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Sample records for cd2019 overcomes inhibition

  1. Does SGLT2 inhibition with dapagliflozin overcome individual therapy resistance to RAAS inhibition?

    NARCIS (Netherlands)

    Petrykiv, Sergei; Laverman, Gozewijn D.; de Zeeuw, Dick; Heerspink, Hiddo J. L.

    Individual patients show a large variation in their response to renin-angiotensin-aldosteron system (RAAS) inhibition (RAASi), both in surrogates such as albuminuria and in hard renal outcomes. Sodium-glucose co-transporter 2 inhibitors (SGLT2) have been shown to lower albuminuria and to confer

  2. Overcoming selfishness: reciprocity, inhibition, and cardiac-autonomic control in the ultimatum game.

    Science.gov (United States)

    Sütterlin, Stefan; Herbert, Cornelia; Schmitt, Michael; Kübler, Andrea; Vögele, Claus

    2011-01-01

    The processes underlying decision-making in response to unfair offers in the ultimatum game (UG) have recently been discussed in light of models of reciprocity and fairness-related behavior. It has been suggested that behavior following norm-oriented, internalized expectations of reciprocity requires overcoming economic self-interest. In this study we investigated both, behavioral and peripheral-physiological indicators of inhibitory capacity related to neuronal networks that are likely to be involved in the behavioral response to unfair offers. Both heart-rate variability as an index of inhibitory capacity, and performance in a motor response inhibition task predicted rejection of unfair offers in an UG, suggesting an important role of inhibitory processes in overcoming economic temptations and regulating behavior conforming to social norms of reciprocity and fairness. The role of parasympathetic activity as a physiological trait-marker predicting inter-individual differences in the rejection of unfair offers is discussed.

  3. Overcoming selfishness: reciprocity, inhibition, and cardiac autonomic control in the ultimatum game

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    Stefan eSütterlin

    2011-07-01

    Full Text Available The processes underlying decision-making in response to unfair offers in the ultimatum game (UG have recently been discussed in light of models of reciprocity and fairness-related behavior. It has been suggested that behavior following norm-oriented, internalized expectations of reciprocity requires overcoming economic self-interest. In this study we investigated both, behavioral and peripheral-physiological indicators of inhibitory capacity related to neuronal networks that are likely to be involved in the behavioral response to unfair offers. Both heart-rate variability as an index of inhibitory capacity, and performance in a motor response inhibition task predicted rejection of unfair offers in an ultimatum game, suggesting an important role of inhibitory processes in overcoming economic temptations and regulating behavior conforming to social norms of reciprocity and fairness. The role of parasympathetic activity as a physiological trait-marker predicting inter-individual differences in the rejection of unfair offers is discussed.

  4. Micelle System Based on Molecular Economy Principle for Overcoming Multidrug Resistance and Inhibiting Metastasis.

    Science.gov (United States)

    Qi, Yan; Qin, Xianya; Yang, Conglian; Wu, Tingting; Qiao, Qi; Song, Qingle; Zhang, Zhiping

    2018-03-05

    The high mortality of cancer is mainly attributed to multidrug resistance (MDR) and metastasis. A simple micelle system was constructed here to codeliver doxorubicin (DOX), adjudin (ADD), and nitric oxide (NO) for overcoming MDR and inhibiting metastasis. It was devised based on the "molecular economy" principle as the micelle system was easy to fabricate and exhibited high drug loading efficiency, and importantly, each component of the micelles would exert one or more active functions. DOX acted as the main cell killing agent supplemented with ADD, NO, and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). MDR was overcome by synergistic effects of mitochondria inhibition agents, TPGS and ADD. A TPGS-based NO donor can be used as a drug carrier, and it can release NO to enhance drug accumulation and penetration in tumor, resulting in a positive cycle of drug delivery. This DOX-ADD conjugate self-assembly system demonstrated controlled drug release, increased cellular uptake and cytotoxicity, enhanced accumulation at tumor site, and improved in vivo metastasis inhibition of breast cancer. The micelles can fully take advantage of the functions of each component, and they provide a potential strategy for nanomedicine design and clinical cancer treatment.

  5. PI3K inhibition to overcome endocrine resistance in breast cancer.

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    Keegan, Niamh M; Gleeson, Jack P; Hennessy, Bryan T; Morris, Patrick G

    2018-01-01

    Activation of the phosphatidylinositol-3 kinase (PI3K) pathway is a critical step in oncogenesis and plays a role in the development of treatment resistance for both estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) positive breast cancers. Hence, there have been efforts to therapeutically inhibit this pathway. Areas covered: Several inhibitors of PI3K are now progressing through clinical trials with varying degrees of efficacy and toxicity to date. Numerous unresolved questions remain concerning the optimal isoform selectivity of PI3K inhibitors and use of predictive biomarkers. This review examines the most important PI3K inhibitors in ER positive breast cancer to date, with a particular focus on their role in overcoming endocrine therapy resistance and the possible use of PIK3CA mutations as a predictive biomarker. Expert opinion: We discuss some of the emerging challenges and questions encountered during the development of PI3K inhibitors from preclinical to phase III studies, including other novel biomarkers and future combinations to overcome endocrine resistance.

  6. Inhibition of autophagy overcomes the nanotoxicity elicited by cadmium-based quantum dots.

    Science.gov (United States)

    Fan, Jiajun; Sun, Yun; Wang, Shaofei; Li, Yubin; Zeng, Xian; Cao, Zhonglian; Yang, Ping; Song, Ping; Wang, Ziyu; Xian, Zongshu; Gao, Hongjian; Chen, Qicheng; Cui, Daxiang; Ju, Dianwen

    2016-02-01

    Cadmium-based quantum dots (QDs) have shown their values in disease diagnosis, cellular and molecular tracking, small-animal imaging, and therapeutic drug delivery. However, the potential safety problems of QDs, mainly due to their nanotoxicities by unclear mechanisms, have greatly limited its applications. To reverse this situation, we investigated the underlying biological mechanisms of the toxicity of Quantum Dots CdTe/CdS 655 (QDs 655) in this work. QDs 655 was found to elicit nanotoxicity in vitro and in vivo. During the process, autophagy was activated, which was characterized by three main stages of autophagic flux including formation of autophagosomes, lysosomes fused with autophagosomes, and degradation of autophagosomes by lysosomes. Furthermore, the autophagic cell death was demonstrated in vitro under QDs 655 treatment while inhibition of autophagy by pharmacological inhibitors or genetic approaches could attenuate the toxicity induced by QDs 655 in vitro and in vivo. These results indicated that autophagic flux and autophagic cell death were triggered by QDs 655, which elucidated the critical role of autophagy in QDs 655 induced toxicity. Our data may suggest the approach to overcome the toxicity of QDs and other nanoparticles by autophagy inhibition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. RITA plus 3-MA overcomes chemoresistance of head and neck cancer cells via dual inhibition of autophagy and antioxidant systems

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    Daiha Shin

    2017-10-01

    Condensed abstract: This study revealed a novel RITA resistant mechanism associated with the sustained induction of autophagy, p62 overexpression, and Keap1-Nrf2 antioxidant system activation. The combined treatment of RITA with the autophagy inhibitor 3-methyladenine overcomes RITA resistance via dual inhibition of autophagy and antioxidant systems in vitro and in vivo.

  8. IFN-γ fails to overcome inhibition of selected macrophage activation events in response to pathogenic mycobacteria.

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    Shyamala Thirunavukkarasu

    Full Text Available According to most models of mycobacterial infection, inhibition of the pro-inflammatory macrophage immune responses contributes to the persistence of bacteria. Mycobacterium avium subsp. paratuberculosis (MAP is a highly successful pathogen in cattle and sheep and is also implicated as the causative agent of Crohn's disease in humans. Pathogenic mycobacteria such as MAP have developed multiple strategies to evade host defence mechanisms including interfering with the macrophages' capacity to respond to IFN-γ, a feature which might be lacking in non-pathogenic mycobacteria such as M. smegmatis. We hypothesized that pre-sensitisation of macrophages with the pro-inflammatory cytokine IFN-γ would help in overcoming the inhibitory effect of MAP or its antigens on macrophage inflammatory responses. Herein we have compared a series of macrophage activation parameters in response to MAP and M. smegmatis as well as mycobacterial antigens. While IFN-γ did overcome the inhibition in immune suppressive mechanisms in response to MAP antigen as well as M. smegmatis, we could not find a clear role for IFN-γ in overcoming the inhibition of macrophage inflammatory responses to the pathogenic mycobacterium, MAP. We demonstrate that suppression of macrophage defence mechanisms by pathogenic mycobacteria is unlikely to be overcome by prior sensitization with IFN-γ alone. This indicates that IFN-γ signaling pathway-independent mechanisms may exist for overcoming inhibition of macrophage effector functions in response to pathogenic mycobacteria. These findings have important implications in understanding the survival mechanisms of pathogenic mycobacteria directed towards finding better therapeutics and vaccination strategies.

  9. By inhibiting PFKFB3, aspirin overcomes sorafenib resistance in hepatocellular carcinoma.

    Science.gov (United States)

    Li, Sainan; Dai, Weiqi; Mo, Wenhui; Li, Jingjing; Feng, Jiao; Wu, Liwei; Liu, Tong; Yu, Qiang; Xu, Shizan; Wang, Wenwen; Lu, Xiya; Zhang, Qinghui; Chen, Kan; Xia, Yujing; Lu, Jie; Zhou, Yingqun; Fan, Xiaoming; Xu, Ling; Guo, Chuanyong

    2017-12-15

    Hepatocellular carcinoma (HCC) is one of the few cancers with a continuous increase in incidence and mortality. Drug resistance is a major problem in the treatment of HCC. In this study, two sorafenib-resistant HCC cell lines and a nude mouse subcutaneously tumor model were used to explore the possible mechanisms leading to sorafenib resistance, and to investigate whether aspirin could increase the sensitivity of hepatoma cells to sorafenib. The combination of aspirin and sorafenib resulted in a synergistic antitumor effect against liver tumors both in vitro and in vivo. High glycolysis and PFKFB3 overexpression occupied a dominant position in sorafenib resistance, and can be targeted and overcome by aspirin. Aspirin plus sorafenib induced apoptosis in tumors without inducing weight loss, hepatotoxicity or inflammation. Our results suggest that aspirin overcomes sorafenib resistance and their combination may be an effective treatment approach for HCC. © 2017 UICC.

  10. Nelfinavir augments proteasome inhibition by bortezomib in myeloma cells and overcomes bortezomib and carfilzomib resistance

    International Nuclear Information System (INIS)

    Kraus, M; Bader, J; Overkleeft, H; Driessen, C

    2013-01-01

    HIV protease inhibitors (HIV-PI) are oral drugs for HIV treatment. HIV-PI have antitumor activity via induction of ER-stress, inhibition of phospho-AKT (p-AKT) and the proteasome, suggesting antimyeloma activity. We characterize the effects of all approved HIV-PI on myeloma cells. HIV-PI were compared regarding cytotoxicity, proteasome activity, ER-stress induction and AKT phosphorylation using myeloma cells in vitro. Nelfinavir is the HIV-PI with highest cytotoxic activity against primary myeloma cells and with an IC 50 near therapeutic drug blood levels (8–14 μM), irrespective of bortezomib sensitivity. Only nelfinavir inhibited intracellular proteasome activity in situ at drug concentrations <40 μℳ. Ritonavir, saquinavir and lopinavir inhibited p-AKT comparable to nelfinavir, and showed similar synergistic cytotoxicity with bortezomib against bortezomib-sensitive cells. Nelfinavir had superior synergistic activity with bortezomib/carfilzomib in particular against bortezomib/carfilzomib-resistant myeloma cells. It inhibited not only the proteasomal β1/β5 active sites, similar to bortezomib/carfilzomib, but in addition the β2 proteasome activity not targeted by bortezomib/carfilzomib. Additional inhibition of β2 proteasome activity is known to sensitize cells for bortezomib and carfilzomib. Nelfinavir has unique proteasome inhibiting activity in particular on the bortezomib/carfilzomib-insensitive tryptic (β2) proteasome activity in intact myeloma cells, and is active against bortezomib/carfilzomib-resistant myeloma cells in vitro

  11. Combined MEK and ERK inhibition overcomes therapy-mediated pathway reactivation in RAS mutant tumors.

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    Mark Merchant

    Full Text Available Mitogen-activated protein kinase (MAPK pathway dysregulation is implicated in >30% of all cancers, rationalizing the development of RAF, MEK and ERK inhibitors. While BRAF and MEK inhibitors improve BRAF mutant melanoma patient outcomes, these inhibitors had limited success in other MAPK dysregulated tumors, with insufficient pathway suppression and likely pathway reactivation. In this study we show that inhibition of either MEK or ERK alone only transiently inhibits the MAPK pathway due to feedback reactivation. Simultaneous targeting of both MEK and ERK nodes results in deeper and more durable suppression of MAPK signaling that is not achievable with any dose of single agent, in tumors where feedback reactivation occurs. Strikingly, combined MEK and ERK inhibition is synergistic in RAS mutant models but only additive in BRAF mutant models where the RAF complex is dissociated from RAS and thus feedback productivity is disabled. We discovered that pathway reactivation in RAS mutant models occurs at the level of CRAF with combination treatment resulting in a markedly more active pool of CRAF. However, distinct from single node targeting, combining MEK and ERK inhibitor treatment effectively blocks the downstream signaling as assessed by transcriptional signatures and phospho-p90RSK. Importantly, these data reveal that MAPK pathway inhibitors whose activity is attenuated due to feedback reactivation can be rescued with sufficient inhibition by using a combination of MEK and ERK inhibitors. The MEK and ERK combination significantly suppresses MAPK pathway output and tumor growth in vivo to a greater extent than the maximum tolerated doses of single agents, and results in improved anti-tumor activity in multiple xenografts as well as in two Kras mutant genetically engineered mouse (GEM models. Collectively, these data demonstrate that combined MEK and ERK inhibition is functionally unique, yielding greater than additive anti-tumor effects and

  12. Overcoming the Constraints of Anti-HIV/CD89 Bispecific Antibodies That Limit Viral Inhibition

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    Xiaocong Yu

    2016-01-01

    Full Text Available Innovative strategies are necessary to maximize the clinical application of HIV neutralizing antibodies. To this end, bispecific constructs of human antibody F240, reactive with well-conserved gp41 epitope and antibody 14A8, reactive with the IgA receptor (CD89 on effector cells, were constructed. A F240 × 14A8 bispecific single chain variable region (scFv molecule was constructed by linking two scFvs using a conventional GGGGS linker. Despite immunoreactivity with HIV gp41 and neutrophils, this bispecific scFv failed to inhibit HIV infection. This is in sharp contrast to viral inhibition using a chemical conjugate of the Fab of these two antibodies. Therefore, we constructed two novel Fab-like bispecific antibody molecules centered on fusion of the IgG1 CH1 domain or CH1-hinge domain to the C-terminus of F240scFv and fusion of the kappa chain CL domain to the C-terminus of 14A8scFv. Both Bi-Fab antibodies showed significant ADCVI activity for multiple clade B and clade C isolates by arming the neutrophils to inhibit HIV infection. The approach presented in this study is unique for HIV immunotherapy in that the impetus of neutralization is to arm and mobilize PMN to destroy HIV and HIV infected cells.

  13. RITA plus 3-MA overcomes chemoresistance of head and neck cancer cells via dual inhibition of autophagy and antioxidant systems.

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    Shin, Daiha; Kim, Eun Hye; Lee, Jaewang; Roh, Jong-Lyel

    2017-10-01

    Reactivation of p53 and induction of tumor cell apoptosis (RITA) is a small molecule that blocks p53-MDM2 interaction, thereby reactivating p53 in tumors. RITA can induce exclusive apoptosis in cancer cells independently of the p53 pathway; however, the resistance of cancer cells remains a major drawback. Here, we found a novel resistance mechanism of RITA treatment and an effective combined treatment to overcome RITA resistance in head and neck cancer (HNC) cells. The effects of RITA and 3-methyladenine (3-MA) were tested in different HNC cell lines, including cisplatin-resistant and acquired RITA-resistant HNC cells. The effects of each drug alone and in combination were assessed by measuring cell viability, apoptosis, cell cycle, glutathione, reactive oxygen species, protein expression, genetic inhibition of p62 and Nrf2, and a mouse xenograft model of cisplatin-resistant HNC. RITA induced apoptosis of HNC cells at different levels without significantly inhibiting normal cell viability. Following RITA treatment, RITA-resistant HNC cells exhibited a sustained expression of other autophagy-related proteins, overexpressed p62, and displayed activation of the Keap1-Nrf2 antioxidant pathway. The autophagy inhibitor 3-MA sensitized resistant HNC cells to RITA treatment via the dual inhibition of molecules related to the autophagy and antioxidant systems. Silencing of the p62 gene augmented the combined effects. The effective antitumor activity of RITA plus 3-MA was also confirmed in vivo in mouse xenograft models transplanted with resistant HNC cells, showing increased oxidative stress and DNA damage. The results indicate that RITA plus 3-MA can help overcome RITA resistance in HNC cells. This study revealed a novel RITA resistant mechanism associated with the sustained induction of autophagy, p62 overexpression, and Keap1-Nrf2 antioxidant system activation. The combined treatment of RITA with the autophagy inhibitor 3-methyladenine overcomes RITA resistance via dual

  14. Understanding Performance Decrements in a Letter-Canceling Task: Overcoming Habits or Inhibition of Reading.

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    Myers, Larry; Downie, Steven; Taylor, Grant; Marrington, Jessica; Tehan, Gerald; Ireland, Michael J

    2018-01-01

    The importance of self-regulation in human behavior is readily apparent and diverse theoretical accounts for explaining self-regulation failures have been proposed. Typically, these accounts are based on a sequential task methodology where an initial task is presented to deplete self-regulatory resources, and carryover effects are then examined on a second outcome task. In the aftermath of high profile replication failures using a popular letter-crossing task as a means of depleting self-regulatory resources and subsequent criticisms of that task, current research into self-control is currently at an impasse. This is largely due to the lack of empirical research that tests explicit assumptions regarding the initial task. One such untested assumption is that for resource depletion to occur, the initial task must first establish an habitual response and then this habitual response must be inhibited, with behavioral inhibition being the causal factor in inducing depletion. This study reports on four experiments exploring performance on a letter-canceling task, where the rules for target identification remained constant but the method of responding differed (Experiment 1) and the coherence of the text was manipulated (Experiments 1-4). Experiment 1 established that habit forming and behavioral inhibition did not produce any performance decrement when the targets were embedded in random letter strings. Experiments 2-4 established that target detection was sensitive to language characteristics and the coherence of the background text, suggesting that participants' automatic reading processes is a key driver of performance in the letter-e task.

  15. Overcoming Chemoresistance of Pediatric Ependymoma by Inhibition of STAT3 Signaling

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    Ji Hoon Phi

    2015-10-01

    Full Text Available The long-term clinical outcome of pediatric intracranial epepdymoma is poor with a high rate of recurrence. One of the main reasons for this poor outcome is the tumor’s inherent resistance to chemotherapy. Signal transducer and activator of transcription 3 (STAT3 is overactive in many human cancers, and inhibition of STAT3 signaling is an emerging area of interest in oncology. In this study, the possibility of STAT3 inhibition as a treatment was investigated in pediatric intracranial ependymoma tissues and cell lines. STAT3 activation status was checked in ependymoma tissues. The responses to conventional chemotherapeutic agents and a STAT3 inhibitor WP1066 in primarily cultured ependymoma cells were measured by cell viability assay. Apoptosis assays were conducted to reveal the cytotoxic mechanism of applied agents. Knockdown of STAT3 was tried to confirm the effects of STAT3 inhibition in ependymoma cells. High levels of phospho-STAT3 (p-STAT3 expression were observed in ependymoma tissue, especially in the anaplastic histology group. There was no cytotoxic effect of cisplatin, ifosfamide, and etoposide. Both brain tumor-initiating cells (BTICs and bulk tumor cells (BCs showed considerably decreased viability after WP1066 treatment. However, BTICs had fewer responses than BCs. No additive or synergistic effect was observed for combination therapy of WP1066 and cisplatin. WP1066 effectively abrogated p-STAT3 expression. An increased apoptosis and decreased Survivin expression were observed after WP1066 treatment. Knockdown of STAT3 also decreased cell survival, supporting the critical role of STAT3 in sustaining ependymoma cells. In this study, we observed a cytotoxic effect of STAT3 inhibitor on ependymoma BTICs and BCs. There is urgent need to develop new therapeutic agents for pediatric ependymoma. STAT3 inhibitors may be a new group of drugs for clinical application.

  16. Chemical inhibition of host toxicity as a means of overcoming tumor resistance

    International Nuclear Information System (INIS)

    Yuhas, J.M.; Pardini, M.C.; Children's Hospital of Philadelphia, PA)

    1983-01-01

    Largely because we have accumulated so much information on WR-2721 in the past decade, we know that this drug is not a universal panacea which will solve all the problems which confront us. However, in those instances where it would appear applicable, clinical testing would appear appropriate. Thanks largely to the efforts of M.M. Kligerman, these studies have been initiated. In those instances where WR-2721 would appear inappropriate or not of sufficient activity, the information we have already accumulated should point the way to the development of qualitatively and/or quantitatively superior drugs which selectively inhibit host toxicity

  17. Inhibition of Apoptosis Overcomes Stage-Related Compatibility Barriers to Chimera Formation in Mouse Embryos.

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    Masaki, Hideki; Kato-Itoh, Megumi; Takahashi, Yusuke; Umino, Ayumi; Sato, Hideyuki; Ito, Keiichi; Yanagida, Ayaka; Nishimura, Toshinobu; Yamaguchi, Tomoyuki; Hirabayashi, Masumi; Era, Takumi; Loh, Kyle M; Wu, Sean M; Weissman, Irving L; Nakauchi, Hiromitsu

    2016-11-03

    Cell types more advanced in development than embryonic stem cells, such as EpiSCs, fail to contribute to chimeras when injected into pre-implantation-stage blastocysts, apparently because the injected cells undergo apoptosis. Here we show that transient promotion of cell survival through expression of the anti-apoptotic gene BCL2 enables EpiSCs and Sox17 + endoderm progenitors to integrate into blastocysts and contribute to chimeric embryos. Upon injection into blastocyst, BCL2-expressing EpiSCs contributed to all bodily tissues in chimeric animals while Sox17 + endoderm progenitors specifically contributed in a region-specific fashion to endodermal tissues. In addition, BCL2 expression enabled rat EpiSCs to contribute to mouse embryonic chimeras, thereby forming interspecies chimeras that could survive to adulthood. Our system therefore provides a method to overcome cellular compatibility issues that typically restrict chimera formation. Application of this type of approach could broaden the use of embryonic chimeras, including region-specific chimeras, for basic developmental biology research and regenerative medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Inhibition of BMP signaling overcomes acquired resistance to cetuximab in oral squamous cell carcinomas.

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    Yin, Jinlong; Jung, Ji-Eun; Choi, Sun Il; Kim, Sung Soo; Oh, Young Taek; Kim, Tae-Hoon; Choi, Eunji; Lee, Sun Joo; Kim, Hana; Kim, Eun Ok; Lee, Yu Sun; Chang, Hee Jin; Park, Joo Yong; Kim, Yeejeong; Yun, Tak; Heo, Kyun; Kim, Youn-Jae; Kim, Hyunggee; Kim, Yun-Hee; Park, Jong Bae; Choi, Sung Weon

    2018-02-01

    Despite expressing high levels of the epidermal growth factor receptor (EGFR), a majority of oral squamous cell carcinoma (OSCC) patients show limited response to cetuximab and ultimately develop drug resistance. However, mechanism underlying cetuximab resistance in OSCC is not clearly understood. Here, using a mouse orthotopic xenograft model of OSCC, we show that bone morphogenic protein-7-phosphorylated Smad-1, -5, -8 (BMP7-p-Smad1/5/8) signaling contributes to cetuximab resistance. Tumor cells isolated from the recurrent cetuximab-resistant xenograft models exhibited low EGFR expression but extremely high levels of p-Smad1/5/8. Treatment with the bone morphogenic protein receptor type 1 (BMPRI) inhibitor, DMH1 significantly reduced cetuximab-resistant OSCC tumor growth, and combined treatment of DMH1 and cetuximab remarkably reduced relapsed tumor growth in vivo. Importantly, p-Smad1/5/8 level was elevated in cetuximab-resistant patients and this correlated with poor prognosis. Collectively, our results indicate that the BMP7-p-Smad1/5/8 signaling is a key pathway to acquired cetuximab resistance, and demonstrate that combination therapy of cetuximab and a BMP signaling inhibitor as potentially a new therapeutic strategy for overcoming acquired resistance to cetuximab in OSCC. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. A novel HDAC inhibitor, CG200745, inhibits pancreatic cancer cell growth and overcomes gemcitabine resistance.

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    Lee, Hee Seung; Park, Soo Been; Kim, Sun A; Kwon, Sool Ki; Cha, Hyunju; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Song, Si Young

    2017-01-30

    Pancreatic cancer is predominantly lethal, and is primarily treated using gemcitabine, with increasing resistance. Therefore, novel agents that increase tumor sensitivity to gemcitabine are needed. Histone deacetylase (HDAC) inhibitors are emerging therapeutic agents, since HDAC plays an important role in cancer initiation and progression. We evaluated the antitumor effect of a novel HDAC inhibitor, CG200745, combined with gemcitabine/erlotinib on pancreatic cancer cells and gemcitabine-resistant pancreatic cancer cells. Three pancreatic cancer-cell lines were used to evaluate the antitumor effect of CG200745 combined with gemcitabine/erlotinib. CG200745 induced the expression of apoptotic proteins (PARP and caspase-3) and increased the levels of acetylated histone H3. CG200745 with gemcitabine/erlotinib showed significant growth inhibition and synergistic antitumor effects in vitro. In vivo, gemcitabine/erlotinib and CG200745 reduced tumor size up to 50%. CG200745 enhanced the sensitivity of gemcitabine-resistant pancreatic cancer cells to gemcitabine, and decreased the level of ATP-binding cassette-transporter genes, especially multidrug resistance protein 3 (MRP3) and MRP4. The novel HDAC inhibitor, CG200745, with gemcitabine/erlotinib had a synergistic anti-tumor effect on pancreatic cancer cells. CG200745 significantly improved pancreatic cancer sensitivity to gemcitabine, with a prominent antitumor effect on gemcitabine-resistant pancreatic cancer cells. Therefore, improved clinical outcome is expected in the future.

  20. Overcoming cetuximab resistance in Ewing's sarcoma by inhibiting lactate dehydrogenase-A.

    Science.gov (United States)

    Fu, Jiaxin; Jiang, Han; Wu, Chenxuan; Jiang, Yi; Xiao, Lianping; Tian, Yonggang

    2016-07-01

    Ewing's sarcoma, the second most common type of malignant bone tumor, generally occurs in children and young adults. The current treatment of Ewing's sarcoma comprises systemic anti‑cancer chemotherapy with complete surgical resection. However, the majority of patients with Ewing's sarcoma develop resistance to chemotherapy. The present study revealed an oncogenic role of lactate dehydrogenase‑A (LDHA) in the resistance of Ewing's sarcoma to cetuximab. LDHA was shown to be upregulated at the protein and mRNA level in cetuximab‑resistant Ewing's sarcoma tissues and a cell line. In addition, a link between LDHA‑induced glycolysis and cetuximab resistance in Ewing's sarcoma cells was revealed. Of note, inhibition of LDHA by either small interfering RNA or LDHA inhibitor oxamate significantly re‑sensitized cetuximab‑resistant cells to cetuximab. Combined treatment with LDHA inhibitor and cetuximab synergistically reduced the viability of cetuximab-resistant cells through the suppression of LDHA. The present study revealed a novel mechanism of cetuximab resistance from the perspective of cancer‑cell metabolism and provided a sensitization approach, which may aid in the development of anti-chemoresistance strategies for the treatment of cetuximab-resistant Ewing's sarcoma.

  1. Inhibition of IGF1-R overcomes IGFBP7-induced chemotherapy resistance in T-ALL

    International Nuclear Information System (INIS)

    Bartram, Isabelle; Erben, Ulrike; Ortiz-Tanchez, Jutta; Blunert, Katja; Schlee, Cornelia; Neumann, Martin; Heesch, Sandra; Baldus, Claudia D.

    2015-01-01

    proliferation inhibiting effect of IGFBP7 by G0/G1 arrest and a drug resistance-inducing effect of IGFBP7 against vincristine and asparaginase in T-ALL. These results provide a model for the previously observed association between high IGFBP7 expression and chemotherapy failure in T-ALL patients. Since the resistance against vincristine was abolished by IGF1-R inhibition, IGFBP7 could serve as biomarker for patients who may benefit from therapies including IGF1-R inhibitors in combination with chemotherapy. The online version of this article (doi:10.1186/s12885-015-1677-z) contains supplementary material, which is available to authorized users

  2. Strategies for improving production performance of probiotic Pediococcus acidilactici viable cell by overcoming lactic acid inhibition.

    Science.gov (United States)

    Othman, Majdiah; Ariff, Arbakariya B; Wasoh, Helmi; Kapri, Mohd Rizal; Halim, Murni

    2017-11-27

    Lactic acid bacteria are industrially important microorganisms recognized for fermentative ability mostly in their probiotic benefits as well as lactic acid production for various applications. Fermentation conditions such as concentration of initial glucose in the culture, concentration of lactic acid accumulated in the culture, types of pH control strategy, types of aeration mode and different agitation speed had influenced the cultivation performance of batch fermentation of Pediococcus acidilactici. The maximum viable cell concentration obtained in constant fed-batch fermentation at a feeding rate of 0.015 L/h was 6.1 times higher with 1.6 times reduction in lactic acid accumulation compared to batch fermentation. Anion exchange resin, IRA 67 was found to have the highest selectivity towards lactic acid compared to other components studied. Fed-batch fermentation of P. acidilactici coupled with lactic acid removal system using IRA 67 resin showed 55.5 and 9.1 times of improvement in maximum viable cell concentration compared to fermentation without resin for batch and fed-batch mode respectively. The improvement of the P. acidilactici growth in the constant fed-batch fermentation indicated the use of minimal and simple process control equipment is an effective approach for reducing by-product inhibition. Further improvement in the cultivation performance of P. acidilactici in fed-bath fermentation with in situ addition of anion-exchange resin significantly helped to enhance the growth of P. acidilactici by reducing the inhibitory effect of lactic acid and thus increasing probiotic production.

  3. Inhibition of c-Myc overcomes cytotoxic drug resistance in acute myeloid leukemia cells by promoting differentiation.

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    Xiao-Na Pan

    Full Text Available Nowadays, drug resistance still represents a major obstacle to successful acute myeloid leukemia (AML treatment and the underlying mechanism is not fully elucidated. Here, we found that high expression of c-Myc was one of the cytogenetic characteristics in the drug-resistant leukemic cells. c-Myc over-expression in leukemic cells induced resistance to chemotherapeutic drugs, enhanced colony formation capacity and inhibited cell differentiation induced by all-trans retinoic acid (ATRA. Meanwhile, inhibition of c-Myc by shRNA or specific c-Myc inhibitor 10058-F4 rescued the sensitivity to cytotoxic drugs, restrained the colony formation ability and promoted differentiation. RT-PCR and western blotting analysis showed that down-regulation of C/EBPβ contributed to the poor differentiation state of leukemic cells induced by c-Myc over-expression. Importantly, over-expression of C/EBPβ could reverse c-Myc induced drug resistance. In primary AML cells, the c-Myc expression was negatively correlated with C/EBPβ. 10058-F4, displayed anti-proliferative activity and increased cellular differentiation with up-regulation of C/EBPβ in primary AML cells. Thus, our study indicated that c-Myc could be a novel target to overcome drug resistance, providing a new approach in AML therapy.

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

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    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.

  5. Intracellular expression of IRF9 Stat fusion protein overcomes the defective Jak-Stat signaling and inhibits HCV RNA replication

    Directory of Open Access Journals (Sweden)

    Balart Luis A

    2010-10-01

    Full Text Available Abstract Interferon alpha (IFN-α binds to a cell surface receptor that activates the Jak-Stat signaling pathway. A critical component of this pathway is the translocation of interferon stimulated gene factor 3 (a complex of three proteins Stat1, Stat2 and IRF9 to the nucleus to activate antiviral genes. A stable sub-genomic replicon cell line resistant to IFN-α was developed in which the nuclear translocation of Stat1 and Stat2 proteins was prevented due to the lack of phosphorylation; whereas the nuclear translocation of IRF9 protein was not affected. In this study, we sought to overcome defective Jak-Stat signaling and to induce an antiviral state in the IFN-α resistant replicon cell line by developing a chimera IRF9 protein fused with the trans activating domain (TAD of either a Stat1 (IRF9-S1C or Stat2 (IRF9-S2C protein. We show here that intracellular expression of fusion proteins using the plasmid constructs of either IRF9-S1C or IRF9-S2C, in the IFN-α resistant cells, resulted in an increase in Interferon Stimulated Response Element (ISRE luciferase promoter activity and significantly induced HLA-1 surface expression. Moreover, we show that transient transfection of IRF9-S1C or IRF9-S2C plasmid constructs into IFN-α resistant replicon cells containing sub-genomic HCV1b and HCV2a viruses resulted in an inhibition of viral replication and viral protein expression independent of IFN-α treatment. The results of this study indicate that the recombinant fusion proteins of IRF9-S1C, IRF9-S2C alone, or in combination, have potent antiviral properties against the HCV in an IFN-α resistant cell line with a defective Jak-Stat signaling.

  6. Overcoming challenges

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    Full Text Available ... breastfeeding Overcoming challenges Common questions about breastfeeding and pain Breastfeeding checklist: How to get a good latch Finding ... myths Overcoming challenges Common questions about breastfeeding and pain Breastfeeding checklist: How to get a good latch Finding ...

  7. Overcoming challenges

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    Full Text Available ... section Back to section menu It's Only Natural Planning ahead Breastfeeding and baby basics Making breastfeeding work ... It's Only Natural Overcoming challenges It's Only Natural Planning ahead Addressing breastfeeding myths Overcoming challenges Common questions ...

  8. Concurrent Autophagy Inhibition Overcomes the Resistance of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Human Bladder Cancer Cells.

    Science.gov (United States)

    Kang, Minyong; Lee, Kyoung-Hwa; Lee, Hye Sun; Jeong, Chang Wook; Kwak, Cheol; Kim, Hyeon Hoe; Ku, Ja Hyeon

    2017-02-04

    Despite the potential therapeutic efficacy of epithelial growth factor receptor (EGFR) inhibitors in the treatment of advanced stage bladder cancer, there currently is no clear evidence to support this hypothesis. In this study, we investigate whether the concurrent treatment of autophagy-blocking agents with EGFR inhibitors exerts synergistic anti-cancer effects in T24 and J82 human bladder cancer cells. Lapatinib and gefitinib were used as EGFR inhibitors, and bafilomycin A1 (BFA1), chloroquine (CQ) and 3-methyladenine (3-MA) were used as the pharmacologic inhibitors of autophagy activities. To assess the proliferative and self-renewal capabilities, the Cell Counting Kit-8 (CCK-8) assay and a clonogenic assay were performed, respectively. To examine apoptotic cell death, flow cytometry using annexin-V/propidium iodide (PI) was used. To measure the autophagy activities, the expression levels of LC3I and II was determined by Western blot analysis. To validate the synergistic effects of autophagy inhibition with EGFR inhibitors, we specifically blocked key autophagy regulatory gene ATG12 by transfection of small interference RNA and examined the phenotypic changes. Of note, lapatinib and gefitinib triggered autophagy activities in T24 and J82 human bladder cancer cells, as indicated by upregulation of LC3II. More importantly, inhibiting autophagy activities with pharmacologic inhibitors (BFA1, CQ or 3-MA) remarkably reduced the cell viabilities and clonal proliferation of T24 and J82 cells, compared to those treated with either of the agents alone. We also obtained similar results of the enhanced anti-cancer effects of EGFR inhibitors by suppressing the expression of ATG12. Notably, the apoptotic assay showed that synergistic anti-cancer effects were induced via the increase of apoptotic cell death. In summary, concomitant inhibition of autophagy activities potentiated the anti-cancer effects of EGFR inhibitors in human bladder cancer cells, indicating a novel

  9. Concurrent Autophagy Inhibition Overcomes the Resistance of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Human Bladder Cancer Cells

    Directory of Open Access Journals (Sweden)

    Minyong Kang

    2017-02-01

    Full Text Available Despite the potential therapeutic efficacy of epithelial growth factor receptor (EGFR inhibitors in the treatment of advanced stage bladder cancer, there currently is no clear evidence to support this hypothesis. In this study, we investigate whether the concurrent treatment of autophagy-blocking agents with EGFR inhibitors exerts synergistic anti-cancer effects in T24 and J82 human bladder cancer cells. Lapatinib and gefitinib were used as EGFR inhibitors, and bafilomycin A1 (BFA1, chloroquine (CQ and 3-methyladenine (3-MA were used as the pharmacologic inhibitors of autophagy activities. To assess the proliferative and self-renewal capabilities, the Cell Counting Kit-8 (CCK-8 assay and a clonogenic assay were performed, respectively. To examine apoptotic cell death, flow cytometry using annexin-V/propidium iodide (PI was used. To measure the autophagy activities, the expression levels of LC3I and II was determined by Western blot analysis. To validate the synergistic effects of autophagy inhibition with EGFR inhibitors, we specifically blocked key autophagy regulatory gene ATG12 by transfection of small interference RNA and examined the phenotypic changes. Of note, lapatinib and gefitinib triggered autophagy activities in T24 and J82 human bladder cancer cells, as indicated by upregulation of LC3II. More importantly, inhibiting autophagy activities with pharmacologic inhibitors (BFA1, CQ or 3-MA remarkably reduced the cell viabilities and clonal proliferation of T24 and J82 cells, compared to those treated with either of the agents alone. We also obtained similar results of the enhanced anti-cancer effects of EGFR inhibitors by suppressing the expression of ATG12. Notably, the apoptotic assay showed that synergistic anti-cancer effects were induced via the increase of apoptotic cell death. In summary, concomitant inhibition of autophagy activities potentiated the anti-cancer effects of EGFR inhibitors in human bladder cancer cells, indicating

  10. Small-molecule inhibition of HIV pre-mRNA splicing as a novel antiretroviral therapy to overcome drug resistance.

    Directory of Open Access Journals (Sweden)

    Nadia Bakkour

    2007-10-01

    Full Text Available The development of multidrug-resistant viruses compromises antiretroviral therapy efficacy and limits therapeutic options. Therefore, it is an ongoing task to identify new targets for antiretroviral therapy and to develop new drugs. Here, we show that an indole derivative (IDC16 that interferes with exonic splicing enhancer activity of the SR protein splicing factor SF2/ASF suppresses the production of key viral proteins, thereby compromising subsequent synthesis of full-length HIV-1 pre-mRNA and assembly of infectious particles. IDC16 inhibits replication of macrophage- and T cell-tropic laboratory strains, clinical isolates, and strains with high-level resistance to inhibitors of viral protease and reverse transcriptase. Importantly, drug treatment of primary blood cells did not alter splicing profiles of endogenous genes involved in cell cycle transition and apoptosis. Thus, human splicing factors represent novel and promising drug targets for the development of antiretroviral therapies, particularly for the inhibition of multidrug-resistant viruses.

  11. Melatonin suppresses thyroid cancer growth and overcomes radioresistance via inhibition of p65 phosphorylation and induction of ROS

    Directory of Open Access Journals (Sweden)

    Zhen-Wei Zou

    2018-06-01

    Full Text Available Thyroid cancer is the most common endocrine carcinoma with increasing incidence worldwide and anaplastic subtypes are frequently associated with cancer related death. Radioresistance of thyroid cancer often leads to therapy failure and cancer-related death. In this study, we found that melatonin showed potent suppressive roles on NF-κB signaling via inhibition of p65 phosphorylation and generated redox stress in thyroid cancer including the anaplastic subtypes. Our data showed that melatonin significantly decreased cell viability, suppressed cell migration and induced apoptosis in thyroid cancer cell lines in vitro and impaired tumor growth in the subcutaneous mouse model in vivo. By contrast, irradiation of thyroid cancer cells resulted in elevated level of phosphorylated p65, which could be reversed by cotreatment with melatonin. Consequently, melatonin synergized with irradiation to induce cytotoxicity to thyroid cancer, especially in the undifferentiated subgroups. Taken together, our results suggest that melatonin may exert anti-tumor activities against thyroid carcinoma by inhibition of p65 phosphorylation and induction of reactive oxygen species. Radio-sensitization by melatonin may have clinical benefits in thyroid cancer. Keywords: Melatonin, Thyroid cancer, Radioresistance, p65, Reactive oxygen species

  12. Inhibiting tumor necrosis factor-alpha diminishes desmoplasia and inflammation to overcome chemoresistance in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Zhao, Xianda; Fan, Wei; Xu, Zhigao; Chen, Honglei; He, Yuyu; Yang, Gui; Yang, Gang; Hu, Hanning; Tang, Shihui; Wang, Ping; Zhang, Zheng; Xu, Peipei; Yu, Mingxia

    2016-12-06

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most common cancer death reasons. Anti-tumor necrosis factor-alpha (TNF-α) antibodies have shown promising effects in PDAC pre-clinical models. However, the prognostic values of TNF-α, underlying mechanisms by which anti-TNF-α treatments inhibit PDAC, and potential synergistic effects of anti-TNF-α treatments with chemotherapy are still unclear. To identify the targeting values of TNF-α in PDAC, we measured TNF-α expression in different stages of PDAC initiation and evaluated its prognostic significance in a pancreatic cancer cohort. We found that TNF-α expression elevated in PDAC initiation process, and high expression of TNF-α was an independent prognostic marker of poor survival. We further evaluated anti-tumor effects of anti-TNF-α treatments in PDAC. Anti-TNF-α treatments resulted in decreased cell viability in both PDAC tumor cells and pancreatic satellite cells in similar dose in vitro. In vivo, anti-TNF-α treatments showed effects in reducing desmoplasia and the tumor promoting inflammatory microenvironment in PDAC. Combination of anti-TNF-α treatments with chemotherapy partly overcame chemoresistance of PDAC tumor cells and prolonged the survival of PDAC mouse model. In conclusion, our findings indicated that TNF-α in PDAC can be a prognostic and therapeutic target. Inhibition of TNF-α synergized with chemotherapy in PDAC resulted in better pre-clinical responses via killing tumor cells as well as diminishing desmoplasia and inflammation in PDAC tumor stroma.

  13. Fisetin, a dietary phytochemical, overcomes Erlotinib-resistance of lung adenocarcinoma cells through inhibition of MAPK and AKT pathways.

    Science.gov (United States)

    Zhang, Liang; Huang, Yi; Zhuo, Wenlei; Zhu, Yi; Zhu, Bo; Chen, Zhengtang

    2016-01-01

    Erlotinib (Tarceva) is a selective epidermal growth factor receptor tyrosine kinase inhibitor for treatment of non-small cell lung cancer (NSCLC). However, its efficacy is usually reduced by the occurrence of drug resistance. Our recent study showed that a flavonoid found in many plants, Fisetin, might have a potential to reverse the acquired Cisplatin-resistance of lung adenocarcinoma. In the present study, we aimed to test whether Fisetin could have the ability to reverse Erlotinib-resistance of lung cancer cells. Erlotinib-resistant lung adenocarcinoma cells, HCC827-ER, were cultured from the cell line HCC827, and the effects of Fisetin and Erlotinib on the cell viability and apoptosis were evaluated. The possible signaling pathways in this process were also detected. As expected, the results showed that Fisetin effectively increased sensitivity of Erlotinib-resistant lung cancer cells to Erlotinib, possibly by inhibiting aberrant activation of MAPK and AKT signaling pathways resulted from AXL suppression. In conclusion, Fisetin was a potential agent for reversing acquired Erlotinib-resistance of lung adenocarcinoma. Inactivation of AXL, MAPK and AKT pathways might play a partial role in this process.

  14. The targeted inhibition of mitochondrial Hsp90 overcomes the apoptosis resistance conferred by Bcl-2 in Hep3B cells via necroptosis

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Chunlan [Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan, 602-714 (Korea, Republic of); Department of Physiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058 (China); Oh, Joon Seok; Yoo, Seung Hee; Lee, Jee Suk [Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan, 602-714 (Korea, Republic of); Yoon, Young Geol [Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan, 602-714 (Korea, Republic of); Department of Biomedical Science, Institute for Biomedical and Health Sciences, Jungwon University, Chungbuk, 367-805 (Korea, Republic of); Oh, Yoo Jin; Jang, Min Seok [Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan, 602-714 (Korea, Republic of); Lee, Sang Yeob [Department of Rheumatology, Dong-A University College of Medicine, Busan, 602-714 (Korea, Republic of); Yang, Jun [Department of Toxicology, Hangzhou Normal University School of Public Health, Hangzhou, Zhejiang, 310036 China (China); Lee, Sang Hwa [Department of Microbiology and, Dong-A University College of Medicine, Busan, 602-714 (Korea, Republic of); Kim, Hye Young [Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan, 602-714 (Korea, Republic of); Yoo, Young Hyun, E-mail: yhyoo@dau.ac.kr [Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan, 602-714 (Korea, Republic of)

    2013-01-01

    Previous studies have reported that a Gamitrinib variant containing triphenylphosphonium (G-TPP) binds to mitochondrial Hsp90 and rapidly inhibits its activity, thus inducing the apoptotic pathway in the cells. Accordingly, G-TPP shows a potential as a promising drug for the treatment of cancer. A cell can die from different types of cell death such as apoptosis, necrosis, necroptosis, and autophagic cell death. In this study, we further investigated the mechanisms and modes of cell death in the G-TPP-treated Hep3B and U937 cell lines. We discovered that G-TPP kills the U937 cells through the apoptotic pathway and the overexpression of Bcl-2 significantly inhibits U937 cell death to G-TPP. We further discovered that G-TPP kills the Hep3B cells by activating necroptosis in combination with the partial activation of caspase-dependent apoptosis. Importantly, G-TPP overcomes the apoptosis resistance conferred by Bcl-2 in Hep3B cells via necroptosis. We also observed that G-TPP induces compensatory autophagy in the Hep3B cell line. We further found that whereas there is a Bcl-2-Beclin 1 interaction in response to G-TPP, silencing the beclin 1 gene failed to block LC3-II accumulation in the Hep3B cells, indicating that G-TPP triggers Beclin 1-independent protective autophagy in Hep3B cells. Taken together, these data reveal that G-TPP induces cell death through a combination of death pathways, including necroptosis and apoptosis, and overcomes the apoptosis resistance conferred by Bcl-2 in Hep3B cells via necroptosis. These findings are important for the therapeutic exploitation of necroptosis as an alternative cell death program to bypass the resistance to apoptosis. Highlights: ► G-TPP binds to mitochondrial Hsp90. ► G-TPP induces apoptosis in U937 human leukemia cancer cells. ► G-TPP induces combination of death pathways in Hep3B cell. ► G-TPP overcomes the resistance conferred by Bcl-2 in Hep3B cells via necroptosis. ► G-TPP triggers Beclin 1-independent

  15. Overcoming challenges

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    Full Text Available ... Disease and Stroke HIV and AIDS Mental Health Pain Pregnancy Reproductive Health Sexual Health Sexually Transmitted Infections ... breastfeeding Overcoming challenges Common questions about breastfeeding and pain Breastfeeding checklist: How to get a good latch ...

  16. Overcoming challenges

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    Full Text Available ... menu It's Only Natural Planning ahead Breastfeeding and baby basics Making breastfeeding work for you Addressing breastfeeding ... in the African-American community Incredible facts about babies, breastmilk, and breastfeeding Overcoming challenges Common questions about ...

  17. Overcoming challenges

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    Full Text Available ... and mission Leadership Programs and activities In your community Funding opportunities Internships and jobs View all pages ... breastfeeding myths Breastfeeding myths in the African-American community Incredible facts about babies, breastmilk, and breastfeeding Overcoming ...

  18. Overcoming challenges

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    Full Text Available ... facts about babies, breastmilk, and breastfeeding Overcoming challenges Common questions about breastfeeding and pain Breastfeeding checklist: How to get a good latch Finding support It takes a village: Building ...

  19. Overcoming challenges

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    Full Text Available ... breastfeeding means to them. Subscribe To receive Breastfeeding email updates Enter email Submit Overcoming challenges Breastfeeding has a long list ... breastfeeding means to them. Subscribe To receive Breastfeeding email updates Enter email Submit All material contained on ...

  20. Overcoming challenges

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    Full Text Available ... into your life Breastfeeding in daily life: At home and in public Laws that support breastfeeding 10 ... and jobs View all pages in this section Home It's Only Natural Overcoming challenges It's Only Natural ...

  1. Overcoming challenges

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    Full Text Available ... Contact Us Blog Popular topics Vision and mission Leadership Programs and activities In your community Funding opportunities Internships and jobs View all pages in this section Home It's Only Natural Overcoming challenges It's Only Natural Planning ahead Addressing breastfeeding myths ...

  2. Overcoming challenges

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    Full Text Available ... we are What we do Programs and activities Work with us Contact Us Blog Popular topics Vision and mission Leadership Programs and activities In your community Funding opportunities Internships and jobs View all pages in this section Home It's Only Natural Overcoming challenges It's Only Natural ...

  3. Overcoming Absence

    DEFF Research Database (Denmark)

    Paldam, Camilla Skovbjerg

    2017-01-01

    In this chapter, I address the rhetoric of modern love correspondence – its various purposes, modes of communication, and meta-reflections on writing and media – from the beginning of the 20th century till today. I analyze how love and the beloved are mediated in the articulated desire and longing...... of love letters, and how love letters are used as a medium to overcome absence. I also reflect on the material status of love letters in relation to the technological development and subsequently the replacement of traditional letters by their digital counterparts such as email, text messages and real...

  4. Inhibition of p70S6K1 Activation by Pdcd4 Overcomes the Resistance to an IGF-1R/IR Inhibitor in Colon Carcinoma Cells.

    Science.gov (United States)

    Zhang, Yan; Wang, Qing; Chen, Li; Yang, Hsin-Sheng

    2015-03-01

    Agents targeting insulin-like growth factor 1 receptor (IGF-1R) are being actively examined in clinical trials. Although there has been some initial success of single-agent targeting IGF-1R, attempts in later studies failed because of resistance. This study aimed to understand the effects of programmed cell death 4 (Pdcd4) on the chemosensitivity of the IGF-1R inhibitor OSI-906 in colorectal cancer cells and the mechanism underlying this impact. Using OSI-906-resistant and -sensitive colorectal cancer cells, we found that the Pdcd4 level directly correlates with cell chemosensitivity to OSI-906. In addition, tumors derived from Pdcd4 knockdown cells resist the growth inhibitory effect of OSI-906 in a colorectal cancer xenograft mouse model. Moreover, Pdcd4 enhances the antiproliferative effect of OSI-906 in resistant cells through suppression of p70S6K1 activation. Knockdown of p70S6K1, but not p70S6K2, significantly increases the chemosensitivity of OSI-906 in cultured colorectal cancer cells. Furthermore, the combination of OSI-906 and PF-4708671, a p70S6K1 inhibitor, efficiently suppresses the growth of OSI-906-resistant colon tumor cells in vitro and in vivo. Taken together, activation of p70S6K1 that is inhibited by Pdcd4 is essential for resistance to the IGF-1R inhibitor in colon tumor cells, and the combinational treatment of OSI-906 and PF-4708671 results in enhanced antiproliferation effects in colorectal cancer cells in vitro and in vivo, providing a novel venue to overcome the resistance to the IGF-1R inhibitor in treating colorectal cancer. ©2015 American Association for Cancer Research.

  5. AP24534, a Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes Mutation-Based Resistance

    Science.gov (United States)

    O’Hare, Thomas; Shakespeare, William C.; Zhu, Xiaotian; Eide, Christopher A.; Rivera, Victor M.; Wang, Frank; Adrian, Lauren T.; Zhou, Tianjun; Huang, Wei-Sheng; Xu, Qihong; Metcalf, Chester A.; Tyner, Jeffrey W.; Loriaux, Marc M.; Corbin, Amie S.; Wardwell, Scott; Ning, Yaoyu; Keats, Jeffrey A.; Wang, Yihan; Sundaramoorthi, Raji; Thomas, Mathew; Zhou, Dong; Snodgrass, Joseph; Commodore, Lois; Sawyer, Tomi K.; Dalgarno, David C.; Deininger, Michael W.N.; Druker, Brian J.; Clackson, Tim

    2009-01-01

    SUMMARY Inhibition of BCR-ABL by imatinib induces durable responses in many patients with chronic myeloid leukemia (CML), but resistance attributable to kinase domain mutations can lead to relapse and a switch to second-line therapy with nilotinib or dasatinib. Despite three approved therapeutic options, the cross-resistant BCR-ABLT315I mutation and compound mutants selected on sequential inhibitor therapy remain major clinical challenges. We report design and pre-clinical evaluation of AP24534, a potent, orally available multi-targeted kinase inhibitor active against T315I and other BCR-ABL mutants. AP24534 inhibited all tested BCR-ABL mutants in cellular and biochemical assays, suppressed BCR-ABLT315I-driven tumor growth in mice, and completely abrogated resistance in cell-based mutagenesis screens. Our work supports clinical evaluation of AP24534 as a pan-BCR-ABL inhibitor for treatment of CML. PMID:19878872

  6. AP24534, a Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes Mutation-Based Resistance

    Energy Technology Data Exchange (ETDEWEB)

    O’Hare, Thomas; Shakespeare, William C.; Zhu, Xiaotian; Eide, Christopher A.; Rivera, Victor M.; Wang, Frank; Adrian, Lauren T.; Zhou, Tianjun; Huang, Wei-Sheng; Xu, Qihong; Metcalf, III, Chester A.; Tyner, Jeffrey W.; Loriaux, Marc M.; Corbin, Amie S.; Wardwell, Scott; Ning, Yaoyu; Keats, Jeffrey A.; Wang, Yihan; Sundaramoorthi, Raji; Thomas, Mathew; Zhou, Dong; Snodgrass, Joseph; Commodore, Lois; Sawyer, Tomi K.; Dalgarno, David C.; Deininger, Michael W.N.; Druker, Brian J.; Clackson, Tim; (OHSU- Cancer Instit.); (ARIAD)

    2010-09-07

    Inhibition of BCR-ABL by imatinib induces durable responses in many patients with chronic myeloid leukemia (CML), but resistance attributable to kinase domain mutations can lead to relapse and a switch to second-line therapy with nilotinib or dasatinib. Despite three approved therapeutic options, the cross-resistant BCR-ABL{sup T315I} mutation and compound mutants selected on sequential inhibitor therapy remain major clinical challenges. We report design and preclinical evaluation of AP24534, a potent, orally available multitargeted kinase inhibitor active against T315I and other BCR-ABL mutants. AP24534 inhibited all tested BCR-ABL mutants in cellular and biochemical assays, suppressed BCR-ABL{sup T315I}-driven tumor growth in mice, and completely abrogated resistance in cell-based mutagenesis screens. Our work supports clinical evaluation of AP24534 as a pan-BCR-ABL inhibitor for treatment of CML.

  7. Prasugrel but not high dose clopidogrel overcomes the lansoprazole neutralizing effect of P2Y12 inhibition: Results of the randomized DOSAPI study.

    Science.gov (United States)

    Collet, Jean-Philippe; Hulot, Jean-Sébastien; Abtan, Jérémie; Anzaha, Ghalia; Kerneis, Mathieu; Silvain, Johanne; Cayla, Guillaume; O'Connor, Stephen A; Barthélémy, Olivier; Beygui, Farzin; Galier, Sophie; Brugier, Delphine; Stanek, Eric J; Charland, Scott L; Gallois, Vanessa; Montalescot, Gilles

    2014-09-01

    The potential negative metabolic interaction between proton pump inhibitors and clopidogrel is an unsolved issue. We hypothesized that doubling the clopidogrel maintenance dose (150 mg) would be less effective than switching to prasugrel 10 mg maintenance dose (MD) to overcome this negative interaction. In a randomized study with a factorial design, 82 stable coronary artery disease patients treated with 75 mg clopidogrel MD and aspirin were assigned to receive in a double blind fashion lansoprazole (30 mg/day) or placebo and to receive in an open fashion 150 mg clopidogrel MD or 10 mg prasugrel MD. The primary endpoint was the relative change in residual platelet reactivity over the 14-day study period [(RPA14day-RPAbaseline)/RPAbaseline]. The effect of doubling the clopidogrel MD on relative change in RPA was neutralized by lansoprazole (-53.6±48.4% versus +0.8±53.7% without and with lansoprazole, respectively, p = 0.02) whereas 10 mg of prasugrel MD dramatically reduced RPA irrespective of lansoprazole co-administration (-81.8 %±24.8% vs. -72.9%±32.9% without and with lansoprazole, respectively, p = NS). Lansoprazole exposure was the only parameter with a significant interaction with RPA among subgroups. The higher platelet inhibitory effect obtained by doubling the clopidogrel MD was totally neutralized by the co-administration of lansoprazole. This drug interaction was not observed with prasugrel 10 mg.

  8. Inhibition of ABCB1 (MDR1 expression by an siRNA nanoparticulate delivery system to overcome drug resistance in osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Michiro Susa

    2010-05-01

    Full Text Available The use of neo-adjuvant chemotherapy in treating osteosarcoma has improved patients' average 5 year survival rate from 20% to 70% in the past 30 years. However, for patients who progress after chemotherapy, its effectiveness diminishes due to the emergence of multi-drug resistance (MDR after prolonged therapy.In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure resulting from MDR, we designed and evaluated a novel drug delivery system for MDR1 siRNA delivery. Novel biocompatible, lipid-modified dextran-based polymeric nanoparticles were used as the platform for MDR1 siRNA delivery; and the efficacy of combination therapy with this system was evaluated. In this study, multi-drug resistant osteosarcoma cell lines (KHOS(R2 and U-2OS(R2 were treated with the MDR1 siRNA nanocarriers and MDR1 protein (P-gp expression, drug retention, and immunofluoresence were analyzed. Combination therapy of the MDR1 siRNA loaded nanocarriers with increasing concentrations of doxorubicin was also analyzed. We observed that MDR1 siRNA loaded dextran nanoparticles efficiently suppresses P-gp expression in the drug resistant osteosarcoma cell lines. The results also demonstrated that this approach may be capable of reversing drug resistance by increasing the amount of drug accumulation in MDR cell lines.Lipid-modified dextran-based polymeric nanoparticles are a promising platform for siRNA delivery. Nanocarriers loaded with MDR1 siRNA are a potential treatment strategy for reversing MDR in osteosarcoma.

  9. Bitter Melon (Momordica charantia) Extract Inhibits Tumorigenicity and Overcomes Cisplatin-Resistance in Ovarian Cancer Cells Through Targeting AMPK Signaling Cascade.

    Science.gov (United States)

    Yung, Mingo M H; Ross, Fiona A; Hardie, D Grahame; Leung, Thomas H Y; Zhan, Jinbiao; Ngan, Hextan Y S; Chan, David W

    2016-09-01

    Objective Acquired chemoresistance is a major obstacle in the clinical management of ovarian cancer. Therefore, searching for alternative therapeutic modalities is urgently needed. Bitter melon (Momordica charantia) is a traditional dietary fruit, but its extract also shows potential medicinal values in human diabetes and cancers. Here, we sought to investigate the extract of bitter melon (BME) in antitumorigenic and cisplatin-induced cytotoxicity in ovarian cancer cells. Three varieties of bitter melon were used to prepare the BME. Ovarian cancer cell lines, human immortalized epithelial ovarian cells (HOSEs), and nude mice were used to evaluate the cell cytotoxicity, cisplatin resistance, and tumor inhibitory effect of BME. The molecular mechanism of BME was examined by Western blotting. Cotreatment with BME and cisplatin markedly attenuated tumor growth in vitro and in vivo in a mouse xenograft model, whereas there was no observable toxicity in HOSEs or in nude mice in vivo Interestingly, the antitumorigenic effects of BME varied with different varieties of bitter melon, suggesting that the amount of antitumorigenic substances may vary. Studies of the molecular mechanism demonstrated that BME activates AMP-activated protein kinase (AMPK) in an AMP-independent but CaMKK (Ca(2+)/calmodulin-dependent protein kinase)-dependent manner, exerting anticancer effects through activation of AMPK and suppression of the mTOR/p70S6K and/or the AKT/ERK/FOXM1 (Forkhead Box M1) signaling cascade. BME functions as a natural AMPK activator in the inhibition of ovarian cancer cell growth and might be useful as a supplement to improve the efficacy of cisplatin-based chemotherapy in ovarian cancer. © The Author(s) 2015.

  10. Overcoming job stress

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000884.htm Overcoming job stress To use the sharing features on this page, ... stay healthy and feel better. Causes of Job Stress Although the cause of job stress is different ...

  11. Rocaglamide overcomes tumor necrosis factor-related apoptosis-inducing ligand resistance in hepatocellular carcinoma cells by attenuating the inhibition of caspase-8 through cellular FLICE-like-inhibitory protein downregulation.

    Science.gov (United States)

    Luan, Zhou; He, Ying; He, Fan; Chen, Zhishui

    2015-01-01

    The enhancement of apoptosis is a therapeutic strategy used in the treatment of cancer. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising antitumor agent. However, hepatocellular carcinoma (HCC) cells exhibit marked resistance to the induction of cell death by TRAIL. The present study investigated whether rocaglamide, a naturally occurring product isolated from the genus Aglaia, is able to sensitize resistant HCC cells to TRAIL-mediated apoptosis. Two HCC cell lines, HepG2 and Huh-7, were treated with rocaglamide and/or TRAIL and the induction of apoptosis and effects on the TRAIL signaling pathway were investigated. The in vivo efficacy of rocaglamide was determined in TRAIL-resistant Huh-7-derived tumor xenografts. Rocaglamide significantly sensitized the TRAIL-resistant HCC cells to apoptosis by TRAIL, which resulted from the rocaglamide-mediated downregulation of cellular FLICE-like inhibitory protein and subsequent caspase-8 activation. Furthermore, rocaglamide markedly inhibited tumor growth from Huh-7 cells propagated in severe combined immunodeficient mice, suggesting that chemosentization also occurred in vivo. These data suggest that rocaglamide acted synergistically with TRAIL against the TRAIL-resistant HCC cells. Thus, it is concluded that rocaglamide as an adjuvant to TRAIL-based therapy may present a promising therapeutic approach for the treatment of HCC.

  12. Overcoming Multidrug Resistance in Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Karobi Moitra

    2015-01-01

    Full Text Available The principle mechanism of protection of stem cells is through the expression of ATP-binding cassette (ABC transporters. These transporters serve as the guardians of the stem cell population in the body. Unfortunately these very same ABC efflux pumps afford protection to cancer stem cells in tumors, shielding them from the adverse effects of chemotherapy. A number of strategies to circumvent the function of these transporters in cancer stem cells are currently under investigation. These strategies include the development of competitive and allosteric modulators, nanoparticle mediated delivery of inhibitors, targeted transcriptional regulation of ABC transporters, miRNA mediated inhibition, and targeting of signaling pathways that modulate ABC transporters. The role of ABC transporters in cancer stem cells will be explored in this paper and strategies aimed at overcoming drug resistance caused by these particular transporters will also be discussed.

  13. Overcoming heat shock protein inhibition at critical temperature vital ...

    African Journals Online (AJOL)

    Bengyella

    2012-06-12

    Jun 12, 2012 ... Lafta and Lorenzen, 1995). The global warming rates .... system ensures rapid adaptation to the environmental changes. ... nuclear HSF during migration to the nucleus for activating ... Effect of climate change on global potato.

  14. ABCG2 inhibition as a therapeutic approach for overcoming ...

    Indian Academy of Sciences (India)

    2016-02-16

    Feb 16, 2016 ... Breast cancer resistance protein (BCRP, ABCP or MXR)/ATP-binding cassette subfamily G member 2 (ABCG2) was characterized as a multidrug resistance efflux transporter in 1998. ABCG2 physiologically acts as a part of a self- defence mechanism for the organism; it enhances eliminating of toxic ...

  15. ABCG2 Inhibition as a Therapeutic Approach for Overcoming ...

    Indian Academy of Sciences (India)

    Breast cancer resistance protein (BCRP, ABCP or MXR) / ATP-binding cassette subfamily G member 2 (ABCG2) was characterized as a multidrug resistance efflux transporter in 1998. ABCG2 physiologically acts as a part of a self-defense mechanism for the organism; it enhances eliminating of toxic xenobiotic substances ...

  16. ABCG2 inhibition as a therapeutic approach for overcoming

    Indian Academy of Sciences (India)

    2016-02-16

    Feb 16, 2016 ... the permeability of multi-protein channel complexes. (receptors) .... ABCG2 overexpression is likely to be the cause of high- ... with low or absent function. ..... derivatives, is a water-soluble topoisomerase I inhibitor that.

  17. Family skills for overcoming adversity

    Directory of Open Access Journals (Sweden)

    Mónica Patricia Ardila Hernández

    2013-12-01

    Full Text Available This section draws on research four families in displacement in Tunja Boyacá step of this research is to present the problem of displacement from another different look that has embargoed regarding this topic. Critical reflection was raised from resilient approach Parsons theory in order to understand families immersed in this conflict as change agents capable of adapting to a new system and overcome adversity. Within this scheme is used to obtain qualitative research of the following categories : adaptation to the new social context risk factors present in families and protective factors.

  18. Seismic signals hard clipping overcoming

    Science.gov (United States)

    Olszowa, Paula; Sokolowski, Jakub

    2018-01-01

    In signal processing the clipping is understand as the phenomenon of limiting the signal beyond certain threshold. It is often related to overloading of a sensor. Two particular types of clipping are being recognized: soft and hard. Beyond the limiting value soft clipping reduces the signal real gain while the hard clipping stiffly sets the signal values at the limit. In both cases certain amount of signal information is lost. Obviously if one possess the model which describes the considered signal and the threshold value (which might be slightly more difficult to obtain in the soft clipping case), the attempt of restoring the signal can be made. Commonly it is assumed that the seismic signals take form of an impulse response of some specific system. This may lead to belief that the sine wave may be the most appropriate to fit in the clipping period. However, this should be tested. In this paper the possibility of overcoming the hard clipping in seismic signals originating from a geoseismic station belonging to an underground mine is considered. A set of raw signals will be hard-clipped manually and then couple different functions will be fitted and compared in terms of least squares. The results will be then analysed.

  19. Heating plant overcomes coal crisis

    International Nuclear Information System (INIS)

    Sobinkovic, B.

    2006-01-01

    At the last moment Kosice managed to overcome the threat of a more than 30-percent heating price increase. The biggest local heat producer, Teplaren Kosice, is running out of coal supplies. The only alternative would be gas, which is far more expensive. The reason for this situation was a dispute of the heating plant with one of its suppliers, Kimex. Some days ago, the dispute was settled and the heating plant is now expecting the first wagon loads of coal to arrive. These are eagerly awaited, as its supplies will not last for more than a month. It all started with a public tender for a coal supplier. Teplaren Kosice (TEKO) announced the tender for the delivery of 120,000 tons of coal in June. Kimex, one of the traditional and biggest suppliers, was disqualified in the course of the tender. The winners of the tender were Slovenergo, Bratislava and S-Plus Trade, Vranov nad Toplou. TEKO signed contracts with them but a district court in Kosice prohibited the company from purchasing coal from these contractors. Kimex filed a complaint claiming that it was disqualified unlawfully. Based on this the court issued a preliminary ruling prohibiting the purchase of coal from the winners of the tender. The heating plant had to wait for the final verdict. The problem was then solved by the company's new Board of Directors, who were appointed in mid October who managed to sign new contracts with the two winners and Kimex. The new contracts cover the purchase of 150-thousand tons of coal, which is 30,000 more than in the original tender specification. Each company will supply one third. (authors)

  20. Intervention: Help a Loved One Overcome Addiction

    Science.gov (United States)

    Intervention: Help a loved one overcome addiction An intervention can motivate someone to seek help for alcohol or drug misuse, compulsive eating, or ... successful. By Mayo Clinic Staff It's challenging to help a loved one struggling with any type of ...

  1. Learning communities and overcoming poverty in Brazil

    Directory of Open Access Journals (Sweden)

    Tatiana Santos Pitanga

    2015-09-01

    Full Text Available Object: Brazil has implemented social programs to meet the Millennium Development Goals of reducing poverty and inequality. Despite the good results still there are ghettos and educational and social inequalities. Moreover Learning Communities are responding to these needs by promoting education based on successful actions scientifically proven of which promote educational change and social inclusion. The aim of this article is to highlight the characteristics of Learning Communities that allow overcoming poverty, and in this perspective, explain the implementation of the Learning Communities in Brazil and how, in this way, it is creating the conditions for effective overcoming give poverty and inequality in this country.Design / methodology: This article is based on documentary analysis of reports of the INCLUD-ED - the project on school education more scientific resources has been funded by the European Union, United Nations / ECLAC, Brazilian public agencies and websites of official institutions that promote Learning Communities in Brazil. Brazilian Institute of Geography and Statistics are also collected.Contributions and results: It highlights successful actions that contribute to overcoming poverty and social exclusion. Such actions are based on dialogic learning, democratic management and the formation of heterogeneous groups. It is observed that in Brazil are carrying out such actions and the ongoing expansion of the project in the country is creating the conditions for effective poverty reduction.Added value: This article reveals specific elements of overcoming poverty through education.

  2. Overcoming Learned Helplessness in Community College Students.

    Science.gov (United States)

    Roueche, John E.; Mink, Oscar G.

    1982-01-01

    Reviews research on the effects of repeated experiences of helplessness and on locus of control. Identifies conditions necessary for overcoming learned helplessness; i.e., the potential for learning to occur; consistent reinforcement; relevant, valued reinforcers; and favorable psychological situation. Recommends eight ways for teachers to…

  3. Learn to Avoid or Overcome Leadership Obstacles

    Science.gov (United States)

    D'Auria, John

    2015-01-01

    Leadership is increasingly recognized as an important factor in moving schools forward, yet we have been relatively random in how we prepare and support them. Four obstacles often block or diminish their effectiveness. Avoiding or overcoming each of these requires an underlying set of skills and knowledge that we believe can be learned and…

  4. Overcoming Barriers in Working with Families

    Science.gov (United States)

    Heru, Alison M.; Drury, Laura

    2006-01-01

    Objective: The Accreditation Council for Graduate Medical Education and the Residency Review Committee for psychiatry outline the expected competencies for residents. These competencies include working with families. This article describes barriers that residents face when working with families, and offers ways to overcome these barriers. Method:…

  5. Successful Writing: Five Roadblocks to Overcome

    Science.gov (United States)

    King, Kathleen P.

    2013-01-01

    This article provides essential strategies to be more successful in one of the major roles in academia: writing. Most academics struggle with roadblocks in their writing process. We are forever battling to complete research articles, manuscripts, grant proposals or other documents. The strategies and perspective shared here help overcome several…

  6. Bacterial resistance to silver nanoparticles and how to overcome it

    Science.gov (United States)

    Panáček, Aleš; Kvítek, Libor; Smékalová, Monika; Večeřová, Renata; Kolář, Milan; Röderová, Magdalena; Dyčka, Filip; Šebela, Marek; Prucek, Robert; Tomanec, Ondřej; Zbořil, Radek

    2018-01-01

    Silver nanoparticles have already been successfully applied in various biomedical and antimicrobial technologies and products used in everyday life. Although bacterial resistance to antibiotics has been extensively discussed in the literature, the possible development of resistance to silver nanoparticles has not been fully explored. We report that the Gram-negative bacteria Escherichia coli 013, Pseudomonas aeruginosa CCM 3955 and E. coli CCM 3954 can develop resistance to silver nanoparticles after repeated exposure. The resistance stems from the production of the adhesive flagellum protein flagellin, which triggers the aggregation of the nanoparticles. This resistance evolves without any genetic changes; only phenotypic change is needed to reduce the nanoparticles' colloidal stability and thus eliminate their antibacterial activity. The resistance mechanism cannot be overcome by additional stabilization of silver nanoparticles using surfactants or polymers. It is, however, strongly suppressed by inhibiting flagellin production with pomegranate rind extract.

  7. Overcoming challenges to secure a renewable future

    Energy Technology Data Exchange (ETDEWEB)

    McGrath, Rob; Philpott, Angie; Bown, Charles W.; Thompson, Robert; Dunderdale, Kathy

    2010-09-15

    Newfoundland and Labrador is on the brink of two extraordinary energy achievements: 1) becoming one of the world's only jurisdictions thermal generation almost entirely; and 2) making a huge contribution of renewable energy to North America. These achievements require the development of the 3,000 MW Lower Churchill Hydroelectric Project; however, the Project will not be developed without a business case to support it. This paper will highlight how the province, through its Energy Plan, has set the path forward for the future development of its renewable resources, including how it plans to overcome some of the challenges ahead.

  8. Overcoming barriers to membrane protein structure determination.

    Science.gov (United States)

    Bill, Roslyn M; Henderson, Peter J F; Iwata, So; Kunji, Edmund R S; Michel, Hartmut; Neutze, Richard; Newstead, Simon; Poolman, Bert; Tate, Christopher G; Vogel, Horst

    2011-04-01

    After decades of slow progress, the pace of research on membrane protein structures is beginning to quicken thanks to various improvements in technology, including protein engineering and microfocus X-ray diffraction. Here we review these developments and, where possible, highlight generic new approaches to solving membrane protein structures based on recent technological advances. Rational approaches to overcoming the bottlenecks in the field are urgently required as membrane proteins, which typically comprise ~30% of the proteomes of organisms, are dramatically under-represented in the structural database of the Protein Data Bank.

  9. Overcoming the isolation of disadvantaged housing areas

    DEFF Research Database (Denmark)

    Stender, Marie; Bech-Danielsen, Claus

    Disadvantaged social housing areas in Denmark are currently subject to more thorough physical refurbishments, aiming to overcome the isolated character of the housing estates. The ambition is to attract new users and residents by opening up the borders of the area and establish attractive, new...... penthouse flats, new urban functions within the area or spectacular new public spaces near it. In this paper the social impact of such transformations are analysed and discussed based on case-studies in 3 Danish areas. The analysis shows that especially everyday-route strategies adding new public functions...

  10. Overcome IMF crisis with idea and invention

    International Nuclear Information System (INIS)

    Wang, Yeon Jung

    1998-01-01

    This book introduces the invention as a tool to overcome IMF crisis. These are the titles of the way to create invention and idea : what is idea? everyone can create something, have a confidence, this is patent, replace or change something, invention is not logical, challenge the normal law, throw away stereotype, movement of idea, original imagination, there are a lot of solutions, there is no expert, have a positive thought, why does inventor invent? necessity is invention of mother, three stage of idea and invention and imitation for invention.

  11. Overcome IMF crisis with idea and invention

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yeon Jung

    1998-01-15

    This book introduces the invention as a tool to overcome IMF crisis. These are the titles of the way to create invention and idea : what is idea? everyone can create something, have a confidence, this is patent, replace or change something, invention is not logical, challenge the normal law, throw away stereotype, movement of idea, original imagination, there are a lot of solutions, there is no expert, have a positive thought, why does inventor invent? necessity is invention of mother, three stage of idea and invention and imitation for invention.

  12. Reshaping transport operations to overcome new challenges

    Energy Technology Data Exchange (ETDEWEB)

    Harari, F.; Blachet, L. [COGEMA Logistics, (AREVA Group) (France)

    2004-07-01

    After more than 30 years of Spent Fuel Nuclear Fuel (SFN) and High Level Waste (HLW) casks shipments to and from the COGEMA reprocessing factories in LA HAGUE, COGEMA LOGISTICS has demonstrated a unique outstanding performance in transportation for the benefit of its international customers and has integrated all feed-back from past successful operations. While maintaining the highest safety and security records, the last 5 years have been a major challenge to overcome the increase in transport throughputs, regulatory requirements, specific customer demands and new environmental approach (both COGEMA-La Hague and COGEMA LOGISTICS have been certified ISO14001 since 2003). Improvements in procedures, equipments, controls, inspection and organization have been undertaken. Additional important logistics means such as cranes, lifting devices, spreaders were put in operations in the dedicated workshop of our road and maritime facilities as well as in our rail terminals. Thus COGEMA LOGISTICS has developed and improved important logistics means in the Cherbourg area for the loading and unloading operations of heavy casks (i.e. whose weight is between 25 and 120 tons) among three modes of freight (road, railway or maritime transportation). In Valognes, which is currently the most important railway terminal in the world for the transfer of nuclear materials, about 1200 transfers of heavy casks were performed in 2003. New transport equipment and assets were integrated successfully to answer the new requirements for the best interest of our customers. This paper will provide information about equipments and management system developed to overcome these challenges.

  13. Reshaping transport operations to overcome new challenges

    International Nuclear Information System (INIS)

    Harari, F.; Blachet, L.

    2004-01-01

    After more than 30 years of Spent Fuel Nuclear Fuel (SFN) and High Level Waste (HLW) casks shipments to and from the COGEMA reprocessing factories in LA HAGUE, COGEMA LOGISTICS has demonstrated a unique outstanding performance in transportation for the benefit of its international customers and has integrated all feed-back from past successful operations. While maintaining the highest safety and security records, the last 5 years have been a major challenge to overcome the increase in transport throughputs, regulatory requirements, specific customer demands and new environmental approach (both COGEMA-La Hague and COGEMA LOGISTICS have been certified ISO14001 since 2003). Improvements in procedures, equipments, controls, inspection and organization have been undertaken. Additional important logistics means such as cranes, lifting devices, spreaders were put in operations in the dedicated workshop of our road and maritime facilities as well as in our rail terminals. Thus COGEMA LOGISTICS has developed and improved important logistics means in the Cherbourg area for the loading and unloading operations of heavy casks (i.e. whose weight is between 25 and 120 tons) among three modes of freight (road, railway or maritime transportation). In Valognes, which is currently the most important railway terminal in the world for the transfer of nuclear materials, about 1200 transfers of heavy casks were performed in 2003. New transport equipment and assets were integrated successfully to answer the new requirements for the best interest of our customers. This paper will provide information about equipments and management system developed to overcome these challenges

  14. Disposition of overcoming students for critical reading

    Directory of Open Access Journals (Sweden)

    Rosangela Miola Galvão

    2018-03-01

    Full Text Available This article aims to present the possibilities of an educational practice that focuses on the formation of Basic Education students in critical readers. For this, understand the concepts of alienation and language from the point of view of Historical and Dialectical Materialism and Historical-Cultural Theory was essential to understand how the students of the 7th year are able to overcome this paradigm that contributes to the naive reading of texts worked in the classroom. It was a qualitative study of bibliographic revision in union with the dialectical practice with students in a public school located in the north of the State of Paraná. As methodology, was developed twelve classes with diversified material in which the teacher's mediation sought to contemplate form and content in the way that occurred the deconstruction of the fictitious hero concept represented at the end by the art of the haicai poem. The use of the cell phone instrument and Whatsapp were important for the development of the poetic sense. It seeks, therefore, to demonstrate the contributions of historical and dialectical materialism to teaching practice and human development. The theorists considerations allow us to note that language contributes to the development of higher psychic functions in man and the alienation of subjects in today's society considerably affects the students interpretation and, consequently, formation for critical reading, which can be overcome with the use of a conscious theoretical current.

  15. Overcoming Obstacles to Drug Repositioning in Japan

    Directory of Open Access Journals (Sweden)

    Yuhei Nishimura

    2017-10-01

    Full Text Available Drug repositioning (DR is the process of identifying new indications for existing drugs. DR usually focuses on drugs that have cleared phase-I safety trials but has yet to show efficacy for the intended indication. Therefore, DR can probably skip the preclinical and phase-I study, which can reduce the cost throughout drug development. However, the expensive phase-II/III trials are required to establish efficacy. The obstacles to DR include identification of new indications with a high success rate in clinical studies, obtaining funding for clinical studies, patent protection, and approval systems. To tackle these obstacles, various approaches have been applied to DR worldwide. In this perspective, we provide representative examples of DR and discuss the ongoing efforts to overcome obstacles to DR in Japan.

  16. Towards overcoming poor readership and building reading culture ...

    African Journals Online (AJOL)

    Towards overcoming poor readership and building reading culture of in schools. ... of this paper is to find strategies that can overcome poor readership in schools. ... Keywords: English First Additional Language, Writing Skills, Spelling Errors, ...

  17. Overcoming fixation with repeated memory suppression.

    Science.gov (United States)

    Angello, Genna; Storm, Benjamin C; Smith, Steven M

    2015-01-01

    Fixation (blocks to memories or ideas) can be alleviated not only by encouraging productive work towards a solution, but, as the present experiments show, by reducing counterproductive work. Two experiments examined relief from fixation in a word-fragment completion task. Blockers, orthographically similar negative primes (e.g., ANALOGY), blocked solutions to word fragments (e.g., A_L_ _GY) in both experiments. After priming, but before the fragment completion test, participants repeatedly suppressed half of the blockers using the Think/No-Think paradigm, which results in memory inhibition. Inhibiting blockers did not alleviate fixation in Experiment 1 when conscious recollection of negative primes was not encouraged on the fragment completion test. In Experiment 2, however, when participants were encouraged to remember negative primes at fragment completion, relief from fixation was observed. Repeated suppression may nullify fixation effects, and promote creative thinking, particularly when fixation is caused by conscious recollection of counterproductive information.

  18. Inhibition Efficiency in Highly Proficient Bilinguals and Simultaneous Interpreters: Evidence from Language Switching and Stroop Tasks

    OpenAIRE

    Aparicio, X.; Heidlmayr, K.; Isel, F.

    2017-01-01

    The present behavioral study aimed to examine the impact of language control expertise on two domain-general control processes, i.e. active inhibition of competing representations and overcoming of inhibition. We compared how Simultaneous Interpreters (SI) and Highly Proficient Bilinguals—two groups assumed to differ in language control capacity—performed executive tasks involving specific inhibition processes. In Experiment 1 (language decision task), both active and overcoming of inhibition...

  19. Evaluative pressure overcomes perceptual load effects.

    Science.gov (United States)

    Normand, Alice; Autin, Frédérique; Croizet, Jean-Claude

    2015-06-01

    Perceptual load has been found to be a powerful bottom-up determinant of distractibility, with high perceptual load preventing distraction by any irrelevant information. However, when under evaluative pressure, individuals exert top-down attentional control by giving greater weight to task-relevant features, making them more distractible from task-relevant distractors. One study tested whether the top-down modulation of attention under evaluative pressure overcomes the beneficial bottom-up effect of high perceptual load on distraction. Using a response-competition task, we replicated previous findings that high levels of perceptual load suppress task-relevant distractor response interference, but only for participants in a control condition. Participants under evaluative pressure (i.e., who believed their intelligence was assessed) showed interference from task-relevant distractor at all levels of perceptual load. This research challenges the assumptions of the perceptual load theory and sheds light on a neglected determinant of distractibility: the self-relevance of the performance situation in which attentional control is solicited.

  20. Cooperative networks overcoming defectors by social influence

    Science.gov (United States)

    Gomez Portillo, Ignacio

    2014-01-01

    We address the cooperation problem in structured populations by considering the prisoner’s dilemma game as a metaphor of the social interactions between individuals with imitation capacity. We present a new strategy update rule called democratic weighted update where the individual’s behavior is socially influenced by each one of their neighbors. In particular, the capacity of an individual to socially influence other ones is proportional to its accumulated payoff. When in a neighborhood there are cooperators and defectors, the focal player is contradictorily influenced by them and, therefore, the effective social influence is given by the difference of the accumulated payoff of each strategy in its neighborhood. First, by considering the growing process of the network and neglecting mutations, we show the evolution of highly cooperative systems. Then, we broadly show that the social influence allows to overcome the emergence of defectors into highly cooperative systems. In this way, we conclude that in a structured system formed by a growing process, the cooperation evolves if the individuals have an imitation capacity socially influenced by each one of their neighbors. Therefore, here we present a theoretical solution of the cooperation problem among genetically unrelated individuals.

  1. Overcoming soil compaction in surface mine reclamation

    Energy Technology Data Exchange (ETDEWEB)

    Sweigard, R.J. (University of Kentucky, Lexington, KY (USA). Dept. of Mining Engineering)

    1991-01-01

    Rubber-tyred soil reconstruction equipment causes compaction of soil and means surface mine operators cannot satisfy crop yield standards defined by the Surface Mining Control and Reclamation Act. Soil compaction can be overcome by either modifying the reconstruction process or alleviating the problem, for example by deep tillage, once it occurs. The Dept. of Mining Engineering at the Institute of Mining and Minerals Research is conducting a laboratory investigation into a method of injecting low density porous organic material into a bin containing soil at the same time as the soil is ripped. This should prevent voids collapsing when subjected to forces from farm equipment and natural sources. Soil analyses are performed before and after the injection. Ripping and injection with ground pecan shells had a residual effect on nuclear bulk density compared to the initially compacted case and also showed an improvement in hydraulic conductivity. Work is in progress on modifying the system to handle other injection material and should lead on to field tests on a prototype involving both soil analysis and crop yield determination. 1 fig.

  2. Overcoming soil compaction in surface mine reclamation

    International Nuclear Information System (INIS)

    Sweigard, R.J.

    1991-01-01

    Rubber-tyred soil reconstruction equipment causes compaction of soil and means surface mine operators cannot satisfy crop yield standards defined by the Surface Mining Control and Reclamation Act. Soil compaction can be overcome by either modifying the reconstruction process or alleviating the problem, for example by deep tillage, once it occurs. The Dept. of Mining Engineering at the Institute of Mining and Minerals Research is conducting a laboratory investigation into a method of injecting low density porous organic material into a bin containing soil at the same time as the soil is ripped. This should prevent voids collapsing when subjected to forces from farm equipment and natural sources. Soil analyses are performed before and after the injection. Ripping and injection with ground pecan shells had a residual effect on nuclear bulk density compared to the initially compacted case and also showed an improvement in hydraulic conductivity. Work is in progress on modifying the system to handle other injection material and should lead on to field tests on a prototype involving both soil analysis and crop yield determination. 1 fig

  3. Overponderabilia: Overcoming Overthinking When Studying "Ourselves"

    Directory of Open Access Journals (Sweden)

    Kasper Tang Vangkilde

    2016-05-01

    Full Text Available This article discusses a key methodological difficulty in conducting qualitative research close to home: the issue of overthinking. Whereas MALINOWSKI's concern regarding imponderabilia, i.e., the risk of not thinking about the subtle phenomena of everyday life, has long haunted ethnographers and qualitative researchers, not least those working "at home," we highlight an issue of overponderabilia, i.e., the risk of overthinking seemingly familiar statements and practices of the people studied. How do we, as qualitative researchers, study very well-known phenomena such as science, bureaucracy, management etc. without reading our own ideas and understandings into the deceptively familiar concepts and accounts of our research subjects? Pondering this issue is inevitably a central concern for the increasing number of qualitative researchers who study people who apparently talk, think and work in a way which is similar to their own. While previous answers or solutions to this issue first and foremost emphasize various means of reflexivity, this article presents the method of "mutual participatory observation" as a particular way of overcoming overthinking: a method which in situ invites our research subjects into our thinking. Thus, in the pursuit of an ever enhanced understanding, qualitative research becomes not so much a reflexive deciphering as an active debate; that is, a mutual induction of the differences between the qualitative researcher and the research subjects. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1602281

  4. Developing an intervention to overcome procrastination.

    Science.gov (United States)

    Otermin-Cristeta, Solange; Hautzinger, Martin

    2018-01-01

    The main goal of this study was the development of a reliable intervention to overcome general procrastination orientated to college students, designed to be used in practical clinical work. The workshops involved six meetings based on behavioral and cognitive techniques, paradox intervention, and psychoeducation. 175 students participated voluntarily. Their procrastination levels were measured in a pretest, post-test, and a 3-month follow-up. After the first interview, the participants were randomly divided into three groups (Intervention A, Intervention B, and a control group with no intervention). There was a significant improvement after the intervention. After 3 months, the average score was still significantly lower than in the pretest, whereas the score of the control group remained unchanged. The participants in Workshop A scored significantly lower in the post-test than the ones in Workshop B. After 3 months, the participants in Workshop B scored significantly lower in the follow up. So both interventions resulted to be effective in reducing procrastination sustainably.

  5. Mid-Atlantic Wind - Overcoming the Challenges

    Energy Technology Data Exchange (ETDEWEB)

    Daniel F. Ancona III; Kathryn E. George; Richard P. Bowers; Dr. Lynn Sparling; Bruce Buckheit; Daniel LoBue

    2012-05-31

    This study, supported by the US Department of Energy, Wind Powering America Program, Maryland Department of Natural Resources and Chesapeake Bay Foundation, analyzed barriers to wind energy development in the Mid-Atlantic region along with options for overcoming or mitigating them. The Mid-Atlantic States including Delaware, Maryland, North Carolina and Virginia, have excellent wind energy potential and growing demand for electricity, but only two utility-scale projects have been installed to date. Reasons for this apathetic development of wind resources were analyzed and quantified for four markets. Specific applications are: 1) Appalachian mountain ridgeline sites, 2) on coastal plains and peninsulas, 3) at shallow water sites in Delaware and Chesapeake Bays, Albemarle and Pamlico Sounds, and 4) at deeper water sites off the Atlantic coast. Each market has distinctly different opportunities and barriers. The primary barriers to wind development described in this report can be grouped into four categories; state policy and regulatory issues, wind resource technical uncertainty, economic viability, and public interest in environmental issues. The properties of these typologies are not mutually independent and do interact. The report concluded that there are no insurmountable barriers to land-based wind energy projects and they could be economically viable today. Likewise potential sites in sheltered shallow waters in regional bay and sounds have been largely overlooked but could be viable currently. Offshore ocean-based applications face higher costs and technical and wind resource uncertainties. The ongoing research and development program, revision of state incentive policies, additional wind measurement efforts, transmission system expansion, environmental baseline studies and outreach to private developers and stakeholders are needed to reduce barriers to wind energy development.

  6. Mid-Atlantic Wind - Overcoming the Challenges

    Energy Technology Data Exchange (ETDEWEB)

    Daniel F. Ancona III; Kathryn E. George; Lynn Sparling; Bruce C. Buckheit; Daniel LoBue; and Richard P. Bowers

    2012-06-29

    This study, supported by the US Department of Energy, Wind Powering America Program, Maryland Department of Natural Resources and Chesapeake Bay Foundation, analyzed barriers to wind energy development in the Mid-Atlantic region along with options for overcoming or mitigating them. The Mid-Atlantic States including Delaware, Maryland, North Carolina and Virginia, have excellent wind energy potential and growing demand for electricity, but only two utility-scale projects have been installed to date. Reasons for this apathetic development of wind resources were analyzed and quantified for four markets. Specific applications are: 1) Appalachian mountain ridgeline sites, 2) on coastal plains and peninsulas, 3) at shallow water sites in Delaware and Chesapeake Bays, Albemarle and Pamlico Sounds, and 4) at deeper water sites off the Atlantic coast. Each market has distinctly different opportunities and barriers. The primary barriers to wind development described in this report can be grouped into four categories; state policy and regulatory issues, wind resource technical uncertainty, economic viability, and public interest in environmental issues. The properties of these typologies are not mutually independent and do interact. The report concluded that there are no insurmountable barriers to land-based wind energy projects and they could be economically viable today. Likewise potential sites in sheltered shallow waters in regional bay and sounds have been largely overlooked but could be viable currently. Offshore ocean-based applications face higher costs and technical and wind resource uncertainties. The ongoing research and development program, revision of state incentive policies, additional wind measurement efforts, transmission system expansion, environmental baseline studies and outreach to private developers and stakeholders are needed to reduce barriers to wind energy development.

  7. Overcoming the Challenges of Co-creation

    Science.gov (United States)

    Pandya, R.; Udu-gama, N.; Goodwin, M.; Otellini, P.

    2016-12-01

    There is growing interest in co-creation, especially for community-related issues like climate change, resilience, pollution, and environmental justice. Nevertheless, co-creation is still not mainstream practice in either geosciences or the world of decision-makers. This presents many challenges. On the science side, challenges include a paucity of training opportunities, lack of funding for co-creation, difficulty publishing or otherwise getting credit for the effort, and a perceived lack of prestige compared to theoretical research. On the community side, parallel challenges include a lack of experience working with scientists or thinking about geoscience's relevance to community issues, tight budgets and competing priorities, the need for outputs beyond publications, and the difficulty including science among a range of factors. Additionally, scientists and community leaders often work across public and private sectors and must navigate different approaches to data, privacy, and accountability. We'll use this session to explore opportunities to overcome the challenges of co-creation. Systems thinking suggests a range of approaches: enabling individuals, reducing specific challenges, changing the relationship between the elements of the systems, and changing the goals or mindsets of the systems - each more powerful than the last. For example, mentoring and coaching enables individuals, and pro-bono work eases the challenge of getting professional credit. New modes of output, like plain language abstracts, change the relationship between publications and other outputs. We can work on changing mindsets by publicizing and celebrating individual successes. With more effort and impact, we can build collaborations in the collective impact model, where we bring scientific and community organizations together around a common agenda and shared measurement. Building on these examples, we will use this session to collect strategies and opportunities from all participants.

  8. Overcoming natural replication barriers: differential helicase requirements.

    Science.gov (United States)

    Anand, Ranjith P; Shah, Kartik A; Niu, Hengyao; Sung, Patrick; Mirkin, Sergei M; Freudenreich, Catherine H

    2012-02-01

    DNA sequences that form secondary structures or bind protein complexes are known barriers to replication and potential inducers of genome instability. In order to determine which helicases facilitate DNA replication across these barriers, we analyzed fork progression through them in wild-type and mutant yeast cells, using 2-dimensional gel-electrophoretic analysis of the replication intermediates. We show that the Srs2 protein facilitates replication of hairpin-forming CGG/CCG repeats and prevents chromosome fragility at the repeat, whereas it does not affect replication of G-quadruplex forming sequences or a protein-bound repeat. Srs2 helicase activity is required for hairpin unwinding and fork progression. Also, the PCNA binding domain of Srs2 is required for its in vivo role of replication through hairpins. In contrast, the absence of Sgs1 or Pif1 helicases did not inhibit replication through structural barriers, though Pif1 did facilitate replication of a telomeric protein barrier. Interestingly, replication through a protein barrier but not a DNA structure barrier was modulated by nucleotide pool levels, illuminating a different mechanism by which cells can regulate fork progression through protein-mediated stall sites. Our analyses reveal fundamental differences in the replication of DNA structural versus protein barriers, with Srs2 helicase activity exclusively required for fork progression through hairpin structures.

  9. Targeted multidrug delivery system to overcome chemoresistance in breast cancer

    Directory of Open Access Journals (Sweden)

    Tang Y

    2017-01-01

    Full Text Available Yuan Tang,1 Fariborz Soroush,1 Zhaohui Tong,2 Mohammad F Kiani,1 Bin Wang1,3 1Department of Mechanical Engineering, Temple University, Philadelphia, PA, 2Department of Agricultural and Biological Engineering, University of Florida, Gainesville, FL, 3Department of Biomedical Engineering, Widener University, Chester, PA, USA Abstract: Chemotherapy has been widely used in breast cancer patients to reduce tumor size. However, most anticancer agents cannot differentiate between cancerous and normal cells, resulting in severe systemic toxicity. In addition, acquired drug resistance during the chemotherapy treatment further decreases treatment efficacy. With the proper treatment strategy, nanodrug carriers, such as liposomes/immunoliposomes, may be able to reduce undesired side effects of chemotherapy, to overcome the acquired multidrug resistance, and to further improve the treatment efficacy. In this study, a novel combinational targeted drug delivery system was developed by encapsulating antiangiogenesis drug bevacizumab into liposomes and encapsulating chemotherapy drug doxorubicin (DOX into immunoliposomes where the human epidermal growth factor receptor 2 (HER2 antibody was used as a targeting ligand. This novel combinational system was tested in vitro using a HER2 positive and multidrug resistant breast cancer cell line (BT-474/MDR, and in vivo using a xenograft mouse tumor model. In vitro cell culture experiments show that immunoliposome delivery led to a high cell nucleus accumulation of DOX, whereas free DOX was observed mostly near the cell membrane and in cytoplasm due to the action of P-gp. Combining liposomal bevacizumab with immunoliposomal DOX achieved the best tumor growth inhibition and the lowest toxicity. Tumor size decreased steadily within a 60-day observation period indicating a potential synergistic effect between DOX and bevacizumab through the targeted delivery. Our findings clearly indicate that tumor growth was significantly

  10. A SYSTEMIC VISION OF BIOLOGY: OVERCOMING LINEARITY

    Directory of Open Access Journals (Sweden)

    M. Mayer

    2005-07-01

    were used to build  a hipermedia  material.  This  technology  permit  overcomes a linear  communication, improving the  comprehension  of the network perspective.   The teachers  speeches revealed  their  conceptual  con- structions along the  course,  showed the development of the  competences  in identify  interconnection points  in the flow and chemical cycling of energy, compatible  with a systemic view of life.

  11. Why Mondragon? Analyzing What Works in Overcoming Inequalities

    Science.gov (United States)

    Redondo, Gisela; Santa Cruz, Ignacio; Rotger, Josep Maria

    2011-01-01

    Research using the critical communicative methodology (CCM) aims to identify the elements that help overcome inequalities. Drawing on research on the Basque Mondragon Corporation (MC), the authors focus on two major elements such as, selecting research cases that have been shown to succeed in overcoming inequalities, and communicative data…

  12. Fear of Public Speaking: How Can I Overcome It?

    Science.gov (United States)

    ... I overcome it? How can I overcome my fear of public speaking? Answers from Craig N. Sawchuk, Ph.D., L.P. Fear of public speaking is a common form of ... It can range from slight nervousness to paralyzing fear and panic. Many people with this fear avoid ...

  13. Interleukin-36 cytokines may overcome microbial immune evasion strategies that inhibit interleukin-1 family signaling.

    Science.gov (United States)

    Jensen, Liselotte E

    2017-08-15

    Pathogens deploy immune evasion strategies to successfully establish infections within their hosts. Naturally, the host responds by acquiring mechanisms to counter these strategies. There is increasing evidence that the three interleukin-36 (IL-36) cytokines, IL-36α, IL-36β and IL-36γ, play important roles in host immunity. With a focus on the skin as a target for microbial and viral invasion, the current knowledge of IL-36 functions is reviewed. Furthermore, the hypothesis that the IL-36s have evolved to counteract virulence factors is presented using viruses as an example. The IL-36s are related to IL-1α, IL-1β, IL-18, and IL-33. Numerous viruses affecting the skin have developed immune evasion strategies that neutralize IL-1α, IL-1β, or IL-18 signaling or combinations of these pathways. Through small differences in activation mechanisms and receptor utilization, it is possible that IL-36 signaling may proceed unhindered in the presence of these viral inhibitors. Thus, one physiological function of the IL-36s may be to counteract microbial immune evasion. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  14. Overcoming IGF1R/IR Resistance Through Inhibition of MEK Signaling in Colorectal Cancer Models

    Science.gov (United States)

    Flanigan, Sara A.; Pitts, Todd M.; Newton, Timothy P.; Kulikowski, Gillian N.; Tan, Aik Choon; McManus, Martine C.; Spreafico, Anna; Kachaeva, Maria I.; Selby, Heather M.; Tentler, John J.; Eckhardt, S. Gail; Leong, Stephen

    2013-01-01

    Purpose Results from clinical trials involving resistance to molecularly targeted therapies have revealed the importance of rational single agent and combination treatment strategies. In this study, we tested the efficacy of a type 1 insulin-like growth factor receptor (IGF1R)/insulin receptor (IR) tyrosine kinase inhibitor (TKI), OSI-906, in combination with a MEK 1/2 inhibitor based on evidence that the MAPK pathway was upregulated in colorectal cancer (CRC) cell lines that were resistant to OSI-906. Experimental Design The antiproliferative effects of OSI-906 and the MEK 1/2 inhibitor U0126, were analyzed both as single agents and in combination in 13 CRC cell lines in vitro. Apoptosis, downstream effector proteins, and cell cycle were also assessed. Additionally, the efficacy of OSI-906 combined with the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886), was evaluated in vivo using human CRC xenograft models. Results The combination of OSI-906 and U0126 resulted in synergistic effects in 11 out of 13 CRC cell lines tested. This synergy was variably associated with apoptosis or cell cycle arrest in addition to molecular effects on pro-survival pathways. The synergy was also reflected in the in vivo xenograft studies following treatment with the combination of OSI-906 and selumetinib. Conclusions Results from this study demonstrate synergistic antiproliferative effects in response to the combination of OSI-906 with a MEK 1/2 inhibitor in CRC cell line models both in vitro and in vivo, which supports the rational combination of OSI-906 with a MEK inhibitor in patients with CRC. PMID:24045180

  15. A novel HDAC inhibitor, CG200745, inhibits pancreatic cancer cell growth and overcomes gemcitabine resistance

    OpenAIRE

    Lee, Hee Seung; Park, Soo Been; Kim, Sun A; Kwon, Sool Ki; Cha, Hyunju; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Song, Si Young

    2017-01-01

    Pancreatic cancer is predominantly lethal, and is primarily treated using gemcitabine, with increasing resistance. Therefore, novel agents that increase tumor sensitivity to gemcitabine are needed. Histone deacetylase (HDAC) inhibitors are emerging therapeutic agents, since HDAC plays an important role in cancer initiation and progression. We evaluated the antitumor effect of a novel HDAC inhibitor, CG200745, combined with gemcitabine/erlotinib on pancreatic cancer cells and gemcitabine-resis...

  16. Corrosion inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, A O

    1965-12-29

    An acid corrosion-inhibiting composition consists essentially of a sugar, and an alkali metal salt selected from the group consisting of iodides and bromides. The weight ratio of the sugar to the alkali metal salt is between 2:1 and about 20,000:1. Also, a corrosion- inhibited phosphoric acid composition comprising at least about 20 wt% of phosphoric acid and between about 0.1 wt% and about 10 wt% of molasses, and between about 0.0005 wt% and about 1 wt% of potassium iodide. The weight ratio of molasses to iodide is greater than about 2:1. (11 claims)

  17. Overcoming weak intrinsic depolarizing resonances with energy-jump

    International Nuclear Information System (INIS)

    Huang, H.; Ahrens, L.; Alessi, J.G.

    1997-01-01

    In the recent polarized proton runs in the AGS, a 5% partial snake was used successfully to overcome the imperfection depolarizing resonances. Polarized proton beam was accelerated up to the required RHIC injection energy of 25 GeV. However, significant amount of polarization was lost at 0+ν y , 12+ν y and 36+ν y , which is believed to be partially due to the coupling resonances. To overcome the coupling resonance, an energy-jump was generated by rapidly changing the beam circumference using the powerful AGS rf system. It clearly demonstrates that the novel energy-jump method can successfully overcome coupling resonances and weak intrinsic resonances

  18. Overcoming Residents Opportunity Apathy in Danish Social Housing Democracy

    DEFF Research Database (Denmark)

    Bertelsen, Olav W.

    2014-01-01

    In this paper, I discuss how various technologies can support democratic collaboration in the social housing sector in Denmark, and help overcome opportunity apathy. I exemplify the discussion with an ongoing process of strategy development, in a Danish housing organization....

  19. Overcoming Family Planning Challenges in Africa: Toward Meeting ...

    African Journals Online (AJOL)

    USER

    Overcoming Family Planning Challenges in Africa: Toward Meeting. Unmet Need ... The challenges posed are greater in ... Gaps in meeting women's needs persist especially ..... WHO. Everybody's business: Strengthening health systems to.

  20. Overcoming Blockages to Collective Innovation in Digital Infrastructures

    DEFF Research Database (Denmark)

    Rukanova, Boriana; Reuver, Mark; Henningsson, Stefan

    2017-01-01

    Decentralized digital technologies increasingly enable multiple organizations to co-create digital infrastructures. However, collective innovation processes often come to a stand-still because of conflicting interests and business models. While existing research suggests various factors that block...... collective innovation processes, there is still little understanding of how organizations can overcome these blockages. In this paper, we identify patterns that explain how organizations overcome blockages of collective innovation processes for digital infrastructures. We follow a processual approach...... and develop a conceptual framework based on collective action theory. We evaluate the framework through a longitudinal case study on mobile payment infrastructure development. We find various reconfiguration processes that organizations use to overcome blockages of collective innovation. Theoretically...

  1. Addressing and overcoming barriers for energy savings in business

    DEFF Research Database (Denmark)

    Dirckinck-Holmfeld, Kasper

    Energy savings are generally viewed as an effective way to cut GHG emissions, as there are huge potentials for improvements because of several barriers and constraining factors for implementing otherwise profitable solutions. Several different polity tools have been applied to overcome these barr......Energy savings are generally viewed as an effective way to cut GHG emissions, as there are huge potentials for improvements because of several barriers and constraining factors for implementing otherwise profitable solutions. Several different polity tools have been applied to overcome...

  2. The facilitation by church leaders in overcoming resistance to change.

    OpenAIRE

    2008-01-01

    Little has been done to address the issue of how to overcome resistance to change in a change effort in the church world. “How to overcome resistance to change?” is a question that requires serious consideration among church leaders. Church leaders continue to act in ways that produce resistance to change and ultimately failed change efforts. These actions on the part of church leaders often strengthen and reinforce the sources of resistance to change, making it very difficult for change to b...

  3. Evaluation of different methods to overcome in vitro seed dormancy ...

    African Journals Online (AJOL)

    SAM

    2014-09-03

    Sep 3, 2014 ... Seeds from yellow passion fruit (Passiflora edulis Sims) present dormancy imposed by the seed-coat. The present study aimed to evaluate some methods to overcome dormancy of seeds from P. edulis grown under in vitro conditions. The experimental design was completely randomized in factorial scheme ...

  4. Overcoming The Problem Of English Sound System Among ...

    African Journals Online (AJOL)

    This paper tries to examine important issues in teaching phonetics. These are the interference problem that can affect one's speech during communication and how the teacher through the use of appropriate techniques and methods can assist the second language learner overcome these problems. Journal of Technology ...

  5. Objections to tubal sterilization: what reversibility can and cannot overcome.

    Science.gov (United States)

    Shain, R N

    1980-09-01

    In a study of 1074 women, 696 and 338 subjects would not seriously consider permanent and hypothetically reversible sterilization, respectively; they were asked to explain their feelings. The reason accounting for most objections to permanent sterilization (65%) was irreversibility and of the subjects who would not consider reversible sterilization or were unsure, 42.7% attributed their principal objection to unnecessary surgery, a factor at least currently intrinsic to the procedure and not readily overcome by education. Many of the remaining objections to both permanent and reversible sterilization may be amenable to change either through education or financial subsidies. In response to a question concerning female attractiveness subsequent to permanent sterilization, 3% of the sample felt attractiveness would decrease and 17.5% were unsure of the surgery's effect. Unsure responses were largely negative in character. This issue is important because of its relationship to intention to undergo sterilization. Upon consideration of reversible sterilization, negative and unsure responses significantly declined, even on the part of those women whose friends have had a poor experience with currently available procedures. Thus, whereas the option of reversibility cannot overcome objections to surgery, it does overcome those regarding permanency; moreover, the "temporary" character it bestows upon surgical sterilization appears to help certain individuals overcome their fears of losing their physical appeal as a result of such procedures.

  6. Overcoming Jealousy: An Experiential Analysis of Common Factors.

    Science.gov (United States)

    Barrell, James J.; Richards, Anne C.

    1982-01-01

    Investigated key aspects of the experience of jealousy through the recorded experiences of a study group consisting of three males and three females. Results indicated that jealousy is a complex experience which may be accompanied by a variety of negative feelings. Provides suggestions for overcoming jealousy. (RC)

  7. Dos Hermanas Chicanas: Overcoming Barriers to Professional Advancement

    Science.gov (United States)

    Prospero, Moises

    2007-01-01

    Women and ethnic minorities face steep barriers to professional advancement, and those who rise to the executive level typically use a variety of strategies to overcome obstacles in their way. This study first reviewed the literature on barriers to professional advancement for women and ethnic minorities and the strategies that they report using…

  8. Overcoming Branding Barriers in Nonprofit, Private Colleges and Universities

    Science.gov (United States)

    Chyr, Fred

    2017-01-01

    Purpose: The purpose of this Delphi study was to explore the views of experts in the field of nonprofit private colleges and universities in the United States to define branding and identify current barriers to branding, to discover how those barriers can be overcome, and to determine what barriers to branding are likely to occur 5 years in the…

  9. Overcoming family planning challenges in Africa: toward meeting ...

    African Journals Online (AJOL)

    Overcoming family planning challenges in Africa: toward meeting unmet need and scaling up service delivery. Andrzej Kulczycki. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL.

  10. Technology Adoption in Higher Education: Overcoming Anxiety through Faculty Bootcamp

    Science.gov (United States)

    Johnson, Terri; Wisniewski, Mary Ann; Kuhlemeyer, Greg; Isaacs, Gerald; Krzykowski, Jamie

    2012-01-01

    The reluctance to design and teach online courses in higher education is often attributed to technology anxiety in faculty. This article documents a faculty development model that has successfully helped faculty overcome this obstacle. "Bootcamps," faculty development programs held at Carroll University in Waukesha, WI, were specifically and…

  11. Six world-class research teams to investigate overcoming ...

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

    Six world-class research teams to investigate overcoming therapeutic resistance in high fatality cancers. 26 octobre 2017. Together with our partners the Canadian Institutes of Health Research, the Azrieli Foundation and the Israel Science Foundation we are pleased to announce the recipients of the Joint Canada-Israel ...

  12. Targeting Metabolic Symbiosis to Overcome Resistance to Anti-angiogenic Therapy

    Directory of Open Access Journals (Sweden)

    Laura Pisarsky

    2016-05-01

    Full Text Available Despite the approval of several anti-angiogenic therapies, clinical results remain unsatisfactory, and transient benefits are followed by rapid tumor recurrence. Here, we demonstrate potent anti-angiogenic efficacy of the multi-kinase inhibitors nintedanib and sunitinib in a mouse model of breast cancer. However, after an initial regression, tumors resume growth in the absence of active tumor angiogenesis. Gene expression profiling of tumor cells reveals metabolic reprogramming toward anaerobic glycolysis. Indeed, combinatorial treatment with a glycolysis inhibitor (3PO efficiently inhibits tumor growth. Moreover, tumors establish metabolic symbiosis, illustrated by the differential expression of MCT1 and MCT4, monocarboxylate transporters active in lactate exchange in glycolytic tumors. Accordingly, genetic ablation of MCT4 expression overcomes adaptive resistance against anti-angiogenic therapy. Hence, targeting metabolic symbiosis may be an attractive avenue to avoid resistance development to anti-angiogenic therapy in patients.

  13. Identification and characterization of SSE15206, a microtubule depolymerizing agent that overcomes multidrug resistance

    KAUST Repository

    Manzoor, Safia

    2018-02-13

    Microtubules are highly dynamic structures that form spindle fibres during mitosis and are one of the most validated cancer targets. The success of drugs targeting microtubules, however, is often limited by the development of multidrug resistance. Here we describe the discovery and characterization of SSE15206, a pyrazolinethioamide derivative [3-phenyl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide] that has potent antiproliferative activities in cancer cell lines of different origins and overcomes resistance to microtubule-targeting agents. Treatment of cells with SSE15206 causes aberrant mitosis resulting in G2/M arrest due to incomplete spindle formation, a phenotype often associated with drugs that interfere with microtubule dynamics. SSE15206 inhibits microtubule polymerization both in biochemical and cellular assays by binding to colchicine site in tubulin as shown by docking and competition studies. Prolonged treatment of cells with the compound results in apoptotic cell death [increased Poly (ADP-ribose) polymerase cleavage and Annexin V/PI staining] accompanied by p53 induction. More importantly, we demonstrate that SSE15206 is able to overcome resistance to chemotherapeutic drugs in different cancer cell lines including multidrug-resistant KB-V1 and A2780-Pac-Res cell lines overexpressing MDR-1, making it a promising hit for the lead optimization studies to target multidrug resistance.

  14. Novel nanostructured enoxaparin sodium-PLGA hybrid carriers overcome tumor multidrug resistance of doxorubicin hydrochloride.

    Science.gov (United States)

    Wang, Jia; Wu, Lei; Kou, Longfa; Xu, Meng; Sun, Jin; Wang, Yongjun; Fu, Qiang; Zhang, Peng; He, Zhonggui

    2016-11-20

    Novel enoxaparin sodium-PLGA hybrid nanocarries (EPNs) were successfully designed for sustained delivery of hydrophilic cationic doxorubicin hydrochloride (DOX) and to overcome multidrug resistance (MDR). By incorporation of the negative polymer of enoxaparin sodium (ES), DOX was highly encapsulated into EPNs with an encapsulation efficiency of 92.49%, and ES effectively inhibited the proliferation of HUVEC cell lines. The in vivo pharmacokinetics study after intravenous injection indicated that DOX-loaded EPNs (DOX-EPNs) exhibited a higher area under the curve (AUC) and a longer half-life (t 1/2 ) in comparison with DOX solution (DOX-Sol). The biodistribution study demonstrated that DOX-EPNs increased the DOX level in plasma and decreased the accumulation of DOX in liver and spleen. Compared with DOX-Sol, DOX-EPNs increased the cytotoxicity in P-gp over-expressing MCF-7/Adr cells, attributed to the higher intracellular efficiency of DOX produced by the EPNs. DOX-EPNs entered into resistant tumor cells by multiple endocytosis pathways, which resulted in overcoming the multidrug resistance of MCF-7/Adr cells by escaping the efflux induced by P-gp transporters. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. CD44-engineered mesoporous silica nanoparticles for overcoming multidrug resistance in breast cancer

    International Nuclear Information System (INIS)

    Wang, Xin; Liu, Ying; Wang, Shouju; Shi, Donghong; Zhou, Xianguang; Wang, Chunyan; Wu, Jiang; Zeng, Zhiyong; Li, Yanjun; Sun, Jing; Wang, Jiandong; Zhang, Longjiang; Teng, Zhaogang; Lu, Guangming

    2015-01-01

    Graphical abstract: - Highlights: • CD44-engineered mesoporous silica nanoparticles are synthesized. • The mechanism of CD44-engineered mesoporous silica nanoparticles is revealed. • This new delivery system increased the drug accumulation in vitro and in vivo. • This new delivery system offers an effective approach to treat multidrug resistance. - Abstract: Multidrug resistance is a major impediment for the successful chemotherapy in breast cancer. CD44 is over-expressed in multidrug resistant human breast cancer cells. CD44 monoclonal antibody exhibits anticancer potential by inhibiting proliferation and regulating P-glycoprotein-mediated drug efflux activity in multidrug resistant cells. Thereby, CD44 monoclonal antibody in combination with chemotherapeutic drug might be result in enhancing chemosensitivity and overcoming multidrug resistance. The purpose of this study is to investigate the effects of the CD44 monoclonal antibody functionalized mesoporous silica nanoparticles containing doxorubicin on human breast resistant cancer MCF-7 cells. The data showed that CD44-modified mesoporous silica nanoparticles increased cytotoxicity and enhanced the downregulation of P-glycoprotein in comparison to CD44 antibody. Moreover, CD44-engineered mesoporous silica nanoparticles provided active target, which promoted more cellular uptake of DOX in the resistant cells and more retention of DOX in tumor tissues than unengineered counterpart. Animal studies of the resistant breast cancer xenografts demonstrated that CD44-engineered drug delivery system remarkably induced apoptosis and inhibited the tumor growth. Our results indicated that the CD44-engineered mesoporous silica nanoparticle-based drug delivery system offers an effective approach to overcome multidrug resistance in human breast cancer

  16. Namaste (counterbalancing) technique: Overcoming warping in costal cartilage.

    Science.gov (United States)

    Agrawal, Kapil S; Bachhav, Manoj; Shrotriya, Raghav

    2015-01-01

    Indian noses are broader and lack projection as compared to other populations, hence very often need augmentation, that too by large volume. Costal cartilage remains the material of choice in large volume augmentations and repair of complex primary and secondary nasal deformities. One major disadvantage of costal cartilage grafts (CCG) which offsets all other advantages is the tendency to warp and become distorted over a period of time. We propose a simple technique to overcome this menace of warping. We present the data of 51 patients of rhinoplasty done using CCG with counterbalancing technique over a period of 4 years. No evidence of warping was found in any patient up to a maximum follow-up period of 4 years. Counterbalancing is a useful technique to overcome the problem of warping. It gives liberty to utilize even unbalanced cartilage safely to provide desired shape and use the cartilage without any wastage.

  17. Namaste (counterbalancing technique: Overcoming warping in costal cartilage

    Directory of Open Access Journals (Sweden)

    Kapil S Agrawal

    2015-01-01

    Full Text Available Background: Indian noses are broader and lack projection as compared to other populations, hence very often need augmentation, that too by large volume. Costal cartilage remains the material of choice in large volume augmentations and repair of complex primary and secondary nasal deformities. One major disadvantage of costal cartilage grafts (CCG which offsets all other advantages is the tendency to warp and become distorted over a period of time. We propose a simple technique to overcome this menace of warping. Materials and Methods: We present the data of 51 patients of rhinoplasty done using CCG with counterbalancing technique over a period of 4 years. Results: No evidence of warping was found in any patient up to a maximum follow-up period of 4 years. Conclusion: Counterbalancing is a useful technique to overcome the problem of warping. It gives liberty to utilize even unbalanced cartilage safely to provide desired shape and use the cartilage without any wastage.

  18. Overcoming obstacles against effective solar lighting interventions in South Asia

    International Nuclear Information System (INIS)

    Wong, Sam

    2012-01-01

    Basing on our devised World Bank’s ‘Design Principles’ for effective renewable energy projects in developing countries and an in-depth analysis of our two solar lighting projects in Bangladesh and India, this paper explores three key obstacles that constrain poor people from obtaining solar lighting: financial exclusion, weak governance, and passive NGO and customer participation. The low take-up rate has a social and psychological impact. This paper recommends creating easy access to credit, establishing a robust complaint system, and developing strategic partnership to overcome the obstacles. - Research Highlights: ► To provide a critical analysis of the World Bank's 'Design Principles' for renewable energy policies in developing countries. ► To explain why some solar lighting projects do not work and how the barriers can be overcome. ► To highlight the roles of poverty, governance and technical support in solar lighting design.

  19. Sesquiterpenes with TRAIL-resistance overcoming activity from Xanthium strumarium.

    Science.gov (United States)

    Karmakar, Utpal K; Ishikawa, Naoki; Toume, Kazufumi; Arai, Midori A; Sadhu, Samir K; Ahmed, Firoj; Ishibashi, Masami

    2015-08-01

    The ability of TRAIL to selectively induce apoptosis in cancer cells while sparing normal cells makes it an attractive target for the development of new cancer therapy. In search of bioactive natural products for overcoming TRAIL-resistance from natural resources, we previously reported a number of active compounds. In our screening program on natural resources targeting overcoming TRAIL-resistance, activity-guided fractionations of the extract of Xanthium strumarium led to the isolation of five sesquiterpene compounds (1-5). 11α,13-dihydroxanthinin (2) and 11α,13-dihydroxanthuminol (3) were first isolated from natural resources and xanthinosin (1), desacetylxanthanol (4), and lasidiol p-methoxybenzoate (5) were known compounds. All compounds (1-5) showed potent TRAIL-resistance overcoming activity at 8, 20, 20, 16, and 16 μM, respectively, in TRAIL-resistant AGS cells. Compounds 1 and 5 enhanced the levels of apoptosis inducing proteins DR4, DR5, p53, CHOP, Bax, cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9 and also decreased the levels of cell survival protein Bcl-2 in TRAIL-resistant AGS cells in a dose-dependent manner. Compound 1 also enhanced the levels of DR4 and DR5 proteins in a time-dependent manner. Thus, compounds 1 and 5 were found to induce both extrinsic and intrinsic apoptotic cell death. Compound 1 also exhibit TRAIL-resistance overcoming activity in DLD1, DU145, HeLa, and MCF7 cells but did not decrease viability in non-cancer HEK293 cells up to 8 μM. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Comment: Kidney exchange to overcome financial barriers to kidney transplantation

    OpenAIRE

    Baines, L.S.; Jindal, R.M.

    2017-01-01

    Rees et al. have shown the feasibility of global kidney exchange (GKE) to overcome financial cost and address the current shortage of organs for transplantation. Wiseman and Gill, question their interpretation of definition of "financial incompatibility". The authors1 do not factor in the well documented cognitive and emotional aspects of kidney transplantation. Particularly, relevant to kidney transplantation is how patients calculate risk and the emotional turmoil characterised by anxiety a...

  1. Namaste (counterbalancing) technique: Overcoming warping in costal cartilage

    OpenAIRE

    Kapil S Agrawal; Manoj Bachhav; Raghav Shrotriya

    2015-01-01

    Background: Indian noses are broader and lack projection as compared to other populations, hence very often need augmentation, that too by large volume. Costal cartilage remains the material of choice in large volume augmentations and repair of complex primary and secondary nasal deformities. One major disadvantage of costal cartilage grafts (CCG) which offsets all other advantages is the tendency to warp and become distorted over a period of time. We propose a simple technique to overcome th...

  2. Fear of examinations and educational factors of its overcoming

    OpenAIRE

    Bagdonas, Algimantas; Merkys, Gediminas

    2005-01-01

    This article, based on the carried out scientific researches' data of late decades, tries to reveal die actuality of the phenomenon of exam fear and opportunities of solving this problem. In this article there is analyzed an actual exam fear phenomenon characteristic of different aged students from various countries and social classes. Exam fear is presented as a constituent part of the complicated phenomenon of school fear, emphasizing educational factors of its overcoming. Exam fear is also...

  3. Debate on science and technology promotion for overcoming economic crisis

    International Nuclear Information System (INIS)

    1990-05-01

    This book records debate point and topic presentation of debate on science and technology promotion for overcoming economic difficulties which lists opening greeting, topic presentation such as innovation of national science technology system, sufficient supply and demand of science and engineering personnel, invigoration of technology research of corporation and general debate. This debate was held by the Policy Board of democratic and liberal party on 22 May 1990 in Press center.

  4. Overcoming violence - a basic task of Christian churches

    Directory of Open Access Journals (Sweden)

    Wolfgang Huber

    2011-06-01

    Full Text Available In this article � based on the second of two keynote lectures at a conference on violence � the view is developed that the task of the church with respect to violence consists mainly in overcoming violence. In the first part of the article dealing with the basic tasks of the church it is argued that the task to overcome violence is close to the essence of the church. The point of departure is taken in Article 7 of the Augsburg Confession, which understands the church as the �communion of saints� and names the pure proclamation of the gospel and the right administration of the sacraments as the two characteristics of the church. The Christian message that the church has to proclaim the gospel entails a preferential option for nonviolence that includes the responsibility to put an end to existing violence. In the second part of the article attention is given to the implications the basic task of the church in overcoming violence holds for the practice of the church. It is argued that the starting point is that the church has to proclaim the gospel of peace and as a community of faith become a community of peace herself. Some of the most important practical consequences the proclamation of the gospel of peace has for the church as a community of action, for her work in education, for her promotion of justice and for her solidarity with those in need, are discussed.

  5. Re-Vitalizing Worthiness: A theory of overcoming suicidality

    Directory of Open Access Journals (Sweden)

    Evelyn Gordon, RPN, Reg. Fam. Ther. & Sup. (FTAI, MSc, Ph.D.

    2011-06-01

    Full Text Available Rates of suicide and suicidality have risen in many countries in recent years and in Ireland this trend has been particularly evident among young men (NOSP, 2005, focusing attention on how best to respond to this group. Although mental health professionals have been identified as a key group to respond to the suicidal person, it has been suggested that they are ill-prepared for working in this area (Maltsberger & Goldblatt, 1996; Ting et al., 2006; Cutcliffe & Stevenson, 2007. This study aimed to address these issues by developing a theoretical understanding of suicidality among young men to inform professional practice. Using Classic Grounded Theory (Glaser & Strauss, 1967, in-depth one-to-one interviews were conducted with 17 young men who had been suicidal and had been in contact with the mental health services. The substantive theory that emerged, re-vitalizing worthiness in overcoming suicidality, describes the psychosocial process that young men go through to resolve their main concern, which centres on their painful pull between life and death. Overcoming suicidality involves moving from a death orientation to a life orientation while incorporating the inevitability of death into their new sense of being. This transition entails identity re-configuration whereby young men emerge as individuals of value who are deserving of life. The process is influenced significantly by personal insights and interpersonal interactions that influence their suicide trajectories and life pathways. The theory contributes to the fields of suicidology and mental health by providing a theoretical understanding of overcoming suicidality and identifying professional and social practices that facilitate and impede this process.

  6. Recognizing and overcoming challenges of couple interview research.

    Science.gov (United States)

    Mellor, Ruth M; Slaymaker, Emma; Cleland, John

    2013-10-01

    In this article we discuss some methodological and ethical challenges we faced when conducting a couple-based study on men's role in contraceptive switching, and how we overcame them. The challenges we discuss include recruiting couples with a range of experiences, ensuring informed consent of participants, maintaining confidentiality within interviews, and participants discussing interview content between interviews. As appropriate, we have drawn on study participants' views of these challenges. We conclude that although couple research poses challenges, they can be overcome or minimized, and that for certain research questions this methodology is well worth using.

  7. Overcoming the Law of the Hidden in Cyberinfrastructures.

    Science.gov (United States)

    Bucksch, Alexander; Das, Abhiram; Schneider, Hannah; Merchant, Nirav; Weitz, Joshua S

    2017-02-01

    Cyberinfrastructure projects (CIPs) are complex, integrated systems that require interaction and organization amongst user, developer, hardware, technical infrastructure, and funding resources. Nevertheless, CIP usability, functionality, and growth do not scale with the sum of these resources. Instead, growth and efficient usage of CIPs require access to 'hidden' resources. These include technical resources within CIPs as well as social and functional interactions among stakeholders. We identify approaches to overcome resource limitations following the conceptual basis of Liebig's Law of the Minimum. In so doing, we recommend practical steps towards efficient and scaleable resource use, taking the iPlant/CyVerse CIP as an example. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. FINAL TECHNICAL REPORT: 20% Wind by 2030: Overcoming the Challenges

    Energy Technology Data Exchange (ETDEWEB)

    Tom Kaiserski; Dan Lloyd

    2012-02-28

    The funds allocated through the Wind Powering America (WPA) grant were utilized by the State of Montana to support broad outreach activities communicating the benefits and opportunities of increased wind energy and transmission development. The challenges to increased wind development were also clearly communicated with the understanding that a clearer comprehension of the challenges would be beneficial in overcoming the obstacles to further development. The ultimate purpose of these activities was to foster the increased development of Montana's rich wind resources through increased public acceptance and wider dissemination of technical resources.

  9. Wind energy: Overcoming inadequate wind and modeling uncertainties

    Energy Technology Data Exchange (ETDEWEB)

    Kane, Vivek

    2010-09-15

    'Green Energy' is the call of the day, and significance of Wind Energy can never be overemphasized. But the key question here is - What if the wind resources are inadequate? Studies reveal that the probability of finding favorable wind at a given place on land is only 15%. Moreover, there are inherent uncertainties associated with wind business. Can we overcome inadequate wind resources? Can we scientifically quantify uncertainty and model it to make business sense? This paper proposes a solution, by way of break-through Wind Technologies, combined with advanced tools for Financial Modeling, enabling vital business decisions.

  10. Overcoming Learning Aversion in Evaluating and Managing Uncertain Risks.

    Science.gov (United States)

    Cox, Louis Anthony Tony

    2015-10-01

    Decision biases can distort cost-benefit evaluations of uncertain risks, leading to risk management policy decisions with predictably high retrospective regret. We argue that well-documented decision biases encourage learning aversion, or predictably suboptimal learning and premature decision making in the face of high uncertainty about the costs, risks, and benefits of proposed changes. Biases such as narrow framing, overconfidence, confirmation bias, optimism bias, ambiguity aversion, and hyperbolic discounting of the immediate costs and delayed benefits of learning, contribute to deficient individual and group learning, avoidance of information seeking, underestimation of the value of further information, and hence needlessly inaccurate risk-cost-benefit estimates and suboptimal risk management decisions. In practice, such biases can create predictable regret in selection of potential risk-reducing regulations. Low-regret learning strategies based on computational reinforcement learning models can potentially overcome some of these suboptimal decision processes by replacing aversion to uncertain probabilities with actions calculated to balance exploration (deliberate experimentation and uncertainty reduction) and exploitation (taking actions to maximize the sum of expected immediate reward, expected discounted future reward, and value of information). We discuss the proposed framework for understanding and overcoming learning aversion and for implementing low-regret learning strategies using regulation of air pollutants with uncertain health effects as an example. © 2015 Society for Risk Analysis.

  11. Overcoming barriers to development of cooperative medical decision support models.

    Science.gov (United States)

    Hudson, Donna L; Cohen, Maurice E

    2012-01-01

    Attempts to automate the medical decision making process have been underway for the at least fifty years, beginning with data-based approaches that relied chiefly on statistically-based methods. Approaches expanded to include knowledge-based systems, both linear and non-linear neural networks, agent-based systems, and hybrid methods. While some of these models produced excellent results none have been used extensively in medical practice. In order to move these methods forward into practical use, a number of obstacles must be overcome, including validation of existing systems on large data sets, development of methods for including new knowledge as it becomes available, construction of a broad range of decision models, and development of non-intrusive methods that allow the physician to use these decision aids in conjunction with, not instead of, his or her own medical knowledge. None of these four requirements will come easily. A cooperative effort among researchers, including practicing MDs, is vital, particularly as more information on diseases and their contributing factors continues to expand resulting in more parameters than the human decision maker can process effectively. In this article some of the basic structures that are necessary to facilitate the use of an automated decision support system are discussed, along with potential methods for overcoming existing barriers.

  12. EXPERIENCES OF OVERCOMING THE MASTER PRIMARY TO USE THE GEOGEBRA

    Directory of Open Access Journals (Sweden)

    María Luz Fuentes-Pérez

    2016-07-01

    Full Text Available This article presents the results of the experience of two researchers in overcoming 15 primary teachers, was used for this purpose a postgraduate course, in order to be trained so that they can use the dynamic geometry software Geogebra in the process of learning that develop in their classrooms. It is an investigation that used the systematization of experiences as a methodology and as research methods participant observation to get to know the moods and difficulties of trainees during class activities, group interview to gather data on participants in the course and with directors of primary education to meet the expectations and results related to the improvement and implementation of PNI for the views after some of the educational activities considered relevant. The results show as advances are obtained in overcoming teachers to use Geogebra and mention some lessons that emerge from the systematization about conception must have a course which is intended to prepare teachers who are not digital natives use the software mentioned.

  13. Overcoming Resistance of Cancer Cells to PARP-1 Inhibitors with Three Different Drug Combinations.

    Directory of Open Access Journals (Sweden)

    Michal Yalon

    Full Text Available Inhibitors of poly[ADP-ribose] polymerase 1 (PARPis show promise for treatment of cancers which lack capacity for homologous recombination repair (HRR. However, new therapeutic strategies are required in order to overcome innate and acquired resistance to these drugs and thus expand the array of cancers that could benefit from them. We show that human cancer cell lines which respond poorly to ABT-888 (a PARPi, become sensitive to it when co-treated with vorinostat (a histone deacetylase inhibitor (HDACi. Vorinostat also sensitized PARPis insensitive cancer cell lines to 6-thioguanine (6-TG-a drug that targets PARPis sensitive cells. The sensitizing effect of vorinostat was associated with increased phosphorylation of eukaryotic initiation factor (eIF 2α which in and of itself increases the sensitivity of cancer cells to ABT-888. Importantly, these drug combinations did not affect survival of normal fibroblasts and breast cells, and significantly increased the inhibition of xenograft tumor growth relative to each drug alone, without affecting the mice weight or their liver and kidney function. Our results show that combination of vorinostat and ABT-888 could potentially prove useful for treatment of cancer with innate resistance to PARPis due to active HRR machinery, while the combination of vorinostat and 6-TG could potentially overcome innate or acquired resistance to PARPis due to secondary or reversal BRCA mutations, to decreased PARP-1 level or to increased expression of multiple drug resistant proteins. Importantly, drugs which increase phosphorylation of eIF2α may mimic the sensitizing effect of vorinostat on cellular response to PARPis or to 6-TG, without activating all of its downstream effectors.

  14. Overcoming dormancy and enhancing germination of Sphaeralcea munroana seeds

    Science.gov (United States)

    Olga A. Kildisheva; R. Kasten Dumroese; Anthony S. Davis

    2011-01-01

    The results of a series of experiments involving a variety of dormancy-breaking treatments indicate that Munro's globemallow [Sphaeralcea munroana (Douglas) Spach] seeds are physically dormant, possess a cap-like structure in the occlusion of the water gap, which inhibits imbibition, and can be artificially dislodged through boiling water scarification. The...

  15. Bacterial mechanisms to overcome inhibitory effects of dietary tannins

    NARCIS (Netherlands)

    Smith, A.H.; Zoetendal, E.G.; Mackie, R.I.

    2005-01-01

    High concentrations of tannins in fodder plants inhibit gastrointestinal bacteria and reduce ruminant performance. Increasing the proportion of tannin-resistant bacteria in the rumen protects ruminants from antinutritional effects. The reason for the protective effect is unclear, but could be

  16. Overcoming the Challenges of siRNA Delivery: Nanoparticle Strategies.

    Science.gov (United States)

    Shajari, Neda; Mansoori, Behzad; Davudian, Sadaf; Mohammadi, Ali; Baradaran, Behzad

    2017-01-01

    Despite therapeutics based on siRNA have an immense potential for the treatment of incurable diseases such as cancers. However, the in vivo utilization of siRNA and also the delivery of this agent to the target site is one of the most controversial challenges. The helpful assistance by nanoparticles can improve stable delivery and also enhance efficacy. More nanoparticle-based siRNA therapeutics is expected to become available in the near future. The search strategy followed the guidelines of the Centre of Reviews and Dissemination. The studies were identified from seven databases (Scopus, Web of Science, Academic Search Premiere, CINAHL, Medline Ovid, Eric and Cochrane Library). Studies was selected based on titles, abstracts and full texts. One hundred twenty nine papers were included in the review. These papers defined hurdles in RNAi delivery and also strategies to overcome these hurdles. This review discussed the existing hurdles for systemic administration of siRNA as therapeutic agents and highlights the various strategies to overcome these hurdles, including lipid-based nanoparticles and polymeric nanoparticles, and we also briefly reviewed chemical modification. Delivery of siRNA to the target site is the biggest challenge for its application in the clinic. The findings of this review confirmed by encapsulation siRNA in the nanoparticles can overcome these challenges. The rapid progress in nanotechnology has enabled the development of effective nanoparticles as the carrier for siRNA delivery. However, our data about siRNA-based therapeutics and also nanomedicine are still limited. More clinical data needs to be completely understood in the benefits and drawbacks of siRNA-based therapeutics. Prospective studies must pay attention to the in vivo safety profiles of the different delivery systems, including uninvited immune system stimulation and cytotoxicity. In essence, the development of nontoxic, biocompatible, and biodegradable delivery systems for

  17. Overcoming Barriers to Successfully Commercializing Carbon Dioxide Utilization

    Energy Technology Data Exchange (ETDEWEB)

    Kant, Marvin, E-mail: marvin.kant@tu-berlin.de [Department of Entrepreneurship and Innovation Management, Technische Universität Berlin, Berlin (Germany)

    2017-09-13

    The successful transition to a low-carbon economy hinges on innovative solutions and collaborative action on a global scale. Sustainable entrepreneurship is thereby recognized as a key driver in the creation and transformation of ecologically and socially sustainable economic systems. The purpose of this article is to contribute to this topic by understanding commercialization barriers for strong sustainability-oriented new technology ventures and to derive recommendations to overcome them. A qualitative multilevel approach is applied to identify barriers and drivers within the internal dynamic capabilities of the organization and within the organization’s external stakeholders. A model of barriers has been developed based on semi-structured interviews with new carbon dioxide utilization ventures and associated industry players in Canada, the USA, and the European Economic Area. Resulting recommendations to facilitate the (re-)design of a dedicated support system are proposed on four levels: (a) actors, (b) resources, (c) institutional settings, and (d) the coordination of the support system.

  18. Overcoming tumor resistance by heterologous adeno-poxvirus combination therapy

    Directory of Open Access Journals (Sweden)

    Markus Vähä-Koskela

    2014-01-01

    Full Text Available Successful cancer control relies on overcoming resistance to cell death and on activation of host antitumor immunity. Oncolytic viruses are particularly attractive in this regard, as they lyse infected tumor cells and trigger robust immune responses during the infection. However, repeated injections of the same virus promote antiviral rather than antitumor immunity and tumors may mount innate antiviral defenses to restrict oncolytic virus replication. In this article, we have explored if alternating the therapy virus could circumvent these problems. We demonstrate in two virus-resistant animal models a substantial delay in antiviral immune- and innate cellular response induction by alternating injections of two immunologically distinct oncolytic viruses, adenovirus, and vaccinia virus. Our results are in support of clinical development of heterologous adeno-/vaccinia virus therapy of cancer.

  19. How insects overcome two-component plant chemical defence

    DEFF Research Database (Denmark)

    Pentzold, Stefan; Zagrobelny, Mika; Rook, Frederik

    2014-01-01

    Insect herbivory is often restricted by glucosylated plant chemical defence compounds that are activated by plant β-glucosidases to release toxic aglucones upon plant tissue damage. Such two-component plant defences are widespread in the plant kingdom and examples of these classes of compounds...... are alkaloid, benzoxazinoid, cyanogenic and iridoid glucosides as well as glucosinolates and salicinoids. Conversely, many insects have evolved a diversity of counteradaptations to overcome this type of constitutive chemical defence. Here we discuss that such counter-adaptations occur at different time points......, before and during feeding as well as during digestion, and at several levels such as the insects’ feeding behaviour, physiology and metabolism. Insect adaptations frequently circumvent or counteract the activity of the plant β-glucosidases, bioactivating enzymes that are a key element in the plant’s two...

  20. Genecialist manifesto: overcoming the “class struggle” in medicine

    Directory of Open Access Journals (Sweden)

    Iwata K

    2013-04-01

    Full Text Available Kentaro Iwata Division of Infectious Diseases, Kobe University Hospital, Kobe, Hyogo, Japan Abstract: Generalists and specialists are often considered two completely distinct species, which culminates in the establishment of a concept of dichotomy. However, these dichotomy can at times fuel tension and even erupt into open conflict. In order to resolve this issue, the author herein proposes the concept of a “genecialist.” The genecialist refers to a hybrid comprising elements inherent to both generalists and specialists. This potentially overcomes the multitude of issues associated with both generalists and specialists in the practical aspects of medicine. The coalescence of these two contrarieties may hold the key to improving the future of health care. Mediating and integrating both categories into one consolidated entity carries the potential to stem the tide of class warfare between generalists and specialists. Keywords: genecialist, aufheben, generalist, specialist, asymmetry

  1. Overcoming Learning Time And Space Constraints Through Technological Tool

    Directory of Open Access Journals (Sweden)

    Nafiseh Zarei

    2015-08-01

    Full Text Available Today the use of technological tools has become an evolution in language learning and language acquisition. Many instructors and lecturers believe that integrating Web-based learning tools into language courses allows pupils to become active learners during learning process. This study investigate how the Learning Management Blog (LMB overcomes the learning time and space constraints that contribute to students’ language learning and language acquisition processes. The participants were 30 ESL students at National University of Malaysia. A qualitative approach comprising an open-ended questionnaire and a semi-structured interview was used to collect data. The results of the study revealed that the students’ language learning and acquisition processes were enhanced. The students did not face any learning time and space limitations while being engaged in the learning process via the LMB. They learned and acquired knowledge using the language learning materials and forum at anytime and anywhere. Keywords: learning time, learning space, learning management blog

  2. [Pain and Christianity. A symbol for overcoming pain?].

    Science.gov (United States)

    Markschies, C

    2007-08-01

    Pain and Christianity appear to belong together: Christ's pain stands at the centre of God's healing; his pain leads to the salvation of mankind. We can learn from Jesus' example how to bear suffering and pain. In early Christian times, the belief that Jesus Christ suffered pain on the cross was usually not accepted. In line with the "apathy axiom", freedom from emotion was something to strive for at that time. Only after the acceptance of Christianity as the state religion of the Roman Empire in 380 AD did the pain of Christ again stand in the centre of the Christian doctrine of salvation. The memory of the fact that Jesus himself had to undergo the worst pain can still help people to overcome their pain and comfort them.

  3. Overcoming Gender Stereotypes & Improving Learning through the Participation of the

    Directory of Open Access Journals (Sweden)

    Carme Garcia

    2012-02-01

    Full Text Available This article presents the results of research on how the daily participation of the "Other Women" women without an academic background or from cultural and ethnic minorities contributes to overcoming sexist stereotypes. The study demonstrates that their participation in instrumental learning activities transforms stereotypical beliefs about the skills of women without academic education, immigrant women, or those from cultural minorities. It can also be observed that their participation in decision-making spaces and in learning activities promotes student learning. In short, this study demonstrates that we need to include the "Other Women" into our diverse schools to progress towards the achievement of gender equity in education and society, and to create more positive learning experiences for all children.

  4. Overcoming Barriers to Successfully Commercializing Carbon Dioxide Utilization

    International Nuclear Information System (INIS)

    Kant, Marvin

    2017-01-01

    The successful transition to a low-carbon economy hinges on innovative solutions and collaborative action on a global scale. Sustainable entrepreneurship is thereby recognized as a key driver in the creation and transformation of ecologically and socially sustainable economic systems. The purpose of this article is to contribute to this topic by understanding commercialization barriers for strong sustainability-oriented new technology ventures and to derive recommendations to overcome them. A qualitative multilevel approach is applied to identify barriers and drivers within the internal dynamic capabilities of the organization and within the organization’s external stakeholders. A model of barriers has been developed based on semi-structured interviews with new carbon dioxide utilization ventures and associated industry players in Canada, the USA, and the European Economic Area. Resulting recommendations to facilitate the (re-)design of a dedicated support system are proposed on four levels: (a) actors, (b) resources, (c) institutional settings, and (d) the coordination of the support system.

  5. Supermolecular drug challenge to overcome drug resistance in cancer cells.

    Science.gov (United States)

    Onishi, Yasuhiko; Eshita, Yuki; Ji, Rui-Cheng; Kobayashi, Takashi; Onishi, Masayasu; Mizuno, Masaaki; Yoshida, Jun; Kubota, Naoji

    2018-06-04

    Overcoming multidrug resistance (MDR) of cancer cells can be accomplished using drug delivery systems in large-molecular-weight ATP-binding cassette transporters before entry into phagolysosomes and by particle-cell-surface interactions. However, these hypotheses do not address the intratumoral heterogeneity in cancer. Anti-MDR must be related to alterations of drug targets, expression of detoxification, as well as altered proliferation. In this study, it is shown that the excellent efficacy and sustainability of anti-MDR is due to a stable ES complex because of the allosteric facilities of artificial enzymes when they are used as supramolecular complexes. The allosteric effect of supermolecular drugs can be explained by the induced-fit model and can provide stable feedback control systems through the loop transfer function of the Hill equation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Overcoming barriers to public understanding of nuclear waste management

    International Nuclear Information System (INIS)

    Wilder, M.; Hall, S.

    1987-01-01

    Communication with the public to promote public understanding of, and participation in, nuclear waste issues is crucial. However, such communication with the public is falling short. One of the major reasons for this failure is that the public feels it cannot trust the motivations or actions of USDOE. The biggest barrier to public involvement in nuclear waste issues is the lack of trust in those who invite us to be involved. Many methods could be employed to increase communication and public involvement in complex and technical nuclear matters. This paper discusses the authors' observations of how USDOE's loss of credibility has affected the high-level nuclear waste repository siting process and suggests methods to overcome this primary barrier

  7. Medical Students' Personal Determinants of Overcoming Strategies in Difficult Situations

    Directory of Open Access Journals (Sweden)

    Veretelnikova Yu.Ya.

    2013-03-01

    Full Text Available Goal of the research was to study conditionality of overcoming strategies in difficult situations of social interaction by personal representations of attitude to others among medical students. Material and methods. 134 first-year students of Saratov State Medical University n.a. V. I. Razumovsky took part in the comparative diagnostic study. Results. Comparison of average indices of various strategies evidence in coping behaviour allowed revealing statistically significant dependence of coping behaviour modi in difficult situations of social interaction upon types of personal representations of attitude toward others and gender features of forming effective strategies of coping behaviour among medical students. Conclusion. Correlation between coping behaviour modi in difficult situations of social interaction and typology of personal representations of attitudes toward others among medical students was marked.

  8. Techniques for overcoming community resistance to family planning programs.

    Science.gov (United States)

    Palley, H A

    1968-01-01

    Methods of overcoming resistance to publicly subsidized family planning programs are discussed. The main sources of opposition include groups that oppose family planning for moral reasons, and those who object to the spending of government funds to provide services and information. Such opposition can be weakened by indicating that family planning clinics fulf: 11 important medical needs. Presenting social justification for family planning can help to lower oppostion. In order to secure participation in the programs by low income groups it is essential to have community leaders involved in policy decisions and to use indigenous community paraprofessionals in the clinics. A coalition of representatives of the poor community and the health and welfare system, aided by the community organization, can lead to an effective family planning program.

  9. Overcoming preexisting humoral immunity to AAV using capsid decoys.

    Science.gov (United States)

    Mingozzi, Federico; Anguela, Xavier M; Pavani, Giulia; Chen, Yifeng; Davidson, Robert J; Hui, Daniel J; Yazicioglu, Mustafa; Elkouby, Liron; Hinderer, Christian J; Faella, Armida; Howard, Carolann; Tai, Alex; Podsakoff, Gregory M; Zhou, Shangzhen; Basner-Tschakarjan, Etiena; Wright, John Fraser; High, Katherine A

    2013-07-17

    Adeno-associated virus (AAV) vectors delivered through the systemic circulation successfully transduce various target tissues in animal models. However, similar attempts in humans have been hampered by the high prevalence of neutralizing antibodies to AAV, which completely block vector transduction. We show in both mouse and nonhuman primate models that addition of empty capsid to the final vector formulation can, in a dose-dependent manner, adsorb these antibodies, even at high titers, thus overcoming their inhibitory effect. To further enhance the safety of the approach, we mutated the receptor binding site of AAV2 to generate an empty capsid mutant that can adsorb antibodies but cannot enter a target cell. Our work suggests that optimizing the ratio of full/empty capsids in the final formulation of vector, based on a patient's anti-AAV titers, will maximize the efficacy of gene transfer after systemic vector delivery.

  10. Study of a family that overcomes poverty issues: family resilience?

    Directory of Open Access Journals (Sweden)

    María Ángela Mattar Yunes

    2015-09-01

    Full Text Available Generally, researches with families focus the difficulties and the negative aspects of family life by bringing up their maladjustments and failures. The interest in family resilience contributes to change this logic by demonstrating the healthy aspects of the family world. Nevertheless, the term resilience presents ideological controversies which are more severe when the discussion is about families and poverty. In order to diminish these contradictions this study adopted a systemic concept of resilience which refers to “those processes that make possible to overcome adversities”. A case study was realized with a low income family who lived in a “very poor” neighborhood in the deep south of Brazil. The methodological strategies to the formal investigation of the family were: life history of the family using the principles of reflexive interview, genograms and data analyses through the approach of the grounded theory. The results showed that the family lived a number of risk experiences such as adoption, privation of basic needs, migration and diseases. Among the indicators of their abilities of “overcoming adversities”, emerged the belief system as the core of the discourses. The family showed that they value the interpersonal relationships through intra and extra familiar interactions based in the patterns of help, learning, affection and solidarity. During the crisis the family gives meaning to the difficulties in order to maintaining the situation controlled through cohesion, open communication, mutual respect and getting support of the extended family/ social network. The pos-adversity period is perceived as benefic and transforming as the family feels stronger and with feelings of solidarity, which is a mark of this family. Their attitude in relation to the neighborhood is active in the sense of promoting the welfare of other families who live in the same social address. Would those above identified processes be adequate to

  11. 'Hidden poverty' of teachers: Status, consequences and overcoming strategies

    Directory of Open Access Journals (Sweden)

    Bogunović Blanka

    2008-01-01

    Full Text Available The consequences of reduced financial and other possibilities in the period of social transition are reflected on the quality of life and work of teachers, and thereby indirectly on education of pupils as well. Aims: (1 to determine teachers' estimation of their own financial status and subjective perception of teachers' poverty; (2 to examine in which way the personal perception of poverty of teachers is linked with the quality of their engagement in curricular and extracurricular activities; (3 to examine which economic and psychological strategies teachers use in overcoming stress because of the lower financial status; (4 to examine whether there are differences between teachers with regard to socio-demographic variables and the previously established goals. Sample consists of 141 teachers of music and general education schools in Belgrade and the interior of the country. Method: research is explorative and uses qualitative and psychometric methods of analysis. Results point out to the structure of 'hidden poverty' of teachers: average and poor financial status, financial and logistic support of the extended family, additional job, unfulfilled financial expectations regarding the educational status and ungratified higher needs. Teachers estimate that real poverty of educational system and 'hidden poverty' of teachers are reflected on the quality of certain aspects of educational process as a whole and in certain elements: teacher's personal life and work motivation, authority in school, quality of teacher's engagement in tuition and the possibility of professional specialization. Teachers use financial and psychological strategies for overcoming stress that can be determined as: moralist compensatory, evasive, inappropriate, emotional, relying on family and friendly supportive systems and activist. Conclusion: primarily subjective and spiritual impoverishment of the stratum of highly educated people, who are, in addition to this, the bearers

  12. INHIBITION IN SPEAKING PERFORMANCE

    OpenAIRE

    Humaera, Isna

    2015-01-01

    The most common problem encountered by the learner in the languageacquisition process is learner inhibition. Inhibition refers to a temperamentaltendency to display wariness, fearfulness, or restrain in response tounfamiliar people, objects, and situations. There are some factors that causeinhibition, such as lack of motivation, shyness, self-confidence, self-esteem,and language ego. There are also levels of inhibition, it refers to kinds ofinhibition and caused of inhibition itself. Teacher ...

  13. OVERCOMING THE ANTINOMIES OF HUMAN EXISTENCE: ONTOLOGY OF TRICKSTER

    Directory of Open Access Journals (Sweden)

    T. V. Danylova

    2014-12-01

    Full Text Available Purpose. This paper aims to study the ontological status of a trickster character in “Panchatantra” and its receptions. Methodology. The author has used analytical methodology of C. Levi-Strauss, C. Jung’s theory of archetypes, and hermeneutical methodology. Theoretical basis and results. Perception of the world in the form of a narrative is inherent in the very specifics of the human thinking. Among the most famous literary narratives that structured cultural experience of different nations are the framed story “Panchatantra” and its receptions “Kalilah and Dimnah” and “Stefanit and Ihnilat”. The framework of the analyzed text is the story about two jackals Karataka and Damanaka, Lion, and Bull. “Panchatantra” is deeply rooted in the animal epos, which is based on the totemic myth. Myths were created by primitive thinking that sought to systematize the world, to give it order through binary oppositions. Their hard core is “Life – Death” opposition. A myth deals with oppositions and seeks to neutralize them. Thus, a myth serves as the logical tool to overcome the fundamental contradictions. This is carried out by introducing a mediator. Two poles, two extreme points are unambiguous; ambiguity “occurs” at an intermediate stage only. Shift from one point to another is impossible directly – for this we need a mediator. In the given narrative the binary opposition “Life – Death” is replaced by its metaphor – Bull and Lion, herbivore (metaphor for life and carnivore (metaphor for death. These oppositions are mediated by Jackal (Karataka&Damanaka that feeds on carrion and has a dual nature. A mediator, which overcomes or at least mitigates the binary opposition, is seen as a compromise between herbivores and carnivores that embody the antinomy of life and death. This mediator is a trickster – bipolar character (good and evil at the same time. A trickster freely acts in unordered world of Chaos without Life

  14. Nose-to-Brain Delivery of Antiviral Drugs: A Way to Overcome Their Active Efflux?

    Directory of Open Access Journals (Sweden)

    Alessandro Dalpiaz

    2018-03-01

    Full Text Available Although several viruses can easily infect the central nervous system (CNS, antiviral drugs often show dramatic difficulties in penetrating the brain from the bloodstream since they are substrates of active efflux transporters (AETs. These transporters, located in the physiological barriers between blood and the CNS and in macrophage membranes, are able to recognize their substrates and actively efflux them into the bloodstream. The active transporters currently known to efflux antiviral drugs are P-glycoprotein (ABCB1 or P-gp or MDR1, multidrug resistance-associated proteins (ABCC1 or MRP1, ABCC4 or MRP4, ABCC5 or MRP5, and breast cancer resistance protein (ABCG2 or BCRP. Inhibitors of AETs may be considered, but their co-administration causes serious unwanted effects. Nasal administration of antiviral drugs is therefore proposed in order to overcome the aforementioned problems, but innovative devices, formulations (thermoreversible gels, polymeric micro- and nano-particles, solid lipid microparticles, nanoemulsions, absorption enhancers (chitosan, papaverine, and mucoadhesive agents (chitosan, polyvinilpyrrolidone are required in order to selectively target the antiviral drugs and, possibly, the AET inhibitors in the CNS. Moreover, several prodrugs of antiretroviral agents can inhibit or elude the AET systems, appearing as interesting substrates for innovative nasal formulations able to target anti-Human Immunodeficiency Virus (HIV agents into macrophages of the CNS, which are one of the most important HIV Sanctuaries of the body.

  15. Overcoming the obstacles: Life stories of scientists with learning disabilities

    Science.gov (United States)

    Force, Crista Marie

    Scientific discovery is at the heart of solving many of the problems facing contemporary society. Scientists are retiring at rates that exceed the numbers of new scientists. Unfortunately, scientific careers still appear to be outside the reach of most individuals with learning disabilities. The purpose of this research was to better understand the methods by which successful learning disabled scientists have overcome the barriers and challenges associated with their learning disabilities in their preparation and performance as scientists. This narrative inquiry involved the researcher writing the life stories of four scientists. These life stories were generated from extensive interviews in which each of the scientists recounted their life histories. The researcher used narrative analysis to "make sense" of these learning disabled scientists' life stories. The narrative analysis required the researcher to identify and describe emergent themes characterizing each scientist's life. A cross-case analysis was then performed to uncover commonalities and differences in the lives of these four individuals. Results of the cross-case analysis revealed that all four scientists had a passion for science that emerged at an early age, which, with strong drive and determination, drove these individuals to succeed in spite of the many obstacles arising from their learning disabilities. The analysis also revealed that these scientists chose careers based on their strengths; they actively sought mentors to guide them in their preparation as scientists; and they developed coping techniques to overcome difficulties and succeed. The cross-case analysis also revealed differences in the degree to which each scientist accepted his or her learning disability. While some demonstrated inferior feelings about their successes as scientists, still other individuals revealed feelings of having superior abilities in areas such as visualization and working with people. These individuals revealed

  16. Overcoming phytoremediation limitations. A case study of Hg contaminated soil

    Science.gov (United States)

    Barbafieri, Meri

    2013-04-01

    Phytoremediation is a broad term that comprises several technologies to clean up water and soil. Despite the numerous articles appearing in scientific journals, very few field applications of phytoextraction have been successfully realized. The research here reported on Phytoextraction, the use the plant to "extract" metals from contaminated soil, is focused on implementations to overcome two main drawbacks: the survival of plants in unfavorable environmental conditions (contaminant toxicity, low fertility, etc.) and the often lengthy time it takes to reduce contaminants to the requested level. Moreover, to overcome the imbalance between the technology's potential and its drawbacks, there is growing interest in the use of plants to reduce only the fraction that is the most hazardous to the environment and human health, that is to target the bioavailable fractions of metals in soil. Bioavailable Contaminant Stripping (BCS) would be a remediation approach focused to remove the bioavailable metal fractions. BCS have been used in a mercury contaminated soil from Italian industrial site. Bioavailable fractions were determined by sequential extraction with H2O and NH4Cl.Combined treatments of plant hormone and thioligand to strength Hg uptake by crop plants (Brassica juncea and Helianthus annuus) were tested. Plant biomass, evapotranspiration, Hg uptake and distribution following treatments were compared. Results indicate the plant hormone, cytokinine (CK) foliar treatment, increased evapotranspiration rate in both tested plants. The Hg uptake and translocation in both tested plants increased with simultaneous addition of CK and TS treatments. B. juncea was the most effective in Hg uptake. Application of CK to plants grown in TS-treated soil lead to an increase in Hg concentration of 232% in shoots and 39% in roots with respect to control. While H. annuus gave a better response in plant biomass production, the application of CK to plants grown in TS-treated soil lead to

  17. Overcoming bottlenecks in the membrane protein structural biology pipeline.

    Science.gov (United States)

    Hardy, David; Bill, Roslyn M; Jawhari, Anass; Rothnie, Alice J

    2016-06-15

    Membrane proteins account for a third of the eukaryotic proteome, but are greatly under-represented in the Protein Data Bank. Unfortunately, recent technological advances in X-ray crystallography and EM cannot account for the poor solubility and stability of membrane protein samples. A limitation of conventional detergent-based methods is that detergent molecules destabilize membrane proteins, leading to their aggregation. The use of orthologues, mutants and fusion tags has helped improve protein stability, but at the expense of not working with the sequence of interest. Novel detergents such as glucose neopentyl glycol (GNG), maltose neopentyl glycol (MNG) and calixarene-based detergents can improve protein stability without compromising their solubilizing properties. Styrene maleic acid lipid particles (SMALPs) focus on retaining the native lipid bilayer of a membrane protein during purification and biophysical analysis. Overcoming bottlenecks in the membrane protein structural biology pipeline, primarily by maintaining protein stability, will facilitate the elucidation of many more membrane protein structures in the near future. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  18. Towards overcoming the Monte Carlo sign problem with tensor networks

    Directory of Open Access Journals (Sweden)

    Bañuls Mari Carmen

    2017-01-01

    Full Text Available The study of lattice gauge theories with Monte Carlo simulations is hindered by the infamous sign problem that appears under certain circumstances, in particular at non-zero chemical potential. So far, there is no universal method to overcome this problem. However, recent years brought a new class of non-perturbative Hamiltonian techniques named tensor networks, where the sign problem is absent. In previous work, we have demonstrated that this approach, in particular matrix product states in 1+1 dimensions, can be used to perform precise calculations in a lattice gauge theory, the massless and massive Schwinger model. We have computed the mass spectrum of this theory, its thermal properties and real-time dynamics. In this work, we review these results and we extend our calculations to the case of two flavours and non-zero chemical potential. We are able to reliably reproduce known analytical results for this model, thus demonstrating that tensor networks can tackle the sign problem of a lattice gauge theory at finite density.

  19. Strategies for Overcoming Resistance in Tumours Harboring BRAF Mutations

    Directory of Open Access Journals (Sweden)

    Nourah Mohammad Obaid

    2017-03-01

    Full Text Available The development of resistance to previously effective treatments has been a challenge for health care providers and a fear for patients undergoing cancer therapy. This is an unfortunately frequent occurrence for patients undergoing targeted therapy for tumours harboring the activating V600E mutation of the BRAF gene. Since the initial identification of the BRAF mutation in 2002, a series of small molecular inhibitors that target the BRAFV600E have been developed, but intrinsic and acquired resistance to these drugs has presented an ongoing challenge. More recently, improvements in therapy have been achieved by combining the use of BRAF inhibitors with other drugs, such as inhibitors of the downstream effector mitogen activated protein kinase (MAPK/extracellular-signal regulated kinase (ERK kinase (MEK. Despite improved success in response rates and in delaying resistance using combination therapy, ultimately, the acquisition of resistance remains a concern. Recent research articles have shed light on some of the underlying mechanisms of this resistance and have proposed numerous strategies that might be employed to overcome or avoid resistance to targeted therapies. This review will explore some of the resistance mechanisms, compare what is known in melanoma cancer to colorectal cancer, and discuss strategies under development to manage the development of resistance.

  20. Overcoming multicollinearity in multiple regression using correlation coefficient

    Science.gov (United States)

    Zainodin, H. J.; Yap, S. J.

    2013-09-01

    Multicollinearity happens when there are high correlations among independent variables. In this case, it would be difficult to distinguish between the contributions of these independent variables to that of the dependent variable as they may compete to explain much of the similar variance. Besides, the problem of multicollinearity also violates the assumption of multiple regression: that there is no collinearity among the possible independent variables. Thus, an alternative approach is introduced in overcoming the multicollinearity problem in achieving a well represented model eventually. This approach is accomplished by removing the multicollinearity source variables on the basis of the correlation coefficient values based on full correlation matrix. Using the full correlation matrix can facilitate the implementation of Excel function in removing the multicollinearity source variables. It is found that this procedure is easier and time-saving especially when dealing with greater number of independent variables in a model and a large number of all possible models. Hence, in this paper detailed insight of the procedure is shown, compared and implemented.

  1. Overcoming complexities: Damage detection using dictionary learning framework

    Science.gov (United States)

    Alguri, K. Supreet; Melville, Joseph; Deemer, Chris; Harley, Joel B.

    2018-04-01

    For in situ damage detection, guided wave structural health monitoring systems have been widely researched due to their ability to evaluate large areas and their ability detect many types of damage. These systems often evaluate structural health by recording initial baseline measurements from a pristine (i.e., undamaged) test structure and then comparing later measurements with that baseline. Yet, it is not always feasible to have a pristine baseline. As an alternative, substituting the baseline with data from a surrogate (nearly identical and pristine) structure is a logical option. While effective in some circumstance, surrogate data is often still a poor substitute for pristine baseline measurements due to minor differences between the structures. To overcome this challenge, we present a dictionary learning framework to adapt surrogate baseline data to better represent an undamaged test structure. We compare the performance of our framework with two other surrogate-based damage detection strategies: (1) using raw surrogate data for comparison and (2) using sparse wavenumber analysis, a precursor to our framework for improving the surrogate data. We apply our framework to guided wave data from two 108 mm by 108 mm aluminum plates. With 20 measurements, we show that our dictionary learning framework achieves a 98% accuracy, raw surrogate data achieves a 92% accuracy, and sparse wavenumber analysis achieves a 57% accuracy.

  2. The telephone effect: Overcoming initiation deficits in two settings.

    Science.gov (United States)

    Vickers, Kayci L; Keesler, Michael E; Williams, Kelli S; Charles, Jeremy Y; Hamilton, Roy H

    2018-04-19

    Disorders of motivation substantially impair an individual's ability to communicate with their families, therapists, and doctors. One method of overcoming initiation deficits is by utilizing the telephone effect, which is the ability for individuals with severe motivation deficits to communicate more readily when speaking on a telephone. However, little is available in the extant literature on how this effect works or how best to integrate this into patient care. This article aims to provide the first report of a proposed mechanism underlying the telephone effect and the first published procedures for eliciting this effect. This is largely a review article that also contains descriptions of clinical procedures for eliciting the telephone effect with 2 patient populations: acute inpatients following brain injury and dementia residents. A case vignette is also provided. We propose that the telephone effect is the result of an interaction between the patient and environment, and occurs because of Gibson's (1979) law of affordances. The use of this theory provides an explanation of the behaviors often observed when attempting to elicit this effect (i.e., disruption of the effect when using a cellular phone). Moreover, we argue that this can, and does, apply to social interactions as well. The telephone effect is an understudied phenomenon that provides a means of improving care for individuals with disorders of motivation. Future directions include systematic research into the telephone effect and further investigation of the mechanism underlying this effect. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  3. Strategies to potentiate antimicrobial photoinactivation by overcoming resistant phenotypes†

    Science.gov (United States)

    Vera, D. Mariano A.; Haynes, Mark H; Ball, Anthony R.; Dai, D. Tianhong; Astrakas, Christos; Kelso, Michael J; Hamblin, Michael R; Tegos, George P.

    2012-01-01

    Conventional antimicrobial strategies have become increasingly ineffective due to the emergence of multidrug resistance among pathogenic microorganisms. The need to overcome these deficiencies has triggered the exploration of alternative treatments and unconventional approaches towards controlling microbial infections. Photodynamic therapy was originally established as an anti-cancer modality and is currently used in the treatment of age related macular degeneration. The concept of photodynamic inactivation requires cell exposure to light energy, typically wavelengths in the visible region that causes the excitation of photosensitizer molecules either exogenous or endogenous, which results in the production of reactive oxygen species. ROS produce cell inactivation and death through modification of intracellular components. The versatile characteristics of PDT prompted its investigation as an anti-infective discovery platform. Advances in understanding of microbial physiology have shed light on a series of pathways, and phenotypes that serve as putative targets for antimicrobial drug discovery. Investigations of these phenotypic elements in concert with PDT have been reported focused on multidrug efflux systems, biofilms, virulence and pathogenesis determinants. In many instances the results are promising but only preliminary and require further investigation. This review discusses the different antimicrobial PDT strategies and highlights the need for highly informative and comprehensive discovery approaches. PMID:22242675

  4. Overcoming PV grid issues in the urban areas

    Energy Technology Data Exchange (ETDEWEB)

    Ehara, T.

    2009-10-15

    This report for the International Energy Agency (IEA) made by Task 10 of the Photovoltaic Power Systems (PVPS) programme takes a look at grid issues in urban photovoltaic electricity and how to overcome them. The mission of the Photovoltaic Power Systems Programme is to enhance the international collaboration efforts which accelerate the development and deployment of photovoltaic solar energy as a significant and sustainable renewable energy option. The objective of Task 10 is stated as being to enhance the opportunities for wide-scale, solution-oriented application of photovoltaics in the urban environment. The paper discusses the goal of mainstreaming PV systems in the urban environment. In this report, PV grid interconnection issues and countermeasures based on the latest studies are identified and summarised. Appropriate and understandable information is provided for all possible stakeholders. Possible impacts and benefits of PV grid interconnection are identified, technical measures designed to eliminate negative impacts and enhance possible benefits are presented. The status of research and demonstration projects is introduced and the latest outcomes are summarised. Recommendations and conclusions based on the review process are summarised and presented.

  5. Overcoming barriers to integrating economic analysis into risk assessment.

    Science.gov (United States)

    Hoffmann, Sandra

    2011-09-01

    Regulatory risk analysis is designed to provide decisionmakers with a clearer understanding of how policies are likely to affect risk. The systems that produce risk are biological, physical, and social and economic. As a result, risk analysis is an inherently interdisciplinary task. Yet in practice, risk analysis has been interdisciplinary in only limited ways. Risk analysis could provide more accurate assessments of risk if there were better integration of economics and other social sciences into risk assessment itself. This essay examines how discussions about risk analysis policy have influenced the roles of various disciplines in risk analysis. It explores ways in which integrated bio/physical-economic modeling could contribute to more accurate assessments of risk. It reviews examples of the kind of integrated economics-bio/physical modeling that could be used to enhance risk assessment. The essay ends with a discussion of institutional barriers to greater integration of economic modeling into risk assessment and provides suggestions on how these might be overcome. © 2011 Society for Risk Analysis.

  6. Methods for overcoming dormancy in Stryphnodendron pulcherrimum seeds

    Directory of Open Access Journals (Sweden)

    Adriano Gonçalves Pereira

    2016-09-01

    Full Text Available Seed dormancy is a phenomenon observed in several tropical species. This condition causes low and non-uniform germination. The present study was designed to identify an efficient method of breaking seed dormancy in Stryphnodendron pulcherrimum. Seeds of four mother plants were subjected to the following treatments: immersion in sulfuric acid for 2, 4, 6, 8, 10 and 12 min and scarification on 150-grit sandpaper. Seeds were sown on substrate containing sand and sawdust (1:1. It was evaluate the days to onset seedlings emergence, seedlings emergence (SE, emergence speed index (ESI, germination (G, hard seeds (HS, dead seeds (DS, dormant seeds (DMS, abnormal seedlings (AS and dry mass of aerial part (DMAP and roots (DMR. The experimental design was completely randomized with four replications of 25 seeds for each treatment. Data were subjected to analysis of variance and means compared by Tukey’s test (p < 0.05. Significant differences among treatments were observed for ESI, SE, G, HS, DMAP and DMR. Highest HS was observed in control treatment (85%. Highest G was observed in seeds scarified with sulfuric acid for 10 min (82% and 12 min (74%. These treatments also showed highest ESI, DMAP and DMR, indicating that these scarification treatments were the most efficient in overcoming dormancy.

  7. Overcoming dormancy in seeds of cotton-silk tree

    Directory of Open Access Journals (Sweden)

    Irinaldo Lima do Nascimento

    2012-06-01

    Full Text Available Cotton-silk tree Ceiba glaziovii (kuntze k. Schu belongs to family Bombacaceas and is locally known as barriguda. It is widely used in landscaping and reforestation, neverdeless seed dormancy affects reproduction in this species. The objective of this study was to evaluate the effectiveness of different methods to overcome dormancy in the germination process. Treatments included mechanical scarification with 85-grit sandpaper, chemical scarification with concentrated sulfuric acid for 5, 10, 15 and 20 minutes, physical scarification with hot water at 60°, 70°, 80°and 90° C for one minute, imbibition in distilled water for 24, 48 and 72 hours, oven heating at 65° C for 1, 2, 3 and 4 hours, and a control treatment. Each treatment included four replicates of 25 seeds, using a completely randomized experimental design, and means were compared by the Scott-Knott test at the 5% probability level. Assessed parameters included emergence percentage, emergence rate index, dry matter and length of plants. The most recommended treatments were mechanical scarification, immersion in sulfuric acid for 5, 10 and 15 minutes and immersion in distilled water for 48 hours.

  8. Dormancy overcome and seedling quality of pecan in nursery

    Directory of Open Access Journals (Sweden)

    Tales Poletto

    Full Text Available ABSTRACT: This study evaluated the efficiency of methods to overcome seed dormancy in different storage periods in the production of pecan seedlings. Seeds were submitted to the following treatments: T1, T4 and T7 - control treatments (seeds with no treatment, stored at room temperature for 30, 60 and 90 days, respectively, T2, T5 and T8 - stratification (seeds were distributed in boxes with wet sand maintained at a temperature of 4°C for 30, 60 and 90 days, respectively, T3, T6 and T9 - scarification + stratification (seeds scarified with sandpaper n.80 and stratified by 30, 60 and 90 days, respectively, in completely random experimental design. Plant height, stem diameter, number of leaves, full emergence and emergence speed index (ESI were evaluated after 14 weeks of sowing. The best development of pecan 'plants, their emergence, and ESI were observed in the stratification treatment for 90 day as well as in the scarification + stratification treatment for 90 day. Storing seeds in uncontrolled environment reduced their viability.

  9. Barriers to women engaging in collective action to overcome sexism.

    Science.gov (United States)

    Radke, Helena R M; Hornsey, Matthew J; Barlow, Fiona Kate

    2016-12-01

    Over centuries women have fought hard to obtain increasing gender equality, but despite these successes absolute equality remains an elusive goal. Theoretically, women's numerical strength makes them well-placed to take effective collective action, and millions of women engage in feminist collective action every day. In this article, however, we argue that women also face barriers to engaging in feminist collective action; barriers that are associated with the social construction and experience of what it means to be a woman. Our review synthesizes sexism research under a contemporary collective action framework to clarify our current understanding of the literature and to offer novel theoretical explanations for why women might be discouraged from engaging in feminist collective action. Using the antecedents of collective action identified by van Zomeren, Postmes, and Spears' (2008) meta-analysis, we critically review the sexism literature to argue that women face challenges when it comes to (a) identifying with other women and feminists, (b) perceiving sexism and expressing group-based anger, and (c) recognizing the efficacy of collective action. We then outline a research agenda with a view to investigating ways of overcoming these barriers. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  10. Overcoming recruitment challenges in palliative care clinical trials.

    Science.gov (United States)

    LeBlanc, Thomas W; Lodato, Jordan E; Currow, David C; Abernethy, Amy P

    2013-11-01

    Palliative care is increasingly viewed as a necessary component of cancer care, especially for patients with advanced disease. Rigorous clinical trials are thus needed to build the palliative care evidence base, but clinical research-especially participant recruitment-is difficult. Major barriers include (1) patient factors, (2) "gatekeeping," and (3) ethical concerns. Here we discuss an approach to overcoming these barriers, using the Palliative Care Trial (PCT) as a case study. The PCT was a 2 × 2 × 2 factorial randomized controlled trial (RCT) of different service delivery models to improve pain control in the palliative setting. It used a recruitment protocol that fused evidence-based strategies with principles of "social marketing," an approach involving the systematic application of marketing techniques. Main components included (1) an inclusive triage algorithm, (2) information booklets targeting particular stakeholders, (3) a specialized recruitment nurse, and (4) standardization of wording across all study communications. From an eligible pool of 607 patients, the PCT enrolled 461 patients over 26 months. Twenty percent of patients referred to the palliative care service were enrolled (76% of those eligible after screening). Several common barriers were minimized; among those who declined participation, family disinterest was uncommon (5%), as was the perception of burden imposed (4%). Challenges to clinical trial recruitment in palliative care are significant but not insurmountable. A carefully crafted recruitment and retention protocol can be effective. Our experience with designing and deploying a social-marketing-based protocol shows the benefits of such an approach.

  11. Biodiesel Production From Algae to Overcome the Energy Crisis

    Directory of Open Access Journals (Sweden)

    Suliman Khan

    2017-10-01

    Full Text Available The use of energy sources has reached at the level that whole world is relying on it. Being the major source of energy, fuels are considered the most important. The fear of diminishing the available sources thirst towards biofuel production has increased during last decades. Considering the food problems, algae gain the most attention to be used as biofuel producers. The use of crop and food-producing plants will never be a best fit into the priorities for biofuel production as they will disturb the food needs. Different types of algae having the different production abilities. Normally algae have 20%–80% oil contents that could be converted into different types of fuels such as kerosene oil and biodiesel. The diesel production from algae is economical and easy. Different species such as tribonema, ulothrix and euglena have good potential for biodiesel production. Gene technology can be used to enhance the production of oil and biodiesel contents and stability of algae. By increasing the genetic expressions, we can find the ways to achieve the required biofuel amounts easily and continuously to overcome the fuels deficiency. The present review article focusses on the role of algae as a possible substitute for fossil fuel as an ideal biofuel reactant.

  12. Overcoming the Social Stigma on Mood Disorders with Dancing.

    Science.gov (United States)

    Tavormina, Romina; Tavormina, Maurilio Giuseppe Maria

    2017-09-01

    In our society, the social stigma against people who suffer from mood disorders is a very powerful factor that negatively affects the healing of patient. He is often isolated from the others for the fear of being judged "fool, crazy or dangerous" or discriminated and emarginated for his mental health problem. For this reason, a cornerstone of mood disorder rehabilitation is the bringing out of the patient from his isolation, the reintegration of the user in the social context with the increase and the improvement in the quality of interpersonal relationships in the family and in the external context. The method used in our project is the dance-therapy one. In particular dancing the "Bachata" becomes a rehabilitation tool to express emotions through the body and to open to the world, on the territory, overcoming the fear of being judged by others, and of the prejudice and the social stigma about mental illness. The strength and cohesion of the rehabilitation group has given to the patients the opportunity to believe in their own abilities, to accept themselves with their difficulties and to improve the relationship with their body in relation to each other.

  13. Rapid parallel evolution overcomes global honey bee parasite.

    Science.gov (United States)

    Oddie, Melissa; Büchler, Ralph; Dahle, Bjørn; Kovacic, Marin; Le Conte, Yves; Locke, Barbara; de Miranda, Joachim R; Mondet, Fanny; Neumann, Peter

    2018-05-16

    In eusocial insect colonies nestmates cooperate to combat parasites, a trait called social immunity. However, social immunity failed for Western honey bees (Apis mellifera) when the ectoparasitic mite Varroa destructor switched hosts from Eastern honey bees (Apis cerana). This mite has since become the most severe threat to A. mellifera world-wide. Despite this, some isolated A. mellifera populations are known to survive infestations by means of natural selection, largely by supressing mite reproduction, but the underlying mechanisms of this are poorly understood. Here, we show that a cost-effective social immunity mechanism has evolved rapidly and independently in four naturally V. destructor-surviving A. mellifera populations. Worker bees of all four 'surviving' populations uncapped/recapped worker brood cells more frequently and targeted mite-infested cells more effectively than workers in local susceptible colonies. Direct experiments confirmed the ability of uncapping/recapping to reduce mite reproductive success without sacrificing nestmates. Our results provide striking evidence that honey bees can overcome exotic parasites with simple qualitative and quantitative adaptive shifts in behaviour. Due to rapid, parallel evolution in four host populations this appears to be a key mechanism explaining survival of mite infested colonies.

  14. Will new antimicrobials overcome resistance among Gram-negatives?

    Science.gov (United States)

    Bassetti, Matteo; Ginocchio, Francesca; Mikulska, Małgorzata; Taramasso, Lucia; Giacobbe, Daniele Roberto

    2011-10-01

    The spread of resistance among Gram-positive and Gram-negative bacteria represents a growing challenge for the development of new antimicrobials. The pace of antibiotic drug development has slowed during the last decade and, especially for Gram-negatives, clinicians are facing a dramatic shortage in the availability of therapeutic options to face the emergency of the resistance problem throughout the world. In this alarming scenario, although there is a shortage of compounds reaching the market in the near future, antibiotic discovery remains one of the keys to successfully stem and maybe overcome the tide of resistance. Analogs of already known compounds and new agents belonging to completely new classes of antimicrobials are in early stages of development. Novel and promising anti-Gram-negative antimicrobials belong both to old (cephalosporins, carbapenems, β-lactamase inhibitors, monobactams, aminoglycosides, polymyxin analogues and tetracycline) and completely new antibacterial classes (boron-containing antibacterial protein synthesis inhibitors, bis-indoles, outer membrane synthesis inhibitors, antibiotics targeting novel sites of the 50S ribosomal subunit and antimicrobial peptides). However, all of these compounds are still far from being introduced into clinical practice. Therefore, infection control policies and optimization in the use of already existing molecules are still the most effective approaches to reduce the spread of resistance and preserve the activity of antimicrobials.

  15. Overcoming the Confucian psychological barrier in government cyberspace.

    Science.gov (United States)

    Lee, Ook; Gong, Sung Jin

    2004-02-01

    The Confucian tradition still dictates the behavior of many people in East Asian countries such as South Korea. Even in e-mail communication, people try their best to show signs of respect which is required by the Confucian tradition. This psychological barrier can be detrimental to the development of democracy as people are educated not to challenge opinions of elders or bosses. After a long military dictatorship, South Korea has emerged as a newly democratized nation where the Confucian tradition is less emphasized. However, this tradition dies hard, and citizens are still afraid of offending government officials who have the power to affect lives of citizens. In light of creating a more democratic society, the e-government project has been implemented, and one of the features of cyber-government is to give citizens a place in cyberspace to express their concerns. Even though citizens have to use their real names, it is found that those who wrote messages in the bulletin board of the city of Seoul government's web pages tend not to use terms that are often used in e-mails for the purpose of expressing respect. A survey was conducted, and results show that people were able to overcome the Confucian psychological barrier in government cyberspace. Self-efficacy is proposed to explain this phenomenon.

  16. Overcoming the Obstacle of Poor Knowledge in Proving Geometry Tasks

    Directory of Open Access Journals (Sweden)

    Zlatan Magajna

    2013-12-01

    Full Text Available Proving in school geometry is not just about validating the truth of a claim. In the school setting, the main function of the proof is to convince someone that a claim is true by providing an explanation. Students consider proving to be difficult; in fact, they find the very concept of proof demanding. Proving a claim in planar geometry involves several processes, the most salient being visual observation and deductive argumentation. These two processes are interwoven, but often poor observation hinders deductive argumentation. In the present article, we consider the possibility of overcoming the obstacle of a student’s poor observation by making use of computer-aided observation with appropriate software. We present the results of two small-scale research projects, both of which indicate that students are able to work out considerably more deductions if computer-aided observation is used. Not all students use computer-aided observation effectively in proving tasks: some find an exhaustive computer-provided list of properties confusing and are not able to choose the properties that are relevant to the task.

  17. A Salmonella nanoparticle mimic overcomes multidrug resistance in tumours.

    Science.gov (United States)

    Mercado-Lubo, Regino; Zhang, Yuanwei; Zhao, Liang; Rossi, Kyle; Wu, Xiang; Zou, Yekui; Castillo, Antonio; Leonard, Jack; Bortell, Rita; Greiner, Dale L; Shultz, Leonard D; Han, Gang; McCormick, Beth A

    2016-07-25

    Salmonella enterica serotype Typhimurium is a food-borne pathogen that also selectively grows in tumours and functionally decreases P-glycoprotein (P-gp), a multidrug resistance transporter. Here we report that the Salmonella type III secretion effector, SipA, is responsible for P-gp modulation through a pathway involving caspase-3. Mimicking the ability of Salmonella to reverse multidrug resistance, we constructed a gold nanoparticle system packaged with a SipA corona, and found this bacterial mimic not only accumulates in tumours but also reduces P-gp at a SipA dose significantly lower than free SipA. Moreover, the Salmonella nanoparticle mimic suppresses tumour growth with a concomitant reduction in P-gp when used with an existing chemotherapeutic drug (that is, doxorubicin). On the basis of our finding that the SipA Salmonella effector is fundamental for functionally decreasing P-gp, we engineered a nanoparticle mimic that both overcomes multidrug resistance in cancer cells and increases tumour sensitivity to conventional chemotherapeutics.

  18. Overcoming Barriers to Successfully Commercializing Carbon Dioxide Utilization

    Directory of Open Access Journals (Sweden)

    Marvin Kant

    2017-09-01

    Full Text Available The successful transition to a low-carbon economy hinges on innovative solutions and collaborative action on a global scale. Sustainable entrepreneurship is thereby recognized as a key driver in the creation and transformation of ecologically and socially sustainable economic systems. The purpose of this article is to contribute to this topic by understanding commercialization barriers for strong sustainability-oriented new technology ventures and to derive recommendations to overcome them. A qualitative multilevel approach is applied to identify barriers and drivers within the internal dynamic capabilities of the organization and within the organization’s external stakeholders. A model of barriers has been developed based on semi-structured interviews with new carbon dioxide utilization ventures and associated industry players in Canada, the USA, and the European Economic Area. Resulting recommendations to facilitate the (re-design of a dedicated support system are proposed on four levels: (a actors, (b resources, (c institutional settings, and (d the coordination of the support system.

  19. Methods to overcome dormancy in tree tomato (Solanum betaceum seeds

    Directory of Open Access Journals (Sweden)

    Carlos Kosera Neto

    2015-12-01

    Full Text Available The tree tomato (Solanum betaceum is a poorly known species that has fruits with great economic potential, as it can be consumed in natura or industrialized. However, for reaching this potential, it is necessary the development of technologies for seedlings production. The propagation of this species is mainly done by seeds, but the seed germination process is usually slow, especially under stress conditions. This study aimed at verifying whether tree tomato seeds have dormancy and which is the best method to obtain fast and uniform germination. A completely randomized design was adopted in a 5 x 2 factorial arrangement (methods to overcome dormancy x light, with four replications of 50 or 60 seeds, depending on the production cycle. The methods tested were cold stratification, hydropriming, priming with GA3 solution and control, with or without light. Seed germination and germination rate index, as well as the beginning and average time of germination, were also evaluated. The use of GA3 at a concentration of 100 mg L-1 or 300 mg L-1 is recommended to the germination of tree tomato seeds.

  20. Challenges confronting female surgical leaders: overcoming the barriers.

    Science.gov (United States)

    Kass, Rena B; Souba, Wiley W; Thorndyke, Luanne E

    2006-05-15

    The number of women reaching top ranks in academic surgery is remarkably low. The purpose of this study was to identify: 1) barriers to becoming a female surgical leader; 2) key attributes that enable advancement and success; and 3) current leadership challenges faced as senior leaders. Semi-structured interviews of ten female surgical leaders queried the following dimensions: attributes for success, lessons learned, mistakes, key career steps, the role of mentoring, gender advantages/disadvantages, and challenges. Perseverance (60%) and drive (50%) were identified as critical success factors, as were good communication skills, a passion for scholarship, a stable home life and a positive outlook. Eighty percent identified discrimination or gender prejudice as a major obstacle in their careers. While 90% percent had mentors, 50% acknowledged that they had not been effectively mentored. Career advice included: develop broad career goals (50%); select a conducive environment (30%); find a mentor (60%); take personal responsibility (40%); organize time and achieve balance (40%); network (30%); create a niche (30%); pursue research (30%); publish (50%); speak in public (30%); and enjoy the process (30%). Being in a minority, being highly visible and being collaborative were identified as advantages. Obtaining buy-in and achieving consensus was the greatest leadership challenge reported. Female academic surgeons face challenges to career advancement. While these barriers are real, they can be overcome by resolve, commitment, and developing strong communication skills. These elements should be taken into consideration in designing career development programs for junior female surgical faculty.

  1. IL-15 Overcomes Hepatocellular Carcinoma-Induced NK Cell Dysfunction

    Directory of Open Access Journals (Sweden)

    Nicholas J. W. Easom

    2018-05-01

    Full Text Available NK cells have potent antitumor capacity. They are enriched in the human liver, with a large subset specialized for tissue-residence. The potential for liver-resident versus liver-infiltrating NK cells to populate, and exert antitumor functions in, human liver tumors has not been studied. We examined liver-resident and liver-infiltrating NK cells directly ex vivo from human hepatocellular carcinomas (HCCs and liver colorectal (CRC metastases, compared with matched uninvolved liver tissue. We found that NK cells were highly prevalent in both HCC and liver CRC metastases, although at lower frequencies than unaffected liver. Up to 79% of intratumoral NK cells had the CXCR6+CD69+ liver-resident phenotype. Direct ex vivo staining showed that liver-resident NK cells had increased NKG2D expression compared to their non-resident counterparts, but both subsets had NKG2D downregulation within liver tumors compared to uninvolved liver. Proliferation of intratumoral NK cells (identified by Ki67 was selectively impaired in those with the most marked NKG2D downregulation. Human liver tumor NK cells were functionally impaired, with reduced capacity for cytotoxicity and production of cytokines, even when compared to the hypo-functional tissue-resident NK cells in unaffected liver. Coculture of human liver NK cells with the human hepatoma cell line PLC/PRF/5, or with autologous HCC, recapitulated the defects observed in NK cells extracted from tumors, with downmodulation of NKG2D, cytokine production, and target cell cytotoxicity. Transwells and conditioned media confirmed a requirement for cell contact with PLC/PRF/5 to impose NK cell inhibition. IL-15 was able to recover antitumor functionality in NK cells inhibited by in vitro exposure to HCC cell lines or extracted directly from HCC. In summary, our data suggest that the impaired antitumor function of local NK cells reflects a combination of the tolerogenic features inherent to liver-resident NK cells

  2. The return to keynesianism in overcoming cyclical fluctuations?

    Directory of Open Access Journals (Sweden)

    Praščević Aleksandra

    2008-01-01

    Full Text Available The problems faced by the American economy in the second half of 2007, which intensified in 2008, have once again asked economic science, and even more so economic policy, questions relating to business cycles - the reasons for cyclical fluctuations, the character of business cycles and, naturally, economic policy measures that can be implemented to alleviate and overcome an economic recession. Since the 1970s, business cycle theories have been intensively developed - ranging from monetary theories, developed within monetarism and the first phase of New Classical Macroeconomics, to the real business cycle theory of New Classical Macroeconomics. Consequently, the triggers for the beginning of a cycle can be monetary (monetary theories or real in the form of technological shocks (real business cycles. In essence economic policy conducted since the 1970s, has rejected the Keynesian explanations of the functioning of the economic system, and thus the policy of aggregate demand management. However, the measures that are now being implemented in the USA point to a return to Keynesianism. This refers, above all, to attempts to compensate for the inefficiency of monetary policy with fiscal expansion. All three psychological propensities (propensity to consume, propensity to invest and liquidity preference in Keynes's theory and applied in Keynesian economic policy, are still the significant determinants of monetary and fiscal policies. The return to Keynesianism points to the depth of the crisis faced by the USA, but also confirms the vitality of Keynesian economics and affirms the view that - although Keynes wished to present his theory as being "general" - it is actually the theory of economic depression.

  3. Overcoming equifinality: Leveraging long time series for stream metabolism estimation

    Science.gov (United States)

    Appling, Alison; Hall, Robert O.; Yackulic, Charles B.; Arroita, Maite

    2018-01-01

    The foundational ecosystem processes of gross primary production (GPP) and ecosystem respiration (ER) cannot be measured directly but can be modeled in aquatic ecosystems from subdaily patterns of oxygen (O2) concentrations. Because rivers and streams constantly exchange O2 with the atmosphere, models must either use empirical estimates of the gas exchange rate coefficient (K600) or solve for all three parameters (GPP, ER, and K600) simultaneously. Empirical measurements of K600 require substantial field work and can still be inaccurate. Three-parameter models have suffered from equifinality, where good fits to O2 data are achieved by many different parameter values, some unrealistic. We developed a new three-parameter, multiday model that ensures similar values for K600 among days with similar physical conditions (e.g., discharge). Our new model overcomes the equifinality problem by (1) flexibly relating K600 to discharge while permitting moderate daily deviations and (2) avoiding the oft-violated assumption that residuals in O2 predictions are uncorrelated. We implemented this hierarchical state-space model and several competitor models in an open-source R package, streamMetabolizer. We then tested the models against both simulated and field data. Our new model reduces error by as much as 70% in daily estimates of K600, GPP, and ER. Further, accuracy benefits of multiday data sets require as few as 3 days of data. This approach facilitates more accurate metabolism estimates for more streams and days, enabling researchers to better quantify carbon fluxes, compare streams by their metabolic regimes, and investigate controls on aquatic activity.

  4. Overcoming the Photovoltage Plateau in Large Bandgap Perovskite Photovoltaics.

    Science.gov (United States)

    Rajagopal, Adharsh; Stoddard, Ryan J; Jo, Sae Byeok; Hillhouse, Hugh W; Jen, Alex K-Y

    2018-05-09

    Development of large bandgap (1.80-1.85 eV E g ) perovskite is crucial for perovskite-perovskite tandem solar cells. However, the performance of 1.80-1.85 eV E g perovskite solar cells (PVKSCs) are significantly lagging their counterparts in the 1.60-1.75 eV E g range. This is because the photovoltage ( V oc ) does not proportionally increase with E g due to lower optoelectronic quality of conventional (MA,FA,Cs)Pb(I,Br) 3 and results in a photovoltage plateau ( V oc limited to 80% of the theoretical limit for ∼1.8 eV E g ). Here, we incorporate phenylethylammonium (PEA) in a mixed-halide perovskite composition to solve the inherent material-level challenges in 1.80-1.85 eV E g perovskites. The amount of PEA incorporation governs the topography and optoelectronic properties of resultant films. Detailed structural and spectroscopic characterization reveal the characteristic trends in crystalline size, orientation, and charge carrier recombination dynamics and rationalize the origin of improved material quality with higher luminescence. With careful interface optimization, the improved material characteristics were translated to devices and V oc values of 1.30-1.35 V were achieved, which correspond to 85-87% of the theoretical limit. Using an optimal amount of PEA incorporation to balance the increase in V oc and the decrease in charge collection, a highest power conversion efficiency of 12.2% was realized. Our results clearly overcome the photovoltage plateau in the 1.80-1.85 eV E g range and represent the highest V oc achieved for mixed-halide PVKSCs. This study provides widely translatable insights, an important breakthrough, and a promising platform for next-generation perovskite tandems.

  5. Scaffold protein enigma homolog 1 overcomes the repression of myogenesis activation by inhibitor of DNA binding 2

    Energy Technology Data Exchange (ETDEWEB)

    Nakatani, Miyuki [Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Nagoya, 464-8106 (Japan); Ito, Jumpei [Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Nagoya, 464-8106 (Japan); Japan Society for the Promotion of Science, Tokyo, 102-0083 (Japan); Koyama, Riko [Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Nagoya, 464-8106 (Japan); Iijima, Masumi; Yoshimoto, Nobuo [The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka, 567-0047 (Japan); Niimi, Tomoaki [Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Nagoya, 464-8106 (Japan); Kuroda, Shun' ichi [Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Nagoya, 464-8106 (Japan); The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka, 567-0047 (Japan); Maturana, Andrés D., E-mail: maturana@agr.nagoya-u.ac.jp [Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Nagoya, 464-8106 (Japan)

    2016-05-27

    Enigma Homolog 1 (ENH1) is a scaffold protein for signaling proteins and transcription factors. Previously, we reported that ENH1 overexpression promotes the differentiation of C2C12 myoblasts. However, the molecular mechanism underlying the role of ENH1 in the C2C12 cells differentiation remains elusive. ENH1 was shown to inhibit the proliferation of neuroblastoma cells by sequestering Inhibitor of DNA binding protein 2 (Id2) in the cytosol. Id2 is a repressor of basic Helix-Loop-Helix transcription factors activity and prevents myogenesis. Here, we found that ENH1 overcome the Id2 repression of C2C12 cells myogenic differentiation and that ENH1 overexpression promotes mice satellite cells activation, the first step toward myogenic differentiation. In addition, we show that ENH1 interacted with Id2 in C2C12 cells and mice satellite cells. Collectively, our results suggest that ENH1 plays an important role in the activation of myogenesis through the repression of Id2 activity. -- Highlights: •Enigma Homolog 1 (ENH1) is a scaffold protein. •ENH1 binds to inhibitor of DNA binding 2 (Id2) in myoblasts. •ENH1 overexpression overcomes the Id2's repression of myogenesis. •The Id2-ENH1 complex play an important role in the activation of myogenesis.

  6. 20% Wind by 2030: Overcoming the Challenges in West Virginia

    Energy Technology Data Exchange (ETDEWEB)

    Patrick Mann; Christine Risch

    2012-02-15

    Final Report for '20% Wind by 2030: Overcoming the Challenges in West Virginia'. The objective of this project was to examine the obstacles and constraints to the development of wind energy in West Virginia as well as the obstacles and constraints to the achievement of the national goal of 20% wind by 2030. For the portion contracted with WVU, there were four tasks in this examination of obstacles and constraints. Task 1 involved the establishment of a Wind Resource Council. Task 2 involved conducting limited research activities. These activities involved an ongoing review of wind energy documents including documents regarding the potential for wind farms being located on reclaimed surface mining sites as well as other brownfield sites. The Principal Investigator also examined the results of the Marshall University SODAR assessment of the potential for placing wind farms on reclaimed surface mining sites. Task 3 involved the conducting of outreach activities. These activities involved working with the members of the Wind Resource Council, the staff of the Regional Wind Energy Institute, and the staff of Penn Future. This task also involved the examination of the importance of transmission for wind energy development. The Principal Investigator kept informed as to transmission developments in the Eastern United States. The Principal Investigator coordinated outreach activities with the activities at the Center for Business and Economic Research at Marshall University. Task 4 involved providing technical assistance. This task involved the provision of information to various parties interested in wind energy development. The Principal Investigator was available to answer requests from interested parties regarding in formation regarding both utility scale as well as small wind development in West Virginia. Most of the information requested regarded either the permitting process for wind facilities of various sizes in the state or information regarding the

  7. Science, Technology and Natural Resources Policy: Overcoming Congressional Gridlock

    Science.gov (United States)

    McCurdy, K. M.

    2015-12-01

    The current status of Science, Technology and Natural Resources (STNR) policy in the United States provides an ideal context to examine the influence of committee seniority within the public policy process. Exemplars of the Policy Entrepreneur have been individuals in leadership positions, whether executive or legislative. The role of junior committee members in shaping policy innovation is less well understood, and is frequently masked either in cross-sectional research designs or in case studies. The House Natural Resources committee seniority patterns are compared to the House of Representatives Chamber data from 1975 to 2015. This expanse of congressional time captures both the policy innovation of the Class of 1974 who helped transform the public lands by pursuing a preservation agenda, along with the contemporaneous gridlock caused by disagreements about reducing the size of the federal government, a policy agenda championed and sustained by the Class of 1994. Several types of political actors have served as policy entrepreneurs, President Kennedy and Secretary of Interior Udall shepherding the Wilderness Act of 1964 from the Executive branch, or in the 111th Congress Committee chairmen Senator Christopher Dodd and Representative Barney Frank, having announced their retirements, spent their final Congress shaping the consensus that produced the Wall Street Reform and Consumer Protection Act of 2010. A less studied policy phenomenon relies on "packing the committee" to outvote the leadership. This tactic can be used by the party leadership to overcome recalcitrant senior committee members, as was the case for Democrats in the House Interior and Insular Affairs Committee shift to preservation in the 1970s, or the tactic can be employed from the grassroots, as may be happening in the case of the House Natural Resources Committee in the 114th Congress. A policy making process analog to rivers is more appropriate than a mechanistic model. As there are multiple

  8. Jumping Hurdles: Peptides Able To Overcome Biological Barriers.

    Science.gov (United States)

    Sánchez-Navarro, Macarena; Teixidó, Meritxell; Giralt, Ernest

    2017-08-15

    diketoperazines (DKPs), (N-MePhe) n , or (PhPro) n . On the other hand, we have investigated BBB-shuttles that utilize active transport mechanisms such as SGV, THRre, or MiniAp-4. For the development of both groups, we have explored several approaches, such as the use of peptide libraries, both chemical and phage display, or hit-to-lead optimization processes. In this Account, we describe, in chronologic order, our contribution to the development of peptides able to overcome various biological barriers and our efforts to understand the mechanisms that they display. In addition, the potential use of both CPPs and BBB-shuttles to improve the transport of promising therapeutic compounds is described.

  9. The Evaluation of Techniques for Overcoming with the Stress in a Physician Group

    OpenAIRE

    Humman Sen; Mehmet Toygar; Turker Turker; Nurhan Ince; Harun Tugcu; Halit Keskin

    2012-01-01

    Objective: This study was made in order to determine the methods of overcoming with stress of the specialist physicians. Material-Method: Our study is a descriptive study. In the study, the scale of overcoming with stress was applied to the 100 specialist physicians who working in 5 different health care institutions in and around the Istanbul in 2009. Results: The scores that the participants takes from sub-categories of scales of overcoming with stress types were measured respectively as; 2...

  10. Overcoming regulatory barriers: DOE environmental technology development program

    International Nuclear Information System (INIS)

    Kurtyka, B.M.; Clodfelter-Schumack, K.; Evans, T.T.

    1995-01-01

    The potential to improve environmental conditions via compliance or restoration is directly related to the ability to produce and apply innovative technological solutions. However, numerous organizations, including the US General Accounting Office (GAO), the EPA National Advisory Council for Environmental Policy and Technology (NACEPT), the DOE Environmental Management Advisory Board (EMAB), and the National Science and Technology Council (NSTC) have determined that significant regulatory barriers exist that inhibit the development and application of these technologies. They have noted the need for improved efforts in identifying and rectifying these barriers for the purpose of improving the technology development process, providing innovative alternatives, and enhancing the likelihood of technology acceptance by all. These barriers include, among others, regulator and user bias against ''unknown/unproven'' technologies; multi-level/multi-media permit disincentives; potential liability of developers and users for failed implementation; wrongly defined or inadequate data quality objectives: and lack of customer understanding and input. The ultimate goal of technology development is the utilization of technologies. This paper will present information on a number of regulatory barriers hindering DOE's environmental technology development program and describe DOE efforts to address these barriers

  11. Overcoming antibiotic resistance: Is siderophore Trojan horse conjugation an answer to evolving resistance in microbial pathogens?

    Science.gov (United States)

    Dhusia, Kalyani; Bajpai, Archana; Ramteke, P W

    2018-01-10

    Comparative study of siderophore biosynthesis pathway in pathogens provides potential targets for antibiotics and host drug delivery as a part of computationally feasible microbial therapy. Iron acquisition using siderophore models is an essential and well established model in all microorganisms and microbial infections a known to cause great havoc to both plant and animal. Rapid development of antibiotic resistance in bacterial as well as fungal pathogens has drawn us at a verge where one has to get rid of the traditional way of obstructing pathogen using single or multiple antibiotic/chemical inhibitors or drugs. 'Trojan horse' strategy is an answer to this imperative call where antibiotic are by far sneaked into the pathogenic cell via the siderophore receptors at cell and outer membrane. This antibiotic once gets inside, generates a 'black hole' scenario within the opportunistic pathogens via iron scarcity. For pathogens whose siderophore are not compatible to smuggle drug due to their complex conformation and stiff valence bonds, there is another approach. By means of the siderophore biosynthesis pathways, potential targets for inhibition of these siderophores in pathogenic bacteria could be achieved and thus control pathogenic virulence. Method to design artificial exogenous siderophores for pathogens that would compete and succeed the battle of intake is also covered with this review. These manipulated siderophore would enter pathogenic cell like any other siderophore but will not disperse iron due to which iron inadequacy and hence pathogens control be accomplished. The aim of this review is to offer strategies to overcome the microbial infections/pathogens using siderophore. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Overcoming Barriers of Age to Enhance Efficacy of Cancer Immunotherapy: The Clout of the Extracellular Matrix

    Directory of Open Access Journals (Sweden)

    Mark Owyong

    2018-03-01

    Full Text Available There is a growing list of cancer immunotherapeutics approved for use in a population with an increasing number of aged individuals. Cancer immunotherapy (CIT mediates tumor destruction by activating anti-tumor immune responses that have been silenced through the oncogenic process. However, in an aging individual, immune deregulation is positively correlated with age. In this context, it is vital to examine the age-related changes in the tumor microenvironment (TME and specifically, those directly affecting critical players to ensure CIT efficacy. Effector T cells, regulatory T cells, myeloid-derived suppressor cells, tumor-associated macrophages, and tumor-associated neutrophils play important roles in promoting or inhibiting the inflammatory response, while cancer-associated fibroblasts are key mediators of the extracellular matrix (ECM. Immune checkpoint inhibitors function optimally in inflamed tumors heavily invaded by CD4 and CD8 T cells. However, immunosenescence curtails the effector T cell response within the TME and causes ECM deregulation, creating a biophysical barrier impeding both effective drug delivery and pro-inflammatory responses. The ability of the chimeric antigen receptor T (CAR-T cell to artificially induce an adaptive immune response can be modified to degrade essential components of the ECM and alleviate the age-related changes to the TME. This review will focus on the age-related alterations in ECM and immune-stroma interactions within the TME. We will discuss strategies to overcome the barriers of immunosenescence and matrix deregulation to ameliorate the efficacy of CIT in aged subjects.

  13. Tumor-specific apoptotic gene targeting overcomes radiation resistance in esophageal adenocarcinoma

    International Nuclear Information System (INIS)

    Chang, Joe Y.; Zhang Xiaochun; Komaki, Ritsuko; Cheung, Rex; Fang Bingliang

    2006-01-01

    Purpose: To overcome radiation resistance in esophageal adenocarcinoma by tumor-specific apoptotic gene targeting using tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Methods and Materials: Adenoviral vector Ad/TRAIL-F/RGD with a tumor-specific human telomerase reverse transcription promoter was used to transfer TRAIL gene to human esophageal adenocarcinoma and normal human lung fibroblastic cells (NHLF). Activation of apoptosis was analyzed by Western blot, fluorescent activated cell sorting, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate labeling (TUNEL) assay. A human esophageal adenocarcinoma mouse model was treated with intratumoral injections of Ad/TRAIL-F/RGD plus local radiotherapy. Results: The combination of Ad/TRAIL-F/RGD and radiotherapy increased the cell-killing effect in all esophageal adenocarcinoma cell lines but not in NHLF cells. This combination also significantly reduced clonogenic formation (p < 0.05) and increased sub-G1 deoxyribonucleic acid accumulation in cancer cells (p < 0.05). Activation of apoptosis by Ad/TRAIL-F/RGD plus radiotherapy was demonstrated by activation of caspase-9, caspase-8, and caspase-3 and cleaved poly (adenosine diphosphate-ribose) polymerase in vitro and TUNEL assay in vivo. Combined Ad/TRAIL-F/RGD and radiotherapy dramatically inhibited tumor growth and prolonged mean survival in the esophageal adenocarcinoma model to 31.6 days from 16.7 days for radiotherapy alone and 21.5 days for Ad/TRAIL-F/RGD alone (p < 0.05). Conclusions: The combination of tumor-specific TRAIL gene targeting and radiotherapy enhances the effect of suppressing esophageal adenocarcinoma growth and prolonging survival

  14. Overcoming Barriers in the Implementation of Environmental Remediation Projects

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-06-15

    characterization techniques and strategies; assessment of remediation technologies; techniques and strategies for post-remediation compliance monitoring; special issues such as the remediation of sites with dispersed radioactive contamination or mixed contamination by hazardous and radioactive substances, as well as monitored natural attenuation; and long term management issues at sites with residual contamination. It was noted that, although the understanding of the need to address radiological liabilities had gained considerable momentum since the end of the Cold War, in many Member States actual remediation programmes have made little progress beyond the assessment and perhaps the planning phase. This publication analyses the various drivers for remediation projects, possible obstacles and potential solutions to overcome those obstacles. It is noted that care must be taken when establishing measures that are intended to foster increased protection, for example a very prescriptive regulatory framework, as such measures may turn out to be counterproductive. The main obstacle in most cases is a lack of funding. A number of creative ways to structure projects and to identify sources of funds are discussed in this book.

  15. Overcoming Barriers in the Implementation of Environmental Remediation Projects

    International Nuclear Information System (INIS)

    2013-01-01

    characterization techniques and strategies; assessment of remediation technologies; techniques and strategies for post-remediation compliance monitoring; special issues such as the remediation of sites with dispersed radioactive contamination or mixed contamination by hazardous and radioactive substances, as well as monitored natural attenuation; and long term management issues at sites with residual contamination. It was noted that, although the understanding of the need to address radiological liabilities had gained considerable momentum since the end of the Cold War, in many Member States actual remediation programmes have made little progress beyond the assessment and perhaps the planning phase. This publication analyses the various drivers for remediation projects, possible obstacles and potential solutions to overcome those obstacles. It is noted that care must be taken when establishing measures that are intended to foster increased protection, for example a very prescriptive regulatory framework, as such measures may turn out to be counterproductive. The main obstacle in most cases is a lack of funding. A number of creative ways to structure projects and to identify sources of funds are discussed in this book.

  16. Neratinib overcomes trastuzumab resistance in HER2 amplified breast cancer.

    Science.gov (United States)

    Canonici, Alexandra; Gijsen, Merel; Mullooly, Maeve; Bennett, Ruth; Bouguern, Noujoude; Pedersen, Kasper; O'Brien, Neil A; Roxanis, Ioannis; Li, Ji-Liang; Bridge, Esther; Finn, Richard; Siamon, Dennis; McGowan, Patricia; Duffy, Michael J; O'Donovan, Norma; Crown, John; Kong, Anthony

    2013-10-01

    Trastuzumab has been shown to improve the survival outcomes of HER2 positive breast cancer patients. However, a significant proportion of HER2-positive patients are either inherently resistant or develop resistance to trastuzumab. We assessed the effects of neratinib, an irreversible panHER inhibitor, in a panel of 36 breast cancer cell lines. We further assessed its effects with or without trastuzumab in several sensitive and resistant breast cancer cells as well as a BT474 xenograft model. We confirmed that neratinib was significantly more active in HER2-amplified than HER2 non-amplified cell lines. Neratinib decreased the activation of the 4 HER receptors and inhibited downstream pathways. However, HER3 and Akt were reactivated at 24 hours, which was prevented by the combination of trastuzumab and neratinib. Neratinib also decreased pHER2 and pHER3 in acquired trastuzumab resistant cells. Neratinib in combination with trastuzumab had a greater growth inhibitory effect than either drug alone in 4 HER2 positive cell lines. Furthermore, trastuzumab in combination with neratinib was growth inhibitory in SKBR3 and BT474 cells which had acquired resistance to trastuzumab as well as in a BT474 xenograft model. Innately trastuzumab resistant cell lines showed sensitivity to neratinib, but the combination did not enhance response compared to neratinib alone. Levels of HER2 and phospho-HER2 showed a direct correlation with sensitivity to neratinib. Our data indicate that neratinib is an effective anti-HER2 therapy and counteracted both innate and acquired trastuzumab resistance in HER2 positive breast cancer. Our results suggest that combined treatment with trastuzumab and neratinib is likely to be more effective than either treatment alone for both trastuzumab-sensitive breast cancer as well as HER2-positive tumors with acquired resistance to trastuzumab.

  17. Strategies of Overcoming Acculturation Stress in Students from Different Parts of the World

    Directory of Open Access Journals (Sweden)

    E Ju Chebotareva

    2012-03-01

    Full Text Available This article describes the results of the study of strategies of acculturation stress overcoming in the students from different regions, as well as the correlations of preferring certain strategies with successful cross-cultural adaptation. It was found out that, in general, the constructive coping strategies contribute to successful adaptation, help to overcome adaptation problems and negative emotional states.

  18. Adolescents' Self-Efficacy to Overcome Barriers to Physical Activity Scale

    Science.gov (United States)

    Dwyer, John J. M.; Chulak, Tala; Maitland, Scott; Allison, Kenneth R.; Lysy, Daria C.; Faulkner, Guy E. J.; Sheeshka, Judy

    2012-01-01

    This paper describes a revised measure of self-efficacy to overcome barriers to moderate and vigorous physical activity in a sample of 484 high school students in Toronto, Ontario. The students had a mean age of 15.3 years. Principal axis factoring with oblique rotation yielded five factors: self-efficacy to overcome internal, harassment, physical…

  19. Disciplinary maintenance of process of overcoming of deformations of professional-pedagogical authentication of future teachers

    Directory of Open Access Journals (Sweden)

    Zhanna P. Pavlova

    2011-04-01

    Full Text Available In the article examined disciplinary maintenance of process of overcoming of deformations of professional-pedagogical authentication of future teachers and maintenance of process of overcoming of deformations, which is built on module principle on the basis of disciplinary connections.

  20. Overcoming the Educational Time Warp: Anticipating a Different Future

    Directory of Open Access Journals (Sweden)

    Garry Jacobs

    2015-10-01

    Full Text Available Education abridges the time required for individual and social progress by preserving and propagating the essence of human experience. It delivers to youth the accumulated knowledge of countless past generations in an organized and abridged form, so that future generations can start off with all the capacities acquired by their predecessors. However, today education confronts a serious dilemma. We are living in an educational time warp. There is a growing gap between contemporary human experience and what is taught in our educational system and that gap is widening rapidly with each passing year. Today humanity confronts challenges of unprecedented scope, magnitude and intensity. The incremental development of educational content and pedagogy in recent decades has not kept with the ever-accelerating pace of technological and social evolution. Education is also subject to a generational time warp resulting from the fact that many of today’s teachers were educated decades ago during very different times and based on different values and perspectives. The challenge of preparing youth for the future is exasperated by the fact that the future for which we are educating youth does not yet exist and to a large extent is unknown or unknowable. The resulting gap between the content of education and societal needs inhibits our capacity to anticipate and effectively respond to social problems. All these factors argue for a major reorientation of educational content and pedagogy from transmission of acquired knowledge based on past experience to development of the knowledge, skills and capacities of personality needed in a future we cannot clearly envision. We may not be able to anticipate the precise nature of the future, but we can provide an education based on the understanding that it will be very different from the present. In terms of content, the emphasis needs to shift from facts regarding the actual state of affairs in the past, present and

  1. Sustainability and energy self-sufficiency; overcoming the barriers

    Directory of Open Access Journals (Sweden)

    Rania Abdel Galil

    2015-12-01

    on the energy sustainability front (WEC, 2013. That is not to say that social barriers do not exist. They are manifested in the hindrance of knowledge transfer between social actors including misinformation, inadequate public consultation, and lack of inertia, access to relevant professional services, expertise and skills. Also, community concern over aesthetics, environmental issues and a perception of unequal distribution of benefits. However, in the MENA there is barely any awareness on the issue of energy security, equity and sustainability among individuals and the society, with lack of education and information on production and consumption, and no incentives for change. The rate of adoption, although not homogenous across the region, has been slow to date. Policy makers will not be persuaded to change, as a bottom-up approach is unlikely and the market will not develop accordingly, for lack of demand. Also, top-bottom approaches will be ineffective as the adoption of new systems are often met with resistance and the uptake will require change of entrenched practices and incentives for adoption.Challenges to the wider adoption of renewable energy lie in two areas; provision and choice. The later can be overcome by awareness campaigns, incentive-based initiatives, and involving and empowering individuals and local communities in the development of renewable energy solutions. There is an urgent need to support initiatives in the MENA region to collaborate on environmental and energy related issues, build capacities to enable civil society engagement in the context of developing and implementing national energy plans and increase awareness on the needed shift towards a sustainable energy future. Meaningful global price for carbon is but one example to provide incentives for everyone to play their role in meeting the world’s increasing energy needs whilst combating climate change and maintaining good air and water quality.  To conclude, a quote by the United

  2. Overcoming the inhibitory effect of serum on lipofection by increasing the charge ratio of cationic liposome to DNA.

    Science.gov (United States)

    Yang, J P; Huang, L

    1997-09-01

    Since cationic liposome was first developed as a lipofection reagent, a drawback has been noted in that the efficiency of lipofection decreases dramatically after addition of serum to the lipofection medium. This drawback hampers the application of cationic liposome for systematic delivery of genes. In the present studies, we found that the effect of serum on DC-chol liposome-mediated lipofection is dependent on the charge ratio of liposome to DNA. Serum inhibited lipofection activity of the lipoplex at low charge ratios, whereas it enhanced the lipofection activity at high charge ratios. This phenomenon was observed using DOTAP/DOPE but not lipofectamine. Measurement of cellular association of DNA showed that serum could reduce the binding of lipoplex to cells at all tested charge ratios, i.e. 0-10.6. Removal of negatively charged proteins from serum by DEAE Sephacel column abolished the inhibitory effect of serum on lipofection. The fraction contained only negatively charged serum proteins which strongly inhibited lipofection at low charge ratios but not at higher charge ratios. Furthermore, preincubation of serum with positively charged polylysine, which neutralized negatively charged serum proteins, eliminated the inhibitory effect of serum on lipofection. In summary, inactivation of cationic liposome by serum is due to negatively charged serum proteins and it can be overcome by increasing charge ratio of cationic liposome-DNA lipoplexes or by neutralizing the serum with polylysine.

  3. Altered Cross-Linking of HSP27 by Zerumbone as a Novel Strategy for Overcoming HSP27-Mediated Radioresistance

    International Nuclear Information System (INIS)

    Choi, Seo-Hyun; Lee, Yoon-Jin; Seo, Woo Duck; Lee, Hae-June; Nam, Joo-Won; Lee, Yoo Jin; Kim, Joon; Seo, Eun-Kyoung; Lee, Yun-Sil

    2011-01-01

    Purpose: HSP27 or HSP25 negatively regulates apoptosis pathways after radiation or chemotherapeutic agents. Abrogation of HSP27 function may be a candidate target for overcoming radio- and chemoresistance. Methods and Materials: Zerumbone (ZER), a cytotoxic component isolated from Zingiber zerumbet smith. Clonogenic survival assay and flow cytometry after Annexin V staining were performed to determine in vitro sensitization effects of ZER with ionizing radiation. A nude mouse xenografting system was also applied to detect in vivo radiosensitizing effects of ZER. Results: ZER produced cross-linking of HSP27, which was dependent on inhibition of the monomeric form of HSP27. ZER was directly inserted between the disulfide bond in the HSP27 dimer and modified normal HSP27 dimerization. Pretreatment with ZER before radiation inhibited the binding affinity between HSP27 and apoptotic molecules, such as cytochrome c and PKCδ, and induced sensitization in vitro and in an in vivo xenografted nude mouse system. Structural analogs lacking only the carbonyl group in ZER, such as α-humulene (HUM) and 8-hydroxy-humulen (8-OH-HUM), did not affect normal cross-linking of HSP27 and did not induce radiosensitization. Conclusions: We suggest that altered cross-linking of HSP27 by ZER is a good strategy for abolishing HSP27-mediated resistance.

  4. Inhibition of lactation.

    Science.gov (United States)

    Llewellyn-Jones, D

    1975-01-01

    The mechanism and hormonal regulation of lactation is explained and illustrated with a schematic representation. Circulating estrogen above a critical amount seems to be the inhibitory factor controlling lactation during pregnancy. Once delivery occurs, the level of estrogen falls, that of prolactin rises, and lactation begins. Nonsuckling can be used to inhibit lactation. Estrogens can also be used to inhibit lactation more quickly and with less pain. The reported association between estrogens and puerperal thromboembolism cannot be considered conclusive due to defects in the reporting studies. There is no reason not to use estrogens in lactation inhibition except for women over 35 who experienced a surgical delivery. Alternative therapy is available for these women. The recently-developed drug, brom-ergocryptine, may replace other methods of lactation inhibition.

  5. Targeting the Warburg effect with a novel glucose transporter inhibitor to overcome gemcitabine resistance in pancreatic cancer cells

    Science.gov (United States)

    Lai, I-Lu; Chou, Chih-Chien; Lai, Po-Ting; Fang, Chun-Sheng; Shirley, Lawrence A.; Yan, Ribai; Mo, Xiaokui; Bloomston, Mark; Kulp, Samuel K.; Bekaii-Saab, Tanios; Chen, Ching-Shih

    2014-01-01

    Gemcitabine resistance remains a significant clinical challenge. Here, we used a novel glucose transporter (Glut) inhibitor, CG-5, as a proof-of-concept compound to investigate the therapeutic utility of targeting the Warburg effect to overcome gemcitabine resistance in pancreatic cancer. The effects of gemcitabine and/or CG-5 on viability, survival, glucose uptake and DNA damage were evaluated in gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer cell lines. Mechanistic studies were conducted to determine the molecular basis of gemcitabine resistance and the mechanism of CG-5-induced sensitization to gemcitabine. The effects of CG-5 on gemcitabine sensitivity were investigated in a xenograft tumor model of gemcitabine-resistant pancreatic cancer. In contrast to gemcitabine-sensitive pancreatic cancer cells, the resistant Panc-1 and Panc-1GemR cells responded to gemcitabine by increasing the expression of ribonucleotide reductase M2 catalytic subunit (RRM2) through E2F1-mediated transcriptional activation. Acting as a pan-Glut inhibitor, CG-5 abrogated this gemcitabine-induced upregulation of RRM2 through decreased E2F1 expression, thereby enhancing gemcitabine-induced DNA damage and inhibition of cell survival. This CG-5-induced inhibition of E2F1 expression was mediated by the induction of a previously unreported E2F1-targeted microRNA, miR-520f. The addition of oral CG-5 to gemcitabine therapy caused greater suppression of Panc-1GemR xenograft tumor growth in vivo than either drug alone. Glut inhibition may be an effective strategy to enhance gemcitabine activity for the treatment of pancreatic cancer. PMID:24879635

  6. Renewable energy strategies to overcome power shortage in Kurdistan Region of Iraq

    Directory of Open Access Journals (Sweden)

    Al-Din Salar Salah Muhy

    2017-01-01

    Full Text Available The aim of this paper is to investigate the possibility of applying renewable energy strategies in Kurdistan Region of Iraq to overcome the shortage of electricity supply. Finding alternative renewable sources could overcome the problem. The renewable energy will reduce CO2 emission in the cities which considers the main source of pollution. That will participate in reducing the effect of global warming. The study tries to investigate the direct solar renewable energy through two of the main renewable energy categories to produce electricity based on a survey of literature review. Photovoltaic and wind power technologies are possible to be conducted in the region to overcome power shortage.

  7. Improved Tumor-Specific Drug Accumulation by Polymer Therapeutics with pH-Sensitive Drug Release Overcomes Chemotherapy Resistance.

    Science.gov (United States)

    Heinrich, Anne-Kathrin; Lucas, Henrike; Schindler, Lucie; Chytil, Petr; Etrych, Tomáš; Mäder, Karsten; Mueller, Thomas

    2016-05-01

    The success of chemotherapy is limited by poor selectivity of active drugs combined with occurrence of tumor resistance. New star-like structured N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based drug delivery systems containing doxorubicin attached via a pH-sensitive hydrazone bond were designed and investigated for their ability to overcome chemotherapy resistance. These conjugates combine two strategies to achieve a high drug concentration selectively at the tumor site: (I) high accumulation by passive tumor targeting based on enhanced permeability and retention effect and (II) pH-sensitive site-specific drug release due to an acidic tumor microenvironment. Mice bearing doxorubicin-resistant xenograft tumors were treated with doxorubicin, PBS, poly HPMA (pHPMA) precursor or pHPMA-doxorubicin conjugate at different equivalent doses of 5 mg/kg bodyweight doxorubicin up to a 7-fold total dose using different treatment schedules. Intratumoral drug accumulation was analyzed by fluorescence imaging utilizing intrinsic fluorescence of doxorubicin. Free doxorubicin induced significant toxicity but hardly any tumor-inhibiting effects. Administering at least a 3-fold dose of pHPMA-doxorubicin conjugate was necessary to induce a transient response, whereas doses of about 5- to 6-fold induced strong regressions. Tumors completely disappeared in some cases. The onset of response was differential delayed depending on the tumor model, which could be ascribed to distinct characteristics of the microenvironment. Further fluorescence imaging-based analyses regarding underlying mechanisms of the delayed response revealed a related switch to a more supporting intratumoral microenvironment for effective drug release. In conclusion, the current study demonstrates that the concept of tumor site-restricted high-dose chemotherapy is able to overcome therapy resistance. Mol Cancer Ther; 15(5); 998-1007. ©2016 AACR. ©2016 American Association for Cancer Research.

  8. Overcoming barriers to ITS : lessons from other technologies : final task E report

    Science.gov (United States)

    1995-12-01

    The Task E report involves an analysis of franchises and license agreements for the provision of public services, which is the fourth in a series in the study. Overcoming Barriers to ITS - Lessons from Other Technologies. This report follows alternat...

  9. Prioritising the implementation of practices to overcome operational barriers in reverse logistics

    Directory of Open Access Journals (Sweden)

    Amanda Badenhorst

    2016-09-01

    Conclusion: The framework developed in this article will enable organisations to identify the operational barriers they experience in reverse logistics and the practices they can implement on a priority basis to overcome these barriers.

  10. Identifying and Overcoming Barriers to Diabetes Management in the Elderly: An Intervention Study

    National Research Council Canada - National Science Library

    Munshi, Medha

    2008-01-01

    .... The interventions are now being implemented with help of a geriatric life specialist (GLS). Intervention by GDT includes focused strategies to overcome barriers in the areas of clinical care, education, social environment, and finances...

  11. Overcoming Resistance to Change: An Analysis to the Department of Defense's Anthrax Vaccine Immunization Program

    National Research Council Canada - National Science Library

    Johnson, Irene

    2004-01-01

    The goal of this research was to investigate the impact of change on organizations, in the absence of a preparedness program and to develop strategies for overcoming resistance to change, in the midst...

  12. Aspirin regulation of c-myc and cyclinD1 proteins to overcome tamoxifen resistance in estrogen receptor-positive breast cancer cells.

    Science.gov (United States)

    Cheng, Ran; Liu, Ya-Jing; Cui, Jun-Wei; Yang, Man; Liu, Xiao-Ling; Li, Peng; Wang, Zhan; Zhu, Li-Zhang; Lu, Si-Yi; Zou, Li; Wu, Xiao-Qin; Li, Yu-Xia; Zhou, You; Fang, Zheng-Yu; Wei, Wei

    2017-05-02

    Tamoxifen is still the most commonly used endocrine therapy drug for estrogen receptor (ER)-positive breast cancer patients and has an excellent outcome, but tamoxifen resistance remains a great impediment to successful treatment. Recent studies have prompted an anti-tumor effect of aspirin. Here, we demonstrated that aspirin not only inhibits the growth of ER-positive breast cancer cell line MCF-7, especially when combined with tamoxifen, but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Aspirin combined with tamoxifen can down regulate cyclinD1 and block cell cycle in G0/G1 phase. Besides, tamoxifen alone represses c-myc, progesterone receptor (PR) and cyclinD1 in MCF-7 cell line but not in MCF-7/TAM, while aspirin combined with tamoxifen can inhibit the expression of these proteins in the resistant cell line. When knocking down c-myc in MCF-7/TAM, cells become more sensitive to tamoxifen, cell cycle is blocked as well, indicating that aspirin can regulate c-myc and cyclinD1 proteins to overcome tamoxifen resistance. Our study discovered a novel role of aspirin based on its anti-tumor effect, and put forward some kinds of possible mechanisms of tamoxifen resistance in ER-positive breast cancer cells, providing a new strategy for the treatment of ER-positive breast carcinoma.

  13. Separating intentional inhibition of prepotent responses and resistance to proactive interference in alcohol-dependent individuals.

    Science.gov (United States)

    Noël, Xavier; Van der Linden, Martial; Brevers, Damien; Campanella, Salvatore; Verbanck, Paul; Hanak, Catherine; Kornreich, Charles; Verbruggen, Frederick

    2013-03-01

    Impulsivity is a hallmark of addictive behaviors. Addicts' weakened inhibition of irrelevant prepotent responses is commonly thought to explain this association. However, inhibition is not a unitary mechanism. This study investigated the efficiency of overcoming competition due to irrelevant responses (i.e., inhibition of a prepotent response) and overcoming competition in memory (i.e., resistance to proactive interference) in sober and recently detoxified alcohol-dependent individuals. Three cognitive tasks assessing the inhibition of a prepotent response (Hayling task, anti-saccade task and Stroop task) and two tasks tapping into the capacity to resist proactive interference (cued recall, Brown-Peterson variant) were administered to 30 non-amnesic recently detoxified alcohol-dependent individuals and 30 matched healthy participants without alcohol dependency. In addition, possible confounds such as verbal updating in working memory was assessed. Alcohol-dependent subjects performed worse than healthy participants on the three cognitive tasks assessing the inhibition of irrelevant prepotent responses but group performance was similar in the tasks assessing overcoming proactive interference in memory, updating of working memory and abstract reasoning. These findings suggest that alcohol-dependence is mainly associated with impaired capacity to intentionally suppress irrelevant prepotent response information. Control of proactive interference from memory is preserved. Theoretical and clinical implications are discussed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Enzyme inhibition by iminosugars

    DEFF Research Database (Denmark)

    López, Óscar; Qing, Feng-Ling; Pedersen, Christian Marcus

    2013-01-01

    Imino- and azasugar glycosidase inhibitors display pH dependant inhibition reflecting that both the inhibitor and the enzyme active site have groups that change protonation state with pH. With the enzyme having two acidic groups and the inhibitor one basic group, enzyme-inhibitor complexes...

  15. Quorum sensing inhibition

    DEFF Research Database (Denmark)

    Persson, T.; Givskov, Michael Christian; Nielsen, J.

    2005-01-01

    /receptor transcriptional regulator in some clinically relevant Gram-negative bacteria. The present review contains all reported compound types that are currently known to inhibit the QS transcriptional regulator in Gram-negative bacteria. These compounds are sub-divided into two main groups, one comprising structural...

  16. Cooperation for Better Inhibiting.

    Science.gov (United States)

    Novoa, Eva Maria; Ribas de Pouplana, Lluís

    2015-06-18

    Cladosporin is an antimalarial drug that acts as an ATP-mimetic to selectively inhibit Plasmodium lysyl-tRNA synthetase. Using multiple crystal structures, Fang et al. (2015) reveal in this issue of Chemistry & Biology the fascinating mechanism responsible for cladosporin selectivity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Myelin-induced inhibition in a spiral ganglion organ culture - Approaching a natural environment in vitro.

    Science.gov (United States)

    Kramer, Benedikt; Tropitzsch, Anke; Müller, Marcus; Löwenheim, Hubert

    2017-08-15

    The performance of a cochlear implant depends on the defined interaction between afferent neurons of the spiral ganglion and the inserted electrode. Neurite outgrowth can be induced by neurotrophins such as brain-derived neurotrophic factor (BDNF) via tropomyosin kinase receptor B (TrkB). However, neurotrophin signaling through the p75 neurotrophin receptor (p75) inhibits neurite outgrowth in the presence of myelin. Organotypic cultures derived from postnatal (P3-5) mice were used to study myelin-induced inhibition in the cochlear spiral ganglion. Neurite outgrowth was analyzed and quantified utilizing an adapted Sholl analysis. Stimulation of neurite outgrowth was quantified after application of BDNF, the selective TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) and a selective inhibitor of the Rho-associated kinase (Y27632), which inhibits the p75 pathway. Myelin-induced inhibition was assessed by application of myelin-associated glycoprotein (MAG-Fc) to stimulate the inhibitory p75 pathway. Inhibition of neurite outgrowth was achieved by the selective TrkB inhibitor K252a. Stimulation of neurite outgrowth was observed after treatment with BDNF, 7,8 DHF and a combination of BDNF and Y27632. The 7,8-DHF-induced growth effects could be inhibited by K252a. Furthermore, inhibition of neurite outgrowth was observed after supplementation with MAG-Fc. Myelin-induced inhibition could be overcome by 7,8-DHF and the combination of BDNF and Y27632. In this study, myelin-induced inhibition of neurite outgrowth was established in a spiral ganglion model. We reveal that 7,8-DHF is a viable novel compound for the stimulation of neurite outgrowth in a myelin-induced inhibitory environment. The combination of TrkB stimulation and ROCK inhibition can be used to overcome myelin inhibition. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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  8. Overcoming Bcr-Abl T315I mutation by combination of GNF-2 and ATP competitors in an Abl-independent mechanism

    International Nuclear Information System (INIS)

    Khateb, Mamduh; Ruimi, Nili; Khamisie, Hazem; Najajreh, Yousef; Mian, Afsar; Metodieva, Anna; Ruthardt, Martin; Mahajna, Jamal

    2012-01-01

    Philadelphia positive leukemias are characterized by the presence of Bcr-Abl fusion protein which exhibits an abnormal kinase activity. Selective Abl kinase inhibitors have been successfully established for the treatment of Ph (+) leukemias. Despite high rates of clinical response, Ph (+) patients can develop resistance against these kinase inhibitors mainly due to point mutations within the Abl protein. Of special interest is the ‘gatekeeper’ T315I mutation, which confers complete resistance to Abl kinase inhibitors. Recently, GNF-2, Abl allosteric kinase inhibitor, was demonstrated to possess cellular activity against Bcr-Abl transformed cells. Similarly to Abl kinase inhibitors (AKIs), GNF-2 failed to inhibit activity of mutated Bcr-Abl carrying the T315I mutation. Ba/F3 cells harboring native or T315I mutated Bcr-Abl constructs were treated with GNF-2 and AKIs. We monitored the effect of GNF-2 with AKIs on the proliferation and clonigenicity of the different Ba/F3 cells. In addition, we monitored the auto-phosphorylation activity of Bcr-Abl and JAK2 in cells treated with GNF-2 and AKIs. In this study, we report a cooperation between AKIs and GNF-2 in inhibiting proliferation and clonigenicity of Ba/F3 cells carrying T315I mutated Bcr-Abl. Interestingly, cooperation was most evident between Dasatinib and GNF-2. Furthermore, we showed that GNF-2 was moderately active in inhibiting the activity of JAK2 kinase, and presence of AKIs augmented GNF-2 activity. Our data illustrated the ability of allosteric inhibitors such as GNF-2 to cooperate with AKIs to overcome T315I mutation by Bcr-Abl-independent mechanisms, providing a possibility of enhancing AKIs efficacy and overcoming resistance in Ph+ leukemia cells

  9. Plastics for corrosion inhibition

    CERN Document Server

    Goldade, Victor A; Makarevich, Anna V; Kestelman, Vladimir N

    2005-01-01

    The development of polymer composites containing inhibitors of metal corrosion is an important endeavour in modern materials science and technology. Corrosion inhibitors can be located in a polymer matrix in the solid, liquid or gaseous phase. This book details the thermodynamic principles for selecting these components, their compatibility and their effectiveness. The various mechanisms of metal protection – barrier, inhibiting and electromechanical – are considered, as are the conflicting requirements placed on the structure of the combined material. Two main classes of inhibited materials (structural and films/coatings) are described in detail. Examples are given of structural plastics used in friction units subjected to mechano-chemical wear and of polymer films/coatings for protecting metal objects against corrosion.

  10. Inhibiting the inevitable

    DEFF Research Database (Denmark)

    Shashoua, Yvonne

    2006-01-01

    conservation is to ‘buy time’ for the object. Inhibitive conservation of plastics involves the removal or reduction of factors causing or accelerating degradation including light, oxygen, acids, relative humidity and acidic breakdown products. Specific approaches to conservation have been developed......Once plastics objects are registered in museum collections, the institution becomes responsible for their long term preservation, until the end of their useful lifetime. Plastics appear to deteriorate faster than other materials in museum collections and have a useful lifetime between 5 and 25...... years. Preventive or inhibitive conservation involves controlling the environments in which objects are placed during storage and display, with the aim of slowing the major deterioration reactions. Once in progress, degradation of plastics cannot be stopped or reversed, so the aim of preventive...

  11. A framework to overcome barriers to green innovation in SMEs using BWM and Fuzzy TOPSIS.

    Science.gov (United States)

    Gupta, Himanshu; Barua, Mukesh Kumar

    2018-08-15

    Recent years have witnessed a significant rise in exploring the barriers which obstruct adoption of green practices by SMEs. There is a constant need to innovate in terms of products, processes, and management so that we can overcome these barriers to green practices adoption and implementation. This study employs a three-phase methodology to identify barriers and solutions to overcome these barriers to green innovation in SMEs. Through extensive literature review and the opinion of selective manager's, seven main category barriers, thirty-six sub-category barriers, and twenty solutions to overcome these barriers were identified. BWM is used to rank these barriers and Fuzzy TOPSIS is used to rank solutions to overcome these barriers. Four Indian SMEs are taken to exemplify the proposed three paged model. To check the robustness of the model, a sensitivity analysis was also performed. The results of the analysis can act as a stepping stone for SME managers to eliminate and overcome barriers to green innovation in their firm and compete healthily in the market. The paper sets a framework for future studies in this area of research-work. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Expression of rabbit IL-4 by recombinant myxoma viruses enhances virulence and overcomes genetic resistance to myxomatosis.

    Science.gov (United States)

    Kerr, P J; Perkins, H D; Inglis, B; Stagg, R; McLaughlin, E; Collins, S V; Van Leeuwen, B H

    2004-06-20

    Rabbit IL-4 was expressed in the virulent standard laboratory strain (SLS) and the attenuated Uriarra (Ur) strain of myxoma virus with the aim of creating a Th2 cytokine environment and inhibiting the development of an antiviral cell-mediated response to myxomatosis in infected rabbits. This allowed testing of a model for genetic resistance to myxomatosis in wild rabbits that have undergone 50 years of natural selection for resistance to myxomatosis. Expression of IL-4 significantly enhanced virulence of both virulent and attenuated virus strains in susceptible (laboratory) and resistant (wild) rabbits. SLS-IL-4 completely overcame genetic resistance in wild rabbits. The pathogenesis of SLS-IL-4 was compared in susceptible and resistant rabbits. The results support a model for resistance to myxomatosis of an enhanced innate immune response controlling virus replication and allowing an effective antiviral cell-mediated immune response to develop in resistant rabbits. Expression of IL-4 did not overcome immunity to myxomatosis induced by immunization.

  13. Methadone, commonly used as maintenance medication for outpatient treatment of opioid dependence, kills leukemia cells and overcomes chemoresistance.

    Science.gov (United States)

    Friesen, Claudia; Roscher, Mareike; Alt, Andreas; Miltner, Erich

    2008-08-01

    The therapeutic opioid drug methadone (d,l-methadone hydrochloride) is the most commonly used maintenance medication for outpatient treatment of opioid dependence. In our study, we found that methadone is also a potent inducer of cell death in leukemia cells and we clarified the unknown mechanism of methadone-induced cell killing in leukemia cells. Methadone inhibited proliferation in leukemia cells and induced cell death through apoptosis induction and activated apoptosis pathways through the activation of caspase-9 and caspase-3, down-regulation of Bcl-x(L) and X chromosome-linked inhibitor of apoptosis, and cleavage of poly(ADP-ribose) polymerase. In addition, methadone induced cell death not only in anticancer drug-sensitive and apoptosis-sensitive leukemia cells but also in doxorubicin-resistant, multidrug-resistant, and apoptosis-resistant leukemia cells, which anticancer drugs commonly used in conventional therapies of leukemias failed to kill. Depending on caspase activation, methadone overcomes doxorubicin resistance, multidrug resistance, and apoptosis resistance in leukemia cells through activation of mitochondria. In contrast to leukemia cells, nonleukemic peripheral blood lymphocytes survived after methadone treatment. These findings show that methadone kills leukemia cells and breaks chemoresistance and apoptosis resistance. Our results suggest that methadone is a promising therapeutic approach not only for patients with opioid dependence but also for patients with leukemias and provide the foundation for new strategies using methadone as an additional anticancer drug in leukemia therapy, especially when conventional therapies are less effective.

  14. Rationally engineered nanoparticles target multiple myeloma cells, overcome cell-adhesion-mediated drug resistance, and show enhanced efficacy in vivo

    International Nuclear Information System (INIS)

    Kiziltepe, T; Ashley, J D; Stefanick, J F; Qi, Y M; Alves, N J; Handlogten, M W; Suckow, M A; Navari, R M; Bilgicer, B

    2012-01-01

    In the continuing search for effective cancer treatments, we report the rational engineering of a multifunctional nanoparticle that combines traditional chemotherapy with cell targeting and anti-adhesion functionalities. Very late antigen-4 (VLA-4) mediated adhesion of multiple myeloma (MM) cells to bone marrow stroma confers MM cells with cell-adhesion-mediated drug resistance (CAM-DR). In our design, we used micellar nanoparticles as dynamic self-assembling scaffolds to present VLA-4-antagonist peptides and doxorubicin (Dox) conjugates, simultaneously, to selectively target MM cells and to overcome CAM-DR. Dox was conjugated to the nanoparticles through an acid-sensitive hydrazone bond. VLA-4-antagonist peptides were conjugated via a multifaceted synthetic procedure for generating precisely controlled number of targeting functionalities. The nanoparticles were efficiently internalized by MM cells and induced cytotoxicity. Mechanistic studies revealed that nanoparticles induced DNA double-strand breaks and apoptosis in MM cells. Importantly, multifunctional nanoparticles overcame CAM-DR, and were more efficacious than Dox when MM cells were cultured on fibronectin-coated plates. Finally, in a MM xenograft model, nanoparticles preferentially homed to MM tumors with ∼10 fold more drug accumulation and demonstrated dramatic tumor growth inhibition with a reduced overall systemic toxicity. Altogether, we demonstrate the disease driven engineering of a nanoparticle-based drug delivery system, enabling the model of an integrative approach in the treatment of MM

  15. Thermoresponsive Supramolecular Chemotherapy by "V"-Shaped Armed β-Cyclodextrin Star Polymer to Overcome Drug Resistance.

    Science.gov (United States)

    Fan, Xiaoshan; Cheng, Hongwei; Wang, Xiaoyuan; Ye, Enyi; Loh, Xian Jun; Wu, Yun-Long; Li, Zibiao

    2018-04-01

    Pump mediated drug efflux is the key reason to result in the failure of chemotherapy. Herein, a novel star polymer β-CD-v-(PEG-β-PNIPAAm) 7 consisting of a β-CD core, grafted with thermo-responsive poly(N-isopropylacrylamide) (PNIPAAm) and biocompatible poly(ethylene glycol) (PEG) in the multiple "V"-shaped arms is designed and further fabricated into supramolecular nanocarriers for drug resistant cancer therapy. The star polymer could encapsulate chemotherapeutics between β-cyclodextrin and anti-cancer drug via inclusion complex (IC). Furthermore, the temperature induced chain association of PNIPAAm segments facilitated the IC to form supramolecular nanoparticles at 37 °C, whereas the presence of PEG impart great stability to the self-assemblies. When incubated with MDR-1 membrane pump regulated drug resistant tumor cells, much higher and faster cellular uptake of the supramolecular nanoparticles were detected, and the enhanced intracellular retention of drugs could lead to significant inhibition of cell growth. Further in vivo evaluation showed high therapeutic efficacy in suppressing drug resistant tumor growth without a significant impact on the normal functions of main organs. This work signifies thermo-responsive supramolecular chemotherapy is promising in combating pump mediated drug resistance in both in vitro and in vivo models, which may be encouraging for the advanced drug delivery platform design to overcome drug resistant cancer. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. A Study on Overcoming Misconceptions of 6th Graders About Equations

    Directory of Open Access Journals (Sweden)

    Gözde AKYÜZ

    2014-01-01

    Full Text Available The aim of this study is to determine and overcome misconceptions of 6th graders about first degree equations with one unknown. The study has a mixed research design and was conducted with 25 sixth graders in a public school during the spring semester of the 2011-2012 academic year. Data were collected through a test of 20 open-ended items developed by the researcher. The misconceptions were detected through descriptive analysis of the test. Then, students were being taught based on activity-based instructional methods for eight hours. The test was also given at the end of the instruction as a post-test to examine the effectiveness of the activity-based instruction with overcoming their misconceptions. Data were analyzed by paired samples t test through SPSS 16.0. Findings indicated that activity-based instruction was effective in overcoming students’ misconceptions.

  17. Overcoming Pedagogical, Social/Cultural, and Attitudinal Barriers to Technology Integration in K-5 Schools

    Science.gov (United States)

    Durff, Lisa

    2017-01-01

    Technology engages and increases academic achievement for K-5 students, but teachers face attitudinal, social/cultural, and pedagogical barriers when they integrate technology for student learning. Although some teachers overcome these barriers, it remains unclear how they do so. The purpose of this qualitative multiple case study was to analyze…

  18. Problem Solving Instruction for Overcoming Students' Difficulties in Stoichiometric Problems

    Science.gov (United States)

    Shadreck, Mandina; Enunuwe, Ochonogor Chukunoye

    2017-01-01

    The study sought to find out difficulties encountered by high school chemistry students when solving stoichiometric problems and how these could be overcome by using a problem-solving approach. The study adopted a quasi-experimental design. 485 participants drawn from 8 highs schools in a local education district in Zimbabwe participated in the…

  19. Modelling Difficulties and Their Overcoming Strategies in the Solution of a Modelling Problem

    Science.gov (United States)

    Dede, Ayse Tekin

    2016-01-01

    The purpose of the study is to reveal the elementary mathematics student teachers' difficulties encountered in the solution of a modelling problem, the strategies to overcome those difficulties and whether the strategies worked or not. Nineteen student teachers solved the modelling problem in their four or five-person groups, and the video records…

  20. Using Ontological Engineering to Overcome AI-ED Problems: Contribution, Impact and Perspectives

    Science.gov (United States)

    Mizoguchi, Riichiro; Bourdeau, Jacqueline

    2016-01-01

    This article reflects on the ontology engineering methodology discussed by the paper entitled "Using Ontological Engineering to Overcome AI-ED Problems" published in this journal in 2000. We discuss the achievements obtained in the last 10 years, the impact of our work as well as recent trends and perspectives in ontology engineering for…

  1. Building America Guidance for Identifying and Overcoming Code, Standard, and Rating Method Barriers

    Energy Technology Data Exchange (ETDEWEB)

    Cole, P. C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Halverson, M. A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2013-09-01

    This guidance document was prepared using the input from the meeting summarized in the draft CSI Roadmap to provide Building America research teams and partners with specific information and approaches to identifying and overcoming potential barriers to Building America innovations arising in and/or stemming from codes, standards, and rating methods.

  2. Qualitative Examination of Strategies to Overcome Resistance to Change in Lean Manufacturing

    Science.gov (United States)

    Burmester, Elizabeth

    2017-01-01

    Approximately 80% of lean manufacturing program initiatives are abandoned in the first year of implementation. Only 2% of organizations that embark on the lean journey complete it with the results and the sustainability they expected. There is a gap in past research regarding, the leadership strategies organizations can use to overcome resistance…

  3. Effectiveness of Targeted Musical Therapy on Sleep Quality and Overcoming Insomnia in Seniors

    Directory of Open Access Journals (Sweden)

    Reza Mottaghi

    2016-07-01

    Conclusion: The present study showed that targeted music therapy can lead to the improvement in the overall sleep quality, daily functioning, and subjective sleep quality thereby resulting in a sharp decline in the number of sleep drugs in seniors with primary insomnia disorder. Therefore, it is highly recommended by the music therapy and mental health experts for overcoming the sleep problems in older adults.

  4. Dental Hygiene Entry-Level Program Administrators' Strategies for Overcoming Challenges of Distance Education

    Science.gov (United States)

    Buchanan, Bette A.

    2009-01-01

    The use of distance education by entry-level dental hygiene programs is increasing. The focus of this study was to determine the number of entry-level dental hygiene program administrators with experience developing and/or maintaining dental hygiene education by distance, the challenges encountered, and the strategies used to overcome the…

  5. Comments by ABCT's first female president on overcoming the glass ceiling.

    Science.gov (United States)

    Nelson-Gray, Rosemery O

    2012-12-01

    At the annual convention of the Association for Behavioral and Cognitive Therapies in New York City in November 2009, a most interesting panel discussion occurred: Overcoming the Glass Ceiling: A Conversation With the Trailblazers. This article is a written version of my oral presentation at this panel discussion in my role as ABCT's first female president. Copyright © 2012. Published by Elsevier Ltd.

  6. The use of ion beam to overcome interspecific hybrid inviability in plants

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Masayoshi [Kyoto Prefectural Univ. (Japan); Watanabe, Hiroshi

    1997-03-01

    In order to overcome sexual incompatibility between distantly related species in Nicotiana, the crosses with {sup 4}He{sup 2+} beam-irradiated pollen were carried out, and survival hybrids were obtained. They were resistant to tobacco mosaic virus and green peach aphid. (author)

  7. Overcoming Uncertainty: Agency, Stance and the Rise of Collective Action in Times of Crisis

    NARCIS (Netherlands)

    Heidemann, Kai

    2017-01-01

    How do people exert their agency in the face of large-scale societal crises? Merging strands of sociolinguistic scholarship with social movement theory, this article offers a way of looking at how grassroots actors work to overcome dramatic episodes of macro-structural instability and uncertainty

  8. The small and rural academic library leveraging resources and overcoming limitations

    CERN Document Server

    Davis Kendrick, Kaetrena

    2016-01-01

    Through the use of case studies, research, and practical interviews, The Small or Rural Academic Library: Leveraging Resources and Overcoming Limitations explores how academic librarians in such environments can keep pace with, create, and improve modern library practices and services, network with colleagues, and access continuing education and professional development opportunities.

  9. BioTwist : overcoming severe distortions in ridge-based biometrics for succesful identification

    NARCIS (Netherlands)

    Kotzerke, J.

    2016-01-01

    This thesis focuses on ridge-based and highly distorted biometrics, the different chal-lenges involved in a verification of identity scenario, and how to overcome them. More specifically, we work on ridge-based biometrics in two different contexts: (i) newborn and infant biometrics and (ii) quality

  10. Using Appropriate Digital Tools to Overcome Barriers to Collaborative Learning in Classrooms

    Science.gov (United States)

    Wardlow, Liane; Harm, Eian

    2015-01-01

    Collaborative learning provides students with vital opportunities to create and build knowledge. Existing technologies can facilitate collaborative learning. However, barriers exist to enacting collaborative practices related to the coverage of material for assessments and classroom management concerns, among others. Teachers can overcome these…

  11. Developing Cultural Competence and Overcoming Ethical Challenges in the Informed Consent Process: An Experience from Egypt

    Science.gov (United States)

    Abdel-Messih, Ibrahim Adib; El-Setouhy, Maged; Crouch, Michael M.; Earhart, Kenneth C.

    2008-01-01

    Research is conducted in a variety of cultural settings. Ethical standards developed in Europe and the Americas are increasingly applied in these settings, many of which are culturally different from the countries in which these standards originated. To overcome these cultural differences, investigators may be tempted to deviate from ethical…

  12. Empowering breeding programs with new approaches to overcome constraints for selecting superior quality traits of rice

    NARCIS (Netherlands)

    Calingacion, M.N.

    2015-01-01

    Empowering breeding programs with new approaches to overcome constraints for selecting superior quality traits of rice

    Mariafe N. Calingacion

    Most rice breeding programs have focused on improving agronomic traits such as yield, while enhancing grain quality traits

  13. Cherokee Adaptation to the Landscape of the West and Overcoming the Loss of Culturally Significant Plants

    Science.gov (United States)

    Vick, R. Alfred

    2011-01-01

    Plant species utilized by Cherokees have been documented by several authors. However, many of the traditional uses of plants were lost or forgotten in the generations following the Trail of Tears. The pressures of overcoming the physical and psychological impact of the removal, adapting to a new landscape, rebuilding a government, rebuilding…

  14. EXTERNAL BORROWING – A SOLUTION IN OVERCOMING THE CURRENT ECONOMIC CRISIS?

    Directory of Open Access Journals (Sweden)

    Maria Pascal (căs. Andriescu

    2010-06-01

    Full Text Available The government decisions to call, in recent years, more and more reimbursable financing gave birth to fierce reactions among politicians and economy specialists. The present article aims to analyze how the external borrowing may be a solution to overcome the difficult situation where we are.

  15. Analyzing pictorial artifacts from psychotherapy and art therapy when overcoming stress and trauma

    DEFF Research Database (Denmark)

    Gerge, Anna; Pedersen, Inge Nygaard

    2017-01-01

    Abstract This process based article tries to zoom into the need for assessment tools from a wider perspective to come to a preliminary understanding of what to analyze in relation to overcome traumatization and dissociation. The article wants to discuss and build understanding on what we ought...

  16. Development of active guidance systems to overcome problems of disorientation and low visibility following severe explosions.

    CSIR Research Space (South Africa)

    Phillips, HR

    1995-01-01

    Full Text Available The objective of this research project was to review methods of overcoming the disorientation of underground mine workers following an explosion or severe fire. The results of this project indicate that different strategies may be required for fires...

  17. Musics of "The Other": Creating Musical Identities and Overcoming Cultural Boundaries in Australian Music Education

    Science.gov (United States)

    Cain, Melissa

    2015-01-01

    The binary opposition between "own music" and "other's music" is the "result of deep conditioning" (Drummond, 2010, p. 118) and is almost impossible to overcome. By exploring the underlying constructs that influence students' and teachers' perceptions of minority cultures and their musics, this paper explores the…

  18. Explaining the Effects of Narrative in an Entertainment Television Program: Overcoming Resistance to Persuasion

    Science.gov (United States)

    Moyer-Guse, Emily; Nabi, Robin L.

    2010-01-01

    Research has examined the ability of entertainment-education (E-E) programs to influence behavior across a variety of health and social issues. However, less is known about the underlying mechanisms that account for these effects. In keeping with the extended elaboration likelihood model (E-ELM) and the entertainment overcoming resistance model…

  19. Show small close comfort and listen - How to overcome barriers in the use of social media

    NARCIS (Netherlands)

    Verjans, Steven

    2011-01-01

    Verjans, S. (2011, 23 November). Show small close comfort and listen - How to overcome barriers in the use of social media. Presentation at the SVEA Final Conference "Next Generation Learning - How to Integrate Social Media in Vocational and Adult Training", Brussels, Belgium.

  20. Math Is Like a Scary Movie? Helping Young People Overcome Math Anxiety

    Science.gov (United States)

    Kulkin, Margaret

    2016-01-01

    Afterschool teachers who tutor students or provide homework help have a unique opportunity to help students overcome the social or emotional barriers that so often block learning. They can embrace a creative and investigative approach to math learning. Margaret Kulkin's interest in being a math attitude "myth-buster" led her to apply to…

  1. Agora: A proposal to overcome the limitations of the current knowledge creation process

    OpenAIRE

    ScientistFive

    2015-01-01

    Agora: A proposal to overcome the limitations of the current knowledge creation process ======================================================================================= By Scientistsfive () Abstract: The knowledge creation process is broken and can be improved by a combination of currently emerging tools. The rationale for this proposal is the notion that the current scientific process is not optimal: * Artificially staged competitions (g...

  2. The Evaluation of Techniques for Overcoming with the Stress in a Physician Group

    Directory of Open Access Journals (Sweden)

    Humman Sen

    2012-04-01

    Full Text Available Objective: This study was made in order to determine the methods of overcoming with stress of the specialist physicians. Material-Method: Our study is a descriptive study. In the study, the scale of overcoming with stress was applied to the 100 specialist physicians who working in 5 different health care institutions in and around the Istanbul in 2009. Results: The scores that the participants takes from sub-categories of scales of overcoming with stress types were measured respectively as; 22.4±3.5 point for self-confident approach, 16.3± 3.6 point for helpless, 14.4± 2.6 point for optimistic, 10.8±2.6 point for submissive, 9.9±2.1 point for seeking social support. It is determined that the self-confident approach method was the most used method among the participants in methods of overcoming with stres. It is determined that the submissive method was the least used method. No statistical significant differences were determined between the men and women, marrieds and singles, subgroup and total score, categories composed according to the age range and institutons. (p>0.05 [TAF Prev Med Bull 2012; 11(2.000: 211-218

  3. Screening of plant extracts for human tyrosinase inhibiting effects.

    Science.gov (United States)

    Kim, M; Park, J; Song, K; Kim, H G; Koh, J-S; Boo, Y C

    2012-04-01

    Screening for tyrosinase (TYR) inhibitors potentially useful for control of skin pigmentation has been hampered by the limited availability of human TYR. To overcome this hurdle, we have established human embryonic kidney (HEK293)-TYR cells that constitutively express human TYR. In the current study, we assayed human TYR inhibition activities of 50 plant extracts using the lysates of transformed HEK293-TYR cells. The strongest inhibition of human TYR was shown by the extract of Vaccinium bracteatum Thunberg, followed by the extract of Morus bombycis Koidzumi. The former extract did not inhibit mushroom TYR activity whereas significant inhibition was observed with the latter extract, demonstrating the importance of using human TYR in the screening for human TYR inhibitors. Upon liquid-liquid partitioning of the extract from V. bracteatum, the active constituents were enriched in the ethyl acetate fraction, and the subsequent preparatory thin-layer chromatography identified p-coumaric acid (PCA) as the main active constituent. The hypo-pigmentation of PCA was verified in the MelanoDerm™ Skin Model. This study demonstrates that transformed HEK293-TYR cells could expedite the discovery of human TYR-specific inhibitors from natural sources which might be useful in the control of skin pigmentation. © 2012 The Authors. ICS © 2012 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  4. Anxiety and retrieval inhibition: support for an enhanced inhibition account.

    Science.gov (United States)

    Nuñez, Mia; Gregory, Josh; Zinbarg, Richard E

    2017-02-01

    Retrieval inhibition of negative associations is important for exposure therapy for anxiety, but the relationship between memory inhibition and anxiety is not well understood-anxiety could either be associated with enhanced or deficient inhibition. The present study tested these two competing hypotheses by measuring retrieval inhibition of negative stimuli by related neutral stimuli. Non-clinically anxious undergraduates completed measures of trait and state anxiety and completed a retrieval induced forgetting task. Adaptive forgetting varied with state anxiety. Low levels of state anxiety were associated with no evidence for retrieval inhibition for either threatening or non-threatening categories. Participants in the middle tertile of state anxiety scores exhibited retrieval inhibition for non-threatening categories but not for threatening categories. Participants in the highest tertile of state anxiety, however, exhibited retrieval inhibition for both threatening and non-threatening categories with the magnitude of retrieval inhibition being greater for threatening than non-threatening categories. The data are in line with the avoidance aspect of the vigilance-avoidance theory of anxiety and inhibition. Implications for cognitive behavioural therapy practices are discussed.

  5. Regorafenib overcomes chemotherapeutic multidrug resistance mediated by ABCB1 transporter in colorectal cancer: In vitro and in vivo study.

    Science.gov (United States)

    Wang, Yi-Jun; Zhang, Yun-Kai; Zhang, Guan-Nan; Al Rihani, Sweilem B; Wei, Meng-Ning; Gupta, Pranav; Zhang, Xiao-Yu; Shukla, Suneet; Ambudkar, Suresh V; Kaddoumi, Amal; Shi, Zhi; Chen, Zhe-Sheng

    2017-06-28

    Chemotherapeutic multidrug resistance (MDR) is a significant challenge to overcome in clinic practice. Several mechanisms contribute to MDR, one of which is the augmented drug efflux induced by the upregulation of ABCB1 in cancer cells. Regorafenib, a multikinase inhibitor targeting the RAS/RAF/MEK/ERK pathway, was approved by the FDA to treat metastatic colorectal cancer and gastrointestinal stromal tumors. We investigated whether and how regorafenib overcame MDR mediated by ABCB1. The results showed that regorafenib reversed the ABCB1-mediated MDR and increased the accumulation of [ 3 H]-paclitaxel in ABCB1-overexpressing cells by suppressing efflux activity of ABCB1, but not altering expression level and localization of ABCB1. Regorafenib inhibited ATPase activity of ABCB1. In mice bearing resistant colorectal tumors, regorafenib raised the intratumoral concentration of paclitaxel and suppressed the growth of resistant colorectal tumors. But regorafenib did not induce cardiotoxicity/myelosuppression of paclitaxel in mice. Strategy to reposition one FDA-approved anticancer drug regorafenib to overcome the resistance of another FDA-approved, widely used chemotherapeutic paclitaxel, may be a promising direction for the field of adjuvant chemotherapy. This study provides clinical rationale for combination of conventional chemotherapy and targeted anticancer agents. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Inhibition of polyphenoloxidase by sulfite

    International Nuclear Information System (INIS)

    Sayavedra-Soto, L.A.; Montgomery, M.W.

    1986-01-01

    When polyphenoloxidase (PPO) was exposed to sulfite prior to substrate addition, inhibition was irreversible. Trials to regenerate PPO activity, using extensive dialysis, column chromatography, and addition of copper salts were not successful. Increased concentrations of sulfite and pH levels less than 5 enhanced the inhibition of PPO by sulfite. At pH 4, concentrations greater than 0.04 mg/mL completely inhibited 1000 units of PPO activity almost instantaneously. This suggested that the HSO 3 - molecule was the main component in the sulfite system inhibiting PPO. Column chromatography, extensive dialysis, and gel electrophoresis did not demonstrate 35 SO 2 bound to purified pear PPO protein. Formation of extra protein bands of sulfite inhibited purified pear PPO fractions on gel electrophoresis was demonstrated. This and other evidence suggested that the major mode of direct irreversible inhibition of PPO was modification of the protein structure, with retention of its molecular unity

  7. A study and meta-analysis of lay attributions of cures for overcoming specific psychological problems.

    Science.gov (United States)

    Furnham, A; Hayward, R

    1997-09-01

    Lay beliefs about the importance of 24 different contributors to overcoming 4 disorders that constitute primarily cognitive deficits were studied. A meta-analysis of previous programmatic studies in the area was performed so that 22 different psychological problems could be compared. In the present study, 107 participants completed a questionnaire indicating how effective 24 factors were in overcoming 4 specific problems: dyslexia, fear of flying, amnesia, and learning difficulties. Factor analysis revealed almost identical clusters (inner control, social consequences, understanding, receiving help, and fate) for each problem. The perceived relevance of those factors differed significantly between problems. Some individual difference factors (sex and religion) were found to predict certain factor attributions for specific disorders. A meta-analysis of the 5 studies in this series yielded a 6-factor structure comparable to those of the individual studies and provided results indicating the benefits and limitations of this kind of investigation. The clinical relevance of studying attributions for cure is considered.

  8. Scientific provision of the problems of overcoming the Chernobyl catastrophe consequences. Chapter 7

    International Nuclear Information System (INIS)

    Konoplya, E.F.; Rolevich, I.V.; Gurachevskij, V.L.; Poplyko, I.Ya.; Semeshko, A.V.

    1998-01-01

    At present in the Republic of Belarus the research works on the problems of overcoming of the Chernobyl accident consequences are carried out in the following directions: radiation protection of the population; health of the population affected by the Chernobyl NPP accident; complex radiation-ecological estimation of the environment and conditions of the life activity of the population; rehabilitation of the contaminated territories; instrumental and methodical provision of the radiation control. The experience of the scientific approach to the decision of wide-scale and multiple-discipline tasks of overcoming of the Chernobyl accident consequences promotes for transformation of separate knowledge about radiation safety in holistic conception of safety and protection of the population in emergency caused by industrial accidents, catastrophes, natural disasters

  9. Devices for overcoming biological barriers: the use of physical forces to disrupt the barriers.

    Science.gov (United States)

    Mitragotri, Samir

    2013-01-01

    Overcoming biological barriers including skin, mucosal membranes, blood brain barrier as well as cell and nuclear membrane constitutes a key hurdle in the field of drug delivery. While these barriers serve the natural protective function in the body, they limit delivery of drugs into the body. A variety of methods have been developed to overcome these barriers including formulations, targeting peptides and device-based technologies. This review focuses on the use of physical methods including acoustic devices, electric devices, high-pressure devices, microneedles and optical devices for disrupting various barriers in the body including skin and other membranes. A summary of the working principles of these devices and their ability to enhance drug delivery is presented. Copyright © 2012. Published by Elsevier B.V.

  10. Overcoming resistance to culture change: nursing home administrators' use of education, training, and communication.

    Science.gov (United States)

    Tyler, Denise A; Lepore, Michael; Shield, Renee R; Looze, Jessica; Miller, Susan C

    2014-01-01

    Nursing home culture change is becoming more prevalent, and research has demonstrated its benefits for nursing home residents and staff-but little is known about the role of nursing home administrators in culture change implementation. The purpose of this study was to determine what barriers nursing home administrators face in implementing culture change practices, and to identify the strategies used to overcome them. The authors conducted in-depth individual interviews with 64 administrators identified through a nationally representative survey. Results showed that a key barrier to culture change implementation reported by administrators was staff, resident, and family member resistance to change. Most nursing home administrators stressed the importance of using communication, education and training to overcome this resistance. Themes emerging around the concepts of communication and education indicate that these efforts should be ongoing, communication should be reciprocal, and that all stakeholders should be included.

  11. Rapid Co-optimization of Processing and Circuit Design to Overcome Carbon Nanotube Variations

    OpenAIRE

    Hills, Gage; Zhang, Jie; Shulaker, Max Marcel; Wei, Hai; Lee, Chi-Shuen; Balasingam, Arjun; Wong, H. -S. Philip; Mitra, Subhasish

    2015-01-01

    Carbon nanotube field-effect transistors (CNFETs) are promising candidates for building energy-efficient digital systems at highly-scaled technology nodes. However, carbon nanotubes (CNTs) are inherently subject to variations that reduce circuit yield, increase susceptibility to noise, and severely degrade their anticipated energy and speed benefits. Joint exploration and optimization of CNT processing options and CNFET circuit design are required to overcome this outstanding challenge. Unfor...

  12. Overcoming the species hybridization barrier by ploidy manipulation in the genus Oryza.

    Science.gov (United States)

    Tonosaki, Kaoru; Sekine, Daisuke; Ohnishi, Takayuki; Ono, Akemi; Furuumi, Hiroyasu; Kurata, Nori; Kinoshita, Tetsu

    2018-02-01

    In most eudicot and monocot species, interspecific and interploidy crosses generally display abnormalities in the endosperm that are the major cause of a post-zygotic hybridization barrier. In some eudicot species, however, this type of hybridization barrier can be overcome by the manipulation of ploidy levels of one parental species, suggesting that the molecular mechanisms underlying the species hybridization barrier can be circumvented by genome dosage. We previously demonstrated that endosperm barriers in interspecific and interploidy crosses in the genus Oryza involve overlapping but different mechanisms. This result contrasts with those in the genus Arabidopsis, which shows similar outcomes in both interploidy and interspecific crosses. Therefore, we postulated that an exploration of pathways for overcoming the species hybridization barrier in Oryza endosperm, by manipulating the ploidy levels in one parental species, might provide novel insights into molecular mechanisms. We showed that fertile hybrid seeds could be produced by an interspecific cross of female tetraploid Oryza sativa and male diploid Oryza longistaminata. Although the rate of nuclear divisions did not return to normal levels in the hybrid endosperm, the timing of cellularization, nucellus degeneration and the accumulation of storage products were close to normal levels. In addition, the expression patterns of the imprinted gene MADS87 and YUCCA11 were changed when the species barrier was overcome. These results suggest that the regulatory machinery for developmental transitions and imprinted gene expression are likely to play a central role in overcoming species hybridization barriers by genome dosage in the genus Oryza. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  13. Measuring women's perceived ability to overcome barriers to healthcare seeking in Burkina Faso

    Directory of Open Access Journals (Sweden)

    Nikiema Béatrice

    2012-02-01

    Full Text Available Abstract Background In sub-Saharan Africa, women must overcome numerous barriers when they need modern healthcare. Respect of gender norms within the household and the community may still influence women's ability to obtain care. A lack of gender-sensitive instruments for measuring women's ability to overcome barriers compromises attempts to adequately quantify the burden and risk of exclusion they face when seeking modern healthcare. The aim of this study was to create and validate a synthetic measure of women's access to healthcare from a publicly available and possibly internationally comparable population-based survey. Method Seven questionnaire items from the Burkina Faso 2003 DHS were combined to create the index. Cronbach's alpha coefficient was used to test the reliability of the index. Exploratory factor analyses (EFA and confirmatory factor analyses (CFA were applied to evaluate the factorial structure and construct validity of the index while taking into account the hierarchical structure of the data. Results The index has a Cronbach's alpha of 0.75, suggesting adequate reliability. In EFA, three correlated factors fitted the data best. In CFA, the construct of perceived ability to overcome barriers to healthcare seeking emerged as a second-order latent variable with three domains: socioeconomic barriers, geographical barriers and psychosocial barriers. Model fit indices support the index's global validity for women of reproductive age in Burkina Faso. Evidence for construct validity comes from the finding that women's index scores increase with household living standard. Conclusion The DHS items can be combined into a reliable and valid, gender-sensitive index quantifying reproductive-age women's perceived ability to overcome barriers to healthcare seeking in Burkina Faso. The index complies conceptually with the sector-cross-cutting capability approach and enables measuring directly the perceived access to healthcare. Therefore it

  14. Spiritual values of heads of general education institutions as a factor of professional crises’ overcoming

    Directory of Open Access Journals (Sweden)

    Алла Степанівна Москальова

    2015-12-01

    Full Text Available The article is devoted to the important problem of psychology – the research of the spiritual values of heads of general education institutions. The content and indicators of development of spiritual values of managers are determined. The results of empirical research levels of spiritual values of managers are presented. It has been proved correlation between the levels of development of spiritual values of heads of general education institutions and their ability to overcome professional crises

  15. Life after abuse : an exploration of women's strategies for overcoming abuse

    OpenAIRE

    2012-01-01

    D.Litt et Phil. The study explored strategies abused women use to overcome power and control in their intimate relationships, using their own self-agency. Data was collected through the technique of triangulation in which three women who were legally divorced, wrote their own stories, after which each was individually interviewed by the researcher to get information about the process of leaving and staying away from their abusive relationships, and clearing up and moving on with their live...

  16. Different sterilization methods for overcoming internal bacterial infection in sunflower seeds

    Directory of Open Access Journals (Sweden)

    Taški-Ajduković Ksenija J.

    2005-01-01

    Full Text Available During culture of protoplasts in agarose droplets, permanent problem was bacterial infection. It was assumed that the seeds are the origin of infection, so different sterilization methods were tested in order to overcome this problem. Germination, infection of seeds and hypocotyls and their growth were examined. Based on these parameters, the best result was obtained with the combined use of 5% commercial bleach and dry heating at 45°C.

  17. SELLING CANANG SARI (As an Alternative of Effort in Informal Sector to overcome household economics problem

    Directory of Open Access Journals (Sweden)

    Desak Putu Eka Nilakusmawati

    2012-11-01

    Full Text Available Decrease in family income represent an impact of economic pressures, as an effect of economic crisis. Other side, the existing problems that extension of the job opportunity in the urban area with existence of development in the various sector do not absorb entire labour force which is progressively growing larger its amount.Economic problem force woman of lower economic class to involved take part in earning for increase family income by working beyond domestic sectors. Involvement of woman in labor market trigered by family’s economic problems, besides existence of the job opportunity factor. Alternative effort being carried out is by selling canang.Increasing of urban community activities in Denpasar City makes them have no time to make banten or canang. To find an easier way to overcome this situation, many people tend to buy canang/banten which is ready to use, also more practical and spent less time than the time spent when they make by themselves . This phenomenon gives a chance to canang sellers to get income additional. In the difficult condition of the economics problem, many woman have to take part to overcome economic problems which they face. One of the alternative is involved into labour market, and involve in trade is one of the choice. Because of the existence of opportunity as explained above, many women overcome their economic problems and try to give contribution to their family income by selling the canang.Phenomenon more and more canang sellers which are spread alongside the road side in Denpasar City shown that the informal sector have a great role to maintaining and also improving household economics. The effort as the canang seller can represent an alternative of effort in informal sector to overcome economics problem in the household level. Roles of woman as a subject of this informal sector, have a big contribution in maintaining household economics.

  18. DNA Repair and Photoprotection: Mechanisms of Overcoming Environmental Ultraviolet Radiation Exposure in Halophilic Archaea

    OpenAIRE

    Daniel L. Jones; Bonnie K. Baxter

    2017-01-01

    Halophilic archaea push the limits of life at several extremes. In particular, they are noted for their biochemical strategies in dealing with osmotic stress, low water activity and cycles of desiccation in their hypersaline environments. Another feature common to their habitats is intense ultraviolet (UV) radiation, which is a challenge that microorganisms must overcome. The consequences of high UV exposure include DNA lesions arising directly from bond rearrangement of adjacent bipyrimidine...

  19. A preliminary survey into ways of overcoming self-incompatibility in theobroma cacao L

    International Nuclear Information System (INIS)

    Adu-Ampomah, Y.; Klu, G.Y.P.; Lamptey, T.V.O.; Novak, F.

    1990-01-01

    Varying concentrations of NAA and GA 3 (100-500 mg/l) were applied to the base of self-incompatible cocoa flowers with the view to delaying floral abscission and thus lengthening the time needed for the fusion of self-incompatible male and female gametes. NAA above 300 mg/l slightly delayed floral abscission but this did not help overcome the self-incompatibility whilst none of the GA 3 concentrations used either delayed floral abscission or promoted self-compatibility. Similar concentrations of both hormones when applied to the stigma before selfing also did not help to overcome the self-incompatibility. Self-incompatibility was partially overcome by treating compatible pollen with 60Gy of gamma rays and mixing it with self-incompatible pollen. Compatible pollen treated at 60Gy and used alone to pollinate self-incompatible flowers resulted in 100 percent flat, non-viable cocoa beans whilst gamma treated pollen mixed with self-incompatible pollen produced about 30 percent fully formed and viable cocoa beans. This appears to suggest that the irradiated compatible pollen is acting as mentor pollen and promoting selfing. (author)

  20. WSB1 overcomes oncogene-induced senescence by targeting ATM for degradation

    Science.gov (United States)

    Kim, Jung Jin; Lee, Seung Baek; Yi, Sang-Yeop; Han, Sang-Ah; Kim, Sun-Hyun; Lee, Jong-Min; Tong, Seo-Yun; Yin, Ping; Gao, Bowen; Zhang, Jun; Lou, Zhenkun

    2017-01-01

    Oncogene-induced senescence (OIS) or apoptosis through the DNA-damage response is an important barrier of tumorigenesis. Overcoming this barrier leads to abnormal cell proliferation, genomic instability, and cellular transformation, and finally allows cancers to develop. However, it remains unclear how the OIS barrier is overcome. Here, we show that the E3 ubiquitin ligase WD repeat and SOCS box-containing protein 1 (WSB1) plays a role in overcoming OIS. WSB1 expression in primary cells helps the bypass of OIS, leading to abnormal proliferation and cellular transformation. Mechanistically, WSB1 promotes ATM ubiquitination, resulting in ATM degradation and the escape from OIS. Furthermore, we identify CDKs as the upstream kinase of WSB1. CDK-mediated phosphorylation activates WSB1 by promoting its monomerization. In human cancer tissue and in vitro models, WSB1-induced ATM degradation is an early event during tumorigenic progression. We suggest that WSB1 is one of the key players of early oncogenic events through ATM degradation and destruction of the tumorigenesis barrier. Our work establishes an important mechanism of cancer development and progression in premalignant lesions. PMID:27958289

  1. Strategies to overcome type 1 diabetes-related social stigma in the Iranian society.

    Science.gov (United States)

    Irani, Mehri Doosti; Abdoli, Samereh; Bijan, Iraj; Parvizy, Soroor; Fatemi, Naimeh Seyed; Amini, Massoud

    2014-09-01

    This study explored the strategies to overcome diabetes-related social stigma in Iran. This paper is part of an action research study which was designed in Iran in 2012 to plan and implement a program for overcoming diabetes-related stigma. Participants were people with type 1 diabetes, their family members, people without diabetes, and care providers in a diabetes center. Data collection was done through unstructured in-depth interviews, focus groups, e-mail, Short Message Service (SMS), and telephone interview. Data were analyzed using inductive content analysis approach. Participants believed that it is impossible to overcome the stigma without community-based strategies. Community-based strategies include education, advocacy, contact, and protest. The anti-stigma strategies obtained in the study are based on the cultural context in Iran. They are extracted from statements of a wide range of people (with and without diabetes). However, during planning for stigma reduction, it is necessary to note that the effectiveness of social strategies varies in different studies and in different stigmatizing conditions and many factors are involved. These strategies should be implemented simultaneously at different levels to produce structural and social changes. It should be accepted that research on reducing health-related stigma has shown that it is very difficult to change beliefs and behavior. Evidence suggests that individuals and their families should be involved in all aspects of the program, and plans should be made according to the local conditions.

  2. Challenges to collaboration in school mental health and strategies for overcoming them.

    Science.gov (United States)

    Weist, Mark D; Mellin, Elizabeth A; Chambers, Kerri L; Lever, Nancy A; Haber, Deborah; Blaber, Christine

    2012-02-01

    This article reviews challenges to collaboration in school mental health (SMH) and presents practical strategies for overcoming them. The importance of collaboration to the success of SMH programs is reviewed, with a particular focus on collaboration between school- and community-employed professionals. Challenges to effective collaboration between school- and community-employed professionals in SMH are considered. Strategies for overcoming challenges to effective collaboration are presented. Marginalization of the SMH agenda, limited interdisciplinary teamwork, restricted coordination mechanisms, confidentiality concerns, and resource and funding issues are key challenges to collaboration. Strategies targeted toward each of these challenges may help improve the effectiveness of SMH programs and ultimately student outcomes. Collaboration between school- and community-employed professionals is critical to the success of SMH programs. Despite its promise, the success of SMH programs can be jeopardized by ineffective collaboration between school- and community-employed professionals. Strategies to overcome marginalization, promote authentic interdisciplinary teamwork, build effective coordination mechanisms, protect student and family confidentiality, and promote policy change and resource enhancements should be addressed in SMH improvement planning. © 2012, American School Health Association.

  3. A new technology to overcome the limits of HCCI engine through fuel modification

    International Nuclear Information System (INIS)

    Bahng, GunWoong; Jang, Dongsoon; Kim, Youngtae; Shin, Misoo

    2016-01-01

    Highlights: • Problems of HCCI engine can be overcome by adopting fuel modification. • Gasoline vapor with HHO gas showed drastic improvement of fuel efficiency. • Performance of single cylinder engine shows fuel efficiency more than double. - Abstract: The energy efficiency of internal combustion engine reached to about 30% only recently. To increase the efficiency, homogeneous charge compression ignition (HCCI) has been proposed, however, there is no available commercial engine yet. The main problem lies in the delayed heating rate in spite of fast reaction of homogeneous charged state of HCCI with excess air. To overcome this difficulty, a modification of fuel by vaporization of liquid gasoline with water electrolysis gas and air was adopted in order to warrant the fast and high temperature rise. Experiments were carried out with single cylinder engines supplied from the four different manufacturers. Experimental results show that fuel consumption was decreased by more than 50% compared to the case of supplying liquid fuel. It is believed it was due to the combined effects of the high and fast heating potential of water electrolysis gas together with the efficient turbulence mixing effect of vaporized fuel with excess air. By this method, the drawbacks caused by lean burn in the HCCI engine such as small power range can be overcome.

  4. Components of Hospital Perioperative Infrastructure Can Overcome the Weekend Effect in Urgent General Surgery Procedures.

    Science.gov (United States)

    Kothari, Anai N; Zapf, Matthew A C; Blackwell, Robert H; Markossian, Talar; Chang, Victor; Mi, Zhiyong; Gupta, Gopal N; Kuo, Paul C

    2015-10-01

    We hypothesized that perioperative hospital resources could overcome the "weekend effect" (WE) in patients undergoing emergent/urgent surgeries. The WE is the observation that surgeon-independent patient outcomes are worse on the weekend compared with weekdays. The WE is often explained by differences in staffing and resources resulting in variation in care between the week and weekend. Emergent/urgent surgeries were identified using the Healthcare Cost and Utilization Project State Inpatient Database (Florida) from 2007 to 2011 and linked to the American Hospital Association (AHA) Annual Survey Database to determine hospital level characteristics. Extended median length of stay (LOS) on the weekend compared with the weekdays (after controlling for hospital, year, and procedure type) was selected as a surrogate for WE. Included were 126,666 patients at 166 hospitals. A total of 17 hospitals overcame the WE during the study period. Logistic regression, controlling for patient characteristics, identified full adoption of electronic medical records (OR 4.74), home health program (OR 2.37), pain management program [odds ratio (OR) 1.48)], increased registered nurse-to-bed ratio (OR 1.44), and inpatient physical rehabilitation (OR 1.03) as resources that were predictors for overcoming the WE. The prevalence of these factors in hospitals exhibiting the WE for all 5 years of the study period were compared with those hospitals that overcame the WE (P surgery procedures. Improved hospital perioperative infrastructure represents an important target for overcoming disparities in surgical care.

  5. Modeling intentional inhibition of actions

    NARCIS (Netherlands)

    Thilakarathne, D.J.; Treur, J.

    2015-01-01

    Inspired by cognitive and neurological literature on action ownership and action awareness, in this paper a computational cognitive model for intentional inhibition (i.e.; the capacity to voluntarily suspend or inhibit an action) is introduced. The interplay between (positive) potential selection of

  6. Can Arousal Modulate Response Inhibition?

    Science.gov (United States)

    Weinbach, Noam; Kalanthroff, Eyal; Avnit, Amir; Henik, Avishai

    2015-01-01

    The goal of the present study was to examine if and how arousal can modulate response inhibition. Two competing hypotheses can be drawn from previous literature. One holds that alerting cues that elevate arousal should result in an impulsive response and therefore impair response inhibition. The other suggests that alerting enhances processing of…

  7. Overcoming acquired drug resistance in colorectal cancer cells by targeted delivery of 5-FU with EGF grafted hollow mesoporous silica nanoparticles

    Science.gov (United States)

    Chen, Lijue; She, Xiaodong; Wang, Tao; He, Li; Shigdar, Sarah; Duan, Wei; Kong, Lingxue

    2015-08-01

    effect and mechanism of 5-FU loaded EGF grafted HMSNs (EGF-HMSNs-5-FU) in overcoming acquired drug resistance in SW480/ADR cells were studied. The EGF-HMSNs were demonstrated to be specifically internalized in EGFR overexpressed SW480/ADR cells via a receptor-mediated endocytosis and can escape from endo-lysosomes. The EGF-HMSNs-5-FU exhibited much higher cytotoxicity on SW480/ADR cells than HMSNs-5-FU and free 5-FU while the plain HMSNs did not show significant cytotoxicity. The mechanism of EGF-HMSNs-5-FU in overcoming drug resistance in SW480/ADR cells could be attributed to the specific internalization of EGF-HMSNs-5-FU in EGFR overexpressed cells which can lead to high intracellular drug accumulation and cause cell death through S phase arrest. Electronic supplementary information (ESI) available: TEM image of EGF-HMSNs, characterization of HMSNs, EGFR expression in colorectal cancer cells, flow cytometry results, inhibition of endocytosis, confocal microscopy images of endosome escape and cell cycle distribution in SW480 cells. See DOI: 10.1039/C5NR03527A

  8. Toll-like receptor triggered dendritic cell maturation and IL-12 secretion are necessary to overcome T-cell inhibition by glioma-associated TGF-beta2.

    NARCIS (Netherlands)

    Grauer, O.M.; Poschl, P.; Lohmeier, A.; Adema, G.J.; Bogdahn, U.

    2007-01-01

    Malignant gliomas are able to secrete large amounts of immunosuppressive cytokines like transforming growth factor beta 2 (TGF-beta2) and regularly escape from immune surveillance. Many strategies have been developed to induce potent anti-glioma responses, among those the use of dendritic cells (DC)

  9. Dual inhibition of DNMTs and EZH2 can overcome both intrinsic and acquired resistance of myeloma cells to IMiDs in a cereblon-independent manner

    DEFF Research Database (Denmark)

    Dimopoulos, Konstantinos; Søgaard Helbo, Alexandra; Fibiger Munch-Petersen, Helga

    2018-01-01

    Thalidomide and its derivatives, lenalidomide and pomalidomide (also known as IMiDs), have significantly changed the treatment landscape of multiple myeloma, and the recent discovery of cereblon (CRBN) as their direct biological target has led to a deeper understanding of their complex mechanism ...

  10. Inhibition of p70S6K1 activation by Pdcd4 overcomes the resistance to an IGF-1R/IR inhibitor in colon carcinoma cells

    OpenAIRE

    Zhang, Yan; Wang, Qing; Chen, Li; Yang, Hsin-Sheng

    2015-01-01

    Agents targeting insulin-like growth factor 1 receptor (IGF-1R) are being actively examined in clinical trials. Although there has been some initial success of single agent targeting IGF-1R, attempts in later studies failed due to resistance. This study aimed to understand the effects of programmed cell death 4 (Pdcd4) on the chemosensitivity of the IGF-1R inhibitor, OSI-906, in colorectal cancer (CRC) cells and the mechanism underlying this impact. Using OSI-906 resistant and sensitive CRC c...

  11. Overcoming Barriers to Skills Training in Borderline Personality Disorder: A Qualitative Interview Study.

    Science.gov (United States)

    Barnicot, Kirsten; Couldrey, Laura; Sandhu, Sima; Priebe, Stefan

    2015-01-01

    Despite evidence suggesting that skills training is an important mechanism of change in dialectical behaviour therapy, little research exploring facilitators and barriers to this process has been conducted. The study aimed to explore clients' experiences of barriers to dialectical behaviour therapy skills training and how they felt they overcame these barriers, and to compare experiences between treatment completers and dropouts. In-depth qualitative interviews were conducted with 40 clients with borderline personality disorder who had attended a dialectical behaviour therapy programme. A thematic analysis of participants' reported experiences found that key barriers to learning the skills were anxiety during the skills groups and difficulty understanding the material. Key barriers to using the skills were overwhelming emotions which left participants feeling unable or unwilling to use them. Key ways in which participants reported overcoming barriers to skills training were by sustaining their commitment to attending therapy and practising the skills, personalising the way they used them, and practising them so often that they became an integral part of their behavioural repertoire. Participants also highlighted a number of key ways in which they were supported with their skills training by other skills group members, the group therapists, their individual therapist, friends and family. Treatment dropouts were more likely than completers to describe anxiety during the skills groups as a barrier to learning, and were less likely to report overcoming barriers to skills training via the key processes outlined above. The findings of this qualitative study require replication, but could be used to generate hypotheses for testing in further research on barriers to skills training, how these relate to dropout, and how they can be overcome. The paper outlines several such suggestions for further research.

  12. Overcoming Barriers to Skills Training in Borderline Personality Disorder: A Qualitative Interview Study.

    Directory of Open Access Journals (Sweden)

    Kirsten Barnicot

    Full Text Available Despite evidence suggesting that skills training is an important mechanism of change in dialectical behaviour therapy, little research exploring facilitators and barriers to this process has been conducted. The study aimed to explore clients' experiences of barriers to dialectical behaviour therapy skills training and how they felt they overcame these barriers, and to compare experiences between treatment completers and dropouts. In-depth qualitative interviews were conducted with 40 clients with borderline personality disorder who had attended a dialectical behaviour therapy programme. A thematic analysis of participants' reported experiences found that key barriers to learning the skills were anxiety during the skills groups and difficulty understanding the material. Key barriers to using the skills were overwhelming emotions which left participants feeling unable or unwilling to use them. Key ways in which participants reported overcoming barriers to skills training were by sustaining their commitment to attending therapy and practising the skills, personalising the way they used them, and practising them so often that they became an integral part of their behavioural repertoire. Participants also highlighted a number of key ways in which they were supported with their skills training by other skills group members, the group therapists, their individual therapist, friends and family. Treatment dropouts were more likely than completers to describe anxiety during the skills groups as a barrier to learning, and were less likely to report overcoming barriers to skills training via the key processes outlined above. The findings of this qualitative study require replication, but could be used to generate hypotheses for testing in further research on barriers to skills training, how these relate to dropout, and how they can be overcome. The paper outlines several such suggestions for further research.

  13. Nanocarrier mediated retinal drug delivery: overcoming ocular barriers to treat posterior eye diseases.

    Science.gov (United States)

    Bisht, Rohit; Mandal, Abhirup; Jaiswal, Jagdish K; Rupenthal, Ilva D

    2018-03-01

    Effective drug delivery to the retina still remains a challenge due to ocular elimination mechanisms and complex barriers that selectively limit the entry of drugs into the eye. To overcome these barriers, frequent intravitreal injections are currently used to achieve high drug concentrations in vitreous and retina. However, these repetitive injections may result in several side effects. Recent advancements in the field of nanoparticle-based drug delivery could overcome some of these unmet needs and various preclinical studies conducted to date have demonstrated promising results of nanotherapies in the treatment of retinal diseases. Compared to the majority of commercially available ocular implants, the biodegradable nature of most nanoparticles (NPs) avoids the need for surgical implantation and removal after the release of the payload. In addition, the sustained drug release from NPs over an extended period of time reduces the need for frequent intravitreal injections and the risk of associated side effects. The nanometer size and highly modifiable surface properties make NPs excellent candidates for targeted ocular drug delivery. Studies have shown that nanocarriers enhance the intravitreal half-life and thus bioavailability of a number of drugs including proteins and peptides. In addition, they have shown promising results in delivering genetic material to the retinal tissues by protecting it from possible intravitreal degradation. This review covers the various challenges associated with drug delivery to the posterior segment of the eye, particularly the retina, and highlights the application of nanocarriers to overcome these challenges in context with recent advances in preclinical studies. WIREs Nanomed Nanobiotechnol 2018, 10:e1473. doi: 10.1002/wnan.1473 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanomaterials and Implants. © 2017 Wiley Periodicals

  14. Age-differences in cognitive flexibility when overcoming a preexisting bias through feedback.

    Science.gov (United States)

    Wilson, Cristina G; Nusbaum, Amy T; Whitney, Paul; Hinson, John M

    2018-08-01

    Older adults are often worse than younger adults at adapting to changing situational demands, and this difference is commonly attributed to an age-related decline in acquiring and updating information. Previous research on aging and cognitive flexibility has used measures that require adapting to novel associations learned during a laboratory task (e.g., choice X led to positive outcomes but now leads to negative outcomes). However, in everyday life people must frequently overcome associations based on preexisting beliefs and biases (e.g., you like to eat cake, but your doctor said to limit your sugar intake). The goal of the present study was to examine possible age-differences in overcoming a preexisting bias and determine whether age-related changes in the acquisition and updating of information influence this form of flexibility. Older (n = 20) and younger (n = 20) adults completed a novel task in which repeated choices were made between a sure option (gain or loss) and one of two risky options that were initially ambiguous. Optimal performance required overcoming a framing bias toward being risk seeking to avoid a sure loss and risk averse when offered a sure gain. Probe questions assessed knowledge of choice outcomes, while skin conductance assessed physiological reactions to choices and choice outcomes. Both older and younger adults demonstrated flexibility by reducing the impact of bias over trials, but younger adults had better performance overall. Age-differences were associated with distinct aspects of processing. Young adults had more precise knowledge of choice outcomes and developed skin conductance responses in anticipation of bad choices that were not apparent in older adults. Older adults showed significant improvement over trials in their ability to decrease bias-driven choices, but younger showed greater flexibility. Age-differences in task performance were based on differences in learning and corresponding representations of task

  15. Exploring How Lay Rescuers Overcome Barriers to Provide Cardiopulmonary Resuscitation: A Qualitative Study.

    Science.gov (United States)

    Mathiesen, Wenche Torunn; Bjørshol, Conrad Arnfinn; Høyland, Sindre; Braut, Geir Sverre; Søreide, Eldar

    2017-02-01

    Survival rates after out-of-hospital cardiac arrest (OHCA) vary considerably among regions. The chance of survival is increased significantly by lay rescuer cardiopulmonary resuscitation (CPR) before Emergency Medical Services (EMS) arrival. It is well known that for bystanders, reasons for not providing CPR when witnessing an OHCA incident may be fear and the feeling of being exposed to risk. The aim of this study was to gain a better understanding of why barriers to providing CPR are overcome. Using a semi-structured interview guide, 10 lay rescuers were interviewed after participating in eight OHCA incidents. Qualitative content analysis was used. The lay rescuers were questioned about their CPR-knowledge, expectations, and reactions to the EMS and from others involved in the OHCA incident. They also were questioned about attitudes towards providing CPR in an OHCA incident in different contexts. The lay rescuers reported that they were prepared to provide CPR to anybody, anywhere. Comprehending the severity in the OHCA incident, both trained and untrained lay rescuers provided CPR. They considered CPR provision to be the expected behavior of any community citizen and the EMS to act professionally and urgently. However, when asked to imagine an OHCA in an unclear setting, they revealed hesitation about providing CPR because of risk to their own safety. Mutual trust between community citizens and towards social institutions may be reasons for overcoming barriers in providing CPR by lay rescuers. A normative obligation to act, regardless of CPR training and, importantly, without facing any adverse legal reactions, also seems to be an important factor behind CPR provision. Mathiesen WT , Bjørshol CA , Høyland S , Braut GS , Søreide E . Exploring how lay rescuers overcome barriers to provide cardiopulmonary resuscitation: a qualitative study. Prehosp Disaster Med. 2017;32(1):27-32.

  16. Understanding and overcoming the “positive profits with negative surplus-value” paradox

    Directory of Open Access Journals (Sweden)

    GUSTAVO DAOU LUCAS

    Full Text Available ABSTRACT This paper explains the “positive profits with negative surplus-value” example of Steedman (1975 and shows that while in joint production systems individual labour values can be negative, the claim that the total labour embodied in the surplus product of the economy (surplus-value can also be negative is based on assumptions that have no economic meaning (such as negative activity levels.The paper also provides a way to measure the surplus-value of joint production systems which overcomes the problems of the traditional concept and restates the proposition that a positive amount of surplus labour is a necessary condition for positive profits.

  17. 20% wind by 2030: Overcoming the challenge - U.S. wind supply chain bottlenecks

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, Meghan

    2010-09-15

    The U.S. Department of Energy (DOE) provided PowerAdvocate with funding to evaluate the challenges facing the supply chain and provide strategic solutions to overcoming the short and long term supply chain challenges. PowerAdvocate conducted market research and interviews with wind developers, turbine and component suppliers and offshore wind development experts. PowerAdvocate created a comprehensive model. The model includes labor statistics, wind facility cost forecasting, and component supplier manufacturing investments in order to estimate the total cost to build a supply chain that supports the DOE's 20% by 2030 wind installation goal.

  18. Overcoming strategy to strengthen the History of Medicine in Santiago of Cuba

    Directory of Open Access Journals (Sweden)

    Ana María Durán-Fonseca

    2018-03-01

    Full Text Available A strategy of improvement in the Medical Sciences is proposed, integrated to the performance of every teacher that forms part of the Cuban educational system associated with health. The overcoming of the teachers of Medical Sciences in History of Medicine, takes into account the new conceptions and demands of the training of the doctor at present, for what constitutes a challenge from recognizing that the History of Medicine is not a appendix of Medicine, or History, but with its own legitimacy erected in science synthesis with structural and methodological architecture, deduced by the independent position that Medicine occupies in the set of Natural and Humanistic sciences.

  19. The Role of Therapy Education of Islamic Meaning to Overcome Today’s Global Human Crisis

    Directory of Open Access Journals (Sweden)

    Nina Aminah

    2016-02-01

    Full Text Available Modern community are exposed to current issues related to the very complex personality. Islam offers a therapeutic meaning to overcome the global human crisis through the holy Qu’ran. This study aims to provide a qualitative analysis of logotherapy alternative to global human who experience critical conditions such as the door of death (sakaratul maut, acute illnesses, HIV Aids, kidney illness, stroke, coma, depression / stress, due to the hazards, and other refractory disease. The study showed that the therapy of Islamic meaning based on the holy Qur’an is broader and more comprehensive than the meaning therapy by Viktor E. Frankl.

  20. Near Real-Time MOPITT Data - Its Architecture, Obstacles Overcome, and Strategic Decisions

    Science.gov (United States)

    Ziskin, D.; Mao, D.; Worden, H. M.; Deeter, M. N.; D'Attilo, G.; Fredrick, T.; Martinez-Alonso, S.; Francis, G.; Drews, C.

    2017-12-01

    Measurements Of Pollution In The Troposphere (MOPITT) is an instrument that has been flying aboard NASA's Terra satellite and collecting CO data since March 2000. The standard MOPITT product uses ancillary data that can delay its production by several weeks. Furthermore, final processing does not occur until after the annual calibration event, creating a lag of up to a year. In contrast, MOPITT produces a Near Real-Time (NRT) product available through the Land, Atmosphere Near real-time Capability for EOS (LANCE) interface with a latency of less than three hours. This presentation details the architecture of the system, obstacles overcome, and strategic decisions made in order become a LANCE node.

  1. Strategies for Overcoming Key Barriers to Development of a National Security Workforce

    Energy Technology Data Exchange (ETDEWEB)

    None

    2008-06-30

    This report documents the strategies for overcoming identified key barriers to development of an adequate national security workforce as part of the National Security Preparedness Project (NSPP) being performed under a Department of Energy (DOE) National Nuclear Security Administration (NNSA) grant. Many barriers currently exist that prevent the development of an adequate number of properly trained national security personnel. The identified strategies to address the barriers will focus on both short-term and long-term efforts, as well as strategies to capture legacy knowledge of retiring national security workforce personnel.

  2. Three principles to improve clinician communication for advance care planning: overcoming emotional, cognitive, and skill barriers.

    Science.gov (United States)

    Weiner, Joseph S; Cole, Steven A

    2004-12-01

    Medical care of patients with life limiting illness remains fraught with serious deficiencies, including inadequate advance care planning, delayed hospice referral, and continued delivery of aggressive treatment that is overtly counter to patients' preferences. This paper describes clinicians' emotional, cognitive, and skill barriers to shared decision-making with seriously ill patients and their loved ones. Thematic literature review. Based on a literature review, as well as clinical and educational experience, we articulate three principles to address these barriers and guide future professional communication training for advance care planning. We argue that these barriers must be overcome before deficiencies in end-of-life care can be fully ameliorated.

  3. Effects arising from charged particles overcoming of the light velocity barrier

    International Nuclear Information System (INIS)

    Afanas'ev, G.N.; Eliseev, S.M.; Stepanovskij, Yu.P.

    1997-01-01

    The effects arising from accelerated and decelerated motion of the charged point particle inside the medium are studied. It is shown explicitly that in addition to the Bremsstrahlung and Cherenkov shock wave, the electromagnetic shock wave arising from the charge overcoming the light velocity in the medium should be observed. This shock wave has the same singularity as the Cherenkov one and, therefore, it is more singular than the Bremsstrahlung shock wave. The space-time regions where these shock waves exist and conditions under which they appear are determined

  4. High-efficiency free-form condenser overcoming rotational symmetry limitations.

    Science.gov (United States)

    Miñano, Juan C; Benítez, Pablo; Blen, José; Santamaría, Asunción

    2008-12-08

    Conventional condensers using rotational symmetric devices perform far from their theoretical limits when transferring optical power from sources such as arc lamps or halogen bulbs to the rectangular entrance of homogenizing prisms (target). We present a free-form condenser design (calculated with the SMS method) that overcomes the limitations inherent to rotational devices and can send to the target 1.8 times the power sent by an equivalent elliptical condenser for a 4:1 target aspect ratio and 1.5 times for 16:9 target and for practical values of target etendue.

  5. Progress toward overcoming hypoxia-induced resistance to solid tumor therapy

    International Nuclear Information System (INIS)

    Karakashev, Sergey V; Reginato, Mauricio J

    2015-01-01

    Hypoxic tumors are associated with poor clinical outcome for multiple types of human cancer. This may be due, in part, to hypoxic cancer cells being resistant to anticancer therapy, including radiation therapy, chemotherapy, and targeted therapy. Hypoxia inducible factor 1, a major regulator of cellular response to hypoxia, regulates the expression of genes that are involved in multiple aspects of cancer biology, including cell survival, proliferation, metabolism, invasion, and angiogenesis. Here, we review multiple pathways regulated by hypoxia/hypoxia inducible factor 1 in cancer cells and discuss the latest advancements in overcoming hypoxia-mediated tumor resistance

  6. Resonant interaction of electromagnetic wave with plasma layer and overcoming the radiocommunication blackout problem

    Science.gov (United States)

    Bogatskaya, A. V.; Klenov, N. V.; Tereshonok, M. V.; Adjemov, S. S.; Popov, A. M.

    2018-05-01

    We present an analysis of the possibility of penetrating electromagnetic waves through opaque media using an optical-mechanical analogy. As an example, we consider the plasma sheath surrounding the vehicle as a potential barrier and analyze the overcoming of radiocommunication blackout problem. The idea is to embed a «resonator» between the surface on the vehicle and plasma sheath which is supposed to provide an effective tunneling of the signal to the receiving antenna. We discuss the peculiarities of optical mechanical analogy applicability and analyze the radio frequency wave tunneling regime in detail. The cases of normal and oblique incidence of radiofrequency waves on the vehicle surface are studied.

  7. How to overcome some of the challenges that African scholars are facing in conducting informetrics research

    Directory of Open Access Journals (Sweden)

    Isola Ajiferuke

    2011-01-01

    Full Text Available This article provides evidence to show that the contributions of African researchers to the informetrics literature are minimal. The three main challenges identified as limiting the contributions of African scholars to the informetrics literature are lack of appropriate skills, inadequate data collection sources, and unaffordable analytical tools. To overcome these challenges, it is suggested that regular pre-conference workshops on informetrics should be organized, an African Citation Index should be developed, and the use of free analytical tools should be encouraged.

  8. A Blockchain-Based Approach Towards Overcoming Financial Fraud in Public Sector Services

    DEFF Research Database (Denmark)

    Hyvärinen, Hissu; Risius, Marten; Friis, Gustav

    2017-01-01

    damage of 1.8 billion USD, for example, in Denmark alone. This paper assesses the potential of a blockchain database to provide a feasible solution for overcoming this problem against the backdrop of recent advances in the public sector and the unique set of blockchain capacities. Towards this end, we...... develop and evaluate a blockchain-based prototype system aimed at eliminating this type of tax fraud and increasing transparency regarding the flow of dividends. While the prototype is based on the specific context of the Danish tax authority, we discuss how it can be generalized for tracking...

  9. Nuclear power in the 21st century. The challenge to overcome the 'trilemma'

    International Nuclear Information System (INIS)

    Yoda, Susumu

    1997-01-01

    In light of the pending explosive growth in world population, massive consumption of energy and resources is required for the sustainable economic growth, which will in turn cause damage to the global environment. The nature of the problem is a sort of complicated chain of causes and effects - a vicious cycle. We must simultaneously solve the problems of economic growth, resources and energy, and the environment. This is the so-called 'trilemma'. Human wisdom and the collective efforts of each nation are indispensable to overcome the trilemma and to ensure sustainable development of the world. Nuclear power will play a key role to do it. (author)

  10. Selective inhibition of distracting input.

    Science.gov (United States)

    Noonan, MaryAnn P; Crittenden, Ben M; Jensen, Ole; Stokes, Mark G

    2017-10-16

    We review a series of studies exploring distractor suppression. It is often assumed that preparatory distractor suppression is controlled via top-down mechanisms of attention akin to those that prepare brain areas for target enhancement. Here, we consider two alternative mechanisms: secondary inhibition and expectation suppression within a predictive coding framework. We draw on behavioural studies, evidence from neuroimaging and some animal studies. We conclude that there is very limited evidence for selective top-down control of preparatory inhibition. By contrast, we argue that distractor suppression often relies secondary inhibition of non-target items (relatively non-selective inhibition) and on statistical regularities of the environment, learned through direct experience. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  11. [Concepts of inhibition in psychiatry].

    Science.gov (United States)

    Auroux, Y; Bourrat, M M; Brun, J P

    1978-01-01

    Following a historical approach, the authors first describe the original development of the concept of inhibition in neurophysiology and then analyze the subsequent adaptations made in psychiatry around such concept including those of: -- Pavlov, Hull, Watson and the behaviorists, -- Freud and the Freudian School, -- clinicians and psychopharmacologists. The concept of inhibition has thus various meanings in psychiatry. Although some unity is achieved on the semiological level, this aspect cannot explain the extent of the process.

  12. Inhibition of MMPs by alcohols

    Science.gov (United States)

    Tezvergil-Mutluay, Arzu; Agee, Kelli A.; Hoshika, Tomohiro; Uchiyama, Toshikazu; Tjäderhane, Leo; Breschi, Lorenzo; Mazzoni, Annalisa; Thompson, Jeremy M.; McCracken, Courtney E.; Looney, Stephen W.; Tay, Franklin R.; Pashley, David H.

    2011-01-01

    Objectives While screening the activity of potential inhibitors of matrix metalloproteinases (MMPs), due to the limited water solubility of some of the compounds, they had to be solubilized in ethanol. When ethanol solvent controls were run, they were found to partially inhibit MMPs. Thus, the purpose of this study was to compare the MMP-inhibitory activity of a series of alcohols. Methods The possible inhibitory activity of a series of alcohols was measured against soluble rhMMP-9 and insoluble matrix-bound endogenous MMPs of dentin in completely demineralized dentin. Increasing concentrations (0.17, 0.86, 1.71 and 4.28 moles/L) of a homologous series of alcohols (i.e. methanol, ethanol, propanols, butanols, pentanols, hexanols, the ethanol ester of methacrylic acid, heptanols and octanol) were compared to ethanediol, and propanediol by regression analysis to calculate the molar concentration required to inhibit MMPs by 50% (i.e. the IC50). Results Using two different MMP models, alcohols were shown to inhibit rhMMP-9 and the endogenous proteases of dentin matrix in a dose-dependent manner. The degree of MMP inhibition by alcohols increased with chain length up to 4 methylene groups. Based on the molar concentration required to inhibit rhMMP-9 fifty percent, 2-hydroxyethylmethacrylate (HEMA), 3-hexanol, 3-heptanol and 1-octanol gave the strongest inhibition. Significance The results indicate that alcohols with 4 methylene groups inhibit MMPs more effectively than methanol or ethanol. MMP inhibition was inversely related to the Hoy's solubility parameter for hydrogen bonding forces of the alcohols (i.e. to their hydrophilicity). PMID:21676453

  13. Internationalization as a strategy to overcome industry barriers-An assessment of the marine energy industry

    Energy Technology Data Exchange (ETDEWEB)

    Lovdal, Nicolai, E-mail: nicolai.lovdal@iot.ntnu.n [Industrial Economics and Technology Management, Norwegian University of Science and Technology, 7491 Trondheim (Norway); Neumann, Frank, E-mail: frank@wave-energy-centre.or [Wave Energy Centre, Av. Manuel Maia, 36, r/c Dto., 1000-201 Lisboa (Portugal)

    2011-03-15

    Research on conditions to develop new innovations within emerging renewable energy industries is often done with a national focus. However, recent research on international entrepreneurship has revealed that firms operate on international levels very early in their life time. Thus, based on former research on international entrepreneurship and case examples, we build the propositions that firms in the marine energy industry use internationalization as a strategy to overcome industry barriers. Our primary source of data is a unique dataset from a global survey of all the companies in the marine energy industry who are aiming to commercialize a wave or tidal energy device. This paper is organized in two steps: first we identified the most challenging industry barriers perceived by companies. Second we use these to form propositions which we assess through empirical data. The two most challenging barriers perceived by the companies are need for capital and need for supportive political schemes. Our findings reveal that internationalization certainly is a common strategy to access capital and attractive support schemes in foreign countries. The early internationalization has implications for researchers, managers and policy makers. - Research highlights: {yields} Industry barriers identified as access to capital and supportive political schemes. {yields} International entrepreneurship is used to overcome industry barriers. {yields} Start-ups in emerging energy industries 'shop' national support schemes. {yields} Future research to provide policy advice should adapt to the international reality. {yields} Research based on a worldwide survey of wave and tidal energy device developers.

  14. Harnessing atomistic simulations to predict the rate at which dislocations overcome obstacles

    Science.gov (United States)

    Saroukhani, S.; Nguyen, L. D.; Leung, K. W. K.; Singh, C. V.; Warner, D. H.

    2016-05-01

    Predicting the rate at which dislocations overcome obstacles is key to understanding the microscopic features that govern the plastic flow of modern alloys. In this spirit, the current manuscript examines the rate at which an edge dislocation overcomes an obstacle in aluminum. Predictions were made using different popular variants of Harmonic Transition State Theory (HTST) and compared to those of direct Molecular Dynamics (MD) simulations. The HTST predictions were found to be grossly inaccurate due to the large entropy barrier associated with the dislocation-obstacle interaction. Considering the importance of finite temperature effects, the utility of the Finite Temperature String (FTS) method was then explored. While this approach was found capable of identifying a prominent reaction tube, it was not capable of computing the free energy profile along the tube. Lastly, the utility of the Transition Interface Sampling (TIS) approach was explored, which does not need a free energy profile and is known to be less reliant on the choice of reaction coordinate. The TIS approach was found capable of accurately predicting the rate, relative to direct MD simulations. This finding was utilized to examine the temperature and load dependence of the dislocation-obstacle interaction in a simple periodic cell configuration. An attractive rate prediction approach combining TST and simple continuum models is identified, and the strain rate sensitivity of individual dislocation obstacle interactions is predicted.

  15. Modeling Governance KB with CATPCA to Overcome Multicollinearity in the Logistic Regression

    Science.gov (United States)

    Khikmah, L.; Wijayanto, H.; Syafitri, U. D.

    2017-04-01

    The problem often encounters in logistic regression modeling are multicollinearity problems. Data that have multicollinearity between explanatory variables with the result in the estimation of parameters to be bias. Besides, the multicollinearity will result in error in the classification. In general, to overcome multicollinearity in regression used stepwise regression. They are also another method to overcome multicollinearity which involves all variable for prediction. That is Principal Component Analysis (PCA). However, classical PCA in only for numeric data. Its data are categorical, one method to solve the problems is Categorical Principal Component Analysis (CATPCA). Data were used in this research were a part of data Demographic and Population Survey Indonesia (IDHS) 2012. This research focuses on the characteristic of women of using the contraceptive methods. Classification results evaluated using Area Under Curve (AUC) values. The higher the AUC value, the better. Based on AUC values, the classification of the contraceptive method using stepwise method (58.66%) is better than the logistic regression model (57.39%) and CATPCA (57.39%). Evaluation of the results of logistic regression using sensitivity, shows the opposite where CATPCA method (99.79%) is better than logistic regression method (92.43%) and stepwise (92.05%). Therefore in this study focuses on major class classification (using a contraceptive method), then the selected model is CATPCA because it can raise the level of the major class model accuracy.

  16. Virtuality and efficiency - overcoming past antinomy in the remote collaboration experience

    International Nuclear Information System (INIS)

    Fernandes, Joao; Bjorkli, Knut; Clavo, David Martin; Baron, Thomas

    2010-01-01

    Several recent initiatives have been put in place by the CERN IT Department to improve the user experience in remote dispersed meetings and remote collaboration at large in the LHC communities worldwide. We will present an analysis of the factors which were historically limiting the efficiency of remote dispersed meetings and describe the consequent actions which were undertaken at CERN to overcome these limitations. After giving a status update of the different equipment available at CERN to enable the virtual sessions and the various collaborative tools which are currently proposed to users, we will focus on the evolution of this market: how can the new technological trends (among others, HD videoconferencing, Telepresence, Unified Communications, etc.) impact positively the user experience and how to attain the best usage of them. Finally, by projecting ourselves in the future, we will give some hints as to how to answer the difficult question of selecting the next generation of collaborative tools: which set of tools among the various offers (systems like Vidyo H264 SVC, next generation EVO, Groupware offers, standard H323 systems, etc.) is best suited for our environment and how to unify this set for the common user. This will finally allow us to definitively overcome the past antinomy between virtuality and efficiency.

  17. Comparison of Strategies to Overcome Drug Resistance: Learning from Various Kingdoms

    Directory of Open Access Journals (Sweden)

    Hiroshi Ogawara

    2018-06-01

    Full Text Available Drug resistance, especially antibiotic resistance, is a growing threat to human health. To overcome this problem, it is significant to know precisely the mechanisms of drug resistance and/or self-resistance in various kingdoms, from bacteria through plants to animals, once more. This review compares the molecular mechanisms of the resistance against phycotoxins, toxins from marine and terrestrial animals, plants and fungi, and antibiotics. The results reveal that each kingdom possesses the characteristic features. The main mechanisms in each kingdom are transporters/efflux pumps in phycotoxins, mutation and modification of targets and sequestration in marine and terrestrial animal toxins, ABC transporters and sequestration in plant toxins, transporters in fungal toxins, and various or mixed mechanisms in antibiotics. Antibiotic producers in particular make tremendous efforts for avoiding suicide, and are more flexible and adaptable to the changes of environments. With these features in mind, potential alternative strategies to overcome these resistance problems are discussed. This paper will provide clues for solving the issues of drug resistance.

  18. Poliovirus intrahost evolution is required to overcome tissue-specific innate immune responses.

    Science.gov (United States)

    Xiao, Yinghong; Dolan, Patrick Timothy; Goldstein, Elizabeth Faul; Li, Min; Farkov, Mikhail; Brodsky, Leonid; Andino, Raul

    2017-08-29

    RNA viruses, such as poliovirus, have a great evolutionary capacity, allowing them to quickly adapt and overcome challenges encountered during infection. Here we show that poliovirus infection in immune-competent mice requires adaptation to tissue-specific innate immune microenvironments. The ability of the virus to establish robust infection and virulence correlates with its evolutionary capacity. We further identify a region in the multi-functional poliovirus protein 2B as a hotspot for the accumulation of minor alleles that facilitate a more effective suppression of the interferon response. We propose that population genetic dynamics enables poliovirus spread between tissues through optimization of the genetic composition of low frequency variants, which together cooperate to circumvent tissue-specific challenges. Thus, intrahost virus evolution determines pathogenesis, allowing a dynamic regulation of viral functions required to overcome barriers to infection.RNA viruses, such as polioviruses, have a great evolutionary capacity and can adapt quickly during infection. Here, the authors show that poliovirus infection in mice requires adaptation to innate immune microenvironments encountered in different tissues.

  19. THE STRATEGY OF EMPOWERMENT BASED ON ESQ POWER: A SOCIAL INNOVATION IN THE POVERTY OVERCOMING

    Directory of Open Access Journals (Sweden)

    Peribadi Peribadi

    2017-12-01

    Full Text Available This research aimed to develop an innovation of empowerment strategy on ESQ Power – Based. It was designed through a phenomenology deductive, a case study and the methodof research and development or the procedure of member check. The three of them were used eclectically in order to design an ideal formulation. The research findings indicated that the actors and actresses of poverty overcoming in Kendari City have not had the emotional intelligence and spiritual intelligence yet as ESQ Power. As a result, they were not optimal in performing their duties, roles and responsibilities. Therefore, the urgency of empowerment paradigm on ESQ Power – Based that has been formulated and validated by the skillful validator must be used in the future to increase the sense of responsibility of the actor network in overcoming the pauperization and poverty. Penelitian ini bertujuan untuk mengembangkan sebuah inovasi strategi pemberdayaan berbasis ESQ Power. Hal itu dirancang melalui deduksi fenomenologis, studi kasus serta metode penelitian dan pengembangan atau prosedur member check. Ketiganya digunakan secara eklektik untuk merancang formulasi ideal. Temuan penelitian menunjukkan bahwa aktor dan aktris penanggulangan kemiskinan di Kota Kendari belum memiliki kecerdasan emosional dan kecerdasan spiritual sebagai ESQ Power. Akibatnya, mereka tidak optimal dalam menjalankan tugas, peran dan tanggung jawabnya. Oleh karena itu, urgensi paradigma pemberdayaan berbasis ESQ Power yang telah dirumuskan dan divalidasi oleh validator ahli tersebut harus mulai digunakan ke depan untuk meningkatkan rasa tanggung jawab jaringan aktor dalam mengatasi pemiskinan dan kemiskinan.

  20. Overcoming Abuse: A Phenomenological Investigation of the Journey to Recovery From Past Intimate Partner Violence.

    Science.gov (United States)

    Flasch, Paulina; Murray, Christine E; Crowe, Allison

    2015-08-10

    To date, minimal research has focused on the recovery process for survivors of intimate partner violence (IPV). This study utilized a phenomenological methodology to understand the lived experiences of survivors of IPV (N = 123) who had overcome abusive relationships and created violence-free and meaningful lives. The researchers aimed to understand key factors involved in their recovery processes. Results indicated two main processes in the IPV recovery process: intrapersonal processes and interpersonal processes. Intrapersonal processes included (a) regaining and recreating one's identity, (b) embracing the freedom and power to direct one's own life, (c) healing from the mental and physical health symptoms of the abuse, (d) fostering acceptance and forgiveness with self and abuser, (e) education and examination of abusive relationships, (f) determining whether and how to enter new intimate relationships, and (g) acknowledging the long-term process of overcoming abuse. Interpersonal processes included themes of (a) building positive social support and relationships and (b) using ones' experiences with abuse to help others. Results of the present study are presented, and implications for practitioners are discussed. © The Author(s) 2015.

  1. Synthesis of Nanodiamond-Daunorubicin Conjugates to Overcome Multidrug Chemoresistance in Leukemia

    Science.gov (United States)

    Man, Han B.; Kim, Hansung; Kim, Ho-Joong; Robinson, Erik; Liu, Wing Kam; Chow, Edward Kai-Hua; Ho, Dean

    2013-01-01

    Nanodiamonds (NDs) are promising candidates in nanomedicine, demonstrating significant potential as gene/drug delivery platforms for cancer therapy. We have synthesized ND vectors capable of chemotherapeutic loading and delivery with applications towards chemoresistant leukemia. The loading of Daunorubicin (DNR) onto NDs was optimized by adjusting reaction parameters such as acidity and concentration. The resulting conjugate, a novel therapeutic payload for NDs, was characterized extensively for size, surface charge, and loading efficiency. A K562 human myelogenous leukemia cell line, with multidrug resistance conferred by incremental DNR exposure, was used to demonstrate the efficacy enhancement resulting from ND-based delivery. While resistant K562 cells were able to overcome treatment from DNR alone, as compared with non-resistant K562 cells, NDs were able to improve DNR delivery into resistant K562 cells. By overcoming efflux mechanisms present in this resistant leukemia line, ND-enabled therapeutics have demonstrated the potential to improve cancer treatment efficacy, especially towards resistant strains. PMID:23916889

  2. Factors in Overcoming Barriers to Implementing Co-management in British Columbia Salmon Fisheries

    Directory of Open Access Journals (Sweden)

    Evelyn Pinkerton

    1999-12-01

    Full Text Available Ten years of research and efforts to implement co-management in British Columbia fisheries have demonstrated that we lack neither good models nor the political will in communities to design and test local and regional institutions for successful involvement in various aspects of management. The barriers lie rather in the distrust and resistance of management agencies and the lack of broadly organized political support. The nature of the barriers and some of the elements of a successful approach to overcoming them are identified and discussed. The analysis is focused around the barriers encountered by two differently situated fishing communities or regions that have launched conservation initiatives through cooperation between local aboriginal and nonaboriginal fishing groups. In attempting to overcome the political barriers, the communities seek to develop expertise in selective fishing technology for more sustainable harvest, principled multi-stakeholder negotiation, marketing, shared databases, and preliminary ecosystem monitoring. The communities exemplify small- and medium-scale bottom-up approaches to adaptive management. The analysis shows the key and possibly unique contributions of processes at these levels, and suggests how they can be scaled up and linked to processes at other levels. Both types of analysis are largely missing in adaptive management theory, which has tended to focus on larger scale processes and to dismiss the potential of smaller scale ones to transform, expand, and link. This analysis focuses on salmon (Oncorhynchus spp. fisheries of British Columbia, Canada, but the literature suggests that the findings have far broader applicability.

  3. METHODS FOR OVERCOMING SEED DORMANCY AND THE INITIAL GROWTH OF Ziziphus joazeiro Mart. IN DIFFERENT SOILS

    Directory of Open Access Journals (Sweden)

    JOSENARA DAIANE DE SOUZA COSTA

    2016-01-01

    Full Text Available Considering the potential and importance of biodiversity of the Caatinga biome, studies on endemic species are relevant to conservation of its natural resources. The objectives of this work was to evaluate seed viability and physical methods for overcoming seed dormancy in juazeiro (Ziziphus joazeiro Mart. and assess the influence of different types of soil on the initial growth of juazeiro plants. The experiments were conducted in three stages. In the first stage, the viability of seeds from different lots was evaluated using the tetrazolium test. The second stage was conducted in a plant nursery, evaluating the application of physical processes (scarification with sandpaper and hammer in overcoming seed dormancy, and the initial growth of the plants. In the third step, the chlorophyll a and b contents, gas exchange and dry matter accumulation were evaluated in young juazeiro plants in three types of soil (Oxisol, Entisol and Vertisol. The results indicate that the viability of juazeiro seeds is greatly influenced by differences between the progenitor plants and by storage conditions, which enable a longevity of two years when stored at 22°C and 16% of relative humidity. The scarification methods with sandpaper and hammer are not efficient to reduce the time and uniform seed germination. The juazeiro plants have high growth potential in different edaphic environments, adapting well to soils of different textures and chemical compositions.

  4. Rwanda after the Genocide: Formal and Informal Institutions in Overcoming Development Traps

    Directory of Open Access Journals (Sweden)

    Ekaterina S. Glazova

    2015-01-01

    Full Text Available Permanent self-reproduction of crises or getting into so called development traps in underdeveloped countries constitutes one of the most significant world problems. An explanatory hypothesisis that antagonistic relationship between formal and informal institutions makes it impossible to overcome path dependence. The problem is illustrated by the case of Rwanda, which, despite the large-scale foreign aid in the 1960s-early 1990s, failed to resolve the growing socio-political contradictions that eventually led to the 1994 genocide. However, since the 2000s Rwanda has been demonstrating an upward trend especially in governance and control of corruption. In the author's view, success in the post-genocidal period was determined by two factors: first, by the institutional vacuum created by the collapse of competitive rules and practices of the President Habyarimana era; second, by the effective leadership shown by the ruling elite support of informal practices to overcome the crisis. Between the possible reform options the choice was made in favor of formalization of autochthonous practices, introduction of traditional or restored (filled with a new meaning institutions into the legal sphere, and creation of new rules. Rwanda is therefore an example of successful institutional transformation.

  5. Effect of storage in overcoming seed dormancy of Annona coriacea Mart. seeds

    Directory of Open Access Journals (Sweden)

    DAIANE M. DRESCH

    2014-12-01

    Full Text Available The aim of this study was to evaluate the effect of pre-treatments on overcoming dormancy of A. coriacea seeds. Seeds were processed and stored in polyethylene bags at temperatures of at -18°C (42% RH, 5°C (34% RH, 15°C (60% RH and 25°C (34% RH, during 0, 30, 60, 90, 120 and 150 days. After storage, seeds were immersed in 350 mg.L−1 gibberellic acid for 144 hours. Sowing was carried out in plastic bags containing Red Latosol + Bioplant®. Moisture content, emergence percentage, emergence speed index, length and dry mass of seedlings, were evaluated. The experimental design was completely randomized in a factorial with four replications of 50 seeds each. The seed storage at 5°C and subsequent immersion in gibberellic acid was efficient to reach high percentage, emergence speed and plant growth. A. coriacea seeds showed non-deep simple morphophysiological dormancy wherein the physiological component can be overcome after the seeds are storage at 5°C for a maximum period of 53 days and subsequent immersed in exogenous GA (350 mg.L−1 for 144 hours.

  6. Effect of storage in overcoming seed dormancy of Annona coriacea Mart. seeds.

    Science.gov (United States)

    Dresch, Daiane M; Scalon, Silvana P Q; Masetto, Tathiana E

    2014-12-01

    The aim of this study was to evaluate the effect of pre-treatments on overcoming dormancy of A. coriacea seeds. Seeds were processed and stored in polyethylene bags at temperatures of at -18°C (42% RH), 5°C (34% RH), 15°C (60% RH) and 25°C (34% RH), during 0, 30, 60, 90, 120 and 150 days. After storage, seeds were immersed in 350 mg.L-1 gibberellic acid for 144 hours. Sowing was carried out in plastic bags containing Red Latosol + Bioplant®. Moisture content, emergence percentage, emergence speed index, length and dry mass of seedlings, were evaluated. The experimental design was completely randomized in a factorial with four replications of 50 seeds each. The seed storage at 5°C and subsequent immersion in gibberellic acid was efficient to reach high percentage, emergence speed and plant growth. A. coriacea seeds showed non-deep simple morphophysiological dormancy wherein the physiological component can be overcome after the seeds are storage at 5°C for a maximum period of 53 days and subsequent immersed in exogenous GA (350 mg.L-1 for 144 hours).

  7. Overcoming Recruitment Barriers in Urban Older Adults Residing in Congregate Living Facilities

    Directory of Open Access Journals (Sweden)

    Adam Simning

    2015-01-01

    Full Text Available Background. Participation of minority older adults in mental health research has been limited by mistrust, transportation difficulties, lack of knowledge, and insufficient community partnership. We describe strategies utilized to overcome these recruitment barriers. Methods. Our target population included 553 public housing residents of older adult high-rise buildings in Rochester, NY. We had a two-stage cross-sectional study: Stage 1 was a health survey for all residents and Stage 2 was a psychiatric interview of English-speaking residents aged 60 years and older. Recruitment occurred through mailings, onsite activities, and resident referrals. Results. Stage 1 had 358 participants (64.7% response and Stage 2 had 190 (61.6% target population response, with higher participation among African Americans. We found some strategies effective for overcoming recruitment barriers. First, we partnered with a community agency and organized onsite educational activities to improve residents’ trust. Second, the study occurred entirely onsite, which facilitated participation of functionally impaired residents. Third, onsite activities allowed the residents to learn about the study and complete surveys in person. Fourth, we provided immediate incentives that resulted in many study referrals. Conclusions. Although recruitment of minority older adults presents unique challenges, a multifaceted community-tailored approach mitigated several recruitment barriers in this mental health study.

  8. Internationalization as a strategy to overcome industry barriers-An assessment of the marine energy industry

    International Nuclear Information System (INIS)

    Lovdal, Nicolai; Neumann, Frank

    2011-01-01

    Research on conditions to develop new innovations within emerging renewable energy industries is often done with a national focus. However, recent research on international entrepreneurship has revealed that firms operate on international levels very early in their life time. Thus, based on former research on international entrepreneurship and case examples, we build the propositions that firms in the marine energy industry use internationalization as a strategy to overcome industry barriers. Our primary source of data is a unique dataset from a global survey of all the companies in the marine energy industry who are aiming to commercialize a wave or tidal energy device. This paper is organized in two steps: first we identified the most challenging industry barriers perceived by companies. Second we use these to form propositions which we assess through empirical data. The two most challenging barriers perceived by the companies are need for capital and need for supportive political schemes. Our findings reveal that internationalization certainly is a common strategy to access capital and attractive support schemes in foreign countries. The early internationalization has implications for researchers, managers and policy makers. - Research highlights: → Industry barriers identified as access to capital and supportive political schemes. → International entrepreneurship is used to overcome industry barriers. → Start-ups in emerging energy industries 'shop' national support schemes. → Future research to provide policy advice should adapt to the international reality. → Research based on a worldwide survey of wave and tidal energy device developers.

  9. Awareness On Microgrids And Various Protection Issues To Overcome In It

    Directory of Open Access Journals (Sweden)

    Rachna Verma

    2015-05-01

    Full Text Available ABSTRACT As we know India faces problem of Power blackout every year due to the overloading on the main electrical grid. To avoid the above problem Microgrids are the best solution. Basically Microgrids are the small version of electrical grid. They are independent power system. Microgrids can be connected with renewable energy sources such as solar and wind. The use of renewable energy introduces the need of various storing devices and supplies it whenever required. Microgrids can provide wide range of applications in buildings military camps and corporateacademic campuses etc. They can have efficient and effective provision of electricity to off-grid areas as well as keep the lights on in times of crisis for critical applications like hospital. Though Microgrids being so advantageous it has several technical challenging issues to overcome i.e. voltage and frequency control islanding and its protection in Microgrids. This paper discusses the overview of Microgrids and issue to overcome in it-its Protection.

  10. Etanercept overcomes P-glycoprotein-induced drug resistance in lymphocytes of patients with intractable rheumatoid arthritis.

    Science.gov (United States)

    Tsujimura, Shizuyo; Saito, Kazuyoshi; Nakayamada, Shingo; Tanaka, Yoshiya

    2010-04-01

    P-glycoprotein (P-gp) on activated lymphocytes is an adenosine triphosphate (ATP)-binding cassette transporter that causes drug resistance by exclusion of intracellular drugs in patients with active rheumatoid arthritis (RA). However, infliximab with methotrexate (MTX) can overcome P-gp-mediated drug resistance. We encounter patients who cannot continue infliximab or MTX. Here we tested how etanercept affected P-gp-mediated drug resistance in such intractable RA patients. Peripheral lymphocytes of 11 RA patients (3 switched from infliximab and 8 who could not be treated with MTX) were analyzed for P-gp expression by flow cytometry and for drug exclusion using radioisotope-labeled dexamethasone. Activated lymphocytes of RA patients overexpressed P-gp and coexpressed CD69. Incubation of these lymphocytes with dexamethasone in vitro reduced intracellular dexamethasone levels. Two-week etanercept therapy significantly reduced P-gp expression and eliminated such P-gp- and CD69-high-expressing subgroup. The reduction in P-gp resulted in recovery of intracellular dexamethasone levels in lymphocytes and improvement of disease activity, thus allowing tapering of corticosteroids. None of the patients experienced any severe adverse effects. Etanercept is useful for overcoming P-gp-mediated treatment resistance in intractable RA patients who have to discontinue infliximab or are intolerant to MTX.

  11. Economic damage and state policy on the overcoming of the Chernobyl NPP catastrophe consequences. Chapter 2

    International Nuclear Information System (INIS)

    Konoplya, E.F.; Rolevich, I.V.

    1998-01-01

    The economic consequences of the Chernobyl NPP accident for the Republic of Belarus are given. The damage, taking into account the 30-years period needed for its overcoming, is estimated to be 235 billion US$ that is equal to 32 annual budgets of the republic of 1985. The losses connected with the deterioration of population health, damage incurred in industry and social sphere, agriculture, building complex, transport and communication, housing, with contamination of raw, mineral, land, water, forest and other resources are shown. The main directions of the state and legislative bodies activity on overcoming of the Chernobyl NPP accident consequences are directed on realization of complex of measures on maximum decreasing the radiation exposure dose; providing safety of people's health at the expense of medical preventive measures, improvement of their health, social insurance and resettlement from the zones where the safe living criteria are not observed; providing safe living conditions in regions subjected to radioactive contamination; rise of population life quality in these regions; scientific research of the problems connected with radiation influence on ecosystem, etc. The medical care and social protection systems of the affected population are describe

  12. Counter-stereotypical pictures as a strategy for overcoming spontaneous gender stereotypes

    Directory of Open Access Journals (Sweden)

    Eimear eFinnegan

    2015-08-01

    Full Text Available The present research investigated the use of counter-stereotypical pictures as a strategy for overcoming spontaneous gender stereotypes when certain social role nouns and professional terms are read. Across two experiments, participants completed a judgement task in which they were presented with word pairs comprised of a role noun with a stereotypical gender bias (e.g. beautician and a kinship term with definitional gender (e.g. brother. Their task was to quickly decide whether or not both terms could refer to one person. In each experiment they completed 2 blocks of such judgement trials separated by a training session in which they were presented with pictures of people working in gender counter-stereotypical (Experiment 1 or gender stereotypical roles (Experiment 2. To ensure participants were focused on the pictures, they were also required to answer 4 questions on each one relating to the character’s leisure activities, earnings, job satisfaction and personal life. Accuracy of judgements to stereotype incongruent pairings was found to improve significantly across blocks when participants were exposed to counter-stereotype images (9.87% as opposed to stereotypical images (0.12%, while response times decreased significantly across blocks in both studies. It is concluded that exposure to counter-stereotypical pictures is a valuable strategy for overcoming spontaneous gender stereotype biases in the short term.

  13. Text Based Analogy in Overcoming Student Misconception on Simple Electricity Circuit Material

    Science.gov (United States)

    Hesti, R.; Maknun, J.; Feranie, S.

    2017-09-01

    Some researcher have found that the use of analogy in learning and teaching physics was effective enough in giving comprehension in a complicated physics concept such as electrical circuits. Meanwhile, misconception become main cause that makes students failed when learning physics. To provide teaching physics effectively, the misconception should be resolved. Using Text Based Analogy is one of the way to identifying misconceptions and it is enough to assist teachers in conveying scientific truths in order to overcome misconceptions. The purpose of the study to investigate the use of text based analogy in overcoming students misconception on simple electrical circuit material. The samples of this research were 28 of junior high school students taken purposively from one high school in South Jakarta. The method use in this research is pre-experimental and design in one shot case study. Students who are the participants of sample have been identified misconception on the electrical circuit material by using the Diagnostic Test of Simple Electricity Circuit. The results of this study found that TBA can replace the misconceptions of the concept possessed by students with scientific truths conveyed in the text in a way that is easily understood so that TBA is strongly recommended to use in other physics materials.

  14. Methanol Extract of Myelophycus caespitosus Inhibits the ...

    African Journals Online (AJOL)

    Methanol Extract of Myelophycus caespitosus Inhibits the Inflammatory Response in Lipopolysaccharidestimulated BV2 Microglial Cells by Downregulating NF-kB via Inhibition of the Akt Signaling Pathway.

  15. Overcoming STC2 mediated drug resistance through drug and gene co-delivery by PHB-PDMAEMA cationic polyester in liver cancer cells.

    Science.gov (United States)

    Cheng, Hongwei; Wu, Zhixian; Wu, Caisheng; Wang, Xiaoyuan; Liow, Sing Shy; Li, Zibiao; Wu, Yun-Long

    2018-02-01

    Stanniocalcin 2 (STC2) overexpression in hepatocellular carcinoma (HCC) could lead to poor prognosis, which might be due to its induced P-glycoprotein and Bcl-2 protein expression level increase. P-glycoprotein or membrane pump induced drug efflux and altered prosurvival Bcl-2 expression are key mechanisms for drug resistance leading to failure of chemotherapy in HCC. However, current strategy to overcome both P-glycoprotein and Bcl-2 protein induced drug resistance was rarely reported. In this work, we utilized an amphiphilic poly[(R)-3-hydroxybutyrate] (PHB)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) cationic polyester to encapsulate chemotherapeutic paclitaxel (PTX) in hydrophobic PHB domain and Bcl-2 convertor Nur77/ΔDBD gene (Nur77 without DNA binding domain for mitochondria localization) by formation of polyplex due to cationic PDMAEMA segment, to effectively inhibit the drug resistant HepG2/STC2 and SMCC7721/STC2 liver cancer cell growth. Thanks to the cationic nanoparticle complex formation ability and high transfection efficiency to express Bcl-2 conversion proteins, PHB-PDMAEMA/PTX@polyplex could partially impair P-glycoprotein induced PTX efflux and activate the apoptotic function of previous prosurvival Bcl-2 protein. This is the pioneer report of cationic amphiphilic polyester PHB-PDMAEMA to codeliver anticancer drug and therapeutic plasmid to overcome both pump and non-pump mediated chemotherapeutic resistance in liver cancer cells, which might be inspiring for the application of polyester in personalized cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Pseudomonas sax genes overcome aliphatic isothiocyanate-mediated non-host resistance in Arabidopsis

    Science.gov (United States)

    Jun Fan; Casey Crooks; Gary Creissen; Lionel Hill; Shirley Fairhurst; Peter Doerner; Chris Lamb

    2011-01-01

    Most plant-microbe interactions do not result in disease; natural products restrict non-host pathogens. We found that sulforaphane (4-methylsulfinylbutyl isothiocyanate), a natural product derived from aliphatic glucosinolates, inhibits growth in Arabidopsis of non-host Pseudomonas bacteria in planta. Multiple sax genes (saxCAB/F/D/G) were identified in Pseudomonas...

  17. PARP Inhibition Restores Extrinsic Apoptotic Sensitivity in Glioblastoma

    Science.gov (United States)

    Karpel-Massler, Georg; Pareja, Fresia; Aimé, Pascaline; Shu, Chang; Chau, Lily; Westhoff, Mike-Andrew; Halatsch, Marc-Eric; Crary, John F.; Canoll, Peter; Siegelin, Markus D.

    2014-01-01

    Background Resistance to apoptosis is a paramount issue in the treatment of Glioblastoma (GBM). We show that targeting PARP by the small molecule inhibitors, Olaparib (AZD-2281) or PJ34, reduces proliferation and lowers the apoptotic threshold of GBM cells in vitro and in vivo. Methods The sensitizing effects of PARP inhibition on TRAIL-mediated apoptosis and potential toxicity were analyzed using viability assays and flow cytometry in established GBM cell lines, low-passage neurospheres and astrocytes in vitro. Molecular analyses included western blots and gene silencing. In vivo, effects on tumor growth were examined in a murine subcutaneous xenograft model. Results The combination treatment of PARP inhibitors and TRAIL led to an increased cell death with activation of caspases and inhibition of formation of neurospheres when compared to single-agent treatment. Mechanistically, pharmacological PARP inhibition elicited a nuclear stress response with up-regulation of down-stream DNA-stress response proteins, e.g., CCAAT enhancer binding protein (C/EBP) homology protein (CHOP). Furthermore, Olaparib and PJ34 increased protein levels of DR5 in a concentration and time-dependent manner. In turn, siRNA-mediated suppression of DR5 mitigated the effects of TRAIL/PARP inhibitor-mediated apoptosis. In addition, suppression of PARP-1 levels enhanced TRAIL-mediated apoptosis in malignant glioma cells. Treatment of human astrocytes with the combination of TRAIL/PARP inhibitors did not cause toxicity. Finally, the combination treatment of TRAIL and PJ34 significantly reduced tumor growth in vivo when compared to treatment with each agent alone. Conclusions PARP inhibition represents a promising avenue to overcome apoptotic resistance in GBM. PMID:25531448

  18. Overcoming obstacles in the design of cancer anorexia/weight loss trials.

    Science.gov (United States)

    Le-Rademacher, Jennifer G; Crawford, Jeffrey; Evans, William J; Jatoi, Aminah

    2017-09-01

    Most advanced cancer patients suffer loss of appetite (anorexia) and loss of weight. Despite the fact that cancer anorexia and weight loss are associated with a poor prognosis and detract from quality of life, no interventions have been demonstrated to palliate this syndrome in its entirety, particularly in patients with treatment-refractory malignancies. Recently, two registration trials - one with anamorelin and another with enobosarm - failed to reach their primary endpoints, thus raising questions. Were both these agents ineffective? Alternatively, did study design issues compromise the ability of these trials to identify effective agents? Thus, this review is timely insofar it serves as an introduction to study design, offers guidance on how to test promising agents for cancer anorexia/weight loss, and provides advice for overcoming trial design obstacles. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Targeting oncoprotein stability overcomes drug resistance caused by FLT3 kinase domain mutations.

    Directory of Open Access Journals (Sweden)

    Chuanjiang Yu

    Full Text Available FLT3 is the most frequently mutated kinase in acute myeloid leukemia (AML. Internal tandem duplications (ITDs in the juxta-membrane region constitute the majority of activating FLT3 mutations. Several FLT3 kinase inhibitors were developed and tested in the clinic with significant success. However, recent studies have reported the development of secondary drug resistance in patients treated with FLT3 inhibitors. Since FLT3-ITD is an HSP90 client kinase, we here explored if targeting the stability of drug-resistant FLT3 mutant protein could be a potential therapeutic option. We observed that HSP90 inhibitor treatment resulted in the degradation of inhibitor-resistant FLT3-ITD mutants and selectively induced toxicity in cells expressing FLT3-ITD mutants. Thus, HSP90 inhibitors provide a potential therapeutic choice to overcome secondary drug resistance following TKI treatment in FLT3-ITD positive AML.

  20. Overcoming barriers to high performance seismic design using lessons learned from the green building industry

    Science.gov (United States)

    Glezil, Dorothy

    NEHRP's Provisions today currently governing conventional seismic resistant design. These provisions, though they ensure the life-safety of building occupants, extensive damage and economic losses may still occur in the structures. This minimum performance can be enhanced using the Performance-Based Earthquake Engineering methodology and passive control systems like base isolation and energy dissipation systems. Even though these technologies and the PBEE methodology are effective reducing economic losses and fatalities during earthquakes, getting them implemented into seismic resistant design has been challenging. One of the many barriers to their implementation has been their upfront costs. The green building community has faced some of the same challenges that the high performance seismic design community currently faces. The goal of this thesis is to draw on the success of the green building industry to provide recommendations that may be used overcome the barriers that high performance seismic design (HPSD) is currently facing.

  1. Overcoming limits to near-field radiative heat transfer in uniform planar media through multilayer optimization.

    Science.gov (United States)

    Jin, Weiliang; Messina, Riccardo; Rodriguez, Alejandro W

    2017-06-26

    Radiative heat transfer between uniform plates is bounded by the narrow range and limited contribution of surface waves. Using a combination of analytical calculations and numerical gradient-based optimization, we show that such a limitation can be overcome in complicated multilayer geometries, allowing the scattering and coupling rates of slab resonances to be altered over a broad range of evanescent wavevectors. We conclude that while the radiative flux between two inhomogeneous slabs can only be weakly enhanced, the flux between a dipolar particle and an inhomogeneous slab-proportional to the local density of states-can be orders of magnitude larger, albeit at the expense of increased frequency selectivity. A brief discussion of hyperbolic metamaterials shows that they provide far less enhancement than optimized inhomogeneous slabs.

  2. Change in CNE boiler control level and stepback to overcome strong grid transients

    International Nuclear Information System (INIS)

    Lorenzetti, J.; Sablic, J.C.

    1991-01-01

    In Argentina the grid distribution is organized in such a way that the Embalse Power Plant is located in a place where power is produced. The most important places of power consumption are located near Buenos Aires city. Just one line connects Embalse with the consumption places. As a result of that condition the power is flowing through the interconnection line in such a way that every time a disturb cuts the line a strong power transient affects the Nuclear Power Plant. The changes in the boiler level control were done in order to avoid reactor trip, reactor stepback or turbine trip based on boiler level upsets. After several years of operation it was possible to verify that the new algorithm reduces the chances of plant outage increasing the confidence in the plant to overcome with success such transient. Every transient in the plant is analyzed in order to improve the control algorithm

  3. Comment on ‘Overcoming misconceptions in quantum mechanics with the time evolution operator’

    International Nuclear Information System (INIS)

    Toyama, F M; Nogami, Y

    2013-01-01

    In their paper ‘Overcoming misconceptions in quantum mechanics with the time evolution operator’, García Quijas and Arévalo Aguilar (2007 Eur. J. Phys. 28 147) examined the time-dependent wave function of a particle in the one-dimensional harmonic oscillator potential using two different methods. The two wave functions that the authors obtained through the methods have different analytical expressions. The authors showed numerically that the two wave functions lead to the same probability density. When the real parts of the wave functions are compared, however, they are different in their details. That was puzzling because both wave functions are supposed to be solutions of the same time-dependent Schrödinger equation with the same initial condition. We point out that the two wave functions are actually identical. We show this analytically. (letters and comments)

  4. Microbial advanced biofuels production: overcoming emulsification challenges for large-scale operation.

    Science.gov (United States)

    Heeres, Arjan S; Picone, Carolina S F; van der Wielen, Luuk A M; Cunha, Rosiane L; Cuellar, Maria C

    2014-04-01

    Isoprenoids and alkanes produced and secreted by microorganisms are emerging as an alternative biofuel for diesel and jet fuel replacements. In a similar way as for other bioprocesses comprising an organic liquid phase, the presence of microorganisms, medium composition, and process conditions may result in emulsion formation during fermentation, hindering product recovery. At the same time, a low-cost production process overcoming this challenge is required to make these advanced biofuels a feasible alternative. We review the main mechanisms and causes of emulsion formation during fermentation, because a better understanding on the microscale can give insights into how to improve large-scale processes and the process technology options that can address these challenges. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. How do new ventures in MNC ecosystems proactively overcome interfirm asymmetries?

    Directory of Open Access Journals (Sweden)

    Shameen Prashantham

    2011-09-01

    Full Text Available Several contemporary large multinational corporations (MNCs have developed interfirm ecosystems that are likely to attract a heterogeneous set of actors, including new ventures. New ventures are asymmetric vis-à-vis the focal MNC in terms of organisational size, structure and power which could be an impediment to the development of social capital between these sets of firms. And yet MNCs are potentially a source of novel information, opportunities and ideas. An interesting question to consider therefore is how new ventures overcome interfirm asymmetries to develop and leverage social capital with large MNCs. Our synthesis of the academic literature suggests that some new ventures are more adept than others at partnering with MNCs because they are more proactive in forming and leveraging interfirm ties with large MNCs. Insightful observations of four panellists shed light on how startups’ proactive behaviours can be vitally important in forming, consolidating and extending relationships with large MNCs.

  6. Overcoming the solubility limit with solubility-enhancement tags: successful applications in biomolecular NMR studies

    International Nuclear Information System (INIS)

    Zhou Pei; Wagner, Gerhard

    2010-01-01

    Although the rapid progress of NMR technology has significantly expanded the range of NMR-trackable systems, preparation of NMR-suitable samples that are highly soluble and stable remains a bottleneck for studies of many biological systems. The application of solubility-enhancement tags (SETs) has been highly effective in overcoming solubility and sample stability issues and has enabled structural studies of important biological systems previously deemed unapproachable by solution NMR techniques. In this review, we provide a brief survey of the development and successful applications of the SET strategy in biomolecular NMR. We also comment on the criteria for choosing optimal SETs, such as for differently charged target proteins, and recent new developments on NMR-invisible SETs.

  7. Measuring and overcoming limits of the Saffman-Delbrück model for soap film viscosities.

    Science.gov (United States)

    Vivek, Skanda; Weeks, Eric R

    2015-01-01

    We observe tracer particles diffusing in soap films to measure the two-dimensional (2D) viscous properties of the films. Saffman-Delbrück type models relate the single-particle diffusivity to parameters of the film (such as thickness h) for thin films, but the relation breaks down for thicker films. Notably, the diffusivity is faster than expected for thicker films, with the crossover at h/d = 5.2 ± 0.9 using the tracer particle diameter d. This indicates a crossover from purely 2D diffusion to diffusion that is more three-dimensional. We demonstrate that measuring the correlations of particle pairs as a function of their separation overcomes the limitations of the Saffman-Delbrück model and allows one to measure the viscosity of a soap film for any thickness.

  8. Overcoming practical challenges to conducting clinical research in the inpatient stroke rehabilitation setting.

    Science.gov (United States)

    Campbell, Grace B; Skidmore, Elizabeth R; Whyte, Ellen M; Matthews, Judith T

    2015-10-01

    There is a shortage of published empirical studies conducted in acute inpatient stroke rehabilitation, though such studies are greatly needed in order to shed light on the most efficacious inpatient stroke rehabilitation interventions. The inherent challenges of inpatient research may dissuade researchers from undertaking this important work. This paper describes our institution's experience devising practical solutions to research barriers in this setting. Through concentrated efforts to overcome research barriers, such as by cultivating collaborative relationships and capitalizing on unanticipated benefits, we successfully facilitated conduct of five simultaneous inpatient stroke studies. Tangible benefits realized include increased effectiveness of research participant identification and enrollment, novel collaborative projects, innovative clinical care initiatives, and enhanced emotional and practical support for patients and their families. We provide recommendations based on lessons learned during our experience, and discuss benefits of this collaboration for our research participants, clinical staff, and the research team.

  9. A separation-integrated cascade reaction to overcome thermodynamic limitations in rare-sugar synthesis.

    Science.gov (United States)

    Wagner, Nina; Bosshart, Andreas; Failmezger, Jurek; Bechtold, Matthias; Panke, Sven

    2015-03-27

    Enzyme cascades combining epimerization and isomerization steps offer an attractive route for the generic production of rare sugars starting from accessible bulk sugars but suffer from the unfavorable position of the thermodynamic equilibrium, thus reducing the yield and requiring complex work-up procedures to separate pure product from the reaction mixture. Presented herein is the integration of a multienzyme cascade reaction with continuous chromatography, realized as simulated moving bed chromatography, to overcome the intrinsic yield limitation. Efficient production of D-psicose from sucrose in a three-step cascade reaction using invertase, D-xylose isomerase, and D-tagatose epimerase, via the intermediates D-glucose and D-fructose, is described. This set-up allowed the production of pure psicose (99.9%) with very high yields (89%) and high enzyme efficiency (300 g of D-psicose per g of enzyme). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. The Understanding of Loyalty in J. Royce and The Role of Loyalty in Overcoming The Evil

    Directory of Open Access Journals (Sweden)

    Emel Koç

    2011-06-01

    Full Text Available Stating that no philosophical issue is more discouraging than misstatement of the problem of evil in theory, Josiah Royce focused his attention on the problem of evil in accordance with the overall trend of philosophy in the 18th and 19th centuries. The most striking characteristic of Royce‟s approach to problem of evil is that he considered a loyalty-based moral perception to overcome this problem. Approaching the problem of evil through an existentialist perspective rather than a rational point of view and underlining that the problem of evil can only be addressed responsibly through experiencing it in practice, Royce emphasized a collective will and responsibility, which for Royce needs to be produced through loyalty, in fighting the evil

  11. Strategies to overcome or circumvent P-glycoprotein mediated multidrug resistance.

    Science.gov (United States)

    Yuan, Hongyu; Li, Xun; Wu, Jifeng; Li, Jinpei; Qu, Xianjun; Xu, Wenfang; Tang, Wei

    2008-01-01

    Cancer patients who receive chemotherapy often experience intrinsic or acquired resistance to a broad spectrum of chemotherapeutic agents. The phenomenon, termed multidrug resistance (MDR), is often associated with the over-expression of P-glycoprotein, a transmembrane protein pump, which can enhance efflux of a various chemicals structurally unrelated at the expense of ATP depletion, resulting in decrease of the intracellular cytotoxic drug accumulation. The MDR has been a big threaten to the human health and the war fight for it continues. Although several other mechanisms for MDR are elucidated in recent years, considerable efforts attempting to inverse MDR are involved in exploring P-glycoprotein modulators and suppressing P-glycoprotein expression. In this review, we will report on the recent advances in various strategies for overcoming or circumventing MDR mediated by P-glycoprotein.

  12. Overcoming barriers to exercise among parents: A social cognitive theory perspective

    Science.gov (United States)

    Mailey, Emily L.; Phillips, Siobhan M.; Dlugonski, Deirdre; Conroy, David E.

    2017-01-01

    Parents face numerous barriers to exercise and exhibit high levels of inactivity. Examining theory-based determinants of exercise among parents may inform interventions for this population. The purpose of this study was to test a social-cognitive model of parental exercise participation over a 12-month period. Mothers (n=226) and fathers (n=70) of children exercise, barriers self-efficacy, perceived barriers, and exercise planning at baseline and one year later. Panel analyses were used to test the hypothesized relationships. Barriers self-efficacy was related to exercise directly and indirectly through perceived barriers and prioritization/planning. Prioritization and planning also mediated the relationship between perceived barriers and exercise. These paths remained significant at 12 months. These results suggest efforts to increase exercise in parents should focus on improving confidence to overcome exercise barriers, reducing perceptions of barriers, and helping parents make specific plans for prioritizing and engaging in exercise. PMID:27108160

  13. Human health and nutrition: How isotopes are helping to overcome ''hidden hunger''

    International Nuclear Information System (INIS)

    Parr, R.M.; Fjeld, C.R.

    1994-01-01

    In a number of ways, the work of the IAEA is contributing to efforts directed at overcoming hidden hunger and other nutrition problems. The rationale for the IAEA's involvement is twofold. First, adequate nutrition is an essential component of any strategy for improving health, and the IAEA's Statute specifically identifies ''enlarging the contribution of atomic energy to peace, health and prosperity'' as the major objective of programmes. Second, isotope techniques have a wide variety of applications -some of them unique - for targeted research in human nutrition, for assessing nutritional status, and for monitoring the effectiveness of nutritional intervention programmes. This article provides a brief overview of these techniques and their main applications in areas of human nutrition

  14. Chromosomocentric approach to overcoming difficulties in implementation of international project Human Proteome

    Directory of Open Access Journals (Sweden)

    A. I. Archakov

    2013-12-01

    Full Text Available The international project Human Proteome (PHP, being a logical continuation of the project Human Genome, was started on September 23, 2010. In correspondence with the genocentric approach, the PHP aim is to prepare a catalogue of all human proteins and to decipher a network of their interactions. The PHP implementation difficulties arise because the research subject itself – proteome – is much more complicated than genome. The major problem is the insufficient sensitivity of proteome methods that does not allow detecting low- and ultralow-copy proteins. Bad reproducibility of proteome methods and the lack of so-called “gold standard” is the second major complicacy in PHP implementation. The third problem is the dynamic character of proteome, its instabili­ty in time. The paper deals with possible variants of overcoming these complicacies, preventing from successful implementation of PHP.

  15. Complementary Health Approaches: Overcoming Barriers to Open Communication During Cancer Therapy
.

    Science.gov (United States)

    Wanchai, Ausanee; Armer, Jane M; Smith, Kandis M; Rodrick, Julia

    2017-12-01

    Complementary health approaches (CHAs) have been widely used by patients with cancer for many reasons. However, some patients choose not to disclose their use of CHAs to their nurses, fearing that this use will be viewed as unacceptable. Nurses may be uncomfortable talking about CHAs because of a lack of evidence-based research on the subject.
. This article promotes ways in which nurses can overcome barriers to open communication about CHAs with patients during cancer therapy.
. The literature related to CHAs and communication was reviewed.
. To encourage open communication between nurses and patients regarding the use of CHAs, nurses need to be more knowledgeable about CHAs through training or by conducting research related to CHAs.

  16. "Closing the Loop": Overcoming barriers to locally sourcing food in Fort Collins, Colorado

    Science.gov (United States)

    DeMets, C. M.

    2012-12-01

    Environmental sustainability has become a focal point for many communities in recent years, and restaurants are seeking creative ways to become more sustainable. As many chefs realize, sourcing food locally is an important step towards sustainability and towards building a healthy, resilient community. Review of literature on sustainability in restaurants and the local food movement revealed that chefs face many barriers to sourcing their food locally, but that there are also many solutions for overcoming these barriers that chefs are in the early stages of exploring. Therefore, the purpose of this research is to identify barriers to local sourcing and investigate how some restaurants are working to overcome those barriers in the city of Fort Collins, Colorado. To do this, interviews were conducted with four subjects who guide purchasing decisions for restaurants in Fort Collins. Two of these restaurants have created successful solutions and are able to source most of their food locally. The other two are interested in and working towards sourcing locally but have not yet been able to overcome barriers, and therefore only source a few local items. Findings show that there are four barriers and nine solutions commonly identified by each of the subjects. The research found differences between those who source most of their food locally and those who have not made as much progress in local sourcing. Based on these results, two solution flowcharts were created, one for primary barriers and one for secondary barriers, for restaurants to assess where they are in the local food chain and how they can more successfully source food locally. As there are few explicit connections between this research question and climate change, it is important to consider the implicit connections that motivate and justify this research. The question of whether or not greenhouse gas emissions are lower for locally sourced food is a topic of much debate, and while there are major developments

  17. The Role of Serbian Higher Business Education in Overcoming the Challenges of SME Managers

    Directory of Open Access Journals (Sweden)

    Maja Kočevar

    2014-06-01

    Full Text Available In this exploratory study, in-depth interviews with Serbian managers of small and medium-sized enterprises (SMEs were conducted to identify their main work-related challenges and the extent to which formal higher business education has helped them to overcome these challenges. Serbian SME managers find the main challenges to be related to HR- and marketing-related issues, followed by country-specific problems, such as dealing with bureaucracy, difficulties in obtaining financial resources, and coping with delayed payments. They see considerable deficits in the current system of higher business education, specifically referring to a lack of practice-oriented teaching methods and insufficient cooperation between the universities and the business sector.

  18. The nature of socio-psychological barriers to peaceful conflict resolution and ways to overcome them

    Directory of Open Access Journals (Sweden)

    Daniel Bar-Tal

    2013-10-01

    Full Text Available The many devastating, violent inter-group conflicts raging in different parts of the world are very current and actual. Such conflicts arise from disputes over incompatible goals and interests in different domains that must be addressed in seeking to find a solution. It is well established that these conflicts might be resolved were it not for strong socio-psychological barriers that help to sustain them. These barriers block progress toward peaceful conflict settlement. They pertain to the integrated operation of cognitive, emotional and motivational processes combined with a pre-existing repertoire of rigid supporting beliefs, worldviews and emotions that favor selective, biased and distorted information processing. This paper elaborates on the nature of socio-psychological barriers and proposes ways to overcome them.

  19. Family constellation as a treatment for overcoming the consequences of violence on victims

    Directory of Open Access Journals (Sweden)

    Hrnčić Jasna

    2017-01-01

    Full Text Available The subject of this paper is the implementation of family constellations by Bert Hellinger in work with clients with special emphasis on victims of physical and sexual violence. Although extremely popular in Europe and the world it has not been presented in Serbian scientific literature. As the approach has been developed in Germany as an answer to the situation where a significant part of population was a victim or perpetrator of violence during the Second World War causing suffering not only to them, but also to their offsprings, it offers a special contribution to the work with victims of violence. The aims of the paper are the presentation and analysis of the implementation of family constellations by Bert Hellinger and their effects generally in work with clients as well as with victims of physical and sexual violence. The technique of family constellations based on systemic and phenomenological approach is presented and discussed. Work is in the group, where participants form the circle and person who seeks problem resolution invites representatives - persons who are crucial for problem solution previously agreed with constellation facilitator - constellator. The constellator communicate with the representatives, encouraging them to express feelings, sensations and movement that will facilitate progress towards finding the optimal solution. The basic theoretical concepts are also analysed, including two types of conscience (individual and family, three basic principles of orders of love (principle of equal right to belong, principle of balance between giving and taking and principle of order and three levels of the soul (individual, family and great soul. The approach to overcoming consequences of violence on victims of physical violence and incest through symbolic interconnecting with the perpetrator is analysed. When it is applied to violence the victim has an opportunity to get a more comprehensive understanding and to experience an

  20. Pretreatment and fermentation strategies to overcome the toxicity of acetic acid in hemicellulosic hydrolysates

    DEFF Research Database (Denmark)

    Mussatto, Solange I.

    Acetic acid is one of the most important toxic compounds present in hemicellulosic hydrolysates. In order to overcome this problem, several strategies were studied for both biomass pretreatment and fermentation steps. Biomass deacetylation by mild alkaline pretreatment or using high pressure CO2...... where acetic acid can also be integrated as a valuable final product. For the fermentation step, it is well known that hemicellulosic hydrolysates usually need to be detoxified prior use as fermentation medium in order to improve the performance of the microorganism to convert sugars in the product...... of interest. Although detoxification improves the fermentability of hydrolysates, this additional step adds cost and complexity to the process and generates extra waste products. In this sense, the adaptation of the fermenting microorganism to increased concentrations of acetic acid can be considered...

  1. Building America Guidance for Identifying and Overcoming Code, Standard, and Rating Method Barriers

    Energy Technology Data Exchange (ETDEWEB)

    Cole, Pamala C.; Halverson, Mark A.

    2013-09-01

    The U.S. Department of Energy’s (DOE) Building America program implemented a new Codes and Standards Innovation (CSI) Team in 2013. The Team’s mission is to assist Building America (BA) research teams and partners in identifying and resolving conflicts between Building America innovations and the various codes and standards that govern the construction of residences. A CSI Roadmap was completed in September, 2013. This guidance document was prepared using the information in the CSI Roadmap to provide BA research teams and partners with specific information and approaches to identifying and overcoming potential barriers to Building America (BA) innovations arising in and/or stemming from codes, standards, and rating methods. For more information on the BA CSI team, please email: CSITeam@pnnl.gov

  2. Retelling the educational pathways of Black women physicists: Stories of experiencing and overcoming obstacles in life

    Science.gov (United States)

    Mensah, Felicia

    This is an empirical study on the underrepresentation of people of color in scientific careers. Grounded in critical race theory, the paper examines the lived experiences of six Black women physicists and addresses obstacles faced in their career paths and strategies used to overcome these obstacles. Data for this study were collected through semi-structured interviews and coded for emergent themes. The findings reveal that college recruitment and funding were fundamental for these women to choose physics over other STEM fields. In addition, Black women experience unique challenges of socialization in STEM, particularly by exclusion of study groups. We suggest physics departments provide a more inclusive environment to support Black women in science. CAPES, the Fulbright Program, Comissão Fulbright Brasil, and the Office of Diversity at Teachers College, Columbia University.

  3. Overcoming the sign problem in 1-dimensional QCD by new integration rules with polynomial exactness

    Energy Technology Data Exchange (ETDEWEB)

    Ammon, A. [IVU-Traffic Technologies AG, Berlin (Germany); Hartung, T. [King' s College London (United Kingdom). Dept. of Mathematics; Jansen, K.; Volmer, J. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC; Leoevey, H. [Humboldt-Universitaet, Berlin (Germany). Inst. fuer Mathematik

    2016-08-15

    In this paper we describe a new integration method for the groups U(N) and SU(N), for which we verified numerically that it is polynomially exact for N≤3. The method is applied to the example of 1-dimensional QCD with a chemical potential. We explore, in particular, regions of the parameter space in which the sign problem appears due the presence of the chemical potential. While Markov Chain Monte Carlo fails in this region, our new integration method still provides results for the chiral condensate on arbitrary precision, demonstrating clearly that it overcomes the sign problem. Furthermore, we demonstrate that our new method leads to orders of magnitude reduced errors also in other regions of parameter space.

  4. TYPICAL BANKING CRISES INTERNATIONAL BUSINESS ENVIRONMENT AND WAYS TO OVERCOME THEM

    Directory of Open Access Journals (Sweden)

    Ion Gr. IONESCU

    2014-06-01

    Full Text Available International financial environment is characterized as consisting of free trade and especially from the free movement of the capital on the financial markets, so very favourable, which also led to the rapid development of global financial markets. We lack the ability to keep the peace (silence for to counter the excesses of the financial markets. Without this ability, the global economy is exposed to the collapse. Financial capital enjoys a privileged position. He is more mobile than other factors of production and even more mobile than direct investment. Yet crises must be overcome. To support the arguments of this paper, we use a flexible methodology, starting from simple to complex, from theoretical to practical, from principle, to particularly, adding, specialty practice examples, from the international sphere, convinced that work-international banking must be healthy, able to generate profitable and dynamic business environments, safe for entrepreneurs and bankers, but also ordinary people.

  5. The Implementation Effort Islamic Law Norms in Activities for Overcoming Pornography and Pornoaction on Mass Media

    Directory of Open Access Journals (Sweden)

    Ramlani Lina Sinaulan

    2017-02-01

    Full Text Available This paper discusses the effort Islamic Law norms in activities for overcoming pornography and porno-action on mass media. By using normative legal research, the result found that the concept of Islamic law, behave based on sharia, shows the importance of shaping the personality traits of Islam (syakhsiyya Islāmiyya and based on the devotion and faith. Because of the relation to the formulation of the rule of law against pornography behavior, it can not be designed, prepared and formulated based on social values. Based on the facts of society, as a result of the moral decadence that led to a permissive attitude towards their cultural infiltration, the social values in assessing the behavior may become more permissive toward behavior. However, the use of religious norms which have universal properties will not change, and even capable of elastic with the times.

  6. Overcoming barriers to electronic medical record (EMR) implementation in the US healthcare system: A comparative study.

    Science.gov (United States)

    Kumar, Sameer; Aldrich, Krista

    2010-12-01

    An EMR system implementation would significantly reduce clinician workload and medical errors while saving the US healthcare system major expense. Yet, compared to other developed nations, the US lags behind. This article examines EMR system efforts, benefits, and barriers, as well as steps needed to move the US closer to a nationwide EMR system. The analysis includes a blueprint for implementation of EMR, industry comparisons to highlight the differences between successful and non-successful EMR ventures, references to costs and benefit information, and identification of root causes. 'Poka-yokes' (avoid (yokeru) mistakes (poka)) will be inserted to provide insight into how to systematically overcome challenges. Implementation will require upfront costs including patient privacy that must be addressed early in the development process. Government structure, incentives and mandates are required for nationwide EMR system in the US.

  7. AID to overcome the limitations of genomic information by introducing somatic DNA alterations.

    Science.gov (United States)

    Honjo, Tasuku; Muramatsu, Masamichi; Nagaoka, Hitoshi; Kinoshita, Kazuo; Shinkura, Reiko

    2006-05-01

    The immune system has adopted somatic DNA alterations to overcome the limitations of the genomic information. Activation induced cytidine deaminase (AID) is an essential enzyme to regulate class switch recombination (CSR), somatic hypermutation (SHM) and gene conversion (GC) of the immunoglobulin gene. AID is known to be required for DNA cleavage of S regions in CSR and V regions in SHM. However, its molecular mechanism is a focus of extensive debate. RNA editing hypothesis postulates that AID edits yet unknown mRNA, to generate specific endonucleases for CSR and SHM. By contrast, DNA deamination hypothesis assumes that AID deaminates cytosine in DNA, followed by DNA cleavage by base excision repair enzymes. We summarize the basic knowledge for molecular mechanisms for CSR and SHM and then discuss the importance of AID not only in the immune regulation but also in the genome instability.

  8. Overcoming barriers to exercise among parents: a social cognitive theory perspective.

    Science.gov (United States)

    Mailey, Emily L; Phillips, Siobhan M; Dlugonski, Deirdre; Conroy, David E

    2016-08-01

    Parents face numerous barriers to exercise and exhibit high levels of inactivity. Examining theory-based determinants of exercise among parents may inform interventions for this population. The purpose of this study was to test a social-cognitive model of parental exercise participation over a 12-month period. Mothers (n = 226) and fathers (n = 70) of children self-efficacy, perceived barriers, and exercise planning at baseline and 1 year later. Panel analyses were used to test the hypothesized relationships. Barriers self-efficacy was related to exercise directly and indirectly through perceived barriers and prioritization/planning. Prioritization and planning also mediated the relationship between perceived barriers and exercise. These paths remained significant at 12 months. These results suggest efforts to increase exercise in parents should focus on improving confidence to overcome exercise barriers, reducing perceptions of barriers, and helping parents make specific plans for prioritizing and engaging in exercise.

  9. Overcoming challenges to gender equality in the workplace leadership and innovation

    CERN Document Server

    Flynn, Patricia M; Kilgour, Maureen A

    2016-01-01

    Many businesses and organizations are increasingly aware of the case for promoting gender equality, both within and outside their organizational boundaries. Evidence suggests that gender equality in the workplace boosts performance, and legal frameworks in many countries mandate specific action on gender inequality in the workplace. However, despite organizational policies on promoting equality and equal opportunities, there remain challenges to be overcome in many businesses, including throughout their supply chains. The book provides research rationales as to why responsible organizations must address the issue of gender equality in the workplace. It also presents case studies, action research and examples of good practices, describing how businesses and organizations are working to promote gender equality in various contexts. The book is designed to support the rationale for gender equality in business and organizations, provide evidence of implementation of gender equality in the workplace, and how to dea...

  10. Dormancy overcoming, temperatures and substrates on germination of Mimosa tenuiflora Willd seeds

    Directory of Open Access Journals (Sweden)

    Clarisse Pereira Benedito

    2017-03-01

    Full Text Available Mimosa tenuiflora Willd., popularly known as jurema-preta, is an arboreal species of great importance for the brazilian Northeast due to its uses as a medicinal plant and in the restoration of degraded soils. No information is available in the Rules for Seed Analysis and the Instructions for Seed Analysis of Forest Species regarding ideal conditions for of this species. Thus, this study aimed at evaluating the influence of pre-germination treatments, in addition to verifying the germination performance at different temperatures and in different substrates. In both experiments, four replicates of 25 seeds were used for each treatment. In experiment I, seeds were submitted to the following methods for overcoming dormancy: witness - Intact seeds (T1 immersion in water at 100 °C for 1 (T2, 2 (T3, 3 (T4, 4 (T5, 5 (T6 and 6 min (T7, immersion in concentrated sulfuric acid for 1 (T8, 4 (T9, 7 (T10, 10 (T11 and 13 min (T12, scarification on sandpaper n° 80 (T13 and lopping in the region opposite the micropyle (T14. In experiment II, seed germination was evaluated in four types of substrates: between sand, paper on, paper roll and between vermiculite and at six different temperatures: 20, 25, 30, 35, 40 °C and alternating between 20 and 30 °C. Immersion in hot water for 1, 2, 3, 4, 5 and 6 min, sulfuric acid treatment for 10 and 13 min, sand paper and lopping were the most appropriate treatments to overcome seed dormancy. The seed germination of M. Tenuiflora should be carried out at 25 °C on paper roll substrate.

  11. Evidence that implementation intentions can overcome the effects of smoking habits.

    Science.gov (United States)

    Armitage, Christopher J

    2016-09-01

    In this study, the aim was to (a) test for the first time whether implementation intentions formed outside the laboratory can overcome the effects of habits, and (b) see whether the operation of implementation intentions could be improved by asking people to form certain "when-then" plans as opposed to uncertain "if-then" plans. The study employed a 2 × 2 fully factorial design with baseline and follow-up measures of smoking status and habits. Smokers (N = 168; circa 33 years of age; 79 women, 89 men) were randomly allocated to 1 of 2 intervention groups to form either if-then plans or when-then plans using supporting tools, or to 1 of 2 control conditions in which they were exposed to identical supporting tools but were not asked to form if-then plans or when-then plans. Certainty did not affect the operation of implementation intentions, but smokers who formed implementation intentions were significantly more likely to quit, χ2(1, N = 168) = 8.86, p smoking habits (95% CI [0.02, 0.14]). Similar effects were observed when cigarettes smoked per day, nicotine dependence, and craving served as the dependent variables. The findings demonstrate that people who have formed implementation intentions can overcome habits, such as smoking, outside the laboratory. The supporting tools described in the present research could be deployed at low cost with high public health reach to support behavior change. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  12. Overcoming diabetes-related stigma in Iran: A participatory action research.

    Science.gov (United States)

    Doosti-Irani, Mehri; Abdoli, Samereh; Parvizy, Soroor; Fatemi, Naimeh Seyed

    2017-08-01

    The study aimed to overcome diabetes-related stigma in individuals living with type 1 Diabetes Mellitus (T1DM) in Iran. The study proposed that if individuals with T1DM and the community work together to develop and implement an anti-stigma program, diabetes-related stigma in individuals with T1DM can be reduced. This study was conducted as a participatory action research study based on Kemmis and McTaggert's (2000) Model to design and implement an anti-stigma program for T1DM. Participants were selected among individuals with T1DM, their family members, health care providers, and residents without diabetes in Isfahan, Iran. Data collection was conducted using interviews, focus groups, emails, and text messages. Content analysis was used to analyze the data to develop anti-stigma interventions. Interventions were prioritized based on the Suitability, Feasibility and Flexibility (SFF) Matrix. Anti-stigma interventions were implemented in different levels in Isfahan, Iran, from 2011 to 2014. The effect of the program was evaluated based on interviews, feedback, and focus groups at the individual level. However, interventions were implemented in different levels including community, organization, family, and individual. Participants with T1DM experienced significant empowerment during the project to overcome diabetes-related stigma. The three main themes indicating this feeling of empowerment are "from doubt to trust", "from shadow to light", and "from me to us". Participatory action research can be an effective way to reduce diabetes-related stigma in individuals living with T1DM. It integrates the voices of the marginalized group reducing stigma and discrimination against diabetes. Copyright © 2017. Published by Elsevier Inc.

  13. OVERCOMING THE CULTURAL DIFFERENCES: PARABLE AS A MEANS OF INTERCULTURAL DIALOGUE

    Directory of Open Access Journals (Sweden)

    Tetyana V. Danylova

    2013-09-01

    Full Text Available Purpose. This article attempts to investigate the ways to overcome negative after-effects of intercultural communication. Methodology and theoretical results: To avoid the negative after-effects of intercultural communication caused by the clash of different reality tunnels, it is necessary to go beyond the framework of the specific symbolical territory, which is seen as the only true reality. Expanding the horizons of life, going beyond the boundaries of a personal reality tunnel can be achieved, in particular, by using parables. Acquaintance with parables helps to extend the set of the world perception models and to change the positions of the communication process participants. Parables act as intermediaries between people of different cultures and mentalities. Owing to its archetypical form, parable becomes one of the most popular narratives illustrating deep and multi-faceted truths that sometimes cannot be expressed by any other way. Parable serves as an open and flexible model of the world and a model of an individual "I self". This model helps people to constitute themselves as a part of their world. Parable requires to reject its interpretation in the oppositions inherent in a given culture and to reconsider the very way of understanding. Rejection of the oppositions provides the possibility of perceiving the world as integrity, unity in diversity, helps to overcome one-sided picture of the inner world of a man and his life in society. Understanding of a parable works towards changing personal position, and human creative nature is actualized. Conclusion: Parables uniquely reflect the real world and contribute to personal understanding of reality. Parables are successfully transplanted into different cultures operating as heritage of a culture-recipient and as a connecting link, which optimizes an intercultural dialogue.

  14. Strategies to overcome obstacles in the facilitation of critical thinking in nursing education.

    Science.gov (United States)

    Mangena, Agnes; Chabeli, Mary M

    2005-05-01

    This paper seeks to describe strategies that can be used to overcome obstacles in the facilitation of critical thinking in nursing education. A qualitative, explorative, descriptive and contextual design was used to conduct the research in which fourth year basic comprehensive students and nurse educators volunteered to take part in the study by signing an informed consent. The participants were purposively selected. Focus group interviews were used to collect data from both groups. Tesch's descriptive method of open coding described in (Creswell, J. 1994. Qualitative and quantitative approach. Sage, London.) was used to analyse data. (Democratic Nursing Organisation of South Africa, 1998. Ethical standards for nurse researchers. Denosa, Pretoria) ethical standards for research were observed to maintain the standard and quality of the research. (Lincoln, Y.S., Guba, E.G. 1985. Naturalistic inquiry. Sage, London.) framework was used to ensure trustworthiness of the study. The following obstacles were identified and recontextualised within the existing literature to be able to describe the strategies to overcome the identified obstacles to the facilitation of critical thinking of students: the educators' lack of knowledge; use of teaching and assessment methods that do not facilitate critical thinking of learners; the negative attitudes of educators and their resistance to change; inappropriate selection process and poor educational background that did not facilitate critical thinking of students; inadequate socialisation, cultural and instructional language incompetence. Findings indicated that there is a need for nurse educators to model critical thinking in all aspects of nursing education. It is recommended that there be a whole paradigm shift in nursing education from the traditional teacher-centred methods to a more learner-centred approach that will facilitate critical thinking of student nurses.

  15. Overcoming Barriers to Public Engagement through a Multi-Institution Consortium

    Science.gov (United States)

    Lambert, K. F.; Weiss, M.; Garlick, S.

    2016-12-01

    A growing body of evidence suggests that public engagement with science (PES) can enhance the relevance and impact of science on society. At the same time, advances in our understanding of public engagement suggest that greater skills, resources, and time horizons are often required to create effective programs. Consequently, despite a proliferation of training programs, many scientists still face the challenge of balancing the demands of public engagement with the requirements of their disciplinary research. Novel institutions are emerging that bring together interdisciplinary networks of principle investigators with PES practitioners to overcome barriers to effective and sustained public engagement in the environmental sciences. We will use the Science Policy Exchange (SPE), a consortium housed at the Harvard Forest, Harvard University, to illustrate how PIs and PES practitioners can collaborate to design public engagement processes, conduct policy-relevant scientific syntheses, and implement science communication strategies. Results from two SPE case studies demonstrate how multi-institutional consortia can help scientists overcome barriers such as lack of knowledge of evidence-based PES approaches, limits on time and funding to implement PES projects, and the need to integrate PES activities with research. The case studies also show how SPE strives to achieve credibility, saliency, and legitimacy in different public policy contexts: (1) engagement between scientists and local stakeholders to develop scenarios of landscape change; and (2) engagement between scientists and policy makers to understand the relationship between power plant emission standards, and air quality, human health and ecosystem function. The presentation will conclude with examples of how SPE programs have led to institutional change (staffing and budget), cultural change (attitudes and expectations of senior leaders), and research change (development of research questions, funding proposals

  16. Mental health care for irregular migrants in Europe: Barriers and how they are overcome

    Directory of Open Access Journals (Sweden)

    Straßmayr Christa

    2012-05-01

    Full Text Available Abstract Background Irregular migrants (IMs are exposed to a wide range of risk factors for developing mental health problems. However, little is known about whether and how they receive mental health care across European countries. The aims of this study were (1 to identify barriers to mental health care for IMs, and (2 to explore ways by which these barriers are overcome in practice. Methods Data from semi-structured interviews with 25 experts in the field of mental health care for IMs in the capital cities of 14 European countries were analysed using thematic analysis. Results Experts reported a range of barriers to mental health care for IMs. These include the absence of legal entitlements to health care in some countries or a lack of awareness of such entitlements, administrative obstacles, a shortage of culturally sensitive care, the complexity of the social needs of IMs, and their fear of being reported and deported. These barriers can be partly overcome by networks of committed professionals and supportive services. NGOs have become important initial points of contact for IMs, providing mental health care themselves or referring IMs to other suitable services. However, these services are often confronted with the ethical dilemma of either acting according to the legislation and institutional rules or providing care for humanitarian reasons, which involves the risk of acting illegally and providing care without authorisation. Conclusions Even in countries where access to health care is legally possible for IMs, various other barriers remain. Some of these are common to all migrants, whilst others are specific for IMs. Attempts at improving mental health care for IMs should consider barriers beyond legal entitlement, including communicating information about entitlement to mental health care professionals and patients, providing culturally sensitive care and ensuring sufficient resources.

  17. Overcoming the rate-distance limit of quantum key distribution without quantum repeaters.

    Science.gov (United States)

    Lucamarini, M; Yuan, Z L; Dynes, J F; Shields, A J

    2018-05-01

    Quantum key distribution (QKD) 1,2 allows two distant parties to share encryption keys with security based on physical laws. Experimentally, QKD has been implemented via optical means, achieving key rates of 1.26 megabits per second over 50 kilometres of standard optical fibre 3 and of 1.16 bits per hour over 404 kilometres of ultralow-loss fibre in a measurement-device-independent configuration 4 . Increasing the bit rate and range of QKD is a formidable, but important, challenge. A related target, which is currently considered to be unfeasible without quantum repeaters 5-7 , is overcoming the fundamental rate-distance limit of QKD 8 . This limit defines the maximum possible secret key rate that two parties can distil at a given distance using QKD and is quantified by the secret-key capacity of the quantum channel 9 that connects the parties. Here we introduce an alternative scheme for QKD whereby pairs of phase-randomized optical fields are first generated at two distant locations and then combined at a central measuring station. Fields imparted with the same random phase are 'twins' and can be used to distil a quantum key. The key rate of this twin-field QKD exhibits the same dependence on distance as does a quantum repeater, scaling with the square-root of the channel transmittance, irrespective of who (malicious or otherwise) is in control of the measuring station. However, unlike schemes that involve quantum repeaters, ours is feasible with current technology and presents manageable levels of noise even on 550 kilometres of standard optical fibre. This scheme is a promising step towards overcoming the rate-distance limit of QKD and greatly extending the range of secure quantum communications.

  18. Overcoming Resistance to Cetuximab with Honokiol, A Small-Molecule Polyphenol.

    Science.gov (United States)

    Pearson, Hannah E; Iida, Mari; Orbuch, Rachel A; McDaniel, Nellie K; Nickel, Kwangok P; Kimple, Randall J; Arbiser, Jack L; Wheeler, Deric L

    2018-01-01

    Overexpression and activation of the EGFR have been linked to poor prognosis in several human cancers. Cetuximab is a mAb against EGFR that is used for the treatment in head and neck squamous cell carcinoma (HNSCC) and metastatic colorectal cancer. Unfortunately, most tumors have intrinsic or will acquire resistance to cetuximab during the course of therapy. Honokiol is a natural compound found in the bark and leaves of the Chinese Magnolia tree and is established to have several anticancer properties without appreciable toxicity. In this study, we hypothesized that combining cetuximab and honokiol treatments could overcome acquired resistance to cetuximab. We previously developed a model of acquired resistance to cetuximab in non-small cell lung cancer H226 cell line. Treatment of cetuximab-resistant clones with honokiol and cetuximab resulted in a robust antiproliferative response. Immunoblot analysis revealed the HER family and their signaling pathways were downregulated after combination treatment, most notably the proliferation (MAPK) and survival (AKT) pathways. In addition, we found a decrease in phosphorylation of DRP1 and reactive oxygen species after combination treatment in cetuximab-resistant clones, which may signify a change in mitochondrial function. Furthermore, we utilized cetuximab-resistant HNSCC patient-derived xenografts (PDX) to test the benefit of combinatorial treatment in vivo There was significant growth delay in PDX tumors after combination treatment with a subsequent downregulation of active MAPK, AKT, and DRP1 signaling as seen in vitro Collectively, these data suggest that honokiol is a promising natural compound in overcoming acquired resistance to cetuximab. Mol Cancer Ther; 17(1); 204-14. ©2017 AACR . ©2017 American Association for Cancer Research.

  19. Overcoming technical and market barriers for distributed wind applications : reaching the mainstream

    International Nuclear Information System (INIS)

    Rhoads-Weaver, H.; Forsyth, T.

    2006-01-01

    Technical and market barriers for distributed wind applications were reviewed. A renewable energy survey has recently suggested that while less than 10 per cent of survey respondents had installed wind turbines, 40 per cent indicated that they plan to use wind energy on-site in the future. It is estimated that global annual sales of wind systems have the potential to reach $110 million by 2010 under ideal conditions. Distributed wind market growth areas include residential grid-connected sites, schools, public facilities and farms, business and industry. Grid-connected wind projects are expected to grow from less than 5 per cent of the total small wind market to over 20 per cent by 2020. However, without a federal investment tax credit, more modest growth is anticipated. Drivers of the distributed wind market were identified as financial incentives and programs; favorable policies and regulations; and increasing retail electricity rates and loads. Challenges and barriers to distributed wind market growth included economics; lack of performance standards and ratings; difficult interconnection processes; prohibitive zoning rules; low manufacturing volumes; and low consumer awareness. While there has been a 5-fold increase in photovoltaics (PV) sales in the United States since 2000, small wind turbines sales have only grown by approximately 70 per cent over the same period. Market increases in distributed wind systems are anticipated with the introduction of hybrid wind/PV systems. Improved designs for small and mid-sized turbines, rotors and towers may help to overcome barriers to wind energy growth. Technology developments in remote-monitored controllers and improved computer tools for analyzing project economics may also help to overcome market barriers. However, significant cost reductions are needed to stimulate widespread market acceptance of distributed wind. It was concluded that distributed wind is well-positioned to play an important role in supplying clean

  20. Overcoming the effects of differential skewness of test items in scale construction

    Directory of Open Access Journals (Sweden)

    Johann M. Schepers

    2004-10-01

    Full Text Available The principal objective of the study was to develop a procedure for overcoming the effects of differential skewness of test items in scale construction. It was shown that the degree of skewness of test items places an upper limit on the correlations between the items, regardless of the contents of the items. If the items are ordered in terms of skewness the resulting inter correlation matrix forms a simplex or a pseudo simplex. Factoring such a matrix results in a multiplicity of factors, most of which are artifacts. A procedure for overcoming this problem was demonstrated with items from the Locus of Control Inventory (Schepers, 1995. The analysis was based on a sample of 1662 first year university students. Opsomming Die hoofdoel van die studie was om ’n prosedure te ontwikkel om die gevolge van differensiële skeefheid van toetsitems, in skaalkonstruksie, teen te werk. Daar is getoon dat die graad van skeefheid van toetsitems ’n boonste grens plaas op die korrelasies tussen die items ongeag die inhoud daarvan. Indien die items gerangskik word volgens graad van skeefheid, sal die interkorrelasiematriks van die items ’n simpleks of pseudosimpleks vorm. Indien so ’n matriks aan faktorontleding onderwerp word, lei dit tot ’n veelheid van faktore waarvan die meerderheid artefakte is. ’n Prosedure om hierdie probleem te bowe te kom, is gedemonstreer met behulp van die items van die Lokus van Beheer-vraelys (Schepers, 1995. Die ontledings is op ’n steekproef van 1662 eerstejaaruniversiteitstudente gebaseer.