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Sample records for bicyclic bis-arylimidazole c-jun

  1. Selection and characterization of a DNA aptamer that can discriminate between cJun/cJun and cJun/cFos.

    Directory of Open Access Journals (Sweden)

    Ryan D Walters

    Full Text Available The AP-1 family of transcriptional activators plays pivotal roles in regulating a wide range of biological processes from the immune response to tumorigenesis. Determining the roles of specific AP-1 dimers in cells, however, has remained challenging because common molecular biology techniques are unable to distinguish between the role of, for example, cJun/cJun homodimers versus cJun/cFos heterodimers. Here we used SELEX (systematic evolution of ligands by exponential enrichment to identify and characterize DNA aptamers that are >100-fold more specific for binding cJun/cJun compared to cJun/cFos, setting the foundation to investigate the biological functions of different AP-1 dimer compositions.

  2. Characterization of c-Jun from orange-spotted grouper, Epinephelus coioides involved in SGIV infection.

    Science.gov (United States)

    Wei, Shina; Huang, Youhua; Huang, Xiaohong; Qin, Qiwei

    2015-03-01

    The nuclear phosphoprotein c-Jun is a member of the AP1 family of transcription activating complex, can be induced by various extracellular stimuli such as virus infection. In this study, the c-Jun gene (Ec-c-Jun) was cloned from orange-spotted grouper, Epinephelus coioides. The full-length Ec-c-Jun cDNA is composed of 2046 bp and encodes a polypeptide of 328 amino acids with 81% identity of zebrafish. Amino acid alignment analysis indicated that Ec-c-Jun contained three conserved domains including a transactivation domain (TAD), a DNA-binding domain (DBD) and leucine zipper domain (LZD). RT-PCR results showed that Ec-c-Jun transcript was most abundant in spleen, kidney, heart and gill. The expression of Ec-c-Jun was up-regulated after challenged with Singapore grouper iridovirus (SGIV). To investigate the roles of Ec-c-Jun during SGIV infection, we constructed its dominant-negative mutant (DN-Ec-c-Jun) by deleting the major TAD that lacks amino acids 3-122. Fluorescence microscopy observation revealed that Ec-c-Jun and DN-Ec-c-Jun were expressed predominantly in the nucleus in transfected cells. Interestingly, the green fluorescence of Ec-c-Jun was congregated and co-localized with virus assembly sites at the late stage of SGIV infection. However, in DN-Ec-c-Jun transfected cells, no virus assembly sites were observed, and the distribution of fluorescence remained unchanged. Moreover, overexpression of DN-Ec-c-Jun in vitro delayed the occurrence of CPE induced by SGIV infection and inhibited the virus gene transcription. In addition, ectopic expression of DN-Ec-c-Jun was able to inhibit SGIV induced c-Jun/AP1 promoter activity in GS cells. Thus, we proposed that c-Jun transcription factor was essential for SGIV replication in vitro. Our results will contribute to understanding the crucial roles of JNK signaling pathway in fish virus infection.

  3. c-Jun activation is associated with proliferation and angiogenesis in invasive breast cancer

    NARCIS (Netherlands)

    Vleugel, M.M.; Greijer, A.E.; Bos, R.; Wall, E. van der; Diest, P.J. van

    2006-01-01

    c-Jun is a component of the transcription factor activator protein 1 (AP-1), which binds and activates transcription at TRE/AP-1 elements. Extra- or intracellular signals, including growth factors, transforming oncoproteins, and UV irradiation, stimulate phosphorylation of c-Jun at serine 63/73 and

  4. Rice From Mercury Contaminated Areas in Guizhou Province Induces c-jun Expression in Rat Brain

    Institute of Scientific and Technical Information of China (English)

    JIN-PING CHENG; WEN-HUA WANG; LI-YA QU; JIN-PING JIA; MIN ZHENG; XIU-LING JI; TAO YUAN

    2005-01-01

    Objective Mercury (Hg), as one of the priority pollutants and also a hot topic of frontier environmental research in many countries, has been paid higher attention in the world since the middle of the last century. Guizhou Province (at N24°30′-29°13′, E103°1′-109°30′, 1 100 m above the sea level, with subtropical humid climate) in southwest China is an important mercury production center. It has been found that the mercury content in most media of aquatics, soil, atmosphere and in biomass of corns, plants and animals, is higher than the national standard.The present study aims to explore the influence of mercury pollution on the health of local citizens. Methods The effect of rice from two mercury polluted experimental plots of Guizhou Province on the expression of c-jun mRNA in rat brain and c-jun protein in cortex, hippocampus and ependyma was observed using reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemical methods. Results The results showed that the mercury polluted rice induced expression of c-jun mRNA and its protein significantly. Selenium can reduce Hg uptake, an antagonism between selenium and mercury on the expression of c-jun mRNA and c-jun protein. Conclusion c-jun participates in the toxicity process of brain injury by mercury polluted rice, the expression of c- jun mRNA in brain, and c-jun protein in rat cortex and hippocampus can predict neurotoxicity of mercury polluted rice. People should be advised to be cautious in eating any kind of Hg-polluted foods. To reveal the relationship between c-jun induction and apoptosis, further examinations are required.

  5. Mammary gland selective excision of c-jun identifies its role in mRNA splicing

    OpenAIRE

    Katiyar, Sanjay; Jiao, Xuanmao; Addya, Sankar; Ertel, Adam; Rose, Vanessa; Casimiro, Mathew C.; Zhou, Jie; Lisanti, Michael P; Nasim, Talat; Fortina, Paolo; Pestell, Richard G.

    2011-01-01

    The c-jun gene regulates cellular proliferation and apoptosis via direct regulation of cellular gene expression. Alternative splicing of pre-mRNA increases the diversity of protein functions and alternate splicing events occur in tumors. Here, by targeting the excision of the endogenous c-jun gene within the mouse mammary epithelium, we have identified its selective role as an inhibitor of RNA splicing. Microarray-based assessment of gene expression, on laser capture micro-dissected c-jun−/− ...

  6. Persistent induction of c-fos and c-jun expression by asbestos

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    Heintz, N.H.; Mossman, B.T. (Univ. of Vermont College of Medicine, Burlington (United States)); Janssen, Y.M. (Univ. of Vermont College of Medicine, Burlington (United States) Univ. of Limburg, Maastricht (Netherlands))

    1993-04-15

    To investigate the mechanisms of asbestos-induced carcinogenesis, expression of c-fos and c-jun protooncogenes was examined in rat pleural mesothelial cells and hamster tracheal epithelial cells after exposure to crocidolite or chrysotile asbestos. In contrast to phorbol 12-myristate 13-acetate, which induces rapid and transient increases in c-fos and c-jun mRNA, asbestos causes 2- to 5-fold increases in c-fos and c-jun mRNA that persist for at least 24 hr in mesothelial cells. The induction of c-fos and c-jun mRNA by asbestos in mesothelial cells is dose-dependent and is most pronounced with crocidolite, the type of asbestos most pathogenic in the causation of pleural mesothelioma. Induction of c-jun gene expression by asbestos occurs in tracheal epithelial cells but is not accompanied by a corresponding induction of c-fos gene expression. In both cell types, asbestos induces increases in protein factors that bind specifically to the DNA sites that mediate gene expression by the AP-1 family of transcription factors. The persistent induction of AP-1 transcription factors by asbestos suggests a model of asbestos-induced carcinogenesis involving chronic stimulation of cell proliferation through activation of the early response gene pathway that includes c-jun and/or c-fos. 30 refs., 5 figs.

  7. Parathyroid hormone induces c-fos and c-jun messenger RNA in rat osteoblastic cells

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    Clohisy, J. C.; Scott, D. K.; Brakenhoff, K. D.; Quinn, C. O.; Partridge, N. C.

    1992-01-01

    PTH is a potent regulator of osteoblast gene expression, yet the nuclear events that mediate PTH action are poorly understood. We were interested in identifying immediate early genes which may regulate PTH-altered gene expression in the osteoblast. Therefore, we examined the effects of PTH on c-fos and c-jun gene expression in a rat osteoblastic cell line (UMR 106-01). Under control conditions, c-fos and c-jun mRNAs were present at low basal levels. After PTH treatment, c-fos mRNA abundance dramatically increased, with a maximal and transient response at 30 min. PTH also stimulated an increase in c-jun mRNA, but in a biphasic manner, with maximal levels at 30 min and 2 h. These responses were dose dependent, not altered by cotreatment with the protein synthesis inhibitor cycloheximide, and preceded PTH-induced expression of matrix metallo-proteinase-1 mRNA. Nuclear run-on assays demonstrated an increased rate of c-fos and c-jun transcription after PTH exposure. To determine the signal transduction pathways involved, second messenger analogs were tested for their ability to mimic the effects of PTH. 8-Bromo-cAMP and phorbol 12-myristate 13-acetate (PMA) caused increases in the abundance of c-fos and c-jun transcripts. Ionomycin had no effect on the expression of these genes. Pretreatment of the cells with PMA resulted in a decrease in basal c-jun expression, but did not alter the PTH-mediated increase in c-fos, c-jun, or matrix metalloproteinase-1 mRNAs.(ABSTRACT TRUNCATED AT 250 WORDS).

  8. P75 and phosphorylated c-Jun are differentially regulated in spinal motoneurons following axotomy in rats

    Institute of Scientific and Technical Information of China (English)

    Qiuju Yuan; Huanxing Su; Wutian Wu; Zhi-Xiu Lin

    2012-01-01

    The neurotrophin receptor (p75) activates the c-Jun N-terminal kinase (JNK) pathway. Activation of JNK and its substrate c-Jun can cause apoptosis. Here we evaluate the role of p75 in spinal motoneurons by comparing immunoreactivity for p75 and phosphorylated c-Jun (p-c-Jun), the production of JNK activation in axotomized motoneurons in postnatal day (PN)1, PN7, PN14 and adult rats. Intensive p-c-Jun was induced in axotomized motoneurons in PN1 and PN7. In PN14, p-c-Jun expression was sharply reduced after the same injury. The decreased expression of p-c-Jun at this age coincided with a developmental switch of re-expression of p75 in axotomized cells. In adult animals, no p-c-Jun but intensive p75 was detected in axotomized motoneurons. These results indicate differential expression or turnover of phosphorylation of c-Jun and p75 in immature versus mature spinal motoneurons in response to axonal injury. The non-co-occurrence of p75 and p-c-Jun in injured motoneurons indicated that p75 may not activate JNK pathway, suggesting that the p75 may not be involved in cell death in axotomized motoneurons.

  9. G12 Signaling through c-Jun NH2-Terminal Kinase Promotes Breast Cancer Cell Invasion

    OpenAIRE

    Juhi Juneja; Ian Cushman; Casey, Patrick J.

    2011-01-01

    Signaling through the heterotrimeric G protein, G12, via Rho induces a striking increase in breast cancer cell invasion. In this study, evidence is provided that the c-Jun NH(2)-terminal kinase (JNK) is a key downstream effector of G12 on this pathway. Expression of constitutively-active Gα12 or activation of G12 signaling by thrombin leads to increased JNK and c-Jun phosphorylation. Pharmacologic inhibition of JNK or knockdown of JNK expression by siRNA significantly decreases G12-induced JN...

  10. c-Jun Promotes whereas JunB Inhibits Epidermal Neoplasia

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    Jin, Jane Yingai; Ke, Hengning; Hall, Russell P.; Zhang, Jennifer Y.

    2011-01-01

    Deregulation of the AP1 family gene regulators have been implicated in a wide range of diseases, including cancer. Here, we report that c-Jun was activated in human squamous cell carcinoma (SCC) and coexpression of c-Jun with oncogenic Ras was sufficient to transform primary human epidermal cells into malignancy in a regenerated human skin grafting model. In contrast, JunB was not induced in a majority of human SCC cells. Moreover, exogenous expression of JunB inhibited tumorigenesis driven b...

  11. The oncogenic transcription factor c-Jun regulates glutaminase expression and sensitizes cells to glutaminase-targeted therapy

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    Lukey, Michael J.; Greene, Kai Su; Erickson, Jon W.; Wilson, Kristin F.; Cerione, Richard A.

    2016-01-01

    Many transformed cells exhibit altered glucose metabolism and increased utilization of glutamine for anabolic and bioenergetic processes. These metabolic adaptations, which accompany tumorigenesis, are driven by oncogenic signals. Here we report that the transcription factor c-Jun, product of the proto-oncogene JUN, is a key regulator of mitochondrial glutaminase (GLS) levels. Activation of c-Jun downstream of oncogenic Rho GTPase signalling leads to elevated GLS gene expression and glutaminase activity. In human breast cancer cells, GLS protein levels and sensitivity to GLS inhibition correlate strongly with c-Jun levels. We show that c-Jun directly binds to the GLS promoter region, and is sufficient to increase gene expression. Furthermore, ectopic overexpression of c-Jun renders breast cancer cells dependent on GLS activity. These findings reveal a role for c-Jun as a driver of cancer cell metabolic reprogramming, and suggest that cancers overexpressing JUN may be especially sensitive to GLS-targeted therapies. PMID:27089238

  12. c-Jun N-Terminal Phosphorylation: Biomarker for Cellular Stress Rather than Cell Death in the Injured Cochlea.

    Science.gov (United States)

    Anttonen, Tommi; Herranen, Anni; Virkkala, Jussi; Kirjavainen, Anna; Elomaa, Pinja; Laos, Maarja; Liang, Xingqun; Ylikoski, Jukka; Behrens, Axel; Pirvola, Ulla

    2016-01-01

    Prevention of auditory hair cell death offers therapeutic potential to rescue hearing. Pharmacological blockade of JNK/c-Jun signaling attenuates injury-induced hair cell loss, but with unsolved mechanisms. We have characterized the c-Jun stress response in the mouse cochlea challenged with acoustic overstimulation and ototoxins, by studying the dynamics of c-Jun N-terminal phosphorylation. It occurred acutely in glial-like supporting cells, inner hair cells, and the cells of the cochlear ion trafficking route, and was rapidly downregulated after exposures. Notably, death-prone outer hair cells lacked c-Jun phosphorylation. As phosphorylation was triggered also by nontraumatic noise levels and none of the cells showing this activation were lost, c-Jun phosphorylation is a biomarker for cochlear stress rather than an indicator of a death-prone fate of hair cells. Preconditioning with a mild noise exposure before a stronger traumatizing noise exposure attenuated the cochlear c-Jun stress response, suggesting that the known protective effect of sound preconditioning on hearing is linked to suppression of c-Jun activation. Finally, mice with mutations in the c-Jun N-terminal phosphoacceptor sites showed partial, but significant, hair cell protection. These data identify the c-Jun stress response as a paracrine mechanism that mediates outer hair cell death. PMID:27257624

  13. c-Jun promotes whereas JunB inhibits epidermal neoplasia.

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    Jin, Jane Y; Ke, Hengning; Hall, Russell P; Zhang, Jennifer Y

    2011-05-01

    Deregulation of the activator protein 1 (AP1) family gene regulators has been implicated in a wide range of diseases, including cancer. In this study we report that c-Jun was activated in human squamous cell carcinoma (SCC) and coexpression of c-Jun with oncogenic Ras was sufficient to transform primary human epidermal cells into malignancy in a regenerated human skin grafting model. In contrast, JunB was not induced in a majority of human SCC cells. Moreover, exogenous expression of JunB inhibited tumorigenesis driven by Ras or spontaneous human SCC cells. Conversely, the dominant-negative JunB mutant (DNJunB) promoted tumorigenesis, which is in contrast to the tumor-suppressor function of the corresponding c-Jun mutant. At the cellular level, JunB induced epidermal cell senescence and slowed cell growth in a cell-autonomous manner. Consistently, coexpression of JunB and Ras induced premature epidermal differentiation concomitant with upregulation of p16 and filaggrin and downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4). These findings indicate that JunB and c-Jun differentially regulate cell growth and differentiation and induce opposite effects on epidermal neoplasia.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://www.nature.com/jid/journalclub. PMID:21289643

  14. c-Jun N-terminal kinase mediates constitutive human eosinophil apoptosis

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    Hasala, Hannele; Zhang, Xianzhi; Saarelainen, Seppo; Moilanen, Eeva; Kankaanranta, Hannu

    2007-01-01

    c-Jun N-terminal kinase mediates constitutive human eosinophil apoptosis correspondence: Corresponding author. Tel.: +358335517318; fax: +358335518082. (Kankaanranta, Hannu) (Kankaanranta, Hannu) The Immunopharmacology Research Group--> , Medical School--> , University of Tampere--> , Tampere--> - FINLAND (Hasala, Hannele) The Immunopharmacology Research Group--> , Medical School--...

  15. Ketamine inhibits c-Jun protein expression in mouse hippocampus following cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Feng Xiao; Liangzhi Xiong; Qingxiu Wang; Long Zhou; Qingshan Zhou

    2012-01-01

    A model of cerebral ischemia and reperfusion was established in mice. Mice were treated with ketamine via intraperitoneal injection immediately following ischemia or ischemia/reperfusion. Ketamine did not remarkably change infarct volume in mice immediately following ischemia, but injection immediately following ischemia/reperfusion significantly decreased infarct volume. Ketamine injection immediately after ischemia or ischemia/reperfusion inhibited c-Jun protein expression in mouse hippocampus, but nuclear factor kappa B expression was unaltered. In addition, the Longa scale score for neural impairment was not reduced in mice following cerebral ischemia/reperfusion. These results indicate that ketamine can protect mice against cerebral ischemia and reperfusion injury by modulating c-Jun protein expression in mouse hippocampus.

  16. HEPATIC APOPTOSIS POST-BURN IS MEDIATED BY C-JUN N-TERMINAL KINASE-2

    OpenAIRE

    Marshall, Alexandra H; Brooks, Natasha C; Hiyama, Yaeko; Qa’aty, Nour; Al-mousawi, Ahmed; Finnerty, Celeste C.; Jeschke, Marc G.

    2013-01-01

    The trauma of a severe burn injury induces a hypermetabolic response that increases morbidity and mortality. Previously, our group showed that insulin resistance post-burn injury is associated with endoplasmic reticulum (ER) stress. Evidence suggests that c-jun N-terminal kinase (JNK) -2 may be involved in ER stress-induced apoptosis. Here, we hypothesized that JNK2 contributes to the apoptotic response after burn injury downstream of ER stress. To test this, we compared JNK2 knockout mice (−...

  17. Modelling the mechanism of GR/c-Jun/Erg crosstalk in apoptosis of acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Daphne eChen

    2012-11-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is one of the most common forms of malignancy that occurs in lymphoid progenitor cells, particularly in children. Synthetic steroid hormones glucocorticoids (GCs are widely used as part of the ALL treatment regimens due to their apoptotic function, but their use also brings about various side effects and drug resistance. The identification of the molecular differences between the GCs responsive and resistant cells therefore are essential to decipher such complexity and can be used to improve therapy. However, the emerging picture is complicated as the activities of genes and proteins involved are controlled by multiple factors. By adapting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data via the building of a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Erg as determinant for GC resistance. The results revealed an alternative potential mechanism where c-Jun may be an indirect GR target that is controlled via an upstream repressor protein. The models also highlight the importance of Erg for GR function, particularly in GC sensitive C7 cells where Erg directly regulates GR in agreement with our previous experimental results. Our models describe potential GR-controlled molecular mechanisms of c-Jun/Bim and Erg regulation. We also demonstrate the importance of using a systematic approach to translate human disease processes into computational models in order to derive information-driven new hypotheses.

  18. A study on the expression of c-jun mRNA after experimental rat brain concussion%实验性大鼠脑震荡后c-jun mRNA表达

    Institute of Scientific and Technical Information of China (English)

    汪枫; 李永宏

    2011-01-01

    Objective To evaluate changes of c-jun mRNA after brain concussion. Methods Fifty-five rats were randomly divided into brain concussion groups ( 0min, 15 min, 30min, 60min, 3 h, 6h, 12h, 24h, 48 h,96h) and control group. The expression of c-jun mRNA in cortex 、thalamus and brain stem was microscopically observed by In site hybridization method. Results There were weak positive expression of c-jun mRNA in some neutrons and neuroglia cells in control group. In brain concussion group, however,positive expression of c-jun mRNA in some neutrons was seen at 15min after brain concussion,and reach to the peak at 30min after brain concussion the level of expression of c-jun mRNA were as well as control group at 96h. Conclusion There findings suggest that detection of c-jun mRNA could be an index of diagnosis of brain concussion and a sensitive marker of timing of injury after brain concussion.%目的 观察实验性大鼠脑震荡后c-jun mRNA的表达变化规律.方法 55只实验大鼠随机分为脑震荡组(0min、15min、30min、60min、3h、6h、12h、24h、48h、96h)和对照组,用原位杂交法观察大鼠脑震荡后各时间点,大脑皮质、脑干和丘脑神经元c-jun mRNA表达的变化规律.结果 对照组大鼠神经元和胶质细胞均可见c-jun mRNA的弱阳性表达.脑震荡组大鼠损伤后15min神经细胞观察到c-jun mRNA阳性表达,随损伤后经过时间的延长阳性表达逐渐增强;30min时c-jun mRNA阳性反应达高峰,随后逐渐降低,至96h时回落至对照组水平.结论 c-jun mRNA表达水平可成为诊断脑震荡和推断伤后经过时间的一项敏感指标.

  19. Bicycle Commuting

    OpenAIRE

    Heinen, E

    2011-01-01

    Cycling is cheaper, healthier and in urban environments often faster than other transport modes. Nevertheless, even at short distances, many individuals do not cycle. This thesis aims to explain why commuters vary in their decision to bicycle. Results indicate that the individual (day-to-day) choice to commute by bicycle is affected by personal attitudes towards cycling to work, social norms, work situation, weather conditions and trip characteristics. Additionally, this thesis provides evide...

  20. Activation of c-Jun N-terminal Kinases by Ribotoxic Stresses

    Institute of Scientific and Technical Information of China (English)

    Dong-Yun Ouyang; Yuan-Yuan Wang; Yong-Tang Zheng

    2005-01-01

    The c-Jun N-terminal kinases (JNKs) are classic stress-activated protein kinases. Many cellular stresses have been shown to stimulate JNK activation. In this review, we focus on ribotoxic stresses based on their multiple biological potencies including anti-HIV-1 activity. Some of the functions of ribotoxins and the signaling transduction pathway that mediated are mentioned. Different from other stimulators, ribotoxic stresses act on special motifs of 28S rRNA in translationally active mammal ribosomes. Binding and damaging on the motif leads to JNK activation and subsequently biological response to the signal initiator, which is named ribotoxic stress response.

  1. HP1a/KDM4A is involved in the autoregulatory loop of the oncogene gene c-Jun.

    Science.gov (United States)

    Liu, Yan; Zhang, Daoyong

    2015-01-01

    The proto-oncogene c-Jun plays crucial roles in tumorigenesis, and its aberrant expression has been implicated in many cancers. Previous studies have shown that the c-Jun gene is positively autoregulated by its product. Notably, it has also been reported that c-Jun proteins are enriched in its gene body region. However, the role of c-Jun proteins in its gene body region has yet to be uncovered. HP1a is an evolutionarily conserved heterochromatin-associated protein, which plays an essential role in heterochromatin-mediated gene silencing. Interestingly, accumulating evidence shows that HP1a is also localized to euchromatic regions to positively regulate gene transcription. However, the underlying mechanism has not been defined. In this study, we demonstrate that HP1a is involved in the positive autoregulatory loop of the Jra gene, the c-Jun homolog in Drosophila. Jra recruits the HP1a/KDM4A complex to its gene body region upon osmotic stress to reduce H3K36 methylation levels and disrupt H3K36 methylation-dependent histone deacetylation, resulting in high levels of histone acetylation in the Jra gene body region, thus promoting gene transcription. These results not only expand our knowledge toward the mechanism of c-Jun regulation, but also reveal the mechanism by which HP1a exerts its positive regulatory function in gene expression.

  2. Bicycling injuries.

    Science.gov (United States)

    Silberman, Marc R

    2013-01-01

    Bicycling injuries can be classified into bicycle contact, traumatic, and overuse injuries. Despite the popularity of cycling, there are few scientific studies regarding injuries. Epidemiological studies are difficult to compare due to different methodologies and the diverse population of cyclists studied. There are only three studies conducted on top level professionals. Ninety-four percent of professionals in 1 year have experienced at least one overuse injury. Most overuse injuries are mild with limited time off the bike. The most common site of overuse injury is the knee, and the most common site of traumatic injury is the shoulder, with the clavicle having the most common fracture. Many overuse and bicycle contact ailments are relieved with simple bike adjustments.

  3. Heterogeneity in c-jun gene expression in normal and malignant cells exposed to either ionizing radiation or hydrogen peroxide

    International Nuclear Information System (INIS)

    We investigated the role of reactive oxygen intermediates and protein kinase C (PKC) in induction of c-jun gene expression in human ML-2 leukemic cells and normal DET-551 fibroblasts by comparing the effects of either ionizing radiation or H2O2 exposure in the presence or absence of appropriate inhibitors. In these cell types, the radiation and H2O2-mediated increase in c-jun mRNA levels could be prevented by pretreatment of the cells with N-acetylcysteine, an antioxidant, or H7, an inhibitor of PKC and cAMP-dependent protein kinase (PKA), but not by HA1004, an inhibitor of PKA. These results suggest a role for PKC and reactive oxygen intermediates in the induction of c-jun gene expression in both normal and tumor cells. We also investigated potential differences in radiation- or H2O2-induced c-jun gene expression in normal and tumor cells by examining steady-state c-jun mRNA levels in a number of human fibroblast, leukemia, melanoma, sarcoma, and carcinoma cell types. We observed heterogeneity in the steady-state level of c-jun mRNA in both the untreated normal and tumor cells and in such cells exposed to ionizing radiation or to H2O2. Exposure to radiation or to hydrogen peroxide produced a varied response which ranged from little or no induction to a more than two orders of magnitude increase in the steady-state level of the c-jun mRNA

  4. c-Jun represses the human insulin promoter activity that depends on multiple cAMP response elements

    Energy Technology Data Exchange (ETDEWEB)

    Inagaki, Nobuya; Seino, Yutaka; Imura, Hiroo (Kyoto Univ. (Japan)); Maekawa, Toshio; Sudo, Tatsuhiko; Ishii, Shunsuke (Inst. of Physical and Chemical Research (RIKEN), Tsukuba (Japan))

    1992-02-01

    Glucose is known to increase the cAMP concentration in pancreatic {beta} cells. To determine the mechanism by which cAMP augments insulin gene expression, the authors first identified the cAMP response elements (CREs) of human insulin gene. In DNase I footprint analysis, the bacterially synthesized CRE-binding protein, CRE-BP1, protected four sites: two sites in the region upstream from the insulin core promoter, one site in the first exon, and one site in the first intron. To examine the roles of those four sites, they constructed a series of DNA plasmids in which the wild-type and mutant insulin promoters were linked to the chloramphenicol acetyltransferase gene. Studies of the transcriptional activity of these plasmids after transfection into hamster insulinoma (HIT) cells showed that these four sites contributed additively to the cAMP inducibility of the insulin promoter. Surprisingly, the c-jun protooncogene product (c-Jun) repressed the cAMP-induced activity of the insulin promoter in a cotransfection assay with the c-Jun expression plasmic. Northern blot analysis demonstrated that the level of c-jun mRNA was dramatically increased by glucose deprivation in HIT cells. These results suggest that glucose deprivation in HIT cells. These results suggest that glucose may regulate expression of the human insulin gene through multiple CREs and c-Jun.

  5. Heterodimer formation between c-Jun and Jun B proteins mediated by Epstein Barr virus encoded latent membrane protein 1

    Institute of Scientific and Technical Information of China (English)

    SONG; Xin; TAO; Yongguang; TAN; Yunnian; Leo; M.; Lee; DENG

    2005-01-01

    Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) may trigger the transcription factor AP-1 including c-Jun and c-fos. In this report, using a Tet-on LMP1 HNE2 cell line which is a dual-stable LMP1 integrated nasopharyngeal carcinoma (NPC) cell line and the expression of LMP1 in which could be regulated by the Tet-on system, we show that Jun B can efficiently form a new heterodimeric complex with the c-Jun protein under the regulation of LMP1, phosphorylation of c-Jun (ser 63, ser 73) and Jun B is involved in the process of the new heterodimeric formation. We also find that this heterodimeric form can bind to the AP-1 consensus sequence. Transfection studies suggest that JNK interaction protein (JIP) could inhibit the heterodimer formation of c-Jun and Jun B through blocking the AP-1 signaling pathway triggered by LMP1. The interaction and function between c-Jun protein and Jun B protein increase the repertoire of possible regulatory complexes by LMP1 that could play an important role in the regulation of transcription of specific cellular genes in the process of genesis of nasopharyngeal carcinoma.

  6. Bicycle accidents.

    Science.gov (United States)

    Lind, M G; Wollin, S

    1986-01-01

    Information concerning 520 bicycle accidents and their victims was obtained from medical records and the victims' replies to questionnaires. The analyzed aspects included risk of injury, completeness of accident registrations by police and in hospitals, types of injuries and influence of the cyclists' age and sex, alcohol, fatigue, hunger, haste, physical disability, purpose of cycling, wearing of protective helmet and other clothing, type and quality of road surface, site of accident (road junctions, separate cycle paths, etc.) and turning manoeuvres.

  7. Correlation between spina bifida manifesta in fetal rats and c-Jun N-terminal kinase signaling

    Institute of Scientific and Technical Information of China (English)

    Yinghuan Ma; Yongxin Bao; Chenghao Li; Fubin Jiao; Hongjie Xin; Zhengwei Yuan

    2012-01-01

    Fetal rat models with neural tube defects were established by injection with retinoic acid at 10 days after conception. The immunofluorescence assay and western blot analysis showed that the number of caspase-3 positive cells in myeloid tissues for spina bifida manifesta was increased. There was also increased phosphorylation of c-Jun N-terminal kinase, a member of the mitogen activated protein kinase family. The c-Jun N-terminal kinase phosphorylation level was positively correlated with caspase-3 expression in myeloid tissues for spina bifida manifesta. Experimental findings indicate that abnormal apoptosis is involved in retinoic acid-induced dominant spina bifida formation in fetal rats, and may be associated with the c-Jun N-terminal kinase signal transduction pathway.

  8. Expression of c-fos and c-jun protooncogenes in the uteri of immature mice neonatally exposed to diethylstilbestrol.

    Science.gov (United States)

    Yamashita, S; Takayanagi, A; Shimizu, N

    2003-01-01

    We studied the cell-type-specific and temporal expression of c-fos and c-jun protooncogenes after 17beta-estradiol (E2) stimulation in the uteri of immature 3-week-old mice neonatally exposed to diethylstilbestrol (DES), DES-mice, and the ontogenic expression of these genes in the uteri of DES-mice using immunohistochemistry and in situ hybridization. A single E2 injection induced the transient and rapid expression of c-fos mRNA and c-Fos protein in the endometrial epithelium and endothelial cells of the blood vessels in both 3-week-old vehicle-treated controls and DES-mice; a peak of mRNA expression was 2 hours after E2 injection and that of protein expression was 2 to 3 hours after the injection. The expression of c-fos mRNA and protein after E2 stimulation was lower in the DES-mice than in the control animals. There were no significant differences in the c-jun expression patterns in both experimental groups before and after the E2 injection. The E2 injection transiently down-regulated the c-jun expression in the epithelium and up-regulated it in the stroma and myometrium. The uterine epithelium of DES-mice showed much stronger c-Jun immunostaining on days 4 and 10, compared with those of controls. Neonatal DES treatment reduced c-Jun immunoreactivity in the uterine epithelium on days 4 and 10, and increased the reaction in the stroma on day 4. These results suggested that the neonatal DES treatment induces permanent changes in the c-fos expression pattern independent of the postpuberal secretion of ovarian steroids. The changes in the expression of c-fos and c-jun protooncogenes, particularly during postnatal development, are likely to play important roles in the production of uterine abnormalities in the DES-mice.

  9. Solar Bicycle

    OpenAIRE

    S. Sridhar; HARSHENDRA. N. SHET. K

    2011-01-01

    The running costs of the present vehicles are rising day by day hence common man is looking for an alternate mode of transport, with low fuel and maintenance cost. Solar bicycle is an attempt to meet these needs. It is an environmentally sustainable and zero running cost vehicle. It uses photovoltaic cells to absorb energy from sunlight. The absorbed energy is stored in battery. The hub motor mounted on the rear wheel uses this energy to run the cycle. A fully charged battery gives a mileage ...

  10. The AP-1 Transcription Factor c-Jun Prevents Stress-Imposed Maladaptive Remodeling of the Heart

    Science.gov (United States)

    Windak, Renata; Müller, Julius; Felley, Allison; Akhmedov, Alexander; Wagner, Erwin F.; Pedrazzini, Thierry; Sumara, Grzegorz; Ricci, Romeo

    2013-01-01

    Systemic hypertension increases cardiac workload and subsequently induces signaling networks in heart that underlie myocyte growth (hypertrophic response) through expansion of sarcomeres with the aim to increase contractility. However, conditions of increased workload can induce both adaptive and maladaptive growth of heart muscle. Previous studies implicate two members of the AP-1 transcription factor family, junD and fra-1, in regulation of heart growth during hypertrophic response. In this study, we investigate the function of the AP-1 transcription factors, c-jun and c-fos, in heart growth. Using pressure overload-induced cardiac hypertrophy in mice and targeted deletion of Jun or Fos in cardiomyocytes, we show that c-jun is required for adaptive cardiac hypertrophy, while c-fos is dispensable in this context. c-jun promotes expression of sarcomere proteins and suppresses expression of extracellular matrix proteins. Capacity of cardiac muscle to contract depends on organization of principal thick and thin filaments, myosin and actin, within the sarcomere. In line with decreased expression of sarcomere-associated proteins, Jun-deficient cardiomyocytes present disarrangement of filaments in sarcomeres and actin cytoskeleton disorganization. Moreover, Jun-deficient hearts subjected to pressure overload display pronounced fibrosis and increased myocyte apoptosis finally resulting in dilated cardiomyopathy. In conclusion, c-jun but not c-fos is required to induce a transcriptional program aimed at adapting heart growth upon increased workload. PMID:24039904

  11. Dentin bonding agents induce c-fos and c-jun protooncogenes expression in human gingival fibroblasts.

    Science.gov (United States)

    Huang, Fu-Mei; Chou, Ming-Yung; Chang, Yu-Chao

    2003-01-01

    An important requirement for a dentin bonding agent is biologic compatibility; the bonding agent usually remains in close contact with living dental tissues over a long period of time. Information on the genotoxicity/mutagenicity and cacinogenicity potentials of dentin bonding agents is rare. It has been shown that c-fos and c-jun are induced rapidly by a variety of chemical and physical stimuli. Little is known about the induction of cellular signaling events and specific gene expression after cell exposure to dentin bonding agents. Therefore, we used primary human gingival fibroblasts to examine the effect of six dentin bonding agents on the expression of c-fos and c-jun protooncogenes to evaluate the genotoxicity/mutagenicity and cacinogenicity potential of the dentin bonding agents. The levels of mRNA were measured by the quantitative RT-PCR analysis. c-fos and c-jun mRNA expression in dentin bonding agents-treated cells revealed a rapid accumulation of the transcript, a significant signal first was detectable after 1h of exposure. Persistent induction of c-jun and c-fos protooncogenes by dentine bonding agents may distribute systemically to cause some unexpected adverse effects on human beings. It would be necessary to identify the severely toxic compounds and replace these substances by better biocompatible components. Otherwise, leaching of those genotoxicity/mutagenicity and cacinogenicity components must be minimized or prevented.

  12. Expression of c-jun in brain stem following moderate lateral fluid percussion brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the expression of c-jun in brain stem following moderate lateral fluid percussion brain injury in rats, and to observe the temporal patterns of its expressions following percussion.METHODS: Male Sprague-Dawley rats were divided into normal control, sham operation control and injury groups. The rats of injury group subjected to moderate lateral fluid percussion injury (0.2 mPa), and then were subdivided into 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h and 12 h groups according to the time elapsed after injury. The expression of c-jun was studied by immunohistochemistry and in situ hybridization. RESULTS: After percussion for 15 min, Jun positive neurons increased in brain stem progressively, and peaked at 12h. At 5min after percussion, the induction of c-jun mRNA was increased, and remained elevated up to 1h-2h after brain injury. CONCLUSION: The induction and expression of the c-jun in brain stem after fluid percussion brain injury were increased rapidly and lasted for a long time.

  13. RhoA regulates invasion of glioma cells via the c-Jun NH2-terminal kinase pathway under hypoxia.

    Science.gov (United States)

    Tong, Jiao Jian; Yan, Zhang; Jian, Ren; Tao, Huang; Hui, Ouyang Tao; Jian, Chen

    2012-09-01

    The purpose of this study was to investigate the mechanism of glioma cell invasion in hypoxic conditions. We demonstrated that hypoxia increased cell invasion, matrix metalloproteinase-2 (MMP2) activity and time-dependent expression of hypoxia inducible factor-1α (HIF-1α) in human glioma cells. These data suggest that MMP2 may play a significant role in tumor invasion in hypoxic conditions. We investigated the mechanisms involved in the increased MMP2 activity and cell invasion in hypoxic conditions. Increased expression of phospho-Jun NH2-terminal kinase (p-JNK) and phospho-c-Jun (p-c-Jun) in glioma cells induced by hypoxia was detected. Furthermore, this effect may be reduced by inhibiting the JNK signaling pathway. We found that inhibition of RhoA geranylgeranylation by geranylgeranyltransferase inhibitor-2147 (GGTI-2147) or knockdown of RhoA by siRNA against RhoA reduced the expression of p-JNK and p-c-Jun, and decreased MMP2 activity and glioma cell invasion in hypoxic conditions. These data suggest a link among RhoA, JNK, c-Jun and MMP2 activity that is functionally involved in the increased glioma cell invasion induced by hypoxia. PMID:23741249

  14. Ginkgo biloba extract individually inhibits JNK activation and induces c-Jun degradation in human chondrocytes: potential therapeutics for osteoarthritis.

    Directory of Open Access Journals (Sweden)

    Ling-Jun Ho

    Full Text Available Osteoarthritis (OA is a common joint disorder with varying degrees of inflammation. The ideal anti-OA drug should have immunomodulatory effects while at the same time having limited or no toxicity. We examined the anti-inflammatory effects of Ginkgo biloba extract (EGb in interleukin-1 (IL-1-stimulated human chondrocytes. Chondrocytes were prepared from cartilage specimens taken from patients with osteoarthritis who had received total hip or total knee replacement. The concentrations of chemokines and the degree of cell migration were determined by ELISA and chemotaxis assays, respectively. The activation of inducible nitric oxide synthase (iNOS, mitogen-activated protein kinases (MAPKs, activator protein-1 (AP-1, and nuclear factor-kappaB (NF-κB was determined by immunoblotting, immunohistochemistry, and electrophoretic mobility shift assay. We found that EGb inhibited IL-1-induced production of chemokines, which in turn resulted in attenuation of THP-1 cell migration toward EGb-treated cell culture medium. EGb also suppressed IL-1-stimulated iNOS expression and release of nitric oxide (NO. The EGb-mediated suppression of the iNOS-NO pathway correlated with the attenuation of activator protein-1 (AP-1 but not nuclear factor-kappaB (NF-κB DNA-binding activity. Of the mitogen-activated protein kinases (MAPKs, EGb inhibited only c-Jun N-terminal kinase (JNK. Unexpectedly, EGb selectively caused degradation of c-Jun protein. Further investigation revealed that EGb-mediated c-Jun degradation was preceded by ubiquitination of c-Jun and could be prevented by the proteosome inhibitor MG-132. The results imply that EGb protects against chondrocyte degeneration by inhibiting JNK activation and inducing ubiquitination-dependent c-Jun degradation. Although additional research is needed, our results suggest that EGb is a potential therapeutic agent for the treatment of OA.

  15. From reptilian phylogenomics to reptilian genomes: analyses of c-Jun and DJ-1 proto-oncogenes.

    Science.gov (United States)

    Katsu, Y; Braun, E L; Guillette, L J; Iguchi, T

    2009-01-01

    Genome projects have revolutionized our understanding of both molecular biology and evolution, but there has been a limited collection of genomic data from reptiles. This is surprising given the pivotal position of reptiles in vertebrate phylogeny and the potential utility of information from reptiles for understanding a number of biological phenomena, such as sex determination. Although there are many potential uses for genomic data, one important and useful approach is phylogenomics. Here we report cDNA sequences for the c-Jun(JUN) and DJ-1(PARK7) proto-oncogenes from 3 reptiles (the American alligator, Nile crocodile, and Florida red-belly turtle), show that both genes are expressed in the alligator, and integrate them into analyses of their homologs from other organisms. With these taxa it was possible to conduct analyses that include all major vertebrate lineages. Analyses of c-Jun revealed an unexpected but well-supported frog-turtle clade while analyses of DJ-1 revealed a topology largely congruent with expectation based upon other data. The conflict between the c-Jun topology and expectation appears to reflect the overlap between c-Jun and a CpG island in most taxa, including crocodilians. This CpG island is absent in the frog and turtle, and convergence in base composition appears to be at least partially responsible for the signal uniting these taxa. Noise reduction approaches can eliminate the unexpected frog-turtle clade, demonstrating that multiple signals are present in the c-Jun alignment. We used phylogenetic methods to visualize these signals; we suggest that examining both historical and non-historical signals will prove important for phylogenomic analyses.

  16. Arsenic trioxide induces apoptosis in human platelets via C-Jun NH2-terminal kinase activation.

    Directory of Open Access Journals (Sweden)

    Yicun Wu

    Full Text Available Arsenic trioxide (ATO, one of the oldest drugs in both Western and traditional Chinese medicine, has become an effective anticancer drug, especially in the treatment of acute promyelocytic leukemia (APL. However, thrombocytopenia occurred in most of ATO-treated patients with APL or other malignant diseases, and the pathogenesis remains unclear. Here we show that ATO dose-dependently induces depolarization of mitochondrial inner transmembrane potential (ΔΨm, up-regulation of Bax and down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation, and phosphotidylserine (PS exposure in platelets. ATO did not induce surface expression of P-selectin and PAC-1 binding, whereas, obviously reduced collagen, ADP, and thrombin induced platelet aggregation. ATO dose-dependently induced c-Jun NH2-terminal kinase (JNK activation, and JNK specific inhibitor dicumarol obviously reduced ATO-induced ΔΨm depolarization in platelets. Clinical therapeutic dosage of ATO was intraperitoneally injected into C57 mice, and the numbers of circulating platelets were significantly reduced after five days of continuous injection. The data demonstrate that ATO induces caspase-dependent apoptosis via JNK activation in platelets. ATO does not incur platelet activation, whereas, it not only impairs platelet function but also reduces circulating platelets in vivo, suggesting the possible pathogenesis of thrombocytopenia in patients treated with ATO.

  17. Arsenic trioxide induces apoptosis in human platelets via C-Jun NH2-terminal kinase activation.

    Science.gov (United States)

    Wu, Yicun; Dai, Jin; Zhang, Weilin; Yan, Rong; Zhang, Yiwen; Ruan, Changgeng; Dai, Kesheng

    2014-01-01

    Arsenic trioxide (ATO), one of the oldest drugs in both Western and traditional Chinese medicine, has become an effective anticancer drug, especially in the treatment of acute promyelocytic leukemia (APL). However, thrombocytopenia occurred in most of ATO-treated patients with APL or other malignant diseases, and the pathogenesis remains unclear. Here we show that ATO dose-dependently induces depolarization of mitochondrial inner transmembrane potential (ΔΨm), up-regulation of Bax and down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation, and phosphotidylserine (PS) exposure in platelets. ATO did not induce surface expression of P-selectin and PAC-1 binding, whereas, obviously reduced collagen, ADP, and thrombin induced platelet aggregation. ATO dose-dependently induced c-Jun NH2-terminal kinase (JNK) activation, and JNK specific inhibitor dicumarol obviously reduced ATO-induced ΔΨm depolarization in platelets. Clinical therapeutic dosage of ATO was intraperitoneally injected into C57 mice, and the numbers of circulating platelets were significantly reduced after five days of continuous injection. The data demonstrate that ATO induces caspase-dependent apoptosis via JNK activation in platelets. ATO does not incur platelet activation, whereas, it not only impairs platelet function but also reduces circulating platelets in vivo, suggesting the possible pathogenesis of thrombocytopenia in patients treated with ATO. PMID:24466103

  18. c-fos/c-jun expression and AP-1 activation in skin fibroblasts from centenarians.

    Science.gov (United States)

    Grassilli, E; Bellesia, E; Salomoni, P; Croce, M A; Sikora, E; Radziszewska, E; Tesco, G; Vergelli, M; Latorraca, S; Barbieri, D; Fagiolo, U; Santacaterina, S; Amaducci, L; Tiozzo, R; Sorbi, S; Franceschi, C

    1996-09-13

    In vitro replicative senescence is characterized by an irreversible growth arrest due to the inability of the cell to induce some key regulators of cell cycle progression, such as c-fos and AP-1, in response to mitogenic stimuli. In vitro replicative senescence and in vivo aging have been assumed to be two related phenomena, likely controlled by overlapping or interacting genes. As a corollary, fibroblasts from centenarians, which have undergone a long process of senescence in vivo should have very limited proliferative capability. On the contrary, in a previous work we found that fibroblasts from centenarians exhibited the same capacity to respond to different mitogenic stimuli as fibroblasts from young donors. Here we provide evidences that the well preserved proliferative response is likely due to the fact that some pivotal regulators- c-fos, c-jun and AP-1-are still fully inducible, despite a long process of in vivo senescence. Our data therefore suggest that in vivo and in vitro aging are separate phenomena whose possible relationships, if any, have to be ascertained very carefully. PMID:8806666

  19. A reinvestigation of the multisite phosphorylation of the transcription factor c-Jun.

    Science.gov (United States)

    Morton, Simon; Davis, Roger J; McLaren, Ann; Cohen, Philip

    2003-08-01

    We have used phospho-specific antibodies to re-examine the multisite phosphorylation of c-Jun in murine RAW macrophages and embryonic fibroblasts. Our results indicate that JNK isoforms are required and sufficient for the phosphorylation of Thr91 and Thr93, as well as the phosphorylation of Ser63 and Ser73, in response to LPS or anisomycin in macrophages and TNFalpha or anisomycin in fibroblasts. However, the phorbol ester (TPA) and EGF-induced phosphorylation of Ser63 and Ser73 is mediated by ERK1/ERK2, as well as JNK1/JNK2, in fibroblasts from wild-type mice and by ERK1/ERK2 alone in fibroblasts from JNK-deficient mice. The phosphorylation of Thr239 is catalysed by GSK3 and the phosphorylation of Ser243 by an as yet unidentified protein kinase. The inhibition of GSK3 is not required for the dephosphorylation of Thr239 in response to LPS, and nor is the phosphorylation of Thr91 and Thr93 required for the TPA- or EGF-induced dephosphorylation of Thr239 in fibroblasts. The agonist-induced dephosphorylation of Thr239 may involve a conformational change that exposes Thr239 to dephosphorylation and/or the activation of a Thr239 phosphatase. PMID:12881422

  20. Solar Bicycle

    Directory of Open Access Journals (Sweden)

    SRIDHAR. S

    2011-07-01

    Full Text Available The running costs of the present vehicles are rising day by day hence common man is looking for an alternate mode of transport, with low fuel and maintenance cost. Solar bicycle is an attempt to meet these needs. It is an environmentally sustainable and zero running cost vehicle. It uses photovoltaic cells to absorb energy from sunlight. The absorbed energy is stored in battery. The hub motor mounted on the rear wheel uses this energy to run the cycle. A fully charged battery gives a mileage of 15-20 km. It is also provided with manual pedaling which increases the cycle’s mileage further. Average speed of the cycle is 15-18 kmph.

  1. Effect of growth hormone and serum on the expression of the proto-oncogenes c-jun and c-fos in insulin producing cells

    DEFF Research Database (Denmark)

    Petersen, Elisabeth D.; Billestrup, N; Nielsen, Jens Høiriis

    1990-01-01

    Expression of the proto-oncogenes c-fos and c-jun was analysed in the insulin producing rat tumor cell line, RIN 5AH. Addition of fetal calf serum (FCS) to serum-starved cells in the presence of cycloheximid induced a modest increase in c-fos and c-jun mRNA levels, whereas growth hormone (GH...

  2. Combined Expression of c-jun, c-fos, and p53 Improves Estimation of Prognosis in Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Wang, Shan; Xu, Xin; Xu, Fei; Meng, Yan; Sun, Changsheng; Shi, Lei; Zhao, Eryang

    2016-09-13

    To identify the prognostic value of c-jun, c-fos, and p53 in oral cancer, we examined the impact of immunohistochemical expression of these markers on tumor progression in 157 oral squamous cell carcinoma (OSCC). We found that c-jun or c-fos was significantly associated with lymph node metastasis, and coexpression of c-jun/c-fos, or c-jun/c-fos/p53 were significantly associated with lymph node metastasis, poor differentiation and clinical stage. The coexpression of c-jun/c-fos/p53 was identified as independent prognostic factors for overall survival. Simultaneous coexpression of these markers in OSCCs might prove to be a useful indicator for differentiation of low and high-risk patients.

  3. HEPATIC APOPTOSIS POST-BURN IS MEDIATED BY C-JUN N-TERMINAL KINASE-2

    Science.gov (United States)

    Marshall, Alexandra H.; Brooks, Natasha C.; Hiyama, Yaeko; Qa’aty, Nour; Al-mousawi, Ahmed; Finnerty, Celeste C.; Jeschke, Marc G.

    2013-01-01

    The trauma of a severe burn injury induces a hypermetabolic response that increases morbidity and mortality. Previously, our group showed that insulin resistance post-burn injury is associated with endoplasmic reticulum (ER) stress. Evidence suggests that c-jun N-terminal kinase (JNK) -2 may be involved in ER stress-induced apoptosis. Here, we hypothesized that JNK2 contributes to the apoptotic response after burn injury downstream of ER stress. To test this, we compared JNK2 knockout mice (−/−) to wildtype mice after inducing a 30% total body surface area thermal injury. Animals were sacrificed after 1, 3 and 5 days. Inflammatory cytokines in the blood were measured by multiplex analysis. Hepatic ER stress and insulin signaling were assessed by Western Blotting and insulin resistance was measured by a peritoneal glucose tolerance test. Apoptosis in the liver was quantified by TUNEL staining. Liver function was quantified by AST and ALT activity assays. ER stress increased after burn in both JNK2−/− and wildtype mice, indicating that JNK2 activation is downstream of ER stress. Knockout of JNK2 did not affect serum inflammatory cytokines; however, the increase in IL-6 mRNA expression was prevented in the knockouts. Serum insulin did not significantly increase in the JNK2−/− group. On the other hand, insulin signaling (PI3K/Akt pathway) and glucose tolerance tests did not improve in JNK2−/−. As expected, apoptosis in the liver increased after burn injury in wildtype mice but not in JNK2−/−. AST/ALT activity revealed that liver function recovered more quickly in JNK2−/−. This study indicates that JNK2 is a central mediator of hepatic apoptosis after a severe burn. PMID:23324888

  4. Fibroin and sericin from Bombyx mori silk stimulate cell migration through upregulation and phosphorylation of c-Jun.

    Directory of Open Access Journals (Sweden)

    Celia Martínez-Mora

    Full Text Available Wound healing is a biological process directed to the restoration of tissue that has suffered an injury. An important phase of wound healing is the generation of a basal epithelium able to wholly replace the epidermis of the wound. A broad range of products derived from fibroin and sericin from Bombyx mori silk are used to stimulate wound healing. However, so far the molecular mechanism underlying this phenomenon has not been elucidated. The aim of this work was to determine the molecular basis underlying wound healing properties of silk proteins using a cell model. For this purpose, we assayed fibroin and sericin in a wound healing scratch assay using MDA-MB-231 and Mv1Lu cells. Both proteins stimulated cell migration. Furthermore, treatment with sericin and fibroin involved key factors of the wound healing process such as upregulation of c-Jun and c-Jun protein phosphorylation. Moreover, fibroin and sericin stimulated the phosphorylation of ERK 1/2 and JNK 1/2 kinases. All these experiments were done in the presence of specific inhibitors for some of the cell signalling pathways referred above. The obtained results revealed that MEK, JNK and PI3K pathways are involved in fibroin and sericin stimulated cells migration. Inhibition of these three kinases prevented c-Jun upregulation and phosphorylation by fibroin or sericin. Fibroin and sericin were tested in the human keratinocyte cell line, HaCaT, with similar results. Altogether, our results showed that fibroin and sericin initiate cell migration by activating the MEK, JNK and PI3K signalling pathways ending in c-Jun activation.

  5. Regulation of Apoptotic c-Jun N-Terminal Kinase Signaling by a Stabilization-Based Feed-Forward Loop†

    OpenAIRE

    Xu, Zhiheng; Kukekov, Nikolay V.; Greene, Lloyd A.

    2005-01-01

    A sequential kinase cascade culminating in activation of c-Jun N-terminal kinases (JNKs) plays a fundamental role in promoting apoptotic death in many cellular contexts. The mechanisms by which this pathway is engaged in response to apoptotic stimuli and suppressed in viable cells are largely unknown. Here, we show that apoptotic stimuli increase endogenous cellular levels of pathway components, including POSH, mixed lineage kinases (MLKs), and JNK interacting protein 1, and that this effect ...

  6. c-Jun N-terminal Kinase (JNK) signaling as a therapeutic target for Alzheimer’s disease

    OpenAIRE

    Yarza, Ramon; Vela, Silvia; Solas, Maite; Ramirez, Maria J

    2016-01-01

    c-Jun N-terminal kinases (JNKs) are a family of protein kinases that play a central role in stress signaling pathways implicated in gene expression, neuronal plasticity, regeneration, cell death, and regulation of cellular senescence. It has been shown that there is a JNK pathway activation after exposure to different stressing factors, including cytokines, growth factors, oxidative stress, unfolded protein response signals or Aβ peptides. Altogether, JNKs have become a focus of screening str...

  7. The effects of vitamin E succinate on the expression of c-jun gene and protein in human gastric cancer SGC-7901 cells

    Institute of Scientific and Technical Information of China (English)

    Yan Zhao; Kun Wu; Wei Xia; Yu-Juan Shan; Li-Jie Wu; Wei-Ping Yu

    2002-01-01

    AIM: To investigate the effects of vitamin E succinate (VES) on the expression of c-jun gene and protein in human gastric cancer SGC-7901 cells.METHODS: After SGC-7901 cells were treated with VES at different doses (5,10,20 mg@L-1) at different time, reverse transcription-PCR technique was used to detect the level of c-jun mRNA; Western Blot was applied to measure the expression of c-jun protei n/RESULTS: After the cells were treated with VES at 20 mg@L-1 for 3 h, the expression rapidly reached its maximum that was 3.5 times of UT control (P<0.01). The level of c-jun mRNA was also increased following treatment of VES for 6 h.However, the expression after treatment of VES at 5 mg@L-1for 24 h was 1.6 times compared with UT control (P<0.01).Western blot analysis showed that the level of c-jun protein was obviously elevated in VES-treated SGC-7901 cells at 20 mg@L-1 for 3 h. The expression of c-jun protein was gradually increased after treatment of VES at 20 mg@L-1 for 3, 6, 12 and 24 h, respectively, with an evident time-effect relationship. CONCLUSION: The levels of c-jun mRNA and protein in VES-treated SGC-7901 cells were increased in a dose- and time-dependent manner; the expression of c-jun was prolonged by VES, indicating that c-jun is involved in VESinduced apoptosis in SGC-7901 cells.

  8. The regulation of p53 up-regulated modulator of apoptosis by JNK/c-Jun pathway in β-amyloid-induced neuron death.

    Science.gov (United States)

    Akhter, Rumana; Sanphui, Priyankar; Das, Hrishita; Saha, Pampa; Biswas, Subhas Chandra

    2015-09-01

    Neuronal loss in selective areas of brain underlies the pathology of Alzheimer's disease (AD). Recent evidences place oligomeric β-amyloid (Aβ) central to the disease. However, mechanism of neuron death in response to Aβ remains elusive. Activation of the c-Jun N-terminal kinase (JNK) pathway and induction of the AP-1 transcription factor c-Jun are reported in AD. However, targets of JNK/c-Jun in Aβ-induced neuron death are mostly unknown. Our study shows that pro-apoptotic proteins, Bim (Bcl-2 interacting mediator of cell death) and Puma (p53 up-regulated modulator of apoptosis) are targets of c-Jun in Aβ-treated neurons. We demonstrate that the JNK/c-Jun pathway is activated, in cultures of cortical neurons following treatment with oligomeric Aβ and in AD transgenic mice, and that inhibition of this pathway by selective inhibitor blocks induction of Puma by Aβ. We also find that both JNK and p53 pathways co-operatively regulate Puma expression in Aβ-treated neurons. Moreover, we identified a novel AP1-binding site on rat puma gene which is necessary for direct binding of c-Jun with Puma promoter. Finally, we find that knocking down of c-Jun by siRNA provides significant protection from Aβ toxicity and that induction of Bim and Puma by Aβ in neurons requires c-Jun. Taken together, our results suggest that both Bim and Puma are target of c-Jun and elucidate the intricate regulation of Puma expression by JNK/c-Jun and p53 pathways in neurons upon Aβ toxicity. JNK/c-Jun pathway is shown to be activated in neurons of the Alzheimer's disease (AD) brain and plays a vital role in neuron death in AD models. However, downstream targets of c-Jun in this disease have not been thoroughly elucidated. Our study shows that two important pro-apoptotic proteins, Bim (Bcl-2 interacting mediator of cell death) and Puma (p53 up-regulated modulator of apoptosis) are targets of c-Jun in Aβ-treated neurons. We demonstrate that the JNK/c-jun pathway is activated, in cultures

  9. Lost Kingdom of Bicycles?

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    For most people born in the 1950s and '60s, the bicycle was a faithful companion of their youth, when China was known as a kingdom of bicycles. A bicycle ride was a favorite pastime during a colorful spring day or in the crisp

  10. The leucine zipper domains of the transcription factors GCN4 and c-Jun have ribonuclease activity.

    Directory of Open Access Journals (Sweden)

    Yaroslav Nikolaev

    Full Text Available Basic-region leucine zipper (bZIP proteins are one of the largest transcription factor families that regulate a wide range of cellular functions. Owing to the stability of their coiled coil structure leucine zipper (LZ domains of bZIP factors are widely employed as dimerization motifs in protein engineering studies. In the course of one such study, the X-ray structure of the retro-version of the LZ moiety of yeast transcriptional activator GCN4 suggested that this retro-LZ may have ribonuclease activity. Here we show that not only the retro-LZ but also the authentic LZ of GCN4 has weak but distinct ribonuclease activity. The observed cleavage of RNA is unspecific, it is not suppressed by the ribonuclease A inhibitor RNasin and involves the breakage of 3',5'-phosphodiester bonds with formation of 2',3'-cyclic phosphates as the final products as demonstrated by HPLC/electrospray ionization mass spectrometry. Several mutants of the GCN4 leucine zipper are catalytically inactive, providing important negative controls and unequivocally associating the enzymatic activity with the peptide under study. The leucine zipper moiety of the human factor c-Jun as well as the entire c-Jun protein are also shown to catalyze degradation of RNA. The presented data, which was obtained in the test-tube experiments, adds GCN4 and c-Jun to the pool of proteins with multiple functions (also known as moonlighting proteins. If expressed in vivo, the endoribonuclease activity of these bZIP-containing factors may represent a direct coupling between transcription activation and controlled RNA turnover. As an additional result of this work, the retro-leucine zipper of GCN4 can be added to the list of functional retro-peptides.

  11. Bile acids-mediated overexpression of MUC4 via FAK-dependent c-Jun activation in pancreatic cancer.

    Science.gov (United States)

    Joshi, Suhasini; Cruz, Eric; Rachagani, Satyanarayana; Guha, Sushovan; Brand, Randall E; Ponnusamy, Moorthy P; Kumar, Sushil; Batra, Surinder K

    2016-08-01

    The majority of pancreatic cancer (PC) patients are clinically presented with obstructive jaundice with elevated levels of circulatory bilirubin and alkaline phosphatases. In the current study, we examined the implications of bile acids (BA), an important component of bile, on the pathophysiology of PC and investigated their mechanistic association in tumor-promoting functions. Integration of results from PC patient samples and autochthonous mouse models showed an elevated levels of BA (p < 0.05) in serum samples compared to healthy controls. Similarly, an elevated BA levels was observed in pancreatic juice derived from PC patients (p < 0.05) than non-pancreatic non-healthy (NPNH) controls, further establishing the clinical association of BA with the pathogenesis of PC. The tumor-promoting functions of BA were established by observed transcriptional upregulation of oncogenic MUC4 expression. Luciferase reporter assay revealed distal MUC4 promoter as the primary responsive site to BA. In silico analysis recognized two c-Jun binding sites at MUC4 distal promoter, which was biochemically established using ChIP assay. Interestingly, BA treatment led to an increased transcription and activation of c-Jun in a FAK-dependent manner. Additionally, BA receptor, namely FXR, which is also upregulated at transcriptional level in PC patient samples, was demonstrated as an upstream molecule in BA-mediated FAK activation, plausibly by regulating Src activation. Altogether, these results demonstrate that elevated levels of BA increase the tumorigenic potential of PC cells by inducing FXR/FAK/c-Jun axis to upregulate MUC4 expression, which is overexpressed in pancreatic tumors and is known to be associated with progression and metastasis of PC. PMID:27185392

  12. c-Jun N-terminal kinase phosphorylates DCP1a to control formation of P bodies

    OpenAIRE

    Rzeczkowski, Katharina; Beuerlein, Knut; Müller, Helmut; Dittrich-Breiholz, Oliver; Schneider, Heike; Kettner-Buhrow, Daniela; Holtmann, Helmut; Kracht, Michael

    2011-01-01

    Cytokines and stress-inducing stimuli signal through c-Jun N-terminal kinase (JNK) using a diverse and only partially defined set of downstream effectors. In this paper, the decapping complex subunit DCP1a was identified as a novel JNK target. JNK phosphorylated DCP1a at residue S315 in vivo and in vitro and coimmunoprecipitated and colocalized with DCP1a in processing bodies (P bodies). Sustained JNK activation by several different inducers led to DCP1a dispersion from P bodies, whereas IL-1...

  13. Role of Muscle c-Jun NH2-Terminal Kinase 1 in Obesity-Induced Insulin Resistance▿

    OpenAIRE

    Sabio, Guadalupe; Kennedy, Norman J.; Cavanagh-Kyros, Julie; Jung, Dae Young; Ko, Hwi Jin; Ong, Helena; Barrett, Tamera; Kim, Jason K.; Davis, Roger J

    2009-01-01

    Obesity caused by feeding of a high-fat diet (HFD) is associated with an increased activation of c-Jun NH2-terminal kinase 1 (JNK1). Activated JNK1 is implicated in the mechanism of obesity-induced insulin resistance and the development of metabolic syndrome and type 2 diabetes. Significantly, Jnk1−/− mice are protected against HFD-induced obesity and insulin resistance. Here we show that an ablation of the Jnk1 gene in skeletal muscle does not influence HFD-induced obesity. However, muscle-s...

  14. Melanocortin-4 receptor activation inhibits c-Jun N-terminal kinase activity and promotes insulin signaling

    OpenAIRE

    Chai, Biaoxin; Li, Ji-Yao; Zhang, Weizhen; Wang, Hui; Mulholland, Michael W.

    2009-01-01

    The melanocortin system is crucial to regulation of energy homeostasis. The melanocortin receptor type 4 (MC4R) modulates insulin signaling via effects on c-Jun N-terminal kinase (JNK). The melanocortin agonist NDP-MSH dose-dependently inhibited JNK activity in HEK293 cells stably expressing the human MC4R; effects were reversed by melanocortin receptor antagonist. NDP-MSH time- and dose-dependently inhibited IRS-1ser307 phosphorylation, effects also reversed by a specific melanocortin recept...

  15. Function of c-Fos-like and c-Jun-like Proteins on Trichostatin A-induced G2/M Arrest in Physarum polycephalum

    Institute of Scientific and Technical Information of China (English)

    Xiao-Xue LI; Jun LU; Yan-Mei ZHAO; Bai-Qu HUANG

    2005-01-01

    The homologs of transcription factors c-Fos and c-Jun have been detected in slime mold Physarum polycephalum during progression of the synchronous cell cycle. Here we demonstrated that cFos-like and c-Jun-like proteins participated in G2/M transition by the regulation of the level of Cyclin B1 protein in P. polycephalum. The study of antibody neutralization revealed that interruption of the functions of c-Fos-like and c-Jun-like proteins resulted in G2/M transition arrest, implicating their functional roles in cell cycle control. When G2/M transition was blocked by histone deacetylase inhibitor trichostatin A, changes in c-Fos- and c-Jun-like protein levels, and hyperacetylation of c-Jun-like protein, were observed. The data suggest that in P. polycephalum, c-Fos- and c-Jun-like proteins may be the key factors in the regulation of histone acetylation-related G2/M transition, involving the coordinated expression and hyperacetylation of these proteins.

  16. Puerarin reduces increased c-fos, c-jun, and type Ⅳ collagen expression caused by high glucose in glomerular mesangial cells

    Institute of Scientific and Technical Information of China (English)

    Cai-ping MAO; Zhen-lun GU

    2005-01-01

    Aim: Increased expression of c-fos, c-jun and type Ⅳ collagen (CoⅣ) in glomerular mesangial cells (GMC) are important characteristics of diabetic nephropathy.Both c-fos and c-jun regulate the gene expression of extracellular matrix components, and CoⅣ is the main component of the extracellular matrix. It has been reported that puerarin inhibits aggregation of the extracellular matrix in diabetic rats by an as yet unknown mechanism. The aim of this study is to investigate the effect of puerarin on c-fos, c-jun and CoⅣ expression in GMC cultured in medium containing 5.6 or 27.8 mmol/L glucose. Methods: The expressions ofc-fos and c-jun were measured at the protein level using flow cytometry. CoⅣ content was detected using radioimmunoassay. Protein kinase C (PKC) activity was measured using liquid scintillation counting. Results: Puerarin (10-5 mmol/L) significantly ameliorated the high-glucose effect on c-fos, c-jun and CoⅣ expression.This effect is accompanied by a reduced PKC activity in these cells. Conclusion:Our results suggest that reduced PKC activity and expression of c-fos and c-jun in GMC might participate in the mechanisms underlying the therapeutic effect of puerarin on diabetic nephropathy.

  17. Physical interaction of the activator protein-1 factors c-Fos and c-Jun with Cbfa1 for collagenase-3 promoter activation

    Science.gov (United States)

    D'Alonzo, Richard C.; Selvamurugan, Nagarajan; Karsenty, Gerard; Partridge, Nicola C.

    2002-01-01

    Previously, we determined that the activator protein-1 (AP-1)-binding site and the runt domain (RD)-binding site and their binding proteins, c-Fos.c-Jun and Cbfa, regulate the collagenase-3 promoter in parathyroid hormone-treated and differentiating osteoblasts. Here we show that Cbfa1 and c-Fos.c-Jun appear to cooperatively bind the RD- and AP-1-binding sites and form ternary structures in vitro. Both in vitro and in vivo co-immunoprecipitation and yeast two-hybrid studies further demonstrate interaction between Cbfa1 with c-Fos and c-Jun in the absence of phosphorylation and without binding to DNA. Additionally, only the runt domain of Cbfa1 was required for interaction with c-Jun and c-Fos. In mammalian cells, overexpression of Cbfa1 enhanced c-Jun activation of AP-1-binding site promoter activity, demonstrating functional interaction. Finally, insertion of base pairs that disrupted the helical phasing between the AP-1- and RD-binding sites also inhibited collagenase-3 promoter activation. Thus, we provide direct evidence that Cbfa1 and c-Fos.c-Jun physically interact and cooperatively bind the AP-1- and RD-binding sites in the collagenase-3 promoter. Moreover, the AP-1- and RD-binding sites appear to be organized in a specific required helical arrangement that facilitates transcription factor interaction and enables promoter activation.

  18. AP-1 Transcription Factors c-FOS and c-JUN Mediate GnRH-Induced Cadherin-11 Expression and Trophoblast Cell Invasion.

    Science.gov (United States)

    Peng, Bo; Zhu, Hua; Ma, Liyang; Wang, Yan-Ling; Klausen, Christian; Leung, Peter C K

    2015-06-01

    GnRH is expressed in first-trimester human placenta and increases cell invasion in extravillous cytotrophoblasts (EVTs). Invasive phenotypes have been reported to be regulated by transcription factor activator protein 1 (AP-1) and mesenchymal cadherin-11. The aim of our study was to investigate the roles of AP-1 components (c-FOS/c-JUN) and cadherin-11 in GnRH-induced cell invasion in human EVT cells. Phosphorylated c-FOS and phosphorylated c-JUN were detected in the cell column regions of human first-trimester placental villi by immunohistochemistry. GnRH treatment increased c-FOS, c-JUN, and cadherin-11 mRNA and protein levels in immortalized EVT (HTR-8/SVneo) cells. Moreover, GnRH treatment induced c-FOS and c-JUN protein phosphorylation and nuclear accumulation. Pretreatment with antide, a GnRH antagonist, attenuated GnRH-induced cadherin-11 expression. Importantly, basal and GnRH-induced cadherin-11 expression and cell invasion were reduced by small interfering RNA-mediated knockdown of c-FOS, c-JUN, and cadherin-11 in HTR-8/SVneo cells. Our results suggest that GnRH induces the expression and phosphorylation of the AP-1 transcription factors c-FOS and c-JUN in trophoblast cells, which contributes to GnRH-induced elevation of cadherin-11 expression and cell invasion. PMID:25794160

  19. Scorpion Venom Heat-Resistant Peptide Attenuates Glial Fibrillary Acidic Protein Expression via c-Jun/AP-1.

    Science.gov (United States)

    Cao, Zhen; Wu, Xue-Fei; Peng, Yan; Zhang, Rui; Li, Na; Yang, Jin-Yi; Zhang, Shu-Qin; Zhang, Wan-Qin; Zhao, Jie; Li, Shao

    2015-11-01

    Scorpion venom has been used in the Orient to treat central nervous system diseases for many years, and the protein/peptide toxins in Buthus martensii Karsch (BmK) venom are believed to be the effective components. Scorpion venom heat-resistant peptide (SVHRP) is an active component of the scorpion venom extracted from BmK. In a previous study, we found that SVHRP could inhibit the formation of a glial scar, which is characterized by enhanced glial fibrillary acidic protein (GFAP) expression, in the epileptic hippocampus. However, the cellular and molecular mechanisms underlying this process remain to be clarified. The results of the present study indicate that endogenous GFAP expression in primary rat astrocytes was attenuated by SVHRP. We further demonstrate that the suppression of GFAP was primarily mediated by inhibiting both c-Jun expression and its binding with AP-1 DNA binding site and other factors at the GFAP promoter. These results support that SVHRP contributes to reducing GFAP at least in part by decreasing the activity of the transcription factor AP-1. In conclusion, the effects of SVHRP on astrocytes with respect to the c-Jun/AP-1 signaling pathway in vitro provide a practical basis for studying astrocyte activation and inhibition and a scientific basis for further studies of traditional medicine.

  20. Bicycle Detection System

    OpenAIRE

    Yu, James; Arellano , Secundino; Carrillo , Alma; Cruz , Melinda; Kunitskiy, Dmitriy; Maynigo , Marlo; Sell , Monica

    2013-01-01

    Project Description:  Bicycle detection has become a popular feature of high demand in cities and agencies across the United States. California has recently mandated that all new limit line detector installations as well as modifications to existing limit line detection must provide bicycle detection. This has created the need to develop detection methodologies which are able to detect bicycles as well as differentiate them from vehicles. The objective of this project is to utilize Econolite ...

  1. Recumbent bicycle design

    OpenAIRE

    Basso Puig, Carlos

    2014-01-01

    The subject of this project is the design of a recumbent bicycle prototype. A recumbent bike is a type of bicycle in which the rider mounts in a reclined position. In order to do this, we will learn about these bicycles by showing the different types there are, its evolution over the years, and so on. After that, it is shown the recumbent bicycle design and all its components. It has been invented the frame and so, it is explained the material choice, a brief anthropometric study and FE...

  2. miR-138 protects cardiomyocytes from hypoxia-induced apoptosis via MLK3/JNK/c-jun pathway

    Energy Technology Data Exchange (ETDEWEB)

    He, Siyi; Liu, Peng; Jian, Zhao; Li, Jingwei; Zhu, Yun; Feng, Zezhou; Xiao, Yingbin, E-mail: xiaoyb@vip.sina.com

    2013-11-29

    Highlights: •First time to find miR-138 is up-regulated in hypoxic cardiomyocytes. •First time to find miR-138 targets MLK3 and regulates JNK/c-jun pathway. •Rare myocardial biopsy of patients with CHD were collected. •Both silence and overexpression of miR-138 were implemented. •Various methods were used to detect cell function. -- Abstract: Cardiomyocytes experience a series of complex endogenous regulatory mechanisms against apoptosis induced by chronic hypoxia. MicroRNAs are a class of endogenous small non-coding RNAs that regulate cellular pathophysiological processes. Recently, microRNA-138 (miR-138) has been found related to hypoxia, and beneficial for cell proliferation. Therefore, we intend to study the role of miR-138 in hypoxic cardiomyocytes and the main mechanism. Myocardial samples of patients with congenital heart disease (CHD) were collected to test miR-138 expression. Agomir or antagomir of miR-138 was transfected into H9C2 cells to investigate its effect on cell apoptosis. Higher miR-138 expression was observed in patients with cyanotic CHD, and its expression gradually increased with prolonged hypoxia time in H9C2 cells. Using MTT and LDH assays, cell growth was significantly greater in the agomir group than in the negative control (NC) group, while antagomir decreased cell survival. Dual luciferase reporter gene and Western-blot results confirmed MLK3 was a direct target of miR-138. It was found that miR-138 attenuated hypoxia-induced apoptosis using TUNEL, Hoechst staining and Annexin V-PE/7-AAD flow cytometry analysis. We further detected expression of apoptosis-related proteins. In the agomir group, the level of pro-apoptotic proteins such as cleaved-caspase-3, cleaved-PARP and Bad significantly reduced, while Bcl-2 and Bcl-2/Bax ratio increased. Opposite changes were observed in the antagomir group. Downstream targets of MLK3, JNK and c-jun, were also suppressed by miR-138. Our study demonstrates that up-regulation of miR-138 plays

  3. Regulation of hemeoxygenase-1 gene expression by Nrf2 and c-Jun in tertiary butylhydroquinone-stimulated rat primary astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jin-Sun; Kim, Hee-Sun, E-mail: hskimp@ewha.ac.kr

    2014-05-16

    Highlights: • tBHQ increased HO-1 mRNA and protein levels in rat primary astrocytes. • tBHQ enhanced HO-1 gene transcription in an ARE-dependent manner. • tBHQ increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to ARE. • Nrf2 and c-Jun are involved in the differential modulation of HO-1 expression. • Nrf2 and c-Jun regulate HO-1 expression via their coordinated interaction. - Abstract: Hemeoxygenase-1 (HO-1) is a phase II antioxidant enzyme that is primarily involved in detoxification and cytoprotection in a variety of tissues. However, the mechanism underlying HO-1 gene expression remains unclear. In the present study, we investigated the regulation of HO-1 expression in primary cultured astrocytes by using the natural antioxidant compound tertiary butylhydroquinone (tBHQ). We found that tBHQ increased HO-1 mRNA and protein levels. Promoter analysis revealed that tBHQ enhanced HO-1 gene transcription in an antioxidant response element (ARE)-dependent manner. In addition, tBHQ increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to ARE. Small interfering RNA (siRNA) experiments demonstrated that Nrf2 and c-Jun are involved in the differential modulation of HO-1 expression. Thus, Nrf2 knockdown reduced the basal level of HO-1 expression but did not affect the fold induction by tBHQ. On the other hand, knockdown of c-Jun diminished tBHQ-mediated induction of HO-1 without affecting basal expression. The data suggest that Nrf2 generally modulates the basal expression of HO-1, while c-Jun mediates HO-1 induction in response to tBHQ. The results of co-immunoprecipitation assays demonstrated a physical interaction between Nrf2 and c-Jun in tBHQ-treated astrocytes. The results suggest that Nrf2 and c-Jun regulate HO-1 expression via their coordinated interaction in tBHQ-treated rat primary astrocytes.

  4. Regulation of hemeoxygenase-1 gene expression by Nrf2 and c-Jun in tertiary butylhydroquinone-stimulated rat primary astrocytes

    International Nuclear Information System (INIS)

    Highlights: • tBHQ increased HO-1 mRNA and protein levels in rat primary astrocytes. • tBHQ enhanced HO-1 gene transcription in an ARE-dependent manner. • tBHQ increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to ARE. • Nrf2 and c-Jun are involved in the differential modulation of HO-1 expression. • Nrf2 and c-Jun regulate HO-1 expression via their coordinated interaction. - Abstract: Hemeoxygenase-1 (HO-1) is a phase II antioxidant enzyme that is primarily involved in detoxification and cytoprotection in a variety of tissues. However, the mechanism underlying HO-1 gene expression remains unclear. In the present study, we investigated the regulation of HO-1 expression in primary cultured astrocytes by using the natural antioxidant compound tertiary butylhydroquinone (tBHQ). We found that tBHQ increased HO-1 mRNA and protein levels. Promoter analysis revealed that tBHQ enhanced HO-1 gene transcription in an antioxidant response element (ARE)-dependent manner. In addition, tBHQ increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to ARE. Small interfering RNA (siRNA) experiments demonstrated that Nrf2 and c-Jun are involved in the differential modulation of HO-1 expression. Thus, Nrf2 knockdown reduced the basal level of HO-1 expression but did not affect the fold induction by tBHQ. On the other hand, knockdown of c-Jun diminished tBHQ-mediated induction of HO-1 without affecting basal expression. The data suggest that Nrf2 generally modulates the basal expression of HO-1, while c-Jun mediates HO-1 induction in response to tBHQ. The results of co-immunoprecipitation assays demonstrated a physical interaction between Nrf2 and c-Jun in tBHQ-treated astrocytes. The results suggest that Nrf2 and c-Jun regulate HO-1 expression via their coordinated interaction in tBHQ-treated rat primary astrocytes

  5. Voxel-based analysis of the immediate early gene, c-jun, in the honey bee brain after a sucrose stimulus.

    Science.gov (United States)

    McNeill, M S; Robinson, G E

    2015-06-01

    Immediate early genes (IEGs) have served as useful markers of brain neuronal activity in mammals, and more recently in insects. The mammalian canonical IEG, c-jun, is part of regulatory pathways conserved in insects and has been shown to be responsive to alarm pheromone in honey bees. We tested whether c-jun was responsive in honey bees to another behaviourally relevant stimulus, sucrose, in order to further identify the brain regions involved in sucrose processing. To identify responsive regions, we developed a new method of voxel-based analysis of c-jun mRNA expression. We found that c-jun is expressed in somata throughout the brain. It was rapidly induced in response to sucrose stimuli, and it responded in somata near the antennal and mechanosensory motor centre, mushroom body calices and lateral protocerebrum, which are known to be involved in sucrose processing. c-jun also responded to sucrose in somata near the lateral suboesophageal ganglion, dorsal optic lobe, ventral optic lobe and dorsal posterior protocerebrum, which had not been previously identified by other methods. These results demonstrate the utility of voxel-based analysis of mRNA expression in the insect brain.

  6. A feedback inhibition between miRNA-127 and TGFβ/c-Jun cascade in HCC cell migration via MMP13.

    Directory of Open Access Journals (Sweden)

    Zhihong Yang

    Full Text Available Hepatocellular carcinoma (HCC is the fifth most common cancer worldwide and is increasing in frequency in the U.S. The major reason for the low postoperative survival rate of HCC is widespread intrahepatic metastasis or invasion, and activation of TGFβ signaling is associated with the invasive phenotype. This study aims at determining the novel function of miR-127 in modulating HCC migration. Overexpression of miR-127 inhibits HCC cell migration, invasion and tumor growth in nude mice. MiR-127 directly represses matrix metalloproteinase 13 (MMP13 3'UTR activity and protein expression, and diminishes MMP13/TGFβ-induced HCC migration. In turn, TGFβ decreases miR-127 expression by enhancing c-Jun-mediated inhibition of miR-127 promoter activity. In contrast, p53 transactivates miR-127 promoter and induces miR-127 expression, which is antagonized by c-Jun. The inhibition of miR-127 by c-Jun is through TGFβ-mediated ERK and JNK pathways. The lower miR-127 expression shows a negative correlation with the higher MMP13 expression in a subset of human HCC specimens. This is the first report elucidating a feedback regulation between miR-127 and the TGFβ/c-Jun cascade in HCC migration via MMP13 that involves a crosstalk between the oncogene c-Jun and tumor suppressor p53.

  7. Role of TGF-β-induced Claudin-4 expression through c-Jun signaling in non-small cell lung cancer.

    Science.gov (United States)

    Rachakonda, Girish; Vu, Trung; Jin, Lin; Samanta, Debangshu; Datta, Pran K

    2016-10-01

    Claudin-4 has been identified as an integral member of tight junctions and has been found to be upregulated in various types of cancers especially in metastatic cancers. However, the molecular mechanism of the upregulation of Claudin-4 and its role in lung tumorigenesis are unknown. The aim of the present study is to investigate the role of Claudin-4 on migration and tumorigenicity of lung cancer cells and to examine the regulatory effects of TGF-β on Claudin-4 expression. We have observed that TGF-β induces the expression of Claudin-4 dramatically in lung cell lines in a time dependent manner. TGF-β-induced Smad signaling is important for enhancing Claudin-4 mRNA level through inducing its promoter activity. Treatment with curcumin, a c-Jun inhibitor, or stable knockdown of c-Jun abrogates TGF-β-induced Claudin-4 expression suggesting an involvement of the c-Jun pathway. Notably, TGF-β-induced Claudin-4 expression through c-Jun pathway plays a role in TGF-β-mediated motility and tumorigenicity of these cells. In support of these observations, we have uncovered that Claudin-4 is upregulated in 14 of 24 (58%) lung tumors when compared with normal lung tissue. This is the first study to show how TGF-β regulates the expression of Claudin-4 through c-Jun signaling and how this pathway contributes to the migratory and tumorigenic phenotype of lung tumor cells. PMID:27424491

  8. Tristetraprolin induces cell cycle arrest in breast tumor cells through targeting AP-1/c-Jun and NF-κB pathway.

    Science.gov (United States)

    Xu, Li; Ning, Huan; Gu, Ling; Wang, Qinghong; Lu, Wenbao; Peng, Hui; Cui, Weiguang; Ying, Baoling; Ross, Christina R; Wilson, Gerald M; Wei, Lin; Wold, William S M; Liu, Jianguo

    2015-12-01

    The main characteristic of cancers, including breast cancer, is the ability of cancer cells to proliferate uncontrollably. However, the underlying mechanisms of cancer cell proliferation, especially those regulated by the RNA binding protein tristetraprolin (TTP), are not completely understood. In this study, we found that TTP inhibits cell proliferation in vitro and suppresses tumor growth in vivo through inducing cell cycle arrest at the S phase. Our studies demonstrate that TTP inhibits c-Jun expression through the C-terminal Zn finger and therefore increases Wee1 expression, a regulatory molecule which controls cell cycle transition from the S to the G2 phase. In contrast to the well-known function of TTP in regulating mRNA stability, TTP inhibits c-Jun expression at the level of transcription by selectively blocking NF-κB p65 nuclear translocation. Reconstitution of NF-κB p65 completely abolishes the inhibition of c-Jun transcription by TTP. Moreover, reconstitution of c-Jun in TTP-expressing breast tumor cells diminishes Wee1 overexpression and promotes cell proliferation. Our results indicate that TTP suppresses c-Jun expression that results in Wee1 induction which causes cell cycle arrest at the S phase and inhibition of cell proliferation. Our study provides a new pathway for TTP function as a tumor suppressor which could be targeted in tumor treatment. PMID:26497679

  9. Role of TGF-β-induced Claudin-4 expression through c-Jun signaling in non-small cell lung cancer.

    Science.gov (United States)

    Rachakonda, Girish; Vu, Trung; Jin, Lin; Samanta, Debangshu; Datta, Pran K

    2016-10-01

    Claudin-4 has been identified as an integral member of tight junctions and has been found to be upregulated in various types of cancers especially in metastatic cancers. However, the molecular mechanism of the upregulation of Claudin-4 and its role in lung tumorigenesis are unknown. The aim of the present study is to investigate the role of Claudin-4 on migration and tumorigenicity of lung cancer cells and to examine the regulatory effects of TGF-β on Claudin-4 expression. We have observed that TGF-β induces the expression of Claudin-4 dramatically in lung cell lines in a time dependent manner. TGF-β-induced Smad signaling is important for enhancing Claudin-4 mRNA level through inducing its promoter activity. Treatment with curcumin, a c-Jun inhibitor, or stable knockdown of c-Jun abrogates TGF-β-induced Claudin-4 expression suggesting an involvement of the c-Jun pathway. Notably, TGF-β-induced Claudin-4 expression through c-Jun pathway plays a role in TGF-β-mediated motility and tumorigenicity of these cells. In support of these observations, we have uncovered that Claudin-4 is upregulated in 14 of 24 (58%) lung tumors when compared with normal lung tissue. This is the first study to show how TGF-β regulates the expression of Claudin-4 through c-Jun signaling and how this pathway contributes to the migratory and tumorigenic phenotype of lung tumor cells.

  10. Regulation of apoptotic c-Jun N-terminal kinase signaling by a stabilization-based feed-forward loop.

    Science.gov (United States)

    Xu, Zhiheng; Kukekov, Nikolay V; Greene, Lloyd A

    2005-11-01

    A sequential kinase cascade culminating in activation of c-Jun N-terminal kinases (JNKs) plays a fundamental role in promoting apoptotic death in many cellular contexts. The mechanisms by which this pathway is engaged in response to apoptotic stimuli and suppressed in viable cells are largely unknown. Here, we show that apoptotic stimuli increase endogenous cellular levels of pathway components, including POSH, mixed lineage kinases (MLKs), and JNK interacting protein 1, and that this effect occurs through protein stabilization and requires the presence of POSH as well as activation of MLKs and JNKs. Our findings suggest a self-amplifying, feed-forward loop mechanism by which apoptotic stimuli promote the stabilization of JNK pathway components, thereby contributing to cell death. PMID:16260609

  11. Regulation of Apoptotic c-Jun N-Terminal Kinase Signaling by a Stabilization-Based Feed-Forward Loop†

    Science.gov (United States)

    Xu, Zhiheng; Kukekov, Nikolay V.; Greene, Lloyd A.

    2005-01-01

    A sequential kinase cascade culminating in activation of c-Jun N-terminal kinases (JNKs) plays a fundamental role in promoting apoptotic death in many cellular contexts. The mechanisms by which this pathway is engaged in response to apoptotic stimuli and suppressed in viable cells are largely unknown. Here, we show that apoptotic stimuli increase endogenous cellular levels of pathway components, including POSH, mixed lineage kinases (MLKs), and JNK interacting protein 1, and that this effect occurs through protein stabilization and requires the presence of POSH as well as activation of MLKs and JNKs. Our findings suggest a self-amplifying, feed-forward loop mechanism by which apoptotic stimuli promote the stabilization of JNK pathway components, thereby contributing to cell death. PMID:16260609

  12. Bicycle Safety in Action.

    Science.gov (United States)

    National Commission on Safety Education, Washington, DC.

    This material was designed to assist schools in teaching bicycle safety. As the population grows and competition for road space increases, it is more imperative than ever that we concentrate attention on the need for caution among pupil cyclists. The pamphlet: (1) discusses the role of bicycle safety in classroom instruction and in student…

  13. Butchers and Bicycles

    DEFF Research Database (Denmark)

    Kahle, Lynn; Eriksen, Steen Mandsfelt

    2016-01-01

    Morten Wagener is a Danish design, and innovator who founded the cargo and personal transportation bicycle company, ”Butchers and Bicycles,”. He identified a business opportunity to improve the future of urban transport. His idea was that most of the trikes) on the market lacked good design, mane...

  14. Bicycling and Hostels.

    Science.gov (United States)

    Kyle, George M., Ed.

    1974-01-01

    This collection of articles focuses on bicycling and hosteling as important recreational activities that can (a) help conserve energy, (b) benefit the economy offering a low-cost pasttime, and (c) stimulate foreign travel to the U.S. Articles include the following: (a) "Bicycling and Hosteling--An American Partnership," (b) "The Return of the…

  15. Bicycles made to measure

    NARCIS (Netherlands)

    Van Dijk, T.

    2007-01-01

    For almost a century and a half, mathematicians have been racking their brains about the bike. How can a rolling bicycle be so stable of its own accord? Delft researchers now say they have completed the model to end all models. Bicycle manufacturer Batavus intends to use it to make better bikes for

  16. Epstein-Barr virus-encoded latent membrane protein 1 modulates cyclin D1 by c-Jun/Jun B heterodimers

    Institute of Scientific and Technical Information of China (English)

    SONG; Xin; TAO; Yongguang; ZENG; Liang; YANG; Jing; TANG; F

    2005-01-01

    In our recent studies, we found that LMP1 encoded by Epstein-Barr virus could accelerate the formation of active c-Jun/Jun B heterodimer. We studied the regulation of cyclinD1 by c-Jun/Jun B heterodimers by laser scanning confocal influorescence microscopy, Western blot, luciferase activity assay, super-EMSA and flow cytometry in the Tet-on-LMP1 HNE2 cell line, in which LMP1 expression was regulated by Tet-on system. c-Jun/Jun B heterodimers induced by LMP1 could up regulate cyclin D1 promoter activity and expression. Overexpression of cyclinD1 accelerated the progression of cell cycle.

  17. NPM-ALK oncogenic kinase promotes cell-cycle progression through activation of JNK/cJun signaling in anaplastic large-cell lymphoma.

    Science.gov (United States)

    Leventaki, Vasiliki; Drakos, Elias; Medeiros, L Jeffrey; Lim, Megan S; Elenitoba-Johnson, Kojo S; Claret, Francois X; Rassidakis, George Z

    2007-09-01

    Anaplastic large-cell lymphoma (ALCL) frequently carries the t(2;5)(p23;q35), resulting in aberrant expression of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). We show that in 293T and Jurkat cells, forced expression of active NPM-ALK, but not kinase-dead mutant NPM-ALK (210K>R), induced JNK and cJun phosphorylation, and this was linked to a dramatic increase in AP-1 transcriptional activity. Conversely, inhibition of ALK activity in NPM-ALK(+) ALCL cells resulted in a concentration-dependent dephosphorylation of JNK and cJun and decreased AP-1 DNA-binding. In addition, JNK physically binds NPM-ALK and is highly activated in cultured and primary NPM-ALK(+) ALCL cells. cJun phosphorylation in NPM-ALK(+) ALCL cells is mediated by JNKs, as shown by selective knocking down of JNK1 and JNK2 genes using siRNA. Inhibition of JNK activity using SP600125 decreased cJun phosphorylation and AP-1 transcriptional activity and this was associated with decreased cell proliferation and G2/M cell-cycle arrest in a dose-dependent manner. Silencing of the cJun gene by siRNA led to a decreased S-phase cell-cycle fraction associated with upregulation of p21 and downregulation of cyclin D3 and cyclin A. Taken together, these findings reveal a novel function of NPM-ALK, phosphorylation and activation of JNK and cJun, which may contribute to uncontrolled cell-cycle progression and oncogenesis.

  18. Induction of c-fos and c-jun protooncogenes expression by formaldehyde-releasing and epoxy resin-based root-canal sealers in human osteoblastic cells.

    Science.gov (United States)

    Huang, Fu-Mei; Hsieh, Yih-Shou; Tai, Kuo-Wei; Chou, Ming-Yung; Chang, Yu-Chao

    2002-03-01

    An important requirement for a root-canal sealer is biologic compatibility; most evaluations have focused on general toxicological and local tissue irritating properties. There is only scant information about mutagenicity or carcinogenicity testing for root-canal sealer. It has been shown that c-fos and c-jun are induced rapidly by a variety of chemical and physical stimuli. Numerous works have extensively investigated the induction mechanisms of c-fos and c-jun protooncogenes by these agents; however, little is known about the induction of cellular signaling events and specific gene expression after cell exposure to root-canal sealers. Therefore, we used osteoblastic cell line U2-OS to examine the effect of zinc-oxide eugenol-based (N2 and Endomethasome), epoxy resin-based (AH Plus), and calcium hydroxide-based (Sealapex) root-canal sealers on the expression of c-fos and c-jun protooncogenes to understand in more detail the molecular mechanisms of root-canal sealer-induced genotoxicity. The cytotoxicity decreased in an order of N2 > Endomethasome > AH Plus > Sealapex. In addition, N2, Endomethasome, and AH Plus rapidly induced c-jun and c-fos mRNA levels in cells. However, Sealapex did not induce c-jun and c-fos mRNA expression at detectable levels all time points. Taken together, persistent induction of c-jun and c-fos protooncogenes by formaldehyde-releasing and epoxy resin-based root-canal sealers may be distributed systemically via apex to cause some unexpected adverse effects on human beings. These data should be taken into consideration when choosing a root-canal sealer.

  19. Pregnane and Xenobiotic Receptor gene expression in liver cells is modulated by Ets-1 in synchrony with transcription factors Pax5, LEF-1 and c-jun

    Energy Technology Data Exchange (ETDEWEB)

    Kumari, Sangeeta; Saradhi, Mallampati; Rana, Manjul; Chatterjee, Swagata [Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067 (India); Aumercier, Marc [IRI, CNRS USR 3078, Université de Lille-Nord de France, Parc CNRS de la Haute Borne, 50 Avenue de Halley, BP 70478, 59658 Villeneuve d’Ascq Cedex (France); Mukhopadhyay, Gauranga [Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067 (India); Tyagi, Rakesh K., E-mail: rktyagi@yahoo.com [Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067 (India)

    2015-01-15

    Nuclear receptor PXR is predominantly expressed in liver and intestine. Expression of PXR is observed to be dysregulated in various metabolic disorders indicating its involvement in disease development. However, information available on mechanisms of PXR self-regulation is fragmentary. The present investigation identifies some of the regulatory elements responsible for its tight regulation and low cellular expression. Here, we report that the PXR-promoter is a target for some key transcription factors like PU.1/Ets-1, Pax5, LEF-1 and c-Jun. Interestingly, we observed that PXR-promoter responsiveness to Pax5, LEF-1 and c-Jun, is considerably enhanced by Ets transcription factors (PU.1 and Ets-1). Co-transfection of cells with Ets-1, LEF-1 and c-Jun increased PXR-promoter activity by 5-fold and also induced expression of endogenous human PXR. Site-directed mutagenesis and transfection studies revealed that two Ets binding sites and two of the three LEF binding sites in the PXR-promoter are functional and have a positive effect on PXR transcription. Results suggest that expression of Ets family members, in conjunction with Pax5, LEF-1 and c-Jun, lead to coordinated up-regulation of PXR gene transcription. Insights obtained on the regulation of PXR gene have relevance in offering important cues towards normal functioning as well as development of several metabolic disorders via PXR signaling. - Highlights: • The study identified cis-regulatory elements in the nuclear receptor PXR promoter. • Several trans-acting factors modulating the PXR-promoter have been identified. • PU.1/Ets-1, Pax5, LEF-1, c-Jun, LyF-VI and NF-1 act as modulators of the PXR-promoter. • Ets-1 in conjunction with LEF-1 and c-Jun exhibit 5-fold activation of the PXR-promoter. • Insights into PXR-regulation have relevance in normal and pathological conditions.

  20. Cucurbitacin-I (JSI-124) activates the JNK/c-Jun signaling pathway independent of apoptosis and cell cycle arrest in B Leukemic Cells

    International Nuclear Information System (INIS)

    Cucurbitacin-I (JSI-124) is potent inhibitor of JAK/STAT3 signaling pathway and has anti-tumor activity in a variety of cancer including B cell leukemia. However, other molecular targets of JSI-124 beyond the JAK/STAT3 pathway are not fully understood. BJAB, I-83, NALM-6 and primary CLL cells were treated with JSI-124 as indicated. Apoptosis was measured using flow cytometry for accumulation of sub-G1 phase cells (indicator of apoptosis) and Annexin V/PI staining. Cell cycle was analyzed by FACS for DNA content of G1 and G2 phases. Changes in phosphorylation and protein expression of p38, Erk1/2, JNK, c-Jun, and XIAP were detected by Western blot analysis. STAT3 and c-Jun genes were knocked out using siRNA transfection. VEGF expression was determined by mRNA and protein levels by RT-PCR and western blotting. Streptavidin Pull-Down Assay was used to determine c-Jun binding to the AP-1 DNA binding site. Herein, we show that JSI-124 activates c-Jun N-terminal kinase (JNK) and increases both the expression and serine phosphorylation of c-Jun protein in the B leukemic cell lines BJAB, I-83 and NALM-6. JSI-124 also activated MAPK p38 and MAPK Erk1/2 albeit at lower levels than JNK activation. Inhibition of the JNK signaling pathway failed to effect cell cycle arrest or apoptosis induced by JSI-124 but repressed JSI-124 induced c-Jun expression in these leukemia cells. The JNK pathway activation c-Jun leads to transcriptional activation of many genes. Treatment of BJAB, I-83, and NALM-6 cells with JSI-124 lead to an increase of Vascular Endothelial Growth Factor (VEGF) at both the mRNA and protein level. Knockdown of c-Jun expression and inhibition of JNK activation significantly blocked JSI-124 induced VEGF expression. Pretreatment with recombinant VEGF reduced JSI-124 induced apoptosis. Taken together, our data demonstrates that JSI-124 activates the JNK signaling pathway independent of apoptosis and cell cycle arrest, leading to increased VEGF expression

  1. Predicting Virulence of Aeromonas Isolates Based-on Changes in Transcription of c-jun and c-fos in Human Tissue Culture Cells

    Science.gov (United States)

    Aims: To assess virulence of Aeromonas isolates based on the change in regulation of c-jun and c-fos in the human intestinal tissue culture cell line Caco-2. Methods and Results: Aeromonas cells were added to Caco-2 cells at approximately a one to one ratio. After 1, 2 and 3 ...

  2. Pregnane and Xenobiotic Receptor gene expression in liver cells is modulated by Ets-1 in synchrony with transcription factors Pax5, LEF-1 and c-Jun.

    Science.gov (United States)

    Kumari, Sangeeta; Saradhi, Mallampati; Rana, Manjul; Chatterjee, Swagata; Aumercier, Marc; Mukhopadhyay, Gauranga; Tyagi, Rakesh K

    2015-01-15

    Nuclear receptor PXR is predominantly expressed in liver and intestine. Expression of PXR is observed to be dysregulated in various metabolic disorders indicating its involvement in disease development. However, information available on mechanisms of PXR self-regulation is fragmentary. The present investigation identifies some of the regulatory elements responsible for its tight regulation and low cellular expression. Here, we report that the PXR-promoter is a target for some key transcription factors like PU.1/Ets-1, Pax5, LEF-1 and c-Jun. Interestingly, we observed that PXR-promoter responsiveness to Pax5, LEF-1 and c-Jun, is considerably enhanced by Ets transcription factors (PU.1 and Ets-1). Co-transfection of cells with Ets-1, LEF-1 and c-Jun increased PXR-promoter activity by 5-fold and also induced expression of endogenous human PXR. Site-directed mutagenesis and transfection studies revealed that two Ets binding sites and two of the three LEF binding sites in the PXR-promoter are functional and have a positive effect on PXR transcription. Results suggest that expression of Ets family members, in conjunction with Pax5, LEF-1 and c-Jun, lead to coordinated up-regulation of PXR gene transcription. Insights obtained on the regulation of PXR gene have relevance in offering important cues towards normal functioning as well as development of several metabolic disorders via PXR signaling.

  3. Butchers and Bicycles

    OpenAIRE

    Kahle, Lynn; Eriksen, Steen Mandsfelt

    2016-01-01

    Morten Wagener is a Danish design, and innovator who founded the cargo and personal transportation bicycle company, ”Butchers and Bicycles,”. He identified a business opportunity to improve the future of urban transport. His idea was that most of the trikes) on the market lacked good design, maneuverability and styling. With his engineering and design background, Wagener set out to design a new trike; which would meet the needs of the target market, which his research identified as well- educ...

  4. Induction of heat shock protein 70 (Hsp70 prevents neuregulin-induced demyelination by enhancing the proteasomal clearance of c-Jun

    Directory of Open Access Journals (Sweden)

    Rick T Dobrowsky

    2012-12-01

    Full Text Available Modulating molecular chaperones is emerging as an attractive approach to treat neurodegenerative diseases associated with protein aggregation, DPN (diabetic peripheral neuropathy and possibly, demyelinating neuropathies. KU-32 [N-(7-((2R,3R,4S,5R-3,4-dihydroxy-5-methoxy-6,6-dimethyl-tetrahydro-2H-pyran-2-yloxy-8-methyl-2-oxo-2H-chromen-3-ylacetamide] is a small molecule inhibitor of Hsp90 (heat shock protein 90 and reverses sensory deficits associated with myelinated fibre dysfunction in DPN. Additionally, KU-32 prevented the loss of myelinated internodes induced by treating myelinated SC (Schwann cell-DRG (dorsal root ganglia sensory neuron co-cultures with NRG1 (neuregulin-1 Type 1. Since KU-32 decreased NRG1-induced demyelination in an Hsp70-dependent manner, the goal of the current study was to clarify how Hsp70 may be mechanistically linked to preventing demyelination. The activation of p42/p44 MAPK (mitogen-activated protein kinase and induction of the transcription factor c-Jun serve as negative regulators of myelination. NRG1 activated MAPK, induced c-Jun expression and promoted a loss of myelin segments in DRG explants isolated from both WT (wild-type and Hsp70 KO (knockout mice. Although KU-32 did not block the activation of MAPK, it blocked c-Jun induction and protected against a loss of myelinated segments in WT mice. In contrast, KU-32 did not prevent the NRG1-dependent induction of c-Jun and loss of myelin segments in explants from Hsp70 KO mice. Overexpression of Hsp70 in myelinated DRG explants prepared from WT or Hsp70 KO mice was sufficient to block the induction of c-Jun and the loss of myelin segments induced by NRG1. Lastly, inhibiting the proteasome prevented KU-32 from decreasing c-Jun levels. Collectively, these data support that Hsp70 induction is sufficient to prevent NRG1-induced demyelination by enhancing the proteasomal degradation of c-Jun.

  5. SUMOylation of the inducible (c-Fos:c-Jun)/AP-1 transcription complex occurs on target promoters to limit transcriptional activation.

    Science.gov (United States)

    Tempé, D; Vives, E; Brockly, F; Brooks, H; De Rossi, S; Piechaczyk, M; Bossis, G

    2014-02-13

    The inducible proto-oncogenic (c-Fos:c-Jun)/AP-1 transcription complex binds 12-O-tetradecanoylphorbol 13-acetate (TPA)-responsive elements (TRE) in its target genes. It is tightly controlled at multiple levels to avoid the deleterious effects of its inappropriate activation. In particular, SUMOylation represses its transactivation capacity in transient reporter assays using constitutively expressed proteins. This led to the presumption that (c-Fos:c-Jun)/AP-1 SUMOylation would be required to turn-off transcription of its target genes, as proposed for various transcription factors. Instead, thanks to the generation of an antibody specific for SUMO-modified c-Fos, we provide here direct evidence that SUMOylated c-Fos is present on a stably integrated reporter TPA-inducible promoter at the onset of transcriptional activation and colocalizes with RNA polymerase II within chromatin. Interestingly, (c-Fos:c-Jun)/AP-1 SUMOylation limits reporter gene induction, as well as the appearance of active transcription-specific histone marks on its promoter. Moreover, non-SUMOylatable mutant (c-Fos:c-Jun)/AP-1 dimers accumulate to higher levels on their target promoter, suggesting that SUMOylation might facilitate the release of (c-Fos:c-Jun)/AP-1 from promoters. Finally, activation of GADD153, an AP-1 target gene, is also associated with a rapid increase in SUMOylation at the level of its TRE and c-Fos SUMOylation dampens its induction by TPA. Taken together, our data suggest that SUMOylation could serve to buffer transcriptional activation of AP-1 target genes.

  6. A novel function of B-cell translocation gene 1 (BTG1) in the regulation of hepatic insulin sensitivity in mice via c-Jun.

    Science.gov (United States)

    Xiao, Fei; Deng, Jiali; Yu, Junjie; Guo, Yajie; Chen, Shanghai; Guo, Feifan

    2016-01-01

    Insulin resistance is one of the major factors contributing to metabolic diseases, but the underlying mechanisms are still poorly understood. As an important cofactor, B-cell translocation gene 1 (BTG1) is involved in many physiologic processes; however, the direct effect of BTG1 on insulin sensitivity has not been described. In our study, BTG1 overexpression or knockdown improved or impaired insulin signaling in vitro, respectively. In addition, adenovirus-mediated BTG1 overexpression improved insulin sensitivity in wild-type (WT) and insulin-resistant leptin-receptor mutated (db/db) mice. In addition, transgenic BTG1-overexpressing mice were resistant to high-carbohydrate diet-induced insulin resistance. Adenovirus-mediated BTG1 knockdown consistently impaired insulin sensitivity in WT and insulin-sensitive leucine-deprived mice. Moreover, hepatic BTG1 expression was increased by leucine deprivation via the mammalian target of rapamycin/ribosomal protein S6 kinase 1 pathway. Furthermore, c-Jun expression was up-regulated by BTG1, and adenovirus-mediated c-Jun knockdown blocked BTG1-improved insulin signaling and insulin sensitivity in vitro and in vivo. Finally, BTG1 promoted c-Jun expression via stimulating c-Jun and retinoic acid receptor activities. Taken together, these results identify a novel function for BTG1 in the regulation of hepatic insulin sensitivity and provide important insights into the nutritional regulation of BTG1 expression.- Xiao, F., Deng, J., Yu, J., Guo, Y., Chen, S., Guo, F. A novel function of B-cell translocation gene 1 (BTG1) in the regulation of hepatic insulin sensitivity in mice via c-Jun.

  7. Inhibition of spinal c-Jun-NH2-terminal kinase (JNK) improves locomotor activity of spinal cord injured rats.

    Science.gov (United States)

    Martini, Alessandra C; Forner, Stefânia; Koepp, Janice; Rae, Giles Alexander

    2016-05-16

    Mitogen-activated protein kinases (MAPKs) have been implicated in central nervous system injuries, yet the roles within neurodegeneration following spinal cord injury (SCI) still remain partially elucidated. We aimed to investigate the changes in expression of the three MAPKs following SCI and the role of spinal c-jun-NH2-terminal kinase (JNK) in motor impairment following the lesion. SCI induced at the T9 level resulted in enhanced expression of phosphorylated MAPKs shortly after trauma. SCI increased spinal cord myeloperoxidase levels, indicating a local neutrophil infiltration, and elevated the number of spinal apoptotic cells. Intrathecal administration of a specific inhibitor of JNK phosphorylation, SP600125, given at 1 and 4h after SCI, reduced the p-JNK expression, the number of spinal apoptotic cells and many of the histological signs of spinal injury. Notably, restoration of locomotor performance was clearly ameliorated by SP600125 treatment. Altogether, the results demonstrate that SCI induces activation of spinal MAPKs and that JNK plays a major role in mediating the deleterious consequences of spinal injury, not only at the spinal level, but also those regarding locomotor function. Therefore, inhibition of JNK activation in the spinal cord shortly after trauma might constitute a feasible therapeutic strategy for the functional recovery from SCI. PMID:27080425

  8. c-Jun-N-terminal kinase 1 is necessary for nicotine-induced enhancement of contextual fear conditioning.

    Science.gov (United States)

    Leach, Prescott T; Kenney, Justin W; Gould, Thomas J

    2016-08-01

    Acute nicotine enhances hippocampus-dependent learning. Identifying how acute nicotine improves learning will aid in understanding how nicotine facilitates the development of maladaptive memories that contribute to drug-seeking behaviors, help development of medications to treat disorders associated with cognitive decline, and advance understanding of the neurobiology of learning and memory. The effects of nicotine on learning may involve recruitment of signaling through the c-Jun N-terminal kinase family (JNK 1-3). Learning in the presence of acute nicotine increases the transcription of mitogen-activated protein kinase 8 (MAPK8, also known as JNK1), likely through a CREB-dependent mechanism. The functional significance of JNK1 in the effects of acute nicotine on learning, however, is unknown. The current studies undertook a backward genetic approach to determine the functional contribution JNK1 protein makes to nicotine-enhanced contextual fear conditioning. JNK1 wildtype (WT) and knockout (KO) mice were administered acute nicotine prior to contextual and cued fear conditioning. 24h later, mice were evaluated for hippocampus-dependent (contextual fear conditioning) and hippocampus-independent (cued fear conditioning) memory. Nicotine selectively enhanced contextual conditioning in WT mice, but not in KO mice. Nicotine had no effect on hippocampus-independent learning in either genotype. JNK1 KO and WT mice given saline showed similar levels of learning. These data suggest that JNK1 may be recruited by nicotine and is functionally necessary for the acute effects of nicotine on learning and memory. PMID:27235579

  9. Monosodium Urate in the Presence of RANKL Promotes Osteoclast Formation through Activation of c-Jun N-Terminal Kinase

    Directory of Open Access Journals (Sweden)

    Jung-Yoon Choe

    2015-01-01

    Full Text Available The aim of this study was to clarify the role of monosodium urate (MSU crystals in receptor activator of nuclear factor kB ligand- (RANKL- RANK-induced osteoclast formation. RAW 264.7 murine macrophage cells were incubated with MSU crystals or RANKL and differentiated into osteoclast-like cells as confirmed by staining for tartrate-resistant acid phosphatase (TRAP and actin ring, pit formation assay, and TRAP activity assay. MSU crystals in the presence of RANKL augmented osteoclast differentiation, with enhanced mRNA expression of NFATc1, cathepsin K, carbonic anhydrase II, and matrix metalloproteinase-9 (MMP-9, in comparison to RAW 264.7 macrophages incubated in the presence of RANKL alone. Treatment with both MSU crystals and RANKL induced osteoclast differentiation by activating downstream molecules in the RANKL-RANK pathway including tumor necrosis factor receptor-associated factor 6 (TRAF-6, JNK, c-Jun, and NFATc1. IL-1b produced in response to treatment with both MSU and RANKL is involved in osteoclast differentiation in part through the induction of TRAF-6 downstream of the IL-1b pathway. This study revealed that MSU crystals contribute to enhanced osteoclast formation through activation of RANKL-mediated pathways and recruitment of IL-1b. These findings suggest that MSU crystals might be a pathologic causative agent of bone destruction in gout.

  10. Speciifc effects of c-Jun NH2-terminal kinase-interacting protein 1 in neuronal axons

    Institute of Scientific and Technical Information of China (English)

    Shu Tang; Qiang Wen; Xiao-jian Zhang; Quan-cheng Kan

    2016-01-01

    c-Jun NH2-terminal kinase (JNK)-interacting protein 3 plays an important role in brain-derived neurotrophic factor/tropomyosin-related kinase B (TrkB) anterograde axonal transport. It remains unclear whether JNK-interacting protein 1 mediates similar effects, or whether JNK-interacting protein 1 affects the regulation of TrkB anterograde axonal transport. In this study, we isolated rat embryonic hippocampus and cultured hippocampal neuronsin vitro. Coimmunoprecipitation results demonstrated that JNK-interacting protein 1 formed TrkB com-plexesin vitro andin vivo. Immunocytochemistry results showed that when JNK-interacting protein 1 was highly expressed, the distribution of TrkB gradually increased in axon terminals. However, the distribution of TrkB reduced in axon terminals after knocking out JNK-interact-ing protein 1. In addition, there were differences in distribution of TrkB after JNK-interacting protein 1 was knocked out compared with not. However, knockout of JNK-interacting protein 1 did not affect the distribution of TrkB in dendrites. These ifndings conifrm that JNK-inter-acting protein 1 can interact with TrkB in neuronal cells, and can regulate the transport of TrkB in axons, but not in dendrites.

  11. C-jun N-terminal Kinase-mediated Signaling Is Essential for Staphylococcus Aureus-induced U937 Apoptosis

    Institute of Scientific and Technical Information of China (English)

    Jia-he Wang; Bo Yu; Hui-yan Niu; Hui Li; Yi Zhang; Xin Wang; Ping He

    2009-01-01

    Objective To investigate the effect of SP600125, a specific c-jun N-terminal protein kinase (JNK) inhibitor, on Staphylococcus aureus (S. aureus)-induced U937 cell death and the underlying mechanism. Methods The human monocytic U937 cells were treated with S. aureus at different time with or without SP600125. Cell apoptosis was analyzed by flow cytometry. JNK, Bax, and caspase-3 activities were detected by Western blotting. Results S. aureus induced apoptosis in cultured U937 cells in a time-dependent manner. Expression of Bax and phospho-JNK significantly increased in S. aureus-treated U937 cells, and the level of activated caspase-3 also increased in a time-dependent manner. Inhibition of JNK with SP600125 significantly inhibited S. aureus-induced apoptosis in U937 cells. Conclusions S. aureus can induce apoptosis in U937 cells by phosphorylation of JNK and activation of Bax and caspase-3. SP600125 protects U937 cells from apoptosis induced by S. aureus via inhibiting the activity of JNK.

  12. The c-Jun N-terminal Kinase 2 Plays a Dominant Role in Human Epidermal Neoplasia

    Science.gov (United States)

    Ke, Hengning; Harris, Rebecca; Coloff, Jonathan; Jin, Jane Y.; Leshin, Benjamin; de Marval, Paula Miliani; Tao, Shiying; Rathmell, Jeffrey C; Hall, Russell P.; Zhang, Jennifer Y.

    2010-01-01

    The c-Jun N-terminal Kinase (JNK) signaling cascade has been implicated in a wide range of diseases, including cancer. It is unclear how different JNK proteins contribute to human cancer. Here, we report that JNK2 is activated in over 70% of human squamous cell carcinoma (SCC) samples and that inhibition of JNK2 pharmacologically or genetically impairs tumorigenesis of human SCC cells. Most importantly, JNK2, but not JNK1, is sufficient to couple with oncogenic Ras to transform primary human epidermal cells into malignancy with features of SCC. JNK2 prevents Ras-induced cell senescence and growth arrest by reducing the expression levels of the cell cycle inhibitor p16 and NF-κB activation. On the other hand, JNK, along with PI3K, is essential for Ras-induced glycolysis, an energy producing process known to benefit cancer growth. These data indicate that JNK2 collaborates with other oncogenes, such as Ras, at multiple molecular levels to promote tumorigenesis and hence represents a promising therapeutic target for cancer. PMID:20354187

  13. Metformin prevents endoplasmic reticulum stress-induced apoptosis through AMPK-PI3K-c-Jun NH2 pathway

    Science.gov (United States)

    Jung, T.W.; Lee, M.W.; Lee, Y.-J.; Kim, S.M.

    2012-01-01

    Type 2 diabetes mellitus is thought to be partially associated with endoplasmic reticulum (ER) stress toxicity on pancreatic beta cells and the result of decreased insulin synthesis and secretion. In this study, we showed that a well-known insulin sensitizer, metformin, directly protects against dysfunction and death of ER stress-induced NIT-1 cells (a mouse pancreatic beta cell line) via AMP-activated protein kinase (AMPK) and phosphatidylinositol-3 (PI3) kinase activation. We also showed that exposure of NIT-1 cells to metformin (5mM) increases cellular resistance against ER stress-induced NIT-1 cell dysfunction and death. AMPK and PI3 kinase inhibitors abolished the effect of metformin on cell function and death. Metformin-mediated protective effects on ER stress-induced apoptosis were not a result of an unfolded protein response or the induced inhibitors of apoptotic proteins. In addition, we showed that exposure of ER stressed-induced NIT-1 cells to metformin decreases the phosphorylation of c-Jun NH(2) terminal kinase (JNK). These data suggest that metformin is an important determinant of ER stress-induced apoptosis in NIT-1 cells and may have implications for ER stress-mediated pancreatic beta cell destruction via regulation of the AMPK-PI3 kinase-JNK pathway.

  14. DNA Damage, Apoptosis and C-myc, C-fos, and C-jun Overexpression Induced by Selenium in Rat Hepatocytes

    Institute of Scientific and Technical Information of China (English)

    RI-AN YU; CHENG-FENG YANG; XUE-MIN CHEN

    2006-01-01

    Objective To study the effects of selenium on DNA damage, apoptosis and c-myc, c-fos, and c-jun expression in rat hepatocytes. Methods Sodium selenite at the doses of 5, 10, and 20 μmol/kg was given to rats by i.p. and there were 5 male SD rats in each group. Hepatocellular DNA damage was detected by single cell gel electrophoresis (or comet assay).Hepatocellular apoptosis was determined by TUNEL (TdT-mediated dUTP nick end labelling) and flow cytometry. C-myc,c-fos, and c-jun expression in rat hepatocytes were assayed by Northern dot hybridization. C-myc, c-fos, and c-jun protein were detected by immunohistochemical method. Results At the doses of 5, 10, and 20 μmol/kg, DNA damage was induced by sodium selenite in rat hepatocytes and the rates of comet cells were 34.40%, 74.80%, and 91.40% respectively. Results also showed an obvious dose-response relationship between the rates of comet cells and the doses of sodium selenite (r=0.9501,P<0.01). Sodium selenite at the doses of 5, 10, and 20 μmol/kg caused c-myc, c-fos, and c-jun overexpression obviously. The positive brown-yellow signal for proteins of c-myc, c-fos, and c-jun was mainly located in the cytoplasm of hepatocytes with immunohistochemical method. TUNEL-positive cells were detected in selenium-treated rat livers. Apoptotic rates (%) of selenium-treated liver cells at the doses of 5, 10, and 20 μmol/kg were (3.72±1.76), (5.82±1.42), and (11.76±1.87) respectively, being much higher than those in the control. Besides an obvious dose-response relationship between apoptotic rates and the doses of sodium selenite (r=0.9897, P<0.01), these results displayed a close relationship between DNA damage rates and apoptotic rates, and the relative coefficient was 0.9021, P<0.01. Conclusion Selenium at 5-20 μmol/kg can induce DNA damage, apoptosis, and overexpression of c-myc, c-fos, and c-jun in rat hepatocytes.

  15. Effect of Qi-protecting powder (Huqi San) on expression of c-jun, c-fos and c-myc in diethylnitrosamine-mediated hepatocarcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Xia Li; Zheng-Ming Shi; Ping Feng; Zhao-Yang Wen; Xue-Jiang Wang

    2007-01-01

    AIM: To study the inhibitory effect of Huqi San (Qiprotecting powder) on rat prehepatocarcinoma induced by diethylinitrosamine (DEN) by analyzing the mutational activation of c-fos proto-oncogene and over-expression of c-jun and c-myc oncogenes.METHODS: A Solt-Farber two-step test model of prehepatocarcinoma was induced in rats by DEN and 2-acetylaminofluorene (AAF) to investigate the modifying effects of Huqi San on the expression of c-jun, c-fos and c-myc in DEN-mediated hepatocarcinogenesis. Huqi San was made of eight medicinal herbs containing glycoprival granules, in which each milliliter contains 0.38 g crude drugs. γ-glutamy-transpeptidase-isoenzyme (γ-GTase)was determined with histochemical methods. Level of 8-hydroxydeoxyguanosine (OHdG) formed in liver and c-jun, c-fos and c-myc proto-oncogenes were detected by immunohistochemical methods.RESULTS: The level of 8-OHdG, a mark of oxidative DNA damage, was significantly decreased in the liver of rats with prehepatocarcinoma induced by DEN who received 8 g/kg body weight or 4 g/kg body weight Huqi San before (1 wk) and after DEN exposure (4 wk). Huqi Santreated rats showed a significant decrease in number of γ-GT positive foci (P < 0.001, prevention group: 4.96 ±0.72 vs 29.46 ± 2.17; large dose therapeutic group: 7.53± 0.88 vs 29.46 ± 2.17). On the other hand, significant changes in expression of c-jun, c-fos and c-myc were found in Huqi San-treated rats.CONCLUSION: Activation of c-jun, c-fos and c-myc plays a crucial role in the pathogenesis of liver cancer.Huqi San can inhibit the over-expression of c-jun, c-fos and c-myc oncogenes and liver preneolastic lesionsinduced by DEN.

  16. Molecular clone and characterization of c-Jun N-terminal kinases 2 from orange-spotted grouper, Epinephelus coioides.

    Science.gov (United States)

    Guo, Minglan; Wei, Jingguang; Zhou, Yongcan; Qin, Qiwei

    2016-02-01

    c-Jun N-terminal kinase 2 (JNK2) is a multifunctional mitogen-activated protein kinases involving in cell differentiation and proliferation, apoptosis, immune response and inflammatory conditions. In this study, we reported a new JNK2 (Ec-JNK2) derived from orange-spotted grouper, Epinephelus coioides. The full-length cDNA of Ec-JNK2 was 1920 bp in size, containing a 174 bp 5'-untranslated region (UTR), 483 bp 3'-UTR, and a 1263 bp open reading frame (ORF), which encoded a putative protein of 420 amino acids. The deduced protein sequence of Ec-JNK2 contained a conserved Thr-Pro-Tyr (TPY) motif in the domain of serine/threonine protein kinase (S-TKc). Ec-JNK2 has been found to involve in the immune response to pathogen challenges in vivo, and the infection of Singapore grouper iridovirus (SGIV) in vitro. Immunofluorescence staining showed that Ec-JNK2 was localized in the cytoplasm of grouper spleen (GS) cells, and moved to the nucleus after infecting with SGIV. Ec-JNK2 distributed in all immune-related tissues examined. After challenging with lipopolysaccharide (LPS), SGIV and polyriboinosinic polyribocytidylic acid (poly I:C), the mRNA expression of Ec-JNK2 was significantly (P orange-spotted grouper. Over-expressing Ec-JNK2 in fathead minnow (FHM) cells increased the SGIV infection and replication, while over-expressing the dominant-negative Ec-JNK2Δ181-183 mutant decreased it. These results indicated that Ec-JNK2 could be an important molecule in the successful infection and evasion of SGIV.

  17. C-Jun N-terminal kinase controls TDP-43 accumulation in stress granules induced by oxidative stress

    Directory of Open Access Journals (Sweden)

    Masters Colin L

    2011-08-01

    Full Text Available Abstract Background TDP-43 proteinopathies are characterized by loss of nuclear TDP-43 expression and formation of C-terminal TDP-43 fragmentation and accumulation in the cytoplasm. Recent studies have shown that TDP-43 can accumulate in RNA stress granules (SGs in response to cell stresses and this could be associated with subsequent formation of TDP-43 ubiquinated protein aggregates. However, the initial mechanisms controlling endogenous TDP-43 accumulation in SGs during chronic disease are not understood. In this study we investigated the mechanism of TDP-43 processing and accumulation in SGs in SH-SY5Y neuronal-like cells exposed to chronic oxidative stress. Cell cultures were treated overnight with the mitochondrial inhibitor paraquat and examined for TDP-43 and SG processing. Results We found that mild stress induced by paraquat led to formation of TDP-43 and HuR-positive SGs, a proportion of which were ubiquitinated. The co-localization of TDP-43 with SGs could be fully prevented by inhibition of c-Jun N-terminal kinase (JNK. JNK inhibition did not prevent formation of HuR-positive SGs and did not prevent diffuse TDP-43 accumulation in the cytosol. In contrast, ERK or p38 inhibition prevented formation of both TDP-43 and HuR-positive SGs. JNK inhibition also inhibited TDP-43 SG localization in cells acutely treated with sodium arsenite and reduced the number of aggregates per cell in cultures transfected with C-terminal TDP-43 162-414 and 219-414 constructs. Conclusions Our studies are the first to demonstrate a critical role for kinase control of TDP-43 accumulation in SGs and may have important implications for development of treatments for FTD and ALS, targeting cell signal pathway control of TDP-43 aggregation.

  18. Myocardial protective effects of a c-Jun N-terminal kinase inhibitor in rats with brain death.

    Science.gov (United States)

    Guo, Wenzhi; Cao, Shengli; Yan, Bing; Zhang, Gong; Li, Jie; Zhao, Yongfu; Zhang, Shuijun

    2016-07-01

    To investigate whether the mitochondrial apoptotic pathway mediates myocardial cell injuries in rats under brain death (BD), and observe the effects and mechanisms of the c-Jun N-terminal kinase (JNK) inhibitor SP600125 on cell death in the heart. Forty healthy male Sprague-Dawley (SD) rats were randomized into four groups: sham group (dural external catheter with no BD); BD group (maintain the induced BD state for 6 hrs); BD + SP600125 group (intraperitoneal injection of SP600125 10 mg/kg 1 hr before inducing BD, and maintain BD for 6 hrs); and BD + Dimethyl Sulphoxide (DMSO) group (intraperitoneal injection of DMSO 1 hr before inducing BD, and maintain BD for 6 hrs). Real-time quantitative PCR was used to evaluate mRNA levels of Cyt-c and caspase-3. Western blot analysis was performed to examine the levels of mitochondrial apoptosis-related proteins p-JNK, Bcl-2, Bax, Cyt-c and Caspase-3. TUNEL assay was employed to evaluate myocardial apoptosis. Compared with the sham group, the BD group exhibited increased mitochondrial apoptosis-related gene expression, accompanied by the elevation of p-JNK expression and myocardial apoptosis. As the vehicle control, DMSO had no treatment effects. The BD + SP600125 group had decreased p-JNK expression, and reduced mitochondrial apoptosis-related gene expression. Furthermore, the apoptosis rate of myocardial cells was reduced. The JNK inhibitor SP600125 could protect myocardial cells under BD through the inhibition of mitochondrial apoptosis-related pathways. PMID:27072084

  19. Bicycle Culture in Denmark

    OpenAIRE

    Pedersenn, Pia; Breitenstein, Marcus Lindgaard; Nilsson, Asbjørn Lupo

    2014-01-01

    The research area involves the cycling culture in Denmark. Cycling is one of the main forms of transport in Denmark today, and it has been a big part of Denmark’s culture since the early 20th century. This project specifically looks at bicycle helmets. Today in Denmark, there is no legislation demanding cyclists to wear helmets. However we would like to investigate what the government’s stance is concerning bicycle helmets. The project will begin by looking at the efficiency of helmets. Some ...

  20. Constitutive hypophosphorylation of extracellular signal-regulated kinases-1/2 and down-regulation of c-Jun in human gastric adenocarcinoma

    International Nuclear Information System (INIS)

    Hyperphosphorylation of extracellular signal-regulated protein kinases-1/2 (ERK1/2) is known to promote cancer cell proliferation. We therefore investigated the constitutive phosphorylation levels of ERK1/2 and the expression of its downstream targets c-Fos, c-Jun, and cyclooxygenase-2 (COX-2) in biopsied human gastric cancer tissues. Results showed that ERK1/2 phosphorylation and c-Jun expression were significantly lowered in gastric cancer compared with the non-cancer adjacent tissues. The expression of c-Fos, however, was not altered while COX-2 was significantly up-regulated. To conclude, we demonstrate that hypophosphorylation of ERK1/2 may occur in gastric cancer. Such discovery may have implication in the application of pathway-directed therapy for this malignant disease

  1. c-Jun N-terminal kinase is required for vitamin E succinate-induced apoptosis in human gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Kun Wu; Yan Zhao; Gui-Chang Li; Wei-Ping Yu

    2004-01-01

    AIM: To investigate the roles of c-Jun N-terminal kinase (JNK)signaling pathway in vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells.METHODS: Human gastric cancer cell lines (SGC-7901)were treated with vitamin E succinate (VES) at 5, 10, 20 mg/L.Succinic acid and vitamin E were used as vehicle controls and condition medium only as an untreated (UT) control.Apoptosis was observed by 4′, 6-diamidine-2′-phenylindole dihydrochloride (DAPI) staining for morphological changes and by DNA fragmentation for biochemical alterations.Western blot analysis was applied to measure the expression ofJNK and phosphorylated JNK. After the cells were transiently transfected with dominant negative mutant of JNK (DNJNK) followed by treatment of VES, the expression of JNK and c-Jun protein was determined.RESULTS: The apoptotic changes were observed after VES treatment by DNA fragmentation. DNA ladder in the 20 mg/L VES group was more clearly seen than that in 10 mg/L VES group and was not detected following treatment of UT control, succinate and vitamin E. VES at 5, 10 and 20 mg/L increased the expression of p-JNK by 2.5-, 2.8- and 4.2-fold, respectively. VES induced the phosphorylation of JNK beginning at 1.5 h and produced a sustained increase for 24 h with the peak level at 12 h. Transient transfection of DN-JNK blocked VES-triggered apoptosis by 52%. DN-JNK significantly increased the level of JNK, while decreasing the expression of VES-induced c-Jun protein.CONCLUSION: VES-induced apoptosis in human gastric cancer SGC-7901 cells involves JNK signaling pathway via c-Jun and its downstream transcription factor.

  2. β-glucan reduces exercise-induced stress through downregulation of c-Fos and c-Jun expression in the brains of exhausted rats.

    Science.gov (United States)

    Hong, Heeok; Kim, Chang-Ju; Kim, Jae-Deung; Seo, Jin-Hee

    2014-05-01

    Immediate-early genes are involved in acute stress responses in the central nervous system. β-glucan stimulates innate immune defenses, exerts an anti-tumor response and increases resistance to a wide variety of types of infection. To date, the effect of β-glucan on the expression of immediate-early genes under stressful conditions has not been elucidated. In the present study, the effects of β-glucan on the expression of the oncogenes c-Fos and c-Jun in the hypothalamus, dentate gyrus and dorsal raphe in rats following exhaustive treadmill running were investigated. Male Sprague Dawley rats were randomly divided into five groups (n=10 in each group) as follows: Control, exercise, exercise and 50 mg/kg β-glucan treatment, exercise and 100 mg/kg β-glucan treatment, and exercise and 200 mg/kg β-glucan treatment. Rats in the β-glucan‑treated groups were administered β-glucan at the respective dose once per day for seven days. Rats in the exercise groups performed treadmill running once per day for six days. On the seventh day of the experiment, the time to exhaustion in response to treadmill running was determined for the exercise groups. The expression of c-Fos and c-Jun in the hypothalamus, dorsal raphe and hippocampus was enhanced by exhaustive treadmill running. Administration of β-glucan resulted in an increase in the time to exhaustion and the suppression of the exercise-induced increment in c-Fos and c-Jun expression. In conclusion, β-glucan may exert an alleviating effect on exercise-induced stress through the suppression of c-Fos and c-Jun expression in the brains of exhausted rats. PMID:24604295

  3. Electric Bicycle Design

    OpenAIRE

    Tovar López, Carlos

    2009-01-01

    The thesis consists of the design of an electric bike. Based on the analysis of the needs arising from urban transport in Sweden and its people.We wanted to develop a bicycle that could be manufactured in the coming years and be widely accepted by the Swedish population and later also in Europe.

  4. Bicycles and Valentines

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    Shanghai municipality's announcement late last year that bicycles were to be banned from the city's main thoroughfares was ill received by many residents. The measure was taken to relieve traffic congestion and reflects how traditional modes of transport fail to meet the changing needs of Chinese contemporary life.

  5. Effect of normothermic liver ischemic preconditioning on the expression of apoptosis-regulating genes C-jun and Bcl-XL in rats

    Institute of Scientific and Technical Information of China (English)

    Guo-Huang Hu; Xin-Sheng Lü

    2005-01-01

    AIM: To explore the expression of apoptosis-regulatinggenes C-jun and Bcl-XL after normothermic liver ischemic preconditioning and its protective effect on hepatocytes in the rat.METHODS: Wistar rats are randomly divided into sham operation group (S group, n = 10), ischemic reperfusion group (IR group, n = 10) and ischemic preconditioning group (IP group, n = 10). After dissection of the hepatoduodenal ligament in S group, and after 30-min reperfusion in IR group and in IP group, the samples of liver tissue were taken for studying the hepatocellular apoptosis, theexpressions of C-jun mRNA, Bcl-XL mRNA and their proteins, and morphologic changes at 0, 3, 6, 20 h. Meanwhile the venous blood samples were drawn at 3, 6 and 20 h for testing ALT, AST and LDH.RESULTS: The levels of ALT, AST and LDH in IR group and IP group were significantly higher than those in S group. Hepatocellular apoptosis was significantly increased in both IR group and IP group, especially in IR group.Expressions of C-jun mRNA and protein were significantly increased in IR group compared with those in both IP group and S group, but no significant difference between IP group and S group (P>0.05). Expressions of Bcl-XL mRNA and protein in IR group and S group were not significant (P>0.05), but were significantly increased in IP group compared with those in both S group and IR group. Patch necrosis of hepatocytes because of severe injury could be seen in IR group microscopically, and the ultrastructural changes were irreversible. Meanwhile in IP group, no hepatocellular necrosis occurred, and the ultrastructural changes were reversible because of mild injury. CONCLUSION: (1) IP can protect the rat liver from normothermic IR injury by modulation of the expressionof apoptosis-regulating genes C-jun and Bcl-XL; (2) IR injury may activate the apoptosis of hepatocytes by increasing the expression of apoptosis-inducing gene C-jun; (3) IP may prohibit the apoptosis of hepatocytes by increasing the

  6. The safety of electrically assisted bicycles compared to classic bicycles.

    Science.gov (United States)

    Schepers, J P; Fishman, E; den Hertog, P; Wolt, K Klein; Schwab, A L

    2014-12-01

    Use of electrically assisted bicycles with a maximum speed of 25 km/h is rapidly increasing. This growth has been particularly rapid in the Netherlands, yet very little research has been conducted to assess the road safety implications. This case-control study compares the likelihood of crashes for which treatment at an emergency department is needed and injury consequences for electric bicycles to classic bicycles in the Netherlands among users of 16 years and older. Data were gathered through a survey of victims treated at emergency departments. Additionally, a survey of cyclists without any known crash experience, drawn from a panel of the Dutch population acted as a control sample. Logistic regression analysis is used to compare the risk of crashes with electric and classical bicycles requiring treatment at an emergency department. Among the victims treated at an emergency department we compared those being hospitalized to those being send home after the treatment at the emergency department to compare the injury consequences between electric and classical bicycle victims. The results suggest that, after controlling for age, gender and amount of bicycle use, electric bicycle users are more likely to be involved in a crash that requires treatment at an emergency department due to a crash. Crashes with electric bicycles are about equally severe as crashes with classic bicycles. We advise further research to develop policies to minimize the risk and maximize the health benefits for users of electric bicycles.

  7. Nerve growth factor downregulates c-jun mRNA and Caspase-3 in striate cortex of rats after transient global cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Dacheng Jin; Tiemin Wang; Xiubin Fang

    2006-01-01

    BACKGROUND: Immediate early gene (LEG) c-jun is a sensitive marker for functional status of nerve cells.Caspase-3 is a cysteine protease,which is a critical regulator of apoptosis. The effect of exogenous nerve growth factor (NGF) on the expression of c-jun Mrna and Caspase-3 protein in striate cortex of rats with transient global cerebral ischemia/reperfusion (IR) is unclear.OBJECTIVE: To study the protective effect of exogenous NGF on the brain of rats with transient global cerebral IR and its effecting pathway by observing the expression of c-jun Mrna and Caspase-3 protein.DESIGN: Randomized controlled animal trial.SETTING: Department of Neural Anatomy, Institute of Brain,China Medical University.MATERTALS:Eighteen healthy male SD rats of clean grade, aged 1 to 3 months, with body mass of 250 to 300 g, were involved in this study. NGF was provided by Dalian Svate Pharmaceutical Co.,Ltd, c-jun in situ hybridization detection kit, Caspase-3 antibody and SABC kit were purchased from Boster Biotechnology Co. ,Ltd.METHODS: This trial was carried out in the Department of Neural Anatomy, Institute of Brain, China Medical University during September 2003 to April 2005. ①Experimental animals were randomized into three groups with 6 in each: sham-operation group,IR group and NGF group. ②After the rats were anesthetized,the bilateral common carotid arteries and right external carotid arteries of rats were bluntly dissected and bilateral common carotid arteries were clamped for 30 minutes with bulldog clamps. Reperfusion began after buldog clamps were removed. Normal saline of 1mL and NGF (1×106 U/L) of 1 Ml was injected into the common carotid artery of rats via right external carotid arteries in the IR group and NGF group respectively.The injection was conducted within 30 minutes, and then the right external carotid arteries were ligated. In the sham-operation group, occlusion of bilateral common carotid arteries and administration of drugs were phosphate buffer

  8. c-Jun N-terminal kinase is required for thermotherapy-induced apoptosis in human gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Feng Xiao; Bin Liu; Qing-Xian Zhu

    2012-01-01

    AIM:To investigate the role of c-Jun N-terminal kinase (JNK) in thermotherapy-induced apoptosis in human gastric cancer SGC-7901 cells.METHODS:Human gastric cancer SGC-7901 cells were cultured in vitro.Following thermotherapy at 43 ℃ for 0,0.5,1,2 or 3 h,the cells were cultured for a further 24 h with or without the JNK specific inhibitor,SP600125 for 2 h.Apoptosis was evaluated by immunohistochemistry [terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)] and flow cytometry (Annexin vs propidium iodide).Cell proliferation was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide.The production of p-JNK,Bcl-2,Bax and caspase-3 proteins was evaluated by Western blotting.The expression of JNK at mRNA level was determined by reverse transcription polymerase chain reaction.RESULTS:The Proliferation of gastric carcinoma SGC-7901 cells was significantly inhibited following thermotherapy,and was 32.7%,30.6%,43.8% and 52.9% at 0.5,1,2 and 3 h post-thermotherapy,respectively.Flow cytometry analysis revealed an increased population of SGC-7901 cells in G0/G1 phase,but a reduced population in S phase following therrnotherapy for 1 or 2 h,compared to untreated cells (P < 0.05).The increased number of SGC-7901 cells in G0/G1 phase was consistent with induced apoptosis (flow cytometry) following thermotherapy for 0.5,1,2 or 3 h,compared to the untreated group (46.5% ± 0.23%,39.9% ± 0.53%,56.6% ±0.35% and 50.4% ± 0.29% vs 7.3% ± 0.10%,P < 0.01),respectively.This was supported by the TUNEL assay (48.2% ± 0.4%,40.1% ± 0.2%,61.2% ± 0.29% and 52.0% ± 0.42% vs 12.2% ± 0.22%,P < 0.01) respectively.More importantly,the expression of p-JNK protein and JNK mRNA levels were significantly higher at 0.5 h than at 0 h post-treatment (P < 0.01),and peaked at 2 h.A similar pattem was detected for Bax and caspase-3 proteins.Bcl-2 increased at 0.5 h,peaked at 1 h,and then decreased

  9. Electric power generating bicycle

    OpenAIRE

    Brito, Nuno; Ribeiro, Luís; Esteves, João Sena

    2006-01-01

    It is manifest the growing interest in both personal health and environmental issues. The device described on this paper contemplates both aspects: generating environment-friendly electric power while keeping fit. A car alternator excited through a 12V battery is coupled to a mountain bicycle, and this arrangement enables the lighting of six halogen lamps, if a cyclist pedals fast enough. Such a machine gives rise to the thought of a self-powered gymnasium. Considerable physical effort is req...

  10. Relations of transcription expression of IL-2 with nuclear factor of activated T cells as well as changes of C-Fos and C-Jun after trauma

    Institute of Scientific and Technical Information of China (English)

    罗艳; 梁华平; 胡承香; 徐祥; 王正国

    2002-01-01

    Objective: To observe the relations among expression of interleukin-2 (IL-2) in spleen lymphocytes, DNA binding activity of nuclear factor of activated T cells (NFAT) and expression of the partly family members C-Fos, C-Jun after trauma. Methods: A murine closed trauma model was used, animals were sacrificed 6, 12 hours and 1, 4, 7, 10, 14 days, respectively after injury. Spleen lymphocytes were isolated from injured mice and stimulated with concanavalin-A. The culture supernatants were harvested and assayed for IL-2 activity. Total RNA was extracted from spleen lymphocytes and assayed for IL-2 mRNA. Nuclear protein was extracted, and the DNA binding activity of NFAT was measured using an electrophoretic mobility shift assay (EMSA), the expressions of C-Fos, C-Jun protein determined by Western blot analysis. Results: The expressions of IL-2 activity and IL-2 mRNA in spleen lymphocytes were decreased in injured mice compared with those in control mice, and the most obvious decrease appeared on the 4th day after injury. The DNA binding activity of NFAT decreased gradually and reached the minimum that was only 41% of the control on the 4th day after injury, which was closely associated with the decline of IL-2 activity and IL-2 mRNA. An decrease in the expression of C-Fos on the 1st and 4th day after injury, trauma had no significant effect on the C-Jun expression.Conclusions: These results suggest that the inhibition of IL-2 expression is partly due to the impairment in the activation of NFAT in injured mice; and the decline in the DNA binding activity of NFAT is partly due to trauma block in the C-Fos expression.

  11. c-Jun NH2-terminal kinase-dependent upregulation of DR5 mediates cooperative induction of apoptosis by perifosine and TRAIL

    Directory of Open Access Journals (Sweden)

    Chen Georgia Z

    2010-12-01

    Full Text Available Abstract Background Perifosine, an alkylphospholipid tested in phase II clinical trials, modulates the extrinsic apoptotic pathway and cooperates with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL to augment apoptosis. The current study focuses on revealing the mechanisms by which perifosine enhances TRAIL-induced apoptosis. Results The combination of perifosine and TRAIL was more active than each single agent alone in inducing apoptosis of head and neck squamous cell carcinoma cells and inhibiting the growth of xenografts. Interestingly, perifosine primarily increased cell surface levels of DR5 although it elevated the expression of both DR4 and DR5. Blockade of DR5, but not DR4 upregulation, via small interfering RNA (siRNA inhibited perifosine/TRAIL-induced apoptosis. Perifosine increased phosphorylated c-Jun NH2-terminal kinase (JNK and c-Jun levels, which were paralleled with DR4 and DR5 induction. However, only DR5 upregulaiton induced by perifosine could be abrogated by both the JNK inhibitor SP600125 and JNK siRNA. The antioxidants, N-acetylcysteine and glutathione, but not vitamin C or tiron, inhibited perifosine-induced elevation of p-c-Jun, DR4 and DR5. Moreover, no increased production of reactive oxygen species was detected in perifosine-treated cells although reduced levels of intracellular GSH were measured. Conclusions DR5 induction plays a critical role in mediating perifosine/TRAIL-induced apoptosis. Perifosine induces DR5 expression through a JNK-dependent mechanism independent of reactive oxygen species.

  12. S-adenosyl-methionine decreases ethanol-induced apoptosis in primary hepatocyte cultures by a c-Jun N-terminal kinase activity-independent mechanism

    Institute of Scientific and Technical Information of China (English)

    María del Pilar Cabrales-Romero; Lucrecia Márquez-Rosado; Samia Fattel-Fazenda; Cristina Trejo-Solís; Evelia Arce-Popoca; Leticia Alemén-Lazarini; Saúl Villa-Trevi(n)o

    2006-01-01

    AIM: To determine the role of c-Jun N-terminal kinase (JNK) activity in ethanol-induced apoptosis and the modulation of this signaling cascade by S-Adenosylmethionine (AdoMet).METHODS: Primary hepatocyte cultures were pretreated with 100 μmol/L SP600125, a selective JNK inhibitor, 1 mL/L DMSO or 4 mmol/L AdoMet and then exposed to 100 mmo/L ethanol. Hepatocyte apoptosis was determined by the TUNEL and DNA ladder assays.JNK activity and its inhibition by SP600125 and AdoMet were determined by Western blot analysis of c-jun phosphorylation and Bid fragmentation. SP600125 and AdoMet effects on the apoptotic signaling pathway were determined by Western blot analysis of cytochrome c release and pro-caspase 3 fragmentation. The AdoMet effect on glutathione levels was measured by Ellman's method and reactive oxygen species (ROS) generation by cell cytometry.RESULTS: The exposure of hepatocytes to ethanol induced JNK activation, c-jun phosphorylation, Bid fragmentation, cytochrome c release and pro-caspase 3 cleavage; these effects were diminished by SP600125, and caused a significant decreasein ethanol-induced apoptosis (P< 0.05). AdoMet exerted an antioxidant effect maintaining glutathione levels and decreasing ROS generation, without a significant effect on JNK activity,and prevented cytochrome c release and pro-caspase 3 cleavage.CONCLUSION: The JNK signaling cascade is a key component of the proapoptotic signaling pathway induced by ethanol. JNK activation may be independent from ROS generation, since AdoMet which exerted antioxidant properties did not have a significant effect on JNK activity. JNK pathway modulator agents and AdoMet may be components of promising therapies for alcoholic liver disease (ALD) treatment.

  13. Apoptosis induced by genipin in human leukemia K562 cells:involvement of C-Jun N-terminal kinase in G2/M arrest

    Institute of Scientific and Technical Information of China (English)

    Qian FENG; Hou-li CAO; Wei XU; Xiao-rong LI; Yan-qin REN; Lin-fang DU

    2011-01-01

    Aim:To investigate the effect of genipin on apoptosis in human leukemia K562 cells in vitro and elucidate the underlying mechanisms.Methods:The effect of genipin on K562 cell viability was measured using trypan blue dye exclusion and cell counting.Morphological changes were detected using phase-contrast microscopy.Apoptosis was analyzed using DNA ladder, propidium iodide(PI)-labeled flow cytometry(FCM)and Hoechst 33258 staining.The infiuence of genipin on cell cycle distribution was determined using Plstaining.Caspase 3 activity was analyzed to detect apoptosis at different time points.Protein levels of phospho-c-Jun,phosphor-C-Jun N-terminal kinase(p-JNK).phosphor-p38-Fas-L,p63,and Bax and the release of cytochrome c were detected using Western blot analysis.Results:Genipin reduced the viability of K562 cells with an IC50 value of approximately 250 μmol/L.Genipin 200-400 μmol/L induced formation of typicaI apoptotic bodies and DNA fragmentation.Additionally,genipin 400 μmol/L significantly increased the caspase 3activity from 8-24 h and arrested the cells in the G2/M phase.After stimulation with genipin 500 μmol/L, the levels of p-JNK, p-c-Jun.Fas-L,Bax.and cytochrome c were remarkably upregulated,but there were no obvious changes of p-p38.Genipin 200-500 μmol/Lsignificantly upregulated the Fas-L expression and downregulated p63 expression.Dicoumarol 100 μmol/L.a JNK1/2 inhibitor,markedly suppressed the formation of apoptotic bodies and JNK activation induced by genipin 400 μmol/L.Conclusion:These results suggest that genipin inhibits the proliferation of K562 cells and induces apoptosis through the activation of JNK and induction of the Fas ligand.

  14. Identification of a c-Jun N-terminal kinase-2-dependent signal amplification cascade that regulates c-Myc levels in ras transformation

    DEFF Research Database (Denmark)

    Mathiasen, D.P.; Egebjerg, C.; Andersen, S.H.;

    2012-01-01

    Ras is one of the most frequently activated oncogenes in cancer. Two mitogen-activated protein kinases (MAPKs) are important for ras transformation: extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase 2 (JNK2). Here we present a downstream signal amplification cascade that is...... essential for ras transformation. Previous studies show that ERK-mediated serine 62 phosphorylation protects c-Myc from proteasomal degradation. ERK is, however, not alone sufficient to stabilize c-Myc but requires the cooperation of cancerous inhibitor of protein phosphatase 2A (CIP2A), an oncogene that...

  15. Aryl hydrocarbon receptor pathway activation enhances gastric cancer cell invasiveness likely through a c-Jun-dependent induction of matrix metalloproteinase-9

    Directory of Open Access Journals (Sweden)

    Song Xin

    2009-04-01

    Full Text Available Abstract Background Abberant aryl hydrocarbon receptor (AhR expression and AhR pathway activation are involved in gastric carcinogenesis. However, the relationship between AhR pathway activation and gastric cancer progression is still unclear. In present study, we used 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD, a classic and most potent ligand of AhR, to activate AhR pathway and investigated the effect of AhR pathway activation on human gastric cancer AGS cell invasion and explored the corresponding mechanism. Results To determine whether AhR pathway can be activated in AGS cells, we examined the expression of CYP1A1, a classic target gene of AhR pathway, following TCDD exposure. RT-PCR and western blot analysis showed that both CYP1A1 mRNA and protein expression were increased in a dose-dependent manner following TCDD treatment and AhR antagonist resveratrol (RSV could reverse this TCDD-induced CYP1A1 expression. To determine whether TCDD treatment of AGS cells results in an induction of MMP-9 expression, we detected MMP-9 mRNA using RT-PCR and detected MMP-9 enzymatic activity using gelatin zymography. The results showed that both MMP-9 mRNA expression and enzymatic activity were gradually increased with the concentration increase of TCDD in media and these changes could be reversed by RSV treatment in a dose-dependent manner. To examine whether AhR activation-induced MMP-9 expression and activity in AGS cells results in increased migration and invasion, we performed wound healing migration assay and transwell migration and invasion assay. After TCDD treatment, the migration distance and the migration and invasion abilities of AGS cells were increased with a dose-dependent manner. To demonstrate AhR activation-induced MMP-9 expression is mediated by c-Jun, siRNA transfection was performed to silence c-Jun mRNA in AGS cells. The results showed that MMP-9 mRNA expression and activity in untreated control AGS cells were very weak; After TCDD

  16. Streptococcus pneumoniae induced c-Jun-N-terminal kinase- and AP-1 -dependent IL-8 release by lung epithelial BEAS-2B cells

    Directory of Open Access Journals (Sweden)

    Rosseau Simone

    2006-07-01

    Full Text Available Abstract Background Although pneumococcal pneumonia is one of the most common causes of death due to infectious diseases, little is known about pneumococci-lung cell interaction. Herein we tested the hypothesis that pneumococci activated pulmonary epithelial cell cytokine release by c-Jun-NH2-terminal kinase (JNK Methods Human bronchial epithelial cells (BEAS-2B or epithelial HEK293 cells were infected with S. pneumoniae R6x and cytokine induction was measured by RT-PCR, ELISA and Bioplex assay. JNK-phosphorylation was detected by Western blot and nuclear signaling was assessed by electrophoretic mobility shift assay (EMSA and chromatin immunoprecipitation (ChIP. JNK was modulated by the small molecule inhibitor SP600125 and AP1 by transfection of a dominant negative mutant. Results S. pneumoniae induced the release of distinct CC and CXC, as well as Th1 and Th2 cytokines and growth factors by human lung epithelial cell line BEAS-2B. Furthermore, pneumococci infection resulted in JNK phosphorylation in BEAS-2B cells. Inhibition of JNK by small molecule inhibitor SP600125 reduced pneumococci-induced IL-8 mRNA expression and release of IL-8 and IL-6. One regulator of the il8 promoter is JNK-phosphorylated activator protein 1 (AP-1. We showed that S. pneumoniae time-dependently induced DNA binding of AP-1 and its phosphorylated subunit c-Jun with a maximum at 3 to 5 h after infection. Recruitment of Ser63/73-phosphorylated c-Jun and RNA polymerase II to the endogenous il8 promoter was found 2 h after S. pneumoniae infection by chromatin immunoprecipitation. AP-1 repressor A-Fos reduced IL-8 release by TLR2-overexpressing HEK293 cells induced by pneumococci but not by TNFα. Antisense-constructs targeting the AP-1 subunits Fra1 and Fra2 had no inhibitory effect on pneumococci-induced IL-8 release. Conclusion S. pneumoniae-induced IL-8 expression by human epithelial BEAS-2B cells depended on activation of JNK and recruitment of phosphorylated c-Jun

  17. Effect of ketamine anesthesia in early pregnancy on the c-fos mRNA and c-jun mRNA expression in offsprings of rats%孕早期氯胺酮麻醉对子代大鼠海马c-fos mRNA和c-jun mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    李钢; 赵为禄; 罗佛全

    2010-01-01

    目的 探讨孕早期氯胺酮麻醉对子代大鼠海马c-fos mRNA和c-jun mRNA表达的影响.方法 孕5~13 d的SD大鼠30只,体重250~300 g,随机分为2组(n=15):对照组(C组)和氯胺酮组(K组).K组经尾静脉注射氯胺酮20 mg/kg,随后以130 mg·kg-1·h-1的速率静脉输注2 h;C组以等量生理盐水替代氯胺酮.子代大鼠于出生后20和30 d时测定认知功能,取海马组织,测定c-fosmRNA和c-jun mRNA表达水平并观察超微结构.结果 与C组比较,K组子代大鼠出生后30 d时认知功能测定第2天逃避潜伏期延长(P<0.05),海马c-fos mRNA和c-jun mRNA的表达水平差异无统计学意义,出生后20 d上述指标差异无统计学意义(P>0.05).K组海马神经元发生损伤.结论 孕早期氯胺酮麻醉抑制子代大鼠认知功能的机制与海马神经元受损有关,但与海马c-fos mRNA和c-jun mRNA表达无关.%Objective To investigate the effect of ketamine anesthesia in the early pregnancy on the c-fos mRNA and c-jun mRNA expression in the offsprings of rats. Methods Thirty pregnant SD rats at 5-13 days of gestation were randomly divided into control group and ketamine group (n = 15 each). Ketamine 20 mg/kg was injected intravenously through tail vein followed by 2 h infusion at a rate of 130 mg·kg-1 ·h-1 in ketmine group.While the equal volume of normal saline was given instead of ketamine in control group. The learning and memory function of the offsprings were tested by Morris water maze test on postnatal day 20 and 30. The hippocampal tissues were taken to detect the expression of c-fos mRNA and c-jun mRNA and to observe the ultrastructure. Results Compared with group C, the escape latency was significantly prolonged at 2 days during the test which was performed on postnatal day 30, but there was no significant difference in the expression of c-fos mRNA and c-jun mRNA on postnatal day 20 and 30 and in the indices mentioned above on postnatal day 20 in ketamine group (P >0.05). The

  18. Bex2 regulates cell proliferation and apoptosis in malignant glioma cells via the c-Jun NH2-terminal kinase pathway

    International Nuclear Information System (INIS)

    Highlights: ► The expression levels of Bex2 markedly increased in glioma tissues. ► Bex2 over-expression promoted cell proliferation, while its down-regulation inhibited cell growth. ► Bex2 down-regulation promoted cell apoptosis via JNK/c-Jun signaling pathway. -- Abstract: The function of Bex2, a member of the Brain Expressed X-linked gene family, in glioma is controversial and its mechanism is largely unknown. We report here that Bex2 regulates cell proliferation and apoptosis in malignant glioma cells via the c-Jun NH2-terminal kinase (JNK) pathway. The expression level of Bex2 is markedly increased in glioma tissues. We observed that Bex2 over-expression promotes cell proliferation, while down-regulation of Bex2 inhibits cell growth. Furthermore, Bex2 down-regulation promotes cell apoptosis and activates the JNK pathway; these effects were abolished by administration of the JNK specific inhibitor, (SP600125). Thus, Bex2 may be an important player during the development of glioma.

  19. Tumor suppressor BLU inhibits proliferation of nasopharyngeal carcinoma cells by regulation of cell cycle, c-Jun N-terminal kinase and the cyclin D1 promoter

    Directory of Open Access Journals (Sweden)

    Zhang Xiangning

    2012-06-01

    Full Text Available Abstract Background Tumor suppressor genes function to regulate and block tumor cell proliferation. To explore the mechanisms underlying the tumor suppression of BLU/ZMYND10 gene on a frequently lost human chromosomal region, an adenoviral vector with BLU cDNA insert was constructed. Methods BLU was re-expressed in nasopharyngeal carcinoma cells by transfection or viral infection. Clonogenic growth was assayed; cell cycle was analyzed by flow cytometry-based DNA content detection; c-Jun N-terminal kinase (JNK and cyclin D1 promoter activities were measured by reporter gene assay, and phosphorylation was measured by immunoblotting. The data for each pair of groups were compared with Student t tests. Results BLU inhibits clonogenic growth of nasopharyngeal carcinoma cells, arrests cell cycle at G1 phase, downregulates JNK and cyclin D1 promoter activities, and inhibits phosphorylation of c-Jun. Conclusions BLU inhibits growth of nasopharyngeal carcinoma cells by regulation of the JNK-cyclin D1 axis to exert tumor suppression.

  20. Momordica charantia polysaccharides could protect against cerebral ischemia/reperfusion injury through inhibiting oxidative stress mediated c-Jun N-terminal kinase 3 signaling pathway.

    Science.gov (United States)

    Gong, Juanjuan; Sun, Fumou; Li, Yihang; Zhou, Xiaoling; Duan, Zhenzhen; Duan, Fugang; Zhao, Lei; Chen, Hansen; Qi, Suhua; Shen, Jiangang

    2015-04-01

    Momordica charantia (MC) is a medicinal plant for stroke treatment in Traditional Chinese Medicine, but its active compounds and molecular targets are unknown yet. M. charantia polysaccharide (MCP) is one of the important bioactive components in MC. In the present study, we tested the hypothesis that MCP has neuroprotective effects against cerebral ischemia/reperfusion injury through scavenging superoxide (O2(-)), nitric oxide (NO) and peroxynitrite (ONOO(-)) and inhibiting c-Jun N-terminal protein kinase (JNK3) signaling cascades. We conducted experiments with in vivo global and focal cerebral ischemia/reperfusion rat models and in vitro oxygen glucose deprivation (OGD) neural cells. The effects of MCP on apoptotic cell death and infarction volume, the bioactivities of scavenging O2(-), NO and ONOO(-), inhibiting lipid peroxidation and modulating JNK3 signaling pathway were investigated. Major results are summarized as below: (1) MCP dose-dependently attenuated apoptotic cell death in neural cells under OGD condition in vitro and reduced infarction volume in ischemic brains in vivo; (2) MCP had directing scavenging effects on NO, O2(-) and ONOO(-) and inhibited lipid peroxidation; (3) MCP inhibited the activations of JNK3/c-Jun/Fas-L and JNK3/cytochrome C/caspases-3 signaling cascades in ischemic brains in vivo. Taken together, we conclude that MCP could be a promising neuroprotective ingredient of M. charantia and its mechanisms could be at least in part attributed to its antioxidant activities and inhibiting JNK3 signaling cascades during cerebral ischemia/reperfusion injury. PMID:25510970

  1. Dynamic acetylation of all lysine 4-methylated histone H3 in the mouse nucleus: analysis at c-fos and c-jun.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available A major focus of current research into gene induction relates to chromatin and nucleosomal regulation, especially the significance of multiple histone modifications such as phosphorylation, acetylation, and methylation during this process. We have discovered a novel physiological characteristic of all lysine 4 (K4-methylated histone H3 in the mouse nucleus, distinguishing it from lysine 9-methylated H3. K4-methylated histone H3 is subject to continuous dynamic turnover of acetylation, whereas lysine 9-methylated H3 is not. We have previously reported dynamic histone H3 phosphorylation and acetylation as a key characteristic of the inducible proto-oncogenes c-fos and c-jun. We show here that dynamically acetylated histone H3 at these genes is also K4-methylated. Although all three modifications are proven to co-exist on the same nucleosome at these genes, phosphorylation and acetylation appear transiently during gene induction, whereas K4 methylation remains detectable throughout this process. Finally, we address the functional significance of the turnover of histone acetylation on the process of gene induction. We find that inhibition of turnover, despite causing enhanced histone acetylation at these genes, produces immediate inhibition of gene induction. These data show that all K4-methylated histone H3 is subject to the continuous action of HATs and HDACs, and indicates that at c-fos and c-jun, contrary to the predominant model, turnover and not stably enhanced acetylation is relevant for efficient gene induction.

  2. The Bicycle Assembly Line Game

    Science.gov (United States)

    Klotz, Dorothy

    2011-01-01

    "The Bicycle Assembly Line Game" is a team-based, in-class activity that helps students develop a basic understanding of continuously operating processes. Each team of 7-10 students selects one of seven prefigured bicycle assembly lines to operate. The lines are run in real-time, and the team that operates the line that yields the…

  3. Expressão dos protooncogenes c-fos, c-myc e c-jun em miométrio normal e mioma humanos Expression of the protooncogenes c-fos, c-myc and c-jun in human normal miometrium and leiomyoma

    Directory of Open Access Journals (Sweden)

    Ana Luiza Ferrari

    2006-10-01

    Full Text Available OBJETIVO: Comparar a expressão gênica (mRNA e protéica dos protooncogenes c-fos, c-myc e c-jun em miométrio normal e mioma humanos. MÉTODOS: Foi realizado um estudo do tipo caso-controle. O material foi coletado de 12 pacientes submetidas a histerectomia no Hospital de Clínicas de Porto Alegre. A expressão do mRNA específico para c-myc, c-fos, c-jun e beta-microglobulina foi avaliada pela técnica de RT-PCR, utilizando primers específicos para cada gene. A expressão protéica destes protooncogenes foi avaliada através de Western blot com anticorpos específicos. RESULTADOS: Não houve diferença significativa para expressão gênica desses protooncogenes entre miométrio normal e mioma (c-myc: 0,87 ± 0,08 vs 0,87 ± 0,08, p = 0,952; c-fos: 1,10 ± 0,17 vs 1,01 ± 0,11, p = 0,21; c-jun: 1,03 ± 0,12 vs 0,96 ± 0,09, p = 0,168, respectivamente. Não houve diferença significativa para expressão protéica desses protooncogenes entre miométrio normal e mioma (c-myc: 1,36 ± 0,48 vs 1,53 ± 0,29, p = 0,569; c-fos: 8,85 ± 5,5 vs 6,56 ± 4,22, p = 0,434; e c-jun: 6,47 ± 3,04 vs 5,42 ± 2,03, p = 0,266, respectivamente. CONCLUSÃO: A expressão gênica (transcrição e a expressão protéica (tradução dos protooncogenes c-myc, c-fos e c-jun em mioma e miométrio normal são semelhantes.Uterine myomas are common benign tumors of the female genital tract. The expression of growth factor signal transduction cascade components including the protooncogenes c-myc, c-fos, and c-jun seem to be involved in the development of myomas. PURPOSE: To compare the gene (mRNA and protein expression of the protooncogenes c-fos, c-myc, and c-jun in human normal myometrium and leiomyoma. METHOD: A case-control study was performed. Samples were collected from 12 patients submitted to hysterectomy at the Hospital de Clínicas at Porto Alegre. The expression of the specific mRNA for c-myc, c-fos, c-jun, and beta-microglobulin was assessed through the RT

  4. Bicycle Rider Control: Observations, Modeling & Experiments

    NARCIS (Netherlands)

    Kooijman, J.D.G.

    2012-01-01

    Bicycle designers traditionally develop bicycles based on experience and trial and error. Adopting modern engineering tools to model bicycle and rider dynamics and control is another method for developing bicycles. This method has the potential to evaluate the complete design space, and thereby dev

  5. The activation of p38 MAPK primarily contributes to UV-induced RhoB expression by recruiting the c-Jun and p300 to the distal CCAAT box of the RhoB promoter

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Jiwon [Genome Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Department of Microbiology, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Choi, Jeong-Hae; Won, Misun [Genome Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Kang, Chang-Mo [Laboratory of Cytogenetics and Tissue Regeneration, KIRAMS, Seoul 139-706 (Korea, Republic of); Gyun, Mi-Rang [Genome Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Functional Genomics, Korea University of Science and Technology, Daejeon 305-350 (Korea, Republic of); Park, Hee-Moon [Department of Microbiology, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Kim, Chun-Ho, E-mail: chkim@kirams.re.kr [Laboratory of Cytogenetics and Tissue Regeneration, KIRAMS, Seoul 139-706 (Korea, Republic of); Chung, Kyung-Sook, E-mail: kschung@kribb.re.kr [Genome Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of)

    2011-06-03

    Highlights: {yields} Regulation of transcriptional activation of RhoB is still unclear. {yields} We examine the effect of p38 MAPK inhibition, and c-Jun and RhoB depletion on UV-induced RhoB expression and apoptosis. {yields} We identify the regions of RhoB promoter necessary to confer UV responsiveness using pRhoB-luciferase reporter assays. {yields} c-Jun, ATF2 and p300 are dominantly associated with NF-Y on the distal CCAAT box. {yields} The activation of p38 MAPK primarily contribute to UV-induced RhoB expression by recruiting the c-Jun and p300 proteins on distal CCAAT box of RhoB promoter. -- Abstract: The Ras-related small GTP-binding protein RhoB is rapidly induced in response to genotoxic stresses caused by ionizing radiation. It is known that UV-induced RhoB expression results from the binding of activating transcription factor 2 (ATF2) via NF-Y to the inverted CCAAT box (-23) of the RhoB promoter. Here, we show that the association of c-Jun with the distal CCAAT box (-72) is primarily involved in UV-induced RhoB expression and p38 MAPK regulated RhoB induction through the distal CCAAT box. UV-induced RhoB expression and apoptosis were markedly attenuated by pretreatment with the p38 MAPK inhibitor. siRNA knockdown of RhoB, ATF2 and c-Jun resulted in decreased RhoB expression and eventually restored the growth of UV-irradiated Jurkat cells. In the reporter assay using luciferase under the RhoB promoter, inhibition of RhoB promoter activity by the p38 inhibitor and knockdown of c-Jun using siRNA occurred through the distal CCAAT box. Immunoprecipitation and DNA affinity protein binding assays revealed the association of c-Jun and p300 via NF-YA and the dissociation of histone deacetylase 1 (HDAC1) via c-Jun recruitment to the CCAAT boxes of the RhoB promoter. These results suggest that the activation of p38 MAPK primarily contributes to UV-induced RhoB expression by recruiting the c-Jun and p300 proteins to the distal CCAAT box of the RhoB promoter in

  6. [Prevention of bicycle accidents].

    Science.gov (United States)

    Zwipp, H; Barthel, P; Bönninger, J; Bürkle, H; Hagemeister, C; Hannawald, L; Huhn, R; Kühn, M; Liers, H; Maier, R; Otte, D; Prokop, G; Seeck, A; Sturm, J; Unger, T

    2015-04-01

    For a very precise analysis of all injured bicyclists in Germany it would be important to have definitions for "severely injured", "seriously injured" and "critically injured". By this, e.g., two-thirds of surgically treated bicyclists who are not registered by the police could become available for a general analysis. Elderly bicyclists (> 60 years) are a minority (10 %) but represent a majority (50 %) of all fatalities. They profit most by wearing a helmet and would be less injured by using special bicycle bags, switching on their hearing aids and following all traffic rules. E-bikes are used more and more (145 % more in 2012 vs. 2011) with 600,000 at the end of 2011 and are increasingly involved in accidents but still have a lack of legislation. So even for pedelecs 45 with 500 W and a possible speed of 45 km/h there is still no legislative demand for the use of a protecting helmet. 96 % of all injured cyclists in Germany had more than 0.5 ‰ alcohol in their blood, 86 % more than 1.1 ‰ and 59 % more than 1.7 ‰. Fatalities are seen in 24.2 % of cases without any collision partner. Therefore the ADFC calls for a limit of 1.1 ‰. Some virtual studies conclude that integrated sensors in bicycle helmets which would interact with sensors in cars could prevent collisions or reduce the severity of injury by stopping the cars automatically. Integrated sensors in cars with opening angles of 180° enable about 93 % of all bicyclists to be detected leading to a high rate of injury avoidance and/or mitigation. Hanging lamps reduce with 35 % significantly bicycle accidents for children, traffic education for children and special trainings for elderly bicyclists are also recommended as prevention tools. As long as helmet use for bicyclists in Germany rates only 9 % on average and legislative orders for using a helmet will not be in force in the near future, coming up campaigns seem to be necessary to be promoted by the Deutscher

  7. [Prevention of bicycle accidents].

    Science.gov (United States)

    Zwipp, H; Barthel, P; Bönninger, J; Bürkle, H; Hagemeister, C; Hannawald, L; Huhn, R; Kühn, M; Liers, H; Maier, R; Otte, D; Prokop, G; Seeck, A; Sturm, J; Unger, T

    2015-04-01

    For a very precise analysis of all injured bicyclists in Germany it would be important to have definitions for "severely injured", "seriously injured" and "critically injured". By this, e.g., two-thirds of surgically treated bicyclists who are not registered by the police could become available for a general analysis. Elderly bicyclists (> 60 years) are a minority (10 %) but represent a majority (50 %) of all fatalities. They profit most by wearing a helmet and would be less injured by using special bicycle bags, switching on their hearing aids and following all traffic rules. E-bikes are used more and more (145 % more in 2012 vs. 2011) with 600,000 at the end of 2011 and are increasingly involved in accidents but still have a lack of legislation. So even for pedelecs 45 with 500 W and a possible speed of 45 km/h there is still no legislative demand for the use of a protecting helmet. 96 % of all injured cyclists in Germany had more than 0.5 ‰ alcohol in their blood, 86 % more than 1.1 ‰ and 59 % more than 1.7 ‰. Fatalities are seen in 24.2 % of cases without any collision partner. Therefore the ADFC calls for a limit of 1.1 ‰. Some virtual studies conclude that integrated sensors in bicycle helmets which would interact with sensors in cars could prevent collisions or reduce the severity of injury by stopping the cars automatically. Integrated sensors in cars with opening angles of 180° enable about 93 % of all bicyclists to be detected leading to a high rate of injury avoidance and/or mitigation. Hanging lamps reduce with 35 % significantly bicycle accidents for children, traffic education for children and special trainings for elderly bicyclists are also recommended as prevention tools. As long as helmet use for bicyclists in Germany rates only 9 % on average and legislative orders for using a helmet will not be in force in the near future, coming up campaigns seem to be necessary to be promoted by the Deutscher

  8. Design of an electric bicycle

    OpenAIRE

    Cabré Viñeta, Anna

    2010-01-01

    The purpose of this study is to make an electrical bicycle. As this bike has an electrical motor, it will not be used as a sport method, the main idea is to use it as a public transport so people can move from side to side of the city without traffic, without pollution and without getting tired. Once selected the purpose of the bicycle, it is necessary to take into account the main features that it must have. A bicycle used as a transport around the city needs to be easy to ...

  9. Stress-induced phosphorylation of c-Jun-N-terminal kinases and nuclear translocation of Hsp70 in the Wistar rat hippocampus

    Directory of Open Access Journals (Sweden)

    Adžić M.

    2009-01-01

    Full Text Available Glucocorticoids are key regulators of the neuroendocrine stress response in the hippocampus. Their action is partly mediated through the subfamily of MAPKs termed c-Jun-N-terminal kinases (JNKs,whose activation correlates with neurodegeneration. The stress response also involves activation of cell protective mechanisms through various heat shock proteins (HSPs that mediate neuroprotection. We followed both JNKs and Hsp70 signals in the cytoplasmic and nuclear compartments of the hippocampus of Wistar male rats exposed to acute, chronic, and combined stress. The activity of JNK1 was decreased in both compartments by all three types of stress, while the activity of cytoplasmic JNK2/3 was elevated in acute and unaltered or lowered in chronic and combined stress. Under all stress conditions, Hsp70 translocation to the nucleus was markedly increased. The results suggest that neurodegenerative signaling of JNKs may be counteracted by increase of nuclear Hsp70,especially under chronic stress.

  10. c-Jun N-terminal kinase 3 expression in the retina of ocular hypertension mice: a possible target to reduce ganglion cell apoptosis

    Directory of Open Access Journals (Sweden)

    Yue He

    2015-01-01

    Full Text Available Glaucoma, a type of optic neuropathy, is characterized by the loss of retinal ganglion cells. It remains controversial whether c-Jun N-terminal kinase (JNK participates in the apoptosis of retinal ganglion cells in glaucoma. This study sought to explore a possible mechanism of action of JNK signaling pathway in glaucoma-induced retinal optic nerve damage. We established a mouse model of chronic ocular hypertension by reducing the aqueous humor followed by photocoagulation using the laser ignition method. Results showed significant pathological changes in the ocular tissues after the injury. Apoptosis of retinal ganglion cells increased with increased intraocular pressure, as did JNK3 mRNA expression in the retina. These data indicated that the increased expression of JNK3 mRNA was strongly associated with the increase in intraocular pressure in the retina, and correlated positively with the apoptosis of retinal ganglion cells.

  11. c-Jun N-terminal kinase 3 expression in the retina of ocular hypertension mice:a possible target to reduce ganglion cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    Yue He; Jie Chen; Shu-guang Zhang; Yuan-sheng Yuan; Yan Li; Hong-bin Lv; Jin-hua Gan

    2015-01-01

    Glaucoma, a type of optic neuropathy, is characterized by the loss of retinal ganglion cells. It remains controversial whether c-Jun N-terminal kinase (JNK) participates in the apoptosis of retinal ganglion cells in glaucoma. This study sought to explore a possible mechanism of action of JNK signaling pathway in glaucoma-induced retinal optic nerve damage. We established a mouse model of chronic ocular hypertension by reducing the aqueous humor followed by pho-tocoagulation using the laser ignition method. Results showed signiifcant pathological changes in the ocular tissues after the injury. Apoptosis of retinal ganglion cells increased with increased intraocular pressure, as did JNK3 mRNA expression in the retina. These data indicated that the increased expression of JNK3 mRNA was strongly associated with the increase in intraocular pressure in the retina, and correlated positively with the apoptosis of retinal ganglion cells.

  12. Resveratrol alleviates diabetes-induced testicular dysfunction by inhibiting oxidative stress and c-Jun N-terminal kinase signaling in rats.

    Science.gov (United States)

    Faid, Iman; Al-Hussaini, Heba; Kilarkaje, Narayana

    2015-12-15

    Diabetes adversely affects reproductive functions in humans and animals. The present study investigated the effects of Resveratrol on diabetes-induced alterations in oxidative stress, c-Jun N-terminal kinase (JNK) signaling and apoptosis in the testis. Adult male Wistar rats (13-15 weeks; n=6/group) were segregated into 1) normal control, 2) Resveratrol-treated (5mg/kg; ip; given during last 3 weeks), 3) Streptozotocin-induced diabetic and, 4) Resveratrol-treated diabetic groups, and euthanized on day 42 after the confirmation of diabetes. Resveratrol did not normalize blood glucose levels in diabetic rats. Resveratrol supplementation recovered diabetes-induced decreases in reproductive organ weights, sperm count and motility, intra-testicular levels of superoxide dismutase, catalase, and glutathione peroxidase and an increase in 4-hydroxynonenal activities (Prats. These results suggest that Resveratrol supplementation may be a useful strategy to treat diabetes-induced testicular dysfunction. PMID:26499206

  13. Calcium has a permissive role in interleukin-1beta-induced c-jun N-terminal kinase activation in insulin-secreting cells

    DEFF Research Database (Denmark)

    Størling, Joachim; Zaitsev, Sergei V; Kapelioukh, Iouri L;

    2005-01-01

    -acetoxymethyl], an inhibitor of calmodulin (W7), and inhibitors of Ca(2+)/calmodulin-dependent kinase (KN62 and KN93) partially reduced IL-1beta-stimulated c-jun phosphorylation in INS-1 or betaTC3 cells. Our data suggest that Ca(2+) plays a permissive role in IL-1beta activation of the JNK signaling pathway in insulin......-cells are largely unknown. In this study, we investigated whether Ca(2+) plays a role for IL-1beta-induced JNK activation. In insulin-secreting rat INS-1 cells cultured in the presence of 11 mm glucose, combined pharmacological blockade of L- and T-type Ca(2+) channels suppressed IL-1beta-induced in vitro...

  14. Involvement of c-Jun N-terminal kinase in reversal of multidrug resistance of human leukemia cells in hypoxia by 5-bromotetrandrine.

    Science.gov (United States)

    Zhang, Wei; Chen, Bao-an; Jin, Jun-fei; He, You-ji; Niu, Yi-qi

    2013-11-01

    5-Bromotetrandrine (BrTet), a candidate multidrug resistance (MDR) modulator, is a potential compound for use in cancer therapy when combined with anticancer agents such as daunorubicin (DNR) and paclitaxel. The purposeof this study was to investigate the mechanism of reversal of P-glycoprotein (P-gp)-mediated MDR by BrTet and the involvement of the c-Jun N-terminal kinase (JNK)/c-Jun signaling pathway in both adriamycin-sensitive K562 and adriamycin-resistant K562 (KA) leukemia cells in hypoxia. The combination of BrTet and DNR decreased both phosphorylated JNK1/2 and MDR1/P-gp levels under hypoxic conditions. Furthermore, a pharmacological inhibitor of JNK, SP600125, or small interfering RNA (siRNA) oligonucleotides to both JNK1 and JNK2 reversed BrTet- or DNR-induced JNK phosphorylation and MDR1/P-gp levels. We further demonstrated that the decreased JNK phosphorylation and MDR1/P-gp levels were associated with a significant increase in intracellular accumulation of DNR, which dramatically enhanced the sensitivity of drug-resistant KA cells to DNR, and led to cellular apoptosis through activation of the caspase-3 pathway. It is concluded that using BrTet in combination with other chemotherapeutic agents and pharmacological inhibitors of JNK can abrogate the P-gp-induced MDR in adriamycin-resistant K562 cells, which has potential clinical relevance in cancer therapy for chemotherapeutic-resistant human leukemia. PMID:23418897

  15. Effect of different therapies of Chinese medicine on the expressions of c-Fos and c-Jun proteins in hippocampus of rats with post-stroke depression

    Institute of Scientific and Technical Information of China (English)

    Hongyan Wang; Mei Chen; Binhui Zhang

    2006-01-01

    BACKGROUND: c-fos and c-jun, the important immediate early genes (IEG), are regarded as the markers for the location and function of neuronal activity, as well as the third signal messengers, they couple the stress stimulation and the gene expression in neuron, and hippocampus is involved in the process of signal transmission after stress stimulation induced depression.OBJECTIVE: To observe the therapeutic effects of Bushen Yiqi (tonifying kidney to benefit qi), Huoxue Huayu (promoting blood circulation to dissipate blood stasis) and Ditan Kaiqiao (eliminating phlegm for resuscitation) on the expressions of c-Fos and c-Jun proteins in hippocampus and spontaneous behaviors of rats with post-stroke depression (PSD), and compare the results with those of fluoxetine, which is known to have definite effect on depression.DESIGN: A randomized controlled trial.SETrING: Zhejiang College of Traditional Chinese Medicine.MATERIALS: The trial was completed in Zhejiang College of Traditional Chinese Medicine from January to July in 2003. Fifty-six healthy adult Wistar male rats of clean grade, weighing (250±50) g, were randomly divided into 7 groups with 8 rats in each group: control group, model group, forced swimming group,Bushen Yiqi group; Huoxue Huayu, Ditan Kaiqiao group and fluoxetine group. The Bushen Yiqi Tang con tained Renshen, Huangqi, Heshouwu, Gouqi, Shudi, etc., crude drugs 1 800 g/L. The Huoxue Huayu Tang contained Danshen, Chuanxiong, Chishao, Yujin, etc., crude drugs 3 600 g/L. The Dian Kaiqiao Tang contained Banxia, Danxing, Changpu, Yuanzhi, etc., crude drug 1 000 g/L.METHODS: ① Except the control group and forced swimming group, rats in the other groups were made into PSD models by deligating the bilateral common carotid arteries permanently. ② Rats in the control group, model group and forced swimming group were intragastrically perfused by saline (3 mL for each time); those in the Bushen Yiqi group, Huoxue Huayu, Ditan Kaiqiao group and fluoxetine

  16. Control for an Autonomous Bicycle

    OpenAIRE

    Getz, Neil H.; Marsden, J. E.

    1995-01-01

    The control of nonholonomic and underactuated systems with symmetry is illustrated by the problem of controlling a bicycle. We derive a controller which, using steering and rear-wheel torque, causes a model of a riderless bicycle to recover its balance from a near fall as well as converge to a time parameterized path in the ground plane. Our construction utilizes new results for both the derivation of equations of motion for nonholonomic systems with symmetry, as well as the control of undera...

  17. Potentiation of the action of phorbol ester by heparin in human CNE2 cells: Association with enhanced expression of c-jun,p53 and p21%肝素增强佛波酯对人鼻咽癌CNE2细胞的作用:调c-jun,p5 3,p21的表达

    Institute of Scientific and Technical Information of China (English)

    李红良; 陈丹丹; 张海伟; 钟玲; 李小红; 罗英儒; 任先达; 司徒锐

    2002-01-01

    目的:观察肝素联合佛波酯对人鼻咽癌细胞的增殖与凋亡的影响及其可能的分子机制.方法: 用细胞记数法、流式细胞术观察肝素联合佛波酯对人鼻咽癌细胞的增殖及细胞周期的影响;而用TUNEL、琼脂糖凝胶电泳、Westernblot等方法观察肝素与佛波酯联合应用对人鼻咽癌细胞凋亡的作用.结果: 肝素与佛波酯联合应用后对鼻咽癌细胞的生长抑制及其凋亡具有显著增强的作用,同佛波酯单独应用于诱导细胞凋亡相比,低剂量的肝素与佛波酯联合应用后发现 :TUNEL阳性细胞明显增多;G1期细胞阻止,S期细胞明显减少,凋亡率增加;DNA"梯形 " 变化更加明显;c-jun,p53,p21基因表达明显升高,而c-fos在整个用药过程中没有改变. 结论: 肝素增强佛波酯对人鼻咽癌细胞的抗增殖及促凋亡,这可能与c- jun,p53,p21的表达上凋有关.%AIM: To measure the effect of addition of hep arin to TPA on cell proli feration and apoptosis in CNE2 cells and investigate the possible molecular mech anisms underlying heparin and TPA interaction on cell proliferation and apoptosi s. METHODS: Cell viability and cell cycle were determined by cel l counting and flow cytometry. Apoptosis was evaluated by terminal deoxynucleotidyl transferase -mediated dUPT nick-end labeling (TUNEL) and agarose gel electrophoresis. The ex pression of c-jun,c-fos,p21 and p53 was examined by Western blot. RESU LTS: TPA alone inhibited CNE2 cell proliferation and evoked apoptosis associated with ty pical morphological changes and DNA fragmentation,which was augmented when hepa rin was added. Compared with TPA or heparin alone,TPA plus heparin obviously en hanced the number of TUNEL-positive cells from 23%±1.2% to 51%±0.9%. After exp os ure to different concentrations of heparin (with or without TPA) for 24 h,CNE2 cells were accumulated G 0/G 1 phase. There was a decrease in the number of ce lls in S phase by the combined heparin and TPA

  18. c-Jun NH2-terminal kinase activity in subcutaneous adipose tissue but not nuclear factor-kappaB activity in peripheral blood mononuclear cells is an independent determinant of insulin resistance in healthy individuals

    DEFF Research Database (Denmark)

    Sourris, Karly C; Lyons, Jasmine G; de Courten, Maximilian;

    2009-01-01

    Chronic low-grade activation of the immune system (CLAIS) predicts type 2 diabetes via a decrease in insulin sensitivity. Our study investigated potential relationships between nuclear factor-kappaB (NF-kappaB) and c-Jun NH(2)-terminal kinase (JNK) pathways-two pathways proposed as the link between...

  19. Valuing public investments to support bicycling

    OpenAIRE

    Götschi, Thomas; Hintermann, Beat

    2014-01-01

    We develop a framework for assessing the net benefits of investments to promote bicycling, which explicitly accounts for internal costs of bicycling. We apply our model to eight Swiss cities using data from the Swiss national travel survey and find that increasing the level of bicycling by reducing internal costs leads to inframarginal benefits that exceed the net benefits from the additional bicycling.  We further find that Swiss cyclists only partially internalize health benefits, which aff...

  20. The Bicycle Rental Market In Hangzhou

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    On May 1, 2008, Hangzhou, capital of east China’s Zhejiang Province, included bicycle rentals in the public transportation system. Now, bicycles have become the most convenient form of transport for Hangzhou residents. Data from the Hangzhou Bureau of Transportation show that on average each bicycle gets rented five times a day.

  1. Systematic analysis of BRAF(V600E) melanomas reveals a role for JNK/c-Jun pathway in adaptive resistance to drug-induced apoptosis.

    Science.gov (United States)

    Fallahi-Sichani, Mohammad; Moerke, Nathan J; Niepel, Mario; Zhang, Tinghu; Gray, Nathanael S; Sorger, Peter K

    2015-03-26

    Drugs that inhibit RAF/MEK signaling, such as vemurafenib, elicit profound but often temporary anti-tumor responses in patients with BRAF(V) (600E) melanoma. Adaptive responses to RAF/MEK inhibition occur on a timescale of hours to days, involve homeostatic responses that reactivate MAP kinase signaling and compensatory mitogenic pathways, and attenuate the anti-tumor effects of RAF/MEK inhibitors. We profile adaptive responses across a panel of melanoma cell lines using multiplex biochemical measurement, single-cell assays, and statistical modeling and show that adaptation involves at least six signaling cascades that act to reduce drug potency (IC50) and maximal effect (i.e., Emax ≪ 1). Among these cascades, we identify a role for JNK/c-Jun signaling in vemurafenib adaptation and show that RAF and JNK inhibitors synergize in cell killing. This arises because JNK inhibition prevents a subset of cells in a cycling population from becoming quiescent upon vemurafenib treatment, thereby reducing drug Emax. Our findings demonstrate the breadth and diversity of adaptive responses to RAF/MEK inhibition and a means to identify which steps in a signaling cascade are most predictive of phenotypic response.

  2. Enediyne lidamycin induces apoptosis in human multiple myeloma cells through activation of p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase.

    Science.gov (United States)

    Zhen, Yong-Zhan; Lin, Ya-Jun; Shang, Bo-Yang; Zhen, Yong-Su

    2009-07-01

    In the present study, the effects of lidamycin (LDM), a member of the enediyne antibiotic family, on two human multiple myeloma (MM) cell lines, U266 and SKO-007, were evaluated. In MTS assay, LDM showed much more potent cytotoxicity than conventional anti-MM agents to both cell lines. The IC(50) values of LDM for the U266 and SKO-007 cells were 0.0575 +/- 0.0015 and 0.1585 +/- 0.0166 nM, respectively, much lower than those of adriamycin, dexamethasone, and vincristine. Mechanistically, LDM triggered MM cells apoptosis by increasing the levels of cleaved poly ADP-ribose polymerase (PARP) and caspase-3/7. In addition, activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) was a critical mediator in LDM-induced cell death. Inhibition of the expression of p38 MAPK and JNK by pharmacological inhibitors reversed the LDM-induced apoptosis through decreasing the level of cleaved PARP and caspase-3/7. Interestingly, phosphorylation of extracellular signal-related kinase was increased by LDM; conversely, MEK inhibitor synergistically enhanced LDM-induced cytotoxicity and apoptosis in MM cells. The results demonstrated that LDM suppresses MM cell growth through the activation of p38 MAPK and JNK, with the potential to be developed as a chemotherapeutic agent for MM. PMID:19468799

  3. The role of p38 MAP kinase and c-Jun N-terminal protein kinase signaling in the differentiation and apoptosis of immortalized neural stem cells

    International Nuclear Information System (INIS)

    The two distinct members of the mitogen-activated protein (MAP) kinase family c-Jun N-terminal protein kinase (JNK) and p38 MAP kinase, play an important role in central nervous system (CNS) development and differentiation. However, their role and functions are not completely understood in CNS. To facilitate in vitro study, we have established an immortal stem cell line using SV40 from fetal rat embryonic day 17. In these cells, MAP kinase inhibitors (SP600125, SB202190, and PD98059) were treated for 1, 24, 48, and 72 h to examine the roles of protein kinases. Early inhibition of JNK did not alter phenotypic or morphological changes of immortalized cells, however overexpression of Bax and decrease of phosphorylated AKT was observed. The prolonged inhibition of JNK induced polyploidization of immortalized cells, and resulted in differentiation and inhibition of cell proliferation. Moreover, JNK and p38 MAP kinase but not ERK1/2 was activated, and p21, p53, and Bax were overexpressed by prolonged inhibition of JNK. These results indicate that JNK and p38 MAP kinase could play dual roles on cell survival and apoptosis. Furthermore, this established cell line could facilitate study of the role of JNK and p38 MAP kinase on CNS development or differentiation/apoptosis

  4. Inhibition of Apoptosis in Prostate Cancer Cells by Androgens Is Mediated through Downregulation of c-Jun N-terminal Kinase Activation

    Directory of Open Access Journals (Sweden)

    Petra Isabel Lorenzo

    2008-05-01

    Full Text Available Androgen deprivation induces the regression of prostate tumors mainly due to an increase in the apoptosis rate; however, the molecular mechanisms underlying the antiapoptotic actions of androgens are not completely understood. We have studied the antiapoptotic effects of androgens in prostate cancer cells exposed to different proapoptotic stimuli. Terminal deoxynucleotidyl transferase-mediated nick-end labeling and nuclear fragmentation analyses demonstrated that androgens protect LNCaP prostate cancer cells from apoptosis induced by thapsigargin, the phorbol ester 12-O-tetradecanoyl-13-phorbol-acetate, or UV irradiation. These three stimuli require the activation of the c-Jun N-terminal kinase (JNK pathway to induce apoptosis and in all three cases, androgen treatment blocks JNK activation. Interestingly, okadaic acid, a phosphatase inhibitor that causes apoptosis in LNCaP cells, induces JNK activation that is also inhibited by androgens. Actinomycin D, the antiandrogen bicalutamide or specific androgen receptor (AR knockdown by small interfering RNA all blocked the inhibition of JNK activation mediated by androgens indicating that this activity requires AR-dependent transcriptional activation. These data suggest that the crosstalk between AR and JNK pathways may have important implications in prostate cancer progression and may provide targets for the development of new therapies.

  5. TAp73-mediated the activation of c-Jun N-terminal kinase enhances cellular chemosensitivity to cisplatin in ovarian cancer cells.

    Directory of Open Access Journals (Sweden)

    Pingde Zhang

    Full Text Available P73, one member of the tumor suppressor p53 family, shares highly structural and functional similarity to p53. Like p53, the transcriptionally active TAp73 can mediate cellular response to chemotherapeutic agents in human cancer cells by up-regulating the expressions of its pro-apoptotic target genes such as PUMA, Bax, NOXA. Here, we demonstrated a novel molecular mechanism for TAp73-mediated apoptosis in response to cisplatin in ovarian cancer cells, and that was irrespective of p53 status. We found that TAp73 acted as an activator of the c-Jun N-terminal kinase (JNK signaling pathway by up-regulating the expression of its target growth arrest and DNA-damage-inducible protein GADD45 alpha (GADD45α and subsequently activating mitogen-activated protein kinase kinase-4 (MKK4. Inhibition of JNK activity by a specific inhibitor or small interfering RNA (siRNA significantly abrogated TAp73-mediated apoptosis induced by cisplatin. Furthermore, inhibition of GADD45α by siRNA inactivated MKK4/JNK activities and also blocked TAp73-mediated apoptosis induction by cisplatin. Our study has demonstrated that TAp73 activated the JNK apoptotic signaling pathway in response to cisplatin in ovarian cancer cells.

  6. EGCG-targeted p57/KIP2 reduces tumorigenicity of oral carcinoma cells: Role of c-Jun N-terminal kinase

    International Nuclear Information System (INIS)

    The green tea polyphenol epigallocatechin-3-gallate (EGCG) regulates gene expression differentially in tumor and normal cells. In normal human primary epidermal keratinocytes (NHEK), one of the key mediators of EGCG action is p57/KIP2, a cyclin-dependent kinase (CDK) inhibitor. EGCG potently induces p57 in NHEK, but not in epithelial cancer cells. In humans, reduced expression of p57 often is associated with advanced tumors, and tumor cells with inactivated p57 undergo apoptosis when exposed to EGCG. The mechanism of p57 induction by EGCG is not well understood. Here, we show that in NHEK, EGCG-induces p57 via the p38 mitogen-activated protein kinase (MAPK) signaling pathway. In p57-negative tumor cells, JNK signaling mediates EGCG-induced apoptosis, and exogenous expression of p57 suppresses EGCG-induced apoptosis via inhibition of c-Jun N-terminal kinase (JNK). We also found that restoration of p57 expression in tumor cells significantly reduced tumorigenicity in athymic mice. These results suggest that p57 expression may be an useful indicator for the clinical course of cancers, and could be potentially useful as a target for cancer therapies

  7. Naringin Mitigates Cardiac Hypertrophy by Reducing Oxidative Stress and Inactivating c-Jun Nuclear Kinase-1 Protein in Type I Diabetes.

    Science.gov (United States)

    Adebiyi, A Olubunmi; Adebiyi, Oluwafeysetan O; Owira, Peter M O

    2016-02-01

    Cardiac hypertrophy (CH) in type 1 diabetes mellitus is attributed to increased oxidative stress-associated activation of c-Jun Nuclear Kinase (JNK). We investigated the effects of naringin on hyperglycemia-associated oxidative stress, activation of JNK-1, and CH. Male Sprague-Dawley rats (225-250 g) (n = 7) were divided into 6 groups. Groups I and II were orally treated with distilled water [3.0 mL/kg body weight/day (BW)] and naringin (50 mg/kg BW), respectively. Groups III-VI were rendered diabetic by a single intraperitoneal injection of 65 mg/kg BW of streptozotocin. Groups III, IV, and V were further treated with insulin (4.0 I.U, s.c, twice daily), naringin (50 mg/kg BW), and ramipril (3.0 mg/kg BW), respectively. After 56 days, the animals were sacrificed and then plasma and cardiac tissues obtained for further analysis. Naringin treatment of diabetic rats significantly reversed oxidative stress, lipid peroxidation, proteins oxidation, CH indices, and JNK protein activation compared with untreated diabetic animals. Our results do suggest that naringin mitigates CH by inhibiting oxidative stress leading to inactivation of JNK-1. Naringin supplements could therefore ameliorate CH in diabetic patients. PMID:26421421

  8. A comparative study of fibrous dysplasia and osteofibrous dysplasia with regard to expressions of c-fos and c-jun products and bone matrix proteins: a clinicopathologic review and immunohistochemical study of c-fos, c-jun, type I collagen, osteonectin, osteopontin, and osteocalcin.

    Science.gov (United States)

    Sakamoto, A; Oda, Y; Iwamoto, Y; Tsuneyoshi, M

    1999-12-01

    Fibrous dysplasia and osteofibrous dysplasia are both benign fibro-osseous lesions of the bone and are generally seen during childhood or adolescence. Histologically, the features of these bone lesions sometimes look quite similar, but their precise nature remains controversial. We retrospectively studied clinicopathologic findings in 62 cases of fibrous dysplasia and 20 cases of osteofibrous dysplasia with regard to their anatomic location and histological appearance. From among these cases, the immunohistochemical expressions of c-fos and c-jun proto-oncogene products and bone matrix proteins of type I collagen, osteonectin, osteopontin, and osteocalcin were evaluated in 20 typical fibrous dysplasias and 17 osteofibrous dysplasias using paraffin sections, and these expressions were then assessed semiquantitatively. Microscopically, fibrous dysplasia showed various secondary changes, such as hyalinization, hemorrhage, xanthomatous reaction, and cystic change in 22 of the 62 cases (35%). This was a higher incidence than in osteofibrous dysplasia, in which only 2 of the 20 cases (10%) showed such changes. In the elderly fibrous dysplasia cases, the cellularity of fibroblast-like cells was rather low, and those cases were hyalinized. Almost all of the cases of fibrous dysplasia and osteofibrous dysplasia showed positive expressions of c-fos and c-jun products. The expressions of type I collagen and osteopontin showed no difference between fibrous dysplasia and osteofibrous dysplasia. Immunoreactivity for osteonectin in bone matrix was detected in only 1 case of fibrous dysplasia (1 of 20), whereas it was recognized in 14 of the 17 cases of osteofibrous dysplasia. Furthermore, the immunoreactivity for osteocalcin in bone matrix and fibroblast-like cells was higher in fibrous dysplasia than it was in osteofibrous dysplasia, semiquantitatively. Our immunohistochemical results regarding osteonectin and osteocalcin suggest that the bone matrix of fibrous dysplasia is

  9. EP BICYCLE POOL - VIGNETTES 2002

    CERN Multimedia

    EP-SMI Help Desk

    2002-01-01

    The vignettes (insurance certificates) for 2002 become obligatory from 1 June. If you have a bicycle from the EP Pool, please bring it to the EP-SMI Help Desk (Building 124) on any working day up to 31 May between 8h.30 - 12h.00 or 13h.30 - 17h.30. EP-SMI Help Desk

  10. Proper fit of the bicycle.

    Science.gov (United States)

    Burke, E R

    1994-01-01

    After cyclists have carefully made adjustments for proper fit, minor aches and pains may develop before the body adjusts to the new riding posture. This is normal--so resist the temptation to fiddle with the position much. They will become accustomed to the new riding position after a few rides, and cycling performance will be improved. Then they can concentrate on bike handling skills and fitness confident that their riding position is as good as can be. Proper bicycle fit requires careful review of bicycle selection, saddle height for proper leg extension, fore-and-aft positioning of the knee over the pedal, saddle tilt, handlebar position, and positioning of the upper body for optimum comfort and performance. Further research on the effects of maintaining an aerodynamic position for extended periods of time needs to be investigated to review fatigue patterns in lower and upper body musculature. The underlying principle of positioning a cyclist on a bicycle is to remember that the bicycle is adjustable, and the cyclist is adaptable. PMID:8111846

  11. Activation of the KCa3.1 channel contributes to traumatic scratch injury-induced reactive astrogliosis through the JNK/c-Jun signaling pathway.

    Science.gov (United States)

    Yi, Mengni; Dou, Fangfang; Lu, Qin; Yu, Zhihua; Chen, Hongzhuan

    2016-06-15

    Reactive astrogliosis is widely considered to contribute to pathogenic responses to stress and brain injury and to diseases as diverse as ischemia and neurodegeneration. We previously found that expression of the intermediate-conductance calcium-activated potassium channel (KCa3.1) involved in TGF-β-activated astrogliosis. In the present study, we investigated whether migration of cortical astrocytes following mechanical scratch injury involves the KCa3.1 channel, which contributes to Ca(2+)-mediated migration in other cells. We found that scratch injury increased the expression of KCa3.1 protein in reactive astrocytes. Application of the KCa3.1 blocker TRAM-34 decreased glial fibrillary acidic protein (GFAP) expression and slowed migration in a concentration-dependent manner. Application of the Ca(2+) chelators, EGTA and BAPTA-AM, also slowed the migration of astrocytes. Blockade or genetic deletion of KCa3.1 both slowed and dramatically reduced the scratch injuries induced the sharp rise in astrocytes Ca(2+) concentrations. The scratch injury-induced phosphorylation of JNK and c-Jun proteins was also attenuated both by blockade of KCa3.1 with TRAM-34 and in KCa3.1(-/-) astrocytes. Using KCa3.1 knockout mice, we further confirmed that deletion of KCa3.1 reduced expression of GFAP in an in vivo stab wound model. Taken together, our findings highlight a novel role for KCa3.1 in phenotypic modulation of reactive astrocytes and in astrocyte mobilization in response to mechanical stress, providing a potential target for therapeutic intervention in brain injuries.

  12. Inhibition of spinal astrocytic c-Jun N-terminal kinase (JNK activation correlates with the analgesic effects of ketamine in neuropathic pain

    Directory of Open Access Journals (Sweden)

    Wang Wen

    2011-01-01

    Full Text Available Abstract Background We have previously reported that inhibition of astrocytic activation contributes to the analgesic effects of intrathecal ketamine on spinal nerve ligation (SNL-induced neuropathic pain. However, the underlying mechanisms are still unclear. c-Jun N-terminal kinase (JNK, a member of mitogen-activated protein kinase (MAPK family, has been reported to be critical for spinal astrocytic activation and neuropathic pain development after SNL. Ketamine can decrease lipopolysaccharide (LPS-induced phosphorylated JNK (pJNK expression and could thus exert its anti-inflammatory effect. We hypothesized that inhibition of astrocytic JNK activation might be involved in the suppressive effect of ketamine on SNL-induced spinal astrocytic activation. Methods Immunofluorescence histochemical staining was used to detect SNL-induced spinal pJNK expression and localization. The effects of ketamine on SNL-induced mechanical allodynia were confirmed by behavioral testing. Immunofluorescence histochemistry and Western blot were used to quantify the SNL-induced spinal pJNK expression after ketamine administration. Results The present study showed that SNL induced ipsilateral pJNK up-regulation in astrocytes but not microglia or neurons within the spinal dorsal horn. Intrathecal ketamine relieved SNL-induced mechanical allodynia without interfering with motor performance. Additionally, intrathecal administration of ketamine attenuated SNL-induced spinal astrocytic JNK activation in a dose-dependent manner, but not JNK protein expression. Conclusions The present results suggest that inhibition of JNK activation may be involved in the suppressive effects of ketamine on SNL-induced spinal astrocyte activation. Therefore, inhibition of spinal JNK activation may be involved in the analgesic effects of ketamine on SNL-induced neuropathic pain.

  13. (-)-Epigallocatechin-3-gallate decreases thrombin/paclitaxel-induced endothelial tissue factor expression via the inhibition of c-Jun terminal NH2 kinase phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Huang-Joe [Institute of Biotechnology, National Tsing Hua University, No. 101, Section 2, Kuang Fu Road, Hsinchu 30013, Taiwan (China); Division of Cardiology, Department of Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 40447, Taiwan (China); Lo, Wan-Yu [Department of Medical Research, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 40447, Taiwan (China); Graduate Integration of Chinese and Western Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan (China); Lu, Te-Ling [School of Pharmacy, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan (China); Huang, Haimei, E-mail: hmhuang@life.nthu.edu.tw [Institute of Biotechnology, National Tsing Hua University, No. 101, Section 2, Kuang Fu Road, Hsinchu 30013, Taiwan (China)

    2010-01-01

    Patients with paclitaxel-eluting stents are concerned with stent thrombosis caused by premature discontinuation of dual antiplatelet therapy or clopidogrel resistance. This study investigates the effect of (-)-epigallocatechin-3-gallate (EGCG) on the expression of thrombin/paclitaxel-induced endothelial tissue factor (TF) expressions in human aortic endothelial cells (HAECs). EGCG was nontoxic to HAECs at 6 h up to a concentration of 25 {mu}mol/L. At a concentration of 25 {mu}mol/L, EGCG pretreatment potently inhibited both thrombin-stimulated and thrombin/paclitaxel-stimulated endothelial TF protein expression. Thrombin and thrombin/paclitaxel-induced 2.6-fold and 2.9-fold increases in TF activity compared with the control. EGCG pretreatment caused a 29% and 38% decrease in TF activity on thrombin and thrombin/paclitaxel treatment, respectively. Real-time polymerase chain reaction (PCR) showed that thrombin and thrombin/paclitaxel-induced 3.0-fold and 4.6-fold TF mRNA expressions compared with the control. EGCG pretreatment caused an 82% and 72% decrease in TF mRNA expression on thrombin and thrombin/paclitaxel treatment, respectively. The c-Jun terminal NH2 kinase (JNK) inhibitor SP600125 reduced thrombin/paclitaxel-induced TF expression. Furthermore, EGCG significantly inhibited the phosphorylation of JNK to 49% of thrombin/paclitaxel-stimulated HAECs at 60 min. Immunofluorescence assay did not show an inhibitory effect of EGCG on P65 NF-{kappa}B nuclear translocation in the thrombin/paclitaxel-stimulated endothelial cells. In conclusion, EGCG can inhibit TF expression in thrombin/paclitaxel-stimulated endothelial cells via the inhibition of JNK phosphorylation. The unique property of EGCG may be used to develop a new drug-eluting stent by co-coating EGCG and paclitaxel.

  14. Protein kinase B/Akt activates c-Jun NH(2)-terminal kinase by increasing NO production in response to shear stress

    Science.gov (United States)

    Go, Y. M.; Boo, Y. C.; Park, H.; Maland, M. C.; Patel, R.; Pritchard, K. A. Jr; Fujio, Y.; Walsh, K.; Darley-Usmar, V.; Jo, H.

    2001-01-01

    Laminar shear stress activates c-Jun NH(2)-terminal kinase (JNK) by the mechanisms involving both nitric oxide (NO) and phosphatidylinositide 3-kinase (PI3K). Because protein kinase B (Akt), a downstream effector of PI3K, has been shown to phosphorylate and activate endothelial NO synthase, we hypothesized that Akt regulates shear-dependent activation of JNK by stimulating NO production. Here, we examined the role of Akt in shear-dependent NO production and JNK activation by expressing a dominant negative Akt mutant (Akt(AA)) and a constitutively active mutant (Akt(Myr)) in bovine aortic endothelial cells (BAEC). As expected, pretreatment of BAEC with the PI3K inhibitor (wortmannin) prevented shear-dependent stimulation of Akt and NO production. Transient expression of Akt(AA) in BAEC by using a recombinant adenoviral construct inhibited the shear-dependent stimulation of NO production and JNK activation. However, transient expression of Akt(Myr) by using a recombinant adenoviral construct did not induce JNK activation. This is consistent with our previous finding that NO is required, but not sufficient on its own, to activate JNK in response to shear stress. These results and our previous findings strongly suggest that shear stress triggers activation of PI3K, Akt, and endothelial NO synthase, leading to production of NO, which (along with O(2-), which is also produced by shear) activates Ras-JNK pathway. The regulation of Akt, NO, and JNK by shear stress is likely to play a critical role in its antiatherogenic effects.

  15. Glycogen synthase kinase 3β sustains invasion of glioblastoma via the focal adhesion kinase, Rac1, and c-Jun N-terminal kinase-mediated pathway.

    Science.gov (United States)

    Chikano, Yuri; Domoto, Takahiro; Furuta, Takuya; Sabit, Hemragul; Kitano-Tamura, Ayako; Pyko, Ilya V; Takino, Takahisa; Sai, Yoshimichi; Hayashi, Yutaka; Sato, Hiroshi; Miyamoto, Ken-ichi; Nakada, Mitsutoshi; Minamoto, Toshinari

    2015-02-01

    The failure of current treatment options for glioblastoma stems from their inability to control tumor cell proliferation and invasion. Biologically targeted therapies offer great hope and one promising target is glycogen synthase kinase-3β (GSK3β), implicated in various diseases, including cancer. We previously reported that inhibition of GSK3β compromises the survival and proliferation of glioblastoma cells, induces their apoptosis, and sensitizes them to temozolomide and radiation. Here, we explore whether GSK3β also contributes to the highly invasive nature of glioblastoma. The effects of GSK3β inhibition on migration and invasion of glioblastoma cells were examined by wound-healing and Transwell assays, as well as in a mouse model of glioblastoma. We also investigated changes in cellular microarchitectures, cytoskeletal components, and proteins responsible for cell motility and invasion. Inhibition of GSK3β attenuated the migration and invasion of glioblastoma cells in vitro and that of tumor cells in a mouse model of glioblastoma. These effects were associated with suppression of the molecular axis involving focal adhesion kinase, guanine nucleotide exchange factors/Rac1 and c-Jun N-terminal kinase. Changes in cellular phenotypes responsible for cell motility and invasion were also observed, including decreased formation of lamellipodia and invadopodium-like microstructures and alterations in the subcellular localization, and activity of Rac1 and F-actin. These changes coincided with decreased expression of matrix metalloproteinases. Our results confirm the potential of GSK3β as an attractive therapeutic target against glioblastoma invasion, thus highlighting a second role in this tumor type in addition to its involvement in chemo- and radioresistance. PMID:25504636

  16. An apoptotic signaling pathway in the interferon antiviral response mediated by RNase L and c-Jun NH2-terminal kinase.

    Science.gov (United States)

    Li, Geqiang; Xiang, Ying; Sabapathy, Kanaga; Silverman, Robert H

    2004-01-01

    Cellular stress responses induced during viral infections are critical to the health and survival of organisms. In higher vertebrates, interferons (IFNs) mediate the innate antiviral response in part through the action of RNase L, a uniquely regulated enzyme. RNase L is activated by 5'-phosphorylated, 2'-5' oligoadenylates (2-5A) produced from IFN-inducible and double stranded RNA-dependent synthetases. We show that viral activation of the c-Jun NH2-terminal kinases (JNK) family of MAP kinases and viral induction of apoptosis are both deficient in mouse cells lacking RNase L. Also, JNK phosphorylation in response to 2-5A was greatly reduced in RNase L-/- mouse cells. In addition, 2-5A treatment of the human ovarian carcinoma cell line, Hey1b, resulted in specific ribosomal RNA cleavage products coinciding with JNK activation. Furthermore, suppression of JNK activity with the chemical inhibitor, SP600125, prevented apoptosis induced by 2-5A. In contrast, inhibition of alternative MAP kinases, p38 and ERK, failed to prevent 2-5A-mediated apoptosis. Short interfering RNA to JNK1/JNK2 mRNAs resulted in JNK ablation while also suppressing 2-5A-mediated apoptosis. Moreover, Jnk1-/- Jnk2-/- cells were highly resistant to the apoptotic effects of IFN and 2-5A. These findings suggest that JNK and RNase L function in an integrated signaling pathway during the IFN response that leads to elimination of virus-infected cells through apoptosis. PMID:14570908

  17. Hydrogen-Rich Saline Attenuates Lipopolysaccharide-Induced Heart Dysfunction by Restoring Fatty Acid Oxidation in Rats by Mitigating C-Jun N-Terminal Kinase Activation.

    Science.gov (United States)

    Tao, Bingdong; Liu, Lidan; Wang, Ni; Tong, Dongyi; Wang, Wei; Zhang, Jin

    2015-12-01

    Sepsis is common in intensive care units (ICU) and is associated with high mortality. Cardiac dysfunction complicating sepsis is one of the most important causes of this mortality. This dysfunction is due to myocardial inflammation and reduced production of energy by the heart. A number of studies have shown that hydrogen-rich saline (HRS) has a beneficial effect on sepsis. Therefore, we tested whether HRS prevents cardiac dysfunction by increasing cardiac energy. Four groups of rats received intraperitoneal injections of one of the following solutions: normal saline (NS), HRS, lipopolysaccharide (LPS), and LPS plus HRS. Cardiac function was measured by echocardiography 8 h after the injections. Gene and protein expression related to fatty acid oxidation (FAO) were measured by quantitative polymerase chain reaction (PCR) and Western blot analysis. The injection of LPS compromised heart function through decreased fractional shortening (FS) and increased left ventricular diameter (LVD). The addition of HRS increased FS, palmitate triphosphate, and the ratio of phosphocreatinine (PCr) to adenosine triphosphate (ATP) as well as decreasing LVD. The LPS challenge reduced the expression of genes related to FAO, including perioxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), perioxisome proliferator-activated receptor alpha (PPARα), Estrogen-related receptor alpha (ERRα), and their downstream targets, in mRNA and protein level, which were attenuated by HRS. However, HRS had little effect on glucose metabolism. Furthermore, HRS inhibited c-Jun N-terminal kinase (JNK) activation in the rat heart. Inhibition of JNK by HRS showed beneficial effects on LPS-challenged rats, at least in part, by restoring cardiac FAO.

  18. Colchicine induces apoptosis in HT‑29 human colon cancer cells via the AKT and c-Jun N-terminal kinase signaling pathways.

    Science.gov (United States)

    Huang, Zhen; Xu, Ye; Peng, Wei

    2015-10-01

    Colchicine is a natural compound, which belongs to the botanical family Colchicaceae and prevents growth of cancer cells via antimitotic activity by interacting with microtubules. Although numerous studies have demonstrated that the effect of colchicine on cell apoptosis is mediated by the activation of caspase‑3, the signaling pathways involved in the process remain unknown. In the current study, evidence is presented regarding the missing information using HT‑29 human colon cancer cells. The effect of colchicine on apoptosis in HT‑29 cells and the apoptosis‑associated signaling pathways were determined using various methods, including cell viability assay, Annexin V/propidium idodide (PI) binding, PI staining, Hoechst 33342 staining, mitochondrial membrane potential (Δψm) assay, reactive oxygen species (ROS) assay and western blot analysis. Colchicine was observed to induce a dose‑dependent reduction in cell viability in HT‑29 cells and early apoptosis occurred when the cells were treated with 1 µg/ml colchicine. Furthermore, colchicine treatment induced a loss of Δψm, increased ROS production, activated caspase‑3, upregulated BAX expression and downregulated Bcl‑2 expression, which evidenced the colchicine activity on apoptosis, potentially by acting via the intrinsic apoptotic signaling pathway. Colchicine increased phosphorylation of p38, although not phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase, which indicates that colchicine activates the p38 signaling pathway in order to induce cell apoptosis. Therefore, colchicine exhibited significant growth inhibition of the HT‑29 colon cancer cell line and induced apoptosis in the cells via the mitochondrial pathway, which is regulated by p38 signaling pathways. PMID:26299305

  19. A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway.

    Science.gov (United States)

    Yao, Z; Zhou, G; Wang, X S; Brown, A; Diener, K; Gan, H; Tan, T H

    1999-01-22

    The yeast serine/threonine kinase STE20 activates a signaling cascade that includes STE11 (mitogen-activated protein kinase kinase kinase), STE7 (mitogen-activated protein kinase kinase), and FUS3/KSS1 (mitogen-activated protein kinase) in response to signals from both Cdc42 and the heterotrimeric G proteins associated with transmembrane pheromone receptors. Using degenerate polymerase chain reaction, we have isolated a human cDNA encoding a protein kinase homologous to STE20. This protein kinase, designated HPK/GCK-like kinase (HGK), has nucleotide sequences that encode an open reading frame of 1165 amino acids with 11 kinase subdomains. HGK was a serine/threonine protein kinase that specifically activated the c-Jun N-terminal kinase (JNK) signaling pathway when transfected into 293T cells, but it did not stimulate either the extracellular signal-regulated kinase or p38 kinase pathway. HGK also increased AP-1-mediated transcriptional activity in vivo. HGK-induced JNK activation was inhibited by the dominant-negative MKK4 and MKK7 mutants. The dominant-negative mutant of TAK1, but not MEKK1 or MAPK upstream kinase (MUK), strongly inhibited HGK-induced JNK activation. TNF-alpha activated HGK in 293T cells, as well as the dominant-negative HGK mutants, inhibited TNF-alpha-induced JNK activation. These results indicate that HGK, a novel activator of the JNK pathway, may function through TAK1, and that the HGK --> TAK1 --> MKK4, MKK7 --> JNK kinase cascade may mediate the TNF-alpha signaling pathway. PMID:9890973

  20. Road characteristics and bicycle accidents.

    Science.gov (United States)

    Nyberg, P; Björnstig, U; Bygren, L O

    1996-12-01

    In Umeå, Sweden, defects in the physical road surface contributed to nearly half of the single bicycle accidents. The total social cost of these injuries to people amount to at least SEK 20 million (SEK 60,000 or about USD 8,500 per accident), which corresponds to the estimated loss of "eight life equivalents a year". Improved winter maintenance seems to have the greatest injury prevention potential and would probably reduce the number of injuries considerably, whereas improved road quality and modification of kerbs would reduce the most severe injuries. A local traffic safety program should try to prevent road accidents instead of handling the consequences of them. In accordance with Parliament decisions on traffic we would like to see increased investment in measures favoring bicycle traffic, where cycling is seen as a solution, not as a problem.

  1. Characterisation of Electric Bicycles Performances

    OpenAIRE

    Cappelle, Jan; Lataire, Philippe; Maggetto, Gaston; Meeusen, Roman; Kempenaers, Farid

    2002-01-01

    The proposed paper reports on characterisation work performed in the scope of the E-tour project. This project has already been presented at EVS-18. At the ‘Vrije Universiteit Brussel’ different EPACs (Electric Power Assisted Cycles) are put at the public’s disposal for testing. To quantify the performances of these electrical bicycles we want to link the subjective experienced driving comfort to some measurable objective parameters. For this purpose we converted a treadmill in...

  2. Mitogen-activated protein kinases (p38 and c-Jun NH2-terminal kinase) are differentially regulated during cardiac volume and pressure overload hypertrophy.

    Science.gov (United States)

    Sopontammarak, Somkiat; Aliharoob, Assad; Ocampo, Catherina; Arcilla, Rene A; Gupta, Mahesh P; Gupta, Madhu

    2005-01-01

    Chronic pressure overload (PO) and volume overload (VO) result in morphologically and functionally distinct forms of myocardial hypertrophy. However, the molecular mechanism initiating these two types of hypertrophy is not yet understood. Data obtained from different cell types have indicated that the mitogen-activated protein kinases (MAPKs) comprising c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 play an important role in transmitting signals of stress stimuli to elicit the cellular response. We tested the hypothesis that early induction of MAPKs differs in two types of overload on the heart and associates with distinct expression of hypertrophic marker genes, namely ANF, alpha-myosin heavy chain (alpha-MHC), and beta-MHC. In rats, VO was induced by aortocaval shunt and PO by constriction of the abdominal aorta. The PO animals were further divided into two groups depending on the severity of the constriction, mild (MPO) and severe pressure overload (SPO), having 35 and 85% aortic constriction, respectively. Early changes in MAPK activity (2-120 min and 1 to 2 d) were analyzed by the in vitro kinase assay using kinase-specific antibodies for p38, JNK, and ERK2. The change in expression of hypertrophy marker genes was examined by Northern blot analysis. In VO hypertrophy, the activity of p38 was markedly increased (10-fold), without changing the activity of ERK and JNK. However, during PO hypertrophy, the activity of JNK was significantly increased (two- to sixfold) and depended on the severity of the load. The activity of p38 was not changed in MPO hypertrophy, whereas it was slightly elevated (50%) in hearts with SPO. Similarly, ERK activity was not changed in hearts with MPO, but a transient rise in activity was observed in hearts with SPO. The expression of ANF and beta-MHC genes was elevated in both PO and VO hypertrophy; however, this change was much greater in hearts subjected to PO than VO hypertrophy. Alpha

  3. The gap junction inhibitor 2-aminoethoxy-diphenyl-borate protects against acetaminophen hepatotoxicity by inhibiting cytochrome P450 enzymes and c-jun N-terminal kinase activation

    Energy Technology Data Exchange (ETDEWEB)

    Du, Kuo; Williams, C. David; McGill, Mitchell R.; Xie, Yuchao [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Farhood, Anwar [Department of Pathology, St. David' s North Austin Medical Center, Austin, TX 78756 (United States); Vinken, Mathieu [Department of Toxicology, Center for Pharmaceutical Sciences, Vrije Universiteit Brussels, 1090 Brussels (Belgium); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2013-12-15

    Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the US. Although many aspects of the mechanism are known, recent publications suggest that gap junctions composed of connexin32 function as critical intercellular communication channels which transfer cytotoxic mediators into neighboring hepatocytes and aggravate liver injury. However, these studies did not consider off-target effects of reagents used in these experiments, especially the gap junction inhibitor 2-aminoethoxy-diphenyl-borate (2-APB). In order to assess the mechanisms of protection of 2-APB in vivo, male C56Bl/6 mice were treated with 400 mg/kg APAP to cause extensive liver injury. This injury was prevented when animals were co-treated with 20 mg/kg 2-APB and was attenuated when 2-APB was administered 1.5 h after APAP. However, the protection was completely lost when 2-APB was given 4–6 h after APAP. Measurement of protein adducts and c-jun-N-terminal kinase (JNK) activation indicated that 2-APB reduced both protein binding and JNK activation, which correlated with hepatoprotection. Although some of the protection was due to the solvent dimethyl sulfoxide (DMSO), in vitro experiments clearly demonstrated that 2-APB directly inhibits cytochrome P450 activities. In addition, JNK activation induced by phorone and tert-butylhydroperoxide in vivo was inhibited by 2-APB. The effects against APAP toxicity in vivo were reproduced in primary cultured hepatocytes without use of DMSO and in the absence of functional gap junctions. We conclude that the protective effect of 2-APB was caused by inhibition of metabolic activation of APAP and inhibition of the JNK signaling pathway and not by blocking connexin32-based gap junctions. - Highlights: • 2-APB protected against APAP-induced liver injury in mice in vivo and in vitro • 2-APB protected by inhibiting APAP metabolic activation and JNK signaling pathway • DMSO inhibited APAP metabolic activation as the solvent of 2-APB

  4. Lower susceptibility of female mice to acetaminophen hepatotoxicity: Role of mitochondrial glutathione, oxidant stress and c-jun N-terminal kinase

    International Nuclear Information System (INIS)

    Acetaminophen (APAP) overdose causes severe hepatotoxicity in animals and humans. However, the mechanisms underlying the gender differences in susceptibility to APAP overdose in mice have not been clarified. In our study, APAP (300 mg/kg) caused severe liver injury in male mice but 69–77% lower injury in females. No gender difference in metabolic activation of APAP was found. Hepatic glutathione (GSH) was rapidly depleted in both genders, while GSH recovery in female mice was 2.6 fold higher in the mitochondria at 4 h, and 2.5 and 3.3 fold higher in the total liver at 4 h and 6 h, respectively. This faster recovery of GSH, which correlated with greater induction of glutamate-cysteine ligase, attenuated mitochondrial oxidative stress in female mice, as suggested by a lower GSSG/GSH ratio at 6 h (3.8% in males vs. 1.4% in females) and minimal centrilobular nitrotyrosine staining. While c-jun N-terminal kinase (JNK) activation was similar at 2 and 4 h post-APAP, it was 3.1 fold lower at 6 h in female mice. However, female mice were still protected by the JNK inhibitor SP600125. 17β-Estradiol pretreatment moderately decreased liver injury and oxidative stress in male mice without affecting GSH recovery. Conclusion: The lower susceptibility of female mice is achieved by the improved detoxification of reactive oxygen due to accelerated recovery of mitochondrial GSH levels, which attenuates late JNK activation and liver injury. However, even the reduced injury in female mice was still dependent on JNK. While 17β-estradiol partially protects male mice, it does not affect hepatic GSH recovery. - Highlights: • Female mice are less susceptible to acetaminophen overdose than males. • GSH depletion and protein adduct formation are similar in both genders. • Recovery of hepatic GSH levels is faster in females and correlates with Gclc. • Reduced oxidant stress in females leads to reduced JNK activation. • JNK activation and mitochondrial translocation are critical

  5. Lower susceptibility of female mice to acetaminophen hepatotoxicity: Role of mitochondrial glutathione, oxidant stress and c-jun N-terminal kinase

    Energy Technology Data Exchange (ETDEWEB)

    Du, Kuo; Williams, C. David; McGill, Mitchell R.; Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu

    2014-11-15

    Acetaminophen (APAP) overdose causes severe hepatotoxicity in animals and humans. However, the mechanisms underlying the gender differences in susceptibility to APAP overdose in mice have not been clarified. In our study, APAP (300 mg/kg) caused severe liver injury in male mice but 69–77% lower injury in females. No gender difference in metabolic activation of APAP was found. Hepatic glutathione (GSH) was rapidly depleted in both genders, while GSH recovery in female mice was 2.6 fold higher in the mitochondria at 4 h, and 2.5 and 3.3 fold higher in the total liver at 4 h and 6 h, respectively. This faster recovery of GSH, which correlated with greater induction of glutamate-cysteine ligase, attenuated mitochondrial oxidative stress in female mice, as suggested by a lower GSSG/GSH ratio at 6 h (3.8% in males vs. 1.4% in females) and minimal centrilobular nitrotyrosine staining. While c-jun N-terminal kinase (JNK) activation was similar at 2 and 4 h post-APAP, it was 3.1 fold lower at 6 h in female mice. However, female mice were still protected by the JNK inhibitor SP600125. 17β-Estradiol pretreatment moderately decreased liver injury and oxidative stress in male mice without affecting GSH recovery. Conclusion: The lower susceptibility of female mice is achieved by the improved detoxification of reactive oxygen due to accelerated recovery of mitochondrial GSH levels, which attenuates late JNK activation and liver injury. However, even the reduced injury in female mice was still dependent on JNK. While 17β-estradiol partially protects male mice, it does not affect hepatic GSH recovery. - Highlights: • Female mice are less susceptible to acetaminophen overdose than males. • GSH depletion and protein adduct formation are similar in both genders. • Recovery of hepatic GSH levels is faster in females and correlates with Gclc. • Reduced oxidant stress in females leads to reduced JNK activation. • JNK activation and mitochondrial translocation are critical

  6. The gap junction inhibitor 2-aminoethoxy-diphenyl-borate protects against acetaminophen hepatotoxicity by inhibiting cytochrome P450 enzymes and c-jun N-terminal kinase activation

    International Nuclear Information System (INIS)

    Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the US. Although many aspects of the mechanism are known, recent publications suggest that gap junctions composed of connexin32 function as critical intercellular communication channels which transfer cytotoxic mediators into neighboring hepatocytes and aggravate liver injury. However, these studies did not consider off-target effects of reagents used in these experiments, especially the gap junction inhibitor 2-aminoethoxy-diphenyl-borate (2-APB). In order to assess the mechanisms of protection of 2-APB in vivo, male C56Bl/6 mice were treated with 400 mg/kg APAP to cause extensive liver injury. This injury was prevented when animals were co-treated with 20 mg/kg 2-APB and was attenuated when 2-APB was administered 1.5 h after APAP. However, the protection was completely lost when 2-APB was given 4–6 h after APAP. Measurement of protein adducts and c-jun-N-terminal kinase (JNK) activation indicated that 2-APB reduced both protein binding and JNK activation, which correlated with hepatoprotection. Although some of the protection was due to the solvent dimethyl sulfoxide (DMSO), in vitro experiments clearly demonstrated that 2-APB directly inhibits cytochrome P450 activities. In addition, JNK activation induced by phorone and tert-butylhydroperoxide in vivo was inhibited by 2-APB. The effects against APAP toxicity in vivo were reproduced in primary cultured hepatocytes without use of DMSO and in the absence of functional gap junctions. We conclude that the protective effect of 2-APB was caused by inhibition of metabolic activation of APAP and inhibition of the JNK signaling pathway and not by blocking connexin32-based gap junctions. - Highlights: • 2-APB protected against APAP-induced liver injury in mice in vivo and in vitro • 2-APB protected by inhibiting APAP metabolic activation and JNK signaling pathway • DMSO inhibited APAP metabolic activation as the solvent of 2-APB

  7. A study on electric bicycle energy efficiency

    Directory of Open Access Journals (Sweden)

    Ivan EVTIMOV

    2015-09-01

    Full Text Available The paper presents a construction of an experimental electric bicycle for evaluation of the energy efficiency. The bicycle is equipped with onboard computer which can store the information about motion and energy consumption. The result concerning power, energy consumption, recharging during brake process, etc. are given. Energy consumption for 3 typical city routes is studied.

  8. Bicycle parking preferences: costs versus walking time

    NARCIS (Netherlands)

    Molin, E.J.E.; Maat, K.

    2014-01-01

    Successful bicycle stimulating policies may increase the need for bicycle parking capacity, especially at main railway stations located in city centers. A potential solution for this problem involves combining paid surveyed indoor parking near the platforms and free open-air parking without surveill

  9. Stabilizing a Bicycle: A Modeling Project

    Science.gov (United States)

    Pennings, Timothy J.; Williams, Blair R.

    2010-01-01

    This article is a project that takes students through the process of forming a mathematical model of bicycle dynamics. Beginning with basic ideas from Newtonian mechanics (forces and torques), students use techniques from calculus and differential equations to develop the equations of rotational motion for a bicycle-rider system as it tips from…

  10. Bicycle helmet use and bicycling-related injury among young Canadians: an equity analysis

    Science.gov (United States)

    2013-01-01

    Introduction Cycling is a major activity for adolescents in Canada and potential differences exist in bicycling-related risk and experience of injury by population subgroup. The overall aim of this study was to inform health equity interventions by profiling stratified analytic methods and identifying potential inequities associated with bicycle-related injury and the use of bicycle helmets among Canadian youth. The two objectives of this study were: (1) To examine national patterns in bicycle ridership and also bicycle helmet use among Canadian youth in a stratified analysis by potentially vulnerable population subgroups, and (2) To examine bicycling-related injury in the same population subgroups of Canadian youth in order to identify possible health inequities. Methods Data for this study were obtained from the 6th cycle (2009/10) of the Health Behaviour in School-aged Children (HBSC) study, which is a general health survey that was completed by 26,078 students in grades 6–10 from 436 Canadian schools. Based on survey responses, we determined point prevalence for bicycle ridership, bicycle helmet use and relative risks for bicycling-related injury. Results Three quarters of all respondents were bicycle riders (n=19,410). Independent factors associated with bicycle ridership among students include being male, being a younger student, being more affluent, and being a resident of a small town. Among bicycle riders, 43% (95%CI ± 0.6%) reported never wearing and 32% (± 0.6%) inconsistently wearing a helmet. Only 26% (± 0.5%) of students reported always wearing a bicycle helmet. Helmets were less frequently used among older students and there were also important patterns by sex, geographic location and socioeconomic status. Adjusting for all other demographic characteristics, boys reported 2.02-fold increase (95% CI: 1.61 to 1.90) and new immigrants a 1.35-fold increase (95%CI: 1.00 to1.82) in the relative risk of bicycling-related injury in the past 12 months

  11. STRESS ANALYSIS OF BICYCLE FRAME

    Directory of Open Access Journals (Sweden)

    Mr.M.V.Pazare

    2014-06-01

    Full Text Available This paper deals with the stress analysis of bicycle frame by using Finite Element Method. The analysis is carried out in Ansys, The F.E.A. results are compared with theoretical results. In theoretical analysis the frame is treated as truss like structure and the stresses in various members of frame like top tube, down tube, seat tube, chain stay and seat stay are determined, considering various condition like, static start up, steady state paddling, vertical impact, horizontal impact, rear wheel braking. Also Finite Element Analysis is done considering the above conditions. From the analysis it is found that there is a good agreement between analytical and F.E.A. results. Result of all the cases reveals that maximum stress is found in top tube of the bicycle frame as compared to other frame members and is equal to 24.84 MPa which is less than yield strength in tension (i.e.Syt = 290 MPa for the material (aluminum T 6061 selected.

  12. Quinacrine induces apoptosis in human leukemia K562 cells via p38 MAPK-elicited BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression

    Energy Technology Data Exchange (ETDEWEB)

    Changchien, Jung-Jung; Chen, Ying-Jung; Huang, Chia-Hui [Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan (China); Cheng, Tian-Lu [Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Lin, Shinne-Ren [Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chang, Long-Sen, E-mail: lschang@mail.nsysu.edu.tw [Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan (China); Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China)

    2015-04-01

    Although previous studies have revealed the anti-cancer activity of quinacrine, its effect on leukemia is not clearly resolved. We sought to explore the cytotoxic effect and mechanism of quinacrine action in human leukemia K562 cells. Quinacrine induced K562 cell apoptosis accompanied with ROS generation, mitochondrial depolarization, and down-regulation of BCL2L1 and BCL2. Upon exposure to quinacrine, ROS-mediated p38 MAPK activation and ERK inactivation were observed in K562 cells. Quinacrine-induced cell death and mitochondrial depolarization were suppressed by the p38MAPK inhibitor SB202190 and constitutively active MEK1 over-expression. Activation of p38 MAPK was shown to promote BCL2 degradation. Further, ERK inactivation suppressed c-Jun-mediated transcriptional expression of BCL2L1. Over-expression of BCL2L1 and BCL2 attenuated quinacrine-evoked mitochondrial depolarization and rescued the viability of quinacrine-treated cells. Taken together, our data indicate that quinacrine-induced K562 cell apoptosis is mediated through mitochondrial alterations triggered by p38 MAPK-mediated BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression. - Highlights: • Quinacrine induces K562 cell apoptosis via down-regulation of BCL2 and BCL2L1. • Quinacrine induces p38 MAPK activation and ERK inactivation in K562 cells. • Quinacrine elicits p38 MAPK-mediated BCL2 down-regulation. • Quinacrine suppresses ERK/c-Jun-mediated BCL2L1 expression.

  13. Rs6295 promoter variants of the serotonin type 1A receptor are differentially activated by c-Jun in vitro and correlate to transcript levels in human epileptic brain tissue.

    Science.gov (United States)

    Pernhorst, Katharina; van Loo, Karen M J; von Lehe, Marec; Priebe, Lutz; Cichon, Sven; Herms, Stefan; Hoffmann, Per; Helmstaedter, Christoph; Sander, Thomas; Schoch, Susanne; Becker, Albert J

    2013-03-01

    Many brain disorders, including epilepsy, migraine and depression, manifest with episodic symptoms that may last for various time intervals. Transient alterations of neuronal function such as related to serotonin homeostasis generally underlie this phenomenon. Several nucleotide polymorphisms (SNPs) in gene promoters associated with these diseases have been described. For obvious reasons, their regulatory roles on gene expression particularly in human brain tissue remain largely enigmatic. The rs6295 G-/C-allelic variant is located in the promoter region of the human HTR1a gene, encoding the G-protein-coupled receptor for 5-hydroxytryptamine (5HT1AR). In addition to reported transcriptional repressor binding, our bioinformatic analyses predicted a reduced binding affinity of the transcription factor (TF) c-Jun for the G-allele. In vitro luciferase transfection assays revealed c-Jun to (a) activate the rs6295 C- significantly stronger than the G-allelic variant and (b) antagonize efficiently the repressive effect of Hes5 on the promoter. The G-allele of rs6295 is known to be associated with aspects of major depression and migraine. In order to address a potential role of rs6295 variants in human brain tissue, we have isolated DNA and mRNA from fresh frozen hippocampal tissue of pharmacoresistant temporal lobe epilepsy (TLE) patients (n=140) after epilepsy surgery for seizure control. We carried out SNP genotyping studies and mRNA analyses in order to determine HTR1a mRNA expression in human hippocampal samples stratified according to the rs6295 allelic variant. The mRNA expression of HTR1a was significantly more abundant in hippocampal mRNA of TLE patients homozygous for the rs6295 C-allele as compared to those with the GG-genotype. These data may point to a novel, i.e., rs6295 allelic variant and c-Jun dependent transcriptional 5HT1AR 'receptoropathy'. PMID:23333373

  14. 大鼠脑挫裂伤后c-jun和c-fos基因快速反应的特点%Quick response of genes c-jun and c-fos after brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    薄爱华; 薛贵平; 张辉; 董建峰; 邢立强; 米坤龙

    2004-01-01

    BACKGROUND: The importance of gene expressions of c-jun and c-fos has been widely recognized. However, there are very few reports on the characters of the expressions of these two genes after brain contusion.OBJECTIVE: To explore the characters of gene expressions of c-jun and c-fos.DESIGN: Randomized case control study.SETTING and MATERIALS: Experimental location: Experimental Centre of Zhangjiakou Medical College. Forty-five adult Wistar rats, with a boby mass about 200 g to 310 g.INTERVENTIONS: Forty-five rats were randomly divided into model group, sham operation group and normal control group. No treatment to normal group. The skulls were opened without strike for sham operation group. Free falling body method was used to make the brain injury model for model group. Rats were executed in 0. 5, 1, 2, 4, 8, 24 and 72 hours. Brain tissues were taken out to make paraffin sections and dyed by PV6000 immunohistochemistry.MAIN OUTCOME MEASURES: The similarities and differences of gene expressions of c-jun and c-fos.RESULTS: There was no positive expression of c-fos in the normal and sham group. However, there was weakly positive of c-jun. In the model group, the positive neurons distributed in the 1.0 - 2.0 mm cortex area surrounding the focus and the hippocampus of the same side. c-jun positive neurons were widely found in the cortex of injury side and hippocampus. The color of c-jun positive cells was dark, especially in hippocampus which c-jun positive cells concentrated. There was hardly expression of c-fos in 72 hours, but there were obvious positive neurons of c-jun existed.CONCLUSION: The gene expression of c-jun in the same side of brain injury is much stronger and more extensive than that of c-fos. The expressive time is much longer.%背景:目前关于c-jun和c-fos基因表达的重要性已逐渐被人们认识,而关于脑挫伤后两种基因表达的特点报道较少.目的:探讨脑挫裂伤后c-jun和c-fos基因表达的特点.设计:随机

  15. Effect of Serum from Overfatigue Rats on JNK/c-Jun/HO-1 Pathway in Human Umbilical Vein Endothelial Cells and the Intervening Effect of Tongxinluo(通心络)Superfine Powder

    Institute of Scientific and Technical Information of China (English)

    梁俊清; 徐海波; 吴以岭; 孙士然; 贾振华; 魏聪; 游佳华

    2009-01-01

    Objective:To cultivate human umbilical vein endothelial cells (HUVECs) in the serum of overfatigue rats with the intervention of Tongxinluo (通心络) superfine powder (TXLSP).By examining the variation of the activity of JNK/c-Jun/HO-1 pathway,the possible mechanisms of vascular endothelial dysfunction under overfatigue conditions and the intervening effect of TXLSP were explored.Methods:The HUVECs were randomly divided into the normal control group,the model group,the SP600125 (a specific antagonist of JNK)...

  16. Tumor Necrosis Factor-α and Apoptosis Signal-Regulating Kinase 1 Control Reactive Oxygen Species Release, Mitochondrial Autophagy and C-Jun N-Terminal Kinase/P38 Phosphorylation During Necrotizing Enterocolitis

    Directory of Open Access Journals (Sweden)

    Naira Baregamian

    2009-01-01

    Full Text Available Background: Oxidative stress and inflammation may contribute to the disruption of the protective gut barrier through various mechanisms; mitochondrial dysfunction resulting from inflammatory and oxidative injury may potentially be a significant source of apoptosis during necrotizing enterocolitis (NEC. Tumor necrosis factor (TNFα is thought to generate reactive oxygen species (ROS and activate the apoptosis signal-regulating kinase 1 (ASK1-c-Jun N-terminal kinase (JNK/p38 pathway. Hence, the focus of our study was to examine the effects of TNFα/ROs on mitochondrial function, ASK1-JNK/p38 cascade activation in intestinal epithelial cells during NEC.

  17. Growth arrest- and DNA-damage-inducible 45beta gene inhibits c-Jun N-terminal kinase and extracellular signal-regulated kinase and decreases IL-1beta-induced apoptosis in insulin-producing INS-1E cells

    DEFF Research Database (Denmark)

    Larsen, Claus Morten; Døssing, M G; Papa, S;

    2006-01-01

    IL-1beta is a candidate mediator of apoptotic beta cell destruction, a process that leads to type 1 diabetes and progression of type 2 diabetes. IL-1beta activates beta cell c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38, all of which are members of the mitogen......-activated protein kinase (MAPK) family. Inhibition of JNK prevents IL-1beta-mediated beta cell destruction. In mouse embryo fibroblasts and 3DO T cells, overexpression of the gene encoding growth arrest and DNA-damage-inducible 45beta (Gadd45b) downregulates pro-apoptotic JNK signalling. The aim of this study...

  18. Electric bicycles in The Netherlands: Current developments and future possibilities

    NARCIS (Netherlands)

    Rooijen, T. van

    2010-01-01

    Developments with electric bicycles in the Netherlands are progressing rapidly. The number of electric bicycles sold is rises every year. Cycling is a very popular mode of transport in The Netherlands. In 2008 more than one million bicycles were sold. At the moment one out of ten bicycles sold is al

  19. Survey of options on legalizing bicycling (VB)

    DEFF Research Database (Denmark)

    Zwahlen, Jurg; Sulewski, Sharon; Sacovitch, Stephen;

    1999-01-01

    the opposition against the proposal was.The goal of this project was to identify categories of users that were opposed to bicycling on the Dosseringen of the Østerbro and Nørrebro District lakes in Copenhagen. The identification of the opposition and its strength, rationale and organization was in terms of age......, gender, residency, frequency of use and their utilization of the area (i.e. walking, jogging, bicycling) as compared to the support for bicycling in the area. This was an Interactive Qualifying Project (IQP), that was designed to merge technical and scientific knowledge with society, and stresses...... the importance of this interaction....

  20. A Sociological Analysis of the Relationship between Attitude towards Bicycle and Using Bicycle in Short Trips in Isfahan

    Directory of Open Access Journals (Sweden)

    Siroos Ahmadi

    2013-07-01

    The main goal of this research is to investigate relationship between attitude toward bicycle and using bicycle among the men in Isfahan. Based on the descriptive research findings, mean using bicycle score is low in Iran. This situation is not satisfactory for a metropolis such as Isfahan that has an increasing population and motor vehicles, and also has many difficulties in urban base facilities and must be changed. In addition to mean attitude toward bicycle is high that is an opportunity for urban planners. Inferential findings show that attitude toward bicycle has a significant impact on using bicycle. In other words, increase attitude toward bicycle means an increase in using bicycle for short trips. This research finding theoretically confirm relation between attitude and behavior. Moreover it is compatible with results of the research that show there is significant relationship between attitude toward bicycle and using bicycle. There is an inverse significant relationship between age and using bicycle and with rising age using bicycle is decreased. This research finding shows that urban infrastructure in Isfahan for using bicycle is not available and consequently with rising age, bicycle risk is increased. There is a direct significant relationship between income rate and using bicycle and with increasing income rate, using bicycle is also increased. This research finding is rooted in social prestige bicycle and higher classes prefer to use motor vehicle for transportation instead of bicycle. There is a significant relationship between marital status and using bicycle and single men use bicycle more than married men but there is no significant relationship between education level and using bicycle. This research findings show that with rising education level in spite of rising income, using bicycle is not decreased. And finally there is no significant relationship between employed and unemployed persons in using bicycle. On the basis of the evidences such

  1. Growth hormone induces expression of c-jun and jun B oncogenes and employs a protein kinase C signal transduction pathway for the induction of c-fos oncogene expression.

    Science.gov (United States)

    Slootweg, M C; de Groot, R P; Herrmann-Erlee, M P; Koornneef, I; Kruijer, W; Kramer, Y M

    1991-04-01

    Although the structure of several members of the GH receptor family has been defined, signal transduction following GH binding to its receptor has not been elucidated. Mouse osteoblasts were used to study the effect of GH on immediate early gene expression and, subsequently, the cellular signal(s) mediating this expression were analysed. GH rapidly and transiently induced the expression of c-jun and jun B in concert with the already reported expression of c-fos. The GH-induced expression of c-fos was completely blocked by the protein kinase inhibitors staurosporine and H7, indicating that the action of GH is mediated by one or several protein kinases. We next analysed the identity of the putative protein kinases in more detail by using a more specific protein kinase inhibitor, namely the ether-lipid 1-O-alkyl-2-O-methylglycerol, understood to be an inhibitor of protein kinase C (PKC). Data obtained from these studies revealed that GH-induced expression of c-fos is mediated by PKC. In addition, we observed a profound increase in formation of the PKC activator diacyglycerol upon addition of GH, a natural activator of PKC. In conclusion, upon binding of GH to mouse osteoblasts, the receptor-mediated cellular signal involves diacyglycerol formation and activation of PKC, leading to the induction of oncogene expression. Finally, the expression of c-fos, c-jun and jun B results in an increased binding of protein complexes to AP-1 binding sites.

  2. NF-kB and c-Jun induce the expression of the oncogenic miR-221 and miR-222 in prostate carcinoma and glioblastoma cells

    Science.gov (United States)

    Galardi, Silvia; Mercatelli, Neri; Farace, Maria G.; Ciafrè, Silvia A.

    2011-01-01

    MicroRNAs (miRNAs) are potent negative regulators of gene expression involved in all aspects of cell biology. They finely modulate virtually all physiological pathways in metazoans, and are deeply implicated in all main pathologies, among which cancer. Mir-221 and miR-222, two closely related miRNAs encoded in cluster from a genomic region on chromosome X, are strongly upregulated in several forms of human tumours. In this work, we report that the ectopic modulation of NF-kB modifies miR-221/222 expression in prostate carcinoma and glioblastoma cell lines, where we had previously shown their oncogenic activity. We identify two separate distal regions upstream of miR-221/222 promoter which are bound by the NF-kB subunit p65 and drive efficient transcription in luciferase reporter assays; consistently, the site-directed mutagenesis disrupting p65 binding sites or the ectopical inhibition of NF-kB activity significantly reduce luciferase activity. In the most distal enhancer region, we also define a binding site for c-Jun, and we show that the binding of this factor cooperates with that of p65, fully accounting for the observed upregulation of miR-221/222. Thus our work uncovers an additional mechanism through which NF-kB and c-Jun, two transcription factors deeply involved in cancer onset and progression, contribute to oncogenesis, by inducing miR-221/222 transcription. PMID:21245048

  3. NF-kB and c-Jun induce the expression of the oncogenic miR-221 and miR-222 in prostate carcinoma and glioblastoma cells.

    Science.gov (United States)

    Galardi, Silvia; Mercatelli, Neri; Farace, Maria G; Ciafrè, Silvia A

    2011-05-01

    MicroRNAs (miRNAs) are potent negative regulators of gene expression involved in all aspects of cell biology. They finely modulate virtually all physiological pathways in metazoans, and are deeply implicated in all main pathologies, among which cancer. Mir-221 and miR-222, two closely related miRNAs encoded in cluster from a genomic region on chromosome X, are strongly upregulated in several forms of human tumours. In this work, we report that the ectopic modulation of NF-kB modifies miR-221/222 expression in prostate carcinoma and glioblastoma cell lines, where we had previously shown their oncogenic activity. We identify two separate distal regions upstream of miR-221/222 promoter which are bound by the NF-kB subunit p65 and drive efficient transcription in luciferase reporter assays; consistently, the site-directed mutagenesis disrupting p65 binding sites or the ectopical inhibition of NF-kB activity significantly reduce luciferase activity. In the most distal enhancer region, we also define a binding site for c-Jun, and we show that the binding of this factor cooperates with that of p65, fully accounting for the observed upregulation of miR-221/222. Thus our work uncovers an additional mechanism through which NF-kB and c-Jun, two transcription factors deeply involved in cancer onset and progression, contribute to oncogenesis, by inducing miR-221/222 transcription. PMID:21245048

  4. H-ras transfection of the rat kidney cell line NRK-52E results in increased induction of c-fos, c-jun and hsp70 following sulofenur treatment.

    Science.gov (United States)

    Gu, H; Smith, M W; Phelps, P C; Berezesky, I K; Merriman, R L; Boder, G B; Trump, B F

    1996-09-10

    The effect of the antineoplastic drug sulofenur on the induction of the immediate-early genes (IEG) c-fos and c-jun and the stress gene hsp70 was compared in the rat kidney epithelial-like cell line NRK-52E and a derivative H-ras-transfected (H/1.2NRK-52E) cell line. Fold induction for each gene after sulofenur (500 microM) treatment was greater in H/1.2NRK-52E. The maximum increases for NRK-2E and H/1.2NRK-52E were as follows: c-fos, approximately 10-fold and approximately 18-fold; c-jun, approximately 2.5-fold and approximately 3.6-fold; hsp70, approximately 13-fold and approximately 30-fold. In cells loaded with EGTA/AM or treated in low or no Ca2+ HBSS, c-fos induction was reduced similarly in both cell types. However, inhibition of protein kinases with staurosporin and calphostin C reduced c-fos by 80% in NRK-52E but by only 10-20% in H/1.2NRK.52E. These results indicate that sulofenur-induced IEG elevation is Ca(2+)-dependent and that the requirement for protein kinase C activation is bypassed in H-ras-transfected cells.

  5. 高+Gx环境对猴咬肌肌细胞c-jun表达影响的研究%Effect of high +Gx on c-jun expression in masseter muscle cell of Rhesus macaque

    Institute of Scientific and Technical Information of China (English)

    施生根; 张建中; 汤楚华; 牛忠英; 张铭

    2008-01-01

    目的 观察高+Gx环境对猴咬肌组织病理学及c-jun表达的影响. 方法以9只雄性猕猴为对象,按受试猴暴露的+Gx环境及持续时间随机分4组,对照组为+1 Gx/300 s;实验组为3组,分别为+15 Gx/200 s、+18 Gx/165 s、+21 Gx/140 s.采用病理学和免疫组织化学方法,观察模拟高正加速度环境下猴咬肌肌细胞组织及c-jun表达的变化. 结果组织病理学观察:对照组猴咬肌肌细胞无明显变化;实验组肌细胞结构趋紊乱,偶见少量间质出血.免疫组织化学观察:对照组咬肌肌细胞c-jun呈阴性或弱阳性表达,主要位于肌细胞核,胞质着色不明显;实验组咬肌细胞核c-jun着色明显,呈强阳性表达,不同高+Gx暴露组之间无明显差别. 结论高于+15 Gx的模拟环境可引起猴咬肌肌细胞c-jun表达增强.%Objective To investigate the changes of c-jun expression in the monkey masseter muscles induced by stress reaction under +Gx loads. Methods Nine male Rhesus macaques were randomly divided in to four groups according to Gx loads and duration: control group was exposed to+1 Gx/300 s overloads, and experimental groups 1, 2 and 3 were exposed to +15 Gx/200 s,+18 Gx/165 s and + 21 Gx/140 s respectively. Masseter tissue was fixed with 10% buffered formaldehyde and embedded with paraffin, and histopathological changes were observed under microscope. The expression of c-jun was detected by immunohistochemical PicTureTM method on the masseters. Results Gross and histological analyses showed that no significant pathological changes were observed in the masseters in control group; there was structural disturbance of masseter with slight stromal hemorrhage in the different experimental groups. Immunohistochemical staining demonstrated that over-expression of c-jun was detected in the nuclei of the muscles in the experimental groups, and negative staining was also observed in the nuclei of muscles in controlanimals. There was no obvious difference in c-jun

  6. Synthesis of Caged Bicyclic Phosphate Derivatives

    Institute of Scientific and Technical Information of China (English)

    FANG Xiao-min; OU Yu-xiang; LUO Rui-bin; WANG Yong; LIAN Dan-jun; LI Xin

    2008-01-01

    Seven caged bicyclic phosphate compounds were synthesized by using 1-oxo-4-hydroxymethy1-2,6,7-trioxa-1-pho-sphabicyclo[2.2.2] octane (PEPA) as starting material. Within them were three PEPA derivatives containing single caged bicyclic phosphate structure(1a,2a,3a), another three PEPA deviratives containing two caged bicyclic phosphate structures(1b,2b,3b) and one devirative(1c) containing three caged bicyclic phosphate structures. Structures of the products were characterized by FTIR, 1H NMR, elemental analysis and TG analysis. The reaction conditions were also discussed. Thermal analysis showed they had high thermal stability and excellent char-forming ability. Besides, these compounds had pentaerythritol bone and flame retardant elements of phosphorus, bromine or nitrogen simultaneously in their molecules, endowed them with good fire retardancy, and made them can be used as intumescent flame retardant.

  7. 36 CFR 1004.30 - Bicycles.

    Science.gov (United States)

    2010-07-01

    ... routes designated for bicycle use; provided, however, that the Board may close any Presidio Trust road or... consistent with the protection of natural, scenic and aesthetic values, safety considerations and...

  8. 36 CFR 4.30 - Bicycles.

    Science.gov (United States)

    2010-07-01

    ... road or parking area to bicycle use pursuant to the criteria and procedures of §§ 1.5 and 1.7 of this... consistent with the protection of a park area's natural, scenic and aesthetic values, safety...

  9. Effect of estrogen and tamoxifen on the expression pattern of AP-1 factors in MCF-7 cells: role of c-Jun, c-Fos, and Fra-1 in cell cycle regulation.

    Science.gov (United States)

    Babu, R L; Naveen Kumar, M; Patil, Rajeshwari H; Devaraju, K S; Ramesh, Govindarajan T; Sharma, S Chidananda

    2013-08-01

    The activated transcription factor ERα plays an important role in the breast development and progression of cancer. In a non-classical pathway ER interacts with other transcription factors AP-1, NFkB, SP1, etc. AP-1 transcription factors control rapid responses of mammalian cells to stimuli that impact proliferation, differentiation, and transformation. AP-1 factors are leucine zipper proteins belonging to members of the Jun family (c-Jun, JunB, and JunD) and Fos family (c-Fos, FosB, Fra-1, and Fra-2) proteins. Although AP-1 factors are well characterized, not much is known about the expression pattern of the AP-1 factors in breast cancer cells. Hence to determine which AP-1 factors are expressed and regulated by estrogen, we used human breast cancer MCF-7 cells as in vitro model system. The MCF-7 cells were treated with or without estradiol-17β (E2) or antiestrogen tamoxifen (TMX) and the cell proliferation and viability was assessed by MTT assay. The expression of different AP-1 factors was analyzed by semi-quantitative RT-PCR. The cells treated with E2 found to increase the cell proliferation by more than 35 % and TMX an antiestrogen decreased by 29 % compared to control. The E2 found to induce the expression of c-Jun, Fra-1, and c-Fos, while TMX decreased the expression. In addition TMX also decreased the mRNA levels of Jun-D and Fra-2. These results suggest that the AP-1 factors c-Jun, c-Fos, and Fra-1 may be involved in the proliferation and transformation of MCF-7 cells. E2 also found to induce cyclin D1 and cyclin E1 mRNA transcripts of cell cycle regulators while TMX significantly decreased compared to control. Further E2 induced the anti-apoptotic Bcl-2 and TMX decreased mRNA transcripts. The data presented here support the E2-ERα-mediated MCF-7 cell proliferation and confirms the role of AP-1 factors in cell cycle regulation. PMID:23625206

  10. Roles of PI3K/Akt and c-Jun signaling pathways in human papillomavirus type 16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis in non-small cell lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Erying Zhang

    Full Text Available Human papillomavirus (HPV-16 infection may be related to non-smoking associated lung cancer. Our previous studies have found that HPV-16 oncoproteins promoted angiogenesis via enhancing hypoxia-inducible factor-1α (HIF-1α, vascular endothelial growth factor (VEGF, and interleukin-8 (IL-8 expression in non-small cell lung cancer (NSCLC cells. In this study, we further investigated the roles of PI3K/Akt and c-Jun signaling pathways in it.Human NSCLC cell lines, A549 and NCI-H460, were stably transfected with pEGFP-16 E6 or E7 plasmids. Western blotting was performed to analyze the expression of HIF-1α, p-Akt, p-P70S6K, p-P85S6K, p-mTOR, p-JNK, and p-c-Jun proteins. VEGF and IL-8 protein secretion and mRNA levels were determined by ELISA and Real-time PCR, respectively. The in vitro angiogenesis was observed by human umbilical vein endothelial cells (HUVECs tube formation assay. Co-immunoprecipitation was performed to analyze the interaction between c-Jun and HIF-1α.HPV-16 E6 and E7 oncoproteins promoted the activation of Akt, P70S6K, P85S6K, mTOR, JNK, and c-Jun. LY294002, a PI3K inhibitor, inhibited HPV-16 oncoprotein-induced activation of Akt, P70S6K, and P85S6K, expression of HIF-1α, VEGF, and IL-8, and in vitro angiogenesis. c-Jun knockdown by specific siRNA abolished HPV-16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis. Additionally, HPV-16 oncoproteins promoted HIF-1α protein stability via blocking proteasome degradation pathway, but c-Jun knockdown abrogated this effect. Furthermore, HPV-16 oncoproteins increased the quantity of c-Jun binding to HIF-1α.PI3K/Akt signaling pathway and c-Jun are involved in HPV-16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis. Moreover, HPV-16 oncoproteins promoted HIF-1α protein stability possibly through enhancing the interaction between c-Jun and HIF-1α, thus making a contribution to angiogenesis in NSCLC cells.

  11. Highly Oxygenated Sesquiterpene Lactones from Cousinia aitchisonii and their Cytotoxic Properties: Rhaserolide Induces Apoptosis in Human T Lymphocyte (Jurkat) Cells via the Activation of c-Jun n-terminal Kinase Phosphorylation.

    Science.gov (United States)

    Iranshahy, Milad; Tayarani-Najaran, Zahra; Kasaian, Jamal; Ghandadi, Morteza; Emami, Seyed Ahmad; Asili, Javad; Chandran, Jima N; Schneider, Bernd; Iranshahi, Mehrdad

    2016-02-01

    Infrared-guided chromatographic fractionation of sesquiterpene lactones from the extracts of Cousinia aitchisonii and Cousinia concolor led to the isolation of five pure compounds. A new sesquiterpene lactone, namely, aitchisonolide, and two known sesquiterpene lactones (desoxyjanerin and rhaserolide) were isolated from C. aitchisonii and two known lignans (arctiin and arctigenin) from C. concolor. The structures of these compounds were elucidated by one-dimensional and two-dimensional nuclear magnetic resonance techniques, as well as high-resolution mass spectrometry. The purified and characterized compounds were subjected to cytotoxicity assay. The sesquiterpene lactones desoxyjanerin and rhaserolide showed significant cytotoxic activities against five different cancer cell lines and the normal human embryonic kidney cell line. Rhaserolide was chosen to evaluate the possible mechanism of action. Western blot analysis revealed that rhaserolide could induce apoptosis in Jurkat cells via the activation of c-Jun n-terminal kinase phosphorylation. PMID:26581585

  12. Highly Oxygenated Sesquiterpene Lactones from Cousinia aitchisonii and their Cytotoxic Properties: Rhaserolide Induces Apoptosis in Human T Lymphocyte (Jurkat) Cells via the Activation of c-Jun n-terminal Kinase Phosphorylation.

    Science.gov (United States)

    Iranshahy, Milad; Tayarani-Najaran, Zahra; Kasaian, Jamal; Ghandadi, Morteza; Emami, Seyed Ahmad; Asili, Javad; Chandran, Jima N; Schneider, Bernd; Iranshahi, Mehrdad

    2016-02-01

    Infrared-guided chromatographic fractionation of sesquiterpene lactones from the extracts of Cousinia aitchisonii and Cousinia concolor led to the isolation of five pure compounds. A new sesquiterpene lactone, namely, aitchisonolide, and two known sesquiterpene lactones (desoxyjanerin and rhaserolide) were isolated from C. aitchisonii and two known lignans (arctiin and arctigenin) from C. concolor. The structures of these compounds were elucidated by one-dimensional and two-dimensional nuclear magnetic resonance techniques, as well as high-resolution mass spectrometry. The purified and characterized compounds were subjected to cytotoxicity assay. The sesquiterpene lactones desoxyjanerin and rhaserolide showed significant cytotoxic activities against five different cancer cell lines and the normal human embryonic kidney cell line. Rhaserolide was chosen to evaluate the possible mechanism of action. Western blot analysis revealed that rhaserolide could induce apoptosis in Jurkat cells via the activation of c-Jun n-terminal kinase phosphorylation.

  13. Hippocampal activation of c-Jun N-terminal kinase,protein kinase B,and p38 mitogen-activated protein kinase in a chronic stress rat model of depression

    Institute of Scientific and Technical Information of China (English)

    Wei Dai; Weidong Li; Jun Lu; Yingge A; Ya Tu

    2010-01-01

    Recent studies have shown that vaned stress stimuli activate c-Jun N-terminal kinase(JNK),protein kinase B(Akt),and p38 mitogen-activated protein kinase(p38)signal transduction pathway,and also regulate various apoptotic cascades.JNK and p38 promote apoptosis,but Akt protects against apoptosis,in hippocampal neurons.However,changes in the transduction pathway in different regions of brain tissues in a chronic stress rat model of depression remain poorly understood.Results from this study showed that JNK phosphorylation levels were significantly greater in the stress group hippocampus compared with the control group(P 0.05).These results suggested that the JNK signal pathway is activated by JNK phosphorylation and participates in pathophysiological changes in rat models of depression.

  14. Hyperoside Downregulates the Receptor for Advanced Glycation End Products (RAGE and Promotes Proliferation in ECV304 Cells via the c-Jun N-Terminal Kinases (JNK Pathway Following Stimulation by Advanced Glycation End-Products In Vitro

    Directory of Open Access Journals (Sweden)

    Zhengyu Zhang

    2013-11-01

    Full Text Available Hyperoside is a major active constituent in many medicinal plants which are traditionally used in Chinese medicines for their neuroprotective, anti-inflammatory and antioxidative effects. The molecular mechanisms underlying these effects are unknown. In this study, quiescent ECV304 cells were treated in vitro with advanced glycation end products (AGEs in the presence or absence of hyperoside. The results demonstrated that AGEs induced c-Jun N-terminal kinases (JNK activation and apoptosis in ECV304 cells. Hyperoside inhibited these effects and promoted ECV304 cell proliferation. Furthermore, hyperoside significantly inhibited RAGE expression in AGE-stimulated ECV304 cells, whereas knockdown of RAGE inhibited AGE-induced JNK activation. These results suggested that AGEs may promote JNK activation, leading to viability inhibition of ECV304 cells via the RAGE signaling pathway. These effects could be inhibited by hyperoside. Our findings suggest a novel role for hyperoside in the treatment and prevention of diabetes.

  15. Pro-life role for c-Jun N-terminal kinase and p38 mitogen-activated protein kinase at rostral ventrolateral medulla in experimental brain stem death

    Directory of Open Access Journals (Sweden)

    Chang Alice YW

    2012-11-01

    Full Text Available Abstract Background Based on an experimental brain stem death model, we demonstrated previously that activation of the mitogen-activated protein kinase kinase 1/2 (MEK1/2/extracellular signal-regulated kinase 1/2 (ERK1/2/mitogen-activated protein kinase signal-interacting kinase 1/2 (MNK1/2 cascade plays a pro-life role in the rostral ventrolateral medulla (RVLM, the origin of a life-and-death signal detected from systemic arterial pressure, which sequentially increases (pro-life and decreases (pro-death to reflect progressive dysfunction of central cardiovascular regulation during the advancement towards brain stem death in critically ill patients. The present study assessed the hypothesis that, in addition to ERK1/2, c-Jun NH2-terminal kinase (JNK and p38 mitogen-activated protein kinase (p38MAPK, the other two mammalian members of MAPKs that are originally identified as stress-activated protein kinases, are activated specifically by MAPK kinase 4 (MAP2K4 or MAP2K6 and play a pro-life role in RVLM during experimental brain stem death. We further delineated the participation of phosphorylating activating transcriptional factor-2 (ATF-2 and c-Jun, the classical transcription factor activated by JNK or p38MAPK, in this process. Results An experimental model of brain stem death that employed microinjection of the organophosphate insecticide mevinphos (Mev; 10 nmol bilaterally into RVLM of Sprague–Dawley rats was used, alongside cardiovascular, pharmacological and biochemical evaluations. Results from ELISA showed that whereas the total JNK, p38MAPK, MAP2K4 and MAP2K6 were not affected, augmented phosphorylation of JNK at Thr183 and Tyr185 and p38MAPK at Thr180 and Tyr182, accompanied by phosphorylation of their upstream activators MAP2K4 at Ser257 and Thr261 and MAP2K6 at Ser207 and Thr211 in RVLM occurred preferentially during the pro-life phase of experimental brain stem death. Moreover, the activity of transcription factors ATF-2 at Thr71 and

  16. Mesenchymal stem cells promote liver regeneration and prolong survival in small-for-size liver grafts: involvement of C-Jun N-terminal kinase, cyclin D1, and NF-κB.

    Directory of Open Access Journals (Sweden)

    Weijie Wang

    Full Text Available BACKGROUND: The therapeutic potential of mesenchymal stem cells (MSCs has been highlighted recently for treatment of acute or chronic liver injury, by possibly differentiating into hepatocyte-like cells, reducing inflammation, and enhancing tissue repair. Despite recent progress, exact mechanisms of action are not clearly elucidated. In this study, we attempted to explore whether and how MSCs protected hepatocytes and stimulated allograft regeneration in small-for-size liver transplantation (SFSLT. METHODS: SFSLT model was established with a 30% partial liver transplantation (30PLT in rats. The differentiation potential and characteristics of bone marrow derived MSCs were explored in vitro. MSCs were infused transvenously immediately after graft implantation in therapy group. Expressions of apoptosis-, inflammatory-, anti-inflammatory-, and growth factor-related genes were measured by RT-PCR, activities of transcription factors AP-1 and NF-κB were analyzed by EMSA, and proliferative responses of the hepatic graft were evaluated by immunohistochemistry and western blot. RESULTS: MSCs were successfully induced into hepatocyte-like cells, osteoblasts and adipocytes in vitro. MSCs therapy could not only alleviate ischemia reperfusion injury and acute inflammation to promote liver regeneration, but also profoundly improve one week survival rate. It markedly up-regulated the mRNA expressions of HGF, Bcl-2, Bcl-XL, IL-6, IL-10, IP-10, and CXCR2, however, down-regulated TNF-α. Increased activities of AP-1 and NF-κB, as well as elevated expressions of p-c-Jun, cyclin D1, and proliferating cell nuclear antigen (PCNA, were also found in MSCs therapy group. CONCLUSION: These data suggest that MSCs therapy promotes hepatocyte proliferation and prolongs survival in SFSLT by reducing ischemia reperfusion injury and acute inflammation, and sustaining early increased expressions of c-Jun N-terminal Kinase, Cyclin D1, and NF-κB.

  17. Public Bicycle Share Programs and Head Injuries

    Science.gov (United States)

    Pless, Barry; Moore, Lynne; Nathens, Avery B.; Hunte, Garth; Rivara, Frederick P.

    2014-01-01

    Objectives. We evaluated the effect of North American public bicycle share programs (PBSPs), which typically do not offer helmets with rentals, on the occurrence of bicycle-related head injuries. Methods. We analyzed trauma center data for bicycle-related injuries from 5 cities with PBSPs and 5 comparison cities. We used logistic regression models to compare the odds that admission for a bicycle-related injury would involve a head injury 24 months before PBSP implementation and 12 months afterward. Results. In PBSP cities, the proportion of head injuries among bicycle-related injuries increased from 42.3% before PBSP implementation to 50.1% after (P < .01). This proportion in comparison cities remained similar before (38.2%) and after (35.9%) implementation (P = .23). Odds ratios for head injury were 1.30 (95% confidence interval = 1.13, 1.67) in PBSP cities and 0.94 (95% confidence interval = 0.79, 1.11) in control cities (adjusted for age and city) when we compared the period after implementation to the period before. Conclusions. Results suggest that steps should be taken to make helmets available with PBSPs. Helmet availability should be incorporated into PBSP planning and funding, not considered an afterthought following implementation. PMID:24922150

  18. Bicycling to school improves the cardiometabolic risk factor profile

    DEFF Research Database (Denmark)

    Ostergaard, Lars; Børrestad, Line A B; Tarp, Jakob;

    2012-01-01

    To investigate whether bicycling to school improves cardiometabolic risk factor profile and cardiorespiratory fitness among children.......To investigate whether bicycling to school improves cardiometabolic risk factor profile and cardiorespiratory fitness among children....

  19. Bicycle helmet promotion programs--Canada, Australia, and United States.

    Science.gov (United States)

    1993-03-26

    The use of bicycle helmets substantially reduces the risk for serious head injuries during bicycle-related crashes. Despite this benefit, epidemiologic data indicate a worldwide low prevalence of helmet use. Strategies to increase the use of bicycle helmets in the United States and other countries include subsidies, legislation, and education. This report summarizes information regarding three strategies to increase bicycle helmet use and the impact of implementing these approaches in Canada (helmet subsidies), Australia (legislation), and the United States (education). PMID:8446097

  20. On the stability of a bicycle on rollers

    Energy Technology Data Exchange (ETDEWEB)

    Cleary, Patricia A [Department of Geosciences, University of Wisconsin-Parkside, Kenosha, WI 53141 (United States); Mohazzabi, Pirooz, E-mail: pirooz.mohazzabi@uwp.edu [Department of Physics, University of Wisconsin-Parkside, Kenosha, WI 53141 (United States)

    2011-09-15

    Riding a bicycle on the newest form of indoor training, rollers, presents a unique experiment on bicycle stability. The stability factors eliminated by riding on rollers are discussed in terms of refined handling and control of the centre of mass on a bicycle. This paper is intended for undergraduate physics majors as well as any other general readership interested in the dynamics of bicycle stability.

  1. Beijing Bicycle - Stories from a Transformative Space

    DEFF Research Database (Denmark)

    Bagger-Petersen, Mai Corlin

    2012-01-01

    ’s Beijing Bicycle can be understood as the result of stories-so-far, as the cinematic representation of the globalized ”space” within the setting of the national. Beijing Bicycle is a production of space as well as a space of production, since it tells a new story in the trajectory of stories......Ideas, words, images and stories travel from west to east – and from east to west. Stories are chosen and retold in different settings and images are reproduced and appropriated into new contexts – and in new times. Cinema, in this case the mainland Chinese, becomes both a space of production...... and a production of space that reveals how transnational and translocal mechanisms affect the cinematic language, transforming the images and stories chosen for the cinematic representation. Wang Xiaoshuai’s Beijing Bicycle (Shiqi Sui de Danche) (2001) is a result of transnational currents weaving the carpet...

  2. On the Stability of a Bicycle on Rollers

    Science.gov (United States)

    Cleary, Patricia A.; Mohazzabi, Pirooz

    2011-01-01

    Riding a bicycle on the newest form of indoor training, rollers, presents a unique experiment on bicycle stability. The stability factors eliminated by riding on rollers are discussed in terms of refined handling and control of the centre of mass on a bicycle. This paper is intended for undergraduate physics majors as well as any other general…

  3. An Analysis of Florida Physical Educators' Knowledge of Bicycle Laws

    Science.gov (United States)

    Connaughton, Daniel P.; Egberts, John B.; Spengler, J. O.; Zhang, James J.; Jin, Liyan

    2012-01-01

    Bicycling among youth is a popular activity, but like all modes of travel it is not without risk. Florida has a particularly high rate of bicycle-related fatalities and injuries. To reduce such risks, the Florida Department of Transportation and Florida Department of Education have developed a youth bicycle safety educational program (Florida…

  4. Successful Swiss solar bicycles in Australia

    International Nuclear Information System (INIS)

    The article takes a look at the Swiss 'Spirit of Bike' team's success in the 'Power Challenge' race across Australia using solar-bicycles based on commercially available models. Apart from the sporting aspects of race, technical details on the cycles and their supply of solar power are given. Also, the history behind the success of the team is presented and the monitoring of man (and woman) and machine during the race is described. The article also discusses the electric bicycles that are commercially available and the potential of these energy-efficient vehicles in Switzerland

  5. C-Jun N-terminal kinase signal pathway and C-Jun N-terminal kinase inhibitor SP600125 in amygdala kindled rats%c-Jun氨基末端激酶信号通路及其抑制剂SP600125在大鼠杏仁核电刺激癫痫模型中的作用

    Institute of Scientific and Technical Information of China (English)

    吴俊; 陈旭; 舒凯; 肖铮铮; 雷霆; 李龄

    2012-01-01

    Objective By injecting SP600125 into ventricle of amygdale kindled rats,to observe the pathological changes of the hippocampus and the change of C-Jun N-terminal kinase (JNK) phosphorylation,and discuss the action mechanism of SP600125.Methods Forty rats were randomly divided into 4 groups (n =10 each):blank group,kindling group,SP600125 group,DMSO group.Whole-cell extracts of tissues were obtained from the right hippocampus,and Western blotting was used to detect the changes of JNK and phosphorylation of JNK.Pathological changes of the hippocampus and amygdla were observed by GFAP stain and Nissl stain.Results The level of JNK phosphorylation in the hippocampus was significantly higher in the kindling group (0.48 ± 0.04 ) than the blank group (0.38 ± 0.04 ) and the SP600125 group (0.37±0.03).Nissl stain positive cells in the hippocampus of the SP600125 group were significantly more than those in the the DMSO group (20.10 ±5.11 ).The expression of GFAP in the hippocampus of kindling group (65.45 ±4.53 ) and DMSO group (67.18 ± 3.52) was significantly stronger than that in the blank group (40.37 ± 3.82) and the SP600125 group (43.51 ± 1.83).Conclusion The role of repeated activation of JNK can be related to the hippocampal sclerosis in these rats.SP600125 had a protective effect on neurons during the kindling procedure.%目的 通过对杏仁核电刺激癫痫模型大鼠脑室内注射c-Jun氨基末端激酶(JNK)特异性抑制剂SP600125,观察海马区的病理变化和JNK水平的变化,探讨SP600125的作用.方法 将40只Wistar大鼠随机分为4组:空白组、点燃组、加药组和加药对照组各10只,10次癫痫发作后灌注取脑,Western blot法检测JNK的表达变化,进行尼氏和胶原纤维酸性蛋白(GFAP)染色,各组间进行比较.结果 Western blot显示点燃组海马区的JNK磷酸化水平(0.48±0.04)较空白组(0.38±0.04)和加药组(0.37±0.03)显著增高(P<0.05),总JNK水平各组之间差异无统计学意义(P>0

  6. Bicyclic semigroups of left I-quotients

    CERN Document Server

    Ghroda, Nassraddin

    2011-01-01

    In this article we study left I-orders in the bicyclic monoid $\\mathcal{B}$. We give necessary and sufficient conditions for a subsemigroup of $\\mathcal{B}$ to be a left I-oreder in $\\mathcal{B}$. We then prove that any left I-order in $\\mathcal{B}$ is straight.

  7. What do we know about bicycle helmets?

    NARCIS (Netherlands)

    Bogerd, C.P. Halldin, P. Houtenbos, M. Otte, D. Rossi, R.M. Walker, L. Willinger, R. & Shinar, D.

    2012-01-01

    Cycling is an excellent sustainable alternative to driving for many journeys. But cyclists have fewer safety options than car-users, with a helmet being the main safety device that is available. However, there are indications that increasing bicycle helmet usage through legislation causes confoundin

  8. 15 CFR 265.22 - Bicycle traffic.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Bicycle traffic. 265.22 Section 265.22... STANDARDS AND TECHNOLOGY, DEPARTMENT OF COMMERCE REGULATIONS GOVERNING TRAFFIC AND CONDUCT REGULATIONS GOVERNING TRAFFIC AND CONDUCT ON THE GROUNDS OF THE NATIONAL INSTITUTE OF STANDARDS &...

  9. Solutions to the Triangular Bicycle Flags Problem

    Science.gov (United States)

    Hartweg, Kim

    2005-01-01

    Students in a fifth-grade general education class and a second-grade gifted class participated in the Triangular Bicycle Flags problem. The results indicated that providing students with geometric experiences at the correct van Hiele level is necessary for helping students move from one level of understanding to the next.

  10. Antiepileptic Effect of Uncaria rhynchophylla and Rhynchophylline Involved in the Initiation of c-Jun N-Terminal Kinase Phosphorylation of MAPK Signal Pathways in Acute Seizures of Kainic Acid-Treated Rats

    Directory of Open Access Journals (Sweden)

    Hsin-Cheng Hsu

    2013-01-01

    Full Text Available Seizures cause inflammation of the central nervous system. The extent of the inflammation is related to the severity and recurrence of the seizures. Cell surface receptors are stimulated by stimulators such as kainic acid (KA, which causes intracellular mitogen-activated protein kinase (MAPK signal pathway transmission to coordinate a response. It is known that Uncaria rhynchophylla (UR and rhynchophylline (RP have anticonvulsive effects, although the mechanisms remain unclear. Therefore, the purpose of this study is to develop a novel strategy for treating epilepsy by investigating how UR and RP initiate their anticonvulsive mechanisms. Sprague-Dawley rats were administered KA (12 mg/kg, i.p. to induce seizure before being sacrificed. The brain was removed 3 h after KA administration. The results indicate that pretreatment with UR (1.0 g/kg, RP (0.25 mg/kg, and valproic acid (VA, 250 mg/kg for 3 d could reduce epileptic seizures and could also reduce the expression of c-Jun aminoterminal kinase phosphorylation (JNKp of MAPK signal pathways in the cerebral cortex and hippocampus brain tissues. Proinflammatory cytokines interleukin (IL-1β, IL-6, and tumor necrosis factor-α remain unchanged, indicating that the anticonvulsive effect of UR and RP is initially involved in the JNKp MAPK signal pathway during the KA-induced acute seizure period.

  11. Traffic conflicts on bicycle paths: a systematic observation of behaviour from video

    NARCIS (Netherlands)

    Horst, A.R.A. van der; Goede, M. de; Hair-Buijssen, S.H.H.M. de; Methorst, R.

    2014-01-01

    In The Netherlands, on bicycle paths, single-bicycle accidents, bicycle-bicycle and bicycle-moped accidents constitute a considerable share of all bicyclist injuries. Over three quarters of all hospitalised bicyclist victims in the Netherlands cannot be directly related to a crash with motorised tra

  12. Physiological and cognitive responses when riding an electrically assisted bicycle versus a classical bicycle.

    Science.gov (United States)

    Theurel, J; Theurel, A; Lepers, R

    2012-01-01

    The present study compared the physiological responses and the subsequent cognitive performance when riding an electrically assisted (EB) versus a classical (CB) bicycle. Oxygen uptake, heart rate and leg extensor muscles electromyographic (EMG) activity were recorded in 10 subjects during a 30-min intermittent cycling exercise performed with EB versus CB. Cognitive performance was evaluated by a mail sorting test, performed at rest and after each cycling session. Averaged oxygen uptake and heat rate were significantly (P cycling than during CB cycling. The EMG activities of the vastus lateralis, rectus femoris and gastrocnemius medialis muscles were significantly (P cycling than during EB cycling. The time to complete the mail sorting test was significantly (P cycling than after CB cycling. Because EB cycling reduced muscle strains and physiological stress, it might offer benefits for those using bicycles in their work, such as postal workers and police officers. STATEMENT OF RELEVANCE: This study compared physiological and cognitive responses when riding an electrically assisted versus a classical bicycle. The results showed that the electrically assisted bicycle led to reduced muscle strains and physiological stress and, therefore, might offer benefits for those using bicycles in their work, such as postal workers and police officers. PMID:22506555

  13. Fatal falls from bicycles: a case report.

    Science.gov (United States)

    Venara, A; Mauillon, D; Gaudin, A; Rouge-Maillart, C; Jousset, N

    2013-03-10

    Though rare occurrences, fatal falls from bicycles are generally linked to the absence of a protective helmet and/or a collision with another vehicle. The case presented here is exceptional due to its circumstances and the consequences of the accident: a fall with no obstacle at a low speed that brought about multiple traumas and the death of a cyclist wearing a protective helmet. Comparing this against a review of cyclist accidentology literature, this case is unique. The increased use of autopsy in terms of forensic accidentology is to be encouraged so as not to misunderstand the possibility of such lesion-based consequences following a simple fall from a bicycle. PMID:23312586

  14. Maximum Estrada Index of Bicyclic Graphs

    CERN Document Server

    Wang, Long; Wang, Yi

    2012-01-01

    Let $G$ be a simple graph of order $n$, let $\\lambda_1(G),\\lambda_2(G),...,\\lambda_n(G)$ be the eigenvalues of the adjacency matrix of $G$. The Esrada index of $G$ is defined as $EE(G)=\\sum_{i=1}^{n}e^{\\lambda_i(G)}$. In this paper we determine the unique graph with maximum Estrada index among bicyclic graphs with fixed order.

  15. Applying riding-posture optimization on bicycle frame design.

    Science.gov (United States)

    Hsiao, Shih-Wen; Chen, Rong-Qi; Leng, Wan-Lee

    2015-11-01

    Customization design is a trend for developing a bicycle in recent years. Thus, the comfort of riding a bike is an important factor that should be paid much attention to while developing a bicycle. From the viewpoint of ergonomics, the concept of "fitting object to the human body" is designed into the bicycle frame in this study. Firstly, the important feature points of riding posture were automatically detected by the image processing method. In the measurement process, the best riding posture was identified experimentally, thus the positions of feature points and joint angles of human body were obtained. Afterwards, according to the measurement data, three key points: the handlebar, the saddle and the crank center, were identified and applied to the frame design of various bicycle types. Lastly, this study further proposed a frame size table for common bicycle types, which is helpful for the designer to design a bicycle. PMID:26154206

  16. Free Use of Bicycles at CERN

    CERN Multimedia

    2000-01-01

    Imagine you have just arrived at CERN. You are from Russia or Japan and have no car but you do need to get around and do not like depending on public transport. What do you do? You go to the EP Service Point (Building 124) and meet Boris Cabaud to get a CERN bicycle. Use of the bicycle is free but you have to fill in an application form which needs to be signed by your Group or Division Secretary. Then the application is filled in, you are put on the waiting list and it might take you from one to four weeks to get your bike depending on the season. “Normally the bikes are only for Users in the EP division as they are paid for by the EP budget,” says Boris, “but some other divisions have made arrangements to cover the costs.” Boris takes care of 350 bicycles at present. Each bike can be lent for maximum one year. During the winter the bikes can be stored in building 301 as it is difficult to ride them in the snow. If a bike is broken or lost all costs will be billed to the group or team account of the bo...

  17. Psychological Delaying Model of Bicycle Passing Events on Physically Separated Bicycle Roadways in China*

    Science.gov (United States)

    Zhao, De; Wang, Wei; Li, Zhibin; Shan, Xiaonian; Sun, Xin

    Bicycle facilities are quite common in China but there are not enough quantitative methods to evaluate the Level of Service (LOS) of bicycle roadways. The number of passing events, which considers the interactions between bicyclists, has been proved to be a proper indicator for evaluating bicycle LOS under the special traffic and roadway conditions in China. The primary objective of this study is to propose a model considering the delay effects of passing events and rider's overtaking motivation. Field data was collected on South Zhongshan Road and Huaihai Road in Nanjing city of China with 639 bicyclists investigated. Then a new mathematical model was built to evaluate those effects through probability and regression analyses. It was found that the delay effect of passing events and rider's overtaking motivation are significant influencing factors which cannot be omitted. Correlation test shows the fitted relationship is greater between the model prediction and field data comparing with the previous model.

  18. Bicycling and walking are associated with different cortical oscillatory dynamics

    Directory of Open Access Journals (Sweden)

    Lena eStorzer

    2016-02-01

    Full Text Available Although bicycling and walking involve similar complex coordinated movements, surprisingly Parkinson’s patients with freezing of gait typically remain able to bicycle despite severe difficulties walking. This observation suggests functional differences in the motor networks subserving bicycling and walking. However, a direct comparison of brain activity related to bicycling and walking has never been performed, neither in healthy participants nor in patients. Such a comparison could potentially help elucidating the cortical involvement in motor control and the mechanisms through which bicycling ability may be preserved in patients with freezing of gait. The aim of this study was to contrast the cortical oscillatory dynamics involved in bicycling and walking in healthy participants.To this end, EEG and EMG data of 14 healthy participants were analyzed, who cycled on a stationary bicycle at a slow cadence of 40 revolutions per minute (rpm and walked at 40 strides per minute (spm, respectively.Relative to walking, bicycling was associated with a stronger power decrease in the high beta band (23-35 Hz during movement initiation and execution, followed by a stronger beta power increase after movement termination. Walking, on the other hand, was characterized by a stronger and persisting alpha power (8-12 Hz decrease. Both bicycling and walking exhibited movement cycle-dependent power modulation in the 24-40 Hz range that was correlated with EMG activity. This modulation was significantly stronger in walking.The present findings reveal differential cortical oscillatory dynamics in motor control for two types of complex coordinated motor behavior, i.e., bicycling and walking. Bicycling was associated with a stronger sustained cortical activation as indicated by the stronger high beta power decrease during movement execution and less cortical motor control within the movement cycle. We speculate this to be due to the more continuous nature of

  19. Technical analysis and market study of electric bicycles

    OpenAIRE

    Matasyan, Artur

    2015-01-01

    This thesis project was done in collaboration with a Prismattery LLC, which is based in Tallinn, Estonia and is interested in entering the market of electric bicycles. For that reason in this report a detailed study concerning the market of electrical bicycles, its current situation and trends were performed and a promising target market was indicated. The market study showed that although in different countries the specifications and preferred types of electric bicycles may vary,...

  20. Will a bicycle friendly policy make passenger travel more sustainably?

    OpenAIRE

    Christensen, Linda; Jensen, Thomas Christian

    2009-01-01

    The purpose of this paper is to analyse the possibility to transfer a larger part of the short car trips to walking or bicycling in order to obtain environmental and health benefits. The project contains a logistic choice model used to explain which circumstances are particularly important for choosing walking and bicycling, and how very different instruments can promote walking and bicycling at the expense of short car trips. Furthermore, the paper describes the most important factors when c...

  1. Potential risk and its influencing factors for separated bicycle paths.

    Science.gov (United States)

    Xu, Cheng; Yang, Ying; Jin, Sheng; Qu, Zhaowei; Hou, Lei

    2016-02-01

    In this paper, we propose two potential risk indicators to define and evaluate the safety of bicycle path at the microscopic level. Field bicycle data were collected from three survey sites under different traffic conditions. These two risk indicators based on speed dispersion were proposed and calculated during each 5-min interval. The risk influences of various widths of bicycle path and traffic conditions were analyzed by using one-way ANOVA. We further proposed a generalized linear model (GLM) for modeling and analyzing the relationships between bicycle risks and v/c ratio and percentages of electric bicycles, male cyclists, young cyclists, and loaded cyclists. The stepwise regression models were applied for determination of coefficients. The results show that the influences of gender and age of cyclists on potential risks are not significant. The risks increase with the width of bicycle path and percentage of electric bicycles, while only for wider bicycle path (4-lane case in this study), the risks are associated with whether or not cyclists are loaded. The findings could contribute for analysis and evaluation of the safety for bicycle path. PMID:26647016

  2. Potential risk and its influencing factors for separated bicycle paths.

    Science.gov (United States)

    Xu, Cheng; Yang, Ying; Jin, Sheng; Qu, Zhaowei; Hou, Lei

    2016-02-01

    In this paper, we propose two potential risk indicators to define and evaluate the safety of bicycle path at the microscopic level. Field bicycle data were collected from three survey sites under different traffic conditions. These two risk indicators based on speed dispersion were proposed and calculated during each 5-min interval. The risk influences of various widths of bicycle path and traffic conditions were analyzed by using one-way ANOVA. We further proposed a generalized linear model (GLM) for modeling and analyzing the relationships between bicycle risks and v/c ratio and percentages of electric bicycles, male cyclists, young cyclists, and loaded cyclists. The stepwise regression models were applied for determination of coefficients. The results show that the influences of gender and age of cyclists on potential risks are not significant. The risks increase with the width of bicycle path and percentage of electric bicycles, while only for wider bicycle path (4-lane case in this study), the risks are associated with whether or not cyclists are loaded. The findings could contribute for analysis and evaluation of the safety for bicycle path.

  3. The relationship between public and private bicycle use: the case of Seville

    OpenAIRE

    José I. Castillo-Manzano; Castro-Nuño, Mercedes; Lopez-Valpuesta, Lourdes

    2015-01-01

    Despite the success achieved by Public Bicycle Sharing Systems (PBSS) across the world, several researchers provide evidence on their limitations and constraints in a medium-long term, and bicycle ownership may be considered as a complementary tool to promote a 'bicycle-culture'. This paper aims to cover the gap about the interaction between both systems (public bicycle / private bicycle) and which are the key aspects to explain the bicycle-buying decision. After a fieldwork based on surveys ...

  4. c-Jun N-terminal kinases 3 (JNK3) from orange-spotted grouper, Epinephelus coioides, inhibiting the replication of Singapore grouper iridovirus (SGIV) and SGIV-induced apoptosis.

    Science.gov (United States)

    Guo, Minglan; Wei, Jingguang; Zhou, Yongcan; Qin, Qiwei

    2016-12-01

    C-Jun N-terminal kinases (JNKs), a subgroup of serine-threonine protein kinases that activated by phosphorylation, are involve in physiological and pathophysiological processes. JNK3 is one of JNK proteins involved in JNK3 signaling transduction. In the present study, two JNK3 isoforms, Ec-JNK3 X1 and Ec-JNK3 X2, were cloned from orange-spotted grouper, Epinephelus coioides. Both Ec-JNK3 X1 and Ec-JNK3 X2 were mainly expressed in liver, gill, skin, brain and muscle of juvenile grouper. The relative expression of Ec-JNK3 X2 mRNA was much higher in muscle and gill than that of Ec-JNK3 X1. Isoform-specific immune response to challenges was revealed by the expression profiles in vivo. Immunofluorescence staining indicated that JNK3 was localized in the cytoplasm of grouper spleen (GS) cells and shown immune response to SGIV infection in vitro. Over-expressing Ec-JNK3 X1 and/or Ec-JNK3 X2 inhibited the SGIV infection and replication and the SGIV-induced apoptosis. To achieve the antiviral and anti-apoptosis activities, JNK3 promoted the activation of genes ISRE and type I IFN in the antiviral IFN signaling pathway, and inhibited the activation of transcription factors NF-κB and p53 relating to apoptosis, respectively. Ec-JNK3 X2 showed stronger activities in antivirus and anti-apoptosis than that of Ec-JNK3 X1. Our results not only define the characterization of JNK3 but also reveal new immune functions and the molecular mechanisms of JNK3 on iridoviruses infection and the virus-induced apoptosis.

  5. Tumor necrosis factor alpha promotes the proliferation of human nucleus pulposus cells via nuclear factor-κB, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase.

    Science.gov (United States)

    Wang, Xiao-Hu; Hong, Xin; Zhu, Lei; Wang, Yun-Tao; Bao, Jun-Ping; Liu, Lei; Wang, Feng; Wu, Xiao-Tao

    2015-04-01

    Although tumor necrosis factor alpha (TNF-α) is known to play a critical role in intervertebral disc (IVD) degeneration, the effect of TNF-α on nucleus pulposus (NP) cells has not yet been elucidated. The aim of this study was to explore the effect of TNF-α on proliferation of human NP cells. NP cells were treated with different concentrations of TNF-α. Cell proliferation was determined by cell counting kit-8 (CCK-8) analysis and Ki67 immunofluorescence staining, and expression of cyclin B1 was studied by quantitative real-time RT-PCR. Cell cycle was measured by flow cytometry and cell apoptosis was analyzed using an Annexin V-fluorescein isothiocyanate (FITC) & propidium iodide (PI) apoptosis detection kit. To identify the mechanism by which TNF-α induced proliferation of NP cells, selective inhibitors of major signaling pathways were used and Western blotting was carried out. Treatment with TNF-α increased cell viability (as determined by CCK-8 analysis) and expression of cyclin B1 and the number of Ki67-positive and S-phase NP cells, indicating enhancement of proliferation. Consistent with this, NP cell apoptosis was suppressed by TNF-α treatment. Moreover, inhibition of NF-κB, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) blocked TNF-α-stimulated proliferation of NP cells. In conclusion, the current findings suggest that the effect of TNF-α on IVD degeneration involves promotion of the proliferation of human NP cells via the NF-κB, JNK, and p38 MAPK pathways.

  6. The Green Tea Component (--Epigallocatechin-3-Gallate Sensitizes Primary Endothelial Cells to Arsenite-Induced Apoptosis by Decreasing c-Jun N-Terminal Kinase-Mediated Catalase Activity.

    Directory of Open Access Journals (Sweden)

    Jee-Youn Kim

    Full Text Available The green tea component (--epigallocatechin-3-gallate (EGCG has been shown to sensitize many different types of cancer cells to anticancer drug-induced apoptosis, although it protects against non-cancerous primary cells against toxicity from certain conditions such as exposure to arsenic (As or ultraviolet irradiation. Here, we found that EGCG promotes As-induced toxicity of primary-cultured bovine aortic endothelial cells (BAEC at doses in which treatment with each chemical alone had no such effect. Increased cell toxicity was accompanied by an increased condensed chromatin pattern and fragmented nuclei, cleaved poly(ADP-ribose polymerase (PARP, activity of the pro-apoptotic enzymes caspases 3, 8 and 9, and Bax translocation into mitochondria, suggesting the involvement of an apoptotic signaling pathway. Fluorescence activated cell sorting analysis revealed that compared with EGCG or As alone, combined EGCG and As (EGCG/As treatment significantly induced production of reactive oxygen species (ROS, which was accompanied by decreased catalase activity and increased lipid peroxidation. Pretreatment with N-acetyl-L-cysteine or catalase reversed EGCG/As-induced caspase activation and EC toxicity. EGCG/As also increased the phosphorylation of c-Jun N-terminal kinase (JNK, which was not reversed by catalase. However, pretreatment with the JNK inhibitor SP600125 reversed all of the observed effects of EGCG/As, suggesting that JNK may be the most upstream protein examined in this study. Finally, we also found that all the observed effects by EGCG/As are true for other types of EC tested. In conclusion, this is firstly to show that EGCG sensitizes non-cancerous EC to As-induced toxicity through ROS-mediated apoptosis, which was attributed at least in part to a JNK-activated decrease in catalase activity.

  7. 阿朴吗啡诱导黑质毁损大鼠腹侧被盖区c-jun表达%Apomorphine induce c-jun expression in ventral tagmental area of 6-OHDA-lesioned rats

    Institute of Scientific and Technical Information of China (English)

    陈晓宇; 姚玉芹; 沈韶辉; 韩卉

    2006-01-01

    目的:观察6-羟基多巴胺(6-hydroxydopamine,6-OHDA)毁损黑质DA能神经元后,不同时间点腹腔注射阿朴吗啡(Apomorphine,APO)大鼠行为学及中脑腹侧被盖区(ventraltagmental area,VTA)形态学、c-jun表达情况,探讨其可能机制.方法:6-OHDA单侧一点注射大鼠右黑质致密区(substantianigracompacta,SNc),特异性毁损DA能神经元;术后1、3、7、14、21d腹腔注射APO,观察旋转行为;利用电镜、尼氏染色、免疫组织化学ABC法,观察各时间点VTA DA能神经元形态学变化和酪氨酸羟化酶(TH)、c-jun表达情况.结果:毁损侧VTA DA能神经元逐渐减少,超微结构损伤逐渐加重;DA神经元丢失≥75%时,APO诱导的旋转实验≥7r/min,VTA毁损侧c-jun表达.结论:APO能诱导毁损侧VTA表达c-jun;c-jun表达与DA能神经元毁损程度有一定的关系.

  8. Neuroprotection by inhibiting the c-Jun N-terminal kinase pathway after cerebral ischemia occurs independently of interleukin-6 and keratinocyte-derived chemokine (KC/CXCL1 secretion

    Directory of Open Access Journals (Sweden)

    Benakis Corinne

    2012-04-01

    Full Text Available Abstract Background Cerebral ischemia is associated with the activation of glial cells, infiltration of leukocytes and an increase in inflammatory mediators in the ischemic brain and systemic circulation. How this inflammatory response influences lesion size and neurological outcome remains unclear. D-JNKI1, an inhibitor of the c-Jun N-terminal kinase pathway, is strongly neuroprotective in animal models of stroke. Intriguingly, the protection mediated by D-JNKI1 is high even with intravenous administration at very low doses with undetectable drug levels in the brain, pointing to a systemic mode of action, perhaps on inflammation. Findings We evaluated whether D-JNKI1, administered intravenously 3 h after the onset of middle cerebral artery occlusion (MCAO, modulates secretion of the inflammatory mediators interleukin-6 and keratinocyte-derived chemokine in the plasma and from the spleen and brain at several time points after MCAO. We found an early release of both mediators in the systemic circulation followed by an increase in the brain and went on to show a later systemic increase in vehicle-treated mice. Release of interleukin-6 and keratinocyte-derived chemokine from the spleen of mice with MCAO was not significantly different from sham mice. Interestingly, the secretion of these inflammatory mediators was not altered in the systemic circulation or brain after successful neuroprotection with D-JNKI1. Conclusions We demonstrate that neuroprotection with D-JNKI1 after experimental cerebral ischemia is independent of systemic and brain release of interleukin-6 and keratinocyte-derived chemokine. Furthermore, our findings suggest that the early systemic release of interleukin-6 and keratinocyte-derived chemokine may not necessarily predict an unfavorable outcome in this model.

  9. Diallyl trisulfide-induced apoptosis in human prostate cancer cells involves c-Jun N-terminal kinase and extracellular-signal regulated kinase-mediated phosphorylation of Bcl-2.

    Science.gov (United States)

    Xiao, Dong; Choi, Sunga; Johnson, Daniel E; Vogel, Victor G; Johnson, Candace S; Trump, Donald L; Lee, Yong J; Singh, Shivendra V

    2004-07-22

    Garlic-derived organosulfides (OSCs) including diallyl trisulfide (DATS) are highly effective in affording protection against chemically induced cancer in animals. Evidence is also mounting to indicate that some naturally occurring OSCs can suppress proliferation of cancer cells by causing apoptosis, but the sequence of events leading to proapoptotic effect of OSCs is poorly defined. Using PC-3 and DU145 human prostate cancer cells as a model, we now demonstrate that DATS is a significantly more potent apoptosis inducer than diallyl sulfide (DAS) or diallyl disulfide (DADS). DATS-induced apoptosis in PC-3 cells was associated with phosphorylation of Bcl-2, reduced Bcl-2 : Bax interaction, and cleavage of procaspase-9 and -3. Bcl-2 overexpressing PC-3 cells were significantly more resistant to apoptosis induction by DATS compared with vector-transfected control cells. DATS treatment resulted in activation of extracellular-signal regulated kinase 1/2 (ERK1/2) and c-jun N-terminal kinase 1 (JNK1) and/or JNK2, but not p38 mitogen-activated protein kinase. Phosphorylation of Bcl-2 in DATS-treated PC-3 cells was fully blocked in the presence of JNK-specific inhibitor SP600125. Moreover, JNK inhibitor afforded significant protection against DATS-induced apoptosis in both cells. DATS-induced Bcl-2 phosphorylation and apoptosis were partially attenuated by pharmacological inhibition of ERK1/2 using PD98059 or U0126. Overexpression of catalase inhibited DATS-mediated activation of JNK1/2, but not ERK1/2, and apoptosis induction in DU145 cells suggesting involvement of hydrogen peroxide as a second messenger in DATS-induced apoptosis. In conclusion, our data point towards important roles for Bcl-2, JNK and ERK in DATS-induced apoptosis in human prostate cancer cells.

  10. c-Jun N-terminal kinase inhibitor favors transforming growth factor-β to antagonize hepatitis B virus X protein-induced cell growth promotion in hepatocellular carcinoma.

    Science.gov (United States)

    Wu, Yan-Hui; Ai, Xi; Liu, Fu-Yao; Liang, Hui-Fang; Zhang, Bi-Xiang; Chen, Xiao-Ping

    2016-02-01

    Transforming growth factor (TGF)-β induces cell growth arrest in well-differentiated hepatocellular carcinoma (HCC) while hepatitis B virus X protein (HBx) minimizes the tumor suppression of TGF-β signaling in early chronic hepatitis B. However, how to reverse the oncogenic effect of HBx and sustain the tumor-suppressive action of TGF-β has yet to be investigated. The present study examined the effect of TGF-β and a c-Jun N-terminal kinase (JNK) inhibitor on cell growth in HCC cells with forced expression of HBx. It was found that HBx promoted cell growth via activation of the JNK/pSMAD3L pathway and inhibition of the transforming growth factor-beta type I receptor (TβRI)/pSMAD3C pathway. pSMAD3L/SMAD4 and pSMAD3C/SMAD4 complexes antagonized each other to regulate c-Myc expression. In the absence of HBx, TGF-β induced cell growth arrest through activation of the TβRI/pSMAD3C pathway in well-differentiated HCC cells. In the presence of HBx, TGF-β had no effect on cell growth. JNK inhibitor SP600125 significantly reversed the oncogenic action of HBx and favored TGF-β to regain the ability to inhibit the cell growth in HBx-expressing well-differentiated HCC cells. In conclusion, targeting JNK signaling favors TGF-β to block HBx-induced cell growth promotion in well-differentiated HCC cells. As an adjunct to anti-viral therapy, the combination of TGF-β and inhibition of JNK signaling is a potential therapy for HBV-infected HCC.

  11. Cadmium induces apoptosis in pancreatic β-cells through a mitochondria-dependent pathway: the role of oxidative stress-mediated c-Jun N-terminal kinase activation.

    Directory of Open Access Journals (Sweden)

    Kai-Chih Chang

    Full Text Available Cadmium (Cd, one of well-known highly toxic environmental and industrial pollutants, causes a number of adverse health effects and diseases in humans. The growing epidemiological studies have suggested a possible link between Cd exposure and diabetes mellitus (DM. However, the toxicological effects and underlying mechanisms of Cd-induced pancreatic β-cell injury are still unknown. In this study, we found that Cd significantly decreased cell viability, and increased sub-G1 hypodiploid cells and annexin V-Cy3 binding in pancreatic β-cell-derived RIN-m5F cells. Cd also increased intracellular reactive oxygen species (ROS generation and malondialdehyde (MDA production and induced mitochondrial dysfunction (the loss of mitochondrial membrane potential (MMP and the increase of cytosolic cytochrome c release, the decreased Bcl-2 expression, increased p53 expression, poly (ADP-ribose polymerase (PARP cleavage, and caspase cascades, which accompanied with intracellular Cd accumulation. Pretreatment with the antioxidant N-acetylcysteine (NAC effectively reversed these Cd-induced events. Furthermore, exposure to Cd induced the phosphorylations of c-jun N-terminal kinases (JNK, extracellular signal-regulated kinases (ERK1/2, and p38-mitogen-activated protein kinase (MAPK, which was prevented by NAC. Additionally, the specific JNK inhibitor SP600125 or JNK-specific small interference RNA (si-RNA transfection suppressed Cd-induced β-cell apoptosis and related signals, but not ERK1/2 and p38-MAPK inhibitors (PD98059 and SB203580 did not. However, the JNK inhibitor or JNK-specific si-RNA did not suppress ROS generation in Cd-treated cells. These results indicate that Cd induces pancreatic β-cell death via an oxidative stress downstream-mediated JNK activation-triggered mitochondria-regulated apoptotic pathway.

  12. Bicycle Sharing in Developing Countries : A proposal towards sustainable transportation in Brazilian median cities

    OpenAIRE

    Dias Batista, Edgard

    2010-01-01

    Bicycle-sharing programs are a new trend in urban transportation. The main difference of a bicycle-sharing program with a regular bicycle rental is that is possible to get a bicycle in one station and return it in any other station. There are many models of bicycle sharing, each model with its pros and cons. This study analyzes the bicycle-sharing models in order to build a proposal of a bicycle-sharing program suitable for Brazilian median cities. The study begins with an overview of bicycle...

  13. Bicycle Helmet Laws are Associated with a Lower Fatality Rate from Bicycle-Motor Vehicle Collisions

    Science.gov (United States)

    Meehan, William P.; Lee, Lois K.; Fischer, Christopher M.; Mannix, Rebekah C.

    2013-01-01

    Objective To assess the association between bicycle helmet legislation and bicycle-related deaths sustained by children involved in bicycle-motor vehicle collisions. Study design We conducted a cross sectional study of all bicyclists aged 0-16 years included in the Fatality Analysis Reporting System (FARS) who died between January 1999 and December 2010. We compared fatality rates per age-specific state populations between states with helmet laws and those without helmet laws. We used a clustered Poisson multivariate regression model to adjust for factors previously associated with rates of motor vehicle fatalities: elderly driver licensure laws, legal blood alcohol limit ( 0.08 between states with helmet laws and those without helmet laws. The mean unadjusted rates of fatalities were lower in states with helmet laws (2.0/1,000,000 vs. 2.5/1,000,000; p= 0.03). After adjusting for potential confounding factors, states with mandatory helmet laws continued to be associated with a lower rate of fatalities (adjusted Incidence Rate Ratio 0.84; 95% CI 0.70, 0.98). Conclusions Bicycle helmet safety laws are associated with a lower incidence of fatalities among child bicyclists involved in motor vehicle collisions. PMID:23706604

  14. Bicycle Freewheeling with Air Drag as a Physics Experiment

    Science.gov (United States)

    Janssen, Paul; Janssens, Ewald

    2015-01-01

    To familiarize first-year students with the important ingredients of a physics experiment, we offer them a project close to their daily life: measuring the effect of air resistance on a bicycle. Experiments are done with a bicycle freewheeling on a downhill slope. The data are compared with equations of motions corresponding to different models…

  15. Methods to assess the stability of a bicycle rider system

    NARCIS (Netherlands)

    Cooke, A.G.; Bulsink, V.E.; Beusenberg, C.M.; Dubbeldam, R.; Bonnema, G.M.; Poelman, W.A.; Koopman, H.F.J.M.

    2012-01-01

    The SOFIE (Intelligent Assisted Bicycles) project wishes to create performance and design guidelines for mechatronic appliances which improve the stability of electric bicycles, so-called intelligent stability assist devices (IAD). To achieve this goal, a stability hypothesis, an advanced rider/bicy

  16. Modeling of speed distribution for mixed bicycle traffic flow

    Directory of Open Access Journals (Sweden)

    Cheng Xu

    2015-11-01

    Full Text Available Speed is a fundamental measure of traffic performance for highway systems. There were lots of results for the speed characteristics of motorized vehicles. In this article, we studied the speed distribution for mixed bicycle traffic which was ignored in the past. Field speed data were collected from Hangzhou, China, under different survey sites, traffic conditions, and percentages of electric bicycle. The statistics results of field data show that the total mean speed of electric bicycles is 17.09 km/h, 3.63 km/h faster and 27.0% higher than that of regular bicycles. Normal, log-normal, gamma, and Weibull distribution models were used for testing speed data. The results of goodness-of-fit hypothesis tests imply that the log-normal and Weibull model can fit the field data very well. Then, the relationships between mean speed and electric bicycle proportions were proposed using linear regression models, and the mean speed for purely electric bicycles or regular bicycles can be obtained. The findings of this article will provide effective help for the safety and traffic management of mixed bicycle traffic.

  17. Bicycle facilities on road segments and intersections of distributor roads.

    NARCIS (Netherlands)

    2008-01-01

    A sustainably safe road environment requires bicycle facilities that separate motorized traffic from relatively vulnerable road users like cyclists. Research indicates that on distributor roads the road sections with adjoining or separate bicycle tracks are safer than the road sections without any b

  18. On Wiener polarity index of bicyclic networks

    Science.gov (United States)

    Ma, Jing; Shi, Yongtang; Wang, Zhen; Yue, Jun

    2016-01-01

    Complex networks are ubiquitous in biological, physical and social sciences. Network robustness research aims at finding a measure to quantify network robustness. A number of Wiener type indices have recently been incorporated as distance-based descriptors of complex networks. Wiener type indices are known to depend both on the network’s number of nodes and topology. The Wiener polarity index is also related to the cluster coefficient of networks. In this paper, based on some graph transformations, we determine the sharp upper bound of the Wiener polarity index among all bicyclic networks. These bounds help to understand the underlying quantitative graph measures in depth.

  19. Solar Electric Bicycle Body Modeling and Simulation

    Directory of Open Access Journals (Sweden)

    Zhikun Wang

    2013-10-01

    Full Text Available A new solar electric bicycle design and study were carried out on in this paper. Application of CAD technology to establish three-dimension geometric model, using the kinetic analysis on the frame and other parts for numerical simulation and static strength analysis for the vehicle model design, virtual assembly, complete frame dynamics analysis and vibration analysis, with considering other factors, first on the frame structure improvement, second on security of design calculation analysis and comparison, finally get the ideal body design.

  20. Revitalization of Cycling in a Former Bicycle Kingdom: Beijing

    DEFF Research Database (Denmark)

    Zhao, Chunli; Carstensen, Trine Agervig; Olafsson, Anton Stahl;

    are revealed by collection and analysis of historical material and interviews with key stakeholders. The historical material is obtained from libraries, online resources, and reports from professionals including urban designers, transportation engineers, research centres and politicians of the Beijing......This paper scrutinizes and analyses the relevant historical policy documents chronologically - from the 1960s to the present - in order to figure out the potentials of revitalizing the bicycle mode share in Beijing. Firstly, we targeted two top-drawer conflicts of the bicycle use, which are travel......- or commuting distance and motorised vehicle-oriented urban development. Secondly, we analysed how the various related policies resulted in the changing landscape of the bicycle mode share, including increasing in the bicycle mode share, created the conflicts and declined the bicycle mode share. The results...

  1. Safety effects of permanent running lights for bicycles

    DEFF Research Database (Denmark)

    Madsen, Jens Chr. Overgaard; Andersen, T.; Lahrmann, Harry

    2013-01-01

    Making the use of daytime running lights mandatory for motor vehicles is generally documented to have had a positive impact upon traffic safety. Improving traffic safety for bicyclists is a focal point in the road traffic safety work in Denmark. In 2004 and 2005 a controlled experiment including...... 3845 cyclists was carried out in Odense, Denmark in order to examine, if permanent running lights mounted to bicycles would improve traffic safety for cyclists. The permanent running lights were mounted to 1845 bicycles and the accident rate was recorded through 12 months for this treatment group......, including all recorded bicycle accidents with personal injury to the participating cyclist, is 19% lower for cyclists with permanent running lights mounted; indicating that the permanent bicycle running light significantly improves traffic safety for cyclists. The study shows that use of permanent bicycle...

  2. Infiuence of Bicycle Traffic on Capacity of Typical Signalized Intersection

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiaoming; SHAO Chunfu; YUE Hao

    2007-01-01

    Bicycle traffic has a significant effect on the capacity of signalized intersections. This paper divides the influence of bicyclists on vehicular flow into four types with the time durations estimated based on probability, shock wave, and gap acceptance theory. Vehicular saturation flow rate is predicted for various conditions on the basis of the speed-flow curve for the capacity of typical intersections influenced by bicycle traffic.The model overcomes the limitations of the Highway Capacity Manual (HCM, 2000) method for left-turns due to data collection, and takes into account the effect of trapped bicycles on the through vehicular traffic.The numerical results show that the left-turn and through capacities predicted by the model are lower than those of the HCM method. The right-turn capacity is close to that of the HCM method at Iow bicycle volumes and higher than that of the HCM method at high bicycle volumes.

  3. In vivo study on the effects of microcystin extracts on the expression profiles of proto-oncogenes (c-fos, c-jun and c-myc) in liver, kidney and testis of male Wistar rats injected i.v. with toxins.

    Science.gov (United States)

    Li, Huiying; Xie, Ping; Li, Guangyu; Hao, Le; Xiong, Qian

    2009-01-01

    Microcystins (MCs) are a potent liver tumor promoter, possessing potent tumor-promoting activity and weak initiating activity. Proto-oncogenes are known to be involved in the tumor-promoting mechanisms of microcystin-LR. However, few data are available on the effects of MCs on proto-oncogenes in the whole animal. To investigate the effects of MCs on the expression profile of the proto-oncogenes in different organs, male Wistar rats were injected intravenously with microcystin extracts at a dose of 86.7 mug MC-LR eq/kg bw (MC-LR eq, MC-LR equivalents). mRNA levels of three proto-oncogenes c-fos, c-jun and c-myc in liver, kidney and testis were analyzed using quantitative real-time PCR at several time points post-injection. Significant induction of these genes at transcriptional level was observed in the three organs. In addition, the increase of mRNA expression of all three genes was much higher in liver than in kidney and testis. Meanwhile, the protein levels of c-Fos and c-Jun were investigated by western blotting. Both proteins were induced in the three organs. However, elevations of protein levels were much lower than those of mRNA levels. These findings suggest that the expression of c-fos, c-jun and c-myc might be one possible mechanism for the tumor-promoting activity and initiating activity of microcystins.

  4. Safe bicycling – Problems and solutions

    Directory of Open Access Journals (Sweden)

    Grecka M.

    2014-01-01

    Full Text Available Herewith a popularity of bicycling, various safety problems of cyclists are researched. Studies are connected with infrastructure, riding culture, choice of cyclist's suit and riding equipment. Overall, 382 respondents (159 cyclists, 119 drivers, 104 pedestrians were involved in the survey. The road participants' mutual communication problems in the traffic and opportunities of solving them were clarified. Most of cyclists wear comfortable daily or sporty clothing with reflective elements, and in their opinion, clothing with light emissive elements must be like daily clothing. The drivers could better notice cyclists, if they wear brightly colored suit with light emissive and reflective elements, but pedestrians – if cyclists use warning sound signals. The opinions of road participants about the placement of light emissive and reflective elements in cyclist's clothing were clarified. The prototype of cycling belt (Fig. 1e has been drawn up with LED stop signals, which are activated by the accelerometer placed in the central back pocket. The results of approbation have shown that the sensor does not provide the proper functioning of signals, due to a high level of riding movements. Using Motion Capture technology and bicycle exercise equipment, the research of oscillation of anthropometric points on the back has been carried out. The accelerometer should be placed between scapulae to design the cycling jacket.

  5. The Design of Sport Bicycle Speed Odometer

    Directory of Open Access Journals (Sweden)

    Dongbing Liu

    2013-04-01

    Full Text Available As bicycle sport equipment, a sport bike needs a speed and distance measuring device, due to the characteristic of road cycling, thereby mastering the state of motion. According to external conditions such as temperature, wind speed, the bike can make the appropriate adjustment to achieve the best movement effect. The bicycle speed odometer is a major accessibility tool that satisfies with needs of the people with fast development. This study elaborated a bike speed odometer design based on Hall element, taking AT89C52 single chip as the core, measuring speed with A44E Hall sensor, to finish the bike mileage/speed measurement and statistics by displaying bike mileage and speed in real time. By using the Hall elements, the hardware of speed odometer input the number of pulse of per circle into the single-chip computer system. Then the signal processed by the single-chip computer displays. The software is programmed with assembly language and modular design idea. The design of the hardware circuit is simple and the subroutine has universal property, which fully meet the design requirements and possess a wide range of application and dissemination value.

  6. Knockout of the c-Jun N-terminal Kinase 2 aggravates the development of mild chronic dextran sulfate sodium colitis independently of expression of intestinal cytokines TNFα, TGFB1, and IL-6

    Directory of Open Access Journals (Sweden)

    Kersting S

    2013-02-01

    Full Text Available Sabine Kersting,1 Kirstin Reinecke,2 Christoph Hilgert,1 Monika S Janot,1 Elisabeth Haarmann,1 Martin Albrecht,1 Annette M Müller,3 Thomas Herdegen,2 Ulrich Mittelkötter,1 Waldemar Uhl,1 Ansgar M Chromik11Department of General and Visceral Surgery, St Josef Hospital, Ruhr-University of Bochum, Bochum, Germany; 2Institute of Experimental and Clinical Pharmacology, University Hospital of Schleswig-Holstein, Campus Kiel, Germany; 3Department of Pediatric Pathology, Rheinische Friedrich-Wilhems-University of Bonn, Bonn, GermanyIntroduction: The c-Jun N-terminal kinases (JNKs are involved in signal transduction of inflammatory bowel diseases. The aim of this study was to examine the function of JNKs by using a low-dose dextran sulfate sodium (DSS model in JNK1 knockout mice (Mapk8–/–, JNK2 knockout mice (Mapk9–/–, and wild-type controls (WT1, WT2.Methods: The animals were evaluated daily using a disease activity index. After 30 days, the intestine was evaluated histologically with a crypt damage score. CD4+ and CD8+ cells were quantified using immunofluorescence. Analysis of tumor necrosis factor-a (TNFα, interleukin-6 (IL-6, and transforming growth factor ß1 (TGFB1 expression was carried out using LightCycler® real-time polymerase chain reaction.Results: Cyclic administration of low-dose DSS (1% was not able to induce features of chronic colitis in Mapk8–/– WT2 mice. By contrast, DSS administration significantly increased the disease activity index in WT1 and Mapk9–/– mice. In Mapk9–/– mice, the crypt damage score and the number of CD4+ and CD8+ cells as features of chronic colitis/inflammation were also significantly elevated. Expression of TNFα, IL-6, and TGFB1 was not altered by the JNK knockout.Conclusion: Administering DSS at a defined low concentration that is unable to induce colitis in WT animals leads to clinically and histologically detectable chronic colitis in Mapk9–/– mice. The reason for this disease

  7. MORINGA TEA BLOCKS ACUTE LUNG INFLAMMATION INDUCED BY SWINE CONFINEMENT DUST THROUGH A MECHANISM INVOLVING TNF-α EXPRESSION, C-JUN N-TERMINAL KINASE ACTIVATION AND NEUTROPHIL REGULATION

    Directory of Open Access Journals (Sweden)

    Mykea Mcknight

    2014-01-01

    Full Text Available Plant based products represent a promising alternative to conventional treatments for inflammation. Moringa oleifera Lam is a tree rich in proteins, vitamins, minerals and a variety of phytochemcals with health benefits. Among the reported health benefits are antioxidant and anti-inflammatory properties. The purpose of this study was to investigate whether tea brewed from dried Moringa leaves would abrogate inflammation in a mouse model of acute lung inflammation induced by LPS or extracts prepared from dust collected from a swine confinement facility (DE. Mice were offered water or Moringa tea for seven days. Tea consumption was significantly greater than that of water consumption on days 1 and 6, but there were no significant differences in weight gain or food consumption. On day seven, mice from both groups were forced to inhale, via intranasal challenge, either Phosphate Buffered Saline (PBS, Lipopolysaccharide (LPS [10 µg mL-1] or DE [10%]. Compared to mice that drank water, mice that drank Moringa tea had significantly less protein (p<0.05 and cellular influx (p<0.0001 into the lung after inhalation of 10% DE. No difference in neutrophil migration into the lungs of water and M. tea groups after LPS or DE challenge was detected. But mice that drank tea had significantly (p<0.05 more neutrophils with apoptotic morphology after DE challenge. TNF-α expression 24 h after inhalation of 10% DE, was significantly higher (p<0.05 in lungs of M. tea mouse group as compared to water group. This increase in TNF-α was accompanied by higher levels of pro and anti-inflammatory cytokines. Finally, activation of c-Jun N-terminal Kinase (JNK in lungs of M. tea+DE group 24 h post inhalation was decreased. Taken together these results suggest that Moringa oleifera leaf tea exerts anti-inflammatory properties on acute lung inflammation induced by swine confinement dust through a mechanism involving neutrophil regulation and JNK

  8. The effect of hedgehog signaling pathway on c - jun, uPA expression of breast cancer cells MDA- MB - 231%Hedgehog通路对乳腺癌细胞MDA—MB-231c—jun、uPA表达的影响和机制

    Institute of Scientific and Technical Information of China (English)

    隆玲; 邓华瑜; 姜容; 陈黎

    2011-01-01

    目的:研究Hedgehog信号转导通路对人乳腺癌细胞MDA—MB-231c—jun、uPA表达的影响和作用机制,认识其在侵袭转移中的意义。方法:应用Hedgehog信号通路抑制剂Cyclopamine作用人乳腺癌细胞MDA—MB-231,Transwell小室进行侵袭迁移实验;Western blotting检测P—c—itin、uPA蛋白的水平:RT—PCR检测Gli1、c—jun和uPA的mRNA水平。结果:应用Cyclopamine后,细胞的侵袭迁移能力明显下降;P—c—Jun、uPA蛋白表达减少;Gli1、c—iun和uPAmRNA水平降低。结论:Hedgehog信号通路可通过活化c—jun上调uPA的表达,促进乳腺癌细胞MDA—MB-231细胞的侵袭转移。%Objective: To explore the effect and the possible mechanisms of Hedgehog singaling pathway on expression of c - jun, uPA in MDA - MB - 231 cells. Methods: Invasion and metastasis of MDA- MB- 231 cells were evaluated with transwell chamber.The expression of P- c- jun and uPA were detected by Western blot. The mRNA levels of Gli 1, c - jun and uPA were measured by reverse transcriplion - poly - merage chain reaction ( RT - PCR ). Results : When MDA - MB - 231 cells were treated with Cyclopamine, invasion and metastasis were depressed. The expression level of P- c- Jun and uPA were decreased. The mRNA levels of Ghl, c-jun and uPA were also reduced. Conclusion: invasion, metastasis and uPA level can be induced by activeled Hedgehog singnaling nathwav with activation of c - iun.

  9. The effect of tyre and rider properties on the stability of a bicycle

    NARCIS (Netherlands)

    Bulsink, V.E.; Doria, A.; Belt, van de D.; Koopman, H.F.J.M.

    2015-01-01

    To work towards an advanced model of the bicycle-rider-environment system, an open-loop bicycle-rider model was developed in the commercial multibody dynamics software ADAMS. The main contribution of this article to bicycle dynamics is the analysis of tyre and rider properties that influence bicycle

  10. Helmet Wearing Among Users of a Public Bicycle-Sharing Program in the District of Columbia and Comparable Riders on Personal Bicycles

    Science.gov (United States)

    Roffenbender, Jason S.; Anderko, Laura

    2012-01-01

    Bicycle-sharing programs are increasingly popular and have the potential to increase physical activity and decrease air pollution, but anecdotal evidence suggests helmet use is lower among users of bicycle-sharing programs than cyclists on private bicycles. We conducted a cross-sectional study to assess helmet use among users of a bicycle-sharing program in Washington, DC. Helmet use was significantly lower among cyclists on shared bicycles than private bicycles, highlighting a need for targeted helmet promotion activities. PMID:22698021

  11. Improving bicycle safety: The role of paediatricians and family physicians.

    Science.gov (United States)

    Leblanc, John C; Huybers, Sherry

    2004-05-01

    Cycling is a complex activity requiring motor, sensory and cognitive skills that develop at different rates from childhood to adolescence. While children can successfully ride a two-wheeled bicycle at age five or six, judgment of road hazards are poor at that age and matures slowly until adult-like judgment is reached in early adolescence. Safe cycling depends on the care, skills and judgment of cyclists and motorists; roadway design that promotes safe coexistence of bicycles and motor vehicles; and the use of safety devices, including bicycle helmets, lights and reflective tape. Whereas, research into optimal roadway design and educational programs for drivers to improve road safety has yielded contradictory results, the benefits of bicycle helmet use and programs to enhance their use have been clearly shown. This paper has the following objectives for paediatricians and family physicians: To understand the relationship between bicycle safety and children's motor and cognitive skills.To understand the effectiveness and limitations of strategies to improve bicycle safety.To describe activities to promote bicycle safety that physicians can undertake in clinical settings and in the community. PMID:19657515

  12. The frequency of single-bicycle crashes (SBCs) in countries with varying bicycle mode shares

    DEFF Research Database (Denmark)

    Schepers, Paul; Agerholm, Niels; Amoros, Emmanuelle;

    In  order  to  encourage  cycling,  we  need  to  reduce  the  hazards  that  cyclists  face. Single-bicycle crashes or ‘bicycle-only crashes’ are falls and obstacle collisions in which only one cyclist is involved. Between 60 and 95% of cyclists admitted to hospital or treated at an emergency...... department are victims of single-bicycle crashes. As proportion of the total number of traffic casualties  the  share  exceeds  20%  in  most  countries  with  medium  to  high  levels  of cycling.  This paper  discusses  the  prevalence  of  the  problem  and  describes  measures  that  may  both reduce...... the risks and make cycling a more attractive transport choice at the same time....

  13. Symbolic derivation of bicycle kinematics with toroidal wheels

    Directory of Open Access Journals (Sweden)

    Wang Everett X.

    2015-01-01

    Full Text Available Bicycle kinematics with toroidal wheels is presented in this paper. Using symbolic mathematic tool Maple, we obtain two holonomic and four nonholonomic constraint equations due to front and rear wheels of a bicycle. We show that the two holonomic constraints cannot be expressed in quartic form for bicycle rear body pitch angle unless the minor (crown radius of the torus are the same for both the front and rear wheels. In addition, we show that all the constraints can be written in differential form, from which a constraint matrix is constructed, according to standard procedure for developing dynamics in robotics.

  14. Associations between a walkability index and bicycle use in Denmark

    DEFF Research Database (Denmark)

    Madsen, T.; Christiansen, L.; Nielsen, Thomas Alexander Sick;

    2012-01-01

    /day, and important health benefits can accrue from regular commuting cycling. Studies have shown a positive correlation between walkability attributes of neighborhood environments (street connectivity, and use mix, residential density, retail floor area ratio) and cycling. Results from Australia/Belgium show...... associations between measures of walkability and bicycle use for transport and the present study focuses on exploring whether these findings can be applied to a Danish setting where cycling culture differs and bicycle share is much higher (17% of all trips are by bicycle)...

  15. Associations between bicycling and carotid arterial stiffness in adolescents

    DEFF Research Database (Denmark)

    Ried-Larsen, M; Grøntved, A; Østergaard, Lars;

    2015-01-01

    The aim of the study was to investigate the associations between bicycling and carotid arterial stiffness, independent of objectively measured moderate-and-vigorous physical activity. This cross-sectional study included 375 adolescents (age 15.7 ± 0.4 years) from the Danish site of the European...... modulus [standard beta -0.48 (95% CI -0.91 to -0.06)]. Similar trends were observed when investigating the association between commuter bicycling and carotid arterial stiffness. These associations were not observed in girls. Our observations suggest that increasing bicycling in adolescence may...

  16. The effect of tyre and rider properties on the stability of a bicycle

    OpenAIRE

    Bulsink, V.E.; Doria, A.; Belt, van de, M.; Koopman, H.F.J.M.

    2015-01-01

    To work towards an advanced model of the bicycle-rider-environment system, an open-loop bicycle-rider model was developed in the commercial multibody dynamics software ADAMS. The main contribution of this article to bicycle dynamics is the analysis of tyre and rider properties that influence bicycle stability. A system identification method is used to extract linear stability properties from time domain analysis. The weave and capsize eigenmodes of the bicycle-rider system are analysed. The e...

  17. Bicyclic graphs with maximal revised Szeged index

    CERN Document Server

    Li, Xueliang

    2011-01-01

    The revised Szeged index $Sz^*(G)$ is defined as $Sz^*(G)=\\sum_{e=uv \\in E}(n_u(e)+ n_0(e)/2)(n_v(e)+ n_0(e)/2),$ where $n_u(e)$ and $n_v(e)$ are, respectively, the number of vertices of $G$ lying closer to vertex $u$ than to vertex $v$ and the number of vertices of $G$ lying closer to vertex $v$ than to vertex $u$, and $n_0(e)$ is the number of vertices equidistant to $u$ and $v$. Hansen used the AutoGraphiX and made the following conjecture about the revised Szeged index for a connected bicyclic graph $G$ of order $n \\geq 6$:

  18. Bicycling induced pudendal nerve pressure neuropathy.

    Science.gov (United States)

    Silbert, P L; Dunne, J W; Edis, R H; Stewart-Wynne, E G

    1991-01-01

    Pudendal neuropathies are well recognised as part of more generalised peripheral neuropathies; however, focal abnormalities of the pudendal nerve due to cycling-related injuries have been infrequently reported. We describe two patients who developed pudendal neuropathies secondary to pressure effects on the perineum from racing-bicycle saddles. Both were male competitive athletes, one of whom developed recurrent numbness of the penis and scrotum after prolonged cycling; the other developed numbness of the penis, an altered sensation of ejaculation, with disturbance of micturition and reduced awareness of defecation. Both patients improved with alterations in saddle position and riding techniques. We conclude that pudendal nerve pressure neuropathy can result from prolonged cycling, particularly when using a poor riding technique. PMID:1821826

  19. Bicycle helmet ventilation and comfort angle dependence.

    Science.gov (United States)

    Brühwiler, Paul A; Ducas, Charline; Huber, Roman; Bishop, Phillip A

    2004-09-01

    Five modern bicycle helmets were studied to elucidate some of the variations in ventilation performance, using both a heated manikin headform and human subjects (n = 7). Wind speed and head angle were varied to test their influence on the measured steady-state heat exchange (cooling power) in the skull section of the headform. The cooling power transmitted by the helmets varied from about 60% to over 90% of that of the nude headform, illustrating the range of present manufacturer designs. Angling the head forward by 30 degrees was found to provide better cooling power to the skull (up to 25%) for three of the helmets and almost equal cooling power in the remaining two cases. Comparisons of skull ventilation at these angles with human subjects strongly supported the headform results.

  20. Bamboo Bicycle – Past or Future?

    Directory of Open Access Journals (Sweden)

    Suzana Jakovljević

    2016-01-01

    Full Text Available In this article the experiment was carried out to establish tensile strength values of two different bamboo species, which are obtained by the static tensile test. The tensile strength results of two tested species Tonkin Cane and Ku Zhu bamboo are presented and compared with traditional materials used for bicycle frame to determine their suitability for designing a frame. Physiology and other properties of bamboo were elaborated as well. The purpose of this study was to gain more knowledge on bamboo and prove his suitability in use as an alternative for ecologically unacceptable materials. Therefore, application of the natural materials is essential for the sustainable development. The fact that they have unlimited resources the use of bamboo has great potential and this article explains why.

  1. Construction and identification of dominant-negative c-Jun N-terminal kinase(DN-JNK)recombinant adenovirus%DN-JNK基因重组腺病毒的构建和鉴定

    Institute of Scientific and Technical Information of China (English)

    张佳妮; 刘慧霞; 陈金虎; 郭敏; 全养雅; 谭莺

    2009-01-01

    Objective To construct and identify replication deficient recombinant adenovirus expressing human c-Jun N-terminal kinase(JNK)by homologous recombination adenovirus dominant-negative type JNK(Ad-DN-JNK).Methods The linearized recombinant shuttle vector pAdTrack-CMV-DN-JNK Was co-transformed with backbone vector pAdEasy-l into bacteria BJ5183 for recombinant adenoviral vector.The recombinant adenoviral vector was transfected into HEK293 packing cells tO construct replication deficient recombinant adenovirus,and then the recombinant edenovirns WaS detected by PCR and DNA sequencing.Western blot analysis was utilized to detect the Cxpression of Ad-DN-JNK and the level of insulin receptor substrate l Serine307 phosphorylation.Results JNK recombinant adenoviral vectorcould be effectively transfeeted into HEK 293 cell and successfully packed by intracellular enzyme.The expression of green fluorescent protein(GFP)Was observed on the 5th day after transfection.The fragment of JNK gene waS amplified by PCR and identified by sequencing.The titer of the prepared Ad-DN-JNK is 2.5×1010 pfu/ml.The animal experiment confirmed that constructed Ad-DN-JNK could be effectively expressed in liver tissue.Conclusion The research successfully constructed recombinant adenoviral vector and recombinant adenoviral particle.Animal experiment demonstrated the Ad-DN-JNK could effectively mediated the expression of DN-JNK gene and down-regulated the level of IRSlscfine307 phosphorylation.The achievement laid a foundation for further investigation of the function and application of JNK.%目的 制备表达人c-jun氨基末端激酶(JNK)复制缺陷型重组腺病毒(Ad-DN-JNK).并通过动物实验进行功能鉴定.方法 将重组穿梭载体pAdTraek-CMV-DN-JNK线性化后,与pAdEasy-1共转化大肠杆菌BJ5138,进行同源重组得到重组腺病毒载体.将重组腺病毒栽体转染入包装细胞HEK293内制备复制缺陷型重组腺病毒,并经PCR及DNA测序鉴定.Western blot检

  2. Will a bicycle friendly policy make passenger travel more sustainably?

    DEFF Research Database (Denmark)

    Christensen, Linda; Jensen, Thomas Christian

    The purpose of this paper is to analyse the possibility to transfer a larger part of the short car trips to walking or bicycling in order to obtain environmental and health benefits. The project contains a logistic choice model used to explain which circumstances are particularly important...... for choosing walking and bicycling, and how very different instruments can promote walking and bicycling at the expense of short car trips. Furthermore, the paper describes the most important factors when choosing between bicycling and walking and car driving, respectively, in case of trips of up to 22 km....... Hills and temperature differences appear to be particularly impor-tant, apart from car ownership. Regarding the socio-economy, particularly the number of children is of importance. Furthermore, the paper elucidates the effect of various instruments to promote the transfer of short car trips to walking...

  3. Fluid Mechanics of a High Performance Racing Bicycle Wheel

    Science.gov (United States)

    Mercat, Jean-Pierre; Cretoux, Brieuc; Huat, Francois-Xavier; Nordey, Benoit; Renaud, Maxime; Noca, Flavio

    2013-11-01

    In 2012, MAVIC released the most aerodynamic bicycle wheel on the market, the CXR 80. The french company MAVIC has been a world leader for many decades in the manufacturing of bicycle wheels for competitive events such as the Olympic Games and the Tour de France. Since 2010, MAVIC has been in a research partnership with the University of Applied Sciences in Geneva, Switzerland, for the aerodynamic development of bicycle wheels. While most of the development up to date has been performed in a classical wind tunnel, recent work has been conducted in an unusual setting, a hydrodynamic towing tank, in order to achieve low levels of turbulence and facilitate quantitative flow visualization (PIV). After a short introduction on the aerodynamics of bicycle wheels, preliminary fluid mechanics results based on this novel setup will be presented.

  4. Improving bicycle safety: The role of paediatricians and family physicians

    OpenAIRE

    LeBlanc, John C.; Huybers, Sherry

    2004-01-01

    Cycling is a complex activity requiring motor, sensory and cognitive skills that develop at different rates from childhood to adolescence. While children can successfully ride a two-wheeled bicycle at age five or six, judgment of road hazards are poor at that age and matures slowly until adult-like judgment is reached in early adolescence. Safe cycling depends on the care, skills and judgment of cyclists and motorists; roadway design that promotes safe coexistence of bicycles and motor vehicl...

  5. On the Skill of Balancing While Riding a Bicycle.

    Science.gov (United States)

    Cain, Stephen M; Ashton-Miller, James A; Perkins, Noel C

    2016-01-01

    Humans have ridden bicycles for over 200 years, yet there are no continuous measures of how skill differs between novice and expert. To address this knowledge gap, we measured the dynamics of human bicycle riding in 14 subjects, half of whom were skilled and half were novice. Each subject rode an instrumented bicycle on training rollers at speeds ranging from 1 to 7 m/s. Steer angle and rate, steer torque, bicycle speed, and bicycle roll angle and rate were measured and steering power calculated. A force platform beneath the roller assembly measured the net force and moment that the bicycle, rider and rollers exerted on the floor, enabling calculations of the lateral positions of the system centers of mass and pressure. Balance performance was quantified by cross-correlating the lateral positions of the centers of mass and pressure. The results show that all riders exhibited similar balance performance at the slowest speed. However at higher speeds, the skilled riders achieved superior balance performance by employing more rider lean control (quantified by cross-correlating rider lean angle and bicycle roll angle) and less steer control (quantified by cross-correlating steer rate and bicycle roll rate) than did novice riders. Skilled riders also used smaller steering control input with less variation (measured by average positive steering power and standard deviations of steer angle and rate) and less rider lean angle variation (measured by the standard deviation of the rider lean angle) independent of speed. We conclude that the reduction in balance control input by skilled riders is not due to reduced balance demands but rather to more effective use of lean control to guide the center of mass via center of pressure movements. PMID:26910774

  6. On the Skill of Balancing While Riding a Bicycle.

    Science.gov (United States)

    Cain, Stephen M; Ashton-Miller, James A; Perkins, Noel C

    2016-01-01

    Humans have ridden bicycles for over 200 years, yet there are no continuous measures of how skill differs between novice and expert. To address this knowledge gap, we measured the dynamics of human bicycle riding in 14 subjects, half of whom were skilled and half were novice. Each subject rode an instrumented bicycle on training rollers at speeds ranging from 1 to 7 m/s. Steer angle and rate, steer torque, bicycle speed, and bicycle roll angle and rate were measured and steering power calculated. A force platform beneath the roller assembly measured the net force and moment that the bicycle, rider and rollers exerted on the floor, enabling calculations of the lateral positions of the system centers of mass and pressure. Balance performance was quantified by cross-correlating the lateral positions of the centers of mass and pressure. The results show that all riders exhibited similar balance performance at the slowest speed. However at higher speeds, the skilled riders achieved superior balance performance by employing more rider lean control (quantified by cross-correlating rider lean angle and bicycle roll angle) and less steer control (quantified by cross-correlating steer rate and bicycle roll rate) than did novice riders. Skilled riders also used smaller steering control input with less variation (measured by average positive steering power and standard deviations of steer angle and rate) and less rider lean angle variation (measured by the standard deviation of the rider lean angle) independent of speed. We conclude that the reduction in balance control input by skilled riders is not due to reduced balance demands but rather to more effective use of lean control to guide the center of mass via center of pressure movements.

  7. On the Skill of Balancing While Riding a Bicycle.

    Directory of Open Access Journals (Sweden)

    Stephen M Cain

    Full Text Available Humans have ridden bicycles for over 200 years, yet there are no continuous measures of how skill differs between novice and expert. To address this knowledge gap, we measured the dynamics of human bicycle riding in 14 subjects, half of whom were skilled and half were novice. Each subject rode an instrumented bicycle on training rollers at speeds ranging from 1 to 7 m/s. Steer angle and rate, steer torque, bicycle speed, and bicycle roll angle and rate were measured and steering power calculated. A force platform beneath the roller assembly measured the net force and moment that the bicycle, rider and rollers exerted on the floor, enabling calculations of the lateral positions of the system centers of mass and pressure. Balance performance was quantified by cross-correlating the lateral positions of the centers of mass and pressure. The results show that all riders exhibited similar balance performance at the slowest speed. However at higher speeds, the skilled riders achieved superior balance performance by employing more rider lean control (quantified by cross-correlating rider lean angle and bicycle roll angle and less steer control (quantified by cross-correlating steer rate and bicycle roll rate than did novice riders. Skilled riders also used smaller steering control input with less variation (measured by average positive steering power and standard deviations of steer angle and rate and less rider lean angle variation (measured by the standard deviation of the rider lean angle independent of speed. We conclude that the reduction in balance control input by skilled riders is not due to reduced balance demands but rather to more effective use of lean control to guide the center of mass via center of pressure movements.

  8. Comparative life cycle assessment of ghana-made bamboo-frame bicycle and conventional bicycles assembled and used in the Netherlands

    NARCIS (Netherlands)

    Agyekum, E.O.; Fortuin, K.P.J.; Harst, van der E.J.M.

    2014-01-01

    In order to assess the sustainability of bamboo-framed bicycles produced in Ghana, an environmental and social life cycle assessments (LCA) were performed. For the environmental LCA, a bamboo-frame bicycle was compared with aluminium- and steel-frame bicycles, focussing on processes related to the f

  9. Bicycle helmet use and non-use - recently published research.

    Science.gov (United States)

    Uibel, Stefanie; Müller, Daniel; Klingelhoefer, Doris; Groneberg, David A

    2012-05-25

    Bicycle traumata are very common and especially neurologic complications lead to disability and death in all stages of the life. This review assembles the most recent findings concerning research in the field of bicycle traumata combined with the factor of bicycle helmet use. The area of bicycle trauma research is by nature multidisciplinary and relevant not only for physicians but also for experts with educational, engineering, judicial, rehabilitative or public health functions. Due to this plurality of global publications and special subjects, short time reviews help to detect recent research directions and provide also information from neighbour disciplines for researchers. It can be stated that to date, that although a huge amount of research has been conducted in this area more studies are needed to evaluate and improve special conditions and needs in different regions, ages, nationalities and to create successful prevention programs of severe head and face injuries while cycling.Focus was explicit the bicycle helmet use, wherefore sledding, ski and snowboard studies were excluded and only one study concerning electric bicycles remained due to similar motion structures within this review. The considered studies were all published between January 2010 and August 2011 and were identified via the online databases Medline PubMed and ISI Web of Science.

  10. Test Verification and Design of the Bicycle Frame Parameters

    Institute of Scientific and Technical Information of China (English)

    ZHANG Long; XIANG Zhongxia; LUO Huan; TIAN Guan

    2015-01-01

    Research on design of bicycles is concentrated on mechanism and auto appearance design, however few on matches between the bike and the rider. Since unreasonable human-bike relationship leads to both riders’ worn-out joints and muscle injuries, the design of bicycles should focus on the matching. In order to find the best position of human-bike system, simulation experiments on riding comfort under different riding postures are done with the lifemode software employed to facilitate the cycling process as well as to obtain the best position and the size function of it. With BP neural network and GA, analyzing simulation data, conducting regression analysis of parameters on different heights and bike frames, the equation of best position of human-bike system is gained at last. In addition, after selecting testers, customized bikes based on testers’ height dimensions are produced according to the size function. By analyzing and comparing the experimental data that are collected from testers when riding common bicycles and customized bicycles, it is concluded that customized bicycles are four times even six times as comfortable as common ones. The equation of best position of human-bike system is applied to improve bikes’ function, and the new direction on future design of bicycle frame parameters is presented.

  11. [Bicycle spoke-related injuries in children: emphasise prevention].

    Science.gov (United States)

    Kramer, William L M; Haaring, Gert-Jan

    2011-01-01

    Three children, a 6-year-old boy and two girls aged 5 and 4 years, were seen at an emergency department due to distal lower-leg injuries sustained from the spokes of bicycle wheels. All three patients had been passengers on rear carrying seats of moving bicycles. Only the third bicyclist had used a special child safety seat. The second girl had drawn her foot up from underneath a strap and suffered a tibial fracture later treated with an osteosynthetic plate. The other two patients recovered after conservative casting treatment. Bicycle spoke-related injuries are sustained when the foot or lower limb makes contact with the spokes of a bicycle wheel and usually by children who are bicycle passengers. In the Netherlands, approximately 4600 children are seen at emergency departments with such injuries each year. Bicycle spoke-related accidents can cause severe damage that can result in lengthy recovery periods. Not only physical complications but also psychological ones can occur. The latter are often overlooked but do deserve proper treatment. The physician treating a spoke-related injury is in a good position to advice parents as to preventive measures, particularly on the use of special child safety seats.

  12. Reviving a ghost in the history of technology: the social construction of the recumbent bicycle.

    Science.gov (United States)

    Ahmed, Hassaan; Qureshi, Omer Masood; Khan, Abid Ali

    2015-02-01

    Recumbent bicycles have never truly been associated with international cycling. Conventional safety (upright) bicycles have long been at the center of the cycling world, for both sport and transportation. This is despite the fact that recumbent bicycles are faster, more comfortable, and more efficient than the upright bicycles. The aim of this article is to explain the historical and social perspectives that led to the rejection of the recumbent bicycle by utilizing the theory of Social Construction of Technology (SCOT) and Bijker's two power theory, providing a contrast with the adoption of the safety bicycle.

  13. ROUTE CHOICE MODELLING FOR BICYCLE TRIPS

    Directory of Open Access Journals (Sweden)

    Ehsan Beheshtitabar

    2014-06-01

    Full Text Available This paper intends to find out which parameters have the highest influence on bicyclists’ route-choice-behaviour and how they contribute. There are many attributes considered throughout different studies that are favoured by cyclists. The attributes are the basis for generating a function which predicts the route choice of cyclists. The paper aims at making a comparison between distance-based routes and attribute-based routes. The model for creating the bicycle route choice program is based on the network model of Norrköping, Sweden. The preferred attributes of the model each assign a weight in the cost function of the model for each link of the urban network. The algorithm of the lowest cost function route searches the shortest path in terms of assigned link costs over the whole network. For comparing the results of the cost function and the shortest route (between an origin-destination, the model has a shortest path finding algorithm between different Origin and Destination pairs implemented. It has been viewed that around 25% of all cumulative routes do not show any distance differences between the shortest path distance and attributes based solution. With the used weights of the Standard scenario, it can be seen that the trade-off between shortest distance and safety respectively comfort can be optimized, fulfilling both criteria (distance and safety/comfort.

  14. Bicycle, city and education: search moves

    Directory of Open Access Journals (Sweden)

    Sheila Hempkemeyer

    2016-07-01

    Full Text Available This study comes from a Master’s degree in Education research, which investigates narratives of “pedaling beings” starting from the relationship bicycle-city. The theoretical assumptions lean on the Cultural Studies and concepts about education, culture, everyday life, experience and narratives. Researching with narratives closes everyday life and promotes co-authorship to the subjects in the paper. The article puts in discussion some forms of contemporary subjectivity, resistance techniques and expression. A study that builds narratives and reflections about the experiences of theses hybrid subjects and their everyday life, questioning their way of life in the city. Thinking in this urban medley is connect the environment and the dynamic of these pedaling bodies, emerging other ways of education and interaction with the medium, weaving multiple affectations in aesthetics, poetry, politics, opening breaches to reflect in the everyday happenings. The article also discusses the movements in research and the effects in those who research and are researched.

  15. Built environment influences on healthy transportation choices: bicycling versus driving.

    Science.gov (United States)

    Winters, Meghan; Brauer, Michael; Setton, Eleanor M; Teschke, Kay

    2010-12-01

    A growing body of evidence links the built environment to physical activity levels, health outcomes, and transportation behaviors. However, little of this research has focused on cycling, a sustainable transportation option with great potential for growth in North America. This study examines associations between decisions to bicycle (versus drive) and the built environment, with explicit consideration of three different spatial zones that may be relevant in travel behavior: trip origins, trip destinations, and along the route between. We analyzed 3,280 utilitarian bicycle and car trips in Metro Vancouver, Canada made by 1,902 adults, including both current and potential cyclists. Objective measures were developed for built environment characteristics related to the physical environment, land use patterns, the road network, and bicycle-specific facilities. Multilevel logistic regression was used to model the likelihood that a trip was made by bicycle, adjusting for trip distance and personal demographics. Separate models were constructed for each spatial zone, and a global model examined the relative influence of the three zones. In total, 31% (1,023 out of 3,280) of trips were made by bicycle. Increased odds of bicycling were associated with less hilliness; higher intersection density; less highways and arterials; presence of bicycle signage, traffic calming, and cyclist-activated traffic lights; more neighborhood commercial, educational, and industrial land uses; greater land use mix; and higher population density. Different factors were important within each spatial zone. Overall, the characteristics of routes were more influential than origin or destination characteristics. These findings indicate that the built environment has a significant influence on healthy travel decisions, and spatial context is important. Future research should explicitly consider relevant spatial zones when investigating the relationship between physical activity and urban form.

  16. Modeling the Distribution Characteristics of Urban Public Bicycle Rental Duration

    Directory of Open Access Journals (Sweden)

    Shuichao Zhang

    2016-01-01

    Full Text Available In order to model the distribution characteristics of public bicycle rental durations, individual journey data for three cities in China (Ningbo, Hangzhou, and Beijing, for weekdays, was obtained. The distribution curves for public bicycle rental duration in the three cities were found to be extremely similar, with small differences among the weekdays. The basic parameters such as the average rental duration, the rental duration corresponding to the maximum rental frequency, and the rental duration corresponding to 75% degree were then calculated. On this basis, the radioactive decay law from physics was used to establish a theoretical model for the relationship between rental frequency and rental duration. The data on public bicycle rental duration in Ningbo, Hangzhou, and Beijing were used to test the model and produce a corrected theoretical model. The results indicate that the relationship between rental frequency and rental duration obeys the decay law. The study results provide important theoretical support for the rental station planning of bicycle sharing systems, as well as the allocation, operation, and dispatch of public bicycles.

  17. Bicycling injury hospitalisation rates in Canadian jurisdictions: analyses examining associations with helmet legislation and mode share

    OpenAIRE

    Teschke, Kay; Koehoorn, Mieke; Shen, Hui; Dennis, Jessica

    2015-01-01

    Objectives The purpose of this study was to calculate exposure-based bicycling hospitalisation rates in Canadian jurisdictions with different helmet legislation and bicycling mode shares, and to examine whether the rates were related to these differences. Methods Administrative data on hospital stays for bicycling injuries to 10 body region groups and national survey data on bicycling trips were used to calculate hospitalisation rates. Rates were calculated for 44 sex, age and jurisdiction st...

  18. Investigation with Bluetooth Sensors of Bicycle Travel Time Estimation on a Short Corridor

    OpenAIRE

    Zhenyu Mei; Dianhai Wang; Jun De Chen

    2012-01-01

    Accurate travel time information acquisition is essential to the effective planning and management of bicycle travel conditions. Traditionally, video camera data have been used as the primary source for measuring the quality of bicycle travel time. This paper deals with an investigation of bicycle travel time estimation on a short corridor, using Bluetooth sensors, based on field survey of travel time at one arterial road in Hangzhou. Usually bicycle travel time estimates with Bluetooth senso...

  19. Influences of infrastructure and attitudes to health on value of travel time savings in bicycle journeys

    OpenAIRE

    Björklund, Gunilla; Mortazavi , Reza

    2013-01-01

    In this paper we investigate how attitudes to health and exercise in connection with cycling influence the estimation of values of travel time savings in different kinds of bicycle environments (mixed traffic, bicycle lane in the road way, bicycle path next to the road, and bicycle path not in connection with the road). The results, based on two Swedish stated choice studies, suggest that the values of travel time savings are lower when cycling in better conditions. Surprisingly, the responde...

  20. Predicting Public Bicycle Adoption Using the Technology Acceptance Model

    Directory of Open Access Journals (Sweden)

    Benjamin T. Hazen

    2015-10-01

    Full Text Available Bicycle sharing programs provide a sustainable mode of urban transportation. Although cities across the globe have developed these systems for their citizens and visitors, usage rates are not as high as anticipated. This research uses the technology acceptance model as the basis to understand one’s intention to adopt bicycle sharing programs. Using survey data derived from 421 participants in Beijing, China, the proposed covariance-based structural equation model consisting of perceived quality, perceived convenience, and perceived value is found to predict 50.5% of the variance in adoption intention. The findings of this research contribute to theory and practice in the burgeoning literature on public bicycle systems and sustainable urban transportation by offering a theoretical lens through which to consider system adoption, and providing information to practitioners as to what factors might contribute most to adoption.

  1. Using magnetorheological fluids in an innovative hybrid bicycle damper

    Science.gov (United States)

    Shiao, Y. J.; Nguyen, T. S.

    2015-12-01

    Magnetorheological fluids are capable of changing their viscosity quickly. This can provide good controllability and fast dynamic response. A conventional passive suspension system with air spring or hydraulic damper has simple design and financial benefit for bicycles, but its operation is uncontrollable and non-adaptive. This paper presented a semi-active hybrid bicycle suspension system which combines conventional air spring and a new magnetorheological damping brake together to reduce vibration of a bicycle. A multi-layer magnetorheological brake and linkage mechanism are connected to bike fork to form the adaptive damping part of the innovative hybrid suspension system. The simulation results proved that the semi-active suspension system can reduce bike vibration effectively.

  2. Interventions in Bicycle Infrastructure, Lessons from Dutch and Danish Cases

    DEFF Research Database (Denmark)

    van Goeverden, K.; Nielsen, Thomas Alexander Sick; Harder, Henrik;

    2015-01-01

    Today the interest in cycling is increasing worldwide and in many countries authorities are faced with the question how cycling can be promoted efficiently. In the Netherlands and Denmark, this question came up already in the 1970s when the downsides of the rapidly increasing motorisation became...... evident. At the time, in both countries large scale interventions in bicycle infrastructure were introduced and evaluated extensively in order to create knowledge on efficient promoting of cycling in urban areas. The interventions included the construction of new bicycle routes on urban arterials in some...... was used in both countries for formulating guidelines for road and bicycle infrastructure design. However, at that time the study results were not shared with the international scientific audience. The paper describes briefly the classical cases and the main study results. The outcomes of the classical...

  3. Bicycling crash characteristics: An in-depth crash investigation study.

    Science.gov (United States)

    Beck, Ben; Stevenson, Mark; Newstead, Stuart; Cameron, Peter; Judson, Rodney; Edwards, Elton R; Bucknill, Andrew; Johnson, Marilyn; Gabbe, Belinda

    2016-11-01

    The aim of this study was to describe the crash characteristics and patient outcomes of a sample of patients admitted to hospital following bicycle crashes. Injured cyclists were recruited from the two major trauma services for the state of Victoria, Australia. Enrolled cyclists completed a structured interview, and injury details and patient outcomes were extracted from the Victorian State Trauma Registry (VSTR) and the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR). 186 cyclists consented to participate in the study. Crashes commonly occurred during daylight hours and in clear weather conditions. Two-thirds of crashes occurred on-road (69%) and were a combination of single cyclist-only events (56%) and multi-vehicle crashes (44%). Of the multi-vehicle crashes, a motor vehicle was the most common impact partner (72%) and distinct pre-crash directional interactions were observed between the cyclist and motor vehicle. Nearly a quarter of on-road crashes occurred when the cyclist was in a marked bicycle lane. Of the 31% of crashes that were not on-road, 28 (15%) occurred on bicycle paths and 29 (16%) occurred in other locations. Crashes on bicycle paths commonly occurred on shared bicycle and pedestrian paths (83%) and did not involve another person or vehicle. Other crash locations included mountain bike trails (39%), BMX parks (21%) and footpaths (18%). While differences in impact partners and crash characteristics were observed between crashes occurring on-road, on bicycle paths and in other locations, injury patterns and severity were similar. Most cyclists had returned to work at 6 months post-injury, however only a third of participants reported a complete functional recovery. Further research is required to develop targeted countermeasures to address the risk factors identified in this study. PMID:27544886

  4. Bicycling crash characteristics: An in-depth crash investigation study.

    Science.gov (United States)

    Beck, Ben; Stevenson, Mark; Newstead, Stuart; Cameron, Peter; Judson, Rodney; Edwards, Elton R; Bucknill, Andrew; Johnson, Marilyn; Gabbe, Belinda

    2016-11-01

    The aim of this study was to describe the crash characteristics and patient outcomes of a sample of patients admitted to hospital following bicycle crashes. Injured cyclists were recruited from the two major trauma services for the state of Victoria, Australia. Enrolled cyclists completed a structured interview, and injury details and patient outcomes were extracted from the Victorian State Trauma Registry (VSTR) and the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR). 186 cyclists consented to participate in the study. Crashes commonly occurred during daylight hours and in clear weather conditions. Two-thirds of crashes occurred on-road (69%) and were a combination of single cyclist-only events (56%) and multi-vehicle crashes (44%). Of the multi-vehicle crashes, a motor vehicle was the most common impact partner (72%) and distinct pre-crash directional interactions were observed between the cyclist and motor vehicle. Nearly a quarter of on-road crashes occurred when the cyclist was in a marked bicycle lane. Of the 31% of crashes that were not on-road, 28 (15%) occurred on bicycle paths and 29 (16%) occurred in other locations. Crashes on bicycle paths commonly occurred on shared bicycle and pedestrian paths (83%) and did not involve another person or vehicle. Other crash locations included mountain bike trails (39%), BMX parks (21%) and footpaths (18%). While differences in impact partners and crash characteristics were observed between crashes occurring on-road, on bicycle paths and in other locations, injury patterns and severity were similar. Most cyclists had returned to work at 6 months post-injury, however only a third of participants reported a complete functional recovery. Further research is required to develop targeted countermeasures to address the risk factors identified in this study.

  5. Bicycle Training for Youth with Down Syndrome and Autism Spectrum Disorders

    Science.gov (United States)

    MacDonald, Megan; Esposito, Phil; Hauck, Janet; Jeong, Irully; Hornyak, Joseph; Argento, Angela; Ulrich, Dale A.

    2012-01-01

    Children with Down syndrome (DS) and autism spectrum disorders (ASD) frequently have difficulty riding a two-wheel bicycle. The purpose of this study was to investigate an intervention using an adapted bicycle and individualized instruction to teach 71 youth to ride a standard two-wheel bicycle. Youth with DS (n = 30) and ASD (n = 41) between the…

  6. A City Plans for Bicycles: A Case Study of Olympia, Washington.

    Science.gov (United States)

    Litman, Todd

    1990-01-01

    Discusses community planning for bicycling programs with emphasis on safety education for children and adults, enforcement of bicycle laws, engineering improvements, and special events. Describes how Olympia improved existing bicycling facilities and summarizes planning, communication, engineering, and policy issues addressed. (SV)

  7. Bicycle cycles and mobility patterns - Exploring and characterizing data from a community bicycle program

    CERN Document Server

    Kaltenbrunner, Andreas; Grivolla, Jens; Codina, Joan; Banchs, Rafael

    2008-01-01

    This paper provides an analysis of human mobility data in an urban area using the amount of available bikes in the stations of the community bicycle program Bicing in Barcelona. The data was obtained by periodic mining of a KML-file accessible through the Bicing website. Although in principle very noisy, after some preprocessing and filtering steps the data allows to detect temporal patterns in mobility as well as identify residential, university, business and leisure areas of the city. The results lead to a proposal for an improvement of the bicing website, including a prediction of the number of available bikes in a certain station within the next minutes/hours. Furthermore a model for identifying the most probable routes between stations is briefly sketched.

  8. Experimental and mathematical car-bicycle collision simulations.

    OpenAIRE

    Huybers, J.J.W. & Janssen, E.G.

    1988-01-01

    The results of 35 mathematical simulations will be used to get a better insight in car-bicycle collisions. This information will be used later on to formulate hypotheses to be tested in an accident investigation project. In this paper special attention is given to the influence of the shape of the car and the dimensions of the bicycle/cyclist on the severity of the impacts. It is known that the speed of the car at impact is an important parameter in the resulting injury severity of the cyclis...

  9. Head injuries and bicycle helmet laws.

    Science.gov (United States)

    Robinson, D L

    1996-07-01

    The first year of the mandatory bicycle helmet laws in Australia saw increased helmet wearing from 31% to 75% of cyclists in Victoria and from 31% of children and 26% of adults in New South Wales (NSW) to 76% and 85%. However, the two major surveys using matched before and after samples in Melbourne (Finch et al. 1993; Report No. 45, Monash Univ. Accident Research Centre) and throughout NSW (Smith and Milthorpe 1993; Roads and Traffic Authority) observed reductions in numbers of child cyclists 15 and 2.2 times greater than the increase in numbers of children wearing helmets. This suggests the greatest effect of the helmet law was not to encourage cyclists to wear helmets, but to discourage cycling. In contrast, despite increases to at least 75% helmet wearing, the proportion of head injuries in cyclists admitted or treated at hospital declined by an average of only 13%. The percentage of cyclists with head injuries after collisions with motor vehicles in Victoria declined by more, but the proportion of head injured pedestrians also declined; the two followed a very similar trend. These trends may have been caused by major road safety initiatives introduced at the same time as the helmet law and directed at both speeding and drink-driving. The initiatives seem to have been remarkably effective in reducing road trauma for all road users, perhaps affecting the proportions of victims suffering head injuries as well as total injuries. The benefits of cycling, even without a helmet, have been estimated to outweigh the hazards by a factor of 20 to 1 (Hillman 1993. Cycle helmets-the case for and against. Policy Studies Institute, London). Consequently, a helmet law, whose most notable effect was to reduce cycling, may have generated a net loss of health benefits to the nation. Despite the risk of dying from head injury per hour being similar for unhelmeted cyclists and motor vehicle occupants, cyclists alone have been required to wear head protection. Helmets for motor

  10. An international review of the frequency of single-bicycle crashes (SBCs) and their relation to bicycle modal share

    DEFF Research Database (Denmark)

    Schepers, Paul; Agerholm, Niels; Amoros, Emmanuelle;

    2015-01-01

    . Different countries show a range of values between 5% and 30%. Between 60% and 95% of cyclists admitted to hospitals or treated at emergency departments are victims of SBCs. The proportion of all injured cyclists who are injured in SBCs is unrelated to the share of cycling in the modal split. The share...... of SBC casualties among the total number of road crash casualties increases proportionally less than the increase in bicycle modal share. Conclusions While most fatal injuries among cyclists are due to motor vehicle–bicycle crashes, most hospital admissions and emergency department attendances result...

  11. "Walking" Along a Free Rotating Bicycle Wheel (Round and Round)

    CERN Document Server

    Guemez, Julio

    2016-01-01

    We describe the kinematics, dynamics and also some energetic issues related to the Marta mouse motion when she walks on top of a horizontal bicycle wheel, which is free to rotate like a merry-to-go round, as presented recently by Paul Hewitt in the Figuring Physics section of this magazine.

  12. The safety impact of a yellow bicycle jacket

    DEFF Research Database (Denmark)

    Lahrmann, Harry; Madsen, Tanja Kidholm Osmann

    2016-01-01

    of the project, i.e. after a year. The safety effect of the bicycle jacket was analysed by comparing the number of self-reported accident for the test and control group. The self-reported accidents showed that the test group had 38 % fewer personal injury accidents with other road users – so-called multi...

  13. Consumers’ preferences for “bicycle poultry” in Benin

    DEFF Research Database (Denmark)

    Sodjinou, Epiphane; Henningsen, Arne; Koudande, Delphin O.;

    2015-01-01

    Village poultry, also termed "bicycle poultry," is produced in scavenging farming systems and is a chewy meat with a low fat content, and constitutes an important source of meat in many African countries. This study investigates consumers’ preferences regarding the physical traits of these birds ...

  14. Mapping Bicycle Crash Risk Patterns on the Local Scale

    Directory of Open Access Journals (Sweden)

    Martin Loidl

    2016-09-01

    Full Text Available Currently, mainly aggregated statistics are used for bicycle crash risk calculations. Thus, the understanding of spatial patterns at local scale levels remains vague. Using an agent-based flow model and a bicycle crash database covering 10 continuous years of observation allows us to calculate and map the crash risk on various spatial scales for the city of Salzburg (Austria. In doing so, we directly account for the spatial heterogeneity of crash occurrences. Additionally, we provide a measure for the statistical robustness on the level of single reference units and consider modifiable areal unit problem (MAUP effects in our analysis. This study is the first of its kind. The results facilitate a better understanding of spatial patterns of bicycle crash rates on the local scale. This is especially important for cities that strive to improve the safety situation for bicyclists in order to address prevailing safety concerns that keep people from using the bicycle as a utilitarian mode of (urban transport.

  15. Utilizing the Bicycle for Non-Traditional Activities

    Science.gov (United States)

    Maina, Michael P.; Maina, Julie Schlegel; Sebek, Ludek; Hoffmanova, Jana; Kane, Jennifer Jackson

    2012-01-01

    This article examines the bicycle as not simply a means of transportation or as an exercise device, but rather as a vehicle for teambuilding and problem solving activities within a physical education curriculum. The activities described in this article focus on bike-centered initiatives that foster creative problem solving. They have universal…

  16. Bicyclic graphs with exactly two main signless Laplacian eigenvalues

    CERN Document Server

    Huang, He

    2012-01-01

    A signless Laplacian eigenvalue of a graph $G$ is called a main signless Laplacian eigenvalue if it has an eigenvector the sum of whose entries is not equal to zero. In this paper, all connected bicyclic graphs with exactly two main eigenvalues are determined.

  17. 77 FR 39927 - Vehicles and Traffic Safety-Bicycles

    Science.gov (United States)

    2012-07-06

    ... family--they bicycle to visit points of interest, to be healthy, and because it's fun. The National Park... that, at a minimum, the plan: Evaluates the suitability of existing trail surface and soil condition... objectives and will not disturb wildlife or park resources. See NPS Management Policies 2006,...

  18. Experimental and mathematical car-bicycle collision simulations.

    NARCIS (Netherlands)

    Huybers, J.J.W. & Janssen, E.G.

    1988-01-01

    The results of 35 mathematical simulations will be used to get a better insight in car-bicycle collisions. This information will be used later on to formulate hypotheses to be tested in an accident investigation project. In this paper special attention is given to the influence of the shape of the

  19. Bicyclic peptide inhibitor of urokinase-type plasminogen activator

    DEFF Research Database (Denmark)

    Roodbeen, Renée; Jensen, Berit Paaske; Jiang, Longguang;

    2013-01-01

    The development of protease inhibitors for pharmacological intervention has taken a new turn with the use of peptide-based inhibitors. Here, we report the rational design of bicyclic peptide inhibitors of the serine protease urokinase-type plasminogen activator (uPA), based on the established...

  20. Bicycle sharing system: role, effects and application to Plymouth

    OpenAIRE

    Wiersma, Bouke

    2010-01-01

    Abstract This thesis investigates the role and effects of a bicycle sharing system, and studies the feasi-bility of such a system in Plymouth. The research consists of a literature review, policy dis-cussion, case studies, and a detailed assessment of t

  1. Expedition Paris-Beijing by Bicycle 2008 Launched

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>From March 15 to17, at the invitation of the Euro-Chinese Friendship Association (ECFA) of France, a CPAFFC representative attended the launching ceremony of the Expedition Paris-Beijing by Bicycle 2008 in Paris, during which he met with officials of the National Commission on Decentralized Cooperation (Commission Nationale de la Cooperation Decentralisee-CNCD) of France.

  2. Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids

    DEFF Research Database (Denmark)

    Conti, Paola; De Amici, Marco; Joppolo Di Ventimiglia, Samuele;

    2003-01-01

    Bicyclic acidic amino acids (+/-)-6 and (+/-)-7, which are conformationally constrained homologues of glutamic acid, were prepared via a strategy based on a 1,3-dipolar cycloaddition. The new amino acids were tested toward ionotropic and metabotropic glutamate receptor subtypes; both of them...

  3. Efficiency of choice set generation methods for bicycle routes

    DEFF Research Database (Denmark)

    Halldórsdóttir, Katrín; Rieser-Schussler, Nadine; Axhausen, Kay W.;

    2014-01-01

    for scenic routes, dedicated cycle lanes, and road type. Data consisted of 778 bicycle trips traced by GPS and carried out by 139 persons living in the Greater Copenhagen Area, in Denmark. Results suggest that both the breadth first search on link elimination and the doubly stochastic generation function...

  4. Use and activity levels on newly built bicycle playgrounds

    DEFF Research Database (Denmark)

    Schipperijn, Jasper; Hansen, Christine Kier; Rask, Simon

    2015-01-01

    Increasing the use of urban green space (UGS) as well as increasing cycling could potentially help address the growing inactivity problem. Three bicycle playgrounds were designed based on a participatory process and afterwards constructed in the UGS along a cycle-route on the historic outer defen...

  5. A Formal Synthesis of ( + )-Cassiol Exploiting Meyers' Bicyclic Lactam Methodology

    Institute of Scientific and Technical Information of China (English)

    SHEN,Xin(沈鑫); WU,Yi-Kang(伍贻康); ZHANG,Fan(张帆)

    2002-01-01

    A formal synthesis of ( + )-cassiol using (1S,2S)-2-amino-1-(4- nitrophenyl)-1,3-propanediol as chiral auxiliary is reported.The quaternary chiral center in the molecule was constructed by sequential alkylation of a bicyclic lactam (prepared from the aforementioned auxiliary and 5-oxo-heptanlic acid) with methyl iodide and benzyloxymethyl chloride.

  6. Bicycle Conversion Factor Calibration at Two-Phase Intersections in Mixed Traffic Flows

    Institute of Scientific and Technical Information of China (English)

    WANG Dianhai; LIANG Chunyan; JING Chunguang; WANG Guohua

    2007-01-01

    Chinese traffic is typically composed of bicycles and motor vehicles on the same road. The efficiency of bicycle traffic in time and space at intersections was investigated for eight typical intersections in the cities of Tianjin, Shenyang, and Changchun, all in China, by means of video recording. Models were developed to calculate the through bicycle traffic and the left-turn bicycle traffic conversion factors in intersections where bicycles and motor vehicles share the same road. The results indicate that the through bicycle conversion factor is 0.28 and the left-turn bicycle conversion factor is 0.33. This conclusion differs from the current value used in China. More research on the conversion factor is necessary to evaluate the impact of intersections.

  7. c-fos与c-jun癌蛋白在溃疡与增生性瘢痕创面联合表达的特征与意义%Expression of oncoproteins c-fos and c-jun in hypertrophic scars and chronic dermal ulcers and their regulation of basic fibroblast growth factor

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    目的探讨c-fos与c-jun两种原癌基因产物在溃疡与增生性瘢痕创面表达的特征与规律以及与不同组织修复结局发生的关系。 方法 16例标本均取自于外科手术患者,其中增生性瘢痕8例,溃疡创面8例,另有正常对照皮肤5例取自增生性瘢痕患者作为对照。用免疫组化法(ABC法)检测c-fos与c-jun两种癌蛋白以及bFGF在三种组织切片的分布特征。 结果在正常皮肤c-fos与c-jun的阳性表达主要见于表皮基底细胞和少量皮下成纤维细胞,但在相应部位c-jun的表达较c-fos为弱。在增生性瘢痕,c-fos与c-jun均出现强阳性表达,主要见于成纤维细胞。在溃疡组织,c-fos与c-jun的联合表达多见于毛细血管内皮细胞、部分炎症细胞以及成纤维细胞胞浆。 结论增生性瘢痕与溃疡创面c-fos与c-jun表达量与部位同正常皮肤存在显著差异,提示这两种原癌基因产物在影响和调控组织修复中有重要作用。%Objective To explore the characteristics of oncoprotein expression of c-fos and c-jun in hypertrophic scars and chronic dermal ulcers and their regulation of basic fibroblast growth factor (bFGF). Methods Tissues of hypertrophic scars (n=8), chronic dermal ulcers (n=8) and normal skin (n=5) were taken from 21 patients with burns and chronic dermal ulcers in operation. The ABC immunohistochemical method was used to characterize the gene product expression of c-fos, c-jun and bFGF in the above tissues. Results In normal skin, both c-fos and c-jun protein expression and bFGF protein expression were observed. The signals of both oncoproteins were localized mainly in subcutaneous fibroblasts, but, positive expression of the bFGF protein was mainly in keratinocytes. In hypertrophic scars, positive expression of both oncoproteins could be found mainly in fibroblasts, but bFGF was mainly in fibroblasts and endothelial cells. In chronic dermal ulcers, endothelial cells, some

  8. Bicycle injuries: a matter of mechanism and age.

    Science.gov (United States)

    Siman-Tov, Maya; Jaffe, Dena H; Peleg, Kobi

    2012-01-01

    Bicycle riding is a popular form of recreation with positive health and environmental effects. These road users are vulnerable to serious injuries, especially when motor vehicles are involved. The goal of this study was to characterize cyclist-related injuries according to motor vehicle involvement for adults versus children. A retrospective study was carried out using data from 11 trauma centers in the Israeli National Trauma Registry (2001-2007). Injuries were classified according to whether a motor vehicle was involved, and differences in injury characteristics were assessed for adults (18+ years) versus children (1-17 years). A total of 5529 patients were hospitalized for bicycle injuries, of whom 1765 were adults and 3764 were children. Thirty percent (n=1662) of all bicycle injuries involved motor vehicles, although the rate of injuries resulting in hospitalization was 37% among adults and 27% among children. Injury characteristics and hospital resource utilization differed substantially by age group. Cyclists struck by a motor vehicle presented with more severe injuries requiring more hospital resources and resulting in poorer outcomes than those not involved with motor vehicles. The interaction effect between motor vehicle involvement and age was significant for torso injuries and need for medical imaging. We found that injury characteristics, hospital resource utilization and health-related outcomes for bicycle injuries are highly dependent on patient's age and mechanism of injury. Effect modification of motor vehicle involvement by age may in part reflect physicians' attitudes toward pediatric imaging. The risks identified in this study should be used for preparedness and management of trauma hospitalizations from bicycle injuries. PMID:22062347

  9. Chest Traumas due to Bicycle accident in Childhood

    Directory of Open Access Journals (Sweden)

    Ufuk Cobanoglu

    2011-09-01

    Full Text Available Aim:Childhood injuries are the leading cause of death in children and result in significant healthcare utilization. Trauma is the second most common cause of mortality in children aged 1-4 years and leading cause of death in children older than 4 years. Thoracic injury is the second most leading cause of death in traumatized children. Multisystemic injury is found in more than 50% of children with thoracic injuries most of which are secondary to blunt traumas. We planned this study to evaluate thorax trauma cases secondary to bicycle driving in childhood and to draw attention to the importance of the regulation of traffic rules, the education of bicycle drivers.Material and Methods:  A retrospective evaluation was performed in 17 pediatric patients admitted to the Department of Thoracic Surgery during 2006-2010 with a diagnosis of chest trauma due to bicycle driving. For every patient, a pediatric trauma score (PTS was calculated. Descriptive statistics were performed for PTS. Results; Eleven (64.70% cases were injured due to the tricycle accidents and six cases 6 (35.29% were injured due to the two-wheeled bicycle accidents. The most frequent thoracic pathologies included pulmonary contusion (41.2% and chest wall contusion (29.41%. Extrathoracic injuries were seen in 35.29%, the extremities (17.64% and abdomino pelvic (11.76% being the most commonly involved. Treatment consisted of symptomatic treatment in 12 patients (70.58%, tube thoracostomy in 2 patients (11.76%, and thoracotomy in 1 patient (5.9%. The morbidity was seen in 3 patients (17.64%. The mortality rate was 5.9% (n:1. The mean PTS of the cases who had additional system injuries were significantly worse than the cases who had isolated chest traumas Conclusions: The pediatric thorax has a greater cartilage content and incomplete ossification of the ribs. Due to the pliability of the pediatric rib cage and mediastinal mobility, significant intrathoracic injury may exist in the

  10. Personal and behavioral factors associated with bicycling in adults from Curitiba, Parana State, Brazil

    Directory of Open Access Journals (Sweden)

    Marilson Kienteka

    2014-01-01

    Full Text Available Bicycling is an important form of physical activity that can promote health benefits. The objective of this study was to analyze the association between personal and behavioral aspects in transportation bicycling and leisure time bicycling in adults. Data was drawn from a household survey involving 677 adults (53.1% female in Curitiba, Paraná State, Brazil. The prevalence of bicycling was 11.2% for transportation and 16.7% for leisure. The frequency of leisure time bicycling was higher among men (PR = 2.08; p < 0.001, young people < 30 and adults aged between 30 and 39.9, bicycle owners (PR = 8.76; p < 0.001 and among the physically active. Transportation bicycling occurred more frequently among men (PR = 3.63; p < 0.001, individuals aged 30 to 39.9, those with a low socioeconomic status (PR = 5.00; p = 0.006, bicycle owners (PR = 10.2; p < 0.001 and individuals with a negative perception of their quality of life. The prevalence of bicycling is low in Curitiba considering its potential as a means of physical activity. Personal and behavioral factors were associated with each form of bicycling.

  11. The fastest bicycle in the world; how a team of Delft students is building a bicycle to break the world speed record

    NARCIS (Netherlands)

    Annega, G.

    2011-01-01

    The Netherlands is a country known for its extensive use of bicycles as a means of everyday transport. However, while it has existed for about two centuries, todays bicycles only differ from those of the 19th century in relatively small details. Human Power Team Delft is building a whole new type of

  12. Efficiency of Choice Set Generation Methods for Bicycle Routes

    DEFF Research Database (Denmark)

    Halldórsdóttir, Katrín; Rieser-Schüssler, Nadine; W. Axhausen, Kay;

    With a growing interest in sustainable transport systems, the interest has increased on encouraging more cycling. To encourage cycling, it is important to identify which network attributes influence cyclists route choice and evaluate the trade-offs among these attributes. To analyse travel...... behaviour, observed choices and alternatives composing the choice set of each cyclist are necessary. However, generating the alternative choice sets can prove challenging. This paper analyses the efficiency of various choice set generation methods for bicycle routes in order to contribute to our...... that might produce inconsistent estimates. There have been some studies on bicycle route choice set generation reported in the literature, whereof few studies focussed on route choice models for bicyclist estimated from GPS observations. Menghini et al. [3] successfully applied a Breadth First Search on Link...

  13. Simultaneous optimization of transit network and public bicycle station network

    Institute of Scientific and Technical Information of China (English)

    刘洋; 朱宁; 马寿峰

    2015-01-01

    The traditional manner to design public transportation system is to sequentially design the transit network and public bicycle network. A new public transportation system design problem that simultaneously considers both bus network design and public bicycle network design is proposed. The chemical reaction optimization (CRO) is designed to solve the problem. A shortcoming of CRO is that, when the two-molecule collisions take place, the molecules are randomly picked from the container. Hence, we improve CRO by employing different mating strategies. The computational results confirm the benefits of the mating strategies. Numerical experiments are conducted on the Sioux-Falls network. A comparison with the traditional sequential modeling framework indicates that the proposed approach has a better performance and is more robust. The practical applicability of the approach is proved by employing a real size network.

  14. [Electrically assisted bicycles: health enhancement or "green" gadget?].

    Science.gov (United States)

    Welker, J; Cornuz, J; Gojanovic, B

    2012-07-25

    Electrically assisted bicycles (EAB) are flourishing in cities throughout the world and capitalize on ecological and practical advantages, helping in the fight against pollution, CO2 emissions and traffic jam. Human power is necessary to activate the electrical support, so that it equals to a moderate intensity physical activity (> 3 MET), or a vigorous one on hilly courses (>6 MET). The ecological benefits are obvious and transportation departments tend to support citizens who purchase one. EAB offer increased mobility at speeds of 15 to 25 km/h depending on hills and fitness of the rider, but could cause more accidents. EAB is linked to a real physical activity beneficial for health, but potentially more dangerous than a traditional bicycle. PMID:22913003

  15. A system for quantifying the cooling effectiveness of bicycle helmets.

    Science.gov (United States)

    Reid, J; Wang, E L

    2000-08-01

    This article describes the design and development of a system that is capable of quantifying the thermal comfort of bicycle helmets. The motivation for the development of the system stems from the desire both to increase helmet use and to provide the designer with a quantitative method of evaluating the thermal comfort of a helmet. The system consists of a heated mannequin head form, a heated reference sphere, a small wind tunnel, and a data acquisition system. Both the head form and the reference sphere were instrumented with thermocouples. The system is capable of simulating riding speeds ranging from 4.5-15.5 m/s. A cooling effectiveness, C1, that is independent of both ambient conditions and wind velocity is defined as a measure of how well the helmet ventilates as compared to the reference sphere. The system was validated by testing six commercially available bicycle helmets manufactured between approximately 1992 and 1998. PMID:11036573

  16. Cellular automata simulation of traffic including cars and bicycles

    Science.gov (United States)

    Vasic, Jelena; Ruskin, Heather J.

    2012-04-01

    As 'greening' of all aspects of human activity becomes mainstream, transportation science is also increasingly focused around sustainability. Modal co-existence between motorised and non-motorised traffic on urban networks is, in this context, of particular interest for traffic flow modelling. The main modelling problems here are posed by the heterogeneity of vehicles, including size and dynamics, and by the complex interactions at intersections. Herein we address these with a novel technique, based on one-dimensional cellular automata components, for modelling network infrastructure and its occupancy by vehicles. We use this modelling approach, together with a corresponding vehicle behaviour model, to simulate combined car and bicycle traffic for two elemental scenarios-examples of components that would be used in the building of an arbitrary network. Results of simulations performed on these scenarios, (i) a stretch of road and (ii) an intersection causing conflict between cars and bicycles sharing a lane, are presented and analysed.

  17. Optimization of electric bicycle for youths with disabilities

    OpenAIRE

    Blumenstein, Tobias; Zeitlmann, Hilar; Alves-Pinto, Ana; Turova, Varvara; Lampe, Renée

    2014-01-01

    Cerebral palsy is a group of neurodevelopmental disorders that affect a person’s ability to move and to maintain balance and posture. People with cerebral palsy have also perception and space orientation deficits so that special assistance devices should be developed to compensate these handicaps. The objective was to optimize an adapted electric bicycle (E-bike) for youths with neurodevelopmental disorders. An adapted E-bike was provided with ultrasonic sensors that measure distances to obje...

  18. Interventions in Bicycle Infrastructure, Lessons from Dutch and Danish Cases

    OpenAIRE

    Van Goeverden, K.; Nielsen, Thomas Alexander Sick; Harder, Henrik; van Nes, Rob

    2015-01-01

    Today the interest in cycling is increasing worldwide and in many countries authorities are faced with the question how cycling can be promoted efficiently. In the Netherlands and Denmark, this question came up already in the 1970s when the downsides of the rapidly increasing motorisation became evident. At the time, in both countries large scale interventions in bicycle infrastructure were introduced and evaluated extensively in order to create knowledge on efficient promoting of cycling in ...

  19. Methodology for a global bicycle real world accidents reconstruction

    OpenAIRE

    Bourdet, Nicolas; Deck, Caroline; Serre, Thierry; Perrin, Christophe; LLARI, Maxime; Willinger, Rémy

    2012-01-01

    The use of the bicycle on a large scale encouraged in the context to develop an eco friendly environment is facing today on a range of barriers. One of these barriers identified by researchers and governments is observed to include ‘road safety’. Hence, it is necessary to set up a protection system for bicyclists especially for the cephalic segment. Currently only few studies are available concerning the head impact loading in case of real accidents. Therefore, the objective of th...

  20. In-depth real-world bicycle accident reconstructions

    OpenAIRE

    Bourdet, Nicolas; Deck, Caroline; Serre, Thierry; Perrin, Christophe; LLARI, Maxime; Willinger, Rémy

    2013-01-01

    Use of bicycles on a large scale, encouraged in the context to develop an eco-friendly environment, is facing today a range of barriers. One of these barriers identified by researchers and governments is observed to include ‘road safety’. Hence, it is necessary to set up a protection system for bicyclists especially for the cephalic segment. Currently only few studies are available concerning the head impact loading in case of real accidents. Therefore, the objective of this work ...

  1. Mobile cockpit system for enhanced electric bicycle use

    OpenAIRE

    João C. Ferreira; Monteiro, Vítor Duarte Fernandes; Afonso, José A.; Afonso, João L.

    2015-01-01

    This paper presents the project of a Mobile Cockpit System (MCS) for smartphones, which provides assistance to Electric Bicycle (EB) cyclists in Smart Cities’ environment. The presented system introduces a mobile application (MCS App) with the goal to provide useful personalized information to the cyclist related with the EB’s use, including EB range prediction considering the intended path, management of the cycling effort performed by the cyclist, handling of the battery charging process an...

  2. The value of time and external benefits in bicycle appraisal

    OpenAIRE

    Börjesson, Maria; ELIASSON, Jonas

    2011-01-01

    We estimate the value of time savings, different cycling environments and additional benefits in cost-benefit analysis of cycling investments. Cyclists’ value of travel time savings turns out to be high, considerably higher than the value of time savings on alternative modes. Cyclists also value other improvements highly, such as separated bicycle lanes. As to additional benefits of cycling improvements in the form of health and reduced car traffic, our results do not support the notion that ...

  3. Harvesting Energy from the Counterbalancing (Weaving) Movement in Bicycle Riding

    OpenAIRE

    Shashank Priya; Jeongjin Yeo; Yoonseok Yang

    2012-01-01

    Bicycles are known to be rich source of kinetic energy, some of which is available for harvesting during speedy and balanced maneuvers by the user. A conventional dynamo attached to the rim can generate a large amount of output power at an expense of extra energy input from the user. However, when applying energy conversion technology to human powered equipments, it is important to minimize the increase in extra muscular activity and to maximize the efficiency of human movements. This study p...

  4. Finite element analysis of advanced bicycle precision brake disk forming technology

    Directory of Open Access Journals (Sweden)

    Chen Dyi-Cheng

    2015-01-01

    Full Text Available In recent years, the bicycle has become an environmentally friendly transportation. The bicycle can be divided into mountain bicycle and highway bicycle. Safe driving is the prior consideration. The bicycle braking system can be divided into oil pressure disk brakes and mechanical disk brakes. The brake disk system is one indispensable component of the safe system. In accordance to overall weight consideration of the bike, the brake disk should also focus on the lightweight design. This paper discussed an innovative brake disk forming technology for 6061 aluminum alloy by the rigid-plastic finite element analysis. The simulation parameters include geometric shapes of the brake disk and mold, die temperature, and friction factors. The stress and strain in forming, brake deformation and vibration modal analysis of brake disk in riding were studied. The paper is expected to offer some precision bicycle brake disk manufacture knowledge for industry.

  5. Harvesting Energy from the Counterbalancing (Weaving) Movement in Bicycle Riding

    Science.gov (United States)

    Yang, Yoonseok; Yeo, Jeongjin; Priya, Shashank

    2012-01-01

    Bicycles are known to be rich source of kinetic energy, some of which is available for harvesting during speedy and balanced maneuvers by the user. A conventional dynamo attached to the rim can generate a large amount of output power at an expense of extra energy input from the user. However, when applying energy conversion technology to human powered equipments, it is important to minimize the increase in extra muscular activity and to maximize the efficiency of human movements. This study proposes a novel energy harvesting methodology that utilizes lateral oscillation of bicycle frame (weaving) caused by user weight shifting movements in order to increase the pedaling force in uphill riding or during quick speed-up. Based on the 3D motion analysis, we designed and implemented the prototype of an electro-dynamic energy harvester that can be mounted on the bicycle's handlebar to collect energy from the side-to-side movement. The harvester was found to generate substantial electric output power of 6.6 mW from normal road riding. It was able to generate power even during uphill riding which has never been shown with other approaches. Moreover, harvesting of energy from weaving motion seems to increase the economy of cycling by helping efficient usage of human power. PMID:23112598

  6. Electric motor assisted bicycle as an aerobic exercise machine.

    Science.gov (United States)

    Nagata, T; Okada, S; Makikawa, M

    2012-01-01

    The goal of this study is to maintain a continuous level of exercise intensity around the aerobic threshold (AT) during riding on an electric motor assisted bicycle using a new control system of electrical motor assistance which uses the efficient pedaling rate of popular bicycles. Five male subjects participated in the experiment, and the oxygen uptake was measured during cycling exercise using this new pedaling rate control system of electrical motor assistance, which could maintain the pedaling rate within a specific range, similar to that in previous type of electrically assisted bicycles. Results showed that this new pedaling rate control system at 65 rpm ensured continuous aerobic exercise intensity around the AT in two subjects, and this intensity level was higher than that observed in previous type. However, certain subjects were unable to maintain the expected exercise intensity because of their particular cycling preferences such as the pedaling rate. It is necessary to adjust the specific pedaling rate range of the electrical motor assist control according to the preferred pedaling rate, so that this system becomes applicable to anyone who want continuous aerobic exercise.

  7. Harvesting energy from the counterbalancing (weaving) movement in bicycle riding.

    Science.gov (United States)

    Yang, Yoonseok; Yeo, Jeongjin; Priya, Shashank

    2012-01-01

    Bicycles are known to be rich source of kinetic energy, some of which is available for harvesting during speedy and balanced maneuvers by the user. A conventional dynamo attached to the rim can generate a large amount of output power at an expense of extra energy input from the user. However, when applying energy conversion technology to human powered equipments, it is important to minimize the increase in extra muscular activity and to maximize the efficiency of human movements. This study proposes a novel energy harvesting methodology that utilizes lateral oscillation of bicycle frame (weaving) caused by user weight shifting movements in order to increase the pedaling force in uphill riding or during quick speed-up. Based on the 3D motion analysis, we designed and implemented the prototype of an electro-dynamic energy harvester that can be mounted on the bicycle's handlebar to collect energy from the side-to-side movement. The harvester was found to generate substantial electric output power of 6.6 mW from normal road riding. It was able to generate power even during uphill riding which has never been shown with other approaches. Moreover, harvesting of energy from weaving motion seems to increase the economy of cycling by helping efficient usage of human power.

  8. Electric motor assisted bicycle as an aerobic exercise machine.

    Science.gov (United States)

    Nagata, T; Okada, S; Makikawa, M

    2012-01-01

    The goal of this study is to maintain a continuous level of exercise intensity around the aerobic threshold (AT) during riding on an electric motor assisted bicycle using a new control system of electrical motor assistance which uses the efficient pedaling rate of popular bicycles. Five male subjects participated in the experiment, and the oxygen uptake was measured during cycling exercise using this new pedaling rate control system of electrical motor assistance, which could maintain the pedaling rate within a specific range, similar to that in previous type of electrically assisted bicycles. Results showed that this new pedaling rate control system at 65 rpm ensured continuous aerobic exercise intensity around the AT in two subjects, and this intensity level was higher than that observed in previous type. However, certain subjects were unable to maintain the expected exercise intensity because of their particular cycling preferences such as the pedaling rate. It is necessary to adjust the specific pedaling rate range of the electrical motor assist control according to the preferred pedaling rate, so that this system becomes applicable to anyone who want continuous aerobic exercise. PMID:23366293

  9. [Mortality due to bicycle accidents in Pernambuco, Brazil].

    Science.gov (United States)

    Galvão, Pauliana Valéria Machado; Pestana, Luciana Pinto; Pestana, Valter Mário; Spíndola, Michelline Oliveira Pedrosa; Campello, Reginaldo Inojosa Carneiro; de Souza, Eliane Helena Alvim

    2013-05-01

    The scope of this paper was to conduct a quantitative analysis of deaths resulting from bicycle accidents in the state of Pernambuco by studying secondary data between 2001 and 2010. The sample consisted of all the Deaths recorded in the Mortality Information System of the Unified Health System Database that reported bicycle accidents between 2001 and 2010. Descriptive measures were determined for all variables. Socio-demographic variables were paired with the basic cause of death in order to find a statistical correlation. In Pernambuco, the aforementioned information system recorded 517 deaths resulting from bicycle accidents, with greater frequency in men between 25 and 59 years of age, Afro-Brazilians, single and of unknown schooling. The mean age was 36.82 years (SD = 17.026), and the minimum and maximum age of 4 and 86 years old, respectively. The findings highlight the need for the creation of adequate infrastructure and effective legal measures to prevent traffic accidents involving this type of vehicle, relying on the evidence of distribution of cases in most Pernambuco municipalities.

  10. Design Analysis And Applications Of A Regenerative Bicycle Ergometer

    Directory of Open Access Journals (Sweden)

    Chukwuneke J. L.

    2015-08-01

    Full Text Available Man needs to do some form of physical work in other to remain healthy this work is similar to the work done by any machine or equipment and thus should be channeled to give useful output but rather it is usually dissipated into the environment in form of heat. The regenerative bicycle ergometer takes advantage of the greater power generated by the limbs and arms thus conserves converts and stores the energy dissipated by the rider with an ideal mechanical advantage of 7.6 it strategically uses simple mechanisms to magnify its work and then converts this mechanical energy into electrical energy by the use of a dynamo with a speed ratio of 108.5 and a transmission efficiency of 89 the rider pedals 27rpm to obtain the dynamos rated input of 2600rpm giving an output of 12.6volts. The regenerative bicycle ergometer is designed and constructed to perform all the core functions of a bicycle ergometer having an allowable load of 116.5kg and a maximum resistance of 65.33N which is equivalent to a mass of 6.66kg. The energy converted is stored in a 12volts battery making its use flexible clean and meeting the energy demands of man.

  11. Conversion Of An Ordinary N Bicycle Into An Electric Bike And Related Research

    OpenAIRE

    Marius Janavičius

    2014-01-01

    An electric bicycle as a transport and leisure vehicle is expected to have a promising future. Currently, he market offers a great choice of factory electric bicycles and conversion kits to remake an ordinary bicycle into an electric bike. Also, the increasing number of electric vehicles is determined by the reduction in costs for manufacturing of batteries and an evolution in battery technology. This article presents the implementation of an electric bike by selecting the “Golden Motor Techn...

  12. A Modified Cellular Automaton Approach for Mixed Bicycle Traffic Flow Modeling

    OpenAIRE

    Xiaonian Shan; Zhibin Li; Xiaohong Chen; Jianhong Ye

    2015-01-01

    Several previous studies have used the Cellular Automaton (CA) for the modeling of bicycle traffic flow. However, previous CA models have several limitations, resulting in differences between the simulated and the observed traffic flow features. The primary objective of this study is to propose a modified CA model for simulating the characteristics of mixed bicycle traffic flow. Field data were collected on physically separated bicycle path in Shanghai, China, and were used to calibrate the C...

  13. "The Mechanisms. Light and Miraculous": The Convivial Bicycle in Literature and Film

    OpenAIRE

    Guevara, J. Josh

    2012-01-01

    This dissertation explores the prevalent representation of the bicycle as a liberatory figure in theoretical texts, novels, films, and poetry. Because the bicycle confers unexpected creativity and autonomy, it alters definitions of technology, modernity, and identity. Chapter one recuperates and employs Ivan Illich's concept of conviviality in order to re-examine the inheritance of the project of modernity and question the definition of technology in the twenty-first century bicycle epoch. Fo...

  14. Automated Analysis Methods for the Assessment of Bicycle Infrastructure and Demand

    OpenAIRE

    Pashkevich, Anton

    2013-01-01

    A first phase of the research activity has been related to the study of the state of art of the infrastructures for cycling, bicycle use and methods for evaluation. In this part, the candidate has studied the "bicycle system" in countries with high bicycle use and in particular in the Netherlands. Has been carried out an evaluation of the questionnaires of the survey conducted within the European project BICY on mobility in general in 13 cities of the participating countries. The questionn...

  15. Development of New Chiral Bicyclic Ligands : Applications in Catalytic Asymmetric Transfer Hydrogenation, Epoxidations, and Epoxide Rearrangements

    OpenAIRE

    Gayet, Arnaud

    2005-01-01

    This thesis describes the synthesis and application of new chiral bicyclic ligands and their application in asymmetric catalysis. The studies involved: [i] The development of novel chiral bicyclic amino sulfur ligands and their use in transfer hydrogenation. [ii] The development of the kinetic resolution of racemic epoxide through the use of chiral lithium amides. [iii] The synthesis and application of chiral bicyclic amine in the organocatalysed epoxidation of alkenes. [iv] Development and a...

  16. Compositions comprising a polypeptide having cellulolytic enhancing activity and a bicyclic compound and uses thereof

    Energy Technology Data Exchange (ETDEWEB)

    Quinlan, Jason; Xu, Feng; Sweeney, Matthew

    2016-10-04

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a bicyclic compound. The present invention also relates to methods of using the compositions.

  17. Compositions comprising a polypeptide having cellulolytic enhancing activity and a bicycle compound and uses thereof

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Feng; Sweeney, Matthew; Quinlan, Jason

    2015-06-16

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a bicyclic compound. The present invention also relates to methods of using the compositions.

  18. JNK通路在新生鼠坏死性小肠结肠炎模型中的表达及其意义%Expression and Significance of c-Jun N-terminal Kinase in Necrotizing Enterocolitis of Neonatal Rats

    Institute of Scientific and Technical Information of China (English)

    习隽丽; 刘先州

    2010-01-01

    目的 观察新生大鼠坏死性小肠结肠炎(necrotizing enterocolitis, NEC)中c-Jun氨基末端激酶(c-Jun N-terminal Kinase, JNK)的激化及胞内分布规律,探讨其在NEC发病机制中的作用.方法 新生鼠随机分为正常对照组和NEC动物模型组,每组10只,于母鼠喂养3d,第4d处死.取回盲部肠组织1~2cm,用10%的甲醛立即固定,常规石蜡包埋,分别作组织形态学检查和免疫组织化学检测JNK的表达.结果 新生大鼠NEC模型中JNK在肠道细胞的胞浆中黄棕色染色颗粒表达并伴有向核转移,其阳性表达明显高于正常对照组.结论 JNK信号通路可能参与了NEC发病过程,并起着信号传导作用.

  19. Thermoregulation during prolonged actual and laboratory-simulated bicycling.

    Science.gov (United States)

    Brown, S L; Banister, E W

    1985-01-01

    Thermoregulatory and cardiorespiratory responses to bicycling 55 km (mean speed 9.7 m X s-1) outdoors (15 degrees C DB) were compared to equivalent cycle ergometry (90 min at 65% VO2max) in the laboratory (20-23 degrees C DB, 50% RH) in 7 trained cyclists. Outdoor environmental conditions were simulated with fans and lamps, and were contrasted with standard no-wind, no-sun laboratory conditions. Sweating rate was similar during outdoor and laboratory simulated outdoor cycling (0.90 and 0.87 to 0.94 1 X h-1 respectively). During outdoor bicycling, mean heart rate (161 bt X min-1) was 7-13% higher (p less than .05) than under laboratory conditions, suggesting a greater strain for a similar external work rate. The increase in rectal temperature (0.8 degrees C) was 33-50% less (p less than 0.05) at the cooler outdoor ambient temperature than in the laboratory. Thermoregulatory stress was greater under the no-fan, no-lamp laboratory condition than during simulated outdoor conditions (36-38% greater (p less than 0.05) sweating rate, 15-18% greater (p less than 0.01) mean skin temperature, 6.4 to 7.8 fold greater (p less than 0.01) amount of clothing-retrained sweat). The cooling wind encountered in actual road bicycling apparently reduces thermoregulatory and circulatory demands compared with stationary cycle ergometry indoors. Failure to account for this enhanced cooling may result in overestimation of the physiological stress of actual road cycling.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Safety effects of permanent running lights for bicycles: A controlled experiment.

    Science.gov (United States)

    Madsen, J C O; Andersen, T; Lahrmann, H S

    2013-01-01

    Making the use of daytime running lights mandatory for motor vehicles is generally documented to have had a positive impact upon traffic safety. Improving traffic safety for bicyclists is a focal point in the road traffic safety work in Denmark. In 2004 and 2005 a controlled experiment including 3845 cyclists was carried out in Odense, Denmark in order to examine, if permanent running lights mounted to bicycles would improve traffic safety for cyclists. The permanent running lights were mounted to 1845 bicycles and the accident rate was recorded through 12 months for this treatment group and 2000 other bicyclists, the latter serving as a control group without bicycle running lights. The safety effect of the running lights is analysed by comparing incidence rates - number of bicycle accidents recorded per man-month - for the treatment group and the control group. The incidence rate, including all recorded bicycle accidents with personal injury to the participating cyclist, is 19% lower for cyclists with permanent running lights mounted; indicating that the permanent bicycle running light significantly improves traffic safety for cyclists. The study shows that use of permanent bicycle running lights reduces the occurrence of multiparty accidents involving cyclists significantly. In the study the bicycle accidents were recorded trough self-reporting on the Internet. Possible shortcomings and problems related to this accident recording are discussed and analysed. PMID:22884376

  1. Advocating Green Transport and Promoting Healthy Urban Development: Strategies for Bicycle Transport Development in Jinan

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>As a green transport means,the bicycle has a history of over two hundred years.Since the 1970s,due to the inf luence of energy crisis and the consciousness of environment protection,the bicycle has regained its popularity in the public for its

  2. Use of Adapted Bicycles on the Learning of Conventional Cycling by Children with Mental Retardation

    Science.gov (United States)

    Burt, Tammy L.; Porretta, David L.; Klein, Richard E.

    2007-01-01

    This study investigated the use of adapted bicycles on the acquisition, maintenance, and generalization of conventional cycling by seven children with mild mental retardation. Feedback was used in addition to the adapted bicycles and consisted of pedal rate, head position, and steering participation. A multiple probe design was used. Participants…

  3. 16 CFR Figure 8 to Part 1512 - Reflectorized Bicycle Wheel Rim Abrasion Test Device

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Reflectorized Bicycle Wheel Rim Abrasion Test Device 8 Figure 8 to Part 1512 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL...—Reflectorized Bicycle Wheel Rim Abrasion Test Device EC03OC91.074...

  4. 77 FR 12761 - Special Regulations; Areas of the National Park System, Saguaro National Park, Bicycle Route

    Science.gov (United States)

    2012-03-02

    ...The National Park Service (NPS) is proposing to designate the Hope Camp Trail as a bicycle route within Saguaro National Park (Park). The National Park Service general regulation at 36 CFR 4.30(b) requires promulgation of a special regulation to designate bicycle routes outside of developed areas and special use...

  5. [A specific sign of the injury inflicted by the front wheel of a bicycle].

    Science.gov (United States)

    Leonov, S V; Pinchuk, P V; Molchanov, D V

    2016-01-01

    The authors report the results of the comprehensive forensic medical expertise of the injury inflicted by the front wheel of a bicycle that revealed a new specific sign of the contact between the protruding part of the wheel of the bicycle (the brake disk) and the pedestrian's body. PMID:27070037

  6. The unexpected stable market share of the bicycle in The Netherlands

    NARCIS (Netherlands)

    Van Goeverden, C.D.; Van Arem, B.; Godefrooij, T.

    2013-01-01

    In the Netherlands, the share of the bicycle as the main mode in all person trips has been highly constant in the past three decades (about 27%). A constant share is remarkable because a number of developments in this period were unfavourable for bicycle use, like ageing of the population, growing n

  7. Bicycle Design: A different approach to improving on the world human powered speed records

    NARCIS (Netherlands)

    Epema, H.K.; Van den Brand, S.; Gregoor, W.; Kooijman, J.D.G.; Pereboom, H.P.; Wielemaker, D.C.; Van der Zweep, C.J.

    2012-01-01

    The current International Human Powered Vehicle Association world records for faired bicycles stand at 133.284km/h for the 200m flying start speed record and 91.562 km for the hour record. Traditionally the recumbent bicycles that have been developed for breaking one of either of these records have

  8. Does pedalling on a recumbent bicycle influence the cyclist’s steering behaviour?

    NARCIS (Netherlands)

    Boon, K.M.; Klap, P.; Van Lanen, J.A.; Letsoin, G.J.; Jansen, A.J.

    2014-01-01

    The paper presents the answer to the question how pedalling on a specific recumbent bicycle, such as the VeloX3, influences a cyclist’s ability to steer the bicycle. The research aims to find the correlation between pedalling and the undesired steering movements it creates. To test this assumption a

  9. Getting Bicycles on Trains - Inter-modal Transport Developments in Denmark

    DEFF Research Database (Denmark)

    Jørgensen, Ulrik; Pedersen, Bjørn Brix

    2001-01-01

    The combined use of bicycles and trains has been favored in contemporary public transport policies in Denmark. Although bicycling has played a major role in Danish personal transportation in more than hundred years, the attitude from public transport authorities towards supporting bicyclists has...

  10. The Dutch Reference Study: Cases of interventions in bicycle infrastructure reviewed in the framework of Bikeability

    NARCIS (Netherlands)

    Van Goeverden, C.D.; Godefrooij, T.

    2011-01-01

    The Netherlands have a tradition of high bicycle usage and a long history of research on effective policies for promoting cycling. Findings in Dutch studies can be useful in the Danish Bikeability-project that has the objective to increase the level of knowledge in relation to bicycle based transpor

  11. Design Analysis And Applications Of A Regenerative Bicycle Ergometer

    OpenAIRE

    Chukwuneke J. L.; Ugwuegbu D. C.; Sinebe J. E.; Enyi L. C.

    2015-01-01

    Man needs to do some form of physical work in other to remain healthy this work is similar to the work done by any machine or equipment and thus should be channeled to give useful output but rather it is usually dissipated into the environment in form of heat. The regenerative bicycle ergometer takes advantage of the greater power generated by the limbs and arms thus conserves converts and stores the energy dissipated by the rider with an ideal mechanical advantage of 7.6 it strategically use...

  12. Can You Ride a Bicycle? The Ability to Ride a Bicycle Prevents Reduced Social Function in Older Adults With Mobility Limitation

    Directory of Open Access Journals (Sweden)

    Ryota Sakura

    2016-06-01

    Full Text Available Background: The health benefits of bicycling in older adults with mobility limitation (ML are unclear. We investigated ML and functional capacity of older cyclists by evaluating their instrumental activities of daily living (IADL, intellectual activity, and social function. Methods: On the basis of interviews, 614 community-dwelling older adults (after excluding 63 participants who never cycled were classified as cyclists with ML, cyclists without ML, non-cyclists with ML (who ceased bicycling due to physical difficulties, or non-cyclists without ML (who ceased bicycling for other reasons. A cyclist was defined as a person who cycled at least a few times per month, and ML was defined as difficulty walking 1 km or climbing stairs without using a handrail. Functional capacity and physical ability were evaluated by standardized tests. Results: Regular cycling was documented in 399 participants, and 74 of them (18.5% had ML; among non-cyclists, 49 had ML, and 166 did not. Logistic regression analysis for evaluating the relationship between bicycling and functional capacity revealed that non-cyclists with ML were more likely to have reduced IADL and social function compared to cyclists with ML. However, logistic regression analysis also revealed that the risk of bicycle-related falls was significantly associated with ML among older cyclists. Conclusions: The ability and opportunity to bicycle may prevent reduced IADL and social function in older adults with ML, although older adults with ML have a higher risk of falls during bicycling. It is important to develop a safe environment for bicycling for older adults.

  13. Vision-Based Bicycle Detection Using Multiscale Block Local Binary Pattern

    Directory of Open Access Journals (Sweden)

    Hongyu Hu

    2014-01-01

    Full Text Available Bicycle traffic has heavy proportion among all travel modes in some developing countries, which is crucial for urban traffic control and management as well as facility design. This paper proposes a real-time multiple bicycle detection algorithm based on video. At first, an effective feature called multiscale block local binary pattern (MBLBP is extracted for representing the moving object, which is a well-classified feature to distinguish between bicycles and nonbicycles; then, a cascaded bicycle classifier trained by AdaBoost algorithm is proposed, which has a good computation efficiency. Finally, the method is tested with video sequence captured from the real-world traffic scenario. The bicycles in the test scenario are successfully detected.

  14. Bicycle Riding: Impact on Lower Urinary Tract Symptoms and Erectile Function in Healthy Men

    Science.gov (United States)

    Baek, Seok; Lee, Sun Young; Kim, Jong Min; Shin, Esther; Kam, Sin

    2011-01-01

    Purpose Recently, reports in the mass media have implicated that bicycle riding increases the risk of erectile dysfunction and prostatic diseases. So, we evaluate the impact of bicycle riding on erectile function and lower urinary tract symptoms (LUTS) in healthy general men. Methods From 26 June 2010 to 20 July 2010, we investigate degree of LUTS (voiding and storage symptoms), using International Continence Society-male Questionnaire (ICS-mQ) and erectile function using International Index of Erectile Function-5 Questionnaire (IIEF-5) in 5 work places (personnel of public office, hospital, university, etc.) of which bicycle riding club members were doing active club activities. Respondents, who participated in club activities for 6 months and longer, were classified as the bicycle club (142 men; age, 44.02±8.56). Ones who do not ride bicycles were classified as the control group (83 men; age, 42.13±7.85). People who were having the history of urological and other chronic diseases (diabetes, vascular disease, heart disease, etc) were excluded from both groups. Results Bicycle club is not significantly associated with increased prevalence of LUTS (bicycle club, 2.1 to 57.7% control, 4.8 to 73.5%) and erectile dysfunction (bicycle club, 46.1% control, 55.4%). The total mean score (storage/voiding/erectile function) of bicycle club (13.93±1.95/11.14±3.49/20.46±5.30) were not significantly different from control (14.35±2.49/11.52±3.38/20.40±4.07) (P=0.190 to 0.968). Conclusions These results suggested that bicycle riding as exercise or hobby has no negative effect on LUTS and erectile function in healthy general men, although this research data were limited to the questionnaire analysis. PMID:21811700

  15. The influence of body mass in endurance bicycling.

    Science.gov (United States)

    Swain, D P

    1994-01-01

    Bicycling is a complex sport in which an athlete's energy cost is related to two principal forces: air resistance when traveling on flat terrain, and gravity when traveling uphill. Both wind tunnel data and physiological measurements suggest that air resistance scales as body mass to about the 1/3 power. Thus, large cyclists have only slightly greater frontal drags than small cyclists. If expressed relative to body mass, the frontal drag of small cyclists is considerably greater than that of large cyclists. The difference in frontal drag (energy cost) is not made up for by the advantage to small cyclists in relative VO2max (energy supply), since the mass exponent for drag (1/3) is closer to zero than that for VO2max (2/3). Thus, small cyclists should be at a disadvantage in flat time trials, which field data support. The energy cost of riding uphill slightly favors the large cyclist, because the weight of the bicycle represents a relatively smaller load than it does to a small cyclist. The mass exponent is 0.79. Since this exponent is greater than that for VO2max, the small cyclists have an advantage in climbing, which is supported by field data. PMID:8133740

  16. Harvesting Energy from the Counterbalancing (Weaving Movement in Bicycle Riding

    Directory of Open Access Journals (Sweden)

    Shashank Priya

    2012-07-01

    Full Text Available Bicycles are known to be rich source of kinetic energy, some of which is available for harvesting during speedy and balanced maneuvers by the user. A conventional dynamo attached to the rim can generate a large amount of output power at an expense of extra energy input from the user. However, when applying energy conversion technology to human powered equipments, it is important to minimize the increase in extra muscular activity and to maximize the efficiency of human movements. This study proposes a novel energy harvesting methodology that utilizes lateral oscillation of bicycle frame (weaving caused by user weight shifting movements in order to increase the pedaling force in uphill riding or during quick speed-up. Based on the 3D motion analysis, we designed and implemented the prototype of an electro-dynamic energy harvester that can be mounted on the bicycle’s handlebar to collect energy from the side-to-side movement. The harvester was found to generate substantial electric output power of 6.6 mW from normal road riding. It was able to generate power even during uphill riding which has never been shown with other approaches. Moreover, harvesting of energy from weaving motion seems to increase the economy of cycling by helping efficient usage of human power.

  17. The involvement of c-Jun N-terminal kinase signaling pathway in the protective effect of estrogen on attenuating ischemia reperfusion injury in a rat flap model%c-Jun氨基末端激酶通路参与雌激素对大鼠皮瓣缺血再灌注损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    李志敏; 巨积辉; 刘跃飞; 金乾衡; 吴建龙; 侯瑞兴

    2016-01-01

    Objeetive To observe the protective effect of estrogen against ischemia reperfusion injury in axial flaps,and investigate the role of the c-Jun N-terminal kinase signaling pathway in estrogen's protective effect.Methods An ischemia reperfusion injury model in the abdominal flap was created in 40 Wistar rats that were randomly divided into 4 groups:control (group A),ischemia reperfusion injury (group B),estrogen (group C) and JUN inhibitor (group D).Seven days postoperatively,gross observation of the flap,measurement of flap survival area and calculation of flap survival rate were carried out.The flap tissues were harvested for hematoxylin-eosin staining to observe histological changes,and for Westem blot to quantify JNK,p-JNK and MKP-5 expression.The relationship between flap survival and JNK expression was analyzed.Results Flaps in groups C and D grew well.Flap survival rates in these two groups were significantly higher than that in group B,while pathological changes were milder.Expressions of JNK and p-JNK were significantly lower in flaps of groups C and D than in flaps of group B,while expression of JNK negative regulator MKP-5 was the opposite.Conclusion Estrogen can significantly improve the ischemia reperfusion injury in flaps and increase flap survival rate.The potential mechanism of estrogen's protective effect can be through regulating Jun N-terminal kinase signaling pathway.%目的 观察雌激素对皮瓣缺血再灌注损伤的保护作用,初步研究c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)通路与雌激素保护作用的相关性.方法 取40只Wistar大鼠建立大鼠腹部皮瓣缺血再灌注损伤模型,随机分为健康对照组(A组)、缺血再灌注损伤组(B组)、雌激素组(C组)、JNK抑制剂组(D组).术后第七天观察各组皮瓣大体情况,测量皮瓣成活面积并计算成活率,HE染色观察各组皮瓣组织学改变,测定皮瓣组织中JNK、p-JNK、丝裂原活化蛋白激酶磷酸酶-5(MKP-5)的表达.

  18. The role of phosphorylation of c-Jun NH2-terminal kinase in airway remodeling of asthmatic rats and the effect of glucocorticoids%c-Jun氨基末端激酶磷酸化在支气管哮喘大鼠气道重塑中的作用及糖皮质激素的影响

    Institute of Scientific and Technical Information of China (English)

    林立; 管小俊; 李昌崇; 苏苗赏; 张维溪; 叶乐平; 王强; 陈小芳

    2010-01-01

    目的 研究c-Jun氨基末端激酶(JNK)磷酸化在支气管哮喘(简称哮喘)气道重塑中的作用,探讨糖皮质激素对白细胞介素(IL)-1β、JNK及哮喘气道重塑的影响.方法 将48只SD大鼠按随机数字表法分为对照组、哮喘组、布地奈德组和地塞米松组,每组12只,实验组以卵清白蛋白致敏和激发复制哮喘气道重塑模型,干预组分别于每次雾化激发前以布地奈德雾化或地塞米松腹腔注射干预,对照组以生理盐水代替卵清白蛋白致敏和激发.采用图像分析技术测定支气管壁厚度(Wat)和平滑肌厚度(Wam),ELISA法测定血清、BALF中IL-1β浓度,免疫组织化学检测肺内磷酸化JNK(P-JNK)及其下游物磷酸化c-Jun蛋白表达,Western blot检测肺匀浆P-JNK表达,直线相关分析Wat、Warn与P-JNK蛋白的平均吸光度(mA)的相关性以及P-JNK蛋白的mA与血清、BALF IL-1β浓度的相关性.结果 哮喘组气道壁厚度较对照组明显增加,其血清和BALF中IL-1β浓度[分别为(81±4)ng/L、(331±15)ns/L]高于对照组[(53±6)ng/L、(130±9)ns/L](t值分别为-8.62、-24.10,均P<0.01);免疫组织化学显示哮喘组P-JNK和P-c-Jun蛋白表达增高;Western blot检测哮喘组P-JNK蛋白的mA为1.66±0.16高于对照组的1.00±0.00(t=-8.35,P<0.01);布地奈德、地塞米松均可抑制JNK的磷酸化;各组Wat、Waln与P-JNK mA均呈高度正相关(r值分别为0.700、0.769,均P<0.01,rg=48),P-JNK的mA与血清、BALF IL-1β浓度均呈显著正相关(r值分别为0.689、0.805,均P<0.01).结论 JNK磷酸化与哮喘气道重塑密切相关;糖皮质激素能抑制JNK磷酸化,其机制之一可能是下调IL-1β表达.%Objective To study the role of phosphorylation of c-Jun NH2-terminal kinase(JNK)in asthmatic airway remodeling and to explore the effect of glucocorticoids on IL-1βJNK and airway remodeling. Methods Forty-eight 4-6 week old male SD rats were randomly divided into 4 groups with 12 rats in each group: the control

  19. Clicinal significance of expression of c-JUN, E-selectin, VEGF-D protein in colorectal carcinoma%结直肠腺癌组织中c-JUN氨基末端激酶、E-选择素、血管内皮生长因子-D蛋白表达的临床意义

    Institute of Scientific and Technical Information of China (English)

    庆琳琳; 胡继春

    2015-01-01

    目的 探讨c-JUN氨基末端激酶(c-JUN)、E-选择素(E-selectin)、血管内皮生长因子-D蛋白(VEGF-D)蛋白在结直肠腺癌发展和转移中的作用.方法 收集2012年8月~2014年9月于北京市海淀医院手术切除的正常大肠黏膜组织标本(20例)和结直肠腺癌标本(50例),应用免疫组化法检测标本中c-JUN、E-selectin、VEGF-D蛋白的表达,观察c-JUN、E-selectin、VEGF-D与临床病理的联系及c-JUN与E-selectin、VEGF-D的相关性.结果 ①结直肠癌组织中,c-JUN、E-selectin、VEGF-D蛋白表达的阳性率(84%、78%、92%)显著高于正常大肠黏膜组织(5%、10%、10%),差异有高度统计学意义(P< 0.01);②c-JUN、E-selectin、VEGF-D蛋白的表达与Dukes分期及有无淋巴结转移有关(P< 0.05);③c-JUN与E-selectin呈正相关(r=0.6394,P<0.05),c-JUN与VEGF-D呈正相关(r=0.6592,P< 0.05).结论 E-selectin、VEGF-D蛋白与结直肠腺癌发展和转移有关,c-JUN可能调控E-selectin、VEGF-D的表达.

  20. An improved multi-value cellular automata model for heterogeneous bicycle traffic flow

    International Nuclear Information System (INIS)

    This letter develops an improved multi-value cellular automata model for heterogeneous bicycle traffic flow taking the higher maximum speed of electric bicycles into consideration. The update rules of both regular and electric bicycles are improved, with maximum speeds of two and three cells per second respectively. Numerical simulation results for deterministic and stochastic cases are obtained. The fundamental diagrams and multiple states effects under different model parameters are analyzed and discussed. Field observations were made to calibrate the slowdown probabilities. The results imply that the improved extended Burgers cellular automata (IEBCA) model is more consistent with the field observations than previous models and greatly enhances the realism of the bicycle traffic model. - Highlights: • We proposed an improved multi-value CA model with higher maximum speed. • Update rules are introduced for heterogeneous bicycle traffic with maximum speed 2 and 3 cells/s. • Simulation results of the proposed model are consistent with field bicycle data. • Slowdown probabilities of both regular and electric bicycles are calibrated

  1. Bicycle Guidelines and Crash Rates on Cycle Tracks in the United States

    Science.gov (United States)

    Morency, Patrick; Miranda-Moreno, Luis F.; Willett, Walter C.; Dennerlein, Jack T.

    2013-01-01

    Objectives. We studied state-adopted bicycle guidelines to determine whether cycle tracks (physically separated, bicycle-exclusive paths adjacent to sidewalks) were recommended, whether they were built, and their crash rate. Methods. We analyzed and compared US bicycle facility guidelines published between 1972 and 1999. We identified 19 cycle tracks in the United States and collected extensive data on cycle track design, usage, and crash history from local communities. We used bicycle counts and crash data to estimate crash rates. Results. A bicycle facility guideline written in 1972 endorsed cycle tracks but American Association of State Highway and Transportation Officials (AASHTO) guidelines (1974–1999) discouraged or did not include cycle tracks and did not cite research about crash rates on cycle tracks. For the 19 US cycle tracks we examined, the overall crash rate was 2.3 (95% confidence interval = 1.7, 3.0) per 1 million bicycle kilometers. Conclusions. AASHTO bicycle guidelines are not explicitly based on rigorous or up-to-date research. Our results show that the risk of bicycle–vehicle crashes is lower on US cycle tracks than published crashes rates on roadways. This study and previous investigations support building cycle tracks. PMID:23678920

  2. An improved multi-value cellular automata model for heterogeneous bicycle traffic flow

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Sheng [College of Civil Engineering and Architecture, Zhejiang University, Hangzhou, 310058 China (China); Qu, Xiaobo [Griffith School of Engineering, Griffith University, Gold Coast, 4222 Australia (Australia); Xu, Cheng [Department of Transportation Management Engineering, Zhejiang Police College, Hangzhou, 310053 China (China); College of Transportation, Jilin University, Changchun, 130022 China (China); Ma, Dongfang, E-mail: mdf2004@zju.edu.cn [Ocean College, Zhejiang University, Hangzhou, 310058 China (China); Wang, Dianhai [College of Civil Engineering and Architecture, Zhejiang University, Hangzhou, 310058 China (China)

    2015-10-16

    This letter develops an improved multi-value cellular automata model for heterogeneous bicycle traffic flow taking the higher maximum speed of electric bicycles into consideration. The update rules of both regular and electric bicycles are improved, with maximum speeds of two and three cells per second respectively. Numerical simulation results for deterministic and stochastic cases are obtained. The fundamental diagrams and multiple states effects under different model parameters are analyzed and discussed. Field observations were made to calibrate the slowdown probabilities. The results imply that the improved extended Burgers cellular automata (IEBCA) model is more consistent with the field observations than previous models and greatly enhances the realism of the bicycle traffic model. - Highlights: • We proposed an improved multi-value CA model with higher maximum speed. • Update rules are introduced for heterogeneous bicycle traffic with maximum speed 2 and 3 cells/s. • Simulation results of the proposed model are consistent with field bicycle data. • Slowdown probabilities of both regular and electric bicycles are calibrated.

  3. Predicting Free Flow Speed and Crash Risk of Bicycle Traffic Flow Using Artificial Neural Network Models

    Directory of Open Access Journals (Sweden)

    Cheng Xu

    2015-01-01

    Full Text Available Free flow speed is a fundamental measure of traffic performance and has been found to affect the severity of crash risk. However, the previous studies lack analysis and modelling of impact factors on bicycles’ free flow speed. The main focus of this study is to develop multilayer back propagation artificial neural network (BPANN models for the prediction of free flow speed and crash risk on the separated bicycle path. Four different models with considering different combinations of input variables (e.g., path width, traffic condition, bicycle type, and cyclists’ characteristics were developed. 459 field data samples were collected from eleven bicycle paths in Hangzhou, China, and 70% of total samples were used for training, 15% for validation, and 15% for testing. The results show that considering the input variables of bicycle types and characteristics of cyclists will effectively improve the accuracy of the prediction models. Meanwhile, the parameters of bicycle types have more significant effect on predicting free flow speed of bicycle compared to those of cyclists’ characteristics. The findings could contribute for evaluation, planning, and management of bicycle safety.

  4. Toll 样受体2介导的 JNK 信号分子在小鼠支气管哮喘发病中的作用机制%Mechanism of c-Jun N-terminal kinase mediated by Toll like receptor 2 in murine asthma

    Institute of Scientific and Technical Information of China (English)

    沈佩婷; 方磊; 吴惠梅; 沈启英; 何芳; 刘荣玉

    2015-01-01

    目的:探讨 Toll 样受体2(TLR2)介导的 c-Jun 氨基末端激酶(JNK)信号分子参与小鼠支气管哮喘发病的作用机制。方法健康 SPF 级 C57(TLR2野生型)鼠和 TLR2基因缺失(TLR2-/-)鼠各14只,按随机数字表法分为4组:C57对照组、C57哮喘组、TLR2-/-对照组、TLR2-/-哮喘组,每组7只,哮喘组以卵清蛋白(OVA)腹腔注射联合雾化吸入致敏和激发建立哮喘模型,对照组以生理盐水代替 OVA致敏和激发。利用免疫组织化学染色技术( ABC 法)检测TLR2蛋白在 C57对照组、C57哮喘组肺内的表达差异,JNK及磷酸化 JNK(P-JNK)蛋白表达在各组肺内的表达差异。结果 HE 染色提示较其余3组,C57哮喘组有较明显的炎症细胞浸润及呼吸道平滑肌增生。以平均吸光度(mA)衡量各组织蛋白相对表达量,免疫组化结果提示 TLR2蛋白在C57哮喘组表达显著高于 C57对照组(P <0.01),JNK 蛋白在各组的表达差异无统计学意义,P-JNK 蛋白在 C57哮喘组肺组织的表达量显著高于 C57对照组、TLR2-/-哮喘组、TLR2-/-对照组(F =43.261,P <0.01)。结论 TLR2介导的 JNK 信号分子通路可能参与了支气管哮喘的发病过程。%Objective To explore the mechanism of c-Jun N-terminal kinase mediated by Toll like receptor 2 in murine asthma. Methods 14 healthy SPF grade C57 wild-type mice and 14 TLR2 knockout (TLR2 - / - ) mice were randomly divided into four groups: C57 control group, C57 asthma group, TLR2 - / - control group, TLR2 - / - asth-ma group (n = 7). We utilized intraperitoneal injection combined with inhalation of ovalbumin (OVA) to sensitize and challenge the mice, thus establishing the experimental models of asthma. Meanwhile, the control group received normal saline instead of OVA. The protein expression of TLR2 was detected by immunohistochemistry(ABC meth-od) in C57 control group and C57 asthma group,as well as JNK and phosphorylation c-Jun(P-JNK) between each group. Results In C57

  5. Cyclist safety on bicycle boulevards and parallel arterial routes in Berkeley, California.

    Science.gov (United States)

    Minikel, Eric

    2012-03-01

    This study compares the safety of bicyclists riding on bicycle boulevards to those riding on parallel arterial routes in Berkeley, California. Literature on the impact of motor vehicle traffic characteristics on cyclist safety shows that high motor vehicle speeds and volumes and the presence of heavy vehicles are all detrimental to cyclist safety. This suggests that cyclists may be safer on side streets than on busy arterials. Bicycle boulevards-traffic-calmed side streets signed and improved for cyclist use-purport to offer cyclists a safer alternative to riding on arterials. Police-reported bicycle collision data and manually collected cyclist count data from bicycle boulevards and parallel arterial routes in Berkeley, California from 2003 to 2010 are used to test the hypothesis that Berkeley's bicycle boulevards have lower cyclist collision rates and a lower proportion of bicycle collisions resulting in severe injury. While no significant difference is found in the proportion of collisions that are severe, results show that collision rates on Berkeley's bicycle boulevards are two to eight times lower than those on parallel, adjacent arterial routes. The difference in collision rate is highly statistically significant, unlikely to be caused by any bias in the collision and count data, and cannot be easily explained away by self-selection or safety in numbers. Though the used dataset is limited and the study design is correlational, this study provides some evidence that Berkeley's bicycle boulevards are safer for cyclists than its parallel arterial routes. The results may be suggestive that, more generally, properly implemented bicycle boulevards can provide cyclists with a safer alternative to riding on arterials. PMID:22269506

  6. Optimal Time-Trial Bicycle Racing with Headwinds and Tailwinds

    CERN Document Server

    Anton, A Brad

    2013-01-01

    Many time-trial and triathlon bicycle races take place on relatively flat, closed-circuit courses. In the absence of hills, riding-speed is limited almost solely by aerodynamic drag; consequently, winds can have a big effect on elapsed times. I analyze the special case of a straight out-and-back race in a steady wind, assuming the rider has a given total amount of energy to expend and can choose only two speeds - the aided speed with tailwind and the hindered speed into headwind. In this ideal circumstance the problem of choosing optimal riding speeds reduces to a constrained nonlinear optimization that can be solved with elementary calculus. My analysis reveals a practical rule of thumb that can be used more generally to choose optimal riding speeds for time-trial racing on closed-circuit courses in the presence of headwinds and tailwinds.

  7. [Prognostic significance of bicycle ergometry test in patients with myocarditis].

    Science.gov (United States)

    Gavalova, R F; Borodina, V I

    1992-04-01

    A total of 42 patients with rheumatic carditis were examined in the acute-subacute period and following 3-5 years. Seventeen patients were diagnosed as having primary rheumatic carditis, 9 presented with tonsillogenic rheumatic carditis, and 16 had viral rheumatic carditis. The diagnosis of myocarditis was established on the basis of clinical, immunological, and virological findings. The study involved ECG, PhCG, PCG, and bicycle ergometer testing recordings. Groups of patients with good and poor prognosis were identified. Low threshold exercise, exercise-inadequate tachycardia, complex cardiac arrhythmias, phasic myocardial hypodynamic syndrome and volume exercise syndrome that are formed during performance are prognostically poor indicators. More profound electric and mechanic dysfunctions were observed in patients with tonsillogenic or viral myocarditis.

  8. Synthesis of bicyclic alkaloids from the iridoid antirrhinoside

    DEFF Research Database (Denmark)

    Frederiksen, Signe Maria

    The present thesis describes the isolation of the iridoid glucoside antirrhinoside from Antirrhinum majus, and the approaches made towards its transformation into analogues of biologically active compounds, with special interest in syntheses of bicyclic alkaloids.A synthetic piperidine monoterpene...... alkaloid was prepared from antirrhinoside by means of an enzymatic cleavage to afford the aglucone, followed by a double reductive amination with benzylamine hydrochloride and sodium cyanoborohydride. The resulting piperidine was modified by opening of the epoxide on the cyclopropane ring by azide...... strategy was therefore abandoned.A one-pot reaction involving ozonolysis and subsequent reduction of the 5,6-O-isopropylidene-2',3',4',6'-tetra-O-acetyl antirrhinoside yielded a diol, which was considered a potential intermediate in the preparation of enantiopure 3-azabicyclo[3.3.0]octane alkaloids...

  9. Consumers’ preferences for “bicycle poultry” in Benin

    DEFF Research Database (Denmark)

    Sodjinou, Epiphane; Henningsen, Arne; Koudande, Delphin O.;

    Village poultry, also termed "bicycle poultry," is produced in scavenging farming systems and is a chewy meat with a low fat content, and constitutes an important source of meat in many African countries. This study investigates consumers’ preferences regarding the physical traits of these birds...... are willing to pay a premium for these types of birds. The factors which significantly influence the price of chicken are the breed of the bird, the plumage color, the meatiness and the age of the bird. Consumers are willing to pay a price premium for meatier birds of traditional breeds with white plumage...... color and aged between six and twelve months. Thus, efforts to improve local breeds should stress these preferred traits....

  10. Aromatic Esters of Bicyclic Amines as Antimicrobials against Streptococcus pneumoniae.

    Science.gov (United States)

    de Gracia Retamosa, María; Díez-Martínez, Roberto; Maestro, Beatriz; García-Fernández, Esther; de Waal, Bas; Meijer, E W; García, Pedro; Sanz, Jesús M

    2015-11-01

    A double approach was followed in the search of novel inhibitors of the surface choline-binding proteins (CBPs) of Streptococcus pneumoniae (pneumococcus) with antimicrobial properties. First, a library of 49 rationally-designed esters of alkyl amines was screened for their specific binding to CBPs. The best binders, being esters of bicyclic amines (EBAs), were then tested for their in vitro effect on pneumococcal growth and morphology. Second, the efficiency of EBA-induced CBP inhibition was enhanced about 45,000-fold by multivalency effects upon synthesizing a poly(propylene imine) dendrimer containing eight copies of an atropine derivative. Both approaches led to compounds that arrest bacterial growth, dramatically decrease cell viability, and exhibit a protection effect in animal disease models, demonstrating that the pneumococcal CBPs are adequate targets for the discovery of novel antimicrobials that overcome the currently increasing antimicrobial resistance issues. PMID:26377931

  11. Synthesis and screening of bicyclic carbohydrate-based compounds: a novel type of antivirals.

    Science.gov (United States)

    Van Hoof, Steven; Ruttens, Bart; Hubrecht, Idzi; Smans, Gert; Blom, Petra; Sas, Benedikt; Van hemel, Johan; Vandenkerckhove, Jan; Van der Eycken, Johan

    2006-03-15

    A small library of bicyclic carbohydrate derivatives was synthesized and screened. A strong and selective activity against cytomegalovirus was found. Structure-activity relationship for this new type of antivirals is discussed.

  12. Prioritization of Integrated Bicycle Network Clusters in Istanbul Using Analytic Hierarchy Process

    Directory of Open Access Journals (Sweden)

    Dilek Çol Yılmaz

    2014-06-01

    Full Text Available In this study, the impact of the integration of nonmotorized transport and public transport on hypermobility was evaluated. The role of bicycle in non-motorized transportation, and its contribution to sustainable travel goals were examined. A decision support model was established in order to plan the phases of a bicycle network integrated with the public transport sytem in Istanbul Metropolitan Area. Data such as public transport routes planned for the target year 2023, locations of transfer centers, number of passengers at transfer centers, and a revised bicycle network were used as layers for the Geographic Information Systems (GIS map produced. Based on the survey data collected from the experts, Analytic Hierarchy Process (AHP which is a multi-criteria decision-making procedure that contains both qualitative and quantitative factors was used to prioritize the bicycle network clusters integrated with public transport system in Istanbul.

  13. EU to Continue 48.5% Anti-dumping Duties on Chinese Bicycles

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    On June 10, European Commission informed the Business Office of the Mission of Ministry of Commerce in EU and disclosed the adjudication on the review of the EU imposing anti-dumping on Chinese bicycles.

  14. Sleep Deprivation Is Associated with Bicycle Accidents and Slip and Fall Injuries in Korean Adolescents.

    Directory of Open Access Journals (Sweden)

    So Young Kim

    Full Text Available This study sought to evaluate associations between sleep time and bicycle accidents, falls under various circumstances, and dental injuries in adolescents.A total of 61,696 participants ranging from 12 to 18 years of age who completed the Korea Youth Risk Behavior Web-based Survey (KYRBWS in 2013 were enrolled in this study. Bicycle riding accidents were analyzed for 17,232 bicycle-riding participants. Data were collected regarding the weekday sleep duration for the most recent 7 days, which was categorized as the 5.5-6.5 h group > the 6.5-7.5 h group. There was no significant relationship between sleep deprivation and dental injury.This study demonstrated that sleep deprivation among Korean adolescents was associated with bicycle accidents and falls at home and school. Thus, adequate sleep may be needed to prevent accidents and falls.

  15. Physiological responses and exercise preference between the Trikke and the bicycle ergometer

    Directory of Open Access Journals (Sweden)

    Eddie T.C. Lam

    2016-06-01

    Conclusion: Participants were more efficient in using the Trikke than the bicycle ergometer. The Trikke may be an enjoyable alternative for those individuals, particularly women, who have lost interest in traditional forms of exercise.

  16. An Analyses of Bicycle Accidents in Ankara: Analyses of 5 Years

    Directory of Open Access Journals (Sweden)

    Muhittin Yilmaz

    2014-12-01

    Full Text Available Aim: Bicycles are used for transportation, exercise and recreation. In this study we aimed to investigate the epidemiological, clinical and economic aspects of bicycle injuries. Material and Method: We included in the study who admitted to the Emergency Department with a bicycle accident between January 2008 and July 2012. Patient age and sex, accident pattern, presence of personal protective measures, injured body part, Glasgow Coma Scale (GCS score, Revised Trauma Score (RTS, radiological findings, requested consultations, duration of hospital stay, season of injury, and average cost rates were recorded. The study population was divided into 2 age groups as 0-14 years and over 14 years. Results: A patients were 238 (81.2% male and their mean age was 31.5±14.1 years. Fifty-five (18.8% patients were female and their mean age was 34.5±15.9 years. Males had significantly higher rate of bicycle injury (p

  17. Isn't it time to take bicycles seriously again in Beijing ?%Isn't it time to take bicycles seriously again in Beijing ?

    Institute of Scientific and Technical Information of China (English)

    Shannon Bufton; Florian Lorenz

    2011-01-01

    The humble bicycle was once the predominant mode of transport in Beijing and it can be argued that the city has previously been one of the best bicycle cities in the world. Now the streets are littered with rusting old bikes and it seems as if Beijing has turned its back on the bicycle in its quest for modernity and evolution. The resultant re-configuration of the city and the rapid speed of development of modern transportation systems (particularly the lightening growth of personal automobiles) have created a complex set of issues and challenges which now put the city under pressure such as sustainability, air quality, health and traffic congestion problems.

  18. Modeling and simulation of the transmission system for a chainless electric bicycle

    OpenAIRE

    Garcia Farreny, Alex

    2015-01-01

    This project, entitled Modeling and Simulation of the Transmission System for a Chainless Electric Bicycle, consists in the design of the controllers’ logics governing a chainless electric bicycle’s transmission in order to accomplish certain behavior in front of inputs such as pedaling torque, slope gradient, frontal wind, gear selected, etc. To better understand it, a chainless electric bicycle replaces the conventional mechanical transmission (chain) by two electric mac...

  19. Teaching children about bicycle safety: an evaluation of the New Jersey Bike School program.

    Science.gov (United States)

    Lachapelle, Ugo; Noland, Robert B; Von Hagen, Leigh Ann

    2013-03-01

    There are multiple health and environmental benefits associated with increasing bicycling among children. However, the use of bicycles is also associated with severe injuries and fatalities. In order to reduce bicycle crashes, a bicycling education program was implemented in selected New Jersey schools and summer camps as part of the New Jersey Safe Routes to School Program. Using a convenience sample of participants to the program, an opportunistic study was designed to evaluate the effectiveness of two bicycle education programs, the first a more-structured program delivered in a school setting, with no on-road component, and the other a less structured program delivered in a summer camp setting that included an on-road component. Tests administered before and after training were designed to assess knowledge acquired during the training. Questions assessed children's existing knowledge of helmet use and other equipment, bicycle safety, as well as their ability to discriminate hazards and understand rules of the road. Participating children (n=699) also completed a travel survey that assessed their bicycling behavior and their perception of safety issues. Response to individual questions, overall pre- and post-training test scores, and changes in test scores were compared using comparison of proportion, t-tests, and ordinary least-squares (OLS) regression. Improvements between the pre-training and post-training test are apparent from the frequency distribution of test results and from t-tests. Both summer camps and school-based programs recorded similar improvements in test results. Children who bicycled with their parents scored higher on the pre-training test but did not improve as much on the post-training test. Without evaluating long-term changes in behavior, it is difficult to ascertain how successful the program is on eventual behavioral and safety outcomes.

  20. 电针对鱼藤酮诱导的帕金森病模型大鼠黑质内c-Jun氨基末端激酶及γ干扰素的影响%Effect of electroacupuncture on c-Jun amino terminal kinase signaling pathway and inflammatory cytokines interferon-γ in substantia nigra cells of rotenone-induced rats model of Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    马骏; 龚元勋; 王述菊; 王彦春; 曾晓玲; 甘水咏; 梁艳

    2014-01-01

    目的 观察电针对帕金森病(PD)模型大鼠黑质内c-Jun氨基末端激酶(JNK)信号通路及γ-干扰素(IFN-γ)的影响.方法 选取雄性健康SD大鼠32只,按照随机数字表法将其分为正常组、假手术组、模型组及电针组,每组8只.模型组和电针组大鼠经颈背部注射鱼藤酮[1 mg/kg,溶于一定比例二甲亚砜(DMSO)和生理盐水中,浓度0.25 mg/ml],假手术组经颈背部注射同剂量的DMSO和生理盐水混合液,正常组不进行特殊干预.PD大鼠造模成功后,在电针组大鼠“风府”、“太冲”穴位进行治疗.治疗结束后,对4组大鼠进行行为学观察及敞箱实验.采用免疫蛋白印迹法检测4组大鼠脑内酪氨酸羟化酶(TH)、磷酸化c-Jun和IFN-γ的表达情况.结果 模型组大鼠表现出明显的PD综合征,与正常组和假手术组比较,差异无统计学意义(P>0.05).敞箱实验结果显示,模型组大鼠水平运动[(19.12±2.34)分]、垂直运动活性[(5.27±1.04)分]较正常组和假手术组明显降低,差异有统计学意义(P<0.05).电针治疗后,大鼠运动活性较模型组明显增强,差异有统计学意义(P<0.05),与正常组和假手术组比较,差异无统计学意义(P>0.05).与正常组比较,模型组大鼠黑质区TH蛋白(0.183 ±0.021)表达显著减少,磷酸化c-Jun(0.388±0.028)和IFN-γ蛋白(0.453 ±0.033)表达显著增加,差异有统计学意义(P<0.05).与正常组比较,电针组大鼠黑质区TH蛋白(0.324 ±0.054)表达有所减少,磷酸化的c-Jun(0.207±0.059)和IFN-γ蛋白(0.239±0.022)表达有所增加,差异无统计学意义(P>0.05).与模型组比较,电针组大鼠黑质区TH蛋白明显增加,磷酸化的c-Jun和IFN-γ蛋白表达明显减少,差异有统计学意义(P<0.05).结论 电针刺激可降低大鼠黑质区c-Jun及炎症因子IFN-γ的表达水平,对PD模型大鼠体内JNK信号通路及疾病进展起到一定的调节作用.%Objective To observe the effects of

  1. A Modified Cellular Automaton Approach for Mixed Bicycle Traffic Flow Modeling

    Directory of Open Access Journals (Sweden)

    Xiaonian Shan

    2015-01-01

    Full Text Available Several previous studies have used the Cellular Automaton (CA for the modeling of bicycle traffic flow. However, previous CA models have several limitations, resulting in differences between the simulated and the observed traffic flow features. The primary objective of this study is to propose a modified CA model for simulating the characteristics of mixed bicycle traffic flow. Field data were collected on physically separated bicycle path in Shanghai, China, and were used to calibrate the CA model using the genetic algorithm. Traffic flow features between simulations of several CA models and field observations were compared. The results showed that our modified CA model produced more accurate simulation for the fundamental diagram and the passing events in mixed bicycle traffic flow. Based on our model, the bicycle traffic flow features, including the fundamental diagram, the number of passing events, and the number of lane changes, were analyzed. We also analyzed the traffic flow features with different traffic densities, traffic components on different travel lanes. Results of the study can provide important information for understanding and simulating the operations of mixed bicycle traffic flow.

  2. Bicycle helmet use and non-use – recently published research

    Science.gov (United States)

    2012-01-01

    Bicycle traumata are very common and especially neurologic complications lead to disability and death in all stages of the life. This review assembles the most recent findings concerning research in the field of bicycle traumata combined with the factor of bicycle helmet use. The area of bicycle trauma research is by nature multidisciplinary and relevant not only for physicians but also for experts with educational, engineering, judicial, rehabilitative or public health functions. Due to this plurality of global publications and special subjects, short time reviews help to detect recent research directions and provide also information from neighbour disciplines for researchers. It can be stated that to date, that although a huge amount of research has been conducted in this area more studies are needed to evaluate and improve special conditions and needs in different regions, ages, nationalities and to create successful prevention programs of severe head and face injuries while cycling. Focus was explicit the bicycle helmet use, wherefore sledding, ski and snowboard studies were excluded and only one study concerning electric bicycles remained due to similar motion structures within this review. The considered studies were all published between January 2010 and August 2011 and were identified via the online databases Medline PubMed and ISI Web of Science. PMID:22632628

  3. Association of Sociodemographic and Perceived Environmental Factors with Public Bicycle Use among Taiwanese Urban Adults

    Directory of Open Access Journals (Sweden)

    Yung Liao

    2016-03-01

    Full Text Available Background: This study examined the sociodemographic and perceived environmental factors associated with public bicycle use among Taiwanese urban adults. Methods: A random-digit-dialing telephone-based cross-sectional survey was administered to Taiwanese urban adults aged 20–64 years in 2015. Data on sociodemographic variables, perceived environmental factors (for attributes identified in the International Physical Activity Questionnaire-Environmental Module, and public bicycle use were obtained from 1002 adults in three cities. Adjusted logistic regression was used. Results: After adjustment for potential confounders, the results showed that adults aged 20–29 years (odds ratio (OR = 4.42 with a university degree or higher (OR = 2.03 were more likely to use public bicycles. In addition, adults living in Kaohsiung City were less likely to use public bicycles (OR = 0.24. Adults who saw people being active (OR = 1.76; 95% CI: 1.05–2.86 and had positive aesthetic experiences of their environment (OR = 1.69 were more likely to use public bicycles. Conclusions: Our findings suggest that seeing physically active people and positive aesthetic perceptions of the environment are key factors for developing transportation policies and intervention strategies for promoting public bicycle use among Taiwanese urban adults.

  4. c-Jun氨基末端激酶1反义真核表达载体及其蛋白缺陷细胞株的构建与鉴定%Construction and identification of antisense c-Jun N-terminal kinase 1 eukaryotic fluorescent expressing plasmids and JNK1+ human embryo lung fibroblasts cell line

    Institute of Scientific and Technical Information of China (English)

    徐辉; 何晓庆; 陈瑞; 尹仕伟; 彭雷; 王国强; 李爱萍; 周建伟; 刘起展

    2008-01-01

    目的 构建反义JNK1荧光真核细胞表达载体,建立JNK1蛋白缺陷人胚肺成纤维细胞(HELF)株.方法 用Trizol试剂抽提HELF细胞中总RNA,以反转录PCR扩增JNK1目的 片断,双酶切,纯化PCR产物后,反向插入pEGFP-C1绿色荧光质粒,构建反义pEGFP-C1-asJNK1真核表达载体;大量抽提质粒并转染至HELF细胞中.24 h后使用G418筛选,挑选单克隆细胞扩大培养,经荧光显微成像和蛋白免疫印迹鉴定.结果 pEGFP-C1-asJNK1表达载体DNA测序结果与预期目的 片断序列一致,且JNK1蛋白表达水平明显抑制.结论 反义pEGFP-C1-asJNK1真核表达载体构建成功,JNK1蛋白质缺陷HELF细胞株成功建立.%Objective To construct antisense c-Jun N-terminal kinase 1 (JNK1) eukaryotic fluorescent expressing vector and JNK1+ human embryo lung fibroblasts cell line. Methods Trizol reagent was used to extract total RNA in HELF. The proper primers of JNK1 were chosen and synthesized. RT-PCR and gene recombinant techniques were used to construct the fragment of JNK1. After purification, the PCR products were cut, and JNK1 were inserted reversely into eukaryotic fluorescent expressing vector pEGFP-C1. Enzyme-cutting and DNA auto-sequencing were used to prove the successful construction of JNK1 eukaryotic expressing vector. Then plasmids were extracted and transfected into HELF cells and screen by G418 24 h later. Monoclone was chosen and cultured. Fluorescent imaging and Western blot were used to identify the JNK+HELF cell line. Results Sequence analysis of pEGFP-C1-as JNK1 plasmids was same as expected. The expression level of JNK1 was inhibited markedly. Conclusion Construction of antisensc JNK1 eukaryotic fluorescent expressing vectors and JNK + HELF cell line is successful.

  5. The Effects of Surface-Induced Loads on Forearm Muscle Activity During Steering a Bicycle

    Science.gov (United States)

    Arpinar-Avsar, Pinar; Birlik, Gülin; Sezgin, Önder C.; Soylu, Abdullah R.

    2013-01-01

    On the bicycle, the human upper extremity has two essential functions in steering the bicycle and in supporting the body. Through the handlebar, surface- induced loads are transmitted to the hand and arm of the bicycle rider under vibration exposure conditions. Thus, the purpose of the study was to investigate the effect of vibration exposure on forearm muscle activity for different road surfaces (i.e. smooth road, concrete stone pavement, rough road) and for different bicycles. Ten subjects participated in experiments and two types of bicycles, i.e. Road Bike (RB) and Mountain Bike (MTB) are compared. The acceleration magnitudes were dominant along x and z-axes. The r.m.s acceleration values in the z direction at the stem of MTB were at most 2.56, 7.04 and 10.76 m·s-2 when pedaling respectively on asphalt road, concrete pavement and rough road. In the case of RB the corresponding values were respectively 4.43, 11.75 and 27.31 m·s-2. The cumulative normalized muscular activity levels during MTB trials on different surfaces had the same tendency as with acceleration amplitudes and have ranked in the same order from lowest to highest value. Although road bike measurements have resulted in a similar trend of increment, the values computed for rough road trials were higher than those in MTB trials. During rough road measurements on MTB, rmsEMG of extensor muscles reached a value corresponding to approximately 50% of MVC (Maximum Voluntary Contraction). During RB trials performed on rough road conditions, rmsEMG (%MVC) values for the forearm flexor muscles reached 45.8% of their maximal. The level of muscular activity of forearm muscles in controlling handlebar movements has been observed to be enhanced by the increase in the level of vibration exposed on the bicycle. Since repeated forceful gripping and pushing forces to a handle of a vibratory tool can create a risk of developing circulatory, neurological, or musculoskeletal disorder, a bicycle rider can be

  6. Incidence and costs of bicycle-related traumatic brain injuries in the Netherlands.

    Science.gov (United States)

    Scholten, Annemieke C; Polinder, Suzanne; Panneman, Martien J M; van Beeck, Ed F; Haagsma, Juanita A

    2015-08-01

    The main cause of death and serious disability in bicycle accidents is traumatic brain injury (TBI). The aim of this population-based study was to assess the incidence and costs of bicycle-related TBI across various age groups, and in comparison to all bicycle-related injuries, to identify main risk groups for the development of preventive strategies. Data from the National Injury Surveillance System and National Medical Registration were used for all patients with bicycle-related injuries and TBI who visited a Dutch emergency department (ED) between 1998 and 2012. Demographics and national, weighted estimates of injury mechanism, injury severity and costs were analysed per age group. Direct healthcare costs and indirect costs were determined using the incidence-based Dutch Burden of Injury Model. Between 1998 and 2012, the incidence of ED treatments due to bicycle-related TBI strongly increased with 54%, to 43 per 100,000 persons in 2012. However, the incidence of all bicycle-related injuries remained stable, from 444 in 1998 to 456/100,000 in 2012. Incidence of hospital admission increased in both TBI (92%) and all injuries from cycling (71%). Highest increase in incidence of both ED treatments and hospital admissions was seen in adults aged 55+. The injury rate of TBI per kilometre travelled increased (44%) except in children, but decreased (-4%) for all injuries, showing a strong decrease in children (-36%) but an increase in men aged 25+, and women aged 15+. Total costs of bicycle-related TBI were €74.5 million annually. Although bicycle-related TBI accounted for 9% of the incidence of all ED treatments due to cycling, it accounted for 18% of the total costs due to all bicycle-related injuries (€410.7 million). Children and adolescents (aged 0-24) had highest incidence of ED treatments due to bicycle-related injuries. Men in the working population (aged 15-64) had highest indirect costs following injuries from cycling, including TBI. Older cyclists (aged

  7. Optimization of electric bicycle for youths with disabilities.

    Science.gov (United States)

    Blumenstein, Tobias; Zeitlmann, Hilar; Alves-Pinto, Ana; Turova, Varvara; Lampe, Renée

    2014-01-01

    Cerebral palsy is a group of neurodevelopmental disorders that affect a person's ability to move and to maintain balance and posture. People with cerebral palsy have also perception and space orientation deficits so that special assistance devices should be developed to compensate these handicaps. The objective was to optimize an adapted electric bicycle (E-bike) for youths with neurodevelopmental disorders. An adapted E-bike was provided with ultrasonic sensors that measure distances to objects. If the distance to other objects reduces, an acoustic signal is sent. Additionally, a self-created force plate was fixed on the pedal to evaluate the muscle performances during biking. An experiment with the ultrasound warning system confirmed that acoustic feedback was helpful in avoiding obstacles. The measurement of the blood pressure, the heart frequency and the pedaling force during biking approved that the training condition of the test person can be registered and enables tuning the power of the electric motor to individual requirements. The results demonstrate that an adapted E-bike can be improved to provide better space orientation for people with perceptual disorders and to measure training conditions of patients. Moreover, these enable individual adjustment of the electric motor power to optimize comfort and therapy effect. PMID:25485189

  8. Big Bicycle Data Processing: from Personal Data to Urban Applications

    Science.gov (United States)

    Pettit, C. J.; Lieske, S. N.; Leao, S. Z.

    2016-06-01

    Understanding the flows of people moving through the built environment is a vital source of information for the planners and policy makers who shape our cities. Smart phone applications enable people to trace themselves through the city and these data can potentially be then aggregated and visualised to show hot spots and trajectories of macro urban movement. In this paper our aim is to develop procedures for cleaning, aggregating and visualising human movement data and translating this into policy relevant information. In conducting this research we explore using bicycle data collected from a smart phone application known as RiderLog. We focus on the RiderLog application initially in the context of Sydney, Australia and discuss the procedures and challenges in processing and cleaning this data before any analysis can be made. We then present some preliminary map results using the CartoDB online mapping platform where data are aggregated and visualised to show hot spots and trajectories of macro urban movement. We conclude the paper by highlighting some of the key challenges in working with such data and outline some next steps in processing the data and conducting higher volume and more extensive analysis.

  9. Environmental Determinants of Bicycling Injuries in Alberta, Canada

    Directory of Open Access Journals (Sweden)

    Nicole T. R. Romanow

    2012-01-01

    Full Text Available This study examined environmental risk factors for bicycling injuries, by combining data on bicyclist injuries collected by interviews in the emergency department (ED with street-level environmental audits of injury locations, capturing path, roadway, safety, land use, and aesthetic characteristics. Cases were bicyclists struck by a motor vehicle (MV or with severe injuries (hospitalized. Controls were bicyclists who were not hit by a car or those seen and discharged from the ED, matched on time and day of injury. Logistic regression odds ratios (ORs adjusted for age, sex, peak time, and bicyclist speed with 95% confidence intervals (CIs were estimated to relate injury risk to environmental characteristics. Factors contributing to MV events included greater traffic volume (OR 5.13; 95% CI [1.44, 18.27], intersections (OR 6.89; 95% CI [1.48, 32.14], retail establishments (OR 5.56; 95% CI [1.72, 17.98], and path obstructions (OR 3.83; 95% CI [1.03, 14.25]. Locations where the road was in good condition (OR 0.25; 95% CI [0.07, 0.96] and where there was high surveillance from surrounding buildings (OR 0.32; 95% CI [0.13, 0.82] were associated with less severe injuries. These findings could be used by bicyclists and transportation planners to improve safety.

  10. Environmental Determinants of Bicycling Injuries in Alberta, Canada

    Science.gov (United States)

    Romanow, Nicole T. R.; Couperthwaite, Amy B.; McCormack, Gavin R.; Nettel-Aguirre, Alberto; Rowe, Brian H.; Hagel, Brent E.

    2012-01-01

    This study examined environmental risk factors for bicycling injuries, by combining data on bicyclist injuries collected by interviews in the emergency department (ED) with street-level environmental audits of injury locations, capturing path, roadway, safety, land use, and aesthetic characteristics. Cases were bicyclists struck by a motor vehicle (MV) or with severe injuries (hospitalized). Controls were bicyclists who were not hit by a car or those seen and discharged from the ED, matched on time and day of injury. Logistic regression odds ratios (ORs) adjusted for age, sex, peak time, and bicyclist speed with 95% confidence intervals (CIs) were estimated to relate injury risk to environmental characteristics. Factors contributing to MV events included greater traffic volume (OR 5.13; 95% CI [1.44, 18.27]), intersections (OR 6.89; 95% CI [1.48, 32.14]), retail establishments (OR 5.56; 95% CI [1.72, 17.98]), and path obstructions (OR 3.83; 95% CI [1.03, 14.25]). Locations where the road was in good condition (OR 0.25; 95% CI [0.07, 0.96]) and where there was high surveillance from surrounding buildings (OR 0.32; 95% CI [0.13, 0.82]) were associated with less severe injuries. These findings could be used by bicyclists and transportation planners to improve safety. PMID:23251192

  11. The Aeroflex: A Bicycle for Mobile Air Quality Measurements

    Directory of Open Access Journals (Sweden)

    Bart Elen

    2012-12-01

    Full Text Available Fixed air quality stations have limitations when used to assess people's real life exposure to air pollutants. Their spatial coverage is too limited to capture the spatial variability in, e.g., an urban or industrial environment. Complementary mobile air quality measurements can be used as an additional tool to fill this void. In this publication we present the Aeroflex, a bicycle for mobile air quality monitoring. The Aeroflex is equipped with compact air quality measurement devices to monitor ultrafine particle number counts, particulate mass and black carbon concentrations at a high resolution (up to 1 second. Each measurement is automatically linked to its geographical location and time of acquisition using GPS and Internet time. Furthermore, the Aeroflex is equipped with automated data transmission, data pre-processing and data visualization. The Aeroflex is designed with adaptability, reliability and user friendliness in mind. Over the past years, the Aeroflex has been successfully used for high resolution air quality mapping, exposure assessment and hot spot identification. 

  12. On the closure of the extended bicyclic semigroup

    CERN Document Server

    Fihel, Iryna

    2012-01-01

    In the paper we study the semigroup $\\mathscr{C}_{\\mathbb{Z}}$ which is a generalization of the bicyclic semigroup. We describe main algebraic properties of the semigroup $\\mathscr{C}_{\\mathbb{Z}}$ and prove that every non-trivial congruence $\\mathfrak{C}$ on the semigroup $\\mathscr{C}_{\\mathbb{Z}}$ is a group congruence, and moreover the quotient semigroup $\\mathscr{C}_{\\mathbb{Z}}/\\mathfrak{C}$ is isomorphic to a cyclic group. Also we show that the semigroup $\\mathscr{C}_{\\mathbb{Z}}$ as a Hausdorff semitopological semigroup admits only the discrete topology. Next we study the closure $\\operatorname{cl}_T(\\mathscr{C}_{\\mathbb{Z}})$ of the semigroup $\\mathscr{C}_{\\mathbb{Z}}$ in a topological semigroup $T$. We show that the non-empty remainder of $\\mathscr{C}_{\\mathbb{Z}}$ in a topological inverse semigroup $T$ consists of a group of units $H(1_T)$ of $T$ and a two-sided ideal $I$ of $T$ in the case when $H(1_T)\

  13. Bicycle accident-related head injuries in India

    Science.gov (United States)

    Munivenkatappa, Ashok; Devi, Bhagavatula Indira; Gregor, Thomas Issac; Bhat, Dhananjay I.; Kumarsamy, Akhil Deepika; Shukla, Dhaval P.

    2013-01-01

    Objectives: To describe the epidemiology of head injuries sustained due to bicycle accidents in India. Materials and Methods: Data were retrospectively collected over a period of six months (15 May 2011 to 15 November 2011). Demography of patients, Glasgow coma scale (GCS), clinical and imaging findings, and mortality and outcome using Glasgow outcome scale (GOS), Rivermead post-concussion symptom questionnaire (RPCSQ) and Rivermead head injury follow-up questionnaire (RHFUQ), were analyzed. Outcome was assessed by telephonic interview. Results: There were 108 patients (100 males) with mean age of 27.7 years. Seventy-four (68.5%) were from rural areas. Accidents due to vehicular collision accounted for 60 (55.6%) cases. None wore a helmet. The admission GCS was 14-15 in 68.5% cases, 13-3 in 31.5%. The risk of moderate to severe injuries was increased among working laborers (OR = 5), and patients with loss of consciousness (OR = 4). Sixty-three (49%) patients had abnormal computed tomography (CT) findings; most common finding was skull fracture 25 (23.1%). Four patients needed surgery. The GOS assessment at three to six months revealed favorable outcome in 66 patients (61.1%) and death in 8 (7.4%). The common post-concussion symptoms were headache, fatigue, and poor concentration. Conclusion: The majority of hospitalized cyclists were from a rural background and of the lower income group. After three months the majority of patients had good recovery with few persistent concussion symptoms. PMID:24250156

  14. The Aeroflex: A Bicycle for Mobile Air Quality Measurements

    Science.gov (United States)

    Elen, Bart; Peters, Jan; Van Poppel, Martine; Bleux, Nico; Theunis, Jan; Reggente, Matteo; Standaert, Arnout

    2013-01-01

    Fixed air quality stations have limitations when used to assess people's real life exposure to air pollutants. Their spatial coverage is too limited to capture the spatial variability in, e.g., an urban or industrial environment. Complementary mobile air quality measurements can be used as an additional tool to fill this void. In this publication we present the Aeroflex, a bicycle for mobile air quality monitoring. The Aeroflex is equipped with compact air quality measurement devices to monitor ultrafine particle number counts, particulate mass and black carbon concentrations at a high resolution (up to 1 second). Each measurement is automatically linked to its geographical location and time of acquisition using GPS and Internet time. Furthermore, the Aeroflex is equipped with automated data transmission, data pre-processing and data visualization. The Aeroflex is designed with adaptability, reliability and user friendliness in mind. Over the past years, the Aeroflex has been successfully used for high resolution air quality mapping, exposure assessment and hot spot identification. PMID:23262484

  15. Optimization of electric bicycle for youths with disabilities.

    Science.gov (United States)

    Blumenstein, Tobias; Zeitlmann, Hilar; Alves-Pinto, Ana; Turova, Varvara; Lampe, Renée

    2014-01-01

    Cerebral palsy is a group of neurodevelopmental disorders that affect a person's ability to move and to maintain balance and posture. People with cerebral palsy have also perception and space orientation deficits so that special assistance devices should be developed to compensate these handicaps. The objective was to optimize an adapted electric bicycle (E-bike) for youths with neurodevelopmental disorders. An adapted E-bike was provided with ultrasonic sensors that measure distances to objects. If the distance to other objects reduces, an acoustic signal is sent. Additionally, a self-created force plate was fixed on the pedal to evaluate the muscle performances during biking. An experiment with the ultrasound warning system confirmed that acoustic feedback was helpful in avoiding obstacles. The measurement of the blood pressure, the heart frequency and the pedaling force during biking approved that the training condition of the test person can be registered and enables tuning the power of the electric motor to individual requirements. The results demonstrate that an adapted E-bike can be improved to provide better space orientation for people with perceptual disorders and to measure training conditions of patients. Moreover, these enable individual adjustment of the electric motor power to optimize comfort and therapy effect.

  16. Heparin-induced circular dichroism of an achiral, bicyclic species.

    Science.gov (United States)

    Stanley, Floyd E; Warner, Andrew M; McWilliams, Kayla M; Stalcup, Apryll M

    2011-01-01

    Antimalarial drugs have shown potential in suppressing the role of glycosaminoglycans (GAGs) in the pathology of prion protein conformational disorders (e.g. "Mad Cow" disease) by competing for sites of electrostatic interaction. In this study, circular dichroism (CD) and UV/Visible (UV/Vis) absorption spectroscopy techniques were used to investigate the interactions between N-methyl-N'-(7-chloro-4-quinolyl)-1,3-diaminopropane (QD), an achiral, bicyclic compound similar to previously investigated antimalarial drugs, and heparin, a complex GAG that is frequently used as a clinical anticoagulant. Relatively intense heparin-induced CD features were observed for QD and were noted to be radically different from previous studies using related chiral drugs, underscoring the importance of the Pfieffer effect on this and similar heparin research. Additionally, the induced CD for QD was observed to be highly dependent upon drug concentration, heparin concentration, system pH, equilibration time, and ionic strength. These results, in connection with recent work, provide new insight into the nature of the association between GAGs and antimalarial species. PMID:21125690

  17. Bicycle Frame Prediction Techniques with Fuzzy Logic Method

    Directory of Open Access Journals (Sweden)

    Rafiuddin Syam

    2015-03-01

    Full Text Available In general, an appropriate size bike frame would get comfort to the rider while biking. This study aims to predict the simulation system on the bike frame sizes with fuzzy logic. Testing method used is the simulation test. In this study, fuzzy logic will be simulated using Matlab language to test their performance. Mamdani fuzzy logic using 3 variables and 1 output variable intake. Triangle function for the input and output. The controller is designed in the type mamdani with max-min composition and the method deffuzification using center of gravity method. The results showed that height, inseam and Crank Size generating appropriate frame size for the rider associated with comfort. Has a height range between 142 cm and 201 cm. Inseam has a range between 64 cm and 97 cm. Crank has a size range between 175 mm and 180 mm. The simulation results have a range of frame sizes between 13 inches and 22 inches. By using the fuzzy logic can be predicted the size frame of bicycle suitable for the biker.

  18. Innovation and the Interrelatedness of Core Competencies: How Taiwan's Giant Bicycles broke into the US Bicycle Market

    Directory of Open Access Journals (Sweden)

    S. Phineas Upham

    2006-03-01

    Full Text Available I argue that capabilities and barriers to entry are, in certain circumstances, interconnected in such a way that sacrificing one of them can lead to the subsequent vulnerability or erosion of another capability or barrier to entry. I illustrate this through a study of the US bicycle market in the 1980's in general, and Schwinn Corporation and Giant Manufacturing in particular, arguing that both the barriers to entry and the firm capabilities were interrelated. A specific set of decisions by Schwinn had broad and unanticipated effects that went beyond the capacity they explicitly relinquished. In this case manufacturing and distribution were tightly linked in such a way that without some form of tight link between them successful incremental innovation became difficult. Seemingly unrelated capabilities and strengths become mutually reinforcing or interconnected. Instead of being able to choose to add a single capability, or choose to discard one, companies may instead be choosing between sets, groups of interlinked, or patterned capabilities. A seemingly small change may require a major reorganization of other core capabilities that its ostensible status belies.

  19. Evaluating the Safety Effects of Bicycle Lanes in New York City

    Science.gov (United States)

    Srinivasan, Raghavan; McKnight, Claire E.; Ewing, Reid; Roe, Matthew

    2012-01-01

    Objectives. We evaluated the effects of on-street bicycle lanes installed prior to 2007 on different categories of crashes (total crashes, bicyclist crashes, pedestrian crashes, multiple-vehicle crashes, and injurious or fatal crashes) occurring on roadway segments and at intersections in New York City. Methods. We used generalized estimating equation methodology to compare changes in police-reported crashes in a treatment group and a comparison group before and after installation of bicycle lanes. Our study approach allowed us to control confounding factors, such as built environment characteristics, that cannot typically be controlled when a comparison group is used. Results. Installation of bicycle lanes did not lead to an increase in crashes, despite the probable increase in the number of bicyclists. The most likely explanations for the lack of increase in crashes are reduced vehicular speeds and fewer conflicts between vehicles and bicyclists after installation of these lanes. Conclusions. Our results indicate that characteristics of the built environment have a direct impact on crashes and that they should thus be controlled in studies evaluating traffic countermeasures such as bicycle lanes. To prevent crashes at intersections, we recommend installation of “bike boxes” and markings that indicate the path of bicycle lanes across intersections. PMID:22095351

  20. The impact response of traditional and BMX-style bicycle helmets at different impact severities.

    Science.gov (United States)

    DeMarco, Alyssa L; Chimich, Dennis D; Gardiner, John C; Siegmund, Gunter P

    2016-07-01

    Bicycle helmets reduce the frequency and severity of severe to fatal head and brain injuries in bicycle crashes. Our goal here was to measure the impact attenuation performance of common bicycle helmets over a range of impact speeds. We performed 127 drop tests using 13 different bicycle helmet models (6 traditional style helmets and 7 BMX-style helmets) at impact speeds ranging from 1 to 10m/s onto a flat anvil. Helmets were struck on their left front and/or right front areas, a common impact location that was at or just below the test line of most bicycle helmet standards. All but one of the 10 certified helmet models remained below the 300g level at an impact speed of 6m/s, whereas none of the 3 uncertified helmets met this criterion. We found that the helmets with expanded polystyrene liners performed similarly and universally well. The single certified helmet with a polyurethane liner performed below the level expected by the Consumer Product Safety Commission (CPSC) standard at our impact location and the helmet structure failed during one of two supplemental tests of this helmet above the test line. Overall, we found that increased liner thickness generally reduced peak headform acceleration, particularly at higher impact speeds. PMID:27077273

  1. Johnson Space Center's Free Range Bicycle Program.- Fall 2015 Intern Report

    Science.gov (United States)

    Lee-Stockton, Willem

    2015-01-01

    NASA's Johnson Space Center is a big place, encompassing 1,620 acres and more than a hundred buildings. Furthermore, there are reportedly 15 thousand employees, all of which have somewhere to be. To facilitate the movement of all these people JSC has historically relied on human power. Pedaling their way towards deep space, bicycles have been the go to method. Currently there are about 200 Free Range Bicycles at JSC. Free Range Bicycles belong to nobody, except NASA, and are available for anybody to use. They are not to be locked or hidden (although frequently are) and the intention is that there will always be a bike to hop on to get where you're going (although it may not be the bike you rode in on). Although not without its own shortcomings, the Free Range Bicycle Program has continued to provide low cost, simple transportation for NASA's JSC. In addition to the approximately 200 Free Range Bicycles, various larger divisions (like engineering) will often buy a few dozen bikes for their team members to use or individuals will bring their own personal bike to either commute or use on site. When these bicycles fall into disrepair or are abandoned (from retirees etc) they become a problem at JSC. They are an eye sore, create a safety hazard and make it harder to find a working bike in a time of need. The Free Range Program hopes to address this first problem by "tagging out" abandoned or out of service bicycles. A bright orange "DO NOT OPERATE" tag is placed on the bike and given a serial number for tracking purposes. See picture to the right. If the bike has an active owner with intentions to repair the bike the bottom of the tag has instructions for how to claim the abandoned bicycle. After being tagged the owner of the bicycle has 30 days to claim the bicycle and either haul it off site or get it repaired (and labeled) in accordance with Johnson's Bicycle Policy. If the abandoned bicycle is not claimed within 30 days it becomes the property of the Government. The

  2. Lateral Drift Behavior Analysis in Mixed Bicycle Traffic: A Cellular Automaton Model Approach

    Directory of Open Access Journals (Sweden)

    Xue Feng

    2016-01-01

    Full Text Available Bicycle movements are always associated with lateral drifts. However, the impacts of lateral drift behavior, as well as variable lateral clearance maintaining behavior due to the variation of drift intensity, on mixed bicycle flow are not clear. This paper establishes a new cellular automata model to study typical characteristics of mixed bicycle traffic induced by lateral drift and its accompanying behavior. Based on derived positive correlation between passing speed and drift speed through survey, the occurrence probability of lateral drift and the degree of maintained lateral clearance are both introduced in accordance with the variance of passing speed. Then, in whole density region, firm conformity between simulation results and actual survey data is reached, which has seldom been achieved in previous studies. It is further verified that speed distortions in intermediate and high density region induced by assumption of constant lateral clearance requirements can be revised by introducing its variability characteristics. In addition, two contrastive impacts of lateral drift behavior are observed. That is, it causes speed fluctuation in low density while alleviating the speed fluctuation in relatively high density. These results are expected to be helpful to improve the simulation performance of mixed bicycle flow as well as depict more realistic vehicle-bicycle conflicts and so on.

  3. Bicycle accident-related head injuries in India

    Directory of Open Access Journals (Sweden)

    Ashok Munivenkatappa

    2013-01-01

    Full Text Available Objectives: To describe the epidemiology of head injuries sustained due to bicycle accidents in India. Materials and Methods: Data were retrospectively collected over a period of six months (15 May 2011 to 15 November 2011. Demography of patients, Glasgow coma scale (GCS, clinical and imaging findings, and mortality and outcome using Glasgow outcome scale (GOS, Rivermead post-concussion symptom questionnaire (RPCSQ and Rivermead head injury follow-up questionnaire (RHFUQ, were analyzed. Outcome was assessed by telephonic interview. Results: There were 108 patients (100 males with mean age of 27.7 years. Seventy-four (68.5% were from rural areas. Accidents due to vehicular collision accounted for 60 (55.6% cases. None wore a helmet. The admission GCS was 14-15 in 68.5% cases, 13-3 in 31.5%. The risk of moderate to severe injuries was increased among working laborers (OR = 5, and patients with loss of consciousness (OR = 4. Sixty-three (49% patients had abnormal computed tomography (CT findings; most common finding was skull fracture 25 (23.1%. Four patients needed surgery. The GOS assessment at three to six months revealed favorable outcome in 66 patients (61.1% and death in 8 (7.4%. The common post-concussion symptoms were headache, fatigue, and poor concentration. Conclusion: The majority of hospitalized cyclists were from a rural background and of the lower income group. After three months the majority of patients had good recovery with few persistent concussion symptoms.

  4. Synthetic strategy for bicyclic tetrapeptides HDAC inhibitors using ring closing metathesis

    Indian Academy of Sciences (India)

    Md Nurul Islam; Md Shahidul Islam; Md Ashraful Hoque; Tamaki Kato; Norikazu Nishino

    2015-09-01

    Cyclic peptides show diverse biological activities and are considered as good therapeutic agents due to structural rigidity, receptor selectivity and biochemical stability. We have developed bicyclic tetrapeptide HDAC inhibitors based on different cyclic tetrapeptide scaffolds. For the synthesis of these bicyclic tetrapeptides, two cyclization steps, namely, peptide cyclization and fusion of aliphatic side chains by ring closing metathesis (RCM) were involved. In the course of these syntheses, we have established two facts: a lower limit of aliphatic loop length and better synthetic route for bicyclic tetrapeptide synthesis. It was found that nine methylene loop length is the lower limit for aliphatic loop and the synthetic route selection depended on the configuration of amino acids in the cyclic tetrapeptide scaffold. RCM followed by peptide cyclization was the proper route for LDLD configuration and the reverse route was suitable for LLLD configuration.

  5. Conversion Of An Ordinary N Bicycle Into An Electric Bike And Related Research

    Directory of Open Access Journals (Sweden)

    Marius Janavičius

    2014-05-01

    Full Text Available An electric bicycle as a transport and leisure vehicle is expected to have a promising future. Currently, he market offers a great choice of factory electric bicycles and conversion kits to remake an ordinary bicycle into an electric bike. Also, the increasing number of electric vehicles is determined by the reduction in costs for manufacturing of batteries and an evolution in battery technology. This article presents the implementation of an electric bike by selecting the “Golden Motor Technology” company’s electric front wheel conversion kit MagicPie3 and 16 cell 10Ah LiFePO4 battery. After installation of the engine and other components, experiments were conducted to evaluate the performance characteristics of the electric bike and check the manufacturer’s specifications.

  6. Study of the health effects of bicycling in an urban atmosphere. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Waldman, M.; Weiss, S.; Articola, W.

    1977-10-14

    This report analyzes data on the health effects of bicycling in an urban environment through intensive study of ten healthy male subjects bicycling or driving in systematically varied conditions in the streets of Washington, D.C. Evaluation criteria for available technology and instrumentation are included and a methodology is developed for route selection. Specific air pollutants (carbon monoxide, ozone, sulfates, nitrates, and particulates) are measured concurrently with exposure and subsequent changes in health status identified through pulmonary function testing, cardiovascular testing, and blood and symptoms analysis. The report concludes that no major adverse short-term health effects were noted for ten healthy male subjects while bicycling or driving in levels of pollution and thermal stress encountered during the study period. Recommendations for further research are also presented.

  7. Association between neighborhood walkability and GPS-measured walking, bicycling and vehicle time in adolescents

    DEFF Research Database (Denmark)

    Carlson, Jordan A.; Saelens, Brian E.; Kerr, Jacqueline;

    2015-01-01

    Objectives: To investigate relations of walking, bicycling and vehicle time to neighborhood walkability and total physical activity in youth. Methods: Participants (N=690) were from 380 census block groups of high/low walkability and income in two US regions. Home neighborhood residential density......, intersection density, retail density, entertainment density and walkability were derived using GIS. Minutes/day of walking, bicycling and vehicle time were derived from processing algorithms applied to GPS. Accelerometers estimated total daily moderate-to-vigorous physical activity (MVPA). Models were adjusted...... for nesting of days (N=2987) within participants within block groups. Results: Walking occurred on 33%, active travel on 43%, and vehicle time on 91% of the days observed. Intersection density and neighborhood walkability were positively related to walking and bicycling and negatively related to vehicle time...

  8. The spatio-temporal Development of Copenhagen's bicycle infrastructure 1912-2013

    DEFF Research Database (Denmark)

    Carstensen, Trine Agervig; Olafsson, Anton Stahl; Bech, Nynne Marie;

    2015-01-01

    Cycling plays an important role in low-carbon transitions. Around the globe, cities are constructing bicycle infrastructure. The city of Copenhagen has a bicycle-friendly infrastructure celebrated for its fine-meshed network. This study documents the spatio-temporal development of Copenhagen....... In search for identifying drivers, the study analyses the city’s spatial growth pattern, migration pattern, development of road network and changes in the transport culture. Analyses reveal that the bicycle infrastructure expanded at a relatively constant pace during distinct periods of urban transformation...... and safety (first cycling city); the flow for cars (car city); urban liveability for soft transport (liveable city); and, finally, to improve the flow for cyclists as part a strategic re-design of urban space (liveable cycling city)....

  9. The effects of operating a touch screen smartphone and other common activities performed while bicycling on cycling behaviour

    NARCIS (Netherlands)

    de Waard, Dick; Lewis Evans, Ben; Jelijs, Bart; Tucha, Oliver; Brookhuis, Karel

    2014-01-01

    Although it has been shown that making phone calls or sending text messages while riding a bicycle can have a negative impact on bicyclist’s behaviour, in countries such as the Netherlands the operation of a mobile phone while cycling on a bicycle is not illegal and is actually quite common. In rece

  10. The role of bicycle sharing systems in normalising the image of cycling: An observational study of London cyclists

    Science.gov (United States)

    Goodman, Anna; Green, Judith; Woodcock, James

    2014-01-01

    Bicycle sharing systems are increasingly popular around the world and have the potential to increase the visibility of people cycling in everyday clothing. This may in turn help normalise the image of cycling, and reduce perceptions that cycling is ‘risky’ or ‘only for sporty people’. This paper sought to compare the use of specialist cycling clothing between users of the London bicycle sharing system (LBSS) and cyclists using personal bicycles. To do this, we observed 3594 people on bicycles at 35 randomly-selected locations across central and inner London. The 592 LBSS users were much less likely to wear helmets (16% vs. 64% among personal-bicycle cyclists), high-visibility clothes (11% vs. 35%) and sports clothes (2% vs. 25%). In total, 79% of LBSS users wore none of these types of specialist cycling clothing, as compared to only 30% of personal-bicycle cyclists. This was true of male and female LBSS cyclists alike (all p>0.25 for interaction). We conclude that bicycle sharing systems may not only encourage cycling directly, by providing bicycles to rent, but also indirectly, by increasing the number and diversity of cycling ‘role models’ visible. PMID:25568838

  11. Outcomes of Home-Support Consultation on the Maintenance of Bicycle-Riding Skills for Youth with Autism Spectrum Disorder

    Science.gov (United States)

    Reynolds, Jennifer L.; Pitchford, E. Andrew; Hauck, Janet L.; Ketcheson, Leah R.; Ulrich, Dale A.

    2016-01-01

    Bicycle riding is a functional motor skill that increases physical activity opportunities, social interaction, and independence. However, bicycle riding is difficult for youth with autism spectrum disorder (ASD) to learn. This study examined the effectiveness of home-support consultation (HSC) on increasing the maintenance of independent bicycle…

  12. Perceiving and Acting on Complex Affordances: How Children and Adults Bicycle across Two Lanes of Opposing Traffic

    Science.gov (United States)

    Grechkin, Timofey Y.; Chihak, Benjamin J.; Cremer, James F.; Kearney, Joseph K.; Plumert, Jodie M.

    2013-01-01

    This investigation examined how children and adults negotiate a challenging perceptual-motor problem with significant real-world implications--bicycling across two lanes of opposing traffic. Twelve- and 14-year-olds and adults rode a bicycling simulator through an immersive virtual environment. Participants crossed intersections with continuous…

  13. Synthesis of a Library of 1,5,2-Dithiazepine 1,1-Dioxides. Part 2: Routes to Bicyclic Sultams

    Science.gov (United States)

    Zang, Qin; Javed, Salim; Zhou, Aihua; Knudtson, Chris A.; Bi, Danse; Basha, Fatima Z.; Hanson, Paul R.

    2013-01-01

    The synthesis of a library of bicyclic sultams incorporating the 1,5,2-dithiazepine 1,1-dioxide moiety is reported. Following scaffold synthesis via a one-pot sulfonylation/intramolecular thia-Michael protocol, several additional cyclization strategies have been realized enabling access to new bicyclic sultams. PMID:24385680

  14. Orthogonal ring-closing alkyne and olefin metathesis for the synthesis of small GTPase-targeting bicyclic peptides.

    Science.gov (United States)

    Cromm, Philipp M; Schaubach, Sebastian; Spiegel, Jochen; Fürstner, Alois; Grossmann, Tom N; Waldmann, Herbert

    2016-01-01

    Bicyclic peptides are promising scaffolds for the development of inhibitors of biological targets that proved intractable by typical small molecules. So far, access to bioactive bicyclic peptide architectures is limited due to a lack of appropriate orthogonal ring-closing reactions. Here, we report chemically orthogonal ring-closing olefin (RCM) and alkyne metathesis (RCAM), which enable an efficient chemo- and regioselective synthesis of complex bicyclic peptide scaffolds with variable macrocycle geometries. We also demonstrate that the formed alkyne macrocycle can be functionalized subsequently. The orthogonal RCM/RCAM system was successfully used to evolve a monocyclic peptide inhibitor of the small GTPase Rab8 into a bicyclic ligand. This modified peptide shows the highest affinity for an activated Rab GTPase that has been reported so far. The RCM/RCAM-based formation of bicyclic peptides provides novel opportunities for the design of bioactive scaffolds suitable for the modulation of challenging protein targets. PMID:27075966

  15. Orthogonal ring-closing alkyne and olefin metathesis for the synthesis of small GTPase-targeting bicyclic peptides.

    Science.gov (United States)

    Cromm, Philipp M; Schaubach, Sebastian; Spiegel, Jochen; Fürstner, Alois; Grossmann, Tom N; Waldmann, Herbert

    2016-04-14

    Bicyclic peptides are promising scaffolds for the development of inhibitors of biological targets that proved intractable by typical small molecules. So far, access to bioactive bicyclic peptide architectures is limited due to a lack of appropriate orthogonal ring-closing reactions. Here, we report chemically orthogonal ring-closing olefin (RCM) and alkyne metathesis (RCAM), which enable an efficient chemo- and regioselective synthesis of complex bicyclic peptide scaffolds with variable macrocycle geometries. We also demonstrate that the formed alkyne macrocycle can be functionalized subsequently. The orthogonal RCM/RCAM system was successfully used to evolve a monocyclic peptide inhibitor of the small GTPase Rab8 into a bicyclic ligand. This modified peptide shows the highest affinity for an activated Rab GTPase that has been reported so far. The RCM/RCAM-based formation of bicyclic peptides provides novel opportunities for the design of bioactive scaffolds suitable for the modulation of challenging protein targets.

  16. Risky riding: Naturalistic methods comparing safety behavior from conventional bicycle riders and electric bike riders.

    Science.gov (United States)

    Langford, Brian Casey; Chen, Jiaoli; Cherry, Christopher R

    2015-09-01

    As electric bicycles (e-bikes) have emerged as a new transportation mode, their role in transportation systems and their impact on users have become important issues for policy makers and engineers. Little safety-related research has been conducted in North America or Europe because of their relatively small numbers. This work describes the results of a naturalistic GPS-based safety study between regular bicycle (i.e., standard bicycle) and e-bike riders in the context of a unique bikesharing system that allows comparisons between instrumented bike technologies. We focus on rider safety behavior under four situations: (1) riding in the correct direction on directional roadway segments, (2) speed on on-road and shared use paths, (3) stopping behavior at stop-controlled intersections, and (4) stopping behavior at signalized intersections. We find that, with few exceptions, riders of e-bike behave very similarly to riders of bicycles. Violation rates were very high for both vehicles. Riders of regular bicycles and e-bikes both ride wrong-way on 45% and 44% of segments, respectively. We find that average on-road speeds of e-bike riders (13.3kph) were higher than regular bicyclists (10.4kph) but shared use path (greenway) speeds of e-bike riders (11.0kph) were lower than regular bicyclists (12.6kph); both significantly different at >95% confidence. At stop control intersections, both bicycle and e-bike riders violate the stop signs at the similar rate with bicycles violating stop signs at a slightly higher rate at low speed thresholds (∼80% violations at 6kph, 40% violations at 11kph). Bicycles and e-bikes violate traffic signals at similar rates (70% violation rate). These findings suggest that, among the same population of users, e-bike riders exhibit nearly identical safety behavior as regular bike riders and should be regulated in similar ways. Users of both technologies have very high violation rates of traffic control devices and interventions should occur to

  17. The Feasibility of Wood and its Derivatives as a Bicycle Frame Building Material

    OpenAIRE

    BRENT TAYLOR, NICHOLAS

    2016-01-01

    [EN] ABSTRACT Nicholas Brent Taylor: The Feasibility of Wood and its Derivatives as a Bicycle Frame Building Material The bicycle is often considered as one of the most important inventions of all time. In addition, it is the most efficient form of human transport in the world. It is non pollutant, uses no fuel other than human power and its carbon footprint is neutralised in a short time. Today, faced with the threat of global warming brought about by fossil fuels, countries such as De...

  18. Device and method to determine perineal artery occlusion during road bicycling.

    Science.gov (United States)

    Parthiban, Sujeeth; Hotaling, James M; Ohlander, Samuel J; Baftiri, Amit P; Freels, Sally; Niederberger, Craig S

    2014-01-01

    Greater than 60 million American men who ride bicycles are at risk of developing erectile dysfunction. One possible reason is occlusion of the perineal arteries. Researchers relied on indirect methods and stationary models to study this problem. We developed a novel system to quantify occlusion among bicycle riders during a road bike ride. Our verification and validation activities show that this system can be safely used on human subjects to measure perineal artery occlusion. The method described in this paper provides a valuable tool to the researchers to study or to develop new solutions that alleviate this problem. The outcomes of these efforts will help millions of cyclists worldwide. PMID:25570811

  19. Pharmacokinetics-Pharmacodynamics Analysis of Bicyclic 4-Nitroimidazole Analogs in a Murine Model of Tuberculosis

    OpenAIRE

    Lakshminarayana, Suresh B.; Helena I M Boshoff; Joseph Cherian; Sindhu Ravindran; Anne Goh; Jan Jiricek; Mahesh Nanjundappa; Amit Nayyar; Meera Gurumurthy; Ramandeep Singh; Thomas Dick; Francesca Blasco; Barry, Clifton E.; Ho, Paul C.; Manjunatha, Ujjini H

    2014-01-01

    PA-824 is a bicyclic 4-nitroimidazole, currently in phase II clinical trials for the treatment of tuberculosis. Dose fractionation pharmacokinetic-pharmacodynamic studies in mice indicated that the driver of PA-824 in vivo efficacy is the time during which the free drug concentrations in plasma are above the MIC (fT>MIC ). In this study, a panel of closely related potent bicyclic 4-nitroimidazoles was profiled in both in vivo PK and efficacy studies. In an established murine TB model, the eff...

  20. Mapping cyclist activity and injury risk in a network combining smartphone GPS data and bicycle counts.

    Science.gov (United States)

    Strauss, Jillian; Miranda-Moreno, Luis F; Morency, Patrick

    2015-10-01

    In recent years, the modal share of cycling has been growing in North American cities. With the increase of cycling, the need of bicycle infrastructure and road safety concerns have also raised. Bicycle flows are an essential component in safety analysis. The main objective of this work is to propose a methodology to estimate and map bicycle volumes and cyclist injury risk throughout the entire network of road segments and intersections on the island of Montreal, achieved by combining smartphone GPS traces and count data. In recent years, methods have been proposed to estimate average annual daily bicycle (AADB) volume and injury risk estimates at both the intersection and segment levels using bicycle counts. However, these works have been limited to small samples of locations for which count data is available. In this work, a methodology is proposed to combine short- and long-term bicycle counts with GPS data to estimate AADB volumes along segments and intersections in the entire network. As part of the validation process, correlation is observed between AADB values obtained from GPS data and AADB values from count data, with R-squared values of 0.7 for signalized intersections, 0.58 for non-signalized intersections and between 0.48 and 0.76 for segments with and without bicycle infrastructure. The methodology is also validated through the calibration of safety performance functions using both sources of AADB estimates, from counts and from GPS data. Using the validated AADB estimates, the factors associated with injury risk were identified using data from the entire population of intersections and segments throughout Montreal. Bayesian injury risk maps are then generated and the concentrations of expected injuries and risk at signalized intersections are identified. Signalized intersections, which are often located at the intersection of major arterials, witness 4 times more injuries and 2.5 times greater risk than non-signalized intersections. A similar

  1. Bicycle-related genitourinary injuries in the USA from 2002–2010

    Science.gov (United States)

    Tasian, Gregory E; Appa, Ayesha A; Bagga, Herman S; Blaschko, Sarah; McCulloch, Charles E; McAninch, Jack W; Breyer, Benjamin N

    2014-01-01

    Among children, the incidence of bicycle-related genitourinary (GU) injuries was 448 per 100 000 (95% CI 383 to 514) and, among adults, was 53 per 100 000 (95% CI 36 to 71). Although children sustained more injuries, adults were more likely to being admitted to the hospital for the GU injury (OR 1.95, 95% CI 1.13 to 3.37). Children sustain nearly 10 times more GU injuries due to bicycles than adults, but adults have higher odds of sustaining injuries requiring admission. PMID:24618096

  2. Risky riding: Naturalistic methods comparing safety behavior from conventional bicycle riders and electric bike riders.

    Science.gov (United States)

    Langford, Brian Casey; Chen, Jiaoli; Cherry, Christopher R

    2015-09-01

    As electric bicycles (e-bikes) have emerged as a new transportation mode, their role in transportation systems and their impact on users have become important issues for policy makers and engineers. Little safety-related research has been conducted in North America or Europe because of their relatively small numbers. This work describes the results of a naturalistic GPS-based safety study between regular bicycle (i.e., standard bicycle) and e-bike riders in the context of a unique bikesharing system that allows comparisons between instrumented bike technologies. We focus on rider safety behavior under four situations: (1) riding in the correct direction on directional roadway segments, (2) speed on on-road and shared use paths, (3) stopping behavior at stop-controlled intersections, and (4) stopping behavior at signalized intersections. We find that, with few exceptions, riders of e-bike behave very similarly to riders of bicycles. Violation rates were very high for both vehicles. Riders of regular bicycles and e-bikes both ride wrong-way on 45% and 44% of segments, respectively. We find that average on-road speeds of e-bike riders (13.3kph) were higher than regular bicyclists (10.4kph) but shared use path (greenway) speeds of e-bike riders (11.0kph) were lower than regular bicyclists (12.6kph); both significantly different at >95% confidence. At stop control intersections, both bicycle and e-bike riders violate the stop signs at the similar rate with bicycles violating stop signs at a slightly higher rate at low speed thresholds (∼80% violations at 6kph, 40% violations at 11kph). Bicycles and e-bikes violate traffic signals at similar rates (70% violation rate). These findings suggest that, among the same population of users, e-bike riders exhibit nearly identical safety behavior as regular bike riders and should be regulated in similar ways. Users of both technologies have very high violation rates of traffic control devices and interventions should occur to

  3. Relationship between Locations of Facial Injury and the Use of Bicycle Helmets: A Systematic Review.

    Science.gov (United States)

    Hwang, Kun; Jeon, Yun Moon; Ko, Yeong Seung; Kim, Yeon Soo

    2015-07-01

    The aim of this study is to review the protective effect of a bicycle helmet on each facial location systematically. PubMed was searched for articles published before December 12, 2014. The data were summarized, and the odds ratio (OR) between the locations of facial injury was calculated. A statistical analysis was performed with Review Manager (The Nordic Cochrane Centre). Bicycle helmets protect the upper and middle face from serious facial injury but do not protect the lower face. Non-wearers had significantly increased risks of upper facial injury (OR, 2.07; Pchin cap might decrease the risk of lower facial injury.

  4. Aminocyclopentanols as sugar mimics. Synthesis from unsaturated bicyclic lactones by Overman rearrangement

    DEFF Research Database (Denmark)

    Bøjstrup, Marie; Fanefjord, Mette; Lundt, Inge

    2007-01-01

    Bicyclic cyclopentane lactones, prepared from bromodeoxyaldonolactones, were transformed into aminocyclopentanols with an Overman rearrangement as the key step. Two of the compounds prepared, 7 and 19, were found to be good inhibitors of jack bean alpha-mannosidase and beta-D-N-acetylglucosaminid......Bicyclic cyclopentane lactones, prepared from bromodeoxyaldonolactones, were transformed into aminocyclopentanols with an Overman rearrangement as the key step. Two of the compounds prepared, 7 and 19, were found to be good inhibitors of jack bean alpha-mannosidase and beta...

  5. Knights of death: introducing bicycles and motor vehicles to Turin, 1890-1907.

    Science.gov (United States)

    Moraglio, Massimo

    2015-04-01

    The aim of this article is to investigate, through a case study from the city of Turin, the reaction to the arrival of bicycles and automobiles in Italy. It focuses on the early years of bicycle and automobile use, using municipal council minutes, local newspapers, and satirical magazines as sources. The introduction of velocipedes and cars disrupted the traditional use of roads as public spaces, generating protests against the new transport devices, especially with regard to safety concerns resulting from the transgression of traditional uses of urban streets, the speed of vehicles, and the anonymity of riders and drivers. PMID:26005084

  6. HSF1/HSP70通路抑制c-Jun氨基末端激酶的活化保护UVA诱导的HaCaT细胞凋亡%Protection of HSF1/HSP70 pathway on UVA-induced HaCaT cells apoptosis via inhibiting the activation of c-Jun N-terminal kinase

    Institute of Scientific and Technical Information of China (English)

    王晓雯; 王春波; 李丙华; 韩彦弢

    2012-01-01

    目的 观察热休克转录因子1( HSF1)与热休克蛋白70( HSP70)对紫外线A(UVA)诱导HaCaT细胞凋亡的保护作用及其机制.方法 建立8mJ/cm2 UVA辐射损伤HaCaT细胞的病理模型.将细胞随机分为对照组、8mJ/cm2 UVA照射组、HSP70转录抑制剂组(50 μmol/L槲皮素).Honechst 33258荧光染色观察细胞凋亡;蛋白质印迹法检测UVA辐射HaCaT细胞后p-HSF1和HSP70蛋白的经时变化及UVA辐射后孵育6h JNK(c-Jun氨基末端激酶)、p-JNK的蛋白表达;Real-Time PCR检测HSP70 mRNA的表达.结果 UVA辐射后HaCaT细胞内p-HSF1、HSP70蛋白表达量均出现先增加后减少的时间依赖性趋势,其中p-HSF1于lh开始增加,3h达高峰,HSP70于6h达高峰,24h基本恢复原始水平;UVA辐射前预先加入HSP70转录抑制剂槲皮素能显著抑制HSP70 mRNA的表达,增加p-JNK的表达量,同时Honechst 33258荧光染色观察其与UVA辐射组比较凋亡率明显升高.结论 8mJ/cm2 UVA辐射HaCaT细胞在一定时间内可使HSF1活化致HSP70表达增加.HSFl/HSP70通路对UVA诱导的HaCaT细胞凋亡具有保护作用,其机制与HSP70大量表达后抑制JNK的活化有关.%Objective To investigate the protective effect of heat shock factorl ( HSF1) and heat shock protein70 ( HSP70) on ultraviolet A ( UVA ) -induced HaCaT cells apoptosis and its mechanism. Methods The apoptotic HaCaT cell model was induced by UVA irradiation (8mJ/cm ). The cells were randomly divided into three groups, including a control group, a model group (8mJ/cm UVA) and a HSP70 transcription inhibitor group (50 μmol/L quercetin). The morphologic alteration of apoptotic cells was investigated by using Hoechst 33258 fluorescent staining. Western blotting was used to investigate protein expression levels of phosphorylated HSF1 and HSP70 at different time points, as well as c-Jun N-terminal kinase ( JNK ) andphosphorylated JNK were investigated after incubating for 6 hours following UVA irradiation. HSP70 mRNA was

  7. 神经干细胞对老化小胶质细胞存活及JNK信号通路的调控作用%Regulation of neural stem cells on viability and c-Jun N-terminal kinase signaling of aging microglia cells

    Institute of Scientific and Technical Information of China (English)

    武爱梅; 赵江明; 吴蕾; 方辉; 王宇; 吴惠梅

    2013-01-01

    Objective To investigate the regulation of neural stem cells (NSCs) on the viability and stress-activated kinase/c-Jun N-terminal kinase (SAPK/JNK) signaling of aging microglia cells.Methods Primary microglia cells were isolated from 12-18 months old ICR mouse and NSCs were isolated from 12.5 days pregnancy ICR mouse.Staining test with Isolectin-B4,the specific marker for microglia,was performed and NSCs were verified by expression of nestin with immunofluorescence.Four groups were chosen in our experiment,including microglia cells group,co-cultured group,Sp600125 stimulated group and Sp600125-stimulation co-cultured group; in the Sp600125 stimulated group,microglia cells were pretreated with 20 ng/mL SP600125,a specific inhibitor of JNK,for four h; in the co-cultured group,microglia and NSC cells (1:4) were co-cultured using a Millicell Hanging Cell Culture Insert plates; and Sp600125-stimulation co-cultured group was also pretreated with 20 ng/mL SP600125 for four h firstly,and then,NSCs were added to co-culture with microglia cells for 3 d.MTT assay was performed to analyze the proliferation ability; Western blotting was used to detect the protein expression level of phosphorylated JNK signaling.Results After culturing for 2 weeks,primary microglia cells had a good adherence ability and strong refractivity.Staining test with Isolectin-B4 showed that the purity reached 80%.Neural stem cells grew like suspended spheres and nestin-positive.As compared with microglia cells group and stem cells group,co-cultured group had a significantly higher proliferation ability in MTT assay (P<0.05).The phosphorylated JNK level in the co-cultured group was significantly up-regulated as compared with that in the microglia cells group (P<0.05);Sp600125-stimulation co-cultured group had obviously higher phosphorylated JNK level than that in the Sp600125-stimulated group (P<0.05).Conclusion NSCs might promote the survival of aging microglia cells through activation of JNK

  8. 16 CFR Figure 1 to Part 1512 - Bicycle Front Fork Cantilever Bending Test Rig

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Bicycle Front Fork Cantilever Bending Test Rig 1 Figure 1 to Part 1512 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS... Fork Cantilever Bending Test Rig EC03OC91.070...

  9. Use of automated video analysis for the evaluation of bicycle movement and interaction

    Science.gov (United States)

    Twaddle, Heather; Schendzielorz, Tobias; Fakler, Oliver; Amini, Sasan

    2014-03-01

    With the purpose of developing valid models of microscopic bicycle behavior, a large quantity of video data is collected at three busy urban intersections in Munich, Germany. Due to the volume of data, the manual processing of this data is infeasible and an automated or semi-automated analysis method must be implemented. An open source software, "Traffic Intelligence", is used and extended to analyze the collected video data with regard to research questions concerning the tactical behavior of bicyclists. In a first step, the feature detection parameters, the tracking parameters and the object grouping parameters are calibrated, making it possible to accurately track and group the objects at intersections used by large volumes of motor vehicles, bicycles and pedestrians. The resulting parameters for the three intersections are presented. A methodology for the classification of road users as cars, bicycles or pedestrians is presented and evaluated. This is achieved by making hypotheses about which features belong to cars, or bicycles and pedestrians, and using grouping parameters specified for that road user group to cluster the features into objects. These objects are then classified based on their dynamic characteristics. A classification structure for the maneuvers of different road users is presented and future applications are discussed.

  10. The Effects of Prompting and Reinforcement on Safe Behavior of Bicycle and Motorcycle Riders

    Science.gov (United States)

    Okinaka, Takeru; Shimazaki, Tsuneo

    2011-01-01

    A reversal design was used to evaluate the effects of vocal and written prompts as well as reinforcement on safe behavior (dismounting and walking bicycles or motorcycles on a sidewalk) on a university campus. Results indicated that an intervention that consisted of vocal and written prompts and reinforcement delivered by security guards was…

  11. A Study of Bicycle and Passenger Car Collisions Based on Insurance Claims Data

    Science.gov (United States)

    Isaksson-Hellman, Irene

    2012-01-01

    In Sweden, bicycle crashes are under-reported in the official statistics that are based on police reports. Statistics from hospital reports show that cyclists constitute the highest percentage of severely injured road users compared to other road user groups. However, hospital reports lack detailed information about the crash. To get a more comprehensive view, additional data are needed to accurately reflect the casualty situation for cyclists. An analysis based on 438 cases of bicycle and passenger car collisions is presented, using data collected from insurance claims. The most frequent crash situations are described with factors as to where and when collisions occur, age and gender of the involved cyclists and drivers. Information on environmental circumstances such as road status, weather- and light conditions, speedlimits and traffic environment is also included. Based on the various crash events, a total of 32 different scenarios have been categorized, and it was found that more than 75% were different kinds of intersection related situations. From the data, it was concluded that factors such as estimated impact speed and age significantly influence injury severity. The insurance claims data complement the official statistics and provide a more comprehensive view of bicycle and passenger car collisions by considering all levels of crash and injury severity. The detailed descriptions of the crash situations also provide an opportunity to find countermeasures to prevent or mitigate collisions. The results provide a useful basis, and facilitates the work of reducing the number of bicycle and passenger car collisions with serious consequences. PMID:23169111

  12. Macroscopic modeling of pedestrian and bicycle crashes: A cross-comparison of estimation methods.

    Science.gov (United States)

    Amoh-Gyimah, Richard; Saberi, Meead; Sarvi, Majid

    2016-08-01

    The paper presents a cross-comparison of different estimation methods to model pedestrian and bicycle crashes. The study contributes to macro level safety studies by providing further methodological and empirical evidence on the various factors that influence the frequency of pedestrian and bicycle crashes at the planning level. Random parameter negative binomial (RPNB) models are estimated to explore the effects of various planning factors associated with total, serious injury and minor injury crashes while accounting for unobserved heterogeneity. Results of the RPNB models were compared with the results of a non-spatial negative binomial (NB) model and a Poisson-Gamma-CAR model. Key findings are, (1) the RPNB model performed best with the lowest mean absolute deviation, mean squared predicted error and Akaiki information criterion measures and (2) signs of estimated parameters are consistent if these variables are significant in models with the same response variables. We found that vehicle kilometers traveled (VKT), population, percentage of commuters cycling or walking to work, and percentage of households without motor vehicles have a significant and positive correlation with the number of pedestrian and bicycle crashes. Mixed land use is also found to have a positive association with the number of pedestrian and bicycle crashes. Results have planning and policy implications aimed at encouraging the use of sustainable modes of transportation while ensuring the safety of pedestrians and cyclist. PMID:27209153

  13. Tertiary Student Attitudes to Bicycle Commuting in a Regional Australian University

    Science.gov (United States)

    Whannell, Patricia; Whannell, Robert; White, Richard

    2012-01-01

    Purpose: The purpose of this paper is to provide executive management at a regional university with empirical data to justify, or otherwise, a substantial outlay of funds to support bicycle commuting as a viable strategy for the reduction of traffic congestion. Design/methodology/approach: A custom designed questionnaire was completed by 270…

  14. [Changes in ECG indicators during bicycle ergometry in patients having suffered myocardial infarction].

    Science.gov (United States)

    Kheifets, Z N

    1984-01-01

    Altogether 218 patients with a history of myocardial infarction were subjected to bicycle ergometry. The ECG recorded at the height of the exercise showed a significant increase in the heart rate and in the amplitudes of P and R waves. The diastole and electric systole shortened. As the load was raised, the rate of A-B conduction was relatively decelerated.

  15. Modeling Mixed Bicycle Traffic Flow: A Comparative Study on the Cellular Automata Approach

    Directory of Open Access Journals (Sweden)

    Dan Zhou

    2015-01-01

    Full Text Available Simulation, as a powerful tool for evaluating transportation systems, has been widely used in transportation planning, management, and operations. Most of the simulation models are focused on motorized vehicles, and the modeling of nonmotorized vehicles is ignored. The cellular automata (CA model is a very important simulation approach and is widely used for motorized vehicle traffic. The Nagel-Schreckenberg (NS CA model and the multivalue CA (M-CA model are two categories of CA model that have been used in previous studies on bicycle traffic flow. This paper improves on these two CA models and also compares their characteristics. It introduces a two-lane NS CA model and M-CA model for both regular bicycles (RBs and electric bicycles (EBs. In the research for this paper, many cases, featuring different values for the slowing down probability, lane-changing probability, and proportion of EBs, were simulated, while the fundamental diagrams and capacities of the proposed models were analyzed and compared between the two models. Field data were collected for the evaluation of the two models. The results show that the M-CA model exhibits more stable performance than the two-lane NS model and provides results that are closer to real bicycle traffic.

  16. Design of an aluminium bicycle path integrated in a steel bridge

    NARCIS (Netherlands)

    Maljaars, J.; Soetens, F.; Burggraaf, H.G.

    2007-01-01

    This paper describes the design of the aluminium structure of a bicycle path which is mounted on an existing steel brige. The benefits of aluminium, being low self weight, freedom in design obtained by extrusion and good corrosion resistance were maximal utilized. One of the main drawbacks of alumin

  17. Sensor design for outdoor racing bicycle field testing for human vibration comfort evaluation

    International Nuclear Information System (INIS)

    This paper is concerned with the vibrational comfort evaluation of the cyclist when cycling a rough surface. Outdoor comfort tests have so far only been done through instrumenting the bicycle with accelerometers. This work instruments a racing bicycle with custom-made contact force sensors and velocity sensors to acquire human comfort through the absorbed power method. Comfort evaluation is assessed at the hand–arm and seat interface of the cyclist with the bicycle. By means of careful finite-element analysis for designing the force gauges at the handlebar and the seat combined with precise calibration of both force and velocity sensors, all sensors have proven to work properly. Initial field tests are focused on the proper functioning of the designed sensors and their suitability for vibration comfort measurements. Tests on a cobblestone road reveal that the outcome of the absorbed power values is within the same range as those from laboratory tests found in the literature. This sensor design approach for outdoor testing with racing bicycles may give a new interpretation on evaluating the cyclist's comfort since the vibrational load is not only quantified in terms of acceleration but also in terms of force and velocity at the bicycle–cyclist contact points. (paper)

  18. Road safety and bicycle usage impacts of unbundling vehicular and cycle traffic in Dutch urban networks.

    NARCIS (Netherlands)

    Schepers, P. Heinen, E. Methorst, R. & Wegman, F.

    2015-01-01

    Bicycle-motor vehicle crashes are concentrated along distributor roads where cyclists are exposed to greater volumes of high-speed motorists than they would experience on access roads. This study examined the road safety impact of network-level separation of vehicular and cycle traffic in Dutch urba

  19. Road safety and bicycle usage impacts of unbundling vehicular and cycle traffic in Dutch urban networks

    NARCIS (Netherlands)

    Schepers, P.; Heinen, E.; Methorst, R.; Wegman, F.C.M.

    2013-01-01

    Bicycle-motor vehicle crashes are concentrated along distributor roads where cyclists are exposed to greater volumes of high-speed motorists than they would experience on access roads. This study examined the road safety impact of network-level separation of vehicular and cycle traffic in Dutch urba

  20. Balance and control of a rear-wheel steered speed-record recumbent bicycle

    NARCIS (Netherlands)

    Schwab, A.L.; Kooijman, J.D.G.

    2014-01-01

    The goal of the Human Power Team from the TU Delft and the Free University of Amsterdam is to break the world speed record in unpaced cycling (Sam Whittingham, 133.28 km/h). The design of such a faired recumbent bicycle is a challenge. The Delft design, called VeloX (Human Power Team (2013)), is a f

  1. Building the fastest bicycle in the world; a year with the Human Power Team Delft & Amsterdam

    NARCIS (Netherlands)

    Schuurman, M.; Roks, G.

    2014-01-01

    “Third time lucky” is the saying, but for the third Human Power Team it almost turned out as a year for nothing. The team has been attempting to set the world record for the fastest bicycle powered only by human muscles for two years already. This endeavor to let a Dutchman be the fastest human on e

  2. Assessing and Prioritizing bicycle projects in Denmark: the CPP-Model

    DEFF Research Database (Denmark)

    Salling, Kim Bang

    2011-01-01

    billion DKK in the period from 2009-2014. This presentation will mainly focus upon the modelling aspect of the prioritization of different bicycle applications for the funds and the experiences from the latter. Accordingly, the modelling approach is based upon the collaborative work between the Technical...

  3. Comparison of dipyridamole-handgrip test and bicycle exercise test for thallium tomographic imaging

    Energy Technology Data Exchange (ETDEWEB)

    Huikuri, H.V.; Korhonen, U.R.; Airaksinen, J.; Ikaeheimo, M.J.H.; Heikkilae, J.T.; Takkunen, J.T.

    1988-02-01

    Seventy-three patients with angina pectoris and 20 with atypical chest pain, who underwent coronary angiography, were examined by single-photon emission computed thallium tomography (TI-SPECT) using a combined dipyridamole-handgrip stress test. Perfusion defects were detected in 78 of 81 patients with angiographically significant coronary artery disease (CAD) (sensitivity 96%). In 9 of 12 patients without CAD, the thallium images were normal (specificity 75%). Thirty-five patients with CAD were reexamined by TI-SPECT using a dynamic bicycle exercise stress test. The sensitivity of the dipyridamole-handgrip test did not differ from the bicycle exercise test in diagnosing the CAD (97% vs 94%). Multiple thallium defects were seen in 19 of 22 (86%) patients with multivessel CAD by the dipyridamole-handgrip test but only in 14 of 22 (64%) by the bicycle exercise test. Noncardiac side-effects occurred in 17 of 93 (18%) patients after dipyridamole infusion. Cardiac symptoms were less common during the dipyridamole-handgrip test than during the bicycle exercise (15% vs 76%, p less than 0.01). These data suggest that the dipyridamole-handgrip test is a useful alternative stress method for thallium perfusion imaging, particularly in detecting multivessel CAD.

  4. 77 FR 60050 - Special Regulations; Areas of the National Park System, Saguaro National Park, Bicycling

    Science.gov (United States)

    2012-10-02

    ... and adopted by NPS leadership after an adequate analysis of the benefits, impacts, and economic cost... Hope Camp Trail as a bicycle route within Saguaro National Park (77 FR 12761). The proposed rule was... solitude and wilderness-like aesthetics that are long-standing attributes in this area and the primary...

  5. Sandia bicycle commuters group -- pollution prevention at Sandia National Laboratories, New Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Wrons, R.

    1998-06-01

    The Sandia Bicycle Commuters Group (SBCG) formed three years ago for the purpose of addressing issues that impact the bicycle commuting option. The meeting that launched the SBCG was scheduled in conjunction with National Bike-to-Work day in May 1995. Results from a survey handed out at the meeting solidly confirmed the issues and that an advocacy group was needed. The purpose statement for the Group headlines its web site and brochure: ``Existing to assist and educate the SNL workforce bicyclist on issues regarding Kirtland Air Force Base (KAFB) access, safety and bicycle-supporting facilities, in order to promote bicycling as an effective and enjoyable means of commuting.`` The SNL Pollution Prevention (P2) Team`s challenge to the SNL workforce is to ``prevent pollution, conserve natural resources, and save money``. In the first winter of its existence, the SBCG sponsored a winter commute contest in conjunction with the City`s Clean Air Campaign (CAC). The intent of the CAC is to promote alternative (to the single-occupant vehicle) commuting during the Winter Pollution Advisory Period (October 1--February 28), when the City runs the greatest risk of exceeding federal pollution limits.

  6. THE EFFECTS OF SURFACE-INDUCED LOADS ON FOREARM MUSCLE ACTIVITY DURING STEERING A BICYCLE

    Directory of Open Access Journals (Sweden)

    Pinar Arpinar-Avsar

    2013-09-01

    Full Text Available On the bicycle, the human upper extremity has two essential functions in steering the bicycle and in supporting the body. Through the handlebar, surface- induced loads are transmitted to the hand and arm of the bicycle rider under vibration exposure conditions. Thus, the purpose of the study was to investigate the effect of vibration exposure on forearm muscle activity for different road surfaces (i.e. smooth road, concrete stone pavement, rough road and for different bicycles. Ten subjects participated in experiments and two types of bicycles, i.e. Road Bike (RB and Mountain Bike (MTB are compared. The acceleration magnitudes were dominant along x and z-axes. The r.m.s acceleration values in the z direction at the stem of MTB were at most 2.56, 7.04 and 10.76 m·s-2 when pedaling respectively on asphalt road, concrete pavement and rough road. In the case of RB the corresponding values were respectively 4.43, 11.75 and 27.31 m·s-2. The cumulative normalized muscular activity levels during MTB trials on different surfaces had the same tendency as with acceleration amplitudes and have ranked in the same order from lowest to highest value. Although road bike measurements have resulted in a similar trend of increment, the values computed for rough road trials were higher than those in MTB trials. During rough road measurements on MTB, rmsEMG of extensor muscles reached a value corresponding to approximately 50% of MVC (Maximum Voluntary Contraction. During RB trials performed on rough road conditions, rmsEMG (%MVC values for the forearm flexor muscles reached 45.8% of their maximal. The level of muscular activity of forearm muscles in controlling handlebar movements has been observed to be enhanced by the increase in the level of vibration exposed on the bicycle. Since repeated forceful gripping and pushing forces to a handle of a vibratory tool can create a risk of developing circulatory, neurological, or musculoskeletal disorder, a bicycle rider

  7. Impact Evaluation of a Public Bicycle Share Program on Cycling: A Case Example of BIXI in Montreal, Quebec

    Science.gov (United States)

    Gauvin, Lise; Kestens, Yan; Fournier, Michel; Morency, Patrick; Drouin, Louis

    2013-01-01

    Objectives. We examined associations between residential exposure to BIXI (BIcycle-taXI)—a public bicycle share program implemented in Montreal, Quebec, in 2009, which increases accessibility to cycling by making available 5050 bicycles at 405 bicycle docking stations—and likelihood of cycling (BIXI and non-BIXI) in Montreal over the first 2 years of implementation. Methods. Three population-based samples of adults participated in telephone surveys. Data collection occurred at the launch of the program (spring 2009), and at the end of the first (fall 2009) and second (fall 2010) seasons of implementation. Difference in differences models assessed whether greater cycling was observed for those exposed to BIXI compared with those not exposed at each time point. Results. We observed a greater likelihood of cycling for those exposed to the public bicycle share program after the second season of implementation (odds ratio = 2.86; 95% confidence interval = 1.85, 4.42) after we controlled for weather, built environment, and individual variables. Conclusions. The implementation of a public bicycle share program can lead to greater likelihood of cycling among persons living in areas where bicycles are made available. PMID:23327280

  8. Determining the Optimal Layout Design for Public Bicycle System within the Attractive Scope of a Metro Station

    Directory of Open Access Journals (Sweden)

    Jingxu Chen

    2015-01-01

    Full Text Available Public bicycle acts as a seamless feeder mode in combination with the citywide public transit, as well as a competitor for the inner-city short trips. The primary objective of this study is to address the layout planning of public bicycle system within the attracted scope of a metro station. Based on the land use function, population, and bicycle mode share, bicycle rental stations are divided into three types, namely, the metro station, district station, and resident station, and later the quantity of bicycle facilities in each rental station is estimated. Then, the service stations are selected from these bicycle rental stations to provide the service of periodical bicycle redistribution. An improved immune algorithm is proposed to determine the number and locations of service stations and the optimal route options for the implement of redistributing strategy. Finally, a case study of Nanjing Tianyin Road metro station is conducted to illustrate the proposed model and clarify some of its implementation details.

  9. Enantioselective Recognition of Calix [4] arene Derivative Bearing Bicyclic Guanidinium for D/L Amino Acid Zwitterions

    Institute of Scientific and Technical Information of China (English)

    刘芳; 陆国元; 何卫江; 王震生; 朱龙根

    2001-01-01

    The p-tetra-tert-butyl calix[4]arene derivatives ( 3 and 4 )with(S,S) chiral bicyclic guanidinium, as the receptors of amino acid zwitterions, have been synthesized via a O-alkylation reaction of p-tetra-tert-rutyi calix [4] arene with chloromethly chiral bicyclic guanidinium 2 in the presence of anhydrous K2CO3 in acetonitrile.The results obtained from liquid-liquid competitive extraction experiments indicate that the two receptors may selectively recognize L-aromatic amino acids, and that the enantioselective recognizability of the receptor 4 with two chiral bicyclic guanidinium units reachs up to about 90% for L-Phe.

  10. Bicycle transport as an object of ecological marketing and innovations in urban transportations

    Directory of Open Access Journals (Sweden)

    O.S. Teletov

    2016-09-01

    Full Text Available The aim of the article. In the modern world society is faced with problems of growing population, increasing environmental problems, lack of minerals and social-economic globalization when necessity of both individual and humanity survival is becoming extremely important. By next few years 80% of the world’s population will live in the cities. This is the main reason which force us to think about the more effective usage of urban space and transport people in cities. Nowadays ecological pollution and increased costs on transport service highlight the importance of seeking alternative types of transport. The youth of many European countries prefer bikes as main transport. Usage of bicycles in Europe is constantly growing due to European and local urban and mobility policies. Therefore, we may consider an opportunity to promote bicycle transport in Ukraine, that requires complex investigation of this question. The purpose of the article is to define features and the ways of bicycle transport implementation in Ukrainian cities as a priority for youth; it includes the best world practices of bicycle transport implementation into urban space and searching for possible ways to apply the European experience in Ukraine. The results of the analysis. As a part of our research we considered investigating international experience of cycling in Europe as an alternative to the public transport and as an example of ecological marketing. The best methods of usage cycling in the urban space were described and analysed. Moreover, we identified the main problems (and the potential solutions with implementation of cycling infrastructure in urban space based on international and national experience (special signs, traffic lights etc.. In the article different opportunities for realization in city Sumy were proposed. Our focus was on atomized network of bike rental services and we confirmed the effectiveness of such program in this city. The bicycle infrastructure

  11. 双圈图的代数连通度%On the algebraic connectivity of bicyclic graphs

    Institute of Scientific and Technical Information of China (English)

    袁西英; 张丽; 孙玉芹

    2007-01-01

    Bicyclic graphs are connected graphs in which the number of edges equals the number of vertices plus one.The aothors study the algebraic connectivity α(G)of a bicyclic graph G on n vertices and prove that α(G)≤1 for all bicyclic graphs G on n(n≥10)vertices.Funhermore they determine all the bicyclic graphs G on n(,n≥10)vertices such that α(G)=1.%边数等于点数加1的连通图称为双圈图.研究双圈图G的代数连通度,记作α(G),证明了结论:对所有的n(n≥10)阶双圈图G都有α(G)≤1成立,并且确定了满足α(G)=1的所有,n(n≥10)阶双圈图.

  12. "Bicycles May Use Full Lane" Signage Communicates U.S. Roadway Rules and Increases Perception of Safety.

    Science.gov (United States)

    Hess, George; Peterson, M Nils

    2015-01-01

    Many global challenges, including obesity, health care costs, and climate change, could be addressed in part by increasing the use of bicycles for transportation. Concern about the safety of bicycling on roadways is frequently cited as a deterrent to increasing bicycle use in the USA. The use of effective signage along roadways might help alleviate these concerns by increasing knowledge about the rights and duties of bicyclists and motorists, ideally reducing crashes. We administered a web-based survey, using Twitter for recruitment, to examine how well three US traffic control devices communicated the message that bicyclists are permitted in the center of the travel lane and do not have to "get out of the way" to allow motorists to pass without changing lanes: "Bicycles May Use Full Lane" and "Share the Road" signage, and Shared Lane Markings on the pavement. Each was compared to an unsigned roadway. We also asked respondents whether it was safe for a bicyclist to occupy the center of the travel lane. "Bicycles May Use Full Lane" signage was the most consistently comprehended device for communicating the message that bicyclists may occupy the travel lane and also increased perceptions of safety. "Share the Road" signage did not increase comprehension or perceptions of safety. Shared Lane Markings fell somewhere between. "Bicycles May Use Full Lane" signage showed notable increases in comprehension among novice bicyclists and private motor vehicle commuters, critical target audiences for efforts to promote bicycling in the USA. Although limited in scope, our survey results are indicative and suggest that Departments of Transportation consider replacing "Share the Road" with "Bicycles May Use Full Lane" signage, possibly combined with Shared Lane Markings, if the intent is to increase awareness of roadway rights and responsibilities. Further evaluation through virtual reality simulations and on-road experiments is merited.

  13. "Bicycles May Use Full Lane" Signage Communicates U.S. Roadway Rules and Increases Perception of Safety.

    Directory of Open Access Journals (Sweden)

    George Hess

    Full Text Available Many global challenges, including obesity, health care costs, and climate change, could be addressed in part by increasing the use of bicycles for transportation. Concern about the safety of bicycling on roadways is frequently cited as a deterrent to increasing bicycle use in the USA. The use of effective signage along roadways might help alleviate these concerns by increasing knowledge about the rights and duties of bicyclists and motorists, ideally reducing crashes. We administered a web-based survey, using Twitter for recruitment, to examine how well three US traffic control devices communicated the message that bicyclists are permitted in the center of the travel lane and do not have to "get out of the way" to allow motorists to pass without changing lanes: "Bicycles May Use Full Lane" and "Share the Road" signage, and Shared Lane Markings on the pavement. Each was compared to an unsigned roadway. We also asked respondents whether it was safe for a bicyclist to occupy the center of the travel lane. "Bicycles May Use Full Lane" signage was the most consistently comprehended device for communicating the message that bicyclists may occupy the travel lane and also increased perceptions of safety. "Share the Road" signage did not increase comprehension or perceptions of safety. Shared Lane Markings fell somewhere between. "Bicycles May Use Full Lane" signage showed notable increases in comprehension among novice bicyclists and private motor vehicle commuters, critical target audiences for efforts to promote bicycling in the USA. Although limited in scope, our survey results are indicative and suggest that Departments of Transportation consider replacing "Share the Road" with "Bicycles May Use Full Lane" signage, possibly combined with Shared Lane Markings, if the intent is to increase awareness of roadway rights and responsibilities. Further evaluation through virtual reality simulations and on-road experiments is merited.

  14. Perceiving and Acting on Complex Affordances: How Children and Adults Bicycle Across Two Lanes of Opposing Traffic

    OpenAIRE

    Grechkin, Timofey Y.; Chihak, Benjamin J.; Cremer, James F.; Kearney, Joseph K.; Plumert, Jodie M.

    2012-01-01

    This investigation examined how children and adults negotiate a challenging perceptual-motor problem with significant real-world implications – bicycling across two lanes of opposing traffic. Twelve- and 14-year-olds and adults rode a bicycling simulator through an immersive virtual environment. Participants crossed intersections with continuous cross traffic coming from opposing directions. Opportunities for crossing were divided into aligned (far gap opens with or before near gap) and rolli...

  15. The risk of pediatric bicycle handlebar injury compared with non-handlebar injury: a retrospective multicenter study in Osaka, Japan

    OpenAIRE

    Hirose, Tomoya; Ogura, Hiroshi; Kiguchi, Takeyuki; Mizushima, Yasuaki; Kimbara, Futoshi; Shimazaki, Junya; Shiono, Shigeru; Yamamura, Hitoshi; Wakai, Akinori; Takegawa, Ryosuke; Matsumoto, Hisatake; Ohnishi, Mitsuo; Shimazu, Takeshi

    2015-01-01

    Background Bicycle accidents are one of the major causes of unintentional traumatic injury in childhood. The purpose of this study was to examine characteristics and risks of handlebar injury in childhood. Methods We conducted a more than 5-year retrospective survey of patients under 15 years of age with bicycle-related injuries admitted to eight urban tertiary emergency centers in Osaka, Japan. Patients were divided into the direct-impact handlebar injury (HI) group and the non-handlebar inj...

  16. The Bicycle – Future’s Solution for an Eco-friendly Urban Transport

    Directory of Open Access Journals (Sweden)

    Cristina Ciovică

    2012-05-01

    Full Text Available Even though more and more cities across the globe impose restrictive measures regarding theuse of cars and offer instead incentives in order to choose alternative means of transport, they do not slowdown their economic growth, but on the contrary they prove their skills towards providing citizens a betterlife. Under these circumstances, the bicycle appears as a viable solution for most of us, and the publicprograms that support its use have started to develop globally, at European level, and in Romania as well.The current paper wishes to point out the stimulating perspectives brought by the slight increase in thenumber of bicycles sold in our country in recent years towards the future of urban transport.

  17. Study of Drive Mechanisms of Bicycle, Tricycle or Like Vehicles to Optimize Operating Performance - A Review

    Directory of Open Access Journals (Sweden)

    Rahul U. Urunkar

    2014-01-01

    Full Text Available A cycle or cycle rickshaw is a small-scale local means of transport. Cycle rickshaws are human-powered, a type of tricycle designed to carry passengers in addition to the driver. Tricycles are used primarily for commercial transportation. Various locally made configurations of bicycle or tricycle are available. The present form of cycle has many shortcomings. One of the major problems faced by available bicycle or tricycle is its less efficiency or mechanical advantage. This paper reviews patent (which are now open for public access and experimental work brought by researchers on drive mechanism of cycle in order to optimize its operating performance. An individual idea or any possible combination of different ideas can be used for optimizing performance of driving mechanism for cycle.

  18. The effect of cannabis on regular cannabis consumers' ability to ride a bicycle.

    Science.gov (United States)

    Hartung, Benno; Schwender, Holger; Roth, Eckhard H; Hellen, Florence; Mindiashvili, Nona; Rickert, Annette; Ritz-Timme, Stefanie; Grieser, Almut; Monticelli, Fabio; Daldrup, Thomas

    2016-05-01

    To assess the effects of cannabis on the ability required to ride a bicycle, repetitive practical cycling tests and medical examinations were carried out before and after inhalative consumption of cannabis. A maximum of three joints with body weight-adapted THC content (300 μg THC per kg body weight) could be consumed by each test subject. Fourteen regular cannabis-consuming test subjects were studied (12 males, 2 females). In summary, only a few driving faults were observed even under the influence of very high THC concentrations. A defined THC concentration that leads to an inability to ride a bicycle cannot be presented. The test subjects showed only slight distinctive features that can be documented using a medical test routinely run for persons under suspicion of driving under the influence of alcohol or drugs. PMID:26739323

  19. Optimal design parameters of the bicycle-rider system for maximal muscle power output.

    Science.gov (United States)

    Yoshihuku, Y; Herzog, W

    1990-01-01

    The purpose of this study was to find the optimal values of design parameters for a bicycle-rider system (crank length, pelvic inclination, seat height, and rate of crank rotation) which maximize the power output from muscles of the human lower limb during bicycling. The human lower limb was modelled as a planar system of five rigid bodies connected by four smooth pin joints and driven by seven functional muscle groups. The muscles were assumed to behave according to an adapted form of Hill's equation. The dependence of the average power on the design parameters was examined. The instantaneous power of each muscle group was studied and simultaneous activity of two seemingly antagonistic muscle groups was analyzed. Average peak power for one full pedal revolution was found to be around 1100 W. The upper body position corresponding to this peak power output was slightly reclined, and the pedalling rate was 155 rpm for a nominal crank length of 170 mm.

  20. Is the three-foot bicycle passing law working in Baltimore, Maryland?

    Science.gov (United States)

    Love, David C; Breaud, Autumn; Burns, Sean; Margulies, Jared; Romano, Max; Lawrence, Robert

    2012-09-01

    Maryland (MD) recently became one of fourteen states in the United States to enact a traffic law requiring motor vehicles to pass bicyclists at a distance of greater than three feet. To our knowledge, motorist compliance with the law has never been assessed. This study measured the distance between overtaking motor vehicles and cyclists [e.g. vehicle passing distance (VPD)], to develop baseline metrics for tracking implementation of the three-foot passing law in Baltimore, MD and to assess risk factors for dangerous passes. During September and October 2011, cyclists (n=5) measured VPD using a previously published video technique (Parkin and Meyers, 2010). Cyclists logged a total of 10.8h of video footage and 586 vehicle passes on 34 bicycle commuting trips. The average trip lasted 19.5±4.9 min and cyclists were passed on average 17.2±11.8 times per trip. VPDs of three feet or less were common when cycling in standard lanes (17%; 78 of 451 passes) and lanes with a shared lane marking (e.g. sharrows) (23%; 11 of 47 passes). No passes of three feet or less occurred in bicycle lanes (0 of 88 passes). A multiple linear regression model was created, which explained 26% of the variability in VPD. Significant model variables were lane width, bicycle infrastructure, cyclist identity, and street identity. Interventions, such as driver education, signage, enforcement, and bicycle infrastructure changes are needed to influence driving behavior in Baltimore to increase motorist compliance with the three-foot law. PMID:22664711

  1. Automatic control of cycling effort using electric bicycles and mobile devices

    OpenAIRE

    Jose A. Afonso; Rodrigues, Filipe J.; Delfim Pedrosa; Joao L. Afonso

    2015-01-01

    This paper describes the development and evaluation of a novel effort control system for cycling, which contributes to promote the users’ mobility and physical health. This system provides automatic control of the motor assistance level of an electric bicycle in order to ensure that the cyclist’s effort remains inside the desired target zone, regardless of changes in other variables which normally affect the effort, such as the slope of the road. The system presented in this paper controls th...

  2. A Universal Design Method for Reflecting Physical Characteristics Variability: Case Study of a Bicycle Frame.

    Science.gov (United States)

    Shimada, Masato; Suzuki, Wataru; Yamada, Shuho; Inoue, Masato

    2016-01-01

    To achieve a Universal Design, designers must consider diverse users' physical and functional requirements for their products. However, satisfying these requirements and obtaining the information which is necessary for designing a universal product is very difficult. Therefore, we propose a new design method based on the concept of set-based design to solve these issues. This paper discusses the suitability of proposed design method by applying bicycle frame design problem. PMID:27534334

  3. The Regional Response to Federal Fundingfor Bicycle and Pedestrian Projects: Executive Summary

    OpenAIRE

    McCann, Barbara; McRee, Lanier; Handy, Susan L; Meharg, Emily; Bailey, Linda; Ewing, Reid; Ernst, Michelle; Wright, Kate

    2009-01-01

    Since its initiation in the early 20th century, the federal transportation funding program has focused on highway construction for automobile travel. In the last few decades, public transportation has received 20% of federal resources, a significant share, but non-motorized modes such as bicycling and walking have historically received very limited funding. Over the past three decades, however, views of non-motorized modes and the federal interest in promoting them have changed dramatically. ...

  4. A simple, enaminone-based approach to some bicyclic pyridazinium tetrafluoroborates

    OpenAIRE

    František Josefík; Markéta Svobodová; Valerio Bertolasi; Petr Šimůnek

    2013-01-01

    Easily obtainable cyclic enaminones (piperidin-2-ylidenealkanones) can be transformed into substituted bicyclic pyridazinium tetrafluoroborates upon treatment with corresponding diazonium salts. The transformation can be performed either in a one-pot way or in a two-step process with the isolation of single azo-coupled enaminone as the intermediate. The former method is superior. Under the optimized conditions, a number of pyridazinium salts substituted with both electron-donating and electro...

  5. 'Cycle thieves, we are watching you': impact of a simple signage intervention against bicycle theft.

    Directory of Open Access Journals (Sweden)

    Daniel Nettle

    Full Text Available BACKGROUND: Bicycle theft is a serious problem in many countries, and there is a lack of evidence concerning effective prevention strategies. Displaying images of 'watching eyes' has been shown to make people behave in more socially desirable ways in a number of settings, but it is not yet clear if this effect can be exploited for purposes of crime prevention. We report the results of a simple intervention on a university campus where signs featuring watching eyes and a related verbal message were displayed above bicycle racks. METHODOLOGY AND PRINCIPAL FINDINGS: We installed durable signs at three locations which had experienced high levels of bicycle theft, and used the rest of the university campus as a control location. Reported thefts were monitored for 12 months before and after the intervention. Bicycle thefts decreased by 62% at the experimental locations, but increased by 65% in the control locations, suggesting that the signs were effective, but displaced offending to locations with no signs. The Odds Ratio for the effect of the intervention was 4.28 (95% confidence interval 2.04-8.98, a large effect compared to other place-based crime prevention interventions. CONCLUSIONS AND SIGNIFICANCE: The effectiveness of this extremely cheap and simple intervention suggests that there can be considerable crime-reduction benefits to engaging the psychology of surveillance, even in the absence of surveillance itself. Simple interventions for high-crime locations based on this principle should be considered as an adjunct to other measures, although a possible negative consequence is displacement of offending.

  6. A sketch planning methodology for determining interventions for bicycle and pedestrian crashes: an ecological approach

    OpenAIRE

    Thakuriah, P.; Cottrill, C.; Thomas, N; Vaughn, S.

    2010-01-01

    Bicycle and pedestrian safety planning have recently been gaining increased attention. With this focus, however, comes increased responsibilities for planning agencies and organizations tasked with evaluating and selecting safety interventions, a potentially arduous task given limited staff and resources. This study presents a sketch planning framework based on ecological factors that attempts to provide an efficient and effective method of selecting appropriate intervention measures. A Chica...

  7. Health effects of the London bicycle sharing system: health impact modelling study

    OpenAIRE

    Woodcock, James; Tainio, Marko; Cheshire, James; O’Brien, Oliver; Goodman, Anna

    2014-01-01

    Objective To model the impacts of the bicycle sharing system in London on the health of its users. Design Health impact modelling and evaluation, using a stochastic simulation model. Setting Central and inner London, England. Data sources Total population operational registration and usage data for the London cycle hire scheme (collected April 2011-March 2012), surveys of cycle hire users (collected 2011), and London data on travel, physical activity, road traffic collisions, and particulate ...

  8. Synthesis and Structure of A Novel Caged Bicyclic Phosphate Flame Retardant

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A novel caged bicyclic phosphate flame retardant tri(1-oxo-2,6,7-trioxa-l-phosphabicyclo [2.2.2] octane-methyl) phosphate (Trimer) was synthesized from 1-oxo-4-hydroxymethyl-2,6,7-trioxa-l-phosphabicyclo [2.2.2] octane (PEPA) and phosphorus oxychloride in this paper.Its structure was characterized by elemental analysis, FTIR, 1H NMR, 31P NMR and X-ray diffraction analysis.

  9. ω-Extension of Bicyclic Semigroup%双循环半群的ω扩张

    Institute of Scientific and Technical Information of China (English)

    朱雯; 詹亮

    2009-01-01

    In this paper,we discussed ω-extension of bicyclic semigroups.Two types of this extension are proposed.In §2 we discussed strong semilattice extension and the structure of the extension is well presented.In §3 we discussed another order extension.We proved that congruence lattice of this extension semigroups is union set of two sublattice.One is the group congruence semilattice,the other is the pure idempotent congruence semilattice.

  10. Pedaling into high gear for bicycle policy in Canada : lessons from bike summit 2008 in Toronto

    International Nuclear Information System (INIS)

    The 2008 bike summit provided a forum for the discussion of international and Canadian best practices related to bicycles and bicycling policy. The aim of the summit was to assist communities across Canada to improve conditions for cycling in the urban environment and help to generate a cultural shift towards greater acceptance of cycling on roads. This paper discussed lessons learned during the summit and outlined new methods of improving cycling in communities. The City of London has recently increased the amount of cyclists using its roads by 200 per cent. Cycling infrastructure is more affordable than constructing major public transit or road infrastructure. Savings in healthcare costs will be accrued over time as a result of the healthier lifestyles promoted by regular cycling activity. Bicycle trips can help to alleviate over-demand on heavy transit routes. Encouraging commuters to cycle will also reduce the amounts of greenhouse gases (GHGs) emitted in urban areas. Lane width reductions will help to reduce speeds as drivers are forced to pay more attention when driving. Public bike sharing programs and bike stations are now being used in many North American cities. It was concluded that strong advocacy is needed to ensure the growth and acceptance of cycling in urban centres. 23 figs

  11. 车锁式打气筒设计%Design of Bicycle Lock Type Pump

    Institute of Scientific and Technical Information of China (English)

    王超; 司慧

    2012-01-01

    The design combines a bicycle lock with a pump, realizing a uniform structure of the two. The application of a dual-pump structure makes the pumping process more efficient. In order to facilitate bicycle riders' relaxation, the air pump can also serve as a stool. Compared with carrying a single air pump or a single bicycle lock, this kind of air pump features lost air pumping cost, easy use, low space requirements, convenience to carry steady and reliable operation.%本设计将自行车车锁与打气筒巧妙地结合在一起,实现了二者结构形式的统一。应用双注气杆式打气结构,使打气效率优于现有的便携式打气筒,为了方便骑行者能够就地休息又附加了凳子的功能。与单独携带气筒、单独使用车锁相比,合二为一的车锁式打气筒成本低,使用、携带方便,节省空间,工作过程稳定、可靠。

  12. Pharmacokinetics-pharmacodynamics analysis of bicyclic 4-nitroimidazole analogs in a murine model of tuberculosis.

    Directory of Open Access Journals (Sweden)

    Suresh B Lakshminarayana

    Full Text Available PA-824 is a bicyclic 4-nitroimidazole, currently in phase II clinical trials for the treatment of tuberculosis. Dose fractionation pharmacokinetic-pharmacodynamic studies in mice indicated that the driver of PA-824 in vivo efficacy is the time during which the free drug concentrations in plasma are above the MIC (fT>MIC. In this study, a panel of closely related potent bicyclic 4-nitroimidazoles was profiled in both in vivo PK and efficacy studies. In an established murine TB model, the efficacy of diverse nitroimidazole analogs ranged between 0.5 and 2.3 log CFU reduction compared to untreated controls. Further, a retrospective analysis was performed for a set of seven nitroimidazole analogs to identify the PK parameters that correlate with in vivo efficacy. Our findings show that the in vivo efficacy of bicyclic 4-nitroimidazoles correlated better with lung PK than with plasma PK. Further, nitroimidazole analogs with moderate-to-high volume of distribution and Lung to plasma ratios of >2 showed good efficacy. Among all the PK-PD indices, total lung T>MIC correlated the best with in vivo efficacy (rs = 0.88 followed by lung Cmax/MIC and AUC/MIC. Thus, lung drug distribution studies could potentially be exploited to guide the selection of compounds for efficacy studies, thereby accelerating the drug discovery efforts in finding new nitroimidazole analogs.

  13. Influence of roadway geometric elements on driver behavior when overtaking bicycles on rural roads

    Directory of Open Access Journals (Sweden)

    Jeremy R. Chapman

    2014-02-01

    Full Text Available The objective of this research was to determine what influence geometric design elements of roadway may have on driver behavior during the overtaking maneuver. This was part of a larger research effort to eliminate crashes (and the resulting fatalities and injuries between bicycles and motorized vehicles. The data collection process produced 1151 observations with approximately 40 different independent variables for each data point through direct observation, sensor logging, or derivation from other independent variables. Prior research by the authors developed a means to collect real-time field data through the use of a bicycle-mounted data collection system. The collected data was then used to model lateral clearance distance between vehicles and bicycles. The developed model confirmed field observations that the lateral clearance distance provided by drivers changes with vehicle speed and oncoming vehicle presence. These observations were presented by the authors previously. The model shows that driver behavior can be adjusted by the inclusion, or exclusion, of geometric elements. Evaluating roadways (or roadway designs based on this model will enable stakeholders to identify those roadway segments where a paved shoulder would prove an effective safety countermeasure. This research will also enable roadway designers to better identify during the design phase those roadway segments that should be constructed with a paved shoulder.

  14. Boris Loutzky – Creator of the world's first motorized bicycle classic layout with a combustion engine

    Directory of Open Access Journals (Sweden)

    Alexander Firsov

    2012-12-01

    Full Text Available The article is dedicated to creation of the first motor vehicles with internal combustion engines. The purpose of article is to establish the name of the designer who was the first to create the world's motorized bicycle classic layout with a combustion engine. This article describes the construction of the first motorized vehicles Gottlieb Daimler, Edward Butler, Felix Millet, Giuseppe Murniotti, Edward Pennington, Alois Wolfmüller and Hans Geisenhof. based on the analysis of structures of motor vehicles. It’s stated that none of the vehicles can be called a «prototype» of modern mopeds and motorcycles. Based on the research it was found that in Germany Russian engineer B. Loutzky was engaged in creation of motorized vehicles with internal combustion engines even before Hildebrand and Pennington. These motorized vehicles were exhibited in Palermo, Erfurt, Vienna, Prague, Lamberg, Stuttgart and other cities in Europe, and were acknowledged and rewarded with gold medals. The paper describes the design of the first motorized bicycle with a classic layout by B. Loutzky and design of the unique internal combustion engines, which B. Loutzky used in his first vehicles. Overall, based on the analysis of patents for inventions, literary and archival sources, the priority of the Russian engineer B. Loutzky in creation of the motorized bicycle classic layout with a combustion engine is established.

  15. Built environment effects on cyclist injury severity in automobile-involved bicycle crashes.

    Science.gov (United States)

    Chen, Peng; Shen, Qing

    2016-01-01

    This analysis uses a generalized ordered logit model and a generalized additive model to estimate the effects of built environment factors on cyclist injury severity in automobile-involved bicycle crashes, as well as to accommodate possible spatial dependence among crash locations. The sample is drawn from the Seattle Department of Transportation bicycle collision profiles. This study classifies the cyclist injury types as property damage only, possible injury, evident injury, and severe injury or fatality. Our modeling outcomes show that: (1) injury severity is negatively associated with employment density; (2) severe injury or fatality is negatively associated with land use mixture; (3) lower likelihood of injuries is observed for bicyclists wearing reflective clothing; (4) improving street lighting can decrease the likelihood of cyclist injuries; (5) posted speed limit is positively associated with the probability of evident injury and severe injury or fatality; (6) older cyclists appear to be more vulnerable to severe injury or fatality; and (7) cyclists are more likely to be severely injured when large vehicles are involved in crashes. One implication drawn from this study is that cities should increase land use mixture and development density, optimally lower posted speed limits on streets with both bikes and motor vehicles, and improve street lighting to promote bicycle safety. In addition, cyclists should be encouraged to wear reflective clothing. PMID:26609666

  16. A Geo-Aware and VRP-Based Public Bicycle Redistribution System

    Directory of Open Access Journals (Sweden)

    J. H. Lin

    2012-01-01

    Full Text Available Public Bicycle System (PBS has been developed for short-distance transportation as a part of the mass transportation system. The supply and demand of bikes in PBS is usually unbalanced at different stations and needs to be continuously and widely monitored and redistributed. The bicycle redistribution is a part of the vehicle routing problem (VRP. We can apply solutions to the VRP to redistribute bicycle efficiently. However, most solutions to the VRP use the Euclidean distance as the condition factor, which does not take road conditions, traffic regulations, and geographical factors into account, resulting in unnecessary waste of delivery time and human resources. In this work, we propose an actual path distance optimization method for the VRP to adapt the several additional constraints of road problems. We also implement a system that integrates real-time station information, Web GIS, the urban road network, and heuristics algorithms for PBS. The system includes a simulator inside that can assist PBS managers to do the route planning efficiently and find the best scheduling strategy to achieve hotspot analysis and the adjustment of station deployment strategies to reduce PBS operation cost.

  17. Factors of the safety in bicycle traffic in the City of Zagreb and its surrounding

    Directory of Open Access Journals (Sweden)

    Sindik Joško

    2014-01-01

    Full Text Available The aim of this study was to determine the differences in underlying factors of Zagreb cycling, compared to the "types of cyclists" (driving style, i.e. different ways of using bicycles as a means of transport. The study included over 3,000 frequent participants in urban traffic cycling, sample of members of the association Cyclist Union (N = 1259 and snowball sample of "typical" of cyclists, i.e. people who are using the bike, but are not the members of the Cyclist Union (N = 1831, using the conveniently assembled questionnaire. Study participants who bike used in various applications prefer the safest driving style (only on sidewalks and bike paths / lines. Barriers of the weather conditions are ubiquitous in the safest driving style. Daily, weekly and yearly riding a bicycle are more often found in those who prefer the safest driving style. Cyclists who drive with medium secure style (roads with less traffic and lower speeds, more often ride a bike, as compared with those who prefer the safest driving style. Having a better bike line / track and other infrastructure is the most often considered at those with the highest risk driving style. The results provide the guidance for local authorities and for the cyclists to improve the conditions for a safer and more often by bicycle circulation in the City of Zagreb and its surroundings.

  18. The effect of alcohol hangover on the ability to ride a bicycle.

    Science.gov (United States)

    Hartung, Benno; Schwender, Holger; Mindiashvili, Nona; Ritz-Timme, Stefanie; Malczyk, Axel; Daldrup, Thomas

    2015-07-01

    To investigate the effects of alcohol on the ability to ride a bicycle, practical cycling tests were carried out at different blood alcohol concentrations (BAC). For this purpose, various alcoholic beverages could be consumed from around 2 p.m. until 11 p.m. Afterwards, the test persons spent the night on the trial site and were provided with dormitory sleeping accommodation. On the following morning, beginning at around 8 a.m., a final cycling test was performed. The performances of those test persons who had returned to state of soberness and of those with residual blood alcohol levels were compared to the performances on the day before. The practical ability to ride a bicycle was significantly reduced in the postalcoholic state compared to the rides of the day before. The relative cycling performance in the postalcoholic state was comparable to the rides under the influence of BAC of around 0.30 g/kg. There were no remarkable differences between the groups with and without residual blood alcohol levels regarding the rides on the next morning. Therefore, it can be assumed that the direct influence of residual blood alcohol levels plays a minor role for the ability to ride a bicycle in the postalcoholic state. Instead, the side effects of the high amounts of alcohol that were consumed the night before are crucial. PMID:25940454

  19. Study of electrode slice forming of bicycle dynamo hub power connector

    Science.gov (United States)

    Chen, Dyi-Cheng; Jao, Chih-Hsuan

    2013-12-01

    Taiwan's bicycle industry has been an international reputation as bicycle kingdom, but the problem in the world makes global warming green energy rise, the development of electrode slice of hub dynamo and power output connector to bring new hope to bike industry. In this study connector power output to gather public opinion related to patent, basis of collected documents as basis for design, structural components in least drawn to power output with simple connector. Power output of this study objectives connector hope at least cost, structure strongest, highest efficiency in output performance characteristics such as use of computer-aided drawing software Solid works to establish power output connector parts of 3D model, the overall portfolio should be considered part types including assembly ideas, weather resistance, water resistance, corrosion resistance to vibration and power flow stability. Moreover the 3D model import computer-aided finite element analysis software simulation of expected the power output of the connector parts manufacturing process. A series of simulation analyses, in which the variables relied on first stage and second stage forming, were run to examine the effective stress, effective strain, press speed, and die radial load distribution when forming electrode slice of bicycle dynamo hub.

  20. Built environment effects on cyclist injury severity in automobile-involved bicycle crashes.

    Science.gov (United States)

    Chen, Peng; Shen, Qing

    2016-01-01

    This analysis uses a generalized ordered logit model and a generalized additive model to estimate the effects of built environment factors on cyclist injury severity in automobile-involved bicycle crashes, as well as to accommodate possible spatial dependence among crash locations. The sample is drawn from the Seattle Department of Transportation bicycle collision profiles. This study classifies the cyclist injury types as property damage only, possible injury, evident injury, and severe injury or fatality. Our modeling outcomes show that: (1) injury severity is negatively associated with employment density; (2) severe injury or fatality is negatively associated with land use mixture; (3) lower likelihood of injuries is observed for bicyclists wearing reflective clothing; (4) improving street lighting can decrease the likelihood of cyclist injuries; (5) posted speed limit is positively associated with the probability of evident injury and severe injury or fatality; (6) older cyclists appear to be more vulnerable to severe injury or fatality; and (7) cyclists are more likely to be severely injured when large vehicles are involved in crashes. One implication drawn from this study is that cities should increase land use mixture and development density, optimally lower posted speed limits on streets with both bikes and motor vehicles, and improve street lighting to promote bicycle safety. In addition, cyclists should be encouraged to wear reflective clothing.

  1. A solid solution to a conjecture on the maximal energy of bipartite bicyclic graphs

    CERN Document Server

    Huo, Bofeng; Li, Xueliang; Shi, Yongtang

    2011-01-01

    The energy of a simple graph $G$, denoted by $E(G)$, is defined as the sum of the absolute values of all eigenvalues of its adjacency matrix. Let $C_n$ denote the cycle of order $n$ and $P^{6,6}_n$ the graph obtained from joining two cycles $C_6$ by a path $P_{n-12}$ with its two leaves. Let $\\mathscr{B}_n$ denote the class of all bipartite bicyclic graphs but not the graph $R_{a,b}$, which is obtained from joining two cycles $C_a$ and $C_b$ ($a, b\\geq 10$ and $a \\equiv b\\equiv 2\\, (\\,\\textmd{mod}\\, 4)$) by an edge. In [I. Gutman, D. Vidovi\\'{c}, Quest for molecular graphs with maximal energy: a computer experiment, {\\it J. Chem. Inf. Sci.} {\\bf41}(2001), 1002--1005], Gutman and Vidovi\\'{c} conjectured that the bicyclic graph with maximal energy is $P^{6,6}_n$, for $n=14$ and $n\\geq 16$. In [X. Li, J. Zhang, On bicyclic graphs with maximal energy, {\\it Linear Algebra Appl.} {\\bf427}(2007), 87--98], Li and Zhang showed that the conjecture is true for graphs in the class $\\mathscr{B}_n$. However, they could not...

  2. The impact of transportation infrastructure on bicycling injuries and crashes: a review of the literature

    Directory of Open Access Journals (Sweden)

    Cripton Peter A

    2009-10-01

    Full Text Available Abstract Background Bicycling has the potential to improve fitness, diminish obesity, and reduce noise, air pollution, and greenhouse gases associated with travel. However, bicyclists incur a higher risk of injuries requiring hospitalization than motor vehicle occupants. Therefore, understanding ways of making bicycling safer and increasing rates of bicycling are important to improving population health. There is a growing body of research examining transportation infrastructure and the risk of injury to bicyclists. Methods We reviewed studies of the impact of transportation infrastructure on bicyclist safety. The results were tabulated within two categories of infrastructure, namely that at intersections (e.g. roundabouts, traffic lights or between intersections on "straightaways" (e.g. bike lanes or paths. To assess safety, studies examining the following outcomes were included: injuries; injury severity; and crashes (collisions and/or falls. Results The literature to date on transportation infrastructure and cyclist safety is limited by the incomplete range of facilities studied and difficulties in controlling for exposure to risk. However, evidence from the 23 papers reviewed (eight that examined intersections and 15 that examined straightaways suggests that infrastructure influences injury and crash risk. Intersection studies focused mainly on roundabouts. They found that multi-lane roundabouts can significantly increase risk to bicyclists unless a separated cycle track is included in the design. Studies of straightaways grouped facilities into few categories, such that facilities with potentially different risks may have been classified within a single category. Results to date suggest that sidewalks and multi-use trails pose the highest risk, major roads are more hazardous than minor roads, and the presence of bicycle facilities (e.g. on-road bike routes, on-road marked bike lanes, and off-road bike paths was associated with the lowest

  3. A Comparison of Static and Dynamic Measures of Lower Limb Joint Angles in Cycling: Application to Bicycle Fitting

    Directory of Open Access Journals (Sweden)

    Bini Rodrigo Rico

    2016-03-01

    Full Text Available Purpose. Configuration of bicycle components to the cyclist (bicycle fitting commonly uses static poses of the cyclist on the bicycle at the 6 o’clock crank position to represent dynamic cycling positions. However, the validity of this approach and the potential use of the different crank position (e.g. 3 o’clock have not been fully explored. Therefore, this study compared lower limb joint angles of cyclists in static poses (3 and 6 o’clock compared to dynamic cycling. Methods. Using a digital camera, right sagittal plane images were taken of thirty cyclists seated on their own bicycles mounted on a stationary trainer with the crank at 3 o’clock and 6 o’clock positions. Video was then recorded during pedalling at a self-selected gear ratio and pedalling cadence. Sagittal plane hip, knee and ankle angles were digitised. Results. Differences between static and dynamic angles were large at the 6 o’clock crank position with greater mean hip angle (4.9 ± 3°, smaller knee angle (8.2 ± 5° and smaller ankle angle (8.2 ± 5.3° for static angles. Differences between static and dynamic angles (< 1.4° were trivial to small for the 3 o’clock crank position. Conclusions. To perform bicycle fitting, joint angles should be measured dynamically or with the cyclist in a static pose at the 3 o’clock crank position.

  4. Angular Impact Mitigation System for Bicycle Helmets to Reduce Head Acceleration and Risk of Traumatic Brain Injury

    Science.gov (United States)

    Hansen, Kirk; Dau, Nathan; Feist, Florian; Deck, Caroline; Willinger, Rémy; Madey, Steven M.; Bottlang, Michael

    2013-01-01

    Angular acceleration of the head is a known cause of traumatic brain injury (TBI), but contemporary bicycle helmets lack dedicated mechanisms to mitigate angular acceleration. A novel Angular Impact Mitigation (AIM) system for bicycle helmets has been developed that employs an elastically suspended aluminum honeycomb liner to absorb linear acceleration in normal impacts as well as angular acceleration in oblique impacts. This study tested bicycle helmets with and without AIM technology to comparatively assess impact mitigation. Normal impact tests were performed to measure linear head acceleration. Oblique impact tests were performed to measure angular head acceleration and neck loading. Furthermore, acceleration histories of oblique impacts were analyzed in a computational head model to predict the resulting risk of TBI in the form of concussion and diffuse axonal injury (DAI). Compared to standard helmets, AIM helmets resulted in a 14% reduction in peak linear acceleration (p < 0.001), a 34% reduction in peak angular acceleration (p < 0.001), and a 22% to 32% reduction in neck loading (p < 0.001). Computational results predicted that AIM helmets reduced the risk of concussion and DAI by 27% and 44%, respectively. In conclusion, these results demonstrated that AIM technology could effectively improve impact mitigation compared to a contemporary expanded polystyrene-based bicycle helmet, and may enhance prevention of bicycle-related TBI. Further research is required. PMID:23770518

  5. The effectiveness of helmets in bicycle collisions with motor vehicles: a case-control study.

    Science.gov (United States)

    Bambach, M R; Mitchell, R J; Grzebieta, R H; Olivier, J

    2013-04-01

    There has been an ongoing debate in Australia and internationally regarding the effectiveness of bicycle helmets in preventing head injury. This study aims to examine the effectiveness of bicycle helmets in preventing head injury amongst cyclists in crashes involving motor vehicles, and to assess the impact of 'risky cycling behaviour' among helmeted and unhelmeted cyclists. This analysis involved a retrospective, case-control study using linked police-reported road crash, hospital admission and mortality data in New South Wales (NSW), Australia during 2001-2009. The study population was cyclist casualties who were involved in a collision with a motor vehicle. Cases were those that sustained a head injury and were admitted to hospital. Controls were those admitted to hospital who did not sustain a head injury, or those not admitted to hospital. Standard multiple variable logistic regression modelling was conducted, with multinomial outcomes of injury severity. There were 6745 cyclist collisions with motor vehicles where helmet use was known. Helmet use was associated with reduced risk of head injury in bicycle collisions with motor vehicles of up to 74%, and the more severe the injury considered, the greater the reduction. This was also found to be true for particular head injuries such as skull fractures, intracranial injury and open head wounds. Around one half of children and adolescents less than 19 years were not wearing a helmet, an issue that needs to be addressed in light of the demonstrated effectiveness of helmets. Non-helmeted cyclists were more likely to display risky riding behaviour, however, were less likely to cycle in risky areas; the net result of which was that they were more likely to be involved in more severe crashes. PMID:23377086

  6. Attention and expectation problems in bicycle-car collisions: an in-depth study.

    Science.gov (United States)

    Räsänen, M; Summala, H

    1998-09-01

    One hundred and eighty-eight bicycle-car accidents in four cities were studied by multidisciplinary in-depth analysis. The sample was representative of the national accident statistics. All the accidents were analyzed in detail to reconstruct the actual movements of those involved and to assess detection of the other party. In 37% of collisions, neither driver nor cyclist realized the danger or had time to yield. In the remaining collisions, the driver (27%), the cyclist (24%) or both (12%) did something to avert the accident. Two common mechanisms underlying the accidents were identified. First, allocation of attention such that others were not detected, and second, unjustified expectations about the behavior of others. These mechanisms were found to be closely related to the system of two-way cycle tracks and to the fact that the general priority rule is applied to the crossings of a cycle track and a roadway. The most frequent accident type among collisions between cyclists and cars at bicycle crossings was a driver turning right and a bicycle coming from the driver's right along a cycle track. The result confirmed an earlier finding (Accident Analysis and Prevention 28, 147-153, 1996) that drivers turning right hit cyclists because they looked left for cars during the critical phase. Only 11% of drivers noticed the cyclist before impact. Cyclists' behavior was in marked contrast to that of drivers. In these cases, 68% of cyclists noticed the driver before the accident, and 92% of those who noticed believed the driver would give way as required by law. Cyclists with a driving license and those who cycled daily through the accident site were involved in different accident types to other cyclists. PMID:9678219

  7. Deaths of bicycle riders in Brazil: characteristics and trends during the period of 2000 - 2010

    Directory of Open Access Journals (Sweden)

    Leila Posenato Garcia

    2013-12-01

    Full Text Available INTRODUCTION: In Brazil, bicycle use has been increasing. Accidents involving cyclists are important causes of morbidity and mortality. OBJECTIVE: To describe the mortality of cyclists injured in transport accidents in Brazil, the characteristics of the victims and of the occurrence, and to investigate its trends during the period between 2000 and 2010. METHODS: A descriptive study with data from the Mortality Information System (SIM was conducted in the period of 2000 - 2010. Crude and age-standardized corrected mortality rates were calculated for Brazil, its macro-regions and states. Linear regression was used to study the trends. RESULTS: In the period of 2000 - 2010, 32,422 bicycle-related deaths were identified in Brazil. In 2010, there were, on average, 8.8 bicycle-related deaths per day. Age-standardized mortality rates for the country were 15.3 and 15.9 deaths per million inhabitants in 2000 and 2010, respectively (p = 0.725. During the whole period, the Center-Western region showed the highest rates, though stable, corresponding to 23.4 deaths per million inhabitants in 2010. Men accounted for 85.4% of deaths, with death risk 5 times higher than women. CONCLUSION: In spite of the stable rates for the country, there was an increase trend in the Northern and Northeastern regions, while a decreasing trend was observed in the Southern and Southeastern regions. The risk of death was higher among men, elderly, and people living in large cities and at the Center-Western region.

  8. A wearable ECG-HR detector and its application to automatic assist-mode selection of an electrically assisted bicycle.

    Science.gov (United States)

    Ueno, Akinori; Miyashita, Osamu; Yoshida, Toshiya; Yamamoto, Junichi; Lataire, Philippe

    2011-01-01

    Recently, an electrically assisted bicycle has been widely used in daily life and becomes very popular. The user selects the stepwise assist-mode to determine the assistive torque for pleasurable running. From the viewpoint of improvement of health by exercise, the electrically assisted bicycle can be an exercise machine like a treadmill. The heart rate (HR) is regarded as an indication of exercise load. This paper presents an automatic assist-mode selection system based on the HR of the bicycle user. The HR is obtained from the R-waves measured by the proposed wearable electrocardiograph on the user. The mode-selection system is simply implemented by a personal computer, USB-connected interface, and some electronic switching circuits. The running experiments confirm that the proposed assist-mode selection method has practicability. PMID:22255925

  9. A review on bicycle and motorcycle rider control with a perspective on handling qualities

    Science.gov (United States)

    Kooijman, J. D. G.; Schwab, A. L.

    2013-11-01

    This paper is a review study on handling and control of bicycles and motorcycles, the so-called single-track vehicles. The first part gives a brief overview on the modelling of the dynamics of single-track vehicles and the experimental validation. The second part focusses on a review of modelling and measuring human rider control. The third part deals with the concepts of handling and manoeuvrability and their experimental validation. Parallels are drawn with the literature on aircraft handling and pilot models. The paper concludes with the open ends and promising directions for future work in the field of handling and control of single-track vehicles.

  10. [The electrical stimulation bicycle: a neuroprosthesis for the everyday use of paraplegic patients].

    Science.gov (United States)

    Szecsi, J; Fiegel, M; Krafczyk, S; Straube, A; Quintern, J; Brandt, Th

    2004-06-24

    Until recently, few patients with complete paraplegia could walk or stand with the help of functional electrical stimulation (FES) of the leg muscles regularly at home. In comparison, FES cycling with an adapted tricycle is easy to put into practice because the legs remain connected to the pedals and through the use of a tricycle or stationary bicycle, the balancing problems of the patient recedes into the background. In the first German feasibility studies for paraplegic cycling, eleven completely paraplegic patients have been tested so far. The goal is to make FES cycling a daily activity in the lives of as many patients as possible.

  11. Feasibility study on a perceived fatigue prediction dependent power control for an electrically assisted bicycle.

    Science.gov (United States)

    Kiryu, T; Minagawa, H

    2013-01-01

    Several types of electric motor assists have been developed, as a result, it is important to control muscular fatigue on-site in terms of health promotion and motor rehabilitation. Predicting the perceived fatigue by several biosignal-related variables with the multiple regression model and polynomial approximation, we try to propose a self control design for the electrically assisted bicycle (EAB). We also determine the meaningful muscles during pedaling by muscle synergies in relation to the motion maturity. In field experiments, prediction of ongoing perceived physical fatigue could have the potential of suitable control of EAB.

  12. Enantiospecific Synthesis of All Four Stereoisomers of Novel Bicyclic Arylacetamides as κ—Opioid Agonists

    Institute of Scientific and Technical Information of China (English)

    龙亚秋; 牟奇勇; 仇达萍; 吴瑞琴

    2002-01-01

    Conformationally constrained bicyclic derivatives of the potent and selective κ-opioid receptor agonist 2-(3,4-dichlorophenyl)-N-methyl-N-[(1S)-1-Phenyl-2-(1-Pyrrolidinyl)-ethyl]acetamide(3,ICI-199,441)were designed to explore the effect of the conformational restriction and stereochemistry of the pharmacophoric ethylenediamine incorporated into the pyrrolidine on the affinity and κ-selectivity.A facile enantiosipecitfic synthetic route was extablished to afford all four stereoisomers starting from readily available amino acids through mild cyclization and amide formation.

  13. Enantiospecific Synthesis of All Four Stereoisomers of Novel Bicyclic Arylacetamides as κ-Opioid Agonists

    Institute of Scientific and Technical Information of China (English)

    LONG,Ya-Qiu(龙亚秋); MOU,Qi-Yong(牟奇勇); QIU,Da-Ping(仇达萍); WU,Rui-Qin(吴瑞琴)

    2002-01-01

    Conformationally constrained bicyclic derivatives of the potent and selective κ-opioid receptor agonist 2-(3,4-dichlorophenyl)-N-methyl- N- [ (1S ) - 1-phenyl-2- (1-pyrrolidinyl)-ethyl] acetamide (3, ICI-199,441) were designed to explore the effect of the conformational restriction and stereochemistry of the pharmacophoric ethylenediamine incorporated into the pyrrolidine on the affinity and κ-selectivity. A facile enantiospecific synthetic route was established to afford all four stereoisomers starting from readily available amino acids through mild cyclization and amide formation.

  14. Feasibility study on a perceived fatigue prediction dependent power control for an electrically assisted bicycle.

    Science.gov (United States)

    Kiryu, T; Minagawa, H

    2013-01-01

    Several types of electric motor assists have been developed, as a result, it is important to control muscular fatigue on-site in terms of health promotion and motor rehabilitation. Predicting the perceived fatigue by several biosignal-related variables with the multiple regression model and polynomial approximation, we try to propose a self control design for the electrically assisted bicycle (EAB). We also determine the meaningful muscles during pedaling by muscle synergies in relation to the motion maturity. In field experiments, prediction of ongoing perceived physical fatigue could have the potential of suitable control of EAB. PMID:24110131

  15. [The electrical stimulation bicycle: a neuroprosthesis for the everyday use of paraplegic patients].

    Science.gov (United States)

    Szecsi, J; Fiegel, M; Krafczyk, S; Straube, A; Quintern, J; Brandt, Th

    2004-06-24

    Until recently, few patients with complete paraplegia could walk or stand with the help of functional electrical stimulation (FES) of the leg muscles regularly at home. In comparison, FES cycling with an adapted tricycle is easy to put into practice because the legs remain connected to the pedals and through the use of a tricycle or stationary bicycle, the balancing problems of the patient recedes into the background. In the first German feasibility studies for paraplegic cycling, eleven completely paraplegic patients have been tested so far. The goal is to make FES cycling a daily activity in the lives of as many patients as possible. PMID:15529690

  16. Unexpected involvement of staple leads to redesign of selective bicyclic peptide inhibitor of Grb7

    OpenAIRE

    Menachem J. Gunzburg; Ketav Kulkarni; Gabrielle M. Watson; Ambaye, Nigus D.; Del Borgo, Mark P.; Rebecca Brandt; Stephanie C. Pero; Patrick Perlmutter; Wilce, Matthew C. J.; Wilce, Jacqueline A

    2016-01-01

    The design of potent and specific peptide inhibitors to therapeutic targets is of enormous utility for both proof-of-concept studies and for the development of potential new therapeutics. Grb7 is a key signaling molecule in the progression of HER2 positive and triple negative breast cancers. Here we report the crystal structure of a stapled bicyclic peptide inhibitor G7-B1 in complex with the Grb7-SH2 domain. This revealed an unexpected binding mode of the peptide, in which the staple forms a...

  17. Action of bicyclic isoxazole GABA analogues on GABA transporters and its relation to anticonvulsant activity

    DEFF Research Database (Denmark)

    Bolvig, T; Larsson, O M; Pickering, D S;

    1999-01-01

    transporter-1 (GAT-1), GAT-2, -3 or -4. It was found that 4,5,6,7-tetrahydroisoxazolo(4,5-c)pyridin-3-ol (THPO) and 5,6,7,8-tetrahydro-4H-isoxazolo[4,5-c]azepin-3-ol (THAO) displayed some inhibitory activity on GAT-1 and GAT-2, where the compounds exhibited a slightly lower potency on GAT-2 compared to GAT-1...... anticonvulsant activity, lack of proconvulsant activity and the ability of THPO to increase extracellular GABA concentration, indicate that these bicyclic isoxazole GABA analogues and their DPB derivatives may be useful lead structures in future search for new antiepileptic drugs....

  18. Aliphatic and aromatic hydrocarbons in Candiota coal samples: novel series of bicyclic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Miranda, A.C.M.L.; Loureiro, M.R.B.; Cardoso, J.N. [Universidade Federal do Rio de Janeiro, Rio de Janeiro (Brazil). Inst. de Quimica

    1999-07-01

    Gas chromatography - mass spectrometry was used to analyse aliphatic and aromatic fractions obtained from nine samples taken from two different seams of five boreholes in the Candiota coalfield (Lower Permian). The occurrence of certain tetracyclic diterpenoids among the aliphatic hydrocarbons, and the tricyclic diterpenoids simonellite and retene in the aromatic hydrocarbon concentrates, suggest an important input from conifers to the sedimentary biomass. This may explain the origin of a novel series of saturated and aromatic bicyclic compounds detected in the extracts which may be structurally related to the same precursor, possibly a conifer resin-derived tricyclic diterpenoid.

  19. Understanding adolescents' intentions to commute by car or bicycle as adults

    DEFF Research Database (Denmark)

    Sigurdardottir, Sigrun Birna; Kaplan, Sigal; Møller, Mette;

    2013-01-01

    This study focuses on the intentions of adolescents to commute by car or bicycle as adults. The behavioral model is based on intrapersonal and interpersonal constructs from the theory of planned behavior extended to include constructs from the institutional, community and policy domains. Data from...... a survey among Danish adolescents is analyzed. It is found that car use intentions are related to positive car passenger experience, general interest in cars, and car ownership norms, and are negatively related to willingness to accept car restrictions and perceived lack of behavioral control. Cycling...

  20. Comparison between treadmill and bicycle ergometer exercise tests in mild-to-moderate hypertensive Nigerians

    Directory of Open Access Journals (Sweden)

    Abiodun OO

    2015-08-01

    Full Text Available Olugbenga O Abiodun, Michael O Balogun, Anthony O Akintomide, Rasaaq A Adebayo, Olufemi E Ajayi, Suraj A Ogunyemi, Valentine N Amadi, Victor O Adeyeye Cardiology Unit, Department of Medicine, Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC, Ile-Ife, Osun state, Nigeria Background: Comparative cardiovascular responses to treadmill and bicycle ergometer (bike exercise tests in hypertensive Nigerians are not known. This study compared cardiovascular responses to the two modes of exercise testing in hypertensives using maximal exercise protocols. Methods: One hundred and ten male subjects with mild-to-moderate hypertension underwent maximal treadmill and bike test one after the other at a single visit in a simple random manner. Paired-sampled t-test was used to compare responses to both exercise tests while chi-squared test was used to compare categorical variables. Results: The maximal heart rate (P<0.001, peak systolic blood pressure (P=0.02, rate pressure product (P<0.001, peak oxygen uptake (P<0.001, and exercise capacity (P<0.001 in metabolic equivalents were significantly higher on the treadmill than on the bike. Conclusion: Higher cardiovascular responses on treadmill in Nigerian male hypertensives in this study, similar to findings in non-hypertensives and non-Nigerians in earlier studies, suggest that treadmill may be of better diagnostic utility in our population. Keywords: maximal exercise, treadmill, bicycle ergometer, hypertension, Nigerians