malaysian Construction Industry with Building Information Modelling (BIM

    Directory of Open Access Journals (Sweden)

    Latiffi Aryani Ahmad

    2016-01-01

    Full Text Available Building Information Modelling (BIM is a revolution of technology and a process that transformed the way building is planned, designed, analysed, constructed and managed. The revolution of technology and process could increase the quality of construction projects. The knowledge of BIM has been expanding in many countries including Malaysia. Since its inception, the use of BIM has broadened up widely with different purposes. The aims of this paper is to investigate the BIM implementation and uses in Malaysian construction projects. The methodologies adopted for structuring this paper are by using literature review and semi-structured interview with construction players that have experienced and being involved in projects using BIM. The purpose of literature review is to illustrate on the pervious research on the subject matter. Meanwhile, the purpose of interviews is to explore the involvement of construction players, years of experience in projects using BIM and BIM uses in construction projects. The findings revealed that BIM has been implemented in Malaysia since 2007 by various construction players, which are client, architect, C&S engineer, M&E engineer, QS, contractor, facilities manager and BIM consultant. The findings also revealed that BIM is used for project’ visualisation, improving project design, detecting design clashes, quantity take off and operation and maintenance. Further work will be focused on the current practices of construction players in projects using BIM.

  5. Building Information Modeling (BIM) for Indoor Environmental Performance Analysis

    DEFF Research Database (Denmark)

    The report is a part of a research assignment carried out by students in the 5ETCS course “Project Byggeri – [entitled as: Building Information Modeling (BIM) – Modeling & Analysis]”, during the 3rd semester of master degree in Civil and Architectural Engineering, Department of Engineering, Aarhus...... University. This includes seven papers describing BIM for Sustainability, concentrating specifically on individual topics regarding to Indoor Environment Performance Analysis....

  6. Understanding BIM Adoption in the AEC Industry: The Case of Jordan

    Science.gov (United States)

    Btoush, M.; Haron, AT

    2017-11-01

    Building information modelling (BIM) is a new and powerful technology implemented by many countries. The construction industry in Jordan plays a vital role and contributes immensely to the economic growth and development. In order to boost the industry and the economy, many industry players including engineers and contractors have recommended the implementation of BIM in Jordan. However, research demonstrates that successful BIM implementation is possible through the awareness of the different levels of BIM, which is a basic precondition for BIM implementation. Without a clear understanding of BIM, many companies would be unable to fully achieve BIM potentials or implement BIM in their building lifecycle. The objective of this study is to assess the current awareness of BIM technology in the Jordanian construction industry. A field interviews were conducted and 15 responses were collected and. The findings indicate that a significant proportion of respondents have little or no understanding of the concept of BIM. Also, the usage was found to be very low. Based on the results, a holistic roadmap was developed to spread the BIM adoption through the Jordanian construction industry. It is expected that this roadmap would lead to a better understanding and enable the industry towards more extensive implementation of BIM.

  7. Implementation of BIM in the Danish Building Sector

    DEFF Research Database (Denmark)

    Ussing, Lene Faber; Larsen, Jesper Kranker

    2014-01-01

    The Danish building sector has now for some years worked for implementation of BIM in the whole building process. In practice, it seems with the long way from the wish of using BIM in the whole building process to what really happens on the projects and building sites. To get an idea of how long...... the BIM implementation has come in the sector, a contractor company at present involved in one of the biggest public construction projects in Denmark was contacted to survey some employees at the project, because such a project ought to be one where BIM is best implemented. This survey shows the building...... sector is implementing BIM, but there are still big challenges to solve both internally in the company and externally both in the immediate environment and distant environment....

  8. CoQ10 Augments Rosuvastatin Neuroprotective Effect in a Model of Global Ischemia via Inhibition of NF-κB/JNK3/Bax and Activation of Akt/FOXO3A/Bim Cues

    Directory of Open Access Journals (Sweden)

    Sarah A. Abd El-Aal

    2017-10-01

    Full Text Available Statins were reported to lower the Coenzyme Q10 (CoQ10 content upon their inhibition of HMG-CoA reductase enzyme and both are known to possess neuroprotective potentials; therefore, the aim is to assess the possible use of CoQ10 as an adds-on therapy to rosuvastatin to improve its effect using global I/R model. Rats were allocated into sham, I/R, rosuvastatin (10 mg/kg, CoQ10 (10 mg/kg and their combination. Drugs were administered orally for 7 days before I/R. Pretreatment with rosuvastatin and/or CoQ10 inhibited the hippocampal content of malondialdehyde, nitric oxide, and boosted glutathione and superoxide dismutase. They also opposed the upregulation of gp91phox, and p47phox subunits of NADPH oxidase. Meanwhile, both agents reduced content/expression of TNF-α, iNOS, NF-κBp65, ICAM-1, and MPO. Besides, all regimens abated cytochrome c, caspase-3 and Bax, but increased Bcl-2 in favor of cell survival. On the molecular level, they increased p-Akt and its downstream target p-FOXO3A, with the inhibition of the nuclear content of FOXO3A to downregulate the expression of Bim, a pro-apoptotic gene. Additionally, both treatments downregulate the JNK3/c-Jun signaling pathway. The effect of the combination regimen overrides that of either treatment alone. These effects were reflected on the alleviation of the hippocampal damage in CA1 region inflicted by I/R. Together, these findings accentuate the neuroprotective potentials of both treatments against global I/R by virtue of their rigorous multi-pronged actions, including suppression of hippocampal oxidative stress, inflammation, and apoptosis with the involvement of the Akt/FOXO3A/Bim and JNK3/c-Jun/Bax signaling pathways. The study also nominates CoQ10 as an adds-on therapy with statins.

  9. Hindered rotational energy barriers of BH4- tetrahedra in β-Mg(BH4)2 from quasielastic neutron scattering and DFT calculations

    DEFF Research Database (Denmark)

    Blanchard, Didier; Maronsson, Jon Bergmann; Riktor, M.D.

    2012-01-01

    , around the 2-fold (C2) and 3-fold (C3) axes were observed at temperatures from 120 to 440 K. The experimentally obtained activation energies (EaC2 = 39 and 76 meV and EaC3 = 214 meV) and mean residence times between reorientational jumps are comparable with the energy barriers obtained from DFT......In this work, hindered rotations of the BH4- tetrahedra in Mg(BH4)2 were studied by quasielastic neutron scattering, using two instruments with different energy resolution, in combination with density functional theory (DFT) calculations. Two thermally activated reorientations of the BH4- units...... calculations. A linear dependency of the energy barriers for rotations around the C2 axis parallel to the Mg-Mg axis with the distance between these two axes was revealed by the DFT calculations. At the lowest temperature (120 K) only 15% of the BH4- units undergo rotational motion and from comparison with DFT...

  10. In silico identification of BIM-1 (2-methyl-1H-indol-3-yl) as a potential ...

    African Journals Online (AJOL)

    In silico identification of BIM-1 (2-methyl-1H-indol-3-yl) as a potential therapeutic agent against elevated protein kinase C beta associated diseases. U Saeed, N Nawaz, Y Waheed, N Chaudry, HT Bhatti, S Urooj, H Waheed, M Ashraf, UHK Naizi ...

  11. Discovery and molecular characterization of a Bcl-2–regulated cell death pathway in schistosomes

    Science.gov (United States)

    Lee, Erinna F.; Clarke, Oliver B.; Evangelista, Marco; Feng, Zhiping; Speed, Terence P.; Tchoubrieva, Elissaveta B.; Strasser, Andreas; Kalinna, Bernd H.; Colman, Peter M.; Fairlie, W. Douglas

    2011-01-01

    Schistosomiasis is an infectious disease caused by parasites of the phylum platyhelminthe. Here, we describe the identification and characterization of a Bcl-2–regulated apoptosis pathway in Schistosoma japonicum and S. mansoni. Genomic, biochemical, and cell-based mechanistic studies provide evidence for a tripartite pathway, similar to that in humans including BH3-only proteins that are inhibited by prosurvival Bcl-2–like molecules, and Bax/Bak-like proteins that facilitate mitochondrial outer-membrane permeabilization. Because Bcl-2 proteins have been successfully targeted with “BH3 mimetic” drugs, particularly in the treatment of cancer, we investigated whether schistosome apoptosis pathways could provide targets for future antischistosomal drug discovery efforts. Accordingly, we showed that a schistosome prosurvival protein, sjA, binds ABT-737, a well-characterized BH3 mimetic. A crystal structure of sjA bound to a BH3 peptide provides direct evidence for the feasibility of developing BH3 mimetics to target Bcl-2 prosurvival proteins in schistosomes, suggesting an alternative application for this class of drugs beyond cancer treatment. PMID:21444803

  12. VIRTUAL REALITY-BASED CLOUD BIM PLATFORM FOR INTEGRATED AEC PROJECTS

    OpenAIRE

    Goulding, Jack Steven; Pour Rahimian Leilabadi, Farzad; Wang, Xiangyu

    2014-01-01

    Building Information Modelling (BIM) has demonstrated the need for integrating collaborative design teams’ “project data”, to not only help coordinate the design, engineering, fabrication, construction, and maintenance of various trades, but also facilitate project integration and interchange. Numerous potential benefits have inspired several countries to consider the implications of implementing BIM Level 3 (Cloud) as an innovative way of further enhancing the design, management and delivery...

  13. Hydrolysis mechanism of BH4- in moist acetonitrile. III. Kinetic isotope effects

    International Nuclear Information System (INIS)

    Meeks, B.S. Jr.; Kreevoy, M.M.

    1979-01-01

    The present work and a concurrent paper show that, in the presence of acetic acid, BH 4 - in acetonitrile is rapidly converted to BH 3 OCOCH 3 - and that previous kinetic studies of the hydrolysis of BH 4 - in such solutions actually referred to the hydrolysis of BH 3 OCOCH 3 - . As previously shown, the substrate (now shown to be BH 3 OCOCH 3 - ) complexes with acetic acid, with a complexing constant of about 160. That complex hydrolyzes by spontaneous and water-catalyzed paths. The present paper shows that the latter reaction is accelerated 15 to 40% by the substitution of D for H on boron. The rate is reduced, by a factor of approx. 1.75, by replacing all the hydroxylic hydrogen with deuterium. These results are consistent with BH 3 OC(CH 3 )O . HOCOCH 3 as the acetic acid-substrate complex. The displacement of the incipient biacetate ion by water is rate determining in this process. Isotopic substitution at either position reduces the rate of the spontaneous process. Its mechanism is uncertain. 2 figures, 3 tables

  14. SPATIAL DMBS ARCHITECTURE FOR A FREE AND OPEN SOURCE BIM

    Directory of Open Access Journals (Sweden)

    S. Logothetis

    2017-08-01

    Full Text Available Recent research on the field of Building Information Modelling (BIM technology, revealed that except of a few, accessible and free BIM viewers there is a lack of Free & Open Source Software (FOSS BIM software for the complete BIM process. With this in mind and considering BIM as the technological advancement of Computer-Aided Design (CAD systems, the current work proposes the use of a FOSS CAD software in order to extend its capabilities and transform it gradually into a FOSS BIM platform. Towards this undertaking, a first approach on developing a spatial Database Management System (DBMS able to store, organize and manage the overall amount of information within a single application, is presented.

  15. Spatial Dmbs Architecture for a Free and Open Source Bim

    Science.gov (United States)

    Logothetis, S.; Valari, E.; Karachaliou, E.; Stylianidis, E.

    2017-08-01

    Recent research on the field of Building Information Modelling (BIM) technology, revealed that except of a few, accessible and free BIM viewers there is a lack of Free & Open Source Software (FOSS) BIM software for the complete BIM process. With this in mind and considering BIM as the technological advancement of Computer-Aided Design (CAD) systems, the current work proposes the use of a FOSS CAD software in order to extend its capabilities and transform it gradually into a FOSS BIM platform. Towards this undertaking, a first approach on developing a spatial Database Management System (DBMS) able to store, organize and manage the overall amount of information within a single application, is presented.

  16. Application of BIM technology in green scientific research office building

    Science.gov (United States)

    Ni, Xin; Sun, Jianhua; Wang, Bo

    2017-05-01

    BIM technology as a kind of information technology, has been along with the advancement of building industrialization application in domestic building industry gradually. Based on reasonable construction BIM model, using BIM technology platform, through collaborative design tools can effectively improve the design efficiency and design quality. Vanda northwest engineering design and research institute co., LTD., the scientific research office building project in combination with the practical situation of engineering using BIM technology, formed in the BIM model combined with related information according to the energy energy model (BEM) and the application of BIM technology in construction management stage made exploration, and the direct experience and the achievements gained by the architectural design part made a summary.

  17. Optimizing Energy Consumption in Building Designs Using Building Information Model (BIM

    Directory of Open Access Journals (Sweden)

    Egwunatum Samuel

    2016-09-01

    Full Text Available Given the ability of a Building Information Model (BIM to serve as a multi-disciplinary data repository, this paper seeks to explore and exploit the sustainability value of Building Information Modelling/models in delivering buildings that require less energy for their operation, emit less CO2 and at the same time provide a comfortable living environment for their occupants. This objective was achieved by a critical and extensive review of the literature covering: (1 building energy consumption, (2 building energy performance and analysis, and (3 building information modeling and energy assessment. The literature cited in this paper showed that linking an energy analysis tool with a BIM model helped project design teams to predict and create optimized energy consumption. To validate this finding, an in-depth analysis was carried out on a completed BIM integrated construction project using the Arboleda Project in the Dominican Republic. The findings showed that the BIM-based energy analysis helped the design team achieve the world’s first 103% positive energy building. From the research findings, the paper concludes that linking an energy analysis tool with a BIM model helps to expedite the energy analysis process, provide more detailed and accurate results as well as deliver energy-efficient buildings. The study further recommends that the adoption of a level 2 BIM and the integration of BIM in energy optimization analyse should be made compulsory for all projects irrespective of the method of procurement (government-funded or otherwise or its size.

  18. The role of managing knowledge and information in BIM implementation processes in the Czech Republic

    Directory of Open Access Journals (Sweden)

    Nývlt Vladimír

    2018-01-01

    Full Text Available Czech construction sector is at the initial stages of implementing and assessing Building Information Management (BIM on pilot projects. Object modeling developed over the last 20 years is seemed as a stable ground for many professionals. 3D data models are basis for further concepts associated with BIM, helping to support Co-ordinated Project Information (CPI and Integrated Project Delivery (IPD. This paper presents the role of managing knowledge, information and critical success factors (CSF associated with BIM implementation within the construction industry in the Czech Republic. Determining the CSF in the context of BIM maturity levels should support BIM implementation processes within the construction industry and also within the associated bodies (education, government, technology.

  19. Theoretical study of the properties of BH3NH3

    International Nuclear Information System (INIS)

    Binkley, J.S.; Thorne, L.R.

    1983-01-01

    Borane monoammoniate (BH 3 NH 3 ) has been studied using several ab initio electronic structure methods and Gaussian basis sets. Equilibrium geometries have been computed at the Hartree--Fock level and, using the electron-correlated Moller--Plesset perturbation method, carried out to third order (MP3) with double-zeta polarized quality basis sets. The computed MP3 geometry is in close agreement with recent microwave data; electron correlation is found to be necessary for a proper description of the B--N distance. Hartree--Fock dipole moments and harmonic vibrational frequencies are presented and discussed. Moller--Plesset perturbation theory carried out to fourth order with triple-zeta plus polarization basis sets is used to compute a B--N dissociation energy of 34.7 kcal mol -1 and a (Hartree--Fock zero-point corrected) rotational barrier of 2.065 kcal mol -1 , which is in excellent agreement with the experimental value. Analysis of the dissociation energy as a function of perturbation order indicates that terms involving triple and quadruple substitutions are required in the dissociation energy

  20. Construction of BIM-based SMART-ITL Facility Management System

    International Nuclear Information System (INIS)

    Jeon, Woo-Jin; Yi, Sung-Jae; Park, Hyun-Sik; Ryu, Sung-Uk; Bae, Hwang; Hwang, Sang-Chul; Min, Byung-Eui

    2015-01-01

    The flow area and volume are scaled down to 1/49. The ratio of the hydraulic diameter is 1/7. Therefore, SMART-ITL is a large-scale thermalhydraulic test facility with about 45 m height, which is consisted of 10 m underground and 35 m from the ground level. Until now, the management of design data and maintenance of large scale test facilities have been managed based on hard-copy information. Recently, Thermal Hydraulics Safety Research Division (THSRD) at Korea Atomic Energy Research Institute (KAERI) has developed Facility Management System (FMS) based Building Information Modeling (BIM) to manage its design data more effectively for these large scale test facilities of SMART-ITL and ATLAS, and this BIM technology has been applied to SMART-ITL at the first. This study proposed a method of effective management and maintenance of design data applied to the SMART-ITL. That is, a FMS was developed based on the BIM technology for SMART-ITL. Figure 2 shows an overview of FMS development process based on BIM technology. SMART-ITL FMS facilitates its management and maintenance more effectively and accurately by 3- dimensional visualization. It enables the shape information of large scale test facilities to be visualized intuitively in a virtual space, and the efficient maintenance of data and instruments is possible by linking 3D shape information

  1. Construction of BIM-based SMART-ITL Facility Management System

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Woo-Jin; Yi, Sung-Jae; Park, Hyun-Sik; Ryu, Sung-Uk; Bae, Hwang [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Hwang, Sang-Chul; Min, Byung-Eui [DDRsoft Co., Daejeon (Korea, Republic of)

    2015-10-15

    The flow area and volume are scaled down to 1/49. The ratio of the hydraulic diameter is 1/7. Therefore, SMART-ITL is a large-scale thermalhydraulic test facility with about 45 m height, which is consisted of 10 m underground and 35 m from the ground level. Until now, the management of design data and maintenance of large scale test facilities have been managed based on hard-copy information. Recently, Thermal Hydraulics Safety Research Division (THSRD) at Korea Atomic Energy Research Institute (KAERI) has developed Facility Management System (FMS) based Building Information Modeling (BIM) to manage its design data more effectively for these large scale test facilities of SMART-ITL and ATLAS, and this BIM technology has been applied to SMART-ITL at the first. This study proposed a method of effective management and maintenance of design data applied to the SMART-ITL. That is, a FMS was developed based on the BIM technology for SMART-ITL. Figure 2 shows an overview of FMS development process based on BIM technology. SMART-ITL FMS facilitates its management and maintenance more effectively and accurately by 3- dimensional visualization. It enables the shape information of large scale test facilities to be visualized intuitively in a virtual space, and the efficient maintenance of data and instruments is possible by linking 3D shape information.

  2. From BIM to life cycle information management in infrastructure

    NARCIS (Netherlands)

    Nederveen, G.A. van; Wolfert, R.; Ruitenbeek, M. van de

    2014-01-01

    In principle, Building Information Modelling (BIM) should provide a basis for infrastructure information management during the whole life-cycle. In practice however, the use of BIM is normally limited to the design and construction phases. It seems that the use of BIM information in other life-cycle

  3. BIM with VR for architectural simulations

    DEFF Research Database (Denmark)

    Hermund, Anders; Klint, Lars; Bundgård, Ture Slot

    2018-01-01

    experienced in physical space conditions and in virtual reality. The research intents to clarify to what extend subjective and objective attributes of architectural space can be conveyed through a direct use of BIM (Building Information Models) in Virtual Reality. Sixty test subjects experienced the same...... architectural BIM models can meaningfully improve architectural representation....

  4. Dehydrogenation mechanism of LiBH{sub 4} by Poly(methyl methacrylate)

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Jianmei [School of Materials Science and Engineering, and Key Laboratory of Advanced Energy Storage Materials of Guangdong Province, South China University of Technology, Guangzhou 510641 (China); China-Australia Joint Laboratory for Energy & Environmental Materials, South China University of Technology, Guangzhou 510641 (China); Yan, Yurong [School of Materials Science and Engineering, and Key Laboratory of Advanced Energy Storage Materials of Guangdong Province, South China University of Technology, Guangzhou 510641 (China); Ouyang, Liuzhang, E-mail: meouyang@scut.edu.cn [School of Materials Science and Engineering, and Key Laboratory of Advanced Energy Storage Materials of Guangdong Province, South China University of Technology, Guangzhou 510641 (China); China-Australia Joint Laboratory for Energy & Environmental Materials, South China University of Technology, Guangzhou 510641 (China); Key Laboratory for Fuel Cell Technology in Guangdong Province, South China University of Technology, Guangzhou 510641 (China); Wang, Hui [School of Materials Science and Engineering, and Key Laboratory of Advanced Energy Storage Materials of Guangdong Province, South China University of Technology, Guangzhou 510641 (China); China-Australia Joint Laboratory for Energy & Environmental Materials, South China University of Technology, Guangzhou 510641 (China); Zhu, Min, E-mail: memzhu@scut.edu.cn [School of Materials Science and Engineering, and Key Laboratory of Advanced Energy Storage Materials of Guangdong Province, South China University of Technology, Guangzhou 510641 (China); China-Australia Joint Laboratory for Energy & Environmental Materials, South China University of Technology, Guangzhou 510641 (China)

    2015-10-05

    Highlights: • LiBH{sub 4} is amorphous after modified with PMMA. • Dehydrogenation temperature of LiBH{sub 4} decreases by 120 °C after modifying with PMMA. • The LiBH{sub 4}@PMMA composite releases 10 wt.% hydrogen at 360 °C within 1 h. • C=O group of PMMA weakens the B−H bonds to lower dehydrogenation temperature. - Abstract: We investigated the dehydrogenation properties and mechanism of Poly(methyl methacrylate) (PMMA) confined LiBH{sub 4}. Thermal stability of LiBH{sub 4} was reduced by PMMA, with a decrease in dehydrogenation temperature by 120 °C. At 360 °C, the composite showed fast dehydrogenation kinetics with 10 wt.% of hydrogen released within 1 h. The improved dehydrogenation performance was mainly attributed to the reaction between LiBH{sub 4} and PMMA forming Li{sub 3}BO{sub 3} as a final product. Furthermore, the presence of electrostatic interaction between B atom of LiBH{sub 4} and O atom in the carbonyl group of PMMA may weaken the B−H bonding of [BH{sub 4}]{sup −} and lower the hydrogen desorption temperature.

  5. BIM Investment, Returns, and Risks in China’s AEC Industries

    OpenAIRE

    Jin, R; Hancock, CM; Tang, L; Wanatowski, D

    2017-01-01

    Building information modeling (BIM), the emerging digital technology, is undergoing increasing application in developing countries including China. Both the governmental policy and industry motivation have indicated that BIM is becoming the mainstream innovation in China’s construction industry. Nevertheless, one major concern lies in the uncertainty of BIM investment for architecture, engineering, and construction (AEC) firms. Specifically, AEC firms should have the knowledge of areas BIM in...

  6. Transforming BIM to BEM: Generation of Building Geometry for the NASA Ames Sustainability Base BIM

    Energy Technology Data Exchange (ETDEWEB)

    O' Donnell, James T. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Maile, Tobias [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Rose, Cody [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Mrazovic, Natasa [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Morrissey, Elmer [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Regnier, Cynthia [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Parrish, Kristen [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Bazjanac, Vladimir [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2013-01-01

    Typical processes of whole Building Energy simulation Model (BEM) generation are subjective, labor intensive, time intensive and error prone. Essentially, these typical processes reproduce already existing data, i.e. building models already created by the architect. Accordingly, Lawrence Berkeley National Laboratory (LBNL) developed a semi-automated process that enables reproducible conversions of Building Information Model (BIM) representations of building geometry into a format required by building energy modeling (BEM) tools. This is a generic process that may be applied to all building energy modeling tools but to date has only been used for EnergyPlus. This report describes and demonstrates each stage in the semi-automated process for building geometry using the recently constructed NASA Ames Sustainability Base throughout. This example uses ArchiCAD (Graphisoft, 2012) as the originating CAD tool and EnergyPlus as the concluding whole building energy simulation tool. It is important to note that the process is also applicable for professionals that use other CAD tools such as Revit (“Revit Architecture,” 2012) and DProfiler (Beck Technology, 2012) and can be extended to provide geometry definitions for BEM tools other than EnergyPlus. Geometry Simplification Tool (GST) was used during the NASA Ames project and was the enabling software that facilitated semi-automated data transformations. GST has now been superseded by Space Boundary Tool (SBT-1) and will be referred to as SBT-1 throughout this report. The benefits of this semi-automated process are fourfold: 1) reduce the amount of time and cost required to develop a whole building energy simulation model, 2) enable rapid generation of design alternatives, 3) improve the accuracy of BEMs and 4) result in significantly better performing buildings with significantly lower energy consumption than those created using the traditional design process, especially if the simulation model was used as a predictive

  7. Coordination between Understanding Historic Buildings and BIM Modelling: A 3D-Output Oriented and typological Data Capture Method

    Directory of Open Access Journals (Sweden)

    K. Li

    2015-08-01

    Full Text Available At the present, in trend of shifting the old 2D-output oriented survey to a new 3D-output oriented survey based on BIM technology, the corresponding working methods and workflow for data capture, process, representation, etc. have to be changed.Based on case study of two buildings in the Summer Palace of Beijing, and Jiayuguan Pass at the west end of the Great Wall (both World Heritage sites, this paper puts forward a “structure-and-type method” by means of typological method used in archaeology, Revit family system, and the tectonic logic of building to realize a good coordination between understanding of historic buildings and BIM modelling.

  8. Enabling BIM for the full Lifecycle of buildings

    DEFF Research Database (Denmark)

    Tamke, Martin

    2016-01-01

    Building Information Modelling (BIM) represents a global industry effort to harmonize the way the professions, designs, constructs and builds the environment. The BIM models, which are currently created are however not sustainable and will be unreadable or outdated in a very short time. The EU...... research project DURAARK presents solutions on how to maintain BIM models and the huge effort put into them by making them usable over long periods and in future projects....

  9. Content validity of governing in Building Information Modelling (BIM) implementation assessment instrument

    Science.gov (United States)

    Hadzaman, N. A. H.; Takim, R.; Nawawi, A. H.; Mohamad Yusuwan, N.

    2018-04-01

    BIM governance assessment instrument is a process of analysing the importance in developing BIM governance solution to tackle the existing problems during team collaboration in BIM-based projects. Despite the deployment of integrative technologies in construction industry particularly BIM, it is still insufficient compare to other sectors. Several studies have been established the requirements of BIM implementation concerning all technical and non-technical BIM adoption issues. However, the data are regarded as inadequate to develop a BIM governance framework. Hence, the objective of the paper is to evaluate the content validity of the BIM governance instrument prior to the main data collection. Two methods were employed in the form of literature review and questionnaire survey. Based on the literature review, 273 items with six main constructs are suggested to be incorporated in the BIM governance instrument. The Content Validity Ratio (CVR) scores revealed that 202 out of 273 items are considered as the utmost critical by the content experts. The findings for Item Level Content Validity Index (I-CVI) and Modified Kappa Coefficient however revealed that 257 items in BIM governance instrument are appropriate and excellent. The instrument is highly reliable for future strategies and the development of BIM projects in Malaysia.

  10. Holistic BIM Adoption and Diffusion in Malaysia

    Directory of Open Access Journals (Sweden)

    Mamter Shahela

    2016-01-01

    Full Text Available Building Information Modeling is modeling technology and associated set of processes to produce, communicate and analyze digital information models for construction life cycle. Although many benefits can gain by the implementation of BIM, the pace adoption of BIM in Malaysia is still slow. There is an abundance of theories and models purporting to describe the drivers and mechanisms of how new technologies are adopted or diffused into a particular section of society or by individuals or stake players. In addition, many acceptance theories, which imply the adoption of new technologies and can be applied in every sector. This paper aims to present a review of the existing literature of BIM adoption and diffusion theory/model/framework in Malaysia. Researcher revealed the list of driven factors of Holistic BIM Adoption. In addition, it will deal with how to work effectively with groups that initially are relatively

  11. Fluoride substitution in LiBH4; destabilization and decomposition

    DEFF Research Database (Denmark)

    Richter, Bo; Ravnsbaek, Dorthe B.; Sharma, Manish

    2017-01-01

    Fluoride substitution in LiBH4 is studied by investigation of LiBH4-LiBF4 mixtures (9:1 and 3:1). Decomposition was followed by in situ synchrotron radiation X-ray diffraction (in situ SR-PXD), thermogravimetric analysis and differential scanning calorimetry with gas analysis (TGA/DSC-MS) and in ......Fluoride substitution in LiBH4 is studied by investigation of LiBH4-LiBF4 mixtures (9:1 and 3:1). Decomposition was followed by in situ synchrotron radiation X-ray diffraction (in situ SR-PXD), thermogravimetric analysis and differential scanning calorimetry with gas analysis (TGA...

  12. Rethinking the contractual context for Building Information Modelling (BIM in the Australian built environment industry

    Directory of Open Access Journals (Sweden)

    Ilsa Kuiper

    2013-12-01

    Full Text Available Building Information Modelling (BIM can be defined as a process of generating and managing information of a building or infrastructure during its life cycle. Whilst the 3D visualisation or dimensional functions of BIM are not necessarily new, it is the usage and integration of this information related to project delivery, management and performance analysis that are challenging current construction industry practices.  Industry has called for the development of more collaborative and integrated contractual arrangements to facilitate the use of BIM. Such recommendations appeal to the ideal use of BIM, but also provide a potential opportunity to seek improvement within the construction industry. This paper proposes a procurement approach to BIM to establish the applicable contractual context to address the potential legal risks and commercial considerations, relative to current practices in Australia. It als ooutlines why BIM, with other enabling technologies, will drive the evolution of contract delivery methodologies.

  13. Formal and informal relations within BIM-enabled supply chain partnerships

    NARCIS (Netherlands)

    Papadonikolaki, E.; Verbraeck, A.; Wamelink, J.W.F.

    2017-01-01

    Supply chain management (SCM) and building information modelling (BIM) are innovations that focus on integration. Recent literature suggests performance benefits from combining these innovations. Within supply chain (SC) partnerships, that use BIM – hereinafter called BIM-enabled SC partnerships

  14. Glycosaminoglycan-Mimetic Signals Direct the Osteo/Chondrogenic Differentiation of Mesenchymal Stem Cells in a Three-Dimensional Peptide Nanofiber Extracellular Matrix Mimetic Environment.

    Science.gov (United States)

    Arslan, Elif; Guler, Mustafa O; Tekinay, Ayse B

    2016-04-11

    Recent efforts in bioactive scaffold development focus strongly on the elucidation of complex cellular responses through the use of synthetic systems. Designing synthetic extracellular matrix (ECM) materials must be based on understanding of cellular behaviors upon interaction with natural and artificial scaffolds. Hence, due to their ability to mimic both the biochemical and mechanical properties of the native tissue environment, supramolecular assemblies of bioactive peptide nanostructures are especially promising for development of bioactive ECM-mimetic scaffolds. In this study, we used glycosaminoglycan (GAG) mimetic peptide nanofiber gel as a three-dimensional (3D) platform to investigate how cell lineage commitment is altered by external factors. We observed that amount of fetal bovine serum (FBS) presented in the cell media had synergistic effects on the ability of GAG-mimetic nanofiber gel to mediate the differentiation of mesenchymal stem cells into osteogenic and chondrogenic lineages. In particular, lower FBS concentration in the culture medium was observed to enhance osteogenic differentiation while higher amount FBS promotes chondrogenic differentiation in tandem with the effects of the GAG-mimetic 3D peptide nanofiber network, even in the absence of externally administered growth factors. We therefore demonstrate that mesenchymal stem cell differentiation can be specifically controlled by the combined influence of growth medium components and a 3D peptide nanofiber environment.

  15. The interdependences of BIM and supply chain partnering : Empirical explorations

    NARCIS (Netherlands)

    Papadonikolaki, E.; Vrijhoef, R.; Wamelink, J.W.F.

    2016-01-01

    Building Information Modelling (BIM) technology and the concept of supply chain management (SCM) could be a potentially compatible and mutually interdependent practice. The existing research on BIM focuses on improving project-based and intra-organisational goals, ignoring the impact of BIM on

  16. Development of a 3D Underground Cadastral System with Indoor Mapping for As-Built BIM: The Case Study of Gangnam Subway Station in Korea

    Directory of Open Access Journals (Sweden)

    Sangmin Kim

    2015-12-01

    Full Text Available The cadastral system provides land ownership information by registering and representing land boundaries on a map. The current cadastral system in Korea, however, focuses mainly on the management of 2D land-surface boundaries. It is not yet possible to provide efficient or reliable land administration, as this 2D system cannot support or manage land information on 3D properties (including architectures and civil infrastructures for both above-ground and underground facilities. A geometrical model of the 3D parcel, therefore, is required for registration of 3D properties. This paper, considering the role of the cadastral system, proposes a framework for a 3D underground cadastral system that can register various types of 3D underground properties using indoor mapping for as-built Building Information Modeling (BIM. The implementation consists of four phases: (1 geometric modeling of a real underground infrastructure using terrestrial laser scanning data; (2 implementation of as-built BIM based on geometric modeling results; (3 accuracy assessment for created as-built BIM using reference points acquired by total station; and (4 creation of three types of 3D underground cadastral map to represent underground properties. The experimental results, based on indoor mapping for as-built BIM, show that the proposed framework for a 3D underground cadastral system is able to register the rights, responsibilities, and restrictions corresponding to the 3D underground properties. In this way, clearly identifying the underground physical situation enables more reliable and effective decision-making in all aspects of the national land administration system.

  17. BIM-Integrated Construction Operation Simulation for Just-In-Time Production Management

    Directory of Open Access Journals (Sweden)

    WoonSeong Jeong

    2016-10-01

    Full Text Available Traditional construction planning, which depends on historical data and heuristic modification, prevents the integration of managerial details such as productivity dynamics. Specifically, the distance between planning and execution brings cost overruns and duration extensions. To minimize variations, this research presents a Building Information Modeling (BIM-integrated simulation framework for predicting productivity dynamics at the construction planning phase. To develop this framework, we examined critical factors affecting productivity at the operational level, and then forecast the productivity dynamics. The resulting plan includes specific commands for retrieving the required information from BIM and executing operation simulations. It consists of the following steps: (1 preparing a BIM model to produce input data; (2 composing a construction simulation at the operational level; and (3 obtaining productivity dynamics from the BIM-integrated simulation. To validate our framework, we applied it to a structural steel model; this was due to the significance of steel erections. By integrating BIM with construction operation simulations, we were able to create reliable construction plans that adapted to project changes. Our results show that the developed framework facilitates the reliable prediction of productivity dynamics, and can contribute to improved schedule reliability, optimized resource allocation, cost savings associated with buffers, and reduced material waste.

  18. BIM Interoperability Limitations: Australian and Malaysian Rail Projects

    Directory of Open Access Journals (Sweden)

    Kenley Russell

    2016-01-01

    Full Text Available Building information modelling (BIM is defined as a process involving the generation and management of digital representation of physical and functional characteristics of a facility. The purpose of interoperability in integrated or “open” BIM is to facilitate the information exchange between different digital systems, models and tools. There has been effort towards data interoperability with development of open source standards and object-oriented models, such as industry foundation classes (IFC for vertical infrastructure. However, the lack of open data standards for the information exchange for horizontal infrastructure limits the adoption and effectiveness of integrated BIM. The paper outlines two interoperability issues for construction of rail infrastructure. The issues are presented in two case study reports, one from Australia and one from Malaysia. The each case study includes: a description of the project, the application of BIM in the project, a discussion of the promised BIM interoperability solution plus the identification of the unresolved lack of interoperability for horizontal infrastructure project management. The Moreton Bay Rail project in Australia introduces general software interoperability issues. The Light Rail Extension project in Kuala Lumpur outlines an example of the integration problems related to two different location data structures. The paper highlights how the continuing lack of data interoperability limits utilisation of integrated BIM for horizontal infrastructure rail projects.

  19. Fluid shear stress suppresses TNF-α-induced apoptosis in MC3T3-E1 cells: Involvement of ERK5-AKT-FoxO3a-Bim/FasL signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Bin, Geng; Bo, Zhang; Jing, Wang; Jin, Jiang; Xiaoyi, Tan; Cong, Chen; Liping, An; Jinglin, Ma; Cuifang, Wang; Yonggang, Chen [The Second Hospital of Lanzhou University, #82 Cuiyingmen, Lanzhou, 730000 Gansu (China); Orthopaedics Key Laboratory of Gansu Province, Lanzhou, 730000 Gansu (China); Yayi, Xia, E-mail: xiayayildey@163.com [The Second Hospital of Lanzhou University, #82 Cuiyingmen, Lanzhou, 730000 Gansu (China); Orthopaedics Key Laboratory of Gansu Province, Lanzhou, 730000 Gansu (China)

    2016-05-01

    TNF-α is known to induce osteoblasts apoptosis, whereas mechanical stimulation has been shown to enhance osteoblast survival. In the present study, we found that mechanical stimulation in the form of fluid shear stress (FSS) suppresses TNF-α induced apoptosis in MC3T3-E1 cells. Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase (MAPK) family that has been implicated in cell survival. We also demonstrated that FSS imposed by flow chamber in vitro leads to a markedly activation of ERK5, which was shown to be protective against TNF-α-induced apoptosis, whereas the transfection of siRNA against ERK5 (ERK5-siRNA) reversed the FSS-medicated anti-apoptotic effects. An initial FSS-mediated activation of ERK5 that phosphorylates AKT to increase its activity, and a following forkhead box O 3a (FoxO3a) was phosphorylated by activated AKT. Phosphorylated FoxO3a is sequestered in the cytoplasm, and prevents it from translocating to nucleus where it can increase the expression of FasL and Bim. The inhibition of AKT-FoxO3a signalings by a PI3K (PI3-kinase)/AKT inhibitor (LY294002) or the transfection of ERK5-siRNA led to the nuclear translocation of non-phosphorylated FoxO3a, and increased the protein expression of FasL and Bim. In addition, the activation of caspase-3 by TNF-α was significantly inhibited by aforementioned FSS-medicated mechanisms. In brief, the activation of ERK5-AKT-FoxO3a signaling pathways by FSS resulted in a decreased expression of FasL and Bim and an inhibition of caspase-3 activation, which exerts a protective effect that prevents osteoblasts from apoptosis. - Highlights: • Fluid shear stress inhibits osteoblast apoptosis induced by TNF-α. • Inhibition of ERK5 activity by transfection of ERK5 siRNA blocks FSS-mediated anti-apoptotic effect in osteoblast. • Activated ERK5-AKT-FoxO3a-Bim/FasL signaling pathways by FSS is required to protect osteoblast from apoptosis.

  20. BIM: enabling sustainability and asset management through knowledge management.

    Science.gov (United States)

    Kivits, Robbert Anton; Furneaux, Craig

    2013-11-10

    Building Information Modeling (BIM) is the use of virtual building information models to develop building design solutions and design documentation and to analyse construction processes. Recent advances in IT have enabled advanced knowledge management, which in turn facilitates sustainability and improves asset management in the civil construction industry. There are several important qualifiers and some disadvantages of the current suite of technologies. This paper outlines the benefits, enablers, and barriers associated with BIM and makes suggestions about how these issues may be addressed. The paper highlights the advantages of BIM, particularly the increased utility and speed, enhanced fault finding in all construction phases, and enhanced collaborations and visualisation of data. The paper additionally identifies a range of issues concerning the implementation of BIM as follows: IP, liability, risks, and contracts and the authenticity of users. Implementing BIM requires investment in new technology, skills training, and development of new ways of collaboration and Trade Practices concerns. However, when these challenges are overcome, BIM as a new information technology promises a new level of collaborative engineering knowledge management, designed to facilitate sustainability and asset management issues in design, construction, asset management practices, and eventually decommissioning for the civil engineering industry.

  1. BIM-Based Timber Structures Refurbishment of the Immovable Heritage Listed Buildings

    Science.gov (United States)

    Henek, Vladan; Venkrbec, Václav

    2017-12-01

    The use of Building information model (BIM) design tools is no longer an exception, but a common issue. When designing new buildings or complex renovations using BIM, the benefits have already been repeatedly published. The essence of BIM is to create a multidimensional geometric model of a planned building electronically on a computer, supplemented with the necessary information in advance of the construction process. Refurbishment is a specific process that combines both - new structures and demolished structures, or structures that need to be dismantled, repaired, and then returned to the original position. Often it can be historically valuable part of the building. BIM-based repairs and refurbishments of the constructions, especially complicated repairs of the structures of roof trusses of immovable heritage listed buildings, have not yet been credibly presented. However, the use of BIM tools may be advantageous in this area, because user can quickly response to the necessary changes that may be needed during refurbishments, but also in connection with the quick assessment and cost estimation of any unexpected additional works. The paper deals with the use of BIM in the field of repairs and refurbishment of the buildings in general. The emphasis on monumentally protected elements was priority. Advantage of the proposal research is demonstrated on case study of the refurbishment of the immovable heritage listed truss roof. According to this study, this construction was realized in the Czech Republic. Case study consists of 3D modelled truss parts and the connected technological workflow base. The project work was carried out in one common model environment.

  2. Characteristics of Al Alloy as a Material for Hydrolysis Reactor of NaBH4

    International Nuclear Information System (INIS)

    Jung, Hyeon-Seong; Oh, Sung-June; Jeong, Jae-Jin; Na, Il-Chai; Chu, Cheun-Ho; Park, Kwon-Pil; Chu, Cheun-Ho

    2015-01-01

    Aluminum alloy was examined as a material of low weight reactor for hydrolysis of NaBH 4 . Aluminum is dissolved with alkali, but there is NaOH as a stabilizer in NaBH 4 solution. To decrease corrosion rate of aluminum, decrease NaOH concentration and this result in loss of NaBH 4 during storage of NaBH 4 solution. Therefore stability of NaBH 4 and corrosion of aluminum should be considered in determining the optimum NaOH concentration. NaBH 4 stability and corrosion rate of aluminum were measured by hydrogen evolution rate. NaBH 4 stability was tested at 20-50 .deg. C and aluminum corrosion was measured at 60-90 .deg. C. The optimum concentration of NaOH was 0.3 wt%, considering both NaBH 4 stability and aluminun corrosion. NaBH 4 hydrolysis reaction continued 200min in aluminum No 6061 alloy reactor with 0.3 wt% NaOH at 80-90 .deg. C.

  3. Utilization of design data on conventional system to building information modeling (BIM)

    Science.gov (United States)

    Akbar, Boyke M.; Z. R., Dewi Larasati

    2017-11-01

    Nowadays infrastructure development becomes one of the main priorities in the developed country such as Indonesia. The use of conventional design system is considered no longer effectively support the infrastructure projects, especially for the high complexity building design, due to its fragmented system issues. BIM comes as one of the solutions in managing projects in an integrated manner. Despite of the all known BIM benefits, there are some obstacles on the migration process to BIM. The two main of the obstacles are; the BIM implementation unpreparedness of some project parties and a concerns to leave behind the existing database and create a new one on the BIM system. This paper discusses the utilization probabilities of the existing CAD data from the conventional design system for BIM system. The existing conventional CAD data's and BIM design system output was studied to examine compatibility issues between two subject and followed by an utilization scheme-strategy probabilities. The goal of this study is to add project parties' eagerness in migrating to BIM by maximizing the existing data utilization and hopefully could also increase BIM based project workflow quality.

  4. The Issues and Considerations Associated with BIM Integration

    Directory of Open Access Journals (Sweden)

    Bataw Anas

    2016-01-01

    Full Text Available The management of data, information and knowledge through the project life cycle of buildings and civil infrastructure projects is becoming increasingly complex. As an attempt to drive efficiencies and address this complexity, the United Kingdom Government has mandated that Building Information Modelling (BIM methods must be adopted in all public sector construction projects in 2016. Emerging from the US Department of Defence, BIM is an approach to the co-ordination of design and production data using object-oriented principles as described in ISO 29481-1:2010. The underlying philosophy of BIM is to ensure the “provision of a single environment to store shared asset data and information, accessible to all individuals who are required to produce, use and maintain it” (PAS 1192-2:2013. A key aspect of BIM lies in the notion of ‘interoperability’ between various software applications used in the design and construction process and a common data format for the efficient exchange of design information and knowledge. Protagonists of BIM argue that this interoperability provides an effective environment for collaboration between actors in the construction process and creates accurate, reliable, repeatable and high-quality information exchange. This UK government mandate presents numerous challenges to the architecture, engineering and construction (AEC professions; in particular, the characteristics of BIM Level 2 remain explicitly undefined and this created a degree of uncertainty amongst the promoters and those professionals charged with delivering projects. This research casts a critical lens on the current literature in the domains of object-oriented modelling of infrastructure and the associated implications for procurement and project management. A mixed-methods approach using questionnaire analysis and secondary case study analysis was used to enact an inductive research approach that captures a range of data on the practical issues and

  5. BIM-enabled Conceptual Modelling and Representation of Building Circulation

    OpenAIRE

    Lee, Jin Kook; Kim, Mi Jeong

    2014-01-01

    This paper describes how a building information modelling (BIM)-based approach for building circulation enables us to change the process of building design in terms of its computational representation and processes, focusing on the conceptual modelling and representation of circulation within buildings. BIM has been designed for use by several BIM authoring tools, in particular with the widely known interoperable industry foundation classes (IFCs), which follow an object-oriented data modelli...

  6. A Framework for BIM-enabled Life-cycle Information Management of Construction Project

    OpenAIRE

    Xu, n; Ma, Ling; Ding, Lieyun

    2014-01-01

    BIM has been widely used in project management, but on the whole the applications have been scattered and the BIM models have not been deployed throughout the whole project life-cycle. Each participant builds their own BIM, so there is a major problem in how to integrate these dynamic and fragmented data together. In order to solve this problem, this paper focuses on BIM- based life-cycle information management and builds a framework for BIM-enabled life-cycle information management. To organ...

  7. Exploitation and Benefits of BIM in Construction Project Management

    Science.gov (United States)

    Mesároš, Peter; Mandičák, Tomáš

    2017-10-01

    BIM is increasingly getting into the awareness in construction industry. BIM is the process of creating and data managing of the building during its life cycle. BIM became a part of management tools in modern construction companies. Construction projects have a number of participants. It means difficulty process of construction project management and a serious requirement for processing the huge amount of information including design, construction, time and cost parameters, economic efficiency and sustainability. Progressive information and communication technologies support cost management and management of construction project. One of them is Building Information Modelling. Aim of the paper is to examine the impact of BIM exploitation and benefits on construction project management in Slovak companies.

  8. Het inbedden van BIM. In interactiekaders en objectbibliotheken

    NARCIS (Netherlands)

    Willems, P.H.; Böhms, M.

    2012-01-01

    Een bouwwerkinformatiemodel (BIM) zelf lost de tekortkomingen van ICTondersteuning in de bouwproductieketen niet adequaat op. Een BIM zou moeten worden ingebed in een formele beschrijving van alle benodigde uitwisselingsvereisten. De ISO/buildingSMART standaard Information Delivery Manual (IDM) is

  9. Instabilities in mimetic matter perturbations

    Energy Technology Data Exchange (ETDEWEB)

    Firouzjahi, Hassan; Gorji, Mohammad Ali [School of Astronomy, Institute for Research in Fundamental Sciences (IPM), P.O. Box 19395-5531, Tehran (Iran, Islamic Republic of); Mansoori, Seyed Ali Hosseini, E-mail: firouz@ipm.ir, E-mail: gorji@ipm.ir, E-mail: shosseini@shahroodut.ac.ir, E-mail: shossein@ipm.ir [Physics Department, Shahrood University of Technology, P.O. Box 3619995161 Shahrood (Iran, Islamic Republic of)

    2017-07-01

    We study cosmological perturbations in mimetic matter scenario with a general higher derivative function. We calculate the quadratic action and show that both the kinetic term and the gradient term have the wrong sings. We perform the analysis in both comoving and Newtonian gauges and confirm that the Hamiltonians and the associated instabilities are consistent with each other in both gauges. The existence of instabilities is independent of the specific form of higher derivative function which generates gradients for mimetic field perturbations. It is verified that the ghost instability in mimetic perturbations is not associated with the higher derivative instabilities such as the Ostrogradsky ghost.

  10. BIM: Enabling Sustainability and Asset Management through Knowledge Management

    Directory of Open Access Journals (Sweden)

    Robbert Anton Kivits

    2013-01-01

    Full Text Available Building Information Modeling (BIM is the use of virtual building information models to develop building design solutions and design documentation and to analyse construction processes. Recent advances in IT have enabled advanced knowledge management, which in turn facilitates sustainability and improves asset management in the civil construction industry. There are several important qualifiers and some disadvantages of the current suite of technologies. This paper outlines the benefits, enablers, and barriers associated with BIM and makes suggestions about how these issues may be addressed. The paper highlights the advantages of BIM, particularly the increased utility and speed, enhanced fault finding in all construction phases, and enhanced collaborations and visualisation of data. The paper additionally identifies a range of issues concerning the implementation of BIM as follows: IP, liability, risks, and contracts and the authenticity of users. Implementing BIM requires investment in new technology, skills training, and development of new ways of collaboration and Trade Practices concerns. However, when these challenges are overcome, BIM as a new information technology promises a new level of collaborative engineering knowledge management, designed to facilitate sustainability and asset management issues in design, construction, asset management practices, and eventually decommissioning for the civil engineering industry.

  11. BIM: Enabling Sustainability and Asset Management through Knowledge Management

    Science.gov (United States)

    2013-01-01

    Building Information Modeling (BIM) is the use of virtual building information models to develop building design solutions and design documentation and to analyse construction processes. Recent advances in IT have enabled advanced knowledge management, which in turn facilitates sustainability and improves asset management in the civil construction industry. There are several important qualifiers and some disadvantages of the current suite of technologies. This paper outlines the benefits, enablers, and barriers associated with BIM and makes suggestions about how these issues may be addressed. The paper highlights the advantages of BIM, particularly the increased utility and speed, enhanced fault finding in all construction phases, and enhanced collaborations and visualisation of data. The paper additionally identifies a range of issues concerning the implementation of BIM as follows: IP, liability, risks, and contracts and the authenticity of users. Implementing BIM requires investment in new technology, skills training, and development of new ways of collaboration and Trade Practices concerns. However, when these challenges are overcome, BIM as a new information technology promises a new level of collaborative engineering knowledge management, designed to facilitate sustainability and asset management issues in design, construction, asset management practices, and eventually decommissioning for the civil engineering industry. PMID:24324392

  12. In situ Fourier transform infrared spectroscopy and on-line differential electrochemical mass spectrometry study of the NH3BH3 oxidation reaction on gold electrodes

    International Nuclear Information System (INIS)

    Belén Molina Concha, M.; Chatenet, Marian; Lima, Fabio H.B.; Ticianelli, Edson A.

    2013-01-01

    The ammonia borane (NH 3 BH 3 ) oxidation reaction (ABOR) was studied on gold electrodes using the rotating disk electrode (RDE) setup and coupled physical techniques: on-line differential electrochemical mass spectrometry (DEMS) and in situ Fourier transform infrared spectroscopy (FTIR). Non-negligible heterogeneous hydrolysis in the low-potential region was asserted via molecular H 2 detection. As a consequence, the number of electron exchanged per BH 3 OH − species is ca. 3 at low potential, and only reaches ca. 6 above 0.6 V vs. RHE. These figures were confirmed by Levich and Koutecki–Levich calculations using the RDE experiments data. The nature of the ABOR intermediates and products was determined using in situ FTIR. While BH 2 species were detected during the ABOR, it seems that its adsorption onto the Au electrode proceeds via the O atom, in opposition to what happens during the borohydride oxidation reaction (BOR). Therefore, it is likely that the mechanism of the ABOR differs from that of the BOR. From the whole set of data (RDE, DEMS, FTIR), a relevant reaction pathway was proposed, including competition between the BH 3 OH − heterogeneous hydrolysis and oxidation at low potential, and preponderant oxidation at higher potential. Finally, a simplified kinetic modeling accounting with this reaction pathway was proposed, which nicely fits the stationary (i vs. E) ABOR plot

  13. Bio-mimetic Flow Control

    Science.gov (United States)

    Choi, Haecheon

    2009-11-01

    Bio-mimetic engineering or bio-mimetics is the application of biological methods and systems found in nature to the study and design of engineering systems and modern technology (from Wikipedia). The concept itself is old, but successful developments have been made recently, especially in the research field of flow control. The objective of flow control based on the bio-mimetic approach is to develop novel concepts for reducing drag, increasing lift and enhancing aerodynamic performance. For skin friction reduction, a few ideas have been suggested such as the riblet from shark, compliant surface from dolphin, microbubble injection and multiple front-body curvature from penguin, and V-shaped protrusion from sailfish. For form drag reduction, several new attempts have been also made recently. Examples include the V-shaped spanwise grooves from saguaro cactus, overall shape of box fish, longitudinal grooves on scallop shell, bill of swordfish, hooked comb on owl wing, trailing-edge protrusion on dragonfly wing, and fillet. For the enhancement of aerodynamic performance, focuses have been made on the birds, fish and insects: e.g., double layered feather of landing bird, leading-edge serration of humpback-whale flipper, pectoral fin of flying fish, long tail on swallowtail-butterfly wing, wing flapping motion of dragonfly, and alula in birds. Living animals adapt their bodies to better performance in multi purposes, but engineering requires single purpose in most cases. Therefore, bio-mimetic approaches often produce excellent results more than expected. However, they are sometimes based on people's wrong understanding of nature and produce unwanted results. Successes and failures from bio-mimetic approaches in flow control will be discussed in the presentation.

  14. A review of BIM (Building Information Modeling) implementation in Indonesia construction industry

    Science.gov (United States)

    Suryadinata Telaga, Abdi

    2018-05-01

    Construction projects in Indonesia have been growing rapidly in the last three years. Therefore, construction management is very important to ensure completion of construction projects are within schedule and budget. Utilization of building information modeling (BIM) can increase the efficiency of a construction project. However, the implementation of BIM in Indonesia is still not known. This paper is intended to review the implementation of BIM in Indonesia through literature analysis. To find BIM articles in Indonesia, Firstly, searching was limited to English articles published in reputed journals or conferences. However the results were limited, then the search was expanded to the article using Indonesian languages that published in journal and conference. Based on the number of articles, the results showed that BIM research in Indonesia is still in a dearth. Furthermore, BIM study cases were conducted in a limited location and within a small population. Nevertheless, the literature shared the conclusion that BIM can increase project efficiency, but the implementation was hindered by high initial investment cost, inadequate human resources, small demand, and technology resistant. The research contributes to providing a current reported level of BIM implementation in Indonesia. In the future research to study of BIM implementation comprehensively in Indonesia is eminent.

  15. Induction of Bim and Bid gene expression during accelerated apoptosis in severe sepsis.

    Science.gov (United States)

    Weber, Stefan U; Schewe, Jens-Christian; Lehmann, Lutz E; Müller, Stefan; Book, Malte; Klaschik, Sven; Hoeft, Andreas; Stüber, Frank

    2008-01-01

    In transgenic animal models of sepsis, members of the Bcl-2 family of proteins regulate lymphocyte apoptosis and survival of sepsis. This study investigates the gene regulation of pro-apoptotic and anti-apoptotic members of the Bcl-2 family of proteins in patients with early stage severe sepsis. In this prospective case-control study, patients were recruited from three intensive care units (ICUs) in a university hospital. Sixteen patients were enrolled when they fulfilled the criteria of severe sepsis. Ten critically ill but non-septic patients and 11 healthy volunteers served as controls. Blood samples were immediately obtained at inclusion. To confirm the presence of accelerated apoptosis in the patient groups, caspase-3 activation and phosphatidylserine externalisation in CD4+, CD8+ and CD19+ lymphocyte subsets were assessed using flow cytometry. Specific mRNAs of Bcl-2 family members were quantified from whole blood by real-time PCR. To test for statistical significance, Kruskal-Wallis testing with Dunn's multiple comparison test for post hoc analysis was performed. In all lymphocyte populations caspase-3 (p < 0.05) was activated, which was reflected in an increased phosphatidylserine externalisation (p < 0.05). Accordingly, lymphocyte counts were decreased in early severe sepsis. In CD4+ T-cells (p < 0.05) and B-cells (p < 0.001) the Bcl-2 protein was decreased in severe sepsis. Gene expression of the BH3-only Bim was massively upregulated as compared with critically ill patients (p < 0.001) and 51.6-fold as compared with healthy controls (p < 0.05). Bid was increased 12.9-fold compared with critically ill patients (p < 0.001). In the group of mitochondrial apoptosis inducers, Bak was upregulated 5.6-fold, while the expression of Bax showed no significant variations. By contrast, the pro-survival members Bcl-2 and Bcl-xl were both downregulated in severe sepsis (p < 0.001 and p < 0.05, respectively). In early severe sepsis a gene expression pattern with

  16. Black hole solutions in mimetic Born-Infeld gravity.

    Science.gov (United States)

    Chen, Che-Yu; Bouhmadi-López, Mariam; Chen, Pisin

    2018-01-01

    The vacuum, static, and spherically symmetric solutions in the mimetic Born-Infeld gravity are studied. The mimetic Born-Infeld gravity is a reformulation of the Eddington-inspired-Born-Infeld (EiBI) model under the mimetic approach. Due to the mimetic field, the theory contains non-trivial vacuum solutions different from those in Einstein gravity. We find that with the existence of the mimetic field, the spacelike singularity inside a Schwarzschild black hole could be altered to a lightlike singularity, even though the curvature invariants still diverge at the singularity. Furthermore, in this case, the maximal proper time for a timelike radially-infalling observer to reach the singularity is found to be infinite.

  17. Black hole solutions in mimetic Born-Infeld gravity

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Che-Yu [National Taiwan University, Department of Physics and Center for Theoretical Sciences, Taipei (China); LeCosPA, National Taiwan University, Taipei (China); Bouhmadi-Lopez, Mariam [University of the Basque Country UPV/EHU, Department of Theoretical Physics, Bilbao (Spain); IKERBASQUE, Basque Foundation for Science, Bilbao (Spain); Chen, Pisin [National Taiwan University, Department of Physics and Center for Theoretical Sciences, Taipei (China); LeCosPA, National Taiwan University, Taipei (China); Stanford University, Kavli Institute for Particle Astrophysics and Cosmology, SLAC National Accelerator Laboratory, Stanford, CA (United States)

    2018-01-15

    The vacuum, static, and spherically symmetric solutions in the mimetic Born-Infeld gravity are studied. The mimetic Born-Infeld gravity is a reformulation of the Eddington-inspired-Born-Infeld (EiBI) model under the mimetic approach. Due to the mimetic field, the theory contains non-trivial vacuum solutions different from those in Einstein gravity. We find that with the existence of the mimetic field, the spacelike singularity inside a Schwarzschild black hole could be altered to a lightlike singularity, even though the curvature invariants still diverge at the singularity. Furthermore, in this case, the maximal proper time for a timelike radially-infalling observer to reach the singularity is found to be infinite. (orig.)

  18. Pokemon Silencing Leads to Bim-Mediated Anoikis of Human Hepatoma Cell QGY7703

    Directory of Open Access Journals (Sweden)

    Kun Liu

    2012-05-01

    Full Text Available Pokemon is an important proto-oncogene that plays a critical role in cellular oncogenic transformation and tumorigenesis. Anoikis, which is regulated by Bim-mediated apoptosis, is critical to cancer cell invasion and metastasis. We investigated the role of Pokemon in anoikis, and our results show that Pokemon renders liver cells resistant to anoikis via suppression of Bim transcription. We knocked-down Pokemon in human hepatoma cells QGY7703 with small interfering RNAs (siRNA. Knockdown of Pokemon alone did not significantly affect the growth and survival of QGY7703 cells but notably enhanced their sensitivity to apoptotic stress due to the presence of chemical agents or cell detachment, thereby inducing anoikis, as evidenced by flow cytometry and caspase-3 activity assays. In contrast, ectopic expression of Pokemon in HL7702 cells led to resistance to anoikis. Dual-luciferase reporter and ChIP assays illustrated that Pokemon suppressed Bim transcription via direct binding to its promoter. Our results suggest that Pokemon prevents anoikis through the suppression of Bim expression, which facilitates tumor cell invasion and metastasis. This Pokemon-Bim pathway may be an effective target for therapeutic intervention for cancer.

  19. Pokemon silencing leads to Bim-mediated anoikis of human hepatoma cell QGY7703.

    Science.gov (United States)

    Liu, Kun; Liu, Feng; Zhang, Nannan; Liu, Shiying; Jiang, Yuyang

    2012-01-01

    Pokemon is an important proto-oncogene that plays a critical role in cellular oncogenic transformation and tumorigenesis. Anoikis, which is regulated by Bim-mediated apoptosis, is critical to cancer cell invasion and metastasis. We investigated the role of Pokemon in anoikis, and our results show that Pokemon renders liver cells resistant to anoikis via suppression of Bim transcription. We knocked-down Pokemon in human hepatoma cells QGY7703 with small interfering RNAs (siRNA). Knockdown of Pokemon alone did not significantly affect the growth and survival of QGY7703 cells but notably enhanced their sensitivity to apoptotic stress due to the presence of chemical agents or cell detachment, thereby inducing anoikis, as evidenced by flow cytometry and caspase-3 activity assays. In contrast, ectopic expression of Pokemon in HL7702 cells led to resistance to anoikis. Dual-luciferase reporter and ChIP assays illustrated that Pokemon suppressed Bim transcription via direct binding to its promoter. Our results suggest that Pokemon prevents anoikis through the suppression of Bim expression, which facilitates tumor cell invasion and metastasis. This Pokemon-Bim pathway may be an effective target for therapeutic intervention for cancer.

  20. Cosmological dynamics of mimetic gravity

    Science.gov (United States)

    Dutta, Jibitesh; Khyllep, Wompherdeiki; Saridakis, Emmanuel N.; Tamanini, Nicola; Vagnozzi, Sunny

    2018-02-01

    We present a detailed investigation of the dynamical behavior of mimetic gravity with a general potential for the mimetic scalar field. Performing a phase-space and stability analysis, we show that the scenario at hand can successfully describe the thermal history of the universe, namely the successive sequence of radiation, matter, and dark-energy eras. Additionally, at late times the universe can either approach a de Sitter solution, or a scaling accelerated attractor where the dark-matter and dark-energy density parameters are of the same order, thus offering an alleviation of the cosmic coincidence problem. Applying our general analysis to various specific potential choices, including the power-law and the exponential ones, we show that mimetic gravity can be brought into good agreement with the observed behavior of the universe. Moreover, with an inverse square potential we find that mimetic gravity offers an appealing unified cosmological scenario where both dark energy and dark matter are characterized by a single scalar field, and where the cosmic coincidence problem is alleviated.

  1. Application Analysis of BIM Technology in Metro Rail Transit

    Science.gov (United States)

    Liu, Bei; Sun, Xianbin

    2018-03-01

    With the rapid development of urban roads, especially the construction of subway rail transit, it is an effective way to alleviate urban traffic congestion. There are limited site space, complex resource allocation, tight schedule, underground pipeline complex engineering problems. BIM technology, three-dimensional visualization, parameterization, virtual simulation and many other advantages can effectively solve these technical problems. Based on the project of Shenzhen Metro Line 9, BIM technology is innovatively researched throughout the lifecycle of BIM technology in the context of the metro rail transit project rarely used at this stage. The model information file is imported into Navisworks for four-dimensional animation simulation to determine the optimum construction scheme of the shield machine. Subway construction management application platform based on BIM and private cloud technology, the use of cameras and sensors to achieve electronic integration, dynamic monitoring of the operation and maintenance of underground facilities. Make full use of the many advantages of BIM technology to improve the engineering quality and construction efficiency of the subway rail transit project and to complete the operation and maintenance.

  2. BCL2-like 11 intron 2 deletion polymorphism is not associated with non-small cell lung cancer risk and prognosis.

    Science.gov (United States)

    Cho, Eun Na; Kim, Eun Young; Jung, Ji Ye; Kim, Arum; Oh, In Jae; Kim, Young Chul; Chang, Yoon Soo

    2015-10-01

    BCL2-Like 11(BIM), which encodes a BH3-only protein, is a major pro-apoptotic molecule that facilitates cell death. We hypothesized that a BIM intron 2 deletion polymorphism increases lung cancer risk and predicts poor prognosis in non-small lung cancer (NSCLC) patients. We prospectively recruited 450 lung cancer patients and 1:1 age, sex, and smoking status matched control subjects from February 2013 to April 2014 among patients treated at Severance, Gangnam Severance, and Chonnam Hwasoon Hospital. The presence of a 2903-bp genomic DNA deletion polymorphism of intron 2 of BIM was analyzed by PCR and validated by sequencing. Odds ratios were calculated by chi-square tests and survival analysis with Kaplan-Meier estimation. Sixty-nine out of 450 (15.3%) lung cancer patients carried the BIM deletion polymorphism, while 66 out of 450 (14.7%) control subjects carried the BIM deletion polymorphism, with an odds ratio of for lung cancer of 1.054 (95% CI; 0.731-1.519). We categorized 406 NSCLC patients according to the presence of the polymorphism and found that there were no statistically significant differences in age, sex, histologic type, or stage between subjects with and without the deletion polymorphism. The BIM deletion polymorphism did not influence overall survival (OS) or progression free survival (PFS) in our sample (OS; 37.6 vs 34.4 months (P=0.759), PFS; 49.6 vs 26.0 months (P=0.434)). These findings indicate that the BIM deletion polymorphism is common in Korean NSCLC patients but does not significantly affect the intrinsic biologic function of BH3-only protein. Furthermore, the BIM deletion polymorphism did not predict clinical outcomes in patients with NSCLC. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Analysis of the Possibility of Required Resources Estimation for Nuclear Power Plant Decommissioning Applying BIM

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Insu [Korea Institute of construction Technology, Goyang (Korea, Republic of); Kim, Woojung [KHNP-Central Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    Estimation of decommissioning cost, decommissioning strategy, and decommissioning quantity at the time when entering into any decommissioning plans are some elements whose inputs are mandatory for nuclear power plant decommissioning. Ways to estimate decommissioning of required resources in the past have imposed great uncertainty since they analyze required resources at the construction stage, analyzing and consulting decommissioning required resources of overseas nuclear power plants. This study aims at analyzing whether required resources for decommissioning nuclear power plants can be estimated, applying BIM. To achieve this goal, this study analyzed the status quo of BIM such as definition, characteristics, and areas applied, and made use of them when drawing out study results by examining types and features of the tools realizing BIM. In order to review how BIM could be used for decommissioning nuclear power plants, the definition, characteristics and applied areas of BIM were discussed. BIM designs objects of the structures (walls, slabs, pillars, stairs, windows and doors, etc.) by 3D technology and endows attribute (function, structure and usage) information for each object, thereby providing visualized information of structures for participants in construction projects. Major characteristics of BIM attribute information are as follows: - Geometry: The information of objects is represented by measurable geometric information - Extensible object attributes: Objects include pre-defined attributes, and allow extension of other attributes. Any model that includes these attributes forms relationships with other various attributes in order to perform analysis and simulation. - All information including the attributes are integrated to ensure continuity, accuracy and accessibility, and all information used during the life cycle of structures are supported. This means that when information of required resources is added as another attributes other than geometric

  4. B-H Bond Activation by an Amidinate-Stabilized Amidosilylene: Non-Innocent Amidinate Ligand.

    Science.gov (United States)

    Khoo, Sabrina; Shan, Yu-Liang; Yang, Ming-Chung; Li, Yongxin; Su, Ming-Der; So, Cheuk-Wai

    2018-05-21

    The activation of B-H and B-Cl bonds in boranes by base-stabilized low-valent silicon compounds is described. The reaction of the amidinato amidosilylene-borane adduct [L{Ar(Me 3 Si)N}SiBH 3 ] [1; L = PhC(N tBu) 2 , and Ar = 2,6- iPr 2 C 6 H 3 ] with MeOTf in toluene at room temperature formed [L{Ar(Me 3 Si)N}SiBH 2 OTf] (2). [LSiN(SiMe 3 )Ar] in compound 2 then underwent a B-H bond activation with BH 2 OTf in refluxing toluene to afford the B-H bond activation product [LB(H)Si(H)(OTf){N(SiMe 3 )Ar}] (3). On the other hand, when compound 2 was reacted with 4-dimethylaminopyridine in refluxing toluene, another B-H bond activation product [(μ-κ1:κ1-L)B(H)(DMAP)Si(H){N(Ar)SiMe 3 }]OTf (4) was afforded. Mechanistic studies show that "(μ-κ1:κ1-L)B(H)(OTf)Si(H){N(Ar)SiMe 3 }" (2A) is the key intermediate in the reactions mentioned above. The formation of 2A is further evidenced by the activation of the B-Cl bond in PhBCl 2 by the amidinato silicon(I) dimer [LSi:] 2 to form the B-Cl bond activation product [(μ-κ1:κ1-L)B(Cl)(Ph)Si(Cl)] 2 (6). Compounds 2-4 and 6 were characterized by nuclear magnetic resonance spectroscopy and X-ray crystallography.

  5. Antibody mimetics: promising complementary agents to animal-sourced antibodies.

    Science.gov (United States)

    Baloch, Abdul Rasheed; Baloch, Abdul Wahid; Sutton, Brian J; Zhang, Xiaoying

    2016-01-01

    Despite their wide use as therapeutic, diagnostic and detection agents, the limitations of polyclonal and monoclonal antibodies have inspired scientists to design the next generation biomedical agents, so-called antibody mimetics that offer many advantages over conventional antibodies. Antibody mimetics can be constructed by protein-directed evolution or fusion of complementarity-determining regions through intervening framework regions. Substantial progress in exploiting human, butterfly (Pieris brassicae) and bacterial systems to design and select mimetics using display technologies has been made in the past 10 years, and one of these mimetics [Kalbitor® (Dyax)] has made its way to market. Many challenges lie ahead to develop mimetics for various biomedical applications, especially those for which conventional antibodies are ineffective, and this review describes the current characteristics, construction and applications of antibody mimetics compared to animal-sourced antibodies. The possible limitations of mimetics and future perspectives are also discussed.

  6. Quantification of construction waste prevented by BIM-based design validation: Case studies in South Korea.

    Science.gov (United States)

    Won, Jongsung; Cheng, Jack C P; Lee, Ghang

    2016-03-01

    Waste generated in construction and demolition processes comprised around 50% of the solid waste in South Korea in 2013. Many cases show that design validation based on building information modeling (BIM) is an effective means to reduce the amount of construction waste since construction waste is mainly generated due to improper design and unexpected changes in the design and construction phases. However, the amount of construction waste that could be avoided by adopting BIM-based design validation has been unknown. This paper aims to estimate the amount of construction waste prevented by a BIM-based design validation process based on the amount of construction waste that might be generated due to design errors. Two project cases in South Korea were studied in this paper, with 381 and 136 design errors detected, respectively during the BIM-based design validation. Each design error was categorized according to its cause and the likelihood of detection before construction. The case studies show that BIM-based design validation could prevent 4.3-15.2% of construction waste that might have been generated without using BIM. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Large-scale structure in mimetic Horndeski gravity

    Science.gov (United States)

    Arroja, Frederico; Okumura, Teppei; Bartolo, Nicola; Karmakar, Purnendu; Matarrese, Sabino

    2018-05-01

    In this paper, we propose to use the mimetic Horndeski model as a model for the dark universe. Both cold dark matter (CDM) and dark energy (DE) phenomena are described by a single component, the mimetic field. In linear theory, we show that this component effectively behaves like a perfect fluid with zero sound speed and clusters on all scales. For the simpler mimetic cubic Horndeski model, if the background expansion history is chosen to be identical to a perfect fluid DE (PFDE) then the mimetic model predicts the same power spectrum of the Newtonian potential as the PFDE model with zero sound speed. In particular, if the background is chosen to be the same as that of LCDM, then also in this case the power spectrum of the Newtonian potential in the mimetic model becomes indistinguishable from the power spectrum in LCDM on linear scales. A different conclusion may be found in the case of non-adiabatic perturbations. We also discuss the distinguishability, using power spectrum measurements from LCDM N-body simulations as a proxy for future observations, between these mimetic models and other popular models of DE. For instance, we find that if the background has an equation of state equal to ‑0.95 then we will be able to distinguish the mimetic model from the PFDE model with unity sound speed. On the other hand, it will be hard to do this distinction with respect to the LCDM model.

  8. BIM Anatomy II: Standardisation Needs & Support Systems

    OpenAIRE

    Hooper, Martin

    2015-01-01

    This thesis presents the results of an investigation into BIM standardisation needs and procedural supporting mechanisms that may enable design, construction and operating (DCO) organisations to advance their deployment of Building Information Modelling (BIM) technology, and improve construction project outcomes. To achieve sustainable development requires effective information management. Building Information Modelling is of strategic importance for the development of effi...

  9. Applications of building information model (BIM) in Malaysian construction industry

    Science.gov (United States)

    Tahir, M. M.; Haron, N. A.; Alias, A. H.; Al-Jumaa, A. T.; Muhammad, I. B.; Harun, A. N.

    2017-12-01

    Since the introduction of BIM in Malaysia in 2009, the technology adoption rate is slow when compared to other countries of the world. Most of the construction companies in Malaysia have an insight on the BIM concept but are yet to implement it in the management of their construction projects. By the year 2020, the Malaysian government will make BIM mandatory, this makes it important to carry out research on the possible applications of the technology. A qualitative method of enquiry was used for this study in Klang Valley using semistructured interview. The responses received were analysed using Principal component analysis (PCA). The result of the analysis showed that “quantity take-off and estimation”, “clash detection and coordination”, “integration and collaboration of stakeholders”, and “design and visualisation” as the main applications of BIM in Malaysia presently. The implication of this findings is that the Malaysian construction industry productivity is likely to increase to meet the demand of the population through the implementations of BIM. More also, BIM technology is regarded as the future of construction industry, which makes it very important for the industry.

  10. Embedding BIM into interaction frameworks and object libraries

    NARCIS (Netherlands)

    Böhms, H.M.; Willems, P.H.

    2012-01-01

    A building information model (BIM) is just one component of the jigsaw puzzle of high quality information management to control the life cycle processes around building structures. A BIM in itself is not sufficient to solve adequately the ICT support shortcomings of the building production chain.

  11. A Framework for BIM-Enabled Life-Cycle Information Management of Construction Project

    Directory of Open Access Journals (Sweden)

    Xun Xu

    2014-08-01

    Full Text Available BIM has been widely used in project management, but on the whole the applications have been scattered and the BIM models have not been deployed throughout the whole project life-cycle. Each participant builds their own BIM, so there is a major problem in how to integrate these dynamic and fragmented data together. In order to solve this problem, this paper focuses on BIM-based life-cycle information management and builds a framework for BIM-enabled life-cycle information management. To organize the life-cycle information well, the information components and information flow during the project life-cycle are defined. Then, the application of BIM in life-cycle information management is analysed. This framework will provide a unified platform for information management and ensure data integrity.

  12. Teaching Sustainable Design Using BIM and Project-Based Energy Simulations

    Directory of Open Access Journals (Sweden)

    Zhigang Shen

    2012-08-01

    Full Text Available The cross-disciplinary nature of energy-efficient building design has created many challenges for architecture, engineering and construction instructors. One of the technical challenges in teaching sustainable building design is enabling students to quantitatively understand how different building designs affect a building’s energy performance. Concept based instructional methods fall short in evaluating the impact of different design choices on a buildings’ energy consumption. Building Information Modeling (BIM with energy performance software provides a feasible tool to evaluate building design parameters. One notable advantage of this tool is its ability to couple 3D visualization of the structure with energy performance analysis without requiring detailed mathematical and thermodynamic calculations. Project-based Learning (PBL utilizing BIM tools coupled with energy analysis software was incorporated into a senior level undergraduate class. Student perceptions and feedback were analyzed to gauge the effectiveness of these techniques as instructional tools. The findings indicated that BIM-PBL can be used to effectively teach energy-efficient building design and construction.

  13. Structural Phase Transitions of Mg(BH4)2 under Pressure

    International Nuclear Information System (INIS)

    George, L.; Drozd, V.; Saxena, S.; Bardaji, E.; Fichtner, M.

    2009-01-01

    The structural stability of Mg(BH4)2, a promising hydrogen storage material, under pressure has been investigated in a diamond anvil cell up to 22 GPa with combined synchrotron X-ray diffraction and Raman spectroscopy. The analyses show a structural phase transition around 2.5 GPa and again around 14.4 GPa. An ambient-pressure phase of Mg(BH4)2 has a hexagonal structure (space group P61, a = 10.047(3) A, c = 36.34(1) A, and V = 3176(1) A3 at 0.2 GPa), which agrees well with early reports. The structure of high-pressure phase is found to be different from reported theoretical predictions; it also does not match the high-temperature phase. The high-pressure polymorph of Mg(BH4)2 is found to be stable on decompression, similar to the case of the high-temperature phase. Raman spectroscopic study shows a similarity in high-pressure behavior of as-prepared Mg(BH4)2 and its high-temperature phase.

  14. Modelat BIM d’un equipament esportiu existent mitjançant escanejat 3D

    OpenAIRE

    Gaspar Martin, Laura

    2015-01-01

    El projecte contempla la elaboració d’un modelat BIM "asbuilt" d’un equipament esportiu existent de uns 55000m2 de superfície per uns 48 m d'alçada màxima. El procés a partir del qual es farà el modelat serà mitjançant els núvols de punts aportats per l'escanejat d’un làser 3D i fotos de 360 graus. El projecte contindrà tot el procés d’elaboració des de la recaptació de punts mitjançant làser 3D i fotos que ens passa una empresa col•laboradora, els quals nosaltres modifiquem pe...

  15. Characteristics of Al Alloy as a Material for Hydrolysis Reactor of NaBH{sub 4}

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Hyeon-Seong; Oh, Sung-June; Jeong, Jae-Jin; Na, Il-Chai; Chu, Cheun-Ho; Park, Kwon-Pil [Sunchon National University, Suncheon (Korea, Republic of); Chu, Cheun-Ho [ETIS Co, Gimpo (Korea, Republic of)

    2015-12-15

    Aluminum alloy was examined as a material of low weight reactor for hydrolysis of NaBH{sub 4}. Aluminum is dissolved with alkali, but there is NaOH as a stabilizer in NaBH{sub 4} solution. To decrease corrosion rate of aluminum, decrease NaOH concentration and this result in loss of NaBH{sub 4} during storage of NaBH{sub 4} solution. Therefore stability of NaBH{sub 4} and corrosion of aluminum should be considered in determining the optimum NaOH concentration. NaBH{sub 4} stability and corrosion rate of aluminum were measured by hydrogen evolution rate. NaBH{sub 4} stability was tested at 20-50 .deg. C and aluminum corrosion was measured at 60-90 .deg. C. The optimum concentration of NaOH was 0.3 wt%, considering both NaBH{sub 4} stability and aluminun corrosion. NaBH{sub 4} hydrolysis reaction continued 200min in aluminum No 6061 alloy reactor with 0.3 wt% NaOH at 80-90 .deg. C.

  16. Ruxolitinib synergizes with DMF to kill via BIM+BAD-induced mitochondrial dysfunction and via reduced SOD2/TRX expression and ROS.

    Science.gov (United States)

    Tavallai, Mehrad; Booth, Laurence; Roberts, Jane L; McGuire, William P; Poklepovic, Andrew; Dent, Paul

    2016-04-05

    We determined whether the myelofibrosis drug ruxolitinib, an inhibitor of Janus kinases 1/2 (JAK1 and JAK2), could interact with the multiple sclerosis drug dimethyl-fumarate (DMF) to kill tumor cells; studies used the in vivo active form of the drug, mono-methyl fumarate (MMF). Ruxolitinib interacted with MMF to kill brain, breast, lung and ovarian cancer cells, and enhanced the lethality of standard of care therapies such as paclitaxel and temozolomide. MMF also interacted with other FDA approved drugs to kill tumor cells including Celebrex® and Gilenya®. The combination of [ruxolitinib + MMF] inactivated ERK1/2, AKT, STAT3 and STAT5; reduced expression of MCL-1, BCL-XL, SOD2 and TRX; increased BIM expression; decreased BAD S112 S136 phosphorylation; and enhanced pro-caspase 3 cleavage. Expression of activated forms of STAT3, MEK1 or AKT each significantly reduced drug combination lethality; prevented BAD S112 S136 dephosphorylation and decreased BIM expression; and preserved TRX, SOD2, MCL-1 and BCL-XL expression. The drug combination increased the levels of reactive oxygen species in cells, and over-expression of TRX or SOD2 prevented drug combination tumor cell killing. Over-expression of BCL-XL or knock down of BAX, BIM, BAD or apoptosis inducing factor (AIF) protected tumor cells. The drug combination increased AIF : HSP70 co-localization in the cytosol but this event did not prevent AIF : eIF3A association in the nucleus.

  17. Dehydriding and rehydriding reactions of LiBH4

    International Nuclear Information System (INIS)

    Orimo, S.; Nakamori, Y.; Kitahara, G.; Miwa, K.; Ohba, N.; Towata, S.; Zuettel, A.

    2005-01-01

    Structural differences in LiBH 4 before and after the melting reaction at approximately 550-bar K were investigated to clarify the experimental method for the confirmation of reversible dehydriding and rehydriding reactions. Since the long-range order of LiBH 4 begins to disappear after the melting reaction was achieved, investigation of the atomistic vibrations of the [BH 4 ]-anion in LiBH 4 was found to be effective for the confirmation of the reversibility. In the present study, LiBH 4 was successively dehydrided (decomposed) into LiH and B under 1-bar MPa of hydrogen at 873-bar K, and then rehydrided (recombined) into LiBH 4 under 35-bar MPa of hydrogen at the same temperature (873-bar K). The temperatures at the beginning and ending of the dehydriding reaction are lowered, by approximately 30-bar K, for LiBH 4 substituted (or mixed) with Mg (atomic ratio of Li:Mg=9:1) as compared to those for LiBH 4 alone. This is similar to the tendency exhibited by LiNH 2

  18. Are all Building Information Models (BIM) the same?; Het ene BIM is het andere niet

    Energy Technology Data Exchange (ETDEWEB)

    Bouwman, J.W. [VolkerWessels, Rotterdam (Netherlands); Kuijer, H.J. [DHV, Amersfoort (Netherlands)

    2011-04-15

    Building Brains has been set up by TNO as a cooperative and started September 21, 2009. The aim of the project was to answer the question how the energy consumption in the Netherlands can be reduced by 50% up to 2030 or how the built environment can be made energy-neutral. This issue of the magazine is dedicated to Building Brains project. BIM (Building Information Modelling) is one of the major buzzwords in the building industry today. However, not every BIM in the market is the same, nor have they the same intentions, nor have they the same functionality. In this article the authors argument the reasons behind the structure of BIM data as used by the project Building Brains as well as its use in the newly developed building process. In the second part of this article the authors demonstrate the advantages of this structure by means of an example in the design process, where, thanks to a BIIM and a suitable library, the data always represents a 100% finished building (however in the early design stage the largest part of the data will be 'in progress' as towards the end of the design the largest part of the data will be 'final') [Dutch] Building Brains is een door TNO opgezet samenwerkingsproject dat op 21 september 2009 van start ging. Het doel van het project is antwoord te geven op de vraag hoe tot 2030 het energiegebruik in Nederland kan worden gehalveerd of hoe de gebouwde omgeving energieneutraal kan worden gemaakt. Deze aflevering van het tijdschrift TVVL is vrijwel geheel gewijd aan het Building Brains project. Het gebouw was een van de onderwerpen in Building Brains. De onderzoeksdoelstelling bij dit onderwerp luidde: 'Onderzoek wat nodig is om te komen tot een breed toepasbaar, bestendig recept met ingredienten en gerei om in de nabije toekomst gebouwen aantoonbaar duurzaam te maken'. Een randvoorwaarde was: 'Hoe en in welke vorm is BIM (Bouwwerk Informatie Model) in dit recept inzetbaar'. Dit artikel gaat in op de

  19. Aprendizaje de los roles de los agentes BIM en la organización de proyectos = Learning the roles of BIM agents in project management

    Directory of Open Access Journals (Sweden)

    Carolina Piña Ramirez

    2017-04-01

    Full Text Available Actualmente la metodología BIM se está desarrollando en todas las ramas de la construcción e ingeniería. La Unión Europea con la Directiva2014/24/UE marca un hito en el mercado, recomendando a los estados miembros el uso de BIM en sus proyectos, y España, por su parte está en fase de desarrollo de una transposición de esa directiva para implantar esa metodología, con el Ministerio de Fomento. Esta transformación del sector nos lleva a la necesidad de instituir profesionales de calidad cuya formación sea la competente para la inmersión en el mercado profesional existente. Por ello, el propósito de este artículo es exportar a la universidad el conocimiento de la relación entre las implicaciones de los agentes intervinientes en la metodología BIM y las fases de un proyecto. Este trabajo tiene como finalidad de conseguir una mejora en la enseñanza del Graduado en Ingeniería de la Edificación de la Universidad Politécnica de Madrid, hacia el cambio BIM. Abstract Currently the BIM methodology is being developed in all branches of construction and engineering. The European Union with the Directive2014/2/EU set a benchmark in the market, recommending to Member States the use of BIM in projects. Spain is actually in the process of developing a transposition of that directive to implement that methodology. This sector transformation makes it necessary to train professionals with adequate training to be immerse in the market. Therefore, the aim of this article is to export to the university the knowledge of the relationship between the implications of the intervening agents in the BIM methodology and the phases of a project. This has the purpose of obtaining an improvement in the teaching of the Graduate in Engineering of the Building of the Polytechnic University of Madrid, towards the BIM change.

  20. BIM Based Virtual Environment for Fire Emergency Evacuation

    Directory of Open Access Journals (Sweden)

    Bin Wang

    2014-01-01

    Full Text Available Recent building emergency management research has highlighted the need for the effective utilization of dynamically changing building information. BIM (building information modelling can play a significant role in this process due to its comprehensive and standardized data format and integrated process. This paper introduces a BIM based virtual environment supported by virtual reality (VR and a serious game engine to address several key issues for building emergency management, for example, timely two-way information updating and better emergency awareness training. The focus of this paper lies on how to utilize BIM as a comprehensive building information provider to work with virtual reality technologies to build an adaptable immersive serious game environment to provide real-time fire evacuation guidance. The innovation lies on the seamless integration between BIM and a serious game based virtual reality (VR environment aiming at practical problem solving by leveraging state-of-the-art computing technologies. The system has been tested for its robustness and functionality against the development requirements, and the results showed promising potential to support more effective emergency management.

  1. BIM based virtual environment for fire emergency evacuation.

    Science.gov (United States)

    Wang, Bin; Li, Haijiang; Rezgui, Yacine; Bradley, Alex; Ong, Hoang N

    2014-01-01

    Recent building emergency management research has highlighted the need for the effective utilization of dynamically changing building information. BIM (building information modelling) can play a significant role in this process due to its comprehensive and standardized data format and integrated process. This paper introduces a BIM based virtual environment supported by virtual reality (VR) and a serious game engine to address several key issues for building emergency management, for example, timely two-way information updating and better emergency awareness training. The focus of this paper lies on how to utilize BIM as a comprehensive building information provider to work with virtual reality technologies to build an adaptable immersive serious game environment to provide real-time fire evacuation guidance. The innovation lies on the seamless integration between BIM and a serious game based virtual reality (VR) environment aiming at practical problem solving by leveraging state-of-the-art computing technologies. The system has been tested for its robustness and functionality against the development requirements, and the results showed promising potential to support more effective emergency management.

  2. Analysis of Uncertainty in a Middle-Cost Device for 3D Measurements in BIM Perspective

    Directory of Open Access Journals (Sweden)

    Alonso Sánchez

    2016-09-01

    Full Text Available Medium-cost devices equipped with sensors are being developed to get 3D measurements. Some allow for generating geometric models and point clouds. Nevertheless, the accuracy of these measurements should be evaluated, taking into account the requirements of the Building Information Model (BIM. This paper analyzes the uncertainty in outdoor/indoor three-dimensional coordinate measures and point clouds (using Spherical Accuracy Standard (SAS methods for Eyes Map, a medium-cost tablet manufactured by e-Capture Research & Development Company, Mérida, Spain. To achieve it, in outdoor tests, by means of this device, the coordinates of targets were measured from 1 to 6 m and cloud points were obtained. Subsequently, these were compared to the coordinates of the same targets measured by a Total Station. The Euclidean average distance error was 0.005–0.027 m for measurements by Photogrammetry and 0.013–0.021 m for the point clouds. All of them satisfy the tolerance for point cloud acquisition (0.051 m according to the BIM Guide for 3D Imaging (General Services Administration; similar results are obtained in the indoor tests, with values of 0.022 m. In this paper, we establish the optimal distances for the observations in both, Photogrammetry and 3D Photomodeling modes (outdoor and point out some working conditions to avoid in indoor environments. Finally, the authors discuss some recommendations for improving the performance and working methods of the device.

  3. INCORPORATION OF BIM IN BUILDING CONSTRUCTION TECHNICIAN COURSE

    Directory of Open Access Journals (Sweden)

    Marcio de Oliveira Cruz

    2017-11-01

    Full Text Available A necessidade de inserir no mercado técnicos qualificados na produçao de modelos de informaçao da construçao, extraçao de dados, detecçao de interferencias e outras açoes relacionadas ao Building Information Modeling (BIM, fez com que a escola Senai Orlando Laviero Ferraiuolo buscasse meios para incorporá-lo ao ensino. Tendo em vista o objetivo de inserçao da formaçao em BIM a nível básico, iniciou-se uma investigaçao das barreiras para a adoçao deste processo no curso e, paralelamente, adotou-se a utilizaçao de estratégias para a incorporaçao do conteúdo em um conjunto abrangente de disciplinas. Neste artigo busca-se relatar o procedimento de diagnóstico das barreiras para adoçao de BIM realizado e o processo simultâneo de açoes para incorporaçao de BIM. Para apoiar este diagnóstico, foi adotado o método de pesquisa etnográfica. Esta investigaçao foi desenvolvida em dois ciclos: no primeiro, aplicou-se o método de diagnóstico de Checcucci, em formato de entrevista em profundidade juntamente com a observaçao participante; no segundo, adaptou-se o método para o formato de levantamento, por meio de um questionário online. Com esta pesquisa foi possível descrever elementos da organizaçao no contexto da incorporaçao de BIM na formaçao do técnico de edificaçoes. Os elementos caracterizados foram a transformaçao na estrutura curricular e a percepçao do corpo docente sobre as barreiras associadas. As contribuiçoes deste trabalho sao o registro do processo e diagnóstico de implementaçao de BIM no curso Técnico em Edificaçoes, as açoes que possibilitaram o amadurecimento do conhecimento dos professores e a adaptaçao do método de Checcucci para diagnóstico da permeabilidade da inserçao de BIM em estruturas curriculares.

  4. Bim and Gis: when Parametric Modeling Meets Geospatial Data

    Science.gov (United States)

    Barazzetti, L.; Banfi, F.

    2017-12-01

    Geospatial data have a crucial role in several projects related to infrastructures and land management. GIS software are able to perform advanced geospatial analyses, but they lack several instruments and tools for parametric modelling typically available in BIM. At the same time, BIM software designed for buildings have limited tools to handle geospatial data. As things stand at the moment, BIM and GIS could appear as complementary solutions, notwithstanding research work is currently under development to ensure a better level of interoperability, especially at the scale of the building. On the other hand, the transition from the local (building) scale to the infrastructure (where geospatial data cannot be neglected) has already demonstrated that parametric modelling integrated with geoinformation is a powerful tool to simplify and speed up some phases of the design workflow. This paper reviews such mixed approaches with both simulated and real examples, demonstrating that integration is already a reality at specific scales, which are not dominated by "pure" GIS or BIM. The paper will also demonstrate that some traditional operations carried out with GIS software are also available in parametric modelling software for BIM, such as transformation between reference systems, DEM generation, feature extraction, and geospatial queries. A real case study is illustrated and discussed to show the advantage of a combined use of both technologies. BIM and GIS integration can generate greater usage of geospatial data in the AECOO (Architecture, Engineering, Construction, Owner and Operator) industry, as well as new solutions for parametric modelling with additional geoinformation.

  5. BIM AND GIS: WHEN PARAMETRIC MODELING MEETS GEOSPATIAL DATA

    Directory of Open Access Journals (Sweden)

    L. Barazzetti

    2017-12-01

    Full Text Available Geospatial data have a crucial role in several projects related to infrastructures and land management. GIS software are able to perform advanced geospatial analyses, but they lack several instruments and tools for parametric modelling typically available in BIM. At the same time, BIM software designed for buildings have limited tools to handle geospatial data. As things stand at the moment, BIM and GIS could appear as complementary solutions, notwithstanding research work is currently under development to ensure a better level of interoperability, especially at the scale of the building. On the other hand, the transition from the local (building scale to the infrastructure (where geospatial data cannot be neglected has already demonstrated that parametric modelling integrated with geoinformation is a powerful tool to simplify and speed up some phases of the design workflow. This paper reviews such mixed approaches with both simulated and real examples, demonstrating that integration is already a reality at specific scales, which are not dominated by “pure” GIS or BIM. The paper will also demonstrate that some traditional operations carried out with GIS software are also available in parametric modelling software for BIM, such as transformation between reference systems, DEM generation, feature extraction, and geospatial queries. A real case study is illustrated and discussed to show the advantage of a combined use of both technologies. BIM and GIS integration can generate greater usage of geospatial data in the AECOO (Architecture, Engineering, Construction, Owner and Operator industry, as well as new solutions for parametric modelling with additional geoinformation.

  6. RNA-Binding Protein Dnd1 Promotes Breast Cancer Apoptosis by Stabilizing the Bim mRNA in a miR-221 Binding Site

    Directory of Open Access Journals (Sweden)

    Feng Cheng

    2017-01-01

    Full Text Available RNA-binding proteins (RBPs and miRNAs are capable of controlling processes in normal development and cancer. Both of them could determine RNA transcripts fate from synthesis to decay. One such RBP, Dead end (Dnd1, is essential for regulating germ-cell viability and suppresses the germ-cell tumors development, yet how it exerts its functions in breast cancer has remained unresolved. The level of Dnd1 was detected in 21 cancerous tissues paired with neighboring normal tissues by qRT-PCR. We further annotated TCGA (The Cancer Genome Atlas mRNA expression profiles and found that the expression of Dnd1 and Bim is positively correlated (p=0.04. Patients with higher Dnd1 expression level had longer overall survival (p=0.0014 by KM Plotter tool. Dnd1 knockdown in MCF-7 cells decreased Bim expression levels and inhibited apoptosis. While knockdown of Dnd1 promoted the decay of Bim mRNA 3′UTR, the stability of Bim-5′UTR was not affected. In addition, mutation of miR-221-binding site in Bim-3′UTR canceled the effect of Dnd1 on Bim mRNA. Knockdown of Dnd1 in MCF-7 cells confirmed that Dnd1 antagonized miR-221-inhibitory effects on Bim expression. Overall, our findings indicate that Dnd1 facilitates apoptosis by increasing the expression of Bim via its competitive combining with miR-221 in Bim-3′UTR. The new function of Dnd1 may contribute to a vital role in breast cancer development.

  7. BIM-Enabled Conceptual Modelling and Representation of Building Circulation

    Directory of Open Access Journals (Sweden)

    Jin Kook Lee

    2014-08-01

    Full Text Available This paper describes how a building information modelling (BIM-based approach for building circulation enables us to change the process of building design in terms of its computational representation and processes, focusing on the conceptual modelling and representation of circulation within buildings. BIM has been designed for use by several BIM authoring tools, in particular with the widely known interoperable industry foundation classes (IFCs, which follow an object-oriented data modelling methodology. Advances in BIM authoring tools, using space objects and their relations defined in an IFC's schema, have made it possible to model, visualize and analyse circulation within buildings prior to their construction. Agent-based circulation has long been an interdisciplinary topic of research across several areas, including design computing, computer science, architectural morphology, human behaviour and environmental psychology. Such conventional approaches to building circulation are centred on navigational knowledge about built environments, and represent specific circulation paths and regulations. This paper, however, places emphasis on the use of ‘space objects’ in BIM-enabled design processes rather than on circulation agents, the latter of which are not defined in the IFCs' schemas. By introducing and reviewing some associated research and projects, this paper also surveys how such a circulation representation is applicable to the analysis of building circulation-related rules.

  8. Cellular responses to a prolonged delay in mitosis are determined by a DNA damage response controlled by Bcl-2 family proteins.

    Science.gov (United States)

    Colin, Didier J; Hain, Karolina O; Allan, Lindsey A; Clarke, Paul R

    2015-03-01

    Anti-cancer drugs that disrupt mitosis inhibit cell proliferation and induce apoptosis, although the mechanisms of these responses are poorly understood. Here, we characterize a mitotic stress response that determines cell fate in response to microtubule poisons. We show that mitotic arrest induced by these drugs produces a temporally controlled DNA damage response (DDR) characterized by the caspase-dependent formation of γH2AX foci in non-apoptotic cells. Following exit from a delayed mitosis, this initial response results in activation of DDR protein kinases, phosphorylation of the tumour suppressor p53 and a delay in subsequent cell cycle progression. We show that this response is controlled by Mcl-1, a regulator of caspase activation that becomes degraded during mitotic arrest. Chemical inhibition of Mcl-1 and the related proteins Bcl-2 and Bcl-xL by a BH3 mimetic enhances the mitotic DDR, promotes p53 activation and inhibits subsequent cell cycle progression. We also show that inhibitors of DDR protein kinases as well as BH3 mimetics promote apoptosis synergistically with taxol (paclitaxel) in a variety of cancer cell lines. Our work demonstrates the role of mitotic DNA damage responses in determining cell fate in response to microtubule poisons and BH3 mimetics, providing a rationale for anti-cancer combination chemotherapies.

  9. Motivation Factors for Adopting Building Information Modeling (BIM in Iraq

    Directory of Open Access Journals (Sweden)

    W. A. Hatem

    2018-04-01

    Full Text Available Building information modeling (BIM is an integrated and comprehensive system including whatever is related to a construction project and its stages. It represents a unified database for all project data through which project documents are available to all stakeholders. This paper evaluates the factors driving the adoption of BIM in Iraqi construction projects in different ministries and adopts quantitative approach to collect data by using a questionnaire survey specially prepared for this purpose which was distributed to experts in the ministries of the Iraqi construction sector. Returned data were subjected to proper statistical analysis. Results showed that the highest motivation for BIM application is to include it in the educational curricula, raise awareness through courses and workshops and contracting with international experts with experience in BIM field.

  10. Best practices of Building Information Modelling (BIM) implementation in design phase for construction project

    Science.gov (United States)

    Kasim, N.; Zainal Abidin, N. A.; Zainal, R.; Sarpin, N.; Rahim, M. H. I. Abd; Saikah, M.

    2017-11-01

    Implementation of Building Information Modelling (BIM) was expected to bring improvement in current practices of Malaysian construction industry. In the design phase, there is a lack of a ready pool of skilled workers who are able to develop BIM strategic plan and effectively utilise it. These create boundaries for BIM nature in Malaysian construction industry specifically in the design phase to achieve its best practices. Therefore, the objectives of this research are to investigate the current practices of BIM implementation in the design phase as well as the best practices factors of BIM implementation in the design phase. The qualitative research approach is carried out through semi-structured interviews with the designers of different organisations which adopt BIM in the design phase. Data collection is analysed by executing content analysis method. From the findings, the best practices factors of BIM implementation in design phase such as the incentive for BIM training, formal approach to monitoring automated Level of Detailing (LOD), run a virtual meeting and improve Industry Foundation Class (IFC). Thus, best practices factors which lead to practices improvements in the design phase of project development which subsequently improves the implementation of BIM in the design phase of Malaysian construction industry.

  11. Expression, purification and characterization of hepatitis B virus X protein BH3-like motif-linker-Bcl-xL fusion protein for structural studies

    Directory of Open Access Journals (Sweden)

    Hideki Kusunoki

    2017-03-01

    Full Text Available Hepatitis B virus X protein (HBx is a multifunctional protein that interacts directly with many host proteins. For example, HBx interacts with anti-apoptotic proteins, Bcl-2 and Bcl-xL, through its BH3-like motif, which leads to elevated cytosolic calcium levels, efficient viral DNA replication and the induction of apoptosis. To facilitate sample preparation and perform detailed structural characterization of the complex between HBx and Bcl-xL, we designed and purified a recombinant HBx BH3-like motif-linker-Bcl-xL fusion protein produced in E. coli. The fusion protein was characterized by size exclusion chromatography, circular dichroism and nuclear magnetic resonance experiments. Our results show that the fusion protein is a monomer in aqueous solution, forms a stable intramolecular complex, and likely retains the native conformation of the complex between Bcl-xL and the HBx BH3-like motif. Furthermore, the HBx BH3-like motif of the intramolecular complex forms an α-helix. These observations indicate that the fusion protein should facilitate structural studies aimed at understanding the interaction between HBx and Bcl-xL at the atomic level.

  12. The benefits of, and barriers to, implementation of 5D BIM for quantity surveying in New Zealand

    Directory of Open Access Journals (Sweden)

    Ryan Stanley

    2014-03-01

    Full Text Available Building Information Modelling (BIM models are relational and parametric in nature, and 5D BIM is where model objects include specification data and other properties which can be directly used for pricing construction work. There is huge potential for its use by quantity surveyors (QSs for such tasks as quantity take-offs, estimation and cost management, in a collaborative project environment. Perceptions regarding the benefits of, and barriers to, the implementation of 5D BIM by quantity surveyors in Auckland are presented, based on structured interviews with 8 QSs. Results suggest that 5D BIM may provide advantages over traditional forms of quantity surveying in Auckland by increasing efficiency, improving visualization of construction details, and earlier risk identification. However there are perceived barriers to 5D BIM implementation within the construction industry: a lack of software compatibility; prohibitive set-up costs; a lack of protocols for coding objects within building information models; lack of an electronic standard for coding BIM software, and the lack of integrated models, which are an essential pre-requisite for full inter-operability, and hence collaborative working, in the industry. Further research is recommended, to find solutions to overcome these barriers to inter-operability between 3D and 5D BIM, in order to facilitate the cost modelling process.

  13. Application of BIM Technology in Building Water Supply and Drainage Design

    Science.gov (United States)

    Wei, Tianyun; Chen, Guiqing; Wang, Junde

    2017-12-01

    Through the application of BIM technology, the idea of building water supply and drainage designers can be related to the model, the various influencing factors to affect water supply and drainage design can be considered more comprehensively. BIM(Building information model) technology assist in improving the design process of building water supply and drainage, promoting the building water supply and drainage planning, enriching the building water supply and drainage design method, improving the water supply and drainage system design level and building quality. Combined with fuzzy comprehensive evaluation method to analyze the advantages of BIM technology in building water supply and drainage design. Therefore, application prospects of BIM technology are very worthy of promotion.

  14. BIM Open Source Software (OSS for the documentation of cultural heritage

    Directory of Open Access Journals (Sweden)

    Sotiris Logothetis

    2016-11-01

    This paper presents a review of some recent research on the topic. We review the recent developments focusing on the OSS that can be used at various stages of BIM process in the digital documentation of cultural heritage. The results show that there is more preference in the commercial software due to the fact that the OSS is not yet complete and covers all stages of the BIM process. However, lately we have the Edificius in architectural BIM design and “BIM Vision” as Industry Foundation Classes (IFC model viewer that try to attract as many users as possible. These tools are free and they could well be used for the digital reconstruction of cultural heritage.

  15. Amelioration of behavioral abnormalities in BH(4-deficient mice by dietary supplementation of tyrosine.

    Directory of Open Access Journals (Sweden)

    Sang Su Kwak

    Full Text Available This study reports an amelioration of abnormal motor behaviors in tetrahydrobiopterin (BH4-deficient Spr (-/- mice by the dietary supplementation of tyrosine. Since BH4 is an essential cofactor for the conversion of phenylalanine into tyrosine as well as the synthesis of dopamine neurotransmitter within the central nervous system, the levels of tyrosine and dopamine were severely reduced in brains of BH4-deficient Spr (-/- mice. We found that Spr (-/- mice display variable 'open-field' behaviors, impaired motor functions on the 'rotating rod', and dystonic 'hind-limb clasping'. In this study, we report that these aberrant motor deficits displayed by Spr (-/- mice were ameliorated by the therapeutic tyrosine diet for 10 days. This study also suggests that dopamine deficiency in brains of Spr (-/- mice may not be the biological feature of aberrant motor behaviors associated with BH4 deficiency. Brain levels of dopamine (DA and its metabolites in Spr (-/- mice were not substantially increased by the dietary tyrosine therapy. However, we found that mTORC1 activity severely suppressed in brains of Spr (-/- mice fed a normal diet was restored 10 days after feeding the mice the tyrosine diet. The present study proposes that brain mTORC1 signaling pathway is one of the potential targets in understanding abnormal motor behaviors associated with BH4-deficiency.

  16. Measuring the effects of using ICT/BIM in construction projects

    DEFF Research Database (Denmark)

    Lambrecht, Jan Fuglsig; Vestergaard, Flemming; Karlshøj, Jan

    2016-01-01

    This paper focuses on presenting part of the findings from a research project completed in the period of 2009-2013.The research project was funded by the Danish Building & Property Agency with the primary aim to identify and measure the economic effects of using ICT/BIM in construction projects....... Firstly, this paper presents a conceptual evaluation method developed in order to define and describe how case studies focusing on use of ICT/BIM in construction projects could be completed in order to measure (both quantitatively and qualitatively) the effects achieved from using ICT/BIM in construction...... projects. In this context effects are defined both as tangible and intangible effects (both economically and non-economically) directly and/or indirectly as a consequence of using ICT/BIM in a construction project. Secondly, the paper presents and analyses findings achieved from completing four case...

  17. Avian reovirus S1133-induced apoptosis is associated with Bip/GRP79-mediated Bim translocation to the endoplasmic reticulum.

    Science.gov (United States)

    Lin, Ping-Yuan; Liu, Hung-Jen; Chang, Ching-Dong; Chen, Yo-Chia; Chang, Chi-I; Shih, Wen-Ling

    2015-04-01

    In this study the mechanism of avian reovirus (ARV) S1133-induced pathogenesis was investigated, with a focus on the contribution of ER stress to apoptosis. Our results showed that upregulation of the ER stress response protein, as well as caspase-3 activation, occurred in ARV S1133-infected cultured cells and in SPF White Leghorn chicks organs. Upon infection, Bim was translocated specifically to the ER, but not mitochondria, in the middle to late infectious stages. In addition, ARV S1133 induced JNK phosphorylation and promoted JNK-Bim complex formation, which correlated with the Bim translocation and apoptosis induction that was observed at the same time point. Knockdown of BiP/GRP78 by siRNA and inhibition of BiP/GRP78 using EGCG both abolished the formation of the JNK-Bim complex, caspase-3 activation, and subsequent apoptosis induction by ARV S1133 efficiently. These results suggest that BiP/GRP78 played critical roles and works upstream of JNK-Bim in response to the ARV S1133-mediated apoptosis process.

  18. BIM and IoT: A Synopsis from GIS Perspective

    Science.gov (United States)

    Isikdag, U.

    2015-10-01

    Internet-of-Things (IoT) focuses on enabling communication between all devices, things that are existent in real life or that are virtual. Building Information Models (BIMs) and Building Information Modelling is a hype that has been the buzzword of the construction industry for last 15 years. BIMs emerged as a result of a push by the software companies, to tackle the problems of inefficient information exchange between different software and to enable true interoperability. In BIM approach most up-to-date an accurate models of a building are stored in shared central databases during the design and the construction of a project and at post-construction stages. GIS based city monitoring / city management applications require the fusion of information acquired from multiple resources, BIMs, City Models and Sensors. This paper focuses on providing a method for facilitating the GIS based fusion of information residing in digital building "Models" and information acquired from the city objects i.e. "Things". Once this information fusion is accomplished, many fields ranging from Emergency Response, Urban Surveillance, Urban Monitoring to Smart Buildings will have potential benefits.

  19. Ionic conductivity and the formation of cubic CaH2 in the LiBH4-Ca(BH4)2 composite

    DEFF Research Database (Denmark)

    Sveinbjörnsson, Dadi Þorsteinn; Blanchard, Didier; Mýrdal, Jón Steinar Garðarsson

    2014-01-01

    LiBH4–Ca(BH4)2 composites were prepared by ball milling. Their crystal structures and phase composition were investigated using synchrotron X-ray diffraction and Rietveld refinement, and their ionic conductivity was measured using impedance spectroscopy. The materials were found to form a physical...... treatment. Concurrent formation of elemental boron may also occur. The ionic conductivity of the composites was measured using impedance spectroscopy, and was found to be lower than that of ball milled LiBH4. Electronic band structure calculations indicate that cubic CaH2 with hydrogen defects...... is electronically conducting. Its formation along with the possible precipitation of boron therefore has an effect on the measured conductivity of the LiBH4–Ca(BH4)2 composites and may increase the risk of an internal short-circuit in the cells....

  20. BIM i vejsektoren

    DEFF Research Database (Denmark)

    Kjems, Erik

    2015-01-01

    BIM er et udtryk de fleste er stødt på i forbindelse med deres erhverv. Det er meget udbredt i byggesektoren, men knap så kendt i vejsektoren. I det følgende vil det blive forsøgt at forklare begrebet, baggrunden og indholdet herfor, og hvorfor det er noget alle bør tage stilling til inden for en...

  1. Towards the Significance of Decision Aid in Building Information Modeling (BIM Software Selection Process

    Directory of Open Access Journals (Sweden)

    Omar Mohd Faizal

    2014-01-01

    Full Text Available Building Information Modeling (BIM has been considered as a solution in construction industry to numerous problems such as delays, increased lead in times and increased costs. This is due to the concept and characteristic of BIM that will reshaped the way construction project teams work together to increase productivity and improve the final project outcomes (cost, time, quality, safety, functionality, maintainability, etc.. As a result, the construction industry has witnesses numerous of BIM software available in market. Each of this software has offers different function, features. Furthermore, the adoption of BIM required high investment on software, hardware and also training expenses. Thus, there is indentified that there is a need of decision aid for appropriated BIM software selection that fulfill the project needs. However, research indicates that there is limited study attempt to guide decision in BIM software selection problem. Thus, this paper highlight the importance of decision making and support for BIM software selection as it is vital to increase productivity, construction project throughout building lifecycle.

  2. The mimetic finite difference method for elliptic problems

    CERN Document Server

    Veiga, Lourenço Beirão; Manzini, Gianmarco

    2014-01-01

    This book describes the theoretical and computational aspects of the mimetic finite difference method for a wide class of multidimensional elliptic problems, which includes diffusion, advection-diffusion, Stokes, elasticity, magnetostatics and plate bending problems. The modern mimetic discretization technology developed in part by the Authors allows one to solve these equations on unstructured polygonal, polyhedral and generalized polyhedral meshes. The book provides a practical guide for those scientists and engineers that are interested in the computational properties of the mimetic finite difference method such as the accuracy, stability, robustness, and efficiency. Many examples are provided to help the reader to understand and implement this method. This monograph also provides the essential background material and describes basic mathematical tools required to develop further the mimetic discretization technology and to extend it to various applications.

  3. Structure-Function Relationship of the Bik1-Bim1 Complex.

    Science.gov (United States)

    Stangier, Marcel M; Kumar, Anil; Chen, Xiuzhen; Farcas, Ana-Maria; Barral, Yves; Steinmetz, Michel O

    2018-04-03

    In budding yeast, the microtubule plus-end tracking proteins Bik1 (CLIP-170) and Bim1 (EB1) form a complex that interacts with partners involved in spindle positioning, including Stu2 and Kar9. Here, we show that the CAP-Gly and coiled-coil domains of Bik1 interact with the C-terminal ETF peptide of Bim1 and the C-terminal tail region of Stu2, respectively. The crystal structures of the CAP-Gly domain of Bik1 (Bik1CG) alone and in complex with an ETF peptide revealed unique, functionally relevant CAP-Gly elements, establishing Bik1CG as a specific C-terminal phenylalanine recognition domain. Unlike the mammalian CLIP-170-EB1 complex, Bik1-Bim1 forms ternary complexes with the EB1-binding motifs SxIP and LxxPTPh, which are present in diverse proteins, including Kar9. Perturbation of the Bik1-Bim1 interaction in vivo affected Bik1 localization and astral microtubule length. Our results provide insight into the role of the Bik1-Bim1 interaction for cell division, and demonstrate that the CLIP-170-EB1 module is evolutionarily flexible. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Scan-to-BIM in the pre-design phase

    DEFF Research Database (Denmark)

    Slavova, Galina

    2017-01-01

    The high demand for energy-efficiency of buildings nowadays has triggered the need for gathering documentation on existing construction conditions. This information is then used to design buildings with high consideration to the site or to allow the renovation of old buildings that can no longer ...... Information Modelling (BIM) and 3D laser scanning....

  5. The Issues and Considerations Associated with BIM Integration

    OpenAIRE

    Bataw Anas; Kirkham Richard; Lou Eric

    2016-01-01

    The management of data, information and knowledge through the project life cycle of buildings and civil infrastructure projects is becoming increasingly complex. As an attempt to drive efficiencies and address this complexity, the United Kingdom Government has mandated that Building Information Modelling (BIM) methods must be adopted in all public sector construction projects in 2016. Emerging from the US Department of Defence, BIM is an approach to the co-ordination of design and production ...

  6. Photochemistry of U(BH4)4 and U(BD4)4

    International Nuclear Information System (INIS)

    Paine, R.T.; Schonberg, P.R.; Light, R.W.; Danen, W.C.; Freund, S.M.

    1979-01-01

    U(BH 4 ) 4 and U(BD 4 ) 4 are observed to undergo complex degradation reactions promoted by broadband UV radiation. The primary products of these reactions appear to be U(BH 4 ) 3 , B 2 H 6 , H 2 , U(BD 4 ) 3 , B 2 D 6 and D 2 . Further, U(BD 4 ) 4 undergoes a related decomposition reaction under the influence of CO 2 laser irradiation at 924.97 cm -1 . (author)

  7. Progress of Mimetic Enzymes and Their Applications in Chemical Sensors.

    Science.gov (United States)

    Yang, Bin; Li, Jianping; Deng, Huan; Zhang, Lianming

    2016-11-01

    The need to develop innovative and reformative approaches to synthesize chemical sensors has increased in recent years because of demands for selectivity, stability, and reproducibility. Mimetic enzymes provide an efficient and convenient method for chemical sensors. This review summarizes the application of mimetic enzymes in chemical sensors. Mimetic enzymes can be classified into five categories: hydrolases, oxidoreductases, transferases, isomerases, and induced enzymes. Potential and recent applications of mimetic enzymes in chemical sensors are reviewed in detail, and the outlook of profound development has been illustrated.

  8. Root causes occurrence of low BIM adoption in Malaysia: System dynamics modelling approach

    Science.gov (United States)

    Mamter, Shahela; Aziz, Abdul Rashid Abdul; Zulkepli, Jafri

    2017-11-01

    The global implementation of BIM in the construction field is increasing worldwide. Due to the advantages offered by BIM, its implementation is considered important in the construction projects. Nevertheless, the Construction Industry Transformation Plan has reported that the adoption of Building Information Modelling (BIM) in Malaysia is still low and it is estimated at only 10 percent adoption amongst construction stake players. The barriers influencing the occurrence of low adoption BIM in Malaysia have been studied by some researchers. However, these researchers did not investigate the root causes which might lead to the recurring of the barriers to BIM adoption. Root causes that immediately occurrence of barriers, also known as precipitants or trigger causes. This conceptual paper developed the causal loop diagram (CLD) which presents the relationship between the perceived variables using system dynamic modelling approach. The findings revealed a novelty validated diagrams that design the holistic dynamic relationship on the root causes occurrence of low BIM adoption. Nonetheless, the diagram subject to more empirical testing for its practicability and further refinement upon more results expected to emerge as the research progresses.

  9. The electronic donation and frequency shifts on the YCCH⋯BH4- boron-bonded complexes (Y = H, CH3, CF3 and CCl3)

    Science.gov (United States)

    Pordeus, Renato Q.; Rego, Danilo G.; Oliveira, Boaz G.

    2015-06-01

    In this theoretical work, the tetrahydroborate ion (BH4-) was used as proton acceptor in the formation of the YCC-H⋯BH4- complexes (Y = H, CH3, CCl3 and CF3). Using B3LYP/6-311++G(d,p) level of theory, the results of structure corroborate with the analyses of infrared spectra showing that the changes in the bond lengths are in good agreement with the frequency shifts of the HCC-H, H3CCC-H, Cl3CCC-H and F3CCC-H proton donors. Based on the calculations carried out by the Quantum Theory of Atoms in Molecules (QTAIM), the reductions of electronic density corroborate with the red shifts in the frequencies of the C-H bonds. In addition to that, the C-H bonds are polarized because the contributions of s orbital diminish whereas of p increase. In line with this, the variations on the atomic radii computed via QTAIM calculations show that carbon outweigh hydrogen as follows (ΔrC > ΔrH). This scenario is indirectly supported by the Bent's rule of the chemical bonding. Although the interaction energies (corrected with BSSE and ZPE) vary between -19 and -67 kJ mol-1, these complexes interact without covalent character.

  10. Promoting Sustainability through Investment in Building Information Modeling (BIM Technologies: A Design Company Perspective

    Directory of Open Access Journals (Sweden)

    Marius Reizgevičius

    2018-02-01

    Full Text Available The aim of this article is to enhance the understanding of how design companies perceive the benefits of Building Information Modeling (BIM technologies application. BIM is recognized in the literature as a (potentially powerful driver leading the construction sector towards sustainability. However, for design companies, the choice to invest in BIM technologies is basically an economic one. Specifically, a design company assesses economic benefits and efficiency improvements thanks to the application of BIM technologies. The article discusses the return on investments (ROI in BIM technologies and reviews ROI calculation methodologies proposed by other authors. In order to evaluate BIM return on investment correctly practical ROI calculations are carried out. Appropriate methods, together with the relevant variables for ROI calculation, are developed. The study allows for adjusting the calculation method making it more accurate and understandable using the Autodesk Revit based ROI calculation of the first year.

  11. Integration of Jeddah Historical BIM and 3D GIS for Documentation and Restoration of Historical Monument

    Science.gov (United States)

    Baik, A.; Yaagoubi, R.; Boehm, J.

    2015-08-01

    This work outlines a new approach for the integration of 3D Building Information Modelling and the 3D Geographic Information System (GIS) to provide semantically rich models, and to get the benefits from both systems to help document and analyse cultural heritage sites. Our proposed framework is based on the Jeddah Historical Building Information Modelling process (JHBIM). This JHBIM consists of a Hijazi Architectural Objects Library (HAOL) that supports higher level of details (LoD) while decreasing the time of modelling. The Hijazi Architectural Objects Library has been modelled based on the Islamic historical manuscripts and Hijazi architectural pattern books. Moreover, the HAOL is implemented using BIM software called Autodesk Revit. However, it is known that this BIM environment still has some limitations with the non-standard architectural objects. Hence, we propose to integrate the developed 3D JHBIM with 3D GIS for more advanced analysis. To do so, the JHBIM database is exported and semantically enriched with non-architectural information that is necessary for restoration and preservation of historical monuments. After that, this database is integrated with the 3D Model in the 3D GIS solution. At the end of this paper, we'll illustrate our proposed framework by applying it to a Historical Building called Nasif Historical House in Jeddah. First of all, this building is scanned by the use of a Terrestrial Laser Scanner (TLS) and Close Range Photogrammetry. Then, the 3D JHBIM based on the HOAL is designed on Revit Platform. Finally, this model is integrated to a 3D GIS solution through Autodesk InfraWorks. The shown analysis presented in this research highlights the importance of such integration especially for operational decisions and sharing the historical knowledge about Jeddah Historical City. Furthermore, one of the historical buildings in Old Jeddah, Nasif Historical House, was chosen as a test case for the project.

  12. THE EXTRACTION OF INDOOR BUILDING INFORMATION FROM BIM TO OGC INDOORGML

    Directory of Open Access Journals (Sweden)

    T.-A. Teo

    2017-07-01

    Full Text Available Indoor Spatial Data Infrastructure (indoor-SDI is an important SDI for geosptial analysis and location-based services. Building Information Model (BIM has high degree of details in geometric and semantic information for building. This study proposed direct conversion schemes to extract indoor building information from BIM to OGC IndoorGML. The major steps of the research include (1 topological conversion from building model into indoor network model; and (2 generation of IndoorGML. The topological conversion is a major process of generating and mapping nodes and edges from IFC to indoorGML. Node represents every space (e.g. IfcSpace and objects (e.g. IfcDoor in the building while edge shows the relationships between nodes. According to the definition of IndoorGML, the topological model in the dual space is also represented as a set of nodes and edges. These definitions of IndoorGML are the same as in the indoor network. Therefore, we can extract the necessary data in the indoor network and easily convert them into IndoorGML based on IndoorGML Schema. The experiment utilized a real BIM model to examine the proposed method. The experimental results indicated that the 3D indoor model (i.e. IndoorGML model can be automatically imported from IFC model by the proposed procedure. In addition, the geometric and attribute of building elements are completely and correctly converted from BIM to indoor-SDI.

  13. Inter- and intra-organizational conditions for supply chain integration with BIM

    NARCIS (Netherlands)

    Papadonikolaki, E.; Wamelink, J.W.F.

    2017-01-01

    Digitizing buildings via building information modelling (BIM) is increasingly gaining traction in the architecture, engineering and construction (AEC) sector. The plethora of BIM-based technologies affects both inter- and intra-organizational relations. Structured inter-organizational networks

  14. Preparation of Zn(BH4)2 and diborane and hydrogen release properties of Zn(BH4)2+xMgH2 (x=1, 5, 10, and 15)

    Science.gov (United States)

    Kwak, Young Jun; Kwon, Sung Nam; Song, Myoung Youp

    2015-09-01

    Zn(BH4)2 was prepared by milling ZnCl2 and NaBH4 in a planetary ball mill under Ar atmosphere, and Zn(BH4)2+xMgH2 (x=1, 5, 10, and 15) samples were prepared. Diborane (B2H6) and hydrogen release characteristics of the Zn(BH4)2 and Zn(BH4)2+xMgH2 samples were studied. The samples synthesized by milling ZnCl2 and NaBH4 contained Zn(BH4)2 and NaCl, together with small amounts of ZnCl2 and NaBH4. We designated these samples as Zn(BH4)2(+NaCl). The weight loss up to 400 °C of the Zn(BH4)2(+NaCl) sample synthesized by milling 4 h was 11.2 wt%. FT-IR analysis showed that Zn(BH4)2 was formed in the Zn(BH4)2(+NaCl) samples. MgH2 was also milled in a planetary ball mill, and mixed with the Zn(BH4)2(+NaCl) synthesized by milling for 4 h in a mortar and pestle. The weight loss up to 400 °C of Zn(BH4)2(+NaCl)+MgH2 was 8.2 wt%, corresponding to the weight % of diborane and hydrogen released from the Zn(BH4)2(+NaCl)+MgH2 sample, with respect to the sample weight. DTA results of Zn(BH4)2(+NaCl)+xMgH2 showed that the decomposition peak of Zn(BH4)2 was at about 61 °C, and that of MgH2 was at about 370-389 °C.

  15. BIM and IoT: A Synopsis from GIS Perspective

    Directory of Open Access Journals (Sweden)

    U. Isikdag

    2015-10-01

    Full Text Available Internet-of-Things (IoT focuses on enabling communication between all devices, things that are existent in real life or that are virtual. Building Information Models (BIMs and Building Information Modelling is a hype that has been the buzzword of the construction industry for last 15 years. BIMs emerged as a result of a push by the software companies, to tackle the problems of inefficient information exchange between different software and to enable true interoperability. In BIM approach most up-to-date an accurate models of a building are stored in shared central databases during the design and the construction of a project and at post-construction stages. GIS based city monitoring / city management applications require the fusion of information acquired from multiple resources, BIMs, City Models and Sensors. This paper focuses on providing a method for facilitating the GIS based fusion of information residing in digital building “Models” and information acquired from the city objects i.e. “Things”. Once this information fusion is accomplished, many fields ranging from Emergency Response, Urban Surveillance, Urban Monitoring to Smart Buildings will have potential benefits.

  16. Overview of Building Information Modelling (BIM) adoption factors for construction organisations

    Science.gov (United States)

    Mohammad, W. N. S. Wan; Abdullah, M. R.; Ismail, S.; Takim, R.

    2018-04-01

    Improvement and innovation in building visualization, project coordination and communication are the major benefits generated by Building Information Modelling (BIM) for construction organisations. Thus, as many firms across the world would adopt BIM, however they do not know the clear direction in which path they are moving as there is no specific reference available for them to refer to. Hence, the paper seeks to identify the factors of BIM adoption from previous research. The methodology used in this paper is based on literature review from various sources such as conference articles and journals. Then, the findings were analysed using content analysis. The findings show that there are 24 factors found from literature that influence the adoption of BIM and four (4) factors such as vendor, organisational vision, knowledge, and implementation plan are among the least factors mentioned by previous researchers.

  17. Research progress of nanoparticles as enzyme mimetics

    Science.gov (United States)

    Hu, XiaoNa; Liu, JianBo; Hou, Shuai; Wen, Tao; Liu, WenQi; Zhang, Ke; He, WeiWei; Ji, YingLu; Ren, HongXuan; Wang, Qi; Wu, XiaoChun

    2011-10-01

    Natural enzymes as biological catalysts possess remarkable advantages, especially their highly efficient and selective catalysis under mild conditions. However, most natural enzymes are proteins, thus exhibiting an inherent low durability to harsh reaction conditions. Artificial enzyme mimetics have been pursued extensively to avoid this drawback. Quite recently, some inorganic nanoparticles (NPs) have been found to exhibit unique enzyme mimetics. In addition, their much higher stability overcomes the inherent disadvantage of natural enzymes. Furthermore, easy mass-production and low cost endow them more benefits. As a new member of artificial enzyme mimetics, they have received intense attention. In this review article, major progress in this field is summarized and future perspectives are highlighted.

  18. Co-{alpha}Al{sub 2}O{sub 3}-Cu as shaped catalyst in NaBH{sub 4} hydrolysis

    Energy Technology Data Exchange (ETDEWEB)

    Chamoun, R. [Universite Lyon 1, CNRS, UMR 5615, Laboratoire des Multimateriaux et Interfaces, 43 boulevard du 11 Novembre 1918, F-69622 Villeurbanne (France); Universite Libanaise, Faculte des Sciences II, Laboratoire de physique appliquee, 90656 Jdeidet El Metn (Lebanon); Demirci, U.B.; Miele, P. [Universite Lyon 1, CNRS, UMR 5615, Laboratoire des Multimateriaux et Interfaces, 43 boulevard du 11 Novembre 1918, F-69622 Villeurbanne (France); Zaatar, Y.; Khoury, A. [Universite Libanaise, Faculte des Sciences II, Laboratoire de physique appliquee, 90656 Jdeidet El Metn (Lebanon)

    2010-07-15

    A study about catalytic films of Co-supported-over-{alpha}Al{sub 2}O{sub 3} fabricated by electrophoretic deposition (EPD) is reported, the as-prepared shaped catalysts being intended to catalyze NaBH{sub 4} hydrolysis. Co-{alpha}Al{sub 2}O{sub 3} supported over Cu substrate can be prepared by a 2-step route: (i) preparation of the supported catalyst Co-{alpha}Al{sub 2}O{sub 3} (in powder form) by wet impregnation of CoCl{sub 2} over {alpha}Al{sub 2}O{sub 3}, followed by a reduction, and (ii) fabrication of Co-{alpha}Al{sub 2}O{sub 3}-Cu (thin film over Cu) by EPD. Both types of catalysts, whatever their form, are highly efficient in hydrolyzing NaBH{sub 4}, conversions of 100% and HGRs of tens of mL(H{sub 2}) min{sup -1} being achieved at 60-80 C. The Co-{alpha}Al{sub 2}O{sub 3}-Cu catalysts are even more reactive than the Co-{alpha}Al{sub 2}O{sub 3} catalysts because the surface of the former materials becomes much more acid than that of the latter ones in the course of the EPD process. The respective rate laws and reaction kinetics have been determined. Independently on the catalyst form, apparent activation energies of about 52 kJ mol{sup -1} and positive reaction orders versus the initial NaBH{sub 4} concentration (i.e. 0.3-0.7) were calculated, suggesting that the EPD does not affect the reaction mechanisms. Besides, it is showed that the hydrolysis is really catalytic as well as typical of a heterogeneous process. For example, an apparent reaction order versus the Co content of 0.9 was calculated. All of these results among others are reported and discussed in the present article. (author)

  19. Complete genome sequence of the biofilm-forming Microbacterium sp. strain BH-3-3-3, isolated from conventional field-grown lettuce (Lactuca sativa) in Norway.

    Science.gov (United States)

    Dees, Merete Wiken; Brurberg, May Bente; Lysøe, Erik

    2017-03-01

    The genus Microbacterium contains bacteria that are ubiquitously distributed in various environments and includes plant-associated bacteria that are able to colonize tissue of agricultural crop plants. Here, we report the 3,508,491 bp complete genome sequence of Microbacterium sp. strain BH-3-3-3, isolated from conventionally grown lettuce ( Lactuca sativa ) from a field in Vestfold, Norway. The nucleotide sequence of this genome was deposited into NCBI GenBank under the accession CP017674.

  20. Hypoxia-Induced Autophagy Is Mediated through Hypoxia-Inducible Factor Induction of BNIP3 and BNIP3L via Their BH3 Domains▿ †

    OpenAIRE

    Bellot, Grégory; Garcia-Medina, Raquel; Gounon, Pierre; Chiche, Johanna; Roux, Danièle; Pouysségur, Jacques; Mazure, Nathalie M.

    2009-01-01

    While hypoxia-inducible factor (HIF) is a major actor in the cell survival response to hypoxia, HIF also is associated with cell death. Several studies implicate the HIF-induced putative BH3-only proapoptotic genes bnip3 and bnip3l in hypoxia-mediated cell death. We, like others, do not support this assertion. Here, we clearly demonstrate that the hypoxic microenvironment contributes to survival rather than cell death by inducing autophagy. The ablation of Beclin1, a major actor of autophagy,...

  1. The Rise Of BIM in Malaysia And Its Impact Towards Quantity Surveying Practices

    Directory of Open Access Journals (Sweden)

    Zainon Nurshuhada

    2016-01-01

    Full Text Available Building Information Modeling (BIM is a new buzzword that is gaining a momentum within the construction industry in Malaysia, and worldwide. BIM is a way of working that involves the automation of the entire project team using a 4D model that can do many of the traditional fuctions of a Quatity Surveyor (QS. As BIM is removing more of the traditional work of QS, there are rising fears that it could threaten the viability of the QS professions especially for small firms that still rely on producing bills of quantities. This paper aims to review the challenges and opportunities gained from BIM advancement in QS profession, especially in Malaysia. Despite of serious cost and commercial challenges of BIM implementation, BIM will work wonder as a tool that will cut the amount of time QS have to spend on analysis and provides opportunities to direct QS talents towards being more efficient. This is resulting to better project coordination with a lot less conflict, a more sustainable building in the final instance and also throughout the process, as less time is spent on each stage.

  2. BIM-based collaborative design and socio-technical analytics of green buildings

    NARCIS (Netherlands)

    El-Diraby, T.; Krijnen, T.; Papagelis, M.

    2017-01-01

    As Building Information Modeling evolves into becoming the central mean for coordinating project design and planning activities, we notice a few limitations/opportunities in the way current BIM tools address the needs for integrated design, collaboration and analysis (the initial objective of BIM).

  3. BIM approach for automated drafting and design for modular construction manufacturing

    NARCIS (Netherlands)

    Alwisy, A.; Al-Hussein, M.; Al-Jibouri, Saad H.S.; Issa, R.R.; Flood, I.

    2012-01-01

    Industrialization creates new requirements for design. Designers need to consider not only building performance, but also production plan needs. This requires a well-structured Building Information Model (BIM) to support the manufacturing needs for design and drafting. BIM, in combination with CAD

  4. The relationship between cost estimates reliability and BIM adoption: SEM analysis

    Science.gov (United States)

    Ismail, N. A. A.; Idris, N. H.; Ramli, H.; Rooshdi, R. R. Raja Muhammad; Sahamir, S. R.

    2018-02-01

    This paper presents the usage of Structural Equation Modelling (SEM) approach in analysing the effects of Building Information Modelling (BIM) technology adoption in improving the reliability of cost estimates. Based on the questionnaire survey results, SEM analysis using SPSS-AMOS application examined the relationships between BIM-improved information and cost estimates reliability factors, leading to BIM technology adoption. Six hypotheses were established prior to SEM analysis employing two types of SEM models, namely the Confirmatory Factor Analysis (CFA) model and full structural model. The SEM models were then validated through the assessment on their uni-dimensionality, validity, reliability, and fitness index, in line with the hypotheses tested. The final SEM model fit measures are: P-value=0.000, RMSEA=0.0790.90, TLI=0.956>0.90, NFI=0.935>0.90 and ChiSq/df=2.259; indicating that the overall index values achieved the required level of model fitness. The model supports all the hypotheses evaluated, confirming that all relationship exists amongst the constructs are positive and significant. Ultimately, the analysis verified that most of the respondents foresee better understanding of project input information through BIM visualization, its reliable database and coordinated data, in developing more reliable cost estimates. They also perceive to accelerate their cost estimating task through BIM adoption.

  5. Molecular Modulation of Inhibitors of Apoptosis as a Novel Approach for Radiosensitization of Human Prostate Cancer

    Science.gov (United States)

    2008-11-01

    in multiple myeloma cells is associated with a cleavage of Mcl-1 and Bim and a decrease in the Mcl-1/Bim...improved tumor control by radiotherapy in vivo [66], advocating a distinct role for XIAP in radiation resistant phenotype of human cancers, and...about the role of endogenous Smac in cells treated with Smac- mimetic IAP-inhibitors and irradiation. In multiple human cancer models,

  6. INTEROPERABILIDADE DE APLICATIVOS BIM USADOS EM ARQUITETURA POR MEIO DO FORMATO IFC

    Directory of Open Access Journals (Sweden)

    Max Lira Veras X. de Andrade

    2009-12-01

    Full Text Available O conceito do Building Information Modeling (BIM pressupõe a interoperabilidade e a colaboração entre os profissionais da indústria da Arquitetura Engenharia e Construção (AEC. Todavia, estes profissionais exploram pouco o recurso da colaboração no processo de projeto com o BIM, além do mais, se os aplicativos BIM não possuírem robustez na interoperabilidade a atividade de colaboração e cooperação pode ser ainda mais dificultada. Visando diagnosticar a eficiência dos aplicativos BIM no uso do recurso da interoperabilidade, o presente trabalho empreende um esforço para identificar as principais não conformidades na troca de informações dos modelos do edifício produzidos em aplicativos BIM voltados para arquitetura. Além do mais, discute como estes aplicativos tratam as informações de mesmas famílias de objetos. Este artigo inicia com uma revisão bibliográfica sobre os conceitos de colaboração, interoperabilidade e Industry Foundation Classes (IFC. Em seguida modela um edifício de dois pavimentos nos aplicativos ArchiCAD e Revit. Salva os modelos em arquivos no formato IFC. Importa os arquivos IFC pelo ArchiCAD, Revit e dois aplicativos de visualização. Analisa as não conformidades dos arquivos importados. Os resultados mostram que: ocorrem perdas na qualidade dos modelos do edifício quando importados de arquivos no formato IFC; aplicativos BIM destinados à arquitetura apresentam limitações na informação do modelo do edifício (parte das informações são geradas apenas em 2D; existem não conformidades de padrão na definição das propriedades dos componentes apresentados por diferentes aplicativos BIM, voltados para arquitetura. Como sugestão apresenta exemplo bem sucedido de sistema de compartilhamento de modelos BIM. Para finalizar, mostra que os tradutores de IFC, apesar das melhorias das últimas versões, ainda não são robustos o suficiente para transportar os dados do modelo com a qualidade do

  7. Revisiting Boundary Objects: ERP and BIM Systems as Multi-Community Artefacts

    DEFF Research Database (Denmark)

    Harty, Chris; Koch, Christian

    2011-01-01

    consultancy and the use of Building Information Modelling (BIM) to coordinate the design and construction of two large hospitals in central London. Both BIM and ERP have complicated and on-going histories, and involve the inclusion of many different groups and actors, as well as a plethora of objects...

  8. Using 3d Bim Model for the Value-Based Land Share Calculations

    Science.gov (United States)

    Çelik Şimşek, N.; Uzun, B.

    2017-11-01

    According to the Turkish condominium ownership system, 3D physical buildings and its condominium units are registered to the condominium ownership books via 2D survey plans. Currently, 2D representations of the 3D physical objects, causes inaccurate and deficient implementations for the determination of the land shares. Condominium ownership and easement right are established with a clear indication of land shares (condominium ownership law, article no. 3). So, the land share of each condominium unit have to be determined including the value differences among the condominium units. However the main problem is that, land share has often been determined with area based over the project before construction of the building. The objective of this study is proposing a new approach in terms of value-based land share calculations of the condominium units that subject to condominium ownership. So, the current approaches and its failure that have taken into account in determining the land shares are examined. And factors that affect the values of the condominium units are determined according to the legal decisions. This study shows that 3D BIM models can provide important approaches for the valuation problems in the determination of the land shares.

  9. Application of BIM technology in green building material management system

    Science.gov (United States)

    Zhineng, Tong

    2018-06-01

    The current green building materials management system in China's construction industry is not perfect, and there are still many shortcomings. Active construction of green building materials management system based on BIM technology, combined with the characteristics of green building materials and its relationship with BIM technology application, is urgently needed to better realize the scientific management of green building materials.

  10. Leveraging Lean in construction: A case study of a BIM-based HVAC manufacturing process

    Directory of Open Access Journals (Sweden)

    Colin J. Conway

    2014-12-01

    Full Text Available The impetus towards efficiency in the AECO (Architecture, Engineering, Construction & Operations sector is driving the implementation of Lean practices. BIM technologies and BIM processes provide methods by which this can be achieved. Major clients of building services contractors have begun to mandate the use of BIM and some are using BIM preparedness/experience as pre-tender qualification criteria. In this case study, an initial review has been conducted of the achievements of a major Irish M&E contractor in implementing BIM. The firm purpose-built a facility for the off-site manufacture of building services components. The operations of the plant are efficient and quality assured through the use of an appropriately skilled workforce at all stages of manufacture, and tracking software that has developed as the knowledge of the contractor grew. Standardised processes have been developed which have resulted in greater efficiencies and lower costs for the contractor as a result of fewer requirements for onsite modifications (such as those caused by clashes, less waste, and greater flexibility. Despite some initial objections, the employees of the company are now more satisfied with their working conditions and are, as a result, more productive. Through investment in BIM-based, Lean processes, the contractor can now better compete when tendering for large-scale projects in Ireland and worldwide, including the rapidly-increasing number where BIM experience and preparedness is mandated.

  11. Co@MWNTs-Plastic: A novel electrode for NaBH4 oxidation

    International Nuclear Information System (INIS)

    Zhang, Dongming; Ye, Ke; Cao, Dianxue; Wang, Bin; Cheng, Kui; Li, Yiju; Wang, Guiling; Xu, Yang

    2015-01-01

    Highlights: • MP substrate was fabricated by adhering MWNTs on a piece of obsoleted plastic bag. • Co nano-thorns were prepared by a simple electrodeposition method on the MP surface. • MP owns a superior stability in strong alkaline environment. • CMP exhibits a high catalytic activity for NaBH 4 electrooxidation. • The possible mechanisms of NaBH 4 electrooxidation on CMP was discussed. - Abstract: A novel multi-walled carbon nanotubes (MWNTs)-Plastic (MP) substrate was first fabricated by adhering MWNTs on a piece of obsoleted plastic bag, and Co nano-thorns were subsequently prepared by a simple electrodeposition method on the MP surface. The morphology and phase structure of the as-prepared Co@MWNTs-Plastic (CMP) catalytic electrode are characterized by scanning electron microscopy, transmission electron microscopy and X-ray diffractometer. The catalytic activity of the CMP electrode for NaBH 4 electrooxidation is investigated by means of cyclic voltammetry and chronoamperometry. The employing of waste plastic bags reduces white pollution and the MP substrate exhibits superior stability in alkaline solution. The 3D CMP catalytic electrode owns a high electrochemical activity for NaBH 4 oxidation. Moreover, we discussed the possible mechanisms of NaBH 4 electrooxidation on the CMP

  12. Aspartate and glutamate mimetic structures in biologically active compounds.

    Science.gov (United States)

    Stefanic, Peter; Dolenc, Marija Sollner

    2004-04-01

    Glutamate and aspartate are frequently recognized as key structural elements for the biological activity of natural peptides and synthetic compounds. The acidic side-chain functionality of both the amino acids provides the basis for the ionic interaction and subsequent molecular recognition by specific receptor sites that results in the regulation of physiological or pathophysiological processes in the organism. In the development of new biologically active compounds that possess the ability to modulate these processes, compounds offering the same type of interactions are being designed. Thus, using a peptidomimetic design approach, glutamate and aspartate mimetics are incorporated into the structure of final biologically active compounds. This review covers different bioisosteric replacements of carboxylic acid alone, as well as mimetics of the whole amino acid structure. Amino acid analogs presented include those with different distances between anionic moieties, and analogs with additional functional groups that result in conformational restriction or alternative interaction sites. The article also provides an overview of different cyclic structures, including various cycloalkane, bicyclic and heterocyclic analogs, that lead to conformational restriction. Higher di- and tripeptide mimetics in which carboxylic acid functionality is incorporated into larger molecules are also reviewed. In addition to the mimetic structures presented, emphasis in this article is placed on their steric and electronic properties. These mimetics constitute a useful pool of fragments in the design of new biologically active compounds, particularly in the field of RGD mimetics and excitatory amino acid agonists and antagonists.

  13. Assessing students' sentiments towards the use of a Building Information Modelling (BIM) learning platform in a construction project management course

    Science.gov (United States)

    Suwal, Sunil; Singh, Vishal

    2018-07-01

    Building Information Modelling (BIM) tools and processes are increasingly adopted and implemented in the construction industry. Consequently, BIM education is considered increasingly important in Architecture, Engineering and Construction (AEC) education. While most of the research and literature on BIM education in engineering studies has focused on BIM implementation strategies, processes, benefits, and challenges, there is limited study on students' perception towards the implementation of BIM courses, or about online BIM learning platforms, or about the BIM tools themselves. Therefore, this paper takes the first steps towards addressing this gap. This study analyses students' (57 students) perception and sentiments towards the use of an online BIM learning platform and explores the potential implications of the findings for BIM education. The findings suggest that online BIM learning platforms are highly rated by students as a positive learning experience, indicating the need for greater integration of such tools and approaches in AEC courses.

  14. Human Pluripotent Stem Cells and Derived Neuroprogenitors Display Differential Degrees of Susceptibility to BH3 Mimetics ABT-263, WEHI-539 and ABT-199.

    Directory of Open Access Journals (Sweden)

    Carolina Paola García

    Full Text Available Human embryonic stem cells (hESCs are hypersensitive to genotoxic stress and display lower survival ability relative to their differentiated progeny. Herein, we attempted to investigate the source of this difference by comparing the DNA damage responses triggered by the topoisomerase I inhibitor camptothecin, in hESCs, human induced pluripotent stem cells (hiPSCs and hESCs-derived neuroprogenitors (NP. We observed that upon camptothecin exposure pluripotent stem cells underwent apoptosis more swiftly and at a higher rate than differentiated cells. However, the cellular response encompassing ataxia-telangiectasia mutated kinase activation and p53 phosphorylation both on serine 15 as well as on serine 46 resulted very similar among the aforementioned cell types. Importantly, we observed that hESCs and hiPSCs express lower levels of the anti-apoptotic protein Bcl-2 than NP. To assess whether Bcl-2 abundance could account for this differential response we treated cells with ABT-263, WEHI-539 and ABT-199, small molecules that preferentially target the BH3-binding pocket of Bcl-xL and/or Bcl-2 and reduce their ability to sequester pro-apoptotic factors. We found that in the absence of stress stimuli, NP exhibited a higher sensitivity to ABT- 263 and WEHI-539 than hESCs and hiPSCs. Conversely, all tested cell types appeared to be highly resistant to the Bcl-2 specific inhibitor, ABT-199. However, in all cases we determined that ABT-263 or WEHI-539 treatment exacerbated camptothecin-induced apoptosis. Importantly, similar responses were observed after siRNA-mediated down-regulation of Bcl-xL or Bcl-2. Taken together, our results suggest that Bcl-xL contrary to Bcl-2 contributes to ensure cell survival and also functions as a primary suppressor of DNA double-strand brake induced apoptosis both in pluripotent and derived NP cells. The emerging knowledge of the relative dependence of pluripotent and progenitor cells on Bcl-2 and Bcl-xL activities may help

  15. Bim: guardian of tissue homeostasis and critical regulator of the immune system, tumorigenesis and bone biology.

    Science.gov (United States)

    Akiyama, Toru; Tanaka, Sakae

    2011-08-01

    One of the most important roles of apoptosis is the maintenance of tissue homeostasis. Impairment of apoptosis leads to a number of pathological conditions. In response to apoptotic signals, various proteins are activated in a pathway and signal-specific manner. Recently, the pro-apoptotic molecule Bim has attracted increasing attention as a pivotal regulator of tissue homeostasis. The Bim expression level is strictly controlled in both transcriptional and post-transcriptional levels. This control is dependent on cell, tissue and apoptotic stimuli. The phenotype of Bim-deficient mice is a systemic lupus erythematosus-like autoimmune disease with an abnormal accumulation of hematopoietic cells. Bim is thus a critical regulator of hematopoietic cells and immune system. Further studies have revealed the critical roles of Bim in various normal and pathological conditions, including bone homeostasis and tumorigenesis. The current understanding of Bim signaling and roles in the maintenance of tissue homeostasis is reviewed in this paper, focusing on the immune system, bone biology and tumorigenesis to illustrate the diversified role of Bim.

  16. Comparative Analysis of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) of Streptococcus thermophilus St-I and its Bacteriophage-Insensitive Mutants (BIM) Derivatives.

    Science.gov (United States)

    Li, Wan; Bian, Xin; Evivie, Smith Etareri; Huo, Gui-Cheng

    2016-09-01

    The CRISPR-Cas (CRISPR together with CRISPR-associated proteins) modules are the adaptive immune system, acting as an adaptive and heritable immune system in bacteria and archaea. CRISPR-based immunity acts by integrating short virus sequences in the cell's CRISPR locus, allowing the cell to remember, recognize, and clear infections. In this study, the homology of CRISPRs sequence in BIMs (bacteriophage-insensitive mutants) of Streptococcus thermophilus St-I were analyzed. Secondary structures of the repeats and the PAMs (protospacer-associated motif) of each CRISPR locus were also predicted. Results showed that CRISPR1 has 27 repeat-spacer units, 5 of them had duplicates; CRISPR2 has one repeat-spacer unit; CRISPR3 has 28 repeat-spacer units. Only BIM1 had a new spacer acquisition in CRISPR3, while BIM2 and BIM3 had no new spacers' insertion, thus indicating that while most CRISPR1 were more active than CRISPR3, new spacer acquisition occurred just in CRSPR3 in some situations. These findings will help establish the foundation for the study of CRSPR-Cas systems in lactic acid bacteria.

  17. Salicylamide and salicylglycine oxidovanadium complexes with insulin-mimetic properties.

    Science.gov (United States)

    Nilsson, Jessica; Shteinman, Albert A; Degerman, Eva; Enyedy, Eva A; Kiss, Tamás; Behrens, Ulrich; Rehder, Dieter; Nordlander, Ebbe

    2011-12-01

    Reaction of N-(2-hydroxybenzyl)-N-(2-picolyl) glycine (H(2)papy) with VOSO(4) in water gives the oxidovanadium(V) oxido-bridged dimer [{(papy)(VO)}(2) μ-O)] (1). Similarly, reaction of N-(2-hydroxybenzyl) glycine (H(2)glysal) with VOSO(4) gives [(glysal)VO(H(2)O)] (2) and reaction of salicylamide (Hsalam) with VOSO(4) in methanol gives [(salam)(2)VO] (3). The crystal structure of the oxido-bridged complex 1 is reported. The insulin-mimetic activity of all three complexes was evaluated with respect to their ability to phosphorylate protein kinase B (PKB). The speciations of complexes 1 and 2 were studied over the pH range 2-10. Complex 1 shows greater stability over the whole pH range but only 2 and 3 exhibit an insulin-mimetic effect. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. BIM Workflow for Mechanical Ventilation Design : Object-Based Modeling with Autodesk Revit®

    OpenAIRE

    Bonduel, Mathias

    2016-01-01

    This study is conducted for the Belgian engineering firm CENERGIE, whose main business activities are within the fields of building systems and sustainable buildings. The company wants to change their current design workflows to adapt the use of Building Information Modeling (BIM) with Autodesk Revit The research focused on the development of a BIM workflow where no models are exchanged between building partners. The aim of this study was to develop such a Revit BIM workflow for the desig...

  19. Integrating and Managing Bim in GIS, Software Review

    Science.gov (United States)

    El Meouche, R.; Rezoug, M.; Hijazi, I.

    2013-08-01

    Since the advent of Computer-Aided Design (CAD) and Geographical Information System (GIS) tools, project participants have been increasingly leveraging these tools throughout the different phases of a civil infrastructure project. In recent years the number of GIS software that provides tools to enable the integration of Building information in geo context has risen sharply. More and more GIS software are added tools for this purposes and other software projects are regularly extending these tools. However, each software has its different strength and weakness and its purpose of use. This paper provides a thorough review to investigate the software capabilities and clarify its purpose. For this study, Autodesk Revit 2012 i.e. BIM editor software was used to create BIMs. In the first step, three building models were created, the resulted models were converted to BIM format and then the software was used to integrate it. For the evaluation of the software, general characteristics was studied such as the user interface, what formats are supported (import/export), and the way building information are imported.

  20. Integration of Jeddah Historical BIM and 3D GIS for Documentation and Restoration of Historical Monument

    Directory of Open Access Journals (Sweden)

    A. Baik

    2015-08-01

    Full Text Available This work outlines a new approach for the integration of 3D Building Information Modelling and the 3D Geographic Information System (GIS to provide semantically rich models, and to get the benefits from both systems to help document and analyse cultural heritage sites. Our proposed framework is based on the Jeddah Historical Building Information Modelling process (JHBIM. This JHBIM consists of a Hijazi Architectural Objects Library (HAOL that supports higher level of details (LoD while decreasing the time of modelling. The Hijazi Architectural Objects Library has been modelled based on the Islamic historical manuscripts and Hijazi architectural pattern books. Moreover, the HAOL is implemented using BIM software called Autodesk Revit. However, it is known that this BIM environment still has some limitations with the non-standard architectural objects. Hence, we propose to integrate the developed 3D JHBIM with 3D GIS for more advanced analysis. To do so, the JHBIM database is exported and semantically enriched with non-architectural information that is necessary for restoration and preservation of historical monuments. After that, this database is integrated with the 3D Model in the 3D GIS solution. At the end of this paper, we’ll illustrate our proposed framework by applying it to a Historical Building called Nasif Historical House in Jeddah. First of all, this building is scanned by the use of a Terrestrial Laser Scanner (TLS and Close Range Photogrammetry. Then, the 3D JHBIM based on the HOAL is designed on Revit Platform. Finally, this model is integrated to a 3D GIS solution through Autodesk InfraWorks. The shown analysis presented in this research highlights the importance of such integration especially for operational decisions and sharing the historical knowledge about Jeddah Historical City. Furthermore, one of the historical buildings in Old Jeddah, Nasif Historical House, was chosen as a test case for the project.

  1. Hydrogen storage properties of rare earth (RE) borohydrides (RE = La, Er) in composite mixtures with LiBH{sub 4} and LiH

    Energy Technology Data Exchange (ETDEWEB)

    Frommen, Christoph; Heere, Michael [Institute for Energy Technology, Physics Department, P.O. Box 40, NO-2027 Kjeller (Norway); Riktor, Marit D. [Institute for Energy Technology, Physics Department, P.O. Box 40, NO-2027 Kjeller (Norway); SINTEF Materials and Chemistry, Forskningsveien 1, NO-0314 Oslo (Norway); Sørby, Magnus H. [Institute for Energy Technology, Physics Department, P.O. Box 40, NO-2027 Kjeller (Norway); Hauback, Bjørn C., E-mail: bjorn.hauback@ife.no [Institute for Energy Technology, Physics Department, P.O. Box 40, NO-2027 Kjeller (Norway)

    2015-10-05

    Highlights: • 6LiBH{sub 4}–RECl{sub 3}–3LiH composites (RE = La, Er) studied for the first time. • Drastically reduced decomposition temperature (300 {sup o}C) compared to LiBH{sub 4} (>400 °C). • Partial reversibility for 6LiBH{sub 4}–LaCl{sub 3}–3LiH: (19% at 340 °C, 10 MPa). • Excellent reversibility for 6LiBH{sub 4}–ErCl{sub 3}–3LiH: (80% at 340 °C, 10 MPa). • Reversibility comparable to that obtained for pure LiBH{sub 4} (76% at 600 °C and 15.5 MPa). - Abstract: Mixtures of 6LiBH{sub 4}–RECl{sub 3}–3LiH (RE = La, Er) have been produced by mechanochemical milling and their structure, thermal decomposition and reversibility have been studied. Hydrogen desorption starts around 300 °C in both composites. Heating to 400 °C yields LaB{sub 6}, ErB{sub 4} and REH{sub 2+δ} as major decomposition products. LiBH{sub 4} is destabilized by REH{sub 2+δ} formed through decomposition of the parent borohydrides LiLa(BH{sub 4}){sub 3}Cl and Er(BH{sub 4}){sub 3}, respectively, and its hydrogen release temperature is reduced by 100 °C as compared to pure ball-milled LiBH{sub 4}. The lanthanum-containing composite releases 4.2 wt.% H between 300 and 350 °C and shows a limited reversibility of ∼20% (340 °C, 10 MPa) probably due to hydrogen uptake by some amorphous boron-containing phases. For 6LiBH{sub 4}–ErCl{sub 3}–3LiH about 3 wt.% H is evolved up to 400 °C. Desorption against 0.5 MPa backpressure results in an increased reversibility (∼80%) as compared to vacuum (∼66%). Rehydrogenation (340 °C, 10 MPa) shows the formation of ErH{sub 3} and LiBH{sub 4} at drastically reduced conditions compared to pure LiBH{sub 4} (>400 °C, >10 MPa)

  2. Research of Ancient Architectures in Jin-Fen Area Based on GIS&BIM Technology

    Science.gov (United States)

    Jia, Jing; Zheng, Qiuhong; Gao, Huiying; Sun, Hai

    2017-05-01

    The number of well-preserved ancient buildings located in Shanxi Province, enjoying the absolute maximum proportion of ancient architectures in China, is about 18418, among which, 9053 buildings have the structural style of wood frame. The value of the application of BIM (Building Information Modeling) and GIS (Geographic Information System) is gradually probed and testified in the corresponding fields of ancient architecture’s spatial distribution information management, routine maintenance and special conservation & restoration, the evaluation and simulation of related disasters, such as earthquake. The research objects are ancient architectures in JIN-FEN area, which were first investigated by Sicheng LIANG and recorded in his work of “Chinese ancient architectures survey report”. The research objects, i.e. the ancient architectures in Jin-Fen area include those in Sicheng LIANG’s investigation, and further adjustments were made through authors’ on-site investigation and literature searching & collection. During this research process, the spatial distributing Geodatabase of research objects is established utilizing GIS. The BIM components library for ancient buildings is formed combining on-site investigation data and precedent classic works, such as “Yingzao Fashi”, a treatise on architectural methods in Song Dynasty, “Yongle Encyclopedia” and “Gongcheng Zuofa Zeli”, case collections of engineering practice, by the Ministry of Construction of Qing Dynasty. A building of Guangsheng temple in Hongtong county is selected as an example to elaborate the BIM model construction process based on the BIM components library for ancient buildings. Based on the foregoing work results of spatial distribution data, attribute data of features, 3D graphic information and parametric building information model, the information management system for ancient architectures in Jin-Fen Area, utilizing GIS&BIM technology, could be constructed to support the

  3. Developing and Testing a Tool to Evaluate BIM Maturity : Sectoral Analysis in the Dutch Construction Industry

    NARCIS (Netherlands)

    Siebelink, Sander; Voordijk, Johannes T.; Adriaanse, Arjen

    2018-01-01

    This study's objective was to evaluate the status of building information modelling (BIM) implementation within the Dutch construction industry by means of a developed BIM maturity tool that could be applied within the construction industry's various disciplines. Existing BIM maturity models tend to

  4. The role of BIM (Building Information Modeling for representation and managing of built and historic artifacts

    Directory of Open Access Journals (Sweden)

    Carlo Bianchini

    2016-06-01

    Full Text Available It’s established that in the design and construc- tion of new buildings, BIM is a fundamental refe- rence especially when the standardization is the typical character of the project. As Architecture, with the management of the entire building pro- cess, requires standardization for greater eco- nomy, thanks to BIM tools the building process seems to have actually moved to a 2.0 phase; on the contrary, when BIM is applied to historical bu- ildings it still reveals not so adequate. In this framework, this paper will not discuss the differences between CAD and BIM or the un- doubted potential of BIM software from a tech- nical or operational standpoint; we would focus instead on the implication of BIM referring to the Representation disciplines and to the issues con- nected with its application to the existing built stock and especially to historic buildings. 

  5. A Review of Application Building Information Modeling (BIM) During Pre-Construction Stage: Retrospective and Future Directions

    Science.gov (United States)

    Edra Nisa Lau, Santi; Zakaria, Rozana; Aminudin, Eeydzah; Saar, Chai Chang; Yusof, Aswadi; Fatihi Hafifi Che Wahid, Che Muhammad

    2018-04-01

    Pre-construction is one of the biggest areas of risk and uncertainty in construction project as it deals with subsurface ground conditions information. The amount of detail data needed in pre-construction especially for existing data modelling and site analysis should be sufficient enough to ensure that significant risks could not reasonably be anticipated. Current practicing method in interpreting data during this stage tasks reveal limitation. Construction industry faced many obstacles due to the depends on the traditional practice; paper-based document which missing and redundant data always happened. In recent years, there has been a shift in construction where people move to BIM application because of its potential to reduce the problem faced by infrastructure world. BIM has become a successful technology and widely popular in the construction world especially in developed countries because of its potential. Nowadays, people are moving one step ahead in BIM which is adoption of BIM during pre-construction stage. Thus, this paper review studies centered on BIM-integrated modelling during preconstruction stage. But there is lack of practical researches have been made during this stage. Although a large number of studies on BIM have been conducted in the past decade, a lack of consensus remains among researchers and practitioners regarding the applications of BIM during pre-construction stage, the availability of subsequent data integration tool for geotechnical activity. A comprehensive literature review was conducted for data collection and analysis. After in-depth review of journal articles widely cover the application of BIM, this study summarizes an overview and critical reflection of geotechnical data integration using BIM during pre-construction stage. The results are useful for the identification of research clusters and topics in the BIM community.

  6. The US Army Corps of Engineers Roadmap for Life-Cycle Building Information Modeling (BIM)

    Science.gov (United States)

    2012-11-01

    that have been incorporated into BIM technologies marketed by competing vendors (e.g., Industry Foundation Class [IFC], Construction Operations...ER D C SR -1 2- 2 The US Army Corps of Engineers Roadmap for Life-Cycle Building Information Modeling ( BIM ) En gi ne er R es ea rc h an...Information Modeling ( BIM ) US Army Corps of Engineers Directorate of Civil Works Engineering and Construction Branch Washington, DC 20314-1000 Final

  7. Smac mimetic-derived augmentation of chemotherapeutic response in experimental pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Schwarz Margaret A

    2011-01-01

    Full Text Available Abstract Background Pancreatic ductal adenocarcinoma (PDAC is highly resistant to conventional chemotherapy, in part due to the overexpression of inhibitors of apoptosis proteins (IAPs. Smac is an endogenous IAP-antagonist, which renders synthetic Smac mimetics attractive anticancer agents. We evaluated the benefits of combining a Smac mimetic, JP1201 (JP, with conventional chemotherapy agents used for PDAC management. Methods Cell viability assays and protein expression analysis were performed using WST-1 reagent and Western blotting, respectively. Apoptosis was detected by annexin V/propidium iodide staining. In vivo tumor growth and survival studies were performed in murine PDAC xenografts. Results JP and gemcitabine (Gem inhibited PDAC cell proliferation with additive effects in combination. The percentage of early apoptotic cells in controls, JP, Gem and JP + Gem was 17%, 26%, 26% and 38%, respectively. JP-induced apoptosis was accompanied by PARP-1 cleavage. Similar additive anti-proliferative effects were seen for combinations of JP with doxorubicin (Dox and docetaxel (DT. The JP + Gem combination caused a 30% decrease in tumor size in vivo compared to controls. Median animal survival was improved significantly in mice treated with JP + Gem (38 d compared to controls (22 d, JP (28 d or Gem (32 d (p = 0.01. Animal survival was also improved with JP + DT treatment (32 d compared to controls (16 d, JP (21 d or DT alone (27 d. Conclusions These results warrant further exploration of strategies that promote chemotherapy-induced apoptosis of tumors and highlight the potential of Smac mimetics in clinical PDAC therapy.

  8. BIM: Promises and reality

    Directory of Open Access Journals (Sweden)

    Svetel Igor

    2014-01-01

    Full Text Available The building information modeling - BIM is a technology developed toward creation of computer based information model that encompasses whole building lifecycle. Toward that goal a number of information technology standards have been developed that enable different professions in AEC to cooperatively develop electronic building model. The paper gives overview of essential technologies, discusses their intended purpose, and gives outline of the currently achieved functionality.

  9. Critical role for BIM in T cell receptor restimulation-induced death

    Directory of Open Access Journals (Sweden)

    Fleisher Thomas A

    2008-08-01

    Full Text Available Abstract Background Upon repeated or chronic antigen stimulation, activated T cells undergo a T cell receptor (TCR-triggered propriocidal cell death important for governing the intensity of immune responses. This is thought to be chiefly mediated by an extrinsic signal through the Fas-FasL pathway. However, we observed that TCR restimulation still potently induced apoptosis when this interaction was blocked, or genetically impaired in T cells derived from autoimmune lymphoproliferative syndrome (ALPS patients, prompting us to examine Fas-independent, intrinsic signals. Results Upon TCR restimulation, we specifically noted a marked increase in the expression of BIM, a pro-apoptotic Bcl-2 family protein known to mediate lymphocyte apoptosis induced by cytokine withdrawal. In fact, T cells from an ALPS type IV patient in which BIM expression is suppressed were more resistant to restimulation-induced death. Strikingly, knockdown of BIM expression rescued normal T cells from TCR-induced death to as great an extent as Fas disruption. Conclusion Our data implicates BIM as a critical mediator of apoptosis induced by restimulation as well as growth cytokine withdrawal. These findings suggest an important role for BIM in eliminating activated T cells even when IL-2 is abundant, working in conjunction with Fas to eliminate chronically stimulated T cells and maintain immune homeostasis. Reviewers This article was reviewed by Dr. Wendy Davidson (nominated by Dr. David Scott, Dr. Mark Williams (nominated by Dr. Neil Greenspan, and Dr. Laurence C. Eisenlohr.

  10. Developing context sensitive BIM based applications

    NARCIS (Netherlands)

    Hartmann, Timo; Underwood, J.; Isikdag, U.

    2010-01-01

    Current Building Information Model (BIM) based applications do not integrate well with the varying and frequently changing work processes of Architectural, Engineering, and Construction (AEC) professionals. One cause for this problem is that traditionally software developers apply software design

  11. The Imipridone ONC201 Induces Apoptosis and Overcomes Chemotherapy Resistance by Up-Regulation of Bim in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Yong-sheng Tu

    2017-10-01

    Full Text Available In multiple myeloma, despite recent improvements offered by new therapies, disease relapse and drug resistance still occur in the majority of patients. Therefore, there is an urgent need for new drugs that can overcome drug resistance and prolong patient survival after failure of standard therapies. The imipridone ONC201 causes downstream inactivation of ERK1/2 signaling and has tumoricidal activity against a variety of tumor types, while its efficacy in preclinical models of myeloma remains unclear. In this study, we treated human myeloma cell lines and patient-derived tumor cells with ONC201. Treatment decreased cellular viability and induced apoptosis in myeloma cell lines, with IC50 values of 1 to 1.5 μM, even in those with high risk features or TP53 loss. ONC201 increased levels of the pro-apoptotic protein Bim in myeloma cells, resulting from decreased phosphorylation of degradation-promoting Bim Ser69 by ERK1/2. In addition, myeloma cell lines made resistant to several standard-of-care agents (by chronic exposure were equally sensitive to ONC201 as their drug-naïve counterparts, and combinations of ONC201 with proteasome inhibitors had synergistic anti-myeloma activity. Overall, these findings demonstrate that ONC201 kills myeloma cells regardless of resistance to standard-of-care therapies, making it promising for clinical testing in relapsed/refractory myeloma.

  12. Exploring Bim for Operational Integrated Asset Management - a Preliminary Study Utilising Real-World Infrastructure Data

    Science.gov (United States)

    Boyes, G. A.; Ellul, C.; Irwin, D.

    2017-10-01

    The use of 3D information models within collaborative working environments and the practice of Building Information Modelling (BIM) are becoming more commonplace within infrastructure projects. Currently used predominantly during the design and construction phase, the use of BIM is capable in theory of providing the information at handover that will satisfy the Asset Information Requirements (AIRs) of the future Infrastructure Manager (IM). One particular challenge is establishing a link between existing construction-centric information and the asset-centric information needed for future operations. Crossrail, a project to build a new high-frequency railway underneath London, is handling many such challenges as they prepare to handover their digital information to the future operator, in particular the need to provide a two-way link between a federated 3D CAD model and an object-relational Asset Information Management System (AIMS). This paper focusses on the potential for improved Asset Management (AM) by integrating BIM and GIS systems and practices, and makes a preliminary report on how 3D spatial queries can be used to establish a two-way relational link between two information systems (3D geometry and asset lists), as well as the challenges being overcome to transform the data to be suitable for AM.

  13. The integration of “building information modeling” (BIM in sustainable architecture and construction education: case study in Pristina University

    Directory of Open Access Journals (Sweden)

    Violeta Nushi

    2017-10-01

    Full Text Available After a comparative review of articles published for used types of “Building Information Modeling” (BIM software, this study provides a wider understanding and critical reflection on integration and synthesis of BIM developments into Kosovo education system in order to provide important guidance to academic researchers, students, and practitioners. As the effectiveness of BIM has been widely accepted in the worldwide “Architecture, Engineering, Construction” (AEC industry, there is an urgent need to establish a synergy between BIM educated and practitioners in Kosovo likewise. This necessarily leads towards finding more intensive and suitable approaches and tools, for an integrated solution through the education system; in particular, to offer worldwide BIM's practices into sustainable AEC education programs, curricula and/or courses. Virtually, the most of the Technical Faculties within universities of Kosovo pretermit viability of BIM in teaching strategy and plan to overcome the barriers to integration of BIM into the curriculum. Through conducted questionnaire to students was surveyed the current state of BIM integration at higher education curricula of Sustainable Architecture and Construction (SAC programs. Based upon their answers, came out the recommendation to increase the appraiser's knowledge for BIM in curricula, followed up by new sustainable didactical concepts and awareness, which will energize the commencement of BIM into SAC programs and establish graduates, equipped with the necessary knowledge and skills for BIM software before they get promoted in professional calling.

  14. Direction for the Estimation of Required Resources for Nuclear Power Plant Decommissioning based on BIM via Case Study

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Insu [Korea Institute of Construction Technology, Goyang (Korea, Republic of); Kim, Woojung [KHNP-Central Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    Ways to estimate decommissioning of required resources in the past have imposed great uncertainty since they analyze required resources at the construction stage, analyzing and consulting decommissioning required resources of overseas nuclear power plants. As demands on efficient management and use of complicated construction information increased these days, demands on the introduction of Building Information Modeling (herein after referred to as BIM) technology has increased. In the area of quotation, considerable effects are expected as to the accuracy and reliability predicting construction costs through the characteristics that can automatically estimate quantities by using attribute information of BIM model. BIM-based estimation and quotation of required resources is more accurate than the existing 2D-based quotations and have many advantages such as reviews over constructability and interference. It can be desirable to estimate decommissioning required resources in nuclear power plants using BIM as well as using tools that are compatible with usual international/industrial standards. As we looked into the cases where required resources were estimated, using BIM in Korea and abroad, they dealt with estimation of required resources, estimation of construction cost and process management at large. In each area, methodologies, classification systems, BIM, and realization tests have been used variably. Nonetheless, several problems have been reported, and among them, it is noticeable that although BIM standard classification system exists, no case was found that has used standard classification system. This means that no interlink among OBS (Object Breakdown Structure), WBS (Work Breakdown Structure) and CBS (Cost Breakdown Structure) was possible. Thus, for nuclear power plant decommissioning, decommissioning method and process, etc. shall be defined clearly in the stage of decommissioning strategy establishment, so that classification systems must be set up

  15. Direction for the Estimation of Required Resources for Nuclear Power Plant Decommissioning based on BIM via Case Study

    International Nuclear Information System (INIS)

    Jung, Insu; Kim, Woojung

    2014-01-01

    Ways to estimate decommissioning of required resources in the past have imposed great uncertainty since they analyze required resources at the construction stage, analyzing and consulting decommissioning required resources of overseas nuclear power plants. As demands on efficient management and use of complicated construction information increased these days, demands on the introduction of Building Information Modeling (herein after referred to as BIM) technology has increased. In the area of quotation, considerable effects are expected as to the accuracy and reliability predicting construction costs through the characteristics that can automatically estimate quantities by using attribute information of BIM model. BIM-based estimation and quotation of required resources is more accurate than the existing 2D-based quotations and have many advantages such as reviews over constructability and interference. It can be desirable to estimate decommissioning required resources in nuclear power plants using BIM as well as using tools that are compatible with usual international/industrial standards. As we looked into the cases where required resources were estimated, using BIM in Korea and abroad, they dealt with estimation of required resources, estimation of construction cost and process management at large. In each area, methodologies, classification systems, BIM, and realization tests have been used variably. Nonetheless, several problems have been reported, and among them, it is noticeable that although BIM standard classification system exists, no case was found that has used standard classification system. This means that no interlink among OBS (Object Breakdown Structure), WBS (Work Breakdown Structure) and CBS (Cost Breakdown Structure) was possible. Thus, for nuclear power plant decommissioning, decommissioning method and process, etc. shall be defined clearly in the stage of decommissioning strategy establishment, so that classification systems must be set up

  16. Sustainable Design Approach: A case study of BIM use

    Science.gov (United States)

    Abdelhameed, Wael

    2017-11-01

    Achieving sustainable design in areas such as energy-efficient design depends largely on the accuracy of the analysis performed after the design is completed with all its components and material details. There are different analysis approaches and methods that predict relevant values and metrics such as U value, energy use and energy savings. Although certain differences in the accuracy of these approaches and methods have been recorded, this research paper does not focus on such matter, where determining the reason for discrepancies between those approaches and methods is difficult, because all error sources act simultaneously. The research paper rather introduces an approach through which BIM, building information modelling, can be utilised during the initial phases of the designing process, by analysing the values and metrics of sustainable design before going into the design details of a building. Managing all of the project drawings in a single file, BIM -building information modelling- is well known as one digital platform that offers a multidisciplinary detailed design -AEC model (Barison and Santos, 2010, Welle et.al., 2011). The paper presents in general BIM use in the early phases of the design process, in order to achieve certain required areas of sustainable design. The paper proceeds to introduce BIM use in specific areas such as site selection, wind velocity and building orientation, in terms of reaching the farther possible sustainable solution. In the initial phases of designing, material details and building components are not fully specified or selected yet. The designer usually focuses on zoning, topology, circulations, and other design requirements. The proposed approach employs the strategies and analysis of BIM use during those initial design phases in order to have the analysis and results of each solution or alternative design. The stakeholders and designers would have a better effective decision making process with a full clarity of each

  17. The Rise Of BIM in Malaysia And Its Impact Towards Quantity Surveying Practices

    OpenAIRE

    Zainon Nurshuhada; Mohd-Rahim Faizul Azli; Salleh Hafez

    2016-01-01

    Building Information Modeling (BIM) is a new buzzword that is gaining a momentum within the construction industry in Malaysia, and worldwide. BIM is a way of working that involves the automation of the entire project team using a 4D model that can do many of the traditional fuctions of a Quatity Surveyor (QS). As BIM is removing more of the traditional work of QS, there are rising fears that it could threaten the viability of the QS professions especially for small firms that still rely on pr...

  18. Planering med BIM

    OpenAIRE

    Larsson, Kristoffer

    2016-01-01

    New technical solutions is popping up all the time. In the construction industry today there is a development to find methods that can take advantage of these modern technological solutions. BIM is a term that stands for this development of information handling and therefore for the streamline and improvement of the construction process. But many in the industry still do not know what the term stands for and therefore not what it means to work with the tools.   A good planning is an important...

  19. Energy-Saving Optimization of Water Supply Pumping Station Life Cycle Based on BIM Technology

    Science.gov (United States)

    Qun, Miao; Wang, Jiayuan; Liu, Chao

    2017-12-01

    In the urban water supply system, pump station is the main unit of energy consumption. In the background of pushing forward the informatization in China, using BIM technology in design, construction and operations of water supply pumping station, can break through the limitations of the traditional model and effectively achieve the goal of energy conservation and emissions reduction. This work researches the way to solve energy-saving optimization problems in the process of whole life cycle of water supply pumping station based on BIM technology, and put forward the feasible strategies of BIM application in order to realize the healthy and sustainable development goals by establishing the BIM model of water supply pumping station of Qingdao Guzhenkou water supply project.

  20. A novel peptide thrombopoietin mimetic designing and optimization using computational approach

    Directory of Open Access Journals (Sweden)

    Vimal kishor Singh

    2016-08-01

    Full Text Available Thrombopoietin receptor (TPOR is a cytokine receptor protein; activation of cell surface TPOR by thrombopoietin (TPO triggers an intracellular cascade of megakaryocytopoiesis for the formation of platelets. TPO is a glycoprotein hormone which stimulates megakaryocytes formation and maturation to platelets in bone marrow. Ex vivo megakaryocytopoiesis is in highlight for its vast role in therapeutics and field of regenerative medicine. For therapeutic uses, various TPO alternatives have been used however they are associated with issues like recombinant TPO administration is associated with the generation of auto antibodies and its production is an expensive process. Moreover, reported thrombopoietin mimetic peptide (TMP has no sequence homology with TPO and low specificity to TPOR. Hence, in this study, a novel peptidic TPO mimetic is designed through computational studies by studying the binding sites of TPO and TMP to TPOR and analogs of known mimetics. Screening of combinatorial library was done through molecular docking using ClusPro and mimetic-9 was found to have better binding score of -938.8 kcal/mol with seven hydrogen bonds and a high number of hydrophobic interactions, than known mimetic TMP with docking score of -798.4 kcal/mol and TMP dimer with docking score of -811.9 kcal/mol for TPOR. Mimetic-9 interaction with TPOR was further assessed by the molecular dynamics simulation and their complex was found to be stable with an RMSD value of 0.091 Aº. Resulting mimetic-9 was found to have overall good physiochemical properties with positive grand average hydropathy (GRAVY score and high instability index score and it was found to be localized in the extracellular region. The designed mimetic-9 might prove to be a useful lead molecule for mimicking the role of TPO and to help for platelet production in vitro with higher efficiency.

  1. Downregulation of proapoptotic Bim augments IL-2-independent T-cell transformation by human T-cell leukemia virus type-1 Tax

    International Nuclear Information System (INIS)

    Higuchi, Masaya; Takahashi, Masahiko; Tanaka, Yuetsu; Fujii, Masahiro

    2014-01-01

    Human T-cell leukemia virus type 1 (HTLV-1), an etiological agent of adult T-cell leukemia, immortalizes and transforms primary human T cells in vitro in both an interleukin (IL)-2-dependent and IL-2-independent manner. Expression of the HTLV-1 oncoprotein Tax transforms the growth of the mouse T-cell line CTLL-2 from being IL-2-dependent to IL-2-independent. Withdrawal of IL-2 from normal activated T cells induces apoptosis, which is mediated through the inducible expression of several proapoptotic proteins, including Bim. In this study, we found that Tax protects IL-2-depleted T cells against Bim-induced apoptosis. Withdrawal of IL-2 from CTLL-2 cells induced a prominent increase in the level of Bim protein in CTLL-2 cells, but not in Tax-transformed CTLL-2 cells. This inhibition of Bim in Tax-transformed CTLL-2 cells was mediated by two mechanisms: downregulation of Bim mRNA and posttranscriptional reduction of Bim protein. Transient expression of Tax in CTLL-2 cells also inhibited IL-2 depletion–induced expression of Bim, however, this decrease in Bim protein expression was not due to downregulation of Bim mRNA, thus indicating that Bim mRNA downregulation in Tax-transformed CTLL-2 occurs only after long-term expression of Tax. Transient expression of Tax in CTLL-2 cells also induced Erk activation, however, this was not involved in the reduction of Bim protein. Knockdown of Bim expression in CTLL-2 cells augmented Tax-induced IL-2-independent transformation. HTLV-1 infection of human T cells also reduced their levels of Bim protein, and restoring Bim expression in HTLV-1-infected cells reduced their proliferation by inducing apoptosis. Taken together, these results indicate that Tax-induced downregulation of Bim in HTLV-1-infected T cells promotes their IL-2-independent growth, thereby supporting the persistence of HTLV-1 infection in vivo

  2. Downregulation of proapoptotic Bim augments IL-2-independent T-cell transformation by human T-cell leukemia virus type-1 Tax.

    Science.gov (United States)

    Higuchi, Masaya; Takahashi, Masahiko; Tanaka, Yuetsu; Fujii, Masahiro

    2014-12-01

    Human T-cell leukemia virus type 1 (HTLV-1), an etiological agent of adult T-cell leukemia, immortalizes and transforms primary human T cells in vitro in both an interleukin (IL)-2-dependent and IL-2-independent manner. Expression of the HTLV-1 oncoprotein Tax transforms the growth of the mouse T-cell line CTLL-2 from being IL-2-dependent to IL-2-independent. Withdrawal of IL-2 from normal activated T cells induces apoptosis, which is mediated through the inducible expression of several proapoptotic proteins, including Bim. In this study, we found that Tax protects IL-2-depleted T cells against Bim-induced apoptosis. Withdrawal of IL-2 from CTLL-2 cells induced a prominent increase in the level of Bim protein in CTLL-2 cells, but not in Tax-transformed CTLL-2 cells. This inhibition of Bim in Tax-transformed CTLL-2 cells was mediated by two mechanisms: downregulation of Bim mRNA and posttranscriptional reduction of Bim protein. Transient expression of Tax in CTLL-2 cells also inhibited IL-2 depletion-induced expression of Bim, however, this decrease in Bim protein expression was not due to downregulation of Bim mRNA, thus indicating that Bim mRNA downregulation in Tax-transformed CTLL-2 occurs only after long-term expression of Tax. Transient expression of Tax in CTLL-2 cells also induced Erk activation, however, this was not involved in the reduction of Bim protein. Knockdown of Bim expression in CTLL-2 cells augmented Tax-induced IL-2-independent transformation. HTLV-1 infection of human T cells also reduced their levels of Bim protein, and restoring Bim expression in HTLV-1-infected cells reduced their proliferation by inducing apoptosis. Taken together, these results indicate that Tax-induced downregulation of Bim in HTLV-1-infected T cells promotes their IL-2-independent growth, thereby supporting the persistence of HTLV-1 infection in vivo. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  3. Tyrosine hydroxylase (TH), its cofactor tetrahydrobiopterin (BH4), other catecholamine-related enzymes, and their human genes in relation to the drug and gene therapies of Parkinson's disease (PD): historical overview and future prospects.

    Science.gov (United States)

    Nagatsu, Toshiharu; Nagatsu, Ikuko

    2016-11-01

    Tyrosine hydroxylase (TH), which was discovered at the National Institutes of Health (NIH) in 1964, is a tetrahydrobiopterin (BH4)-requiring monooxygenase that catalyzes the first and rate-limiting step in the biosynthesis of catecholamines (CAs), such as dopamine, noradrenaline, and adrenaline. Since deficiencies of dopamine and noradrenaline in the brain stem, caused by neurodegeneration of dopamine and noradrenaline neurons, are mainly related to non-motor and motor symptoms of Parkinson's disease (PD), we have studied human CA-synthesizing enzymes [TH; BH4-related enzymes, especially GTP-cyclohydrolase I (GCH1); aromatic L-amino acid decarboxylase (AADC); dopamine β-hydroxylase (DBH); and phenylethanolamine N-methyltransferase (PNMT)] and their genes in relation to PD in postmortem brains from PD patients, patients with CA-related genetic diseases, mice with genetically engineered CA neurons, and animal models of PD. We purified all human CA-synthesizing enzymes, produced their antibodies for immunohistochemistry and immunoassay, and cloned all human genes, especially the human TH gene and the human gene for GCH1, which synthesizes BH4 as a cofactor of TH. This review discusses the historical overview of TH, BH4-, and other CA-related enzymes and their genes in relation to the pathophysiology of PD, the development of drugs, such as L-DOPA, and future prospects for drug and gene therapy for PD, especially the potential of induced pluripotent stem (iPS) cells.

  4. Distinct apoptotic blocks mediate resistance to panHER inhibitors in HER2+ breast cancer cells.

    Science.gov (United States)

    Karakas, Bahriye; Ozmay, Yeliz; Basaga, Huveyda; Gul, Ozgur; Kutuk, Ozgur

    2018-05-04

    Despite the development of novel targeted therapies, de novo or acquired chemoresistance remains a significant factor for treatment failure in breast cancer therapeutics. Neratinib and dacomitinib are irreversible panHER inhibitors, which block their autophosphorylation and downstream signaling. Moreover, neratinib and dacomitinib have been shown to activate cell death in HER2-overexpressing cell lines. Here we showed that increased MCL1 and decreased BIM and PUMA mediated resistance to neratinib in ZR-75-30 and SKBR3 cells while increased BCL-XL and BCL-2 and decreased BIM and PUMA promoted neratinib resistance in BT474 cells. Cells were also cross-resistant to dacomitinib. BH3 profiles of HER2+ breast cancer cells efficiently predicted antiapoptotic protein dependence and development of resistance to panHER inhibitors. Reactivation of ERK1/2 was primarily responsible for acquired resistance in SKBR3 and ZR-75-30 cells. Adding specific ERK1/2 inhibitor SCH772984 to neratinib or dacomitinib led to increased apoptotic response in neratinib-resistant SKBR3 and ZR-75-30 cells, but we did not detect a similar response in neratinib-resistant BT474 cells. Accordingly, suppression of BCL-2/BCL-XL by ABT-737 was required in addition to ERK1/2 inhibition for neratinib- or dacomitinib-induced apoptosis in neratinib-resistant BT474 cells. Our results showed that different mitochondrial apoptotic blocks mediated acquired panHER inhibitor resistance in HER2+ breast cancer cell lines as well as highlighted the potential of BH3 profiling assay in prediction of panHER inhibitor resistance in breast cancer cells. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Research of Ancient Architectures in Jin-Fen Area Based on GIS and BIM Technology

    International Nuclear Information System (INIS)

    Jia, Jing; Zheng, Qiuhong; Gao, Huiying; Sun, Hai

    2017-01-01

    The number of well-preserved ancient buildings located in Shanxi Province, enjoying the absolute maximum proportion of ancient architectures in China, is about 18418, among which, 9053 buildings have the structural style of wood frame. The value of the application of BIM (Building Information Modeling) and GIS (Geographic Information System) is gradually probed and testified in the corresponding fields of ancient architecture’s spatial distribution information management, routine maintenance and special conservation and restoration, the evaluation and simulation of related disasters, such as earthquake. The research objects are ancient architectures in JIN-FEN area, which were first investigated by Sicheng LIANG and recorded in his work of “Chinese ancient architectures survey report”. The research objects, i.e. the ancient architectures in Jin-Fen area include those in Sicheng LIANG’s investigation, and further adjustments were made through authors’ on-site investigation and literature searching and collection. During this research process, the spatial distributing Geodatabase of research objects is established utilizing GIS. The BIM components library for ancient buildings is formed combining on-site investigation data and precedent classic works, such as “Yingzao Fashi”, a treatise on architectural methods in Song Dynasty, “Yongle Encyclopedia” and “Gongcheng Zuofa Zeli”, case collections of engineering practice, by the Ministry of Construction of Qing Dynasty. A building of Guangsheng temple in Hongtong county is selected as an example to elaborate the BIM model construction process based on the BIM components library for ancient buildings. Based on the foregoing work results of spatial distribution data, attribute data of features, 3D graphic information and parametric building information model, the information management system for ancient architectures in Jin-Fen Area, utilizing GIS and BIM technology, could be constructed to support

  6. On (in)stabilities of perturbations in mimetic models with higher derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Yunlong; Shen, Liuyuan [Department of Physics, Nanjing University, Nanjing 210093 (China); Mou, Yicen; Li, Mingzhe, E-mail: zylakx@163.com, E-mail: sly12271103@163.com, E-mail: moinch@mail.ustc.edu.cn, E-mail: limz@ustc.edu.cn [Interdisciplinary Center for Theoretical Study, University of Science and Technology of China, Hefei, Anhui 230026 (China)

    2017-08-01

    Usually when applying the mimetic model to the early universe, higher derivative terms are needed to promote the mimetic field to be dynamical. However such models suffer from the ghost and/or the gradient instabilities and simple extensions cannot cure this pathology. We point out in this paper that it is possible to overcome this difficulty by considering the direct couplings of the higher derivatives of the mimetic field to the curvature of the spacetime.

  7. Research on the Mechanism of Cross Organizational Knowledge Sharing in BIM Competitive Environment

    Directory of Open Access Journals (Sweden)

    Zhong Wei

    2017-01-01

    Full Text Available Co-opetition under the environment of BIM implementation process because the level is not high resulting in the project BIM application value of incomplete knowledge sharing among organizations, thus establishing good knowledge can effectively solve this problem and achieve the overall benefit and benefit sharing mechanism in the project organization. This paper defines five competing modes according to the competing degree of organization between different BIM applications, including imperfect competition, competition, competition and cooperation, full cooperation and cooperation, and put forward the conceptual model and related assumptions. Analysis of the effect of path and effect of project determined in BIM application mode, the concurrence of knowledge sharing, efficiency and overall efficiency of the project within the organization through the survey and empirical results, and according to the proposed contract, the distribution of benefits and work three kinds of knowledge sharing mechanism implementation path.

  8. Challenges of the expansive use of Building Information Modeling (BIM in construction projects

    Directory of Open Access Journals (Sweden)

    Hannele Kerosuo

    2015-06-01

    Full Text Available Building information modeling (BIM is an emerging modeling technology which challenges existing work procedures and practices in the construction industry. In this article we study the challenges, problems and potential expansions of BIM as a tool in the design, construction and operation of buildings. For this purpose the interfaces between different parties are examined in Finnish construction projects. The methodological approach of the study is cultural-historical activity theory, according to which a new artifact becomes a mediating instrument when the participatory subjects reconfigure the entire activity. The implementation of BIM is now spreading from the design activity to other phases of the construction projects, but its use is still limited in the projects' other three interfaces. BIM is an evolving set of software developed for various purposes which is locally 'combined' to fit the circumstances and capabilities of the stakeholders of the construction process.

  9. NEC violation in mimetic cosmology revisited

    Directory of Open Access Journals (Sweden)

    Anna Ijjas

    2016-09-01

    Full Text Available In the context of Einstein gravity, if the null energy condition (NEC is satisfied, the energy density in expanding space–times always decreases while in contracting space–times the energy density grows and the universe eventually collapses into a singularity. In particular, no non-singular bounce is possible. It is, though, an open question if this energy condition can be violated in a controlled way, i.e., without introducing pathologies, such as unstable negative-energy states or an imaginary speed of sound. In this letter, we will re-examine the claim that the recently proposed mimetic scenario can violate the NEC without pathologies. We show that mimetic cosmology is prone to gradient instabilities even in cases when the NEC is satisfied (except for trivial examples. Most interestingly, the source of the instability is always the Einstein–Hilbert term in the action. The matter stress-energy component does not contribute spatial gradient terms but instead makes the problematic curvature modes dynamical. We also show that mimetic cosmology can be understood as a singular limit of known, well-behaved theories involving higher-derivative kinetic terms and discuss ways of removing the instability.

  10. Dual role of proapoptotic BAD in insulin secretion and beta cell survival.

    Science.gov (United States)

    Danial, Nika N; Walensky, Loren D; Zhang, Chen-Yu; Choi, Cheol Soo; Fisher, Jill K; Molina, Anthony J A; Datta, Sandeep Robert; Pitter, Kenneth L; Bird, Gregory H; Wikstrom, Jakob D; Deeney, Jude T; Robertson, Kirsten; Morash, Joel; Kulkarni, Ameya; Neschen, Susanne; Kim, Sheene; Greenberg, Michael E; Corkey, Barbara E; Shirihai, Orian S; Shulman, Gerald I; Lowell, Bradford B; Korsmeyer, Stanley J

    2008-02-01

    The proapoptotic BCL-2 family member BAD resides in a glucokinase-containing complex that regulates glucose-driven mitochondrial respiration. Here, we present genetic evidence of a physiologic role for BAD in glucose-stimulated insulin secretion by beta cells. This novel function of BAD is specifically dependent upon the phosphorylation of its BH3 sequence, previously defined as an essential death domain. We highlight the pharmacologic relevance of phosphorylated BAD BH3 by using cell-permeable, hydrocarbon-stapled BAD BH3 helices that target glucokinase, restore glucose-driven mitochondrial respiration and correct the insulin secretory response in Bad-deficient islets. Our studies uncover an alternative target and function for the BAD BH3 domain and emphasize the therapeutic potential of phosphorylated BAD BH3 mimetics in selectively restoring beta cell function. Furthermore, we show that BAD regulates the physiologic adaptation of beta cell mass during high-fat feeding. Our findings provide genetic proof of the bifunctional activities of BAD in both beta cell survival and insulin secretion.

  11. Udvikling af systemleverancer, parametri og BIM

    DEFF Research Database (Denmark)

    Kortegaard, Per

    2016-01-01

    Seminaret rummede indlæg fra både nogle af projektets tidligere ph.d.-studerende og forskellige kompetente professionelle personer fra forskellige grene af praksis. Seminaret gav samlet et fint billede af status indenfor udviklingen af systemleverancer og deres anvendelse i relation til BIM...

  12. Thermal Performance and Reliability Characterization of Bonded Interface Materials (BIMs): Preprint

    Energy Technology Data Exchange (ETDEWEB)

    DeVoto, D.; Paret, P.; Mihalic, M.; Narumanchi, S.; Bar-Cohen, A.; Matin, K.

    2014-08-01

    Thermal interface materials are an important enabler for low thermal resistance and reliable electronics packaging for a wide array of applications. There is a trend towards bonded interface materials (BIMs) because of their potential for low thermal resistivity (< 1 mm2K/W). However, BIMs induce thermomechanical stresses in the package and can be prone to failures and integrity risks. Deteriorated interfaces can result in high thermal resistance in the package and degradation and/or failure of the electronics. DARPA's Thermal Management Technologies program has addressed this challenge, supporting the development of mechanically-compliant, low resistivity nano-thermal interface (NTI) materials. In this work, we describe the testing procedure and report the results of NREL's thermal performance and reliability characterization of an initial sample of four different NTI-BIMs.

  13. BIM-based Modeling and Data Enrichment of Classical Architectural Buildings

    Directory of Open Access Journals (Sweden)

    Fabrizio Ivan Apollonio

    2012-12-01

    Full Text Available EnIn this paper we presented a BIM-based approach for the documentation of Architectural Heritage. Knowledge of classical architecture is first extracted from the treatises for parametric modeling in object level. Then we established a profile library based on semantic studies to sweep out different objects. Variants grow out from the parametric models by editing or regrouping parameters based on grammars. Multiple data including material, structure and real-life state are enriched with respect to different research motivations. The BIM models are expected to ease the modeling process and provide comprehensive data shared among different platforms for further simulations.ItIn questo articolo è presentata una procedura definita nell'ambito dei sistemi BIM con l'obiettivo di documentare il Patrimonio Architettonico. I dati conoscitivi relativi all'architettura classica sono, in una prima fase, ottenuti dai trattati al fine di modellare in maniera parametrica a livello di oggetti. Successivamente è stata definita una libreria di profili, basata su principi semantici, dalla quale è possibile ottenere oggetti differenti. Dati di natura differente, relativi ad esempio ai materiali, alle strutture, allo stato di fatto, sono implementati in funzione delle differenti esigenze. I modelli BIM hanno la potenzialità di facilitare le procedure di modellazione e di fornire informazioni e dati completi che possono essere condivisi tra piattaforme differenti per ulteriori simulazioni ed analisi.

  14. Study of Collaborative Management for Transportation Construction Project Based on BIM Technology

    Science.gov (United States)

    Jianhua, Liu; Genchuan, Luo; Daiquan, Liu; Wenlei, Li; Bowen, Feng

    2018-03-01

    Abstract. Building Information Modeling(BIM) is a building modeling technology based on the relevant information data of the construction project. It is an advanced technology and management concept, which is widely used in the whole life cycle process of planning, design, construction and operation. Based on BIM technology, transportation construction project collaborative management can have better communication through authenticity simulation and architectural visualization and can obtain the basic and real-time information such as project schedule, engineering quality, cost and environmental impact etc. The main services of highway construction management are integrated on the unified BIM platform for collaborative management to realize information intercommunication and exchange, to change the isolated situation of information in the past, and improve the level of information management. The final BIM model is integrated not only for the information management of project and the integration of preliminary documents and design drawings, but also for the automatic generation of completion data and final accounts, which covers the whole life cycle of traffic construction projects and lays a good foundation for smart highway construction.

  15. Evaluation of the application of BIM technology based on PCA - Q Clustering Algorithm and Choquet Integral

    Directory of Open Access Journals (Sweden)

    Wei Xiaozhao

    2016-03-01

    Full Text Available For the development of the construction industry, the construction of data era is approaching, BIM (building information model with the actual needs of the construction industry has been widely used as a building information clan system software, different software for the practical application of different maturity, through the expert scoring method for the application of BIM technology maturity index mark, establish the evaluation index system, using PCA - Q clustering algorithm for the evaluation index system of classification, comprehensive evaluation in combination with the Choquet integral on the classification of evaluation index system, to achieve a reasonable assessment of the application of BIM technology maturity index. To lay a foundation for the future development of BIM Technology in various fields of construction, at the same time provides direction for the comprehensive application of BIM technology.

  16. Development of a cultural heritage object BIM model

    Science.gov (United States)

    Braila, Natalya; Vakhrusheva, Svetlana; Martynenko, Elena; Kisel, Tatyana

    2017-10-01

    The BIM technology during her creation has been aimed, first of all, at design and construction branch, but its application in the field of studying and operation of architectural heritage can essentially change and transfer this kind of activity to new qualitative level. The question of effective introduction of BIM technologies at the solution of administrative questions of operation and development of monuments of architecture is considered in article. Creation of the information model of the building object of cultural heritage including a full complex of information on an object is offered: historical and archival, legal, technical, administrative, etc. The 3D model of an object of cultural heritage with color marking of elements on degree of wear and a first priority of carrying out repair will become one of components of model. This model will allow to estimate visually technical condition of the building in general and to gain general idea about scales of necessary repair and construction actions that promotes improvement of quality of operation of an object, and also simplifies and accelerates processing of information and in need of a memorial building assessment as subject to investment.

  17. Bio-Mimetic Sensors Based on Molecularly Imprinted Membranes

    Directory of Open Access Journals (Sweden)

    Catia Algieri

    2014-07-01

    Full Text Available An important challenge for scientific research is the production of artificial systems able to mimic the recognition mechanisms occurring at the molecular level in living systems. A valid contribution in this direction resulted from the development of molecular imprinting. By means of this technology, selective molecular recognition sites are introduced in a polymer, thus conferring it bio-mimetic properties. The potential applications of these systems include affinity separations, medical diagnostics, drug delivery, catalysis, etc. Recently, bio-sensing systems using molecularly imprinted membranes, a special form of imprinted polymers, have received the attention of scientists in various fields. In these systems imprinted membranes are used as bio-mimetic recognition elements which are integrated with a transducer component. The direct and rapid determination of an interaction between the recognition element and the target analyte (template was an encouraging factor for the development of such systems as alternatives to traditional bio-assay methods. Due to their high stability, sensitivity and specificity, bio-mimetic sensors-based membranes are used for environmental, food, and clinical uses. This review deals with the development of molecularly imprinted polymers and their different preparation methods. Referring to the last decades, the application of these membranes as bio-mimetic sensor devices will be also reported.

  18. Bio-Mimetic Sensors Based on Molecularly Imprinted Membranes

    Science.gov (United States)

    Algieri, Catia; Drioli, Enrico; Guzzo, Laura; Donato, Laura

    2014-01-01

    An important challenge for scientific research is the production of artificial systems able to mimic the recognition mechanisms occurring at the molecular level in living systems. A valid contribution in this direction resulted from the development of molecular imprinting. By means of this technology, selective molecular recognition sites are introduced in a polymer, thus conferring it bio-mimetic properties. The potential applications of these systems include affinity separations, medical diagnostics, drug delivery, catalysis, etc. Recently, bio-sensing systems using molecularly imprinted membranes, a special form of imprinted polymers, have received the attention of scientists in various fields. In these systems imprinted membranes are used as bio-mimetic recognition elements which are integrated with a transducer component. The direct and rapid determination of an interaction between the recognition element and the target analyte (template) was an encouraging factor for the development of such systems as alternatives to traditional bio-assay methods. Due to their high stability, sensitivity and specificity, bio-mimetic sensors-based membranes are used for environmental, food, and clinical uses. This review deals with the development of molecularly imprinted polymers and their different preparation methods. Referring to the last decades, the application of these membranes as bio-mimetic sensor devices will be also reported. PMID:25196110

  19. EXPLORING BIM FOR OPERATIONAL INTEGRATED ASSET MANAGEMENT – A PRELIMINARY STUDY UTILISING REAL-WORLD INFRASTRUCTURE DATA

    Directory of Open Access Journals (Sweden)

    G. A. Boyes

    2017-10-01

    Full Text Available The use of 3D information models within collaborative working environments and the practice of Building Information Modelling (BIM are becoming more commonplace within infrastructure projects. Currently used predominantly during the design and construction phase, the use of BIM is capable in theory of providing the information at handover that will satisfy the Asset Information Requirements (AIRs of the future Infrastructure Manager (IM. One particular challenge is establishing a link between existing construction-centric information and the asset-centric information needed for future operations. Crossrail, a project to build a new high-frequency railway underneath London, is handling many such challenges as they prepare to handover their digital information to the future operator, in particular the need to provide a two-way link between a federated 3D CAD model and an object-relational Asset Information Management System (AIMS. This paper focusses on the potential for improved Asset Management (AM by integrating BIM and GIS systems and practices, and makes a preliminary report on how 3D spatial queries can be used to establish a two-way relational link between two information systems (3D geometry and asset lists, as well as the challenges being overcome to transform the data to be suitable for AM.

  20. First-principles calculated decomposition pathways for LiBH4 nanoclusters

    Science.gov (United States)

    Huang, Zhi-Quan; Chen, Wei-Chih; Chuang, Feng-Chuan; Majzoub, Eric H.; Ozoliņš, Vidvuds

    2016-05-01

    We analyze thermodynamic stability and decomposition pathways of LiBH4 nanoclusters using grand-canonical free-energy minimization based on total energies and vibrational frequencies obtained from density-functional theory (DFT) calculations. We consider (LiBH4)n nanoclusters with n = 2 to 12 as reactants, while the possible products include (Li)n, (B)n, (LiB)n, (LiH)n, and Li2BnHn; off-stoichiometric LinBnHm (m ≤ 4n) clusters were considered for n = 2, 3, and 6. Cluster ground-state configurations have been predicted using prototype electrostatic ground-state (PEGS) and genetic algorithm (GA) based structural optimizations. Free-energy calculations show hydrogen release pathways markedly differ from those in bulk LiBH4. While experiments have found that the bulk material decomposes into LiH and B, with Li2B12H12 as a kinetically inhibited intermediate phase, (LiBH4)n nanoclusters with n ≤ 12 are predicted to decompose into mixed LinBn clusters via a series of intermediate clusters of LinBnHm (m ≤ 4n). The calculated pressure-composition isotherms and temperature-pressure isobars exhibit sloping plateaus due to finite size effects on reaction thermodynamics. Generally, decomposition temperatures of free-standing clusters are found to increase with decreasing cluster size due to thermodynamic destabilization of reaction products.

  1. Hydrogen Generation from Al-NiCl2/NaBH4 Mixture Affected by Lanthanum Metal

    Directory of Open Access Journals (Sweden)

    Wen Qiang Sun

    2012-01-01

    Full Text Available The effect of La on Al/NaBH4 hydrolysis was elaborated in the present paper. Hydrogen generation amount increases but hydrogen generation rate decreases with La content increasing. There is an optimized composition that Al-15 wt% La-5 wt% NiCl2/NaBH4 mixture (Al-15 wt% La-5 wt% NiCl2/NaBH4 weight ratio, 1 : 3 has 126 mL g−1 min−1 maximum hydrogen generation rate and 1764 mL g−1 hydrogen generation amount within 60 min. The efficiency is 88%. Combined with NiCl2, La has great effect on NaBH4 hydrolysis but has little effect on Al hydrolysis. Increasing La content is helpful to decrease the particle size of Al-La-NiCl2 in the milling process, which induces that the hydrolysis byproduct Ni2B is highly distributed into Al(OH3 and the catalytic reactivity of Ni2B/Al(OH3 is increased therefore. But hydrolysis byproduct La(OH3 deposits on Al surface and leads to some side effect. The Al-La-NiCl2/NaBH4 mixture has good stability in low temperature and its hydrolytic performance can be improved with increasing global temperature. Therefore, the mixture has good safety and can be applied as on board hydrogen generation material.

  2. Hydrogen generation from Al-NiCl2/NaBH4 mixture affected by lanthanum metal.

    Science.gov (United States)

    Sun, Wen Qiang; Fan, Mei-Qiang; Fei, Yong; Pan, Hua; Wang, Liang Liang; Yao, Jun

    2012-01-01

    The effect of La on Al/NaBH(4) hydrolysis was elaborated in the present paper. Hydrogen generation amount increases but hydrogen generation rate decreases with La content increasing. There is an optimized composition that Al-15 wt% La-5 wt% NiCl(2)/NaBH(4) mixture (Al-15 wt% La-5 wt% NiCl(2)/NaBH(4) weight ratio, 1 : 3) has 126 mL g(-1 )min(-1) maximum hydrogen generation rate and 1764 mL g(-1) hydrogen generation amount within 60 min. The efficiency is 88%. Combined with NiCl(2), La has great effect on NaBH(4) hydrolysis but has little effect on Al hydrolysis. Increasing La content is helpful to decrease the particle size of Al-La-NiCl(2) in the milling process, which induces that the hydrolysis byproduct Ni(2)B is highly distributed into Al(OH)(3) and the catalytic reactivity of Ni(2)B/Al(OH)(3) is increased therefore. But hydrolysis byproduct La(OH)(3) deposits on Al surface and leads to some side effect. The Al-La-NiCl(2)/NaBH(4) mixture has good stability in low temperature and its hydrolytic performance can be improved with increasing global temperature. Therefore, the mixture has good safety and can be applied as on board hydrogen generation material.

  3. Aplicación de la tecnología BIM en la asignatura de proyecto del Grado de Ingeniería Industrial en la UNEX = Application of BIM technology in the project subject of the industrial engineering degree in UNEX

    Directory of Open Access Journals (Sweden)

    Antonio M. Reyes

    2017-04-01

    Full Text Available Un gran número de estudios indican que la necesidad de profesionales con conocimientos BIM  está sufriendo un rápido crecimiento. Este crecimiento está dando lugar a problemas en la implantación del BIM en el sector, siendo el principal de ellos la falta de formación de los técnicos en este ámbito [1-4]. Las enseñanzas universitarias actuales, se fundamentan en la adquisición de habilidades por parte del alumnado. En línea con las exigencias del Espacio Europeo de Educación Superior que denomina competencias a las habilidades a adquirir por el alumno. En este trabajo se trata de exponer la experiencia docente de la implantación de la tecnología BIM en la asignatura de proyectos. Esta asignatura tiene carácter obligatorio para las tres disciplinas del Grado de Ingeniería Industrial. El objetivo es deducir si el uso docente de la tecnología BIM facilita la adquisición de conocimientos y mejora la comprensión de la asignatura. La educación BIM debe centrarse en el desarrollo de los conocimientos básicos, habilidades y actitudes de los estudiantes [5]. Además, hay que enfatizar en la necesidad de que los técnicos de la industria de la construcción tengan habilidades como la colaboración, comunicación, liderazgo y la gestión de cambios, junto a habilidades técnicas relacionadas con BIM [6]. El mundo académico tiene un papel importante en la transformación de la industria impulsada por BIM [7]. Mientras que las entidades gubernamentales y el sector privado utilizan BIM para la nueva construcción, los programas universitarios han sido mucho más lentos en incorporar la tecnología [8]. Las universidades se están quedando detrás de la industria de la construcción en cuanto a la adopción de la tecnología BIM en la formación de los alumnos [9]. Realmente lo que se evalúa en este trabajo son precisamente los beneficios y dificultades que ha supuesto la implantación de la tecnología BIM en el desarrollo de la

  4. Expanding the Cancer Arsenal with Targeted Therapies: Disarmament of the Antiapoptotic Bcl-2 Proteins by Small Molecules.

    Science.gov (United States)

    Yap, Jeremy L; Chen, Lijia; Lanning, Maryanna E; Fletcher, Steven

    2017-02-09

    A hallmark of cancer is the evasion of apoptosis, which is often associated with the upregulation of the antiapoptotic members of the Bcl-2 family of proteins. The prosurvival function of the antiapoptotic Bcl-2 proteins is manifested by capturing and neutralizing the proapoptotic Bcl-2 proteins via their BH3 death domains. Accordingly, strategies to antagonize the antiapoptotic Bcl-2 proteins have largely focused on the development of low-molecular-weight, synthetic BH3 mimetics ("magic bullets") to disrupt the protein-protein interactions between anti- and proapoptotic Bcl-2 proteins. In this way, apoptosis has been reactivated in malignant cells. Moreover, several such Bcl-2 family inhibitors are presently being evaluated for a range of cancers in clinical trials and show great promise as new additions to the cancer armamentarium. Indeed, the selective Bcl-2 inhibitor venetoclax (Venclexta) recently received FDA approval for the treatment of a specific subset of patients with chronic lymphocytic leukemia. This review focuses on the major developments in the field of Bcl-2 inhibitors over the past decade, with particular emphasis on binding modes and, thus, the origins of selectivity for specific Bcl-2 family members.

  5. BIM Guidelines Inform Facilities Management Databases: A Case Study over Time

    Directory of Open Access Journals (Sweden)

    Karen Kensek

    2015-08-01

    Full Text Available A building information model (BIM contains data that can be accessed and exported for other uses during the lifetime of the building especially for facilities management (FM and operations. Working under the guidance of well-designed BIM guidelines to insure completeness and compatibility with FM software, architects and contractors can deliver an information rich data model that is valuable to the client. Large owners such as universities often provide these detailed guidelines and deliverable requirements to their building teams. Investigation of the University of Southern California (USC Facilities Management Service’s (FMS website showed a detailed plan including standards, file names, parameter lists, and other requirements of BIM data, which were specifically designated for facilities management use, as deliverables on new construction projects. Three critical details were also unearthed in the reading of these documents: Revit was the default BIM software; COBie was adapted to help meet facilities management goals; and EcoDomus provided a display of the collected data viewed through Navisworks. Published accounts about the Cinema Arts Complex developed with and under these guidelines reported positive results. Further examination with new projects underway reveal the rapidly changing relational database landscape evident in the new USC “Project Record Revit Requirement Execution Plan (PRxP”.

  6. The Imipridone ONC201 Induces Apoptosis and Overcomes Chemotherapy Resistance by Up-Regulation of Bim in Multiple Myeloma.

    Science.gov (United States)

    Tu, Yong-Sheng; He, Jin; Liu, Huan; Lee, Hans C; Wang, Hua; Ishizawa, Jo; Allen, Joshua E; Andreeff, Michael; Orlowski, Robert Z; Davis, Richard E; Yang, Jing

    2017-10-01

    In multiple myeloma, despite recent improvements offered by new therapies, disease relapse and drug resistance still occur in the majority of patients. Therefore, there is an urgent need for new drugs that can overcome drug resistance and prolong patient survival after failure of standard therapies. The imipridone ONC201 causes downstream inactivation of ERK1/2 signaling and has tumoricidal activity against a variety of tumor types, while its efficacy in preclinical models of myeloma remains unclear. In this study, we treated human myeloma cell lines and patient-derived tumor cells with ONC201. Treatment decreased cellular viability and induced apoptosis in myeloma cell lines, with IC50 values of 1 to 1.5 μM, even in those with high risk features or TP53 loss. ONC201 increased levels of the pro-apoptotic protein Bim in myeloma cells, resulting from decreased phosphorylation of degradation-promoting Bim Ser69 by ERK1/2. In addition, myeloma cell lines made resistant to several standard-of-care agents (by chronic exposure) were equally sensitive to ONC201 as their drug-naïve counterparts, and combinations of ONC201 with proteasome inhibitors had synergistic anti-myeloma activity. Overall, these findings demonstrate that ONC201 kills myeloma cells regardless of resistance to standard-of-care therapies, making it promising for clinical testing in relapsed/refractory myeloma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Diabetes-impaired wound healing is improved by matrix therapy with heparan sulfate glycosaminoglycan mimetic OTR4120 in rats

    NARCIS (Netherlands)

    M. Tong (Miao); B. Tuk (Bastiaan); P. Shang (Peng); J.M. Hekking-Weijma (Ineke); E.M.G. Fijneman (Esther ); M. Guijt (Marnix); S.E.R. Hovius (Steven); J.W. van Neck (Han)

    2012-01-01

    textabstractWound healing in diabetes is frequently impaired, and its treatment remains a challenge. We tested a therapeutic strategy of potentiating intrinsic tissue regeneration by restoring the wound cellular environment using a heparan sulfate glycosaminoglycan mimetic, OTR4120. The effect of

  8. BIM in Europe: innovation networks in the construction sectors of Sweden, France and the UK

    OpenAIRE

    Davies, Richard; Crespin-Mazet, Florence; Linne, Ase; Pardo, Catherine; Havenvid, Malena Ingemannson; Harty, Chris; Ivory, Chris; Salle, Robert

    2015-01-01

    European countries are developing or implementing policies that promote or require the use of Building Information Modelling (BIM) and give BIM a central role in strategies for national sector-level transformation. It is necessary to understand BIM as a systemic innovation that is enacted and adopted by firms, projects and users but also by national actors. The Industrial Marketing and Purchasing (IMP) approach has shown how the evolution of innovations can be understood in terms of networks ...

  9. Fibronectin- and collagen-mimetic ligands regulate bone marrow stromal cell chondrogenesis in three-dimensional hydrogels

    Directory of Open Access Journals (Sweden)

    JT Connelly

    2011-09-01

    Full Text Available Modification of tissue engineering scaffolds with bioactive molecules is a potential strategy for modulating cell behavior and guiding tissue regeneration. While adhesion to RGD peptides has been shown to inhibit in vitro chondrogenesis, the effects of extracellular matrix (ECM-mimetic ligands with complex secondary and tertiary structures are unknown. This study aimed to determine whether collagen- and fibronectin-mimetic ligands would retain biologic functionality in three-dimensional (3D hydrogels, whether different ECM-mimetic ligands differentially influence in vitro chondrogenesis, and if effects of ligands on differentiation depend on soluble biochemical stimuli. A linear RGD peptide, a recombinant fibronectin fragment containing the seven to ten Type III repeats (FnIII7-10 and a triple helical, collagen mimetic peptide with the GFOGER motif were covalently coupled to agarose gels using the sulfo-SANPAH crosslinker, and bone marrow stromal cells (BMSCs were cultured within the 3D hydrogels. The ligands retained biologic functionality within the agarose gels and promoted density-dependent BMSC spreading. Interactions with all adhesive ligands inhibited stimulation by chondrogenic factors of collagen Type II and aggrecan mRNA levels and deposition of sulfated glycosaminoglycans. In medium containing fetal bovine serum, interactions with the GFOGER peptide enhanced mRNA expression of the osteogenic gene osteocalcin whereas FnIII7-10 inhibited osteocalcin expression. In conclusion, modification of agarose hydrogels with ECM-mimetic ligands can influence the differentiation of BMSCs in a manner that depends strongly on the presence and nature of soluble biochemical stimuli.

  10. Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model.

    Science.gov (United States)

    Zeng, Lingling; Yang, Yang; Hu, Yujuan; Sun, Yu; Du, Zhengde; Xie, Zhen; Zhou, Tao; Kong, Weijia

    2014-01-01

    Age-related dysfunction of the central auditory system, also known as central presbycusis, can affect speech perception and sound localization. Understanding the pathogenesis of central presbycusis will help to develop novel approaches to prevent or treat this disease. In this study, the mechanisms of central presbycusis were investigated using a mimetic aging rat model induced by chronic injection of D-galactose (D-Gal). We showed that malondialdehyde (MDA) levels were increased and manganese superoxide dismutase (SOD2) activity was reduced in the auditory cortex in natural aging and D-Gal-induced mimetic aging rats. Furthermore, mitochondrial DNA (mtDNA) 4834 bp deletion, abnormal ultrastructure and cell apoptosis in the auditory cortex were also found in natural aging and D-Gal mimetic aging rats. Sirt3, a mitochondrial NAD+-dependent deacetylase, has been shown to play a crucial role in controlling cellular reactive oxygen species (ROS) homeostasis. However, the role of Sirt3 in the pathogenesis of age-related central auditory cortex deterioration is still unclear. Here, we showed that decreased Sirt3 expression might be associated with increased SOD2 acetylation, which negatively regulates SOD2 activity. Oxidative stress accumulation was likely the result of low SOD2 activity and a decline in ROS clearance. Our findings indicate that Sirt3 might play an essential role, via the mediation of SOD2, in central presbycusis and that manipulation of Sirt3 expression might provide a new approach to combat aging and oxidative stress-related diseases.

  11. TRAIL enhances paracetamol-induced liver sinusoidal endothelial cell death in a Bim- and Bid-dependent manner

    Science.gov (United States)

    Badmann, A; Langsch, S; Keogh, A; Brunner, T; Kaufmann, T; Corazza, N

    2012-01-01

    Paracetamol (acetaminophen, APAP) is a universally used analgesic and antipyretic agent. Considered safe at therapeutic doses, overdoses cause acute liver damage characterized by centrilobular hepatic necrosis. One of the major clinical problems of paracetamol-induced liver disease is the development of hemorrhagic alterations. Although hepatocytes represent the main target of the cytotoxic effect of paracetamol overdose, perturbations within the endothelium involving morphological changes of liver sinusoidal endothelial cells (LSECs) have also been described in paracetamol-induced liver disease. Recently, we have shown that paracetamol-induced liver damage is synergistically enhanced by the TRAIL signaling pathway. As LSECs are constantly exposed to activated immune cells expressing death ligands, including TRAIL, we investigated the effect of TRAIL on paracetamol-induced LSEC death. We here demonstrate for the first time that TRAIL strongly enhances paracetamol-mediated LSEC death with typical features of apoptosis. Inhibition of caspases using specific inhibitors resulted in a strong reduction of cell death. TRAIL appears to enhance paracetamol-induced LSEC death via the activation of the pro-apoptotic BH3-only proteins Bid and Bim, which initiate the mitochondrial apoptotic pathway. Taken together this study shows that the liver endothelial layer, mainly LSECs, represent a direct target of the cytotoxic effect of paracetamol and that activation of TRAIL receptor synergistically enhances paracetamol-induced LSEC death via the mitochondrial apoptotic pathway. TRAIL-mediated acceleration of paracetamol-induced cell death may thus contribute to the pathogenesis of paracetamol-induced liver damage. PMID:23254290

  12. Destabilized LiBH4-NaAlH4 Mixtures Doped with Titanium Based Catalysts

    DEFF Research Database (Denmark)

    Shi, Qing; Yu, Xuebin; Feidenhans'l, Robert

    2008-01-01

    We investigate the hydrogen storage properties of the mixed complex hydride LiBH4-NaAlH4 system, both undoped and doped with a TiCl3 additive. The mixed system is found to initiate a transformation to LiBH4-NaAlH4 after ball-milling, and the doped system is found to have a significant lower hydro...

  13. Dihydroartemisinin induces apoptosis preferentially via a Bim-mediated intrinsic pathway in hepatocarcinoma cells.

    Science.gov (United States)

    Qin, Guiqi; Zhao, ChuBiao; Zhang, Lili; Liu, Hongyu; Quan, Yingyao; Chai, Liuying; Wu, Shengnan; Wang, Xiaoping; Chen, Tongsheng

    2015-08-01

    This report is designed to dissect the detail molecular mechanism by which dihydroartemisinin (DHA), a derivative of artemisinin, induces apoptosis in human hepatocellular carcinoma (HCC) cells. DHA induced a loss of the mitochondrial transmemberane potential (ΔΨm), release of cytochrome c, activation of caspases, and externalization of phosphatidylserine indicative of apoptosis induction. Compared with the modest inhibitory effects of silencing Bax, silencing Bak largely prevented DHA-induced ΔΨm collapse and apoptosis though DHA induced a commensurable activation of Bax and Bak, demonstrating a key role of the Bak-mediated intrinsic apoptosis pathway. DHA did not induce Bid cleavage and translocation from cytoplasm to mitochondria and had little effects on the expressions of Puma and Noxa, but did increase Bim and Bak expressions and decrease Mcl-1 expression. Furthermore, the cytotoxicity of DHA was remarkably reduced by silencing Bim, and modestly but significantly reduced by silencing Puma or Noxa. Silencing Bim or Noxa preferentially reduced DHA-induced Bak activation, while silencing Puma preferentially reduced DHA-induced Bax activation, demonstrating that Bim and to a lesser extent Noxa act as upstream mediators to trigger the Bak-mediated intrinsic apoptosis pathway. In addition, silencing Mcl-1 enhanced DHA-induced Bak activation and apoptosis. Taken together, our data demonstrate a crucial role of Bim in preferentially regulating the Bak/Mcl-1 rheostat to mediate DHA-induced apoptosis in HCC cells.

  14. Aligning BIM with FM: streamlining the process for future projects

    Directory of Open Access Journals (Sweden)

    Colleen Kasprzak

    2012-12-01

    Full Text Available A study performed by the National Institute of Standards and Technology (NIST, USA in 2004 found that owners account for approximately $10.6 billion of the $15.8 billion total inadequate interoperability costs of U.S. capital facility projects in 2002. Because of these inefficiency costs, it becomes vital that information produced during the design and construction phases of a project be transferred into operations with maximum leverage to the end users. However, very few owners have defined these informational needs or developed an integration strategy into existing maintenance management systems. To increase operational efficiency, an organization must first develop an understanding of their operating systems, as well as identify how Building Information Modeling (BIM will add value to their daily tasks. The Pennsylvania State University (PSU has a unique opportunity to diversely implement BIM processes because not only does the University act as an owner, but also as designer and construction manager on the majority of projects. The struggle that PSU faces is one that is unique only to owners with a large, existing, multifaceted building inventory. This paper outlines the current initiative by the Office of Physical Plant (OPP, the asset manager at PSU, to develop an information exchange framework between BIM and FM applications to be used internally. As a result of this research, PSU has been able to define owner operational requirements for future projects and develop a flexible integration framework to support additional BIM tasks and information exchanges.

  15. Building Information Modelling: Challenges and Barriers in Implement of BIM for Interior Design Industry in Malaysia

    Science.gov (United States)

    Hamid, A. B. Abd; Taib, M. Z. Mohd; Razak, A. H. N. Abdul; Embi, M. R.

    2018-04-01

    Building Information Modelling (BIM) is an innovative approach that has developed crossways the global in architecture, engineering and construction (AEC) industry. The construction industry of Malaysia has undergone a rapid development and dynamic technology adoption in advance and methods between the players industry and stakeholders. Consequently, limited technologies and devices have not been successful as it should have been. This study will be emphasizing scenarios of challenges and barriers in adopting BIM in interior design industry in Malaysia. The study was emphasizing the challenges and barriers in BIM usage from the designer’s perspective. The data are collected through the questionnaires as to identifying the barriers, knowledge, readiness and awareness and distributed to interior design firms were selected randomly. The finding of this research is to examine the barriers and causes of variables BIM usage for interior design industry in Malaysia. The outcome of this study is to identify the constraint of adoption BIM in interior design industry compare to others players in same industry.

  16. Tool for Benchmarking BIM Performance of Design Engineering and Construction Firms in The Netherlands

    NARCIS (Netherlands)

    Sebastian, R.; Berlo, L. van

    2010-01-01

    Building information modelling (BIM) is becoming more and more important to manage complex communication and information sharing processes in collaborative building projects. A growing number of design, engineering and construction firms have made attempts to adopt BIM to enhance their services and

  17. Understanding effects of BIM on collaborative design and construction : An empirical study in China

    NARCIS (Netherlands)

    Liu, Y.; van Nederveen, G.A.; Hertogh, M.J.C.M.

    2016-01-01

    In construction projects, Building Information Modeling (BIM) influences on the common way of collaboration, including the roles of different participants. The goal of this research is to explore current practices and identify the critical effects of BIM on collaborative design and construction.

  18. Density functional theory study of neutral and singly-charged (NaBH{sub 4}){sub n} (n = 1–6) nanoclusters

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yongpeng [State Key Laboratory of Organic–Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China); Wu, Xiangming [Ping Xiang Sports School, Jiangxi 337000 (China); Liu, Chuan [State Key Laboratory of Organic–Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China); Huang, Shiping, E-mail: huangsp@mail.buct.edu.cn [State Key Laboratory of Organic–Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China)

    2014-10-31

    Highlights: • Structures of (NaBH{sub 4}){sub n} (n = 1–6) clusters are optimized by DFT calculation. • The Kubas interaction is observed in each cationic cluster. • Hydrogen molecule interacts with attached boron atom by Kubas interaction. • Cationic NaBH{sub 4} nanoclusters exhibit more easily H{sub 2} desorption. - Abstract: We report the global minimum structures of (NaBH{sub 4}){sub n} (n = 1–6) clusters by combining the particle swarm optimization algorithm with density functional theory. A newly formed hydrogen molecule is observed in each cationic structure, and the H{sub 2} interacts with adjacent boron atom by Kubas interaction. The results of localized orbital locator and natural bond orbital analysis reveal that the hydrogen molecule interacts with attached boron atom by the σ-bond and σ{sup ∗}-antibond of H{sub 2} in [NaBH{sub 4}]{sub n}{sup +} (n = 1, 2, 3 and 5), and the σ{sup ∗}-antibond dominates this interaction in [NaBH{sub 4}]{sub 4}{sup +} and [NaBH{sub 4}]{sub 6}{sup +}. The desorption energy of the hydrogen molecule is relatively small for [NaBH{sub 4}]{sup +} (1.05 eV), [NaBH{sub 4}]{sub 2}{sup +} (0.99 eV) and [NaBH{sub 4}]{sub 3}{sup +} (0.97 eV). It is also found that the negative desorption energy of the [NaBH{sub 4}]{sub 4}{sup +} (−0.26 eV), [NaBH{sub 4}]{sub 5}{sup +} (−0.26 eV) and [NaBH{sub 4}]{sub 6}{sup +} (−0.54 eV) shows that the hydrogen molecule can be released easily.

  19. Behavior of solvent-exposed hydrophobic groove in the anti-apoptotic Bcl-XL protein: clues for its ability to bind diverse BH3 ligands from MD simulations.

    Directory of Open Access Journals (Sweden)

    Dilraj Lama

    Full Text Available Bcl-XL is a member of Bcl-2 family of proteins involved in the regulation of intrinsic pathway of apoptosis. Its overexpression in many human cancers makes it an important target for anti-cancer drugs. Bcl-XL interacts with the BH3 domain of several pro-apoptotic Bcl-2 partners. This helical bundle protein has a pronounced hydrophobic groove which acts as a binding region for the BH3 domains. Eight independent molecular dynamics simulations of the apo/holo forms of Bcl-XL were carried out to investigate the behavior of solvent-exposed hydrophobic groove. The simulations used either a twin-range cut-off or particle mesh Ewald (PME scheme to treat long-range interactions. Destabilization of the BH3 domain-containing helix H2 was observed in all four twin-range cut-off simulations. Most of the other major helices remained stable. The unwinding of H2 can be related to the ability of Bcl-XL to bind diverse BH3 ligands. The loss of helical character can also be linked to the formation of homo- or hetero-dimers in Bcl-2 proteins. Several experimental studies have suggested that exposure of BH3 domain is a crucial event before they form dimers. Thus unwinding of H2 seems to be functionally very important. The four PME simulations, however, revealed a stable helix H2. It is possible that the H2 unfolding might occur in PME simulations at longer time scales. Hydrophobic residues in the hydrophobic groove are involved in stable interactions among themselves. The solvent accessible surface areas of bulky hydrophobic residues in the groove are significantly buried by the loop LB connecting the helix H2 and subsequent helix. These observations help to understand how the hydrophobic patch in Bcl-XL remains stable in the solvent-exposed state. We suggest that both the destabilization of helix H2 and the conformational heterogeneity of loop LB are important factors for binding of diverse ligands in the hydrophobic groove of Bcl-XL.

  20. Multinuclear NMR spectroscopy of the tetrahedral uranium(IV) complex U(BH3CH3)4

    International Nuclear Information System (INIS)

    Gamp, E.; Shinomoto, R.; Edelstein, N.; McGarvey, B.R.

    1987-01-01

    The temperature dependence of the 1 H, 11 B, and 13 C NMR spectra of T/sub d/ U(BH 3 CH 3 ) 4 in solution is reported. The paramagnetic shifts are interpreted as originating purely from spin delocalization mechanisms with no contribution from the metal-orbital dipolar interaction. It is shown that the temperature dependence of both 1 H shifts (bridging and terminal protons) is identical with that calculated from a polarization theory which assumes the shift is proportional to the average value of electron spin in the inner 5f orbitals. The proportionality constant is -5.64 MHz for the bridging protons and -0.59 MHz for the terminal protons. The temperature dependences of 11 B and 13 shifts are found to depart significantly from that predicted by the polarization theory with the largest deviations shown by the 11 B shifts. It is shown how those deviations can be accounted for by postulating a second spin delocalization through direct covalency involving molecular orbitals formed from the uranium 5f orbitals and ligand s and p orbitals. 29 references, 4 figures, 3 tables

  1. Temperature-sensitive elastin-mimetic dendrimers: Effect of peptide length and dendrimer generation to temperature sensitivity.

    Science.gov (United States)

    Kojima, Chie; Irie, Kotaro; Tada, Tomoko; Tanaka, Naoki

    2014-06-01

    Dendrimers are synthetic macromolecules with unique structure, which are a potential scaffold for peptides. Elastin is one of the main components of extracellular matrix and a temperature-sensitive biomacromolecule. Previously, Val-Pro-Gly-Val-Gly peptides have been conjugated to a dendrimer for designing an elastin-mimetic dendrimer. In this study, various elastin-mimetic dendrimers using different length peptides and different dendrimer generations were synthesized to control the temperature dependency. The elastin-mimetic dendrimers formed β-turn structure by heating, which was similar to the elastin-like peptides. The elastin-mimetic dendrimers exhibited an inverse phase transition, largely depending on the peptide length and slightly depending on the dendrimer generation. The elastin-mimetic dendrimers formed aggregates after the phase transition. The endothermal peak was observed in elastin-mimetic dendrimers with long peptides, but not with short ones. The peptide length and the dendrimer generation are important factors to tune the temperature dependency on the elastin-mimetic dendrimer. Copyright © 2013 Wiley Periodicals, Inc.

  2. Development of Kinematic 3D Laser Scanning System for Indoor Mapping and As-Built BIM Using Constrained SLAM

    Directory of Open Access Journals (Sweden)

    Jaehoon Jung

    2015-10-01

    Full Text Available The growing interest and use of indoor mapping is driving a demand for improved data-acquisition facility, efficiency and productivity in the era of the Building Information Model (BIM. The conventional static laser scanning method suffers from some limitations on its operability in complex indoor environments, due to the presence of occlusions. Full scanning of indoor spaces without loss of information requires that surveyors change the scanner position many times, which incurs extra work for registration of each scanned point cloud. Alternatively, a kinematic 3D laser scanning system, proposed herein, uses line-feature-based Simultaneous Localization and Mapping (SLAM technique for continuous mapping. Moreover, to reduce the uncertainty of line-feature extraction, we incorporated constrained adjustment based on an assumption made with respect to typical indoor environments: that the main structures are formed of parallel or orthogonal line features. The superiority of the proposed constrained adjustment is its reduction for uncertainties of the adjusted lines, leading to successful data association process. In the present study, kinematic scanning with and without constrained adjustment were comparatively evaluated in two test sites, and the results confirmed the effectiveness of the proposed system. The accuracy of the 3D mapping result was additionally evaluated by comparison with the reference points acquired by a total station: the Euclidean average distance error was 0.034 m for the seminar room and 0.043 m for the corridor, which satisfied the error tolerance for point cloud acquisition (0.051 m according to the guidelines of the General Services Administration for BIM accuracy.

  3. Ensino de BIM em curso de graduação em engenharia civil em uma universidade dos EUA: estudo de caso

    Directory of Open Access Journals (Sweden)

    Priscilla Elisa de Azevedo Basto

    Full Text Available Resumo Com o crescente avanço da tecnologia, os empreendimentos da construção civil se tornam cada vez mais complexos. Como forma de acompanhar esse processo, foi desenvolvido o paradigma denominado de Building Information Modeling (BIM, que se baseia na colaboração entre as equipes para a elaboração de um modelo integrado e 3D da edificação do qual serão retiradas as informações necessárias para a gestão do empreendimento. O BIM vem sendo utilizado por diversas empresas, devido aos benefícios potenciais, entretanto sua difusão continua sendo restrita em razão do fato de ser dominado por pequena quantidade de profissionais. Dessa forma, este trabalho objetiva descrever um método de abordagem do ensino de BIM, permitindo a sua avaliação para potencial difusão e utilização, e demonstrar a importância desse método. Para isso foram realizadas a descrição detalhada e a análise da experiência de ensino do BIM na disciplina de Gerenciamento de Projeto da Construção I, ministrada na Arizona State University (ASU, localizada nos Estados Unidos. Através dos resultados obtidos, constatou-se que a disciplina realiza a abordagem do BIM em conjunto com os outros assuntos, pode ser classificada como de nível intermediário, formando um analista BIM, e se mostrou efetiva em apresentar os principais conceitos e usos do BIM aos discentes.

  4. When less may be more: calorie restriction and response to cancer therapy

    OpenAIRE

    O?Flanagan, Ciara H.; Smith, Laura A.; McDonell, Shannon B.; Hursting, Stephen D.

    2017-01-01

    Calorie restriction (CR) extends lifespan and has been shown to reduce age-related diseases including cancer, diabetes, and cardiovascular and neurodegenerative diseases in experimental models. Recent translational studies have tested the potential of CR or CR mimetics as adjuvant therapies to enhance the efficacy of chemotherapy, radiation therapy, and novel immunotherapies. Chronic CR is challenging to employ in cancer patients, and therefore intermittent fasting, CR mimetic drugs, or alter...

  5. Crystallization and preliminary X-ray characterization of Epstein–Barr virus BHRF1 in complex with a benzoylurea peptidomimetic

    International Nuclear Information System (INIS)

    Caria, Sofia; Chugh, Srishti; Nhu, Duong; Lessene, Guillaume; Kvansakul, Marc

    2012-01-01

    The expression and purification of Epstein–Barr virus BHRF1 as well as its co-crystallization with a peptidomimetic are described. BHRF1 is a pro-survival Bcl-2 homologue encoded by Epstein–Barr virus (EBV) that plays a key role in preventing premature host cell death during viral infection and may contribute to the development of malignancies associated with chronic EBV infections. The anti-apoptotic action of BHRF1 is based on its ability to sequester pro-apoptotic Bcl-2 family proteins, in particular Bim and Bak. These interactions have been previously studied in three dimensions by determining crystal structures of BHRF1 in complex with both Bim and Bak BH3 domains. Screening of a library of peptidomimetic compounds based on the benzoylurea scaffold that mimics critical Bim BH3 domain side chains against BHRF1 led to the identification of an inhibitor of BHRF1 that displays micromolar affinity. Single crystals were obtained from the co-crystallization of recombinant BHRF1 protein with this peptidomimetic compound. The crystals belonged to the orthorhombic space group P2 1 2 1 2 1 , with unit-cell parameters a = 66.8, b = 91.1, c = 151.9 Å. Diffraction data were collected to 2.11 Å resolution on the MX2 beamline at the Australian Synchrotron

  6. BIM – New rules of measurement ontology for construction cost estimation

    Directory of Open Access Journals (Sweden)

    F.H. Abanda

    2017-04-01

    Full Text Available For generations, the process of cost estimation has been manual, time-consuming and error-prone. Emerging Building Information Modelling (BIM can exploit standard measurement methods to automate cost estimation process and improve inaccuracies. Structuring standard measurement methods in an ontologically and machine readable format for a BIM software can greatly facilitate the process of improving inaccuracies in cost estimation. This study explores the development of an ontology based on New Rules of Measurement (NRM for cost estimation during the tendering stages. The methodology adopted is methontology, one of the most widely used ontology engineering methodologies. To ensure the ontology is fit for purpose, cost estimation experts are employed to check the semantics, descriptive logic-based reasoners are used to syntactically check the ontology and a leading 4D BIM modelling software is used on a case study building to test/validate the proposed ontology.

  7. Mimetic Gravity: A Review of Recent Developments and Applications to Cosmology and Astrophysics

    Directory of Open Access Journals (Sweden)

    Lorenzo Sebastiani

    2017-01-01

    Full Text Available Mimetic gravity is a Weyl-symmetric extension of General Relativity, related to the latter by a singular disformal transformation, wherein the appearance of a dust-like perfect fluid can mimic cold dark matter at a cosmological level. Within this framework, it is possible to provide a unified geometrical explanation for dark matter, the late-time acceleration, and inflation, making it a very attractive theory. In this review, we summarize the main aspects of mimetic gravity, as well as extensions of the minimal formulation of the model. We devote particular focus to the reconstruction technique, which allows the realization of any desired expansionary history of the universe by an accurate choice of potential or other functions defined within the theory (as in the case of mimetic f(R gravity. We briefly discuss cosmological perturbation theory within mimetic gravity. As a case study within which we apply the concepts previously discussed, we study a mimetic Hořava-like theory, of which we explore solutions and cosmological perturbations in detail. Finally, we conclude the review by discussing static spherically symmetric solutions within mimetic gravity and apply our findings to the problem of galactic rotation curves. Our review provides an introduction to mimetic gravity, as well as a concise but self-contained summary of recent findings, progress, open questions, and outlooks on future research directions.

  8. BIM in the Facility Manager's Toolkit

    Science.gov (United States)

    Peglow, Timothy M.

    2010-01-01

    There has been a tremendous increase in use of Building Information Modeling (BIM) in the design and construction industry. There have been numerous case studies that have documented the improvements. The majority of these improvements have focused on better coordination of design resulting in fewer Requests for Information and/or change orders.…

  9. Molecular epidemiology, genotype-phenotype correlation and BH4 responsiveness in Spanish patients with phenylketonuria.

    Science.gov (United States)

    Aldámiz-Echevarría, Luis; Llarena, Marta; Bueno, María A; Dalmau, Jaime; Vitoria, Isidro; Fernández-Marmiesse, Ana; Andrade, Fernando; Blasco, Javier; Alcalde, Carlos; Gil, David; García, María C; González-Lamuño, Domingo; Ruiz, Mónica; Ruiz, María A; Peña-Quintana, Luis; González, David; Sánchez-Valverde, Felix; Desviat, Lourdes R; Pérez, Belen; Couce, María L

    2016-08-01

    Phenylketonuria (PKU), the most common inborn error of amino acid metabolism, is caused by mutations in the phenylalanine-4-hydroxylase (PAH) gene. This study aimed to assess the genotype-phenotype correlation in the PKU Spanish population and the usefulness in establishing genotype-based predictions of BH4 responsiveness in our population. It involved the molecular characterization of 411 Spanish PKU patients: mild hyperphenylalaninemia non-treated (mild HPA-NT) (34%), mild HPA (8.8%), mild-moderate (20.7%) and classic (36.5%) PKU. BH4 responsiveness was evaluated using a 6R-BH4 loading test. We assessed genotype-phenotype associations and genotype-BH4 responsiveness in our population according to literature and classification of the mutations. The mutational spectrum analysis showed 116 distinct mutations, most missense (70.7%) and located in the catalytic domain (62.9%). The most prevalent mutations were c.1066-11G>A (9.7%), p.Val388Met (6.6%) and p.Arg261Gln (6.3%). Three novel mutations (c.61-13del9, p.Ile283Val and p.Gly148Val) were reported. Although good genotype-phenotype correlation was observed, there was no exact correlation for some genotypes. Among the patients monitored for the 6R-BH4 loading test: 102 were responders (87, carried either one or two BH4-responsive alleles) and 194 non-responders (50, had two non-responsive mutations). More discrepancies were observed in non-responders. Our data reveal a great genetic heterogeneity in our population. Genotype is quite a good predictor of phenotype and BH4 responsiveness, which is relevant for patient management, treatment and follow-up.

  10. Evaluation of Tetrahydrobiopterin Therapy with Large Neutral Amino Acid Supplementation in Phenylketonuria: Effects on Potential Peripheral Biomarkers, Melatonin and Dopamine, for Brain Monoamine Neurotransmitters.

    Directory of Open Access Journals (Sweden)

    Shoji Yano

    Full Text Available Phenylketonuria (PKU is due to a defective hepatic enzyme, phenylalanine (Phe hydroxylase. Transport of the precursor amino acids from blood into the brain for serotonin and dopamine synthesis is reported to be inhibited by high blood Phe concentrations. Deficiencies of serotonin and dopamine are involved in neurocognitive dysfunction in PKU.(1 To evaluate the effects of sapropterin (BH4 and concurrent use of large neutral amino acids (LNAA on the peripheral biomarkers, melatonin and dopamine with the hypothesis they reflect brain serotonin and dopamine metabolism. (2 To evaluate synergistic effects with BH4 and LNAA. (3 To determine the effects of blood Phe concentrations on the peripheral biomarkers concentrations.Nine adults with PKU completed our study consisting of four 4-week phases: (1 LNAA supplementation, (2 Washout, (3 BH4 therapy, and (4 LNAA with BH4 therapy. An overnight protocol measured plasma amino acids, serum melatonin, and 6-sulfatoxymelatonin and dopamine in first void urine after each phase.(1 Three out of nine subjects responded to BH4. A significant increase of serum melatonin levels was observed in BH4 responders with decreased blood Phe concentration. No significant change in melatonin, dopamine or Phe levels was observed with BH4 in the subjects as a whole. (2 Synergistic effects with BH4 and LNAA were observed in serum melatonin in BH4 responders. (3 The relationship between serum melatonin and Phe showed a significant negative slope (p = 0.0005 with a trend toward differing slopes among individual subjects (p = 0.066. There was also a negative association overall between blood Phe and urine 6-sulfatoxymelatonin and dopamine (P = 0.040 and 0.047.Blood Phe concentrations affected peripheral monoamine neurotransmitter biomarker concentrations differently in each individual with PKU. Melatonin levels increased with BH4 therapy only when blood Phe decreased. Monitoring peripheral neurotransmitter metabolites may assist in

  11. BIM aplicado ao projeto de fôrmas de madeira em estrutura de concreto armado

    Directory of Open Access Journals (Sweden)

    Romeu da Silva Neiva Neto

    Full Text Available ResumoO Projeto Construtivo de Fôrmas de Madeira (PCFM faz uso tradicionalmente de ferramentas CAD na representação bidimensional, limitando sua inserção no contexto de Building Information Modeling (BIM. Considerando que BIM se encontra em grande expansão no mercado nacional esta pesquisa visa apontar um caminho para se vencer esta limitação. Propõe-se uma biblioteca de componentes para o projeto de fôrmas de madeira, incluindo usos de BIM tais como a Modelagem, a Quantificação, a Simulação 4D e procedimentos associados. O método de pesquisa utilizado foi a Constructive Research. Os componentes para a biblioteca foram desenvolvidos na ferramenta BIM Revit Structure. A proposta foi validada: em ambiente de ensino, escritório de projeto e na prática. Verifica-se que a pesquisa é consonante com os poucos estudos internacionais pioneiros e semelhantes, sendo contextualizada para o cenário nacional. Observa-se também que todas as pesquisas que tratam de BIM associado a fôrmas requerem um modelo de informação que inclua a modelagem de fôrmas no mesmo. Desta forma, este estudo é também fundamental, pois amplia desdobramentos da incorporação de BIM na cadeia produtiva da construção civil.

  12. BIM cost analysis of transport infrastructure projects

    Science.gov (United States)

    Volkov, Andrey; Chelyshkov, Pavel; Grossman, Y.; Khromenkova, A.

    2017-10-01

    The article describes the method of analysis of the energy costs of transport infrastructure objects using BIM software. The paper consideres several options of orientation of a building using SketchUp and IES VE software programs. These options allow to choose the best direction of the building facades. Particular attention is given to a distribution of a temperature field in a cross-section of the wall according to the calculation made in the ELCUT software. The issues related to calculation of solar radiation penetration into a building and selection of translucent structures are considered in the paper. The article presents data on building codes relating to the transport sector, on the basis of which the calculations were made. The author emphasizes that BIM-programs should be implemented and used in order to optimize a thermal behavior of a building and increase its energy efficiency using climatic data.

  13. Mito-priming as a method to engineer Bcl-2 addiction.

    Science.gov (United States)

    Lopez, Jonathan; Bessou, Margaux; Riley, Joel S; Giampazolias, Evangelos; Todt, Franziska; Rochegüe, Tony; Oberst, Andrew; Green, Douglas R; Edlich, Frank; Ichim, Gabriel; Tait, Stephen W G

    2016-02-02

    Most apoptotic stimuli require mitochondrial outer membrane permeabilization (MOMP) in order to execute cell death. As such, MOMP is subject to tight control by Bcl-2 family proteins. We have developed a powerful new technique to investigate Bcl-2-mediated regulation of MOMP. This method, called mito-priming, uses co-expression of pro- and anti-apoptotic Bcl-2 proteins to engineer Bcl-2 addiction. On addition of Bcl-2 targeting BH3 mimetics, mito-primed cells undergo apoptosis in a rapid and synchronous manner. Using this method we have comprehensively surveyed the efficacy of BH3 mimetic compounds, identifying potent and specific MCL-1 inhibitors. Furthermore, by combining different pro- and anti-apoptotic Bcl-2 pairings together with CRISPR/Cas9-based genome editing, we find that tBID and PUMA can preferentially kill in a BAK-dependent manner. In summary, mito-priming represents a facile and robust means to trigger mitochondrial apoptosis.

  14. Role of phosphate on stability and catalase mimetic activity of cerium oxide nanoparticles.

    Science.gov (United States)

    Singh, Ragini; Singh, Sanjay

    2015-08-01

    Cerium oxide nanoparticles (CeNPs) have been recently shown to scavenge reactive oxygen and nitrogen species (ROS and RNS) in different experimental model systems. CeNPs (3+) and CeNPs (4+) have been shown to exhibit superoxide dismutase (SOD) and catalase mimetic activity, respectively. Due to their nanoscale dimension, CeNPs are expected to interact with the components of biologically relevant buffers and medium, which could alter their catalytic properties. We have demonstrated earlier that CeNPs (3+) interact with phosphate and lose the SOD activity. However, very little is known about the interaction of CeNPs (4+) with the phosphate and other anions, predominantly present in biological buffers and their effects on the catalase mimetic-activity of these nanoparticles. In this study, we report that catalase mimetic-activity of CeNPs (4+) is resistant to the phosphate anions, pH changes and composition of cell culture media. Given the abundance of phosphate anions in the biological system, it is likely that internalized CeNPs would be influenced by cytoplasmic and nucleoplasmic concentration of phosphate. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Efavirenz and 8-hydroxyefavirenz induce cell death via a JNK- and BimEL-dependent mechanism in primary human hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Bumpus, Namandje N., E-mail: nbumpus1@jhmi.edu

    2011-12-15

    Chronic use of efavirenz (EFV) has been linked to incidences of hepatotoxicity in patients receiving EFV to treat HIV-1. While recent studies have demonstrated that EFV stimulates hepatic cell death a role for the metabolites of efavirenz in this process has yet to be examined. In the present study, incubation of primary human hepatocytes with synthetic 8-hydroxyEFV (8-OHEFV), which is the primary metabolite of EFV, resulted in cell death, caspase-3 activation and reactive oxygen species formation. The metabolite exerted these effects at earlier time points and using lower concentrations than were required for the parent compound. In addition, pharmacological inhibition of cytochrome P450-dependent metabolism of EFV using 1-aminobenzotriazole markedly decreased reactive oxygen species formation and cell death. Treatment of primary human hepatocytes with EFV and 8-OHEFV also stimulated phosphorylation of c-Jun N-terminal kinase (JNK) as well as phosphorylation of the JNK substrate c-Jun. Further, the mRNA and protein expression of an isoform of Bim (Bcl-2 interacting mediator of cell death) denoted as BimEL, which is proapoptotic and has been shown to be modulated by JNK, was increased. Inhibition of JNK using SP600125 prevented the EFV- and 8-OHEFV-mediated cell death. Silencing of Bim using siRNA transfected into hepatocytes also prevented cell death resulting from 8-OHEFV-treatment. These data suggest that the oxidative metabolite 8-OHEFV is a more potent inducer of hepatic cell death than the parent compound EFV. Further, activation of the JNK signaling pathway and BimEL mRNA expression appear to be required for EFV- and 8-OHEFV-mediated hepatocyte death. -- Highlights: Black-Right-Pointing-Pointer 8-Hydroxyefavirenz is a more potent stimulator of cell death than efavirenz. Black-Right-Pointing-Pointer Efavirenz and 8-hydroxyefavirenz increase JNK activity and BimEL mRNA expression. Black-Right-Pointing-Pointer JNK and Bim are required for efavirenz- and 8

  16. Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model.

    Directory of Open Access Journals (Sweden)

    Lingling Zeng

    Full Text Available Age-related dysfunction of the central auditory system, also known as central presbycusis, can affect speech perception and sound localization. Understanding the pathogenesis of central presbycusis will help to develop novel approaches to prevent or treat this disease. In this study, the mechanisms of central presbycusis were investigated using a mimetic aging rat model induced by chronic injection of D-galactose (D-Gal. We showed that malondialdehyde (MDA levels were increased and manganese superoxide dismutase (SOD2 activity was reduced in the auditory cortex in natural aging and D-Gal-induced mimetic aging rats. Furthermore, mitochondrial DNA (mtDNA 4834 bp deletion, abnormal ultrastructure and cell apoptosis in the auditory cortex were also found in natural aging and D-Gal mimetic aging rats. Sirt3, a mitochondrial NAD+-dependent deacetylase, has been shown to play a crucial role in controlling cellular reactive oxygen species (ROS homeostasis. However, the role of Sirt3 in the pathogenesis of age-related central auditory cortex deterioration is still unclear. Here, we showed that decreased Sirt3 expression might be associated with increased SOD2 acetylation, which negatively regulates SOD2 activity. Oxidative stress accumulation was likely the result of low SOD2 activity and a decline in ROS clearance. Our findings indicate that Sirt3 might play an essential role, via the mediation of SOD2, in central presbycusis and that manipulation of Sirt3 expression might provide a new approach to combat aging and oxidative stress-related diseases.

  17. New fundamental experimental studies on α-Mg(BH4)2 and other borohydrides

    International Nuclear Information System (INIS)

    Hagemann, Hans; D'Anna, Vincenza; Rapin, Jean-Philippe; Cerny, Radovan; Filinchuk, Yaroslav; Kim, Ki Chul; Sholl, David S.; Parker, Stewart F.

    2011-01-01

    Research highlights: → Eutectic behavior is observed in the LiBH4 -Mg(BH4)2 system. → New INS data show good agreement with theoretical DFT calculations. → Temperature dependent Raman spectra complement previous NMR studies. - Abstract: Several new studies of Mg(BH 4 ) 2 are reported. A 1:1 LiBH 4 :Mg(BH 4 ) 2 mixture was studied by in situ synchrotron X-ray diffraction and reveals an eutectic behavior with the eutectic composition more rich in Mg(BH 4 ) 2 , and the eutectic temperature lower than 456 K. No dual cation compound was observed in this experiment. New vibrational spectra including INS data have been obtained and are compared with theoretical DFT calculations and recent NMR studies, showing good agreement.

  18. Hydrolysis of Mg(BH4)2 and its coordination compounds as a way to obtain hydrogen

    Science.gov (United States)

    Solovev, Mikhail V.; Chashchikhin, Oleg V.; Dorovatovskii, Pavel V.; Khrustalev, Victor N.; Zyubin, A. S.; Zyubina, T. S.; Kravchenko, O. V.; Zaytsev, Alexey A.; Dobrovolsky, Yu. A.

    2018-02-01

    Three ligand-stabilized Mg(BH4)2-based complexes have been synthesized and evaluated as potential hydrogen storage media for portable fuel cell applications. The new borohydrides: Mg(BH4)2 × 0.5Et2O and Mg(BH4)2 × diglyme (diglyme - CH3O(CH2)2O(CH2)2OCH3) have been synthesized and examined by X-ray single crystal diffraction method. Hydrolysis reactions of the compounds liberate hydrogen in quantities ranging from 46 to 96% of the theoretical yield. The hydrolysis of Mg(BH4)2 and other borohydrides is also accompanied by the diborane formation. The amount of liberated diborane depends on the Mg-coordination environment. To explain this fact quantum-chemical calculations have been performed. It is shown that formation of Mg-O-Mg-bridges enables the side process of diborane generation. It means that the size and denticity of the ligand directly affects the amount of released diborane. In general, the larger the ligand and the higher its denticity, the smaller is amount of diborane produced. The new compound Mg(BH4)2 × diglyme decomposes without diborane formation that allows one to be considered as a new promising chemical hydrogen storage compound for the practical usage.

  19. The HDAC inhibitor SB939 overcomes resistance to BCR-ABL kinase Inhibitors conferred by the BIM deletion polymorphism in chronic myeloid leukemia.

    Directory of Open Access Journals (Sweden)

    Muhammad Rauzan

    Full Text Available Chronic myeloid leukemia (CML treatment has been improved by tyrosine kinase inhibitors (TKIs such as imatinib mesylate (IM but various factors can cause TKI resistance in patients with CML. One factor which contributes to TKI resistance is a germline intronic deletion polymorphism in the BCL2-like 11 (BIM gene which impairs the expression of pro-apoptotic splice isoforms of BIM. SB939 (pracinostat is a hydroxamic acid based HDAC inhibitor with favorable pharmacokinetic, physicochemical and pharmaceutical properties, and we investigated if this drug could overcome BIM deletion polymorphism-induced TKI resistance. We found that SB939 corrects BIM pre-mRNA splicing in CML cells with the BIM deletion polymorphism, and induces apoptotic cell death in CML cell lines and primary cells with the BIM deletion polymorphism. More importantly, SB939 both decreases the viability of CML cell lines and primary CML progenitors with the BIM deletion and restores TKI-sensitivity. Our results demonstrate that SB939 overcomes BIM deletion polymorphism-induced TKI resistance, and suggest that SB939 may be useful in treating CML patients with BIM deletion-associated TKI resistance.

  20. Insight to the Thermal Decomposition and Hydrogen Desorption Behaviors of NaNH2-NaBH4 Hydrogen Storage Composite.

    Science.gov (United States)

    Pei, Ziwei; Bai, Ying; Wang, Yue; Wu, Feng; Wu, Chuan

    2017-09-20

    The lightweight compound material NaNH 2 -NaBH 4 is regarded as a promising hydrogen storage composite due to the high hydrogen density. Mechanical ball milling was employed to synthesize the composite NaNH 2 -NaBH 4 (2/1 molar ratio), and the samples were investigated utilizing thermogravimetric-differential thermal analysis-mass spectroscopy (TG-DTA-MS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) analyses. The full-spectrum test (range of the ratio of mass to charge: 0-200) shows that the released gaseous species contain H 2 , NH 3 , B 2 H 6 , and N 2 in the heating process from room temperature to 400 °C, and possibly the impurity gas B 6 H 12 also exists. The TG/DTA analyses show that the composite NaNH 2 -NaBH 4 (2/1 molar ratio) is conductive to generate hydrogen so that the dehydrogenation process can be finished before 400 °C. Moreover, the thermal decomposition process from 200 to 400 °C involves two-step dehydrogenation reactions: (1) Na 3 (NH 2 ) 2 BH 4 hydride decomposes into Na 3 BN 2 and H 2 (200-350 °C); (2) remaining Na 3 (NH 2 ) 2 BH 4 reacts with NaBH 4 and Na 3 BN 2 , generating Na, BN, NH 3 , N 2 , and H 2 (350-400 °C). The better mechanism understanding of the thermal decomposition pathway lays a foundation for tailoring the hydrogen storage performance of the composite complex hydrides system.

  1. Evalution of BIM and Ecotect for Conceptual Architectural Design Analysis

    DEFF Research Database (Denmark)

    Thuesen, Niels; Kirkegaard, Poul Henning; Jensen, Rasmus Lund

    2010-01-01

    The main goal of the present paper is to investigate how BIM tools and Ecotect can be integrated as active part of an integrated design process for conceptual architectural design. The integrated design has an interaction between the skills of the architect and the engineer thought-out the process...... and thereby avoiding problems solving after the design has been finalised. The process has been analysed from an architect's point of view dealing with design at fictive sites in Copenhagen. The results of the research indicate that BIM tools combined with Ecotect can deliver useable qualitative input...

  2. Micro poly(3-sulfopropyl methacrylate) hydrogel synthesis for in situ metal nanoparticle preparation and hydrogen generation from hydrolysis of NaBH4

    International Nuclear Information System (INIS)

    Turhan, Tugce; Güvenilir, Yuksel Avcıbası; Sahiner, Nurettin

    2013-01-01

    Polymeric hydrogels derived from SPM (3-sulfopropyl methacrylate) of micrometer size were used in the preparation of a composite-catalyst system for hydrogen generation from hydrolysis of NaBH 4 . In situ Co and Ni nanoparticles were prepared by chemical reduction of absorbed Co (II) and Ni (II) ions inside the hydrogel networks, and the whole composite was used as a catalyst system. The catalytic activity of the metal nanoparticles within the p(SPM) hydrogel matrix was better and faster using Co than with Ni. Additionally, other parameters that affect the hydrogen generation rate, such as temperature, metal reloading, the catalyst amounts as well as reusability, were also investigated. It was found that p(SPM)–Co micro hydrogels were even effective for hydrogen generation at 0 °C with a hydrogen generation rate of 966 (mL H 2 ) (min) −1 (g of Co) −1 . The activation energy, activation enthalpy, and activation entropy for the hydrolysis reaction of NaBH 4 with micro p(SPM)–Co catalyst system were calculated as 44.3 kJ/mol, 43.26 kJ/mol K, and −150.93 J/mol K, respectively. - Highlights: ► Microgel embedding metal catalyst for H 2 production. ► Advanced materials for green energy. ► Soft microgel reactors for H 2 production from NaBH 4 hydrolysis

  3. All-MOCVD-grown BH laser on P-InP substrates

    Science.gov (United States)

    Nishimura, Tadashi; Ishimura, E.; Nakajima, Yasuo; Tada, Hitoshi; Kimura, T.; Ohkura, Y.; Goto, Katsuhiko; Omura, Etsuji; Aiga, Masao

    1993-07-01

    A very low cw threshold current of 2.5 mA ( 25 degree(s)C) and 8.0 mA ( 80 degree(s)C) with high reliability has been realized in the all-MOCVD grown BH lasers on p-InP substrates. A strained MQW active layer of 1.3 micrometers wavelength and the precise carrier confinement buried structure by MOCVD is employed for the BH lasers. The excellent potential of long lifetime of the all-MOCVD grown laser has also been confirmed. After the high temperature and the high current (100 degree(s)C, 200 mA) aging test, no significant degradation is observed which is comparable with the well-established LPE grown lasers. The BH laser is also operating stably over 3700 hrs under the APC condition of 50 degree(s)C, 10 mW. Finally, an extremely uniform 10-element all-MOCVD grown LD array is demonstrated, which has the threshold current uniformity of 2.4 +/- 0.1 mA ( 25 degree(s)C) and 9.2 +/- 0.2 mA ( 80 degree(s)C). The growth mechanism in the MOCVD is also described.

  4. Trends and Opportunities of BIM-GIS Integration in the Architecture, Engineering and Construction Industry: A Review from a Spatio-Temporal Statistical Perspective

    Directory of Open Access Journals (Sweden)

    Yongze Song

    2017-12-01

    Full Text Available The integration of building information modelling (BIM and geographic information system (GIS in construction management is a new and fast developing trend in recent years, from research to industrial practice. BIM has advantages on rich geometric and semantic information through the building life cycle, while GIS is a broad field covering geovisualization-based decision making and geospatial modelling. However, most current studies of BIM-GIS integration focus on the integration techniques but lack theories and methods for further data analysis and mathematic modelling. This paper reviews the applications and discusses future trends of BIM-GIS integration in the architecture, engineering and construction (AEC industry based on the studies of 96 high-quality research articles from a spatio-temporal statistical perspective. The analysis of these applications helps reveal the evolution progress of BIM-GIS integration. Results show that the utilization of BIM-GIS integration in the AEC industry requires systematic theories beyond integration technologies and deep applications of mathematical modeling methods, including spatio-temporal statistical modeling in GIS and 4D/nD BIM simulation and management. Opportunities of BIM-GIS integration are outlined as three hypotheses in the AEC industry for future research on the in-depth integration of BIM and GIS. BIM-GIS integration hypotheses enable more comprehensive applications through the life cycle of AEC projects.

  5. Vorinostat and metformin sensitize EGFR-TKI resistant NSCLC cells via BIM-dependent apoptosis induction.

    Science.gov (United States)

    Chen, Hengyi; Wang, Yubo; Lin, Caiyu; Lu, Conghua; Han, Rui; Jiao, Lin; Li, Li; He, Yong

    2017-11-07

    There is a close relationship between low expression of BIM and resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Vorinostat is a pan-histone deacetylase inhibitor (HDACi) that augments BIM expression in various types of tumor cells, however, this effect is attenuated by the high expression of anti-apoptotic proteins in EGFR-TKI resistant non-small cell lung cancer (NSCLC) cells. Vorinostat in combination with metformin - a compound that can inhibit anti-apoptotic proteins expression, might cooperate to activate apoptotic signaling and overcome EGFR-TKI resistance. This study aimed to investigate the cooperative effect and evaluate possible molecular mechanisms. The results showed that vorinostat combined with gefitinib augmented BIM expression and increased the sensitivity of EGFR-TKI resistant NSCLC cells to gefitinib, adding metformin simultaneously could obviously inhibit the expression of anti-apoptotic proteins, and further increased expression levels of BIM and BAX, and as a result, further improved the sensitivity of gefitinib both on the NSCLC cells with intrinsic and acquired resistance to EGFR-TKI. In addition, autophagy induced by gefitinib and vorinostat could be significantly suppressed by metformin, which might also contribute to enhance apoptosis and improve sensitivity of gefitinib. These results suggested that the combination of vorinostat and metformin might represent a novel strategy to overcome EGFR-TKI resistance associated with BIM-dependent apoptosis in larger heterogeneous populations.

  6. Elaborate Mimetic Vocal Displays by Female Superb Lyrebirds

    Directory of Open Access Journals (Sweden)

    Anastasia H Dalziell

    2016-04-01

    Full Text Available Some of the most striking vocalizations in birds are made by males that incorporate vocal mimicry in their sexual displays. Mimetic vocalization in females is largely undescribed, but it is unclear whether this is because of a lack of selection for vocal mimicry in females, or whether the phenomenon has simply been overlooked. These issues are thrown into sharp relief in the superb lyrebird, Menura novaehollandiae, a basal oscine passerine with a lek-like mating system and female uniparental care. The spectacular mimetic song display produced by courting male lyrebirds is a textbook example of a sexually selected trait, but the vocalizations of female lyrebirds are largely unknown. Here, we provide the first analysis of the structure and context of the vocalizations of female lyrebirds. Female lyrebirds were completely silent during courtship; however, females regularly produced sophisticated vocal displays incorporating both lyrebird-specific vocalizations and imitations of sounds within their environment. The structure of female vocalizations varied significantly with context. While foraging, females mostly produced a complex lyrebird-specific song, whereas they gave lyrebird-specific alarm calls most often during nest defense. Within their vocal displays females also included a variety of mimetic vocalizations, including imitations of the calls of dangerous predators, and of alarm calls and song of harmless heterospecifics. Females gave more mimetic vocalizations during nest defense than while foraging, and the types of sounds they imitated varied between these contexts, suggesting that mimetic vocalizations have more than one function. These results are inconsistent with previous portrayals of vocalizations by female lyrebirds as rare, functionless by-products of sexual selection on males. Instead, our results support the hypotheses that complex female vocalizations play a role in nest defense and mediate female-female competition for

  7. Li7(BH)5(+): a new thermodynamically favored star-shaped molecule.

    Science.gov (United States)

    Torres-Vega, Juan J; Vásquez-Espinal, Alejandro; Beltran, Maria J; Ruiz, Lina; Islas, Rafael; Tiznado, William

    2015-07-15

    The potential energy surfaces (PESs) of Lin(BH)5(n-6) systems (where n = 5, 6, and 7) were explored using the gradient embedded genetic algorithm (GEGA) program, in order to find their global minima conformations. This search predicts that the lowest-energy isomers of Li6(BH)5 and Li7(BH)5(+) contain a (BH)5(6-) pentagonal fragment, which is isoelectronic and structurally analogous to the prototypical aromatic hydrocarbon anion C5H5(-). Li7(BH)5(+), along with Li7C5(+), Li7Si5(+) and Li7Ge5(+), joins a select group of clusters that adopt a seven-peak star-shape geometry, which is favored by aromaticity in the central five-membered ring, and by the preference of Li atoms for bridging positions. The theoretical analysis of chemical bonding, based on magnetic criteria, supports the notion that electronic delocalization is an important stabilization factor in all these star-shaped clusters.

  8. Assessment Schemes for Sustainability Design through BIM: Lessons Learnt

    Directory of Open Access Journals (Sweden)

    Kamaruzzaman Syahrul Nizam

    2016-01-01

    Full Text Available There is increasing demand on sustainability-led design to reduce negative impacts brought by construction development. The capability of Building Information Modeling (BIM to achieve sustainability is widely acknowledged. Various sustainability analysis and calculation can be performed at early stages to help the designers in decision making. However, the level of implementation is still not popular in the construction industry. Many of the industry players are still rely on traditional 2D method for designing and analysis. Hence, this study aims to demonstrate a proof concept of using BIM for sustainability design. The first phase of this study conducted a critical review of existing assessment schemes: BREEAM, LEED, SBTool, CASBEE, BEAM Plus, Green Star, Green Mark and GBI, to develop a set of main criteria to be considered for sustainability design. The findings revealed that fourteen criteria are considered, which are management, sustainable site, transport, indoor environmental quality, energy, waste, water, material, pollution, innovation, economics, social, culture and quality of services. It was found that most of the existing schemes emphasized on environmental aspect as compared to economics, social and culture except SBTool. The next phase of this study will conduct a case study to demonstrate sustainability design through BIM by using the criteria developed from the first phase.

  9. Internationalt samarbejde om BIM og digitale vejmodeller

    DEFF Research Database (Denmark)

    Rasmussen, Christian Fuglsang; Kjems, Erik

    2016-01-01

    Begrebet BIM (BygningsInformationsModellering) har for alvor ramt infrastruktursektoren, og der arbejdes i mange lande på at optimere håndteringen og udnyttelsen af data. Der er en generel enighed om effektiviseringspotentialet, samt at der er behov for internationale standarder. Følgende giver et...

  10. The First Simultaneous X-Ray/Radio Detection of the First Be/BH System MWC 656

    Energy Technology Data Exchange (ETDEWEB)

    Ribó, M.; Paredes, J. M.; Marcote, B.; Moldón, J.; Paredes-Fortuny, X. [Departament de Física Quàntica i Astrofísica, Institut de Ciències del Cosmos (ICCUB), Universitat de Barcelona, IEEC-UB, Martí i Franquès 1, E08028 Barcelona (Spain); Munar-Adrover, P. [INAF/IAPS-Roma, I-00133 Roma (Italy); Iwasawa, K. [ICREA, Institut de Ciències del Cosmos (ICCUB), Universitat de Barcelona, IEEC-UB, Martí i Franquès 1, E-08028 Barcelona (Spain); Casares, J. [Instituto de Astrofísica de Canarias, E-38200 La Laguna, Tenerife (Spain); Migliari, S. [European Space Astronomy Centre, Apartado/P.O. Box 78, Villanueva de la Canada, E-28691 Madrid (Spain)

    2017-02-01

    MWC 656 is the first known Be/black hole (BH) binary system. Be/BH binaries are important in the context of binary system evolution and sources of detectable gravitational waves because they are possible precursors of coalescing neutron star/BH binaries. X-ray observations conducted in 2013 revealed that MWC 656 is a quiescent high-mass X-ray binary (HMXB), opening the possibility to explore X-ray/radio correlations and the accretion/ejection coupling down to low luminosities for BH HMXBs. Here we report on a deep joint Chandra /VLA observation of MWC 656 (and contemporaneous optical data) conducted in 2015 July that has allowed us to unambiguously identify the X-ray counterpart of the source. The X-ray spectrum can be fitted with a power law with Γ ∼ 2, providing a flux of ≃4 × 10{sup −15} erg cm{sup −2} s{sup −1} in the 0.5–8 keV energy range and a luminosity of L {sub X} ≃ 3 × 10{sup 30} erg s{sup −1} at a 2.6 kpc distance. For a 5 M{sub ⊙} BH this translates into ≃5 × 10{sup −9} L {sub Edd}. These results imply that MWC 656 is about 7 times fainter in X-rays than it was two years before and reaches the faintest X-ray luminosities ever detected in stellar-mass BHs. The radio data provide a detection with a peak flux density of 3.5 ± 1.1 μ Jy beam{sup −1}. The obtained X-ray/radio luminosities for this quiescent BH HMXB are fully compatible with those of the X-ray/radio correlations derived from quiescent BH low-mass X-ray binaries. These results show that the accretion/ejection coupling in stellar-mass BHs is independent of the nature of the donor star.

  11. Reissner–Nordström Anti-de Sitter Black Holes in Mimetic F(R Gravity

    Directory of Open Access Journals (Sweden)

    V. K. Oikonomou

    2016-05-01

    Full Text Available In this paper, we study under which conditions the Reissner–Nordström anti-de Sitter black hole can be a solution of the vacuum mimetic F ( R gravity with Lagrange multiplier and mimetic scalar potential. As the author demonstrates, the resulting picture in the mimetic F ( R gravity case is a trivial extension of the standard F ( R approach, and in effect, the metric perturbations in the mimetic F ( R gravity case, for the Reissner–Nordström anti-de Sitter black hole metric, at the first order of the perturbed variables are the same at the leading order.

  12. SOCIAL BIM as driver for creativity and innovation?

    DEFF Research Database (Denmark)

    Buhl, Henrik; Kerosuo, Hannele; Andersen, Michael

    -created processes. Social BIM emphasizes—inter-organizational collaboration—the integrated project teams and collaborative ways of working. Despite welldocumented potential, digitized technologies and new methods of working have still been considered difficult to implement in the industry....

  13. Elementary dispersion analysis of some mimetic discretizations on triangular C-grids

    Energy Technology Data Exchange (ETDEWEB)

    Korn, P., E-mail: peter.korn@mpimet.mpg.de [Max Planck Institute for Meteorology, Hamburg (Germany); Danilov, S. [Alfred Wegener Institute for Polar and Marine Research, Bremerhaven (Germany); A.M. Obukhov Institute of Atmospheric Physics, Moscow (Russian Federation)

    2017-02-01

    Spurious modes supported by triangular C-grids limit their application for modeling large-scale atmospheric and oceanic flows. Their behavior can be modified within a mimetic approach that generalizes the scalar product underlying the triangular C-grid discretization. The mimetic approach provides a discrete continuity equation which operates on an averaged combination of normal edge velocities instead of normal edge velocities proper. An elementary analysis of the wave dispersion of the new discretization for Poincaré, Rossby and Kelvin waves shows that, although spurious Poincaré modes are preserved, their frequency tends to zero in the limit of small wavenumbers, which removes the divergence noise in this limit. However, the frequencies of spurious and physical modes become close on shorter scales indicating that spurious modes can be excited unless high-frequency short-scale motions are effectively filtered in numerical codes. We argue that filtering by viscous dissipation is more efficient in the mimetic approach than in the standard C-grid discretization. Lumping of mass matrices appearing with the velocity time derivative in the mimetic discretization only slightly reduces the accuracy of the wave dispersion and can be used in practice. Thus, the mimetic approach cures some difficulties of the traditional triangular C-grid discretization but may still need appropriately tuned viscosity to filter small scales and high frequencies in solutions of full primitive equations when these are excited by nonlinear dynamics.

  14. Towards an integration of GIS and BIM data : What are the geometric and topological issues?

    NARCIS (Netherlands)

    Arroyo Ohori, G.A.K.; Biljecki, F.; Diakite, A.A.; Krijnen, Thomas; Ledoux, H.; Stoter, J.E.; Kalantari, M.; Rajabifard, A.

    2017-01-01

    Geographic information and building information modelling both model buildings and infrastructure, but the way in which they are modelled is usually complimentary and BIM-GIS integration is widely considered as a way forward for both domains. For one, more detailed BIM data can feed more general

  15. Towards an integration of GIS and BIM data : what are the geometric and topological issues?

    NARCIS (Netherlands)

    Arroyo Ohori, K.; Biljecki, F.; Diakité, A.; Krijnen, T.F.; Ledoux, H.; Stoter, J.

    2017-01-01

    Geographic information and building information modelling both model buildings and infrastructure, but the way in which they are modelled is usually complimentary and BIM-GIS integration is widely considered as a way forward for both domains. For one, more detailed BIM data can feed more general GIS

  16. B.I.M. for representing historical building heritage.

    Directory of Open Access Journals (Sweden)

    Enrico Cicalò

    2016-06-01

    Full Text Available In this paper, it is discussed the application of B.I.M (Building Information Modelling techno- logies on the survey and on the representation of the decorations in the façades of late Liberty and Art Deco buildings, built in Sardinian cities. The decorative languages analysed spread in one of the most marginal regions with some delay, by the insertion of serial decorations placed both on existing and new buildings. The study, still in pro- gress, discusses how the B.I.M. can be used in the analysis of the decorated elements that are se- rially inserted in the buildings, particularly in the perspective of the integration with GIS systems, which can allows the localisation of the elements into the urban landscape, also by using procedu- ral semiautomatic modelling systems of façades. 

  17. HT_BIM: La modellazione parametrica per l’analisi del rischio nei centri storici

    Directory of Open Access Journals (Sweden)

    Assunta Pelliccio

    2017-06-01

    Full Text Available I centri storici minori sono dei monumenti d’ambiente da salvaguardare perché vulnerabili sia dal punto di vista sismico che ambientale. La gestione di queste realtà urbane è particolarmente complessa a causa dell’eterogeneità dei dati relativi alle singole unità edilizie, aggregati strutturali e intero ambito urbano. Negli ultimi anni i sistemi parametrici BIM hanno dato un enorme contributo alla progettazione, pianificazione, costruzione etc. di nuovi edifici e anche alla gestione del patrimonio culturale. L’obiettivo di questo lavoro è lo sviluppo del sistema Historical Town Building Information Modeling (HT_BIM, ovvero di un sistema BIM specifico per gli aggregati di edifici storici che, sulla base del rilievo, consente di individuare vulnerabilità legate sia ad aspetti strutturali sia a fenomeni di degrado da vento e soleggiamento.

  18. TOWARDS AN INTEGRATION OF GIS AND BIM DATA: WHAT ARE THE GEOMETRIC AND TOPOLOGICAL ISSUES?

    Directory of Open Access Journals (Sweden)

    K. Arroyo Ohori

    2017-10-01

    Full Text Available Geographic information and building information modelling both model buildings and infrastructure, but the way in which they are modelled is usually complimentary and BIM-GIS integration is widely considered as a way forward for both domains. For one, more detailed BIM data can feed more general GIS data and GIS data can provide the context that is necessary to BIM data. While previous studies have focused on the theoretical aspects of such an integration at a schema level, in this paper we focus on explaining the geometric and topological issues we have found while trying to develop software to realise such an integration in practice and at a data level. In our preliminary results, which are presented here, we have found that many issues for such an integration remain: handling the geometric and topological problems in BIM models, dealing with bad georeferencing and figuring out the best way to convert data between IFC and CityGML are all open issues.

  19. Towards AN Integration of GIS and Bim Data: what are the Geometric and Topological Issues?

    Science.gov (United States)

    Arroyo Ohori, K.; Biljecki, F.; Diakité, A.; Krijnen, T.; Ledoux, H.; Stoter, J.

    2017-10-01

    Geographic information and building information modelling both model buildings and infrastructure, but the way in which they are modelled is usually complimentary and BIM-GIS integration is widely considered as a way forward for both domains. For one, more detailed BIM data can feed more general GIS data and GIS data can provide the context that is necessary to BIM data. While previous studies have focused on the theoretical aspects of such an integration at a schema level, in this paper we focus on explaining the geometric and topological issues we have found while trying to develop software to realise such an integration in practice and at a data level. In our preliminary results, which are presented here, we have found that many issues for such an integration remain: handling the geometric and topological problems in BIM models, dealing with bad georeferencing and figuring out the best way to convert data between IFC and CityGML are all open issues.

  20. High Prevalence of the BIM Deletion Polymorphism in Young Female Breast Cancer in an East Asian Country.

    Directory of Open Access Journals (Sweden)

    Ching-Hung Lin

    Full Text Available A rapid surge of female breast cancer has been observed in young women in several East Asian countries. The BIM deletion polymorphism, which confers cell resistance to apoptosis, was recently found exclusively in East Asian people with prevalence rate of 12%. We aimed to evaluate the possible role of this genetic alteration in carcinogenesis of breast cancer in East Asians.Female healthy volunteers (n = 307, patients in one consecutive stage I-III breast cancer cohort (n = 692 and one metastatic breast cancer cohort (n = 189 were evaluated. BIM wild-type and deletion alleles were separately genotyped in genomic DNAs.Both cancer cohorts consistently showed inverse associations between the BIM deletion polymorphism and patient age (≤35 y vs. 36-50 y vs. >50 y: 29% vs. 22% vs. 15%, P = 0.006 in the consecutive cohort, and 40% vs. 23% vs. 13%, P = 0.023 in the metastatic cohort. In healthy volunteers, the frequencies of the BIM deletion polymorphism were similar (13%-14% in all age groups. Further analyses indicated that the BIM deletion polymorphism was not associated with specific clinicopathologic features, but it was associated with poor overall survival (adjusted hazard ratio 1.71 in the consecutive cohort.BIM deletion polymorphism may be involved in the tumorigenesis of the early-onset breast cancer among East Asians.

  1. Efficacy and safety of canagliflozin when used in conjunction with incretin-mimetic therapy in patients with type 2 diabetes

    NARCIS (Netherlands)

    Fulcher, G.; Matthews, D. R.; Perkovic, V.; de Zeeuw, D.; Mahaffey, K. W.; Mathieu, C.; Woo, V.; Wysham, C.; Capuano, G.; Desai, M.; Shaw, W.; Vercruysse, F.; Meininger, G.; Neal, B.

    Aims: To assess the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes enrolled in the CANagliflozin cardioVascular Assessment Study (CANVAS) who were on an incretin mimetic [dipeptidyl peptidase-4 (DPP-4) inhibitor or

  2. A review of underwater bio-mimetic propulsion: cruise and fast-start

    Science.gov (United States)

    Chao, Li-Ming; Cao, Yong-Hui; Pan, Guang

    2017-08-01

    This paper reviews recent developments in the understanding of underwater bio-mimetic propulsion. Two impressive models of underwater propulsion are considered: cruise and fast-start. First, we introduce the progression of bio-mimetic propulsion, especially underwater propulsion, where some primary conceptions are touched upon. Second, the understanding of flapping foils, considered as one of the most efficient cruise styles of aquatic animals, is introduced, where the effect of kinematics and the shape and flexibility of foils on generating thrust are elucidated respectively. Fast-start propulsion is always exhibited when predator behaviour occurs, and we provide an explicit introduction of corresponding zoological experiments and numerical simulations. We also provide some predictions about underwater bio-mimetic propulsion.

  3. A review of underwater bio-mimetic propulsion: cruise and fast-start

    Energy Technology Data Exchange (ETDEWEB)

    Chao, Li-Ming; Cao, Yong-Hui; Pan, Guang, E-mail: PanGuang_010@163.com [School of Marine Science and Technology, Northwestern Polytechnical University, Xian 710072 (China)

    2017-08-15

    This paper reviews recent developments in the understanding of underwater bio-mimetic propulsion. Two impressive models of underwater propulsion are considered: cruise and fast-start. First, we introduce the progression of bio-mimetic propulsion, especially underwater propulsion, where some primary conceptions are touched upon. Second, the understanding of flapping foils, considered as one of the most efficient cruise styles of aquatic animals, is introduced, where the effect of kinematics and the shape and flexibility of foils on generating thrust are elucidated respectively. Fast-start propulsion is always exhibited when predator behaviour occurs, and we provide an explicit introduction of corresponding zoological experiments and numerical simulations. We also provide some predictions about underwater bio-mimetic propulsion. (review)

  4. Building Envelope Thermal Performance Assessment Using Visual Programming and BIM, based on ETTV requirement of Green Mark and GreenRE

    Directory of Open Access Journals (Sweden)

    Taki Eddine Seghier

    2017-09-01

    Full Text Available Accomplishment of green building design requirements and the achievement of the targeted credit points under a specific green rating system are known to be a task that is very challenging. Building Information Modeling (BIM design process and tools have already made considerable advancements in green building design and performance analysis. However, Green building design process is still lack of tools and workflows that can provide real-time feedback of building sustainability and rating during the design stage. In this paper, a new workflow of green building design assessment and rating is proposed based on the integration of Visual Programing Language (VPL and BIM. Thus, the aim of this study is to develop a BIM-VPL based tool for building envelope design and assessment support. The focus performance metric in this research is building Envelope Thermal Transfer Value (ETTV which is an Energy Efficiency (EE prerequisite requirement (up to 15 credits in both Green Mark and GreenRE rating systems. The development of the tool begins first by creating a generic integration framework between BIM-VPL functionalities and ETTV requirements. Then, data is extracted from the BIM 3D model and managed using Revit, Excel and Dynamo for visual scripting. A sample project consisting of a hypothetical residential building is run and its envelope ETTV performance and rating score are obtained for the validation of the tool. This tool will support project team in building envelope design and assessment by allowing them to select the most appropriate façade configuration according to its performance efficiency and the green rating. Furthermore, this tool serves as proof of concept that building sustainability rating and compliance checking can be automatically processed through customized workflows developed based on BIM and VPL technologies.

  5. Synthesis, molecular docking and biological evaluation as HDAC inhibitors of cyclopeptide mimetics by a tandem three-component reaction and intramolecular [3+2] cycloaddition.

    Science.gov (United States)

    Pirali, Tracey; Faccio, Valeria; Mossetti, Riccardo; Grolla, Ambra A; Di Micco, Simone; Bifulco, Giuseppe; Genazzani, Armando A; Tron, Gian Cesare

    2010-02-01

    Novel macrocyclic peptide mimetics have been synthesized by exploiting a three-component reaction and an azide-alkyne [3 + 2] cycloaddition. The prepared compounds were screened as HDAC inhibitors allowing us to identify a new compound with promising biological activity. In order to rationalize the biological results, computational studies have also been performed.

  6. Smac Mimetic Bypasses Apoptosis Resistance in FADD- or Caspase-8-Deficient Cells by Priming for Tumor Necrosis Factor α-Induced Necroptosis

    Directory of Open Access Journals (Sweden)

    Bram Laukens

    2011-10-01

    Full Text Available Searching for new strategies to bypass apoptosis resistance, we investigated the potential of the Smac mimetic BV6 in Jurkat leukemia cells deficient in key molecules of the death receptor pathway. Here, we demonstrate for the first time that Smac mimetic primes apoptosis-resistant, FADD- or caspase-8-deficient leukemia cells for TNFα-induced necroptosis in a synergistic manner. In contrast to TNFα, Smac mimetic significantly enhances CD95-induced apoptosis in wild-type but not in FADD-deficient cells. Interestingly, Smac mimetic- and TNFα-mediated cell death occurs without characteristic features of apoptosis (i.e., caspase activation, DNA fragmentation in FADD-deficient cells. By comparison, Smac mimetic and TNFα trigger activation of caspase-8, -9, and -3 and DNA fragmentation in wild-type cells. Consistently, the caspase inhibitor zVAD.fmk fails to block Smac mimetic- and TNFα-triggered cell death in FADD- or caspase-8-deficient cells, while it confers protection in wild-type cells. By comparison, necrostatin-1, an RIP1 kinase inhibitor, abolishes Smac mimetic- and TNFα-induced cell death in FADD- or caspase-8-deficient. Thus, Smac mimetic enhances TNFα-induced cell death in leukemia cells via two distinct pathways in a context-dependent manner: it primes apoptosis-resistant cells lacking FADD or caspase-8 to TNFα-induced, RIP1-dependent and caspase-independent necroptosis, whereas it sensitizes apoptosis-proficient cells to TNFα-mediated, caspase-dependent apoptosis. These findings have important implications for the therapeutic exploitation of necroptosis as an alternative cell death program to overcome apoptosis resistance.

  7. Aplicación de sistemas BIM y fotogrametría en implantación de modelos de franquicias

    OpenAIRE

    Loredo Conde, Antonio José

    2017-01-01

    BIM para la ingeniería y la construcción es más que un dibujo en 3D, más que una maqueta virtual. Todavía es habitual proyectar bajo protocolo CAD, con sistemas de toma de datos pensados para este sistema, soluciones gráficas finales 2D y no vinculadas a datos auxiliares o metadatos. Nuestro objetivo es plasmar con un estudio multidisciplinar las ventajas en gestión de obra propiciados por el uso de sistemas BIM, y demostrar que arroja ventajas y mejoras, en especial en un modelo de trabajo d...

  8. Photochemistry of U(BH/sub 4/)/sub 4/ and U(BD/sub 4/)/sub 4/

    Energy Technology Data Exchange (ETDEWEB)

    Paine, R T; Schonberg, P R; Light, R W [New Mexico Univ., Albuquerque (USA). Dept. of Chemistry; Danen, W C; Freund, S M

    1979-01-01

    U(BH/sub 4/)/sub 4/ and U(BD/sub 4/)/sub 4/ are observed to undergo complex degradation reactions promoted by broadband UV radiation. The primary products of these reactions appear to be U(BH/sub 4/)/sub 3/, B/sub 2/H/sub 6/, H/sub 2/, U(BD/sub 4/)/sub 3/, B/sub 2/D/sub 6/ and D/sub 2/. Further, U(BD/sub 4/)/sub 4/ undergoes a related decomposition reaction under the influence of CO/sub 2/ laser irradiation at 924.97 cm/sup -1/.

  9. Sustainable Design Approach: A case study of BIM use

    Directory of Open Access Journals (Sweden)

    Abdelhameed Wael

    2017-01-01

    The paper describes the methodology of this design approach through BIM strategies adopted in design creation. Case studies of architectural designs are used to highlight the details and benefits of this proposed approach.

  10. Reproductive isolation related to mimetic divergence in the poison frog Ranitomeya imitator

    DEFF Research Database (Denmark)

    Twomey, Evan; Vestergaard, Jacob Schack; Summers, Kyle

    2014-01-01

    study the Peruvian poison frog Ranitomeya imitator, a species that has undergone a mimetic radiation into four distinct morphs. Using a combination of colour–pattern analysis, landscape genetics and mate-choice experiments, we show that a mimetic shift in R. imitator is associated with a narrow...

  11. A mucosa-mimetic material for the mucoadhesion testing of thermogelling semi-solids.

    Science.gov (United States)

    da Silva, Jéssica Bassi; Khutoryanskiy, Vitaliy V; Bruschi, Marcos L; Cook, Michael T

    2017-08-07

    Mucosa-mimetic materials are synthetic substrates which aim to replace animal tissue in mucoadhesion experiments. One potential mucosa-mimetic material is a hydrogel comprised of N-acryloyl-d-glucosamine and 2-hydroxyethylmethacrylate, which has been investigated as a surrogate for animal mucosae in the mucoadhesion testing of tablets and solution formulations. This study aims to investigate the efficacy of this mucosa-mimetic material in the testing of thermogelling semi-solid formulations, which transition from solution to gel upon warming. Two methods for assessing mucoadhesion have been used; tensile testing and a flow-through system, which allow for investigation under dramatically different conditions. It was found that the mucosa-mimetic material was a good surrogate for buccal mucosa using both testing methods. This material may be used to replace animal tissue in these experiments, potentially reducing the number of laboratory animals used in studies of this type. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. René Girard and the Mimetic Nature of Eating Disorders.

    Science.gov (United States)

    Strand, Mattias

    2018-03-07

    French historian and literary critic René Girard (1923-2015), most widely known for the concepts of mimetic desire and scapegoating, also engaged in the discussion of the surge of eating disorders in his 1996 essay Eating Disorders and Mimetic Desire. This article explores Girard's ideas on the mimetic nature and origin of eating disorders from a clinical psychiatric perspective and contextualizes them within the field of eating disorders research as well as in relation to broader psychological, sociological and anthropological models of social comparison and non-consumption. Three main themes in Girard's thinking on the topic of eating disorders are identified and explored: the 'end of prohibitions' as a driving force in the emergence of eating disorders, eating disorders as a phenomenon specific to modernity, and the significance of 'conspicuous non-consumption' in the emergence of eating disorders.

  13. Studies on the ANN implementation in the macro BIM cost analyzes

    Directory of Open Access Journals (Sweden)

    Michał Juszczyk

    2017-06-01

    Full Text Available The paper presents an approach which combines the concept of macro-level BIM-based cost analyzes and application of artificial intelligence tools – namely artificial neural networks. Discussion and foundations of the proposed approach are introduced in the paper to clarify the problem’s core. An exemplary case study reports the results of initial studies on the application of neural networks for the purposes of BIM-based cost analysis of a buildings’ floor structural frame. The results obtained justify the proposal of application of neural networks as a supportive mathematical tool in the problem presented in the paper.

  14. Investigation of the role of NaBH4 in the chemical synthesis of gold nanorods

    International Nuclear Information System (INIS)

    Samal, Akshaya K.; Sreeprasad, Theruvakkattil S.; Pradeep, Thalappil

    2010-01-01

    An improvement in the previously reported seed-mediated chemical synthesis of gold nanorods (GNRs) is reported. Monodisperse GNRs have been synthesized in a one-step protocol. The addition of controlled quantity of sodium borohydride (NaBH 4 ) directly into the growth solution produced uniform GNRs, formed by in situ nucleation and growth. In order to arrive at the conclusion, we studied the formation of GNRs with various seeds, of metals of widely differing crystal structures, and there were no variations in the properties of the GNRs formed. The role of NaBH 4 in the growth of GNR, which has not been covered in previous reports, is discussed in detail. The dependence of longitudinal plasmon peak on the concentration of NaBH 4 is compared with the dependence of residual concentration of NaBH 4 in the seed solution, which is added to the growth solution in seed-mediated synthesis. The study shows that NaBH 4 plays an important role in the formation of GNRs. This proposed protocol offers a number of advantages: one-step preparation of GNRs, significant reduction in the preparation time to 10 min, high monodispersity of GNRs, and tailorability of the aspect ratio depending on NaBH 4 concentration. It is suggested that NaBH 4 added to the growth solution leads to in situ formation of the seed particles of the size of 3-5 nm which enables the growth of GNRs. The growth of GNRs suggested here is likely to have an impact on the preparation of other anisotropic structures. Our single-pot methodology makes the procedure directly adaptable for commercial-scale production of GNRs and for their synthesis even in undergraduate laboratories.

  15. Oestrogene mimetic isoflavones’ pharmacokinetics and pharmacodynamics

    Directory of Open Access Journals (Sweden)

    Anca Dragomirescu,

    2008-12-01

    Full Text Available Genisteine is the most abundant and the most studied estrogen-mimetic izoflavone. It's chemical formula is 4',5,7 – trihidroxyisoflavone. It has also estrogen-modulated properties by its binding ability to the beta type estrogen receptor. Genisteine presents the following farmacodinamic effects: antiaterogen effect, prevention of estrogen-dependent cancers, especially breast cancer, prevention of skin aging body, osteoprogen effect, prevention of osteoporosis at the menopauses women. Despite all these real benefits, there are also many adverse effects, registered both in humans and animals. Thus, the sheep feeding with some Fabaceae species, containing estrogen-mimetic isoflavones were stopped their reproductive function(isoflavones acted as an oral contraceptive. In humans, phytoestroges influence is still under evaluation, being suspected effects such as cerebral involution - via abusive apoptosis - or disturbance in hormonal status, in male children. All these are added to already known allergies, caused by soy proteins.

  16. Millennium bim managing growing demand

    OpenAIRE

    Lopes, Francisca Barbosa Malpique de Paiva

    2014-01-01

    Millennium bim, the Mozambican operation of Millennium bcp group, was the Company selected to serve as background for the development of a teaching case in Marketing. This case is followed by a teaching note, and is intended to be used as a pedagogical tool in undergraduate and/or graduate programs. Even though Mozambique is still characterized by high financial exclusion, the number of people entering within the banking industry has been growing at a fast pace. Actually, the demand for fi...

  17. BIM, realidad aumentada y técnicas holográficas aplicadas a la construcción = BIM, increased reality and holographic techniques applied to construction

    Directory of Open Access Journals (Sweden)

    Jaime Santamarta Martínez

    2018-05-01

    Full Text Available La metodología BIM (Building Information Modelling, ampliamente implantada en el sector de la edificación y de la arquitectura, ha transformado la manera de desarrollar tanto los proyectos como las obras de construcción. Si bien la esencia de esta metodología se basa en la generación de un modelo tridimensional, la visualización de éste a través de dispositivos bidimensionales hace que la experiencia e interacción con el modelo no sea plena. Es por ello que la aparición en el mercado de nuevas tecnologías como la realidad virtual y la realidad aumentada, abren un amplio abanico de posibilidades ligadas al sector de la construcción. En este sentido, en Acciona Ingeniería se ha desarrollado un proyecto piloto en colaboración con Trimble y Microsoft donde a partir de un modelo BIM se ha creado una realidad aumentada basada en hologramas, que permitan recrear una simulación aplicada a la construcción Abstract The BIM (Building Information Modeling methodology, widely implemented in the building and architecture sector, has transformed the way to develop both projects and construction works. Although the essence of this methodology is based on the generation of a three-dimensional model, the visualization of it through two-dimensional devices means that the experience and interaction with the model is not complete. That is why the appearance in the market of new technologies such as virtual reality and augmented reality, open a wide range of possibilities linked to the construction sector. In this sense, Acciona Engineering has developed a pilot project in collaboration with Trimble and Microsoft where, based on a BIM model, an augmented reality based on holograms has been created, allowing to recreate a simulation applied to construction

  18. Synthesis of Zn(BH{sub 4}){sub 2} and Gas Absorption and Release Characteristics of Zn(BH{sub 4}){sub 2}, Ni, or Ti-Added MgH{sub 2}–Based Alloys

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Young Jun; Lee, Seong Ho; Kwon, Sung Nam; Park Il Woo; Song, Myoung Youp [Chonbuk National University, Jeonju (Korea, Republic of)

    2015-07-15

    A sample [named Zn(BH{sub 4}){sub 2}(+NaCl)] was synthesized by milling ZnCl{sub 2} and NaBH{sub 4} at 400 rpm under argon gas for 2 h. And Zn(BH{sub 4}){sub 2}(+NaCl)+MgH{sub 2} sample was prepared by milling MgH{sub 2} in a planetary ball mill and mixing with the Zn(BH{sub 4}){sub 2}(+NaCl) synthesized by milling for 4 h in a mortar with a pestle. Then the gas-release characteristics of the two samples were investrigated. Analyses of XRD patterns and FT-IR spectra, as well as TGA, DTA, and SEM observations, were also performed. After heating the samples to 400 ℃, the weight losses of Zn(BH{sub 4}){sub 2}(+NaCl) and Zn(BH{sub 4}){sub 2}(+NaCl)+MgH{sub 2} were 11.2 and 8.2 wt%, respectively, with respect to the sample weight. The DTA results for the two samples showed a decomposition peak for Zn(BH{sub 4}){sub 2} at about 61 ℃. The DTA result of Zn(BH{sub 4}){sub 2}(+NaCl) + MgH{sub 2} showed a decomposition peak for MgH{sub 2} at about 374 ℃. A sample of Zn(BH{sub 4}){sub 2}(+NaCl)+MgH{sub 2} to which Ni, and Ti were added, with a composition of 90 wt% MgH{sub 2}-5 wt% Zn(BH{sub 4}){sub 2}(+NaCl)-2.5 wt% Ni-2.5 wt% Ti, in which a large amount of MgH2 is contained in order to make a large quantity of hydrogen be absorbed and released reversibly, was also prepared. The experimental results showed that addition of Zn(BH{sub 4}){sub 2}(+NaCl), Ni, or Ti increased the dehydriding rate of MgH{sub 2}, while decreased its initial hydriding rate.

  19. BH5047 type depth sand moisture-meter of high sensitivity

    International Nuclear Information System (INIS)

    Ji Changsong; Xie Liangnian; Zhang Shulan; Zhang Shuheng

    2000-01-01

    A new depth neutron moisture meter BH5047 has been developed. BH5047 neutron moisture meter is characterised by it is high sensitivity and used for sand water content measurement at concrete mixer. Calibration function is obtained by the Method of Least Squares. Linear correlation efficiency is as good as 0.9977

  20. Pokemon Silencing Leads to Bim-Mediated Anoikis of Human Hepatoma Cell QGY7703

    OpenAIRE

    Liu, Kun; Liu, Feng; Zhang, Nannan; Liu, Shiying; Jiang, Yuyang

    2012-01-01

    Pokemon is an important proto-oncogene that plays a critical role in cellular oncogenic transformation and tumorigenesis. Anoikis, which is regulated by Bim-mediated apoptosis, is critical to cancer cell invasion and metastasis. We investigated the role of Pokemon in anoikis, and our results show that Pokemon renders liver cells resistant to anoikis via suppression of Bim transcription. We knocked-down Pokemon in human hepatoma cells QGY7703 with small interfering RNAs (siRNA). Knockdown of P...

  1. Effect of Mg, Ca, and Zn on stability of LiBH{sub 4} through computational thermodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sung Hoon; Manga, Venkateswara Rao; Liu, Zi-Kui [Department of Materials Science and Engineering, The Pennsylvania State University, University Park, PA 16802 (United States)

    2010-07-15

    The effect of divalent metal-dopants, Mg, Ca, and Zn, on the stability of LiBH{sub 4} is studied by using the first-principles calculations and CALPHAD (CALculation of PHAse Diagram) modeling. The ground states of Mg{sub 1/2}BH{sub 4}, Ca{sub 1/2}BH{sub 4}, and Zn{sub 1/2}BH{sub 4} are shown to be I anti 4m2, F2dd, and I anti 4m2, respectively, through first-principles calculations. Positive enthalpy of mixing between Li and the alloying element is predicted, indicating unfavorable solubility of alloying elements in LiBH{sub 4} and thus offering possibility to decrease the stability of LiBH{sub 4}. The ionic sublattice model of (Li{sup +}, M{sup 2+}, Va){sub 1}(BH{sub 4}{sup -}){sub 1} is adopted for the metal substituted LiBH{sub 4} phase. It is observed that the addition of Mg or Zn has limited effect as the decomposition temperature is between those of LiBH{sub 4} and M{sub 1/2}BH{sub 4} for Mg and Zn substitutions. LiBH{sub 4} is destabilized with magnesium borides or LiZn{sub 4} formation but its decomposition temperature is higher than that of M{sub 1/2}BH{sub 4}. On the other hand, the addition of Ca significantly reduces the H{sub 2} releasing temperature due to the formation of highly stable CaB{sub 6}. (author)

  2. Modeling seismic wave propagation using staggered-grid mimetic finite differences

    Directory of Open Access Journals (Sweden)

    Freysimar Solano-Feo

    2017-04-01

    Full Text Available Mimetic finite difference (MFD approximations of continuous gradient and divergence operators satisfy a discrete version of the Gauss-Divergence theorem on staggered grids. On the mimetic approximation of this integral conservation principle, an unique boundary flux operator is introduced that also intervenes on the discretization of a given boundary value problem (BVP. In this work, we present a second-order MFD scheme for seismic wave propagation on staggered grids that discretized free surface and absorbing boundary conditions (ABC with same accuracy order. This scheme is time explicit after coupling a central three-level finite difference (FD stencil for numerical integration. Here, we briefly discuss the convergence properties of this scheme and show its higher accuracy on a challenging test when compared to a traditional FD method. Preliminary applications to 2-D seismic scenarios are also presented and show the potential of the mimetic finite difference method.

  3. Parametric Modelling of As-Built Beam Framed Structure in Bim Environment

    Science.gov (United States)

    Yang, X.; Koehl, M.; Grussenmeyer, P.

    2017-02-01

    A complete documentation and conservation of a historic timber roof requires the integration of geometry modelling, attributional and dynamic information management and results of structural analysis. Recently developed as-built Building Information Modelling (BIM) technique has the potential to provide a uniform platform, which provides possibility to integrate the traditional geometry modelling, parametric elements management and structural analysis together. The main objective of the project presented in this paper is to develop a parametric modelling tool for a timber roof structure whose elements are leaning and crossing beam frame. Since Autodesk Revit, as the typical BIM software, provides the platform for parametric modelling and information management, an API plugin, able to automatically create the parametric beam elements and link them together with strict relationship, was developed. The plugin under development is introduced in the paper, which can obtain the parametric beam model via Autodesk Revit API from total station points and terrestrial laser scanning data. The results show the potential of automatizing the parametric modelling by interactive API development in BIM environment. It also integrates the separate data processing and different platforms into the uniform Revit software.

  4. Building Information Modeling (BIM) Primer. Report 1: Facility Life-Cycle Process and Technology Innovation

    Science.gov (United States)

    2012-08-01

    design. Negatives of the software, Melendez said, was that it was too time consuming and demanding at the initial design phase. Also, her learning...manage the building using BIM as part of the WO process. ii. Today it is preferred that installations prepare for delivery of BIM and have inplace...offices, a theater, exhibition hall, and cafe Project Team Urban Design Group, Hathaway Dinwiddie, TBD Consultants, IBE Consulting Engineers, KPFF

  5. BIM Methodology Approach to Infrastructure Design: Case Study of Paniga Tunnel

    Science.gov (United States)

    Osello, Anna; Rapetti, Niccolò; Semeraro, Francesco

    2017-10-01

    Nowadays, the implementation of Building Information Modelling (BIM) in civil design represent a new challenge for the AECO (Architecture, Engineering, Construction, Owner and Operator) world, which will involve the interest of many researchers in the next years. It is due to the incentives of Public Administration and European Directives that aim to improve the efficiency and to enhance a better management of the complexity of infrastructure projects. For these reasons, the goal of this research is to propose a methodology for the use of BIM in a tunnel project, analysing the definition of a correct level of detail (LOD) and the possibility to share information via interoperability for FEM analysis.

  6. Healthy imperfect dark matter from effective theory of mimetic cosmological perturbations

    International Nuclear Information System (INIS)

    Hirano, Shin'ichi; Nishi, Sakine; Kobayashi, Tsutomu

    2017-01-01

    We study the stability of a recently proposed model of scalar-field matter called mimetic dark matter or imperfect dark matter. It has been known that mimetic matter with higher derivative terms suffers from gradient instabilities in scalar perturbations. To seek for an instability-free extension of imperfect dark matter, we develop an effective theory of cosmological perturbations subject to the constraint on the scalar field's kinetic term. This is done by using the unifying framework of general scalar-tensor theories based on the ADM formalism. We demonstrate that it is indeed possible to construct a model of imperfect dark matter which is free from ghost and gradient instabilities. As a side remark, we also show that mimetic F (R) theory is plagued with the Ostrogradsky instability.

  7. Healthy imperfect dark matter from effective theory of mimetic cosmological perturbations

    Energy Technology Data Exchange (ETDEWEB)

    Hirano, Shin' ichi; Nishi, Sakine; Kobayashi, Tsutomu, E-mail: s.hirano@rikkyo.ac.jp, E-mail: sakine@rikkyo.ac.jp, E-mail: tsutomu@rikkyo.ac.jp [Department of Physics, Rikkyo University, Toshima, Tokyo 171-8501 (Japan)

    2017-07-01

    We study the stability of a recently proposed model of scalar-field matter called mimetic dark matter or imperfect dark matter. It has been known that mimetic matter with higher derivative terms suffers from gradient instabilities in scalar perturbations. To seek for an instability-free extension of imperfect dark matter, we develop an effective theory of cosmological perturbations subject to the constraint on the scalar field's kinetic term. This is done by using the unifying framework of general scalar-tensor theories based on the ADM formalism. We demonstrate that it is indeed possible to construct a model of imperfect dark matter which is free from ghost and gradient instabilities. As a side remark, we also show that mimetic F (R) theory is plagued with the Ostrogradsky instability.

  8. The deprotonation energies of BH5 and AlH5: Comparisons to GaH5

    International Nuclear Information System (INIS)

    Speakman, Lucas D.; Turney, Justin M.; Schaefer, Henry F.

    2007-01-01

    Hypercoordinate boron is most unusual, leading to considerable theoretical and experimental research on the parent BH 5 molecule. The deprotonation energies of BH 5 and the related molecules AlH 5 and GaH 5 have been of particular interest. Here the energy differences for XH 5 ->XH 4 - +H(X=BandAl) are computed to be 332.4 and 326.3kcalmol -1 , respectively, with an aug-cc-pVQZ basis set at the CCSD(T) level of theory. Vibrational frequencies for BH 4 - and AlH 4 - are also reported as 1098, 1210, 2263, and 2284cm -1 and 760, 779, 1658, and 1745cm -1 , respectively, again at the CCSD(T) aug-cc-pVQZ level of theory. Comparisons with the valence isoelectronic GaH 5 molecule are made

  9. Antifungal Potential of Host Defense Peptide Mimetics in a Mouse Model of Disseminated Candidiasis

    Directory of Open Access Journals (Sweden)

    Mobaswar Hossain Chowdhury

    2018-02-01

    Full Text Available Invasive candidiasis caused by Candida albicans and non-albicans Candida (NAC present a serious disease threat. Although the echinocandins are recommended as the first line of antifungal drug class, resistance to these agents is beginning to emerge, demonstrating the need for new antifungal agents. Host defense peptides (HDP exhibit potent antifungal activity, but as drugs they are difficult to manufacture efficiently, and they are often inactivated by serum proteins. HDP mimetics are low molecular weight non-peptide compounds that can alleviate these problems and were shown to be membrane-active against C. albicans and NAC. Here, we expand upon our previous works to describe the in vitro and in vivo activity of 11 new HDP mimetics that are active against C. albicans and NAC that are both sensitive and resistant to standard antifungal drugs. These compounds exhibit minimum inhibitory/fungicidal concentration (MIC/MFC in the µg/mL range in the presence of serum and are inhibited by divalent cations. Rapid propidium iodide influx into the yeast cells following in vitro exposure suggested that these HDP mimetics were also membrane active. The lead compounds were able to kill C. albicans in an invasive candidiasis CD-1 mouse model with some mimetic candidates decreasing kidney burden by 3–4 logs after 24 h in a dose-dependent manner. The data encouraged further development of this new anti-fungal drug class for invasive candidiasis.

  10. DEVELOPMENT OF EDIFICATION’S PROJECT – A COMPARATIVE STUDY ODF CAD AND BIM PLATAFORMS

    Directory of Open Access Journals (Sweden)

    Lúcio Campos Neto

    2017-12-01

    Full Text Available Several technologies are used to simplify the process and creation of design, highlighting the CAD and the BIM. At CAD, the elements are represented by lines, while at BIM the objects are ruled by attributes and parametric information, allowing the virtual simulation of the edification. Although the BIM is a novelty in design’s process, the largest part of professionals still makes use of CAD. In front of these facts, the objective of this research is to evaluate the difference of using each plataform. The research was guided by the hypothesis that BIM concept presents pros and cons to the process of projects development once it is compared to CAD software. For this, one same project has been developed in both plataforms in order to demonstrate which plataform has the best characteristics at the development process and final result, indicating its difficulties, facilies, esthetics, reading, handling, interface and tools. With the proposed methodology execution, it has been noticed that each plataform possesses positive and negative characteristics, influencing each professional’s choice for a software. This choice will vary according to the situation, to what plataform the professional gets better used to and according to the investment potential.

  11. Advantages of fibre lasers in 3D metal cutting and welding applications supported by a 'beam in motion (BIM)' beam delivery system

    Science.gov (United States)

    Scheller, Torsten; Bastick, André; Griebel, Martin

    2012-03-01

    Modern laser technology is continuously opening up new fields of applications. Driven by the development of increasingly efficient laser sources, the new technology is successfully entering classical applications such as 3D cutting and welding of metals. Especially in light weight applications in the automotive industry laser manufacturing is key. Only by this technology the reduction of welding widths could be realised as well as the efficient machining of aluminium and the abrasion free machining of hardened steel. The paper compares the operation of different laser types in metal machining regarding wavelength, laser power, laser brilliance, process speed and welding depth to give an estimation for best use of single mode or multi mode lasers in this field of application. The experimental results will be presented by samples of applied parts. In addition a correlation between the process and the achieved mechanical properties will be made. For this application JENOPTIK Automatisierungstechnik GmbH is using the BIM beam control system in its machines, which is the first one to realize a fully integrated combination of beam control and robot. The wide performance and wavelength range of the laser radiation which can be transmitted opens up diverse possibilities of application and makes BIM a universal tool.

  12. Hydrogen dynamics in the low temperature phase of LiBH{sub 4} probed by quasielastic neutron scattering

    Energy Technology Data Exchange (ETDEWEB)

    Remhof, Arndt, E-mail: arndt.remhof@empa.ch [Empa, Swiss Federal Institute for Materials Science and Technology, Hydrogen and Energy, CH-8600 Dübendorf (Switzerland); Züttel, Andreas [Empa, Swiss Federal Institute for Materials Science and Technology, Hydrogen and Energy, CH-8600 Dübendorf (Switzerland); Ramirez-Cuesta, Timmy; García-Sakai, Victoria [ISIS Facility, Rutherford Appleton Laboratory, Chilton, Didcot, Oxon OX11 0QX (United Kingdom); Frick, Bernhard [Institut Laue-Langevin, F-38002 Grenoble (France)

    2013-12-12

    Highlights: • Inelastic fixed window sans offer new possibilities in neutron backscattering spectrometers. • Two different kind of reorientational motion were identified in the low temperature phase of LiBH{sub 4}. • Thermally activated jump rotation. - Abstract: LiBH{sub 4} contains 18.5 wt% hydrogen and undergoes a structural phase transition (orthorhombic → hexagonal) at 381 K which is associated with a large increase in hydrogen and lithium solid-state mobility. We investigated the hydrogen dynamics in the low temperature phase of LiBH{sub 4} by quasielastic neutron scattering, including a new kind of inelastic fixed window scan (IFWS). In the temperature range from 175 to 380 K the H-dynamics is dominated by thermally activated rotational jumps of the [BH{sub 4}]{sup −} anion around the c3 axis with an activation energy of about 162 meV. In agreement with earlier NMR data, a second type of thermally activated motion with an activation energy of about 232 meV could be identified using the IFWS. The present study of hydrogen dynamics in LiBH{sub 4} illustrates the feasibility of using IFWS on neutron backscattering spectrometers as a probe of localised motion.

  13. Late-time cosmological approach in mimetic f(R, T) gravity

    Energy Technology Data Exchange (ETDEWEB)

    Baffou, E.H. [Institut de Mathematiques et de Sciences Physiques (IMSP), Porto-Novo (Benin); Houndjo, M.J.S. [Institut de Mathematiques et de Sciences Physiques (IMSP), Porto-Novo (Benin); Faculte des Sciences et Techniques de Natitingou, Natitingou (Benin); Hamani-Daouda, M. [Universite de Niamey, Departement de Physique, Niamey (Niger); Alvarenga, F.G. [Universidade Federal do Espirito Santo, Departamento de Engenharia e Ciencias Naturais, CEUNES, Sao Mateus, ES (Brazil)

    2017-10-15

    In this paper, we investigate the late-time cosmic acceleration in mimetic f(R, T) gravity with the Lagrange multiplier and potential in a Universe containing, besides radiation and dark energy, a self-interacting (collisional) matter. We obtain through the modified Friedmann equations the main equation that can describe the cosmological evolution. Then, with several models from Q(z) and the well-known particular model f(R, T), we perform an analysis of the late-time evolution. We examine the behavior of the Hubble parameter, the dark energy equation of state and the total effective equation of state and in each case we compare the resulting picture with the non-collisional matter (assumed as dust) and also with the collisional matter in mimetic f(R, T) gravity. The results obtained are in good agreement with the observational data and show that in the presence of the collisional matter the dark energy oscillations in mimetic f(R, T) gravity can be damped. (orig.)

  14. SPL8 Acts Together with the Brassinosteroid-Signaling Component BIM1 in Controlling Arabidopsis thaliana Male Fertility

    Directory of Open Access Journals (Sweden)

    Shuping Xing

    2013-06-01

    Full Text Available The non-miR156 targeted SBP-box gene SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 8 (SPL8, plays an important role in Arabidopsis anther development, where its loss-of-function results in a semi-sterile phenotype. Fully male-sterile plants are obtained when a spl8 loss-of-function mutation is introduced into a 35S:MIR156 genetic background, thereby revealing functional redundancy between SPL8 and miR156-targeted SBP-box genes. Here, we show that BIM1, a gene encoding a bHLH protein involved in brassinosteroid signaling and embryonic patterning, functions redundantly with SPL8 in its requirement for male fertility. Although bim1 single mutants displayed a mild fertility problem due to shortened filaments in some flowers, mutation of BIM1 significantly enhanced the semi-sterile phenotype of the spl8 mutant. Expression of both SPL8 and BIM1 was detected in overlapping expression domains during early anther developmental stages. Our data suggest that in regulating anther development, SPL8 and BIM1 function cooperatively in a common complex or in synergistic pathways. Phylogenetic analysis supports the idea of an evolutionary conserved function for both genes in angiosperm anther development.

  15. New fundamental experimental studies on {alpha}-Mg(BH{sub 4}){sub 2} and other borohydrides

    Energy Technology Data Exchange (ETDEWEB)

    Hagemann, Hans, E-mail: Hans-Rudolf.Hagemann@unige.ch [Dept. de Chim. Phys, Univ. of Geneva (Switzerland); D' Anna, Vincenza [Dept. de Chim. Phys, Univ. of Geneva (Switzerland); Rapin, Jean-Philippe; Cerny, Radovan [Lab. Crystallography, Univ. of Geneva (Switzerland); Filinchuk, Yaroslav [Swiss-Norwegian Beam Lines at ESRF, Grenoble (France); Kim, Ki Chul; Sholl, David S. [School of Chemical and Biomolecular Engineering, Georgia Inst. Technol., Atlanta (United States); Parker, Stewart F. [ISIS Facility, STFC Rutherford Appleton Laboratory, Chilton, Didcot, Oxon OX11 0QX (United Kingdom)

    2011-09-15

    Research highlights: > Eutectic behavior is observed in the LiBH4 -Mg(BH4)2 system. > New INS data show good agreement with theoretical DFT calculations. > Temperature dependent Raman spectra complement previous NMR studies. - Abstract: Several new studies of Mg(BH{sub 4}){sub 2} are reported. A 1:1 LiBH{sub 4}:Mg(BH{sub 4}){sub 2} mixture was studied by in situ synchrotron X-ray diffraction and reveals an eutectic behavior with the eutectic composition more rich in Mg(BH{sub 4}){sub 2}, and the eutectic temperature lower than 456 K. No dual cation compound was observed in this experiment. New vibrational spectra including INS data have been obtained and are compared with theoretical DFT calculations and recent NMR studies, showing good agreement.

  16. Effect of MoS2 on hydrogenation storage properties of LiBH4

    International Nuclear Information System (INIS)

    Liang, Dan; Han, Shumin; Wang, Jiasheng; Zhang, Wei; Zhao, Xin; Zhao, Ziyang

    2014-01-01

    The hydrogen storage properties of LiBH 4 ball milled with 20 wt% MoS 2 have been investigated. It shows that the LiBH 4 doped with MoS 2 exhibits favorable hydrogenation and dehydrogenation properties in terms of decomposition temperature and hydriding/dehydriding reversibility. The sample with MoS 2 starts to release hydrogen at 230 °C and has a decrease of 80 °C in contrast with pristine LiBH 4 . Furthermore, for the second cycle, the LiBH 4 with MoS 2 maintains a reversible hydrogen storage capacity of about 8.0 wt% which is almost identical with the first cycle under 5 MPa at 550 °C. Analyzed by the XRD and the FTIR results, LiBH 4 can be regenerated after re-hydrogenation under a relatively mild condition by adding MoS 2 . The improvement of the hydrogenation and dehydrogenation properties mainly results from the formation of Li 2 S and MoB 2 during ball milling. -- Graphical abstract: Hydrogen absorption curves of LiBH 4 doped with MoS 2 for five cycles at 400 °C. Highlights: • The hydrogen absorption capacity is nearly the same for 5 cycles at 400 °C. • The sample with MoS 2 starts to release hydrogen at 230 °C. • The coexistence of MoB 2 and Li 2 S catalyzes the decomposition of LiBH 4

  17. "iBIM"--internet-based interactive modules: an easy and interesting learning tool for general surgery residents.

    Science.gov (United States)

    Azer, Nader; Shi, Xinzhe; de Gara, Chris; Karmali, Shahzeer; Birch, Daniel W

    2014-04-01

    The increased use of information technology supports a resident- centred educational approach that promotes autonomy, flexibility and time management and helps residents to assess their competence, promoting self-awareness. We established a web-based e-learning tool to introduce general surgery residents to bariatric surgery and evaluate them to determine the most appropriate implementation strategy for Internet-based interactive modules (iBIM) in surgical teaching. Usernames and passwords were assigned to general surgery residents at the University of Alberta. They were directed to the Obesity101 website and prompted to complete a multiple-choice precourse test. Afterwards, they were able to access the interactive modules. Residents could review the course material as often as they wanted before completing a multiple-choice postcourse test and exit survey. We used paired t tests to assess the difference between pre- and postcourse scores. Out of 34 residents who agreed to participate in the project, 12 completed the project (35.3%). For these 12 residents, the precourse mean score was 50 ± 17.3 and the postcourse mean score was 67 ± 14 (p = 0.020). Most residents who participated in this study recommended using the iBIMs as a study tool for bariatric surgery. Course evaluation scores suggest this novel approach was successful in transferring knowledge to surgical trainees. Further development of this tool and assessment of implementation strategies will determine how iBIM in bariatric surgery may be integrated into the curriculum.

  18. Assessing Implicit Knowledge in BIM Models with Machine Learning

    DEFF Research Database (Denmark)

    Krijnen, Thomas; Tamke, Martin

    2015-01-01

    architects and engineers are able to deduce non-explicitly explicitly stated information, which is often the core of the transported architectural information. This paper investigates how machine learning approaches allow a computational system to deduce implicit knowledge from a set of BIM models....

  19. A dental perspective on the taxonomic affinity of the Balanica mandible (BH-1).

    Science.gov (United States)

    Skinner, Matthew M; de Vries, Dorien; Gunz, Philipp; Kupczik, Kornelius; Klassen, R Paul; Hublin, Jean-Jacques; Roksandic, Mirjana

    2016-04-01

    The Middle Pleistocene represents a period of critical importance in human evolution, marked by encephalisation and dental reduction, and increasing diversification of temporally and spatially distributed hominin lineages in Africa, Asia and Europe. New specimens, especially from areas less well represented in the fossil record, can inform the debate on morphological changes to the skeleton and teeth and the phylogenetic course of human evolution during this period. The mandible from the cave of Mala Balanica, Serbia has recently been re-dated to at least 400 ka, and its well-preserved dentition presents an excellent opportunity to characterize molar crown morphology at this time period, and re-examine claims for a lack of Neandertal affinities in the specimen. In this study we employ microtomography to image the internal structure of the mandibular molars (focusing on the morphology of the enamel-dentine junction, or EDJ) of the BH-1 specimen and a comparative sample (n = 141) of Homo erectus sensu lato, Homo neanderthalensis, Pleistocene Homo sapiens, and recent H. sapiens. We quantitatively assess EDJ morphology using 3D geometric morphometrics and examine the expression of discrete dental traits at the dentine surface. We also compare third molar enamel thickness in BH-1 to those of H. neanderthalensis and both Pleistocene and recent H. sapiens, and document previously unreported morphology of the BH-1 premolar and molar roots. Our results highlight the reliability of the EDJ surface for classifying hominin taxa, indicate a primitive dental morphology for BH-1 molars, and confirm a general lack of derived Neandertal features for the Balanica individual. The plesiomorphic character of BH-1 is consistent with several competing models of Middle Pleistocene hominin evolution and provides an important regional and temporal example for reconstructing morphological changes in the mandible and teeth during this time period. Copyright © 2016 Elsevier Ltd. All

  20. An estimation framework for building information modeling (BIM)-based demolition waste by type.

    Science.gov (United States)

    Kim, Young-Chan; Hong, Won-Hwa; Park, Jae-Woo; Cha, Gi-Wook

    2017-12-01

    Most existing studies on demolition waste (DW) quantification do not have an official standard to estimate the amount and type of DW. Therefore, there are limitations in the existing literature for estimating DW with a consistent classification system. Building information modeling (BIM) is a technology that can generate and manage all the information required during the life cycle of a building, from design to demolition. Nevertheless, there has been a lack of research regarding its application to the demolition stage of a building. For an effective waste management plan, the estimation of the type and volume of DW should begin from the building design stage. However, the lack of tools hinders an early estimation. This study proposes a BIM-based framework that estimates DW in the early design stages, to achieve an effective and streamlined planning, processing, and management. Specifically, the input of construction materials in the Korean construction classification system and those in the BIM library were matched. Based on this matching integration, the estimates of DW by type were calculated by applying the weight/unit volume factors and the rates of DW volume change. To verify the framework, its operation was demonstrated by means of an actual BIM modeling and by comparing its results with those available in the literature. This study is expected to contribute not only to the estimation of DW at the building level, but also to the automated estimation of DW at the district level.

  1. INTEGRATION OF BIM, WEB MAPS AND IOT FOR SUPPORTING COMFORT ANALYSIS

    Directory of Open Access Journals (Sweden)

    M. Gunduz

    2017-11-01

    Full Text Available The use of the Internet is expanding and the technological capabilities of electronic devices are evolving. Today, Internet of Things (IoT solutions can be developed that were never even imaginable before. In this paper, a case study is presented on the joint use of Building Information Model (BIM, Geographical Information Systems (GIS and Internet of Things (IoT technologies. It is a part of an ongoing study that intends to overcome some problems about the management of complex facilities. In the study, a BIM has been converted and displayed in 2D on Google Maps, and information on various sensors have been represented on the web with geographic coordinates in real-time.

  2. Integration of Bim, Web Maps and Iot for Supporting Comfort Analysis

    Science.gov (United States)

    Gunduz, M.; Isikdag, U.; Basaraner, M.

    2017-11-01

    The use of the Internet is expanding and the technological capabilities of electronic devices are evolving. Today, Internet of Things (IoT) solutions can be developed that were never even imaginable before. In this paper, a case study is presented on the joint use of Building Information Model (BIM), Geographical Information Systems (GIS) and Internet of Things (IoT) technologies. It is a part of an ongoing study that intends to overcome some problems about the management of complex facilities. In the study, a BIM has been converted and displayed in 2D on Google Maps, and information on various sensors have been represented on the web with geographic coordinates in real-time.

  3. New hydrogen-rich ammonium metal borohydrides, NH4[M(BH4)4], M = Y, Sc, Al, as potential H2 sources.

    Science.gov (United States)

    Starobrat, A; Jaroń, T; Grochala, W

    2018-03-26

    Three metal-ammonium borohydrides, NH4[M(BH4)4] M = Y, Sc, Al, denoted 1, 2, 3, respectively, were prepared via a low temperature mechanochemical synthesis and characterized using PXRD, FTIR and TGA/DSC/MS. The compounds 1 and 2 adopt the P21/c space group while the compound 3 crystallizes in an orthorhombic unit cell (Fddd). The first decomposition step of all three derivatives of ammonium borohydride has the maximum rate at 48 °C, 53 °C and 35 °C for 1, 2 and 3, respectively, which are comparable to that for NH4BH4 (53 °C). The thermal decomposition of these metal-ammonium borohydrides is a multistep process, with predominantly exothermic low-temperature stages. The compound 1 decomposes via known Y(BH4)3, however, some of the solid decomposition products of the other two compounds have not been fully identified. In the system containing compound 2, a new, more dense polymorph of the previously reported LiSc(BH4)4 has been detected as the intermediate of slow decomposition at room temperature.

  4. Prey from the eyes of predators: Color discriminability of aposematic and mimetic butterflies from an avian visual perspective.

    Science.gov (United States)

    Su, Shiyu; Lim, Matthew; Kunte, Krushnamegh

    2015-11-01

    Predation exerts strong selection on mimetic butterfly wing color patterns, which also serve other functions such as sexual selection. Therefore, specific selection pressures may affect the sexes and signal components differentially. We tested three predictions about the evolution of mimetic resemblance by comparing wing coloration of aposematic butterflies and their Batesian mimics: (a) females gain greater mimetic advantage than males and therefore are better mimics, (b) due to intersexual genetic correlations, sexually monomorphic mimics are better mimics than female-limited mimics, and (c) mimetic resemblance is better on the dorsal wing surface that is visible to predators in flight. Using a physiological model of avian color vision, we quantified mimetic resemblance from predators' perspective, which showed that female butterflies were better mimics than males. Mimetic resemblance in female-limited mimics was comparable to that in sexually monomorphic mimics, suggesting that intersexual genetic correlations did not constrain adaptive response to selection for female-limited mimicry. Mimetic resemblance on the ventral wing surface was better than that on the dorsal wing surface, implying stronger natural and sexual selection on ventral and dorsal surfaces, respectively. These results suggest that mimetic resemblance in butterfly mimicry rings has evolved under various selective pressures acting in a sex- and wing surface-specific manner. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  5. Cafestol overcomes ABT-737 resistance in Mcl-1-overexpressed renal carcinoma Caki cells through downregulation of Mcl-1 expression and upregulation of Bim expression.

    Science.gov (United States)

    Woo, S M; Min, K-J; Seo, B R; Nam, J-O; Choi, K S; Yoo, Y H; Kwon, T K

    2014-11-06

    Although ABT-737, a small-molecule Bcl-2/Bcl-xL inhibitor, has recently emerged as a novel cancer therapeutic agent, ABT-737-induced apoptosis is often blocked in several types of cancer cells with elevated expression of Mcl-1. Cafestol, one of the major compounds in coffee beans, has been reported to have anti-carcinogenic activity and tumor cell growth-inhibitory activity, and we examined whether cafestol could overcome resistance against ABT-737 in Mcl-1-overexpressed human renal carcinoma Caki cells. ABT-737 alone had no effect on apoptosis, but cafestol markedly enhanced ABT-737-mediated apoptosis in Mcl-1-overexpressed Caki cells, human glioma U251MG cells, and human breast carcinoma MDA-MB231 cells. By contrast, co-treatment with ABT-737 and cafestol did not induce apoptosis in normal human skin fibroblast. Furthermore, combined treatment with cafestol and ABT-737 markedly reduced tumor growth compared with either drug alone in xenograft models. We found that cafestol inhibited Mcl-1 protein expression, which is important for ABT-737 resistance, through promotion of protein degradation. Moreover, cafestol increased Bim expression, and siRNA-mediated suppression of Bim expression reduced the apoptosis induced by cafestol plus ABT-737. Taken together, cafestol may be effectively used to enhance ABT-737 sensitivity in cancer therapy via downregulation of Mcl-1 expression and upregulation of Bim expression.

  6. PARADIGMAS DE REPRESENTAÇÃO DE MODULAÇÃO DE ALVENARIAS EM FERRAMENTAS BIM

    Directory of Open Access Journals (Sweden)

    Ari Monteiro

    2009-12-01

    Full Text Available As novas ferramentas CAD que suportam o conceito de Building Information Modeling (BIM baseiam-se na modelagem 3D da geometria do edifício instanciando objetos contidos em famílias de componentes. Alguns destes objetos possuem geometria bastante detalhada, enquanto outros se restringem às suas fronteiras mais externas. No caso do objeto “parede”, esta representação normalmente limita-se às suas faces externas e uma lista de camadas utilizadas para representar sua composição interna (núcleo e revestimentos. Esta representação torna o arquivo leve, favorecendo o desempenho da aplicação. No entanto, para projetos que necessitam de um nível de detalhe superior àquele oferecido por esta solução, como o projeto para produção de vedações verticais em alvenaria (PPVVA, uma representação 3D completa dos elementos da parede é importante. Neste cenário, surge uma questão: como representar os elementos da parede de maneira a atender aos requisitos do PPVVA e, ao mesmo tempo, não degradar o desempenho de manipulação do modelo BIM? Este trabalho apresenta algumas abordagens para a representação da modulação: uma explícita (famílias de objetos e outras implícitas (array / modelagem generativa. Uma análise comparativa destas abordagens é apresentada, destacando-se as suas vantagens e desvantagens, tais como dificuldade de implementação, facilidade de utilização e impacto no desempenho da aplicação. A viabilidade de cada método foi estudada, restringindo-se ao software Autodesk Revit® Architecture 2009/2010, considerando-se os processamentos para geração de vistas 2D e quantificação de componentes, bem como consumo de memória e processamento ligados a cada abordagem, permitindo a tomada de decisão no nível de implementação. * Artigo disponível em versão completa em inglês REPRESENTATION PARADIGMS FOR MASONRY MODULATION IN BIM TOOLS ABSTRACT New CAD tools which support the BIM (Building Information

  7. Core--strategy leading to high reversible hydrogen storage capacity for NaBH4.

    Science.gov (United States)

    Christian, Meganne L; Aguey-Zinsou, Kondo-François

    2012-09-25

    Owing to its high storage capacity (10.8 mass %), sodium borohydride (NaBH(4)) is a promising hydrogen storage material. However, the temperature for hydrogen release is high (>500 °C), and reversibility of the release is unachievable under reasonable conditions. Herein, we demonstrate the potential of a novel strategy leading to high and stable hydrogen absorption/desorption cycling for NaBH(4) under mild pressure conditions (4 MPa). By an antisolvent precipitation method, the size of NaBH(4) particles was restricted to a few nanometers (hydrogen at 400 °C. Further encapsulation of these nanoparticles upon reaction of nickel chloride at their surface allowed the synthesis of a core--shell nanostructure, NaBH(4)@Ni, and this provided a route for (a) the effective nanoconfinement of the melted NaBH(4) core and its dehydrogenation products, and (b) reversibility and fast kinetics owing to short diffusion lengths, the unstable nature of nickel borohydride, and possible modification of reaction paths. Hence at 350 °C, a reversible and steady hydrogen capacity of 5 mass % was achieved for NaBH(4)@Ni; 80% of the hydrogen could be desorbed or absorbed in less than 60 min, and full capacity was reached within 5 h. To the best of our knowledge, this is the first time that such performances have been achieved with NaBH(4). This demonstrates the potential of the strategy in leading to major advancements in the design of effective hydrogen storage materials from pristine borohydrides.

  8. Oral delivery of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3, synthetic peptide leptin mimetics: Immunofluorescent localization in the mouse hypothalamus.

    Science.gov (United States)

    Anderson, Brian M; Jacobson, Lauren; Novakovic, Zachary M; Grasso, Patricia

    2017-06-01

    This study describes the localization of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3, synthetic peptide leptin mimetics, in the hypothalamus of Swiss Webster and C57BL/6J wild-type mice, leptin-deficient ob/ob mice, and leptin-resistant diet-induced obese (DIO) mice. The mice were given [D-Leu-4]-OB3 or MA-[D-Leu-4]-OB3 in 0.3% dodecyl maltoside by oral gavage. Once peak serum concentrations were reached, the mice received a lethal dose of pentobarbital and were subjected to intracardiac perfusion fixation. The brains were excised, post-fixed in paraformaldehyde, and cryo-protected in sucrose. Free-floating frozen coronal sections were cut at 25-µm and processed for imaging by immunofluorescence microscopy. In all four strains of mice, dense staining was concentrated in the area of the median eminence, at the base and/or along the inner wall of the third ventricle, and in the brain parenchyma at the level of the arcuate nucleus. These results indicate that [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 cross the blood-brain barrier and concentrate in an area of the hypothalamus known to regulate energy balance and glucose homeostasis. Most noteworthy is the localization of [D-Leu-4]-OB3 immunoreactivity within the hypothalamus of DIO mice via a conduit that is closed to leptin in this rodent model, and in most cases of human obesity. Together with our previous studies describing the effects of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 on energy balance, glucose regulation, and signal transduction pathway activation, these findings are consistent with a central mechanism of action for these synthetic peptide leptin mimetics, and suggest their potential usefulness in the management of leptin-resistant obesity and type 2 diabetes in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Biofouling inhibition in MBR by Rhodococcus sp. BH4 isolated from real MBR plant.

    Science.gov (United States)

    Oh, Hyun-Suk; Kim, Sang-Ryoung; Cheong, Won-Suk; Lee, Chung-Hak; Lee, Jung-Kee

    2013-12-01

    It has been reported that an indigenous quorum quenching bacterium, Rhodococcus sp. BH4, which was isolated from a real plant of membrane bioreactor (MBR) has promising potential to control biofouling in MBR. However, little is known about quorum quenching mechanisms by the strain BH4. In this study, various characteristics of strain BH4 were investigated to elucidate its behavior in more detail in the mixed liquor of MBR. The N-acyl homoserine lactone hydrolase (AHL-lactonase) gene of strain BH4 showed a high degree of identity to qsdA in Rhodococcus erythropolis W2. The LC-ESI-MS analysis of the degradation product by strain BH4 confirmed that it inactivated AHL activity by hydrolyzing the lactone bond of AHL. It degraded a wide range of N-acyl homoserine lactones (AHLs), but there was a large difference in the degradation rate of each AHL compared to other reported AHL-lactonase-producing strains belonging to Rhodococcus genus. Its quorum quenching activity was confirmed not only in the Luria-Bertani medium, but also in the synthetic wastewater. Furthermore, the amount of strain BH4 encapsulated in the vessel as well as the material of the vessel substantially affected the quorum quenching activity of strain BH4, which provides useful information, particularly for the biofouling control in a real MBR plant from an engineering point of view.

  10. Near infrared magnetic circular dichroism of uranium borohydride, U(BH4)4

    International Nuclear Information System (INIS)

    Keiderling, T.A.; Schulz, W.C.

    1980-01-01

    The magnetic circular dichroism of U(BH 4 ) 4 in Hf(BH 4 ) 4 at low temperatures has been measured in the near. The A terms resulting can be interpreted to confirm the E symmetry ground state and three excited state assignments. (orig.)

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

    National Research Council Canada - National Science Library

    Liu, Junwei

    2004-01-01

    ... (death, survival, proliferation/division, etc). Our hypothesis is that, under normal, unstimulated conditions, with its apoptotic function blocked, the upregulated Bim in PCa cells play an apoptosis-independent function...

  12. Integration of Environmental Sensors with BIM: case studies using Arduino, Dynamo, and the Revit API

    Directory of Open Access Journals (Sweden)

    Kensek, K. M.

    2014-12-01

    Full Text Available This paper investigates the feasibility of connecting environmental sensors such as light, humidity, or CO2 receptors to a building information model (BIM. A base case was created in Rhino; using Grasshopper and Firefly, a simple digital model responded to lighting-levels detected by a photoresistor on an Arduino board. The case study was duplicated using Revit Architecture, a popular BIM software, and Dynamo, a visual programming environment, in an innovative application. Another case study followed a similar procedure by implementing the Revit API directly instead of using Dynamo. Then the process was reversed to demonstrate that not only could data could be sent from sensors to change the 3D model, but changes to parameters of a 3D model could effect a physical model through the use of actuators. It is intended that these virtual/physical prototypes could be used as the basis for testing intelligent façade systems before constructing full size mock-ups.Este estudio investiga la posibilidad de conectar sensores ambientales como de luz, humedad, o dióxido de carbono con un modelo de información de un edificio (siglas BIM en inglés. Un caso base fue creado en Rhino; usando Grasshopper and Firefly, donde un simple modelo digital respondió a niveles de luz detectados por un foto resistor en una tarjeta Arduino. El caso de estudio fue duplicado usando Revit Architecture, una herramienta popular en BIM, y Dynamo, un ambiente de programación gráfica, en una creativa aplicación. Un segundo caso de estudio siguió un procedimiento similar implementando Revit API directamente en vez de usar Dynamo. Entonces el proceso fue revertido para demostrar que no solamente la información podría ser enviada desde sensores para cambiar el modelo tridimensional, pero cambios en los parámetros de un modelo tridimensional podrían afectar un modelo físico mediante el uso de actuadores. Se espera que esos modelos virtuales puedan ser usados como base para

  13. Nanostructured graphite-induced destabilization of LiBH4 for reversible hydrogen storage

    CSIR Research Space (South Africa)

    Wang, K

    2016-11-01

    Full Text Available been conducted to gain insight into the promoting effect of nano-G on the reversible dehydrogenation of the LiBH(sub4). Our study found that nano-G exerts its promoting effect via interaction with LiBH(sub4) and as grinding aid....

  14. Static spherically symmetric solutions in mimetic gravity: rotation curves and wormholes

    International Nuclear Information System (INIS)

    Myrzakulov, Ratbay; Sebastiani, Lorenzo; Vagnozzi, Sunny; Zerbini, Sergio

    2016-01-01

    In this work, we analyse static spherically symmetric solutions in the framework of mimetic gravity, an extension of general relativity where the conformal degree of freedom of gravity is isolated in a covariant fashion. Here we extend previous works by considering, in addition, a potential for the mimetic field. An appropriate choice of such a potential allows for the reconstruction of a number of interesting cosmological and astrophysical scenarios. We explicitly show how to reconstruct such a potential for a general static spherically symmetric space-time. A number of applications and scenarios are then explored, among which are traversable wormholes. Finally, we analytically reconstruct potentials, which leads to solutions to the equations of motion featuring polynomial corrections to the Schwarzschild space-time. Accurate choices for such corrections could provide an explanation for the inferred flat rotation curves of spiral galaxies within the mimetic gravity framework, without the need for particle dark matter. (paper)

  15. Minor cell-death defects but reduced tumor latency in mice lacking the BH3-only proteins Bad and Bmf.

    Science.gov (United States)

    Baumgartner, F; Woess, C; Pedit, V; Tzankov, A; Labi, V; Villunger, A

    2013-01-31

    Proapoptotic Bcl-2 family members of the Bcl-2 homology (BH)3-only subgroup are critical for the establishment and maintenance of tissue homeostasis and can mediate apoptotic cell death in response to developmental cues or exogenously induced forms of cell stress. On the basis of the biochemical experiments as well as genetic studies in mice, the BH3-only proteins Bad and Bmf have been implicated in different proapoptotic events such as those triggered by glucose- or trophic factor-deprivation, glucocorticoids, or histone deacetylase inhibition, as well as suppression of B-cell lymphomagenesis upon aberrant expression of c-Myc. To address possible redundancies in cell death regulation and tumor suppression, we generated compound mutant mice lacking both genes. Our studies revealed lack of redundancy in most paradigms of lymphocyte apoptosis tested in tissue culture. Only spontaneous cell death of thymocytes kept in low glucose or that of pre-B cells deprived of cytokines was significantly delayed when both genes were lacking. Of note, despite these minor apoptosis defects we observed compromised lymphocyte homeostasis in vivo that affected mainly the B-cell lineage. Long-term follow-up revealed significantly reduced latency to spontaneous tumor formation in aged mice when both genes were lacking. Together our study suggests that Bad and Bmf co-regulate lymphocyte homeostasis and limit spontaneous transformation by mechanisms that may not exclusively be linked to the induction of lymphocyte apoptosis.

  16. Modelling and Accuracy in a Bim Environment for Planned Conservation: the Apartment of Troia of Giulio Romano

    Science.gov (United States)

    Adami, A.; Scala, B.; Spezzoni, A.

    2017-02-01

    research about the modelling of Cultural Heritage for BIM application. The proposed solution aims to give as much information as possible about the architecture, and, at the same time, to guarantee a higher efficiency. In this case we considered commercial BIM software like Revit or Archicad. They are the most widespread and well-known software BIM oriented and they also allow the use of their embedded database structure. The core of our solution is to describe the architecture not only by a 3D model but also by the representation of the reliability of the accuracy of the model itself. In this way we try to combine the necessity of working with commercial software, in which it is difficult to be very accurate, and the information about the real object. In historical complex architecture, for example, it is very difficult to find a straight and planar wall. It is quite difficult, or at least time consuming, to model that kind of wall with high accuracy. But it is possible to represent the real wall by a schematic wall with a false color map which describes where the 3D model is well fitting and where there are some differences. In this way we don't lose any information but, at the same time, we have a very usable BIM model.

  17. Knockout Serum Replacement Promotes Cell Survival by Preventing BIM from Inducing Mitochondrial Cytochrome C Release.

    Directory of Open Access Journals (Sweden)

    Yuki Ishii

    Full Text Available Knockout serum replacement (KOSR is a nutrient supplement commonly used to replace serum for culturing stem cells. We show here that KOSR has pro-survival activity in chronic myelogenous leukemia (CML cells transformed by the BCR-ABL oncogene. Inhibitors of BCR-ABL tyrosine kinase kill CML cells by stimulating pro-apoptotic BIM and inhibiting anti-apoptotic BCL2, BCLxL and MCL1. We found that KOSR protects CML cells from killing by BCR-ABL inhibitors--imatinib, dasatinib and nilotinib. The protective effect of KOSR is reversible and not due to the selective outgrowth of drug-resistant clones. In KOSR-protected CML cells, imatinib still inhibited the BCR-ABL tyrosine kinase, reduced the phosphorylation of STAT, ERK and AKT, down-regulated BCL2, BCLxL, MCL1 and up-regulated BIM. However, these pro-apoptotic alterations failed to cause cytochrome c release from the mitochondria. With mitochondria isolated from KOSR-cultured CML cells, we showed that addition of recombinant BIM protein also failed to cause cytochrome c release. Besides the kinase inhibitors, KOSR could protect cells from menadione, an inducer of oxidative stress, but it did not protect cells from DNA damaging agents. Switching from serum to KOSR caused a transient increase in reactive oxygen species and AKT phosphorylation in CML cells that were protected by KOSR but not in those that were not protected by this nutrient supplement. Treatment of KOSR-cultured cells with the PH-domain inhibitor MK2206 blocked AKT phosphorylation, abrogated the formation of BIM-resistant mitochondria and stimulated cell death. These results show that KOSR has cell-context dependent pro-survival activity that is linked to AKT activation and the inhibition of BIM-induced cytochrome c release from the mitochondria.

  18. C. pneumoniae CdsL regulates CdsN ATPase activity, and disruption with a peptide mimetic prevents bacterial invasion

    Directory of Open Access Journals (Sweden)

    Chris Blair Stone

    2011-02-01

    Full Text Available Chlamydiae are obligate intracellular pathogens that likely require type III secretion (T3S to invade cells and replicate intracellulary within a cytoplasmic vacuole called an inclusion body. C. pneumoniae possess a YscL ortholog, CdsL, that has been shown to interact with the T3S ATPase (CdsN. In this report we demonstrate that CdsL down-regulates CdsN enzymatic activity in a dose-dependent manner. Using PepScan epitope mapping we identified two separate binding domains to which CdsL binds viz. CdsN 221-229 and CdsN265-270. We confirmed the binding domains using a pull-down assay and showed that GST-CdsN221-270, which encompasses these peptides, co-purified with His-CdsL. Next, we used orthology modeling based on the crystal structure of a T3S ATPase ortholog from E. coli, EscN, to map the binding domains on the predicted three dimensional structure of CdsN. The CdsL binding domains mapped to the catalytic domain of the ATPase, one in the central channel of the ATPase hexamer and one on the outer face. Since peptide mimetics have been used to disrupt essential protein interactions of the chlamydial T3S system and inhibit T3S-mediated invasion of HeLa cells, we hypothesized that if CdsL – CdsN binding is essential for regulating T3S then a CdsN peptide mimetic could be used to potentially block T3S and Chlamydial invasion. Treatment of EBs with a CdsN peptide mimetic inhibited C. pneumoniae invasion into HeLa cells in a dose-dependent fashion. This report represents the first use of Pepscan technology to identify binding domains for specific T3S proteins viz. CdsL on the ATPase, CdsN, and demonstrates that peptide mimetics can be used as anti-virulence factors to block bacterial invasion.

  19. Getting the sigma in the M_BH - sigma relation right

    Science.gov (United States)

    van der Marel, Roeland

    2017-08-01

    The relation between the mass of the central supermassive black hole (M_BH) and the velocity dispersion of its host spheroid (sigma) is fundamental for our understanding of galaxy evolution and its relation to their nuclei. Correspondingly many HST orbits have been invested in determining accurate M_BH masses. Surprisingly little has been done on standardizing the other axis, i.e. sigma measurements. These values are often derived from various long-slit datasets at different physical radii of the galaxy and no homogeneous definition has been given. We propose to remedy this situation by using our dataset of MUSE and PPAK kinematic maps out to 1 R_e of galaxies with a secure black hole mass. These data are useful for large scale kinematics, however, obtaining velocity dispersions at small radii is not possible. To measure velocity dispersions at small radii we require high-spatial resolution spectroscopy as provided by HST/STIS. In addtion, high-resolution photometric data is needed to define consistent apertures in each galaxy. We therefore propose to use the unique capabilities of HST and harvest years of efforts to collect archival spectroscopic and imaging data for BH host galaxies. This will allow creating a catalog of sigma values, calculated in various ways and at various radii and to re-calibrate the M_BH - sigma relation.

  20. Structural disorder of natural BimSen superlattices grown by molecular beam epitaxy

    Science.gov (United States)

    Springholz, G.; Wimmer, S.; Groiss, H.; Albu, M.; Hofer, F.; Caha, O.; Kriegner, D.; Stangl, J.; Bauer, G.; Holý, V.

    2018-05-01

    The structure and morphology of BimSen epitaxial layers with compositions ranging from Bi2Se3 to the Bi1Se1 grown by molecular beam epitaxy with different flux compositions are investigated by transmission electron microscopy, high-resolution x-ray diffraction, and atomic force microscopy. It is shown that the lattice structure changes significantly as a function of the beam flux composition, i.e., Se/BiSe flux ratio that determines the stoichiometry of the layers. A perfect Bi2Se3 phase is formed only with a sufficiently high additional Se flux, whereas Bi1Se1 is obtained when only a BiSe compound source without additional Se is used. For intermediate values of the excess Se flux during growth, Bi2Se3 -δ layers are obtained with the Se deficit δ varying between 0 and 1. This Se deficit is accommodated by incorporation of additional Bi-Bi double layers into the Bi2Se3 structure that otherwise exclusively consists of Se-Bi-Se-Bi-Se quintuple layers. While a periodic insertion of such Bi double layers would result in the formation of natural BimSen superlattices, we find that this Bi double-layer insertion is rather stochastic with a high degree of disorder depending on the film composition. Therefore, the structure of such epilayers is better described by a one-dimensional paracrystal model, consisting of disordered sequences of quintuple and double layers rather than by strictly periodic natural superlattices. From detailed analysis of the x-ray diffraction data, we determine the dependence of the lattice parameters a and c and distances of the individual (0001) planes dj as a function of composition, evidencing that only the in-plane lattice parameter a shows a linear dependence on composition. The simulation of the diffraction curves with the random stacking paracrystal model yields an excellent agreement with the experimental data and it brings quantitative information on the randomness of the stacking sequence, which is compared to growth modeling using Monte

  1. SU-F-T-123: The Simulated Effect of the Breath-Hold Reproducibility Treating Locally-Advanced Lung Cancer with Pencil Beam Scanned Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Dueck, J [Paul Scherrer Institut, Villigen PSI (Switzerland); Department of Oncology, Rigshospitalet, Copenhagen (Denmark); Niels Bohr Institute, University of Copenhagen, Copenhagen (Denmark); Perrin, R [Paul Scherrer Institut, Villigen PSI (Switzerland); Persson, G F; Engelholm, S A [Department of Oncology, Rigshospitalet, Copenhagen (Denmark); Lomax, A [Paul Scherrer Institut, Villigen PSI (Switzerland); Department of Physics, ETH, Zürich (Switzerland); Josipovic, M; Rosenschöld, AF [Department of Oncology, Rigshospitalet, Copenhagen (Denmark); Niels Bohr Institute, University of Copenhagen, Copenhagen (Denmark); Weber, D C [Paul Scherrer Institut, Villigen PSI (Switzerland); University of Zürich, Zürich (Switzerland); Munck, P

    2016-06-15

    Purpose: The breath-hold (BH) technique has been suggested to mitigate motion and reduce target coverage degradation due to motion effects. The aim of this study was to investigate the effect of inter-BH residual motion on the dose distribution for pencil beam scanned (PBS) proton therapy of locally-advanced lung cancer patients. Methods: A dataset of visually-guided BH CT scans was acquired (10 scans per patient) taken from five lung cancer patients: three intra-fractionally repeated CT scans on treatment days 2,16 and 31, in addition to the day 0 planning CT scan. Three field intensity-modulated proton therapy (IMPT) plans were constructed on the planning CT scan. Dose delivery on fraction 2, 16 and 31 were simulated on the three consecutive CT scans, assuming BH duration of 20s and soft tissue match. The dose was accumulated in the planning CT using deformable image registration, and scaled to simulate the full treatment of 66Gy(RBE) in 33 fractions. Results: The mean dose to the lungs and heart, and maximum dose to the spinal cord and esophagus were within 1% of the planned dose. The CTV V95% decreased and the inhomogeneity (D5%–D95%) increased on average 4.1% (0.4–12.2%) and 5.8% (2.2–13.4%), respectively, over the five patient cases. Conclusion: The results showed that the BH technique seems to spare the OARs in spite of inter-BH residual motion. However, small degradation of target coverage occurred for all patients, with 3/5 patients having a decrease in V95% ≤1%. For the remaining two patients, where V95% decreased up to 12%, the cause could be related to treatment related anatomical changes and, as in photon therapy, plan adaptation may be necessary to ensure target coverage. This study showed that BH could be a potential treatment option to reliably mitigate motion for the treatment of locally-advanced lung cancer using PBS proton therapy.

  2. A BIM-based system for demolition and renovation waste estimation and planning

    International Nuclear Information System (INIS)

    Cheng, Jack C.P.; Ma, Lauren Y.H.

    2013-01-01

    Highlights: ► We developed a waste estimation system leveraging the BIM technology. ► The system can calculate waste disposal charging fee and pick-up truck demand. ► We presented an example scenario demonstrating this system. ► Automatic, time-saving and wide applicability are the features of the system. - Abstract: Due to the rising worldwide awareness of green environment, both government and contractors have to consider effective construction and demolition (C and D) waste management practices. The last two decades have witnessed the growing importance of demolition and renovation (D and R) works and the growing amount of D and R waste disposed to landfills every day, especially in developed cities like Hong Kong. Quantitative waste prediction is crucial for waste management. It can enable contractors to pinpoint critical waste generation processes and to plan waste control strategies. In addition, waste estimation could also facilitate some government waste management policies, such as the waste disposal charging scheme in Hong Kong. Currently, tools that can accurately and conveniently estimate the amount of waste from construction, renovation, and demolition projects are lacking. In the light of this research gap, this paper presents a building information modeling (BIM) based system that we have developed for estimation and planning of D and R waste. BIM allows multi-disciplinary information to be superimposed within one digital building model. Our system can extract material and volume information through the BIM model and integrate the information for detailed waste estimation and planning. Waste recycling and reuse are also considered in our system. Extracted material information can be provided to recyclers before demolition or renovation to make recycling stage more cooperative and more efficient. Pick-up truck requirements and waste disposal charging fee for different waste facilities will also be predicted through our system. The results

  3. A BIM-based system for demolition and renovation waste estimation and planning

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Jack C.P., E-mail: cejcheng@ust.hk [Department of Civil and Environmental Engineering, The Hong Kong University of Science and Technology (Hong Kong); Ma, Lauren Y.H., E-mail: yingzi@ust.hk [Department of Civil and Environmental Engineering, The Hong Kong University of Science and Technology (Hong Kong)

    2013-06-15

    Highlights: ► We developed a waste estimation system leveraging the BIM technology. ► The system can calculate waste disposal charging fee and pick-up truck demand. ► We presented an example scenario demonstrating this system. ► Automatic, time-saving and wide applicability are the features of the system. - Abstract: Due to the rising worldwide awareness of green environment, both government and contractors have to consider effective construction and demolition (C and D) waste management practices. The last two decades have witnessed the growing importance of demolition and renovation (D and R) works and the growing amount of D and R waste disposed to landfills every day, especially in developed cities like Hong Kong. Quantitative waste prediction is crucial for waste management. It can enable contractors to pinpoint critical waste generation processes and to plan waste control strategies. In addition, waste estimation could also facilitate some government waste management policies, such as the waste disposal charging scheme in Hong Kong. Currently, tools that can accurately and conveniently estimate the amount of waste from construction, renovation, and demolition projects are lacking. In the light of this research gap, this paper presents a building information modeling (BIM) based system that we have developed for estimation and planning of D and R waste. BIM allows multi-disciplinary information to be superimposed within one digital building model. Our system can extract material and volume information through the BIM model and integrate the information for detailed waste estimation and planning. Waste recycling and reuse are also considered in our system. Extracted material information can be provided to recyclers before demolition or renovation to make recycling stage more cooperative and more efficient. Pick-up truck requirements and waste disposal charging fee for different waste facilities will also be predicted through our system. The results

  4. From Dalek half balls to Daft Punk helmets: Mimetic fandom and the crafting of replicas

    Directory of Open Access Journals (Sweden)

    Matt Hills

    2014-06-01

    Full Text Available Mimetic fandom is a surprisingly understudied mode of (culturally masculinized fan activity in which fans research and craft replica props. Mimetic fandom can be considered as (inauthentic and (immaterial, combining noncommercial status with grassroots marketing or brand reinforcement as well as fusing an emphasis on material artifacts with Web 2.0 collective intelligence. Simply analyzing mimetic fandom as part of fannish material culture fails to adequately assess the nonmaterial aspects of this collaborative creativity. Two fan cultures are taken as case studies: Dalek building groups and Daft Punk helmet constructors. These diverse cases indicate that mimetic fandom has a presence and significance that moves across media fandoms and is not restricted to the science fiction, fantasy, and horror followings with which it is most often associated. Mimetic fandom may be theorized as an oscillatory activity that confuses binaries and constructions of (academic/fan authenticity. This fan practice desires and pursues a kind of ontological bridging or unity—from text to reality—that is either absent or less dominant in many other fan activities such as cosplay, screen-used prop collecting, and geographical pilgrimage. Fan studies may benefit from reassessing the place of mimesis, especially in order to theorize fan practices that are less clearly transformative in character.

  5. Automatic Code Checking Applied to Fire Fighting and Panic Projects in a BIM Environment - BIMSCIP

    Directory of Open Access Journals (Sweden)

    Marcelo Franco Porto

    2017-06-01

    Full Text Available This work presents a computational implementation of an automatic conformity verification of building projects using a 3D modeling platform for BIM. This program was developed in C# language and based itself on the 9th Technical Instruction from Military Fire Brigade of the State of Minas Gerais which covers regulations of fire load in buildings and hazardous areas.

  6. Mg{sub x}Mn{sub (1-x)}(BH{sub 4}){sub 2} (x = 0-0.8), a cation solid solution in a bimetallic borohydride

    Energy Technology Data Exchange (ETDEWEB)

    Cerny, Radovan, E-mail: radovan.cerny@unige.ch [Laboratory of Crystallography, University of Geneva, 1211 Geneva (Switzerland); Penin, Nicolas [Laboratory of Crystallography, University of Geneva, 1211 Geneva (Switzerland); CNRS, Universite de Bordeaux 1, ICMCB, 87 Avenue du Docteur Albert Schweitzer, F-33608 Pessac Cedex (France); D' Anna, Vincenza; Hagemann, Hans [Department of Physical Chemistry, University of Geneva, 1211 Geneva (Switzerland); Durand, Etienne [CNRS, Universite de Bordeaux 1, ICMCB, 87 Avenue du Docteur Albert Schweitzer, F-33608 Pessac Cedex (France); Ruzicka, Jakub [Charles University, Faculty of Science, Department of Inorganic Chemistry, Hlavova 2030, 128 40, Prague 2 (Czech Republic)

    2011-08-15

    Highlights: {yields} The magnesium and manganese borohydrides form a solid solution Mg{sub x}Mn{sub (1-x)}(BH{sub 4}){sub 2} (x = 0-0.8) which conserves the trigonal structure of Mn{sub (}(BH{sub 4}){sub 2}. {yields} Coexistence of both trigonal and hexagonal borohydrides occurs within nominal composition ranging from x{sub Mg} = 0.8-0.9. {yields} The decomposition temperature of trigonal Mg{sub x}Mn{sub (1-x)}(BH{sub 4}){sub 2} (x = 0-0.8) does not vary significantly with magnesium content (433-453 K). {yields} The desorbed gas contains mostly hydrogen and 3-7.5 mol.% of diborane B{sub 2}H{sub 6}. - Abstract: A solid solution of magnesium and manganese borohydrides was studied by in situ synchrotron radiation X-ray powder diffraction and infrared spectroscopy. A combination of thermogravimetry, mass and infrared spectroscopy, and atomic emission spectroscopy were applied to clarify the thermal gas desorption of pure Mn(BH{sub 4}){sub 2} and a solid solution of composition Mg{sub 0.5}Mn{sub 0.5}(BH{sub 4}){sub 2}. Mg{sub x}Mn{sub (1-x)}(BH{sub 4}){sub 2} (x = 0-0.8) conserves the trigonal structure of Mn(BH{sub 4}){sub 2} at room temperature. Manganese is dissolved in the hexagonal structure of {alpha}-Mg(BH{sub 4}){sub 2}, with the upper solubility limit not exceeding 10 mol.% at room temperature. There exists a two-phase region of trigonal and hexagonal borohydrides within the compositional range x = 0.8-0.9 at room temperature. Infrared spectra show splitting of various vibrational modes, indicating the presence of two cations in the trigonal Mg{sub x}Mn{sub (1-x)}(BH{sub 4}){sub 2} solid solutions, as well as the appearance of a second phase, hexagonal {alpha}-Mg(BH{sub 4}){sub 2}, at higher magnesium contents. All vibrational frequencies are shifted to higher values with increasing magnesium content. The decomposition temperature of the trigonal Mg{sub x}Mn{sub (1-x)}(BH{sub 4}){sub 2} (x = 0-0.8) does not vary significantly as a function of the magnesium

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

    National Research Council Canada - National Science Library

    Tang, Dean; Liu, Junwei

    2005-01-01

    ... (death, survival, proliferation/division, etc.). Our hypothesis is that, under normal, unstimulated conditions, with its apoptotic function blocked, the upregulated Bim in PCa cells plays an apoptosis-independent function...

  8. Interference with the HSF1/HSP70/BAG3 Pathway Primes Glioma Cells to Matrix Detachment and BH3 Mimetic-Induced Apoptosis.

    Science.gov (United States)

    Antonietti, Patrick; Linder, Benedikt; Hehlgans, Stephanie; Mildenberger, Iris C; Burger, Michael C; Fulda, Simone; Steinbach, Joachim P; Gessler, Florian; Rödel, Franz; Mittelbronn, Michel; Kögel, Donat

    2017-01-01

    Malignant gliomas exhibit a high intrinsic resistance against stimuli triggering apoptotic cell death. HSF1 acts as transcription factor upstream of HSP70 and the HSP70 co-chaperone BAG3 that is overexpressed in glioblastoma. To specifically target this resistance mechanism, we applied the selective HSF1 inhibitor KRIBB11 and the HSP70/BAG3 interaction inhibitor YM-1 in combination with the pan-Bcl-2 inhibitor AT-101. Here, we demonstrate that lentiviral BAG3 silencing significantly enhances AT-101-induced cell death and reactivates effector caspase-mediated apoptosis in U251 glioma cells with high BAG3 expression, whereas these sensitizing effects were less pronounced in U343 cells expressing lower BAG3 levels. KRIBB11 decreased protein levels of HSP70, BAG3, and the antiapoptotic Bcl-2 protein Mcl-1, and both KRIBB11 and YM-1 elicited significantly increased mitochondrial dysfunction, effector caspase activity, and apoptotic cell death after combined treatment with AT-101 and ABT-737. Depletion of BAG3 also led to a pronounced loss of cell-matrix adhesion, FAK phosphorylation, and in vivo tumor growth in an orthotopic mouse glioma model. Furthermore, it reduced the plating efficiency of U251 cells in three-dimensional clonogenic assays and limited clonogenic survival after short-term treatment with AT-101. Collectively, our data suggest that the HSF1/HSP70/BAG3 pathway plays a pivotal role for overexpression of prosurvival Bcl-2 proteins and cell death resistance of glioma. They also support the hypothesis that interference with BAG3 function is an effective novel approach to prime glioma cells to anoikis. Mol Cancer Ther; 16(1); 156-68. ©2016 AACR. ©2016 American Association for Cancer Research.

  9. The role of the BH3-only protein Noxa in bone homeostasis.

    Science.gov (United States)

    Idrus, Erik; Nakashima, Tomoki; Wang, Ling; Hayashi, Mikihito; Okamoto, Kazuo; Kodama, Tatsuhiko; Tanaka, Nobuyuki; Taniguchi, Tadatsugu; Takayanagi, Hiroshi

    2011-07-08

    Bone homeostasis is maintained by a dynamic balance between bone resorption by osteoclasts and bone formation by osteoblasts. Since excessive osteoclast activity is implicated in pathological bone resorption, understanding the mechanism underlying osteoclast differentiation, function and survival is of both scientific and clinical importance. Osteoclasts are monocyte/macrophage lineage cells with a short life span that undergo rapid apoptosis, the rate of which critically determines the level of bone resorption in vivo. However, the molecular basis of rapid osteoclast apoptosis remains obscure. Here we report the role of a BH3-only protein, Noxa (encoded by the Pmaip1 gene), in bone homeostasis using Noxa-deficient mice. Among the Bcl-2 family members, Noxa was selectively induced during osteoclastogenesis. Mice lacking Noxa exhibit a severe osteoporotic phenotype due to an increased number of osteoclasts. Noxa deficiency did not have any effect on the number of osteoclast precursor cells or the expression of osteoclast-specific genes, but led to a prolonged survival of osteoclasts. Furthermore, adenovirus-mediated Noxa overexpression remarkably reduced bone loss in a model of inflammation-induced bone destruction. This study reveals Noxa to be a crucial regulator of osteoclast apoptosis, and may provide a molecular basis for a new therapeutic approach to bone diseases. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. A single nucleotide polymorphism in cBIM is associated with a slower achievement of major molecular response in chronic myeloid leukaemia treated with imatinib.

    Directory of Open Access Journals (Sweden)

    Vanessa Augis

    Full Text Available BIM is essential for the response to tyrosine-kinase inhibitors (TKI in chronic myeloid leukaemia (CML patients. Recently, a deletion polymorphism in intron 2 of the BIM gene was demonstrated to confer an intrinsic TKI resistance in Asian patients. The present study aimed at identifying mutations in the BIM sequence that could lead to imatinib resistance independently of BCR-ABL mutations.BIM coding sequence analysis was performed in 72 imatinib-treated CML patients from a French population of our centre and in 29 healthy controls (reference population as a case-control study. Real-time quantitative PCR (RT qPCR was performed to assess Bim expression in our reference population.No mutation with amino-acid change was found in the BIM coding sequence. However, we observed a silent single nucleotide polymorphism (SNP c465C>T (rs724710. A strong statistical link was found between the presence of the T allele and the high Sokal risk group (p = 0.0065. T allele frequency was higher in non responsive patients than in the reference population (p = 0.0049. Similarly, this T allele was associated with the mutation frequency on the tyrosine kinase domain of BCR-ABL (pT SNP of BIM could be useful for predicting the outcome of imatinib-treated CML patients.

  11. Interactions of Bio-Inspired Membranes with Peptides and Peptide-Mimetic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Michael Sebastiano

    2015-08-01

    Full Text Available Via Dissipative Particle Dynamics (DPD and implicit solvent coarse-grained (CG Molecular Dynamics (MD we examine the interaction of an amphiphilic cell-penetrating peptide PMLKE and its synthetic counterpart with a bio-inspired membrane. We use the DPD technique to investigate the interaction of peptide-mimetic nanoparticles, or nanopins, with a three-component membrane. The CG MD approach is used to investigate the interaction of a cell-penetrating peptide PMLKE with single-component membrane. We observe the spontaneous binding and subsequent insertion of peptide and nanopin in the membrane by using CG MD and DPD approaches, respectively. In addition, we find that the insertion of peptide and nanopins is mainly driven by the favorable enthalpic interactions between the hydrophobic components of the peptide, or nanopin, and the membrane. Our study provides insights into the mechanism underlying the interactions of amphiphilic peptide and peptide-mimetic nanoparticles with a membrane. The result of this study can be used to guide the functional integration of peptide and peptide-mimetic nanoparticles with a cell membrane.

  12. Potential and Benefits of Building Information Modeling (BIM During Pre-Construction, Construction and Post Construction Stage

    Directory of Open Access Journals (Sweden)

    Aw Nien Wei

    2017-11-01

    Full Text Available The construction industry is the main economic support for all countries around the world in which continually adapting to meet competitive challenges around the global market. Nevertheless, the construction project is becoming much more complex and difficult to manage. This is because the construction project involves a large number of stakeholder, for example, the consultant companies, architects, engineers, building surveyors and quantity surveyors. The technology currently used in the construction industry is the AutoCAD (Automatic computeraided design. AutoCAD is a commercial software application for 2D and 3D computer-aided design (CAD and drafting develop by Autodesk. Generally, all the drawing design from Autocad will be exchanged among the stakeholder in the form of paper. Information exchanged among them mostly involves a lot of documents and drawings. This practice creates errors because of documents and drawings are mostly in a paper-based format that is not properly managed which results in miscommunication among them. Having wrong information in the construction process could hinder the productivity of projects because in a construction project information is one of the important construction materials. Building Information Modeling (BIM is one of the newly software in the architecture, engineering, and construction (AEC industries to ensure all parties receive the right information. BIM technology is also an intelligent model of a building constructed digitally in the way of 3D. The software will generate model containing the information needed to support the construction, fabrication, and procurement activities that needed to realize the building. This paper will discuss on potential and benefits of BIM during pre-construction stage, construction stage and during post construction stage

  13. HDL mimetic CER-001 targets atherosclerotic plaques in patients.

    Science.gov (United States)

    Zheng, Kang He; van der Valk, Fleur M; Smits, Loek P; Sandberg, Mara; Dasseux, Jean-Louis; Baron, Rudi; Barbaras, Ronald; Keyserling, Constance; Coolen, Bram F; Nederveen, Aart J; Verberne, Hein J; Nell, Thijs E; Vugts, Danielle J; Duivenvoorden, Raphaël; Fayad, Zahi A; Mulder, Willem J M; van Dongen, Guus A M S; Stroes, Erik S G

    2016-08-01

    Infusion of high-density lipoprotein (HDL) mimetics aimed at reducing atherosclerotic burden has led to equivocal results, which may relate in part to the inability of HDL mimetics to adequately reach atherosclerotic lesions in humans. This study evaluated delivery of recombinant human apolipoprotein A-I (apoA-I) containing HDL mimetic CER-001 in carotid plaques in patients. CER-001 was radiolabeled with the long-lived positron emitter zirconium-89 ((89)Zr) to enable positron emission tomography with computed tomography (PET/CT) imaging. Eight patients with atherosclerotic carotid artery disease (>50% stenosis) received a single infusion of unlabeled CER-001 (3 mg/kg), co-administered with 10 mg of (89)Zr-labeled CER-001 (18 MBq). Serial PET/CT imaging and contrast enhanced-magnetic resonance imaging (CE-MRI) were performed to evaluate targeted delivery of CER-001. One hour after infusion, mean plasma apoA-I levels increased by 9.9 mg/dL (p = 0.026), with a concomitant relative increase in the plasma cholesterol efflux capacity of 13.8% (p CER-001 expressed as target-to-background ratio (TBRmax) increased significantly 24 h after infusion, and remained increased up to 48 h (TBRmax t = 10 min: 0.98; t = 24 h: 1.14 (p = 0.001); t = 48 h: 1.12 (p = 0.007)). TBRmax was higher in plaque compared with non-plaque segments (1.18 vs. 1.05; p CER-001 increases plasma apoA-I concentration and plasma cholesterol efflux capacity. Our data support the concept that CER-001 targets plaque regions in patients, which correlates with plaque contrast enhancement. These clinical findings may also guide future nanomedicine development using HDL particles for drug delivery in atherosclerosis. Netherlands Trial Registry - NTR5178. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5178. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  14. Bim and Mcl-1 exert key roles in regulating JAK2V617F cell survival

    International Nuclear Information System (INIS)

    Rubert, Joëlle; Qian, Zhiyan; Andraos, Rita; Guthy, Daniel A; Radimerski, Thomas

    2011-01-01

    The JAK2 V617F mutation plays a major role in the pathogenesis of myeloproliferative neoplasms and is found in the vast majority of patients suffering from polycythemia vera and in roughly every second patient suffering from essential thrombocythemia or from primary myelofibrosis. The V617F mutation is thought to provide hematopoietic stem cells and myeloid progenitors with a survival and proliferation advantage. It has previously been shown that activated JAK2 promotes cell survival by upregulating the anti-apoptotic STAT5 target gene Bcl-xL. In this study, we have investigated the role of additional apoptotic players, the pro-apoptotic protein Bim as well as the anti-apoptotic protein Mcl-1. Pharmacological inhibition of JAK2/STAT5 signaling in JAK2 V617F mutant SET-2 and MB-02 cells was used to study effects on signaling, cell proliferation and apoptosis by Western blot analysis, WST-1 proliferation assays and flow cytometry. Cells were transfected with siRNA oligos to deplete candidate pro- and anti-apoptotic proteins. Co-immunoprecipitation assays were performed to assess the impact of JAK2 inhibition on complexes of pro- and anti-apoptotic proteins. Treatment of JAK2 V617F mutant cell lines with a JAK2 inhibitor was found to trigger Bim activation. Furthermore, Bim depletion by RNAi suppressed JAK2 inhibitor-induced cell death. Bim activation following JAK2 inhibition led to enhanced sequestration of Mcl-1, besides Bcl-xL. Importantly, Mcl-1 depletion by RNAi was sufficient to compromise JAK2 V617F mutant cell viability and sensitized the cells to JAK2 inhibition. We conclude that Bim and Mcl-1 have key opposing roles in regulating JAK2 V617F cell survival and propose that inactivation of aberrant JAK2 signaling leads to changes in Bim complexes that trigger cell death. Thus, further preclinical evaluation of combinations of JAK2 inhibitors with Bcl-2 family antagonists that also tackle Mcl-1, besides Bcl-xL, is warranted to assess the therapeutic potential

  15. Federal Act on Protection against Nuisances (BImSchG) and supplementing regulations. 11. ed.

    International Nuclear Information System (INIS)

    Hansmann, K.

    1993-01-01

    This handy booklet contains the BImSchG and related implementing regulations as well as the Technical Codes Clean Air and Noise Abatement. The contribution on the BImSchG explains the origin of the Act, the scope of application, its concept and principles. The contents of the Act is portrayed by emphasizing subject-related connections. Dealt with are also regulations for installations requiring licensing, the measurement of airborne pollution, stipulations concerning the area of installations and transport, as well as the regulation concerning the monitoring of airborne pollution in the Federal Republic of Germany. (orig.) [de

  16. BIM som Informationsbärare in i Förvaltningen : En studie vid Forsmarks Kraftgrupp

    OpenAIRE

    Svens, Therése

    2013-01-01

    BIM, Building Information Modeling, börjar vinna mark inom byggbranschen i Sverige och är en vedertagen process i vart och vartannat byggprojekt. Forsmarks Kraftgrupp står inför både upprustningar av sina anläggningar och nyproduktion av bland annat kontor, verkstad och hotell. BIM framstår nu som en lukrativ metod för att dra ner på projektkostnaderna, men även för att få ytterligare ordning och struktur på den enorma mängd dokumentation som ackumulerat under de dryga trettio åren av drift. ...

  17. Federal Act on Protection against Nuisances (BImSchG) and supplementing regulations. 9. ed.

    International Nuclear Information System (INIS)

    Hansmann, K.

    1992-01-01

    This handy booklet contains the BImSchG and related implementing regulations as well as the Technical Codes Clean Air and Noise Abatement. The contribution on the BImSchG explains the origin of the Act, the scope of application, its concept and principles. The contents of the Act is portrayed by emphasizing subject-related connections. Dealt with are also regulations for installations requiring licensing, the measurement of airborne pollution, stipulations concerning the area of installations and transport, as well as the regulation concerning the monitoring of airborne pollution in the Federal Republic of Germany. (orig.) [de

  18. Deciphering the molecular events necessary for synergistic tumor cell apoptosis mediated by the histone deacetylase inhibitor vorinostat and the BH3 mimetic ABT-737

    NARCIS (Netherlands)

    Wiegmans, Adrian P.; Alsop, Amber E.; Bots, Michael; Cluse, Leonie A.; Williams, Steven P.; Banks, Kellie-Marie; Ralli, Rachael; Scott, Clare L.; Frenzel, Anna; Villunger, Andreas; Johnstone, Ricky W.

    2011-01-01

    The concept of personalized anticancer therapy is based on the use of targeted therapeutics through in-depth knowledge of the molecular mechanisms of action of these agents when used alone and in combination. We have identified the apoptotic proteins and pathways necessary for synergistic tumor cell

  19. Dual stimuli-sensitive dendrimers: Photothermogenic gold nanoparticle-loaded thermo-responsive elastin-mimetic dendrimers.

    Science.gov (United States)

    Fukushima, Daichi; Sk, Ugir Hossain; Sakamoto, Yasuhiro; Nakase, Ikuhiko; Kojima, Chie

    2015-08-01

    Dendrimers are synthetic macromolecules with unique structures that can work as nanoplatforms for both photothermogenic gold nanoparticles (AuNPs) and thermosensitive elastin-like peptides (ELPs) with valine-proline-glycine-valine-glycine (VPGVG) repeats. In this study, photothermogenic AuNPs were loaded into thermo-responsive elastin-mimetic dendrimers (dendrimers conjugating ELPs at their periphery) to produce dual stimuli-sensitive nanoparticles. Polyamidoamine G4 dendrimers were modified with acetylated VPGVG and (VPGVG)2, and the resulting materials were named ELP1-den and ELP2-den, respectively. The AuNPs were prepared by the reduction of Au ions using a dendrimer-nanotemplated method. The AuNP-loaded elastin-mimetic dendrimers exhibited photothermal properties. ELP1-den and ELP2-den showed similar temperature-dependent changes in their conformations. Phase transitions were observed at around 55°C and 35°C for the AuNP-loaded ELP1-den and AuNP-loaded ELP2-den, respectively, but not for the corresponding PEGylated dendrimer. In contrast to the AuNP-loaded PEGylated dendrimer, AuNP-loaded ELP2-den readily associated with cells and induced efficient photocytotoxicity at 37°C. The cell association and the photocytotoxicity properties of AuNP-loaded ELP2-den could be controlled by temperature. These results therefore suggest that dual stimuli-sensitive dendrimer nanoparticles of this type could be used for photothermal therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Hydrolysis and regeneration of sodium borohydride (NaBH4) - A combination of hydrogen production and storage

    Science.gov (United States)

    Chen, W.; Ouyang, L. Z.; Liu, J. W.; Yao, X. D.; Wang, H.; Liu, Z. W.; Zhu, M.

    2017-08-01

    Sodium borohydride (NaBH4) hydrolysis is a promising approach for hydrogen generation, but it is limited by high costs, low efficiency of recycling the by-product, and a lack of effective gravimetric storage methods. Here we demonstrate the regeneration of NaBH4 by ball milling the by-product, NaBO2·2H2O or NaBO2·4H2O, with MgH2 at room temperature and atmospheric pressure without any further post-treatment. Record yields of NaBH4 at 90.0% for NaBO2·2H2O and 88.3% for NaBO2·4H2O are achieved. This process also produces hydrogen from the splitting of coordinate water in hydrated sodium metaborate. This compensates the need for extra hydrogen for generating MgH2. Accordingly, we conclude that our unique approach realizes an efficient and cost-effective closed loop system for hydrogen production and storage.

  1. Archive of digital chirp subbottom profile data collected during USGS cruises 13BIM02 and 13BIM07 offshore of the Chandeleur Islands, Louisiana, 2013

    Science.gov (United States)

    Forde, Arnell S.; Miselis, Jennifer L.; Flocks, James G.; Bernier, Julie C.; Wiese, Dana S.

    2014-01-01

    On July 5–19 (cruise 13BIM02) and August 22–September 1 (cruise 13BIM07), 2013, the U.S. Geological Survey (USGS) conducted geophysical surveys to investigate the geologic controls on barrier island evolution and medium-term and interannual sediment transport along the oil spill mitigation sand berm constructed at the north end and offshore of the Chandeleur Islands, Louisiana. This investigation is part of a broader USGS study, which seeks to understand barrier island evolution better over medium time scales (months to years). This report serves as an archive of unprocessed digital chirp subbottom data, trackline maps, navigation files, Geographic Information System (GIS) files, Field Activity Collection System (FACS) logs, and formal Federal Geographic Data Committee (FGDC) metadata. Gained–showing a relative increase in signal amplitude–digital images of the seismic profiles are provided. Refer to the Abbreviations page for explanations of acronyms and abbreviations used in this report.

  2. Effect of fat level on the perception of five flavor chemicals in ice cream with or without fat mimetics by using a descriptive test.

    Science.gov (United States)

    Liou, B K; Grün, I U

    2007-10-01

    Fat mimetics are commonly used in the manufacture of low-fat and fat-free ice creams. However, the use of fat mimetics affects flavor and texture characteristics of ice cream, which results in decreased overall acceptability by consumers. The initial objective of this study was to investigate the release behavior of 5 strawberry flavor compounds in ice creams with Simplesse((R)), Litesse((R)), and Litesse((R))/Simplesse((R)) mixes using descriptive analysis. Fat mimetics and flavor formulation significantly influenced the perception of Furaneoltrade mark (cooked sugar flavor), alpha-ionone (violet flavor), and gamma-undecalactone (peach flavor), but there was no interaction between ice cream type and flavor formulation for the 3 flavors. Furaneol and ethyl-3-methyl-3-phenylglycidate (candy flavor) were perceived more strongly in full-fat ice cream, while cis-3-hexen-1-ol (grassy flavor), alpha-ionone, and gamma-undecalactone were perceived more strongly in low-fat ice cream. Ice creams with Simplesse and full-fat ice cream had similar sensory characteristics, while ice creams with Litesse were similar to low-fat ice creams in flavor characteristics, and ice creams with Litesse/Simplesse mixes were closer in flavor profile to low-fat ice cream but had similar texture properties to those of full-fat ice cream. Simplesse was found to be a better fat mimetic for duplicating the flavor profiles and mouthfeel of full-fat ice cream.

  3. Evaluating The Impact Of Building Information Modeling (BIM) On Construction

    Science.gov (United States)

    2009-01-01

    and interrelated processes. The flowchart in Figure 4-26 shows a visual interpretation of the Project Delivery Process Map. Figure 4-26. PMBP...they participated in training that was not effective at the beginning of LRL’s BIM initiative. The beginner courses provided by Bentley proved to be

  4. Mimetics of Suppressor of cytokine signalling 3: novel potential therapeutics in triple breast cancer.

    Science.gov (United States)

    La Manna, Sara; Lee, Eunmi; Ouzounova, Maria; Di Natale, Concetta; Novellino, Ettore; Merlino, Antonello; Korkaya, Hasan; Marasco, Daniela

    2018-05-11

    Suppressor of cytokine signaling (SOCS) family of proteins plays critical role in the regulation of immune responses controlling JAK/STAT mediated inflammatory cytokines. Among the members, SOCS1 and SOCS3 contain a kinase inhibitory region (KIR) and SOCS3 binds to JAK/STAT/gp130 complex by inhibiting the downstream signaling and suppressing inflammatory cytokines. Loss or reduced levels of SOCS3 have been linked to cancer-associated inflammation and suppressive immunity leading to enhanced tumour growth and metastasis. In line with these reports, we previously demonstrated that proteolytic degradation of SOCS3 in triple negative breast cancer (TNBC) subtype drives the expression of inflammatory cytokines. Therefore, we postulated that SOCS3 mimetics might suppress the inflammatory cytokine production in TNBC subtype and inhibit tumor growth and metastasis. Here we designed and characterized five linear peptides derived from the N-terminal region of SOCS3 encompassing regions that interface with the JAK2/gp130 complex by using the Circular Dichroism and Surface Plasmon Resonance spectroscopies. The KIRESS peptide resulted the sequence containing the most part of the hot-spots required for binding to JAK2 and was further investigated in vivo in mouse xenografts of MDA-MB-231-luci tumours as models of human TNBC subtype. Expectedly, this peptide showed a significant inhibition of primary tumour growth and pulmonary metastasis. Our studies suggest that SOCS3 peptidomimetics may possess a therapeutic potential in aggressive cancers, such as TNBC subtype, with activated inflammatory cytokines. This article is protected by copyright. All rights reserved. © 2018 UICC.

  5. Regression of coronary atherosclerosis with infusions of the high-density lipoprotein mimetic CER-001 in patients with more extensive plaque burden.

    Science.gov (United States)

    Kataoka, Yu; Andrews, Jordan; Duong, MyNgan; Nguyen, Tracy; Schwarz, Nisha; Fendler, Jessica; Puri, Rishi; Butters, Julie; Keyserling, Constance; Paolini, John F; Dasseux, Jean-Louis; Nicholls, Stephen J

    2017-06-01

    CER-001 is an engineered pre-beta high-density lipoprotein (HDL) mimetic, which rapidly mobilizes cholesterol. Infusion of CER-001 3 mg/kg exhibited a potentially favorable effect on plaque burden in the CHI-SQUARE (Can HDL Infusions Significantly Quicken Atherosclerosis Regression) study. Since baseline atheroma burden has been shown as a determinant for the efficacy of HDL infusions, the degree of baseline atheroma burden might influence the effect of CER-001. CHI-SQUARE compared the effect of 6 weekly infusions of CER-001 (3, 6 and 12 mg/kg) vs. placebo on coronary atherosclerosis in 369 patients with acute coronary syndrome (ACS) using serial intravascular ultrasound (IVUS). Baseline percent atheroma volume (B-PAV) cutoff associated with atheroma regression following CER-001 infusions was determined by receiver-operating characteristics curve analysis. 369 subjects were stratified according to the cutoff. The effect of CER-001 at different doses was compared to placebo in each group. A B-PAV ≥30% was the optimal cutoff associated with PAV regression following CER-001 infusions. CER-001 induced PAV regression in patients with B-PAV ≥30% but not in those with B-PAV CER-001 3mg/kg in patients with B-PAV ≥30% (-0.96%±0.34% vs. -0.25%±0.31%, P=0.01), whereas there were no differences between placebo (+0.09%±0.36%) versus CER-001 in patients with B-PAV CER-001 3 mg/kg induced the greatest atheroma regression in ACS patients with higher B-PAV. These findings identify ACS patients with more extensive disease as most likely to benefit from HDL mimetic therapy.

  6. Novel thrombopoietin mimetic peptides bind c-Mpl receptor: Synthesis, biological evaluation and molecular modeling.

    Science.gov (United States)

    Liu, Yaquan; Tian, Fang; Zhi, Dejuan; Wang, Haiqing; Zhao, Chunyan; Li, Hongyu

    2017-02-01

    Thrombopoietin (TPO) acts in promoting the proliferation of hematopoietic stem cells and by initiating specific maturation events in megakaryocytes. Now, TPO-mimetic peptides with amino acid sequences unrelated to TPO are of considerable pharmaceutical interest. In the present paper, four new TPO mimetic peptides that bind and activate c-Mpl receptor have been identified, synthesized and tested by Dual-Luciferase reporter gene assay for biological activities. The molecular modeling research was also approached to understand key molecular mechanisms and structural features responsible for peptide binding with c-Mpl receptor. The results presented that three of four mimetic peptides showed significant activities. In addition, the molecular modeling approaches proved hydrophobic interactions were the driven positive forces for binding behavior between peptides and c-Mpl receptor. TPO peptide residues in P7, P13 and P7' positions were identified by the analysis of hydrogen bonds and energy decompositions as the key ones for benefiting better biological activities. Our data suggested the synthesized peptides have considerable potential for the future development of stable and highly active TPO mimetic peptides. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Comparative Allometric Growth of the Mimetic Ephippid Reef Fishes Chaetodipterus faber and Platax orbicularis.

    Directory of Open Access Journals (Sweden)

    Breno Barros

    Full Text Available Mimesis is a relatively widespread phenomenon among reef fish, but the ontogenetic processes relevant for mimetic associations in fish are still poorly understood. In the present study, the allometric growth of two allopatric leaf-mimetic species of ephippid fishes, Chaetodipterus faber from the Atlantic and Platax orbicularis from the Indo-Pacific, was analyzed using ten morphological variables. The development of fins was considered owing to the importance of these structures for mimetic behaviors during early life stages. Despite the anatomical and behavioral similarities in both juvenile and adult stages, C. faber and P. orbicularis showed distinct patterns of growth. The overall shape of C. faber transforms from a rounded-shape in mimetic juveniles to a lengthened profile in adults, while in P. orbicularis, juveniles present an oblong profile including dorsal and anal fins, with relative fin size diminishing while the overall profile grows rounder in adults. Although the two species are closely-related, the present results suggest that growth patterns in C. faber and P. orbicularis are different, and are probably independent events in ephippids that have resulted from similar selective processes.

  8. Measurement of 3H in soil cores from the Hyrax Event (U3bh) subsidence crater

    Energy Technology Data Exchange (ETDEWEB)

    Kreek, S.; Hudson, G.B.; Ruth, M.

    1996-07-01

    Core samples were collected from two boreholes drilled in the subsidence crater of the Hyrax event (U3bh). The moisture in the core samples was extracted via freeze drying and tritiw-n was measured in the extracted moisture via `He accumulation mass spectrometry or liquid scintillation counting. Elevated tritium concentrations (IE4 - IE6 pCi/L extracted moisture as of the time of measurement) were observed in the extracted moisture from virtually all of the core samples with significant increases beginning at about 30 ft depth. No longer-lived fission products (144 Ce) or activation products (`OCo, `Eu, 114 En) were observed by gamma-ray spectroscopy in a subset of the core samples. This likely indicates that a catastrophic failure of containment (if it occurred) did not release significant radioactivities to this shallow depth (30 ft). The presence of `Cs at much greater depths (@210 ft, 64 m) may indicate that gaseous and/or vapor products were released shortly after the Hyrax event to a depth of about 210 ft. The relatively shallow depth where the elevated tritium is observed makes highly improbable any significant linkage between the elevated tritium concentrations and a Hyrax event containment failure. This may indicate that an additional source of enriched `H was introduced at this site.

  9. A BIM-based system for demolition and renovation waste estimation and planning.

    Science.gov (United States)

    Cheng, Jack C P; Ma, Lauren Y H

    2013-06-01

    Due to the rising worldwide awareness of green environment, both government and contractors have to consider effective construction and demolition (C&D) waste management practices. The last two decades have witnessed the growing importance of demolition and renovation (D&R) works and the growing amount of D&R waste disposed to landfills every day, especially in developed cities like Hong Kong. Quantitative waste prediction is crucial for waste management. It can enable contractors to pinpoint critical waste generation processes and to plan waste control strategies. In addition, waste estimation could also facilitate some government waste management policies, such as the waste disposal charging scheme in Hong Kong. Currently, tools that can accurately and conveniently estimate the amount of waste from construction, renovation, and demolition projects are lacking. In the light of this research gap, this paper presents a building information modeling (BIM) based system that we have developed for estimation and planning of D&R waste. BIM allows multi-disciplinary information to be superimposed within one digital building model. Our system can extract material and volume information through the BIM model and integrate the information for detailed waste estimation and planning. Waste recycling and reuse are also considered in our system. Extracted material information can be provided to recyclers before demolition or renovation to make recycling stage more cooperative and more efficient. Pick-up truck requirements and waste disposal charging fee for different waste facilities will also be predicted through our system. The results could provide alerts to contractors ahead of time at project planning stage. This paper also presents an example scenario with a 47-floor residential building in Hong Kong to demonstrate our D&R waste estimation and planning system. As the BIM technology has been increasingly adopted in the architectural, engineering and construction industry

  10. THE M bh-σ DIAGRAM AND THE OFFSET NATURE OF BARRED ACTIVE GALAXIES

    International Nuclear Information System (INIS)

    Graham, Alister W.; Li Ihui

    2009-01-01

    From a sample of 50 predominantly inactive galaxies with direct supermassive black hole mass measurements, it has recently been established that barred galaxies tend to reside rightward of the M bh -σ relation defined by nonbarred galaxies. Either black holes in barred galaxies tend to be anemic or the central velocity dispersions in these galaxies have a tendency to be elevated by the presence of the bar. The latter option is in accord with studies connecting larger velocity dispersions in galaxies with old bars, while the former scenario is at odds with the observation that barred galaxies do not deviate from the M bh -luminosity relation. Using a sample of 88 galaxies with active galactic nuclei, whose supermassive black hole masses have been estimated from their associated emission lines, we reveal for the first time that they also display this same general behavior in the M bh -σ diagram depending on the presence of a bar or not. A new symmetrical and nonsymmetrical 'barless' M bh -σ relation is derived using 82 nonbarred galaxies. The barred galaxies are shown to reside on or up to ∼1 dex below this relation. This may explain why narrow-line Seyfert 1 galaxies appear offset from the 'barless' M bh -σ relation, and has far-reaching implications given that over half of the disk galaxy population are barred.

  11. Gemini spectroscopy of the outer disk star cluster BH176

    Science.gov (United States)

    Sharina, M. E.; Donzelli, C. J.; Davoust, E.; Shimansky, V. V.; Charbonnel, C.

    2014-10-01

    Context. BH176 is an old metal-rich star cluster. It is spatially and kinematically consistent with belonging to the Monoceros Ring. It is larger in size and more distant from the Galactic plane than typical open clusters, and it does not belong to the Galactic bulge. Aims: Our aim is to determine the origin of this unique object by accurately determining its distance, metallicity, and age. The best way to reach this goal is to combine spectroscopic and photometric methods. Methods: We present medium-resolution observations of red clump and red giant branch stars in BH176 obtained with the Gemini South Multi-Object Spectrograph. We derive radial velocities, metallicities, effective temperatures, and surface gravities of the observed stars and use these parameters to distinguish member stars from field objects. Results: We determine the following parameters for BH176: Vh = 0 ± 15 km s-1, [Fe/H] = -0.1 ± 0.1, age 7 ± 0.5 Gyr, E(V - I) = 0.79 ± 0.03, distance 15.2 ± 0.2 kpc, α-element abundance [α/Fe] ~ 0.25 dex (the mean of [Mg/Fe], and [Ca/Fe]). Conclusions: BH176 is a member of old Galactic open clusters that presumably belong to the thick disk. It may have originated as a massive star cluster after the encounter of the forming thin disk with a high-velocity gas cloud or as a satellite dwarf galaxy. Appendix A is available in electronic form at http://www.aanda.org

  12. Anoikis evasion in inflammatory breast cancer cells is mediated by Bim-EL sequestration.

    Science.gov (United States)

    Buchheit, C L; Angarola, B L; Steiner, A; Weigel, K J; Schafer, Z T

    2015-08-01

    Inflammatory breast cancer (IBC) is a rare and highly invasive type of breast cancer, and patients diagnosed with IBC often face a very poor prognosis. IBC is characterized by the lack of primary tumor formation and the rapid accumulation of cancerous epithelial cells in the dermal lymphatic vessels. Given that normal epithelial cells require attachment to the extracellular matrix (ECM) for survival, a comprehensive examination of the molecular mechanisms underlying IBC cell survival in the lymphatic vessels is of paramount importance to our understanding of IBC pathogenesis. Here we demonstrate that, in contrast to normal mammary epithelial cells, IBC cells evade ECM-detachment-induced apoptosis (anoikis). ErbB2 and EGFR knockdown in KPL-4 and SUM149 cells, respectively, causes decreased colony growth in soft agar and increased caspase activation following ECM detachment. ERK/MAPK signaling was found to operate downstream of ErbB2 and EGFR to protect cells from anoikis by facilitating the formation of a protein complex containing Bim-EL, LC8, and Beclin-1. This complex forms as a result of Bim-EL phosphorylation on serine 59, and thus Bim-EL cannot localize to the mitochondria and cause anoikis. These results reveal a novel mechanism that could be targeted with innovative therapeutics to induce anoikis in IBC cells.

  13. Automated Classification of Heritage Buildings for As-Built Bim Using Machine Learning Techniques

    Science.gov (United States)

    Bassier, M.; Vergauwen, M.; Van Genechten, B.

    2017-08-01

    Semantically rich three dimensional models such as Building Information Models (BIMs) are increasingly used in digital heritage. They provide the required information to varying stakeholders during the different stages of the historic buildings life cyle which is crucial in the conservation process. The creation of as-built BIM models is based on point cloud data. However, manually interpreting this data is labour intensive and often leads to misinterpretations. By automatically classifying the point cloud, the information can be proccesed more effeciently. A key aspect in this automated scan-to-BIM process is the classification of building objects. In this research we look to automatically recognise elements in existing buildings to create compact semantic information models. Our algorithm efficiently extracts the main structural components such as floors, ceilings, roofs, walls and beams despite the presence of significant clutter and occlusions. More specifically, Support Vector Machines (SVM) are proposed for the classification. The algorithm is evaluated using real data of a variety of existing buildings. The results prove that the used classifier recognizes the objects with both high precision and recall. As a result, entire data sets are reliably labelled at once. The approach enables experts to better document and process heritage assets.

  14. Integración de sensores medioambientales con BIM: casos de estudio usando Arduino, Dynamo, y Revit API

    OpenAIRE

    Kensek, K. M.

    2014-01-01

    This paper investigates the feasibility of connecting environmental sensors such as light, humidity, or CO2 receptors to a building information model (BIM). A base case was created in Rhino; using Grasshopper and Firefly, a simple digital model responded to lighting-levels detected by a photoresistor on an Arduino board. The case study was duplicated using Revit Architecture, a popular BIM software, and Dynamo, a visual programming environment, in an innovative application. Another case study...

  15. THE LICK AGN MONITORING PROJECT: THE M BH-σ* RELATION FOR REVERBERATION-MAPPED ACTIVE GALAXIES

    International Nuclear Information System (INIS)

    Woo, Jong-Hak; Treu, Tommaso; Bennert, Vardha N.; Barth, Aaron J.; Walsh, Jonelle L.; Bentz, Misty C.; Wright, Shelley A.; Filippenko, Alexei V.; Li, Weidong; Martini, Paul; Canalizo, Gabriela; Gates, Elinor; Greene, Jenny; Malkan, Matthew A.; Stern, Daniel; Minezaki, Takeo

    2010-01-01

    To investigate the black hole mass versus stellar velocity dispersion (M BH -σ * ) relation of active galaxies, we measured the velocity dispersions of a sample of local Seyfert 1 galaxies, for which we have recently determined black hole masses using reverberation mapping. For most objects, stellar velocity dispersions were measured from high signal-to-noise ratio optical spectra centered on the Ca II triplet region (∼8500 A), obtained at the Keck, Palomar, and Lick Observatories. For two objects, in which the Ca II triplet region was contaminated by nuclear emission, the measurement was based on high-quality H-band spectra obtained with the OH-Suppressing Infrared Imaging Spectrograph at the Keck-II telescope. Combining our new measurements with data from the literature, we assemble a sample of 24 active galaxies with stellar velocity dispersions and reverberation-based black hole mass measurements in the range of black hole mass 10 6 BH /M sun 9 . We use this sample to obtain reverberation-mapping constraints on the slope and intrinsic scatter of the M BH -σ * relation of active galaxies. Assuming a constant virial coefficient f for the reverberation-mapping black hole masses, we find a slope β = 3.55 ± 0.60 and the intrinsic scatter σ int = 0.43 ± 0.08 dex in the relation log(M BH /M sun ) = α + β log(σ * /200 km s -1 ), which are consistent with those found for quiescent galaxies. We derive an updated value of the virial coefficient f by finding the value which places the reverberation masses in best agreement with the M BH -σ * relation of quiescent galaxies; using the quiescent M BH -σ * relation determined by Gueltekin et al., we find log f = 0.72 +0.09 -0.10 with an intrinsic scatter of 0.44 ± 0.07 dex. No strong correlations between f and parameters connected to the physics of accretion (such as the Eddington ratio or line-shape measurements) are found. The uncertainty of the virial coefficient remains one of the main sources of the

  16. Applying Bim to Built Heritage with Complex Shapes: the Ice House of Filarete's Ospedale Maggiore in Milan, Italy

    Science.gov (United States)

    Oreni, D.; Karimi, G.; Barazzetti, L.

    2017-08-01

    This paper presents the development of a BIM model for a stratified historic structure characterized by a complex geometry: Filarete's Ospedale Maggiore ice house, one of the few remaining historic ice houses in Milan (Fig. 1). Filarete, a well-known Renaissance architect and theorist, planned the hospital in the 15th century, but the ice house was built two centuries later with a double-storey irregular octagonal brick structure, half under and half above ground, that enclosed another circular structure called the ice room. The purpose of the double-walled structure was to store ice in the middle and store and preserve perishable food and medicine at the outer side of the ice room. During World War II, major portions of the hospital and the above-ground section of the ice house was bombed and heavily damaged. Later, in 1962, the hospital was restored and rehabilitated into a university, with the plan to conceal the ice house's remaining structure in the courtyard, which ultimately was excavated and incorporated into a new library for the university. A team of engineers, architects, and students from Politecnico di Milano and Carleton University conducted two heritage recording surveys in 2015 and 2016 to fully document the existing condition of the ice house, resulting in an inclusive laser scanner and photogrammetric point cloud dataset. The point cloud data was consolidated and imported into two leading parametric modelling software, Autodesk Revitand Graphisoft ArchiCAD©, with the goal to develop two BIMs in parallel in order to study and compare the software BIM workflow, parametric capabilities, attributes to capture the complex geometry with high accuracy, and the duration for parametric modelling. The comparison study of the two software revealed their workflow limitations, leading to integration of the BIM generative process with other pure modelling software such as Rhinoceros©. The integrative BIM process led to the production of a comprehensive BIM

  17. Assessing Performance of Three BIM-Based Views of Buildings for Communication and Management of Vertically Stratified Legal Interests

    Directory of Open Access Journals (Sweden)

    Behnam Atazadeh

    2017-07-01

    Full Text Available Multistorey buildings typically include stratified legal interests which provide entitlements to a community of owners to lawfully possess private properties and use communal and public properties. The spatial arrangements of these legal interests are often defined by multiplexing cognitively outlined spaces and physical elements of a building. In order to support 3D digital management and communication of legal arrangements of properties, a number of spatial data models have been recently developed in Geographic Information Systems (GIS and Building Information Modelling (BIM domains. While some data models, such as CityGML, IndoorGML or IFC, provide a merely physical representation of the built environment, others, e.g., LADM, mainly rely on legal data elements to support a purely legal view of multistorey buildings. More recently, spatial data models integrating legal and physical notions of multistorey buildings have been proposed to overcome issues associated with purely legal models and purely physical ones. In previous investigations, it has been found that the 3D digital data environment of BIM has the flexibility to utilize either only physical elements or only legal spaces, or an integrated view of both legal spaces and physical elements to represent spatial arrangements of stratified legal interests. In this article, the performance of these three distinct BIM-based representations of legal interests defined inside multistorey buildings is assessed in the context of the Victorian jurisdiction of Australia. The assessment metrics are a number of objects and geometry batches, visualization speed in terms of frame rate, query time, modelling legal boundaries, and visual communication of legal boundaries.

  18. Apolipoprotein Mimetic Peptides: A New Approach for the Treatment of Asthma

    Directory of Open Access Journals (Sweden)

    Xianglan eYao

    2012-03-01

    Full Text Available New treatments are needed for severe asthmatics to improve disease control and avoid severe toxicities associated with oral corticosteroids. We have used a murine model of house dust mite (HDM-induced asthma to identify steroid-unresponsive genes that might represent targets for new therapeutic approaches for severe asthma. This strategy identified apolipoprotein E as a steroid-unresponsive gene with increased mRNA expression in the lungs of HDM-challenged mice. Furthermore, apolipoprotein E functioned as an endogenous negative regulator of airway hyperreactivity and goblet cell hyperplasia in experimental HDM-induced asthma. The ability of apolipoprotein E, which is expressed by lung macrophages, to attenuate AHR and goblet cell hyperplasia is mediated by low density lipoprotein (LDL receptors expressed by airway epithelial cells. Consistent with this, administration of an apolipoprotein E mimetic peptide, corresponding to amino acids 130 to 149 of the LDL receptor-binding domain of the holo-apoE protein, significantly reduced AHR and goblet cell hyperplasia in HDM-challenged apoE-/- mice. These findings identified the apolipoprotein E - LDL receptor pathway as a new druggable target for asthma that can be activated by administration of apoE mimetic peptides. Similarly, apolipoprotein A-I may have therapeutic potential in asthma based upon its anti-inflammatory, anti-oxidative and anti-fibrotic properties. Furthermore, administration of apolipoprotein A-I mimetic peptides has attenuated airway inflammation, airway remodeling and airway hyperreactivity in murine models of experimental asthma. Thus, site-directed delivery of inhaled apolipoprotein E or apolipoprotein A-I mimetic peptides may represent novel treatment approaches that can be developed for asthma, including severe disease.

  19. An Investigation on Some Benefits of BIM Application

    OpenAIRE

    Dalcı, Aliye

    2014-01-01

    ABSTRACT: Building Information Modeling (BIM) is a new technology in construction industry. It uses real-time models to increase efficiency and productivity in construction projects. With the help of this technology, projects can be completed on time and within budget. Client satisfaction is increased because the clients know what will be the end product during the design stage. Reworks can also be minimized due to better understanding of project and visualization ability. This thesis is ...

  20. Case04: BIM hos større entreprenør

    DEFF Research Database (Denmark)

    Vestergaard, Flemming; Karlshøj, Jan; Hauch, Peter

    Casen repræsenterer et koncept, hvor både byg- og driftsherren og en byg- og driftsherrerådgiver er aktive i anvendelsen af en BIM-orienteret arbejdsmetode og modelbaserede værktøjer, som omfatter følgende aktiviteter: Design, Projektering, Udbud/tilbud, produktionsforberedelse, Udførelse og Drift...

  1. Design for safety: theoretical framework of the safety aspect of BIM system to determine the safety index

    Directory of Open Access Journals (Sweden)

    Ai Lin Evelyn Teo

    2016-12-01

    Full Text Available Despite the safety improvement drive that has been implemented in the construction industry in Singapore for many years, the industry continues to report the highest number of workplace fatalities, compared to other industries. The purpose of this paper is to discuss the theoretical framework of the safety aspect of a proposed BIM System to determine a Safety Index. An online questionnaire survey was conducted to ascertain the current workplace safety and health situation in the construction industry and explore how BIM can be used to improve safety performance in the industry. A safety hazard library was developed based on the main contributors to fatal accidents in the construction industry, determined from the formal records and existing literature, and a series of discussions with representatives from the Workplace Safety and Health Institute (WSH Institute in Singapore. The results from the survey suggested that the majority of the firms have implemented the necessary policies, programmes and procedures on Workplace Safety and Health (WSH practices. However, BIM is still not widely applied or explored beyond the mandatory requirement that building plans should be submitted to the authorities for approval in BIM format. This paper presents a discussion of the safety aspect of the Intelligent Productivity and Safety System (IPASS developed in the study. IPASS is an intelligent system incorporating the buildable design concept, theory on the detection, prevention and control of hazards, and the Construction Safety Audit Scoring System (ConSASS. The system is based on the premise that safety should be considered at the design stage, and BIM can be an effective tool to facilitate the efforts to enhance safety performance. IPASS allows users to analyse and monitor key aspects of the safety performance of the project before the project starts and as the project progresses.

  2. Reducing agent (NaBH4) dependent structure, morphology and magnetic properties of nickel ferrite (NiFe2O4) nanorods

    International Nuclear Information System (INIS)

    Saravanakumar, B.; Rani, B. Jansi; Ravi, G.; Thambidurai, M.; Yuvakkumar, R.

    2017-01-01

    Nickel ferrite (Ni-Fe 2 O 4 ) nanorods were synthesized employing a simple chemical reduction method. Reducing agent (NaBH 4 ) influence on structural, morphological and magnetic properties of NiFe 2 O 4 nanorods was investigated. XRD results clearly revealed the presence of inverse cubic spinel nickel ferrite structure characteristic peaks and confirmed the site inversion of inverse spinel structure of Fe 3+ tetrahedral A site and Ni 2+ octahedral B site. The observed Raman characteristic peak at 488 and 683 cm −1 were corresponded to E 1 g and A 1 g mode whereas A and B site respectively corresponded to tetrahedral and octahedral site of NiFe 2 O 4 inverse spinel structure. The obtained PL peaks at 530 and 542 nm were attributed to the emission spectra of Fe 3+ ions in site A of inverse spinel structure and Ni 2+ ions in site B of inverse spinel structure respectively. SEM result clearly revealed that increase in NaBH 4 concentration had remarkable impact on nanorods formation, nano-octahedron structure, homogeneity and regularity of Ni-Ferrites. VSM studies clearly revealed the soft ferromagnetic nature of NiFe 2 O 4 and increase in NaBH 4 concentration further induced raise in metal cations concentration in A- and B- site which might impact the resultant magnetization of ferrites. - Highlights: • Nano rod formation has been initiated while increase of NaBH 4 concentration. • Further increasing NaBH 4 concentration favors nano-octahedron formation. • VSM studies revealed soft ferromagnetic nature of NiFe 2 O 4 .

  3. Copper Complexes of Nicotinic-Aromatic Carboxylic Acids as Superoxide Dismutase Mimetics

    Directory of Open Access Journals (Sweden)

    Virapong Prachayasittikul

    2008-12-01

    Full Text Available Nicotinic acid (also known as vitamin B3 is a dietary element essential for physiological and antihyperlipidemic functions. This study reports the synthesis of novel mixed ligand complexes of copper with nicotinic and other select carboxylic acids (phthalic, salicylic and anthranilic acids. The tested copper complexes exhibited superoxide dismutase (SOD mimetic activity and antimicrobial activity against Bacillus subtilis ATCC 6633, with a minimum inhibition concentration of 256 μg/mL. Copper complex of nicotinic-phthalic acids (CuNA/Ph was the most potent with a SOD mimetic activity of IC50 34.42 μM. The SOD activities were observed to correlate well with the theoretical parameters as calculated using density functional theory (DFT at the B3LYP/LANL2DZ level of theory. Interestingly, the SOD activity of the copper complex CuNA/Ph was positively correlated with the electron affinity (EA value. The two quantum chemical parameters, highest occupied molecular orbital (HOMO and lowest unoccupied molecular orbital (LUMO, were shown to be appropriate for understanding the mechanism of the metal complexes as their calculated energies show good correlation with the SOD activity. Moreover, copper complex with the highest SOD activity were shown to possess the lowest HOMO energy. These findings demonstrate a great potential for the development of value-added metallovitamin-based therapeutics.

  4. Peptide mimetic of the S100A4 protein modulates peripheral nerve regeneration and attenuates the progression of neuropathy in myelin protein P0 null mice

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Pinchenko, Volodymyr; Dmytriyeva, Oksana

    2013-01-01

    and mimicked the S100A4-induced neuroprotection in brain trauma. Here, we investigated a possible function of S100A4 and its mimetics in the pathologies of the peripheral nervous system (PNS). We found that S100A4 was expressed in the injured PNS and that its peptide mimetic (H3) affected the regeneration......, these effects were attributed to the modulatory effect of H3 on initial axonal sprouting. In contrast to the modest effect of H3 on the time course of regeneration, H3 had a long-term neuroprotective effect in the myelin protein P0 null mice, a model of dysmyelinating neuropathy (Charcot-Marie-Tooth type 1...... disease), where the peptide attenuated the deterioration of nerve conduction, demyelination and axonal loss. From these results, S100A4 mimetics emerge as a possible means to enhance axonal sprouting and survival, especially in the context of demyelinating neuropathies with secondary axonal loss...

  5. INCITE: A randomised trial comparing constraint induced movement therapy and bimanual training in children with congenital hemiplegia

    Directory of Open Access Journals (Sweden)

    Gilmore Rose

    2010-01-01

    Full Text Available Abstract Background Congenital hemiplegia is the most common form of cerebral palsy (CP accounting for 1 in 1300 live births. These children have limitations in capacity to use the impaired upper limb and bimanual coordination deficits which impact on daily activities and participation in home, school and community life. There are currently two diverse intensive therapy approaches. Traditional therapy has adopted a bimanual approach (BIM training and recently, constraint induced movement therapy (CIMT has emerged as a promising unimanual approach. Uncertainty remains about the efficacy of these interventions and characteristics of best responders. This study aims to compare the efficacy of CIMT to BIM training to improve outcomes across the ICF for school children with congenital hemiplegia. Methods/Design A matched pairs randomised comparison design will be used with children matched by age, gender, side of hemiplegia and level of upper limb function. Based on power calculations a sample size of 52 children (26 matched pairs will be recruited. Children will be randomised within pairs to receive either CIMT or BIM training. Both interventions will use an intensive activity based day camp model, with groups receiving the same dosage of intervention delivered in the same environment (total 60 hours over 10 days. A novel circus theme will be used to enhance motivation. Groups will be compared at baseline, then at 3, 26 and 52 weeks following intervention. Severity of congenital hemiplegia will be classified according to brain structure (MRI and white matter fibre tracking, cortical excitability using Transcranial Magnetic Stimulation (TMS, functional use of the hand in everyday tasks (Manual Ability Classification System and Gross Motor Function Classification System (GMFCS. Outcomes will address neurovascular changes (functional MRI, functional connectivity, and brain (reorganisation (TMS, body structure and function (range of motion, spasticity

  6. TREATMENT OF DIABETES MELLITUS IN A GOLDEN LION TAMARIN (LEONTOPITHECUS ROSALIA) WITH THE GLUCAGON-LIKE PEPTIDE-1 MIMETIC EXENATIDE.

    Science.gov (United States)

    Johnson, James G; Langan, Jennifer N; Gilor, Chen

    2016-09-01

    An 8-yr-old male golden lion tamarin ( Leontopithecus rosalia ) was diagnosed with diabetes mellitus based on hyperglycemia and persistent glycosuria. Initial treatment consisted of the oral antihyperglycemic medications glipizide and metformin that resulted in decreased blood glucose concentrations; however, marked glycosuria persisted. Insufficient improvement on oral antihyperglycemic therapy and poor feasibility of daily subcutaneous insulin therapy led to an investigation into an alternative therapy with extended-release exenatide, a glucagon-like peptide-1 (GLP-1) mimetic, at a dosage of 0.13 mg/kg subcutaneously once per month. Following treatment with exenatide, the persistent glycosuria resolved, the animal maintained normal blood glucose concentrations, and had lower serum fructosamine concentrations compared to pretreatment levels. Based on these findings, extended-release exenatide could be considered as a therapeutic option in nonhuman primates with diabetes mellitus that do not respond to oral antihyperglycemics and in which daily subcutaneous insulin is not feasible.

  7. Estudos para automação do projeto a alvenaria racionalizada em plataformas BIM

    Directory of Open Access Journals (Sweden)

    Levi Teixeira Pinheiro

    2016-07-01

    Full Text Available A presente pesquisa se trata da investigação de caminhos para automação do projeto de alvenaria em sistemas computacionais. Logo se propõe a desenvolver diagramas aplicáveis em plataformas BIM, que permitam a geração automática da paginação de alvenarias racionalizadas em dois tipos de amarração ½ e 1/3. A estratégia de pesquisa utilizada foi o constructive reasearch, tendo como base para o método de notação do comportamento do objeto paramétrico, denominado originalmente de building object behavior (BOB desenvolvido no período de 2001 a 2004 por pesquisadores Norte Americanos como Chang Lee, Rafael Sacks e Charles Eastman. A pesquisa tem sua importância por contribuir para o desenvolvimento das plataformas BIM, em específico na etapa de projeto, otimizando na produtividade e eficiência. Ao fim da pesquisa foi possível gerar o desenvolvimento dos mesmos, ainda compreender o grau de convergências e divergências existentes entre os mesmos no quesito de diagramas computacionais.

  8. An Energy Dense-AI-NaBH4-PEMFC Based Power Generator for Unmanned Undersea Vehicles

    Science.gov (United States)

    2016-03-01

    From- To) 03/01/2016 Final 01/28/2013-12/31/2015 4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER An Energy-Dense AI-NaBH4- PEMFC Based Power Generator for...combination of polymer electrolyte membrane fuel cell ( PEMFC ) with a compact hydrogen generator util izing AI-NaBH4 composite fuel. The conditions...ANSI Std. Z39.18 FLORIDA SOLAR ENERGY CENTER. Crl’nrmg EnPrgy lnrll’pendrnr£’ An Energy-Dense Al-NaBH4- PEMFC Based Power Generator for Unmanned

  9. miR-148a is upregulated by Twist1 and T-bet and promotes Th1-cell survival by regulating the proapoptotic gene Bim.

    Science.gov (United States)

    Haftmann, Claudia; Stittrich, Anna-Barbara; Zimmermann, Jakob; Fang, Zhuo; Hradilkova, Kristyna; Bardua, Markus; Westendorf, Kerstin; Heinz, Gitta A; Riedel, René; Siede, Julia; Lehmann, Katrin; Weinberger, Esther E; Zimmel, David; Lauer, Uta; Häupl, Thomas; Sieper, Joachim; Backhaus, Marina; Neumann, Christian; Hoffmann, Ute; Porstner, Martina; Chen, Wei; Grün, Joachim R; Baumgrass, Ria; Matz, Mareen; Löhning, Max; Scheffold, Alexander; Wittmann, Jürgen; Chang, Hyun-Dong; Rajewsky, Nikolaus; Jäck, Hans-Martin; Radbruch, Andreas; Mashreghi, Mir-Farzin

    2015-04-01

    Repeatedly activated T helper 1 (Th1) cells present during chronic inflammation can efficiently adapt to the inflammatory milieu, for example, by expressing the transcription factor Twist1, which limits the immunopathology caused by Th1 cells. Here, we show that in repeatedly activated murine Th1 cells, Twist1 and T-bet induce expression of microRNA-148a (miR-148a). miR-148a regulates expression of the proapoptotic gene Bim, resulting in a decreased Bim/Bcl2 ratio. Inhibition of miR-148a by antagomirs in repeatedly activated Th1 cells increases the expression of Bim, leading to enhanced apoptosis. Knockdown of Bim expression by siRNA in miR-148a antagomir-treated cells restores viability of the Th1 cells, demonstrating that miR-148a controls survival by regulating Bim expression. Thus, Twist1 and T-bet not only control the differentiation and function of Th1 cells, but also their persistence in chronic inflammation. © 2014 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Evaluating the Alignment of Organizational and Project Contexts for BIM Adoption: A Case Study of a Large Owner Organization

    Directory of Open Access Journals (Sweden)

    Hasan Burak Cavka

    2015-11-01

    Full Text Available Building information modeling (BIM has been presented as a potential solution to current facilities management problems related to information exchange during handover, and facilities information management during operations. However, implementing BIM in an owner organization is a complex challenge that necessitates reconfiguration of work practices and internal structures to fully realize the benefits. Owners are often unsure about how or whether they should go through the challenges related to implementation. Although previous studies have documented the potential benefits of BIM adoption for owners, such as improvements in work order processing, very little research has specifically looked at the transition to BIM and the scale of the effort required for large and diverse owner organizations. This paper presents the results of a long-term embedded case study analysis of a large owner-operator institutional organization that investigated the alignment of facility management (FM practices across organizational and project contexts. The research objective was to examine current organizational practices in order to understand the potential, as well as the challenges, of transitioning from a paper-based to a model-based approach in handover and operations. We describe the current state of handover, information management and facility management practices and developed a framework to characterize the alignment between organizational constructs, available technology, project artifacts and owner requirements. This investigation of the current state of practice enables us to understand the gap between available and required information, processes and technology, and to better understand the enormous challenges owners face when considering the transition to BIM.

  11. The deprotonation energies of BH{sub 5} and AlH{sub 5}: Comparisons to GaH{sub 5}

    Energy Technology Data Exchange (ETDEWEB)

    Speakman, Lucas D. [Center for Computational Chemistry, University of Georgia, 1004 Cedar Street, Athens, GA 30602-2556 (United States)], E-mail: speakman@ccqc.uga.edu; Turney, Justin M. [Center for Computational Chemistry, University of Georgia, 1004 Cedar Street, Athens, GA 30602-2556 (United States); Schaefer, Henry F. [Center for Computational Chemistry, University of Georgia, 1004 Cedar Street, Athens, GA 30602-2556 (United States)

    2007-01-08

    Hypercoordinate boron is most unusual, leading to considerable theoretical and experimental research on the parent BH{sub 5} molecule. The deprotonation energies of BH{sub 5} and the related molecules AlH{sub 5} and GaH{sub 5} have been of particular interest. Here the energy differences for XH{sub 5}->XH{sub 4}{sup -}+H(X=BandAl) are computed to be 332.4 and 326.3kcalmol{sup -1}, respectively, with an aug-cc-pVQZ basis set at the CCSD(T) level of theory. Vibrational frequencies for BH{sub 4}{sup -} and AlH{sub 4}{sup -} are also reported as 1098, 1210, 2263, and 2284cm{sup -1} and 760, 779, 1658, and 1745cm{sup -1}, respectively, again at the CCSD(T) aug-cc-pVQZ level of theory. Comparisons with the valence isoelectronic GaH{sub 5} molecule are made.

  12. Synthesis of new enantiopure poly(hydroxyaminooxepanes as building blocks for multivalent carbohydrate mimetics

    Directory of Open Access Journals (Sweden)

    Léa Bouché

    2014-01-01

    Full Text Available New compounds with carbohydrate-similar structure (carbohydrate mimetics are presented in this article. Starting from enantiopure nitrones and lithiated TMSE-allene we prepared three 1,2-oxazine derivatives which underwent a highly stereoselective Lewis acid-induced rearrangement to give bicyclic products in good yield. Subsequent reductive transformations delivered a library of new poly(hydroxyaminooxepane derivatives. The crucial final palladium-catalyzed hydrogenolysis of the 1,2-oxazine moiety was optimized resulting in a reasonably efficient approach to a series of new seven-membered carbohydrate mimetics.

  13. Superstretchable Nacre-Mimetic Graphene/Poly(vinyl alcohol) Composite Film Based on Interfacial Architectural Engineering.

    Science.gov (United States)

    Zhao, Nifang; Yang, Miao; Zhao, Qian; Gao, Weiwei; Xie, Tao; Bai, Hao

    2017-05-23

    Through designing hierarchical structures, particularly optimizing the chemical and architectural interactions at its inorganic/organic interface, nacre has achieved an excellent combination of contradictory mechanical properties such as strength and toughness, which is highly demanded yet difficult to achieve by most synthetic materials. Most techniques applied to develop nacre-mimetic composites have been focused on mimicking the "brick-and-mortar" structure, but the interfacial architectural features, especially the asperities and mineral bridges of "bricks", have been rarely concerned, which are of equal importance for enhancing mechanical properties of nacre. Here, we used a modified bidirectional freezing method followed by uniaxial pressing and chemical reduction to assemble a nacre-mimetic graphene/poly(vinyl alcohol) composite film, with both asperities and bridges introduced in addition to the lamellar layers to mimic the interfacial architectural interactions found in nacre. As such, we have developed a composite film that is not only strong (up to ∼150.9 MPa), but also tough (up to ∼8.50 MJ/m 3 ), and highly stretchable (up to ∼10.44%), difficult to obtain by other methods. This was all achieved by only interfacial architectural engineering within the traditional "brick-and-mortar" structure, without introducing a third component or employing chemical cross-linker as in some other nacre-mimetic systems. More importantly, we believe that the design principles and processing strategies reported here can also be applied to other material systems to develop strong and stretchable materials.

  14. Geo-Information Technology of 8-Level Responsibility: Concept and Standard of Construction Management for Implementation of The BIM-Technology in Russia

    Science.gov (United States)

    Komosko, Vladimir; Serebryakov, Sergey; Strokov, Vladimir

    2017-12-01

    Currently, the increase in construction efficiency in the world is associated with the introduction and development of information modelling of construction objects (BIM-technology). The BIM-technology is a process of collective creation and use of information about a structure that forms the basis for all decisions throughout the life cycle of an object. The BIM-technology with the help of a number of software products provides automation of production, it does not provide a methodology for the introduction of these products. The article describes the technology of 8-level responsibility, which is guaranteed to give systematically a new quality of management in construction, related to the requirements of the Russian Government Decree No. 87 of February 16, 2008. The technology of 8-level responsibility (8LR) in the detailed specification of GD No. 87, (territory, construction stage, master plan object, section (part) of the project) extends the number of inseparable levels to 8 (part of the object, element, mark, position), where the “position” is the last indivisible detail of the object. There is reason to argue that the use of the “8LR Technology” in addition to the BIM-technology will provide a synergistic effect and will remove a number of obstacles to the BIM introduction in Russia and system control in the construction and operation of objects of any complexity in Russia.

  15. Measurement of 3H in soil cores from the Hyrax Event (U3bh) subsidence crater

    International Nuclear Information System (INIS)

    Kreek, S.; Hudson, G.B.; Ruth, M.

    1996-01-01

    Core samples were collected from two boreholes drilled in the subsidence crater of the Hyrax event (U3bh). The moisture in the core samples was extracted via freeze drying and tritiw-n was measured in the extracted moisture via 'He accumulation mass spectrometry or liquid scintillation counting. Elevated tritium concentrations (IE4 - IE6 pCi/L extracted moisture as of the time of measurement) were observed in the extracted moisture from virtually all of the core samples with significant increases beginning at about 30 ft depth. No longer-lived fission products (144 Ce) or activation products ('OCo, 'Eu, 114 En) were observed by gamma-ray spectroscopy in a subset of the core samples. This likely indicates that a catastrophic failure of containment (if it occurred) did not release significant radioactivities to this shallow depth (30 ft). The presence of 'Cs at much greater depths (at sign 210 ft, 64 m) may indicate that gaseous and/or vapor products were released shortly after the Hyrax event to a depth of about 210 ft. The relatively shallow depth where the elevated tritium is observed makes highly improbable any significant linkage between the elevated tritium concentrations and a Hyrax event containment failure. This may indicate that an additional source of enriched 'H was introduced at this site

  16. All-Solid-State Lithium-Sulfur Battery based on a nanoconfined LiBH 4 Electrolyte

    NARCIS (Netherlands)

    Das, Supti; Ngene, Peter; Norby, Poul; Vegge, Tejs; de Jongh, P.E.; Blanchard, Didier

    2016-01-01

    In this work we characterize all-solid-state lithium-sulfur batteries based on nano-confined LiBH4in mesoporous silica as solid electrolytes. The nano-confined LiBH4has fast ionic lithium conductivity at room temperature, 0.1 mScm-1, negligible electronic conductivity and its cationic transport

  17. BAX/BAK–Independent Mitoptosis during Cell Death Induced by Proteasome Inhibition?

    OpenAIRE

    Lomonosova, Elena; Ryerse, Jan; Chinnadurai, G.

    2009-01-01

    Proteasome inhibitors induce rapid death of cancer cells. We show that in epithelial cancer cells, such death is associated with dramatic and simultaneous up-regulation of several BH3-only proteins, including BIK, BIM, MCL-1S, NOXA, and PUMA, as well as p53. Elevated levels of these proteins seem to be the result of direct inhibition of their proteasomal degradation, induction of transcription, and active translation. Subsequent cell death is independent of BAX, and probably BAK, and proceeds...

  18. Improved surface bioactivity of stainless steel substrates using osteocalcin mimetic peptide

    International Nuclear Information System (INIS)

    Hosseini, Samaneh; Naderi-Manesh, Hossein; Vali, Hojatollah; Faghihi, Shahab

    2014-01-01

    Although stainless steel has a good biocompatibility for most clinical cases, the higher tissue response (bone bonding property) is required in orthopedic field. In this study, to improve bone-bonding ability of stainless steel substrates, a specific sequence of osteocalcin mimetic peptide is used as bioactive coating material to biochemically modify the surface of metallic samples. This sequence consists of thirteen amino acids present in the first helix of osteocalcin is synthesized in amidic form and physically adsorbed on the surface of 316LS (316 low carbon surgical grade) stainless steel substrates. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) are used to characterize the surface of peptide coated and uncoated substrates. The bioactivity and bone bonding ability of coated and uncoated substrates are assessed by level of hydroxyapatite formation, using transmission electron microscopy (TEM), energy-dispersive x-ray (EDS), and scanning electron microscopy (SEM). The pre-osteoblast cell attachment and proliferation are also evaluated by MTT assay. The results show that the surface of coated sample is homogenously covered by the peptide and display a rougher surface relative to uncoated sample. TEM images reveal the formation of plate-like hydroxyapatite crystals in the presence of the peptide and an amorphous calcium phosphate phase without the peptide. Pre-osteoblast cells proliferation is significantly higher on the surface of peptide coated substrate, while cell attachment remains unaffected by the peptide coatings. Pre-osteoblast cells also demonstrate a higher degree of spreading on the surface of coated sample. It is believed that osteocalcin mimetic peptide improve surface bioactivity and promote hydroxyapatite crystal formation may lead to increased mineralization and bone formation on the surface of metallic biomedical devices. - Graphical abstract: A peptide sequence located in the first helix of OC is selected based on its

  19. Improved surface bioactivity of stainless steel substrates using osteocalcin mimetic peptide

    Energy Technology Data Exchange (ETDEWEB)

    Hosseini, Samaneh [Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Tissue Engineering and Biomaterials Division, National Institute of Genetic Engineering and Biotechnology, Tehran 14965/161 (Iran, Islamic Republic of); Naderi-Manesh, Hossein, E-mail: naderman@modares.ac.ir [Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Vali, Hojatollah [Department of Anatomy and Cell Biology, McGill University, 3640 University Street, Montréal, QC H3A 0C7 (Canada); Faghihi, Shahab, E-mail: sfaghihi@nigeb.ac.ir [Tissue Engineering and Biomaterials Division, National Institute of Genetic Engineering and Biotechnology, Tehran 14965/161 (Iran, Islamic Republic of)

    2014-02-14

    Although stainless steel has a good biocompatibility for most clinical cases, the higher tissue response (bone bonding property) is required in orthopedic field. In this study, to improve bone-bonding ability of stainless steel substrates, a specific sequence of osteocalcin mimetic peptide is used as bioactive coating material to biochemically modify the surface of metallic samples. This sequence consists of thirteen amino acids present in the first helix of osteocalcin is synthesized in amidic form and physically adsorbed on the surface of 316LS (316 low carbon surgical grade) stainless steel substrates. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) are used to characterize the surface of peptide coated and uncoated substrates. The bioactivity and bone bonding ability of coated and uncoated substrates are assessed by level of hydroxyapatite formation, using transmission electron microscopy (TEM), energy-dispersive x-ray (EDS), and scanning electron microscopy (SEM). The pre-osteoblast cell attachment and proliferation are also evaluated by MTT assay. The results show that the surface of coated sample is homogenously covered by the peptide and display a rougher surface relative to uncoated sample. TEM images reveal the formation of plate-like hydroxyapatite crystals in the presence of the peptide and an amorphous calcium phosphate phase without the peptide. Pre-osteoblast cells proliferation is significantly higher on the surface of peptide coated substrate, while cell attachment remains unaffected by the peptide coatings. Pre-osteoblast cells also demonstrate a higher degree of spreading on the surface of coated sample. It is believed that osteocalcin mimetic peptide improve surface bioactivity and promote hydroxyapatite crystal formation may lead to increased mineralization and bone formation on the surface of metallic biomedical devices. - Graphical abstract: A peptide sequence located in the first helix of OC is selected based on its

  20. Synthesis and characterizations of CoPt nanoparticles supported on poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) functionalized multi-walled carbon nanotubes with superior activity for NaBH{sub 4} hydrolysis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiao; Zhao, Yanchun, E-mail: yanchunzhao@aliyun.com; Peng, Xinglan; Wang, Jing; Jing, Chen; Tian, Jianniao, E-mail: birdtjn@sina.com

    2015-10-15

    Highlights: • Simple strategy for the synthesis of CoPt-PEDOT:PSS/MWCNTs. • PEDOT:PSS as a modifier of MWCNTs can improve the particles dispersion. • Superior catalytic activities for the NaBH{sub 4} hydrolysis reaction. - Abstract: We present here a facile strategy for synthesis of CoPt nanoparticles supported on poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT:PSS) functionalized multi-walled carbon nanotubes (MWCNTs). The as-prepared CoPt-PEDOT:PSS/MWCNT catalyst was characterized with UV–vis spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray diffraction and X-ray photoelectron. The well-supported and low-Pt-content nanostructure catalyst exhibits superior catalytic activity for the NaBH{sub 4} hydrolysis reaction with a 47.3 kJ mol{sup −1} of activation energy. The maximum hydrogen generation rate is 6900 mL min{sup −1} g{sup −1} at 298 K.