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Sample records for c-flip degradation mediates

  1. Celecoxib promotes c-FLIP degradation through Akt-independent inhibition of GSK3.

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    Chen, Shuzhen; Cao, Wei; Yue, Ping; Hao, Chunhai; Khuri, Fadlo R; Sun, Shi-Yong

    2011-10-01

    Celecoxib is a COX-2 inhibitor that reduces the risk of colon cancer. However, the basis for its cancer chemopreventive activity is not fully understood. In this study, we defined a mechanism of celecoxib action based on degradation of cellular FLICE-inhibitory protein (c-FLIP), a major regulator of the death receptor pathway of apoptosis. c-FLIP protein levels are regulated by ubiquitination and proteasome-mediated degradation. We found that celecoxib controlled c-FLIP ubiquitination through Akt-independent inhibition of glycogen synthase kinase-3 (GSK3), itself a candidate therapeutic target of interest in colon cancer. Celecoxib increased the levels of phosphorylated GSK3, including the α and β forms, even in cell lines, where phosphorylated Akt levels were not increased. Phosphoinositide 3-kinase inhibitors abrogated Akt phosphorylation as expected but had no effect on celecoxib-induced GSK3 phosphorylation. In contrast, protein kinase C (PKC) inhibitors abolished celecoxib-induced GSK3 phosphorylation, implying that celecoxib influenced GSK3 phosphorylation through a mechanism that relied upon PKC and not Akt. GSK3 blockade either by siRNA or kinase inhibitors was sufficient to attenuate c-FLIP levels. Combining celecoxib with GSK3 inhibition enhanced attenuation of c-FLIP and increased apoptosis. Proteasome inhibitor MG132 reversed the effects of GSK3 inhibition and increased c-FLIP ubiquitination, confirming that c-FLIP attenuation was mediated by proteasomal turnover as expected. Our findings reveal a novel mechanism through which the regulatory effects of c-FLIP on death receptor signaling are controlled by GSK3, which celecoxib acts at an upstream level to control independently of Akt.

  2. Novel Phosphorylation and Ubiquitination Sites Regulate Reactive Oxygen Species-dependent Degradation of Anti-apoptotic c-FLIP Protein*

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    Wilkie-Grantham, Rachel P.; Matsuzawa, Shu-Ichi; Reed, John C.

    2013-01-01

    The cytosolic protein c-FLIP (cellular Fas-associated death domain-like interleukin 1β-converting enzyme inhibitory protein) is an inhibitor of death receptor-mediated apoptosis that is up-regulated in a variety of cancers, contributing to apoptosis resistance. Several compounds found to restore sensitivity of cancer cells to TRAIL, a TNF family death ligand with promising therapeutic potential, act by targeting c-FLIP ubiquitination and degradation by the proteasome. The generation of reactive oxygen species (ROS) has been implicated in c-FLIP protein degradation. However, the mechanism by which ROS post-transcriptionally regulate c-FLIP protein levels is not well understood. We show here that treatment of prostate cancer PPC-1 cells with the superoxide generators menadione, paraquat, or buthionine sulfoximine down-regulates c-FLIP long (c-FLIPL) protein levels, which is prevented by the proteasome inhibitor MG132. Furthermore, pretreatment of PPC-1 cells with a ROS scavenger prevented ubiquitination and loss of c-FLIPL protein induced by menadione or paraquat. We identified lysine 167 as a novel ubiquitination site of c-FLIPL important for ROS-dependent degradation. We also identified threonine 166 as a novel phosphorylation site and demonstrate that Thr-166 phosphorylation is required for ROS-induced Lys-167 ubiquitination. The mutation of either Thr-166 or Lys-167 was sufficient to stabilize c-FLIP protein levels in PPC-1, HEK293T, and HeLa cancer cells treated with menadione or paraquat. Accordingly, expression of c-FLIP T166A or K167R mutants protected cells from ROS-mediated sensitization to TRAIL-induced cell death. Our findings reveal novel ROS-dependent post-translational modifications of the c-FLIP protein that regulate its stability, thus impacting sensitivity of cancer cells to TRAIL. PMID:23519470

  3. The novel Akt inhibitor API-1 induces c-FLIP degradation and synergizes with TRAIL to augment apoptosis independent of Akt inhibition.

    Science.gov (United States)

    Li, Bo; Ren, Hui; Yue, Ping; Chen, Mingwei; Khuri, Fadlo R; Sun, Shi-Yong

    2012-04-01

    API-1 (pyrido[2,3-d]pyrimidines) is a novel small-molecule inhibitor of Akt, which acts by binding to Akt and preventing its membrane translocation and has promising preclinical antitumor activity. In this study, we reveal a novel function of API-1 in regulation of cellular FLICE-inhibitory protein (c-FLIP) levels and TRAIL-induced apoptosis, independent of Akt inhibition. API-1 effectively induced apoptosis in tested cancer cell lines including activation of caspase-8 and caspase-9. It reduced the levels of c-FLIP without increasing the expression of death receptor 4 (DR4) or DR5. Accordingly, it synergized with TRAIL to induce apoptosis. Enforced expression of ectopic c-FLIP did not attenuate API-1-induced apoptosis but inhibited its ability to enhance TRAIL-induced apoptosis. These data indicate that downregulation of c-FLIP mediates enhancement of TRAIL-induced apoptosis by API-1 but is not sufficient for API-1-induced apoptosis. API-1-induced reduction of c-FLIP could be blocked by the proteasome inhibitor MG132. Moreover, API-1 increased c-FLIP ubiquitination and decreased c-FLIP stability. These data together suggest that API-1 downregulates c-FLIP by facilitating its ubiquitination and proteasome-mediated degradation. Because other Akt inhibitors including API-2 and MK2206 had minimal effects on reducing c-FLIP and enhancement of TRAIL-induced apoptosis, it is likely that API-1 reduces c-FLIP and enhances TRAIL-induced apoptosis independent of its Akt-inhibitory activity. 2012 AACR

  4. Hyperthermia enhances mapatumumab-induced apoptotic death through ubiquitin-mediated degradation of cellular FLIP(long) in human colon cancer cells.

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    Song, X; Kim, S-Y; Zhou, Z; Lagasse, E; Kwon, Y T; Lee, Y J

    2013-04-04

    Colorectal cancer is the third leading cause of cancer-related mortality in the world; the main cause of death of colorectal cancer is hepatic metastases, which can be treated with hyperthermia using isolated hepatic perfusion (IHP). In this study, we report that mild hyperthermia potently reduced cellular FLIP(long), (c-FLIP(L)), a major regulator of the death receptor (DR) pathway of apoptosis, thereby enhancing humanized anti-DR4 antibody mapatumumab (Mapa)-mediated mitochondria-independent apoptosis. We observed that overexpression of c-FLIP(L) in CX-1 cells abrogated the synergistic effect of Mapa and hyperthermia, whereas silencing of c-FLIP in CX-1 cells enhanced Mapa-induced apoptosis. Hyperthermia altered c-FLIP(L) protein stability without concomitant reductions in FLIP mRNA. Ubiquitination of c-FLIP(L) was increased by hyperthermia, and proteasome inhibitor MG132 prevented heat-induced downregulation of c-FLIP(L). These results suggest the involvement of the ubiquitin-proteasome system in this process. We also found lysine residue 195 (K195) to be essential for c-FLIP(L) ubiquitination and proteolysis, as mutant c-FLIP(L) lysine 195 arginine (arginine replacing lysine) was left virtually un-ubiquitinated and was refractory to hyperthermia-triggered degradation, and thus partially blocked the synergistic effect of Mapa and hyperthermia. Our observations reveal that hyperthermia transiently reduced c-FLIP(L) by proteolysis linked to K195 ubiquitination, which contributed to the synergistic effect between Mapa and hyperthermia. This study supports the application of hyperthermia combined with other regimens to treat colorectal hepatic metastases.

  5. Withanolide E sensitizes renal carcinoma cells to TRAIL-induced apoptosis by increasing cFLIP degradation.

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    Henrich, C J; Brooks, A D; Erickson, K L; Thomas, C L; Bokesch, H R; Tewary, P; Thompson, C R; Pompei, R J; Gustafson, K R; McMahon, J B; Sayers, T J

    2015-02-26

    Withanolide E, a steroidal lactone from Physalis peruviana, was found to be highly active for sensitizing renal carcinoma cells and a number of other human cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Withanolide E, the most potent and least toxic of five TRAIL-sensitizing withanolides identified, enhanced death receptor-mediated apoptotic signaling by a rapid decline in the levels of cFLIP proteins. Other mechanisms by which TRAIL sensitizers have been reported to work: generation of reactive oxygen species (ROS), changes in pro-and antiapoptotic protein expression, death receptor upregulation, activation of intrinsic (mitochondrial) apoptotic pathways, ER stress, and proteasomal inhibition proved to be irrelevant to withanolide E activity. Loss of cFLIP proteins was not due to changes in expression, but rather destabilization and/or aggregation, suggesting impairment of chaperone proteins leading to degradation. Indeed, withanolide E treatment altered the stability of a number of HSP90 client proteins, but with greater apparent specificity than the well-known HSP90 inhibitor geldanamycin. As cFLIP has been reported to be an HSP90 client, this provides a potentially novel mechanism for sensitizing cells to TRAIL. Sensitization of human renal carcinoma cells to TRAIL-induced apoptosis by withanolide E and its lack of toxicity were confirmed in animal studies. Owing to its novel activity, withanolide E is a promising reagent for the analysis of mechanisms of TRAIL resistance, for understanding HSP90 function, and for further therapeutic development. In marked contrast to bortezomib, among the best currently available TRAIL sensitizers, withanolide E's more specific mechanism of action suggests minimal toxic side effects.

  6. Human T-Cell Leukemia Virus Type 1 Tax-Deregulated Autophagy Pathway and c-FLIP Expression Contribute to Resistance against Death Receptor-Mediated Apoptosis

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    Wang, Weimin; Zhou, Jiansuo; Shi, Juan; Zhang, Yaxi; Liu, Shilian

    2014-01-01

    ABSTRACT The human T-cell leukemia virus type 1 (HTLV-1) Tax protein is considered to play a central role in the process that leads to adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 Tax-expressing cells show resistance to apoptosis induced by Fas ligand (FasL) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). The regulation of Tax on the autophagy pathway in HeLa cells and peripheral T cells was recently reported, but the function and underlying molecular mechanism of the Tax-regulated autophagy are not yet well defined. Here, we report that HTLV-1 Tax deregulates the autophagy pathway, which plays a protective role during the death receptor (DR)-mediated apoptosis of human U251 astroglioma cells. The cellular FLICE-inhibitory protein (c-FLIP), which is upregulated by Tax, also contributes to the resistance against DR-mediated apoptosis. Both Tax-induced autophagy and Tax-induced c-FLIP expression require Tax-induced activation of IκB kinases (IKK). Furthermore, Tax-induced c-FLIP expression is regulated through the Tax-IKK-NF-κB signaling pathway, whereas Tax-triggered autophagy depends on the activation of IKK but not the activation of NF-κB. In addition, DR-mediated apoptosis is correlated with the degradation of Tax, which can be facilitated by the inhibitors of autophagy. IMPORTANCE Our study reveals that Tax-deregulated autophagy is a protective mechanism for DR-mediated apoptosis. The molecular mechanism of Tax-induced autophagy is also illuminated, which is different from Tax-increased c-FLIP. Tax can be degraded via manipulation of autophagy and TRAIL-induced apoptosis. These results outline a complex regulatory network between and among apoptosis, autophagy, and Tax and also present evidence that autophagy represents a new possible target for therapeutic intervention for the HTVL-1 related diseases. PMID:24352466

  7. FLIP the Switch: Regulation of Apoptosis and Necroptosis by cFLIP

    Directory of Open Access Journals (Sweden)

    Yuichi Tsuchiya

    2015-12-01

    Full Text Available cFLIP (cellular FLICE-like inhibitory protein is structurally related to caspase-8 but lacks proteolytic activity due to multiple amino acid substitutions of catalytically important residues. cFLIP protein is evolutionarily conserved and expressed as three functionally different isoforms in humans (cFLIPL, cFLIPS, and cFLIPR. cFLIP controls not only the classical death receptor-mediated extrinsic apoptosis pathway, but also the non-conventional pattern recognition receptor-dependent apoptotic pathway. In addition, cFLIP regulates the formation of the death receptor-independent apoptotic platform named the ripoptosome. Moreover, recent studies have revealed that cFLIP is also involved in a non-apoptotic cell death pathway known as programmed necrosis or necroptosis. These functions of cFLIP are strictly controlled in an isoform-, concentration- and tissue-specific manner, and the ubiquitin-proteasome system plays an important role in regulating the stability of cFLIP. In this review, we summarize the current scientific findings from biochemical analyses, cell biological studies, mathematical modeling, and gene-manipulated mice models to illustrate the critical role of cFLIP as a switch to determine the destiny of cells among survival, apoptosis, and necroptosis.

  8. HTLV-1 Tax protects against CD95-mediated apoptosis by induction of the cellular FLICE-inhibitory protein (c-FLIP).

    Science.gov (United States)

    Krueger, Andreas; Fas, Stefanie C; Giaisi, Marco; Bleumink, Marc; Merling, Anette; Stumpf, Christine; Baumann, Sven; Holtkotte, Denise; Bosch, Valerie; Krammer, Peter H; Li-Weber, Min

    2006-05-15

    The HTLV-1 transactivator protein Tax is essential for malignant transformation of CD4 T cells, ultimately leading to adult T-cell leukemia/lymphoma (ATL). Malignant transformation may involve development of apoptosis resistance. In this study we investigated the molecular mechanisms by which HTLV-1 Tax confers resistance toward CD95-mediated apoptosis. We show that Tax-expressing T-cell lines derived from HTLV-1-infected patients express elevated levels of c-FLIP(L) and c-FLIP(S). The levels of c-FLIP correlated with resistance toward CD95-mediated apoptosis. Using an inducible system we demonstrated that both resistance toward CD95-mediated apoptosis and induction of c-FLIP are dependent on Tax. In addition, analysis of early cleavage of the BH3-only Bcl-2 family member Bid, a direct caspase-8 substrate, revealed that apoptosis is inhibited at a CD95 death receptor proximal level in Tax-expressing cells. Finally, using siRNA we directly showed that c-FLIP confers Tax-mediated resistance toward CD95-mediated apoptosis. In conclusion, our data suggest an important mechanism by which expression of HTLV-1 Tax may lead to immune escape of infected T cells and, thus, to persistent infection and transformation.

  9. Sodium arsenite accelerates TRAIL-mediated apoptosis in melanoma cells through upregulation of TRAIL-R1/R2 surface levels and downregulation of cFLIP expression

    International Nuclear Information System (INIS)

    Ivanov, Vladimir N.; Hei, Tom K.

    2006-01-01

    AP-1/cJun, NF-κB and STAT3 transcription factors control expression of numerous genes, which regulate critical cell functions including proliferation, survival and apoptosis. Sodium arsenite is known to suppress both the IKK-NF-κB and JAK2-STAT3 signaling pathways and to activate the MAPK/JNK-cJun pathways, thereby committing some cancers to undergo apoptosis. Indeed, sodium arsenite is an effective drug for the treatment of acute promyelocytic leukemia with little nonspecific toxicity. Malignant melanoma is highly refractory to conventional radio- and chemotherapy. In the present study, we observed strong effects of sodium arsenite treatment on upregulation of TRAIL-mediated apoptosis in human and mouse melanomas. Arsenite treatment upregulated surface levels of death receptors, TRAIL-R1 and TRAIL-R2, through increased translocation of these proteins from cytoplasm to the cell surface. Furthermore, activation of cJun and suppression of NF-κB by sodium arsenite resulted in upregulation of the endogenous TRAIL and downregulation of the cFLIP gene expression (which encodes one of the main anti-apoptotic proteins in melanomas) followed by cFLIP protein degradation and, finally, by acceleration of TRAIL-induced apoptosis. Direct suppression of cFLIP expression by cFLIP RNAi also accelerated TRAIL-induced apoptosis in these melanomas, while COX-2 suppression substantially increased levels of both TRAIL-induced and arsenite-induced apoptosis. In contrast, overexpression of permanently active AKTmyr inhibited TRAIL-mediated apoptosis via downregulation of TRAIL-R1 levels. Finally, AKT overactivation increased melanoma survival in cell culture and dramatically accelerated growth of melanoma transplant in vivo, highlighting a role of AKT suppression for effective anticancer treatment

  10. Targeting the Anti-Apoptotic Protein c-FLIP for Cancer Therapy

    International Nuclear Information System (INIS)

    Safa, Ahmad R.; Pollok, Karen E.

    2011-01-01

    Cellular FLICE (FADD-like IL-1beta-converting enzyme)-inhibitory protein (c-FLIP) is a major resistance factor and critical anti-apoptotic regulator that inhibits tumor necrosis factor-alpha (TNF-alpha), Fas-L, and TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis as well as chemotherapy-triggered apoptosis in malignant cells. c-FLIP is expressed as long (c-FLIP L ), short (c-FLIP S ), and c-FLIP R splice variants in human cells. c-FLIP binds to FADD and/or caspase-8 or -10 in a ligand-dependent and-independent fashion, which in turn prevents death-inducing signaling complex (DISC) formation and subsequent activation of the caspase cascade. Moreover, c-FLIP L and c-FLIP S are known to have multifunctional roles in various signaling pathways, as well as activating and/or upregulating several cytoprotective signaling molecules. Upregulation of c-FLIP has been found in various tumor types, and its downregulation has been shown to restore apoptosis triggered by cytokines and various chemotherapeutic agents. Hence, c-FLIP is an important target for cancer therapy. For example, small interfering RNAs (siRNAs) that specifically knockdown the expression of c-FLIP L in diverse human cancer cell lines augmented TRAIL-induced DISC recruitment and increased the efficacy of chemotherapeutic agents, thereby enhancing effector caspase stimulation and apoptosis. Moreover, small molecules causing degradation of c-FLIP as well as decreasing mRNA and protein levels of c-FLIP L and c-FLIP S splice variants have been found, and efforts are underway to develop other c-FLIP-targeted cancer therapies. This review focuses on (1) the functional role of c-FLIP splice variants in preventing apoptosis and inducing cytokine and drug resistance; (2) the molecular mechanisms that regulate c-FLIP expression; and (3) strategies to inhibit c-FLIP expression and function

  11. cFLIP expression is altered in severe corticosteroid-resistant asthma

    Directory of Open Access Journals (Sweden)

    Dennis Lazarev

    2014-12-01

    Full Text Available Dysregulation of alternative splicing of mRNA precursors is known to contribute to numerous human diseases. In this study we carried out the first systematic search for asthma-associated changes in alternative splicing events, using a model of Aspergillus fumigatus (A. fumigatus-sensitized mice and an exon junction microarray to detect potential changes in alternative splicing. One of the sensitization-associated changes identified in the search was a shift in alternative splicing of the mRNA encoding cFLIP, a modulator of the caspase-mediated extrinsic apoptosis pathway. Expanding these studies to human asthma patients, we discovered a significant decrease in the expression of both cFLIP isoforms in severe corticosteroid-resistant asthmatics. Although it is unclear whether these changes were due solely to differences in alternative splicing, these findings provide evidence that dysregulation of the extrinsic apoptosis pathway is part of the underlying immunopathogenesis of severe refractory asthma.

  12. NOX4-mediated ROS production induces apoptotic cell death via down-regulation of c-FLIP and Mcl-1 expression in combined treatment with thioridazine and curcumin

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    Seung Un Seo

    2017-10-01

    Full Text Available Thioridazine is known to have anti-tumor effects by inhibiting PI3K/Akt signaling, which is an important signaling pathway in cell survival. However, thioridazine alone does not induce apoptosis in head and neck squamous cell carcinoma (AMC-HN4, human breast carcinoma (MDA-MB231, and human glioma (U87MG cells. Therefore, we investigated whether combined treatment with thioridazine and curcumin induces apoptosis. Combined treatment with thioridazine and curcumin markedly induced apoptosis in cancer cells without inducing apoptosis in human normal mesangial cells and human normal umbilical vein cells (EA.hy926. We found that combined treatment with thioridazine and curcumin had synergistic effects in AMC-HN4 cells. Among apoptosis-related proteins, thioridazine plus curcumin induced down-regulation of c-FLIP and Mcl-1 expression at the post-translational levels in a proteasome-dependent manner. Augmentation of proteasome activity was related to the up-regulation of proteasome subunit alpha 5 (PSMA5 expression in curcumin plus thioridazine-treated cells. Combined treatment with curcumin and thioridazine produced intracellular ROS in a NOX4-dependent manner, and ROS-mediated activation of Nrf2/ARE signaling played a critical role in the up-regulation of PSMA5 expression. Furthermore, ectopic expression of c-FLIP and Mcl-1 inhibited apoptosis in thioridazine and curcumin-treated cells. Therefore, we demonstrated that thioridazine plus curcumin induces proteasome activity by up-regulating PSMA5 expression via NOX4-mediated ROS production and that down-regulation of c-FLIP and Mcl-1 expression post-translationally is involved in apoptosis.

  13. Cyclophilin C Participates in the US2-Mediated Degradation of Major Histocompatibility Complex Class I Molecules.

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    Chapman, Daniel C; Stocki, Pawel; Williams, David B

    2015-01-01

    Human cytomegalovirus uses a variety of mechanisms to evade immune recognition through major histocompatibility complex class I molecules. One mechanism mediated by the immunoevasin protein US2 causes rapid disposal of newly synthesized class I molecules by the endoplasmic reticulum-associated degradation pathway. Although several components of this degradation pathway have been identified, there are still questions concerning how US2 targets class I molecules for degradation. In this study we identify cyclophilin C, a peptidyl prolyl isomerase of the endoplasmic reticulum, as a component of US2-mediated immune evasion. Cyclophilin C could be co-isolated with US2 and with the class I molecule HLA-A2. Furthermore, it was required at a particular expression level since depletion or overexpression of cyclophilin C impaired the degradation of class I molecules. To better characterize the involvement of cyclophilin C in class I degradation, we used LC-MS/MS to detect US2-interacting proteins that were influenced by cyclophilin C expression levels. We identified malectin, PDIA6, and TMEM33 as proteins that increased in association with US2 upon cyclophilin C knockdown. In subsequent validation all were shown to play a functional role in US2 degradation of class I molecules. This was specific to US2 rather than general ER-associated degradation since depletion of these proteins did not impede the degradation of a misfolded substrate, the null Hong Kong variant of α1-antitrypsin.

  14. cFLIP Regulates Skin Homeostasis and Protects against TNF-Induced Keratinocyte Apoptosis

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    Diana Panayotova-Dimitrova

    2013-10-01

    Full Text Available FADD, caspase-8, and cFLIP regulate the outcome of cell death signaling. Mice that constitutively lack these molecules die at an early embryonic age, whereas tissue-specific constitutive deletion of FADD or caspase-8 results in inflammatory skin disease caused by increased necroptosis. The function of cFLIP in the skin in vivo is unknown. In contrast to tissue-specific caspase-8 knockout, we show that mice constitutively lacking cFLIP in the epidermis die around embryonic days 10 and 11. When cFLIP expression was abrogated in adult skin of cFLIPfl/fl-K14CreERtam mice, severe inflammation of the skin with concomitant caspase activation and apoptotic, but not necroptotic, cell death developed. Apoptosis was dependent of autocrine tumor necrosis factor production triggered by loss of cFLIP. In addition, epidermal cFLIP protein was lost in patients with severe drug reactions associated with epidermal apoptosis. Our data demonstrate the importance of cFLIP for the integrity of the epidermis and for silencing of spontaneous skin inflammation.

  15. NOX4-mediated ROS production induces apoptotic cell death via down-regulation of c-FLIP and Mcl-1 expression in combined treatment with thioridazine and curcumin.

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    Seo, Seung Un; Kim, Tae Hwan; Kim, Dong Eun; Min, Kyoung-Jin; Kwon, Taeg Kyu

    2017-10-01

    Thioridazine is known to have anti-tumor effects by inhibiting PI3K/Akt signaling, which is an important signaling pathway in cell survival. However, thioridazine alone does not induce apoptosis in head and neck squamous cell carcinoma (AMC-HN4), human breast carcinoma (MDA-MB231), and human glioma (U87MG) cells. Therefore, we investigated whether combined treatment with thioridazine and curcumin induces apoptosis. Combined treatment with thioridazine and curcumin markedly induced apoptosis in cancer cells without inducing apoptosis in human normal mesangial cells and human normal umbilical vein cells (EA.hy926). We found that combined treatment with thioridazine and curcumin had synergistic effects in AMC-HN4 cells. Among apoptosis-related proteins, thioridazine plus curcumin induced down-regulation of c-FLIP and Mcl-1 expression at the post-translational levels in a proteasome-dependent manner. Augmentation of proteasome activity was related to the up-regulation of proteasome subunit alpha 5 (PSMA5) expression in curcumin plus thioridazine-treated cells. Combined treatment with curcumin and thioridazine produced intracellular ROS in a NOX4-dependent manner, and ROS-mediated activation of Nrf2/ARE signaling played a critical role in the up-regulation of PSMA5 expression. Furthermore, ectopic expression of c-FLIP and Mcl-1 inhibited apoptosis in thioridazine and curcumin-treated cells. Therefore, we demonstrated that thioridazine plus curcumin induces proteasome activity by up-regulating PSMA5 expression via NOX4-mediated ROS production and that down-regulation of c-FLIP and Mcl-1 expression post-translationally is involved in apoptosis. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  16. The regulation and role of c-FLIP in human Th cell differentiation.

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    Kyläniemi, Minna K; Kaukonen, Riina; Myllyviita, Johanna; Rasool, Omid; Lahesmaa, Riitta

    2014-01-01

    The early differentiation of T helper (Th) cells is a tightly controlled and finely balanced process, which involves several factors including cytokines, transcription factors and co-stimulatory molecules. Recent studies have shown that in addition to the regulation of apoptosis, caspase activity is also needed for Th cell proliferation and activation and it might play a role in Th cell differentiation. The isoforms of the cellular FLICE inhibitory protein (c-FLIP) are regulators of CASPASE-8 activity and the short isoform, c-FLIPS, has been shown to be up-regulated by IL-4, the Th2 driving cytokine. In this work, we have studied the expression and functional role of three c-FLIP isoforms during the early Th cell differentiation. Only two of the isoforms, c-FLIPS and c-FLIPL, were detected at the protein level although c-FLIPR was expressed at the mRNA level. The knockdown of c-FLIPL led to enhanced Th1 differentiation and elevated IL-4 production by Th2 cells, whereas the knockdown of c-FLIPS diminished GATA3 expression and IL-4 production by Th2 cells. In summary, our results provide new insight into the role of c-FLIP proteins in the early differentiation of human Th cells.

  17. Monensin, a polyether ionophore antibiotic, overcomes TRAIL resistance in glioma cells via endoplasmic reticulum stress, DR5 upregulation and c-FLIP downregulation.

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    Yoon, Mi Jin; Kang, You Jung; Kim, In Young; Kim, Eun Hee; Lee, Ju Ahn; Lim, Jun Hee; Kwon, Taeg Kyu; Choi, Kyeong Sook

    2013-08-01

    Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) is preferentially cytotoxic to cancer cells over normal cells. However, many cancer cells, including malignant glioma cells, tend to be resistant to TRAIL. Monensin (a polyether ionophore antibiotic that is widely used in veterinary medicine) and salinomycin (a compound that is structurally related to monensin and shows cancer stem cell-inhibiting activity) are currently recognized as anticancer drug candidates. In this study, we show that monensin effectively sensitizes various glioma cells, but not normal astrocytes, to TRAIL-mediated apoptosis; this occurs at least partly via monensin-induced endoplasmic reticulum (ER) stress, CHOP-mediated DR5 upregulation and proteasome-mediated downregulation of c-FLIP. Interestingly, other polyether antibiotics, such as salinomycin, nigericin, narasin and lasalocid A, also stimulated TRAIL-mediated apoptosis in glioma cells via ER stress, CHOP-mediated DR5 upregulation and c-FLIP downregulation. Taken together, these results suggest that combined treatment of glioma cells with TRAIL and polyether ionophore antibiotics may offer an effective therapeutic strategy.

  18. Increased cFLIP expression in thymic epithelial tumors blocks autophagy via NF-κB signalling.

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    Belharazem, Djeda; Grass, Albert; Paul, Cornelia; Vitacolonna, Mario; Schalke, Berthold; Rieker, Ralf J; Körner, Daniel; Jungebluth, Philipp; Simon-Keller, Katja; Hohenberger, Peter; Roessner, Eric M; Wiebe, Karsten; Gräter, Thomas; Kyriss, Thomas; Ott, German; Geserick, Peter; Leverkus, Martin; Ströbel, Philipp; Marx, Alexander

    2017-10-27

    The anti-apoptotic cellular FLICE-like inhibitory protein cFLIP plays a pivotal role in normal tissues homoeostasis and the development of many tumors, but its role in normal thymus (NT), thymomas and thymic carcinomas (TC) is largely unknown. Expression, regulation and function of cFLIP were analyzed in biopsies of NT, thymomas, thymic squamous cell carcinomas (TSCC), thymic epithelial cells (TECs) derived thereof and in the TC line 1889c by qRT-PCR, western blot, shRNA techniques, and functional assays addressing survival, senescence and autophagy. More than 90% of thymomas and TSCCs showed increased cFLIP expression compared to NT. cFLIP expression declined with age in NTs but not in thymomas. During short term culture cFLIP expression levels declined significantly slower in neoplastic than non-neoplastic primary TECs. Down-regulation of cFLIP by shRNA or NF-κB inhibition accelerated senescence and induced autophagy and cell death in neoplastic TECs. The results suggest a role of cFLIP in the involution of normal thymus and the development of thymomas and TSCC. Since increased expression of cFLIP is a known tumor escape mechanism, it may serve as tissue-based biomarker in future clinical trials, including immune checkpoint inhibitor trials in the commonly PD-L1 high thymomas and TCs.

  19. SIAH1-induced p34SEI-1 polyubiquitination/degradation mediates p53 preferential vitamin C cytotoxicity.

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    Lee, Soonduck; Kim, Jinsun; Jung, Samil; Li, Chengping; Yang, Young; Kim, Keun Il; Lim, Jong-Seok; Kim, Yonghwan; Cheon, Choong-Il; Lee, Myeong-Sok

    2015-03-01

    Vitamin C is considered as an important anticancer therapeutic agent although this view is debatable. In this study, we introduce a physiological mechanism demonstrating how vitamin C exerts anticancer activity that induces cell cycle arrest and apoptosis. Our previous and current data reveal that p53 tumor suppressor is the prerequisite factor for stronger anticancer effects of vitamin C. In addition, vitamin C-mediated cancer cell cytotoxicity appears to be achieved at least partly through the downregulation of the p34SEI-1 oncoprotein. Our previous study showed that p34SEI-1 increases the survival of various types of cancer cells by inhibiting their apoptosis. Present data suggest that vitamin C treatment decreases the p34SEI-1 expression at the protein level and therefore alleviates its anti-apoptotic activity. Of note, SIAH1, E3 ubiquitin ligase, appears to be responsible for the p34SEI-1 polyubiquitination and its subsequent degradation, which is dependent on p53. In summary, vitamin C increases cancer cell death by inducing SIAH1-mediated polyubiquitination/degradation of the p34SEI-1 oncoprotein in a p53-dependent manner.

  20. Rates and energetics of tyrosine ring flips in yeast iso-2-cytochrome c

    International Nuclear Information System (INIS)

    Nall, B.T.; Zuniga, E.H.

    1990-01-01

    Isotope-edited nuclear magnetic resonance spectroscopy is used to monitor ring flip motion of the five tyrosine side chains in the oxidized and reduced forms of yeast iso-2-cytochrome c. With specifically labeled protein purified from yeast grown on media containing [3,5- 13 C]tyrosine, isotope-edited one-dimensional proton spectra have been collected over a 5-55 degree C temperature range. The spectra allow selective observation of the 10 3,5 tyrosine ring proton resonances and, using a two-site exchange model, allow estimation of the temperature dependence of ring flip rates from motion-induced changes in proton line shapes. For the reduced protein, tyrosines II and IV are in fast exchange throughout the temperature range investigated, or lack resolvable differences in static chemical shifts for the 3,5 ring protons. Tyrosines I, III, and V are in sloe exchange at low temperatures and in fast exchange at high temperatures. Spectral simulations give flip rates for individual tyrosines in a range of one flip per second at low temperatures to thousands of flips per second at high temperatures. Eyring plots show that two of the tyrosines (I and III) have essentially the same activation parameters. Tentative sequence-specific assignments for the tyrosines in reduced iso-2 are suggested by comparison to horse cytochrome c. For oxidized iso-2, five resonances are observed at high temperatures, suggesting flip rates for all five tyrosines sufficient to average static chemical shift differences. At lower temperatures, there is evidence of intermediate and slow flipping for some of the rings

  1. Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-Flip

    Directory of Open Access Journals (Sweden)

    Jongeun Lee

    2013-05-01

    Keratin 8 and 18 (K8/K18 are major intermediate filament proteins of liver hepatocytes. They provide mechanical and nonmechanical stability, thereby protecting cells from stress. Hence, K8-null mice are highly sensitive to Fas-mediated liver cell apoptosis. However, the role of c-Flip protein in K8-null related susceptibility to liver injury is controversial. Here we analyzed c-Flip protein expression in various K8 or K18 null/mutant transgenic livers and show that they are similar in all analyzed transgenic livers and that previously reported c-Flip protein changes are due to antibody cross-reaction with mouse K18. Furthermore, analysis of various apoptosis- or cell survival-related proteins demonstrated that inhibition of phosphorylation of NF-κB and various stress activated protein kinases (SAPKs, such as p38 MAPK, p44/42 MAPK and JNK1/2, is related to the higher sensitivity of K8-null hepatocytes whose nuclear NF-κB is rapidly depleted through Fas-mediated apoptosis. Notably, we found that NF-κB and the studied protein kinases are associated with the K8/K18 complex and are released upon phosphorylation. Therefore, interaction of keratins with cell survival-related protein kinases and transcription factors is another important factor for hepatocyte survival.

  2. Mechanisms of c-myc degradation by nickel compounds and hypoxia.

    Directory of Open Access Journals (Sweden)

    Qin Li

    2009-12-01

    Full Text Available Nickel (Ni compounds have been found to cause cancer in humans and animal models and to transform cells in culture. At least part of this effect is mediated by stabilization of hypoxia inducible factor (HIF1a and activating its downstream signaling. Recent studies reported that hypoxia signaling might either antagonize or enhance c-myc activity depending on cell context. We investigated the effect of nickel on c-myc levels, and demonstrated that nickel, hypoxia, and other hypoxia mimetics degraded c-myc protein in a number of cancer cells (A549, MCF-7, MDA-453, and BT-474. The degradation of the c-Myc protein was mediated by the 26S proteosome. Interestingly, knockdown of both HIF-1alpha and HIF-2alpha attenuated c-Myc degradation induced by Nickel and hypoxia, suggesting the functional HIF-1alpha and HIF-2alpha was required for c-myc degradation. Further studies revealed two potential pathways mediated nickel and hypoxia induced c-myc degradation. Phosphorylation of c-myc at T58 was significantly increased in cells exposed to nickel or hypoxia, leading to increased ubiquitination through Fbw7 ubiquitin ligase. In addition, nickel and hypoxia exposure decreased USP28, a c-myc de-ubiquitinating enzyme, contributing to a higher steady state level of c-myc ubiquitination and promoting c-myc degradation. Furthermore, the reduction of USP28 protein by hypoxia signaling is due to both protein degradation and transcriptional repression. Nickel and hypoxia exposure significantly increased the levels of dimethylated H3 lysine 9 at the USP28 promoter and repressed its expression. Our study demonstrated that Nickel and hypoxia exposure increased c-myc T58 phosphorylation and decreased USP28 protein levels in cancer cells, which both lead to enhanced c-myc ubiquitination and proteasomal degradation.

  3. ERK controls epithelial cell death receptor signalling and cellular FLICE-like inhibitory protein (c-FLIP) in ulcerative colitis

    DEFF Research Database (Denmark)

    Seidelin, Jakob Benedict; Coskun, Mehmet; Vainer, Ben

    2013-01-01

    Intestinal epithelial cell (IEC) death signalling through the Fas receptor is impaired in active ulcerative colitis (UC). This is possibly due to the activation of cytoprotective pathways resulting in limitation of the tissue injury secondary to inflammation. We hypothesized that inflammatory...... the resistance to receptor mediated epithelial apoptosis in active UC. Oncogenic c-FLIP could promote propagation of DNA-damaged IECs and contribute to cancer development in UC....

  4. DomFLIP++

    International Nuclear Information System (INIS)

    Hendrysiak, W.; Raggl, A.; Slany, W.

    1996-01-01

    DomFLIP++ is the knowledge engineering module of the *FLIP++ project. *FLIP++ is a tool for optimizing multiple criteria problems. It uses fuzzy constraints to model optimizing criteria and applies algorithms such as Tabu search or genetic algorithms to the problems. DomFLIP++ is a C++ library. It allows the definition of new optimization problems. It helps a domain engineer to design the structure of a new problem. However, there is a domain independent interface to other *FLIP++ modules such as OptiFLIP++, DynaFLIP++, and InterFLIP++. After each iteration in the optimization process, the considered instantiations of the problem are evaluated. Each evaluation produces a list of violated constraints. For each constraint in further iterations of the optimization. A domain can be fine-tuned through modifications of constraints, through editing their repair lists, and through change in the optimizing parameters. A well-tuned domain can be successfully applied for optimization. Object-oriented design and implementation makes this module easy to modify and to reuse. Definition of new domains, system extensions with new optimizing algorithms, and definition of specific domain-dependent repair steps can be done efficiently. DomFLIP++ is tested on real-world example, namely scheduling the steel plant LD3 in Linz, Austria

  5. Independent Induction of Caspase-8 and cFLIP Expression during Colorectal Carcinogenesis in Sporadic and HNPCC Adenomas and Carcinomas

    Directory of Open Access Journals (Sweden)

    D. M. Heijink

    2007-01-01

    Full Text Available Background: TNF-Related Apoptosis Inducing Ligand (TRAIL is a promising agent for the induction of apoptosis in neoplastic tissues. Important determinants of TRAIL sensitivity are two intracellular proteins of the TRAIL pathway, caspase-8 and its anti-apoptotic competitor cellular Flice-Like Inhibitory Protein (cFLIP. Methods: The aim of this study was to investigate basic expression of caspase-8 and cFLIP in normal colorectal epithelium (n = 20, colorectal adenomas (n = 66 and colorectal carcinomas (n = 44 using immunohistochemistry performed on both sporadic and Hereditary Non-Polyposis Colorectal Cancer (HNPCC or Lynch syndrome-associated adenomas and carcinomas. Results: Expression of both caspase-8 and cFLIP was similar in cases with sporadic and hereditary origin. Expression of caspase-8 in colorectal adenomas and carcinomas was increased when compared to normal colon tissue (P = 0.02. Nuclear, paranuclear as well as cytoplasmic localizations of caspase-8 were detected. Immunohistochemistry revealed an upregulation of cFLIP in colorectal carcinomas in comparison to normal epithelium and colorectal adenomas (P < 0.001. A large variation in the caspase-8/cFLIP ratio was observed between the individual adenomas and carcinomas. Conclusion: Caspase-8 and cFLIP are upregulated during colorectal carcinogenesis. Upregulation of caspase-8 and/or downregulation of cFLIP may be interesting approaches to maximize TRAIL sensitivity in colorectal neoplasms.

  6. Induction of increased cAMP levels in articular chondrocytes blocks matrix metalloproteinase-mediated cartilage degradation, but not aggrecanase-mediated cartilage degradation

    DEFF Research Database (Denmark)

    Karsdal, Morten Asser; Sumer, Eren Ufuk; Wulf, Helle

    2007-01-01

    OBJECTIVE: Calcitonin has been suggested to have chondroprotective effects. One signaling pathway of calcitonin is via the second messenger cAMP. We undertook this study to investigate whether increased cAMP levels in chondrocytes would be chondroprotective. METHODS: Cartilage degradation......-dependently inhibited by forskolin and IBMX. The highest concentration of IBMX lowered cytokine-induced release of sGAG by 72%. CONCLUSION: Levels of cAMP in chondrocytes play a key role in controlling catabolic activity. Increased cAMP levels in chondrocytes inhibited MMP expression and activity and consequently...... strongly inhibited cartilage degradation. Specific cAMP modulators in chondrocytes may be potential treatments for cartilage degenerative diseases....

  7. Cdc20 mediates D-box-dependent degradation of Sp100

    International Nuclear Information System (INIS)

    Wang, Ran; Li, Ke-min; Zhou, Cai-hong; Xue, Jing-lun; Ji, Chao-neng; Chen, Jin-zhong

    2011-01-01

    Highlights: ► Cdc20 is a co-activator of APC/C complex. ► Cdc20 recruits Sp100 and mediates its degradation. ► The D-box of Sp100 is required for Cdc20-mediated degradation. ► Sp100 expresses consistently at both the mRNA and protein levels in cell cycle. -- Abstract: Cdc20 is a co-activator of the anaphase-promoting complex/cyclosome (APC/C complex), which recruits substrates at particular phases of the cell cycle and mediates their degradation. Sp100 is a PML-NB scaffold protein, which localizes to nuclear particles during interphase and disperses from them during mitosis, participates in viral resistance, transcriptional regulation, and apoptosis. However, its metabolism during the cell cycle has not yet been fully characterized. We found a putative D-box in Sp100 using the Eukaryotic Linear Motif (ELM) predictor database. The putative D-box of Sp100 was verified by mutational analysis. Overexpression of Cdc20 resulted in decreased levels of both endogenous Sp100 protein and overexpressed Sp100 mRNA in HEK 293 cells. Only an overexpressed D-box deletion mutant of Sp100 accumulated in HEK293 cells that also overexpressed Cdc20. Cdc20 knockdown by cdc20 specific siRNA resulted in increased Sp100 protein levels in cells. Furthermore, we discovered that the Cdc20 mediated degradation of Sp100 is diminished by the proteasome inhibitor MG132, which suggests that the ubiquitination pathway is involved in this process. However, unlike the other Cdc20 substrates, which display oscillating protein levels, the level of Sp100 protein remains constant throughout the cell cycle. Additionally, both overexpression and knockdown of endogenous Sp100 had no effect on the cell cycle. Our results suggested that sp100 is a novel substrate of Cdc20 and it is degraded by the ubiquitination pathway. The intact D-box of Sp100 was necessary for this process. These findings expand our knowledge of both Sp100 and Cdc20 as well as their role in ubiquitination.

  8. Nanoscale zerovalent iron-mediated degradation of DDT in soil.

    Science.gov (United States)

    Han, Yuling; Shi, Nan; Wang, Huifang; Pan, Xiong; Fang, Hua; Yu, Yunlong

    2016-04-01

    Nanoscale zerovalent iron (nZVI)-mediated degradation of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) was investigated in a spiked soil under different conditions (iron sources, iron dosage, soil moisture, temperature, and soil types) and DDT-contaminated field. The degradation efficiency of p,p'-DDT by nZVI and nZVI coated with sodium oleate (SO-nZVI) was much higher than that by nZVI coated with polyimide (PI-nZVI). The rapid degradation of p,p'-DDT by nZVI only occurred in flooded soil. The degradation half-life of p,p'-DDT decreased significantly from 58.3 to 27.6 h with nZVI dosage from 0.5 to 2.0% and from 46.5 to 32.0 h with temperature from 15 to 35 °C. The degradation efficiency of p,p'-DDT by nZVI differed in Jinhua (JH), Jiaxing (JX), Xiaoshan (XS), Huajiachi (HJC), and Heilongjiang (HLJ) soils. A good correlation was found between the degradation half-life of p,p'-DDT and multiple soil properties. The probable nZVI-mediated degradation pathway of p,p'-DDT in soil was proposed as DDT → DDD/DDE → DDNS → DDOH based on the metabolites identified by GC-MS. The in situ degradation efficiency of residual DDTs in a contaminated field was profoundly enhanced by the addition of nZVI as compared to the control. It is concluded that nZVI might be an efficient agent for the remediation of DDT-contaminated soil under anaerobic environment.

  9. Ubiquitin ligase RNF123 mediates degradation of heterochromatin protein 1α and β in lamin A/C knock-down cells.

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    Pankaj Chaturvedi

    Full Text Available The nuclear lamina is a key determinant of nuclear architecture, integrity and functionality in metazoan nuclei. Mutations in the human lamin A gene lead to highly debilitating genetic diseases termed as laminopathies. Expression of lamin A mutations or reduction in levels of endogenous A-type lamins leads to nuclear defects such as abnormal nuclear morphology and disorganization of heterochromatin. This is accompanied by increased proteasomal degradation of certain nuclear proteins such as emerin, nesprin-1α, retinoblastoma protein and heterochromatin protein 1 (HP1. However, the pathways of proteasomal degradation have not been well characterized.To investigate the mechanisms underlying the degradation of HP1 proteins upon lamin misexpression, we analyzed the effects of shRNA-mediated knock-down of lamins A and C in HeLa cells. Cells with reduced levels of expression of lamins A and C exhibited proteasomal degradation of HP1α and HP1β but not HP1γ. Since specific ubiquitin ligases are upregulated in lamin A/C knock-down cells, further studies were carried out with one of these ligases, RNF123, which has a putative HP1-binding motif. Ectopic expression of GFP-tagged RNF123 directly resulted in degradation of HP1α and HP1β. Mutational analysis showed that the canonical HP1-binding pentapeptide motif PXVXL in the N-terminus of RNF123 was required for binding to HP1 proteins and targeting them for degradation. The role of endogenous RNF123 in the degradation of HP1 isoforms was confirmed by RNF123 RNAi experiments. Furthermore, FRAP analysis suggested that HP1β was displaced from chromatin in laminopathic cells.Our data support a role for RNF123 ubiquitin ligase in the degradation of HP1α and HP1β upon lamin A/C knock-down. Hence lamin misexpression can cause degradation of mislocalized proteins involved in key nuclear processes by induction of specific components of the ubiquitin-proteasome system.

  10. Cdc20 mediates D-box-dependent degradation of Sp100

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ran; Li, Ke-min; Zhou, Cai-hong; Xue, Jing-lun [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai (China); Ji, Chao-neng, E-mail: Chnji@fudan.edu.cn [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai (China); Chen, Jin-zhong, E-mail: kingbellchen@fudan.edu.cn [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai (China)

    2011-12-02

    Highlights: Black-Right-Pointing-Pointer Cdc20 is a co-activator of APC/C complex. Black-Right-Pointing-Pointer Cdc20 recruits Sp100 and mediates its degradation. Black-Right-Pointing-Pointer The D-box of Sp100 is required for Cdc20-mediated degradation. Black-Right-Pointing-Pointer Sp100 expresses consistently at both the mRNA and protein levels in cell cycle. -- Abstract: Cdc20 is a co-activator of the anaphase-promoting complex/cyclosome (APC/C complex), which recruits substrates at particular phases of the cell cycle and mediates their degradation. Sp100 is a PML-NB scaffold protein, which localizes to nuclear particles during interphase and disperses from them during mitosis, participates in viral resistance, transcriptional regulation, and apoptosis. However, its metabolism during the cell cycle has not yet been fully characterized. We found a putative D-box in Sp100 using the Eukaryotic Linear Motif (ELM) predictor database. The putative D-box of Sp100 was verified by mutational analysis. Overexpression of Cdc20 resulted in decreased levels of both endogenous Sp100 protein and overexpressed Sp100 mRNA in HEK 293 cells. Only an overexpressed D-box deletion mutant of Sp100 accumulated in HEK293 cells that also overexpressed Cdc20. Cdc20 knockdown by cdc20 specific siRNA resulted in increased Sp100 protein levels in cells. Furthermore, we discovered that the Cdc20 mediated degradation of Sp100 is diminished by the proteasome inhibitor MG132, which suggests that the ubiquitination pathway is involved in this process. However, unlike the other Cdc20 substrates, which display oscillating protein levels, the level of Sp100 protein remains constant throughout the cell cycle. Additionally, both overexpression and knockdown of endogenous Sp100 had no effect on the cell cycle. Our results suggested that sp100 is a novel substrate of Cdc20 and it is degraded by the ubiquitination pathway. The intact D-box of Sp100 was necessary for this process. These findings expand

  11. Re-Visiting the Flipped Classroom in a Design Context

    Science.gov (United States)

    Coyne, Richard David; Lee, John; Denitsa, Petrova

    2017-01-01

    After explaining our experience with a flipped classroom model of learning, we argue that the approach brings to light the dramaturgical and mediatized aspects of learning experiences that favour a closer connection between recorded content and "live" presentation by the lecturer. We adopted the flipped classroom approach to learning and…

  12. A Comparison of Student Academic Performance with Traditional, Online, and Flipped Instructional Approaches in a C# Programming Course

    Science.gov (United States)

    Sharp, Jason H.; Sharp, Laurie A.

    2017-01-01

    Aim/Purpose: Compared student academic performance on specific course requirements in a C# programming course across three instructional approaches: traditional, online, and flipped. Background: Addressed the following research question--When compared to the online and traditional instructional approaches, does the flipped instructional approach…

  13. Neutrino helicity flips via electroweak interactions

    International Nuclear Information System (INIS)

    Gaemers, K.J.F.; Gandhi, R.; Lattimer, J.M.; Department of Earth and Space Sciences, State University of New York, Stony Brook, New York 11794)

    1989-01-01

    Electroweak mechanisms via which neutrinos may flip helicity are examined in detail. Exact and approximate expressions for a variety of flip processes relevant in astrophysics and cosmology, mediated by W, Z, and γ exchange, including their interference, are derived for both Dirac and Majorana neutrinos (with emphasis on the former). It is shown that in general flip and nonflip cross sections differ by more than just a multiplicative factor of m/sub ν/ 2 /4E/sub ν/ 2 contrary to what might be expected and that this additional dependence on helicities can be significant. It is also shown that within the context of the standard model with massive neutrinos, for νe yields νe scattering, σ/sub Z//sup flip//σ/sub γ//sup flip/ ∼ 10 4 , independent of particle masses and energies to a good approximation. As an application, using some general considerations and the fact that the observed bar nu/sub e/ burst from SN 1987A lasted several seconds, these weak-interaction flip cross sections are used to rule out μ and tau neutrino masses above 30 keV. Finally, some other consequences for astrophysics in general and supernovae in particular are briefly discussed

  14. Identification of critical regions in human SAMHD1 required for nuclear localization and Vpx-mediated degradation.

    Science.gov (United States)

    Guo, Haoran; Wei, Wei; Wei, Zhenhong; Liu, Xianjun; Evans, Sean L; Yang, Weiming; Wang, Hong; Guo, Ying; Zhao, Ke; Zhou, Jian-Ying; Yu, Xiao-Fang

    2013-01-01

    The sterile alpha motif (SAM) and HD domain-containing protein-1 (SAMHD1) inhibits the infection of resting CD4+ T cells and myeloid cells by human and related simian immunodeficiency viruses (HIV and SIV). Vpx inactivates SAMHD1 by promoting its proteasome-dependent degradation through an interaction with CRL4 (DCAF1) E3 ubiquitin ligase and the C-terminal region of SAMHD1. However, the determinants in SAMHD1 that are required for Vpx-mediated degradation have not been well characterized. SAMHD1 contains a classical nuclear localization signal (NLS), and NLS point mutants are cytoplasmic and resistant to Vpx-mediated degradation. Here, we demonstrate that NLS-mutant SAMHD1 K11A can be rescued by wild-type SAMHD1, restoring its nuclear localization; consequently, SAMHD1 K11A became sensitive to Vpx-mediated degradation in the presence of wild-type SAMHD1. Surprisingly, deletion of N-terminal regions of SAMHD1, including the classical NLS, generated mutant SAMHD1 proteins that were again sensitive to Vpx-mediated degradation. Unlike SAMHD1 K11A, these deletion mutants could be detected in the nucleus. Interestingly, NLS-defective SAMHD1 could still bind to karyopherin-β1 and other nuclear proteins. We also determined that the linker region between the SAM and HD domain and the HD domain itself is important for Vpx-mediated degradation but not Vpx interaction. Thus, SAMHD1 contains an additional nuclear targeting mechanism in addition to the classical NLS. Our data indicate that multiple regions in SAMHD1 are critical for Vpx-mediated nuclear degradation and that association with Vpx is not sufficient for Vpx-mediated degradation of SAMHD1. Since the linker region and HD domain may be involved in SAMHD1 multimerization, our results suggest that SAMHD1 multimerization may be required for Vpx-mediation degradation.

  15. Bacteria-mediated bisphenol A degradation.

    Science.gov (United States)

    Zhang, Weiwei; Yin, Kun; Chen, Lingxin

    2013-07-01

    Bisphenol A (BPA) is an important monomer in the manufacture of polycarbonate plastics, food cans, and other daily used chemicals. Daily and worldwide usage of BPA and BPA-contained products led to its ubiquitous distribution in water, sediment/soil, and atmosphere. Moreover, BPA has been identified as an environmental endocrine disruptor for its estrogenic and genotoxic activity. Thus, BPA contamination in the environment is an increasingly worldwide concern, and methods to efficiently remove BPA from the environment are urgently recommended. Although many factors affect the fate of BPA in the environment, BPA degradation is mainly depended on the metabolism of bacteria. Many BPA-degrading bacteria have been identified from water, sediment/soil, and wastewater treatment plants. Metabolic pathways of BPA degradation in specific bacterial strains were proposed, based on the metabolic intermediates detected during the degradation process. In this review, the BPA-degrading bacteria were summarized, and the (proposed) BPA degradation pathway mediated by bacteria were referred.

  16. CADM1 is essential for KSHV-encoded vGPCR-and vFLIP-mediated chronic NF-κB activation.

    Directory of Open Access Journals (Sweden)

    Richard Hunte

    2018-04-01

    Full Text Available Approximately 12% of all human cancers worldwide are caused by infections with oncogenic viruses. Kaposi's sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV8 is one of the oncogenic viruses responsible for human cancers, including Kaposi's sarcoma (KS, Primary Effusion Lymphoma (PEL, and the lymphoproliferative disorder multicentric Castleman's disease (MCD. Chronic inflammation mediated by KSHV infection plays a decisive role in the development and survival of these cancers. NF-κB, a family of transcription factors regulating inflammation, cell survival, and proliferation, is persistently activated in KSHV-infected cells. The KSHV latent and lytic expressing oncogenes involved in NF-κB activation are vFLIP/K13 and vGPCR, respectively. However, the mechanisms by which NF-κB is activated by vFLIP and vGPCR are poorly understood. In this study, we have found that a host molecule, Cell Adhesion Molecule 1 (CADM1, is robustly upregulated in KSHV-infected PBMCs and KSHV-associated PEL cells. Further investigation determined that both vFLIP and vGPCR interacted with CADM1. The PDZ binding motif localized at the carboxyl terminus of CADM1 is essential for both vGPCR and vFLIP to maintain chronic NF-κB activation. Membrane lipid raft associated CADM1 interaction with vFLIP is critical for the initiation of IKK kinase complex and NF-κB activation in the PEL cells. In addition, CADM1 played essential roles in the survival of KSHV-associated PEL cells. These data indicate that CADM1 plays key roles in the activation of NF-κB pathways during latent and lytic phases of the KSHV life cycle and the survival of KSHV-infected cells.

  17. Microbial surfactant mediated degradation of anthracene in aqueous phase by marine Bacillus licheniformis MTCC 5514

    Directory of Open Access Journals (Sweden)

    Sreethar Swaathy

    2014-12-01

    Full Text Available The present study emphasizes the biosurfactant mediated anthracene degradation by a marine alkaliphile Bacillus licheniformis (MTCC 5514. The isolate, MTCC 5514 degraded >95% of 300 ppm anthracene in an aqueous medium within 22 days and the degradation percentage reduced significantly when the concentration of anthracene increased to above 500 ppm. Naphthalene, naphthalene 2-methyl, phthalic acid and benzene acetic acid are the products of degradation identified based on thin layer chromatography, high performance liquid chromatography, gas chromatography and mass analyses. It has been observed that the degradation is initiated by the biosurfactant of the isolate for solubilization through micellation and then the alkali pH and intra/extra cellular degradative enzymes accomplish the degradation process. Encoding of genes responsible for biosurfactant production (licA3 as well as catabolic reactions (C23O made with suitable primers designed. The study concludes in situ production of biosurfactant mediates the degradation of anthracene by B. licheniformis.

  18. Degradation of antibiotic norfloxacin in aqueous solution by visible-light-mediated C-TiO2 photocatalysis

    International Nuclear Information System (INIS)

    Chen, Meijuan; Chu, W.

    2012-01-01

    Highlights: ► Vis/C-TiO 2 process was employed to degrade norfloxacin for the first time. ► An original schematic diagram for deciphering the catalyst surface property was proposed. ► OH· radicals are verified to play a major role in the norfloxacin decomposition. ► Hole scavenger of ammonium did not show negative influence. ► Fluoride presented a unique restriction in the norfloxacin decay. - Abstract: A visible-light-mediated C-TiO 2 photocatalytic process (Vis/C-TiO 2 ) was employed to degrade antibiotic norfloxacin. The influences of catalyst dosage, initial probe compound concentration and solution pH levels on the decay performance and reaction kinetics were investigated and optimized. Based on the experimental results, an equation was established to predict the observed rate constant under neutral pH. In addition, the decay rate was accelerated under weak alkali in the presence of moderate OH − anions. Hydroxyl radical was confirmed to play a major role in the Vis/TiO 2 process, where in the presence of ·OH quencher and electron acceptor, retardation and improvement were found respectively. Furthermore, an original schematic diagram describing the surface property of C-TiO 2 was built and further verified, in which, NH 4 + cations normally served as hole scavengers showed a negligible effect because the adsorbed OH − formed a barrier for NH 4 + ions to approach the holes, and the F − anions presented a significant suppression on norfloxacin decay due to the formation of hydrogen bond (O-H⋯F) around the C-TiO 2 surface. Besides, the recycling and sedimentation tests justified that the Vis/C-TiO 2 process is a cost-effective and feasible way for wastewater treatment.

  19. β-Elemene piperazine derivatives induce apoptosis in human leukemia cells through downregulation of c-FLIP and generation of ROS.

    Directory of Open Access Journals (Sweden)

    Zhiying Yu

    Full Text Available β-Elemene is an active component of the herb medicine Curcuma Wenyujin with reported antitumor activity. To improve its antitumor ability, five novel piperazine derivatives of β-elemene, 13-(3-methyl-1-piperazinyl-β-elemene (DX1, 13-(cis-3,5-dimethyl-1-piperazinyl-β-elemene (DX2, 13-(4-ethyl-1-piperazinyl-β-elemene (DX3, 13-(4-isopropyl-1-piperazinyl-β-elemene (DX4 and 13-piperazinyl-β-elemene (DX5, were synthesized. The antiproliferative and apoptotic effects of these derivatives were determined in human leukemia HL-60, NB4, K562 and HP100-1 cells. DX1, DX2 and DX5, which contain a secondary amino moiety, were more active in inhibiting cell growth and in inducing apoptosis than DX3 and DX4. The apoptosis induction ability of DX1 was associated with the generation of hydrogen peroxide (H(2O(2, a decrease of mitochondrial membrane potential (MMP, and the activation of caspase-8. Pretreatment with the antioxidants N-acetylcysteine and catalase completely blocked DX1-induced H(2O(2 production, but only partially its activation of caspase-8 and induction of apoptosis. HL-60 cells were more sensitive than its H(2O(2-resistant subclone HP100-1 cells to DX1-induced apoptosis. The activation of caspase-8 by these compounds was correlated with the decrease in the levels of cellular FLICE-inhibitory protein (c-FLIP. The proteasome inhibitor MG-132 augmented the decrease in c-FLIP levels and apoptosis induced by these derivatives. FADD- and caspase-8-deficient Jurkat subclones have a decreased response to DX1-induced apoptosis. Our data indicate that these novel β-elemene piperazine derivatives induce apoptosis through the decrease in c-FLIP levels and the production of H(2O(2 which leads to activation of both death receptor- and mitochondrial-mediated apoptotic pathways.

  20. Evaluation of esophageal motility utilizing the functional lumen imaging probe (FLIP)

    Science.gov (United States)

    Carlson, Dustin A.; Kahrilas, Peter J.; Lin, Zhiyue; Hirano, Ikuo; Gonsalves, Nirmala; Listernick, Zoe; Ritter, Katherine; Tye, Michael; Ponds, Fraukje A.; Wong, Ian; Pandolfino, John E.

    2016-01-01

    Background Esophagogastric junction (EGJ) distensibility and distension-mediated peristalsis can be assessed with the functional lumen imaging probe (FLIP) during a sedated upper endoscopy. We aimed to describe esophageal motility assessment using FLIP topography in patients presenting with dysphagia. Methods 145 patients (ages 18 – 85, 54% female) with dysphagia that completed upper endoscopy with a 16-cm FLIP assembly and high-resolution manometry (HRM) were included. HRM was analyzed according to the Chicago Classification of esophageal motility disorders; major esophageal motility disorders were considered ‘abnormal’. FLIP studies were analyzed using a customized program to calculate the EGJ-distensibility index (DI) and generate FLIP topography plots to identify esophageal contractility patterns. FLIP topography was considered ‘abnormal’ if EGJ-DI was esophageal motility and 29 normal motility. 17 (50%) had abnormal FLIP topography including 13 (37%) with abnormal EGJ-DI. Conclusions FLIP topography provides a well-tolerated method for esophageal motility assessment (especially to identify achalasia) at the time of upper endoscopy. FLIP topography findings that are discordant with HRM may indicate otherwise undetected abnormalities of esophageal function, thus FLIP provides an alternative and complementary method to HRM for evaluation of non-obstructive dysphagia. PMID:27725650

  1. The Role of c-FLIP(L) in Regulating Apoptotic Pathways in Prostate Cancer

    Science.gov (United States)

    2008-12-01

    and 0.1 to 0.5 ng of 32P-labeled double- stranded specific oligonucleotides (5,000–25,000 cpm ) in the presence of 2 Ag of poly(deoxyinosinic... advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. c-Fos Represses c-FLIP(L) www.aacrjournals.org 9433 Cancer Res 2007; 67...of this article were defrayed in part by the payment of page charges.This article must therefore be hereby marked advertisement in accordance with18

  2. A Comparison of Student Academic Performance with Traditional, Online, And Flipped Instructional Approaches in a C# Programming Course

    Directory of Open Access Journals (Sweden)

    Jason H. Sharp

    2017-08-01

    Full Text Available Aim/Purpose: Compared student academic performance on specific course requirements in a C# programming course across three instructional approaches: traditional, online, and flipped. Background: Addressed the following research question: When compared to the online and traditional instructional approaches, does the flipped instructional approach have a greater impact on student academic performance with specific course requirements in a C# programming course? Methodology: Quantitative research design conducted over eight 16-week semesters among a total of 271 participants who were undergraduate students en-rolled in a C# programming course. Data collected were grades earned from specific course requirements and were analyzed with the nonparametric Kruskal Wallis H-Test using IBM SPSS Statistics, Version 23. Contribution: Provides empirical findings related to the impact that different instructional approaches have on student academic performance in a C# programming course. Also describes implications and recommendations for instructors of programming courses regarding instructional approaches that facilitate active learning, student engagement, and self-regulation. Findings: Resulted in four statistically significant findings, indicating that the online and flipped instructional approaches had a greater impact on student academic performance than the traditional approach. Recommendations for Practitioners: Implement instructional approaches such as online, flipped, or blended which foster active learning, student engagement, and self-regulation to increase student academic performance. Recommendation for Researchers: Build upon this study and others similar to it to include factors such as gender, age, ethnicity, and previous academic history. Impact on Society: Acknowledge the growing influence of technology on society as a whole. Higher education coursework and programs are evolving to encompass more digitally-based learning contexts, thus

  3. Neutrino helicity flips via electroweak interactions and SN1987a

    International Nuclear Information System (INIS)

    Gaemers, K.J.F.; Gandhi, R.; Lattimer, J.M.

    1988-10-01

    Electroweak mechanisms via which neutrinos may flip helicity and become sterile are examined in detail. Exact and approximate expressions for a variety of flip processes relevant in astrophysics and cosmology, mediated by W,Z, and γ exchange, including their interference, are derived. It is shown that within the context of the Standard Model with massive neutrinos, for νe→νe scattering, σ Z flip /σ γ flip ∼ 6 X 10 3 , independent of particle masses and energies to a good approximation. It is also shown that using some general considerations and the fact that the observed anti ν e burst from SN1987a lasted several seconds, these weak interaction flip cross-sections can be used to derive an upper limit on μ and τ neutrino masses of ∼ 40 keV. Finally, some other consequences for astrophysics in general and supernovae in particular are briefly discussed. 29 refs.; 47 schemes

  4. SU(5): to flip or not to flip

    International Nuclear Information System (INIS)

    Nanopoulos, D.V.; Wisconsin Univ., Madison,

    1988-01-01

    Flipped SU(5) possesses some unique features as a grand unified theory: elegant missing partner mechanism, see-saw neutrino masses, no Higgs adjoints. This last property makes flipped SU(5) the only known grand unified theory derivable from 4-dimensional superstrings. When derived from the superstrings, flipped SU(5) possesses, in addition a hierarchical fermion mass spectrum. All these recent developments involving flipped SU(5) are discussed in a detailed but simple way, including phenomenological consequences at low energies

  5. Perforin rapidly induces plasma membrane phospholipid flip-flop.

    Directory of Open Access Journals (Sweden)

    Sunil S Metkar

    Full Text Available The cytotoxic cell granule secretory pathway is essential for host defense. This pathway is fundamentally a form of intracellular protein delivery where granule proteases (granzymes from cytotoxic lymphocytes are thought to diffuse through barrel stave pores generated in the plasma membrane of the target cell by the pore forming protein perforin (PFN and mediate apoptotic as well as additional biological effects. While recent electron microscopy and structural analyses indicate that recombinant PFN oligomerizes to form pores containing 20 monomers (20 nm when applied to liposomal membranes, these pores are not observed by propidium iodide uptake in target cells. Instead, concentrations of human PFN that encourage granzyme-mediated apoptosis are associated with pore structures that unexpectedly favor phosphatidylserine flip-flop measured by Annexin-V and Lactadherin. Efforts that reduce PFN mediated Ca influx in targets did not reduce Annexin-V reactivity. Antigen specific mouse CD8 cells initiate a similar rapid flip-flop in target cells. A lipid that augments plasma membrane curvature as well as cholesterol depletion in target cells enhance flip-flop. Annexin-V staining highly correlated with apoptosis after Granzyme B (GzmB treatment. We propose the structures that PFN oligomers form in the membrane bilayer may include arcs previously observed by electron microscopy and that these unusual structures represent an incomplete mixture of plasma membrane lipid and PFN oligomers that may act as a flexible gateway for GzmB to translocate across the bilayer to the cytosolic leaflet of target cells.

  6. FlipADAM: a potential new SPECT imaging agent for the serotonin transporter

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Julie L.; Deutsch, Eric C. [Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 (United States); Oya, Shunichi [Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 (United States); Kung, Hank F., E-mail: kunghf@gmail.co [Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 (United States); Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 (United States)

    2010-07-15

    Introduction: Single photon emission computed tomography (SPECT) imaging of the serotonin transporter (SERT) in the brain is a useful tool for examining normal physiological functions and disease states involving the serotonergic system. The goal of this study was to develop an improved SPECT radiotracer with faster kinetics than the current leading SPECT tracer, [{sup 123}I]ADAM, for selective SERT imaging. Methods: The in vitro binding affinities of (2-(2'-((dimethylamino)methyl)-4'-iodophenylthio)benzenamine) (FlipADAM) (1c), were determined using Hampshire pig kidney cells stably overexpressing the serotonin, norepinephrine (NET) or dopamine transporter (DAT). Localization of [{sup 125}I]FlipADAM (1c) was evaluated through biodistribution and autoradiography in male Sprague Dawley rats, and the specificity of binding was assessed by injecting selective SERT or NET inhibitors prior to [{sup 125}I]FlipADAM (1c). Results: FlipADAM (1c) displayed a high binding affinity for SERT (K{sub i}=1.0 nM) and good selectivity over NET and DAT binding (43-fold and 257-fold, respectively). [{sup 125}I]FlipADAM (1c) successfully penetrated the blood brain barrier, as evidenced by the brain uptake at 2 min (1.75% dose/g). [{sup 125}I]FlipADAM(1c) also had a good target to non-target (hypothalamus/cerebellum) ratio of 3.35 at 60 min post-injection. In autoradiography studies, [{sup 125}I]FlipADAM (1c) showed selective localization in SERT-rich brain regions such as the thalamic nuclei, amygdala, dorsal raphe nuclei and other areas. Conclusion: [{sup 125}I]FlipADAM (1c) exhibited faster clearance from the brain and time to binding equilibrium when compared to [{sup 125}I]2-(2'-((dimethylamino)methyl)-phenylthio)-5-iodophenylamine [{sup 125}I]ADAM (1b) and a higher target to non-target ratio when compared to [{sup 125}I]5-iodo-2-(2'-((dimethylamino)methyl)-phenylthio)benzyl alcohol [{sup 125}I]IDAM (1a). Therefore, [{sup 123}I]FlipADAM (1c) may be an improved

  7. Flipped Learning

    DEFF Research Database (Denmark)

    Holmboe, Peter; Hachmann, Roland

    I FLIPPED LEARNING – FLIP MED VIDEO kan du læse om, hvordan du som underviser kommer godt i gang med at implementere video i undervisning, der har afsæt i tankerne omkring flipped learning. Bogen indeholder fire dele: I Del 1 fokuserer vi på det metarefleksive i at tænke video ind i undervisningen...

  8. Spermidine mediates degradation of ornithine decarboxylase by a non-lysosomal, ubiquitin-independent mechanism

    International Nuclear Information System (INIS)

    Glass, J.R.; Gerner, E.W.

    1987-01-01

    The mechanism of spermidine-induced ornithine decarboxylase (OCD, E.C. 4.1.1.17) inactivation was investigated using Chinese hamster ovary (CHO) cells, maintained in serum-free medium, which display a stabilization of ODC owing to the lack of accumulation of putrescine and spermidine. Treatment of cells with 10 μM exogenous spermidine leads to rapid decay of ODC activity accompanied by a parallel decrease in enzyme protein. Analysis of the decay of [ 35 S]methionine-labeled ODC and separation by two-dimensional electrophoresis revealed no detectable modification in ODC structure during enhanced degradation. Spermidine-mediated inactivation of ODC occurred in a temperature-dependent manner exhibiting pseudo-first-order kinetics over a temperature range of 22-37 0 C. In cultures treated continuously, an initial lag was observed after treatment with spermidine, followed by a rapid decline in activity as an apparent critical concentration of intracellular spermidine was achieved. Treating cells at 22 0 C for 3 hours with 10 μ M spermidine, followed by removal of exogenous polyamine, and then shifting to varying temperatures, resulted in rates of ODC inactivation identical with that determined with a continuous treatment. Arrhenius analysis showed that polyamine mediated inactivation of ODC occurred with an activation energy of approximately 16 kcal/mol. Treatment of cells with lysosomotrophic agents had no effect of ODC degradation. ODC turnover was not dependent on ubiquitin-dependent proteolysis. These data support the hypothesis that spermidine regulates ODC degradation via a mechanism requiring new protein synthesis, and that this occurs via a non-lysosomal, ubiquitin-independent pathway

  9. Calpain-Mediated Degradation of Drebrin by Excitotoxicity In vitro and In vivo.

    Directory of Open Access Journals (Sweden)

    Takahiko Chimura

    Full Text Available The level of drebrin, an evolutionarily conserved f-actin-binding protein that regulates synaptic structure and function, is reduced in the brains of patients with chronic neurodegenerative diseases such as Alzheimer's disease (AD and Down's syndrome (DS. It was suggested that excitotoxic neuronal death caused by overactivation of NMDA-type glutamate receptors (NMDARs occurs in AD and DS; however, the relationship between excitotoxicity and drebrin loss is unknown. Here, we show that drebrin is a novel target of calpain-mediated proteolysis under excitotoxic conditions induced by the overactivation of NMDARs. In cultured rodent neurons, degradation of drebrin was confirmed by the detection of proteolytic fragments, as well as a reduction in the amount of full-length drebrin. Notably, the NMDA-induced degradation of drebrin in mature neurons occurred concomitantly with a loss of f-actin. Furthermore, pharmacological inhibition of f-actin loss facilitated the drebrin degradation, suggesting a functional linkage between f-actin and drebrin degradation. Biochemical analyses using purified drebrin and calpain revealed that calpain degraded drebrin directly in vitro. Furthermore, cerebral ischemia also induced the degradation of drebrin in vivo. These findings suggest that calpain-mediated degradation of drebrin is a fundamental pathology of neurodegenerative diseases mediated by excitotoxicity, regardless of whether they are acute or chronic. Drebrin regulates the synaptic clustering of NMDARs; therefore, degradation of drebrin under excitotoxic conditions may modulate NMDAR-mediated signal transductions, including pro-survival signaling. Overall, the results presented here provide novel insights into the molecular basis of cellular responses to excitotoxicity in vitro and in vivo.

  10. Spin-flip and spin orbit interactions in heavy ion systems

    International Nuclear Information System (INIS)

    Bybell, D.P.

    1983-01-01

    The role of spin orbit forces in heavy ion reactions is not completely understood. Experimental data is scarce for these systems but the data that does exist indicates a stronger spin orbit force than predicted by the folding models. The spin-flip probability of non-spin zero projectiles is one technique used for these measurements and is often taken as a direct indicator of a spin orbit interaction. This work measures the projectile spin-flip probability for three inelastic reactions; 13 C + 24 Mg, E/sub cm/ = 22.7 MeV; 13 C + 12 C, E/sub cm/ = 17.3 MeV; and 6 Li + 12 C, E/sub cm/ = 15.2 MeV, all leading to the first J/sup π/ = 2 + state of the target. The technique of particle-γ angular correlations was used for measuring the final state density matrix elements, of which the absolute value M = 1 magnetic substate population is equivalent to the spin-flip probability. The method was explored in detail and found to be sensitive to spin-flip probabilities smaller than 1%. The technique was also found to be a good indicator of the reaction mechanism involved. Nonzero and occasionally large spin-flip probabilities were observed in all systems, much larger than the folding model predictions. Information was obtained on the non-spin-flip density matrix elements. In the 13 C + 24 Mg reaction, these were found to agree with calculations when the finite size of the particle detector is included

  11. 25-OCH3-PPD induces the apoptosis of activated t-HSC/Cl-6 cells via c-FLIP-mediated NF-κB activation.

    Science.gov (United States)

    Wu, Yan-ling; Wan, Ying; Jin, Xue-Jun; OuYang, Bing-Qing; Bai, Ting; Zhao, Yu-Qing; Nan, Ji-Xing

    2011-11-15

    25-OCH(3)-PPD is a dammarane-type triterpene sapogenin isolated from the roots, leaves and seeds of Panax notoginseng, which has shown anti-tumor effects in several human cancer lines. In this study, we evaluated the effects of 25-OCH(3)-PPD on apoptosis of activated t-HSC/Cl-6 cells induced by tumor necrosis factor-α (TNF-α). The inhibitory effects of eleven compounds isolated from Panax ginseng and P. notoginseng were detected in activated t-HSC/Cl-6 cells. 25-OCH(3)-PPD produced a significant inhibitory effect on activated t-HSC/Cl-6 cells. However, 25-OCH(3)-PPD showed almost no effect on the cell viability of Chang liver cells, a type of normal human hepatic cell line. Therefore, we aimed to determine the anti-fibrotic potential of 25-OCH(3)-PPD and to characterize the signal transduction pathways involved in activated HSCs. 25-OCH(3)-PPD decreased the fibrosis markers, including α-smooth muscle actin (α-SMA), transforming growth factor β-1 (TGF-β1) and tissue inhibitors of metalloproteinases-1 (TIMP-1). 25-OCH(3)-PPD elevated the level of cellular GSH in activated HSCs, which demonstrated that 25-OCH(3)-PPD might inhibit HSC activation by its antioxidant capacity. Further analyses revealed that 25-OCH(3)-PPD increased the levels of cleaved caspase-3, decreased the ratio of Bcl-2/Bax and the expression of survivin via c-FLIP-mediated NF-κB activation and shed light on the regulation of apoptosis. Therefore, 25-OCH(3)-PPD may prove to be an excellent candidate agent for the therapy of hepatic fibrosis. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Selective base excision repair of DNA damage by the non-base-flipping DNA glycosylase AlkC

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Rongxin; Mullins, Elwood A.; Shen, Xing; #8208; Xing; Lay, Kori T.; Yuen, Philip K.; David, Sheila S.; Rokas, Antonis; Eichman, Brandt F. (UCD); (Vanderbilt)

    2017-10-20

    DNA glycosylases preserve genome integrity and define the specificity of the base excision repair pathway for discreet, detrimental modifications, and thus, the mechanisms by which glycosylases locate DNA damage are of particular interest. Bacterial AlkC and AlkD are specific for cationic alkylated nucleobases and have a distinctive HEAT-like repeat (HLR) fold. AlkD uses a unique non-base-flipping mechanism that enables excision of bulky lesions more commonly associated with nucleotide excision repair. In contrast, AlkC has a much narrower specificity for small lesions, principally N3-methyladenine (3mA). Here, we describe how AlkC selects for and excises 3mA using a non-base-flipping strategy distinct from that of AlkD. A crystal structure resembling a catalytic intermediate complex shows how AlkC uses unique HLR and immunoglobulin-like domains to induce a sharp kink in the DNA, exposing the damaged nucleobase to active site residues that project into the DNA. This active site can accommodate and excise N3-methylcytosine (3mC) and N1-methyladenine (1mA), which are also repaired by AlkB-catalyzed oxidative demethylation, providing a potential alternative mechanism for repair of these lesions in bacteria.

  13. Flip-flop of phospholipids in proteoliposomes reconstituted from detergent extract of chloroplast membranes: kinetics and phospholipid specificity.

    Directory of Open Access Journals (Sweden)

    Archita Rajasekharan

    Full Text Available Eukaryotic cells are compartmentalized into distinct sub-cellular organelles by lipid bilayers, which are known to be involved in numerous cellular processes. The wide repertoire of lipids, synthesized in the biogenic membranes like the endoplasmic reticulum and bacterial cytoplasmic membranes are initially localized in the cytosolic leaflet and some of these lipids have to be translocated to the exoplasmic leaflet for membrane biogenesis and uniform growth. It is known that phospholipid (PL translocation in biogenic membranes is mediated by specific membrane proteins which occur in a rapid, bi-directional fashion without metabolic energy requirement and with no specificity to PL head group. A recent study reported the existence of biogenic membrane flippases in plants and that the mechanism of plant membrane biogenesis was similar to that found in animals. In this study, we demonstrate for the first time ATP independent and ATP dependent flippase activity in chloroplast membranes of plants. For this, we generated proteoliposomes from Triton X-100 extract of intact chloroplast, envelope membrane and thylakoid isolated from spinach leaves and assayed for flippase activity using fluorescent labeled phospholipids. Half-life time of flipping was found to be 6 ± 1 min. We also show that: (a intact chloroplast and envelope membrane reconstituted proteoliposomes can flip fluorescent labeled analogs of phosphatidylcholine in ATP independent manner, (b envelope membrane and thylakoid reconstituted proteoliposomes can flip phosphatidylglycerol in ATP dependent manner, (c Biogenic membrane ATP independent PC flipping activity is protein mediated and (d the kinetics of PC translocation gets affected differently upon treatment with protease and protein modifying reagents.

  14. Targeting Neutrophil Protease-Mediated Degradation of Tsp-1 to Induce Metastatic Dormancy

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0615 TITLE: Targeting Neutrophil Protease-Mediated Degradation of Tsp-1 to Induce Metastatic Dormancy PRINCIPAL...29 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting Neutrophil Protease-Mediated Degradation of Tsp-1 to Induce Metastatic Dormancy...infection or cigarette smoke enhanced pulmonary metastasis from breast cancer in humans and mice. Similarly, autoimmune arthritis, characterized by

  15. Some comments on flipped SU(5) times U(1) and flipped unification in general

    Energy Technology Data Exchange (ETDEWEB)

    Barr, S.M. (Bartol Research Institute, University of Delaware, Newark, Delaware 19716 (US))

    1989-10-01

    A general group-theoretical discussion of flipped embeddings is given. In addition to the well-known flipped SU(5) and flipped SO(10), the existence of flipped E{sub 6} and E{sub 7} is shown, as well as several families and special cases of flipped embeddings. A possible physical reason, essentially based on the group theory of flipped embeddings, why nature prefers the low-energy group SU(3){times}SU(2){times}U(1) to alternatives such as SU(4){times}U(1) and SU(5) is pointed out.

  16. Some comments on flipped SU(5)xU(1) and flipped unification in general

    International Nuclear Information System (INIS)

    Barr, S.M.

    1989-01-01

    A general group-theoretical discussion of flipped embeddings is given. In addition to the well-known flipped SU(5) and flipped SO(10), the existence of flipped E 6 and E 7 is shown, as well as several families and special cases of flipped embeddings. A possible physical reason, essentially based on the group theory of flipped embeddings, why nature prefers the low-energy group SU(3)xSU(2)xU(1) to alternatives such as SU(4)xU(1) and SU(5) is pointed out

  17. Flipped SO(10)

    Energy Technology Data Exchange (ETDEWEB)

    Tamvakis, K.

    1988-01-28

    We construct an N=1 supersymmetric SO(10) GUT broken down to SU(3)c x SU(2)/sub L/ x U(1)/sub ..gamma../ with an intermediate flipped SU(5) x U(1)/sub chi/ gauge symmetry. A solution to the triplet-doublet mass-splitting problem is proposed in terms of a non-minimal missing-partner mechanism.

  18. Flipped Learning, Flipped Satisfaction, Getting the Balance Right

    Science.gov (United States)

    Swinburne, Rosemary Fisher; Ross, Bella; LaFerriere, Richard; Maritz, Alex

    2017-01-01

    This paper explores students' perceptions of their learning outcomes, engagement, and satisfaction with a technology-facilitated flipped approach in a third-year core subject at an Australian university during 2014. In this pilot study, findings reveal that students preferred the flipped approach to the traditional face-to-face delivery and…

  19. The flipped classroom

    DEFF Research Database (Denmark)

    Triantafyllou, Evangelia

    2015-01-01

    One of the novel ideas in teaching that heavily relies on current technology is the “flipped classroom” approach. In a flipped classroom the traditional lecture and homework sessions are inverted. Students are provided with online material in order to gain necessary knowledge before class, while...... class time is devoted to clarifications and application of this knowledge. The hypothesis is that there could be deep and creative discussions when teacher and students physically meet. This paper presents design considerations for flipped classrooms, and discusses how Moodle can facilitate...... with a discussion of the opportunities and challenges when implementing the flipped model in a virtual learning environment (VLE) like Moodle....

  20. Flipped Classroom Approach

    Directory of Open Access Journals (Sweden)

    Fezile Ozdamli

    2016-07-01

    Full Text Available Flipped classroom is an active, student-centered approach that was formed to increase the quality of period within class. Generally this approach whose applications are done mostly in Physical Sciences, also attracts the attention of educators and researchers in different disciplines recently. Flipped classroom learning which wide-spreads rapidly in the world, is not well recognized in our country. That is why the aim of study is to attract attention to its potential in education field and provide to make it recognize more by educators and researchers. With this aim, in the study what flipped classroom approach is, flipped classroom technology models, its advantages and limitations were explained.

  1. Degradation of AF1Q by chaperone-mediated autophagy

    International Nuclear Information System (INIS)

    Li, Peng; Ji, Min; Lu, Fei; Zhang, Jingru; Li, Huanjie; Cui, Taixing; Li Wang, Xing; Tang, Dongqi; Ji, Chunyan

    2014-01-01

    AF1Q, a mixed lineage leukemia gene fusion partner, is identified as a poor prognostic biomarker for pediatric acute myeloid leukemia (AML), adult AML with normal cytogenetic and adult myelodysplastic syndrome. AF1Q is highly regulated during hematopoietic progenitor differentiation and development but its regulatory mechanism has not been defined clearly. In the present study, we used pharmacological and genetic approaches to influence chaperone-mediated autophagy (CMA) and explored the degradation mechanism of AF1Q. Pharmacological inhibitors of lysosomal degradation, such as chloroquine, increased AF1Q levels, whereas activators of CMA, including 6-aminonicotinamide and nutrient starvation, decreased AF1Q levels. AF1Q interacts with HSPA8 and LAMP-2A, which are core components of the CMA machinery. Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. Using an amino acid deletion AF1Q mutation plasmid, we identified that AF1Q had a KFERQ-like motif which was recognized by HSPA8 for CMA-dependent proteolysis. In conclusion, we demonstrate for the first time that AF1Q can be degraded in lysosomes by CMA. - Highlights: • Chaperone-mediated autophagy (CMA) is involved in the degradation of AF1Q. • Macroautophagy does not contribute to the AF1Q degradation. • AF1Q has a KFERQ-like motif that is recognized by CMA core components

  2. Degradation of AF1Q by chaperone-mediated autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Li, Peng; Ji, Min; Lu, Fei; Zhang, Jingru [Department of Hematology, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan 250012 (China); Li, Huanjie; Cui, Taixing; Li Wang, Xing [Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan 250012 (China); Tang, Dongqi, E-mail: tangdq@sdu.edu.cn [Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan 250012 (China); Center for Stem Cell and Regenerative Medicine, The Second Hospital of Shandong University, Jinan 250033 (China); Ji, Chunyan, E-mail: jichunyan@sdu.edu.cn [Department of Hematology, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan 250012 (China)

    2014-09-10

    AF1Q, a mixed lineage leukemia gene fusion partner, is identified as a poor prognostic biomarker for pediatric acute myeloid leukemia (AML), adult AML with normal cytogenetic and adult myelodysplastic syndrome. AF1Q is highly regulated during hematopoietic progenitor differentiation and development but its regulatory mechanism has not been defined clearly. In the present study, we used pharmacological and genetic approaches to influence chaperone-mediated autophagy (CMA) and explored the degradation mechanism of AF1Q. Pharmacological inhibitors of lysosomal degradation, such as chloroquine, increased AF1Q levels, whereas activators of CMA, including 6-aminonicotinamide and nutrient starvation, decreased AF1Q levels. AF1Q interacts with HSPA8 and LAMP-2A, which are core components of the CMA machinery. Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. Using an amino acid deletion AF1Q mutation plasmid, we identified that AF1Q had a KFERQ-like motif which was recognized by HSPA8 for CMA-dependent proteolysis. In conclusion, we demonstrate for the first time that AF1Q can be degraded in lysosomes by CMA. - Highlights: • Chaperone-mediated autophagy (CMA) is involved in the degradation of AF1Q. • Macroautophagy does not contribute to the AF1Q degradation. • AF1Q has a KFERQ-like motif that is recognized by CMA core components.

  3. Detection of trans–cis flips and peptide-plane flips in protein structures

    Energy Technology Data Exchange (ETDEWEB)

    Touw, Wouter G., E-mail: wouter.touw@radboudumc.nl [Radboud University Medical Center, Geert Grooteplein-Zuid 26-28, 6525 GA Nijmegen (Netherlands); Joosten, Robbie P. [Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Vriend, Gert, E-mail: wouter.touw@radboudumc.nl [Radboud University Medical Center, Geert Grooteplein-Zuid 26-28, 6525 GA Nijmegen (Netherlands)

    2015-07-28

    A method is presented to detect peptide bonds that need either a trans–cis flip or a peptide-plane flip. A coordinate-based method is presented to detect peptide bonds that need correction either by a peptide-plane flip or by a trans–cis inversion of the peptide bond. When applied to the whole Protein Data Bank, the method predicts 4617 trans–cis flips and many thousands of hitherto unknown peptide-plane flips. A few examples are highlighted for which a correction of the peptide-plane geometry leads to a correction of the understanding of the structure–function relation. All data, including 1088 manually validated cases, are freely available and the method is available from a web server, a web-service interface and through WHAT-CHECK.

  4. Detection of trans–cis flips and peptide-plane flips in protein structures

    International Nuclear Information System (INIS)

    Touw, Wouter G.; Joosten, Robbie P.; Vriend, Gert

    2015-01-01

    A method is presented to detect peptide bonds that need either a trans–cis flip or a peptide-plane flip. A coordinate-based method is presented to detect peptide bonds that need correction either by a peptide-plane flip or by a trans–cis inversion of the peptide bond. When applied to the whole Protein Data Bank, the method predicts 4617 trans–cis flips and many thousands of hitherto unknown peptide-plane flips. A few examples are highlighted for which a correction of the peptide-plane geometry leads to a correction of the understanding of the structure–function relation. All data, including 1088 manually validated cases, are freely available and the method is available from a web server, a web-service interface and through WHAT-CHECK

  5. Flip-J: Development of the System for Flipped Jigsaw Supported Language Learning

    Science.gov (United States)

    Yamada, Masanori; Goda, Yoshiko; Hata, Kojiro; Matsukawa, Hideya; Yasunami, Seisuke

    2016-01-01

    This study aims to develop and evaluate a language learning system supported by the "flipped jigsaw" technique, called "Flip-J". This system mainly consists of three functions: (1) the creation of a learning material database, (2) allocation of learning materials, and (3) formation of an expert and jigsaw group. Flip-J was…

  6. Biosurfactant and Degradative Enzymes Mediated Crude Oil Degradation by Bacterium Bacillus subtilis A1

    Science.gov (United States)

    Parthipan, Punniyakotti; Preetham, Elumalai; Machuca, Laura L.; Rahman, Pattanathu K. S. M.; Murugan, Kadarkarai; Rajasekar, Aruliah

    2017-01-01

    In this work, the biodegradation of the crude oil by the potential biosurfactant producing Bacillus subtilis A1 was investigated. The isolate had the ability to synthesize degradative enzymes such as alkane hydroxylase and alcohol dehydrogenase at the time of biodegradation of hydrocarbon. The biosurfactant producing conditions were optimized as pH 7.0, temperature 40°C, 2% sucrose and 3% of yeast extract as best carbon and nitrogen sources for maximum production of biosurfactant (4.85 g l-1). Specifically, the low molecular weight compounds, i.e., C10–C14 were completely degraded, while C15–C19 were degraded up to 97% from the total hydrocarbon pools. Overall crude oil degradation efficiency of the strain A1 was about 87% within a short period of time (7 days). The accumulated biosurfactant from the biodegradation medium was characterized to be lipopeptide in nature. The strain A1 was found to be more robust than other reported biosurfactant producing bacteria in degradation efficiency of crude oil due to their enzyme production capability and therefore can be used to remove the hydrocarbon pollutants from contaminated environment. PMID:28232826

  7. MAPKs are essential upstream signaling pathways in proteolytic cartilage degradation--divergence in pathways leading to aggrecanase and MMP-mediated articular cartilage degradation

    DEFF Research Database (Denmark)

    Sondergaard, B-C; Schultz, N; Madsen, S H

    2010-01-01

    Matrix metalloproteinases (MMPs) and aggrecanases are essential players in cartilage degradation. However, the signaling pathways that results in MMP and/or aggrecanase synthesis and activation are not well understood. We investigated the molecular events leading to MMP- and aggrecanase-mediated ......Matrix metalloproteinases (MMPs) and aggrecanases are essential players in cartilage degradation. However, the signaling pathways that results in MMP and/or aggrecanase synthesis and activation are not well understood. We investigated the molecular events leading to MMP- and aggrecanase......-mediated cartilage degradation....

  8. Flipped Learning

    DEFF Research Database (Denmark)

    Hachmann, Roland; Holmboe, Peter

    arbejde med faglige problemstillinger gennem problembaserede og undersøgende didaktiske designs. Flipped Learning er dermed andet og mere end at distribuere digitale materialer til eleverne forud for undervisning. Flipped Learning er i lige så høj grad et syn på, hvordan undervisning med digitale medier...

  9. Rescue of p53 function by small-molecule RITA in cervical carcinoma by blocking E6-mediated degradation.

    Science.gov (United States)

    Zhao, Carolyn Ying; Szekely, Laszlo; Bao, Wenjie; Selivanova, Galina

    2010-04-15

    Proteasomal degradation of p53 by human papilloma virus (HPV) E6 oncoprotein plays a pivotal role in the survival of cervical carcinoma cells. Abrogation of HPV-E6-dependent p53 destruction can therefore be a good strategy to combat cervical carcinomas. Here, we show that a small-molecule reactivation of p53 and induction of tumor cell apoptosis (RITA) is able to induce the accumulation of p53 and rescue its tumor suppressor function in cells containing high-risk HPV16 and HPV18 by inhibiting HPV-E6-mediated proteasomal degradation. RITA blocks p53 ubiquitination by preventing p53 interaction with E6-associated protein, required for HPV-E6-mediated degradation. RITA activates the transcription of proapoptotic p53 targets Noxa, PUMA, and BAX, and repressed the expression of pro-proliferative factors CyclinB1, CDC2, and CDC25C, resulting in p53-dependent apoptosis and cell cycle arrest. Importantly, RITA showed substantial suppression of cervical carcinoma xenografts in vivo. These results provide a proof of principle for the treatment of cervical cancer in a p53-dependent manner by using small molecules that target p53. (c)2010 AACR.

  10. Caspase-10 Negatively Regulates Caspase-8-Mediated Cell Death, Switching the Response to CD95L in Favor of NF-κB Activation and Cell Survival

    Directory of Open Access Journals (Sweden)

    Sebastian Horn

    2017-04-01

    Full Text Available Formation of the death-inducing signaling complex (DISC initiates extrinsic apoptosis. Caspase-8 and its regulator cFLIP control death signaling by binding to death-receptor-bound FADD. By elucidating the function of the caspase-8 homolog, caspase-10, we discover that caspase-10 negatively regulates caspase-8-mediated cell death. Significantly, we reveal that caspase-10 reduces DISC association and activation of caspase-8. Furthermore, we extend our co-operative/hierarchical binding model of caspase-8/cFLIP and show that caspase-10 does not compete with caspase-8 for binding to FADD. Utilizing caspase-8-knockout cells, we demonstrate that caspase-8 is required upstream of both cFLIP and caspase-10 and that DISC formation critically depends on the scaffold function of caspase-8. We establish that caspase-10 rewires DISC signaling to NF-κB activation/cell survival and demonstrate that the catalytic activity of caspase-10, and caspase-8, is redundant in gene induction. Thus, our data are consistent with a model in which both caspase-10 and cFLIP coordinately regulate CD95L-mediated signaling for death or survival.

  11. Flipped Classroom Experiences: Student Preferences and Flip Strategy in a Higher Education Context

    Science.gov (United States)

    McNally, Brenton; Chipperfield, Janine; Dorsett, Pat; Del Fabbro, Letitia; Frommolt, Valda; Goetz, Sandra; Lewohl, Joanne; Molineux, Matthew; Pearson, Andrew; Reddan, Gregory; Roiko, Anne; Rung, Andrea

    2017-01-01

    Despite the popularity of the flipped classroom, its effectiveness in achieving greater engagement and learning outcomes is currently lacking substantial empirical evidence. This study surveyed 563 undergraduate and postgraduate students (61% female) participating in flipped teaching environments and ten convenors of the flipped courses in which…

  12. How to Flip the Classroom--"Productive Failure or Traditional Flipped Classroom" Pedagogical Design?

    Science.gov (United States)

    Song, Yanjie; Kapur, Manu

    2017-01-01

    The paper reports a quasi-experimental study comparing the "traditional flipped classroom" pedagogical design with the "productive failure" (Kapur, 2016) pedagogical design in the flipped classroom for a 2-week curricular unit on polynomials in a Hong Kong Secondary school. Different from the flipped classroom where students…

  13. Human macrophage foam cells degrade atherosclerotic plaques through cathepsin K mediated processes

    DEFF Research Database (Denmark)

    Barascuk, Natasha; Skjøt-Arkil, Helene; Register, Thomas C

    2010-01-01

    BACKGROUND: Proteolytic degradation of Type I Collagen by proteases may play an important role in remodeling of atherosclerotic plaques, contributing to increased risk of plaque rupture.The aim of the current study was to investigate whether human macrophage foam cells degrade the extracellular...... matrix (ECM) of atherosclerotic plaques by cathepsin K mediated processes. METHODS: We 1) cultured human macrophages on ECM and measured cathepsin K generated fragments of type I collagen (C-terminal fragments of Type I collagen (CTX-I) 2) investigated the presence of CTX-I in human coronary arteries......-I in areas of intimal hyperplasia and in shoulder regions of advanced plaques. Treatment of human monocytes with M-CSF or M-CSF+LDL generated macrophages and foam cells producing CTX-I when cultured on type I collagen enriched matrix. Circulating levels of CTX-I were not significantly different in women...

  14. Flipped Learning in the Workplace

    Science.gov (United States)

    Nederveld, Allison; Berge, Zane L.

    2015-01-01

    Purpose: The purpose of this paper is to serve as a summary of resources on flipped learning for workplace learning professionals. A recent buzzword in the training world is "flipped". Flipped learning and the flipped classroom are hot topics that have emerged in K-12 education, made their way to the university and are now being noticed…

  15. Flipping Excel

    Science.gov (United States)

    Frydenberg, Mark

    2013-01-01

    The "flipped classroom" model has become increasingly popular in recent years as faculty try new ways to engage students in the classroom. In a flipped classroom setting, students review the lecture online prior to the class session and spend time in class working on problems or exercises that would have been traditionally assigned as…

  16. Flipped classroom

    DEFF Research Database (Denmark)

    Skov, Tobias Kidde; Jørgensen, Søren

    2016-01-01

    Artiklen beskriver Flipped Classroom som et didaktisk princip, der kan være med til at organisere og tilrettelægge en undervisning, med fokus på forskellige læringsformer. Det handler om at forstå Flipped Classroom som en opdeling i 2 faser og 3 led, som samlet set skaber en didaktisk organisering....

  17. To Flip or Not to Flip? An Exploratory Study Comparing Student Performance in Calculus I

    Science.gov (United States)

    Schroeder, Larissa B.; McGivney-Burelle, Jean; Xue, Fei

    2015-01-01

    The purpose of this exploratory, mixed-methods study was to compare student performance in flipped and non-flipped sections of Calculus I. The study also examined students' perceptions of the flipping pedagogy. Students in the flipped courses reported spending, on average, an additional 1-2 hours per week outside of class on course content.…

  18. APC/C-mediated degradation of dsRNA-binding protein 4 (DRB4 involved in RNA silencing.

    Directory of Open Access Journals (Sweden)

    Katia Marrocco

    Full Text Available Selective protein degradation via the ubiquitin-26S proteasome is a major mechanism underlying DNA replication and cell division in all Eukaryotes. In particular, the APC/C (Anaphase Promoting Complex or Cyclosome is a master ubiquitin protein ligase (E3 that targets regulatory proteins for degradation allowing sister chromatid separation and exit from mitosis. Interestingly, recent work also indicates that the APC/C remains active in differentiated animal and plant cells. However, its role in post-mitotic cells remains elusive and only a few substrates have been characterized.In order to identify novel APC/C substrates, we performed a yeast two-hybrid screen using as the bait Arabidopsis APC10/DOC1, one core subunit of the APC/C, which is required for substrate recruitment. This screen identified DRB4, a double-stranded RNA binding protein involved in the biogenesis of different classes of small RNA (sRNA. This protein interaction was further confirmed in vitro and in plant cells. Moreover, APC10 interacts with DRB4 through the second dsRNA binding motif (dsRBD2 of DRB4, which is also required for its homodimerization and binding to its Dicer partner DCL4. We further showed that DRB4 protein accumulates when the proteasome is inactivated and, most importantly, we found that DRB4 stability depends on APC/C activity. Hence, depletion of Arabidopsis APC/C activity by RNAi leads to a strong accumulation of endogenous DRB4, far beyond its normal level of accumulation. However, we could not detect any defects in sRNA production in lines where DRB4 was overexpressed.Our work identified a first plant substrate of the APC/C, which is not a regulator of the cell cycle. Though we cannot exclude that APC/C-dependent degradation of DRB4 has some regulatory roles under specific growth conditions, our work rather points to a housekeeping function of APC/C in maintaining precise cellular-protein concentrations and homeostasis of DRB4.

  19. Flipping the Graduate Qualitative Research Methods Classroom: Did It Lead to Flipped Learning?

    Science.gov (United States)

    Earley, Mark

    2016-01-01

    The flipped, or inverted, classroom has gained popularity in a variety of fields and at a variety of educational levels, from K-12 through higher education. This paper describes the author's positive experience flipping a graduate qualitative research methods classroom. After a review of the current literature on flipped classrooms in higher…

  20. Mechanisms controlling the temporal degradation of Nek2A and Kif18A by the APC/C-Cdc20 complex

    DEFF Research Database (Denmark)

    Sedgwick, G.G.; Hayward, D.G.; Nilsson, J.

    2013-01-01

    The Anaphase Promoting Complex/Cyclosome (APC/C) in complex with its co-activator Cdc20 is responsible for targeting proteins for ubiquitin-mediated degradation during mitosis. The activity of APC/C-Cdc20 is inhibited during prometaphase by the Spindle Assembly Checkpoint (SAC) yet certain...... substrates escape this inhibition. Nek2A degradation during prometaphase depends on direct binding of Nek2A to the APC/C via a C-terminal MR dipeptide but whether this motif alone is sufficient is not clear. Here, we identify Kif18A as a novel APC/C-Cdc20 substrate and show that Kif18A degradation depends...... by the APC/C. Nek2A and the mitotic checkpoint complex (MCC) have an overlap in APC/C subunit requirements for binding and we propose that Nek2A binds with high affinity to apo-APC/C and is degraded by the pool of Cdc20 that avoids inhibition by the SAC....

  1. Sharpening the flipped SU(5) string model

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, J.L. (Center for Theoretical Physics, Dept. of Physics, Texas A and M Univ., College Station, TX (United States) Astroparticle Physics Group, Houston Advanced Research Center (HARC), The Woodlands, TX (United States)); Nanopoulos, D.V. (Center for Theoretical Physics, Dept. of Physics, Texas A and M Univ., College Station, TX (United States) Astroparticle Physics Group, Houston Advanced Research Center (HARC), The Woodlands, TX (United States) Theoretical Physics Div., CERN, Geneva (Switzerland))

    1991-10-17

    We present an improved version of the flipped SU(5) string model which accommodates numerous existing and expected features of the low-energy physics world, such as (i) two Higgs doublets with adequate mixing between them; (ii) hierarchy of quark and lepton masses, including relations such as m{sub s}/m{sub b}{proportional to}m{sub {mu}}/m{sub {tau}}, and m{sub c}/m{sub t}{sup 1/2.}, (iii) sufficiently suppressed proton decay operators, with gauge-boson mediated decays favoring p{yields}anti {nu}{sub {tau}}{pi}{sup +} and n{yields}anti {nu}{sub {tau}}, {pi}{sup 0}, (iv) nearly massless {nu}{sub {mu}} and {nu}{sub {tau}}, and {nu}{sub e} in the eV range; (v) heavy top quark (m{sub t} < or approx. 170 GeV) and large ratio of vacuum expectation values (tan {beta} < or approx. 33). (orig.).

  2. Flipping qubits

    International Nuclear Information System (INIS)

    Martini De, F.; Sciarrino, F.; Sias, C.; Buzek, V.

    2003-01-01

    On a classical level the information can be represented by bits, each of which can be either 0 or 1. Quantum information, on the other hand, consists of qubits which can be represented as two-level quantum systems with one level labeled |0> and the other |1>. Unlike bits, qubits cannot only be in one of the two levels, but in any superposition of them as well. This superposition principle makes quantum information fundamentally different from its classical counterpart. One of the most striking difference between the classical and quantum information is as follows: it is not a problem to flip a classical bit, i.e., to change the value of a bit, a 0 to a 1 and vice versa. This is accomplished by a NOT gate. Flipping a qubit, however, is another matter: there exists the fundamental bound which prohibits to flip a qubit prepared in an arbitrary state |Ψ>=α|0> and to obtain the state |Ψ T >=β*|0>-α*|1> which is orthogonal to it, i.e., T |Ψ>=0. We experimentally realize the best possible approximation of the qubit flipping that achieves bounds imposed by complete positivity of quantum mechanics

  3. Advanced flip chip packaging

    CERN Document Server

    Lai, Yi-Shao; Wong, CP

    2013-01-01

    Advanced Flip Chip Packaging presents past, present and future advances and trends in areas such as substrate technology, material development, and assembly processes. Flip chip packaging is now in widespread use in computing, communications, consumer and automotive electronics, and the demand for flip chip technology is continuing to grow in order to meet the need for products that offer better performance, are smaller, and are environmentally sustainable. This book also: Offers broad-ranging chapters with a focus on IC-package-system integration Provides viewpoints from leading industry executives and experts Details state-of-the-art achievements in process technologies and scientific research Presents a clear development history and touches on trends in the industry while also discussing up-to-date technology information Advanced Flip Chip Packaging is an ideal book for engineers, researchers, and graduate students interested in the field of flip chip packaging.

  4. Flip Video for Dummies

    CERN Document Server

    Hutsko, Joe

    2010-01-01

    The full-color guide to shooting great video with the Flip Video camera. The inexpensive Flip Video camera is currently one of the hottest must-have gadgets. It's portable and connects easily to any computer to transfer video you shoot onto your PC or Mac. Although the Flip Video camera comes with a quick-start guide, it lacks a how-to manual, and this full-color book fills that void! Packed with full-color screen shots throughout, Flip Video For Dummies shows you how to shoot the best possible footage in a variety of situations. You'll learn how to transfer video to your computer and then edi

  5. To Flip or Not to Flip? Analysis of a Flipped Classroom Pedagogy in a General Biology Course

    Science.gov (United States)

    Heyborne, William H.; Perrett, Jamis J.

    2016-01-01

    In an attempt to better understand the flipped technique and evaluate its purported superiority in terms of student learning gains, the authors conducted an experiment comparing a flipped classroom to a traditional lecture classroom. Although the outcomes were mixed, regarding the superiority of either pedagogical approach, there does seem to be a…

  6. A modified implementation of tristate inverter based static master-slave flip-flop with improved power-delay-area product.

    Science.gov (United States)

    Singh, Kunwar; Tiwari, Satish Chandra; Gupta, Maneesha

    2014-01-01

    The paper introduces novel architectures for implementation of fully static master-slave flip-flops for low power, high performance, and high density. Based on the proposed structure, traditional C(2)MOS latch (tristate inverter/clocked inverter) based flip-flop is implemented with fewer transistors. The modified C(2)MOS based flip-flop designs mC(2)MOSff1 and mC(2)MOSff2 are realized using only sixteen transistors each while the number of clocked transistors is also reduced in case of mC(2)MOSff1. Postlayout simulations indicate that mC(2)MOSff1 flip-flop shows 12.4% improvement in PDAP (power-delay-area product) when compared with transmission gate flip-flop (TGFF) at 16X capacitive load which is considered to be the best design alternative among the conventional master-slave flip-flops. To validate the correct behaviour of the proposed design, an eight bit asynchronous counter is designed to layout level. LVS and parasitic extraction were carried out on Calibre, whereas layouts were implemented using IC station (Mentor Graphics). HSPICE simulations were used to characterize the transient response of the flip-flop designs in a 180 nm/1.8 V CMOS technology. Simulations were also performed at 130 nm, 90 nm, and 65 nm to reveal the scalability of both the designs at modern process nodes.

  7. Comparing the Effectiveness of Blended, Semi-Flipped, and Flipped Formats in an Engineering Numerical Methods Course

    Science.gov (United States)

    Clark, Renee M.; Kaw, Autar; Besterfield-Sacre, Mary

    2016-01-01

    Blended, flipped, and semi-flipped instructional approaches were used in various sections of a numerical methods course for undergraduate mechanical engineers. During the spring of 2014, a blended approach was used; in the summer of 2014, a combination of blended and flipped instruction was used to deliver a semi-flipped course; and in the fall of…

  8. Spin flip in inelastic scattering of protons on 28Si nuclei

    International Nuclear Information System (INIS)

    Wang Syn Chan; Komsan, M.N.Kh.; Osetinskij, G.M.; Golubev, S.L.; Kurepin, A.B.; Likhosherstov, V.N.

    1975-01-01

    We measured the energy and angular dependences of the spin-flip probability and of the differential cross section for inelastic scattering of protons in the resonance region of the reaction 28 Si(p,p') 23 Si* (2 + , 1.78 MeV) at E sub(p) = 3.095 and 3.34 MeV. The energy dependence of the spin-flip probability was found to have a resonance character. The angular distribution of the inelastic scattering and of the spin-flip probability is asymmetrical with respect to 90 deg in the c.m.s

  9. Lysosomal ceramide generated by acid sphingomyelinase triggers cytosolic cathepsin B-mediated degradation of X-linked inhibitor of apoptosis protein in natural killer/T lymphoma cell apoptosis.

    Science.gov (United States)

    Taniguchi, M; Ogiso, H; Takeuchi, T; Kitatani, K; Umehara, H; Okazaki, T

    2015-04-09

    We previously reported that IL-2 deprivation induced acid sphingomyelinase-mediated (ASM-mediated) ceramide elevation and apoptosis in an NK/T lymphoma cell line KHYG-1. However, the molecular mechanism of ASM-ceramide-mediated apoptosis during IL-2 deprivation is poorly understood. Here, we showed that IL-2 deprivation induces caspase-dependent apoptosis characterized by phosphatidylserine externalization, caspase-8, -9, and -3 cleavage, and degradation of X-linked inhibitor of apoptosis protein (XIAP). IL-2 re-supplementation rescued apoptosis via inhibition of XIAP degradation without affecting caspase cleavage. However, IL-2 deprivation induced ceramide elevation via ASM in lysosomes and activated lysosomal cathepsin B (CTSB) but not cathepsin D. A CTSB inhibitor CA-074 Me and knockdown of CTSB inhibited ceramide-mediated XIAP degradation and apoptosis. Inhibition of ceramide accumulation in lysosomes using an ASM inhibitor, desipramine, decreased cytosolic activation of CTSB by inhibiting its transfer into cytosol from the lysosome. Knockdown of ASM also inhibited XIAP degradation and apoptosis. Furthermore, cell permeable N-acetyl sphingosine (C2-ceramide), which increases mainly endogenous d18:1/16:0 and d18:1/24:1 ceramide-like IL-2 deprivation, induced caspase-dependent apoptosis with XIAP degradation through CTSB. These findings suggest that lysosomal ceramide produced by ASM mediates XIAP degradation by activation of cytosolic CTSB and caspase-dependent apoptosis. The ASM-ceramide-CTSB signaling axis is a novel pathway of ceramide-mediated apoptosis in IL-2-deprived NK/T lymphoma cells.

  10. Non-flipping 13C spins near an NV center in diamond: hyperfine and spatial characteristics by density functional theory simulation of the C510[NV]H252 cluster

    Science.gov (United States)

    Nizovtsev, A. P.; Kilin, S. Ya; Pushkarchuk, A. L.; Pushkarchuk, V. A.; Kuten, S. A.; Zhikol, O. A.; Schmitt, S.; Unden, T.; Jelezko, F.

    2018-02-01

    Single NV centers in diamond coupled by hyperfine interaction (hfi) to neighboring 13C nuclear spins are now widely used in emerging quantum technologies as elements of quantum memory adjusted to a nitrogen-vacancy (NV) center electron spin qubit. For nuclear spins with low flip-flop rate, single shot readout was demonstrated under ambient conditions. Here we report on a systematic search for such stable NV-13C systems using density functional theory to simulate the hfi and spatial characteristics of all possible NV-13C complexes in the H-terminated cluster C510[NV]-H252 hosting the NV center. Along with the expected stable ‘NV-axial-13C’ systems wherein the 13C nuclear spin is located on the NV axis, we found for the first time new families of positions for the 13C nuclear spin exhibiting negligible hfi-induced flipping rates due to near-symmetric local spin density distribution. Spatially, these positions are located in the diamond bilayer passing through the vacancy of the NV center and being perpendicular to the NV axis. Analysis of available publications showed that, apparently, some of the predicted non-axial near-stable NV-13C systems have already been observed experimentally. A special experiment performed on one of these systems confirmed the prediction made.

  11. Flipped Classroom Approach

    Science.gov (United States)

    Ozdamli, Fezile; Asiksoy, Gulsum

    2016-01-01

    Flipped classroom is an active, student-centered approach that was formed to increase the quality of period within class. Generally this approach whose applications are done mostly in Physical Sciences, also attracts the attention of educators and researchers in different disciplines recently. Flipped classroom learning which wide-spreads rapidly…

  12. Flipping Freshman Mathematics

    Science.gov (United States)

    Zack, Laurie; Fuselier, Jenny; Graham-Squire, Adam; Lamb, Ron; O'Hara, Karen

    2015-01-01

    Our study compared a flipped class with a standard lecture class in four introductory courses: finite mathematics, precalculus, business calculus, and calculus 1. The flipped sections watched video lectures outside of class and spent time in class actively working on problems. The traditional sections had lectures in class and did homework outside…

  13. C/EBPα regulates CRL4Cdt2-mediated degradation of p21 in response to UVB-induced DNA damage to control the G1/S checkpoint

    Science.gov (United States)

    Hall, Jonathan R; Bereman, Michael S; Nepomuceno, Angelito I; Thompson, Elizabeth A; Muddiman, David C; Smart, Robert C

    2014-01-01

    The bZIP transcription factor, C/EBPα is highly inducible by UVB and other DNA damaging agents in keratinocytes. C/EBPα-deficient keratinocytes fail to undergo cell cycle arrest in G1 in response to UVB-induced DNA damage and mice lacking epidermal C/EBPα are highly susceptible to UVB-induced skin cancer. The mechanism through which C/EBPα regulates the cell cycle checkpoint in response to DNA damage is unknown. Here we report untreated C/EBPα-deficient keratinocytes have normal levels of the cyclin-dependent kinase inhibitor, p21, however, UVB-treated C/EBPα-deficient keratinocytes fail to up-regulate nuclear p21 protein levels despite normal up-regulation of Cdkn1a mRNA levels. UVB-treated C/EBPα-deficient keratinocytes displayed a 4-fold decrease in nuclear p21 protein half-life due to the increased proteasomal degradation of p21 via the E3 ubiquitin ligase CRL4Cdt2. Cdt2 is the substrate recognition subunit of CRL4Cdt2 and Cdt2 mRNA and protein levels were up-regulated in UVB-treated C/EBPα-deficient keratinocytes. Knockdown of Cdt2 restored p21 protein levels in UVB-treated C/EBPα-deficient keratinocytes. Lastly, the failure to accumulate p21 in response to UVB in C/EBPα-deficient keratinocytes resulted in decreased p21 interactions with critical cell cycle regulatory proteins, increased CDK2 activity, and inappropriate entry into S-phase. These findings reveal C/EBPα regulates G1/S cell cycle arrest in response to DNA damage via the control of CRL4Cdt2 mediated degradation of p21. PMID:25483090

  14. Flipping Radiology Education Right Side Up.

    Science.gov (United States)

    O'Connor, Erin E; Fried, Jessica; McNulty, Nancy; Shah, Pallav; Hogg, Jeffery P; Lewis, Petra; Zeffiro, Thomas; Agarwal, Vikas; Reddy, Sravanthi

    2016-07-01

    In flipped learning, medical students independently learn facts and concepts outside the classroom, and then participate in interactive classes to learn to apply these facts. Although there are recent calls for medical education reform using flipped learning, little has been published on its effectiveness. Our study compares the effects of flipped learning to traditional didactic instruction on students' academic achievement, task value, and achievement emotions. At three institutions, we alternated flipped learning with traditional didactic lectures during radiology clerkships, with 175 medical students completing a pretest on general diagnostic imaging knowledge to assess baseline cohort comparability. Following instruction, posttests and survey examinations of task value and achievement emotions were administered. Linear mixed effects analysis was used to examine the relationship between test scores and instruction type. Survey responses were modeled using ordinal category logistic regression. Instructor surveys were also collected. There were no baseline differences in test scores. Mean posttest minus pretest scores were 10.5% higher in the flipped learning group than in the didactic instruction group (P = 0.013). Assessment of task value and achievement emotions showed greater task value, increased enjoyment, and decreased boredom with flipped learning (all P flipped learning condition. Flipped learning was associated with increased academic achievement, greater task value, and more positive achievement emotions when compared to traditional didactic instruction. Further investigation of flipped learning methods in radiology education is needed to determine whether flipped learning improves long-term retention of knowledge, academic success, and patient care. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  15. Spin flipping a stored polarized proton beam

    International Nuclear Information System (INIS)

    Caussyn, D.D.; Derbenev, Y.S.; Ellison, T.J.P.; Lee, S.Y.; Rinckel, T.; Schwandt, P.; Sperisen, F.; Stephenson, E.J.; von Przewoski, B.; Blinov, B.B.; Chu, C.M.; Courant, E.D.; Crandell, D.A.; Kaufman, W.A.; Krisch, A.D.; Nurushev, T.S.; Phelps, R.A.; Ratner, L.G.; Wong, V.K.; Ohmori, C.

    1994-01-01

    We recently studied the spin flipping of a vertically polarized, stored 139-MeV proton beam. To flip the spin, we induced an rf depolarizing resonance by sweeping our rf solenoid magnet's frequency through the resonance frequency. With multiple spin flips, we found a polarization loss of 0.0000±0.0005 per spin flip under the best conditions; this loss increased significantly for small changes in the conditions. Minimizing the depolarization during each spin flip is especially important because frequent spin flipping could significantly reduce the systematic errors in stored polarized-beam experiments

  16. Identification of a Cullin5-ElonginB-ElonginC E3 complex in degradation of feline immunodeficiency virus Vif-mediated feline APOBEC3 proteins.

    Science.gov (United States)

    Wang, Jiawen; Zhang, Wenyan; Lv, Mingyu; Zuo, Tao; Kong, Wei; Yu, Xianghui

    2011-12-01

    Various feline APOBEC3 (fA3) proteins exhibit broad antiviral activities against a wide range of viruses, such as feline immunodeficiency virus (FIV), feline foamy virus (FFV), and feline leukemia virus (FeLV), as well as those of other species. This activity can be counteracted by the FIV Vif protein, but the mechanism by which FIV Vif suppresses fA3s is unknown. In the present study, we demonstrated that FIV Vif could act via a proteasome-dependent pathway to overcome fA3s. FIV Vif interacted with feline cellular proteins Cullin5 (Cul5), ElonginB, and ElonginC to form an E3 complex to induce degradation of fA3s. Both the dominant-negative Cul5 mutant and a C-terminal hydrophilic replacement ElonginC mutant potently disrupted the FIV Vif activity against fA3s. Furthermore, we identified a BC-box motif in FIV Vif that was essential for the recruitment of E3 ubiquitin ligase and also required for FIV Vif-mediated degradation of fA3s. Moreover, despite the lack of either a Cul5-box or a HCCH zinc-binding motif, FIV Vif specifically selected Cul5. Therefore, FIV Vif may interact with Cul5 via a novel mechanism. These finding imply that SOCS proteins may possess distinct mechanisms to bind Cul5 during formation of the Elongin-Cullin-SOCS box complex.

  17. High-energy hadron spin-flip amplitude at small momentum transfer and new AN data from RHIC

    International Nuclear Information System (INIS)

    Cudell, J.-R.; Selyugin, O.V.; Predazzi, E.

    2004-01-01

    In the case of elastic high-energy hadron-hadron scattering, the impact of the large-distance contributions on the behaviour of the slopes of the spin-non-flip and of the spin-flip amplitudes is analysed. It is shown that the long tail of the hadronic potential in impact parameter space leads to a value of the slope of the reduced spin-flip amplitude larger than that of the spin-non-flip amplitude. This effect is taken into account in the calculation of the analysing power in proton-nucleus reactions at high energies. It is shown that the preliminary measurement of A N for p 12 C obtained by the E950 Collaboration indeed favours a spin-flip amplitude with a large slope. Predictions for A N at p L =250/ GeV/c are given. (orig.)

  18. Parasite-Mediated Degradation of Synthetic Ozonide Antimalarials Impacts In Vitro Antimalarial Activity.

    Science.gov (United States)

    Giannangelo, Carlo; Stingelin, Lukas; Yang, Tuo; Tilley, Leann; Charman, Susan A; Creek, Darren J

    2018-03-01

    The peroxide bond of the artemisinins inspired the development of a class of fully synthetic 1,2,4-trioxolane-based antimalarials, collectively known as the ozonides. Similar to the artemisinins, heme-mediated degradation of the ozonides generates highly reactive radical species that are thought to mediate parasite killing by damaging critical parasite biomolecules. We examined the relationship between parasite dependent degradation and antimalarial activity for two ozonides, OZ277 (arterolane) and OZ439 (artefenomel), using a combination of in vitro drug stability and pulsed-exposure activity assays. Our results showed that drug degradation is parasite stage dependent and positively correlates with parasite load. Increasing trophozoite-stage parasitemia leads to substantially higher rates of degradation for both OZ277 and OZ439, and this is associated with a reduction in in vitro antimalarial activity. Under conditions of very high parasitemia (∼90%), OZ277 and OZ439 were rapidly degraded and completely devoid of activity in trophozoite-stage parasite cultures exposed to a 3-h drug pulse. This study highlights the impact of increasing parasite load on ozonide stability and in vitro antimalarial activity and should be considered when investigating the antimalarial mode of action of the ozonide antimalarials under conditions of high parasitemia. Copyright © 2018 American Society for Microbiology.

  19. The evidence for 'flipping out': A systematic review of the flipped classroom in nursing education.

    Science.gov (United States)

    Betihavas, Vasiliki; Bridgman, Heather; Kornhaber, Rachel; Cross, Merylin

    2016-03-01

    The flipped classroom has generated interest in higher education providing a student-centred approach to learning. This has the potential to engage nursing students in ways that address the needs of today's students and the complexity of contemporary healthcare. Calls for educational reform, particularly in healthcare programs such as nursing, highlight the need for students to problem-solve, reason and apply theory into practice. The drivers towards student-based learning have manifested in team, problem and case-based learning models. Though there has been a shift towards the flipped classroom, comparatively little is known about how it is used in nursing curricula. The aims of this systematic review were to examine how the flipped classroom has been applied in nursing education and outcomes associated with this style of teaching. Five databases were searched and resulted in the retrieval of 21 papers: PubMed, CINAHL, EMBASE, Scopus and ERIC. After screening for inclusion/exclusion criteria, each paper was evaluated using a critical appraisal tool. Data extraction and analysis were completed on all included studies. This systematic review screened 21 titles and abstracts resulting in nine included studies. All authors critically appraised the quality of the included studies. Five studies were identified and themes identified were: academic performance outcomes, and student satisfaction implementing the flipped classroom. Use of the flipped classroom in higher education nursing programmes yielded neutral or positive academic outcomes and mixed results for satisfaction. Engagement of students in the flipped classroom model was achieved when academics informed and rationalised the purpose of the flipped classroom model to students. However, no studies in this review identified the evaluation of the process of implementing the flipped classroom. Studies examining the process and ongoing evaluation and refinement of the flipped classroom in higher education nursing

  20. Achieving 99.9% proton spin-flip efficiency at higher energy with a small rf dipole

    CERN Document Server

    Leonova, M A; Gebel, R; Hinterberger, F; Krisch, A D; Lehrach, A; Lorentz, B; Maier, R; Morozov, V S; Prasuhn, D; Raymond, R S; Schnase, A; Stockhorst, H; Ulbrich, K; Wong, V K; 10.1103/PhysRevLett.93.224801

    2004-01-01

    We recently used a new ferrite rf dipole to study spin flipping of a 2.1 GeV/c vertically polarized proton beam stored in the COSY Cooler Synchrotron in Julich, Germany. We swept the rf dipole's frequency through an rf-induced spin resonance to flip the beam's polarization direction. After determining the resonance's frequency, we varied the frequency range, frequency ramp time, and number of flips. At the rf dipole's maximum strength and optimum frequency range and ramp time, we measured a spin-flip efficiency of 99.92+or-0.04%. This result, along with a similar 0.49 GeV/c IUCF result, indicates that, due to the Lorentz invariance of an rf dipole's transverse integral Bdl and the weak energy dependence of its spin-resonance strength, an only 35% stronger rf dipole should allow efficient spin flipping in the 100 GeV BNL RHIC Collider or even the 7 TeV CERN Large Hadron Collider.

  1. The Partially Flipped Classroom: The Effects of Flipping a Module on "Junk Science" in a Large Methods Course

    Science.gov (United States)

    Burgoyne, Stephanie; Eaton, Judy

    2018-01-01

    Flipped classrooms are gaining popularity, especially in psychology statistics courses. However, not all courses lend themselves to a fully flipped design, and some instructors might not want to commit to flipping every class. We tested the effectiveness of flipping just one component (a module on junk science) of a large methods course. We…

  2. Pt/C Fuel Cell Catalyst Degradation

    DEFF Research Database (Denmark)

    Zana, Alessandro

    This thesis investigates the degradation behavior of Pt/C catalysts under simulated automotive conditions. By using the “tool box” synthesis method the Pt loading has been changed from low to high Pt loadings, therefore permitting to study the role of Pt on the degradation of high surface area (H...

  3. Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels

    Science.gov (United States)

    Khetan, Sudhir; Guvendiren, Murat; Legant, Wesley R.; Cohen, Daniel M.; Chen, Christopher S.; Burdick, Jason A.

    2013-05-01

    Although cell-matrix adhesive interactions are known to regulate stem cell differentiation, the underlying mechanisms, in particular for direct three-dimensional encapsulation within hydrogels, are poorly understood. Here, we demonstrate that in covalently crosslinked hyaluronic acid (HA) hydrogels, the differentiation of human mesenchymal stem cells (hMSCs) is directed by the generation of degradation-mediated cellular traction, independently of cell morphology or matrix mechanics. hMSCs within HA hydrogels of equivalent elastic moduli that permit (restrict) cell-mediated degradation exhibited high (low) degrees of cell spreading and high (low) tractions, and favoured osteogenesis (adipogenesis). Moreover, switching the permissive hydrogel to a restrictive state through delayed secondary crosslinking reduced further hydrogel degradation, suppressed traction, and caused a switch from osteogenesis to adipogenesis in the absence of changes to the extended cellular morphology. Furthermore, inhibiting tension-mediated signalling in the permissive environment mirrored the effects of delayed secondary crosslinking, whereas upregulating tension induced osteogenesis even in the restrictive environment.

  4. Confchem Conference on Flipped Classroom: Student Engagement with Flipped Chemistry Lectures

    Science.gov (United States)

    Seery, Michael K.

    2015-01-01

    This project introduces the idea of "flipped lecturing" to a group of second-year undergraduate students. The aim of flipped lecturing is to provide much of the "content delivery" of the lecture in advance, so that the lecture hour can be devoted to more in-depth discussion, problem solving, and so on. As well as development of…

  5. The space of colored interval exchange transformations with flips

    International Nuclear Information System (INIS)

    Zaw, Myint

    2002-04-01

    We study the space Cr(2h, c) of c-colored exchange transformations with flips on 2h-intervals. We describe its relation to the moduli space M g,c *c of non-orientable Riemann surfaces of genus g≥0 with one boundary curve and c≥0 extra points where g=h-c-1. (author)

  6. Rictor regulates FBXW7-dependent c-Myc and cyclin E degradation in colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Zheng [Markey Cancer Center, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States); Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Dadao Bei, Guangzhou 510515 (China); Zhou, Yuning [Markey Cancer Center, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States); Evers, B. Mark [Markey Cancer Center, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States); Department of Surgery, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States); Wang, Qingding, E-mail: qingding.wang@uky.edu [Markey Cancer Center, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States); Department of Surgery, The University of Kentucky, 800 Rose Street, Lexington, KY 40536 (United States)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Rictor associates with FBXW7 to form an E3 complex. Black-Right-Pointing-Pointer Knockdown of rictor decreases ubiquitination of c-Myc and cylin E. Black-Right-Pointing-Pointer Knockdown of rictor increases protein levels of c-Myc and cylin E. Black-Right-Pointing-Pointer Overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. Black-Right-Pointing-Pointer Rictor regulation of c-Myc and cyclin E requires FBXW7. -- Abstract: Rictor (Rapamycin-insensitive companion of mTOR) forms a complex with mTOR and phosphorylates and activates Akt. Activation of Akt induces expression of c-Myc and cyclin E, which are overexpressed in colorectal cancer and play an important role in colorectal cancer cell proliferation. Here, we show that rictor associates with FBXW7 to form an E3 complex participating in the regulation of c-Myc and cyclin E degradation. The Rictor-FBXW7 complex is biochemically distinct from the previously reported mTORC2 and can be immunoprecipitated independently of mTORC2. Moreover, knocking down of rictor in serum-deprived colorectal cancer cells results in the decreased ubiquitination and increased protein levels of c-Myc and cyclin E while overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. Genetic knockout of FBXW7 blunts the effects of rictor, suggesting that rictor regulation of c-Myc and cyclin E requires FBXW7. Our findings identify rictor as an important component of FBXW7 E3 ligase complex participating in the regulation of c-Myc and cyclin E protein ubiquitination and degradation. Importantly, our results suggest that elevated growth factor signaling may contribute to decrease rictor/FBXW7-mediated ubiquitination of c-Myc and cyclin E, thus leading to accumulation of cyclin E and c-Myc in colorectal cancer cells.

  7. Rictor regulates FBXW7-dependent c-Myc and cyclin E degradation in colorectal cancer cells

    International Nuclear Information System (INIS)

    Guo, Zheng; Zhou, Yuning; Evers, B. Mark; Wang, Qingding

    2012-01-01

    Highlights: ► Rictor associates with FBXW7 to form an E3 complex. ► Knockdown of rictor decreases ubiquitination of c-Myc and cylin E. ► Knockdown of rictor increases protein levels of c-Myc and cylin E. ► Overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. ► Rictor regulation of c-Myc and cyclin E requires FBXW7. -- Abstract: Rictor (Rapamycin-insensitive companion of mTOR) forms a complex with mTOR and phosphorylates and activates Akt. Activation of Akt induces expression of c-Myc and cyclin E, which are overexpressed in colorectal cancer and play an important role in colorectal cancer cell proliferation. Here, we show that rictor associates with FBXW7 to form an E3 complex participating in the regulation of c-Myc and cyclin E degradation. The Rictor–FBXW7 complex is biochemically distinct from the previously reported mTORC2 and can be immunoprecipitated independently of mTORC2. Moreover, knocking down of rictor in serum-deprived colorectal cancer cells results in the decreased ubiquitination and increased protein levels of c-Myc and cyclin E while overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. Genetic knockout of FBXW7 blunts the effects of rictor, suggesting that rictor regulation of c-Myc and cyclin E requires FBXW7. Our findings identify rictor as an important component of FBXW7 E3 ligase complex participating in the regulation of c-Myc and cyclin E protein ubiquitination and degradation. Importantly, our results suggest that elevated growth factor signaling may contribute to decrease rictor/FBXW7-mediated ubiquitination of c-Myc and cyclin E, thus leading to accumulation of cyclin E and c-Myc in colorectal cancer cells.

  8. Fungal bio-degradation of 14C-parathion

    International Nuclear Information System (INIS)

    Mohamed, G. A.; Abo-El Seoud, M. A.

    2012-12-01

    1 4 'C-parathion (670 Bq) was applied to mineral salt medium (MSM) to examine and evaluate its biodegradation by some fungi. The studied isolates were Alternaria alternate, Fusarium oxysporim and trichoderma viride. The inoculated media were incubated at 30 o C for periods of 2, 4, 6 and 8 days. Ta each interval, mycelia were separated from nutrient solution and extracted for its radioactivity. However, non extractable compounds were liberated by combustion. Quantitative and qualitative analysis were carried out for the radioactive compound in mycelia l extracts and residues as well as the fungal culture filtrate. Balance sheet for total recovered radioactive compounds was concluded 1 4 'C-parathion metabolism was expressed as original compound, polar metabolite, non polar metabolites and non extractable residues and then degradation rate was calculated. araesults indicated that there was continuous penetration for the radioactivity into mycelia tissues and the maximum, accumulation was recorded by Fusarium Oxysporium. The fungi under investigation showed considerable variations regarding their capacity to degrade the radioactive pesticide. Trichoderma viride exhibited the maximum capability to catabolism the the 1 4C -parathion as it exerted the maximum degradation rate. Fusarium and Alternate alter nata showed less degradation rates for the 1 4C - pesticide under investigation. (Author)

  9. Uncertainty in T1 mapping using the variable flip angle method with two flip angles

    International Nuclear Information System (INIS)

    Schabel, Matthias C; Morrell, Glen R

    2009-01-01

    Propagation of errors, in conjunction with the theoretical signal equation for spoiled gradient echo pulse sequences, is used to derive a theoretical expression for uncertainty in quantitative variable flip angle T 1 mapping using two flip angles. This expression is then minimized to derive a rigorous expression for optimal flip angles that elucidates a commonly used empirical result. The theoretical expressions for uncertainty and optimal flip angles are combined to derive a lower bound on the achievable uncertainty for a given set of pulse sequence parameters and signal-to-noise ratio (SNR). These results provide a means of quantitatively determining the effect of changing acquisition parameters on T 1 uncertainty. (note)

  10. The FLIP fuel experience at Washington State University

    International Nuclear Information System (INIS)

    Lovas, Thomas A.

    1977-01-01

    The Washington State University TRIGA-fueled modified G.E. reactor was refueled with a partial TRIGA-FLIP core in February, 1976. The final core loading consisted of 35 FLIP and 75 Standard TRIGA fuel rods and provided a core excess reactivity of $7.98. The observed performance of the reactor did not deviate significantly from the design predictions and specifications. Pulsing tests revealed a maximum power output of 1850 MW with a fuel temperature of 449 deg. C from a $2.50 pulse. Slight power fluctuations at 1 Megawatt steady-state operation and post-pulse power oscillations were observed. (author)

  11. Detection of trans-cis flips and peptide-plane flips in protein structures

    NARCIS (Netherlands)

    Touw, W.G.; Joosten, R.P.; Vriend, G.

    2015-01-01

    A coordinate-based method is presented to detect peptide bonds that need correction either by a peptide-plane flip or by a trans-cis inversion of the peptide bond. When applied to the whole Protein Data Bank, the method predicts 4617 trans-cis flips and many thousands of hitherto unknown

  12. Tin-Silver Alloys for Flip-Chip Bonding Studied with a Rotating Cylinder Electrode

    DEFF Research Database (Denmark)

    Tang, Peter Torben; Pedersen, E.H.; Bech-Nielsen, G.

    1999-01-01

    Electrodeposition of solder for flip-chip bonding is studied in the form of a pyrophosphate/iodide tin-silver alloy bath. The objective is to obtain a uniform alloy composition, with 3.8 At.% silver, over a larger area. This specific alloy will provide an eutectic solder melting at 221°C (or 10°C...... photoresist, have shown a stable and promising alternative to pure tin and tin-lead alloys for flip-chip bonding applications....

  13. Vibration characteristics of an inclined flip-flow screen panel in banana flip-flow screens

    Science.gov (United States)

    Xiong, Xiaoyan; Niu, Linkai; Gu, Chengxiang; Wang, Yinhua

    2017-12-01

    A banana flip-flow screen is an effective solution for the screening of high-viscosity, high-water and fine materials. As one of the key components, the vibration characteristics of the inclined flip-flow screen panel largely affects the screen performance and the processing capacity. In this paper, a mathematical model for the vibration characteristic of the inclined flip-flow screen panel is proposed based on Catenary theory. The reasonability of Catenary theory in analyzing the vibration characteristic of flip-flow screen panels is verified by a published experiment. Moreover, the effects of the rotation speed of exciters, the incline angle, the slack length and the characteristics of the screen on the vertical deflection, the vertical velocity and the vertical acceleration of the screen panel are investigated parametrically. The results show that the rotation speed of exciters, the incline angle, the slack length and the characteristics of the screen have significant effects on the vibrations of an inclined flip-flow screen panel, and these parameters should be optimized.

  14. The Flipped Journal Club.

    Science.gov (United States)

    Bounds, Richard; Boone, Stephen

    2018-01-01

    Educators struggle to develop a journal club format that promotes active participation from all levels of trainees. The explosion of social media compels residencies to incorporate the evaluation and application of these resources into evidence-based practice. We sought to design an innovative "flipped journal club" to achieve greater effectiveness in meeting goals and objectives among residents and faculty. Each journal club is focused on a specific clinical question based on a landmark article, a background article, and a podcast or blog post. With the "flipped" model, residents are assigned to prepare an in-depth discussion of one of these works based on their level of training. At journal club, trainees break into small groups and discuss their assigned readings with faculty facilitation. Following the small-group discussions, all participants convene to summarize key points. In redesigning our journal club, we sought to achieve specific educational outcomes, and improve participant engagement and overall impressions. Sixty-one residents at our emergency medicine program participated in the flipped journal club during the 2015-2016 academic year, with supervision by core faculty. Program evaluation for the flipped journal club was performed using an anonymous survey, with response rates of 70% and 56% for residents and faculty, respectively. Overall, 95% of resident respondents and 100% of faculty respondents preferred the flipped format. The "flipped journal club" hinges upon well-selected articles, incorporation of social media, and small-group discussions. This format engages all residents, holds learners accountable, and encourages greater participation among residents and faculty.

  15. The Flipped Classroom in Counselor Education

    Science.gov (United States)

    Moran, Kristen; Milsom, Amy

    2015-01-01

    The flipped classroom is proposed as an effective instructional approach in counselor education. An overview of the flipped-classroom approach, including advantages and disadvantages, is provided. A case example illustrates how the flipped classroom can be applied in counselor education. Recommendations for implementing or researching flipped…

  16. Quantitative framework for ordered degradation of APC/C substrates.

    Science.gov (United States)

    Lu, Dan; Girard, Juliet R; Li, Weihan; Mizrak, Arda; Morgan, David O

    2015-11-16

    During cell-cycle progression, substrates of a single master regulatory enzyme can be modified in a specific order. Here, we used experimental and computational approaches to dissect the quantitative mechanisms underlying the ordered degradation of the substrates of the ubiquitin ligase APC/C(Cdc20), a key regulator of chromosome segregation in mitosis. We show experimentally that the rate of catalysis varies with different substrates of APC/C(Cdc20). Using a computational model based on multi-step ubiquitination, we then show how changes in the interaction between a single substrate and APC/C(Cdc20) can alter the timing of degradation onset relative to APC/C(Cdc20) activation, while ensuring a fast degradation rate. Degradation timing and dynamics depend on substrate affinity for the enzyme as well as the catalytic rate at which the substrate is modified. When two substrates share the same pool of APC/C(Cdc20), their relative enzyme affinities and rates of catalysis influence the partitioning of APC/C(Cdc20) among substrates, resulting in substrate competition. Depending on how APC/C(Cdc20) is partitioned among its substrates, competition can have minor or major effects on the degradation of certain substrates. We show experimentally that increased expression of the early APC/C(Cdc20) substrate Clb5 does not delay the degradation of the later substrate securin, arguing against a role for competition with Clb5 in establishing securin degradation timing. The degradation timing of APC/C(Cdc20) substrates depends on the multi-step nature of ubiquitination, differences in substrate-APC/C(Cdc20) interactions, and competition among substrates. Our studies provide a conceptual framework for understanding how ordered modification can be established among substrates of the same regulatory enzyme, and facilitate our understanding of how precise temporal control is achieved by a small number of master regulators to ensure a successful cell division cycle.

  17. Association of Increased F4/80high Macrophages With Suppression of Serum-Transfer Arthritis in Mice With Reduced FLIP in Myeloid Cells.

    Science.gov (United States)

    Huang, Qi-Quan; Birkett, Robert; Doyle, Renee E; Haines, G Kenneth; Perlman, Harris; Shi, Bo; Homan, Philip; Xing, Lianping; Pope, Richard M

    2017-09-01

    Macrophages are critical in the pathogenesis of rheumatoid arthritis (RA). We recently demonstrated that FLIP is necessary for the differentiation and/or survival of macrophages. We also showed that FLIP is highly expressed in RA synovial macrophages. This study was undertaken to determine if a reduction in FLIP in mouse macrophages reduces synovial tissue macrophages and ameliorates serum-transfer arthritis. Mice with Flip deleted in myeloid cells (Flip f/f LysM c/+ mice) and littermate controls were used. Arthritis was induced by intraperitoneal injection of K/BxN serum. Disease severity was evaluated by clinical score and change in ankle thickness, and joints were examined by histology and immunohistochemistry. Cells were isolated from the ankles and bone marrow of the mice and examined by flow cytometry, real-time quantitative reverse transcriptase-polymerase chain reaction, or Western blotting. In contrast to expectations, Flip f/f LysM c/+ mice developed more severe arthritis early in the clinical course, but peak arthritis was attenuated and the resolution phase more complete than in control mice. Prior to the induction of serum-transfer arthritis, the number of tissue-resident macrophages was reduced. On day 9 after arthritis induction, the number of F4/80 high macrophages in the joints of the Flip f/f LysM c/+ mice was not decreased, but increased. FLIP was reduced in the F4/80 high macrophages in the ankles of the Flip f/f LysM c/+ mice, while F4/80 high macrophages expressed an antiinflammatory phenotype in both the Flip f/f LysM c/+ and control mice. Our observations suggest that reducing FLIP in macrophages by increasing the number of antiinflammatory macrophages may be an effective therapeutic approach to suppress inflammation, depending on the disease stage. © 2017, American College of Rheumatology.

  18. Down-regulation of cellular FLICE-inhibitory protein (Long Form contributes to apoptosis induced by Hsp90 inhibition in human lung cancer cells

    Directory of Open Access Journals (Sweden)

    Wang Qilin

    2012-12-01

    Full Text Available Abstract Background Cellular FLICE-Inhibitory Protein (long form, c-FLIPL is a critical negative regulator of death receptor-mediated apoptosis. Overexpression of c-FLIPL has been reported in many cancer cell lines and is associated with chemoresistance. In contrast, down-regulation of c-FLIP may drive cancer cells into cellular apoptosis. This study aims to demonstrate that inhibition of the heat shock protein 90 (Hsp90 either by inhibitors geldanamycin/17-N-Allylamino-17-demethoxygeldanamycin (GA/17-AAG or siRNA technique in human lung cancer cells induces c-FLIPL degradation and cellular apoptosis through C-terminus of Hsp70-interacting protein (CHIP-mediated mechanisms. Methods Calu-1 and H157 cell lines (including H157-c-FLIPL overexpressing c-FLIPL and control cell H157-lacZ were treated with 17-AAG and the cell lysates were prepared to detect the given proteins by Western Blot and the cell survival was assayed by SRB assay. CHIP and Hsp90 α/β proteins were knocked down by siRNA technique. CHIP and c-FLIPL plasmids were transfected into cells and immunoprecipitation experiments were performed to testify the interactions between c-FLIPL, CHIP and Hsp90. Results c-FLIPL down-regulation induced by 17-AAG can be reversed with the proteasome inhibitor MG132, which suggested that c-FLIPL degradation is mediated by a ubiquitin-proteasome system. Inhibition of Hsp90α/β reduced c-FLIPL level, whereas knocking down CHIP expression with siRNA technique inhibited c-FLIPL degradation. Furthermore, c-FLIPL and CHIP were co-precipitated in the IP complexes. In addition, overexpression of c-FLIPL can rescue cancer cells from apoptosis. When 17-AAG was combined with an anti-cancer agent celecoxib(CCB, c-FLIPL level declined further and there was a higher degree of caspase activation. Conclusion We have elucidated c-FLIPL degradation contributes to apoptosis induced by Hsp90 inhibition, suggesting c-FLIP and Hsp90 may be the promising combined targets

  19. Flipped Classroom, active Learning?

    DEFF Research Database (Denmark)

    Andersen, Thomas Dyreborg; Levinsen, Henrik; Philipps, Morten

    2015-01-01

    Action research is conducted in three physics classes over a period of eighteen weeks with the aim of studying the effect of flipped classroom on the pupils agency and learning processes. The hypothesis is that flipped classroom teaching will potentially allocate more time to work actively...

  20. Dependence of plasmin-mediated degradation of platelet adhesive receptors on temperature and Ca2+

    International Nuclear Information System (INIS)

    Winters, K.J.; Eisenberg, P.R.; Jaffe, A.S.; Santoro, S.A.

    1990-01-01

    The effects of activation of plasminogen by streptokinase and tissue-type-plasminogen activator on platelet activation and the membrane glycoproteins (GPs) that mediate platelet adhesion and aggregation are not yet fully defined. To clarify effects on platelets during activation of plasminogen in vitro, we used monoclonal antibodies (MoAbs), flow cytometry, and platelets surface-labeled with 125 I to characterize changes in receptors for fibrinogen (GPIIb-IIIa), von Willebrand factor (GPIb), and collagen (GPIa-IIa). Activation of plasminogen in plasma with pharmacologic concentrations of plasminogen activators did not degrade GPIIb-IIIa or GPIb, and caused only a modest decrease in GPIa. In washed platelets GPIIb-IIIa was extensively degraded by plasmin at 37 degrees C in the absence of exogenous Ca 2+ , conditions that destabilize the IIb-IIIa complex. Degradation of GPIb in washed platelets displayed a similar although less-marked dependence on temperature and the absence of Ca 2+ . The binding of activation-specific MoAbs did not increase during activation of plasminogen in plasma. We conclude that during pharmacologic fibrinolysis, reported inhibition of platelet function in plasma is not due to degradation of platelet-adhesive receptors. In addition, platelet activation observed during thrombolytic therapy does not appear to be a direct consequence of plasminogen activation

  1. FULLPROF as a new tool for flipping ratio analysis: further improvements

    International Nuclear Information System (INIS)

    Frontera, C.; Rodriguez-Carvajal, J.

    2004-01-01

    In the international workshop on polarized neutron for condensed matter investigation (Juelich, September 2002), we presented the implementations done in FULLPROF in order to introduce the ability of performing flipping ratio analysis. During this year we have modified the program in order to extend the initial features. We have tested these new implementations by re-analyzing flipping ratio data on Metrz-Nit (C 10 H 16 N 5 O 2 ) compound

  2. Overexpression of PLK3 Mediates the Degradation of Abnormal Prion Proteins Dependent on Chaperone-Mediated Autophagy.

    Science.gov (United States)

    Wang, Hui; Tian, Chan; Sun, Jing; Chen, Li-Na; Lv, Yan; Yang, Xiao-Dong; Xiao, Kang; Wang, Jing; Chen, Cao; Shi, Qi; Shao, Qi-Xiang; Dong, Xiao-Ping

    2017-08-01

    Polo-like kinase 3 (PLK3) is the main cause of cell cycle reentry-related neuronal apoptosis which has been implicated in the pathogenesis of prion diseases. Previous work also showed the regulatory activity of exogenous PLK3 on the degradation of PrP (prion protein) mutants and pathogenic PrP Sc ; however, the precise mechanisms remain unknown. In this study, we identified that the overexpression of PLK3-mediated degradation of PrP mutant and PrP Sc was repressed by lysosome rather than by proteasomal and macroautophagy inhibitors. Core components of chaperone-mediated autophagy (CMA) effectors, lysosome-associated membrane protein type 2A (LAMP2a), and heat shock cognate protein 70 (Hsc70) are markedly decreased in the HEK293T cells expressing PrP mutant and scrapie-infected cell line SMB-S15. Meanwhile, PrP mutant showed ability to interact with LAMP2a and Hsc70. Overexpression of PLK3 sufficiently increased the cellular levels of LAMP2a and Hsc70, accompanying with declining the accumulations of PrP mutant and PrP Sc . The kinase domain (KD) of PLK3 was responsible for elevating LAMP2a and Hsc70. Knockdown of endogenous PLK3 enhanced the activity of macroautophagy in the cultured cells. Moreover, time-dependent reductions of LAMP2a and Hsc70 were also observed in the brain tissues of hamster-adapted scrapie agent 263K-infected hamsters, indicating an impairment of CMA during prion infection. Those data indicate that the overexpression of PLK3-mediated degradation of abnormal PrP is largely dependent on CMA pathway.

  3. The cAMP signaling system inhibits the repair of {gamma}-ray-induced DNA damage by promoting Epac1-mediated proteasomal degradation of XRCC1 protein in human lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Eun-Ah [Department of Biochemistry and Molecular Biology, Cancer Research Center, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Juhnn, Yong-Sung, E-mail: juhnn@snu.ac.kr [Department of Biochemistry and Molecular Biology, Cancer Research Center, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of)

    2012-06-01

    Highlights: Black-Right-Pointing-Pointer cAMP signaling system inhibits repair of {gamma}-ray-induced DNA damage. Black-Right-Pointing-Pointer cAMP signaling system inhibits DNA damage repair by decreasing XRCC1 expression. Black-Right-Pointing-Pointer cAMP signaling system decreases XRCC1 expression by promoting its proteasomal degradation. Black-Right-Pointing-Pointer The promotion of XRCC1 degradation by cAMP signaling system is mediated by Epac1. -- Abstract: Cyclic AMP is involved in the regulation of metabolism, gene expression, cellular growth and proliferation. Recently, the cAMP signaling system was found to modulate DNA-damaging agent-induced apoptosis by regulating the expression of Bcl-2 family proteins and inhibitors of apoptosis. Thus, we hypothesized that the cAMP signaling may modulate DNA repair activity, and we investigated the effects of the cAMP signaling system on {gamma}-ray-induced DNA damage repair in lung cancer cells. Transient expression of a constitutively active mutant of stimulatory G protein (G{alpha}sQL) or treatment with forskolin, an adenylyl cyclase activator, augmented radiation-induced DNA damage and inhibited repair of the damage in H1299 lung cancer cells. Expression of G{alpha}sQL or treatment with forskolin or isoproterenol inhibited the radiation-induced expression of the XRCC1 protein, and exogenous expression of XRCC1 abolished the DNA repair-inhibiting effect of forskolin. Forskolin treatment promoted the ubiquitin and proteasome-dependent degradation of the XRCC1 protein, resulting in a significant decrease in the half-life of the protein after {gamma}-ray irradiation. The effect of forskolin on XRCC1 expression was not inhibited by PKA inhibitor, but 8-pCPT-2 Prime -O-Me-cAMP, an Epac-selective cAMP analog, increased ubiquitination of XRCC1 protein and decreased XRCC1 expression. Knockdown of Epac1 abolished the effect of 8-pCPT-2 Prime -O-Me-cAMP and restored XRCC1 protein level following {gamma}-ray irradiation. From

  4. A brief description of the biomechanics and physiology of a strongman event: the tire flip.

    Science.gov (United States)

    Keogh, Justin W L; Payne, Amenda L; Anderson, Brad B; Atkins, Paul J

    2010-05-01

    The purpose of this study was to (a) characterize the temporal aspects of a popular strongman event, the tire flip; (b) gain some insight into the temporal factors that could distinguish the slowest and fastest flips; and (c) obtain preliminary data on the physiological stress of this exercise. Five resistance-trained subjects with experience in performing the tire flip gave informed consent to participate in this study. Each subject performed 2 sets of 6 tire flips with a 232-kg tire with 3 minutes of rest between sets. Temporal variables were obtained from video cameras positioned 10 m from the tire, perpendicular to the intended direction of the tire flip. Using the "stopwatch" function in Silicon Coach, the duration of each tire flip and that of the first pull, second pull, transition, and push phases were recorded. Physiological stress was estimated via heart rate and finger-prick blood lactate response. Independent T-tests revealed that the 2 faster subjects (0.38 +/- 0.17 s) had significantly (p tire flip performance and that this exercise provides relatively high degrees of physiological stress.

  5. Vitamin C degradation products and pathways in the human lens.

    Science.gov (United States)

    Nemet, Ina; Monnier, Vincent M

    2011-10-28

    Vitamin C and its degradation products participate in chemical modifications of proteins in vivo through non-enzymatic glycation (Maillard reaction) and formation of different products called advanced glycation end products. Vitamin C levels are particularly high in selected tissues, such as lens, brain and adrenal gland, and its degradation products can inflict substantial protein damage via formation of advanced glycation end products. However, the pathways of in vivo vitamin C degradation are poorly understood. Here we have determined the levels of vitamin C oxidation and degradation products dehydroascorbic acid, 2,3-diketogulonic acid, 3-deoxythreosone, xylosone, and threosone in the human lens using o-phenylenediamine to trap both free and protein-bound adducts. In the protein-free fraction and water-soluble proteins (WSP), all five listed degradation products were identified. Dehydroascorbic acid, 2,3-diketogulonic acid, and 3-deoxythreosone were the major products in the protein-free fraction, whereas in the WSP, 3-deoxythreosone was the most abundant measured dicarbonyl. In addition, 3-deoxythreosone in WSP showed positive linear correlation with age (p degradation product bound to human lens proteins provides in vivo evidence for the non-oxidative pathway of dehydroascorbate degradation into erythrulose as a major pathway for vitamin C degradation in vivo.

  6. Flipped Classroom Approach

    OpenAIRE

    Fezile Ozdamli; Gulsum Asiksoy

    2016-01-01

    Flipped classroom is an active, student-centered approach that was formed to increase the quality of period within class. Generally this approach whose applications are done mostly in Physical Sciences, also attracts the attention of educators and researchers in different disciplines recently. Flipped classroom learning which wide-spreads rapidly in the world, is not well recognized in our country. That is why the aim of study is to attract attention to its potential in education field and pr...

  7. Does "Flipping" Promote Engagement?: A Comparison of a Traditional, Online, and Flipped Class

    Science.gov (United States)

    Burke, Alison S.; Fedorek, Brian

    2017-01-01

    "Flipped" or inverted classrooms are designed to utilize class time for application and knowledge building, while course content is delivered through the use of online lectures and watched at home on the students' time. It is believed that flipped classrooms promote student engagement and a deeper understanding of the class material. The…

  8. Degradable and porous Fe-Mn-C alloy for biomaterials candidate

    Science.gov (United States)

    Pratesa, Yudha; Harjanto, Sri; Larasati, Almira; Suharno, Bambang; Ariati, Myrna

    2018-02-01

    Nowadays, degradable implants attract attention to be developed because it can improve the quality of life of patients. The degradable implant is expected to degrade easily in the body until the bone healing process already achieved. However, there is limited material that could be used as a degradable implant, polymer, magnesium, and iron. In the previous study, Fe-Mn-C alloys had succesfully produced austenitic phase. However, the weakness of the alloy is degradation rate of materials was considered below the expectation. This study aimed to produce porous Fe-Mn-C materials to improve degradation rate and reduce the density of alloy without losing it non-magnetic properties. Potassium carbonate (K2CO3) were chosen as filler material to produce foam structure by sintering and dissolution process. Multisteps sintering process under argon gas environment was performed to generate austenite phase. The product showed an increment of the degradation rate of the foamed Fe-Mn-C alloy compared with the solid Fe-Mn-C alloy without losing the Austenitic Structure

  9. Variable-flip-angle spin-echo imaging (VFSE)

    International Nuclear Information System (INIS)

    Kasai, Toshifumi; Sugimura, Kazuro; Kawamitsu, Hideaki; Yasui, Kiyoshi; Ishida, Tetsuya; Tsukamoto, Tetsuji.

    1990-01-01

    T 2 weighted imaging provides images with high object contrast for pathologic conditions in which the water content of tissues is increased. The authors predicted theoretical analysis of the effects of changing flip angle, and analyzed the effects in MR imaging of both phantoms and humans. Variable flip angle spin echo MR imaging (VFSE) with a 1,000/80 (repetition time msec/echo time msec) can obtain T 2 weighted image when flip angle is smaller than 80 degrees. VFSE with 40 to 60 degrees flip angle have higher contrast than other flip angle images. Signal to noise ratio (S/N) of VFSE are 55% at a 30 degree, 76% at a 45 degree, 92% at a 60 degree respectively as compared with conventional spin echo image (2000/80, flip angle 90 degree). VFSE is applicable to obtain T 2 weighted image reduced imaging time. (author)

  10. The Fas-associated death domain protein/caspase-8/c-FLIP signaling pathway is involved in TNF-induced activation of ERK

    International Nuclear Information System (INIS)

    Lueschen, Silke; Falk, Markus; Scherer, Gudrun; Ussat, Sandra; Paulsen, Maren; Adam-Klages, Sabine

    2005-01-01

    The cytokine TNF activates multiple signaling pathways leading to cellular responses ranging from proliferation and survival to apoptosis. While most of these pathways have been elucidated in detail over the past few years, the molecular mechanism leading to the activation of the MAP kinases ERK remains ill defined and is controversially discussed. Therefore, we have analyzed TNF-induced ERK activation in various human and murine cell lines and show that it occurs in a cell-type-specific manner. In addition, we provide evidence for the involvement of the signaling components Fas-associated death domain protein (FADD), caspase-8, and c-FLIP in the pathway activating ERK in response to TNF. This conclusion is based on the following observations: (I) Overexpression of FADD, caspase-8, or a c-FLIP protein containing the death effector domains only leads to enhanced and prolonged ERK activation after TNF treatment. (II) TNF-induced ERK activation is strongly diminished in the absence of FADD. Interestingly, the enzymatic function of caspase-8 is not required for TNF-induced ERK activation. Additional evidence suggests a role for this pathway in the proliferative response of murine fibroblasts to TNF

  11. Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Yu-Chin Lin

    2012-06-01

    Full Text Available Epidermal growth factor receptor (EGFR is an important oncoprotein that promotes cell growth and proliferation. Dasatinib, a bcr-abl inhibitor, has been approved clinically for the treatment of chronic myeloid leukemia and demonstrated to be effective against solid tumors in vitro through Src inhibition. Here, we disclose that EGFR degradation mediated dasatinib-induced apoptosis in head and neck squamous cell carcinoma (HNSCC cells. HNSCC cells, including Ca9-22, FaDu, HSC3, SAS, SCC-25, and UMSCC1, were treated with dasatinib, and cell viability, apoptosis, and underlying signal transduction were evaluated. Dasatinib exhibited differential sensitivities against HNSCC cells. Growth inhibition and apoptosis were correlated with its inhibition on Akt, Erk, and Bcl-2, irrespective of Src inhibition. Accordingly, we found that down-regulation of EGFR was a determinant of dasatinib sensitivity. Lysosome inhibitor reversed dasatinib-induced EGFR down-regulation, and c-cbl activity was increased by dasatinib, indicating that dasatinib-induced EGFR down-regulation might be through c-cbl-mediated lysosome degradation. Increased EGFR activation by ligand administration rescued cells from dasatinib-induced apoptosis, whereas inhibition of EGFR enhanced its apoptotic effect. Estrogen receptor α (ERα was demonstrated to play a role in Bcl-2 expression, and dasatinib inhibited ERα at the pretranslational level. ERα was associated with EGFR in dasatinib-treated HNSCC cells. Furthermore, the xenograft model showed that dasatinib inhibited HSC3 tumor growth through in vivo down-regulation of EGFR and ERα. In conclusion, degradation of EGFR is a novel mechanism responsible for dasatinib-induced apoptosis in HNSCC cells.

  12. Flipped classroom: a review of recent literature

    Directory of Open Access Journals (Sweden)

    Huseyin Uzunboylu

    2015-07-01

    Full Text Available The use of learning technologies, especially multimedia provide varied facilities for students’ learning that are not possible with other media. Pedagogical literature has proved that individuals have different learning styles. Flipped classroom is a pedagogical approach which means that activities that have traditionally taken place inside the classroom take place outside the classroom and vice versa. Flipped classroom environment ensures that students become more active participants compared with the traditional classroom. The purpose of this paper is to fulfil the needs regarding the review of recent literature on the use of flipped classroom approach in education. The contribution of flipped classroom to education is discussed in relation to the change of students' and instructors' role. Subsequently, flipped classroom applications in various disciplines of education are illustrated. The recommendations made in the literature for design specifications that integrate flipped classrooms with technology are discussed. The paper concludes that a careful consideration of the warnings and recommendations made in the literature can help to produce effective flipped classroom environments and also this paper attempts to inform those who are thinking of using new technologies and approaches to deliver courses.

  13. C/EBP{delta} targets cyclin D1 for proteasome-mediated degradation via induction of CDC27/APC3 expression.

    Science.gov (United States)

    Pawar, Snehalata A; Sarkar, Tapasree Roy; Balamurugan, Kuppusamy; Sharan, Shikha; Wang, Jun; Zhang, Youhong; Dowdy, Steven F; Huang, A-Mei; Sterneck, Esta

    2010-05-18

    The transcription factor CCAAT/enhancer binding protein delta (C/EBPdelta, CEBPD, NFIL-6beta) has tumor suppressor function; however, the molecular mechanism(s) by which C/EBPdelta exerts its effect are largely unknown. Here, we report that C/EBPdelta induces expression of the Cdc27 (APC3) subunit of the anaphase promoting complex/cyclosome (APC/C), which results in the polyubiquitination and degradation of the prooncogenic cell cycle regulator cyclin D1, and also down-regulates cyclin B1, Skp2, and Plk-1. In C/EBPdelta knockout mouse embryo fibroblasts (MEF) Cdc27 levels were reduced, whereas cyclin D1 levels were increased even in the presence of activated GSK-3beta. Silencing of C/EBPdelta, Cdc27, or the APC/C coactivator Cdh1 (FZR1) in MCF-10A breast epithelial cells increased cyclin D1 protein expression. Like C/EBPdelta, and in contrast to cyclin D1, Cdc27 was down-regulated in several breast cancer cell lines, suggesting that Cdc27 itself may be a tumor suppressor. Cyclin D1 is a known substrate of polyubiquitination complex SKP1/CUL1/F-box (SCF), and our studies show that Cdc27 directs cyclin D1 to alternative degradation by APC/C. These findings shed light on the role and regulation of APC/C, which is critical for most cellular processes.

  14. Vitamin C Degradation Products and Pathways in the Human Lens*

    OpenAIRE

    Nemet, Ina; Monnier, Vincent M.

    2011-01-01

    Vitamin C and its degradation products participate in chemical modifications of proteins in vivo through non-enzymatic glycation (Maillard reaction) and formation of different products called advanced glycation end products. Vitamin C levels are particularly high in selected tissues, such as lens, brain and adrenal gland, and its degradation products can inflict substantial protein damage via formation of advanced glycation end products. However, the pathways of in vivo vitamin C degradation ...

  15. Dynamics of spin-flip photon-assisted tunneling

    NARCIS (Netherlands)

    Braakman, F.R.; Danon, J.; Schreiber, L.R.; Wegscheider, W.; Vandersypen, L.M.K.

    2014-01-01

    We present time-resolved measurements of spin-flip photon-assisted tunneling and spin-flip relaxation in a doubly occupied double quantum dot. The photon-assisted excitation rate as a function of magnetic field indicates that spin-orbit coupling is the dominant mechanism behind the spin-flip under

  16. The Marriage of Constructivism and Flipped Learning

    Science.gov (United States)

    Chang, Sau Hou

    2016-01-01

    This report talks about how a constructivist teacher used flipped learning in a college class. To illustrate how to use flipped learning in a constructivist classroom, examples were given with the four pillars of F-L-I-P: Flexible environment, learning culture, intentional content, and professional educator.

  17. Does tryptophan degradation along the kynurenine pathway mediate the association between pro-inflammatory immune activity and depressive symptoms?

    Science.gov (United States)

    Quak, Jacqueline; Doornbos, Bennard; Roest, Annelieke M; Duivis, Hester E; Vogelzangs, Nicole; Nolen, Willem A; Penninx, Brenda W J H; Kema, Ido P; de Jonge, Peter

    2014-07-01

    Several studies have suggested that induced tryptophan (TRP) degradation through the kynurenine (KYN) pathway by the enzyme indoleamine 2,3-dioxygenase (IDO) is implicated in the relation between depression and inflammation. We investigated the role of tryptophan degradation in the relationship between inflammatory markers and depressive symptoms in the Netherlands Study of Depression and Anxiety (NESDA) and hypothesized that tryptophan degradation would mediate (part of) this association. 2812 Participants of NESDA were included in this study including 1042 persons with current major depressive disorder (MDD). Assessments of C-reactive protein (CRP), interleukin (IL)-6, tumor-necrosis factor (TNF)-α, KYN and TRP were obtained from fasting blood samples at the baseline assessment. Tryptophan degradation was estimated by calculating the ratio [KYN/TRP]. Depressive symptoms were measured with the Inventory of Depressive Symptomatology. Significant associations between inflammation and depressive symptoms were found for CRP and IL-6, for the total group and the subgroup of patients with current MDD. Adjustment for KYN/TRP did not attenuate these associations. There were no significant indirect effects for CRP on depressive symptoms mediated by KYN/TRP for the whole group (B=-0.032; 95% CI: -0.103 to 0.028) and for the subgroup of patients with current MDD (B=0.059; 95% CI: -0.037 to 0.165). Also IL-6 did not indirectly affect depressive symptoms through KYN/TRP in the total group (B=-0.023; 95% CI: -0.093 to 0.045) and in the MDD subgroup B=0.052; 95% CI: -0.019 to 0.144). Finally, no significant relation between depressive symptoms and KYN/TRP was found in the whole group (β=-0.019, p=0.311) nor in the subgroup with MDD (β=0.025, p=0.424). We did not find indications for tryptophan degradation, measured by KYN/TRP, to mediate the relationship between inflammation and depressive symptoms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. High-Tc dc-SQUID gradiometers in flip-chip configuration

    International Nuclear Information System (INIS)

    Peiselt, K; Schmidl, F; Linzen, S; Anton, A S; Huebner, U; Seidel, P

    2003-01-01

    We describe a new design of a gradiometric flip-chip antenna, which is inductively coupled to a dc-SQUID gradiometer. Both components are patterned out of thin films of the high-T c superconductor YBa 2 Cu 3 O 7-x (YBCO). For the flip-chip antenna, a 40 mm x 10 mm SrTiO 3 single crystalline substrate is used, while the gradiometer sensors are prepared on 10 mm x 10 mm SrTiO 3 bicrystal substrates. Special attention is paid to the inductive coupling between the flip-chip antenna and the read-out gradiometer antenna. We investigate different designs of coupling loops in order to optimize the coupling inductance between both components of the sensor. With optimized coupling the sensor achieves a field-gradient resolution of 12 fT cm -1 Hz -1/2 in the white noise region and of 310 fT cm -1 Hz -1/2 at 1 Hz in the unshielded laboratory environment

  19. Memory formation for trace fear conditioning requires ubiquitin-proteasome mediated protein degradation in the prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    David S Reis

    2013-10-01

    Full Text Available The cellular mechanisms supporting plasticity during memory consolidation have been a subject of considerable interest. De novo protein and mRNA synthesis in several brain areas are critical, and more recently protein degradation, mediated by the ubiquitin-proteasome system (UPS, has been shown to be important. Previous work clearly establishes a relationship between protein synthesis and protein degradation in the amygdala, but it is unclear whether cortical mechanisms of memory consolidation are similar to those in the amygdala. Recent work demonstrating a critical role for prefrontal cortex (PFC in the acquisition and consolidation of fear memory allows us to address this question. Here we use a PFC-dependent fear conditioning protocol to determine whether UPS mediated protein degradation is necessary for memory consolidation in PFC. Groups of rats were trained with auditory delay or trace fear conditioning and sacrificed 60 min after training. PFC tissue was then analyzed to quantify the amount of polyubiquinated protein. Other animals were trained with similar procedures but were infused with either a proteasome inhibitor (clasto-lactacystin β-lactone or a translation inhibitor (anisomycin in the PFC immediately after training. Our results show increased UPS-mediated protein degradation in the PFC following trace but not delay fear conditioning. Additionally, post-training proteasome or translation inhibition significantly impaired trace but not delay fear memory when tested the next day. Our results further support the idea that the PFC is critical for trace but not delay fear conditioning highlight the role of UPS-mediated degradation as critical for synaptic plasticity.

  20. Interferon-β-induced activation of c-Jun NH2-terminal kinase mediates apoptosis through up-regulation of CD95 in CH31 B lymphoma cells

    International Nuclear Information System (INIS)

    Takada, Eiko; Shimo, Kuniaki; Hata, Kikumi; Abiake, Maira; Mukai, Yasuo; Moriyama, Masami; Heasley, Lynn; Mizuguchi, Junichiro

    2005-01-01

    Type I interferon (IFN)-induced antitumor action is due in part to apoptosis, but the molecular mechanisms underlying IFN-induced apoptosis remain largely unresolved. In the present study, we demonstrate that IFN-β induced apoptosis and the loss of mitochondrial membrane potential (ΔΨm) in the murine CH31 B lymphoma cell line, and this was accompanied by the up-regulation of CD95, but not CD95-ligand (CD95-L), tumor necrosis factor (TNF), or TNF-related apoptosis-inducing ligand (TRAIL). Pretreatment with anti-CD95-L mAb partially prevented the IFN-β-induced loss of ΔΨm, suggesting that the interaction of IFN-β-up-regulated CD95 with CD95-L plays a crucial role in the induction of fratricide. IFN-β induced a sustained activation of c-Jun NH 2 -terminal kinase 1 (JNK1), but not extracellular signal-regulated kinases (ERKs). The IFN-β-induced apoptosis and loss of ΔΨm were substantially compromised in cells overexpressing a dominant-negative form of JNK1 (dnJNK1), and it was slightly enhanced in cells carrying a constitutively active JNK construct, MKK7-JNK1 fusion protein. The IFN-β-induced up-regulation of CD95 together with caspase-8 activation was also abrogated in the dnJNK1 cells while it was further enhanced in the MKK7-JNK1 cells. The levels of cellular FLIP (c-FLIP), competitively interacting with caspase-8, were down-regulated by stimulation with IFN-β but were reversed by the proteasome inhibitor lactacystin. Collectively, the IFN-β-induced sustained activation of JNK mediates apoptosis, at least in part, through up-regulation of CD95 protein in combination with down-regulation of c-FLIP protein

  1. Quantitative assessment of the degradation of aggregated TDP-43 mediated by the ubiquitin proteasome system and macroautophagy.

    Science.gov (United States)

    Cascella, Roberta; Fani, Giulia; Capitini, Claudia; Rusmini, Paola; Poletti, Angelo; Cecchi, Cristina; Chiti, Fabrizio

    2017-12-01

    Amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions are neurodegenerative disorders that share the cytosolic deposition of TDP-43 (TAR DNA-binding protein 43) in the CNS. TDP-43 is well known as being actively degraded by both the proteasome and macroautophagy. The well-documented decrease in the efficiency of these clearance systems in aging and neurodegeneration, as well as the genetic evidence that many of the familial forms of TDP-43 proteinopathies involve genes that are associated with them, suggest that a failure of these protein degradation systems is a major factor that contributes to the onset of TDP-43-associated disorders. Here, we inserted preformed human TDP-43 aggregates in the cytosol of murine NSC34 and N2a cells in diffuse form and observed their degradation under conditions in which exogenous TDP-43 is not expressed and endogenous nuclear TDP-43 is not recruited, thereby allowing a time zero to be established in TDP-43 degradation and to observe its disposal kinetically and analytically. TDP-43 degradation was observed in the absence and presence of selective inhibitors and small interfering RNAs against the proteasome and autophagy. We found that cytosolic diffuse aggregates of TDP-43 can be distinguished in 3 different classes on the basis of their vulnerability to degradation, which contributed to the definition-with previous reports-of a total of 6 distinct classes of misfolded TDP-43 species that range from soluble monomer to undegradable macroaggregates. We also found that the proteasome and macroautophagy-degradable pools of TDP-43 are fully distinguishable, rather than in equilibrium between them on the time scale required for degradation, and that a significant crosstalk exists between the 2 degradation processes.-Cascella, R., Fani, G., Capitini, C., Rusmini, P., Poletti, A., Cecchi, C., Chiti, F. Quantitative assessment of the degradation of aggregated TDP-43 mediated by the ubiquitin

  2. Flipping a Calculus Class: One Instructor's Experience

    Science.gov (United States)

    Palmer, Katrina

    2015-01-01

    This paper describes one instructor's experiences during a year of flipping four calculus classes. The first exploration attempts to understand student expectations of a math class and their preference towards a flipped classroom. The second examines success of students from a flipped classroom, and the last investigates relationships with student…

  3. Studenters erfaringer med Flipped Classroom i en helsefagutdanning

    Directory of Open Access Journals (Sweden)

    Christine Tørris

    2015-12-01

    Full Text Available Background: The flipped classroom approach has gained increased attention in educational research literature. The purpose of this study was to investigate how students experience a flipped classroom approach in health education, compared to ordinary lectures. Method: Bachelor students (n=25 who watched the video-based material in the flipped classrooms pre-session, answered a questionnaire to evaluate their flipped classroom experience. The questionnaire consisted of both closed and open questions. Results: Ninety six per cent (24/25 of respondents found the video-based material in the pre-session useful. Seventy six per cent (19/25 of respondents found that the flipped classroom approach resulted in the highest learning outcome, over the traditional approach (16%, 4/25. Barriers to the flipped classroom approach was technical problems with the video-based material, such as screen view. Conclusion: The flipped classroom approach is promising as an acceptable approach for teaching in health science curricular in higher education.

  4. FLIPPED LEARNING: PRACTICAL ASPECTS

    Directory of Open Access Journals (Sweden)

    Olena Kuzminska

    2016-03-01

    Full Text Available The article is devoted to issues of implementation of the flipped learning technology in the practice of higher education institutions. The article defines the principles of technology and a model of the educational process, it notes the need to establish an information support system. The article defines online platforms and resources; it describes recommendations for the design of electronic training courses and organization of the students in the process of implementing the proposed model, as well as tools for assessing its effectiveness. The article provides a description of flipped learning implementation scenario and formulates suggestions regarding the use of this model as a mechanism to improve the efficiency of the learning process in the ICT-rich environment of high school: use of learning management systems (LMS and personal learning environments (PLE of participants in a learning process. The article provides an example of implementation of the flipped learning model as a part of the Information Technologies course in the National University of Life and Environmental Sciences of Ukraine (NULES. The article gives examples of tasks, resources and services, results of students’ research activity, as well as an example of the personal learning network, established in the course of implementation of the flipped learning model and elements of digital student portfolios. It presents the results of the monitoring of learning activities and students’ feedback. The author describes cautions against the mass introduction of the flipped learning model without monitoring of readiness of the participants of the educational process for its implementation

  5. The Flipped Journal Club

    Directory of Open Access Journals (Sweden)

    Richard Bounds

    2017-12-01

    Full Text Available Introduction Educators struggle to develop a journal club format that promotes active participation from all levels of trainees. The explosion of social media compels residencies to incorporate the evaluation and application of these resources into evidence-based practice. We sought to design an innovative “flipped journal club” to achieve greater effectiveness in meeting goals and objectives among residents and faculty. Methods Each journal club is focused on a specific clinical question based on a landmark article, a background article, and a podcast or blog post. With the “flipped” model, residents are assigned to prepare an in-depth discussion of one of these works based on their level of training. At journal club, trainees break into small groups and discuss their assigned readings with faculty facilitation. Following the small-group discussions, all participants convene to summarize key points. In redesigning our journal club, we sought to achieve specific educational outcomes, and improve participant engagement and overall impressions. Results Sixty-one residents at our emergency medicine program participated in the flipped journal club during the 2015–2016 academic year, with supervision by core faculty. Program evaluation for the flipped journal club was performed using an anonymous survey, with response rates of 70% and 56% for residents and faculty, respectively. Overall, 95% of resident respondents and 100% of faculty respondents preferred the flipped format. Conclusion The “flipped journal club” hinges upon well-selected articles, incorporation of social media, and small-group discussions. This format engages all residents, holds learners accountable, and encourages greater participation among residents and faculty.

  6. c-FLIP and the NOXA/Mcl-1 axis participate in the synergistic effect of pemetrexed plus cisplatin in human choroidal melanoma cells.

    Science.gov (United States)

    Zhao, Xiaofei; Kong, Feng; Wang, Lei; Zhang, Han

    2017-01-01

    Choroidal melanoma is the most common primary malignant intraocular tumor, and very few effective therapies are available to treat it. Our study aimed to understand whether pemetrexed plus cisplatin exerts a beneficial synergistic effect in human choroidal melanoma cells and to delineate the underlying molecular mechanism. To accomplish these aims, we treated choroidal melanoma cells with pemetrexed and cisplatin and assessed cell survival with SRB and MTT assays. Proteins were detected using western blotting analysis. NOXA and CHOP were knocked down with siRNA. We found that pemetrexed or cisplatin alone inhibited survival and induced apoptosis in human choroidal melanoma cells. Furthermore, the expression levels of c-FLIP, an anti-apoptotic protein in the extrinsic apoptosis pathway, and Mcl-1, an anti-apoptotic protein in the intrinsic apoptosis pathway, were decreased by pemetrexed or cisplatin respectively, while the expression of a pro-apoptotic protein in the intrinsic apoptosis pathway, NOXA, was up-regulated. Moreover, pemetrexed or cisplatin alone increased the protein expression of the endoplasmic reticulum stress markers IRE1α, Bip and CHOP. Silencing CHOP expression reduced NOXA expression. These findings suggest that the pemetrexed or cisplatin induced intrinsic apoptosis via activation of the ER stress response. Importantly, combining the two compounds more strongly induced apoptosis. Following the cotreatment, CHOP and NOXA expression increased, while c-FLIP and Mcl-1 expression decreased, and these effects were more pronounced than when using either compound alone. This result suggests that pemetrexed and cisplatin synergistically activate ER stress response-induced apoptosis in choroidal melanoma cells. To summarize, the c-FLIP and NOXA/Mcl-1 axis participated in the synergistic effect of pemetrexed plus cisplatin in human choroidal melanoma cells. Intrinsic apoptosis was induced via activation of the ER stress response. Our study provides

  7. A Flipped Classroom Redesign in General Chemistry

    Science.gov (United States)

    Reid, Scott A.

    2016-01-01

    The flipped classroom continues to attract significant attention in higher education. Building upon our recent parallel controlled study of the flipped classroom in a second-term general chemistry course ("J. Chem. Educ.," 2016, 93, 13-23), here we report on a redesign of the flipped course aimed at scaling up total enrollment while…

  8. Upregulation of c-FLIP-short in response to TRAIL promotes survival of NSCLC cells, which could be suppressed by inhibition of Ca2+/calmodulin signaling

    Czech Academy of Sciences Publication Activity Database

    Kaminskyy, V.O.; Surova, O.V.; Piskunova, T.; Zborovskaya, I.B.; Tchevkina, E.M.; Anděra, Ladislav; Zhivotovsky, B.

    2013-01-01

    Roč. 4, březen 2013 (2013), e522 ISSN 2041-4889 Institutional support: RVO:68378050 Keywords : TRAIL * DR4 * c-FLIPS * calcium * calmodulin * lung adenocarcinoma Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.177, year: 2013

  9. Just in Time to Flip Your Classroom

    Science.gov (United States)

    Lasry, Nathaniel; Dugdale, Michael; Charles, Elizabeth

    2014-01-01

    With advocates like Sal Khan and Bill Gates, flipped classrooms are attracting an increasing amount of media and research attention.2 We had heard Khan's TED talk and were aware of the concept of inverted pedagogies in general. Yet it really hit home when we accidentally flipped our classroom. Our objective was to better prepare our students for class. We set out to effectively move some of our course content outside of class and decided to tweak the Just-in-Time Teaching approach (JiTT).3 To our surprise, this tweak—which we like to call the flip-JiTT—ended up completely flipping our classroom. What follows is narrative of our experience and a procedure that any teacher can use to extend JiTT to a flipped classroom.

  10. En didaktisk model for Flipped Classroom

    DEFF Research Database (Denmark)

    Levinsen, Henrik; Foss, Kristian Kildemoes; Andersen, Thomas Dyreborg

    2016-01-01

    I artiklen præsenterer vi en model over flipped classroom som didaktisk metode udviklet med henblik på at stilladsere både de lærere, som gerne vil prøve kræfter med en flipped classroom-baseret praksis, og dem som allerede har erfaring, men kan have glæde af at bruge modellen til at kvalificere...... deres flipped classroom-undervisning. Modellen kan bidrage til erkendelsen af, at flipped classroom er noget nær et paradigmeskifte i forståelsen af god undervisning. Her tænkes på det skift i fokus metoden indebærer fra, at læreren er mest aktiv, til at eleverne er de mest aktive. Særligt for den...

  11. Spin-flip measurements in the proton inelastic scattering on 12C and giant resonance effects

    International Nuclear Information System (INIS)

    De Leo, R.; D'Erasmo, G.; Ferrero, F.; Pantaleo, A.; Pignanelli, M.

    1975-01-01

    Differential cross sections and spin-flip probabilities (SFP) for the inelastic scattering of protons, exciting the 2 + state at 4.43 MeV in 12 C, have been measured at several incident energies between 15.9 and 37.6 MeV. The changes in the shape of the SFP angular distributions are rather limited, while the absolute values show a pronounced increase, resonant like, in two energy regions centered at about 20 and 29 MeV. The second resonance reproduces very closely the energy dependence of the E2 giant quadrupole strength found in a previous experiment. The resonance at 20 MeV should correspond to a substructure of the E1 giant dipole resonance. (Auth.)

  12. Propuesta de modelo tecnológico para Flipped Classroom (T-FliC en educación superior

    Directory of Open Access Journals (Sweden)

    Matilde Basso-Aránguiz

    2018-02-01

    Full Text Available Se presenta una propuesta de modelo tecnológico para Flipped Classroom (FC o aula invertida, denominado T-FliC. El objetivo es dar un soporte mediado por las tecnologías de la información y comunicación (TIC al modelo pedagógico homónimo existente, para ser considerado en futuras implementaciones en asignaturas de distintos niveles de formación en educación superior. T-FliC se basa, fundamentalmente, en la utilización de recursos tecnológicos gratuitos, teniendo como base las aplicaciones de Google (Classroom, Drive y Youtube, entre otras, debido a su uso masivo por parte de estudiantes y docentes, lo que posibilita replicar este modelo en distintos contextos educativos. T-FliC incorpora cinco fases mediadas por las TIC, que van desde la planificación de las actividades de enseñanza-aprendizaje hasta la evaluación continua de los aprendizajes. En su implementación, el modelo T-FliC considera una clase digital (aprendizaje fuera del aula con la orientación asincrónica de personal tutor virtual, un taller que comprende el desarrollo de actividades dinámicas para el trabajo colaborativo (aprendizaje en el aula con la guía de personal tutor presencial y un proceso evaluativo permanente y continuo mediado por herramientas tecnológicas tales como teclera, portafolio y foro que permitirá tener el registro digital de la ruta de aprendizaje del estudiantado. Este artículo incluye una revisión bibliográfica acerca del rol de las TIC en los procesos educativos y de los fundamentos de la metodología Flipped Classroom (FC. Se incorporan antecedentes de experiencias de implementación de FC en educación superior, seguido de la presentación del modelo T-FliC como una propuesta tecnológica para esta metodología. Finalmente, en las conclusiones se presentan reflexiones sobre la propuesta.

  13. Relationships in the Flipped Classroom

    Science.gov (United States)

    McCollum, Brett M.; Fleming, Cassidy L.; Plotnikoff, Kara M.; Skagen, Darlene N.

    2017-01-01

    This study examines the effectiveness of flipped classrooms in chemistry, and identifies relationships as a major factor impacting the success of flipped instruction methods. Examination of student interview data reveals factors that affect the development of peer-peer, peer-peer leader, and peer-expert relationships in firstyear general chemistry…

  14. Mapping of low flip angles in magnetic resonance

    International Nuclear Information System (INIS)

    Balezeau, Fabien; Saint-Jalmes, Herve; Eliat, Pierre-Antoine; Cayamo, Alejandro Bordelois

    2011-01-01

    Errors in the flip angle have to be corrected in many magnetic resonance imaging applications, especially for T1 quantification. However, the existing methods of B1 mapping fail to measure lower values of the flip angle despite the fact that these are extensively used in dynamic acquisition and 3D imaging. In this study, the nonlinearity of the radiofrequency (RF) transmit chain, especially for very low flip angles, is investigated and a simple method is proposed to accurately determine both the gain of the RF transmitter and the B1 field map for low flip angles. The method makes use of the spoiled gradient echo sequence with long repetition time (TR), such as applied in the double-angle method. It uses an image acquired with a flip angle of 90 0 as a reference image that is robust to B1 inhomogeneity. The ratio of the image at flip angle alpha to the image at a flip angle of 90 0 enables us to calculate the actual value of alpha. This study was carried out at 1.5 and 4.7 T, showing that the linearity of the RF supply system is highly dependent on the hardware. The method proposed here allows us to measure the flip angle from 1 0 to 60 0 with a maximal uncertainty of 10% and to correct T1 maps based on the variable flip angle method.

  15. Evaluation of the flipped classroom approach in a veterinary professional skills course

    OpenAIRE

    Moffett, Jenny; Mill, Aileen C

    2014-01-01

    Jenny Moffett,1 Aileen C Mill2 1Ross University School of Veterinary Medicine, West Farm, St Kitts, West Indies; 2Modelling Suite, School of Biology, Newcastle University, Newcastle upon Tyne, UK Background: The flipped classroom is an educational approach that has had much recent coverage in the literature. Relatively few studies, however, use objective assessment of student performance to measure the impact of the flipped classroom on learning. The purpose of this study was to evaluate the...

  16. Evaluation of the flipped classroom approach in a veterinary professional skills course

    Directory of Open Access Journals (Sweden)

    Moffett J

    2014-11-01

    Full Text Available Jenny Moffett,1 Aileen C Mill2 1Ross University School of Veterinary Medicine, West Farm, St Kitts, West Indies; 2Modelling Suite, School of Biology, Newcastle University, Newcastle upon Tyne, UK Background: The flipped classroom is an educational approach that has had much recent coverage in the literature. Relatively few studies, however, use objective assessment of student performance to measure the impact of the flipped classroom on learning. The purpose of this study was to evaluate the use of a flipped classroom approach within a medical education setting to the first two levels of Kirkpatrick and Kirkpatrick's effectiveness of training framework. Methods: This study examined the use of a flipped classroom approach within a professional skills course offered to postgraduate veterinary students. A questionnaire was administered to two cohorts of students: those who had completed a traditional, lecture-based version of the course (Introduction to Veterinary Medicine [IVM] and those who had completed a flipped classroom version (Veterinary Professional Foundations I [VPF I]. The academic performance of students within both cohorts was assessed using a set of multiple-choice items (n=24 nested within a written examination. Data obtained from the questionnaire were analyzed using Cronbach's alpha, Kruskal–Wallis tests, and factor analysis. Data obtained from student performance in the written examination were analyzed using the nonparametric Wilcoxon rank sum test. Results: A total of 133 IVM students and 64 VPF I students (n=197 agreed to take part in the study. Overall, study participants favored the flipped classroom approach over the traditional classroom approach. With respect to student academic performance, the traditional classroom students outperformed the flipped classroom students on a series of multiple-choice items (IVM mean =21.4±1.48 standard deviation; VPF I mean =20.25±2.20 standard deviation; Wilcoxon test, w=7,578; P<0

  17. Use of Flipped Classroom Technology in Language Learning

    OpenAIRE

    Evseeva, Arina Mikhailovna; Solozhenko, Anton

    2015-01-01

    The flipped classroom as a key component of blended learning arouses great interest among researchers and educators nowadays. The technology of flipped classroom implies such organization of the educational process in which classroom activities and homework assignments are reversed. The present paper gives the overview of the flipped classroom technology and explores its potential for both teachers and students. The authors present the results obtained from the experience of the flipped class...

  18. An Integrative Review of Flipped Classroom Teaching Models in Nursing Education.

    Science.gov (United States)

    Njie-Carr, Veronica P S; Ludeman, Emilie; Lee, Mei Ching; Dordunoo, Dzifa; Trocky, Nina M; Jenkins, Louise S

    Nursing care is changing dramatically given the need for students to address complex and multiple patient comorbidities. Students experience difficulties applying knowledge gained from didactic instruction to make important clinical decisions for optimal patient care. To optimize nursing education pedagogy, innovative teaching strategies are required to prepare future nurses for practice. This integrative review synthesized the state of the science on flipped classroom models from 13 empirical studies published through May 2016. The purpose of the review was to evaluate studies conducted on flipped classroom models among nursing students using a validated framework by Whittemore and Knafl. Multiple academic databases were searched, ranging in scope including PubMed, Embase (Elsevier), CINAHL (Ebsco), Scopus, Web of Science, and Google Scholar, resulting in 95 unique records. After screening and full-text reviews, 82 papers were removed. Thirteen empirical studies were included in the final analysis and results provided (a) design and process information on flipped classroom models in nursing education, (b) a summary of the state of the evidence to inform the implementation of flipped classrooms, and (c) a foundation to build future research in this area of nursing education. To develop sound evidence-based teaching strategies, rigorous scientific methods are needed to inform the implementation of flipped classroom approaches. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. How we flipped the medical classroom.

    Science.gov (United States)

    Sharma, Neel; Lau, C S; Doherty, Iain; Harbutt, Darren

    2015-04-01

    Flipping the classroom centres on the delivery of print, audio or video based material prior to a lecture or class session. The class session is then dedicated to more active learning processes with application of knowledge through problem solving or case based scenarios. The rationale behind this approach is that teachers can spend their face-to-face time supporting students in deeper learning processes. In this paper we provide a background literature review on the flipped classroom along with a three step approach to flipping the classroom comprising implementing, enacting and evaluating this form of pedagogy. Our three step approach is based on actual experience of delivering a flipped classroom at the University of Hong Kong. This initiative was evaluated with positive results. We hope our experience will be transferable to other medical institutions.

  20. Adventures in Flipping College Algebra

    Science.gov (United States)

    Van Sickle, Jenna

    2015-01-01

    This paper outlines the experience of a university professor who implemented flipped learning in two sections of college algebra courses for two semesters. It details how the courses were flipped, what technology was used, advantages, challenges, and results. It explains what students do outside of class, what they do inside class, and discusses…

  1. Information Literacy and the Flipped Classroom: Examining the Impact of a One-Shot Flipped Class on Student Learning and Perceptions

    Directory of Open Access Journals (Sweden)

    Andrea Wilcox Brooks

    2014-12-01

    Full Text Available This article examines the flipped classroom approach in higher education and its use in one-shot information literacy instruction sessions. The author presents findings from a pilot study of student learning and student perceptions pertaining to flipped model IL instruction. Students from two sections of the same course participated in this study. One section received one-shot information literacy instruction using a flipped approach, while the other section received traditional one-shot instruction. No difference was found between the two groups on a pre- and post-test analysis; however, an analysis of students’ final papers from the flipped section showed more bibliography citations to scholarly journal articles. In addition, a survey was conducted showing the majority of students preferred the flipped approach.

  2. Flipped Learning With Simulation in Undergraduate Nursing Education.

    Science.gov (United States)

    Kim, HeaRan; Jang, YounKyoung

    2017-06-01

    Flipped learning has proliferated in various educational environments. This study aimed to verify the effects of flipped learning on the academic achievement, teamwork skills, and satisfaction levels of undergraduate nursing students. For the flipped learning group, simulation-based education via the flipped learning method was provided, whereas traditional, simulation-based education was provided for the control group. After completion of the program, academic achievement, teamwork skills, and satisfaction levels were assessed and analyzed. The flipped learning group received higher scores on academic achievement, teamwork skills, and satisfaction levels than the control group, including the areas of content knowledge and clinical nursing practice competency. In addition, this difference gradually increased between the two groups throughout the trial. The results of this study demonstrated the positive, statistically significant effects of the flipped learning method on simulation-based nursing education. [J Nurs Educ. 2017;56(6):329-336.]. Copyright 2017, SLACK Incorporated.

  3. Twelve tips for "flipping" the classroom.

    Science.gov (United States)

    Moffett, Jennifer

    2015-04-01

    The flipped classroom is a pedagogical model in which the typical lecture and homework elements of a course are reversed. The following tips outline the steps involved in making a successful transition to a flipped classroom approach. The tips are based on the available literature alongside the author's experience of using the approach in a medical education setting. Flipping a classroom has a number of potential benefits, for example increased educator-student interaction, but must be planned and implemented carefully to support effective learning.

  4. Flip-flopping binary black holes.

    Science.gov (United States)

    Lousto, Carlos O; Healy, James

    2015-04-10

    We study binary spinning black holes to display the long term individual spin dynamics. We perform a full numerical simulation starting at an initial proper separation of d≈25M between equal mass holes and evolve them down to merger for nearly 48 orbits, 3 precession cycles, and half of a flip-flop cycle. The simulation lasts for t=20 000M and displays a total change in the orientation of the spin of one of the black holes from an initial alignment with the orbital angular momentum to a complete antialignment after half of a flip-flop cycle. We compare this evolution with an integration of the 3.5 post-Newtonian equations of motion and spin evolution to show that this process continuously flip flops the spin during the lifetime of the binary until merger. We also provide lower order analytic expressions for the maximum flip-flop angle and frequency. We discuss the effects this dynamics may have on spin growth in accreting binaries and on the observational consequences for galactic and supermassive binary black holes.

  5. Development of a Flipped Medical School Dermatology Module.

    Science.gov (United States)

    Fox, Joshua; Faber, David; Pikarsky, Solomon; Zhang, Chi; Riley, Richard; Mechaber, Alex; O'Connell, Mark; Kirsner, Robert S

    2017-05-01

    The flipped classroom module incorporates independent study in advance of in-class instructional sessions. It is unproven whether this methodology is effective within a medical school second-year organ system module. We report the development, implementation, and effectiveness of the flipped classroom methodology in a second-year medical student dermatology module at the University of Miami Leonard M. Miller School of Medicine. In a retrospective cohort analysis, we compared attitudinal survey data and mean scores for a 50-item multiple-choice final examination of the second-year medical students who participated in this 1-week flipped course with those of the previous year's traditional, lecture-based course. Each group comprised nearly 200 students. Students' age, sex, Medical College Admission Test scores, and undergraduate grade point averages were comparable between the flipped and traditional classroom students. The flipped module students' mean final examination score of 92.71% ± 5.03% was greater than that of the traditional module students' 90.92% ± 5.51% ( P flipped methodology to attending live lectures or watching previously recorded lectures. The flipped classroom can be an effective instructional methodology for a medical school second-year organ system module.

  6. Acetylation-Mediated Proteasomal Degradation of Core Histones during DNA Repair and Spermatogenesis

    Science.gov (United States)

    Qian, Min-Xian; Pang, Ye; Liu, Cui Hua; Haratake, Kousuke; Du, Bo-Yu; Ji, Dan-Yang; Wang, Guang-Fei; Zhu, Qian-Qian; Song, Wei; Yu, Yadong; Zhang, Xiao-Xu; Huang, Hai-Tao; Miao, Shiying; Chen, Lian-Bin; Zhang, Zi-Hui; Liang, Ya-Nan; Liu, Shan; Cha, Hwangho; Yang, Dong; Zhai, Yonggong; Komatsu, Takuo; Tsuruta, Fuminori; Li, Haitao; Cao, Cheng; Li, Wei; Li, Guo-Hong; Cheng, Yifan; Chiba, Tomoki; Wang, Linfang; Goldberg, Alfred L.; Shen, Yan; Qiu, Xiao-Bo

    2013-01-01

    SUMMARY Histone acetylation plays critical roles in chromatin remodeling, DNA repair, and epigenetic regulation of gene expression, but the underlying mechanisms are unclear. Proteasomes usually catalyze ATP- and polyubiquitin-dependent proteolysis. Here we show that the proteasomes containing the activator PA200 catalyze the polyubiquitin-independent degradation of histones. Most proteasomes in mammalian testes (“spermatoproteasomes”) contain a spermatid/sperm-specific α-subunit α4s/PSMA8 and/or the catalytic β-subunits of immunoproteasomes in addition to PA200. Deletion of PA200 in mice abolishes acetylation-dependent degradation of somatic core histones during DNA double-strand breaks, and delays core histone disappearance in elongated spermatids. Purified PA200 greatly promotes ATP-independent proteasomal degradation of the acetylated core histones, but not polyubiquitinated proteins. Furthermore, acetylation on histones is required for their binding to the bromodomain-like regions in PA200 and its yeast ortholog, Blm10. Thus, PA200/Blm10 specifically targets the core histones for acetylation-mediated degradation by proteasomes, providing mechanisms by which acetylation regulates histone degradation, DNA repair, and spermatogenesis. PMID:23706739

  7. DPFFs: C2MOS Direct Path Flip-Flops for Process-Resilient Ultradynamic Voltage Scaling

    Directory of Open Access Journals (Sweden)

    Myeong-Eun Hwang

    2016-01-01

    Full Text Available We propose two master-slave flip-flops (FFs that utilize the clocked CMOS (C2MOS technique with an internal direct connection along the main signal propagation path between the master and slave latches and adopt an adaptive body bias technique to improve circuit robustness. C2MOS structure improves the setup margin and robustness while providing full compatibility with the standard cell characterization flow. Further, the direct path shortens the logic depth and thus speeds up signal propagation, which can be optimized for less power and smaller area. Measurements from test circuits fabricated in 130 nm technology show that the proposed FF operates down to 60 mV, consuming 24.7 pW while improving the propagation delay, dynamic power, and leakage by 22%, 9%, and 13%, respectively, compared with conventional FFs at the iso-output-load condition. The proposed FFs are integrated into an 8×8 FIR filter which successfully operates all the way down to 85 mV.

  8. Unifying flipped SU(5) in five dimensions

    International Nuclear Information System (INIS)

    Barr, S.M.; Dorsner, Ilja

    2002-01-01

    It is shown that embedding a four-dimensional flipped SU(5) model in a five-dimensional SO(10) model preserves the best features of both flipped SU(5) and SO(10). The missing partner mechanism, which naturally achieves both doublet-triplet splitting and suppression of d=5 proton decay operators, is realized as in flipped SU(5), while the gauge couplings are unified as in SO(10). The masses of down quarks and charged leptons, which are independent in flipped SU(5), are related by the SO(10). Distinctive patterns of quark and lepton masses can result. The gaugino mass M 1 is independent of M 3 and M 2 , which are predicted to be equal

  9. Assessing Behavioral Engagement in Flipped and Non-Flipped Mathematics Classrooms: Teacher Abilities and Other Potential Factors

    Science.gov (United States)

    Hodgson, Theodore R.; Cunningham, Abby; McGee, Daniel; Kinne, Lenore J.; Murphy, Teri J.

    2017-01-01

    There is a growing evidence that flipped classrooms are associated with increased levels of student engagement, as compared to engagement in "traditional" settings. Much of this research, however, occurs in post-secondary classrooms and is based upon self-reported engagement data. This study seeks to extend existing flipped classroom…

  10. Degradation of sulfadimethoxine catalyzed by laccase with soybean meal extract as natural mediator: Mechanism and reaction pathway.

    Science.gov (United States)

    Liang, Shangtao; Luo, Qi; Huang, Qingguo

    2017-08-01

    Natural laccase-mediator systems have been well recognized as an eco-friendly and energy-saving approach in environmental remediation, whose further application is however limited by the high cost of natural mediators and relatively long treatment time span. This study evaluated the water extract of soybean meal, a low-cost compound system, in mediating the laccase catalyzed degradation of a model contaminant of emerging concern, sulfadimethoxine (SDM), and demonstrated it as a promising alternative mediator for soil and water remediation. Removal of 73.3% and 65.6% was achieved in 9 h using soybean meal extract (SBE) as the mediating system for laccase-catalyzed degradation of sulfadimethoxine at the concentration of 1 ppm and 10 ppm, respectively. Further degradation of sulfadimethoxine was observed with multiple SBE additions. Using SBE as mediator increased the 9-h removal of SDM at 1 ppm initial concentration by 52.9%, 49.4%, and 36.3% in comparison to the system mediated by 1-Hydroxybenzotriazole (HBT), p-Coumaric acid (COU) and 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonate) (ABTS), respectively. With the detection of stable coupling products formed with radical scavenger (5,5-Dimethyl-1-pyrroline N-oxide, DMPO), three phenolic compounds (vanillin, apocynin, and daidzein) in SBE were confirmed to serve as mediators for Trametes versicolor laccase. Reaction pathways were proposed based on the results of High Resolution Mass Spectrometry. SO 2 excursion happened during SDM transformation, leading to elimination of antimicrobial activity. Therefore, as a natural, phenol rich, and affordable compound system, the future application of SBE in wastewater and soil remediation is worth exploring. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Identification and Characterization of the Interaction Site between cFLIPL and Calmodulin.

    Directory of Open Access Journals (Sweden)

    Gabriel Gaidos

    Full Text Available Overexpression of the cellular FLICE-like inhibitory protein (cFLIP has been reported in a number of tumor types. As an inactive procaspase-8 homologue, cFLIP is recruited to the intracellular assembly known as the Death Inducing Signaling Complex (DISC where it inhibits apoptosis, leading to cancer cell proliferation. Here we characterize the molecular details of the interaction between cFLIPL and calmodulin, a ubiquitous calcium sensing protein. By expressing the individual domains of cFLIPL, we demonstrate that the interaction with calmodulin is mediated by the N-terminal death effector domain (DED1 of cFLIPL. Additionally, we mapped the interaction to a specific region of the C-terminus of DED1, referred to as DED1 R4. By designing DED1/DED2 chimeric constructs in which the homologous R4 regions of the two domains were swapped, calmodulin binding properties were transferred to DED2 and removed from DED1. Furthermore, we show that the isolated DED1 R4 peptide binds to calmodulin and solve the structure of the peptide-protein complex using NMR and computational refinement. Finally, we demonstrate an interaction between cFLIPL and calmodulin in cancer cell lysates. In summary, our data implicate calmodulin as a potential player in DISC-mediated apoptosis and provide evidence for a specific interaction with the DED1 of cFLIPL.

  12. Flipped Science Inquiry@Crescent Girls' School

    Directory of Open Access Journals (Sweden)

    Peishi Goh

    2017-06-01

    Full Text Available This study shares the findings of a school-based Action Research project to explore how inquiry-based science practical lessons designed using the Flipped Science Inquiry@CGS classroom pedagogical model influence the way students learn scientific knowledge and also students' development of 21st century competencies, in particular, in the area of Knowledge Construction. Taking on a broader definition of the flipped classroom pedagogical model, the Flipped Science Inquiry@CGS framework adopts a structure that inverted the traditional science learning experience. Scientific knowledge is constructed through discussions with their peers, making use of their prior knowledge and their experiences while engaging in hands-on activities. Through the study, it is found that with the use of the Flipped Science Inquiry@CGS framework, learning experiences that are better aligned to the epistemology of science while developing 21st century competencies in students are created.

  13. Vodcasts and active-learning exercises in a "flipped classroom" model of a renal pharmacotherapy module.

    Science.gov (United States)

    Pierce, Richard; Fox, Jeremy

    2012-12-12

    To implement a "flipped classroom" model for a renal pharmacotherapy topic module and assess the impact on pharmacy students' performance and attitudes. Students viewed vodcasts (video podcasts) of lectures prior to the scheduled class and then discussed interactive cases of patients with end-stage renal disease in class. A process-oriented guided inquiry learning (POGIL) activity was developed and implemented that complemented, summarized, and allowed for application of the material contained in the previously viewed lectures. Students' performance on the final examination significantly improved compared to performance of students the previous year who completed the same module in a traditional classroom setting. Students' opinions of the POGIL activity and the flipped classroom instructional model were mostly positive. Implementing a flipped classroom model to teach a renal pharmacotherapy module resulted in improved student performance and favorable student perceptions about the instructional approach. Some of the factors that may have contributed to students' improved scores included: student mediated contact with the course material prior to classes, benchmark and formative assessments administered during the module, and the interactive class activities.

  14. Ku70 acetylation and modulation of c-Myc/ATF4/CHOP signaling axis by SIRT1 inhibition lead to sensitization of HepG2 cells to TRAIL through induction of DR5 and down-regulation of c-FLIP

    DEFF Research Database (Denmark)

    Kim, Mi-Ju; Hong, Kyung-Soo; Kim, Hak-Bong

    2013-01-01

    In this study, we investigated the role of c-Myc/ATF4/CHOP signaling pathway in sensitization of human hepatoma HepG2 cells to TRAIL. Knockdown of SIRT1 or treatment with SIRT1 inhibitor caused the up-regulation of DR5 and down-regulation of c-FLIP through modulation of c-Myc/ATF4/CHOP pathway, a...

  15. Deep Exploration of the Flipped Classroom before Implementing

    Science.gov (United States)

    Logan, Brenda

    2015-01-01

    This paper is a review of the literature that attempts to explain and document the literature on the flipped classroom. It examines 49 studies that explain the flipped approach in the classroom. This paper, particularly, delineates the history, the theory, benefits, criticisms, recommended practices, and what the research on flipping reveals.…

  16. Using lightboard to flip the course

    DEFF Research Database (Denmark)

    Timcenko, Olga; Triantafyllou, Evangelia; Nilsson, Niels Chr.

    , and exercises for in-class work. However, the quality of videos that students have to watch before coming to the class is also important. In this paper, we will describe videos prepared for flipped classroom using light board, an invention from 2014. That allows natural flow of presentation, as it combines......Authors of the paper have several years of experience with flipping parts of the courses, and the whole courses. Crucial for successful flipping the class are well-chosen exercises that students need to do before the class, as a confirmation that they come prepared for in-class exercises...

  17. The F-box Protein FBXO44 Mediates BRCA1 Ubiquitination and Degradation*

    Science.gov (United States)

    Lu, Yunzhe; Li, Jiezhi; Cheng, Dongmei; Parameswaran, Balaji; Zhang, Shaohua; Jiang, Zefei; Yew, P. Renee; Peng, Junmin; Ye, Qinong; Hu, Yanfen

    2012-01-01

    BRCA1 mutations account for a significant proportion of familial breast and ovarian cancers. In addition, reduced BRCA1 protein is associated with sporadic cancer cases in these tissues. At the cellular level, BRCA1 plays a critical role in multiple cellular functions such as DNA repair and cell cycle checkpoint control. Its protein level is regulated in a cell cycle-dependent manner. However, regulation of BRCA1 protein stability is not fully understood. Our earlier study showed that the amino terminus of BRCA1 harbors a degron sequence that is sufficient and necessary for conferring BRCA1 degradation. In the current study, we used mass spectrometry to identify Skp1 that regulates BRCA1 protein stability. Small interfering RNA screening that targets all human F-box proteins uncovered FBXO44 as an important protein that influences BRCA1 protein level. The Skp1-Cul1-F-box-protein44 (SCFFBXO44) complex ubiquitinates full-length BRCA1 in vitro. Furthermore, the N terminus of BRCA1 mediates the interaction between BRCA1 and FBXO44. Overexpression of SCFFBXO44 reduces BRCA1 protein level. Taken together, our work strongly suggests that SCFFBXO44 is an E3 ubiquitin ligase responsible for BRCA1 degradation. In addition, FBXO44 expression pattern in breast carcinomas suggests that SCFFBXO44-mediated BRCA1 degradation might contribute to sporadic breast tumor development. PMID:23086937

  18. Effect of solvents on the enzyme mediated degradation of copolymers

    International Nuclear Information System (INIS)

    Banerjee, Aditi; Chatterjee, Kaushik; Madras, Giridhar

    2015-01-01

    The biodegradation of polycaprolactone (PCL), polylactic acid (PLA), polyglycolide (PGA) and their copolymers, poly (lactide-co-glycolide) and poly (D, L-lactide-co-caprolactone) (PLCL) was investigated. The influence of different solvents on the degradation of these polymers at 37 °C in the presence of two different lipases namely Novozym 435 and the free lipase of porcine pancreas was investigated. The rate coefficients for the polymer degradation and enzyme deactivation were determined using continuous distribution kinetics. Among the homopolymers, the degradation of PGA was nearly an order of magnitude lower than that for PCL and PLA. The overall rate coefficients of the copolymers were higher than their respective homopolymers. Thus, PLCL degraded faster than either PCL or PLA. The degradation was highly dependent on the viscosity of the solvent used with the highest degradation observed in acetone. The degradation of the polymers in acetone was nearly twice that observed in dimethyl sulfoxide indicating that the degradation decreases with increase in the solvent viscosity. The degradation of the polymers in water-solvent mixtures indicated an optimal water content of 2.5 wt% of water. (paper)

  19. The Fbw7 tumor suppressor targets KLF5 for ubiquitin-mediated degradation and suppresses breast cell proliferation.

    Science.gov (United States)

    Zhao, Dong; Zheng, Han-Qiu; Zhou, Zhongmei; Chen, Ceshi

    2010-06-01

    Fbw7 is a tumor suppressor frequently inactivated in cancers. The KLF5 transcription factor promotes breast cell proliferation and tumorigenesis through upregulating FGF-BP. The KLF5 protein degrades rapidly through the ubiquitin proteasome pathway. Here, we show that the Skp1-CUL1-Fbw7 E3 ubiquitin ligase complex (SCF(Fbw7)) targets KLF5 for ubiquitin-mediated degradation in a GSK3beta-mediated KLF5 phosphorylation-dependent manner. Mutation of the critical S303 residue in the KLF5 Cdc4 phospho-degrons motif ((303)SPPSS) abolishes the protein interaction, ubiquitination, and degradation by Fbw7. Inactivation of endogenous Fbw7 remarkably increases the endogenous KLF5 protein abundances. Endogenous Fbw7 suppresses the FGF-BP gene expression and breast cell proliferation through targeting KLF5 for degradation. These findings suggest that Fbw7 inhibits breast cell proliferation at least partially through targeting KLF5 for proteolysis. This new regulatory mechanism of KLF5 degradation may result in useful diagnostic and therapeutic targets for breast cancer and other cancers. Copyright 2010 AACR.

  20. Evaluation of flipped teaching

    OpenAIRE

    Henderson, K.; Hobbs, C.; Last, K.

    2017-01-01

    We report on our evaluation of flipping the classroom for two modules: a compulsory first year calculus module and an optional second year coding theory module taken by Mathe-matics students at the University of the West of England, Bristol (UWE). Flipped teaching is a change to the traditional lecture model used in universities for hundreds of years. In the traditional model the lecturer is in charge of the class and largely dictates the content and pace at which this is delivered. The idea ...

  1. Degradation of carbazole, dibenzothiophene, and dibenzofuran at low temperature by Pseudomonas sp. strain C3211.

    Science.gov (United States)

    Jensen, Anne-Mette; Finster, Kai Waldemar; Karlson, Ulrich

    2003-04-01

    Pseudomonas sp. strain C3211 was isolated from a temperate climate soil contaminated with creosote. This strain was able to degrade carbazole, dibenzothiophene and dibenzofuran at 10 degrees C with acetone as a co-substrate. When dibenzothiophene was degraded by strain C3211, an orange compound, which absorbed at 472 nm, accumulated in the medium. Degradation of dibenzofuran was followed by accumulation of a yellowish compound, absorbing at 462 nm. The temperature optimum of strain C3211 for degradation of dibenzothiophene and dibenzofuran was at 20 to 21 degrees C, while the maximum temperature for degradation was at 27 degrees C. Both compounds were degraded at 4 degrees C. Degradation at 10 degrees C was faster than degradation at 25 degrees C. This indicates that strain C3211 is adapted to life at low temperatures.

  2. Retention of Content Utilizing a Flipped Classroom Approach.

    Science.gov (United States)

    Shatto, Bobbi; LʼEcuyer, Kristine; Quinn, Jerod

    The flipped classroom experience promotes retention and accountability for learning. The authors report their evaluation of a flipped classroom for accelerated second-degree nursing students during their primary medical-surgical nursing course. Standardized HESI® scores were compared between a group of students who experienced the flipped classroom and a previous group who had traditional teaching methods. Short- and long-term retention was measured using standardized exams 3 months and 12 months following the course. Results indicated that short-term retention was greater and long- term retention was significantly great in the students who were taught using flipped classroom methodology.

  3. Nogo-B (Reticulon-4B) functions as a negative regulator of the apoptotic pathway through the interaction with c-FLIP in colorectal cancer cells.

    Science.gov (United States)

    Kawaguchi, Nao; Tashiro, Keitaro; Taniguchi, Kohei; Kawai, Masaru; Tanaka, Keitaro; Okuda, Junji; Hayashi, Michihiro; Uchiyama, Kazuhisa

    2018-08-01

    Nogo-B is a member of the Nogo/Reticulon-4 family and has been reported to be an inducer of apoptosis in certain types of cancer cells. However, the role of Nogo-B in human cancer remains less understood. Here, we demonstrated the functions of Nogo-B in colorectal cancer cells. In clinical colorectal cancer specimens, Nogo-B was obviously overexpressed, as determined by immunohistochemistry; and Western blot analysis showed its expression level to be significantly up-regulated. Furthermore, knockdown of Nogo-B in two colorectal cancer cell lines, SW480 and DLD-1, by transfection with si-RNA (siR) resulted in significantly reduced cell viability and a dramatic increase in apoptosis with insistent overexpression of cleaved caspase-8 and cleaved PARP. The transfection with Nogo-B plasmid cancelled that apoptosis induced by siRNogoB in SW480 cells. Besides, combinatory treatment with siR-Nogo-B/staurosporine (STS) or siR-Nogo-B/Fas ligand (FasL) synergistically reduced cell viability and increased the expression of apoptotic signaling proteins in colorectal cancer cells. These results strongly support our contention that Nogo-B most likely played an oncogenic role in colorectal cancer cells, mainly by negatively regulating the extrinsic apoptotic pathway in them. Finally, we revealed that suppression of Nogo-B caused down-regulation of c-FLIP, known as a major anti-apoptotic protein, and activation of caspase-8 in the death receptor pathway. Interaction between Nogo-B and c-FLIP was shown by immunoprecipitation and immunofluorescence studies. In conclusion, Nogo-B was shown to play an important negative role in apoptotic signaling through its interaction with c-FLIP in colorectal cancer cells, and may thus become a novel therapeutic target for colorectal cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Conceptualizing "Homework" in Flipped Mathematics Classes

    Science.gov (United States)

    de Araujo, Zandra; Otten, Samuel; Birisci, Salih

    2017-01-01

    Flipped instruction is becoming more common in the United States, particularly in mathematics classes. One of the defining characteristics of this increasingly popular instructional format is the homework teachers assign. In contrast to traditional mathematics classes in which homework consists of problem sets, homework in flipped classes often…

  5. Flipped Classroom Instruction for Inclusive Learning

    Science.gov (United States)

    Altemueller, Lisa; Lindquist, Cynthia

    2017-01-01

    The flipped classroom is a teaching methodology that has gained recognition in primary, secondary and higher education settings. The flipped classroom inverts traditional teaching methods, delivering lecture instruction outside class, and devoting class time to problem solving, with the teacher's role becoming that of a learning coach and…

  6. High energy hadron spin-flip amplitude

    International Nuclear Information System (INIS)

    Selyugin, O.V.

    2016-01-01

    The high-energy part of the hadron spin-flip amplitude is examined in the framework of the new high-energy general structure (HEGS) model of the elastic hadron scattering at high energies. The different forms of the hadron spin-flip amplitude are compared in the impact parameter representation. It is shown that the existing experimental data of the proton-proton and proton-antiproton elastic scattering at high energy in the region of the diffraction minimum and at large momentum transfer give support in the presence of the energy-independent part of the hadron spin-flip amplitude with the momentum dependence proposed in the works by Galynskii-Kuraev. [ru

  7. Estimate the thermomechanical fatigue life of two flip chip packages

    International Nuclear Information System (INIS)

    Pash, R.A.; Ullah, H.S.; Khan, M.Z.

    2005-01-01

    The continuing demand towards high density and low profile integrated circuit packaging has accelerated the development of flip chip structures as used in direct chip attach (DCA) technology, ball grid array (BOA) and chip scale package (CSP). In such structures the most widely used flip chip interconnects are solder joints. The reliability of flip chip structures largely depends on the reliability of solder joints. In this work solder joint fatigue life prediction for two chip scale packages is carried out. Elasto-plastic deformation behavior of the solder was simulated using ANSYS. Two dimensional plain strain finite element models were developed for each package to numerically compute the stress and total strain of the solder joints under temperature cycling. These stress and strain values are then used to predict the solder joint lifetime through modified Coffin Manson equation. The effect of solder joint's distance from edge of silicon die on life of the package is explored. The solder joint fatigue response is modeled for a typical temperature cycling of -60 to 140 degree C. (author)

  8. Interaction-flip identities in spin glasses

    NARCIS (Netherlands)

    Contucci, P.; Giardinà, C.; Giberti, C.

    2009-01-01

    We study the properties of fluctuation for the free energies and internal energies of two spin glass systems that differ for having some set of interactions flipped. We show that their difference has a variance that grows like the volume of the flipped region. Using a new interpolation method, which

  9. STEM Teacher Efficacy in Flipped Classrooms

    Science.gov (United States)

    Kelly, Daniel; Denson, Cameron

    2017-01-01

    The flipped classroom instructional model continues to grow in adoption and use in K-12 classrooms. Although there are an increasing number of studies into the implementation of the flipped classroom, there is limited empirical research into its effectiveness and even fewer into the educational, psychological, and theoretical constructs underlying…

  10. Potential role of recombinant secretory leucoprotease inhibitor in the prevention of neutrophil mediated matrix degradation.

    Science.gov (United States)

    Llewellyn-Jones, C G; Lomas, D A; Stockley, R A

    1994-06-01

    Neutrophil elastase is able to degrade connective tissue matrices and is thought to be involved in the pathogenesis of destructive lung diseases. The ability of recombinant secretory leucoprotease inhibitor (rSLPI) to inhibit neutrophil mediated degradation of fibronectin in vitro is demonstrated and its efficacy compared with native alpha-1-proteinase inhibitor (n alpha 1-PI), recombinant alpha-1-proteinase inhibitor (r alpha 1-PI), and the chemical elastase inhibitor ICI 200,355. When preincubated with neutrophils both rSLPI and r alpha 1-PI were effective inhibitors of fibronectin degradation although n alpha 1-PI and ICI 200,355 were less effective. Recombinant SLPI was the most effective inhibitor when the cells were allowed to adhere to fibronectin before the addition of the inhibitors. Preincubation of rSLPI (0.1 mumol/l) with the fibronectin plate resulted in almost total inhibition of fibronectin degradation (reduced to 3.3 (SE 0.9)% of control). Pretreating the fibronectin plate with 1 mumol/l rSLPI, r alpha 1-PI and ICI 200,355 followed by thorough washing before the addition of cells resulted in no inhibition of fibronectin degradation with r alpha 1-PI and the ICI inhibitor, but rSLPI retained its inhibitory effect. This effect could be reduced by adding rSLPI in high pH buffer or 2 mol/1 NaCl. It is postulated that rSLPI binds to fibronectin to form a protective layer which prevents its degradation by neutrophil elastase. It may prove to be the most useful therapeutic agent in the prevention of neutrophil mediated lung damage.

  11. The F-box protein FBXO44 mediates BRCA1 ubiquitination and degradation.

    Science.gov (United States)

    Lu, Yunzhe; Li, Jiezhi; Cheng, Dongmei; Parameswaran, Balaji; Zhang, Shaohua; Jiang, Zefei; Yew, P Renee; Peng, Junmin; Ye, Qinong; Hu, Yanfen

    2012-11-30

    BRCA1 mutations account for a significant proportion of familial breast and ovarian cancers. In addition, reduced BRCA1 protein is associated with sporadic cancer cases in these tissues. At the cellular level, BRCA1 plays a critical role in multiple cellular functions such as DNA repair and cell cycle checkpoint control. Its protein level is regulated in a cell cycle-dependent manner. However, regulation of BRCA1 protein stability is not fully understood. Our earlier study showed that the amino terminus of BRCA1 harbors a degron sequence that is sufficient and necessary for conferring BRCA1 degradation. In the current study, we used mass spectrometry to identify Skp1 that regulates BRCA1 protein stability. Small interfering RNA screening that targets all human F-box proteins uncovered FBXO44 as an important protein that influences BRCA1 protein level. The Skp1-Cul1-F-box-protein44 (SCF(FBXO44)) complex ubiquitinates full-length BRCA1 in vitro. Furthermore, the N terminus of BRCA1 mediates the interaction between BRCA1 and FBXO44. Overexpression of SCF(FBXO44) reduces BRCA1 protein level. Taken together, our work strongly suggests that SCF(FBXO44) is an E3 ubiquitin ligase responsible for BRCA1 degradation. In addition, FBXO44 expression pattern in breast carcinomas suggests that SCF(FBXO44)-mediated BRCA1 degradation might contribute to sporadic breast tumor development.

  12. CRM1-mediated nuclear export is required for 26 S proteasome-dependent degradation of the TRIP-Br2 proto-oncoprotein.

    Science.gov (United States)

    Cheong, Jit Kong; Gunaratnam, Lakshman; Hsu, Stephen I-Hong

    2008-04-25

    Overexpression of the proto-oncogene TRIP-Br2 (SERTAD2) has been shown to induce E2F activity and promote tumorigenesis, whereas ablation of TRIP-Br2 arrests cell proliferation. Timely degradation of many cell cycle regulators is fundamental to the maintenance of proper cell cycle progression. Here we report novel mechanism(s) that govern the tight regulation of TRIP-Br2 levels during cell cycle progression. TRIP-Br2 was observed to be a short-lived protein in which the expression level peaks at the G(1)/S boundary. TRIP-Br2 accumulated in cells treated with 26 S proteasome inhibitors. Co-immunoprecipitation studies revealed that TRIP-Br2 forms ubiquitin conjugates. In silico analysis identified a putative leucine-rich nuclear export signal (NES) motif that overlaps with the PHD-Bromo interaction domain in the acidic C-terminal transactivation domain (TAD) of TRIP-Br2. This NES motif is highly conserved in widely divergent species and in all TRIP-Br family members. TRIP-Br2 was shown to be stabilized in G(2)/M phase cells through nuclear entrapment, either by deletion of the acidic C-terminal TAD, which includes the NES motif, or by leptomycin B-mediated inhibition of the CRM1-dependent nuclear export machinery. Mutation of leucine residue 238 of this NES motif abolished the interaction between CRM1 and TRIP-Br2, as well as the nuclear export of TRIP-Br2 and its subsequent 26 S proteasome-dependent degradation. These data suggest that CRM1-mediated nuclear export may be required for the proper execution of ubiquitin-proteasome-dependent degradation of TRIP-Br2.

  13. Online Learning Room for ”Flipped Classroom”

    DEFF Research Database (Denmark)

    Bugge, Ellen Margrethe; Nielsen, Linda Susanna Hauschildt

    2014-01-01

    working actively and innovatively to create a didactic design in our online learning rooms in our LMS that satisfy the demands for flipped learning and at the same time adapted to the special needs of each learning module at the nursing education programme. Keywords: Online learning, flipped classroom......Abstract The “flipped classroom” learning concept is an alternative way of teaching & learning. The fundamental idea of the "flipped classroom" is to change the way students prepare for classes and the work that takes place when the students are together in the classroom. This integrates online...... learning with learning in the classroom. The learning room must support the students’ unassisted learning, their preparation for class and their preparation for supervision in both a motivating and clear way. At the Nursing Education Programme at University College Lillebaelt in Denmark, we have been...

  14. Experimental resin cements containing bioactive fillers reduce matrix metalloproteinase-mediated dentin collagen degradation.

    Science.gov (United States)

    Osorio, Raquel; Yamauti, Monica; Sauro, Salvatore; Watson, Thimoty F; Toledano, Manuel

    2012-09-01

    Collagen dentin matrix may represent a suitable scaffold to be remineralized in the presence of bioactive materials. The purpose of this study was to determine if experimental resin cements containing bioactive fillers may modulate matrix metalloproteinase-mediated collagen degradation of etched dentin. Human dentin beams demineralized using 10% phosphoric acid or 0.5 mol/L EDTA were infiltrated with the following experimental resins: (1) unfilled resin, (2) resin with Bioglass 45S5 particles (Sylc; OSspray Ltd, London, UK), and (3) resin with β-tricalcium phosphate-modified calcium silicate cement (HCAT-β) particles. The filler/resin ratio was 40/60 wt%. The specimens were stored in artificial saliva, and the determination of C-terminal telopeptide (ICTP) was performed by radioimmunoassay after 24 hours, 1 week, and 4 weeks. Scanning electron microscopic analysis of dentin surfaces after 4 weeks of storage was also executed. Collagen degradation was prominent both in phosphoric acid and EDTA-treated dentin. Resin infiltration strongly reduced the MMP activity in demineralized dentin. Resin-containing Bioglass 45S5 particles exerted higher and more stable protection of collagen at all tested dentin states and time points. HCAT-β induced collagen protection from MMPs only in EDTA-treated specimens. Dentin remineralization was achieved when dentin was infiltrated with the resin cements containing bioactive fillers. MMP degradation of dentin collagen is strongly reduced in resin-infiltrated dentin. The inclusion of Bioglass 45S5 particles exerted an additional protection of collagen during dentin remineralization. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  15. Teaching & Learning Tips 6: The flipped classroom.

    Science.gov (United States)

    Shi, Connie R; Rana, Jasmine; Burgin, Susan

    2018-04-01

    Challenge: The "flipped classroom" is a pedagogical model in which instructional materials are delivered to learners outside of class, reserving class time for application of new principles with peers and instructors. Active learning has forever been an elusive ideal in medical education, but the flipped class model is relatively new to medical education. What is the evidence for the "flipped classroom," and how can these techniques be applied to the teaching of dermatology to trainees at all stages of their medical careers? © 2018 The International Society of Dermatology.

  16. Use of high flip angle in T1-prepared FAST sequences for myocardial perfusion quantification

    International Nuclear Information System (INIS)

    Vallee, Jean-Paul; Ivancevic, Marko; Lazeyras, Francois; Didier, Dominique; Kasuboski, Larry; Chatelain, Pascal; Righetti, Alberto

    2003-01-01

    This study reports on the first use of high flip angle and radio-frequency (RF) spoiling in T1-prepared fast acquisition in steady state (FAST) sequence for myocardial perfusion in patients. T1 dynamic range was measured in vitro with a FAST, an RF FAST and a snapshot fast low-angle shot (FLASH) sequences with a 90 flip angle. Myocardial perfusion was then measured twice in 6 patients during the same MR session. The RF FAST and FLASH, but not the FAST sequence, demonstrated an extended T1 dynamic range; however, the FLASH images were degraded by artifacts not present on the RF FAST images. The myocardial perfusion indices K1 (first-order transfer constant from the blood to the myocardium for the Gd-DTPA) and Vd (distribution volume of Gd-DTPA in myocardium) did not differ significantly between the two injections. K1 was 0.48±0.12 ml/min g -1 and Vd was 12.5±2.9%. With an extended T1 dynamic range and the sensitivity required for myocardial perfusion quantification, the RF FAST sequence with a 90 flip angle outperformed the snapshot FLASH sequence in terms of image quality and the FAST sequence in terms of contrast dynamic range. (orig.)

  17. Impacts of Flipped Classroom in High School Health Education

    Science.gov (United States)

    Chen, Li-Ling

    2016-01-01

    As advanced technology increasingly infiltrated into classroom, the flipped classroom has come to light in secondary educational settings. The flipped classroom is a new instructional approach that intends to flip the traditional teacher-centered classroom into student centered. The purpose of this research is to investigate the impact of the…

  18. Do Students Learn More from a Flip? An Exploration of the Efficacy of Flipped and Traditional Lessons

    Science.gov (United States)

    DeSantis, Joshua; Van Curen, Rebecca; Putsch, Jake; Metzger, Justin

    2015-01-01

    Flipped lesson planning, as popularized by Bergman & Sams (2012a), has been viewed by many as a revolutionary pedagogy, tailor-made for the twenty-first century classroom. Enthusiasm for flipped lesson planning has out-paced the collection of data that might determine its effectiveness. This paper presents the results of a study that compared…

  19. A new functional and structural generation of JK edge-triggered flip-flops

    International Nuclear Information System (INIS)

    Stefanescu, I.

    1977-01-01

    A new type of logical structure for a JK edge-triggered flip-flop is proposed by the author. The structure facilitates flip-flop realizations, named ''jk-JK edge-triggered flip-flops'', satisfying more functional requirements, and offering an increased flexibility in logical design, with respect to the conventional JK edge-triggered flip-flops. The function of new flip-flops covers the function of JK edge-triggered flip-flops, known as integrated circuits. (author)

  20. The Flipped Learning Approach in Nursing Education: A Literature Review.

    Science.gov (United States)

    Presti, Carmen Rosa

    2016-05-01

    This integrative review examines the application of the pedagogical methodology-the flipped classroom-in nursing education. A literature search of the CINAHL, ERIC, and the National Library of Medicine (PubMed and MEDLINE) databases was conducted, using the following key words: flipped classroom, inverted classroom, and nursing education. Results of a literature search yielded 94 articles, with 13 meeting the criteria of the flipped classroom approach in nursing education. Themes identified include the theoretical underpinning, strategies for implementation of a flipped classroom, and student satisfaction with and outcomes of the flipped classroom approach. Syntheses of the findings indicate that the flipped classroom approach can yield positive outcomes, but further study of this methodology is needed to guide future implementation. [J Nurs Educ. 2016;55(5):252-257.]. Copyright 2016, SLACK Incorporated.

  1. Flipped physics

    International Nuclear Information System (INIS)

    Nanopoulos, D.V.

    1991-01-01

    This paper is a revamp of a flipped SU(5) x U(1) model derived from the heterotic superstring. The author assumes that the reader is familiar with the general structure of the flipped SU(5) x U(1) model, either in its (pointlike) field theory form, or its stringy derivation. Ideally, one would like to derive directly from the superstring the standard model SU(3) x SU(2) x U(1), without possibly any extra structure (gauge or particle content). Well, this has been proven to be very difficult. Until now, always the standard model is accompanied with extra structure and usually one needs the ordinary Higgs mechanism to get rid of unwanted forms. This may happen at a superhigh energy scale (close to M Planck ) or at intermediate seals (10 13 --10 15 GeV). But if so, our original motivation of deriving directly the standard model from the superstring has been dispersed

  2. Degradation of 14C-glyphosate in compost amended soils.

    Science.gov (United States)

    Alexa, E; Bragea, M; Sumalan, R; Negrea, M; Lazureanu, A

    2009-01-01

    Glyphosate (N-phosphonomethyl-glycine), the active ingredient in several herbicide formulations, is a non-selective, post-emergent herbicide used in a variety of crop and non-crop situations. Glyphosate is a non-volatile herbicide that is relatively immobile in soil. Its degradation is due to microbiological processes and most laboratory studies have been conducted with 14C-glyphosate with the rate of 14CO2 evolution being used as an indication of herbicide breakdown. In this paper we have studied the glyphosate degradation in compost amendment soils using Scientilator Liquid TRIATHLER and Glyphosate-phosphonomethyl-14C-labeled with specific activity 2,2mCi/mmol. Four types of soils have been taken under study: Black Chernozem, Vertisol, Gleysol and Phaeozem with different characteristics. For the each type of soil have been realized four experimental variants (glyphosate blind sample with 1,5 ppm, concentration, autoclaved soil, soil with glyphosate and addition of compost in field concentration of 40 t/ha, respectively 60 t/ha. The mineralization curves of 14CO2 accumulated were compared during of 40 days. All the mineralization curves for the soils exhibited same patterns, with only two phases, the initial rapid phase of degradation, for about 20 days, attributed to microbial action on the free glyphosate and the second slow phase, when the curves attained plateaus. Compost applied with different concentrations to Vertisol and Black Chernozem did not appear to stimulate the microbial degradation of glyphosate. In Gleysol and Phaeozem with lower humus content, the mineralization curve of 14C indicate the increase degradation capacity, expressed as accumulated 14CO2 as % total 14C, with the increase of compost concentration.

  3. Chemical display of pyrimidine bases flipped out by modification-dependent restriction endonucleases of MspJI and PvuRts1I families.

    Directory of Open Access Journals (Sweden)

    Evelina Zagorskaitė

    Full Text Available The epigenetic DNA modifications 5-methylcytosine (5mC and 5-hydroxymethylcytosine (5hmC in eukaryotes are recognized either in the context of double-stranded DNA (e.g., by the methyl-CpG binding domain of MeCP2, or in the flipped-out state (e.g., by the SRA domain of UHRF1. The SRA-like domains and the base-flipping mechanism for 5(hmC recognition are also shared by the recently discovered prokaryotic modification-dependent endonucleases of the MspJI and PvuRts1I families. Since the mechanism of modified cytosine recognition by many potential eukaryotic and prokaryotic 5(hmC "readers" is still unknown, a fast solution based method for the detection of extrahelical 5(hmC would be very useful. In the present study we tested base-flipping by MspJI- and PvuRts1I-like restriction enzymes using several solution-based methods, including fluorescence measurements of the cytosine analog pyrrolocytosine and chemical modification of extrahelical pyrimidines with chloroacetaldehyde and KMnO4. We find that only KMnO4 proved an efficient probe for the positive display of flipped out pyrimidines, albeit the method required either non-physiological pH (4.3 or a substitution of the target cytosine with thymine. Our results imply that DNA recognition mechanism of 5(hmC binding proteins should be tested using a combination of all available methods, as the lack of a positive signal in some assays does not exclude the base flipping mechanism.

  4. Flipping the Continuing Medical Education Classroom: Validating a Measure of Attendees' Perceptions.

    Science.gov (United States)

    Stephenson, Christopher R; Wang, Amy T; Szostek, Jason H; Bonnes, Sara L; Ratelle, John T; Mahapatra, Saswati; Mandrekar, Jayawant N; Beckman, Thomas J; Wittich, Christopher M

    2016-01-01

    New teaching approaches for CME are needed. In flipped classrooms, coursework is completed beforehand and applied during class time. Studies of flipped classrooms and their potential benefits in CME have not been published. We sought to develop and validate an instrument measuring flipped classroom perceptions, identify whether participation changed perceptions, and determine which flipped classroom components were perceived as most effective. In this cross-sectional validation study, 167 participants in the Mayo Clinic's 2015 Internal Medicine Board Review course received surveys. Online modules were developed to deliver content before flipped classroom courses on acid-base disorders and electrolyte disorders. A flipped classroom perception instrument (FCPI) was developed and validated. The FCPI, with eight items structured on 5-point Likert scales, was given to participants before and after their flipped classroom experiences. Of the 167 participants, 111 returned surveys. Flipped classroom perceptions improved, with mean (SD) FCPI scores increasing from 3.74 (0.75) to 3.94 (0.76) (P flipped classrooms increased from 38% before the course to 53% after (P = .002). Positive changes in FCPI scores were unrelated to module completion. Most participants thought knowledge was enhanced by in-class sessions and online modules equally. The FCPI, the first validated measure of participants' perceptions of a CME flipped classroom, has strong validity evidence. Participants' perceptions of and preference for the flipped classroom improved after experiencing the flipped CME classroom. These findings support the need to further explore flipped classroom models in CME.

  5. An evaluation of flipped e-learning experiences.

    Science.gov (United States)

    Jones-Bonofiglio, Kristen Dawn; Willett, Timothy; Ng, Stella

    2017-12-22

    The "flipped" classroom is an educational strategy gaining popularity for its growing evidence base that suggests it may successfully improve learning outcomes. Also known as reverse instruction, this approach has been typically implemented and studied in in-person post-secondary settings. The utilization of a flipped approach in the healthcare education literature has been examined in a wide range of contexts, but little has been written regarding continuing professional development (CPD). Therefore, with success in other contexts there is potential for the flipped classroom approach to enhance student satisfaction, learner engagement, and learning outcomes in the context of online education for CPD. In this paper, we describe the structure and format of such a course using a qualitative case study framework. This study contributes to a more comprehensive understanding of effective ways of overcoming distributed learning challenges in online CPD using a flipped approach.

  6. Fat fraction bias correction using T1 estimates and flip angle mapping.

    Science.gov (United States)

    Yang, Issac Y; Cui, Yifan; Wiens, Curtis N; Wade, Trevor P; Friesen-Waldner, Lanette J; McKenzie, Charles A

    2014-01-01

    To develop a new method of reducing T1 bias in proton density fat fraction (PDFF) measured with iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL). PDFF maps reconstructed from high flip angle IDEAL measurements were simulated and acquired from phantoms and volunteer L4 vertebrae. T1 bias was corrected using a priori T1 values for water and fat, both with and without flip angle correction. Signal-to-noise ratio (SNR) maps were used to measure precision of the reconstructed PDFF maps. PDFF measurements acquired using small flip angles were then compared to both sets of corrected large flip angle measurements for accuracy and precision. Simulations show similar results in PDFF error between small flip angle measurements and corrected large flip angle measurements as long as T1 estimates were within one standard deviation from the true value. Compared to low flip angle measurements, phantom and in vivo measurements demonstrate better precision and accuracy in PDFF measurements if images were acquired at a high flip angle, with T1 bias corrected using T1 estimates and flip angle mapping. T1 bias correction of large flip angle acquisitions using estimated T1 values with flip angle mapping yields fat fraction measurements of similar accuracy and superior precision compared to low flip angle acquisitions. Copyright © 2013 Wiley Periodicals, Inc.

  7. Thermal and oxidative degradation studies of formulated C-ethers by gel-permeation chromatography

    Science.gov (United States)

    Jones, W. R., Jr.; Morales, W.

    1982-01-01

    Gel-permeation chromatography was used to analyze C-ether lubricant formulations from high-temperature bearing tests and from micro-oxidation tests. Three mu-styragel columns (one 500 and two 100 A) and a tetrahydrofuran mobile phase were found to adequately separate the C-ether degradation products. The micro-oxidation tests yielded degradation results qualitatively similar to those observed from the bearing tests. Micro-oxidation tests conducted in air yielded more degradation than did tests in nitrogen. No great differences were observed between the thermal-oxidative stabilities of the two C-ether formulations or between the catalytic degradation activities of silver and M-50 steel. C-ether formulation I did yield more degradation than did formulation II in 111- and 25-hour bearing tests, respectively.

  8. Spin flipping a stored polarized proton beam with an rf magnetic field

    International Nuclear Information System (INIS)

    Hu, S.Q.; Blinov, B.B.; Caussyn, D.D.

    1995-01-01

    The authors studied the spin flipping of a vertically polarized, stored 139 MeV proton beam with an rf solenoid magnetic field. By sweeping the rf frequency through an rf depolarizing resonance, they made the spin flip. The spin flipping was more efficient for slower ramp times, and the spin flip efficiency peaked at some optimum ramp time that is not yet fully understood. Since frequent spin flipping could significantly reduce the systematic errors in scattering experiments using a stored polarized beam, it is very important to minimize the depolarization after each spin flip. In this experiment, with multiple spin flips, the authors found a polarization loss of 0.0000 ± 0.0005 per spin flip under the best conditions; this loss increased significantly for small changes in the conditions

  9. Flipping and Still Learning: Experiences of a Flipped Classroom Approach for a Third-Year Undergraduate Human Geography Course

    Science.gov (United States)

    Graham, Marnie; McLean, Jessica; Read, Alexander; Suchet-Pearson, Sandie; Viner, Venessa

    2017-01-01

    The flipped classroom approach, a form of blended learning, is currently popular in education praxis. Initial reports on the flipped classroom include that it offers opportunities to increase student engagement and build meaningful learning and teaching experiences. In this article, we analyse teacher and student experiences of a trial flipped…

  10. Fitness Probability Distribution of Bit-Flip Mutation.

    Science.gov (United States)

    Chicano, Francisco; Sutton, Andrew M; Whitley, L Darrell; Alba, Enrique

    2015-01-01

    Bit-flip mutation is a common mutation operator for evolutionary algorithms applied to optimize functions over binary strings. In this paper, we develop results from the theory of landscapes and Krawtchouk polynomials to exactly compute the probability distribution of fitness values of a binary string undergoing uniform bit-flip mutation. We prove that this probability distribution can be expressed as a polynomial in p, the probability of flipping each bit. We analyze these polynomials and provide closed-form expressions for an easy linear problem (Onemax), and an NP-hard problem, MAX-SAT. We also discuss a connection of the results with runtime analysis.

  11. Teachers' development and reflection in the flipped classroom

    DEFF Research Database (Denmark)

    Triantafyllou, Evangelia; Timcenko, Olga; Kofoed, Lise

    2017-01-01

    The flipped classroom is an instruction method that has gained momentum during the last years due to technological advances allowing the online sharing of teaching material and learning activities. Bishop and Verleger defined the flipped classroom as “...an educational technique that consists...... of two parts: interactive group learning activities inside the classroom, and direct computer-based individual instruction outside the classroom” (Bishop & Verleger, 2013). So far, research on flipped classroom has mostly concentrated on student perceptions, engagement and achievement level, e...... course in order to adjust it to the flipped classroom model. We have also seen that these considerations have forced teachers to also reconsider the learning objectives of specific activities. Another aspect that promoted reflection was the production of video lectures. Finally, teachers reflected...

  12. Photocatalytic Degradation of 4-Nitrophenol by C, N-TiO2: Degradation Efficiency vs. Embryonic Toxicity of the Resulting Compounds

    Science.gov (United States)

    Osin, Oluwatomiwa A.; Yu, Tianyu; Cai, Xiaoming; Jiang, Yue; Peng, Guotao; Cheng, Xiaomei; Li, Ruibin; Qin, Yao; Lin, Sijie

    2018-06-01

    The photocatalytic activity of TiO2 based photocatalysts can be improved by structural modification and elemental doping. In this study, through rational design, one type of carbon and nitrogen co-doped TiO2 (C, N-TiO2) photocatalyst with mesoporous structure was synthesized with improved photocatalytic activity in degrading 4-nitrophenol under simulated sunlight irradiation. The photocatalytic degradation efficiency of the C, N-TiO2 was much higher than the anatase TiO2 (A-TiO2) based on absorbance and HPLC analyses. Moreover, using zebrafish embryos, we showed that the intermediate degradation compounds generated by photocatalytic degradation of 4-nitrophenol had higher toxicity than the parent compound. A repeated degradation process was necessary to render complete degradation and non-toxicity to the zebrafish embryos. Our results demonstrated the importance of evaluating the photocatalytic degradation efficiency in conjunction with the toxicity assessment of the degradation compounds.

  13. Rework of flip chip bonded radiation pixel detectors

    International Nuclear Information System (INIS)

    Vaehaenen, S.; Heikkinen, H.; Pohjonen, H.; Salonen, J.; Savolainen-Pulli, S.

    2008-01-01

    In this paper, some practical aspects of reworking flip chip hybridized pixel detectors are discussed. As flip chip technology has been advancing in terms of placement accuracy and reliability, large-area hybrid pixel detectors have been developed. The area requirements are usually fulfilled by placing several readout chips (ROCs) on single sensor chip. However, as the number of ROCs increases, the probability of failure in the hybridization process and the ROC operation also increases. Because high accuracy flip chip bonding takes time, a significant part of the price of a pixel detector comes from the flip chip assembly process itself. As large-area detector substrates are expensive, and many flip chip placements are required, the price of an assembled detector can become very high. In a typical case, there is just one bad ROC (out of several) on a faulty detector to be replaced. Considering the high price of pixel detectors and the fact that reworking faulty ROCs does not take much longer than the original placement, it is worthwhile to investigate the feasibility of a rework process

  14. Rework of flip chip bonded radiation pixel detectors

    Energy Technology Data Exchange (ETDEWEB)

    Vaehaenen, S. [VTT MEMS and Micropackaging, Espoo 02150 (Finland)], E-mail: sami.vahanen@vtt.fi; Heikkinen, H.; Pohjonen, H.; Salonen, J.; Savolainen-Pulli, S. [VTT MEMS and Micropackaging, Espoo 02150 (Finland)

    2008-06-11

    In this paper, some practical aspects of reworking flip chip hybridized pixel detectors are discussed. As flip chip technology has been advancing in terms of placement accuracy and reliability, large-area hybrid pixel detectors have been developed. The area requirements are usually fulfilled by placing several readout chips (ROCs) on single sensor chip. However, as the number of ROCs increases, the probability of failure in the hybridization process and the ROC operation also increases. Because high accuracy flip chip bonding takes time, a significant part of the price of a pixel detector comes from the flip chip assembly process itself. As large-area detector substrates are expensive, and many flip chip placements are required, the price of an assembled detector can become very high. In a typical case, there is just one bad ROC (out of several) on a faulty detector to be replaced. Considering the high price of pixel detectors and the fact that reworking faulty ROCs does not take much longer than the original placement, it is worthwhile to investigate the feasibility of a rework process.

  15. What millennial medical students say about flipped learning

    Directory of Open Access Journals (Sweden)

    Pettit RK

    2017-07-01

    Full Text Available Robin K Pettit, Lise McCoy, Marjorie Kinney School of Osteopathic Medicine in Arizona, A. T. Still University, Mesa, AZ, USA Abstract: Flipped instruction is gaining popularity in medical schools, but there are unanswered questions such as the optimum amount of the curriculum to flip and whether flipped sessions should be mandatory. We were in a unique position to evaluate feedback from first-year medical students who had experienced both flipped and lecture-based courses during their first semester of medical school. A key finding was that the students preferred a variety of different learning formats over an “all or nothing” learning format. Learning format preferences did not necessarily align with perceptions of which format led to better course exam performance. Nearly 70% of respondents wanted to make their own decisions regarding attendance. Candid responses to open-ended survey prompts reflected millennial preferences for choice, flexibility, efficiency, and the ability to control the pace of their learning, providing insight to guide ­curricular improvements. Keywords: flipped classroom, mandatory attendance, medical education, lecture-based, variety

  16. On flipping first-semester calculus: a case study

    Science.gov (United States)

    Petrillo, Joseph

    2016-05-01

    High failure rates in calculus have plagued students, teachers, and administrators for decades, while science, technology, engineering, and mathematics programmes continue to suffer from low enrollments and high attrition. In an effort to affect this reality, some educators are 'flipping' (or inverting) their classrooms. By flipping, we mean administering course content outside of the classroom and replacing the traditional in-class lectures with discussion, practice, group work, and other elements of active learning. This paper presents the major results from a three-year study of a flipped, first-semester calculus course at a small, comprehensive, American university with a well-known engineering programme. The data we have collected help quantify the positive and substantial effects of our flipped calculus course on failure rates, scores on the common final exam, student opinion of calculus, teacher impact on measurable outcomes, and success in second-semester calculus. While flipping may not be suitable for every teacher, every student, and in every situation, this report provides some evidence that it may be a viable option for those seeking an alternative to the traditional lecture model.

  17. Flipping Preservice Elementary Teachers' Mathematics Anxieties

    Science.gov (United States)

    Dove, Anthony; Dove, Emily

    2017-01-01

    In preparing future elementary educators in mathematics, helping them overcome their anxieties of mathematics and teaching mathematics is paramount. This study examined how different instructional practices (in-class lecture, flipped learning with teacher-created videos, flipped classroom with Khan Academy videos) compared in improving students'…

  18. The Flipped Classroom: A Twist on Teaching

    Science.gov (United States)

    Schmidt, Stacy M. P.; Ralph, David L.

    2016-01-01

    The traditional classroom has utilized the "I Do", "We Do", "You Do" as a strategy for teaching for years. The flipped classroom truly flips that strategy. The teacher uses "You Do", "We Do", "I Do" instead. Homework, inquiry, and investigation happen in the classroom. At home students…

  19. Errors and corrections in the separation of spin-flip and non-spin-flip thermal neutron scattering using the polarization analysis technique

    International Nuclear Information System (INIS)

    Williams, W.G.

    1975-01-01

    The use of the polarization analysis technique to separate spin-flip from non-spin-flip thermal neutron scattering is especially important in determining magnetic scattering cross-sections. In order to identify a spin-flip ratio in the scattering with a particular scattering process, it is necessary to correct the experimentally observed 'flipping-ratio' to allow for the efficiencies of the vital instrument components (polarizers and spin-flippers), as well as multiple scattering effects in the sample. Analytical expressions for these corections are presented and their magnitudes in typical cases estimated. The errors in measurement depend strongly on the uncertainties in the calibration of the efficiencies of the polarizers and the spin-flipper. The final section is devoted to a discussion of polarization analysis instruments

  20. Flipped SO(10) model

    Energy Technology Data Exchange (ETDEWEB)

    Maekawa, Nobuhiro; Yamashita, Toshifumi

    2003-08-14

    This Letter demonstrates that, as in flipped SU(5) models, doublet-triplet splitting is accomplished by a missing partner mechanism in flipped SO(10) models. The gauge group SO(10){sub F}xU(1){sub V'{sub F}} includes SU(2){sub E} gauge symmetry, which plays an important role in solving the supersymmetric (SUSY) flavor problem by introducing non-abelian horizontal gauge symmetry and anomalous U(1){sub A} gauge symmetry. The gauge group can be broken into the standard model gauge group by VEVs of only spinor fields; such models may be easier to derive than E{sub 6} models from superstring theory.

  1. Control of phospholipid flip-flop by transmembrane peptides

    International Nuclear Information System (INIS)

    Kaihara, Masanori; Nakao, Hiroyuki; Yokoyama, Hirokazu; Endo, Hitoshi; Ishihama, Yasushi; Handa, Tetsurou; Nakano, Minoru

    2013-01-01

    Highlights: ► Phospholipid flip-flop in transmembrane peptide-containing vesicles was investigated. ► Peptides that contained polar residues in the center of the transmembrane region promoted phospholipid flip-flop. ► A bioinformatics approach revealed the presence of polar residues in the transmembrane region of ER membrane proteins. ► Polar residues in ER membrane proteins possibly provide flippase-like activity. - Abstract: We designed three types of transmembrane model peptides whose sequence originates from a frequently used model peptide KALP23, and we investigated their effects on phospholipid flip-flop. Time-resolved small-angle neutron scattering and a dithionite fluorescent quenching assay demonstrated that TMP-L, which has a fully hydrophobic transmembrane region, did not enhance phospholipid flip-flop, whereas TMP-K and TMP-E, which have Lys and Glu, respectively, in the center of their transmembrane regions, enhanced phospholipid flip-flop. Introduction of polar residues in the membrane-spanning helices is considered to produce a locally polar region and enable the lipid head group to interact with the polar side-chain inside the bilayers, thereby reducing the activation energy for the flip-flop. A bioinformatics approach revealed that acidic and basic residues account for 4.5% of the central region of the transmembrane domain in human ER membrane proteins. Therefore, polar residues in ER membrane proteins are considered to provide flippase-like activity

  2. Best Practices for Launching a Flipped Classroom

    Science.gov (United States)

    Hall, Ashley A.; DuFrene, Debbie D.

    2016-01-01

    Popularity is growing for flipped classroom instruction, which replaces lectures with out-of-class delivery of streaming video, reading materials, online chats, and other modalities. Face-to-face class time is spent on instructor-student and student-student interaction, including small group problem solving and discussion. Classroom flipping has…

  3. Sildenafil (Viagra) sensitizes prostate cancer cells to doxorubicin-mediated apoptosis through CD95

    Science.gov (United States)

    Das, Anindita; Durrant, David; Mitchell, Clint; Dent, Paul; Batra, Surinder K.; Kukreja, Rakesh C.

    2016-01-01

    We previously reported that Sildenafil enhances apoptosis and antitumor efficacy of doxorubicin (DOX) while attenuating its cardiotoxic effect in prostate cancer. In the present study, we investigated the mechanism by which sildenafil sensitizes DOX in killing of prostate cancer (PCa) cells, DU145. The death receptor Fas (APO-1 or CD95) induces apoptosis in many carcinoma cells, which is negatively regulated by anti-apoptotic molecules such as FLIP (Fas-associated death domain (FADD) interleukin-1-converting enzyme (FLICE)-like inhibitory protein). Co-treatment of PCa cells with sildenafil and DOX for 48 hours showed reduced expression of both long and short forms of FLIP (FLIP-L and -S) as compared to individual drug treatment. Over-expression of FLIP-s with an adenoviral vector attentuated the enhanced cell-killing effect of DOX and sildenafil. Colony formation assays also confirmed that FLIP-S over-expression inhibited the DOX and sildenafil-induced synergistic killing effect as compared to the cells infected with an empty vector. Moreover, siRNA knock-down of CD95 abolished the effect of sildenafil in enhancing DOX lethality in cells, but had no effect on cell killing after treatment with a single agent. Sildenafil co-treatment with DOX inhibited DOX-induced NF-κB activity by reducing phosphorylation of IκB and nuclear translocation of the p65 subunit, in addition to down regulation of FAP-1 (Fas associated phosphatase-1, a known inhibitor of CD95-mediated apoptosis) expression. This data provides evidence that the CD95 is a key regulator of sildenafil and DOX mediated enhanced cell death in prostate cancer. PMID:26716643

  4. Step to improve neural cryptography against flipping attacks.

    Science.gov (United States)

    Zhou, Jiantao; Xu, Qinzhen; Pei, Wenjiang; He, Zhenya; Szu, Harold

    2004-12-01

    Synchronization of neural networks by mutual learning has been demonstrated to be possible for constructing key exchange protocol over public channel. However, the neural cryptography schemes presented so far are not the securest under regular flipping attack (RFA) and are completely insecure under majority flipping attack (MFA). We propose a scheme by splitting the mutual information and the training process to improve the security of neural cryptosystem against flipping attacks. Both analytical and simulation results show that the success probability of RFA on the proposed scheme can be decreased to the level of brute force attack (BFA) and the success probability of MFA still decays exponentially with the weights' level L. The synchronization time of the parties also remains polynomial with L. Moreover, we analyze the security under an advanced flipping attack.

  5. Flipped Classroom as an Alternative Strategy for Teaching Stoichiometry

    Directory of Open Access Journals (Sweden)

    Norrie E. Gayeta

    2017-11-01

    Full Text Available This study aimed to compare the effectiveness of flipped classroom and traditional classroom instruction in measuring conceptual change and to determine if flipped classroom instruction would be an alternative method of teaching to traditional lecture method. This study covered the level of conceptual understanding of students on stoichiometry and the type of conceptual change before and after exposure to flipped and traditional classroom environment. Qualitative and quantitative research methods were used in the study. Respondents were two sections of third year Bachelor of Secondary Education, Biological Science. Frequency, percentage, ranking, mean, standard deviation, Hake factor test, and t-test were the statistical tools applied to answer specific questions. Results showed profound increase towards conceptual change representing a shift from intuitive understanding to correct incomplete understanding level. Thus, change for the better, in theoretical type was determined from pretest to posttest of students exposed to flipped and traditional classroom. Results also indicated that there is no significant difference on students’ conceptual change on stoichiometry exposed to flipped and traditional classroom environment thus, flipped classroom instruction can be used as an alternative teaching method to traditional lecture method in teaching stoichiometry

  6. Applying the Flipped Classroom Model to English Language Arts Education

    Science.gov (United States)

    Young, Carl A., Ed.; Moran, Clarice M., Ed.

    2017-01-01

    The flipped classroom method, particularly when used with digital video, has recently attracted many supporters within the education field. Now more than ever, language arts educators can benefit tremendously from incorporating flipped classroom techniques into their curriculum. "Applying the Flipped Classroom Model to English Language Arts…

  7. Examining the Flipped Classroom through Action Research

    Science.gov (United States)

    Lo, Chung Kwan

    2017-01-01

    There is a growing interest in using a flipped classroom format in day-to-day teaching. Direct computer-based individual instruction outside the classroom and interactive group learning activities inside the classroom are the two essential components of the flipped classroom model. By watching instructional videos, students can work through some…

  8. Flipped Classroom as an Alternative Strategy for Teaching Stoichiometry

    OpenAIRE

    Norrie E. Gayeta

    2017-01-01

    This study aimed to compare the effectiveness of flipped classroom and traditional classroom instruction in measuring conceptual change and to determine if flipped classroom instruction would be an alternative method of teaching to traditional lecture method. This study covered the level of conceptual understanding of students on stoichiometry and the type of conceptual change before and after exposure to flipped and traditional classroom environment. Qualitative and quantitative ...

  9. Degradation of Trichloroethene with a Novel Ball Milled Fe–C Nanocomposite

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Jie; Wang, Wei [Environmental Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Rondinone, Adam J. [Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); He, Feng, E-mail: fenghe@zjut.edu.cn [College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310032 (China); Liang, Liyuan [Environmental Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States)

    2015-12-30

    Highlights: • Novel, inexpensive iron–carbon (Fe–C) nanocomposite was obtained by milling. • Fe–C instantaneously sorbed >90% of trichloroethene and continuously degraded them. • The carbon reduced the generation of C{sub 3}−C{sub 6} intermediates and mainly produced C{sub 2}H{sub 4}. • Fe–C can attach to the DNAPL phase thus enhancing degradation efficiency. - Abstract: Nanoscale zero-valent iron (NZVI) is effective in reductively degrading dense non-aqueous phase liquids (DNAPLs), such as trichloroethene (TCE), in groundwater (i.e., dechlorination) although the NZVI technology itself still suffers from high material costs and inability to target hydrophobic contaminants in source zones. To address these problems, we developed a novel, inexpensive iron–carbon (Fe–C) nanocomposite material by simultaneously milling micron-size iron and activated carbon powder. Microscopic and X-ray diffraction (XRD) characterization of the composite material revealed that nanoparticles of Fe were dispersed in activated carbon and a new iron carbide phase was formed. Bench-scale studies showed that this material instantaneously sorbed >90% of TCE from aqueous solutions and subsequently decomposed TCE into non-chlorinated products. Compared to milled Fe, Fe–C nanocomposite dechlorinated TCE at a slightly slower rate and favored the production of ethene over other TCE degradation products such as C{sub 3}−C{sub 6} compounds. When placed in hexane-water mixture, the Fe–C nanocomposite materials are preferentially partitioned into the organic phase, indicating the ability of the composite materials to target DNAPL during remediation.

  10. Performance and Motivation in a Middle School Flipped Learning Course

    Science.gov (United States)

    Winter, Joshua W.

    2018-01-01

    Flipped learning is a teaching approach that promotes collaboration by using technology to 'flip' traditional instruction. Content is delivered outside of class in the individual space (online) and the group space (classroom) is used to engage in collaborative activities. Flipped learning shifts the teacher's role toward facilitation. Research on…

  11. Flipped Learning fra et elevperspektiv

    DEFF Research Database (Denmark)

    Holmboe, Peter; Hachmann, Roland

    2016-01-01

    Antologi er et resultat af et toårigt udviklingsprojekt om Flipped Learning baseret på et samarbejde mellem IT-Center Fyn og Region Syddanmark. Bidraget her præsenterer en række overvejelser, vi har gjort os på baggrund af observationer af undervisning og interviews med elever i projektet. Vores...... overordnede undersøgelsesspørgsmål var: "Hvilke forhold i undervisning og læringsmiljø fremme hhv. begrænser elevens opfattelse af mening og fagligt udbytte i et Flipped Learning design?"....

  12. Does the Flipped Classroom Improve Learning in Graduate Medical Education?

    Science.gov (United States)

    Riddell, Jeff; Jhun, Paul; Fung, Cha-Chi; Comes, James; Sawtelle, Stacy; Tabatabai, Ramin; Joseph, Daniel; Shoenberger, Jan; Chen, Esther; Fee, Christopher; Swadron, Stuart P

    2017-08-01

    The flipped classroom model for didactic education has recently gained popularity in medical education; however, there is a paucity of performance data showing its effectiveness for knowledge gain in graduate medical education. We assessed whether a flipped classroom module improves knowledge gain compared with a standard lecture. We conducted a randomized crossover study in 3 emergency medicine residency programs. Participants were randomized to receive a 50-minute lecture from an expert educator on one subject and a flipped classroom module on the other. The flipped classroom included a 20-minute at-home video and 30 minutes of in-class case discussion. The 2 subjects addressed were headache and acute low back pain. A pretest, immediate posttest, and 90-day retention test were given for each subject. Of 82 eligible residents, 73 completed both modules. For the low back pain module, mean test scores were not significantly different between the lecture and flipped classroom formats. For the headache module, there were significant differences in performance for a given test date between the flipped classroom and the lecture format. However, differences between groups were less than 1 of 10 examination items, making it difficult to assign educational importance to the differences. In this crossover study comparing a single flipped classroom module with a standard lecture, we found mixed statistical results for performance measured by multiple-choice questions. As the differences were small, the flipped classroom and lecture were essentially equivalent.

  13. What millennial medical students say about flipped learning.

    Science.gov (United States)

    Pettit, Robin K; McCoy, Lise; Kinney, Marjorie

    2017-01-01

    Flipped instruction is gaining popularity in medical schools, but there are unanswered questions such as the optimum amount of the curriculum to flip and whether flipped sessions should be mandatory. We were in a unique position to evaluate feedback from first-year medical students who had experienced both flipped and lecture-based courses during their first semester of medical school. A key finding was that the students preferred a variety of different learning formats over an "all or nothing" learning format. Learning format preferences did not necessarily align with perceptions of which format led to better course exam performance. Nearly 70% of respondents wanted to make their own decisions regarding attendance. Candid responses to open-ended survey prompts reflected millennial preferences for choice, flexibility, efficiency, and the ability to control the pace of their learning, providing insight to guide curricular improvements.

  14. Flipped Physics

    Science.gov (United States)

    Kettle, Maria

    2013-01-01

    This paper defines flipped learning and then examines its practical implementation in AS and A2 level physics classes, that is, classes for 16-18 year olds. The effect of this teaching style on student learning behaviour and its impact on test results are evaluated. The paper recounts the difficulties of implementing it and evaluates student…

  15. Effects of B4C control rod degradation under severe accident

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Si-Won; Park, Sang-Gil; Han, Sang-Ku [Atomic Creative Technology Co., Daejeon (Korea, Republic of)

    2016-10-15

    Boron carbide (B4C) is widely used as absorber material in western boiling water reactor (BWR), some PWR, EPR and Russian RBMK and VVERs. B4C oxidation is one of the important phenomena of in-vessel. In the present paper, the main results and knowledge gained regarding the B4C control rod degradation from above mentioned experiments are reviewed and arranged to inform its significance on the severe accident consequences. In this paper, the role of B4C control rod oxidation and the subsequent degradation on the severe accident consequences is reviewed with available literature and report of previous experimental program regarding the B4C oxidation. From this review, it seems that the contribution of this B4C oxidation on the accident progression to the further severe accident situation is not negligible. For the future work, the extensive experimental data interpretation will be performed to assess quantitatively the effect of B4C oxidation and degradation on the various postulated severe accident conditions.

  16. The flipped classroom: practices and opportunities for health sciences librarians.

    Science.gov (United States)

    Youngkin, C Andrew

    2014-01-01

    The "flipped classroom" instructional model is being introduced into medical and health sciences curricula to provide greater efficiency in curriculum delivery and produce greater opportunity for in-depth class discussion and problem solving among participants. As educators employ the flipped classroom to invert curriculum delivery and enhance learning, health sciences librarians are also starting to explore the flipped classroom model for library instruction. This article discusses how academic and health sciences librarians are using the flipped classroom and suggests opportunities for this model to be further explored for library services.

  17. Model studies of lipid flip-flop in membranes

    DEFF Research Database (Denmark)

    Parisio, Giulia; Ferrarini, Alberta; Sperotto, Maria Maddalena

    2016-01-01

    , and growth heavily depend. Such transverse motion—commonly called flip-flop—has been studied both experimentally and computationally. Experimental investigations face difficulties related to time-scales and probe-induced membrane perturbation issues. Molecular dynamics simulations play an important role...... for the molecular-level understanding of flip-flop. In this review we present a summary of the state of the art of computational studies of spontaneous flip-flop of phospholipids, sterols and fatty acids. Also, we highlight critical issues and strategies that have been developed to solve them, and what remains...

  18. Polarizing a stored proton beam by spin flip?

    International Nuclear Information System (INIS)

    Oellers, D.; Barion, L.; Barsov, S.; Bechstedt, U.; Benati, P.; Bertelli, S.; Chiladze, D.; Ciullo, G.; Contalbrigo, M.; Dalpiaz, P.F.; Dietrich, J.; Dolfus, N.; Dymov, S.; Engels, R.; Erven, W.; Garishvili, A.; Gebel, R.; Goslawski, P.

    2009-01-01

    We discuss polarizing a proton beam in a storage ring, either by selective removal or by spin flip of the stored ions. Prompted by recent, conflicting calculations, we have carried out a measurement of the spin-flip cross section in low-energy electron-proton scattering. The experiment uses the cooling electron beam at COSY as an electron target. The measured cross sections are too small for making spin flip a viable tool in polarizing a stored beam. This invalidates a recent proposal to use co-moving polarized positrons to polarize a stored antiproton beam.

  19. Diverse Perspectives on a Flipped Biostatistics Classroom

    Science.gov (United States)

    Schwartz, Todd A.; Andridge, Rebecca R.; Sainani, Kirstin L.; Stangle, Dalene K.; Neely, Megan L.

    2016-01-01

    "Flipping" the classroom refers to a pedagogical approach in which students are first exposed to didactic content outside the classroom and then actively use class time to apply their newly attained knowledge. The idea of the flipped classroom is not new, but has grown in popularity in recent years as the necessary technology has…

  20. Characterization of hybrid integrated all-optical flip-flop

    NARCIS (Netherlands)

    Liu, Y.; McDougall, R.; Seoane, J.; Kehayas, E.; Hill, M.T.; Maxwell, G.D.; Zhang, S.; Harmon, R.; Huijskens, Frans; Rivers, L.; Van Holm-Nielsen, P.; Martinez, J.M.; Herrera Llorente, J.; Ramos, F.; Marti, J.; Avramopoulos, H.; Jeppesen, P.; Koonen, A.M.J.; Poustie, A.; Dorren, H.J.S.

    2006-01-01

    We present a fully-packaged, hybrid-integrated all-optical flip-flop with separate optical set and reset operation. The flip-flop can control a wavelength converter to route 40 Gb/s data packets all-optically. The experimental results are given

  1. Out of Classroom Instruction in the Flipped Classroom

    DEFF Research Database (Denmark)

    Triantafyllou, Evangelia; Timcenko, Olga

    2015-01-01

    This article presents experiences and student perceptions on the introduction of the flipped classroom model in two consecutive semesters at Media Technology department of Aalborg University, Copenhagen, Denmark. We introduced the flipped instruction model to a statistics course and a mathematics...

  2. Characterisation of hybrid integrated all-optical flip-flop

    DEFF Research Database (Denmark)

    Liu, Y.; McDougall, R.; Seoane, Jorge

    2006-01-01

    We present a fully-packaged, hybrid-integrated all-optical flip-flop with separate optical set and reset operation. The flip-flop can control a wavelength converter to route 40 Gb/s data packets all-optically. The experimental results are given....

  3. Enhancing student engagement using the flipped classroom.

    Science.gov (United States)

    Gilboy, Mary Beth; Heinerichs, Scott; Pazzaglia, Gina

    2015-01-01

    The flipped classroom is an innovative pedagogical approach that focuses on learner-centered instruction. The purposes of this report were to illustrate how to implement the flipped classroom and to describe students' perceptions of this approach within 2 undergraduate nutrition courses. The template provided enables faculty to design before, during, and after class activities and assessments based on objectives using all levels of Bloom's taxonomy. The majority of the 142 students completing the evaluation preferred the flipped method compared with traditional pedagogical strategies. The process described in the report was successful for both faculty and students. Copyright © 2015 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

  4. A flipped 331 model

    Energy Technology Data Exchange (ETDEWEB)

    Fonseca, Renato M.; Hirsch, Martin [AHEP Group, Instituto de Física Corpuscular, C.S.I.C./Universitat de València,Parc Científic de Paterna. Calle Catedrático José Beltrán,2 E-46980 Paterna (Valencia) (Spain)

    2016-08-01

    Models based on the extended SU(3){sub C}×SU(3){sub L}×U(1){sub X} (331) gauge group usually follow a common pattern: two families of left-handed quarks are placed in anti-triplet representations of the SU(3){sub L} group; the remaining quark family, as well as the left-handed leptons, are assigned to triplets (or vice-versa). In this work we present a flipped 331 model where this scheme is reversed: all three quark families are in the same representation and it is the lepton families which are discriminated by the gauge symmetry. We discuss fermion masses and mixing, as well as Z{sup ′} interactions, in a minimal model implementing this idea.

  5. Evaluation of a flipped classroom approach to learning introductory epidemiology.

    Science.gov (United States)

    Shiau, Stephanie; Kahn, Linda G; Platt, Jonathan; Li, Chihua; Guzman, Jason T; Kornhauser, Zachary G; Keyes, Katherine M; Martins, Silvia S

    2018-04-02

    Although the flipped classroom model has been widely adopted in medical education, reports on its use in graduate-level public health programs are limited. This study describes the design, implementation, and evaluation of a flipped classroom redesign of an introductory epidemiology course and compares it to a traditional model. One hundred fifty Masters-level students enrolled in an introductory epidemiology course with a traditional format (in-person lecture and discussion section, at-home assignment; 2015, N = 72) and a flipped classroom format (at-home lecture, in-person discussion section and assignment; 2016, N = 78). Using mixed methods, we compared student characteristics, examination scores, and end-of-course evaluations of the 2016 flipped classroom format and the 2015 traditional format. Data on the flipped classroom format, including pre- and post-course surveys, open-ended questions, self-reports of section leader teaching practices, and classroom observations, were evaluated. There were no statistically significant differences in examination scores or students' assessment of the course between 2015 (traditional) and 2016 (flipped). In 2016, 57.1% (36) of respondents to the end-of-course evaluation found watching video lectures at home to have a positive impact on their time management. Open-ended survey responses indicated a number of strengths of the flipped classroom approach, including the freedom to watch pre-recorded lectures at any time and the ability of section leaders to clarify targeted concepts. Suggestions for improvement focused on ways to increase regular interaction with lecturers. There was no significant difference in students' performance on quantitative assessments comparing the traditional format to the flipped classroom format. The flipped format did allow for greater flexibility and applied learning opportunities at home and during discussion sections.

  6. Spin-flipping a stored polarized proton beam with an rf dipole

    International Nuclear Information System (INIS)

    Blinov, B.B.; Derbenev, Ya.S.; Kageya, T.; Kantsyrev, D.Yu.; Krisch, A.D.; Morozov, V.S.; Sivers, D.W.; Wong, V.K.; Anferov, V.A.; Schwandt, P.; Przewoski, B. von

    2000-01-01

    Frequent polarization reversals, or spin-flips, of a stored polarized high-energy beam may greatly reduce systematic errors of spin asymmetry measurements in a scattering asymmetry experiment. We studied the spin-flipping of a 120 MeV horizontally-polarized proton beam stored in the IUCF Cooler Ring by ramping an rf-dipole magnet's frequency through an rf-induced depolarizing resonance in the presence of a nearly-full Siberian snake. After optimizing the frequency ramp parameters, we used multiple spin-flips to measure a spin-flip efficiency of 86.5±0.5%. The spin-flip efficiency was apparently limited by the rf-dipole's field strength. This result indicates that an efficient spin-flipping a stored polarized beam should be possible in high energy rings such as RHIC and HERA where Siberian snakes are certainly needed and only dipole rf-flipper-magnets are practical

  7. thermal degradation and estimation of dietary intakes of vitamin c

    African Journals Online (AJOL)

    IBRAHIM GARBA

    ABSTRACT. Thermal degradation of vitamin C in eight different vegetables were determined. These comprised Onion,. Tomato, Red Pepper, Spinach, Okra, Green Beans, Cauliflower, and Cabbage. Maximum degradation was observed in Tomato with 83% loss while minimum loss of 37% was in Red Pepper. An estimate ...

  8. Just in Time to Flip Your Classroom

    Science.gov (United States)

    Lasry, Nathaniel; Dugdale, Michael; Charles, Elizabeth

    2014-01-01

    With advocates like Sal Khan and Bill Gates, flipped classrooms are attracting an increasing amount of media and research attention. We had heard Khan's TED talk and were aware of the concept of inverted pedagogies in general. Yet it really hit home when we accidentally flipped our classroom. Our objective was to better prepare our students…

  9. Study and practice of flipped classroom in optoelectronic technology curriculum

    Science.gov (United States)

    Shi, Jianhua; Lei, Bing; Liu, Wei; Yao, Tianfu; Jiang, Wenjie

    2017-08-01

    "Flipped Classroom" is one of the most popular teaching models, and has been applied in more and more curriculums. It is totally different from the traditional teaching model. In the "Flipped Classroom" model, the students should watch the teaching video afterschool, and in the classroom only the discussion is proceeded to improve the students' comprehension. In this presentation, "Flipped Classroom" was studied and practiced in opto-electronic technology curriculum; its effect was analyzed by comparing it with the traditional teaching model. Based on extensive and deep investigation, the phylogeny, the characters and the important processes of "Flipped Classroom" are studied. The differences between the "Flipped Classroom" and the traditional teaching model are demonstrated. Then "Flipped Classroom" was practiced in opto-electronic technology curriculum. In order to obtain high effectiveness, a lot of teaching resources were prepared, such as the high-quality teaching video, the animations and the virtual experiments, the questions that the students should finish before and discussed in the class, etc. At last, the teaching effect was evaluated through analyzing the result of the examination and the students' surveys.

  10. Assessment of learning gains in a flipped biochemistry classroom.

    Science.gov (United States)

    Ojennus, Deanna Dahlke

    2016-01-01

    The flipped classroom has become an increasingly popular pedagogical approach to teaching and learning. In this study, learning gains were assessed in a flipped biochemistry course and compared to gains in a traditional lecture. Although measured learning gains were not significantly different between the two courses, student perception of learning gains did differ and indicates a higher level of satisfaction with the flipped lecture format. © 2015 The International Union of Biochemistry and Molecular Biology.

  11. The C-terminal amino acid of the MHC-I heavy chain is critical for binding to Derlin-1 in human cytomegalovirus US11-induced MHC-I degradation.

    Science.gov (United States)

    Cho, Sunglim; Kim, Bo Young; Ahn, Kwangseog; Jun, Youngsoo

    2013-01-01

    Derlin-1 plays a critical role in endoplasmic reticulum-associated protein degradation (ERAD) of a particular subset of proteins. Although it is generally accepted that Derlin-1 mediates the export of ERAD substrates from the ER to the cytosol, little is known about how Derlin-1 interacts with these substrates. Human cytomegalovirus (HCMV) US11 exploits Derlin-1-dependent ERAD to degrade major histocompatibility complex class I (MHC-I) molecules and evade immune surveillance. US11 requires the cytosolic tail of the MHC-I heavy chain to divert MHC-I molecules into the ERAD pathway for degradation; however, the underlying mechanisms remain unknown. Here, we show that the cytosolic tail of the MHC-I heavy chain, although not required for interaction with US11, is required for tight binding to Derlin-1 and thus for US11-induced dislocation of the MHC-I heavy chain to the cytosol for proteasomal degradation. Surprisingly, deletion of a single C-terminal amino acid from the cytosolic tail disrupted the interaction between MHC-I molecules and Derlin-1, rendering mutant MHC-I molecules resistant to US11-induced degradation. Consistently, deleting the C-terminal cytosolic region of Derlin-1 prevented it from binding to MHC-I molecules. Taken together, these results suggest that the cytosolic region of Derlin-1 is involved in ERAD substrate binding and that this interaction is critical for the Derlin-1-mediated dislocation of the MHC-I heavy chain to the cytosol during US11-induced MHC-I degradation.

  12. HD domain of SAMHD1 influences Vpx-induced degradation at a post-interaction step

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Jian; Hou, Jingwei; Zhao, Ke; Yu, Xiao-Fang; Du, Juan, E-mail: jdu@jlu.edu.cn

    2016-02-12

    Primate SAMHD1 proteins are potent inhibitors of viruses, including retroviruses such as HIV-1, HIV-2, and SIV. Vpx, a distinctive viral protein expressed by HIV-2 and some SIVs, induces SAMHD1 degradation by forming a Vpx-DCAF1-based ubiquitin ligase complex. Either the N- or the C-terminus of SAMHD1 is critical for Vpx-induced degradation, depending on the types of SAMHD1 and Vpx proteins. However, it was not fully understood whether other regions of SAMHD1 also contribute to its depletion by Vpx. In the present study, we report that SAMHD1 from chicken (SAMHD1{sub GG}) was not degraded by SIVmac Vpx, in contrast with results for human SAMHD1 (SAMHD1{sub HS}). Results regarding to SAMHD1{sub HS} and SAMHD1{sub GG} fusion proteins supported previous findings that the C-terminus of SAMHD1{sub HS} is essential for Vpx-induced degradation. Internal domain substitution, however, revealed that the HD domain also contributes to Vpx-mediated SAMHD1 degradation. Interestingly, the HD domain influenced Vpx-mediated SAMHD1 degradation without affecting Vpx-SAMHD1 interaction. Therefore, our findings revealed that factors in addition to Vpx-SAMHD1 binding influence the efficiency of Vpx-mediated SAMHD1 degradation. - Highlights: • SAMHD1{sub GG} from chicken could not be depleted by SIVmac Vpx. • The C-terminus of human SAMHD1{sub HS} is critical for its degradation by Vpx. • The HD domain is essential for Vpx-induced degradation of SAMHD1{sub HS}. • Altering the HD domain does not affect Vpx-SAMHD1 interaction.

  13. Glucose Deprivation Triggers Protein Kinase C-dependent β-Catenin Proteasomal Degradation*

    Science.gov (United States)

    Choi, Seung-Won; Song, Jun-Kyu; Yim, Ye-Seal; Yun, Ho-Geun; Chun, Kyung-Hee

    2015-01-01

    Autophagy is a conserved process that contributes to cell homeostasis. It is well known that induction mainly occurs in response to nutrient starvation, such as starvation of amino acids and insulin, and its mechanisms have been extensively characterized. However, the mechanisms behind cellular glucose deprivation-induced autophagy are as of now poorly understood. In the present study, we determined a mechanism by which glucose deprivation induced the PKC-dependent proteasomal degradation of β-catenin, leading to autophagy. Glucose deprivation was shown to cause a sub-G1 transition and enhancement of the LC3-II protein levels, whereas β-catenin protein underwent degradation in a proteasome-dependent manner. Moreover, the inhibition of GSK3β was unable to abolish the glucose deprivation-mediated β-catenin degradation or up-regulation of LC3-II protein levels, which suggested GSK3β-independent protein degradation. Intriguingly, the inhibition of PKCα using a pharmacological inhibitor and transfection of siRNA for PKCα was observed to effectively block glucose deprivation-induced β-catenin degradation as well as the increase in LC3-II levels and the accumulation of a sub-G1 population. Together, our results demonstrated a molecular mechanism by which glucose deprivation can induce the GSK3β-independent protein degradation of β-catenin, leading to autophagy. PMID:25691573

  14. Specific cell components of Bacteroides gingivalis mediate binding and degradation of human fibrinogen

    Energy Technology Data Exchange (ETDEWEB)

    Lantz, M.S.; Allen, R.D.; Vail, T.A.; Switalski, L.M.; Hook, M. (Univ. of Alabama at Birmingham (USA))

    1991-01-01

    Bacteroides (Porphyromonas) gingivalis, which has been implicated as an etiologic agent in human periodontal diseases, has been shown to bind and degrade human fibrinogen. B. gingivalis strains bind fibrinogen reversibly and with high affinity and bind to a specific region of the fibrinogen molecule that appears to be located between the D and E domains. The authors now report that human fibrinogen is bound and then degraded by specific B. gingivalis components that appear to be localized at the cell surface. Fibrinogen binding to bacterial cells occurred at 4, 22, and 37{degree}C. A functional fibrinogen-binding component (M{sub r}, 150 000) was identified when sodium dodecyl sulfate-solubilized bacteria were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose membranes, and probed with {sup 125}I-fibrinogen. Fibrinogen degradation did not occur at 4{degree}C but did occur at 22 and 37{degree}C. When bacteria and iodinated fibrinogen were incubated at 37{degree}C, two major fibrinogen fragments (M{sub r}, 97 000 and 50 000) accumulated in incubation mixture supernatant fractions. Two major fibrinogen-degrading components (M{sub r}, 120 000 and 150 000) have been identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in substrate-containing gels. Fibrinogen degradation by the M{sub r}-120 000 and -150 000 proteases was enhanced by reducing agents, completely inhibited by N-{alpha}-p-tosyl-L-lysyl chloromethyl ketone, and partially inhibited by n-ethyl maleimide, suggesting that these enzymes are thiol-dependent proteases with trypsinlike substrate specificity. The fibrinogen-binding component could be separated from the fibrinogen-degrading components by selective solubilization of bacteria in sodium deoxycholate.

  15. Specific cell components of Bacteroides gingivalis mediate binding and degradation of human fibrinogen

    International Nuclear Information System (INIS)

    Lantz, M.S.; Allen, R.D.; Vail, T.A.; Switalski, L.M.; Hook, M.

    1991-01-01

    Bacteroides (Porphyromonas) gingivalis, which has been implicated as an etiologic agent in human periodontal diseases, has been shown to bind and degrade human fibrinogen. B. gingivalis strains bind fibrinogen reversibly and with high affinity and bind to a specific region of the fibrinogen molecule that appears to be located between the D and E domains. The authors now report that human fibrinogen is bound and then degraded by specific B. gingivalis components that appear to be localized at the cell surface. Fibrinogen binding to bacterial cells occurred at 4, 22, and 37 degree C. A functional fibrinogen-binding component (M r , 150 000) was identified when sodium dodecyl sulfate-solubilized bacteria were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose membranes, and probed with 125 I-fibrinogen. Fibrinogen degradation did not occur at 4 degree C but did occur at 22 and 37 degree C. When bacteria and iodinated fibrinogen were incubated at 37 degree C, two major fibrinogen fragments (M r , 97 000 and 50 000) accumulated in incubation mixture supernatant fractions. Two major fibrinogen-degrading components (M r , 120 000 and 150 000) have been identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in substrate-containing gels. Fibrinogen degradation by the M r -120 000 and -150 000 proteases was enhanced by reducing agents, completely inhibited by N-α-p-tosyl-L-lysyl chloromethyl ketone, and partially inhibited by n-ethyl maleimide, suggesting that these enzymes are thiol-dependent proteases with trypsinlike substrate specificity. The fibrinogen-binding component could be separated from the fibrinogen-degrading components by selective solubilization of bacteria in sodium deoxycholate

  16. What millennial medical students say about flipped learning

    Science.gov (United States)

    Pettit, Robin K; McCoy, Lise; Kinney, Marjorie

    2017-01-01

    Flipped instruction is gaining popularity in medical schools, but there are unanswered questions such as the optimum amount of the curriculum to flip and whether flipped sessions should be mandatory. We were in a unique position to evaluate feedback from first-year medical students who had experienced both flipped and lecture-based courses during their first semester of medical school. A key finding was that the students preferred a variety of different learning formats over an “all or nothing” learning format. Learning format preferences did not necessarily align with perceptions of which format led to better course exam performance. Nearly 70% of respondents wanted to make their own decisions regarding attendance. Candid responses to open-ended survey prompts reflected millennial preferences for choice, flexibility, efficiency, and the ability to control the pace of their learning, providing insight to guide curricular improvements. PMID:28769600

  17. Switched Flip-Flop based Preprocessing Circuit for ISFETs

    Directory of Open Access Journals (Sweden)

    Martin Kollár

    2005-03-01

    Full Text Available In this paper, a preprocessing circuit for ISFETs (Ion-sensitive field-effecttransistors to measure hydrogen-ion concentration in electrolyte is presented. A modifiedflip-flop is the main part of the circuit. The modification consists in replacing the standardtransistors by ISFETs and periodically switching the supply voltage on and off.Concentration of hydrogen ions to be measured discontinues the flip-flop value symmetry,which means that by switching the supply voltage on the flip-flop goes to one of two stablestates, ‘one’ or ‘zero’. The recovery of the value symmetry can be achieved by changing abalanced voltage, which is incorporated to the flip-flop, to bring the flip-flop to a 50%position (probability of ‘one’ equals to probability of ‘zero’. Thus, the balanced voltagereflects the measured concentration of hydrogen ions. Its magnitude is set automatically byusing a feedback circuit whose input is connected to the flip-flop output. The preprocessingcircuit, as the whole, is the well-known δ modulator in which the switched flip-flop servesas a comparator and a sampling circuit. The advantages of this approach in comparison tothose of standard approaches are discussed. Finally, theoretical results are verified bysimulations with TSPICE and a good agreement is reported.

  18. FLIP-MHD: A particle-in-cell mehtod for magnetohydrodynamics

    International Nuclear Information System (INIS)

    Brackbill, J.U.

    1990-01-01

    A particle-in-cell (PIC) method, FLIP is extended to magnetohydrodynamic (MHD) flow in two dimensions. Particles are used to reduce computational diffusion of the magnetic field. FLIP is an extension of ''classical'' PIC, where particles have mass, but every other property of the fluid is stored on a grid. In FLIP, particles have every property of the fluid, so that they provide a complete Lagrangian description not only to resolve contact discontinuities but also to reduce computational diffusion of linear and angular momentum. The interactions among the particles are calculated on a grid, for convenience and economy. The present study extends FLIP to MHD, by including information about the magnetic field among the attributes of the particles. 6 refs

  19. Dominant spin-flip effects for the hadronic-produced J/ψ polarization at the Tevatron

    International Nuclear Information System (INIS)

    Wu Xinggang; Fang Zhenyun

    2009-01-01

    Dominant spin-flip effects for the direct and prompt J/ψ polarizations at Tevatron run II with collision energy 1.96 TeV and rapidity cut |y J/ψ | 8 [ 3 S 1 ] into J/ψ is especially discussed with care. It is found that the spin-flip effect shall always dilute the J/ψ polarization, and with a suitable choice of the parameters a 0,1 and c 0,1,2 , the J/ψ polarization puzzle can be solved to a certain degree. At large transverse momentum p t , α for the prompt J/ψ is reduced by ∼50% for f 0 =v 2 and by ∼80% for f 0 =1. We also study the indirect J/ψ polarization from the b decays, which however is slightly affected by the same spin-flip effect and then shall provide a better platform to determine the color-octet matrix elements.

  20. Intracellular collagen degradation mediated by uPARAP/Endo180 is a major pathway of extracellular matrix turnover during malignancy

    DEFF Research Database (Denmark)

    Curino, Alejandro C; Engelholm, Lars H; Yamada, Susan S

    2005-01-01

    We recently reported that uPARAP/Endo180 can mediate the cellular uptake and lysosomal degradation of collagen by cultured fibroblasts. Here, we show that uPARAP/Endo180 has a key role in the degradation of collagen during mammary carcinoma progression. In the normal murine mammary gland, uPARAP/...

  1. Results of a Flipped Classroom Teaching Approach in Anesthesiology Residents.

    Science.gov (United States)

    Martinelli, Susan M; Chen, Fei; DiLorenzo, Amy N; Mayer, David C; Fairbanks, Stacy; Moran, Kenneth; Ku, Cindy; Mitchell, John D; Bowe, Edwin A; Royal, Kenneth D; Hendrickse, Adrian; VanDyke, Kenneth; Trawicki, Michael C; Rankin, Demicha; Guldan, George J; Hand, Will; Gallagher, Christopher; Jacob, Zvi; Zvara, David A; McEvoy, Matthew D; Schell, Randall M

    2017-08-01

    In a flipped classroom approach, learners view educational content prior to class and engage in active learning during didactic sessions. We hypothesized that a flipped classroom improves knowledge acquisition and retention for residents compared to traditional lecture, and that residents prefer this approach. We completed 2 iterations of a study in 2014 and 2015. Institutions were assigned to either flipped classroom or traditional lecture for 4 weekly sessions. The flipped classroom consisted of reviewing a 15-minute video, followed by 45-minute in-class interactive sessions with audience response questions, think-pair-share questions, and case discussions. The traditional lecture approach consisted of a 55-minute lecture given by faculty with 5 minutes for questions. Residents completed 3 knowledge tests (pretest, posttest, and 4-month retention) and surveys of their perceptions of the didactic sessions. A linear mixed model was used to compare the effect of both formats on knowledge acquisition and retention. Of 182 eligible postgraduate year 2 anesthesiology residents, 155 (85%) participated in the entire intervention, and 142 (78%) completed all tests. The flipped classroom approach improved knowledge retention after 4 months (adjusted mean = 6%; P  = .014; d  = 0.56), and residents preferred the flipped classroom (pre = 46%; post = 82%; P  flipped classroom approach to didactic education resulted in a small improvement in knowledge retention and was preferred by anesthesiology residents.

  2. Vitamin C. Biosynthesis, recycling and degradation in mammals.

    Science.gov (United States)

    Linster, Carole L; Van Schaftingen, Emile

    2007-01-01

    Vitamin C, a reducing agent and antioxidant, is a cofactor in reactions catalyzed by Cu(+)-dependent monooxygenases and Fe(2+)-dependent dioxygenases. It is synthesized, in vertebrates having this capacity, from d-glucuronate. The latter is formed through direct hydrolysis of uridine diphosphate (UDP)-glucuronate by enzyme(s) bound to the endoplasmic reticulum membrane, sharing many properties with, and most likely identical to, UDP-glucuronosyltransferases. Non-glucuronidable xenobiotics (aminopyrine, metyrapone, chloretone and others) stimulate the enzymatic hydrolysis of UDP-glucuronate, accounting for their effect to increase vitamin C formation in vivo. Glucuronate is converted to l-gulonate by aldehyde reductase, an enzyme of the aldo-keto reductase superfamily. l-Gulonate is converted to l-gulonolactone by a lactonase identified as SMP30 or regucalcin, whose absence in mice leads to vitamin C deficiency. The last step in the pathway of vitamin C synthesis is the oxidation of l-gulonolactone to l-ascorbic acid by l-gulonolactone oxidase, an enzyme associated with the endoplasmic reticulum membrane and deficient in man, guinea pig and other species due to mutations in its gene. Another fate of glucuronate is its conversion to d-xylulose in a five-step pathway, the pentose pathway, involving identified oxidoreductases and an unknown decarboxylase. Semidehydroascorbate, a major oxidation product of vitamin C, is reconverted to ascorbate in the cytosol by cytochrome b(5) reductase and thioredoxin reductase in reactions involving NADH and NADPH, respectively. Transmembrane electron transfer systems using ascorbate or NADH as electron donors serve to reduce semidehydroascorbate present in neuroendocrine secretory vesicles and in the extracellular medium. Dehydroascorbate, the fully oxidized form of vitamin C, is reduced spontaneously by glutathione, as well as enzymatically in reactions using glutathione or NADPH. The degradation of vitamin C in mammals is

  3. Flipped classroom model for learning evidence-based medicine

    Directory of Open Access Journals (Sweden)

    Rucker SY

    2017-08-01

    Full Text Available Sydney Y Rucker,1 Zulfukar Ozdogan,1 Morhaf Al Achkar2 1School of Education, Indiana University, Bloomington, IN, 2Department of Family Medicine, School of Medicine, University of Washington, Seattle, WA, USA Abstract: Journal club (JC, as a pedagogical strategy, has long been used in graduate medical education (GME. As evidence-based medicine (EBM becomes a mainstay in GME, traditional models of JC present a number of insufficiencies and call for novel models of instruction. A flipped classroom model appears to be an ideal strategy to meet the demands to connect evidence to practice while creating engaged, culturally competent, and technologically literate physicians. In this article, we describe a novel model of flipped classroom in JC. We present the flow of learning activities during the online and face-to-face instruction, and then we highlight specific considerations for implementing a flipped classroom model. We show that implementing a flipped classroom model to teach EBM in a residency program not only is possible but also may constitute improved learning opportunity for residents. Follow-up work is needed to evaluate the effectiveness of this model on both learning and clinical practice. Keywords: evidence-based medicine, flipped classroom, residency education

  4. Multi spin-flip dynamics: a solution of the one-dimensional Ising model

    International Nuclear Information System (INIS)

    Novak, I.

    1990-01-01

    The Glauber dynamics of interacting Ising spins (the single spin-flip dynamics) is generalized to p spin-flip dynamics with a simultaneous flip of up to p spins in a single configuration move. The p spin-flip dynamics is studied of the one-dimensional Ising model with uniform nearest-neighbour interaction. For this case, an exact relation is given for the time dependence of magnetization. It was found that the critical slowing down in this model could be avoided when p spin-flip dynamics with p>2 was considered. (author). 17 refs

  5. FliO Regulation of FliP in the Formation of the Salmonella enterica Flagellum

    Science.gov (United States)

    Barker, Clive S.; Meshcheryakova, Irina V.; Kostyukova, Alla S.; Samatey, Fadel A.

    2010-01-01

    The type III secretion system of the Salmonella flagellum consists of 6 integral membrane proteins: FlhA, FlhB, FliO, FliP, FliQ, and FliR. However, in some other type III secretion systems, a homologue of FliO is apparently absent, suggesting it has a specialized role. Deleting the fliO gene from the chromosome of a motile strain of Salmonella resulted in a drastic decrease of motility. Incubation of the ΔfliO mutant strain in motility agar, gave rise to pseudorevertants containing extragenic bypass mutations in FliP at positions R143H or F190L. Using membrane topology prediction programs, and alkaline phosphatase or GFPuv chimeric protein fusions into the FliO protein, we demonstrated that FliO is bitopic with its N-terminus in the periplasm and C-terminus in the cytoplasm. Truncation analysis of FliO demonstrated that overexpression of FliO43–125 or FliO1–95 was able to rescue motility of the ΔfliO mutant. Further, residue leucine 91 in the cytoplasmic domain was identified to be important for function. Based on secondary structure prediction, the cytoplasmic domain, FliO43–125, should contain beta-structure and alpha-helices. FliO43–125-Ala was purified and studied using circular dichroism spectroscopy; however, this domain was disordered, and its structure was a mixture of beta-sheet and random coil. Coexpression of full-length FliO with FliP increased expression levels of FliP, but coexpression with the cytoplasmic domain of FliO did not enhance FliP expression levels. Overexpression of the cytoplasmic domain of FliO further rescued motility of strains deleted for the fliO gene expressing bypass mutations in FliP. These results suggest FliO maintains FliP stability through transmembrane domain interaction. The results also demonstrate that the cytoplasmic domain of FliO has functionality, and it presumably becomes structured while interacting with its binding partners. PMID:20941389

  6. FliO regulation of FliP in the formation of the Salmonella enterica flagellum.

    Directory of Open Access Journals (Sweden)

    Clive S Barker

    2010-09-01

    Full Text Available The type III secretion system of the Salmonella flagellum consists of 6 integral membrane proteins: FlhA, FlhB, FliO, FliP, FliQ, and FliR. However, in some other type III secretion systems, a homologue of FliO is apparently absent, suggesting it has a specialized role. Deleting the fliO gene from the chromosome of a motile strain of Salmonella resulted in a drastic decrease of motility. Incubation of the ΔfliO mutant strain in motility agar, gave rise to pseudorevertants containing extragenic bypass mutations in FliP at positions R143H or F190L. Using membrane topology prediction programs, and alkaline phosphatase or GFPuv chimeric protein fusions into the FliO protein, we demonstrated that FliO is bitopic with its N-terminus in the periplasm and C-terminus in the cytoplasm. Truncation analysis of FliO demonstrated that overexpression of FliO₄₃-₁₂₅ or FliO₁-₉₅ was able to rescue motility of the ΔfliO mutant. Further, residue leucine 91 in the cytoplasmic domain was identified to be important for function. Based on secondary structure prediction, the cytoplasmic domain, FliO₄₃-₁₂₅, should contain beta-structure and alpha-helices. FliO₄₃-₁₂₅-Ala was purified and studied using circular dichroism spectroscopy; however, this domain was disordered, and its structure was a mixture of beta-sheet and random coil. Coexpression of full-length FliO with FliP increased expression levels of FliP, but coexpression with the cytoplasmic domain of FliO did not enhance FliP expression levels. Overexpression of the cytoplasmic domain of FliO further rescued motility of strains deleted for the fliO gene expressing bypass mutations in FliP. These results suggest FliO maintains FliP stability through transmembrane domain interaction. The results also demonstrate that the cytoplasmic domain of FliO has functionality, and it presumably becomes structured while interacting with its binding partners.

  7. On Flipping First-Semester Calculus: A Case Study

    Science.gov (United States)

    Petrillo, Joseph

    2016-01-01

    High failure rates in calculus have plagued students, teachers, and administrators for decades, while science, technology, engineering, and mathematics programmes continue to suffer from low enrollments and high attrition. In an effort to affect this reality, some educators are "flipping" (or inverting) their classrooms. By flipping, we…

  8. Evaluating the Flipped Classroom: A Randomized Controlled Trial

    Science.gov (United States)

    Wozny, Nathan; Balser, Cary; Ives, Drew

    2018-01-01

    Despite recent interest in flipped classrooms, rigorous research evaluating their effectiveness is sparse. In this study, the authors implement a randomized controlled trial to evaluate the effect of a flipped classroom technique relative to a traditional lecture in an introductory undergraduate econometrics course. Random assignment enables the…

  9. Flipped classroom model for learning evidence-based medicine.

    Science.gov (United States)

    Rucker, Sydney Y; Ozdogan, Zulfukar; Al Achkar, Morhaf

    2017-01-01

    Journal club (JC), as a pedagogical strategy, has long been used in graduate medical education (GME). As evidence-based medicine (EBM) becomes a mainstay in GME, traditional models of JC present a number of insufficiencies and call for novel models of instruction. A flipped classroom model appears to be an ideal strategy to meet the demands to connect evidence to practice while creating engaged, culturally competent, and technologically literate physicians. In this article, we describe a novel model of flipped classroom in JC. We present the flow of learning activities during the online and face-to-face instruction, and then we highlight specific considerations for implementing a flipped classroom model. We show that implementing a flipped classroom model to teach EBM in a residency program not only is possible but also may constitute improved learning opportunity for residents. Follow-up work is needed to evaluate the effectiveness of this model on both learning and clinical practice.

  10. Flipped classrooms and student learning: not just surface gains.

    Science.gov (United States)

    McLean, Sarah; Attardi, Stefanie M; Faden, Lisa; Goldszmidt, Mark

    2016-03-01

    The flipped classroom is a relatively new approach to undergraduate teaching in science. This approach repurposes class time to focus on application and discussion; the acquisition of basic concepts and principles is done on the students' own time before class. While current flipped classroom research has focused on student preferences and comparative learning outcomes, there remains a lack of understanding regarding its impact on students' approaches to learning. Focusing on a new flipped classroom-based course for basic medical sciences students, the purpose of the present study was to evaluate students' adjustments to the flipped classroom, their time on task compared with traditional lectures, and their deep and active learning strategies. Students in this course worked through interactive online learning modules before in-class sessions. Class time focused on knowledge application of online learning module content through active learning methods. Students completed surveys and optional prequiz questions throughout the term to provide data regarding their learning approaches. Our results showed that the majority of students completed their prework in one sitting just before class. Students reported performing less multitasking behavior in the flipped classroom compared with lecture-based courses. Students valued opportunities for peer-peer and peer-instructor interactions and also valued having multiple modes of assessment. Overall, this work suggests that there is the potential for greater educational gains from the flipped classroom than the modest improvements in grades previously demonstrated in the literature; in this implementation of the flipped classroom, students reported that they developed independent learning strategies, spent more time on task, and engaged in deep and active learning. Copyright © 2016 The American Physiological Society.

  11. The Implementation of A Flipped Classroom in Foreign Language Teaching

    Directory of Open Access Journals (Sweden)

    Ahmet BASAL

    2015-10-01

    Full Text Available Alongside the rise of educational technology, many teachers have been taking gradual but innovative steps to redesign their teaching methods. For example, in flipped learning or a flipped classroom, students watch instructional videos outside the classroom and do assignments or engage in activities inside the classroom. Language teachers are one group of educators exploring the flipped classroom. In foreign language classes, such an approach may offer great benefits for both the teachers and students since classroom time can be applied to more interactive tasks. By extending classroom hours in this way, language teachers can focus on successfully addressing all subjects in the curriculum. The aim of this study is (a to gain insights into the perceptions of prospective English language teachers at a state university in Turkey on flipped classrooms and (b to introduce the implementation of a flipped classroom into an English language class. A total of 47 prospective English teachers participated in the study. Qualitative research design was used and data were collected via an open-ended question. Findings of the study indicated that pre-service English teachers had positive perceptions towards the use of the flipped classroom as an integral part of face-to-face courses. It can be concluded that flipped classroom was beneficial in terms of 4 categories based on the content analysis of the responses: learning at one’s own pace, advance student preparation, overcoming the limitations of class time, increasing the participation in the classroom. The study also provides recommendations towards LMS integration into courses in other English language teaching departments and for implementing flipped classrooms in language teaching.

  12. Restricted active space spin-flip configuration interaction: theory and examples for multiple spin flips with odd numbers of electrons.

    Science.gov (United States)

    Zimmerman, Paul M; Bell, Franziska; Goldey, Matthew; Bell, Alexis T; Head-Gordon, Martin

    2012-10-28

    The restricted active space spin flip (RAS-SF) method is extended to allow ground and excited states of molecular radicals to be described at low cost (for small numbers of spin flips). RAS-SF allows for any number of spin flips and a flexible active space while maintaining pure spin eigenfunctions for all states by maintaining a spin complete set of determinants and using spin-restricted orbitals. The implementation supports both even and odd numbers of electrons, while use of resolution of the identity integrals and a shared memory parallel implementation allow for fast computation. Examples of multiple-bond dissociation, excited states in triradicals, spin conversions in organic multi-radicals, and mixed-valence metal coordination complexes demonstrate the broad usefulness of RAS-SF.

  13. Quenching of spin-flip quadrupole transitions

    International Nuclear Information System (INIS)

    Castel, B.; Blunden, P.; Okuhara, Y.

    1985-01-01

    An increasing amount of experimental data indicates that spin-flip quadrupole transitions exhibit quenching effects similar to those reported earlier in (p,n) reactions involving l = 0 and l = 1 transitions. We present here two model calculations suggesting that the E2 spin-flip transitions are more affected than their M1 and M3 counterparts by the tensor and spin-orbit components of the nuclear force and should exhibit the largest quenching. We also review the experimental evidence corroborating our observations

  14. Blended Course with Flipped Classroom Approach

    DEFF Research Database (Denmark)

    Timcenko, Olga; Purwins, Hendrik; Triantafyllou, Evangelia

    2015-01-01

    This paper presents and analyses design decisions and development process of producing teaching materials for a blended course with flipped classroom approach at bachelor level at Aalborg University in Copenhagen, Denmark. Our experiences, as well as students’ reactions and opinions will be descr......This paper presents and analyses design decisions and development process of producing teaching materials for a blended course with flipped classroom approach at bachelor level at Aalborg University in Copenhagen, Denmark. Our experiences, as well as students’ reactions and opinions...

  15. Application of electronic speckle-pattern interferometry to measure in-plane thermal displacement in flip-chip packages

    International Nuclear Information System (INIS)

    Lee, Baik-Woo; Jang, Woosoon; Kim, Dong-Won; Jeong, Jeung-hyun; Nah, Jae-Woong; Paik, Kyung-Wook; Kwon, Dongil

    2004-01-01

    Electronic speckle-pattern interferometry (ESPI) was applied for noncontact, real-time evaluation of thermal deformation in a flip-chip package. The spatial resolution of ESPI was increased to submicron scale by magnifying the areas studied in order to measure the deformation of such small-scale components as the solder in the flip-chip package. Thermal deformation in the horizontal and vertical directions around the solder joints was measured as two-dimensional mappings during heating from 25 to 125 deg. C. ESPI was successful in obtaining information on the complicated deformation field around the solder joints. Furthermore, the shear strain could also be calculated using the measured thermal deformation around each solder joint. The applicability of ESPI to flip-chip packages was verified by comparing the ESPI results with those of finite-element analysis (FEA)

  16. Spin flipping a stored polarized proton beam at the IUCF cooler ring

    International Nuclear Information System (INIS)

    Phelps, R.A.

    1995-01-01

    We recently studied the spin flip of a vertically polarized 139 MeV proton beam stored in the IUCF Cooler Ring. We used an rf solenoid to induce a depolarizing resonance in the ring; we flipped the spin by varying the solenoid field's frequency through this resonance. We found a polarization loss after multiple spin flips less than 0.1% per flip; we also found that this loss increased for very slow frequency changes. This spin flip could reduce systematic errors in stored polarization beam experiments by allowing frequent beam polarization reversals during the experiment. copyright 1995 American Institute of Physics

  17. Hyperfine interaction mediated electric-dipole spin resonance: the role of frequency modulation

    International Nuclear Information System (INIS)

    Li, Rui

    2016-01-01

    The electron spin in a semiconductor quantum dot can be coherently controlled by an external electric field, an effect called electric-dipole spin resonance (EDSR). Several mechanisms can give rise to the EDSR effect, among which there is a hyperfine mechanism, where the spin-electric coupling is mediated by the electron–nucleus hyperfine interaction. Here, we investigate the influence of frequency modulation (FM) on the spin-flip efficiency. Our results reveal that FM plays an important role in the hyperfine mechanism. Without FM, the electric field almost cannot flip the electron spin; the spin-flip probability is only about 20%. While under FM, the spin-flip probability can be improved to approximately 70%. In particular, we find that the modulation amplitude has a lower bound, which is related to the width of the fluctuated hyperfine field. (paper)

  18. Nonlinear stability of spin-flip excitations

    International Nuclear Information System (INIS)

    Arunasalam, V.

    1975-01-01

    A rather complete discussion of the nonlinear electrodynamic behavior of a negative-temperature spin system is presented. The method presented here is based on a coupled set of master equations, one describing the time evolution of the photon (i.e., the spin-flip excitation) distribution function and the other describing the time evolution of the particle distribution function. It is found that the initially unstable (i.e., growing) spin-flip excitations grow to such a large amplitude that their nonlinear reaction on the particle distribution function becomes important. It is then shown that the initially totally inverted two-level spin system evolves rapidly (through this nonlinear photon-particle coupling) towards a quasilinear steady state where the populations of the spin-up and the spin-down states are equal to each other. Explicit expressions for the time taken to reach this quasilinear steady state and the energy in the spin-flip excitations at this state are also presented

  19. Element nodes of sports equipment double back flip factions and double back flip hunched performed gymnast in floor exercise

    Directory of Open Access Journals (Sweden)

    V.A. Potop

    2014-07-01

    Full Text Available Purpose: to identify the node elements of sports equipment double back somersault tuck and double back flip bent. To compare the two types of nodes for double somersault. Material : the study involved eight gymnasts (age 12 - 14 years. All finalists in the competition floor exercise - reserve team Romania. The method of video - computer research and method of postural orientation movements. Results : identified nodal elements of sports equipment double back somersault tuck and double back flip bent. In the preparatory phase of motor actions - launcher body posture for reaching is repulsive to flip. In the phase of basic motor action - animation body postures (double back somersault tuck and bent (bent double back flip. Exercises are performed on the ascending and descending parts of the flight path of the demonstration of individual maximum lift height common center of mass. In the final phase of motor actions - final body posture - steady landing. Conclusions : indicators of key elements of sports equipment acrobatic exercises contain new scientific facts kinematic and dynamic structures of motor actions. They are necessary for the development of modern training programs acrobatic exercises in step specialized base preparation.

  20. Research, Perspectives, and Recommendations on Implementing the Flipped Classroom.

    Science.gov (United States)

    Rotellar, Cristina; Cain, Jeff

    2016-03-25

    Flipped or inverted classrooms have become increasingly popular, and sometimes controversial, within higher education. Many educators have touted the potential benefits of this model and initial research regarding implementation has been primarily positive. The rationale behind the flipped classroom methodology is to increase student engagement with content, increase and improve faculty contact time with students, and enhance learning. This paper presents a summary of primary literature regarding flipped classrooms, discusses concerns and unanswered questions from both a student and faculty member perspective, and offers recommendations regarding implementation.

  1. The flipped classroom for professional development: part I. Benefits and strategies.

    Science.gov (United States)

    McDonald, Katie; Smith, Charlene M

    2013-10-01

    Individualizing the educational encounter is supported by flipping the classroom experience. This column offers an overview and describes the benefits of flipping the classroom. Part II will explore the practicalities and pedagogy of lecture capture using podcasts and videos, a technology strategy used in flipping the classroom. Copyright 2013, SLACK Incorporated.

  2. Flipped Instruction with English Language Learners at a Newcomer High School

    Science.gov (United States)

    Graziano, Kevin J.; Hall, John D.

    2017-01-01

    Research on flipped instruction with English Language Learners (ELLs) is sparse. Data-driven flipped research conducted with ELLs primarily involves adult learners attending a college or university. This study examined the academic performance of secondary ELLs who received flipped instruction in an algebra course at a newcomer school compared to…

  3. Carbon isotope effects associated with Fenton-like degradation of toluene: Potential for differentiation of abiotic and biotic degradation

    International Nuclear Information System (INIS)

    Ahad, Jason M.E.; Slater, Greg F.

    2008-01-01

    Hydrogen peroxide (H 2 O 2 )-mediated oxygenation to enhance subsurface aerobic biodegradation is a frequently employed remediation technique. However, it may be unclear whether observed organic contaminant mass loss is caused by biodegradation or chemical oxidation via hydroxyl radicals generated during catalyzed Fenton-like reactions. Compound-specific carbon isotope analysis has the potential to discriminate between these processes. Here we report laboratory experiments demonstrating no significant carbon isotope fractionation during Fenton-like hydroxyl radical oxidation of toluene. This implies that observation of significant isotopic fractionation of toluene at a site undergoing H 2 O 2 -mediated remediation would provide direct evidence of biodegradation. We applied this approach at a field site that had undergone 27 months of H 2 O 2 -mediated subsurface oxygenation. Despite substantial decreases (> 68%) in groundwater toluene concentrations carbon isotope signatures of toluene (δ 13 C tol ) showed no significant variation (mean = - 27.5 ±0.3 per mille, n = 13) over a range of concentrations from 11.1 to 669.0 mg L -1 . Given that aerobic degradation by ring attack has also been shown to result in no significant isotopic fractionation during degradation, at this site we were unable to discern the mechanism of degradation. However, such differentiation is possible at sites where aerobic degradation by methyl group attack results in significant isotopic fractionation

  4. Re-Envisioning the Archaic Higher Education Learning Environment: Implementation Processes for Flipped Classrooms

    Science.gov (United States)

    Rabidoux, Salena; Rottmann, Amy

    2018-01-01

    Flipped classrooms are often utilized in PK-12 classrooms; however, there is also a growing trend of flipped classrooms in higher education. This paper presents the benefits and limitations of implementing flipped classrooms in higher education as well as resources for integrating a flipped classroom design to instruction. The various technology…

  5. Flipping the Calculus Classroom: A Cost-Effective Approach

    Science.gov (United States)

    Young, Andrea

    2015-01-01

    This article discusses a cost-effective approach to flipping the calculus classroom. In particular, the emphasis is on low-cost choices, both monetarily and with regards to faculty time, that make the daunting task of flipping a course manageable for a single instructor. Student feedback and overall impressions are also presented.

  6. Intersecting Branes Flip SU(5)

    CERN Document Server

    Ellis, Jonathan Richard; Nanopoulos, Dimitri V; Ellis, John

    2002-01-01

    Within a toroidal orbifold framework, we exhibit intersecting brane-world constructions of flipped SU(5) \\times U(1) GUT models with various numbers of generations, other chiral matter representations and Higgs representations. We exhibit orientifold constructions with integer winding numbers that yield 8 or more conventional SU(5) generations, and orbifold constructions with fractional winding numbers that yield flipped SU(5) \\times U(1) models with just 3 conventional generations. Some of these models have candidates for the 5 and {\\bar 5} Higgs representations needed for electroweak symmetry breaking, but not for the 10 and {\\bar 10} representations needed for GUT symmetry breaking, or vice-versa.

  7. Implementeringen af flipped learning i fysik/kemi undervisningen i grundskolen

    DEFF Research Database (Denmark)

    Nissen, Stine Karen; Levinsen, Henrik

    2017-01-01

    This paper presents the preliminary findings and methodological framework from a study on the implementation of Flipped Learning in science classrooms in the Danish elementary school system. As a mixed methods case study consisting of observations and interviews, three science classrooms have bee...... for changes in classroom practices as expected. However, the experience of Flipped Learning by students and teachers offers a different and more optimistic set of narratives.......This paper presents the preliminary findings and methodological framework from a study on the implementation of Flipped Learning in science classrooms in the Danish elementary school system. As a mixed methods case study consisting of observations and interviews, three science classrooms have been...... and cultural contexts, the empirical contributions are few. The purpose of this study is to gain insight into the experiences and practice of teachers and students when engaging in Flipped Learning. The preliminary findings suggest that the implementation of Flipped Learning does not necessarily make way...

  8. Flipped Classrooms for Advanced Science Courses

    Science.gov (United States)

    Tomory, Annette; Watson, Sunnie Lee

    2015-12-01

    This article explains how issues regarding dual credit and Advanced Placement high school science courses could be mitigated via a flipped classroom instructional model. The need for advanced high school courses will be examined initially, followed by an analysis of advanced science courses and the reform they are experiencing. Finally, it will conclude with an explanation of flipped classes as well as how they may be a solution to the reform challenges teachers are experiencing as they seek to incorporate more inquiry-based activities.

  9. Scutellarein antagonizes the tumorigenesis by modulating cytokine VEGF mediated neoangiogenesis and DFF-40 actuated nucleosomal degradation

    International Nuclear Information System (INIS)

    Thirusangu, Prabhu; Vigneshwaran, V.; Vijay Avin, B.R.; Rakesh, H.; Vikas, H.M.; Prabhakar, B.T.

    2017-01-01

    Neoplastic cells often reside in distinctive tumor hypoxia armed with a series of adaptive responses including oxidative stress, defective apoptotic machinery and neoangiogenesis, through that further confer cell survival improvement. Plants still acts as reservoir of natural chemicals to provide newer active pharmacophores. Scutellarein is flavones which has wide range of pharmacophoral effects. In our current research, scutellarein employed for targeting oxidative stress mediated tumor angiogenesis and apoptotic nuclear fragmentation. Experimental results revealed that scutellarein has antiproliferative index against multiple cancer cell lines and diminished the oxidative stress and tumor development of murine ascitic lymphoma & inflammatory hepatocellular carcinoma. Eventual consequences lead to reduced neovessel formation by abrogating angiogeneic factors cytokine-VEGF-A, Flt-1, HIF-1α, MMP-2 and MMP-9 and reversing of evading apoptosis by activating caspase-3 activated DNA fragmentation factor (DFF-40) mediated nucleosomal degradation. In summary, our experimental evidences suggest that scutellarein has strong potentiality to attenuate the tumor development by modulating sprouting neovasculature and DFF-40 mediated apoptosis. - Highlights: • Scutellarein exhibits potent neoplastic effect against ascitic and DEN-induced liver carcinoma in-vivo. • Scutellarein reticence the oxidative stress and angiogenesis on tumor and non-tumor models. • Scutellarein modulates tumor vasculature by altering tumor angiogenic factor’s expressions. • Scutellarein actuates the DFF-40 mediated nucleosomal degradation in DLA tumor.

  10. Scaffolded Semi-Flipped General Chemistry Designed to Support Rural Students' Learning

    Science.gov (United States)

    Lenczewski, Mary S.

    2016-01-01

    Students who lack academic maturity can sometimes feel overwhelmed in a fully flipped classroom. Here an alternative, the Semi-Flipped method, is discussed. Rural students, who face unique challenges in transitioning from high school learning to college-level learning, can particularly profit from the use of the Semi-Flipped method in the General…

  11. Identifying Professional Competencies of the Flip-Chip Packaging Engineer in Taiwan

    Science.gov (United States)

    Guu, Y. H.; Lin, Kuen-Yi; Lee, Lung-Sheng

    2014-01-01

    This study employed a literature review, expert interviews, and a questionnaire survey to construct a set of two-tier competencies for a flip-chip packaging engineer. The fuzzy Delphi questionnaire was sent to 12 flip-chip engineering experts to identify professional competencies that a flip-chip packaging engineer must have. Four competencies,…

  12. Partially Flipped Linear Algebra: A Team-Based Approach

    Science.gov (United States)

    Carney, Debra; Ormes, Nicholas; Swanson, Rebecca

    2015-01-01

    In this article we describe a partially flipped Introductory Linear Algebra course developed by three faculty members at two different universities. We give motivation for our partially flipped design and describe our implementation in detail. Two main features of our course design are team-developed preview videos and related in-class activities.…

  13. Flipped @ SBU: Student Satisfaction and the College Classroom

    Science.gov (United States)

    Gross, Benjamin; Marinari, Maddalena; Hoffman, Mike; DeSimone, Kimberly; Burke, Peggy

    2015-01-01

    In this paper, the authors find empirical support for the effectiveness of the flipped classroom model. Using a quasi-experimental method, the authors compared students enrolled in flipped courses to their counterparts in more traditional lecture-based ones. A survey instrument was constructed to study how these two different groups of students…

  14. Spin Flipping in the Presence of a Full Siberian Snake

    International Nuclear Information System (INIS)

    Blinov, B.B.; Anferov, V.A.; Derbenev, Y.S.; Kageya, T.; Krisch, A.D.; Lorenzon, W.; Ratner, L.G.; Sivers, D.W.; Sourkont, K.V.; Wong, V.K.; Chu, C.M.; Lee, S.Y.; Rinckel, T.; Schwandt, P.; Sperisen, F.; Przewoski, B. von; Sato, H.

    1998-01-01

    We have demonstrated for the first time spin flipping of a polarized proton beam stored in a ring containing a nearly 100% Siberian snake; we did this using a 'snake' depolarizing resonance induced by an rf solenoid magnet. By varying the rf solenoid close-quote s ramp time, frequency range, and voltage, we reached a spin-flip efficiency of about 91% . This spin-flip efficiency was probably reduced because the horizontal stable spin direction was not perpendicular to the longitudinal field of the rf solenoid, and was possibly reduced by nearby synchrotron sideband resonances. The planned use of a vertical rf dipole may improve the spin-flip efficiency. copyright 1998 The American Physical Society

  15. PENGARUH FLIPPED MASTERY CLASSROM TERHADAP PEROLEHAN HASIL BELAJAR KOGNITIF MAHASISWA

    Directory of Open Access Journals (Sweden)

    Muhammad Ridha

    2016-04-01

    Tujuan dari penelitian ini adalah untuk mengetahui pengaruh penerapan strategi flipped mastery classroom terhadap perolehan hasil belajar kognitif mahasiswa pada matakuliah psikologi pendidikan. Subjek dalam penelitian ini adalah mahasiswa Jurusan Teknologi Pendidikan Universitas Negeri Malang semester genap tahun ajaran 2015/2016 pada kelas utuh. Kelas eksperimen dibelajarkan dengan strategi flipped-mastery classroom dan kelas kontrol dibelajarkan dengan strategi tradisional.  Penelitian ini menggunakan rancangan kuasi eksperimen Non Equivalent Control Group Design. Hasil penelitian menunjukkan bahwa penerapan strategi flipped mastery classroom memberikan pengaruh positif terhadap perolehan hasil belajar kognitif mahasiswa. Perolehan hasil belajar kognitif mahasiswa yang dibelajarkan dengan strategi flipped-mastery lebih tinggi secara signifikan dari pada perolehan hasil belajar mahasiswa yang dibelajarkan dengan strategi tradisional.

  16. Integral Optimization of Systematic Parameters of Flip-Flow Screens

    Institute of Scientific and Technical Information of China (English)

    翟宏新

    2004-01-01

    The synthetic index Ks for evaluating flip-flow screens is proposed and systematically optimized in view of the whole system. A series of optimized values of relevant parameters are found and then compared with those of the current industrial specifications. The results show that the optimized value Ks approaches the one of those famous flip-flow screens in the world. Some new findings on geometric and kinematics parameters are useful for improving the flip-flow screens with a low Ks value, which is helpful in developing clean coal technology.

  17. Geldanamycin-induced degradation of Chk1 is mediated by proteasome

    International Nuclear Information System (INIS)

    Nomura, M.; Nomura, N.; Yamashita, J.

    2005-01-01

    Checkpoint kinase 1 (Chk1) is a cell cycle regulator and a heat shock protein 90 (Hsp90) client. It is essential for cell proliferation and survival. In this report, we analyzed the mechanisms of Chk1 regulation in U87MG glioblastoma cells using Geldanamycin (GA), which interferes with the function of Hsp90. GA reduced Chk1 protein level but not its mRNA level in glioblastoma cells. Co-treatment with GA and cycloheximide (CHX), a protein synthesis inhibitor, induced a decrease of half-life of the Chk1 protein to 3 h and resulted in Chk1 down-regulation. CHX alone induced only 32% reduction of Chk1 protein even after 24 h. These findings indicated that reduction of Chk1 by GA was due to destabilization and degradation of the protein. In addition, GA-induced down-regulation of Chk1 was reversed by MG132, a specific proteasome inhibitor. And it was revealed that Chk1 was ubiquitinated by GA. These results have indicated that degradation of Chk1 by GA was mediated by the ubiquitin-proteasome pathway in U87MG glioblastoma cells

  18. Using the Flipped Classroom to Enhance EFL Learning

    Science.gov (United States)

    Chen Hsieh, Jun Scott; Wu, Wen-Chi Vivian; Marek, Michael W.

    2017-01-01

    Instruction in English is a priority around the globe, but instructional methodologies have not always kept pace with the changing needs of students. To explore the benefits of the flipped classroom model for learners of English as a Foreign Language, the researchers used flipped learning and Wen's Output-driven/Input-enabled model to design a…

  19. Flipped Learning in TESOL: Definitions, Approaches, and Implementation

    Science.gov (United States)

    Bauer-Ramazani, Christine; Graney, John M.; Marshall, Helaine W.; Sabieh, Christine

    2016-01-01

    As the use of flipped learning spreads throughout educational disciplines, TESOL educators need to consider its potential for our field. This article, based on a computer-aided language learning (CALL) interest session at TESOL 2015, first looks at how best to describe and define flipped learning and examines the factors needed to make it…

  20. Flipping a College Calculus Course: A Case Study

    Science.gov (United States)

    Sahin, Alpaslan; Cavlazoglu, Baki; Zeytuncu, Yunus E.

    2015-01-01

    As online videos have become more easily available and more attractive to the new generation of students, and as new student-learning approaches tend to have more technology integration, the flipped classroom model has become very popular. The purpose of this study was to understand college students' views on flipped courses and investigate how…

  1. Flipped Instruction in a High School Science Classroom

    Science.gov (United States)

    Leo, Jonathan; Puzio, Kelly

    2016-01-01

    This paper reports on a quasi-experimental study examining the effectiveness of flipped instruction in a 9th grade biology classroom. This study included four sections of freshmen-level biology taught by the first author at a private secondary school in the Pacific Northwest. Using a block randomized design, two sections were flipped and two…

  2. The Implementation of A Flipped Classroom in Foreign Language Teaching

    OpenAIRE

    Ahmet BASAL

    2015-01-01

    Alongside the rise of educational technology, many teachers have been taking gradual but innovative steps to redesign their teaching methods. For example, in flipped learning or a flipped classroom, students watch instructional videos outside the classroom and do assignments or engage in activities inside the classroom. Language teachers are one group of educators exploring the flipped classroom. In foreign language classes, such an approach may offer great benefits for both the teachers and ...

  3. Flipped Instruction in a High School Science Classroom

    Science.gov (United States)

    Leo, Jonathan; Puzio, Kelly

    2016-10-01

    This paper reports on a quasi-experimental study examining the effectiveness of flipped instruction in a 9th grade biology classroom. This study included four sections of freshmen-level biology taught by the first author at a private secondary school in the Pacific Northwest. Using a block randomized design, two sections were flipped and two remained traditional. The quiz and posttest data were adjusted for pretest differences using ANCOVA. The results suggest that flipped instruction had a positive effect student achievement, with effect sizes ranging from +0.16 to +0.44. In addition, some students reported that they preferred watching video lectures outside of class and appreciated more active approaches to learning.

  4. Strange attractors in a chaotic coin flip simulation

    International Nuclear Information System (INIS)

    Cooper, Crystal

    2006-01-01

    Presented is a computer simulation used to model a variation of the game known as the gambler's ruin. A rich player gambles with a set amount of money m. The poor player starts out with zero capital, and is allowed to flip a coin in order to try to win the money. If the coin is heads, the poor player wins a dollar but if it is tails, the player loses a dollar. The poor player is always allowed to win the first flip, and is allowed to flip n times, even when the amount of money lost reaches zero. The dynamics of this process is chaotic due to fluctuations in the variance of the amount of money

  5. Flipped Library Instruction Does Not Lead to Learning Gains for First-Year English Students

    Directory of Open Access Journals (Sweden)

    Kimberly Miller

    2017-09-01

    Full Text Available A Review of: Rivera, E. (2017. Flipping the classroom in freshman English library instruction: A comparison study of a flipped class versus a traditional lecture method. New Review of Academic Librarianship, 23(1, 18-27. http://dx.doi.org/10.1080/13614533.2016.1244770 Abstract Objective – To determine whether a flipped classroom approach to freshman English information literacy instruction improves student learning outcomes. Design – Quasi-experimental. Setting – Private suburban university with 7,000 graduate and undergraduate students. Subjects – First-year English students. Methods – Students in six sections of first-year “English 2” received library instruction; three sections received flipped library instruction and three sections received traditional library instruction. Students in the flipped classroom sections were assigned two videos to watch before class, as an introduction to searching the Library’s catalog and key academic databases. These students were also expected to complete pre-class exercises that allowed them to practice what they learned through the videos. The face-to-face classes involved a review of the flipped materials alongside additional activities. Works cited pages from the students’ final papers were collected from all six sections, 31 from the flipped sections and 34 from the non-flipped sections. A rubric was used to rate the works cited pages. The rubric was based on the Association of College and Research Libraries’ Information Literacy Competency Standards for Higher Education (ACRL, 2000, Standard Two, Outcome 3a, and included three criteria: “authority,” “timeliness,” and “variety.” Each criterion was rated at one of three levels: “exemplary,” “competent,” or “developing.” Main Results – Works cited pages from the students who received non-flipped instruction were more likely to score “exemplary” for at least one of the three criteria when compared to works

  6. DDB1-Mediated CRY1 Degradation Promotes FOXO1-Driven Gluconeogenesis in Liver.

    Science.gov (United States)

    Tong, Xin; Zhang, Deqiang; Charney, Nicholas; Jin, Ethan; VanDommelen, Kyle; Stamper, Kenneth; Gupta, Neil; Saldate, Johnny; Yin, Lei

    2017-10-01

    Targeted protein degradation through ubiquitination is an important step in the regulation of glucose metabolism. Here, we present evidence that the DDB1-CUL4A ubiquitin E3 ligase functions as a novel metabolic regulator that promotes FOXO1-driven hepatic gluconeogenesis. In vivo, hepatocyte-specific Ddb1 deletion leads to impaired hepatic gluconeogenesis in the mouse liver but protects mice from high-fat diet-induced hyperglycemia. Lack of Ddb1 downregulates FOXO1 protein expression and impairs FOXO1-driven gluconeogenic response. Mechanistically, we discovered that DDB1 enhances FOXO1 protein stability via degrading the circadian protein cryptochrome 1 (CRY1), a known target of DDB1 E3 ligase. In the Cry1 depletion condition, insulin fails to reduce the nuclear FOXO1 abundance and suppress gluconeogenic gene expression. Chronic depletion of Cry1 in the mouse liver not only increases FOXO1 protein but also enhances hepatic gluconeogenesis. Thus, we have identified the DDB1-mediated CRY1 degradation as an important target of insulin action on glucose homeostasis. © 2017 by the American Diabetes Association.

  7. Degradation of Alzheimer's amyloid fibrils by microglia requires delivery of ClC-7 to lysosomes

    Science.gov (United States)

    Majumdar, Amitabha; Capetillo-Zarate, Estibaliz; Cruz, Dana; Gouras, Gunnar K.; Maxfield, Frederick R.

    2011-01-01

    Incomplete lysosomal acidification in microglia inhibits the degradation of fibrillar forms of Alzheimer's amyloid β peptide (fAβ). Here we show that in primary microglia a chloride transporter, ClC-7, is not delivered efficiently to lysosomes, causing incomplete lysosomal acidification. ClC-7 protein is synthesized by microglia but it is mistargeted and appears to be degraded by an endoplasmic reticulum–associated degradation pathway. Activation of microglia with macrophage colony-stimulating factor induces trafficking of ClC-7 to lysosomes, leading to lysosomal acidification and increased fAβ degradation. ClC-7 associates with another protein, Ostm1, which plays an important role in its correct lysosomal targeting. Expression of both ClC-7 and Ostm1 is increased in activated microglia, which can account for the increased delivery of ClC-7 to lysosomes. Our findings suggest a novel mechanism of lysosomal pH regulation in activated microglia that is required for fAβ degradation. PMID:21441306

  8. Flips for 3-folds and 4-folds

    CERN Document Server

    Corti, Alessio

    2007-01-01

    This edited collection of chapters, authored by leading experts, provides a complete and essentially self-contained construction of 3-fold and 4-fold klt flips. A large part of the text is a digest of Shokurov's work in the field and a concise, complete and pedagogical proof of the existence of 3-fold flips is presented. The text includes a ten page glossary and is accessible to students and researchers in algebraic geometry.

  9. EFFECTIVENESS OF FLIPPED CLASSROOM IN MATHEMATICS TEACHING

    OpenAIRE

    Dr. N. Ramakrishnan; Mrs. J. Johnsi Priya

    2016-01-01

    Flipped Classroom is an instructional strategy and a type of blended learning that reverses the traditional learning environment by delivering instructional content, often online, outside of the classroom. It moves activities, including those that may have traditionally been considered homework, into the classroom. In a flipped classroom, students watch online lectures, collaborate in online discussions, or carry out research at home and engage in concepts in the classroom with the guidance o...

  10. Particulate matter air pollution disrupts endothelial cell barrier via calpain-mediated tight junction protein degradation

    Directory of Open Access Journals (Sweden)

    Wang Ting

    2012-08-01

    Full Text Available Abstract Background Exposure to particulate matter (PM is a significant risk factor for increased cardiopulmonary morbidity and mortality. The mechanism of PM-mediated pathophysiology remains unknown. However, PM is proinflammatory to the endothelium and increases vascular permeability in vitro and in vivo via ROS generation. Objectives We explored the role of tight junction proteins as targets for PM-induced loss of lung endothelial cell (EC barrier integrity and enhanced cardiopulmonary dysfunction. Methods Changes in human lung EC monolayer permeability were assessed by Transendothelial Electrical Resistance (TER in response to PM challenge (collected from Ft. McHenry Tunnel, Baltimore, MD, particle size >0.1 μm. Biochemical assessment of ROS generation and Ca2+ mobilization were also measured. Results PM exposure induced tight junction protein Zona occludens-1 (ZO-1 relocation from the cell periphery, which was accompanied by significant reductions in ZO-1 protein levels but not in adherens junction proteins (VE-cadherin and β-catenin. N-acetyl-cysteine (NAC, 5 mM reduced PM-induced ROS generation in ECs, which further prevented TER decreases and atteneuated ZO-1 degradation. PM also mediated intracellular calcium mobilization via the transient receptor potential cation channel M2 (TRPM2, in a ROS-dependent manner with subsequent activation of the Ca2+-dependent protease calpain. PM-activated calpain is responsible for ZO-1 degradation and EC barrier disruption. Overexpression of ZO-1 attenuated PM-induced endothelial barrier disruption and vascular hyperpermeability in vivo and in vitro. Conclusions These results demonstrate that PM induces marked increases in vascular permeability via ROS-mediated calcium leakage via activated TRPM2, and via ZO-1 degradation by activated calpain. These findings support a novel mechanism for PM-induced lung damage and adverse cardiovascular outcomes.

  11. Can land degradation drive differences in the C exchange of two similar semiarid ecosystems?

    Science.gov (United States)

    López-Ballesteros, Ana; Oyonarte, Cecilio; Kowalski, Andrew S.; Serrano-Ortiz, Penélope; Sánchez-Cañete, Enrique P.; Rosario Moya, M.; Domingo, Francisco

    2018-01-01

    Currently, drylands occupy more than one-third of the global terrestrial surface and are recognized as areas vulnerable to land degradation. The concept of land degradation stems from the loss of an ecosystem's biological productivity due to long-term loss of natural vegetation or depletion of soil nutrients. Drylands' key role in the global carbon (C) balance has been recently demonstrated, but the effects of land degradation on C sequestration by these ecosystems still need to be investigated. In the present study, we compared net C and water vapor fluxes, together with satellite, meteorological and vadose zone (CO2, water content and temperature) measurements, between two nearby (˜ 23 km) experimental sites representing natural (i.e., site of reference) and degraded grazed semiarid grasslands. We utilized data acquired over 6 years from two eddy covariance stations located in southeastern Spain with highly variable precipitation magnitude and distribution. Results show a striking difference in the annual C balances with an average net CO2 exchange of 196 ± 40 (C release) and -23 ± 2 g C m-2 yr-1 (C fixation) for the degraded and natural sites, respectively. At the seasonal scale, differing patterns in net CO2 fluxes were detected over both growing and dry seasons. As expected, during the growing seasons, greater net C uptake over longer periods was observed at the natural site. However, a much greater net C release, probably derived from subterranean ventilation, was measured at the degraded site during drought periods. After subtracting the nonbiological CO2 flux from net CO2 exchange, flux partitioning results point out that, during the 6 years of study, gross primary production, ecosystem respiration and water use efficiency were, on average, 9, 2 and 10 times higher, respectively, at the natural site versus the degraded site. We also tested differences in all monitored meteorological and soil variables and CO2 at 1.50 m belowground was the variable

  12. The Flipped Classroom Teaching Model and Its Use for Information Literacy Instruction

    Directory of Open Access Journals (Sweden)

    Sara Arnold-Garza

    2014-07-01

    Full Text Available The “flipped classroom” teaching model has emerged in a variety of educational settings. It provides many advantages for students and exploits the affordances of modern technology. This article describes some of the pedagogical and logistical characteristics of the flipped teaching model. It situates the flipped classroom in higher education and library instruction, and make the case that there are characteristics of information literacy instruction that fit well with the flipped teaching model, in addition to providing some unique challenges.

  13. Application of 13C-stable isotope probing to identify RDX-degrading microorganisms in groundwater

    International Nuclear Information System (INIS)

    Cho, Kun-Ching; Lee, Do Gyun; Roh, HyungKeun; Fuller, Mark E.; Hatzinger, Paul B.; Chu, Kung-Hui

    2013-01-01

    We employed stable isotope probing (SIP) with 13 C-labeled hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) to identify active microorganisms responsible for RDX biodegradation in groundwater microcosms. Sixteen different 16S rRNA gene sequences were derived from microcosms receiving 13 C-labeled RDX, suggesting the presence of microorganisms able to incorporate carbon from RDX or its breakdown products. The clones, residing in Bacteroidia, Clostridia, α-, β- and δ-Proteobacteria, and Spirochaetes, were different from previously described RDX degraders. A parallel set of microcosms was amended with cheese whey and RDX to evaluate the influence of this co-substrate on the RDX-degrading microbial community. Cheese whey stimulated RDX biotransformation, altered the types of RDX-degrading bacteria, and decreased microbial community diversity. Results of this study suggest that RDX-degrading microorganisms in groundwater are more phylogenetically diverse than what has been inferred from studies with RDX-degrading isolates. Highlights: •SIP identified sixteen groundwater bacteria capable of using RDX and/or its metabolites as a carbon source. •The RDX degraders in groundwater are phylogenetically diverse and different from known RDX degraders. •Cheese whey induced community shift and altered diversity of the RDX-degrading microorganisms over time. -- RDX-degrading bacteria in contaminated groundwater, identified by SIP with 13 C-labeled RDX, are phylogenetically diverse and different from known RDX degraders

  14. Best voltage bias-flipping strategy towards maximum piezoelectric power generation

    International Nuclear Information System (INIS)

    Liang, Junrui; Chung, Henry Shu-Hung

    2013-01-01

    In piezoelectric energy harvesting (PEH) systems, energy extracted from piezoelectric structure can be increased by making piezoelectric voltage in phase with vibration velocity and raising the voltage amplitude. Such voltage manipulations can be realized by synchronously flipping the piezoelectric voltage with respect to a bias dc source at every displacement extremum. Given that net harvested energy is obtained by deducting dissipated energy from total extracted energy, a sophisticated voltage bias-flipping scheme, which can maximize extracted energy at low dissipative cost, is required towards harvested energy optimization. This paper extends the state of the art by proposing the best bias-flip strategy, which is delivered on conceptual synchronized multiple bias-flip (SMBF) interface circuits. The proposed strategy coordinates both requirements on larger voltage change in synchronized instant for more extracted energy and smaller voltage change in each bias-flip action for less dissipated energy. It not only leads to further enhancement of harvesting capability beyond existing solutions, but also provides an unprecedented physical insight on maximum achievable harvesting capability of PEH interface circuit

  15. Diphoton resonance in F-theory inspired flipped SO(10)

    Energy Technology Data Exchange (ETDEWEB)

    Leontaris, George K. [Ioannina University, Physics Department, Theory Division, Ioannina (Greece); Shafi, Qaisar [University of Delaware, Department of Physics and Astronomy, Bartol Research Institute, Newark, DE (United States)

    2016-10-15

    Motivated by the di-photon excess at 750 GeV reported by the ATLAS and CMS experiments, we present an F-theory inspired flipped SO(10) model embedded in E{sub 6}. The low energy spectrum includes the three MSSM chiral families, vector-like colour triplets, several pairs of charged SU(2){sub L} singlet fields (E{sup c}, anti E{sup c}), as well as MSSM singlets, one or more of which could contribute to the di-photon resonance. A total decay width in the multi-GeV range can arise from couplings involving the singlet and MSSM fields. (orig.)

  16. Hierarchical 3C-SiC nanowires as stable photocatalyst for organic dye degradation under visible light irradiation

    International Nuclear Information System (INIS)

    Zhang, Judong; Chen, Jianjun; Xin, Lipeng; Wang, Mingming

    2014-01-01

    Graphical abstract: The photocatalytic performance was enhanced by hierarchical nanostructural SiC nanowires due to the increased specific surface areas and efficient incident light scattering. The positive effect of SiO 2 layer growth on the surface of nanowires during the catalytic process on the high decolorization efficiency of SiC nanowires was attributed to SiO 2 surface oxygen vacancies. -- Highlights: • High decolorization rate of methylene blue using hierarchical 3C-SiC nanowires was obtained. • The effect of methylene blue with different concentration to catalytic result was investigated. • The photocatalytic reaction mechanism of degrading methylene blue was explained. • The SiO 2 layer generating on nanowire surface in the catalytic process was analyzed. -- Abstract: 3C-SiC nanowires with hierarchical structure were synthesized by sol–gel carbothermal reduction method. The photocatalytic property of SiC nanowires was investigated. 3C-SiC hierarchical nanowires exhibited an enhanced photocatalytic activity by accelerating the photocatalytic degradation of methylene blue solution under visible light irradiation. Methylene blue was degraded efficiently after 5 h irradiation over the photocatalyst. The photocatalytic activity was affected by the initial concentration of the methylene blue solution. Silicon dioxide layer was observed on the surface of nanowires after the catalytic process. The positive effect of SiO 2 surface oxygen vacancies and 3C-SiC hierarchical nanostructures on the high decolorization efficiency of SiC nanowires was discussed. The detailed photocatalytic redox processes were also explained

  17. Calpain activation by ROS mediates human ether-a-go-go-related gene protein degradation by intermittent hypoxia.

    Science.gov (United States)

    Wang, N; Kang, H S; Ahmmed, G; Khan, S A; Makarenko, V V; Prabhakar, N R; Nanduri, J

    2016-03-01

    Human ether-a-go-go-related gene (hERG) channels conduct delayed rectifier K(+) current. However, little information is available on physiological situations affecting hERG channel protein and function. In the present study we examined the effects of intermittent hypoxia (IH), which is a hallmark manifestation of sleep apnea, on hERG channel protein and function. Experiments were performed on SH-SY5Y neuroblastoma cells, which express hERG protein. Cells were exposed to IH consisting of alternating cycles of 30 s of hypoxia (1.5% O2) and 5 min of 20% O2. IH decreased hERG protein expression in a stimulus-dependent manner. A similar reduction in hERG protein was also seen in adrenal medullary chromaffin cells from IH-exposed neonatal rats. The decreased hERG protein was associated with attenuated hERG K(+) current. IH-evoked hERG protein degradation was not due to reduced transcription or increased proteosome/lysomal degradation. Rather it was mediated by calcium-activated calpain proteases. Both COOH- and NH2-terminal sequences of the hERG protein were the targets of calpain-dependent degradation. IH increased reactive oxygen species (ROS) levels, intracellular Ca(2+) concentration ([Ca(2+)]i), calpain enzyme activity, and hERG protein degradation, and all these effects were prevented by manganese-(111)-tetrakis-(1-methyl-4-pyridyl)-porphyrin pentachloride, a membrane-permeable ROS scavenger. These results demonstrate that activation of calpains by ROS-dependent elevation of [Ca(2+)]i mediates hERG protein degradation by IH. Copyright © 2016 the American Physiological Society.

  18. Characteristics of magnetic resonance imaging with partial flip angle and gradient field echo

    International Nuclear Information System (INIS)

    Hamada, Tatsumi; Uto, Tatsurou; Okafuji, Tatsumasa; Ookusa, Akihiko; Oonishi, Takuya; Mabuchi, Nobuhisa; Fujii, Kouichi; Yoshioka, Hiroyasu; Ishida, Osamu

    1988-01-01

    Characteristics of a magnetic resonance (MR) imaging pulse sequence with short repetition time (Tr), short echo time (Te), partial flip angle and gradient field echo, at 0.5 T, were studied. A series of sagittal images of the cerebrospinal region was obtained with varied Tr, Te and flip angle, signal intensities were measured by means of a region of interest (ROI) function, and optimal parameters to achieve maximum tissue contrast were found. Of the parameters flip angle had the greatest effect on tissue contrast. Flip angles less than 20 or more than 60 degrees were necessary to discriminate between spinal cord and cerebrospinal fluid. So called MR myelography was obtained with the flip angle of 15 degrees. Opposed and inphase images were obtained at the Te levels of 21 and 28 ms, respectively. Likewise, a series of transverse images of the abdomen with short Tr, short Te and varied flip angles was obtained in a breath-holding interval, and signal intensities of ROIs were measured. Maximum intensities of the liver, the spleen and perirenal fat were obtained at the flip angles of 40, 30 and 60 degrees, respectively. Although maximum intensity was found at the flip angle of 30 degrees for both of the renal cortex and medulla, the maximum contrast between the two tissues was obtained at the flip angles of 50-60 degrees. The image contrast obtained by these pulse sequences was also theoretically predictable, and so it is thought possible that flip angle, Tr and Te are manipulated to yield a desired contrast. (author)

  19. Thermal cycling reliability of Cu/SnAg double-bump flip chip assemblies for 100 μm pitch applications

    Science.gov (United States)

    Son, Ho-Young; Kim, Ilho; Lee, Soon-Bok; Jung, Gi-Jo; Park, Byung-Jin; Paik, Kyung-Wook

    2009-01-01

    A thick Cu column based double-bump flip chip structure is one of the promising alternatives for fine pitch flip chip applications. In this study, the thermal cycling (T/C) reliability of Cu/SnAg double-bump flip chip assemblies was investigated, and the failure mechanism was analyzed through the correlation of T/C test and the finite element analysis (FEA) results. After 1000 thermal cycles, T/C failures occurred at some Cu/SnAg bumps located at the edge and corner of chips. Scanning acoustic microscope analysis and scanning electron microscope observations indicated that the failure site was the Cu column/Si chip interface. It was identified by a FEA where the maximum stress concentration was located during T/C. During T/C, the Al pad between the Si chip and a Cu column bump was displaced due to thermomechanical stress. Based on the low cycle fatigue model, the accumulation of equivalent plastic strain resulted in thermal fatigue deformation of the Cu column bumps and ultimately reduced the thermal cycling lifetime. The maximum equivalent plastic strains of some bumps at the chip edge increased with an increased number of thermal cycles. However, equivalent plastic strains of the inner bumps did not increase regardless of the number of thermal cycles. In addition, the z-directional normal plastic strain ɛ22 was determined to be compressive and was a dominant component causing the plastic deformation of Cu/SnAg double bumps. As the number of thermal cycles increased, normal plastic strains in the perpendicular direction to the Si chip and shear strains were accumulated on the Cu column bumps at the chip edge at low temperature region. Thus it was found that the Al pad at the Si chip/Cu column interface underwent thermal fatigue deformation by compressive normal strain and the contact loss by displacement failure of the Al pad, the main T/C failure mode of the Cu/SnAg flip chip assembly, then occurred at the Si chip/Cu column interface shear strain deformation

  20. Collagen-binding peptidoglycans inhibit MMP mediated collagen degradation and reduce dermal scarring.

    Directory of Open Access Journals (Sweden)

    Kate Stuart

    Full Text Available Scarring of the skin is a large unmet clinical problem that is of high patient concern and impact. Wound healing is complex and involves numerous pathways that are highly orchestrated, leaving the skin sealed, but with abnormal organization and composition of tissue components, namely collagen and proteoglycans, that are then remodeled over time. To improve healing and reduce or eliminate scarring, more rapid restoration of healthy tissue composition and organization offers a unique approach for development of new therapeutics. A synthetic collagen-binding peptidoglycan has been developed that inhibits matrix metalloproteinase-1 and 13 (MMP-1 and MMP-13 mediated collagen degradation. We investigated the synthetic peptidoglycan in a rat incisional model in which a single dose was delivered in a hyaluronic acid (HA vehicle at the time of surgery prior to wound closure. The peptidoglycan treatment resulted in a significant reduction in scar tissue at 21 days as measured by histology and visual analysis. Improved collagen architecture of the treated wounds was demonstrated by increased tensile strength and transmission electron microscopy (TEM analysis of collagen fibril diameters compared to untreated and HA controls. The peptidoglycan's mechanism of action includes masking existing collagen and inhibiting MMP-mediated collagen degradation while modulating collagen organization. The peptidoglycan can be synthesized at low cost with unique design control, and together with demonstrated preclinical efficacy in reducing scarring, warrants further investigation for dermal wound healing.

  1. Implementing and Assessing a Flipped Classroom Model for First-Year Engineering Design

    Science.gov (United States)

    Saterbak, Ann; Volz, Tracy; Wettergreen, Matthew

    2016-01-01

    Faculty at Rice University are creating instructional resources to support teaching first-year engineering design using a flipped classroom model. This implementation of flipped pedagogy is unusual because content-driven, lecture courses are usually targeted for flipping, not project-based design courses that already incorporate an abundance of…

  2. Resonant Homoclinic Flips Bifurcation in Principal Eigendirections

    Directory of Open Access Journals (Sweden)

    Tiansi Zhang

    2013-01-01

    Full Text Available A codimension-4 homoclinic bifurcation with one orbit flip and one inclination flip at principal eigenvalue direction resonance is considered. By introducing a local active coordinate system in some small neighborhood of homoclinic orbit, we get the Poincaré return map and the bifurcation equation. A detailed investigation produces the number and the existence of 1-homoclinic orbit, 1-periodic orbit, and double 1-periodic orbits. We also locate their bifurcation surfaces in certain regions.

  3. Teachers’ development in a flipped classroom for applied mathematics

    DEFF Research Database (Denmark)

    Triantafyllou, Evangelia; Timcenko, Olga; Kofoed, Lise

    2016-01-01

    In this paper, we discuss how the flipped classroom approach promoted teacher reflection and development. We look at the teaching cycle from a flipped instruction model perspective and we adjust it to cater for the reflection loops teachers are involved when designing, implementing and re-designi...

  4. Packaged and hybrid integrated all-optical flip-flop memory

    NARCIS (Netherlands)

    Liu, Y.; McDougall, R.; Hill, M.T.; Maxwell, G.D.; Zhang, S.; Harmon, R.; Huijskens, Frans; Rivers, L.; Dorren, H.J.S.; Poustie, A.

    2006-01-01

    A fully-packaged hybrid-integrated all-optical flip-flop, where InP-based semiconductor optical amplifiers are assembled onto a planar silica waveguide board, is demonstrated. It is shown experimentally that the flip-flop can dynamically toggle between its two states by injecting 150 ps optical

  5. Experimental plug and play quantum coin flipping

    Science.gov (United States)

    Pappa, Anna; Jouguet, Paul; Lawson, Thomas; Chailloux, André; Legré, Matthieu; Trinkler, Patrick; Kerenidis, Iordanis; Diamanti, Eleni

    2014-04-01

    Performing complex cryptographic tasks will be an essential element in future quantum communication networks. These tasks are based on a handful of fundamental primitives, such as coin flipping, where two distrustful parties wish to agree on a randomly generated bit. Although it is known that quantum versions of these primitives can offer information-theoretic security advantages with respect to classical protocols, a demonstration of such an advantage in a practical communication scenario has remained elusive. Here we experimentally implement a quantum coin flipping protocol that performs strictly better than classically possible over a distance suitable for communication over metropolitan area optical networks. The implementation is based on a practical plug and play system, developed by significantly enhancing a commercial quantum key distribution device. Moreover, we provide combined quantum coin flipping protocols that are almost perfectly secure against bounded adversaries. Our results offer a useful toolbox for future secure quantum communications.

  6. The flipped classroom allows for more class time devoted to critical thinking.

    Science.gov (United States)

    DeRuisseau, Lara R

    2016-12-01

    The flipped classroom was utilized in a two-semester, high-content science course that enrolled between 50 and 80 students at a small liberal arts college. With the flipped model, students watched ~20-min lectures 2 days/wk outside of class. These videos were recorded via screen capture and included a detailed note outline, PowerPoint slides, and review questions. The traditional format included the same materials, except that lectures were delivered in class each week and spanned the entire period. During the flipped course, the instructor reviewed common misconceptions and asked questions requiring higher-order thinking, and five graded case studies were performed each semester. To determine whether assessments included additional higher-order thinking skills in the flipped vs. traditional model, questions across course formats were compared via Blooms Taxonomy. Application-level questions that required prediction of an outcome in a new scenario comprised 38 ± 3 vs. 12 ± 1% of summative assessment questions (flipped vs. traditional. Final letter grades in both formats of the course were compared with major GPA. Students in the flipped model performed better than their GPA predicted, as 85.5% earned a higher grade (vs. 42.2% in the traditional classroom) compared with their major GPA. These data demonstrate that assessments transitioned to more application-level compared with factual knowledge-based questions with this particular flipped model, and students performed better in their final letter grade compared with the traditional lecture format. Although the benefits to a flipped classroom are highlighted, student evaluations did suffer. More detailed studies comparing the traditional and flipped formats are warranted. Copyright © 2016 the American Physiological Society.

  7. The flipped classroom and cooperative learning: Evidence from a randomised experiment

    OpenAIRE

    Foldnes, Njål

    2016-01-01

    This article describes a study which compares the effectiveness of the flipped classroom relative to the traditional lecturebased classroom.We investigated two implementations of the flipped classroom. The first implementation did not actively encourage cooperative learning, with students progressing through the course at their own pace. With this implementation student examination scores did not differ between the lecture classes and the flipped classroom. The second implementation ...

  8. Chaotic spin exchange: is the spin non-flip rate observable?

    International Nuclear Information System (INIS)

    Senba, Masayoshi

    1994-01-01

    If spin exchange is of the Poisson nature, that is, if the time distribution of collisions obeys an exponential distribution function and the collision process is random, the muon spin depolarization is determined only by the spin flip rate regardless of the spin non-flip rate. In this work, spin exchange is discussed in the case of chaotic spin exchange, where the distribution of collision time sequences, generated by a deterministic equation, is exponential but not random (deterministic chaos). Even though this process has the same time distribution as a Poisson process, the muon polarization is affected by the spin non-flip rate. Having an exponential time distribution function is not a sufficient condition for the non-observation of the spin non-flip rate and it is essential that the process is also random. (orig.)

  9. Flipped neutrino emissivity from strange matter

    Energy Technology Data Exchange (ETDEWEB)

    Goyal, A.; Dutta, S. (Department of Physics and Astrophysics, University of Delhi, Delhi 110007 (India))

    1994-04-15

    Energy loss due to wrong helicity sterile neutrinos through spin flip processes leads to rapid cooling of nascent neutron stars. The observed cooling of neutron stars associated with SN 1987A seems to preclude the existence of Dirac neutrinos with a mass in excess of 20 keV. Assuming that nuclear matter in the core of the neutron star undergoes a phase transition to quark matter leading to a strange star or a neutron star with a strange matter core, we examine the emission of flipped Dirac neutrinos for two dominant processes: quark-neutrino scattering [[ital q]+[nu][sub [minus

  10. Implementing the Flipped Classroom: An Exploration of Study Behaviour and Student Performance

    Science.gov (United States)

    Boevé, Anja J.; Meijer, Rob R.; Bosker, Roel J.; Vugteveen, Jorien; Hoekstra, Rink; Albers, Casper J.

    2017-01-01

    The flipped classroom is becoming more popular as a means to support student learning in higher education by requiring students to prepare before lectures and actively engaging students during lectures. While some research has been conducted into student performance in the flipped classroom, students' study behaviour throughout a flipped course…

  11. Ubiquitin-proteasomal degradation of COX-2 in TGF-β stimulated human endometrial cells is mediated through endoplasmic reticulum mannosidase I.

    Science.gov (United States)

    Singh, Mohan; Chaudhry, Parvesh; Parent, Sophie; Asselin, Eric

    2012-01-01

    Cyclooxygenase (COX)-2 is a key regulatory enzyme in the production of prostaglandins (PG) during various physiological processes. Mechanisms of COX-2 regulation in human endometrial stromal cells (human endometrial stromal cells) are not fully understood. In this study, we investigate the role of TGF-β in the regulation of COX-2 in human uterine stromal cells. Each TGF-β isoform decreases COX-2 protein level in human uterine stromal cells in Smad2/3-dependent manner. The decrease in COX-2 is accompanied by a decrease in PG synthesis. Knockdown of Smad4 using specific small interfering RNA prevents the decrease in COX-2 protein, confirming that Smad pathway is implicated in the regulation of COX-2 expression in human endometrial stromal cells. Pretreatment with 26S proteasome inhibitor, MG132, significantly restores COX-2 protein and PG synthesis, indicating that COX-2 undergoes proteasomal degradation in the presence of TGF-β. In addition, each TGF-β isoform up-regulates endoplasmic reticulum (ER)-mannosidase I (ERManI) implying that COX-2 degradation is mediated through ER-associated degradation pathway in these cells. Furthermore, inhibition of ERManI activity using the mannosidase inhibitor (kifunensine), or small interfering RNA-mediated knockdown of ERManI, prevents TGF-β-induced COX-2 degradation. Taken together, these studies suggest that TGF-β promotes COX-2 degradation in a Smad-dependent manner by up-regulating the expression of ERManI and thereby enhancing ER-associated degradation and proteasomal degradation pathways.

  12. Pharmacy student engagement, performance, and perception in a flipped satellite classroom.

    Science.gov (United States)

    McLaughlin, Jacqueline E; Griffin, LaToya M; Esserman, Denise A; Davidson, Christopher A; Glatt, Dylan M; Roth, Mary T; Gharkholonarehe, Nastaran; Mumper, Russell J

    2013-11-12

    To determine whether "flipping" a traditional basic pharmaceutics course delivered synchronously to 2 satellite campuses would improve student academic performance, engagement, and perception. In 2012, the basic pharmaceutics course was flipped and delivered to 22 satellite students on 2 different campuses. Twenty-five condensed, recorded course lectures were placed on the course Web site for students to watch prior to class. Scheduled class periods were dedicated to participating in active-learning exercises. Students also completed 2 course projects, 3 midterm examinations, 8 graded quizzes, and a cumulative and comprehensive final examination. Results of a survey administered at the beginning and end of the flipped course in 2012 revealed an increase in students' support for learning content prior to class and using class time for more applied learning (p=0.01) and in the belief that learning key foundational content prior to coming to class greatly enhanced in-class learning (p=0.001). Significantly more students preferred the flipped classroom format after completing the course (89.5%) than before completing the course (34.6%). Course evaluation responses and final examination performance did not differ significantly for 2011 when the course was taught using a traditional format and the 2012 flipped-course format. Qualitative findings suggested that the flipped classroom promoted student empowerment, development, and engagement. The flipped pharmacy classroom can enhance the quality of satellite students' experiences in a basic pharmaceutics course through thoughtful course design, enriched dialogue, and promotion of learner autonomy.

  13. Facing the challenges in ophthalmology clerkship teaching: Is flipped classroom the answer?

    Directory of Open Access Journals (Sweden)

    Ying Lin

    Full Text Available Recent reform of medical education highlights the growing concerns about the capability of the current educational model to equip medical school students with essential skills for future career development. In the field of ophthalmology, although many attempts have been made to address the problem of the decreasing teaching time and the increasing load of course content, a growing body of literature indicates the need to reform the current ophthalmology teaching strategies. Flipped classroom is a new pedagogical model in which students develop a basic understanding of the course materials before class, and use in-class time for learner-centered activities, such as group discussion and presentation. However, few studies have evaluated the effectiveness of the flipped classroom in ophthalmology education. This study, for the first time, assesses the use of flipped classroom in ophthalmology, specifically glaucoma and ocular trauma clerkship teaching. A total number of 44 international medical school students from diverse background were enrolled in this study, and randomly divided into two groups. One group took the flipped glaucoma classroom and lecture-based ocular trauma classroom, while the other group took the flipped ocular trauma classroom and lecture-based glaucoma classroom. In the traditional lecture-based classroom, students attended the didactic lecture and did the homework after class. In the flipped classroom, students were asked to watch the prerecorded lectures before the class, and use the class time for homework discussion. Both the teachers and students were asked to complete feedback questionnaires after the classroom. We found that the two groups did not show differences in the final exam scores. However, the flipped classroom helped students to develop skills in problem solving, creative thinking and team working. Also, compared to the lecture-based classroom, both teachers and students were more satisfied with the flipped

  14. Facing the challenges in ophthalmology clerkship teaching: Is flipped classroom the answer?

    Science.gov (United States)

    Lin, Ying; Zhu, Yi; Chen, Chuan; Wang, Wei; Chen, Tingting; Li, Tao; Li, Yonghao; Liu, Bingqian; Lian, Yu; Lu, Lin; Zou, Yuxian; Liu, Yizhi

    2017-01-01

    Recent reform of medical education highlights the growing concerns about the capability of the current educational model to equip medical school students with essential skills for future career development. In the field of ophthalmology, although many attempts have been made to address the problem of the decreasing teaching time and the increasing load of course content, a growing body of literature indicates the need to reform the current ophthalmology teaching strategies. Flipped classroom is a new pedagogical model in which students develop a basic understanding of the course materials before class, and use in-class time for learner-centered activities, such as group discussion and presentation. However, few studies have evaluated the effectiveness of the flipped classroom in ophthalmology education. This study, for the first time, assesses the use of flipped classroom in ophthalmology, specifically glaucoma and ocular trauma clerkship teaching. A total number of 44 international medical school students from diverse background were enrolled in this study, and randomly divided into two groups. One group took the flipped glaucoma classroom and lecture-based ocular trauma classroom, while the other group took the flipped ocular trauma classroom and lecture-based glaucoma classroom. In the traditional lecture-based classroom, students attended the didactic lecture and did the homework after class. In the flipped classroom, students were asked to watch the prerecorded lectures before the class, and use the class time for homework discussion. Both the teachers and students were asked to complete feedback questionnaires after the classroom. We found that the two groups did not show differences in the final exam scores. However, the flipped classroom helped students to develop skills in problem solving, creative thinking and team working. Also, compared to the lecture-based classroom, both teachers and students were more satisfied with the flipped classroom

  15. Assessment of Learning Gains in a Flipped Biochemistry Classroom

    Science.gov (United States)

    Ojennus, Deanna Dahlke

    2016-01-01

    The flipped classroom has become an increasingly popular pedagogical approach to teaching and learning. In this study, learning gains were assessed in a flipped biochemistry course and compared to gains in a traditional lecture. Although measured learning gains were not significantly different between the two courses, student perception of…

  16. Enhancing the Design and Analysis of Flipped Learning Strategies

    Science.gov (United States)

    Jenkins, Martin; Bokosmaty, Rena; Brown, Melanie; Browne, Chris; Gao, Qi; Hanson, Julie; Kupatadze, Ketevan

    2017-01-01

    There are numerous calls in the literature for research into the flipped learning approach to match the flood of popular media articles praising its impact on student learning and educational outcomes. This paper addresses those calls by proposing pedagogical strategies that promote active learning in "flipped" approaches and improved…

  17. Flipping College Algebra: Effects on Student Engagement and Achievement

    Science.gov (United States)

    Ichinose, Cherie; Clinkenbeard, Jennifer

    2016-01-01

    This study compared student engagement and achievement levels between students enrolled in a traditional college algebra lecture course and students enrolled in a "flipped" course. Results showed that students in the flipped class had consistently higher levels of achievement throughout the course than did students in the traditional…

  18. Evaluation of a "Flipped Classroom" Approach in Management Education

    Science.gov (United States)

    Bergfjord, Ole Jakob; Heggernes, Tarjei

    2016-01-01

    In this paper, a "flipped classroom" approach is evaluated using three different datasets. We use student evaluations of the "flipped classroom" in particular, in addition to regular course evaluations and exam results for the past three years in order to allow for statistical comparisons. Overall, the results are quite…

  19. The Perceived Effects of Flipped Teaching on Knowledge Acquisition

    Science.gov (United States)

    Newman, Galen; Kim, Jun-Hyun; Lee, Ryun Jung; Brown, Brandy A.; Huston, Sharon

    2016-01-01

    Increased demands for technological integration in higher education have resulted in new forms of course instruction. Under a flipped approach, students learn course materials outside the classroom while active learning methods are employed inside. This study focuses on the perceived effects of flipped instruction on knowledge acquisition in…

  20. RECOILING SUPERMASSIVE BLACK HOLES IN SPIN-FLIP RADIO GALAXIES

    International Nuclear Information System (INIS)

    Liu, F. K.; Wang Dong; Chen Xian

    2012-01-01

    Numerical relativity simulations predict that coalescence of supermassive black hole (SMBH) binaries leads not only to a spin flip but also to a recoiling of the merger remnant SMBHs. In the literature, X-shaped radio sources are popularly suggested to be candidates for SMBH mergers with spin flip of jet-ejecting SMBHs. Here we investigate the spectral and spatial observational signatures of the recoiling SMBHs in radio sources undergoing black hole spin flip. Our results show that SMBHs in most spin-flip radio sources have mass ratio q ∼> 0.3 with a minimum possible value q min ≅ 0.05. For major mergers, the remnant SMBHs can get a kick velocity as high as 2100 km s –1 in the direction within an angle ∼< 40° relative to the spin axes of remnant SMBHs, implying that recoiling quasars are biased to be with high Doppler-shifted broad emission lines while recoiling radio galaxies are biased to large apparent spatial off-center displacements. We also calculate the distribution functions of line-of-sight velocity and apparent spatial off-center displacements for spin-flip radio sources with different apparent jet reorientation angles. Our results show that the larger the apparent jet reorientation angle is, the larger the Doppler-shifting recoiling velocity and apparent spatial off-center displacement will be. We investigate the effects of recoiling velocity on the dust torus in spin-flip radio sources and suggest that recoiling of SMBHs would lead to 'dust-poor' active galactic nuclei. Finally, we collect a sample of 19 X-shaped radio objects and for each object give the probability of detecting the predicted signatures of recoiling SMBH.

  1. Hardened Flip-Flop Optimized for Subthreshold Operation Heavy Ion Characterization of a Radiation

    Directory of Open Access Journals (Sweden)

    Eric Bozeman

    2012-05-01

    Full Text Available A novel Single Event Upset (SEU tolerant flip-flop design is proposed, which is well suited for very-low power electronics that operate in subthreshold ( < Vt ≈ 500 mV. The proposed flip-flop along with a traditional (unprotected flip-flop, a Sense-Amplifier-based Rad-hard Flip-Flop (RSAFF and a Dual Interlocked storage Cell (DICE flip-flop were all fabricated in MIT Lincoln Lab’s XLP 0.15 μm fully-depleted SOI CMOS technology—a process optimized for subthreshold operation. At the Cyclotron Institute at Texas A&M University, all four cells were subjected to heavy ion characterization in which the circuits were dynamically updated with alternating data and then checked for SEUs at both subthreshold (450 mV and superthreshold (1.5 V levels. The proposed flip-flop never failed, while the traditional and DICE designs did demonstrate faulty behavior. Simulations were conducted with the XLP process and the proposed flip-flop provided an improved energy delay product relative to the other non-faulty rad-hard flip-flop at subthreshold voltage operation. According to the XLP models operating in subthreshold at 250 mV, performance was improved by 31% and energy consumption was reduced by 27%.

  2. Spin-flip processes in low-energy Fe17+ + He collisions

    International Nuclear Information System (INIS)

    Bruch, R.; Altick, P.L.; Rauscher, E.; Wang, H.; Schneider, D.

    1993-01-01

    Spin-nonconserving electron transfer processes violating the ''Wigner rule'' have been studied for slow multiply charged ion-atom collisions. Experimentally a strong population of highly metastable sodium-like quartet states in low energy Fe 17+ + He single collision events has been observed. The possibility of double-electron capture plus spin-flip mechanisms has been discussed experimentally and theoretically, Our theoretical model using time dependent perturbation theory predicts that spin-flip processes are as likely as no spin flip under the conditions of our experiment

  3. Flipping Every Student? A Case Study of Content-Based Flipped Language Classrooms

    Science.gov (United States)

    Sun, Yu-Chih

    2017-01-01

    The study aims to explore university-level foreign language learners' perceptions of the content-based flipped classroom approach and factors influencing their perceptions. The research questions guiding the study are three-fold. (a) What attitudes and perceptions do students have about language and knowledge acquisition in the content-based…

  4. Enhanced mitochondrial degradation of yeast cytochrome c with amphipathic structures.

    Science.gov (United States)

    Chen, Xi; Moerschell, Richard P; Pearce, David A; Ramanan, Durga D; Sherman, Fred

    2005-02-01

    The dispensable N-terminus of iso-1-cytochrome c (iso-1) in the yeast Saccharomyces cerevisiae was replaced by 11 different amphipathic structures. Rapid degradation of the corresponding iso-1 occurred, with the degree of degradation increasing with the amphipathic moments; and this amphipathic-dependent degradation was designated ADD. ADD occurred with the holo-forms in the mitochondria but not as the apo-forms in the cytosol. The extreme mutant type degraded with a half-life of approximately 12 min, whereas the normal iso-1 was stable over hours. ADD was influenced by the rho+/rho- state and by numerous chromosomal genes. Most importantly, ADD appeared to be specifically suppressed to various extents by deletions of any of the YME1, AFG3, or RCA1 genes encoding membrane-associated mitochondrial proteases, probably because the amphipathic structures caused a stronger association with the mitochondrial inner membrane and its associated proteases. The use of ADD assisted in the differentiation of substrates of different mitochondrial degradation pathways.

  5. Timing of APC/C substrate degradation is determined by fzy/fzr specificity of destruction boxes

    OpenAIRE

    Zur, Amit; Brandeis, Michael

    2002-01-01

    The anaphase promoting complex/cyclosome (APC/C), activated by fzy and fzr, degrades cell cycle proteins that carry RXXL or KEN destruction boxes (d-boxes). APC/C substrates regulate sequential events and must be degraded in the correct order during mitosis and G1. We studied how d-boxes determine APC/Cfzy/APC/Cfzr specificity and degradation timing. Cyclin B1 has an RXXL box and is degraded by both APC/Cfzy and APC/Cfzr; fzy has a KEN box and is degraded by APC/Cfzr only. We characterized th...

  6. F-Box Protein FBXO22 Mediates Polyubiquitination and Degradation of CD147 to Reverse Cisplatin Resistance of Tumor Cells.

    Science.gov (United States)

    Wu, Bo; Liu, Zhen-Yu; Cui, Jian; Yang, Xiang-Min; Jing, Lin; Zhou, Yang; Chen, Zhi-Nan; Jiang, Jian-Li

    2017-01-20

    Drug resistance remains a major clinical obstacle to successful treatment of cancer. As posttranslational modification is becoming widely recognized to affect the function of oncoproteins, targeting specific posttranslational protein modification provides an attractive strategy for anticancer drug development. CD147 is a transmembrane glycoprotein contributing to chemo-resistance of cancer cells in a variety of human malignancies. Ubiquitination is an important posttranslational modification mediating protein degradation. Degradation of oncoproteins, CD147 included, emerges as an attractive alternative for tumor inhibition. However, the ubiquitination of CD147 remains elusive. Here in this study, we found that deletion of the CD147 intracellular domain (CD147-ICD) prolonged the half-life of CD147 in HEK293T cells, and we identified that CD147-ICD interacts with FBXO22 using mass spectrometry and Western blot. Then, we demonstrated that FBXO22 mediates the polyubiquitination and degradation of CD147 by recognizing CD147-ICD. While knocking down of FBXO22 prolonged the half-life of CD147 in HEK293T cells, we found that FBXO22 regulates CD147 protein turnover in SMMC-7721, Huh-7 and A549 cells. Moreover, we found that the low level of FBXO22 contributes to the accumulation of CD147 and thereafter the cisplatin resistance of A549/DDP cells. To conclude, our study demonstrated that FBXO22 mediated the polyubiquitination and degradation of CD147 by interacting with CD147-ICD, and CD147 polyubiquitination by FBXO22 reversed cisplatin resistance of tumor cells.

  7. F-Box Protein FBXO22 Mediates Polyubiquitination and Degradation of CD147 to Reverse Cisplatin Resistance of Tumor Cells

    Directory of Open Access Journals (Sweden)

    Bo Wu

    2017-01-01

    Full Text Available Drug resistance remains a major clinical obstacle to successful treatment of cancer. As posttranslational modification is becoming widely recognized to affect the function of oncoproteins, targeting specific posttranslational protein modification provides an attractive strategy for anticancer drug development. CD147 is a transmembrane glycoprotein contributing to chemo-resistance of cancer cells in a variety of human malignancies. Ubiquitination is an important posttranslational modification mediating protein degradation. Degradation of oncoproteins, CD147 included, emerges as an attractive alternative for tumor inhibition. However, the ubiquitination of CD147 remains elusive. Here in this study, we found that deletion of the CD147 intracellular domain (CD147-ICD prolonged the half-life of CD147 in HEK293T cells, and we identified that CD147-ICD interacts with FBXO22 using mass spectrometry and Western blot. Then, we demonstrated that FBXO22 mediates the polyubiquitination and degradation of CD147 by recognizing CD147-ICD. While knocking down of FBXO22 prolonged the half-life of CD147 in HEK293T cells, we found that FBXO22 regulates CD147 protein turnover in SMMC-7721, Huh-7 and A549 cells. Moreover, we found that the low level of FBXO22 contributes to the accumulation of CD147 and thereafter the cisplatin resistance of A549/DDP cells. To conclude, our study demonstrated that FBXO22 mediated the polyubiquitination and degradation of CD147 by interacting with CD147-ICD, and CD147 polyubiquitination by FBXO22 reversed cisplatin resistance of tumor cells.

  8. Quantifying the Impact of Single Bit Flips on Floating Point Arithmetic

    Energy Technology Data Exchange (ETDEWEB)

    Elliott, James J [ORNL; Mueller, Frank [North Carolina State University; Stoyanov, Miroslav K [ORNL; Webster, Clayton G [ORNL

    2013-08-01

    In high-end computing, the collective surface area, smaller fabrication sizes, and increasing density of components have led to an increase in the number of observed bit flips. If mechanisms are not in place to detect them, such flips produce silent errors, i.e. the code returns a result that deviates from the desired solution by more than the allowed tolerance and the discrepancy cannot be distinguished from the standard numerical error associated with the algorithm. These phenomena are believed to occur more frequently in DRAM, but logic gates, arithmetic units, and other circuits are also susceptible to bit flips. Previous work has focused on algorithmic techniques for detecting and correcting bit flips in specific data structures, however, they suffer from lack of generality and often times cannot be implemented in heterogeneous computing environment. Our work takes a novel approach to this problem. We focus on quantifying the impact of a single bit flip on specific floating-point operations. We analyze the error induced by flipping specific bits in the most widely used IEEE floating-point representation in an architecture-agnostic manner, i.e., without requiring proprietary information such as bit flip rates and the vendor-specific circuit designs. We initially study dot products of vectors and demonstrate that not all bit flips create a large error and, more importantly, expected value of the relative magnitude of the error is very sensitive on the bit pattern of the binary representation of the exponent, which strongly depends on scaling. Our results are derived analytically and then verified experimentally with Monte Carlo sampling of random vectors. Furthermore, we consider the natural resilience properties of solvers based on the fixed point iteration and we demonstrate how the resilience of the Jacobi method for linear equations can be significantly improved by rescaling the associated matrix.

  9. Physical and transportation requirements for a FLIP fueled TRIGA

    International Nuclear Information System (INIS)

    Johnson, A.G.; Ringle, J.C.; Anderson, T.V.

    1977-01-01

    Several major changes to the OSTR Physical Security Plan were required by the NRC prior to the August 1976 receipt and installation of a new core consisting entirely of FLIP fuel. The general nature of these changes will be reviewed along with several decisions we faced during their implementation. At the previous TRIGA Owners' Conference in Salt Lake City, Utah, we reported on Oregon's regulatory program for research reactor emergency response planning and physical security. The latter program was of particular interest to us in light of the projected FLIP fuel shipments. The impact of the State's program for physical security of FLIP fuel during transportation will be presented. (author)

  10. Detection and Analysis of Cell Cycle-Associated APC/C-Mediated Cellular Ubiquitylation In Vitro and In Vivo.

    Science.gov (United States)

    Cedeño, Cesyen; La Monaca, Esther; Esposito, Mara; Gutierrez, Gustavo J

    2016-01-01

    The anaphase-promoting complex or cyclosome (APC/C) is one of the major orchestrators of the cell division cycle in mammalian cells. The APC/C acts as a ubiquitin ligase that triggers sequential ubiquitylation of a significant number of substrates which will be eventually degraded by proteasomes during major transitions of the cell cycle. In this chapter, we present accessible methodologies to assess both in in vitro conditions and in cellular systems ubiquitylation reactions mediated by the APC/C. In addition, we also describe techniques to evidence the changes in protein stability provoked by modulation of the activity of the APC/C. Finally, specific methods to analyze interactors or posttranslational modifications of particular APC/C subunits are also discussed. Given the crucial role played by the APC/C in the regulation of the cell cycle, this review only focuses on its action and effects in actively proliferating cells.

  11. Flipped Classrooms and Student Learning: Not Just Surface Gains

    Science.gov (United States)

    McLean, Sarah; Attardi, Stefanie M.; Faden, Lisa; Goldszmidt, Mark

    2016-01-01

    The flipped classroom is a relatively new approach to undergraduate teaching in science. This approach repurposes class time to focus on application and discussion; the acquisition of basic concepts and principles is done on the students' own time before class. While current flipped classroom research has focused on student preferences and…

  12. CYP3A5 mRNA degradation by nonsense-mediated mRNA decay.

    Science.gov (United States)

    Busi, Florent; Cresteil, Thierry

    2005-09-01

    The total CYP3A5 mRNA level is significantly greater in carriers of the CYP3A5*1 allele than in CYP3A5*3 homozygotes. Most of the CYP3A5*3 mRNA includes an intronic sequence (exon 3B) containing premature termination codons (PTCs) between exons 3 and 4. Two models were used to investigate the degradation of CYP3A5 mRNA: a CYP3A5 minigene consisting of CYP3A5 exons and introns 3 to 6 transfected into MCF7 cells, and the endogenous CYP3A5 gene expressed in HepG2 cells. The 3'-untranslated region g.31611C>T mutation has no effect on CYP3A5 mRNA decay. Splice variants containing exon 3B were more unstable than wild-type (wt) CYP3A5 mRNA. Cycloheximide prevents the recognition of PTCs by ribosomes: in transfected MCF7 and HepG2 cells, cycloheximide slowed down the degradation of exon 3B-containing splice variants, suggesting the participation of nonsense-mediated decay (NMD). When PTCs were removed from pseudoexon 3B or when UPF1 small interfering RNA was used to impair the NMD mechanism, the decay of the splice variant was reduced, confirming the involvement of NMD in the degradation of CYP3A5 splice variants. Induction could represent a source of variability for CYP3A5 expression and could modify the proportion of splice variants. The extent of CYP3A5 induction was investigated after exposure to barbiturates or steroids: CYP3A4 was markedly induced in a pediatric population compared with untreated neonates. However, no effect could be detected in either the total CYP3A5 RNA, the proportion of splice variant RNA, or the protein level. Therefore, in these carriers, induction is unlikely to switch on the phenotypic CYP3A5 expression in carriers of CYP3A5*3/*3.

  13. Observation of Beam Size Flip-Flop in PEP-II

    International Nuclear Information System (INIS)

    Holtzapple, Robert luther

    2002-01-01

    The asymmetric B-factory, PEP-II, has delivered a peak luminosity of 4.6 x 10 33 cm -2 s -1 with less than half the design number of bunches, requiring a luminosity per bunch crossing more than three times larger than the design. As a result, strong beam-beam effects are present. The strong beam-beam forces between colliding electron and positron bunches can result in a ''flip-flop'' of the transverse beam size of some bunches. Focusing on one positron-electron colliding bunch pair, a flip-flop occurs when the transverse size of the positron bunch shrinks and the electron bunch grows. The flip-flop accounts for a reduction in luminosity, a lower positron lifetime, and increased background in the BABAR detector. The flip-flop phenomenon occurs not for all of the colliding bunches, but for the bunches at the front of a mini-train. Once a colliding pair has flipped to its reduced luminosity state it can be changed back to its normal state by raising the horizontal tune in the low-energy ring (LER, positrons) by 0.01. Afterwards the LER x-tune can be reduced nearly back to its original point, resulting in higher luminosity. These observations were verified and quantified with a new time-gated camera with a resolution of 2 ns, making it possible to observe single bunches

  14. Quasilinear theory of a spin-flip laser

    International Nuclear Information System (INIS)

    Arunasalam, V.

    1973-09-01

    A discussion of the nonlinear electrodynamic behavior of a gas of spin 1/2 particles in a uniform external magnetic field is presented. In particular, the quasilinear time evolution of a spin-flip laser system is examined in detail both from the point of view of the thermodynamics of negative temperature systems and the quantum kinetic methods of nonequilibrium statistical mechanics. It is shown that the quasilinear steady state of a spin-flip laser system is that state at which the populations of the spin-up and the spin-down states are equal to each other, and this quasilinear steady state is the state of minimum entropy production. The maximum output power of the spin-flip laser predicted by the theory presented in this paper is shown to be in reasonably good agreement with experimental results. The method used here is based on the general principles of nonrelativistic quantum theory and takes account of the Doppler broadening, collisional broadening, and Compton recoil effects. 30 refs., 1 fig

  15. Flipped classroom improves student learning in health professions education: a meta-analysis.

    Science.gov (United States)

    Hew, Khe Foon; Lo, Chung Kwan

    2018-03-15

    The use of flipped classroom approach has become increasingly popular in health professions education. However, no meta-analysis has been published that specifically examines the effect of flipped classroom versus traditional classroom on student learning. This study examined the findings of comparative articles through a meta-analysis in order to summarize the overall effects of teaching with the flipped classroom approach. We focused specifically on a set of flipped classroom studies in which pre-recorded videos were provided before face-to-face class meetings. These comparative articles focused on health care professionals including medical students, residents, doctors, nurses, or learners in other health care professions and disciplines (e.g., dental, pharmacy, environmental or occupational health). Using predefined study eligibility criteria, seven electronic databases were searched in mid-April 2017 for relevant articles. Methodological quality was graded using the Medical Education Research Study Quality Instrument (MERSQI). Effect sizes, heterogeneity estimates, analysis of possible moderators, and publication bias were computed using the COMPREHENSIVE META-ANALYSIS software. A meta-analysis of 28 eligible comparative studies (between-subject design) showed an overall significant effect in favor of flipped classrooms over traditional classrooms for health professions education (standardized mean difference, SMD = 0.33, 95% confidence interval, CI = 0.21-0.46, p flipped classroom approach was more effective when instructors used quizzes at the start of each in-class session. More respondents reported they preferred flipped to traditional classrooms. Current evidence suggests that the flipped classroom approach in health professions education yields a significant improvement in student learning compared with traditional teaching methods.

  16. Malaysian Students' Perceptions of Flipped Classroom: A Case Study

    Science.gov (United States)

    Zainuddin, Zamzami; Attaran, Mohammad

    2016-01-01

    The purpose of this study was to evaluate a class in University of Malaya where flipped learning was applied, and to examine students' perceptions and feedback towards flipped classroom. Data were collected using both quantitative and qualitative methods, i.e. survey, focus group and individual interviews. The results indicated that most students…

  17. Efektivitas Flipped Classroom Terhadap Sikap Dan Ketrampilan Belajar Matematika Di Smk

    OpenAIRE

    Damayanti, Herry Novis; Sutama, Sutama

    2016-01-01

    The aim of the research is developed attitude resposiility, and skill learning of mathematic teaching based Flipped Classroom. The final result of the research is to taste effectiveness of mathematic teaching model based Flipped Classroom. The research method is research and development that includes introduction, field study of teaching management in the school, planning and preparing Flipped Classroom model, implementation of teaching first cycle, second cycle, and third cycle, and exam of ...

  18. The flipped classroom for medical students.

    Science.gov (United States)

    Morgan, Helen; McLean, Karen; Chapman, Chris; Fitzgerald, James; Yousuf, Aisha; Hammoud, Maya

    2015-06-01

    The objectives of this curricular innovation project were to implement a flipped classroom curriculum for the gynaecologic oncology topics of the obstetrics and gynaecology medical student clerkship, and to evaluate student satisfaction with the change. Four short online videos on the topics of endometrial hyperplasia, cervical dysplasia, evaluation of an adnexal mass, and ovarian cancer were created, and students were instructed to view them prior to a class-time active learning session. The Learning Activity Management System (lams) open-source online platform was used to create an active learning class-time activity that consisted of a coached discussion of cases. Student satisfaction with the two aspects of the flipped curriculum was obtained. In addition, lecture assessment for the gynaecologic oncology topics and aggregate student performance on the gynaecological oncology questions of the US National Board of Medical Examiners (NBME) Subject Examination were compared before and after implementation of the curriculum. Eighty-nine students rotated on the clerkship during the pilot period of analysis. Seventy-one students (80%) viewed the videos prior to the class session, and 84 (94%) attended the session. Student satisfaction was very high for both parts of the curriculum. There was no significant difference in aggregate student performance on the gynaecological oncology questions of the NBME Subject Examination. The flipped classroom curriculum demonstrates a promising platform for using technology to make better use of students' time Our implementation of the flipped classroom curriculum for the gynaecologic oncology topics successfully demonstrates a promising platform for using technology to make better use of our students' time, and for increasing their satisfaction with the necessary didactic learning of the clerkship. © 2015 John Wiley & Sons Ltd.

  19. Development of gold based solder candidates for flip chip assembly

    DEFF Research Database (Denmark)

    Chidambaram, Vivek; Hald, John; Hattel, Jesper Henri

    2009-01-01

    Flip chip technology is now rapidly replacing the traditional wire bonding interconnection technology in the first level packaging applications due to the miniaturization drive in the microelectronics industry. Flip chip assembly currently involves the use of high lead containing solders...

  20. Just in Time to Flip Your Classroom

    OpenAIRE

    Lasry, Nathaniel; Dugdale, Michael; Charles, Elizabeth

    2013-01-01

    With advocates like Sal Khan and Bill Gates, flipped classrooms are attracting an increasing amount of media and research attention. We had heard Khan's TED talk and were aware of the concept of inverted pedagogies in general. Yet, it really hit home when we accidentally flipped our classroom. Our objective was to better prepare our students for class. We set out to effectively move some of our course content outside of class and decided to tweak the Just-in-Time-Teaching approach (JiTT). To ...

  1. Phosphorylation prevents C/EBPβ from the calpain-dependent degradation

    International Nuclear Information System (INIS)

    Zhang, Yuan-yuan; Li, Shu-fen; Qian, Shu-wen; Zhang, You-you; Liu, Yuan; Tang, Qi-Qun; Li, Xi

    2012-01-01

    Highlights: ► Phosphorylation protected C/EBPβ from μ-calpain-mediated proteolysis in vitro. ► Phosphorylation mimic C/EBPβ was insensitive to calpain accelerator and inhibitor. ► Phosphorylation on Thr 188 contributed more to the stabilization of C/EBPβ. -- Abstract: CCAAT/enhancer-binding protein (C/EBP) β plays an important role in proliferation and differentiation of 3T3-L1 preadipocytes. C/EBPβ is sequentially phosphorylated during the 3T3-L1 adipocyte differentiation program, first by MAPK/Cyclin A/cdk2 on Thr 188 and subsequently by GSK3β on Ser 184 or Thr 179 . Dual phosphorylation is critical for the gain of DNA binding activity of C/EBPβ. In this manuscript, we found that phosphorylation also contributed to the stability of C/EBPβ. Both ex vivo and in vitro experiments showed that phosphorylation by MAPK/Cyclin A/cdk2 and GSK3β protected C/EBPβ from μ-calpain-mediated proteolysis, while phosphorylation on Thr 188 by MAPK/Cyclin A/cdk2 contributed more to the stabilization of C/EBPβ, Further studies indicated that phosphorylation mimic C/EBPβ was insensitive to both calpain accelerator and calpain inhibitor. Thus, phosphorylation might contribute to the stability as well as the gain of DNA binding activity of C/EBPβ.

  2. Flipping the Classroom Revisited

    Science.gov (United States)

    Riendeau, Diane

    2013-02-01

    I received many emails following the first column on flipping the classroom. Many of my local colleagues also approached me at our physics alliance, Physics Northwest. Teachers are very interested in this new pedagogy. As I result, I wanted to share some more videos to inspire you.

  3. Aging analysis of high performance FinFET flip-flop under Dynamic NBTI simulation configuration

    Science.gov (United States)

    Zainudin, M. F.; Hussin, H.; Halim, A. K.; Karim, J.

    2018-03-01

    A mechanism known as Negative-bias Temperature Instability (NBTI) degrades a main electrical parameters of a circuit especially in terms of performance. So far, the circuit design available at present are only focussed on high performance circuit without considering the circuit reliability and robustness. In this paper, the main circuit performances of high performance FinFET flip-flop such as delay time, and power were studied with the presence of the NBTI degradation. The aging analysis was verified using a 16nm High Performance Predictive Technology Model (PTM) based on different commands available at Synopsys HSPICE. The results shown that the circuit under the longer dynamic NBTI simulation produces the highest impact in the increasing of gate delay and decrease in the average power reduction from a fresh simulation until the aged stress time under a nominal condition. In addition, the circuit performance under a varied stress condition such as temperature and negative stress gate bias were also studied.

  4. Dimer-flipping-assisted diffusion on a Si(001) surface

    International Nuclear Information System (INIS)

    Zi, J.; Min, B. J.; Lu, Y.; Wang, C. Z.; Ho, K. M.

    2000-01-01

    The binding sites and diffusion pathways of Si adatoms on a c(4x2) reconstructed Si(001) surface are investigated by a tight-binding method with an environment-dependent silicon potential in conjunction with ab initio calculations using the Car--Parrinello method. A new diffusion pathway along the trough edge driven by dimer flipping is found with a barrier of 0.74 eV, comparable to that of 0.68 eV along the top of the dimer rows

  5. Dual action of vitamin C versus degradation and supplementation

    OpenAIRE

    Katarzyna Kaliś

    2015-01-01

    The article discusses vitamin C from the point of view of its supplementation with food and in the form of oral supplements. The dual action of vitamin C is connected with the presence of oxygen, which may reduce the amount of the vitamin in food products, influence thermal resistance, cause degradation and show an antioxidation effect. Vitamin C stimulates the immune cells and collagen synthesis. It may protect the LDL fraction against oxidation, and therefore it is interesting for cosmetolo...

  6. Quark loops and spin-flip effects in pomeron exchange

    International Nuclear Information System (INIS)

    Goloskokov, S.V.

    1991-01-01

    On the basis of QCD at large distances with taking account of some nonperturbative properties of the theory, the possibility of spin-flip effects in high energy hadron processes at fixed momenta transfer is investigated. It is shown that the diagrams with the quark loops in QCD at large distances may lead to the spin-flip amplitude growing as s for s→∞, t-fixed. The confirmation of this result is obtained by calculations of the nonleading contributions from quark loops in t-channel exchange in QED up to the end. Physical mechanisms leading to that behaviour of the spin-flip amplitude is discussed. So we conclude that the pomeron has a complicated spin structure. (orig.)

  7. Polarizing a stored proton beam by spin-flip?

    International Nuclear Information System (INIS)

    Oellers, Dieter Gerd Christian

    2010-01-01

    The present thesis discusses the extraction of the electron-proton spin-flip cross-section. The experimental setup, the data analysis and the results are pictured in detail. The proton is described by a QCD-based parton model. In leading twist three functions are needed. The quark distribution, the helicity distribution and the transversity distribution. While the first two are well-known, the transversity distribution is largely unknown. A self-sufficient measurement of the transversity is possible in double polarized proton-antiproton scattering. This rises the need of a polarized antiproton beam. So far spin filtering is the only tested method to produce a polarized proton beam, which may be capable to hold also for antiprotons. In-situ polarization build-up of a stored beam either by selective removal or by spin-flip of a spin-(1)/(2) beam is mathematically described. A high spin-flip cross-section would create an effective method to produce a polarized antiproton beam by polarized positrons. Prompted by conflicting calculations, a measurement of the spin-flip cross-section in low-energy electron-proton scattering was carried out. This experiment uses the electron beam of the electron cooler at COSY as an electron target. The depolarization of the stored proton beam is detected. An overview of the experiment is followed by detailed descriptions of the cycle setup, of the electron target and the ANKE silicon tracking telescopes acting as a beam polarimeter. Elastic protondeuteron scattering is the analyzing reaction. The event selection is depicted and the beam polarization is calculated. Upper limits of the two electron-proton spin-flip cross-sections σ parallel and σ perpendicular to are deduced using the likelihood method. (orig.)

  8. [Dual action of vitamin C versus degradation and supplementation].

    Science.gov (United States)

    Kaliś, Katarzyna

    2015-11-17

    The article discusses vitamin C from the point of view of its supplementation with food and in the form of oral supplements. The dual action of vitamin C is connected with the presence of oxygen, which may reduce the amount of the vitamin in food products, influence thermal resistance, cause degradation and show an antioxidation effect. Vitamin C stimulates the immune cells and collagen synthesis. It may protect the LDL fraction against oxidation, and therefore it is interesting for cosmetology, rheumatology, immunology and dietetics. The latest research with respect to vitamin C proved that it has the ability to dissolve neurotoxic senile plaques. Equally effective in the treatment of Alzheimer's disease is the oxidised form of vitamin C, i.e. dehydroascorbic acid. Vitamin C may be used in a combined vitamin E supplementation to avoid the pro-oxidative effect and reduce the risk of diabetes mellitus type 2 complications. In the review there is a description of the types of vitamin C degradation depending on a specific factor such as pH, temperature, oxygen, enzyme and the impact of diet on the quantity of the supplied vitamin. The literature data confirmed the positive influence of vitamin C as an addition to food. The last part of the article presents the methods of vitamin C protection used in food processing technology and of determining its content in food products. Additionally, the article describes the problems related to vitamin C oxidation processes during food processing and storage. The presented research results indicate that an adequate diet contains a sufficient amount of vitamin C for healthy people. In the case of chronic patients it is better to use supplementation.

  9. Flipped SU(5) times U(1) in superconformal models

    Energy Technology Data Exchange (ETDEWEB)

    Bailin, D.; Katechou, E.K. (Sussex Univ., Brighton (United Kingdom). School of Mathematical and Physical Sciences); Love, A. (London Univ. (United Kingdom))

    1992-01-10

    This paper reports that flipped SU(5) {times} U(1) models are constructed in the framework of tensoring of N = 2 superconformal minimal models quotiented by discrete symmetries. Spontaneous breaking of flipped SU(5) {times} U(1) and extra U(1) factors in the gauge group along F-flat directions of the effective potential is studied.

  10. Microbial ecology of bacterially mediated PCB biodegradation

    International Nuclear Information System (INIS)

    Pettigrew, C.A. Jr.

    1989-01-01

    The roles of plasmid mediated and consortia mediated polychlorinated biphenyl (PCB) biodegradation by bacterial populations isolated from PCB contaminated freshwater sediments were investigated. PCB degrading bacteria were isolated by DNA:DNA colony hybridization, batch enrichments, and chemostat enrichment. Analysis of substrate removal and metabolite production were done using chlorinated biphenyl spray plates, reverse phase high pressure liquid chromatography, Cl - detection, and 14 C-labeled substrate mineralization methods. A bacterial consortium, designated LPS10, involved in a concerted metabolic attack on chlorinated biphenyls, was shown to mineralize 4-chlorobiphenyl (4CB) and 4,4'-dichlorobiphenyl (4,4' CB). The LPS10 consortium was isolated by both batch and chemostat enrichment using 4CB and biphenyl (BP) as sole carbon source and was found to have tree bacterial isolates that predominated; these included: Pseudomonas, testosteroni LPS10A which mediated the breakdown of 4CB and 4,4' CB to the putative meta-cleavage product and subsequently to 4-chlorobenzoic acid (4CBA), an isolate tentatively identified as an Arthrobacter sp. LPS10B which mediated 4CBA degradation, and Pseudomonas putida by A LPS10C whose role in the consortium has not been determined

  11. Yeast Interacting Proteins Database: YLR377C, YLR377C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available sis pathway, required for glucose metabolism; undergoes either proteasome-mediated or autophagy-mediated degradation depending...utophagy-mediated degradation depending on growth conditions; interacts with Vid30p Rows with this prey as p...d or autophagy-mediated degradation depending on growth conditions; interacts wit...me-mediated or autophagy-mediated degradation depending on growth conditions; int

  12. Development and validation of an enzyme-linked immunosorbent assay for the quantification of a specific MMP-9 mediated degradation fragment of type III collagen--A novel biomarker of atherosclerotic plaque remodeling

    DEFF Research Database (Denmark)

    Barascuk, Natasha; Vassiliadis, Efstathios; Larsen, Lise

    2011-01-01

    Degradation of collagen in the arterial wall by matrix metalloproteinases is the hallmark of atherosclerosis. We have developed an ELISA for the quantification of type III collagen degradation mediated by MMP-9 in urine.......Degradation of collagen in the arterial wall by matrix metalloproteinases is the hallmark of atherosclerosis. We have developed an ELISA for the quantification of type III collagen degradation mediated by MMP-9 in urine....

  13. Using the Flipped Classroom to Bridge the Gap to Generation Y.

    Science.gov (United States)

    Gillispie, Veronica

    2016-01-01

    The flipped classroom is a student-centered approach to learning that increases active learning for the student compared to traditional classroom-based instruction. In the flipped classroom model, students are first exposed to the learning material through didactics outside of the classroom, usually in the form of written material, voice-over lectures, or videos. During the formal teaching time, an instructor facilitates student-driven discussion of the material via case scenarios, allowing for complex problem solving, peer interaction, and a deep understanding of the concepts. A successful flipped classroom should have three goals: (1) allow the students to become critical thinkers, (2) fully engage students and instructors, and (3) stimulate the development of a deep understanding of the material. The flipped classroom model includes teaching and learning methods that can appeal to all four generations in the academic environment. During the 2015 academic year, we implemented the flipped classroom in the obstetrics and gynecology clerkship for the Ochsner Clinical School in New Orleans, LA. Voice-over presentations of the lectures that had been given to students in prior years were recorded and made available to the students through an online classroom. Weekly problem-based learning sessions matched to the subjects of the traditional lectures were held, and the faculty who had previously presented the information in the traditional lecture format facilitated the problem-based learning sessions. The knowledge base of students was evaluated at the end of the rotation via a multiple-choice question examination and the Objective Structured Clinical Examination (OSCE) as had been done in previous years. We compared demographic information and examination scores for traditional teaching and flipped classroom groups of students. The traditional teaching group consisted of students from Rotation 2 and Rotation 3 of the 2014 academic year who received traditional

  14. Flipping to Teach the Conceptual Foundations of Successful Workplace Writing

    Science.gov (United States)

    Campbell, Kim Sydow

    2016-01-01

    Flipping originated in science, technology, engineering, and mathematics fields, where didactic transmission of conceptual knowledge has been the standard pedagogy. Flipping has resulted in additional focus on procedural knowledge within class meetings. This article argues that business and professional writing pedagogy, which already focuses…

  15. Flipping a Dental Anatomy Course: A Retrospective Study Over Four Years

    Directory of Open Access Journals (Sweden)

    Mahmoud M. Bakr

    2016-01-01

    Full Text Available Flipped classrooms have been successfully used to increase student engagement and support student learning in a range of educational fields, including health education. These advantages for student learning supported implementation of the flipped classroom in introductory sciences and preclinical courses in dental education. We report on a 4-year retrospective study which compared two methods of delivery of a first-year dental anatomy course. The first method used the traditional method, consisting of face to face contact teaching hours, which was compared to a partial flipped classroom, where lecture contact was maintained but practical classes were flipped. A series of online videos demonstrating different practical tasks such as wax carving and tooth identification. An online digital library and online quizzes for self-reflected learning were developed and trialled. Students’ Evaluations of Course (SEC and students’ overall performance in practical and theoretical assessments were used to evaluate the impact on student engagement and success, respectively, after implementation of the modified course offerings. This study evidences the success of the transition to a partially flipped course design. Careful design and consideration of implementation of the flipped classroom method in dental education are recommended to ensure that there is reliable availability of online resources and dedicated teaching staff for construction of resources and delivery of relevant in-class activities.

  16. [Flipped classroom as a strategy to enhance active learning].

    Science.gov (United States)

    Wakabayashi, Noriyuki

    2015-03-01

    This paper reviews the introduction of a flipped class for fourth grade dentistry students, and analyzes the characteristics of the learning method. In fiscal 2013 and 2014, a series of ten three-hour units for removable partial prosthodontics were completed with the flipped class method; a lecture video of approximately 60 minutes was made by the teacher (author) and uploaded to the university's e-learning website one week before each class. Students were instructed to prepare for the class by watching the streaming video on their PC, tablet, or smartphone. In the flipped class, students were not given a lecture, but were asked to solve short questions displayed on screen, to make a short presentation about a part of the video lecture, and to discuss a critical question related to the main subject of the day. An additional team-based learning (TBL) session with individual and group answers was implemented. The average individual scores were considerably higher in the last two years, when the flipped method was implemented, than in the three previous years when conventional lectures were used. The following learning concepts were discussed: the role of the flipped method as an active learning strategy, the efficacy of lecture videos and short questions, students' participation in the class discussion, present-day value of the method, cooperation with TBL, the significance of active learning in relation with the students' learning ability, and the potential increase in the preparation time and workload for students.

  17. Student performance in a flipped classroom dental anatomy course.

    Science.gov (United States)

    Chutinan, S; Riedy, C A; Park, S E

    2017-11-09

    The purpose of this study was to assess dental student learning in a dental anatomy module between traditional lecture and flipped classroom cohorts. Two cohorts of predoctoral dental students (N = 70 within each cohort) participated in a dental anatomy module within an Introduction to the Dental Patient (IDP) course ([traditional/lecture cohort: academic year (AY) 2012, 2013] and [flipped classroom cohort: AY 2014, 2015]). For the dental anatomy module, both cohorts were evaluated on pre-clinical tooth waxing exercises immediately after each of five lectures and tooth identification after all lectures were given. Additionally, the cohorts' performance on the overall IDP course examination was compared. The flipped classroom cohort had statistically significant higher waxing scores (dental anatomy module) than students in the traditional classroom. There was no statistically significant difference for tooth identification scores and the overall IDP course examination between the traditional vs flipped approach cohorts. This is due to the latter two assessments conducted at the end of the course gave all students enough time to review the lecture content prior to the assessment resulting in similar scores for both cohorts. The flipped classroom cohort promoted students' individual learning and resulted in improved students' performance on immediate evaluation but not on the end of the course evaluation. Redesign of courses to include a new pedagogical approach should be carefully implemented and evaluated for student's educational success. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Cheliensisin A (Chel A) induces apoptosis in human bladder cancer cells by promoting PHLPP2 protein degradation.

    Science.gov (United States)

    Zhang, Ruowen; Che, Xun; Zhang, Jingjie; Li, Yang; Li, Jingxia; Deng, Xu; Zhu, Junlan; Jin, Honglei; Zhao, Qinshi; Huang, Chuanshu

    2016-10-11

    Cheliensisin A (Chel A), a styryl-lactone compound extracted from Goniothalamus cheliensis, is reported to have significant anti-cancer effects in various cancer cells. Here we demonstrated that Chel A treatment resulted in apoptosis and an inhibition of anchorage-independent growth in human bladder cancer T24, T24T and U5637 cells. Mechanistic studies showed that such effect is mediated by PH domain and Leucine rich repeat Protein Phosphatases (PHLPP2) protein. Chel A treatment led to PHLPP2 degradation and subsequently increased in c-Jun phosphorylation. Moreover PHLPP2 degradation could be attenuated by inhibition of autophagy, which was mediated by Beclin 1. Collectively, we discover that Chel A treatment induces Beclin-dependent autophagy, consequently mediates PHLPP2 degradation and JNK/C-Jun phosphorylation and activation, further in turn contributing to apoptosis in human bladder cancer cells. Current studies provide a significant insight into understanding of anticancer effect of Chel A in treatment of human bladder cancer.

  19. The influence of flip angle on the magic angle effect

    International Nuclear Information System (INIS)

    Zurlo, J.V.; Blacksin, M.F.; Karimi, S.

    2000-01-01

    Objective. To assess the impact of flip angle with gradient sequences on the ''magic angle effect''. We characterized the magic angle effect in various gradient echo sequences and compared the signal- to-noise ratios present on these sequences with the signal-to-noise ratios of spin echo sequences.Design. Ten normal healthy volunteers were positioned such that the flexor hallucis longus tendon remained at approximately at 55 to the main magnetic field (the magic angle). The tendon was imaged by a conventional spin echo T1- and T2-weighted techniques and by a series of gradient techniques. Gradient sequences were altered by both TE and flip angle. Signal-to-noise measurements were obtained at segments of the flexor hallucis longus tendon demonstrating the magic angle effect to quantify the artifact. Signal-to-noise measurements were compared and statistical analysis performed. Similar measurements were taken of the anterior tibialis tendon as an internal control.Results and conclusions. We demonstrated the magic angle effect on all the gradient sequences. The intensity of the artifact was affected by both the TE and flip angle. Low TE values and a high flip angle demonstrated the greatest magic angle effect. At TE values less than 30 ms, a high flip angle will markedly increase the magic angle effect. (orig.)

  20. Critical role of DNA intercalation in enzyme-catalyzed nucleotide flipping

    Science.gov (United States)

    Hendershot, Jenna M.; O'Brien, Patrick J.

    2014-01-01

    Nucleotide flipping is a common feature of DNA-modifying enzymes that allows access to target sites within duplex DNA. Structural studies have identified many intercalating amino acid side chains in a wide variety of enzymes, but the functional contribution of these intercalating residues is poorly understood. We used site-directed mutagenesis and transient kinetic approaches to dissect the energetic contribution of intercalation for human alkyladenine DNA glycosylase, an enzyme that initiates repair of alkylation damage. When AAG flips out a damaged nucleotide, the void in the duplex is filled by a conserved tyrosine (Y162). We find that tyrosine intercalation confers 140-fold stabilization of the extrahelical specific recognition complex, and that Y162 functions as a plug to slow the rate of unflipping by 6000-fold relative to the Y162A mutant. Surprisingly, mutation to the smaller alanine side chain increases the rate of nucleotide flipping by 50-fold relative to the wild-type enzyme. This provides evidence against the popular model that DNA intercalation accelerates nucleotide flipping. In the case of AAG, DNA intercalation contributes to the specific binding of a damaged nucleotide, but this enhanced specificity comes at the cost of reduced speed of nucleotide flipping. PMID:25324304

  1. Degradation of anthracene by laccase of Trametes versicolor in the presence of different mediator compounds.

    Science.gov (United States)

    Johannes, C; Majcherczyk, A; Hüttermann, A

    1996-10-01

    Laccase of Trametes versicolor was generally able to oxidize anthracene in vitro. After 72 h incubation about 35% of the anthracene was transformed stoichiometrically to 9,10-anthraquinone. Transformation of anthracene increased rapidly in the presence of different mediators that readily generate stable radicals: 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and 1-hydroxybenzotriazole. For the reaction, the presence of both the laccase and the mediator was necessary. In the presence of 0.005 mM 1-hydroxybenzotriazole this conversion had removed 47% of the anthracene after 72 h; 75% of the substrate was oxidized during this period when ABTS (1 mM) was used as mediator. In contrast to reactions without or with only low concentrations of a mediator, there was a discrepancy between the disappearance of anthracene and the formation of 9,10-anthraquinone in mediator-forced reactions. Coupling-products of mediators with anthracene degradation products were found. Anthracene disappeared nearly completely after incubation for 72 h with laccase in a 0.1 mM solution of 1-hydroxybenzotriazole and was transformed to 9,10-anthraquinone in about 80% yield; 90% of the substrate was transformed in the presence of ABTS (2.0 mM) resulting again in 80% quinone. Phenothiazine was not effective in this system.

  2. The Flipped Classroom - From Theory to Practice in Health Professional Education.

    Science.gov (United States)

    Persky, Adam M; McLaughlin, Jacqueline E

    2017-08-01

    The flipped classroom is growing in popularity in health professional education. As such, instructors are experiencing various growing pains in functionalizing this model, from justifying the approach to managing time inside and outside of class to assessing impact on learning. This review focuses on some key theories that support the flipped model and translates those key theories into practice across core aspects of the flipped classroom: pre-class preparation, in-class activities, after-class activities and assessment of student learning.

  3. Separation of flip and non-flip parts of np → pn charge exchange at energies Tn = 0,5-2,0 GeV

    International Nuclear Information System (INIS)

    Shindin, R.A.; Gur'ev, D.K.; Morozov, A.A.; Nomofilov, A.A.; Strunov, L.N.

    2011-01-01

    The new 'Delta-Sigma' experimental data on the ratio R dp allowed separating the Flip and Non-Flip parts of the differential cross section of np → pn charge exchange process at the zero angle by the Dean formula. The PSA solutions for the np → np elastic scattering are transformed to the np → pn charge exchange representation using unitary transition, and good agreement is obtained

  4. Selection of the new position for the instrumented fuel Flip type; Seleccion de la nueva posicion para el combustible instrumentado tipo Flip

    Energy Technology Data Exchange (ETDEWEB)

    Paredes G, L C

    1991-12-15

    It was selected and proved the new position for the instrumented fuel, in function of the smallest influence on the temperature of the fuel due to movements of the control bars, as well as to its functionality regarding their geometric localization in the core. Therefore, it intends that the instrumented fuel Flip type, pass from the position C-9 to the C-6. It was selected the turn angle of the fuel of 180 C, for to be the one that presents a smaller influence of the control bars and it allows to register the values of temperature but high. It was as the movements of the control bars they produce local interferences of the neutron flow in the fuels and that in the case of the ring C, these interferences became maximum variations of the fuel temperature of 125 C, for operations to 1 MW in the thermal column. (Author)

  5. Formation of very short pulse by neutron spin flip chopper for J-PARC

    International Nuclear Information System (INIS)

    Ebisawa, T.; Soyama, K.; Yamazaki, D.; Tasaki, S.; Sakai, K.; Oku, T.; Maruyama, R.; Hino, M.

    2004-01-01

    We have developed neutron spin flip choppers with high S/N ratio and high intensity for pulsed sources using multi-stage spin flip choppers. It is not easy for us to obtain a very short neutron pulse less than 10 μs using a spin flip chopper, due to the time constant L/R in the normal LR circuit. We will discuss a method obtaining a very short neutron pulse applying the modified push-pull circuit proposed by Ito and Takahashi [4] to the double spin flip chopper with polarizing guides

  6. Students' Perceptions and Emotions Toward Learning in a Flipped General Science Classroom

    Science.gov (United States)

    Jeong, Jin Su; González-Gómez, David; Cañada-Cañada, Florentina

    2016-10-01

    Recently, the inverted instruction methodologies are gaining attentions in higher educations by claiming that flipping the classroom engages more effectively students with the learning process. Besides, students' perceptions and emotions involved in their learning process must be assessed in order to gauge the usability of this relatively new instruction methodology, since it is vital in the educational formation. For this reason, this study intends to evaluate the students' perceptions and emotions when a flipped classroom setting is used as instruction methodology. This research was conducted in a general science course, sophomore of the Primary Education bachelor degree in the Training Teaching School of the University of Extremadura (Spain). The results show that the students have the overall positive perceptions to a flipped classroom setting. Particularly, over 80 % of them considered that the course was a valuable learning experience. They also found this course more interactive and were willing to have more courses following a flipped model. According to the students' emotions toward a flipped classroom course, the highest scores were given to the positive emotions, being fun and enthusiasm along with keyword frequency test. Then, the lowest scores were corresponded to negative emotions, being boredom and fear. Therefore, the students attending to a flipped course demonstrated to have more positive and less negative emotions. The results obtained in this study allow drawing a promising tendency about the students' perceptions and emotions toward the flipped classroom methodology and will contribute to fully frame this relatively new instruction methodology.

  7. The Flipped Classroom in Systems Analysis & Design: Leveraging Technology to Increase Student Engagement

    Science.gov (United States)

    Saulnier, Bruce M.

    2015-01-01

    Problems associated with the ubiquitous presence of technology on college campuses are discussed and the concept of the flipped classroom is explained. Benefits of using the flipped classroom to offset issues associated with the presence of technology in the classroom are explored. Fink's Integrated Course Design is used to develop a flipped class…

  8. A Conserved C-terminal Element in the Yeast Doa10 and Human MARCH6 Ubiquitin Ligases Required for Selective Substrate Degradation.

    Science.gov (United States)

    Zattas, Dimitrios; Berk, Jason M; Kreft, Stefan G; Hochstrasser, Mark

    2016-06-03

    Specific proteins are modified by ubiquitin at the endoplasmic reticulum (ER) and are degraded by the proteasome, a process referred to as ER-associated protein degradation. In Saccharomyces cerevisiae, two principal ER-associated protein degradation ubiquitin ligases (E3s) reside in the ER membrane, Doa10 and Hrd1. The membrane-embedded Doa10 functions in the degradation of substrates in the ER membrane, nuclear envelope, cytoplasm, and nucleoplasm. How most E3 ligases, including Doa10, recognize their protein substrates remains poorly understood. Here we describe a previously unappreciated but highly conserved C-terminal element (CTE) in Doa10; this cytosolically disposed 16-residue motif follows the final transmembrane helix. A conserved CTE asparagine residue is required for ubiquitylation and degradation of a subset of Doa10 substrates. Such selectivity suggests that the Doa10 CTE is involved in substrate discrimination and not general ligase function. Functional conservation of the CTE was investigated in the human ortholog of Doa10, MARCH6 (TEB4), by analyzing MARCH6 autoregulation of its own degradation. Mutation of the conserved Asn residue (N890A) in the MARCH6 CTE stabilized the normally short lived enzyme to the same degree as a catalytically inactivating mutation (C9A). We also report the localization of endogenous MARCH6 to the ER using epitope tagging of the genomic MARCH6 locus by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated genome editing. These localization and CTE analyses support the inference that MARCH6 and Doa10 are functionally similar. Moreover, our results with the yeast enzyme suggest that the CTE is involved in the recognition and/or ubiquitylation of specific protein substrates. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. An Investigation of the Use of the ‘Flipped Classroom’ Pedagogy in Secondary English Language Classrooms

    OpenAIRE

    Chi Cheung Ruby Yang

    2017-01-01

    Aim/Purpose : To examine the use of a flipped classroom in the English Language subject in secondary classrooms in Hong Kong. Background: The research questions addressed were: (1) What are teachers’ perceptions towards the flipped classroom pedagogy? (2) How can teachers transfer their flipped classroom experiences to teaching other classes/subjects? (3) What are students’ perceptions towards the flipped classroom pedagogy? (4) How can students transfer their flipped classroom experience...

  10. THE IMPLEMENTATION OF FLIPPED CLASSROOM MODEL IN EFL WRITING

    Directory of Open Access Journals (Sweden)

    Rida Afrilyasanti

    2016-10-01

    Full Text Available Flipped classroom is an approach to learning to write that allows teachers to have one-on-one assistance to help learners in the “during writing” stage in the classroom. Theories are given to the students in a video lectures to watch before class. Because problems in writing mostly occur in “during writing” stage, teacher assistance is crucial. This paper aims to share theoretical review and research findings pertaining to the implementation of flipped classroom model to EFL writing. Research findings show that flipped classroom is able to give greater opportunities for interactive sessions in class which focus on the students’ own concerns, questions, and needs. Therefore, students’ difficulties in “during writing” stage can be minimized

  11. CNPY2 inhibits MYLIP-mediated AR protein degradation in prostate cancer cells.

    Science.gov (United States)

    Ito, Saya; Ueno, Akihisa; Ueda, Takashi; Nakagawa, Hideo; Taniguchi, Hidefumi; Kayukawa, Naruhiro; Fujihara-Iwata, Atsuko; Hongo, Fumiya; Okihara, Koji; Ukimura, Osamu

    2018-04-03

    The androgen receptor (AR) is a ligand-dependent transcription factor that promotes prostate cancer (PC) cell growth through control of target gene expression. This report suggests that Canopy FGF signaling regulator 2 (CNPY2) controls AR protein levels in PC cells. We found that AR was ubiquitinated by an E3 ubiquitin ligase, myosin regulatory light chain interacting protein (MYLIP) and then degraded through the ubiquitin-proteasome pathway. CNPY2 decreased the ubiquitination activity of MYLIP by inhibition of interaction between MYLIP and UBE2D1, an E2 ubiquitin ligase. CNPY2 up-regulated gene expression of AR target genes such as KLK3 gene which encodes the prostate specific antigen (PSA) and promoted cell growth of PC cells. The cell growth inhibition by CNPY2 knockdown was rescued by AR overexpression. Furthermore, positive correlation of expression levels between CNPY2 and AR/AR target genes was observed in tissue samples from human prostate cancer patients. Together, these results suggested that CNPY2 promoted cell growth of PC cells by inhibition of AR protein degradation through MYLIP-mediated AR ubiquitination.

  12. 99.9% Spin-Flip Efficiency in the Presence of a Strong Siberian Snake

    International Nuclear Information System (INIS)

    Morozov, V.S.; Blinov, B.B.; Etienne, Z.B.; Krisch, A.D.; Leonova, M.A.; Lin, A.M.T.; Lorenzon, W.; Peters, C.C.; Sivers, D.W.; Wong, V.K.; Yonehara, K.; Anferov, V. A.; Schwandt, P.; Stephenson, E.J.; Przewoski, B. von; Sato, H.

    2003-01-01

    We recently studied the spin-flipping efficiency of an rf-dipole magnet using a 120-MeV horizontally polarized proton beam stored in the Indiana University Cyclotron Facility Cooler Ring, which contained a full Siberian snake. We flipped the spin by ramping the rf dipole's frequency through an rf-induced depolarizing resonance. By adiabatically turning on the rf dipole, we minimized the beam loss, while preserving almost all of the beam's polarization. After optimizing the frequency ramp parameters, we used up to 400 multiple spin flips to measure a spin-flip efficiency of 99.93 ± 0.02%. This result indicates that spin flipping should be possible in very-high-energy polarized storage rings, where Siberian snakes are certainly needed and only dipole rf-flipper magnets are practical

  13. Evaluation of the Effects of Flipped Learning of a Nursing Informatics Course.

    Science.gov (United States)

    Oh, Jina; Kim, Shin-Jeong; Kim, Sunghee; Vasuki, Rajaguru

    2017-08-01

    This study evaluated the effects of flipped learning in a nursing informatics course. Sixty-four undergraduate students attending a flipped learning nursing informatics course at a university in South Korea participated in this study in 2013. Of these, 43 students participated at University A, and 46 students participated at University B, as a comparison group. Three levels of Kirkpatrick's evaluation model were used: level one (the students' satisfaction), level two (achievement on the course outcomes), and level three (self-perceived nursing informatics competencies). Students of the flipped learning course reported positive effects above the middle degree of satisfaction (level one) and achieved the course outcomes (level two). In addition, self-perceived nursing informatics competencies (level three) of the flipped learning group were higher than those of the comparison group. A flipped learning nursing informatics course is an effective teaching strategy for preparing new graduate nurses in the clinical setting. [J Nurs Educ. 2017;56(8):477-483.]. Copyright 2017, SLACK Incorporated.

  14. FLIP for FLAG model visualization

    Energy Technology Data Exchange (ETDEWEB)

    Wooten, Hasani Omar [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-11-15

    A graphical user interface has been developed for FLAG users. FLIP (FLAG Input deck Parser) provides users with an organized view of FLAG models and a means for efficiently and easily navigating and editing nodes, parameters, and variables.

  15. Evaluation of the flipped classroom approach in a veterinary professional skills course.

    Science.gov (United States)

    Moffett, Jenny; Mill, Aileen C

    2014-01-01

    The flipped classroom is an educational approach that has had much recent coverage in the literature. Relatively few studies, however, use objective assessment of student performance to measure the impact of the flipped classroom on learning. The purpose of this study was to evaluate the use of a flipped classroom approach within a medical education setting to the first two levels of Kirkpatrick and Kirkpatrick's effectiveness of training framework. This study examined the use of a flipped classroom approach within a professional skills course offered to postgraduate veterinary students. A questionnaire was administered to two cohorts of students: those who had completed a traditional, lecture-based version of the course (Introduction to Veterinary Medicine [IVM]) and those who had completed a flipped classroom version (Veterinary Professional Foundations I [VPF I]). The academic performance of students within both cohorts was assessed using a set of multiple-choice items (n=24) nested within a written examination. Data obtained from the questionnaire were analyzed using Cronbach's alpha, Kruskal-Wallis tests, and factor analysis. Data obtained from student performance in the written examination were analyzed using the nonparametric Wilcoxon rank sum test. A total of 133 IVM students and 64 VPF I students (n=197) agreed to take part in the study. Overall, study participants favored the flipped classroom approach over the traditional classroom approach. With respect to student academic performance, the traditional classroom students outperformed the flipped classroom students on a series of multiple-choice items (IVM mean =21.4±1.48 standard deviation; VPF I mean =20.25±2.20 standard deviation; Wilcoxon test, w=7,578; Pflipped classroom approach. The flipped classroom was rated more positively than the traditional classroom on many different characteristics. This preference, however, did not translate into improved student performance, as assessed by a series of

  16. Assisted crack tip flipping under Mode I thin sheet tearing

    DEFF Research Database (Denmark)

    Felter, Christian Lotz; Nielsen, Kim Lau

    2017-01-01

    Crack tip flipping, where the fracture surface alternates from side to side in roughly 45° shear bands, seems to be an overlooked propagation mode in Mode I thin sheet tearing. In fact, observations of crack tip flipping is rarely found in the literature. Unlike the already established modes...

  17. The Flipped Class: Experience in a University Business Communication Course

    Science.gov (United States)

    Sherrow, Tammy; Lang, Brenda; Corbett, Rod

    2016-01-01

    Business, like many other programs in higher education, continues to rely largely on traditional classroom environments. In this article, another approach to teaching and learning, the flipped classroom, is explored. After a review of relevant literature, the authors present their experience with the flipped classroom approach to teaching and…

  18. Flipped Classroom: Effects on Education for the Case of Economics

    Science.gov (United States)

    Kurihara, Yutaka

    2016-01-01

    The notion of the flipped classroom has been received much attention in the literature as it may increase learning outcomes and learning effectiveness elementary and secondary education as well as university learning. In the author's class on international finance (economics) features a blended flipped classroom and lecture; questionnaires were…

  19. Exploring Flipped Classroom Effects on Second Language Learners' Cognitive Processing

    Science.gov (United States)

    Kim, Jeong-eun; Park, Hyunjin; Jang, Mijung; Nam, Hosung

    2017-01-01

    This study investigated the cognitive effects of the flipped classroom approach in a content-based instructional context by comparing second language learners' discourse in flipped vs. traditional classrooms in terms of (1) participation rate, (2) content of comments, (3) reasoning skills, and (4) interactional patterns. Learners in two intact…

  20. Curriculum Design of a Flipped Classroom to Enhance Haematology Learning

    Science.gov (United States)

    Porcaro, Pauline A.; Jackson, Denise E.; McLaughlin, Patricia M.; O'Malley, Cindy J.

    2016-01-01

    A common trend in higher education is the "flipped" classroom, which facilitates active learning during class. The flipped approach to teaching was instituted in a haematology "major" class and the students' attitudes and preferences for the teaching materials were surveyed. The curriculum design was explicit and involved four…

  1. Student evaluation of the flipped classroom instruction method: is it aligned with Problem-Based Learning?

    DEFF Research Database (Denmark)

    Triantafyllou, Evangelia; Timcenko, Olga; Kofoed, Lise

    2017-01-01

    The flipped classroom approach is an instructional method that has gained momentum in the last years. In a flipped classroom the traditional lecture and homework sessions are inverted. We believe that the flipped classroom, which employs computer-based individual instruction outside the classroom...... presents data from the second year, where we conducted a survey study among students participating in the flipped statistics course. This study consisted of two surveys designed to gather student perceptions on the out-of-classroom preparation material (videos and quizzes) and the flipped classroom...

  2. Plant species influence on soil C after afforestation of Mediterranean degraded soils

    Science.gov (United States)

    Dominguez, Maria T.; García-Vargas, Carlos; Madejón, Engracia; Marañón, Teodoro

    2015-04-01

    Increasing C sequestration in terrestrial ecosystems is one of the main current environmental challenges to mitigate climate change. Afforestation of degraded and contaminated lands is one of the key strategies to achieve an increase in C sequestration in ecosystems. Plant species differ in their mechanisms of C-fixation, C allocation into different plant organs, and interaction with soil microorganisms, all these factors influencing the dynamics of soil C following the afforestation of degraded soils. In this work we examine the influence of different woody plant species on soil C dynamics in degraded and afforested Mediterranean soils. The soils were former agricultural lands that were polluted by a mining accident and later afforested with different native plant species. We analysed the effect of four of these species (Olea europaea var. sylvestris Brot., Populus alba L., Pistacia lentiscus L. and Retama sphaerocarpa (L.) Boiss.) on different soil C fractions, soil nutrient availability, microbial activity (soil enzyme activities) and soil CO2 fluxes 15 years after the establishment of the plantations. Results suggest that the influence of the planted trees and shrubs is still limited, being more pronounced in the more acidic and nutrient-poor soils. Litter accumulation varied among species, with the highest C accumulated in the litter under the deciduous species (Populus alba L.). No differences were observed in the amount of total soil organic C among the studied species, or in the concentrations of phenols and sugars in the dissolved organic C (DOC), which might have indicated differences in the biodegradability of the DOC. Microbial biomass and activity was highly influenced by soil pH, and plant species had a significant influence on soil pH in the more acidic site. Soil CO2 fluxes were more influenced by the plant species than total soil C content. Our results suggest that changes in total soil C stocks after the afforestation of degraded Mediterranean

  3. K-12 Teacher Perceptions Regarding the Flipped Classroom Model for Teaching and Learning

    Science.gov (United States)

    Gough, Evan; DeJong, David; Grundmeyer, Trent; Baron, Mark

    2017-01-01

    A great deal of evidence can be cited from higher education literature on the effectiveness of the flipped classroom; however, very little research was discovered on the flipped classroom at the K-12 level. This study examined K-12 teachers' perceptions regarding the flipped classroom and differences in teachers' perceptions based on grade level…

  4. Polarizing a stored proton beam by spin-flip?

    Energy Technology Data Exchange (ETDEWEB)

    Oellers, Dieter Gerd Christian

    2010-04-15

    The present thesis discusses the extraction of the electron-proton spin-flip cross-section. The experimental setup, the data analysis and the results are pictured in detail. The proton is described by a QCD-based parton model. In leading twist three functions are needed. The quark distribution, the helicity distribution and the transversity distribution. While the first two are well-known, the transversity distribution is largely unknown. A self-sufficient measurement of the transversity is possible in double polarized proton-antiproton scattering. This rises the need of a polarized antiproton beam. So far spin filtering is the only tested method to produce a polarized proton beam, which may be capable to hold also for antiprotons. In-situ polarization build-up of a stored beam either by selective removal or by spin-flip of a spin-(1)/(2) beam is mathematically described. A high spin-flip cross-section would create an effective method to produce a polarized antiproton beam by polarized positrons. Prompted by conflicting calculations, a measurement of the spin-flip cross-section in low-energy electron-proton scattering was carried out. This experiment uses the electron beam of the electron cooler at COSY as an electron target. The depolarization of the stored proton beam is detected. An overview of the experiment is followed by detailed descriptions of the cycle setup, of the electron target and the ANKE silicon tracking telescopes acting as a beam polarimeter. Elastic protondeuteron scattering is the analyzing reaction. The event selection is depicted and the beam polarization is calculated. Upper limits of the two electron-proton spin-flip cross-sections {sigma} {sub parallel} and {sigma} {sub perpendicular} {sub to} are deduced using the likelihood method. (orig.)

  5. Dual action of vitamin C versus degradation and supplementation

    Directory of Open Access Journals (Sweden)

    Katarzyna Kaliś

    2015-11-01

    Full Text Available The article discusses vitamin C from the point of view of its supplementation with food and in the form of oral supplements. The dual action of vitamin C is connected with the presence of oxygen, which may reduce the amount of the vitamin in food products, influence thermal resistance, cause degradation and show an antioxidation effect. Vitamin C stimulates the immune cells and collagen synthesis. It may protect the LDL fraction against oxidation, and therefore it is interesting for cosmetology, rheumatology, immunology and dietetics. The latest research with respect to vitamin C proved that it has the ability to dissolve neurotoxic senile plaques. Equally effective in the treatment of Alzheimer’s disease is the oxidised form of vitamin C, i.e. dehydroascorbic acid. Vitamin C may be used in a combined vitamin E supplementation to avoid the pro-oxidative effect and reduce the risk of diabetes mellitus type 2 complications. In the review there is a description of the types of vitamin C degradation depending on a specific factor such as pH, temperature, oxygen, enzyme and the impact of diet on the quantity of the supplied vitamin. The literature data confirmed the positive influence of vitamin C as an addition to food. The last part of the article presents the methods of vitamin C protection used in food processing technology and of determining its content in food products. Additionally, the article describes the problems related to vitamin C oxidation processes during food processing and storage. The presented research results indicate that an adequate diet contains a sufficient amount of vitamin C for healthy people. In the case of chronic patients it is better to use supplementation.

  6. Extracellular collagenases and the endocytic receptor, urokinase plasminogen activator receptor-associated protein/Endo180, cooperate in fibroblast-mediated collagen degradation

    DEFF Research Database (Denmark)

    Madsen, Daniel H; Engelholm, Lars H; Ingvarsen, Signe

    2007-01-01

    in these events. A recently discovered turnover route with importance for tumor growth involves intracellular collagen degradation and is governed by the collagen receptor, urokinase plasminogen activator receptor-associated protein (uPARAP or Endo180). The interplay between this mechanism and extracellular...... collagenolysis is not known. In this report, we demonstrate the existence of a new, composite collagen breakdown pathway. Thus, fibroblast-mediated collagen degradation proceeds preferentially as a sequential mechanism in which extracellular collagenolysis is followed by uPARAP/Endo180-mediated endocytosis......The collagens of the extracellular matrix are the most abundant structural proteins in the mammalian body. In tissue remodeling and in the invasive growth of malignant tumors, collagens constitute an important barrier, and consequently, the turnover of collagen is a rate-limiting process...

  7. Flipping around the classroom: Accelerated Bachelor of Science in Nursing students' satisfaction and achievement.

    Science.gov (United States)

    El-Banna, Majeda M; Whitlow, Malinda; McNelis, Angela M

    2017-09-01

    The flipped classroom approach is based on shared responsibility for learning by students and teachers, and empowers students to take an active role in the learning process. While utilization of this approach has resulted in higher exam scores compared to traditional approaches in prior studies, the flipped classroom has not included learners in Accelerated Bachelor of Science in Nursing (ABSN) programs. To examine differences on exam scores and satisfaction of teaching between a 3-week flipped and traditional classroom approach. Mixed methods, crossover repeated measures design. Private school of nursing located in the eastern United States. 76 ABSN students. Two separate sections of a Pharmacology course received either 3-weeks of flipped or traditional classroom during Period 1, then switched approaches during Period 2. Two exam scores measuring knowledge and a questionnaire assessing satisfaction of teaching were collected. Focus groups were conducted to learn about students' experience in the flipped classroom. Descriptive statistics, Wilcoxon rank sum test, and stepwise linear mixed model were used to analyze quantitative data. Focus group data were transcribed, coded, and categorized in themes. Students in the flipped classroom achieved significantly higher scores on the first Pharmacology exam than students in the traditional classroom, but there was no significant difference on the second exam. Three themes emerged from focus groups on student perception of integrating the flipped approach: don't fix what isn't broken; treat me as an adult; and remember the work is overwhelming. Both traditional and flipped classroom approaches successfully prepared students for the Pharmacology exams. While results support the use of the flipped approach, judicious use of this instructional pedagogy with dense or difficult content, particularly in accelerated programs, is recommended. Instructors should also provide students with enough information and rationale for using

  8. Preliminary investigations of a mixed standard-flip core for a TRIGA Mark II

    International Nuclear Information System (INIS)

    Ringle, John C.; Johnson, A.G.; Anderson, T.V.

    1974-01-01

    Several years ago it became apparent that due to our rapidly- increasing use rate, we would need a substantial amount of new fuel by late 1974 or early 1975. After investigations and discussions with GA, we decided that FLIP fuel would best meet our requirements for maximum fuel economy and high peak pulsing power. A proposal was submitted to the AEC for fuel assistance, and late in 1973 we were awarded a grant of $61,875. This will allow us to buy 3 FLIP-fueled-follower control rods, 1 instrumented FLIP fuel element, and 26 standard FLIP elements, giving us then a mixed core of approximately one-third FLIP and two-thirds standard elements. License amendments to accommodate this change are rather straightforward; modifications to the Technical Specifications will be somewhat more involved. The largest revisions which we envision are to our Safety Analysis Report. Although a few reactors have operated with a full FLIP core, and a few others have converted to mixed standard-FLIP cores, none of these has a standard Mark II core configuration. Those who have already converted to a mixed core have data and calculations which may be helpful to us, but the extent to which we can use these remains to be seen. The present status of our investigations into the analysis of a mixed standard-FLIP core will be presented. Any problems in calculational methods, finding appropriate data, modifications to Technical Specifications, etc., will be identified, and suggestions and help in these areas will be welcomed. (author)

  9. Preliminary investigations of a mixed standard-flip core for a TRIGA Mark II

    Energy Technology Data Exchange (ETDEWEB)

    Ringle, John C; Johnson, A G; Anderson, T V [Oregon State University (United States)

    1974-07-01

    Several years ago it became apparent that due to our rapidly- increasing use rate, we would need a substantial amount of new fuel by late 1974 or early 1975. After investigations and discussions with GA, we decided that FLIP fuel would best meet our requirements for maximum fuel economy and high peak pulsing power. A proposal was submitted to the AEC for fuel assistance, and late in 1973 we were awarded a grant of $61,875. This will allow us to buy 3 FLIP-fueled-follower control rods, 1 instrumented FLIP fuel element, and 26 standard FLIP elements, giving us then a mixed core of approximately one-third FLIP and two-thirds standard elements. License amendments to accommodate this change are rather straightforward; modifications to the Technical Specifications will be somewhat more involved. The largest revisions which we envision are to our Safety Analysis Report. Although a few reactors have operated with a full FLIP core, and a few others have converted to mixed standard-FLIP cores, none of these has a standard Mark II core configuration. Those who have already converted to a mixed core have data and calculations which may be helpful to us, but the extent to which we can use these remains to be seen. The present status of our investigations into the analysis of a mixed standard-FLIP core will be presented. Any problems in calculational methods, finding appropriate data, modifications to Technical Specifications, etc., will be identified, and suggestions and help in these areas will be welcomed. (author)

  10. Assessing the Flipped Classroom in Operations Management: A Pilot Study

    Science.gov (United States)

    Prashar, Anupama

    2015-01-01

    The author delved into the results of a flipped classroom pilot conducted for an operations management course module. It assessed students' perception of a flipped learning environment after making them experience it in real time. The classroom environment was construed using a case research approach and students' perceptions were studied using…

  11. Examining Student Perceptions of Flipping an Agricultural Teaching Methods Course

    Science.gov (United States)

    Conner, Nathan W.; Rubenstein, Eric D.; DiBenedetto, Cathy A.; Stripling, Christopher T.; Roberts, T. Grady; Stedman, Nicole L. P.

    2014-01-01

    To meet the needs of the 21st century student, college instructors have been challenged to transform their classrooms from passive to active, "minds-on" learning environments. This qualitative study examined an active learning approach known as a flipped classroom and sought to explore student perceptions of flipping a teaching methods…

  12. The Implementation of a Flipped Classroom in Foreign Language Teaching

    Science.gov (United States)

    Basal, Ahmet

    2015-01-01

    Alongside the rise of educational technology, many teachers have been taking gradual but innovative steps to redesign their teaching methods. For example, in flipped learning or a flipped classroom, students watch instructional videos outside the classroom and do assignments or engage in activities inside the classroom. Language teachers are one…

  13. Structural insights into 2,2'-azino-Bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)-mediated degradation of reactive blue 21 by engineered Cyathus bulleri Laccase and characterization of degradation products.

    Science.gov (United States)

    Kenzom, T; Srivastava, P; Mishra, S

    2014-12-01

    Advanced oxidation processes are currently used for the treatment of different reactive dyes which involve use of toxic catalysts. Peroxidases are reported to be effective on such dyes and require hydrogen peroxide and/or metal ions. Cyathus bulleri laccase, expressed in Pichia pastoris, catalyzes efficient degradation (78 to 85%) of reactive azo dyes (reactive black 5, reactive orange 16, and reactive red 198) in the presence of synthetic mediator ABTS [2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)]. This laccase was engineered to degrade effectively reactive blue 21 (RB21), a phthalocyanine dye reported to be decolorized only by peroxidases. The 816-bp segment (toward the C terminus) of the lcc gene was subjected to random mutagenesis and enzyme variants (Lcc35, Lcc61, and Lcc62) were selected based on increased ABTS oxidizing ability. Around 78 to 95% decolorization of RB21 was observed with the ABTS-supplemented Lcc variants in 30 min. Analysis of the degradation products by mass spectrometry indicated the formation of several low-molecular-weight compounds. Mapping the mutations on the modeled structure implicated residues both near and far from the T1 Cu site that affected the catalytic efficiency of the mutant enzymes on ABTS and, in turn, the rate of oxidation of RB21. Several inactive clones were also mapped. The importance of geometry as well as electronic changes on the reactivity of laccases was indicated. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  14. Serial composition of quantum coin flipping and bounds on cheat detection for bit commitment

    International Nuclear Information System (INIS)

    Mochon, Carlos

    2004-01-01

    Quantum protocols for coin flipping can be composed in series in such a way that a cheating party gains no extra advantage from using entanglement between different rounds. This composition principle applies to coin-flipping protocols with cheat sensitivity as well, and is used to derive two results: There are no quantum strong coin-flipping protocols with cheat sensitivity that is linear in the bias (or bit-commitment protocols with linear cheat detection) because these can be composed to produce strong coin flipping with arbitrarily small bias. On the other hand, it appears that quadratic cheat detection cannot be composed in series to obtain even weak coin flipping with arbitrarily small bias

  15. Higgs Mass Textures in Flipped SU(5)

    CERN Document Server

    Ellis, Jonathan Richard; Rizos, J; Ellis, John

    1999-01-01

    We analyze the Higgs doublet-triplet mass splitting problem in the version of flipped SU(5) derived from string theory. Analyzing non-renormalizable terms up to tenth order in the superpotential, we identify a pattern of field vev's that keeps one pair of electroweak Higgs doublets light, while all other Higgs doublets and all Higgs triplets are kept heavy, with the aid of the economical missing-doublet mechanism found in the field-theoretical version of flipped SU(5). The solution predicts that second-generation charge -1/3 quarks and charged leptons are much lighter than those in the third generation.

  16. Investigating Flipped Learning: Student Self-Regulated Learning, Perceptions, and Achievement in an Introductory Biology Course

    Science.gov (United States)

    Sletten, Sarah Rae

    2017-06-01

    In flipped classrooms, lectures, which are normally delivered in-class, are assigned as homework in the form of videos, and assignments that were traditionally assigned as homework, are done as learning activities in class. It was hypothesized that the effectiveness of the flipped model hinges on a student's desire and ability to adopt a self-directed learning style. The purpose of this study was twofold; it aimed at examining the relationship between two variables—students' perceptions of the flipped model and their self-regulated learning (SRL) behaviors—and the impact that these variables have on achievement in a flipped class. For the study, 76 participants from a flipped introductory biology course were asked about their SRL strategy use and perceptions of the flipped model. SRL strategy use was measured using a modified version of the Motivated Strategies for Learning Questionnaire (MSLQ; Wolters et al. 2005), while the flipped perceptions survey was newly derived. Student letter grades were collected as a measure of achievement. Through regression analysis, it was found that students' perceptions of the flipped model positively predict students' use of several types of SRL strategies. However, the data did not indicate a relationship between student perceptions and achievement, neither directly nor indirectly, through SRL strategy use. Results suggest that flipped classrooms demonstrate their successes in the active learning sessions through constructivist teaching methods. Video lectures hold an important role in flipped classes, however, students may need to practice SRL skills to become more self-directed and effectively learn from them.

  17. Quantum protocol for cheat-sensitive weak coin flipping.

    Science.gov (United States)

    Spekkens, R W; Rudolph, Terry

    2002-11-25

    We present a quantum protocol for the task of weak coin flipping. We find that, for one choice of parameters in the protocol, the maximum probability of a dishonest party winning the coin flip if the other party is honest is 1/sqrt[2]. We also show that if parties restrict themselves to strategies wherein they cannot be caught cheating, their maximum probability of winning can be even smaller. As such, the protocol offers additional security in the form of cheat sensitivity.

  18. Case Study: Guidelines for Producing Videos to Accompany Flipped Cases

    Science.gov (United States)

    Prud'homme-Généreux, Annie; Schiller, Nancy A.; Wild, John H.; Herreid, Clyde Freeman

    2017-01-01

    Three years ago, the "National Center for Case Study Teaching in Science" (NCCSTS) was inspired to merge the case study and flipped classroom approaches. The resulting project aimed to create the materials required to teach a flipped course in introductory biology by assigning videos as homework and case studies in the classroom. Three…

  19. An Inquiry into Flipped Learning in Fourth Grade Math Instruction

    Science.gov (United States)

    D'addato, Teresa; Miller, Libbi R.

    2016-01-01

    The objective of this action research project was to better understand the impact of flipped learning on fourth grade math students in a socioeconomically disadvantaged setting. A flipped instructional model was implemented with the group of students enrolled in the researcher's class. Data was collected in the form of classroom observations,…

  20. Implementing the Flipped Classroom in Teacher Education: Evidence from Turkey

    Science.gov (United States)

    Kurt, Gökçe

    2017-01-01

    The flipped classroom, a form of blended learning, is an emerging instructional strategy reversing a traditional lecture-based teaching model to improve the quality and efficiency of the teaching and learning process. The present article reports a study that focused on the implementation of the flipped approach in a higher education institution in…

  1. Flipped Classroom Research and Trends from Different Fields of Study

    Science.gov (United States)

    Zainuddin, Zamzami; Halili, Siti Hajar

    2016-01-01

    This paper aims to analyse the trends and contents of flipped classroom research based on 20 articles that report on flipped learning classroom initiatives from 2013-2015. The content analysis was used as a methodology to investigate methodologies, area of studies, technology tools or online platforms, the most frequently used keywords and works…

  2. A New Pixels Flipping Method for Huge Watermarking Capacity of the Invoice Font Image

    Directory of Open Access Journals (Sweden)

    Li Li

    2014-01-01

    Full Text Available Invoice printing just has two-color printing, so invoice font image can be seen as binary image. To embed watermarks into invoice image, the pixels need to be flipped. The more huge the watermark is, the more the pixels need to be flipped. We proposed a new pixels flipping method in invoice image for huge watermarking capacity. The pixels flipping method includes one novel interpolation method for binary image, one flippable pixels evaluation mechanism, and one denoising method based on gravity center and chaos degree. The proposed interpolation method ensures that the invoice image keeps features well after scaling. The flippable pixels evaluation mechanism ensures that the pixels keep better connectivity and smoothness and the pattern has highest structural similarity after flipping. The proposed denoising method makes invoice font image smoother and fiter for human vision. Experiments show that the proposed flipping method not only keeps the invoice font structure well but also improves watermarking capacity.

  3. A new pixels flipping method for huge watermarking capacity of the invoice font image.

    Science.gov (United States)

    Li, Li; Hou, Qingzheng; Lu, Jianfeng; Xu, Qishuai; Dai, Junping; Mao, Xiaoyang; Chang, Chin-Chen

    2014-01-01

    Invoice printing just has two-color printing, so invoice font image can be seen as binary image. To embed watermarks into invoice image, the pixels need to be flipped. The more huge the watermark is, the more the pixels need to be flipped. We proposed a new pixels flipping method in invoice image for huge watermarking capacity. The pixels flipping method includes one novel interpolation method for binary image, one flippable pixels evaluation mechanism, and one denoising method based on gravity center and chaos degree. The proposed interpolation method ensures that the invoice image keeps features well after scaling. The flippable pixels evaluation mechanism ensures that the pixels keep better connectivity and smoothness and the pattern has highest structural similarity after flipping. The proposed denoising method makes invoice font image smoother and fiter for human vision. Experiments show that the proposed flipping method not only keeps the invoice font structure well but also improves watermarking capacity.

  4. Isolation and characterization of a tomato non-specific lipid transfer protein involved in polygalacturonase-mediated pectin degradation.

    Science.gov (United States)

    Tomassen, Monic M M; Barrett, Diane M; van der Valk, Henry C P M; Woltering, Ernst J

    2007-01-01

    An important aspect of the ripening process of tomato fruit is softening. Softening is accompanied by hydrolysis of the pectin in the cell wall by pectinases, causing loss of cell adhesion in the middle lamella. One of the most significant pectin-degrading enzymes is polygalacturonase (PG). Previous reports have shown that PG in tomato may exist in different forms (PG1, PG2a, PG2b, and PGx) commonly referred to as PG isoenzymes. The gene product PG2 is differentially glycosylated and is thought to associate with other proteins to form PG1 and PGx. This association is thought to modulate its pectin-degrading activity in planta. An 8 kDa protein that is part of the tomato PG1 multiprotein complex has been isolated, purified, and functionally characterized. This protein, designated 'activator' (ACT), belongs to the class of non-specific lipid transfer proteins (nsLTPs). ACT is capable of 'converting' the gene product PG2 into a more active and heat-stable form, which increases PG-mediated pectin degradation in vitro and stimulates PG-mediated tissue breakdown in planta. This finding suggests a new, not previously identified, function for nsLTPs in the modification of hydrolytic enzyme activity. It is proposed that ACT plays a role in the modulation of PG activity during tomato fruit softening.

  5. Flipped Classroom Research: From “Black Box” to “White Box” Evaluation

    OpenAIRE

    Christian Stöhr; Tom Adawi

    2018-01-01

    The flipped (or inverted) classroom model has gained increasing interest among university teachers in recent years. In the flipped classroom approach, students are encouraged to watch short video lectures as preparation for class, and classroom time is dedicated to more active forms of learning. In this editorial, we provide a thumbnail sketch of the origins and concept of the flipped classroom followed by a summary of the contributions to this special issue, which highlight the importance of...

  6. Thermally excited proton spin-flip laser emission in tokamaks

    International Nuclear Information System (INIS)

    Arunasalam, V.; Greene, G.J.

    1993-07-01

    Based on statistical thermodynamic fluctuation arguments, it is shown here for the first time that thermally excited spin-flip laser emission from the fusion product protons can occur in large tokamak devices that are entering the reactor regime of operation. Existing experimental data from TFTR supports this conjecture, in the sense that these measurements are in complete agreement with the predictions of the quasilinear theory of the spin-flip laser

  7. The Flipped Classroom in Medical Education: Engaging Students to Build Competency

    Directory of Open Access Journals (Sweden)

    Larry Hurtubise

    2015-01-01

    Full Text Available The flipped classroom represents an essential component in curricular reform. Technological advances enabling asynchronous and distributed learning are facilitating the movement to a competency-based paradigm in healthcare education. At its most basic level, flipping the classroom is the practice of assigning students didactic material, traditionally covered in lectures, to be learned before class while using face-to-face time for more engaging and active learning strategies. The development of more complex learning systems is creating new opportunities for learning across the continuum of medical education as well as interprofessional education. As medical educators engage in the process of successfully flipping a lecture, they gain new teaching perspectives, which are foundational to effectively engage in curricular reform. The purpose of this article is to build a pedagogical and technological understanding of the flipped classroom framework and to articulate strategies for implementing it in medical education to build competency.

  8. Menadione induces G2/M arrest in gastric cancer cells by down-regulation of CDC25C and proteasome mediated degradation of CDK1 and cyclin B1

    Science.gov (United States)

    Lee, Min Ho; Cho, Yoonjung; Kim, Do Hyun; Woo, Hyun Jun; Yang, Ji Yeong; Kwon, Hye Jin; Yeon, Min Ji; Park, Min; Kim, Sa-Hyun; Moon, Cheol; Tharmalingam, Nagendran; Kim, Tae Ue; Kim, Jong-Bae

    2016-01-01

    Menadione (vitamin K3) has been reported to induce apoptotic cell death and growth inhibition in various types of cancer cells. However, involvement of menadione in cell cycle control has not been considered in gastric cancer cells yet. In the current study, we have investigated whether menadione is involved in the cell cycle regulation and suppression of growth in gastric cancer cells. In the cell cycle analysis, we found that menadione induced G2/M cell cycle arrest in AGS cells. To elucidate the underlying mechanism, we investigated the cell cycle regulatory molecules involved in the G2/M cell cycle transition. After 24 h of menadione treatment, the protein level of CDK1, CDC25C and cyclin B1 in AGS cells was decreased in a menadione dose-dependent manner. In the time course experiment, the protein level of CDC25C decreased in 6 h, and CDK1and cyclin B1 protein levels began to decrease after 18 h of menadione treatment. We found that mRNA level of CDC25C decreased by menadione treatment in 6 h. Menadione did not have an influence on mRNA level of CDK1 and cyclin B1 though the protein levels were decreased. However, the decreased protein levels of CDK1 and cyclin B1 were recovered by inhibition of proteasome. Collectively, these results suggest that menadione inhibits growth of gastric cancer cells by reducing expression of CDC25C and promoting proteasome mediated degradation of CDK1 and cyclin B1 thereby blocking transition of the cell cycle from G2 phase to M phase. PMID:28077999

  9. FLIPPED: A Case Study in Fundamental of Accounting in Malaysian Polytechnic

    Science.gov (United States)

    Jamaludin, Rozinah; Osman, Siti Zuraidah Md; Yusof, Wan Mustaffa Wan; Jasni, Nur Farrah Azwa

    2016-01-01

    The new pedagogical flipped classroom was designed, developed and implemented using Flexible environments, Learning culture, Intentional content, Professional educators, Progressive activities, Engaging experiences, and Diversified platforms, also known as the FLIPPED model. The objective of this study is to investigate the effect of student…

  10. Akt Kinase-Mediated Checkpoint of cGAS DNA Sensing Pathway

    Directory of Open Access Journals (Sweden)

    Gil Ju Seo

    2015-10-01

    Full Text Available Upon DNA stimulation, cyclic GMP-AMP synthase (cGAS synthesizes the second messenger cyclic GMP-AMP (cGAMP that binds to the STING, triggering antiviral interferon-β (IFN-β production. However, it has remained undetermined how hosts regulate cGAS enzymatic activity after the resolution of DNA immunogen. Here, we show that Akt kinase plays a negative role in cGAS-mediated anti-viral immune response. Akt phosphorylated the S291 or S305 residue of the enzymatic domain of mouse or human cGAS, respectively, and this phosphorylation robustly suppressed its enzymatic activity. Consequently, expression of activated Akt led to the reduction of cGAMP and IFN-β production and the increase of herpes simplex virus 1 replication, whereas treatment with Akt inhibitor augmented cGAS-mediated IFN-β production. Furthermore, expression of the phosphorylation-resistant cGAS S291A mutant enhanced IFN-β production upon DNA stimulation, HSV-1 infection, and vaccinia virus infection. Our study identifies an Akt kinase-mediated checkpoint to fine-tune hosts’ immune responses to DNA stimulation.

  11. C1q protein binds to the apoptotic nucleolus and causes C1 protease degradation of nucleolar proteins.

    Science.gov (United States)

    Cai, Yitian; Teo, Boon Heng Dennis; Yeo, Joo Guan; Lu, Jinhua

    2015-09-11

    In infection, complement C1q recognizes pathogen-congregated antibodies and elicits complement activation. Among endogenous ligands, C1q binds to DNA and apoptotic cells, but whether C1q binds to nuclear DNA in apoptotic cells remains to be investigated. With UV irradiation-induced apoptosis, C1q initially bound to peripheral cellular regions in early apoptotic cells. By 6 h, binding concentrated in the nuclei to the nucleolus but not the chromatins. When nucleoli were isolated from non-apoptotic cells, C1q also bound to these structures. In vivo, C1q exists as the C1 complex (C1qC1r2C1s2), and C1q binding to ligands activates the C1r/C1s proteases. Incubation of nucleoli with C1 caused degradation of the nucleolar proteins nucleolin and nucleophosmin 1. This was inhibited by the C1 inhibitor. The nucleoli are abundant with autoantigens. C1q binding and C1r/C1s degradation of nucleolar antigens during cell apoptosis potentially reduces autoimmunity. These findings help us to understand why genetic C1q and C1r/C1s deficiencies cause systemic lupus erythematosus. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Proteasome-mediated degradation of integral inner nuclear membrane protein emerin in fibroblasts lacking A-type lamins

    International Nuclear Information System (INIS)

    Muchir, Antoine; Massart, Catherine; Engelen, Baziel G. van; Lammens, Martin; Bonne, Gisele; Worman, Howard J.

    2006-01-01

    We previously identified and characterized a homozygous LMNA nonsense mutation leading to the absence of A-type lamins in a premature neonate who died at birth. We show here that the absence of A-type lamins is due to degradation of the aberrant mRNA transcript with a premature termination codon. In cultured fibroblasts from the subject with the homozygous LMNA nonsense mutation, there was a decreased steady-state expression of the integral inner nuclear membrane proteins emerin and nesprin-1α associated with their mislocalization to the bulk endoplasmic reticulum and a hyperphosphorylation of emerin. To determine if decreased emerin expression occurred post-translationally, we treated cells with a selective proteasome inhibitor and observed an increase in expression. Our results show that mislocalization of integral inner nuclear membrane proteins to the endoplasmic reticulum in human cells lacking A-type lamins leads to their degradation and provides the first evidence that their degradation is mediated by the proteasome

  13. ConfChem Conference on Flipped Classroom: Using a Blog to Flip a Classroom

    Science.gov (United States)

    Haile, January D.

    2015-01-01

    This communication summarizes one of the invited papers to the Flipped Classroom ACS Division of Chemical Education Committee on Computers in Chemical Education online ConfChem held from May 18 to June 24, 2014. Just in Time Teaching is a technique in which students read the material before class and respond to a few questions. In a first-year…

  14. Variable flip angle excitation for reduced acquisition time magnetic resonance imaging

    International Nuclear Information System (INIS)

    Mills, T.C.; Ortendahl, D.A.; Hylton, N.M.; Carlson, J.W.; Crooks, L.E.; Kaufman, L.

    1987-01-01

    This paper describes an MRI technique which can be used to acquire images at short TR values while maintaining the sensitivity to disease found in longer TR images. For spin echo imaging there are three acquisition parameters that can be set in the imaging protocol; TR, the repetition interval; TE, the time of echo and Θ, the excitation flip angle. Standard imaging techniques set Θ to 90 degrees regardless of the TR value. With Θ fixed, imaging systems have been optimized by varying the value for TE and TR with the results in general indicating the need for long TR values. However, if the flip angle is included as a variable acquisition parameter the optimal operating point can be changed. The solution to the Bloch equation shows a functional relationship between the flip angle and the ratio TR/T1. This functionality was first observed by Ernst and Anderson as a method to increase the signal generated in fourier transform magnetic resonance spectroscopy. When TR/T1<1 the optimum flip angle for producing maximum magnetization in the transverse plane is less then 90 degrees. Therefore, by reducing both TR and flip angle it is possible to maintain signal intensity while reducing the time of data acquisition

  15. Flip-chip bonded optoelectronic integration based on ultrathin silicon (UTSi) CMOS

    Science.gov (United States)

    Hong, Sunkwang; Ho, Tawei; Zhang, Liping; Sawchuk, Alexander A.

    2003-06-01

    We describe the design and test of flip-chip bonded optoelectronic CMOS devices based on Peregrine Semiconductor's 0.5 micron Ultra-Thin Silicon on sapphire (UTSi) technology. The UTSi process eliminates the substrate leakage that typically results in crosstalk and reduces parasitic capacitance to the substrate, providing many benefits compared to bulk silicon CMOS. The low-loss synthetic sapphire substrate is optically transparent and has a coefficient of thermal expansion suitable for flip-chip bonding of vertical cavity surface emitting lasers (VCSELs) and detectors. We have designed two different UTSi CMOS chips. One contains a flip-chip bonded 1 x 4 photodiode array, a receiver array, a double edge triggered D-flip flop-based 2047-pattern pseudo random bit stream (PRBS) generator and a quadrature-phase LC-voltage controlled oscillator (VCO). The other chip contains a flip-chip bonded 1 x 4 VCSEL array, a driver array based on high-speed low-voltage differential signals (LVDS) and a full-balanced differential LC-VCO. Each VCSEL driver and receiver has individual input and bias voltage adjustments. Each UTSi chip is mounted on different printed circuit boards (PCBs) which have holes with about 1 mm radius for optical output and input paths through the sapphire substrate. We discuss preliminary testing of these chips.

  16. Polarizing a stored proton beam by spin flip? - A high statistic reanalysis

    International Nuclear Information System (INIS)

    Oellers, Dieter

    2011-01-01

    Prompted by recent, conflicting calculations, we have carried out a measurement of the spin flip cross section in low-energy electron-proton scattering. The experiment uses the cooling electron beam at COSY as an electron target. A reanalysis of the data leeds to a reduced statistical errors resulting in a factor of 4 reduced upper limit for the spin flip cross section. The measured cross sections are too small for making spin flip a viable tool in polarizing a stored beam.

  17. The Flipped Classroom – From Theory to Practice in Health Professional Education

    Science.gov (United States)

    McLaughlin, Jacqueline E.

    2017-01-01

    The flipped classroom is growing in popularity in health professional education. As such, instructors are experiencing various growing pains in functionalizing this model, from justifying the approach to managing time inside and outside of class to assessing impact on learning. This review focuses on some key theories that support the flipped model and translates those key theories into practice across core aspects of the flipped classroom: pre-class preparation, in-class activities, after-class activities and assessment of student learning. PMID:28970619

  18. Moving toward heutagogical learning: Illuminating undergraduate nursing students' experiences in a flipped classroom.

    Science.gov (United States)

    Green, Rebecca D; Schlairet, Maura C

    2017-02-01

    Nurse educators rely on the tenets of educational theory and evidence-based education to promote the most effective curriculum and facilitate the best outcomes. The flipped classroom model, in which students assume personal responsibility for knowledge acquisition in a highly engaging and interactive environment, supports self-directed learning and the unique needs of clinical education. To understand how students perceived their experiences in the flipped classroom and how students' learning dispositions were affected by the flipped classroom experience. A phenomenological approach was used to gain deeper understanding about students' perspectives, perceptions and subjective experiences of the flipped classroom model. The focus of the study was on characteristics of student learning. Fourteen Bachelors of Science of Nursing (BSN) students at a regional university in the southeastern United States. Using data transcribed from face-to-face, semi-structured interviews, experiential themes were extracted from the qualitative data (student-reported experiences, attributes, thoughts, values, and beliefs regarding teaching and learning in the context of their experience of the flipped classroom) using Graneheim's and Lundman's (2004) guidelines; and were coded and analyzed within theoretical categories based on pedagogical, andragogical or heutagogical learning dispositions. Experiential themes that emerged from students' descriptions of their experiences in the flipped classroom included discernment, challenge, relevance, responsibility, and expertise. The flipped classroom model offers promising possibilities for facilitating students' movement from learning that is characteristic of pedagogy and andragogy toward heutagogical learning. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Calculability and stability in the flipped string

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, J.L.; Nanopoulos, D.V. (Texas A and M Univ., College Station, TX (USA). Center for Theoretical Physics Houston Advanced Research Center (HARC), The Woodlands, TX (USA). Astroparticle Physics Group)

    1991-03-07

    We show that the highly successful structure of the recently proposed superstring flipped SU(5) model remains intact after the inclusion in the superpotential of the low-energy effective theory of all relevant string-induced nonrenormalizable terms. This structure provides for only two light Higgs doublets, hierarchical fermion mass matrices, and an adequate proton lifetime. We reach this conclusion explicit calculations using a recently derived set of rules to evaluate nonrenormalizable terms in the four-dimensional free fermionic formulation of superstrings. This remarkable stability of the infrared limit of the flipped string makes its experimental predictions trustworthy and hence its physical existence falsifiable. (orig.).

  20. I mål med flipped learning

    DEFF Research Database (Denmark)

    Hachmann, Roland

    2016-01-01

    Kapitlet belyser, hvordan synlige læringsmål og stilladsering er to vigtige elementer i Flipped Learning. Kapitlet belyser en række metoder til at bringe eleven i centrum for sin egen læring og hvorledes underviseren kan differentiere sin undervisning for netop at støtte denne proces......Kapitlet belyser, hvordan synlige læringsmål og stilladsering er to vigtige elementer i Flipped Learning. Kapitlet belyser en række metoder til at bringe eleven i centrum for sin egen læring og hvorledes underviseren kan differentiere sin undervisning for netop at støtte denne proces...

  1. Flipped learning: should it replace didactic learning?

    Directory of Open Access Journals (Sweden)

    Osman A

    2017-10-01

    Full Text Available Abdirahman Osman, Seyed Ramin Jalal, Saeed Azizi Faculty of Medicine, St George’s Hospital Medical School, London, UKWe read with great interest the article by Pettit et al1 on the implementation of flipped learning. We wish to offer our perspective as medical students. The study concluded that a combination of lecture-based teaching accompanied with flipped learning activities appealed to most students. We find this response unsurprising. Pettit et al’s1 article documents the reason – the need for a variation in teaching styles for different themes by millennial learners of the modern student community.View the original paper by Pettit and colleagues.  

  2. Structural Insights into 2,2′-Azino-Bis(3-Ethylbenzothiazoline-6-Sulfonic Acid) (ABTS)-Mediated Degradation of Reactive Blue 21 by Engineered Cyathus bulleri Laccase and Characterization of Degradation Products

    Science.gov (United States)

    Kenzom, T.; Srivastava, P.

    2014-01-01

    Advanced oxidation processes are currently used for the treatment of different reactive dyes which involve use of toxic catalysts. Peroxidases are reported to be effective on such dyes and require hydrogen peroxide and/or metal ions. Cyathus bulleri laccase, expressed in Pichia pastoris, catalyzes efficient degradation (78 to 85%) of reactive azo dyes (reactive black 5, reactive orange 16, and reactive red 198) in the presence of synthetic mediator ABTS [2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)]. This laccase was engineered to degrade effectively reactive blue 21 (RB21), a phthalocyanine dye reported to be decolorized only by peroxidases. The 816-bp segment (toward the C terminus) of the lcc gene was subjected to random mutagenesis and enzyme variants (Lcc35, Lcc61, and Lcc62) were selected based on increased ABTS oxidizing ability. Around 78 to 95% decolorization of RB21 was observed with the ABTS-supplemented Lcc variants in 30 min. Analysis of the degradation products by mass spectrometry indicated the formation of several low-molecular-weight compounds. Mapping the mutations on the modeled structure implicated residues both near and far from the T1 Cu site that affected the catalytic efficiency of the mutant enzymes on ABTS and, in turn, the rate of oxidation of RB21. Several inactive clones were also mapped. The importance of geometry as well as electronic changes on the reactivity of laccases was indicated. PMID:25261507

  3. Calpain-mediated proteolysis of polycystin-1 C-terminus induces JAK2 and ERK signal alterations

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyunho [Transplantation Research Institute, Seoul National University Medical Research Center, Seoul (Korea, Republic of); Department of Medicine, University of Maryland, Baltimore, MD (United States); Kang, Ah-Young [Transplantation Research Institute, Seoul National University Medical Research Center, Seoul (Korea, Republic of); Department of Medicine, Program of Immunology, Graduate School, Seoul National University, Seoul (Korea, Republic of); Ko, Ah-ra [Clinical Research Center, Samsung Biomedical Research Institute, Seoul (Korea, Republic of); Park, Hayne Cho [Transplantation Research Institute, Seoul National University Medical Research Center, Seoul (Korea, Republic of); Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul (Korea, Republic of); So, Insuk [Department of Physiology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Park, Jong Hoon [Department of Biological Science, Sookmyung Women’s University, Seoul (Korea, Republic of); Cheong, Hae Il [Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul (Korea, Republic of); Department of Pediatrics, Seoul National University Children’s Hospital, Seoul (Korea, Republic of); Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul (Korea, Republic of); Hwang, Young-Hwan [Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul (Korea, Republic of); Department of Internal Medicine, Eulji General Hospital, Eulji University College of Medicine, Seoul (Korea, Republic of); and others

    2014-01-01

    Autosomal dominant polycystic kidney disease (ADPKD), a hereditary renal disease caused by mutations in PKD1 (85%) or PKD2 (15%), is characterized by the development of gradually enlarging multiple renal cysts and progressive renal failure. Polycystin-1 (PC1), PKD1 gene product, is an integral membrane glycoprotein which regulates a number of different biological processes including cell proliferation, apoptosis, cell polarity, and tubulogenesis. PC1 is a target of various proteolytic cleavages and proteosomal degradations, but its role in intracellular signaling pathways remains poorly understood. Herein, we demonstrated that PC1 is a novel substrate for μ- and m-calpains, which are calcium-dependent cysteine proteases. Overexpression of PC1 altered both Janus-activated kinase 2 (JAK2) and extracellular signal-regulated kinase (ERK) signals, which were independently regulated by calpain-mediated PC1 degradation. They suggest that the PC1 function on JAK2 and ERK signaling pathways might be regulated by calpains in response to the changes in intracellular calcium concentration. - Highlights: • Polycystin-1 is a target of ubiquitin-independent degradation by calpains. • The PEST domain is required for calpain-mediated degradation of polycystin-1. • Polycystin-1 may independently regulate JAK2 and ERK signaling pathways.

  4. Grounding the Flipped Classroom Approach in the Foundations of Educational Technology

    Science.gov (United States)

    Lo, Chung Kwan

    2018-01-01

    The flipped classroom approach is becoming increasingly popular. This instructional approach allows more in-class time to be spent on interactive learning activities, as the direct lecturing component is shifted outside the classroom through instructional videos. However, despite growing interest in the flipped classroom approach, no robust…

  5. Correlations between Learners' Initial EFL Proficiency and Variables of Clicker-Aided Flipped EFL Class

    Science.gov (United States)

    Yu, Zhonggen; Yu, Liheng

    2017-01-01

    Although the flipped class has been hotly discussed, the clicker-aided flipped EFL class (CFEC) still remains a mystery for most scholars. This study aims to determine the correlations between the initial EFL proficiency and other variables of the clicker-aided EFL flipped class. The sample was made up of randomly selected 79 participants (Female…

  6. The flipped classroom: A learning model to increase student engagement not academic achievement

    Directory of Open Access Journals (Sweden)

    Masha Smallhorn

    2017-07-01

    Full Text Available A decrease in student attendance at lectures both nationally and internationally, has prompted educators to re-evaluate their teaching methods and investigate strategies which promote student engagement. The flipped classroom model, grounded in active learning pedagogy, transforms the face-to-face classroom. Students prepare for the flipped classroom in their own time by watching short online videos and completing readings. Face-to-face time is used to apply learning through problem-solving with peers. To improve the engagement and learning outcomes of our second year cohort, lectures were replaced with short online videos and face-to-face time was spent in a flipped classroom. The impact of the flipped classroom was analysed through surveys, attendance records, learning analytics and exam data before and after the implementation of the flipped classroom. Results suggest an increase in student engagement and a positive attitude towards the learning method. However, there were no measurable increases in student learning outcomes.

  7. Fully simulatable quantum-secure coin-flipping and applications

    DEFF Research Database (Denmark)

    Lunemann, Carolin; Nielsen, Jesper Buus

    2011-01-01

    schemes which we show how to construct in the given setting. We then show that the interactive generation of random coins at the beginning or during outer protocols allows for quantum-secure realizations of classical schemes, again without any set-up assumptions. As example applications we discuss quantum...... zero-knowledge proofs of knowledge and quantum-secure two-party function evaluation. Both applications assume only fully simulatable coin-flipping and mixed commitments. Since our framework allows to construct fully simulatable coin-flipping from mixed commitments, this in particular shows that mixed...

  8. Introducing a Flipped Classroom for a Statistics Course

    DEFF Research Database (Denmark)

    Triantafyllou, Eva; Timcenko, Olga

    2014-01-01

    before class, while class time is devoted to clarifications and application of this knowledge. The hypothesis is that there could be deep and creative discussions when teacher and students physically meet. This has inspired an experiment utilizing this approach in a statistics course for fourth semester......One of the novel ideas in teaching that heavily relies on current technology is the “flipped classroom” approach, or “inverse teaching”. In a flipped classroom the traditional lecture and homework sessions are inverted. Students are provided with online material in order to gain necessary knowledge...

  9. Highly enhanced photocatalytic degradation of methylene blue over the indirect all-solid-state Z-scheme g-C{sub 3}N{sub 4}-RGO-TiO{sub 2} nanoheterojunctions

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Fangjun [College of Materials and Energy, South China Agricultural University, Guangzhou 510642 (China); Li, Xin [College of Materials and Energy, South China Agricultural University, Guangzhou 510642 (China); Institute of New Energy and New Materials, Key Laboratory of Energy Plants Resource and Utilization, Ministry of Agriculture, South China Agricultural University, Guangzhou 510642 (China); College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou 510642 (China); Liu, Wei, E-mail: wlscau@163.com [College of Materials and Energy, South China Agricultural University, Guangzhou 510642 (China); Zhang, Shuting [College of Materials and Energy, South China Agricultural University, Guangzhou 510642 (China)

    2017-05-31

    Highlights: • The indirect Z-scheme g-C{sub 3}N{sub 4}-RGO-TiO{sub 2} photocatalysts were successfully fabricated. • A 3.2-fold activity enhancement was achieved by inserting RGO into g-C{sub 3}N{sub 4}- TiO{sub 2}. • The indirect Z-scheme mechanism was verified by PL spectra and radical trapping. • The multi-functional roles of RGO in enhancing photodegradation were revealed. - Abstract: In the present research work, the ternary indirect all-solid-state Z-scheme nanoheterojunctions, graphitic-C{sub 3}N{sub 4}/reduced graphene oxide/anatase TiO{sub 2} (g-C{sub 3}N{sub 4}-RGO-TiO{sub 2}) with highly enhanced photocatalytic performance were successfully prepared via a simple liquid-precipitation strategy. The photocatalytic activities of indirect all-solid-state Z-scheme g-C{sub 3}N{sub 4}-RGO-TiO{sub 2} nanoheterojunctions were evaluated by the degradation of methylene blue (MB). The results showed that the introduction of RGO as an interfacial mediator into direct Z-scheme g-C{sub 3}N{sub 4}-TiO{sub 2} nanocomposites can remarkably enhance their photocatalytic activities. The as-obtained indirect all-solid-state Z-scheme g-C{sub 3}N{sub 4}-RGO-TiO{sub 2} nanoheterojunctions, with the optimal loading amount of 10 wt% RGO, exhibited the highest rate towards the photocatalytic degradation of MB under simulated solar light irradiation. The degradation kinetics of MB can be described by the apparent first-order kinetics model. The highest degradation rate constant of 0.0137 min{sup −1} is about 4.7 and 3.2 times greater than those of the pure g-C{sub 3}N{sub 4} (0.0029 min{sup −1}) and direct Z-scheme g-C{sub 3}N{sub 4}-TiO{sub 2} (0.0043 min{sup −1}), respectively. An indirect all-solid-state Z-scheme charge-separation mechanism was proposed based on the photoluminescence spectra and the trapping experiment procedure of the photo-generated active species. It was believed that the indirect all-solid-state Z-scheme charge separation mechanism in g-C{sub 3}N

  10. Comparison between flipped classroom and lecture-based classroom in ophthalmology clerkship

    Science.gov (United States)

    Tang, Fen; Chen, Chuan; Zhu, Yi; Zuo, Chengguo; Zhong, Yimin; Wang, Nan; Zhou, Lijun; Zou, Yuxian; Liang, Dan

    2017-01-01

    ABSTRACT Background: In recent years, the flipped classroom method of teaching has received much attention in health sciences education. However, the application of flipped classrooms in ophthalmology education has not been well investigated. Objective: The goal of this study was to investigate the effectiveness and acceptability of the flipped classroom approach to teaching ophthalmology at the clerkship level. Design: Ninety-five fourth year medical students in an ophthalmology clerkship were randomly divided into two groups. An ocular trauma module was chosen for the content of this study. One group (FG (flipped group), n = 48) participated in flipped classroom instruction and was asked to watch a recorded lecture video and to read study materials before a face-to-face class meeting. They used the in-class time for discussion. The other group (TG (traditional group), n = 47) was assigned to traditional lecture-based instruction. These students attended a didactic lecture and completed assigned homework after the lecture. Feedback questionnaires were collected to compare students’ perspectives on the teaching approach they experienced and to evaluate students’ self-perceived competence and interest in ocular trauma. Pre- and post-tests were performed to assess student learning of the course materials. Results: More students in the FG agreed that the classroom helped to promote their learning motivation, improve their understanding of the course materials, and enhance their communication skill and clinical thinking. However, students in the FG did not show a preference for this method of teaching, and also reported more burden and pressure than those from the TG. Students from the FG performed better on the post test over the ocular trauma-related questions when compared to those from the TG. Conclusions: The flipped classroom approach shows promise in ophthalmology clerkship teaching. However, it has some drawbacks. Further evaluation and modifications

  11. Comparison between flipped classroom and lecture-based classroom in ophthalmology clerkship.

    Science.gov (United States)

    Tang, Fen; Chen, Chuan; Zhu, Yi; Zuo, Chengguo; Zhong, Yimin; Wang, Nan; Zhou, Lijun; Zou, Yuxian; Liang, Dan

    2017-01-01

    In recent years, the flipped classroom method of teaching has received much attention in health sciences education. However, the application of flipped classrooms in ophthalmology education has not been well investigated. The goal of this study was to investigate the effectiveness and acceptability of the flipped classroom approach to teaching ophthalmology at the clerkship level. Ninety-five fourth year medical students in an ophthalmology clerkship were randomly divided into two groups. An ocular trauma module was chosen for the content of this study. One group (FG (flipped group), n = 48) participated in flipped classroom instruction and was asked to watch a recorded lecture video and to read study materials before a face-to-face class meeting. They used the in-class time for discussion. The other group (TG (traditional group), n = 47) was assigned to traditional lecture-based instruction. These students attended a didactic lecture and completed assigned homework after the lecture. Feedback questionnaires were collected to compare students' perspectives on the teaching approach they experienced and to evaluate students' self-perceived competence and interest in ocular trauma. Pre- and post-tests were performed to assess student learning of the course materials. More students in the FG agreed that the classroom helped to promote their learning motivation, improve their understanding of the course materials, and enhance their communication skill and clinical thinking. However, students in the FG did not show a preference for this method of teaching, and also reported more burden and pressure than those from the TG. Students from the FG performed better on the post test over the ocular trauma-related questions when compared to those from the TG. The flipped classroom approach shows promise in ophthalmology clerkship teaching. However, it has some drawbacks. Further evaluation and modifications are required before it can be widely accepted and implemented

  12. A gross anatomy flipped classroom effects performance, retention, and higher-level thinking in lower performing students.

    Science.gov (United States)

    Day, Leslie J

    2018-01-22

    A flipped classroom is a growing pedagogy in higher education. Many research studies on the flipped classroom have focused on student outcomes, with the results being positive or inconclusive. A few studies have analyzed confounding variables, such as student's previous achievement, or the impact of a flipped classroom on long-term retention and knowledge transfer. In the present study, students in a Doctor of Physical Therapy program in a traditional style lecture of gross anatomy (n = 105) were compared to similar students in a flipped classroom (n = 112). Overall, students in the flipped anatomy classroom had an increase in semester average grades (P = 0.01) and performance on higher-level analytical questions (P flipped anatomy classroom performing at a higher level in kinesiology (P flipped anatomy class, outperformed their traditional anatomy class counterparts in anatomy semester grades (P flipped classroom may benefit lower performing student's knowledge acquisition and transfer to a greater degree than higher performing students. Future studies should explore the underlying reasons for improvement in lower performing students. Anat Sci Educ. © 2018 American Association of Anatomists. © 2018 American Association of Anatomists.

  13. Flipping the Classroom for English Language Learners to Foster Active Learning

    Science.gov (United States)

    Hung, Hsiu-Ting

    2015-01-01

    This paper describes a structured attempt to integrate flip teaching into language classrooms using a WebQuest active learning strategy. The purpose of this study is to examine the possible impacts of flipping the classroom on English language learners' academic performance, learning attitudes, and participation levels. Adopting a…

  14. The Flipped Classroom and Cooperative Learning: Evidence from a Randomised Experiment

    Science.gov (United States)

    Foldnes, Njål

    2016-01-01

    This article describes a study which compares the effectiveness of the flipped classroom relative to the traditional lecture-based classroom. We investigated two implementations of the flipped classroom. The first implementation did not actively encourage cooperative learning, with students progressing through the course at their own pace. With…

  15. Enhancing Academic Achievement and Satisfaction by Flipping the Teacher Preparation Classroom

    Science.gov (United States)

    Zuniga, Rene R.

    2015-01-01

    This study compared flipped classrooms versus online courses to study the effects of the two instructional methodologies on student achievement and satisfaction in an undergraduate "Introduction to Education," EDUC 1301, course. Students self-matriculated in either traditional EDUC 1301 courses which were flipped or in EDUC 1301 online…

  16. Comparison of Flipped Model to Traditional Classroom Learning in a Professional Pharmacy Course

    Directory of Open Access Journals (Sweden)

    Colleen McCabe

    2017-09-01

    Full Text Available The flipped classroom is an approach to incorporate active learning that is being used in secondary education, higher education, and professional schools. This study investigates its impact on student learning and confidence in a professional degree program course. A quasi-experimental study was conducted to evaluate pharmacy students enrolled in a semester-long didactic traditional classroom course compared to students learning the same material using a flipped model through online self-study modules in a hands-on experiential learning course. Before and after each learning experience, students of each group completed a 16-item knowledge assessment on four topic areas and rated their level of confidence with each topic area on a Likert scale. There was a significant difference in knowledge with students in the traditional course scoring higher than students using flipped approach in the experiential course. Furthermore, the flipped experiential course students did not improve assessment scores from pre-test to post-test. For confidence rating, the traditional course group ranked confidence higher than the flipped experiential group for all topics. These findings challenge the notion that the flipped model using self-study in an experiential setting can be a substitution for didactic delivery of pharmacy education.

  17. Degradation of Paracetamol by Photolysis Using C-N-codoped TiO2

    Directory of Open Access Journals (Sweden)

    Vanny Yulia Safitri

    2017-11-01

    Full Text Available Paracetamol is generally used as analgesic and antipyretic drugs. Contamination paracetamol in the environment can occur because of waste material disposal from production site and immediate disposal of household that cause water pollution. Paracetamol is degraded by photolysis method under irradiation 10 watt UV-light (λ=365 nm, visible-light (Philips LED 13 watt 1400 lux and solar-light with and without addition C-N-codoped TiO2catalyst. The solution is analyzed by UV-Vis spectrophotometer at λ 200-400 nm. Optimum weight of C-N-codoped TiO2 catalyst obtained is 20 mg under UV-light photolysis. Paracetamol 4 mg/L is degraded 45.48% after 120 minutes under UV-light irradiation without catalyst, and increases to be 69.31% by using 20 mg catalyst. While degradation percentage of paracetamol is 16.96 % without catalyst, the percentage increases to be 34.29% after using 20 mg catalyst for 120 minutes photolysis under visible-light. Degradation of paracetamol by solar light achieves only 12.27% in absance of catalyst for 120 minutes irradiation, but it increases significantly until 70.39% in presence of 20 mg catalyst.

  18. An Investigation of the Use of the ‘Flipped Classroom’ Pedagogy in Secondary English Language Classrooms

    Directory of Open Access Journals (Sweden)

    Chi Cheung Ruby Yang

    2017-01-01

    Full Text Available Aim/Purpose\t: To examine the use of a flipped classroom in the English Language subject in secondary classrooms in Hong Kong. Background:\tThe research questions addressed were: (1 What are teachers’ perceptions towards the flipped classroom pedagogy? (2 How can teachers transfer their flipped classroom experiences to teaching other classes/subjects? (3 What are students’ perceptions towards the flipped classroom pedagogy? (4 How can students transfer their flipped classroom experiences to studying other subjects? (5 Will students have significant gain in the knowledge of the lesson topic trialled in this study? Methodology: A total of 57 students from two Secondary 2 classes in a Band 3 secondary school together with two teachers teaching these two classes were involved in this study. Both quantitative and quantitative data analyses were conducted. Contribution: Regarding whether the flipped classroom pedagogy can help students gain significantly in their knowledge of a lesson topic, only one class of students gained statistically significantly in the subject knowledge but not for another class. Findings: Students in general were positive about the flipped classroom. On the other hand, although the teachers considered that the flipped classroom pedagogy was creative, they thought it may only be useful for teaching English grammar. Recommendations for Practitioners: Teachers thought that flipping a classroom may only be useful for more motivated students, and the extra workload of finding or making suitable pre-lesson online videos is the main concern for teachers. Recommendations for Researchers: Both quantitative and qualitative analyses should be conducted to investigate the effectiveness of a flipped classroom on students’ language learning. Impact on Society\t: Teachers and students can transfer their flipped classroom experiences in English Language to teaching and studying other subjects. Future Research:\tMore classes should be

  19. Changes in Structural-Mechanical Properties and Degradability of Collagen during Aging-associated Modifications*

    Science.gov (United States)

    Panwar, Preety; Lamour, Guillaume; Mackenzie, Neil C. W.; Yang, Heejae; Ko, Frank; Li, Hongbin; Brömme, Dieter

    2015-01-01

    During aging, changes occur in the collagen network that contribute to various pathological phenotypes in the skeletal, vascular, and pulmonary systems. The aim of this study was to investigate the consequences of age-related modifications on the mechanical stability and in vitro proteolytic degradation of type I collagen. Analyzing mouse tail and bovine bone collagen, we found that collagen at both fibril and fiber levels varies in rigidity and Young's modulus due to different physiological changes, which correlate with changes in cathepsin K (CatK)-mediated degradation. A decreased susceptibility to CatK-mediated hydrolysis of fibrillar collagen was observed following mineralization and advanced glycation end product-associated modification. However, aging of bone increased CatK-mediated osteoclastic resorption by ∼27%, and negligible resorption was observed when osteoclasts were cultured on mineral-deficient bone. We observed significant differences in the excavations generated by osteoclasts and C-terminal telopeptide release during bone resorption under distinct conditions. Our data indicate that modification of collagen compromises its biomechanical integrity and affects CatK-mediated degradation both in bone and tissue, thus contributing to our understanding of extracellular matrix aging. PMID:26224630

  20. The implementation of flipped classroom model in CIE in the environment of non-target language

    Science.gov (United States)

    Xiao, Renfei; Mustofa, Ali; Zhang, Fang; Su, Xiaoxue

    2018-01-01

    This paper sets a theoretical framework that it’s both feasible and indispensable of flipping classroom in Chinese International Education (CIE) in the non-target language environments. There are mainly three sections included: 1) what is flipped classroom and why it becomes inevitable existence; 2) why should we flip the classroom in CIE environments, especially in non-target language environments; 3) take Pusat Bahasa Mandarin Universitas Negeri Surabaya as an instance to discuss the application of flipped classroom in non-target language environments.

  1. Student performance and attitudes in a collaborative and flipped linear algebra course

    Science.gov (United States)

    Murphy, Julia; Chang, Jen-Mei; Suaray, Kagba

    2016-07-01

    Flipped learning is gaining traction in K-12 for enhancing students' problem-solving skills at an early age; however, there is relatively little large-scale research showing its effectiveness in promoting better learning outcomes in higher education, especially in mathematics classes. In this study, we examined the data compiled from both quantitative and qualitative measures such as item scores on a common final and attitude survey results between a flipped and a traditional Introductory Linear Algebra class taught by two individual instructors at a state university in California in Fall 2013. Students in the flipped class were asked to watch short video lectures made by the instructor and complete a short online quiz prior to each class attendance. The class time was completely devoted to problem solving in group settings where students were prompted to communicate their reasoning with proper mathematical terms and structured sentences verbally and in writing. Examination of the quality and depth of student responses from the common final exam showed that students in the flipped class produced more comprehensive and well-explained responses to the questions that required reasoning, creating examples, and more complex use of mathematical objects. Furthermore, students in the flipped class performed superiorly in the overall comprehension of the content with a 21% increase in the median final exam score. Overall, students felt more confident about their ability to learn mathematics independently, showed better retention of materials over time, and enjoyed the flipped experience.

  2. Spin-polarized free electron beam interaction with radiation and superradiant spin-flip radiative emission

    Directory of Open Access Journals (Sweden)

    A. Gover

    2006-06-01

    Full Text Available The problems of spin-polarized free-electron beam interaction with electromagnetic wave at electron-spin resonance conditions in a magnetic field and of superradiant spin-flip radiative emission are analyzed in the framework of a comprehensive classical model. The spontaneous emission of spin-flip radiation from electron beams is very weak. We show that the detectivity of electron spin resonant spin-flip and combined spin-flip/cyclotron-resonance-emission radiation can be substantially enhanced by operating with ultrashort spin-polarized electron beam bunches under conditions of superradiant (coherent emission. The proposed radiative spin-state modulation and the spin-flip radiative emission schemes can be used for control and noninvasive diagnostics of polarized electron/positron beams. Such schemes are of relevance in important scattering experiments off nucleons in nuclear physics and off magnetic targets in condensed matter physics.

  3. Competency-Based Blended Learning: Flipping Professional Practice Classes to Enhance Competence Development

    Directory of Open Access Journals (Sweden)

    Mark Ragg

    2017-08-01

    Full Text Available In the past decade, health and human service educational programs have transitioned to competence-based outcomes to enhance the quality of graduating professionals. While such outcomes are a critical step in ensuring professional quality, they require curricular and pedagogical adjustments that do not fit easily within university environments. Technology has eased many problems of fit through the development of hybrid and flipped courses that allow on-campus time to be better focused on developing professional skills. This study explored the question: Can flipped delivery improve competence-based outcomes in social work practice classes? The study assessed pedagogical adjustments that integrated competence-based learning principles with flipped classroom delivery. Principles of organizing the class to maximize competence development are explored and illustrated. Improved competence development and student satisfaction were demonstrated in three flipped practice courses with a combined sample size of 269 Bachelor of Social Work (BSW and Masters of Social Work (MSW students. Researchers concluded that using flipped-classroom methods enhanced the students’ capacity to apply concepts and develop skills. In particular, the ability to receive and process feedback on applied skills was improved.

  4. The effectiveness of flipped classroom learning model in secondary physics classroom setting

    Science.gov (United States)

    Prasetyo, B. D.; Suprapto, N.; Pudyastomo, R. N.

    2018-03-01

    The research aimed to describe the effectiveness of flipped classroom learning model on secondary physics classroom setting during Fall semester of 2017. The research object was Secondary 3 Physics group of Singapore School Kelapa Gading. This research was initiated by giving a pre-test, followed by treatment setting of the flipped classroom learning model. By the end of the learning process, the pupils were given a post-test and questionnaire to figure out pupils' response to the flipped classroom learning model. Based on the data analysis, 89% of pupils had passed the minimum criteria of standardization. The increment level in the students' mark was analysed by normalized n-gain formula, obtaining a normalized n-gain score of 0.4 which fulfil medium category range. Obtains from the questionnaire distributed to the students that 93% of students become more motivated to study physics and 89% of students were very happy to carry on hands-on activity based on the flipped classroom learning model. Those three aspects were used to generate a conclusion that applying flipped classroom learning model in Secondary Physics Classroom setting is effectively applicable.

  5. Healthcare students' experiences when integrating e-learning and flipped classroom instructional approaches.

    Science.gov (United States)

    Telford, Mark; Senior, Emma

    2017-06-08

    This article describes the experiences of undergraduate healthcare students taking a module adopting a 'flipped classroom' approach. Evidence suggests that flipped classroom as a pedagogical tool has the potential to enhance student learning and to improve healthcare practice. This innovative approach was implemented within a healthcare curriculum and in a module looking at public health delivered at the beginning of year two of a 3-year programme. The focus of the evaluation study was on the e-learning resources used in the module and the student experiences of these; with a specific aim to evaluate this element of the flipped classroom approach. A mixed-methods approach was adopted and data collected using questionnaires, which were distributed across a whole cohort, and a focus group involving ten participants. Statistical analysis of the data showed the positive student experience of engaging with e-learning. The thematic analysis identified two key themes; factors influencing a positive learning experience and the challenges when developing e-learning within a flipped classroom approach. The study provides guidance for further developments and improvements when developing e-learning as part of the flipped classroom approach.

  6. Effectiveness of the Surgery Core Clerkship Flipped Classroom: a prospective cohort trial.

    Science.gov (United States)

    Liebert, Cara A; Lin, Dana T; Mazer, Laura M; Bereknyei, Sylvia; Lau, James N

    2016-02-01

    The flipped classroom has been proposed as an alternative curricular approach to traditional didactic lectures but has not been previously applied to a surgery clerkship. A 1-year prospective cohort of students (n = 89) enrolled in the surgery clerkship was taught using a flipped classroom approach. A historical cohort of students (n = 92) taught with a traditional lecture curriculum was used for comparison. Pretest and post-test performance, end-of-clerkship surveys, and National Board of Medical Examiners (NBME) scores were analyzed to assess effectiveness. Mean pretest and post-test scores increased across all modules (P flipped classroom contributed to this increase. Implementation of a flipped classroom in the surgery clerkship is feasible and results in high learner satisfaction, effective knowledge acquisition, and increased career interest in surgery with noninferior NBME performance. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Flipped clinical training: a structured training method for undergraduates in complete denture prosthesis.

    Science.gov (United States)

    K, Anbarasi; K, Kasim Mohamed; Vijayaraghavan, Phagalvarthy; Kandaswamy, Deivanayagam

    2016-12-01

    To design and implement flipped clinical training for undergraduate dental students in removable complete denture treatment and predict its effectiveness by comparing the assessment results of students trained by flipped and traditional methods. Flipped training was designed by shifting the learning from clinics to learning center (phase I) and by preserving the practice in clinics (phase II). In phase I, student-faculty interactive session was arranged to recap prior knowledge. This is followed by a display of audio synchronized video demonstration of the procedure in a repeatable way and subsequent display of possible errors that may occur in treatment with guidelines to overcome such errors. In phase II, live demonstration of the procedure was given. Students were asked to treat three patients under instructor's supervision. The summative assessment was conducted by applying the same checklist criterion and rubric scoring used for the traditional method. Assessment results of three batches of students trained by flipped method (study group) and three traditionally trained previous batches (control group) were taken for comparison by chi-square test. The sum of traditionally trained three batch students who prepared acceptable dentures (score: 2 and 3) and unacceptable dentures (score: 1) was compared with the same of flipped trained three batch students revealed that the number of students who demonstrated competency by preparing acceptable dentures was higher for flipped training (χ 2 =30.996 with p<0.001). The results reveal the supremacy of flipped training in enhancing students competency and hence recommended for training various clinical procedures.

  8. A Mixed Methods Study on the Effect of Flipping the Undergraduate Medical Classroom

    Directory of Open Access Journals (Sweden)

    Kelly W. Burak

    2017-11-01

    Full Text Available The flipped classroom model is increasingly being adopted in healthcare education, despite the fact that recent systematic reviews in the nursing and medical education literature suggest that this method of instructional design is not inherently better or worse than the traditional classroom. In this study, we used a sequential, explanatory mixed methods design to assess the impact of flipping the hepatology classroom for preclinical medical students. Compared to students in the traditional classroom, students in the flipped classroom had significantly lower mean (SD ratings of their learning experiences (3.48 (1.10 vs. 4.50 (0.72, p < 0.001, d = 1.10, but better performance on the hepatology content of the end-of-course examination (78.0% (11.7% vs. 74.2 (15.1%, respectively, p < 0.01, d = 0.3. Based upon our qualitative data analyses, we propose that the flipped classroom induced a change in the learning process of students by requiring increased preparation for classroom learning and promoting greater learner autonomy, which resulted in better retention of learned material, but reduced enjoyment of the learning experience. This dissonance in outcomes is captured in the words of one flipped classroom student: “…I hated it while I was learning it, but boy did I remember it…”. Based upon our dissonant outcomes and the inconsistent findings in the literature, we feel that there is still equipoise regarding the effectiveness of the flipped classroom, and further studies are needed to describe ways of making the flipped classroom a more effective (±more enjoyable learning experience.

  9. Comparison of Pharmaceutical Calculations Learning Outcomes Achieved Within a Traditional Lecture or Flipped Classroom Andragogy

    Science.gov (United States)

    Frazier, Lisa; Anderson, Stephanie L.; Stanton, Robert; Gillette, Chris; Broedel-Zaugg, Kim; Yingling, Kevin

    2017-01-01

    Objective. To compare learning outcomes achieved from a pharmaceutical calculations course taught in a traditional lecture (lecture model) and a flipped classroom (flipped model). Methods. Students were randomly assigned to the lecture model and the flipped model. Course instructors, content, assessments, and instructional time for both models were equivalent. Overall group performance and pass rates on a standardized assessment (Pcalc OSCE) were compared at six weeks and at six months post-course completion. Results. Student mean exam scores in the flipped model were higher than those in the lecture model at six weeks and six months later. Significantly more students passed the OSCE the first time in the flipped model at six weeks; however, this effect was not maintained at six months. Conclusion. Within a 6 week course of study, use of a flipped classroom improves student pharmacy calculation skill achievement relative to a traditional lecture andragogy. Further study is needed to determine if the effect is maintained over time. PMID:28630511

  10. Comparison of Pharmaceutical Calculations Learning Outcomes Achieved Within a Traditional Lecture or Flipped Classroom Andragogy.

    Science.gov (United States)

    Anderson, H Glenn; Frazier, Lisa; Anderson, Stephanie L; Stanton, Robert; Gillette, Chris; Broedel-Zaugg, Kim; Yingling, Kevin

    2017-05-01

    Objective. To compare learning outcomes achieved from a pharmaceutical calculations course taught in a traditional lecture (lecture model) and a flipped classroom (flipped model). Methods. Students were randomly assigned to the lecture model and the flipped model. Course instructors, content, assessments, and instructional time for both models were equivalent. Overall group performance and pass rates on a standardized assessment (Pcalc OSCE) were compared at six weeks and at six months post-course completion. Results. Student mean exam scores in the flipped model were higher than those in the lecture model at six weeks and six months later. Significantly more students passed the OSCE the first time in the flipped model at six weeks; however, this effect was not maintained at six months. Conclusion. Within a 6 week course of study, use of a flipped classroom improves student pharmacy calculation skill achievement relative to a traditional lecture andragogy. Further study is needed to determine if the effect is maintained over time.

  11. Short-Circuit Degradation of 10-kV 10-A SiC MOSFET

    DEFF Research Database (Denmark)

    Eni, Emanuel-Petre; Beczkowski, Szymon; Munk-Nielsen, Stig

    2017-01-01

    The short-circuit behavior of power devices is highly relevant for converter design and fault protection. In this work, the degradation during short-circuit of a 10 kV 10 A 4H-SiC MOSFET is investigated at 6 kV DC-link voltage. The study aims to present the behavior of the device during short-circuit...... transients as it sustains increasing short-circuit pulses during its life-time. As the short-circuit pulse length increases, degradation of the device can be observed in periodically performed characterizations. The initial degradation seems to be associated with the channel region, and continuous stressing...

  12. Simulation of light-induced degradation of μc-Si in a-Si/μc-Si tandem solar cells by the diode equivalent circuit

    Science.gov (United States)

    Weicht, J. A.; Hamelmann, F. U.; Behrens, G.

    2016-02-01

    Silicon-based thin film tandem solar cells consist of one amorphous (a-Si) and one microcrystalline (μc-Si) silicon solar cell. The Staebler - Wronski effect describes the light- induced degradation and temperature-dependent healing of defects of silicon-based solar thin film cells. The solar cell degradation depends strongly on operation temperature. Until now, only the light-induced degradation (LID) of the amorphous layer was examined in a-Si/μc-Si solar cells. The LID is also observed in pc-Si single function solar cells. In our work we show the influence of the light-induced degradation of the μc-Si layer on the diode equivalent circuit. The current-voltage-curves (I-V-curves) for the initial state of a-Si/pc-Si modules are measured. Afterwards the cells are degraded under controlled conditions at constant temperature and constant irradiation. At fixed times the modules are measured at standard test conditions (STC) (AM1.5, 25°C cell temperature, 1000 W/m2) for controlling the status of LID. After the degradation the modules are annealed at dark conditions for several hours at 120°C. After the annealing the dangling bonds in the amorphous layer are healed, while the degradation of the pc-Si is still present, because the healing of defects in pc-Si solar cells needs longer time or higher temperatures. The solar cells are measured again at STC. With this laboratory measured I-V-curves we are able to separate the values of the diode model: series Rs and parallel resistance Rp, saturation current Is and diode factor n.

  13. Akt Kinase-Mediated Checkpoint of cGAS DNA Sensing Pathway.

    Science.gov (United States)

    Seo, Gil Ju; Yang, Aerin; Tan, Brandon; Kim, Sungyoon; Liang, Qiming; Choi, Younho; Yuan, Weiming; Feng, Pinghui; Park, Hee-Sung; Jung, Jae U

    2015-10-13

    Upon DNA stimulation, cyclic GMP-AMP synthase (cGAS) synthesizes the second messenger cyclic GMP-AMP (cGAMP) that binds to the STING, triggering antiviral interferon-β (IFN-β) production. However, it has remained undetermined how hosts regulate cGAS enzymatic activity after the resolution of DNA immunogen. Here, we show that Akt kinase plays a negative role in cGAS-mediated anti-viral immune response. Akt phosphorylated the S291 or S305 residue of the enzymatic domain of mouse or human cGAS, respectively, and this phosphorylation robustly suppressed its enzymatic activity. Consequently, expression of activated Akt led to the reduction of cGAMP and IFN-β production and the increase of herpes simplex virus 1 replication, whereas treatment with Akt inhibitor augmented cGAS-mediated IFN-β production. Furthermore, expression of the phosphorylation-resistant cGAS S291A mutant enhanced IFN-β production upon DNA stimulation, HSV-1 infection, and vaccinia virus infection. Our study identifies an Akt kinase-mediated checkpoint to fine-tune hosts' immune responses to DNA stimulation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  14. [Evaluation of flipped classroom teaching model in undergraduates education of oral and maxillofacial surgery].

    Science.gov (United States)

    Cai, Ming; Cao, Xia; Fang, Xiao; Wang, Xu-dong; Zhang, Li-li; Zheng, Jia-wei; Shen, Guo-fang

    2015-12-01

    Flipped classroom is a new teaching model which is different from the traditional teaching method. The history and characteristics of flipped classroom teaching model were introduced in this paper. A discussion on how to establish flipped classroom teaching protocol in oral and maxillofacial surgery education was carried out. Curriculum transformation, construction of education model and possible challenges were analyzed and discussed.

  15. When ab ≠ c - c': published errors in the reports of single-mediator models.

    Science.gov (United States)

    Petrocelli, John V; Clarkson, Joshua J; Whitmire, Melanie B; Moon, Paul E

    2013-06-01

    Accurate reports of mediation analyses are critical to the assessment of inferences related to causality, since these inferences are consequential for both the evaluation of previous research (e.g., meta-analyses) and the progression of future research. However, upon reexamination, approximately 15% of published articles in psychology contain at least one incorrect statistical conclusion (Bakker & Wicherts, Behavior research methods, 43, 666-678 2011), disparities that beget the question of inaccuracy in mediation reports. To quantify this question of inaccuracy, articles reporting standard use of single-mediator models in three high-impact journals in personality and social psychology during 2011 were examined. More than 24% of the 156 models coded failed an equivalence test (i.e., ab = c - c'), suggesting that one or more regression coefficients in mediation analyses are frequently misreported. The authors cite common sources of errors, provide recommendations for enhanced accuracy in reports of single-mediator models, and discuss implications for alternative methods.

  16. An Investigation of the Use of the "Flipped Classroom" Pedagogy in Secondary English Language Classrooms

    Science.gov (United States)

    Yang, Chi Cheung Ruby

    2017-01-01

    Aim/Purpose: To examine the use of a flipped classroom in the English Language subject in secondary classrooms in Hong Kong. Background: The research questions addressed were: (1) What are teachers' perceptions towards the flipped classroom pedagogy?; (2) How can teachers transfer their flipped classroom experiences to teaching other…

  17. Implementation of a Flipped Classroom for Nuclear Medicine Physician CME.

    Science.gov (United States)

    Komarraju, Aparna; Bartel, Twyla B; Dickinson, Lisa A; Grant, Frederick D; Yarbrough, Tracy L

    2018-06-21

    Increasingly, emerging technologies are expanding instructional possibilities, with new methods being adopted to improve knowledge acquisition and retention. Within medical education, many new techniques have been employed in the undergraduate setting, with less utilization thus far in the continuing medical education (CME) sphere. This paper discusses the use of a new method for CME-the "flipped classroom," widely used in undergraduate medical education. This method engages learners by providing content before the live ("in class") session that aids in preparation and fosters in-class engagement. A flipped classroom method was employed using an online image-rich case-based module and quiz prior to a live CME session at a national nuclear medicine meeting. The preparatory material provided a springboard for in-depth discussion at the live session-a case-based activity utilizing audience response technology. Study participants completed a survey regarding their initial experience with this new instructional method. In addition, focus group interviews were conducted with session attendees who had or had not completed the presession material; transcripts were qualitatively analyzed. Quantitative survey data (completed by two-thirds of the session attendees) suggested that the flipped method was highly valuable and met attendee educational objectives. Analysis of focus group data yielded six themes broadly related to two categories-benefits of the flipped method for CME and programmatic considerations for successfully implementing the flipped method in CME. Data from this study have proven encouraging and support further investigations around the incorporation of this innovative teaching method into CME for nuclear imaging specialists.

  18. A Flipped Writing Classroom: Effects on EFL Learners’ Argumentative Essays

    Directory of Open Access Journals (Sweden)

    Fatemeh Soltanpour

    2018-02-01

    Full Text Available According to the literature, flipped teaching is a relatively new pedagogical approach in which the typical activities of classroom lectures followed by homework in common teaching practice are reversed in order, and most often integrated or supplemented with some types of instructional materials, such as instructional videos or PowerPoint files. This experimental study, using a pre-test-treatment-posttest-delayed posttest design, was aimed at investigating the effect of flipped instruction on Iranian EFL learners’ quality of argumentative essays. The participants were 55 students, who were assigned to two groups: the flipped classroom (FC and the traditional classroom (TC. Each group received 3 sessions of treatment. First, whether there was any significant difference between the FC and TC in the overall quality of the essays was investigated. The FC group significantly outperformed the TC one. Then, whether the difference between the groups varied over time was explored, and it was revealed that the FC was still significantly superior over the TC. Next, whether there would be any significant change in the FC in the long run was examined, and no significant change was seen. The promising results found in FC group can be attributed to not only the flipped instruction but also the process of actively engaging the learners in their learning in addition to incorporating different techniques, such as the video screencasting, collaborative writing, as well as in-class teacher-learner interaction and negotiation because it is argued that the crucial point in flipped instruction is how teachers best use in-class-time with students.

  19. Relationships in the Flipped Classroom

    Directory of Open Access Journals (Sweden)

    Brett M. McCollum

    2017-12-01

    Full Text Available This study examines the effectiveness of flipped classrooms in chemistry, and identifies relationships as a major factor impacting the success of flipped instruction methods. Examination of student interview data reveals factors that affect the development of peer-peer, peer-peer leader, and peer-expert relationships in first-year general chemistry and second-year organic chemistry flipped classrooms. Success was measured in terms of student perceptions of the effectiveness of the instruction, as well as student academic development. Furthermore, analysis of research participant interviews reveals that academic reading circles, open-response multiple-attempt group quizzes, and peer leaders are important elements of a text-centric flipped approach at a small-classroom, commuter-campus university. Student reflections and classroom observations provide further support for these conclusions. Cet étude examine l’efficacité des salles de classe inversées en chimie et identifie la création de liens en tant que facteur important qui affecte la réussite des méthodes d’instruction inversée. L’examen des données provenant d’entrevues avec les étudiants révèle les facteurs qui affectent le développement des rapports d’étudiant à étudiant, d’étudiant à leader et d’étudiant à expert dans un cours inversé de chimie générale de première année et dans un cours de chimie organique de deuxième année. La réussite a été mesurée en termes de perceptions des étudiants de l’efficacité de l’instruction, ainsi que du développement académique des étudiants. De plus, l’analyse des entrevues des participants à la recherche révèle que les cercles de lecture universitaires, les tests de groupes à essais multiples et à réponses ouvertes, ainsi que les leaders de groupes sont des éléments importants d’une approche inversée centrée sur un texte en petite salle de classe, dans une université de banlieusards. Les

  20. Using Flipped Classroom Approach to Explore Deep Learning in Large Classrooms

    Science.gov (United States)

    Danker, Brenda

    2015-01-01

    This project used two Flipped Classroom approaches to stimulate deep learning in large classrooms during the teaching of a film module as part of a Diploma in Performing Arts course at Sunway University, Malaysia. The flipped classes utilized either a blended learning approach where students first watched online lectures as homework, and then…

  1. The effect of flipped teaching combined with modified team-based learning on student performance in physiology.

    Science.gov (United States)

    Gopalan, Chaya; Klann, Megan C

    2017-09-01

    Flipped classroom is a hybrid educational format that shifts guided teaching out of class, thus allowing class time for student-centered learning. Although this innovative teaching format is gaining attention, there is limited evidence on the effectiveness of flipped teaching on student performance. We compared student performance and student attitudes toward flipped teaching with that of traditional lectures using a partial flipped study design. Flipped teaching expected students to have completed preclass material, such as assigned reading, instructor-prepared lecture video(s), and PowerPoint slides. In-class activities included the review of difficult topics, a modified team-based learning (TBL) session, and an individual assessment. In the unflipped teaching format, students were given PowerPoint slides and reading assignment before their scheduled lectures. The class time consisted of podium-style lecture, which was captured in real time and was made available for students to use as needed. Comparison of student performance between flipped and unflipped teaching showed that flipped teaching improved student performance by 17.5%. This was true of students in both the upper and lower half of the class. A survey conducted during this study indicated that 65% of the students changed the way they normally studied, and 69% of the students believed that they were more prepared for class with flipped learning than in the unflipped class. These findings suggest that flipped teaching, combined with TBL, is more effective than the traditional lecture. Copyright © 2017 the American Physiological Society.

  2. Complementary roles of intracellular and pericellular collagen degradation pathways in vivo

    DEFF Research Database (Denmark)

    Wagenaar-Miller, Rebecca A; Engelholm, Lars H; Gavard, Julie

    2007-01-01

    Collagen degradation is essential for cell migration, proliferation, and differentiation. Two key turnover pathways have been described for collagen: intracellular cathepsin-mediated degradation and pericellular collagenase-mediated degradation. However, the functional relationship between these ...

  3. Equine First Aid Information Flip Booklet

    OpenAIRE

    Nay, Karah; Hoopes, Karl

    2017-01-01

    This is a flip chart type booklet with first aid information for horses, including checking vitals, pulse rate, respiration, mucus membrane color and capillary refill, signs of colic, deworming, vaccinations recommended for Utah, hoof care, and dental care.

  4. NMR investigation of spin flip in TmCrO3

    International Nuclear Information System (INIS)

    Karnachev, A.S.; Klechin, Yu.I.; Kovtun, N.M.; Moskvin, A.S.; Solov'ev, E.E.; Tkachenko, A.A.

    1987-01-01

    Spin flip in the rare earth orthochromate TmCrO 3 is studied by the double-pulse NMR technique. It is shown that below 5.6 K spin flip in the absence of an external magnetic field takes place as a first order phase transition from the high temperature phase Γ 2 to the low temperature phase Γ 4 with a region of coexistence of the two phases of more than 3.8 K. The spin flip phase transitions Γ 2 ↔ Γ 4 induced by an external magnetic field and the attendant phenomenon of magnetic and electric nonequivalence of 53 Cr nuclei from different magnetic sublattices are investigated. The anisotropy parameters of the hyperfine interactions and nuclear quadrupole interactions are calculated on the basis of the experimental data

  5. Is neutralino dark matter compatible with flipped SU(5) models

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, J.

    1989-07-13

    We consider the possibility that the lightest supersymmetric particle in flipped SUSY SU(5)xU(1) models is cosmologically stable and corresponds to a neutralino. Previous studies of dark matter in flipped SUSY SU(5) models have suggested that the decay of the oscillations of the SU(5) breaking scalar field would result in too many neutralinos, if they are stable. We show that it is possible for an acceptable density of neutralinos to occur in the case where the neutralino corresponds to a light photino, if the temperature at the end of the oscillation dominated period is flipped SU(5) models. Direct detection of dark matter in forthcoming experiments will therefore not eliminate this class of models. (orig.).

  6. THE IMPLEMENTATION OF FLIPPED CLASSROOM MODEL IN EFL WRITING

    OpenAIRE

    Rida Afrilyasanti

    2016-01-01

    Flipped classroom is an approach to learning to write that allows teachers to have one-on-one assistance to help learners in the “during writing” stage in the classroom. Theories are given to the students in a video lectures to watch before class. Because problems in writing mostly occur in “during writing” stage, teacher assistance is crucial. This paper aims to share theoretical review and research findings pertaining to the implementation of flipped classroom model to EFL writing. Research...

  7. Implementing the Flipped Classroom : An exploration of study behaviour and student performance

    NARCIS (Netherlands)

    Boevé, Anna J.; Meijer, Rob R.; Bosker, Roel J.; Vugteveen, Jorien; Hoekstra, Rink; Albers, Casper J.

    2017-01-01

    The flipped classroom is becoming more popular as a means to support student learning in higher education by requiring students to prepare before lectures and actively engaging students during lectures. While some research has been conducted into student performance in the flipped classroom,

  8. Search Strategy Development in a Flipped Library Classroom: A Student-Focused Assessment

    Science.gov (United States)

    Goates, Michael C.; Nelson, Gregory M.; Frost, Megan

    2017-01-01

    Librarians at Brigham Young University compared search statement development between traditional lecture and flipped instruction sessions. Students in lecture sessions scored significantly higher on developing search statements than those in flipped sessions. However, student evaluations show a strong preference for pedagogies that incorporate…

  9. Flipping HCI

    Directory of Open Access Journals (Sweden)

    C. Evans

    2016-08-01

    Full Text Available This paper presents the results of two studies involving “flipping the classroom”. Teaching material was delivered via interactive “e-lectures”, allowing face-to-face sessions to focus instead on practice. The e-lectures were designed according to standard usability principles coupled with recent research into the effect of interactivity on learning. The effectiveness of the use of e-lectures was then evaluated using an online survey. The results suggest that students prefer the flexibility offered by e-lectures compared to conventional lectures. The results contribute to our understanding of how this technology fits with face-to-face teaching in the digital age.

  10. Scientific Impact of MODIS C5 Calibration Degradation and C6+ Improvements

    Science.gov (United States)

    Lyapustin, A.; Wang, Y.; Xiong, X.; Meister, G.; Platnick, S.; Levy, R.; Franz, B.; Korkin, S.; Hilker, T.; Tucker, J.; hide

    2014-01-01

    The Collection 6 (C6) MODIS (Moderate Resolution Imaging Spectroradiometer) land and atmosphere data sets are scheduled for release in 2014. C6 contains significant revisions of the calibration approach to account for sensor aging. This analysis documents the presence of systematic temporal trends in the visible and near-infrared (500 m) bands of the Collection 5 (C5) MODIS Terra and, to lesser extent, in MODIS Aqua geophysical data sets. Sensor degradation is largest in the blue band (B3) of the MODIS sensor on Terra and decreases with wavelength. Calibration degradation causes negative global trends in multiple MODIS C5 products including the dark target algorithm's aerosol optical depth over land and Ångstrom exponent over the ocean, global liquid water and ice cloud optical thickness, as well as surface reflectance and vegetation indices, including the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI). As the C5 production will be maintained for another year in parallel with C6, one objective of this paper is to raise awareness of the calibration-related trends for the broad MODIS user community. The new C6 calibration approach removes major calibrations trends in the Level 1B (L1B) data. This paper also introduces an enhanced C6C calibration of the MODIS data set which includes an additional polarization correction (PC) to compensate for the increased polarization sensitivity of MODIS Terra since about 2007, as well as detrending and Terra- Aqua cross-calibration over quasi-stable desert calibration sites. The PC algorithm, developed by the MODIS ocean biology processing group (OBPG), removes residual scan angle, mirror side and seasonal biases from aerosol and surface reflectance (SR) records along with spectral distortions of SR. Using the multiangle implementation of atmospheric correction (MAIAC) algorithm over deserts, we have also developed a detrending and cross-calibration method which removes residual decadal trends on

  11. Flip chip assembly of thinned chips for hybrid pixel detector applications

    International Nuclear Information System (INIS)

    Fritzsch, T; Zoschke, K; Rothermund, M; Oppermann, H; Woehrmann, M; Ehrmann, O; Lang, K D; Huegging, F

    2014-01-01

    There is a steady trend to ultra-thin microelectronic devices. Especially for future particle detector systems a reduced readout chip thickness is required to limit the loss of tracking precision due to scattering. The reduction of silicon thickness is performed at wafer level in a two-step thinning process. To minimize the risk of wafer breakage the thinned wafer needs to be handled by a carrier during the whole process chain of wafer bumping. Another key process is the flip chip assembly of thinned readout chips onto thin sensor tiles. Besides the prevention of silicon breakage the minimization of chip warpage is one additional task for a high yield and reliable flip chip process. A new technology using glass carrier wafer will be described in detail. The main advantage of this technology is the combination of a carrier support during wafer processing and the chip support during flip chip assembly. For that a glass wafer is glue-bonded onto the backside of the thinned readout chip wafer. After the bump deposition process the glass-readout chip stack is diced in one step. Finally the glass carrier chip is released by laser illumination after flip chip assembly of the readout chip onto sensor tile. The results of the flip chip assembly process development for the ATLAS IBL upgrade are described more in detail. The new ATLAS FEI4B chip with a size of 20 × 19 mm 2 is flip chip bonded with a thickness of only 150 μm, but the capability of this technology has been demonstrated on hybrid modules with a reduced readout chip thickness of down to 50 μm which is a major step for ultra-thin electronic systems

  12. A Study on the Motivational Strategies in College English Flipped Classroom

    Science.gov (United States)

    Suo, Jia; Hou, Xiuying

    2017-01-01

    Flipped classroom is a great reform that brings a huge impact on the classroom teaching. Its essence is autonomous leaning, whose effect is determined by students' motivation. Therefore, to bring the advantages of the flipped classroom into full play, the top priority is to stimulate students' motivation. The paper makes a study on the…

  13. Acceptability of the flipped classroom approach for in-house teaching in emergency medicine.

    Science.gov (United States)

    Tan, Eunicia; Brainard, Andrew; Larkin, Gregory L

    2015-10-01

    To evaluate the relative acceptability of the flipped classroom approach compared with traditional didactics for in-house teaching in emergency medicine. Our department changed its learning model from a 'standard' lecture-based model to a 'flipped classroom' model. The 'flipped classroom' included provided pre-session learning objectives and resources before each 2 h weekly session. In-session activities emphasised active learning strategies and knowledge application. Feedback was sought from all medical staff regarding the acceptability of the new approach using an online anonymous cross-sectional qualitative survey. Feedback was received from 49/57 (86%) medical staff. Ninety-eight per cent (48/49) of respondents preferred the flipped classroom over the traditional approach. Aspects of the flipped classroom learners liked most included case-based discussion, interaction with peers, application of knowledge, self-directed learning and small-group learning. Barriers to pre-session learning include work commitments, 'life', perceived lack of time, family commitments, exam preparation and high volume of learning materials. Reported motivational factors promoting pre-session learning include formal assessment, participation requirements, more time, less material, more clinical relevance and/or more interesting material. Case studies and 'hands-on' activities were perceived to be the most useful in-session activities. The flipped classroom shows promise as an acceptable approach to in-house emergency medicine teaching. © 2015 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

  14. Directing-Group-mediated C-H-Alkynylations.

    Science.gov (United States)

    Caspers, Lucien D; Nachtsheim, Boris J

    2018-05-18

    C-C triple bonds are amongst the most versatile functional groups in synthetic chemistry. Complementary to the Sonogashira coupling the direct metal-catalyzed alkynylation of C-H bonds has emerged as a highly promising approach in recent years. To guarantee a high regioselectivity suitable directing groups (DGs) are necessary to guide the transition metal (TM) into the right place. In this Focus Review we present the current developments in DG-mediated C(sp 2 )-H and C(sp 3 )-H modifications with terminal alkynes under oxidative conditions and with electrophilic alkynylation reagents. We will discuss further modifications of the alkyne, in particular subsequent cyclizations to carbo- and heterocycles and modifications of the DG in the presence of the alkyne. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. To What Extent Does 'Flipping' Make Lessons Effective in a Multimedia Production Class?

    Science.gov (United States)

    Choi, Jaeho; Lee, Youngju

    2018-01-01

    This study examines the effects of a flipped classroom in a technology integration course for pre-service teachers. In total, 79 students were randomly assigned into a flipped classroom or a traditional classroom group and given three multimedia production tasks. Students in the flipped group reviewed an e-book for lessons on multimedia…

  16. The features of the Cosmic Web unveiled by the flip-flop field

    Science.gov (United States)

    Shandarin, Sergei F.; Medvedev, Mikhail V.

    2017-07-01

    Currently the dark matter environment is widely accepted as a framework for understanding of the observed structure in the universe. N-body simulations are indispensable for the analysis of the formation and evolution of the dark matter web. Two primary fields - density and velocity fields - are used in most of studies. Dark matter provides two additional fields that are unique for collisionless media only. They are the multistream field in Eulerian space and flip-flop field in Lagrangian space. The flip-flop field represents the number of sign reversals of an elementary volume of each collisionless fluid element. This field can be estimated by counting the sign reversals of the Jacobian at each particle at every time step of the simulation. The Jacobian is evaluated by numerical differentiation of the Lagrangian submanifold, I.e. the three-dimensional dark matter sheet in the six-dimensional space formed by three Lagrangian and three Eulerian coordinates. We present the results of the statistical study of the evolution of the flip-flop field from z = 50 to the present time z = 0. A number of statistical characteristics show that the pattern of the flip-flop field remains remarkably stable from z ≈ 30 to the present time. As a result the flip-flop field evaluated at z = 0 stores a wealth of information about the dynamical history of the dark matter web. In particular one of the most intriguing properties of the flip-flop is a unique capability to preserve the information about the merging history of haloes.

  17. High-Tc dc-SQUID gradiometers in flip-chip configuration

    Science.gov (United States)

    Peiselt, K.; Schmidl, F.; Linzen, S.; Anton, A. S.; Hübner, U.; Seidel, P.

    2003-12-01

    We describe a new design of a gradiometric flip-chip antenna, which is inductively coupled to a dc-SQUID gradiometer. Both components are patterned out of thin films of the high-Tc superconductor YBa2Cu3O7-x (YBCO). For the flip-chip antenna, a 40 mm × 10 mm SrTiO3 single crystalline substrate is used, while the gradiometer sensors are prepared on 10 mm × 10 mm SrTiO3 bicrystal substrates. Special attention is paid to the inductive coupling between the flip-chip antenna and the read-out gradiometer antenna. We investigate different designs of coupling loops in order to optimize the coupling inductance between both components of the sensor. With optimized coupling the sensor achieves a field-gradient resolution of 12 fT cm-1 Hz-1/2 in the white noise region and of 310 fT cm-1 Hz-1/2 at 1 Hz in the unshielded laboratory environment.

  18. The effects of flipped learning for bystander cardiopulmonary resuscitation on undergraduate medical students.

    Science.gov (United States)

    Nakanishi, Taizo; Goto, Tadahiro; Kobuchi, Taketsune; Kimura, Tetsuya; Hayashi, Hiroyuki; Tokuda, Yasuharu

    2017-12-22

    To compare bystander cardiopulmonary resuscitation skills retention between conventional learning and flipped learning for first-year medical students. A post-test only control group design. A total of 108 participants were randomly assigned to either the conventional learning or flipped learning. The primary outcome measures of time to the first chest compression and the number of total chest compressions during a 2-minute test period 6 month after the training were assessed with the Mann-Whitney U test. Fifty participants (92.6%) in the conventional learning group and 45 participants (83.3%) in the flipped learning group completed the study. There were no statistically significant differences 6 months after the training in the time to the first chest compression of 33.0 seconds (interquartile range, 24.0-42.0) for the conventional learning group and 31.0 seconds (interquartile range, 25.0-41.0) for the flipped learning group (U=1171.0, p=0.73) or in the number of total chest compressions of 101.5 (interquartile range, 90.8-124.0) for the conventional learning group and 104.0 (interquartile range, 91.0-121.0) for the flipped learning group (U=1083.0, p=0.75). The 95% confidence interval of the difference between means of the number of total chest compressions 6 months after the training did not exceed a clinically important difference defined a priori. There were no significant differences between the conventional learning group and the flipped learning group in our main outcomes. Flipped learning might be comparable to conventional learning, and seems a promising approach which requires fewer resources and enables student-centered learning without compromising the acquisition of CPR skills.

  19. Flipped GUT inflation

    OpenAIRE

    Ellis, John; Gonzalo, Tomás E.; Harz, Julia; Huang, Wei-Chih

    2015-01-01

    We analyse the prospects for constructing hybrid models of inflation that provide a dynamical realisation of the apparent closeness between the supersymmetric GUT scale and the possible scale of cosmological inflation. In the first place, we consider models based on the flipped SU(5)×U(1) gauge group, which has no magnetic monopoles. In one model, the inflaton is identified with a sneutrino field, and in the other model it is a gauge singlet. In both cases we find regions of the model paramet...

  20. Flipping for success: evaluating the effectiveness of a novel teaching approach in a graduate level setting.

    Science.gov (United States)

    Moraros, John; Islam, Adiba; Yu, Stan; Banow, Ryan; Schindelka, Barbara

    2015-02-28

    Flipped Classroom is a model that's quickly gaining recognition as a novel teaching approach among health science curricula. The purpose of this study was four-fold and aimed to compare Flipped Classroom effectiveness ratings with: 1) student socio-demographic characteristics, 2) student final grades, 3) student overall course satisfaction, and 4) course pre-Flipped Classroom effectiveness ratings. The participants in the study consisted of 67 Masters-level graduate students in an introductory epidemiology class. Data was collected from students who completed surveys during three time points (beginning, middle and end) in each term. The Flipped Classroom was employed for the academic year 2012-2013 (two terms) using both pre-class activities and in-class activities. Among the 67 Masters-level graduate students, 80% found the Flipped Classroom model to be either somewhat effective or very effective (M = 4.1/5.0). International students rated the Flipped Classroom to be significantly more effective when compared to North American students (X(2) = 11.35, p Students' perceived effectiveness of the Flipped Classroom had no significant association to their academic performance in the course as measured by their final grades (r s = 0.70). However, students who found the Flipped Classroom to be effective were also more likely to be satisfied with their course experience. Additionally, it was found that the SEEQ variable scores for students enrolled in the Flipped Classroom were significantly higher than the ones for students enrolled prior to the implementation of the Flipped Classroom (p = 0.003). Overall, the format of the Flipped Classroom provided more opportunities for students to engage in critical thinking, independently facilitate their own learning, and more effectively interact with and learn from their peers. Additionally, the instructor was given more flexibility to cover a wider range and depth of material, provide in-class applied learning