Sample records for bicyclic bis-arylimidazole c-jun

  1. NANOG upregulates c-Jun oncogene expression through binding the c-Jun promoter. (United States)

    Lin, Yanli; Xiong, Fuyin; Zhou, Yanrong; Wu, Xiaojie; Liu, Fang; Xue, Shiwei; Chen, Hongxing


    NANOG plays important roles in neoplastic processes. However, the molecular mechanism of NANOG in tumorigenesis remains to be elucidated. In this report, we demonstrated that forced expression of NANOG in 293 cells and cancer cells led to increased c-Jun expression, whereas downregulation of endogenous NANOG significantly reduced c-Jun expression in cancer cells. Dual luciferase reporter assays demonstrated that NANOG binds the c-Jun proximal promoter and transactivates the c-Jun gene. An ATTA consensus motif between the -160 and -268 region of the c-Jun promoter was identified as the NANOG-responsive element. Electromobility shift assay and chromatin immunoprecipitation results confirmed the direct binding of NANOG protein to the c-Jun promoter in vitro and in vivo. NANOG directly bound c-Jun protein as shown by GST pulldown and immunoprecipitation assays. Taking these findings together, we conclude that c-Jun is a direct target gene of NANOG and that c-Jun protein may be a novel co-activator of NANOG in cancer cells. We suggest the possibility that NANOG may play a significant role in carcinogenesis via its activation of c-Jun expression.

  2. c-Jun N-terminal kinase - c-Jun pathway transactivates Bim to promote osteoarthritis. (United States)

    Ye, Zhiqiang; Chen, Yuxian; Zhang, Rongkai; Dai, Haitao; Zeng, Chun; Zeng, Hua; Feng, Hui; Du, Gengheng; Fang, Hang; Cai, Daozhang


    Osteoarthritis (OA) is a chronic degenerative joint disorder. Previous studies have shown abnormally increased apoptosis of chondrocytes in patients and animal models of OA. TNF-α and nitric oxide have been reported to induce chondrocyte ageing; however, the mechanism of chondrocyte apoptosis induced by IL-1β has remained unclear. The aim of this study is to identify the role of the c-Jun N-terminal kinase (JNK) - c-Jun pathway in regulating induction of Bim, and its implication in chondrocyte apoptosis. This study showed that Bim is upregulated in chondrocytes obtained from the articular cartilage of OA patients and in cultured mouse chondrocytes treated with IL-1β. Upregulation of Bim was found to be critical for chondrocyte apoptosis induced by IL-1β, as revealed by the genetic knockdown of Bim, wherein apoptosis was greatly reduced in the chondrocytes. Moreover, activation of the JNK-c-Jun pathway was observed under IL-1β treatment, as indicated by the increased expression levels of c-Jun protein. Suppression of the JNK-c-Jun pathway, using chemical inhibitors and RNA interference, inhibited the Bim upregulation induced by IL-1β. These findings suggest that the JNK-c-Jun pathway is involved in the upregulation of Bim during OA and that the JNK-c-Jun-Bim pathway is vital for chondrocyte apoptosis.

  3. c-Jun transactivates Puma gene expression to promote osteoarthritis. (United States)

    Lu, Huading; Hou, Gang; Zhang, Yongkai; Dai, Yuhu; Zhao, Huiqing


    Osteoarthritis (OA) is a chronic degenerative joint disorder in which genetic, hormonal, mechanical and ageing factors affect its progression. Current studies are focusing on chondrocytes as a key mediator of OA at a cellular level. however, the mechanism underlying chondrocyte apoptosis remains unclear. PUMA is a pro-apoptotic member of the BH3-only subgroup of the Bcl-2 family and is involved in a large number of physiological and pathological processes. In the present study, we examined whether PUMA has a role in IL-1β-induced apoptosis and whether the c-Jun N-terminal kinase (JNK)/c-Jun pathway mediates the induction of PUMA, thus contributing to chondrocyte apoptosis. The results demonstrated an increase in PUMA protein and mRNA levels in cultured mouse chondrocytes following 4 h of IL-1β treatment. Furthermore, this upregulation of PUMA was critical for chondrocyte apoptosis as knockdown of PUMA using PUMA-specific siRNA significantly reduced apoptosis in cultured cells. Upon pharmacological inhibition of the JNK/c-Jun pathway with CE11004 or SP600125, the expression of PUMA was notably suppressed with a concomitant decrease in apoptosis observed in IL-1β-treated chondrocytes. Also, immunohistochemical studies revealed that the PUMA and c-Jun proteins were upregulated in chondrocytes from the articular cartilage of OA patients. Together, these data suggest a role for PUMA and the JNK/c-Jun pathway in the regulation of chondrocyte apoptosis during OA.

  4. c-jun is differentially expressed in embryonic and adult neural precursor cells. (United States)

    Kawashima, Fumiaki; Saito, Kengo; Kurata, Hirofumi; Maegaki, Yoshihiro; Mori, Tetsuji


    c-jun, a major component of AP-1 transcription factor, has a wide variety of functions. In the embryonic brain, c-jun mRNA is abundantly expressed in germinal layers around the ventricles. Although the subventricular zone (SVZ) of the adult brain is a derivative of embryonic germinal layers and contains neural precursor cells (NPCs), the c-jun expression pattern is not clear. To study the function of c-jun in adult neurogenesis, we analyzed c-jun expression in the adult SVZ by immunohistochemistry and compared it with that of the embryonic brain. We found that almost all proliferating embryonic NPCs expressed c-jun, but the number of c-jun immunopositive cells among proliferating adult NPCs was about half. In addition, c-jun was hardly expressed in post-mitotic migrating neurons in the embryonic brain, but the majority of c-jun immunopositive cells were tangentially migrating neuroblasts heading toward the olfactory bulb in the adult brain. In addition, status epilepticus is known to enhance the transient proliferation of adult NPCs, but the c-jun expression pattern was not significantly affected. These expression patterns suggest that c-jun has a pivotal role in the proliferation of embryonic NPCs, but it has also other roles in adult neurogenesis.

  5. Characterization of c-Jun from orange-spotted grouper, Epinephelus coioides involved in SGIV infection. (United States)

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


    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.

  6. 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


    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

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

    Institute of Scientific and Technical Information of China (English)



    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.

  8. Bicycle safety (United States)

    ... states have bike lanes and laws that protect bicycle riders. But riders are still at risk of ... stop or take evasive action. While riding your bicycle: Watch for opening car doors, potholes, children, and ...

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

    Energy Technology Data Exchange (ETDEWEB)

    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))


    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.

  10. Parathyroid hormone induces c-fos and c-jun messenger RNA in rat osteoblastic cells (United States)

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


    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).

  11. Differential regulation of c-jun and CREB by acrolein and 4-hydroxynonenal. (United States)

    Pugazhenthi, Subbiah; Phansalkar, Ketaki; Audesirk, Gerald; West, Anne; Cabell, Leigh


    In Alzheimer's disease (AD), oxidative stress-induced lipid peroxidation leads to accumulation of unsaturated aldehydes including acrolein and 4-hydroxynonenal (4HNE) in brain. In this study, we examined the effects of these lipid peroxidation products on apoptotic pathways in cultured neurons. Acrolein and 4HNE increased the levels of active phosphorylated forms of c-jun and CREB, the transcription factors that promote apoptosis and cell survival, respectively. However, they decreased the activity of CREB-dependent BDNF promoter while they increased the activity of promoters responsive to c-jun. We hypothesized that this differential regulation could be due to competition between proapoptotic c-jun and cytoprotective CREB for CBP (CREB-binding protein), a coactivator shared by several transcription factors. In support of this hypothesis, we demonstrate that the decrease of BDNF promoter activity by acrolein and 4HNE could be restored (i) by cotransfection with CBP, (ii) by cotransfection with VP 16-CREB, a constitutively active form of CREB that does not depend on CBP for its activation, or (iii) by inhibiting JNK-mediated c-jun activation. Finally, adenoviral transduction of hippocampal neurons with VP 16-CREB resulted in significant reduction in caspase-3 activation by acrolein and 4HNE. These observations suggest that lipid peroxidation-induced differential regulation of CREB and c-jun might play a role in neurodegeneration in AD.

  12. c-Jun Promotes whereas JunB Inhibits Epidermal Neoplasia


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


    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...

  13. c-Jun promotes whereas JunB inhibits epidermal neoplasia. (United States)

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


    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

  14. Bicycling injuries. (United States)

    Silberman, Marc R


    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.

  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


    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. Modeling the Mechanism of GR/c-Jun/Erg Crosstalk in Apoptosis of Acute Lymphoblastic Leukemia. (United States)

    Chen, Daphne Wei-Chen; Krstic-Demonacos, Marija; Schwartz, Jean-Marc


    Acute lymphoblastic leukemia (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 adopting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data by building a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Ets-related gene (Erg) as potential biomarker of GC resistance. The results revealed an alternative possible 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.

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

    Directory of Open Access Journals (Sweden)

    Daphne eChen


    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. Bicycle Wheel (United States)


    An aerodynamic bicycle wheel developed by two DuPont engineers and a California company incorporates research into NASA airfoils. Computer modeling was accomplished with MSC/NASTRAN. Each of the three spokes in the wheel is, in effect, an airfoil, maximizing aerodynamic efficiency for racing.

  19. Bicycle accidents. (United States)

    Lind, M G; Wollin, S


    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.

  20. HP1a/KDM4A is involved in the autoregulatory loop of the oncogene gene c-Jun. (United States)

    Liu, Yan; Zhang, Daoyong


    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.

  1. The MLK family mediates c-Jun N-terminal kinase activation in neuronal apoptosis. (United States)

    Xu, Z; Maroney, A C; Dobrzanski, P; Kukekov, N V; Greene, L A


    Neuronal apoptotic death induced by nerve growth factor (NGF) deprivation is reported to be in part mediated through a pathway that includes Rac1 and Cdc42, mitogen-activated protein kinase kinases 4 and 7 (MKK4 and -7), c-Jun N-terminal kinases (JNKs), and c-Jun. However, additional components of the pathway remain to be defined. We show here that members of the mixed-lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper kinase [DLK]) are expressed in neuronal cells and are likely to act between Rac1/Cdc42 and MKK4 and -7 in death signaling. Overexpression of MLKs effectively induces apoptotic death of cultured neuronal PC12 cells and sympathetic neurons, while expression of dominant-negative forms of MLKs suppresses death evoked by NGF deprivation or expression of activated forms of Rac1 and Cdc42. CEP-1347 (KT7515), which blocks neuronal death caused by NGF deprivation and a variety of additional apoptotic stimuli and which selectively inhibits the activities of MLKs, effectively protects neuronal PC12 cells from death induced by overexpression of MLK family members. In addition, NGF deprivation or UV irradiation leads to an increase in both level and phosphorylation of endogenous DLK. These observations support a role for MLKs in the neuronal death mechanism. With respect to ordering the death pathway, dominant-negative forms of MKK4 and -7 and c-Jun are protective against death induced by MLK overexpression, placing MLKs upstream of these kinases. Additional findings place the MLKs upstream of mitochondrial cytochrome c release and caspase activation.

  2. 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


    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.

  3. 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 Xiyun; WU Qiao; CAO Ya


    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.

  4. 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


    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.

  5. Expression of c-fos and c-jun protooncogenes in the uteri of immature mice neonatally exposed to diethylstilbestrol. (United States)

    Yamashita, S; Takayanagi, A; Shimizu, N


    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.

  6. A new role for the Kruppel-like transcription factor KLF6 as an inhibitor of c-Jun proto-oncoprotein function. (United States)

    Slavin, Daniela A; Koritschoner, Nicolás P; Prieto, Claudio C; López-Díaz, Fernando J; Chatton, Bruno; Bocco, José Luis


    Kruppel-like transcription factors (KLFs) represent one of the most diverse set of regulators in vertebrate organisms. KLF family members are involved in cell proliferation and differentiation control in normal as well as in pathological situations. Here, we demonstrate that KLF6 behaves as a functional antagonist of the c-Jun proto-oncoprotein. Thus, KLF6 overexpression downregulated c-Jun-dependent transcription and a physical interaction between c-Jun and KLF6 was detected. Moreover, cell proliferation induced by c-Jun was significantly decreased by KLF6. The inhibition of c-Jun functions correlates directly with c-Jun protein degradation induced by KLF6. We also show that all KLF6 effects on c-Jun were largely dependent on phorbol ester (TPA/ionomycin) extracellular stimulation, which enhanced KLF6 nuclear translocation and transcriptional activity and modified its phosphorylation status. Our data are consistent with a novel mechanism of KLF6's role as an inhibitor of cell proliferation by counteracting the function of the c-Jun proto-oncoprotein involving enhanced c-Jun degradation by the proteasome-dependent pathway, and further reinforces KLF6 as a potential tumor suppressor gene product.

  7. Role for c-jun N-terminal kinase in treatment-refractory acute myeloid leukemia (AML): signaling to multidrug-efflux and hyperproliferation. (United States)

    Cripe, L D; Gelfanov, V M; Smith, E A; Spigel, D R; Phillips, C A; Gabig, T G; Jung, S-H; Fyffe, J; Hartman, A D; Kneebone, P; Mercola, D; Burgess, G S; Boswell, H S


    A relationship was proved between constitutive activity of leukemic cell c-jun-N-terminal kinase (JNK) and treatment failure in AML. Specifically, early treatment failure was predicted by the presence of constitutive JNK activity. The mechanistic origins of this association was sought. A multidrug resistant leukemic cell line, HL-60/ADR, characterized by hyperexpression of c-jun and JNK activity, was transfected with a mutant c-jun vector, whose substrate N-terminal c-jun serines were mutated. Down-regulated expression occurred of c-jun/AP-1-dependent genes, catalase and glutathione-S-transferase (GST) pi, which participate in cellular homeostasis to oxidative stress and xenobiotic exposure. MRP-efflux was abrogated in HL-60/ADR cells with dominant-negative c-jun, perhaps because MRP1 protein expression was also lost. Heightened sensitivity to daunorubicin resulted in cells subjected to this change. Biochemical analysis in 67 primary adult AML samples established a statistical correlation between cellular expression of c-jun and JNK activity, JNK activity with hyperleukocytosis at presentation of disease, and with exuberant MRP efflux. These findings reflect the survival role for c-jun/AP-1 and its regulatory kinase previously demonstrated for yeast in homeostatic response to oxidative stress and in operation of ATP-binding cassette efflux pumps, and may support evolutionary conservation of such function. Thus, JNK and c-jun may be salient drug targets in multidrug resistant AML.

  8. Induction of c-Jun by air particulate matter (PM₁₀) of Mexico city: Participation of polycyclic aromatic hydrocarbons. (United States)

    Salcido-Neyoy, Martha Estela; Sánchez-Pérez, Yesennia; Osornio-Vargas, Alvaro Román; Gonsebatt, María Eugenia; Meléndez-Zajgla, Jorge; Morales-Bárcenas, Rocío; Petrosyan, Pavel; Molina-Servin, Edith Danny; Vega, Elizabeth; Manzano-León, Natalia; García-Cuellar, Claudia M


    The carcinogenic potential of urban particulate matter (PM) has been partly attributed to polycyclic aromatic hydrocarbons (PAHs) content, which activates the aryl hydrocarbon receptor (AhR). Here we report the effect of PM with an aerodynamic size of 10 μm (PM10) on the induction of AhR pathway in A549 cells, evaluating its downstream targets CYP1B1, IL-6, IL-8 and c-Jun. Significant increases in CYP1B1 protein and enzyme activity; IL-6 and IL-8 secretion and c-Jun protein were found in response to PM10. The formation of PAH-DNA adducts was also detected. The involvement of AhR pathway was confirmed with Resveratrol as AhR antagonist, which reversed CYP1B1 and c-Jun induction. Nevertheless, in IL-6 and IL-8 secretion, the Resveratrol was ineffective, suggesting an effect independent of this pathway. Considering the role of c-Jun in oncogenesis, its induction by PM may be contributing to its carcinogenic potential through induction of AhR pathway by PAHs present in PM10.

  9. The proapoptotic dp5 gene is a direct target of the MLK-JNK-c-Jun pathway in sympathetic neurons. (United States)

    Towers, Emily; Gilley, Jonathan; Randall, Rebecca; Hughes, Rosie; Kristiansen, Mark; Ham, Jonathan


    The death of sympathetic neurons after nerve growth factor (NGF) withdrawal requires de novo gene expression. Dp5 was one of the first NGF withdrawal-induced genes to be identified and it encodes a proapoptotic BH3-only member of the Bcl-2 family. To study how dp5 transcription is regulated by NGF withdrawal we cloned the regulatory regions of the rat dp5 gene and constructed a series of dp5-luciferase reporter plasmids. In microinjection experiments with sympathetic neurons we found that three regions of dp5 contribute to its induction after NGF withdrawal: the promoter, a conserved region in the single intron, and sequences in the 3' untranslated region of the dp5 mRNA. A construct containing all three regions is efficiently activated by NGF withdrawal and, like the endogenous dp5, its induction requires mixed-lineage kinase (MLK) and c-Jun N-terminal kinase (JNK) activity. JNKs phosphorylate the AP-1 transcription factor c-Jun, and thereby increase its activity. We identified a conserved ATF site in the dp5 promoter that binds c-Jun and ATF2, which is critical for dp5 promoter induction after NGF withdrawal. These results suggest that part of the mechanism by which the MLK-JNK-c-Jun pathway promotes neuronal apoptosis is by activating the transcription of the dp5 gene.

  10. 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)


    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.

  11. Palbociclib inhibits epithelial-mesenchymal transition and metastasis in breast cancer via c-Jun/COX-2 signaling pathway. (United States)

    Qin, Ge; Xu, Fei; Qin, Tao; Zheng, Qiufan; Shi, Dingbo; Xia, Wen; Tian, Yun; Tang, Yanlai; Wang, Jingshu; Xiao, Xiangshen; Deng, Wuguo; Wang, Shusen


    Palbociclib, a highly selective CDK4/6 inhibitor, has been shown to be a novel anti-tumor agent that suppresses breast cancer cell proliferation. However, its anti-metastasis activity remains controversial. In the present study, we evaluated whether palbociclib prevented breast cancer cell metastasis and revealed its regulatory mechanism. We found that palbociclib inhibited migration and invasion in the breast cancer cells MDA-MB-231 and T47D. The epithelial-mesenchymal transition (EMT) markers, vimentin and Snail, were down-regulated with palbociclib treatment. Moreover, we revealed that this inhibition was mediated by the c-Jun/COX-2 pathway. COX-2 was decreased after palbociclib treatment. The production of PGE2 was also reduced along with COX-2. Additionally, our data showed that c-Jun, a crucial transcriptional regulator of COX-2, was down-regulated by palbociclib. We found that palbociclib weakened the COX-2 promoter binding activity of c-Jun and prevented its translocation from the cytoplasm to cell nuclei. Bioluminescence imaging and tail intravenous injection were used to evaluate the anti-metastasis effect of palbociclib in vivo. The data demonstrated that palbociclib reduced breast cancer metastasis to the lung. These results therefore demonstrated that the anti-metastasis activity of palbociclib is mediated via the c-Jun/COX-2 signaling pathway by inhibiting EMT in breast cancer cells.

  12. MPTP-induced increase in c-Fos- and c-Jun-like immunoreactivity in the monkey cerebellum

    Directory of Open Access Journals (Sweden)

    D Necchi


    Full Text Available The transcription factors c-Fos and c-Jun have been described to be overexpressed following many pathological stimuli, but whether they are required for neurodegeneration or neuroprotection is still open. In the present report, we analyzed the role of c-Fos and c-Jun proteins in Purkinje cell degeneration caused by the neurotoxin MPTP (1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine in the monkey cerebellum, and determined the neuroprotective effect of the antioxidant drug a-dihydroergocryptine (DHEC, whose prior and simultaneous administration reduced the MPTP-induced neuronal loss in the substantia nigra. Immunocytochemistry for c-Fos- and c-Jun-like proteins showed persistent increased staining in Purkinje cells of MPTP-treated monkeys. The staining was greatly reduced in animals receiving DHEC. Similar results were observed in white matter glial cells after immunoreaction for c-Fos. The results suggest that, at least as far as the cerebellum is concerned, the increase in c-Fos and c-Jun expression correlate with cell damage, rather than with preservation.

  13. MPTP-induced increase in c-Fos- and c-Jun-like immunoreactivity in the monkey cerebellum. (United States)

    Necchi, Daniela; Soldani, C; Ronchetti, F; Bernocchi, G; Scherini, E


    The transcription factors c-Fos and c-Jun have been described to be overexpressed following many pathological stimuli, but whether they are required for neurodegeneration or neuroprotection is still open. In the present report, we analyzed the role of c-Fos and c-Jun proteins in Purkinje cell degeneration caused by the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in the monkey cerebellum, and determined the neuroprotective effect of the antioxidant drug a-dihydroergocryptine (DHEC), whose prior and simultaneous administration reduced the MPTP-induced neuronal loss in the substantia nigra. Immunocytochemistry for c-Fos- and c-Jun-like proteins showed persistent increased staining in Purkinje cells of MPTP-treated monkeys. The staining was greatly reduced in animals receiving DHEC. Similar results were observed in white matter glial cells after immunoreaction for c-Fos. The results suggest that, at least as far as the cerebellum is concerned, the increase in c-Fos and c-Jun expression correlate with cell damage, rather than with preservation.

  14. Dentin bonding agents induce c-fos and c-jun protooncogenes expression in human gingival fibroblasts. (United States)

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


    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.

  15. Mkp1 is a c-Jun target gene that antagonizes JNK-dependent apoptosis in sympathetic neurons. (United States)

    Kristiansen, Mark; Hughes, Rosie; Patel, Pritika; Jacques, Thomas S; Clark, Andrew R; Ham, Jonathan


    Developing sympathetic neurons depend on NGF for survival. When sympathetic neurons are deprived of NGF in vitro, a well documented series of events, including c-Jun N-terminal kinase (JNK) pathway activation, release of cytochrome c from the mitochondria, and caspase activation, culminates in the death of the neuron by apoptosis within 24-48 h. This process requires de novo gene expression, suggesting that increased expression of specific genes activates the cell death program. Using rat gene microarrays, we found that NGF withdrawal induces the expression of many genes, including mkp1, which encodes a MAPK phosphatase that can dephosphorylate JNKs. The increase in mkp1 mRNA level requires the MLK-JNK-c-Jun pathway, and we show that Mkp1 is an important regulator of JNK-dependent apoptosis in sympathetic neurons. In microinjection experiments, Mkp1 overexpression can inhibit JNK-mediated phosphorylation of c-Jun and protect sympathetic neurons from apoptosis, while Mkp1 knockdown accelerates NGF withdrawal-induced death. Accordingly, the number of superior cervical ganglion (SCG) neurons is reduced in mkp1-/- mice at P1 during the period of developmental sympathetic neuron death. We also show that c-Jun and ATF2 bind to two conserved ATF binding sites in the mkp1 promoter in vitro and in chromatin. Both of these ATF sites contribute to basal promoter activity and are required for mkp1 promoter induction after NGF withdrawal. These results demonstrate that Mkp1 is part of a negative feedback loop induced by the MLK-JNK-c-Jun signaling pathway that modulates JNK activity and the rate of neuronal death in rat sympathetic neurons following NGF withdrawal.

  16. The ornithine decarboxylase, NO-synthase activities and phospho-c-Jun content under experimental gastric mucosa malignancy

    Directory of Open Access Journals (Sweden)

    Mariia Tymoshenko


    Full Text Available Ornithine decarboxylase is the first and key regulatory enzyme in synthesis of polyamines, which are essential for cell proliferation and differentiation, so its aberrant regulation is reported to play a role in neoplastic transformation and tumours growth. That's why, there were analysed some major links of metabolic pathways that are closely related to tumorigenesis: ornithine decarboxylase, and the NADPH-dependent enzyme nitric oxide synthase, the nuclear phosphoprotein c-Jun, that could play an important role in the development of gastric cancer malignancy.The gastric carcinogenesis was initiated in rats by 10-week replacement of drinking water by 0.01% N-methyl-N-nitro-N-nitrosoguanidine solution, at the same time they were redefined on the diet containing 5% NaCl. After this period expiry the animals were fed with standard diet till the end of the 24th week. The gastric mucosa cells were extracted at the end of the 4th, 6th, 8th, 10th, 12th, 18th and 24th week and underwent biochemical examinations. It was established the elevated phospho-c-Jun content, ornithine decarboxylase and inducible nitric oxide synthase activities from 6th to 24th week of gastric cancer development compared to the control references. The increasing of ornithine decarboxylase activity could probably be caused by the growth of phospho-c-Jun, it is also belonging to an ornithine decarboxylase transactivation effects. Thus, it was shown that the increase of ornithine decarboxylase and inducible nitric oxide synthase activities, phospho-c-Jun and nitrite-ions accumulation in gastric mucosa epithelial cells were associated with the gastric malignant progression. The complex relationships between the examined enzymes and transcription activator that pointed to an aggravation of pathological disturbances due to reciprocal action between ornithine decarboxylase and c-Jun and nitric oxide synthase participation. [Biomed Res Ther 2016; 3(4.000: 596-604

  17. From reptilian phylogenomics to reptilian genomes: analyses of c-Jun and DJ-1 proto-oncogenes. (United States)

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


    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.

  18. Cadmium promotes breast cancer cell proliferation by potentiating the interaction between ERalpha and c-Jun. (United States)

    Siewit, Christina L; Gengler, Bridget; Vegas, Esera; Puckett, Rachel; Louie, Maggie C


    Cadmium is an environmental contaminant that enters the body through diet or cigarette smoke. It affects multiple cellular processes, including cell proliferation, differentiation, and apoptosis. Recently, cadmium has been shown to function as an endocrine disruptor, to stimulate estrogen receptor alpha (ERalpha) activity and promote uterine and mammary gland growth in mice. Although cadmium exposure has been associated with the development of breast cancer, the mechanism of action of cadmium remains unclear. To address this deficit, we examined the effects of cadmium treatment on breast cancer cells. We found that ERalpha is required for both cadmium-induced cell growth and modulation of gene expression. We also determined that ERalpha translocates to the nucleus in response to cadmium exposure. Additionally, we provide evidence that cadmium potentiates the interaction between ERalpha and c-Jun and enhances recruitment of this transcription factor complex to the proximal promoters of cyclin D1 and c-myc, thus increasing their expression. This study provides a mechanistic link between cadmium exposure and ERalpha and demonstrates that cadmium plays an important role in the promotion of breast cancer.

  19. Lost Kingdom of Bicycles?

    Institute of Scientific and Technical Information of China (English)


    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

  20. Combined Expression of c-jun, c-fos, and p53 Improves Estimation of Prognosis in Oral Squamous Cell Carcinoma. (United States)

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


    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.

  1. 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


    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.

  2. Temporal and spatial expression of c-jun and jun-B proto-oncogenes in pulp cells involved with reparative dentinogenesis after cavity preparation of rat molars. (United States)

    Kitamura, C; Kimura, K; Nakayama, T; Terashita, M


    c-jun and jun-B are nuclear proto-oncogenes induced by growth factors such as bone morphogenetic proteins (BMPs). These gene products enhance the expression of many genes, including osteocalcin and collagen types, indicating that c-jun and jun-B play important roles in the cell differentiation process. It is also known that BMPs affect the differentiation of pulp cells to odontoblast-like cells during reparative dentinogenesis, but little is known about the transcriptional regulation of genes in cells associated with reparative dentinogenesis. In this study, we examined the expression of c-jun and jun-B in pulp cells during reparative dentinogenesis after cavity preparation of rat molars by in situ hybridization. In rat tooth germs, c-jun and jun-B were co-expressed in the odontoblastic lineage. In rat adult molars, c-jun was expressed in the odontoblast layer, but the jun-B expression was absent in all pulp cells. After cavity preparation, we found that c-jun and jun-B were coexpressed in pulp cells underneath cavities. During the early phase of reparative dentinogenesis, levels of c-jun and jun-B greatly increased in pulp cells within and around the reparative dentin matrix formed adjacent to the cavity floor. Fourteen days after cavity preparation, c-jun and jun-B were expressed only in pulp cells lining the irregular surface of the thick reparative dentin. These results suggest that c-jun and jun-B may play important roles both in physiological and in reparative dentinogenesis; in particular, the limited distribution of the jun-B expression suggests a specific role of jun-B only in cells involved with the active formation of the dentin matrix during primary and reparative dentinogenesis.

  3. 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


    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......RNA levels. These results suggest that the effects of GH on insulin producing cells are not mediated by activation of c-fos and c-jun transcription....

  4. The regulation of p53 up-regulated modulator of apoptosis by JNK/c-Jun pathway in β-amyloid-induced neuron death. (United States)

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


    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

  5. Bicycle Braking System


    Brady, Noel


    A bicycle braking system for permitting controlled rotation and continuous power to the wheels of a bicycle during braking of the bicycle to enhance control of the bicycle during braking includes a cylindrical brake pad that is spring loaded within angled slots in a casing. The brake pad is positioned proximate the rim of a wheel and a cable assembly is coupled to the brake pad for urging the brake pad towards an end of the angled slots and against the rim of the wheel to slow rotation of the...

  6. Resveratrol increases anti-aging Klotho gene expression via the activating transcription factor 3/c-Jun complex-mediated signaling pathway. (United States)

    Hsu, Shih-Che; Huang, Shih-Ming; Chen, Ann; Sun, Chiao-Yin; Lin, Shih-Hua; Chen, Jin-Shuen; Liu, Shu-Ting; Hsu, Yu-Juei


    The Klotho gene functions as an aging suppressor gene. Evidence from animal models suggests that induction of Klotho expression may be a potential treatment for age-associated diseases. However, the molecular mechanism involved in regulating renal Klotho gene expression remains unclear. In this study, we determined that resveratrol, a natural polyphenol, induced renal Klotho expression both in vivo and in vitro. In the mouse kidney, resveratrol administration markedly increased both Klotho mRNA and protein expression. In resveratrol-treated NRK-52E cells, increased Klotho expression was accompanied by the upregulation and nuclear translocation of activating transcription factor 3 (ATF3) and c-Jun. ATF3 or c-Jun overexpression enhanced the transcriptional activation of Klotho. Conversely, resveratrol-induced Klotho expression was attenuated in the presence of dominant-negative ATF3 or c-Jun. Coimmunoprecipitation and a chromatin immunoprecipitation assay revealed that ATF3 physically interacted with c-Jun and that the ATF3/c-Jun complex directly bound to the Klotho promoter through ATF3- and AP-1-binding elements. c-Jun cotransfection augmented the effects of ATF3 on Klotho transcription in vitro. Although Sirtuin 1 mRNA expression was induced by resveratrol and involved in regulating Klotho mRNA expression, it was not the primary cause for the aforementioned ATF3/c-Jun pathway. In summary, resveratrol enhances the renal expression of the anti-aging Klotho gene, and the transcriptional factors ATF3 and c-Jun functionally interact and coordinately regulate the resveratrol-mediated transcriptional activation of Klotho.

  7. 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


    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.

  8. 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


    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.

  9. The sequence-specific transcription factor c-Jun targets Cockayne syndrome protein B to regulate transcription and chromatin structure.

    Directory of Open Access Journals (Sweden)

    Robert J Lake


    Full Text Available Cockayne syndrome is an inherited premature aging disease associated with numerous developmental and neurological defects, and mutations in the gene encoding the CSB protein account for the majority of Cockayne syndrome cases. Accumulating evidence suggests that CSB functions in transcription regulation, in addition to its roles in DNA repair, and those defects in this transcriptional activity might contribute to the clinical features of Cockayne syndrome. Transcription profiling studies have so far uncovered CSB-dependent effects on gene expression; however, the direct targets of CSB's transcriptional activity remain largely unknown. In this paper, we report the first comprehensive analysis of CSB genomic occupancy during replicative cell growth. We found that CSB occupancy sites display a high correlation to regions with epigenetic features of promoters and enhancers. Furthermore, we found that CSB occupancy is enriched at sites containing the TPA-response element. Consistent with this binding site preference, we show that CSB and the transcription factor c-Jun can be found in the same protein-DNA complex, suggesting that c-Jun can target CSB to specific genomic regions. In support of this notion, we observed decreased CSB occupancy of TPA-response elements when c-Jun levels were diminished. By modulating CSB abundance, we found that CSB can influence the expression of nearby genes and impact nucleosome positioning in the vicinity of its binding site. These results indicate that CSB can be targeted to specific genomic loci by sequence-specific transcription factors to regulate transcription and local chromatin structure. Additionally, comparison of CSB occupancy sites with the MSigDB Pathways database suggests that CSB might function in peroxisome proliferation, EGF receptor transactivation, G protein signaling and NF-κB activation, shedding new light on the possible causes and mechanisms of Cockayne syndrome.

  10. Alternative Polyadenylation in Triple-Negative Breast Tumors Allows NRAS and c-JUN to Bypass PUMILIO Posttranscriptional Regulation. (United States)

    Miles, Wayne O; Lembo, Antonio; Volorio, Angela; Brachtel, Elena; Tian, Bin; Sgroi, Dennis; Provero, Paolo; Dyson, Nicholas


    Alternative polyadenylation (APA) is a process that changes the posttranscriptional regulation and translation potential of mRNAs via addition or deletion of 3' untranslated region (3' UTR) sequences. To identify posttranscriptional-regulatory events affected by APA in breast tumors, tumor datasets were analyzed for recurrent APA events. Motif mapping of the changed 3' UTR regions found that APA-mediated removal of Pumilio regulatory elements (PRE) was unusually common. Breast tumor subtype-specific APA profiling identified triple-negative breast tumors as having the highest levels of APA. To determine the frequency of these events, an independent cohort of triple-negative breast tumors and normal breast tissue was analyzed for APA. APA-mediated shortening of NRAS and c-JUN was seen frequently, and this correlated with changes in the expression of downstream targets. mRNA stability and luciferase assays demonstrated APA-dependent alterations in RNA and protein levels of affected candidate genes. Examination of clinical parameters of these tumors found those with APA of NRAS and c-JUN to be smaller and less proliferative, but more invasive than non-APA tumors. RT-PCR profiling identified elevated levels of polyadenylation factor CSTF3 in tumors with APA. Overexpression of CSTF3 was common in triple-negative breast cancer cell lines, and elevated CSTF3 levels were sufficient to induce APA of NRAS and c-JUN. Our results support the hypothesis that PRE-containing mRNAs are disproportionately affected by APA, primarily due to high sequence similarity in the motifs utilized by polyadenylation machinery and the PUM complex. Cancer Res; 76(24); 7231-41. ©2016 AACR.

  11. 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.

  12. Bicycles made to measure

    NARCIS (Netherlands)

    Van Dijk, T.


    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

  13. Bicycle Promotion Plan

    Energy Technology Data Exchange (ETDEWEB)

    Simone, G. A.


    The objective of this Bicycle Promotion Plan is to outline a set of recommendations and supporting strategies for implementation by the US DOE toward increased use of the bicycle for energy conservation. The recommendations are designed in such a way as to function in concert with: (1) bicycle programs administered by other Federal government agencies; and (2) related programs and activities already sponsored by DOE. The approach to preparation of the Plan involved a review of all current and planned bicycle promotion programs at the Federal level as well as a review of the array of lierature on the subject. The UniWorld project staff also interacted with several DOE program offices, in order to determine the extent to which they might appropriately contribute to the implementation of bicycle promotional efforts. A synthesis of all the information gathered was published in January of 1981 as a part of the project (The Bicycle Program Review). Based upon this information and an examination of the barriers to bicycle use identified by bicycle transportation specialists in the field, UniWorld developed a series of the most potentially effective recommendations and program strategies for implementation by DOE. The recommendations address activities that could be undertaken in conjunction with existing DOE programs, new developments that might be considered to fulfill critical needs in the field, and interagency efforts that DOE could play a role in.

  14. Activation of c-Jun-N-terminal kinase and decline of mitochondrial pyruvate dehydrogenase activity during brain aging. (United States)

    Zhou, Qiongqiong; Lam, Philip Y; Han, Derick; Cadenas, Enrique


    Mitochondrial dysfunction is often associated with aging and neurodegeneration. c-Jun-N-terminal kinase (JNK) phosphorylation and its translocation to mitochondria increased as a function of age in rat brain. This was associated with a decrease of pyruvate dehydrogenase (PDH) activity upon phosphorylation of the E(1alpha) subunit of PDH. Phosphorylation of PDH is likely mediated by PDH kinase, the protein levels and activity of which increased with age. ATP levels were diminished, whereas lactic acid levels increased, thus indicating a shift toward anaerobic glycolysis. The energy transduction deficit due to impairment of PDH activity during aging may be associated with JNK signaling.

  15. Heme oxygenase-1 suppresses the apoptosis of acute myeloid leukemia cells via the JNK/c-JUN signaling pathway. (United States)

    Lin, Xiaojing; Fang, Qin; Chen, Shuya; Zhe, Nana; Chai, Qixiang; Yu, Meisheng; Zhang, Yaming; Wang, Ziming; Wang, Jishi


    There are few studies on the correlation between heme oxygenase-1 (HO-1) and acute myeloid leukemia (AML). We found that HO-1 was aberrantly overexpressed in the majority of AML patients, especially in patients with acute monocytic leukemia (M5) and leukocytosis, and inhibited the apoptosis of HL-60 and U937 cells. Moreover, silencing HO-1 prolonged the survival of xenograft mouse models. Further studies demonstrated that HO-1 suppressed the apoptosis of AML cells through activating the JNK/c-JUN signaling pathway. These data indicate a molecular role of HO-1 in inhibiting cell apoptosis, allowing it to be a potential target for treating AML.

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


    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.

  17. 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:


    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.

  18. Role of TGF-β-induced Claudin-4 expression through c-Jun signaling in non-small cell lung cancer. (United States)

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


    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.

  19. 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.

  20. Voxel-based analysis of the immediate early gene, c-jun, in the honey bee brain after a sucrose stimulus. (United States)

    McNeill, M S; Robinson, G E


    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.

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


    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.

  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:


    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. Quantifying bicycle network connectivity. (United States)

    Lowry, Michael; Loh, Tracy Hadden


    The intent of this study was to compare bicycle network connectivity for different types of bicyclists and different neighborhoods. Connectivity was defined as the ability to reach important destinations, such as grocery stores, banks, and elementary schools, via pathways or roads with low vehicle volumes and low speed limits. The analysis was conducted for 28 neighborhoods in Seattle, Washington under existing conditions and for a proposed bicycle master plan, which when complete will provide over 700 new bicycle facilities, including protected bike lanes, neighborhood greenways, and multi-use trails. The results showed different levels of connectivity across neighborhoods and for different types of bicyclists. Certain projects were shown to improve connectivity differently for confident and non-confident bicyclists. The analysis showed a positive correlation between connectivity and observed utilitarian bicycle trips. To improve connectivity for the majority of bicyclists, planners and policy-makers should provide bicycle facilities that allow immediate, low-stress access to the street network, such as neighborhood greenways. The analysis also suggests that policies and programs that build confidence for bicycling could greatly increase connectivity.

  4. MEKKs, GCKs, MLKs, PAKs, TAKs, and tpls: upstream regulators of the c-Jun amino-terminal kinases? (United States)

    Fanger, G R; Gerwins, P; Widmann, C; Jarpe, M B; Johnson, G L


    Regulation of the mitogen-activated protein kinase (MAPK) family members - which include the extracellular response kinases (ERKs), p38/HOG1, and the c-Jun amino-terminal kinases (JNKs) - plays a central role in mediating the effects of diverse stimuli encompassing cytokines, hormones, growth factors and stresses such as osmotic imbalance, heat shock, inhibition of protein synthesis and irradiation. A rapidly increasing number of kinases that activate the JNK pathways has been described recently, including the MAPK/ERK kinase kinases, p21-activated kinases, germinal center kinase, mixed lineage kinases, tumor progression locus 2, and TGF-beta-activated kinase. Thus, regulation of the JNK pathway provides an interesting example of how many different stimuli can converge into regulating pathways critical for the determination of cell fate.

  5. 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


    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.

  6. Identification of a c-Jun homolog from Litopenaeus vannamei as a downstream substrate of JNK in response to WSSV infection. (United States)

    Yao, Defu; Ruan, Lingwei; Xu, Xun; Shi, Hong


    c-Jun, a major substrate of c-Jun N-terminal kinase (JNK), participates in regulating gene transcription in response to various stimuli, including cytokines, stress signals, bacterial and viral infection. Results from our previous studies suggested that Litopenaeus vannamei JNK (LvJNK) could be utilized by white spot syndrome virus (WSSV) to facilitate viral replication and gene expression. In this article, a c-Jun homolog from Litopenaeus vannamei (designated as Lvc-Jun) was cloned and its role in WSSV infection was studied. Sequence analysis displayed that Lvc-Jun was a novel homolog of c-Jun family, which contained characteristic Jun and basic leucine zipper (bZIP) domains, and two conserved serine phosphorylation sites (Ser49/59). Semi-quantitative RT-PCR analysis showed that Lvc-Jun mRNAs were expressed in all examined tissues. Further investigation determined that Lvc-Jun was located in the nucleus through self-interaction and its phosphorylation levels could be reduced by JNK inhibitor, suggesting that Lvc-Jun could be regulated by LvJNK through phosphorylation and function as a transcription regulator in a homodimer. During the process of WSSV infection, the transcription levels of Lvc-Jun were up-regulated associating with the raising expression and phosphorylation levels of its protein. Moreover, TPA (12-O-tetradecanoylphorbol-13-acetate), a potent inducer of c-Jun, could remarkably promote viral immediate-early gene wsv069 transcription in crayfish hemocytes. Conclusively, our results provided experimental evidences that Lvc-Jun was engaged in WSSV infection and further implied that JNK-c-Jun signaling pathway might be important for WSSV replication and viral gene expression.

  7. NPM-ALK oncogenic kinase promotes cell-cycle progression through activation of JNK/cJun signaling in anaplastic large-cell lymphoma. (United States)

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


    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.

  8. Stimulation of T cells up-regulates expression of Ifi202, an interferon-inducible lupus susceptibility gene, through activation of JNK/c-Jun pathway (United States)

    Chen, Jianming; Panchanathan, Ravichandran; Choubey, Divaker


    Studies have revealed that increased expression of interferon (IFN)-inducible Ifi202 gene (encoding p202 protein) in splenic B and T cells from B6.Nba2 congenic (congenic for Nb2 locus derived from NZB mice) female mice is associated with lupus susceptibility. However, signaling pathways that regulate Ifi202 expression in immune cells remain to be elucidated. Here we report that stimulation of T cells up-regulates the Ifi202 expression. We found that steady-state levels of Ifi202 mRNA and protein were detectable in splenic T cells from NZB mice and stimulation of T cells with anti-CD3 and anti-CD28 up-regulated expression of the Ifi202 gene. Similarly, stimulation of cells of a mouse T-cell hybridoma cell line (2B4.11) also activated transcription of the Ifi202 gene. Significantly, up-regulation of Ifi202 expression in stimulated T cells was inhibited by treatment of cells with SP600125, a specific inhibitor of c-Jun N-terminal kinase (JNK). Conversely, treatment of cells with anisomycin, a potent activator of the JNK and c-Jun, up-regulated Ifi202 expression. Consistent with the activation of JNK/c-Jun pathway by T cell stimulation, forced expression of c-Jun in 2B4 T-cells and in mouse embryonic fibroblasts (MEFs) also up-regulated the Ifi202 expression. Furthermore, we found that stimulation of T cells increased association of the activated c-Jun to the 5′-regulatory region of the Ifi202 gene in chromatin immunoprecipitation assays (ChIPs). Together, our observations demonstrate that stimulation of T cells up-regulates the Ifi202 expression in part through the JNK/c-Jun pathway. PMID:18374989

  9. 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: [Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067 (India)


    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.

  10. Induction of c-fos and c-jun protooncogenes expression by formaldehyde-releasing and epoxy resin-based root-canal sealers in human osteoblastic cells. (United States)

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


    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.

  11. Krüppel-like factor (KLF) 5 mediates cyclin D1 expression and cell proliferation via interaction with c-Jun in Ang II-induced VSMCs


    Liu, Yu; Wen, Jin-kun; Dong, Li-Hua; Zheng, Bin; Han, Mei


    Aim: To elucidate how krüppel-like factor (KLF5) activates cyclin D1 expression in Ang II-induced vascular smooth muscle cells (VSMC) proliferation. Methods: An adenoviral vector containing the full-length cDNA of KLF5 and a recombinant plasmid expressing c-Jun were constructed. MTT assay and flow cytometric analysis were used to determine the effect of Ang II on cell growth. The luciferase assay and chromatin immunoprecipitation were used to detect the relationship between KLF5 and c-Jun in ...

  12. On a Bicycle in Beijing

    Institute of Scientific and Technical Information of China (English)



    @@ Other expats here in Beijing have all bought bicycles.One friend who was excited about his new bicycle told me he spent about 2,100 yuan($300).Another mentioned he had spent what would be equivalent to $500.

  13. Oxidant exposure induces cysteine-rich protein 61 (CCN1 via c-Jun/AP-1 to reduce collagen expression in human dermal fibroblasts.

    Directory of Open Access Journals (Sweden)

    Zhaoping Qin

    Full Text Available Human skin is a primary target of oxidative stress from reactive oxygen species (ROS generated from both extrinsic and intrinsic sources. Oxidative stress inhibits the production of collagen, the most abundant protein in skin, and thus contributes to connective tissue aging. Here we report that cysteine-rich protein 61 (CCN1, a negative regulator of collagen production, is markedly induced by ROS and mediates loss of type I collagen in human dermal fibroblasts. Conversely, antioxidant N-acetyl-L-cysteine significantly reduced CCN1 expression and prevented ROS-induced loss of type I collagen in both human dermal fibroblasts and human skin in vivo. ROS increased c-Jun, a critical member of transcription factor AP-1 complex, and increased c-Jun binding to the AP-1 site of the CCN1 promoter. Functional blocking of c-Jun significantly reduced CCN1 promoter and gene expression and thus prevented ROS-induced loss of type I collagen. Targeting the c-Jun/CCN1 axis may provide clinical benefit for connective tissue aging in human skin.

  14. 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. (United States)

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


    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.

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

  16. Up-regulation of c-Jun inhibits proliferation and induces apoptosis via caspase-triggered c-Abl cleavage in human multiple myeloma. (United States)

    Podar, Klaus; Raab, Marc S; Tonon, Giovanni; Sattler, Martin; Barilà, Daniela; Zhang, Jing; Tai, Yu-Tzu; Yasui, Hiroshi; Raje, Noopur; DePinho, Ronald A; Hideshima, Teru; Chauhan, Dharminder; Anderson, Kenneth C


    Here we show the antimyeloma cytotoxicity of adaphostin and carried out expression profiling of adaphostin-treated multiple myeloma (MM) cells to identify its molecular targets. Surprisingly, c-Jun was the most up-regulated gene even at the earliest point of analysis (2 h). We also observed adaphostin-induced c-Abl cleavage in immunoblot analysis. Proteasome inhibitor bortezomib, but not melphalan or dexamethasone, induced similar effects, indicating unique agent-dependent mechanisms. Using caspase inhibitors, as well as caspase-resistant mutants of c-Abl (TM-c-Abl and D565A-Abl), we then showed that c-Abl cleavage in MM cells requires caspase activity. Importantly, both overexpression of the c-Abl fragment or c-Jun and knockdown of c-Abl and c-Jun expression by small interfering RNA confirmed that adaphostin-induced c-Jun up-regulation triggers downstream caspase-mediated c-Abl cleavage, inhibition of MM cell growth, and induction of apoptosis. Finally, our data suggest that this mechanism may not only be restricted to MM but may also be important in a broad range of malignancies including erythroleukemia and solid tumors.

  17. 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


    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.

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

    Li, Chengyuan; Ma, Jiacheng; Zhao, Huiping; Blagg, Brian S J; Dobrowsky, Rick T


    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-yl)acetamide] 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.

  19. Immediate expression of c-fos and c-jun mRNA in a model of intestinal autotransplantation and ischemia-reperfusion in situ (United States)

    Santos, Maria Mercês; Tannuri, Ana Cristina Aoun; Coelho, Maria Cecilia Mendonça; de Oliveira Gonçalves, Josiane; Serafini, Suellen; da Silva, Luiz Fernando Ferraz; Tannuri, Uenis


    OBJECTIVE: Intestinal ischemia-reperfusion injury occurs in several clinical conditions and after intestinal transplantation. The aim of the present study was to investigate the phenomena of apoptosis and cell proliferation in a previously described intestinal ischemia-reperfusion injury autograft model using immunohistochemical markers. The molecular mechanisms involved in ischemia-reperfusion injury repair were also investigated by measuring the expression of the early activation genes c-fos and c-jun, which induce apoptosis and cell proliferation. MATERIALS AND METHODS: Thirty adult male Wistar rats were subjected to surgery for a previously described ischemia-reperfusion model that preserved the small intestine, the cecum and the ascending colon. Following reperfusion, the cecum was harvested at different time points as a representative segment of the intestine. The rats were allocated to the following four subgroups according to the reperfusion time: subgroup 1: 5 min; subgroup 2: 15 min; subgroup 3: 30 min; and subgroup 4: 60 min. A control group of cecum samples was also collected. The expression of c-fos, c-jun and immunohistochemical markers of cell proliferation and apoptosis (Ki67 and TUNEL, respectively) was studied. RESULTS: The expression of both c-fos and c-jun in the cecum was increased beginning at 5 min after ischemia-reperfusion compared with the control. The expression of c-fos began to increase at 5 min, peaked at 30 min, and exhibited a declining tendency at 60 min after reperfusion. A progressive increase in c-jun expression was observed. Immunohistochemical analyses confirmed these observations. CONCLUSION: The early activation of the c-fos and c-jun genes occurred after intestinal ischemia-reperfusion injury, and these genes can act together to trigger cell proliferation and apoptosis. PMID:26039956

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

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


    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.

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

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


    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.

  2. Bicycles and Valentines

    Institute of Scientific and Technical Information of China (English)


    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.

  3. Bicycle Trailers Increase Mobility (United States)

    Exceptional Parent, 2006


    This article describes the experiences of an exceptional parent who always takes his daughter for rides in a CycleTote special needs bicycle trailer. Dennis Foster, an exceptional parent from Commerce, Oklahoma, found that taking his twenty-eight-year-old daughter Hasha for rides has made her happy. Hasha has been diagnosed with cerebral palsy.

  4. 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


    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.

  5. Role of the Caenorhabditis elegans Shc adaptor protein in the c-Jun N-terminal kinase signaling pathway. (United States)

    Mizuno, Tomoaki; Fujiki, Kota; Sasakawa, Aya; Hisamoto, Naoki; Matsumoto, Kunihiro


    Mitogen-activated protein kinases (MAPKs) are integral to the mechanisms by which cells respond to physiological stimuli and a wide variety of environmental stresses. In Caenorhabditis elegans, the stress response is controlled by a c-Jun N-terminal kinase (JNK)-like mitogen-activated protein kinase (MAPK) signaling pathway, which is regulated by MLK-1 MAPK kinase kinase (MAPKKK), MEK-1 MAPK kinase (MAPKK), and KGB-1 JNK-like MAPK. In this study, we identify the shc-1 gene, which encodes a C. elegans homolog of Shc, as a factor that specifically interacts with MEK-1. The shc-1 loss-of-function mutation is defective in activation of KGB-1, resulting in hypersensitivity to heavy metals. A specific tyrosine residue in the NPXY motif of MLK-1 creates a docking site for SHC-1 with the phosphotyrosine binding (PTB) domain. Introduction of a mutation that perturbs binding to the PTB domain or the NPXY motif abolishes the function of SHC-1 or MLK-1, respectively, thereby abolishing the resistance to heavy metal stress. These results suggest that SHC-1 acts as a scaffold to link MAPKKK to MAPKK activation in the KGB-1 MAPK signal transduction pathway.

  6. 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


    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.

  7. 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


    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.

  8. Differences in c-Jun N-terminal kinase recognition and phosphorylation of closely related stathmin-family members. (United States)

    Yip, Yan Y; Yeap, Yvonne Y C; Bogoyevitch, Marie A; Ng, Dominic C H


    The stathmin (STMN) family of tubulin-binding phosphoproteins are critical regulators of interphase microtubule dynamics and organization in a broad range of cellular processes. c-Jun N-terminal kinase (JNK) signalling to STMN family proteins has been implicated specifically in neuronal maturation, degeneration and cell stress responses more broadly. Previously, we characterized mechanisms underlying JNK phosphorylation of STMN at proline-flanked serine residues (Ser25 and Ser38) that are conserved across STMN-like proteins. In this study, we demonstrated using in vitro kinase assays and alanine replacement of serine residues that JNK phosphorylated the STMN-like domain (SLD) of SCG10 on Ser73, consistent with our previous finding that STMN Ser38 was the primary JNK target site. In addition, we confirmed that a JNK binding motif ((41)KKKDLSL(47)) that facilitates JNK targeting of STMN is conserved in SCG10. In contrast, SCLIP was phosphorylated by JNK primarily on Ser60 which corresponds to Ser25 on STMN. Moreover, although the JNK-binding motif identified in STMN and SCG10 was not conserved in SCLIP, JNK phosphorylation of SCLIP was inhibited by a substrate competitive peptide (TI-JIP) highlighting kinase-substrate interaction as required for JNK targeting. Thus, STMN and SCG10 are similarly targeted by JNK but there are clear differences in JNK recognition and phosphorylation of the closely related family member, SCLIP.

  9. Metformin prevents endoplasmic reticulum stress-induced apoptosis through AMPK-PI3K-c-Jun NH2 pathway (United States)

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


    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.

  10. c-Jun N-terminal kinase (JNK signaling as a therapeutic target for Alzheimer´s disease

    Directory of Open Access Journals (Sweden)

    Ramón eYarza


    Full Text Available 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 A peptides. Altogether, JNKs have become a focus of screening strategies searching for new therapeutic approaches to diabetes, cancer or liver diseases. In addition, activation of JNK has been identified as a key element responsible for the regulation of apoptotic apoptosis signals and therefore, it is critical for pathological occurring cell death associated with neurodegenerative diseases and, among them, with Alzheimer's disease (AD. In addition, in vitro and in vivo studies have reported alterations of JNK pathways potentially associated with pathogenesis and neuronal death in AD. JNK’s, particularly JNK3, not only enhance Aβ production, moreover it plays a key role in the maturation and development of neurofibrillary tangles.This review aims to explain the rationale behind testing therapies based on inhibition of JNK signalling for AD in terms of current knowledge about the pathophysiology of the disease. Keeping in mind that JNK3 is specifically expressed in the brain and activated by stress-stimuli, it is possible to hypothesize that inhibition of JNK3 might be considered as a potential target for treating neurodegenerative mechanisms associated with AD.

  11. Novel role of c-jun N-terminal kinase in regulating the initiation of cap-dependent translation. (United States)

    Patel, Manish R; Sadiq, Ahad A; Jay-Dixon, Joe; Jirakulaporn, Tanawat; Jacobson, Blake A; Farassati, Faris; Bitterman, Peter B; Kratzke, Robert A


    Initiation of protein translation by the 5' mRNA cap is a tightly regulated step in cell growth and proliferation. Aberrant activation of cap-dependent translation is a hallmark of many cancers including non-small cell lung cancer. The canonical signaling mechanisms leading to translation initiation include activation of the Akt/mTOR pathway in response to the presence of nutrients and growth factors. We have previously observed that inhibition of c-jun N-terminal kinase (JNK) leads to inactivation of cap-dependent translation in mesothelioma cells. Since JNK is involved in the genesis of non-small cell lung cancer (NSCLC), we hypothesized that JNK could also be involved in activating cap-dependent translation in NSCLC cells and could represent an alternative pathway regulating translation. In a series of NSCLC cell lines, inhibition of JNK using SP600125 resulted in inhibition of 4E-BP1 phosphorylation and a decrease in formation of the cap-dependent translation complex, eIF4F. Furthermore, we show that JNK-mediated inhibition of translation is independent of mTOR. Our data provide evidence that JNK is involved in the regulation of translation and has potential as a therapeutic target in NSCLC.

  12. Expression and regulation of c-Jun N-terminal kinase (JNK) in endometrial cells in vivo and in vitro. (United States)

    Kizilay, Gulnur; Cakmak, Hakan; Yen, Chih-Feng; Atabekoglu, Cem; Arici, Aydin; Kayisli, Umit Ali


    JNK(c-Jun N-terminal kinase) is one of the main types of mitogen-activated protein kinases. JNK modulates inflammation and apoptosis in response to stress. Our hypothesis is that temporal and spatial changes in JNK activity regulate inflammation in human endometrium and that fluctuation in estrogen and progesterone levels may play a role in JNK activation. Therefore, we aimed to determine total-(t-) and active-(phosphorylated, p-) JNK expression in endometrial tissues in vivo by immunohistochemistry, and in vitro by immunocytochemistry and Western blot analysis. Immunohistochemistry revealed moderate cytoplasmic and nuclear t-JNK immunoreactivity, and mostly nuclear p-JNK immunoreactivity throughout the menstrual cycle and early pregnancy. The highest p- and t-JNK immunoreactivity was detected in late secretory phase (P estrogen combined with progesterone (E(2) + P(4)) withdrawal from the culture conditions, compared to control and non-withdrawal groups (P < 0.05). Upon treatment with JNK inhibitor SP600125, we observed a significantly decreased interleukin (IL)-8 level (P < 0.05) in the presence and absence of E(2). These results demonstrate that JNK expression increases during the late secretory phase when the inflammatory response is highest. Inhibition of IL-8 expression by SP600125 suggests that JNK is involved in regulation of proinflammatory mediators of endometrium.

  13. The safety of electrically assisted bicycles compared to classic bicycles. (United States)

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


    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.

  14. 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


    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.

  15. Butchers and Bicycles

    DEFF Research Database (Denmark)

    Kahle, Lynn; Eriksen, Steen Mandsfelt


    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- educated individuals who were very interested in aesthetics. Furthermore, Wagener was convinced that trikes were...... between order and delivery. From a marketing perspective, one of the differentiating factors of Morten’s product is the quality of the ride (compared to competing products) and so his marketing team coined the slogan “Built-to-Tilt” because even though it’s a trike it feels like riding a two...

  16. Land of Bicycles

    Institute of Scientific and Technical Information of China (English)

    ZhangHua; LuRucai


    There are currently more than 500 million cyclists in China,10million of them in Bejing.Despite efficient bus networks,legions of taxis and surging private car ownership,the bicycle remains a firm fixture in Chinese daily life.But it is much more than just a means of transport to cyclists today,who demand a afr greater chioce of design and function than ever before.

  17. c-Jun N-terminal kinase regulates mitochondrial bioenergetics by modulating pyruvate dehydrogenase activity in primary cortical neurons. (United States)

    Zhou, Qiongqiong; Lam, Philip Y; Han, Derick; Cadenas, Enrique


    This study examines the role of c-jun N-terminal kinase (JNK) in mitochondrial signaling and bioenergetics in primary cortical neurons and isolated rat brain mitochondria. Exposure of neurons to either anisomycin (an activator of JNK/p38 mitogen-activated protein kinases) or H2O2 resulted in activation (phosphorylation) of JNK (mostly p46(JNK1)) and its translocation to mitochondria. Experiments with mitochondria isolated from either rat brain or primary cortical neurons and incubated with proteinase K revealed that phosphorylated JNK was associated with the outer mitochondrial membrane; this association resulted in the phosphorylation of the E(1alpha) subunit of pyruvate dehydrogenase, a key enzyme that catalyzes the oxidative decarboxylation of pyruvate and that links two major metabolic pathways: glycolysis and the tricarboxylic acid cycle. JNK-mediated phosphorylation of pyruvate dehydrogenase was not observed in experiments carried out with mitoplasts, thus suggesting the requirement of intact, functional mitochondria for this effect. JNK-mediated phosphorylation of pyruvate dehydrogenase was associated with a decline in its activity and, consequently, a shift to anaerobic pyruvate metabolism: the latter was confirmed by increased accumulation of lactic acid and decreased overall energy production (ATP levels). Pyruvate dehydrogenase appears to be a specific phosphorylation target for JNK, for other kinases, such as protein kinase A and protein kinase C did not elicit pyruvate dehydrogenase phosphorylation and did not decrease the activity of the complex. These results suggest that JNK mediates a signaling pathway that regulates metabolic functions in mitochondria as part of a network that coordinates cytosolic and mitochondrial processes relevant for cell function.

  18. Molecular clone and characterization of c-Jun N-terminal kinases 2 from orange-spotted grouper, Epinephelus coioides. (United States)

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


    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.

  19. Radiation-induced apoptosis in developing rats and kainic acid-induced excitotoxicity in adult rats are associated with distinctive morphological and biochemical c-Jun/AP-1 (N) expression

    Energy Technology Data Exchange (ETDEWEB)

    Pozas, E. [Unitat de Neuropatologia, Servei d' Anatomia Patologica, Hospital Princeps d' Espanya, Universitat de Barcelona, 08907 Hospitalet de Llobregat (Spain); Planas, A.M. [Departament de Farmacologia i Toxicologia, IIBB, CSIC Barcelona (Spain); Ferrer, I. [Unitat de Neuropatologia, Servei d' Anatomia Patologica, Hospital Princeps d' Espanya, Universitat de Barcelona, 08907 Hospitalet de Llobregat (Spain)


    Ionizing radiation produces apoptosis in the developing rat brain. Strong c-Jun immunoreactivity, as revealed with the antibody c-Jun/AP-1 (N) which is raised against the amino acids 91-105 mapping with the amino terminal domain of mouse c-Jun p39, is simultaneously observed in the nucleus and cytoplasm of apoptotic cells. Western blotting of total brain homogenates, using the same antibody, shows a p39 band in control rats which is accompanied by a strong, phosphorylated p62 double-band in irradiated animals. In addition, increased c-Jun N-terminal kinase 1 expression, as found on western blots, is found in irradiated rats when compared with controls. Intraperitoneal injection of kainic acid at convulsant doses to the adult rat produces cell death with morphological features of necrosis, together with the appearance of cells with fine granular chromatin degeneration and small numbers of apoptotic-like cells, in the entorhinal and piriform cortices, basal amygdala, certain thalamic nuclei, and CA1 region of the hippocampus. c-Jun expression in kainic acid-treated rats, as revealed with the c-Jun/AP-1 (N) antibody, is found in the nuclei of a minority of cells in the same areas. The vast majority of c-Jun-immunoreactive cells have normal nuclear morphology, whereas necrotic cells are negative and only a few cells with fine granular chromatin condensation and apoptotic cells following kainic acid injection are stained with c-Jun antibodies. Western blotting, using the same antibody, shows a p39 band in control rats, which is accompanied by a band at about p26 from 6 h onwards following kainic acid injection. Decreased c-Jun N-terminal kinase 1 expression, as revealed on western blots, is observed in kainic acid-treated rats.These results show that the antibody c-Jun/AP-1 (N) recognizes three different forms of c-Jun-related immunoreactivity in normal and pathological states, which are associated with the different outcome of cells. These results stress the necessity

  20. 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


    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.

  1. 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


    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

  2. The Bicycle Assembly Line Game (United States)

    Klotz, Dorothy


    "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. 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


    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

  4. 36 CFR 13.914 - Bicycle use. (United States)


    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Bicycle use. 13.914 Section... § 13.914 Bicycle use. The use of a bicycle is prohibited— (a) On the Savage River Loop Trail; the... in public parking areas, or on trails and areas designated for bicycle use by the Superintendent....

  5. 15 CFR 265.22 - Bicycle traffic. (United States)


    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Bicycle traffic. 265.22 Section 265.22... Bicycle traffic. No person shall ride a bicycle other than in a manner exercising due caution for pedestrian and other traffic. No person shall ride a bicycle on sidewalks or inside any building, nor...

  6. Bicycle Rider Control: Observations, Modeling & Experiments

    NARCIS (Netherlands)

    Kooijman, J.D.G.


    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

  7. [Prevention of bicycle accidents]. (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


    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. Differential induction of c-Jun and Fos-like proteins in rat hippocampus and dorsal striatum after training in two water maze tasks. (United States)

    Teather, Lisa A; Packard, Mark G; Smith, Diane E; Ellis-Behnke, Rutledge G; Bazan, Nicolas G


    Research examining the neuroanatomical bases of memory in mammals suggests that the hippocampus and dorsal striatum are parts of independent memory systems that mediate "cognitive" and stimulus-response "habit" memory, respectively. At the molecular level, increasing evidence indicates a role for immediate early gene (IEG) expression in memory formation. The present experiment examined whether acquisition of cognitive and habit memory result in differential patterns of IEG protein product expression in these two brain structures. Adult male Long-Evans rats were trained in either a hippocampal-dependent spatial water maze task, or a dorsal striatal-dependent cued water maze task. Ninety minutes after task acquisition, brains were removed and processed for immunocytochemical procedures, and the number of cells expressing Fos-like immunoreactivity (Fos-like-IR) and c-Jun-IR in sections from the dorsal hippocampus and the dorsal striatum were counted. In the dorsal hippocampus of rats trained in the spatial task, there were significantly more c-Jun-IR pyramidal cells in the CA1 and CA3 regions, relative to rats that had acquired the cued task, yoked controls (free-swim), or naïve (home cage) rats. Relative to rats receiving cued task training and control conditions, increases in Fos-like IR were also observed in the CA1 region of rats trained in the spatial task. In rats that had acquired the cued task, patches of c-Jun-IR were observed in the posteroventral striatum; no such patches were evident in rats trained in the spatial task, yoked-control rats, or naïve rats. The results demonstrate that IEG protein product expression is up-regulated in a task-dependent and brain structure-specific manner shortly after acquisition of cognitive and habit memory tasks.

  9. 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


    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.

  10. 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


    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

  11. 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


    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

  12. 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


    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

  13. Moracin M inhibits airway inflammation by interrupting the JNK/c-Jun and NF-κB pathways in vitro and in vivo. (United States)

    Lee, Ju Hee; Ko, Hae Ju; Woo, Eun-Rhan; Lee, Sang Kook; Moon, Bong Soo; Lee, Chan Woo; Mandava, Suresh; Samala, Mallesham; Lee, Jongkook; Kim, Hyun Pyo


    The therapeutic effectiveness of moracins as 2-arylbenzofuran derivatives against airway inflammation was examined. Moracin M, O, and R were isolated from the root barks of Morus alba, and they inhibited interleukin (IL)-6 production from IL-1β-treated lung epithelial cells (A549) at 101-00μM. Among them, moracin M showed the strongest inhibitory effect (IC50=8.1μM). Downregulation of IL-6 expression by moracin M was mediated by interrupting the c-Jun N-terminal kinase (JNK)/c-Jun pathway. Moracin derivatives inhibited inducible nitric oxide synthase (iNOS)-catalyzed NO production from lipopolysaccharide (LPS)-treated alveolar macrophages (MH-S) at 50-100μM. In particular, moracin M inhibited NO production by downregulating iNOS. When orally administered, moracin M (20-60mg/kg) showed comparable inhibitory action with dexamethasone (30mg/kg) against LPS-induced lung inflammation, acute lung injury, in mice with that of dexamethasone (30mg/kg). The action mechanism included interfering with the activation of nuclear transcription factor-κB in inflamed lungs. Therefore, it is concluded that moracin M inhibited airway inflammation in vitro and in vivo, and it has therapeutic potential for treating lung inflammatory disorders.

  14. Activation of c-Jun N-terminal kinase and apoptosis in endothelial cells mediated by endogenous generation of hydrogen peroxide (United States)

    Ramachandran, Anup; Moellering, Douglas; Go, Young-Mi; Shiva, Sruti; Levonen, Anna-Liisa; Jo, Hanjoong; Patel, Rakesh P.; Parthasarathy, Sampath; Darley-Usmar, Victor M.


    Reactive oxygen species have been implicated in the activation of signal transduction pathways. However, extracellular addition of oxidants such as hydrogen peroxide (H2O2) often requires concentrations that cannot be readily achieved under physiological conditions to activate biological responses such as apoptosis. Explanations for this discrepancy have included increased metabolism of H2O2 in the extracellular environment and compartmentalization within the cell. We have addressed this issue experimentally by examining the induction of apoptosis of endothelial cells induced by exogenous addition of H2O2 and by a redox cycling agent, 2,3-dimethoxy-1,4-naphthoquinone, that generates H2O2 in cells. Here we show that low nanomolar steady-state concentrations (0.1-0.5 nmol x min(-1) x 10(6) cells) of H2O2 generated intracellularly activate c-Jun N terminal kinase and initiate apoptosis in endothelial cells. A comparison with bolus hydrogen peroxide suggests that the low rate of intracellular formation of this reactive oxygen species results in a similar profile of activation for both c-Jun N terminal kinase and the initiation of apoptosis. However, a detailed analysis reveals important differences in both the duration and profile for activation of these signaling pathways.

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

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


    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.

  16. Perfluorocarbon inhibits lipopolysaccharide-induced macrophage inflammatory protein-2 expression and activation of ATF-2 and c-Jun in A549 pulmonary epithelial cells. (United States)

    Hu, Y; Li, C S; Li, Y Q; Liang, Y; Cao, L; Chen, L A


    The signaling pathway that mediates the anti-inflammatory effects of perfluorocarbon (PFC) in alveolar epithelial cells treated with lipopolysaccharide (LPS) remains unclear. To evaluate the role of macrophage-inflammatory protein-2 (MIP-2), four A549 treatment groups were utilized: (1) untreated control, (2) 10 μg/mL of LPS, (3) 10 μg/mL of LPS+30% PFC and (4) 30% PFC. MIP-2 mRNA expression was determined by qPCR and ELISA. Mitogen-activated protein kinase (MAPK) activation was determined by Western blot analysis, and MIP-2 expression was determined by qPCR following treatment with MAPK inhibitors. PFC suppressed LPS-induced MIP-2 mRNA levels (P≤0.035) and MIP-2 secretion (P≤0.046). LPS induced ATF-2 and c-Jun phosphorylation, which was suppressed by PFC. Finally, inhibitors of ERK, JNK, and p38 suppressed LPS-induced MIP-2 mRNA expression. Thus, PFC inhibits LPS-induced MIP-2 expression and ATF-2 and c-Jun phosphorylation. To fully explore the therapeutic potential of PFC for acute lung injury (ALI), in vivo analyses are required to confirm these effects.

  17. 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)


    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.

  18. Bicycle Use and Cyclist Safety Following Boston’s Bicycle Infrastructure Expansion, 2009–2012 (United States)

    Angriman, Federico; Bellows, Alexandra L.; Taylor, Kathryn


    Objectives. To evaluate changes in bicycle use and cyclist safety in Boston, Massachusetts, following the rapid expansion of its bicycle infrastructure between 2007 and 2014. Methods. We measured bicycle lane mileage, a surrogate for bicycle infrastructure expansion, and quantified total estimated number of commuters. In addition, we calculated the number of reported bicycle accidents from 2009 to 2012. Bicycle accident and injury trends over time were assessed via generalized linear models. Multivariable logistic regression was used to examine factors associated with bicycle injuries. Results. Boston increased its total bicycle lane mileage from 0.034 miles in 2007 to 92.2 miles in 2014 (P cyclist safety. PMID:27736203

  19. 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


    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

  20. 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: [Laboratory of Cytogenetics and Tissue Regeneration, KIRAMS, Seoul 139-706 (Korea, Republic of); Chung, Kyung-Sook, E-mail: [Genome Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of)


    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

  1. 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


    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.

  2. 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.


    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.

  3. 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


    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

  4. The Bicycle Rental Market In Hangzhou

    Institute of Scientific and Technical Information of China (English)


    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.


    CERN Multimedia

    EP-SMI Help Desk


    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

  6. Bicycle Safety: Sport Education Style (United States)

    Sinelnikov, Oleg A.; Hastie, Peter A.; Cole, Amy; Schneulle, Deanna


    Although the benefits of regular physical activity are well-documented and very well known, Americans are still becoming more sedentary and obese. As some experts envision the potential of nonmotorized transport in the future, especially in urban settings, it is not surprising that diverse groups view walking and bicycling as a solution to an…

  7. Car Hits Boy on Bicycle (United States)

    Ruiz, Michael J.


    In this article we present the fascinating reconstruction of an accident where a car hit a boy riding his bicycle. The boy dramatically flew several metres through the air after the collision and was injured, but made a swift and complete recovery from the accident with no long-term after-effects. Students are challenged to determine the speed of…

  8. 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;


    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...

  9. 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


    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...

  10. Road characteristics and bicycle accidents. (United States)

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


    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.

  11. Electric-bicycle propulsion power

    Energy Technology Data Exchange (ETDEWEB)

    Oman, H.; Morchin, W.C. [Electro-Bicycle, Inc., Auburn, WA (United States); Jamerson, F.E. [Electric Battery Bicycle Co., Naples, FL (United States)


    In a human-powered hybrid electric vehicle (HPHEV) the travel distance available from a single battery charge can be lengthened with power from another source, the cyclist`s leg muscles. In a battery-powered electric bicycle the propulsion power goes mostly into overcoming aerodynamic drag. For example, at 18 km per hour (11 miles per hour) this drag represents 200 watts at the tire-to-road interface for a typical cyclist`s shape and clothing. Today`s typical electrical bicycle is propelled by a high-speed dc motor which is powered from a lead-acid battery. The combined efficiency of the motor and its speed-reducing gears is 50 to 65 percent. In this paper we calculate available travel distances, as a function of speed, grade, and the battery energy-content as measured in watt-hours per kg. We show the effect of battery cost and charge/discharge cycle-life on travel cost in terms of cents per kilometer travelled. Designs used in today`s electric bicycles are illustrated.

  12. Pharmacological Inhibition of c-Jun N-terminal Kinase Reduces Food Intake and Sensitizes Leptin’s Anorectic Signaling Actions (United States)

    Gao, Su; Howard, Shannon; LoGrasso, Philip V.


    The role for c-Jun N-terminal Kinase (JNK) in the control of feeding and energy balance is not well understood. Here, by use of novel and highly selective JNK inhibitors, we investigated the actions of JNK in the control of feeding and body weight homeostasis. In lean mice, intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of SR-3306, a brain-penetrant and selective pan-JNK (JNK1/2/3) inhibitor, reduced food intake and body weight. Moreover, i.p. and i.c.v. administrations of SR11935, a brain-penetrant and JNK2/3 isoform-selective inhibitor, exerted similar anorectic effects as SR3306, which suggests JNK2 or JNK3 mediates aspect of the anorectic effect by pan-JNK inhibition. Furthermore, daily i.p. injection of SR3306 (7 days) prevented the increases in food intake and weight gain in lean mice upon high-fat diet feeding, and this injection paradigm reduced high-fat intake and obesity in diet-induced obese (DIO) mice. In the DIO mice, JNK inhibition sensitized leptin’s anorectic effect, and enhanced leptin-induced STAT3 activation in the hypothalamus. The underlying mechanisms likely involve the downregulation of SOCS3 by JNK inhibition. Collectively, our data suggest that JNK activity promotes positive energy balance, and the therapeutic intervention inhibiting JNK activities represents a promising approach to ameliorate diet-induced obesity and leptin resistance. PMID:28165482

  13. Protective Effect of Lupeol Against Lipopolysaccharide-Induced Neuroinflammation via the p38/c-Jun N-Terminal Kinase Pathway in the Adult Mouse Brain. (United States)

    Badshah, Haroon; Ali, Tahir; Shafiq-ur Rehman; Faiz-ul Amin; Ullah, Faheem; Kim, Tae Hyun; Kim, Myeong Ok


    Recent studies have demonstrated a close interaction between neuroinflammatory responses, increased production of inflammatory mediators, and neurodegeneration. Pathological findings in neurological diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease have shown common signs of neuroinflammation and neurodegeneration. Lupeol, a natural pentacyclic triterpene, has revealed a number of pharmacological properties including an anti-inflammatory activity. This study aimed to evaluate the effect of lupeol against lipopolysaccharide (LPS)-induced neuroinflammation in the cortex and hippocampus of adult mice. Our results showed that systemic administration of LPS induced glial cell production of proinflammatory cytokines, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), and interleukin (IL)-1β, while co-treatment with lupeol significantly inhibited the LPS-induced activation of microglia and astrocytes, and decreased the LPS-induced generation of TNF-α, iNOS, and IL-1β. The intracellular mechanism involved in the LPS-induced activation of inflammatory responses includes phosphorylation of P38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), which was significantly inhibited by lupeol. We further elucidated that lupeol inhibited the LPS-induced activation of the mitochondrial apoptotic pathway and reversed the LPS-induced expression of apoptotic markers such as Bax, cytochrome C, caspase-9, and caspase-3. Taken together; our results suggest that lupeol inhibits LPS-induced microglial neuroinflammation via the P38-MAPK and JNK pathways and has therapeutic potential to treat various neuroinflammatory disorders.

  14. The Caenorhabditis elegans Ste20-related kinase and Rac-type small GTPase regulate the c-Jun N-terminal kinase signaling pathway mediating the stress response. (United States)

    Fujiki, Kota; Mizuno, Tomoaki; Hisamoto, Naoki; Matsumoto, Kunihiro


    Mitogen-activated protein kinases (MAPKs) are integral to the mechanisms by which cells respond to physiological stimuli and a wide variety of environmental stresses. In Caenorhabditis elegans, the stress response is controlled by a c-Jun N-terminal kinase (JNK)-like MAPK signaling pathway, which is regulated by MLK-1 MAPK kinase kinase (MAPKKK), MEK-1 MAPKK, and KGB-1 JNK-like MAPK. In this study, we identify the max-2 gene encoding a C. elegans Ste20-related protein kinase as a component functioning upstream of the MLK-1-MEK-1-KGB-1 pathway. The max-2 loss-of-function mutation is defective in activation of KGB-1, resulting in hypersensitivity to heavy metals. Biochemical analysis reveals that MAX-2 activates MLK-1 through direct phosphorylation of a specific residue in the activation loop of the MLK-1 kinase domain. Our genetic data presented here also show that MIG-2 small GTPase functions upstream of MAX-2 in the KGB-1 pathway. These results suggest that MAX-2 and MIG-2 play a crucial role in mediating the heavy metal stress response regulated by the KGB-1 pathway.

  15. The phosphatidylinositol 3-kinase/Akt and c-Jun N-terminal kinase signaling in cancer: Alliance or contradiction? (Review). (United States)

    Zhao, Hua-Fu; Wang, Jing; Tony To, Shing-Shun


    The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and c-Jun N-terminal kinase (JNK) pathway are responsible for regulating a variety of cellular processes including cell growth, migration, invasion and apoptosis. These two pathways are essential to the development and progression of tumors. The dual roles of JNK signaling in apoptosis and tumor development determine the different interactions between the PI3K/Akt and JNK pathways. Activation of PI3K/Akt signaling can inhibit stress- and cytokine-induced JNK activation through Akt antagonizing and the formation of the JIP1-JNK module, as well as the activities of upstream kinases ASK1, MKK4/7 and MLK. On the other hand, hyperactivation of Akt and JNK is also found in cancers that harbor EGFR overexpression or loss of PTEN. Understanding the activation mechanism of PI3K/Akt and JNK pathways, as well as the interplays between these two pathways in cancer may contribute to the identification of novel therapeutic targets. In the present report, we summarized the current understanding of the PI3K/Akt and JNK signaling networks, as well as their biological roles in cancers. In addition, the interactions and regulatory network between PI3K/Akt and JNK pathways in cancer were discussed.

  16. 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


    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.

  17. 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.

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

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


    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.

  19. Effects of c-Jun N-terminal kinase on Activin A/Smads signaling in PC12 cell suffered from oxygen-glucose deprivation. (United States)

    Wang, J Q; Xu, Z H; Liang, W Z; He, J T; Cui, Y; Liu, H Y; Xue, L X; Shi, W; Shao, Y K; Mang, J; Xu, Z X


    Activin A (Act A), a member of transforming growth factor-β (TGF-β) superfamily, is an early gene in response to cerebral ischemia. Growing evidences confirm the neuroprotective effect of Act A in ischemic injury through Act A/Smads signal activation. In this process, regulation networks are involved in modulating the outcomes of Smads signaling. Among these regulators, crosstalk between c-Jun N-terminal kinase (JNK) and Smads signaling has been found in the TGF-β induced epithelial-mesenchymal transition. However, in neural ischemia, the speculative regulation between JNK and Act A/Smads signaling pathways has not been clarified. To explore this issue, an Oxygen Glucose Deprivation (OGD) model was introduced to nerve-like PC12 cells. We found that JNK signal activation occurred at the early time of OGD injury (1 h). Act A administration suppressed JNK phosphorylation. In addition, JNK inhibition could elevate the strength of Smads signaling and attenuate neural apoptosis after OGD injury. Our results indicated a negative regulation effect of JNK on Smads signaling in ischemic injury. Taken together, JNK, as a critical site for neural apoptosis and negative regulator for Act A/Smads signaling, was presumed to be a molecular therapeutic target for ischemia.

  20. Inhibition of development of experimental abdominal aortic aneurysm by c-jun N-terminal protein kinase inhibitor combined with lysyl oxidase gene modified smooth muscle progenitor cells. (United States)

    Chen, Feng; Zhang, ZhenDong; Zhu, XianHua


    Chronic inflammation, imbalance between the extracellular matrix synthesis and degradation, and loss of vascular smooth muscle cells (SMCs) contribute to the development of abdominal aortic aneurysm (AAA). The purpose of this study was to investigate the effect of the therapy with periaortic incubation of c-Jun N-terminal protein kinase inhibitor SP600125 infused from an osmotic pump and subadventitial injection of lysyl oxidase (LOX) gene modified autologous smooth muscle progenitor cells (SPCs) on treatment of AAA in a rabbit model. Obvious dilation of the abdominal aorta in the control group was caused by periaortic incubation of calcium chloride and elastase. But the progression of aortic dilation was significantly decreased after the treatment with SP600125 and LOX gene modified SPCs compared to the treatment with phosphate-buffered saline. This therapy could inhibit matrix metalloproteinases expression, enhance elastin synthesis, improve preservation of elastic laminar integrity, benefit SPCs survival and restore SMCs population. It seemed that this method might provide a novel therapeutic strategy to treat AAA.

  1. Tolerance to the antinociceptive and hypothermic effects of morphine is mediated by multiple isoforms of c-Jun N-terminal kinase. (United States)

    Yuill, Matthew B; Zee, Michael L; Marcus, David; Morgan, Daniel J


    The abuse and overdose of opioid drugs are growing public health problems worldwide. Although progress has been made toward understanding the mechanisms governing tolerance to opioids, the exact cellular machinery involved remains unclear. However, there is growing evidence to suggest that c-Jun N-terminal kinases (JNKs) play a major role in mu-opioid receptor regulation and morphine tolerance. In this study, we aimed to determine the potential roles of different JNK isoforms in the development of tolerance to the antinociceptive and hypothermic effects of morphine. We used the hot-plate and tail-flick tests for thermal pain to measure tolerance to the antinociceptive effects of once-daily subcutaneous injections with 10 mg/kg morphine. Body temperature was also measured to determine tolerance to the hypothermic effects of morphine. Tolerance to morphine was assessed in wild-type mice and compared with single knockout mice each lacking the JNK isoforms (JNK1, JNK2, or JNK3). We found that loss of each individual JNK isoform causes impairment in tolerance for the antinociceptive and hypothermic effects of daily morphine. However, disruption of JNK2 seems to have the most profound effect on morphine tolerance. These results indicate a clear role for JNK signaling pathways in morphine tolerance. This complements previous studies suggesting that the JNK2 isoform is required for morphine tolerance, but additionally presents novel data suggesting that additional JNK isoforms also contribute toward this process.

  2. 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. (United States)

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


    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

  3. BMX bicycles: accident comparison with other models.



    A comparison has been made between BMX bicycle accidents and those occurring when children ride other types of bicycle. The injuries sustained are compared to see if the clinical impressions that BMX are more dangerous, and produce more facial injuries, are correct. This was found not to be true as half the children involved rode BMX bicycles, and the injuries sustained were similar to those occurring to non BMX riders. BMX riders had a lower proportion of serious injuries than riders of raci...

  4. SOFIE, a bicycle that supports older cyclists? (United States)

    Dubbeldam, R; Baten, C; Buurke, J H; Rietman, J S


    Older cyclists remain at high risk of sustaining an injury after a fall with their bicycle. A growing awareness for the need and possibilities to support safety of older cyclists has been leading to bicycle design ideas. However, the effectiveness and acceptance of such designs has not been studied yet. This study aims to analyse the effect of 3 support systems: an automatic adjustable saddle height, optimised frame and wheel geometry and drive-off assistance. The support systems are integrated on the SOFIE bicycle, a prototype bicycle designed to support older cyclists during (dis-)mounting and at lower cycling speeds. Nine older cyclists (65-80 years) were asked to cycle on a 'normal' and on the 'SOFIE' bicycle. They cycled on a parking lot to avoid interaction with traffic. The following tasks were analysed: cycling at comfortable and low speed avoiding an obstacle and (dis-)mounting the bicycle. Bicycle and cyclist motions were recorded with 10 Inertial Measurement Units and by 2 video cameras. FUSION software (LABVIEW) was used to assess kinematic parameters. First, a subjective analysis of the different cycling tasks was made, supported by video analysis. Second, differences in cyclist and bicycle kinematic parameters between the normal and SOFIE bicycle were studied for the various cycling tasks. The SOFIE bicycle was experienced as a 'supportive' and comfortable bicycle and objectively performed 'safer' on various cycling tasks. For example: The optimised frame geometry with low step-in enabled a faster (dis-)mounting time and less sternum roll angle and angular acceleration. The adjustable saddle height enabled the participants to keep both feet on the ground till they started cycling with the 'drive-off' support. The latter reduces steering activity: maximum steer angle and angular acceleration. During sudden obstacle avoidance, less upper body and thigh accelerations are recorded. In conclusion, the SOFIE bicycle was able to support older cyclists during

  5. Effect of c-Jun NH2-terminal kinase-mediated p53 expression on neuron autophagy following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    HONG Ming-yan; GAO Jun-ling; CUI Jian-zhong; WANG Kai-jie; TIAN Yan-xia; LI Ran; WANG Hai-tao; WANG Huan


    Background Activation of c-Jun NH2-terminal kinase (JNK) has been implicated in neuron apoptosis as well as autophagy in response to various stressors after traumatic brain injury (TBI).However,the underlying molecular pathway remains unclear.Our study assessed whether JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI.Methods A total of 186 male Sprague-Dawley (SD) rats (300-350 g) were used in this study.By randomized block method rats were randomly divided into four groups:sham-operated (n=46),TBI (n=60),TBI + dimethyl sulfoxide (DMSO) (n=40),and TBI + SP600125 (n=40).JNK was treated with SP600125,a specific JNK inhibitor.JNK,p-P53,Beclin-1,damage-regulated autophagy modulator (DRAM) and p-bcl-2 were evaluated by Western blotting analysis.The cellular localization and expression of Beclin-1 and DRAM was observed by immunofluorescence and immunohistochemistry,and the expression of Beclin-1-Bcl-2/Bcl-xL complexes was evaluated by immunoprecipitation.Multiple-group comparisons were conducted using analysis of variance (ANOVA).P values of less than 0.05 were considered statistically significant.Results It was observed that the expression of JNK,p-P53,Beclin-1,DRAM and p-bcl-2 was increasing after TBI,and the expression of Beclin-1 and DRAM was mainly located in the cytoplasm of neurons.But these were significantly inhibited in SP600125 group compared with sham group and TBI+SP600125 group (P <0.05).The expression of Beclin-1-Bcl-2/Bcl-xL complexes was reduced after TBI.Conclusion JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI.

  6. Puerarin attenuates carbon tetrachloride-induced liver oxidative stress and hyperlipidaemia in mouse by JNK/c-Jun/CYP7A1 pathway. (United States)

    Ma, Jie-Qiong; Ding, Jie; Zhao, Hai; Liu, Chan-Min


    Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. The aim of this study was to investigate the effects of puerarin on hepatic oxidative stress and hyperlipidaemia in mice exposed to carbon tetrachloride (CCl4). Male ICR mice were injected with CCl4 with or without puerarin co-administration (200 and 400 mg/kg intragastrically once-daily) for 8 weeks. Our data showed that puerarin significantly prevented CCl4-induced hepatotoxicity, indicated by both diagnostic indicators of the liver damage (serum aminotransferase levels) and histopathological analysis. Puerarin decreased the thiobarbituric acid reactive substances (TBARS) and the protein carbonyl content (PCO) in the liver of CCl4-treated mice. Puerarin also restored the levels of reduced glutathione (GSH) and total antioxidant capacity (TAC) in the liver. Furthermore, the increase in serum cholesterol, triglycerides and low-density lipoproteins (LDL) induced by CCl4 was effectively suppressed by puerarin. The high-density lipoprotein (HDL) level in the CCl4 treatment mice was also increased by puerarin. Western blot analysis showed that puerarin remarkably inhibited hyperlipidaemia by regulating the expression of phosphorylated Jun N-terminal kinases (JNK), phosphorylated c-Jun protein and cholesterol 7a-hydroxylase (CYP7A1) in the liver of CCl4-treated mice. Altogether, these results suggest that puerarin could protect the CCl4-induced liver injury and hyperlipidaemia by reducing reactive oxygen species S production, renewing the total antioxidant capacity and influencing expression of hepatic lipid biosynthesis and metabolism genes.

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

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


    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.

  8. The c-Fos and c-Jun from Litopenaeus vannamei play opposite roles in Vibrio parahaemolyticus and white spot syndrome virus infection. (United States)

    Li, Chaozheng; Li, Haoyang; Wang, Sheng; Song, Xuan; Zhang, Zijian; Qian, Zhe; Zuo, Hongliang; Xu, Xiaopeng; Weng, Shaoping; He, Jianguo


    Growing evidence indicates that activator protein-1 (AP-1) plays a major role in stimulating the transcription of immune effector molecules in cellular response to an incredible array of stimuli, including growth factors, cytokines, cellular stresses and bacterial and viral infection. Here, we reported the isolation and characterization of a cDNA from Litopenaeus vannamei encoding the full-length c-Fos protein (named as Lvc-Fos). The predicted amino acid sequences of Lvc-Fos contained a basic-leucine zipper (bZIP) domain, which was characteristic of members of the AP-1 family. Immunoprecipitation and native-PAGE assays determined that Lvc-Fos could interact with the Lvc-Jun, a homolog of c-Jun family in L. vannamei, in a heterodimer manner. Further investigation demonstrated that Lvc-Fos and Lvc-Jun were expressed in all tested tissues and located in the nucleus. Real-time RT-PCR analysis showed both Lvc-Fos and Lvc-Jun in gills were up-regulated during Vibrio parahaemolyticus and white spot syndrome virus (WSSV) challenges. In addition, reporter gene assays indicated Lvc-Fos and Lvc-Jun could activate the expression of antimicrobial peptides (AMPs) of Drosophila and shrimp, as well as WSSV immediate early (IE) genes wsv069 and wsv249, in a different manner. Knockdown of Lvc-Fos or Lvc-Jun by RNA interference (RNAi) resulted in higher mortalities of L. vannamei after infection with V. parahaemolyticus, suggesting that Lvc-Fos and Lvc-Jun might play protective roles in bacterial infection. However, silencing of Lvc-Fos or Lvc-Jun in shrimp caused lower mortalities and virus loads under WSSV infection, suggesting that Lvc-Fos and Lvc-Jun could be engaged for WSSV replication and pathogenesis. In conclusion, our results provided experimental evidence and novel insight into the roles of L. vannamei AP-1 in bacterial and viral infection.

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


    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.

  10. I-mfa domain proteins interact with Axin and affect its regulation of the Wnt and c-Jun N-terminal kinase signaling pathways. (United States)

    Kusano, Shuichi; Raab-Traub, Nancy


    I-mfa has been identified as an inhibitor of myogenic basic helix-loop-helix transcription factors, and a related human I-mfa domain-containing protein (HIC) also has been identified as a protein that regulates Tat- and Tax-mediated expression of viral promoters. HIC and I-mfa represent a family of proteins that share a highly conserved cysteine-rich domain, termed the I-mfa domain. We show here that both I-mfa domain proteins, HIC and I-mfa, interacted in vivo with the Axin complex through their C-terminal I-mfa domains. This interaction inhibited Axin-mediated downregulation of free levels of cytosolic beta-catenin. I-mfa and HIC also both directly interacted with lymphocyte enhancer factor (LEF); however, I-mfa but not HIC significantly inhibited reporter constructs regulated by beta-catenin. The overexpression of HIC but not I-mfa decreased the inhibitory effects of Axin on beta-catenin-regulated reporter constructs, while both HIC and I-mfa decreased Axin-mediated c-Jun N-terminal kinase (JNK) activation. These data reveal for the first time that I-mfa domain proteins interact with the Axin complex and affect Axin regulation of both the Wnt and the JNK activation pathways. Interestingly, HIC differs from I-mfa in that I-mfa affects both Axin function and T-cell factor- or LEF-regulated transcription in the Wnt signaling pathway while HIC affects primarily Axin function.

  11. (-)-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: [Institute of Biotechnology, National Tsing Hua University, No. 101, Section 2, Kuang Fu Road, Hsinchu 30013, Taiwan (China)


    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.

  12. Low Dose Acetaminophen Induces Reversible Mitochondrial Dysfunction Associated with Transient c-Jun N-Terminal Kinase Activation in Mouse Liver. (United States)

    Hu, Jiangting; Ramshesh, Venkat K; McGill, Mitchell R; Jaeschke, Hartmut; Lemasters, John J


    Acetaminophen (APAP) overdose causes hepatotoxicity involving mitochondrial dysfunction and c-jun N-terminal kinase (JNK) activation. Because the safe limit of APAP dosing is controversial, our aim was to evaluate the role of the mitochondrial permeability transition (MPT) and JNK in mitochondrial dysfunction after APAP dosing considered nontoxic by criteria of serum alanine aminotransferase (ALT) release and histological necrosis in vivo. C57BL/6 mice were given APAP with and without the MPT inhibitor, N-methyl-4-isoleucine cyclosporin (NIM811), or the JNK inhibitor, SP600125. Fat droplet formation, cell viability, and mitochondrial function in vivo were monitored by intravital multiphoton microscopy. Serum ALT, liver histology, total JNK, and activated phospho(p)JNK were also assessed. High APAP (300 mg/kg) caused ALT release, necrosis, irreversible mitochondrial dysfunction, and hepatocellular death. By contrast, lower APAP (150 mg/kg) caused reversible mitochondrial dysfunction and fat droplet formation in hepatocytes without ALT release or necrosis. Mitochondrial protein N-acetyl-p-benzoquinone imine adducts correlated with early JNK activation, but irreversible mitochondrial depolarization and necrosis at high dose were associated with sustained JNK activation and translocation to mitochondria. NIM811 prevented cell death and/or mitochondrial depolarization after both high and low dose APAP. After low dose, SP600125 decreased mitochondrial depolarization. In conclusion, low dose APAP produces reversible MPT-dependent mitochondrial dysfunction and steatosis in hepatocytes without causing ALT release or necrosis, whereas high dose leads to irreversible mitochondrial dysfunction and cell death associated with sustained JNK activation. Thus, nontoxic APAP has the potential to cause transient mitochondrial dysfunction that may synergize with other stresses to promote liver damage and steatosis.

  13. 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


    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.

  14. Pharmacokinetic and tissue distribution studies of 1,9-pyrazoloanthrone, a c-Jun-N-terminal kinase inhibitor in Wistar rats by a simple and sensitive HPLC method. (United States)

    Ambhore, Nilesh Sudhakar; Yamjala, Karthik; Mohire, Shubhashri; Raju, Kalidhindi Rama Satyanarayana; Mulukutla, Shashank; Murthy, Vishakantha; Tondhawada, Mahesh; Elango, Kannan


    JNK pathway activates c-Jun(s) which are responsible for cell apoptosis; as a result, inhibitors of JNK pathway have the potential to prevent dopaminergic neurons from death and decrease the loss of dopamine in substantia nigra pars compacta (SNpc). Recent in-vitro studies show that 1,9-pyrazoloanthrone (1,9-P) a potent JNK-3 inhibitor prevents the apoptosis of dopaminergic cells of brain. In the present study we formulated liposomes to increase the bioavailability of 1,9-P in the brain and developed a simple, sensitive and selective high performance liquid chromatographic method and validated for the estimation of 1,9-P in Wistar rat plasma and tissue samples. Plasma and tissue samples were extracted by protein precipitation technique using acetonitrile (ACN) and rasagiline as the internal standards. Chromatography was performed on Hibar C18 column with mobile phase of ammonium acetate (10mM, pH 8.0 adjusted with ammonia) and ACN at a flow rate of 1mL/min. The lower limit of quantification of the developed method was found to be 2.0ng/mL and 4.0ng/g in plasma and tissue samples respectively. The liposomes of 1,9-P administered to animals at the dose equivalent to 15mg/kg orally demonstrated remarkable absorption into the systemic circulation with maximum concentration (∼7500ng/mL) within 2.0h. The order of the area under curve was found to be kidney>liver>brain>lungs>spleen>heart. The liposomes of 1,9-P were rapidly taken up into brain and showed a good brain concentration after 2.0h; sustenance up to 4.0h was achieved which is better than 1,9-P solution.

  15. Intrathecal administration of low-dose nociceptin/orphanin FQ induces allodynia via c-Jun N-terminal kinase and monocyte chemoattractant protein-1. (United States)

    Kawabata, Kenta; Nishimura, Isamu; Fujiwara, Takeshi; Terauchi, Shoko; Minami, Toshiaki; Ito, Seiji; Okuda-Ashitaka, Emiko


    Pathological chronic pain, which is frequently associated with prolonged tissue damage, inflammation, tumour invasion, and neurodegenerative diseases, gives rise to hyperalgesia and allodynia. We previously reported that intrathecal administration of nociceptin/orphanin FQ (N/OFQ), an endogenous ligand for the orphan opioid receptor-like receptor, in the femtomole range induces touch-evoked allodynia. N/OFQ has been implicated in multiple signalling pathways, such as inhibition of cAMP production and Ca(2+) channels, or activation of K(+) channels and mitogen-activated protein kinase, although the signalling pathways of N/OFQ-induced allodynia remain unclear. To address these issues, we developed an ex vivo mitogen-activated protein kinase assay by using intact slices of mouse spinal cord. N/OFQ markedly increased the phosphorylation of c-Jun N-terminal kinase (JNK) in the superficial dorsal horn of the spinal cord. The N/OFQ-stimulated JNK phosphorylation was significantly inhibited by pertussis toxin, the phospholipase C inhibitor U73122, and the inositol trisphosphate receptor antagonist Xestospongin C. Intrathecal administration of the JNK inhibitor SP600125 inhibited N/OFQ-evoked allodynia. The N/OFQ-induced increase in JNK phosphorylation was observed in astrocytes that expressed glial fibrillary acidic protein. N/OFQ also induced monocyte chemoattractant protein-1 (MCP-1) release via the JNK pathway, and N/OFQ-induced JNK phosphorylation was observed in MCP-1-immunoreactive astrocytes. Intrathecal administration of the MCP-1 receptor antagonist RS504393 inhibited N/OFQ-evoked allodynia. These results suggest that, in the spinal dorsal horn, N/OFQ induces allodynia through activation of JNK via the phospholipase C-inositol trisphosphate pathway, which is coupled to pertussis toxin-sensitive G-protein, and following the release of MCP-1 from astrocytes.

  16. Activation of the KCa3.1 channel contributes to traumatic scratch injury-induced reactive astrogliosis through the JNK/c-Jun signaling pathway. (United States)

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


    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.

  17. Testosterone supplementation reverses sarcopenia in aging through regulation of myostatin, c-Jun NH2-terminal kinase, Notch, and Akt signaling pathways. (United States)

    Kovacheva, Ekaterina L; Hikim, Amiya P Sinha; Shen, Ruoqing; Sinha, Indranil; Sinha-Hikim, Indrani


    Aging in rodents and humans is characterized by loss of muscle mass (sarcopenia). Testosterone supplementation increases muscle mass in healthy older men. Here, using a mouse model, we investigated the molecular mechanisms by which testosterone prevents sarcopenia and promotes muscle growth in aging. Aged mice of 22 months of age received a single sc injection of GnRH antagonist every 2 wk to suppress endogenous testosterone production and were implanted subdermally under anesthesia with 0.5 or 1.0 cm testosterone-filled implants for 2 months (n = 15/group). Young and old mice (n = 15/group), of 2 and 22 months of age, respectively, received empty implants and were used as controls. Compared with young animals, a significant (P muscle cell apoptosis coupled with a decrease in gastrocnemius muscles weight (by 16.7%) and muscle fiber cross-sectional area, of both fast and slow fiber types, was noted in old mice. Importantly, such age-related changes were fully reversed by higher dose (1 cm) of testosterone treatment. Testosterone treatment effectively suppressed age-specific increases in oxidative stress, processed myostatin levels, activation of c-Jun NH(2)-terminal kinase, and cyclin-dependent kinase inhibitor p21 in aged muscles. Furthermore, it restored age-related decreases in glucose-6-phosphate dehydrogenase levels, phospho-Akt, and Notch signaling. These alterations were associated with satellite cell proliferation and differentiation. Collectively these results suggest involvement of multiple signal transduction pathways in sarcopenia. Testosterone reverses sarcopenia through stimulation of cellular metabolism and survival pathway together with inhibition of death pathway.

  18. Immunohistochemical analysis of the expression of cellular transcription NFκB (p65), AP-1 (c-Fos and c-Jun), and JAK/STAT in leprosy. (United States)

    Silva, Luciana Mota; Hirai, Kelly Emi; de Sousa, Jorge Rodrigues; de Souza, Juarez; Fuzii, Hellen Thais; Dias, Leonidas Braga; Carneiro, Francisca Regina Oliveira; de Souza Aarão, Tinara Leila; Quaresma, Juarez Antonio Simões


    Leprosy is a disease whose clinical spectrum depends on the cytokine patterns produced during the early stages of the immune response. The main objective of this study was to describe the activation pattern of cellular transcription factors and to correlate these factors with the clinical forms of leprosy. Skin samples were obtained from 16 patients with the tuberculoid (TT) form and 14 with the lepromatous (LL) form. The histologic sections were immunostained with anti-c-Fos and anti-c-Jun monoclonal antibodies for investigation of AP-1, anti-NFκB p65 for the study of NFκB, and anti-JAK2, STAT1, STAT3, and STAT4 for investigation of the JAK/STAT pathway. Cells expressing STAT1 were more frequent in the TT form than in LL lesions (P = .0096), in agreement with the protective immunity provided by IFN-γ. STAT4 was also more highly expressed in the TT form than in the LL form (P = .0098). This transcription factor is essential for the development of a Th1 response because it is associated with interleukin-12. NFκB (p65) and STAT4 expression in the TT form showed a strong and significant correlation (r = 0.7556 and P = .0007). A moderate and significant correlation was observed between JAK2 and STAT4 in the TT form (r = 0.6637 and P = .0051), with these factors responding to interleukin-12 in Th1 profiles. The results suggest that STAT1, JAK2, and NFκB, together with STAT4, contribute to the development of cell-mediated immunity, which is able to contain the proliferation of Mycobacterium leprae.

  19. A study on electric bicycle energy efficiency

    Directory of Open Access Journals (Sweden)

    Ivan EVTIMOV


    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.

  20. Evaluation electric bicycles; Evaluation velos electriques

    Energy Technology Data Exchange (ETDEWEB)



    Leovelo service is the first measure in favor of the bicycle to control the air pollution and to conserve energy. It provides in the city of Clermont-Ferrand (France) a service of bicycle hiring. This document evaluates the project after two years of operating. It provides a technical evaluation (maintenance, equipment, financing) and also the socio-economic impacts. (A.L.B.)

  1. Stabilizing a Bicycle: A Modeling Project (United States)

    Pennings, Timothy J.; Williams, Blair R.


    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…

  2. Bicycle parking preferences: costs versus walking time

    NARCIS (Netherlands)

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


    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

  3. Good Practices Guide for Bicycle Safety Education. (United States)

    Department of Transportation, Washington, DC.

    The purpose of this guide is to serve as an informational resource for educators and other interested professionals in planning and developing bicycle safety education programs. The guide examines 15 existing bicycle safety education programs in the United States and one from Canada. (Author)

  4. Targeting Mcl-1 for multiple myeloma (MM) therapy: drug-induced generation of Mcl-1 fragment Mcl-1(128-350) triggers MM cell death via c-Jun upregulation. (United States)

    Fan, Fengjuan; Tonon, Giovanni; Bashari, Muhammad Hasan; Vallet, Sonia; Antonini, Elena; Goldschmidt, Hartmut; Schulze-Bergkamen, Henning; Opferman, Joseph T; Sattler, Martin; Anderson, Kenneth C; Jäger, Dirk; Podar, Klaus


    Myeloid cell leukemia-1 (Mcl-1, HGNC: 6943), a pro-survival member of the Bcl-2 family, plays a crucial role in Multiple Myeloma (MM) pathogenesis and drug resistance, thus representing a promising therapeutic target in MM. A novel strategy to inhibit Mcl-1 activity is the induction of ubiquitin-independent Mcl-1 degradation. Our own and other previous studies have demonstrated caspase-dependent generation of a 28kDa Mcl-1 fragment, Mcl-1(128-350), which inhibits MM cell proliferation and survival. Here, we show that similar to bortezomib, the novel proteasome inhibitors carfilzomib and ixazomib, as well as staurosporine and adaphostin, induce the generation of Mcl-1(128-350) in MM cells. Next, the molecular sequelae downstream of Mcl-1(128-350), which mediate its pro-apoptotic activity, were delineated. Surprisingly, we observed nuclear accumulation of drug-induced or exogenously overexpressed Mcl-1(128-350), followed by elevated mRNA and protein levels of c-Jun, as well as enhanced AP-1 reporter activity. Moreover, drug-induced AP-1 activity was blocked after introducing a point mutation into the highly conserved Mcl-1 caspase-cleavage site Asp127, but not Asp157. Consequently, drug-triggered cell death was significantly decreased in MM cells transfected with Mcl-1 D127A, but not with Mcl-1 D157A. Consistent with these data, treatment with bortezomib triggered c-Jun upregulation followed by apoptosis in Mcl-1(wt/wt), but not Mcl-1(Δ/null) murine embryonic fibroblasts (MEFs). Transfection of a plasmid carrying Mcl-1(wt) into Mcl-1(Δ/null) MEFs restored bortezomib-induced Mcl-1 fragmentation, c-Jun upregulation and AP-1 reporter activity. Finally, our data indicate that drug-induced generation of a pro-apoptotic Mcl-1 fragment followed by c-Jun upregulation may also be a novel therapeutic approach in other tumor entities.


    Directory of Open Access Journals (Sweden)



    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.

  6. Ketamine inhibits tumor necrosis factor-alpha and interleukin-6 gene expressions in lipopolysaccharide-stimulated macrophages through suppression of toll-like receptor 4-mediated c-Jun N-terminal kinase phosphorylation and activator protein-1 activation. (United States)

    Wu, Gone-Jhe; Chen, Ta-Liang; Ueng, Yune-Fang; Chen, Ruei-Ming


    Our previous study showed that ketamine, an intravenous anesthetic agent, has anti-inflammatory effects. In this study, we further evaluated the effects of ketamine on the regulation of tumor necrosis factor-alpha (TNF-alpha) and interlukin-6 (IL-6) gene expressions and its possible signal-transducing mechanisms in lipopolysaccharide (LPS)-activated macrophages. Exposure of macrophages to 1, 10, and 100 microM ketamine, 100 ng/ml LPS, or a combination of ketamine and LPS for 1, 6, and 24 h was not cytotoxic to macrophages. A concentration of 1000 microM of ketamine alone or in combined treatment with LPS caused significant cell death. Administration of LPS increased cellular TNF-alpha and IL-6 protein levels in concentration- and time-dependent manners. Meanwhile, treatment with ketamine concentration- and time-dependently alleviated the enhanced effects. LPS induced TNF-alpha and IL-6 mRNA syntheses. Administration of ketamine at a therapeutic concentration (100 microM) significantly inhibited LPS-induced TNF-alpha and IL-6 mRNA expressions. Application of toll-like receptor 4 (TLR4) small interfering (si)RNA into macrophages decreased cellular TLR4 levels. Co-treatment of macrophages with ketamine and TLR4 siRNA decreased the LPS-induced TNF-alpha and IL-6 productions more than alone administration of TLR4 siRNA. LPS stimulated phosphorylation of c-Jun N-terminal kinase and translocation of c-Jun and c-Fos from the cytoplasm to nuclei. However, administration of ketamine significantly decreased LPS-induced activation of c-Jun N-terminal kinase and translocation of c-Jun and c-Fos. LPS increased the binding of nuclear extracts to activator protein-1 consensus DNA oligonucleotides. Administration of ketamine significantly ameliorated LPS-induced DNA binding activity of activator protein-1. Therefore, a clinically relevant concentration of ketamine can inhibit TNF-alpha and IL-6 gene expressions in LPS-activated macrophages. The suppressive mechanisms occur through

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

    NARCIS (Netherlands)

    Rooijen, T. van


    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

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

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


    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

  9. Protocatechuic aldehyde inhibits TNF-α-induced fibronectin expression in human umbilical vein endothelial cells via a c-Jun N-terminal kinase dependent pathway. (United States)

    Tong, Yue-Feng; Liu, Yong; Hu, Zhi-Xing; Li, Zhe-Cheng; A, Agula


    Fibronectin (FN) is one of the most important extracellular matrix proteins and plays an important role in the pathogenesis of atherosclerosis (AS). The aim of the present study was to evaluate the effect of a potent, water-soluble antioxidant, protocatechuic aldehyde (PA), which is derived from the Chinese herb Salvia miltiorrhiza, on the expression of FN in human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis factor-α (TNF-α). The pharmacological effects of PA on the production of FN were investigated using ELISA and western blot analysis. In addition, ELISA and western blot analysis were used to examine the activation and suppression of the mitogen-activated protein kinase (MAPK) pathways and nuclear factor (NF)-κB in TNF-α-stimulated HUVECs, in order to explore the underlying pharmacological mechanism of PA. The inhibitory effect of PA on the total generation of reactive oxygen species (ROS) in TNF-α-stimulated HUVECs was assessed using 2',7'-dichlorofluorescein diacetate. Pretreatment of HUVECs with PA (0.15, 0.45 and 1.35 mM) for 18 h markedly attenuated the TNF-α-stimulated FN surface expression and secretion in a dose-dependent manner. Intracellular ROS generation and the expression of extracellular signal-regulated kinase 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 MAPK (p38) were significantly induced by TNF-α (2 ng/ml) in HUVECs. TNF-α-induced ROS generation and JNK activation were inhibited by PA in a concentration-dependent manner. By contrast, ERK1/2 and p38 activation was not significantly affected by PA. Pretreatment of HUVECs with PA for 18 h markedly attenuated TNF-α-stimulated NF-κB activation. In conclusion, the present findings suggest that PA inhibits TNF-α-induced FN expression in HUVECs through a mechanism that involves ROS/JNK and NF-κB.

  10. 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:


    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

  11. 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: [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)


    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

  12. Muscle fatigue based evaluation of bicycle design. (United States)

    Balasubramanian, V; Jagannath, M; Adalarasu, K


    Bicycling posture leads to considerable discomfort and a variety of chronic injuries. This necessitates a proper bicycle design to avoid injuries and thereby enhance rider comfort. The objective of this study was to investigate the muscle activity during cycling on three different bicycle designs, i.e., rigid frame (RF), suspension (SU) and sports (SP) using surface electromyography (sEMG). Twelve male volunteers participated in this study. sEMG signals were acquired bilaterally from extensor carpi radialis (ECR), trapezius medial (TM), latissimus dorsi medial (LDM) and erector spinae (ES), during 30 min of cycling on each bicycle and after cycling. Time domain (RMS) and frequency domain (MPF) parameters were extracted from acquired sEMG signals. From the sEMG study, it was found that the fatigue in right LDM and ES were significantly (p bicycle. This was corroborated by a psychophysical assessment based on RBG pain scale. The study also showed that there was a significantly lesser fatigue with the SU bicycle than the RF and SP bicycles.

  13. Survey of options on legalizing bicycling (VB)

    DEFF Research Database (Denmark)

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


    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...

  14. The self-stabilising dynamics of bicycles

    CERN Document Server

    Warner, Mark


    We analyse the classical problem of the stability of bicycles when moving quickly and upright. Developing a lean causes the front wheel to turn thereby setting the bicycle instantaneously into circular motion. The centripetal force associated with the lean-dependent turning circle gives a restoring torque which corrects the lean. The force also helps self-steer the front wheel, ensuring the bicycle continues in an essentially straight path. We give the frequency of lean oscillations about the vertical executed during riding. As in the literature, we discuss the neglect of gyroscopic effects, which experiment suggests are negligible.

  15. Policy to promote bicycle use or bicycle to promote politicians? Bicycles in the imagery of urban mobility in Brazil

    Directory of Open Access Journals (Sweden)

    Rafael Milani Medeiros


    Full Text Available During the last 15 years an increasing number of presidents, prime ministers, governors and mayors in developed and developing countries have been riding bicycles to promote a more sustainable and friendly form of urban mobility. We believe that these images also reveal and influence the image of contemporary urban mobility – the way in which people see what urban mobility is and how it should be. In this paper we discuss how the image of the bicycle has changed in Brazil and how this may influence an increase in its actual 1% bicycle modal share in big cities. We conclude that the importance of the bicycle in the image of urban mobility has been changing cyclically, and what seems to be a positive trend today might end up as being just an ephemeral positive image, with the risk of having no further practical consequences.

  16. 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


    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

  17. 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


    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.

  18. On-road Bicycle Pavement Markings (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — A mile by mile breakdown of the on-street bicycle pavement markings installed within the City of Pittsburgh. These include bike lanes, shared lane markings...

  19. A Geographical Analysis of Bicycle Sharing Systems


    Médard De Chardon, Cyrille


    This thesis evaluates the performance of bicycle sharing systems (BSS), autonomous systems of accessible bicycles that can be easily used for one way trips, and determines whether they are successful at achieving promoted social and environmental outcomes through quantitative and qualitative methods. Such systems are typically surrounded by positive narratives of success, health, environmental and social benefits. This work challenges these notions. This thesis begins with the formalisation o...

  20. 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: [Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan (China); Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China)


    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.

  1. 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


    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.

  2. Expression and significance of c-Jun N-terminal protein kinase 1/2 protein in chronic hibernated myocardium of domestic pigs%家猪慢性冬眠心肌中C-Jun N末端蛋白激酶1/2蛋白的表达及意义

    Institute of Scientific and Technical Information of China (English)

    李东野; 朱红; 夏勇; 潘德峰; 杨煜; 李雷; 祁春梅


    背景:急性心肌缺血时c-Jun N末端蛋白激酶(c-Jun N-terminal protein kinase,JNK)被激活,并使得缺血损伤加重.慢性冬眠心肌组织中JNK的亚型--JNK1/2是否被激活及其在慢性冬眠心肌发生发展机制中的作用又是什么呢?目的:明确慢性冬眠心肌组织中JNK1/2的蛋白表达及其磷酸化(p-JNK1/2)的变化.设计:随机对照的实验研究.单位:徐州医学院附属医院心血管病研究所.材料和方法:在徐州医学院附属医院导管室进行动物模型的制备、在徐州医学院生化教研室测定JNK1/2的蛋白表达及其磷酸化(p-JNK1/2)的变化.将14只小型中国家猪随机分为实验组(n=8)与对照组(n=6).实验组以右冠状动脉为靶血管,经右股动脉送入自制的缩窄器,制备成慢性冬眠心肌及心肌梗死的模型.获取对照组心肌组织、实验组中的正常心肌组织及慢性冬眠心肌组织的样本进行光镜、电镜检查并采用免疫印迹(Western blotting)分析3组心肌组织的JNK1/2的蛋白表达及其磷酸化的变化.主要观察指标:慢性冬眠心肌组织中JNK1/2是否被活化.结果:实验组慢性冬眠心肌组织p-JNK1/2比实验组正常心肌组织、对照组心肌组织高.对照组、实验组正常心肌组织、实验组慢性冬眠心肌组织p-JNK1/2的免疫活性分别为1,1.42±0.52,2.6±0.59.结论:慢性冬眠心肌组织中JNK1/2被激活,并参与了慢性冬眠心肌的发生和发展.%BACKGROUND: Acute myocardial ischemia can activate the c-Jun N-terminal protein kinase(JNK) and, in turn, the ischemia damage can be aggravated by JNK. While in chronic hibernating myocardium, whether chronic myocardial ischemia can activate JNK1/2 or not and what is the role of JNK1/2 in developing the chronic hibernating myocardium, is not clear.OBJECTIVE :To identify protein expression of JNK1/2 and the p-JNK1/2 changes in chronic hibernating myocardium.DESIGN: Randomly controlled experimental research.SETTING: This

  3. 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. (United States)

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


    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.

  4. 转录因子c-fos/c-jun调控成釉细胞基质金属蛋白酶20基因的表达%c-fos/c-jun regulates extracellular matrix metalloproteinase 20 expression in ameloblasts

    Institute of Scientific and Technical Information of China (English)

    唐培娟; 王长磊; 宫春梅; 唐培倩; 郝建忠


    BACKGROUND:Matrix metaloproteinase 20 is a protease specificaly expressed in ameloblasts, which has an important role in dental enamel development. To study the regulatory mechanisms for matrix metaloproteinase 20 at the molecular level lays the foundation for further animal experiments. OBJECTIVE:To explore the regulatory effects of transcription factor c-fos/c-jun for matrix metaloproteinase 20 in mouse ameloblasts and to preliminarily confirm the role of c-fos/c-jun in enamel development. METHODS:First of al, a recombinant plasmid containing c-fos was established, and then dual-luciferase reporter assay system and RT-PCR were used to analyze the effects of c-fos, c-jun transfection of ameloblasts on the activity of matrix metaloproteinase 20. Furthermore, the effect of c-fos, c-jun on matrix metaloproteinase 20 was explored based on gene site-directed mutation and dual-luciferase reporter assay system. RESULTS AND CONCLUSION:Double luciferase report assay system and RT-PCR analysis showed that the mRNA expression of matrix metaloproteinase-20 was significantly upregulated after c-fos, c-jun transfection of ameloblasts, but c-fos/c-jun could not upregulate the transcriptional activity of matrix metaloproteinase 20 promoter when mutation occurred at AP1 binging site. These findings indicate that c-fos/c-jun has significant effects in regulating the mRNA expression of matrix metaloproteinase 20, which shows c-fos/c-jun plays an important biological meaning in enamel development.%背景:基质金属蛋白酶20是在成釉细胞中特异性表达的一种蛋白酶,其在牙齿釉质发育过程中具有重要作用。从分子角度研究基质金属蛋白酶20可受到的调控机制,为进一步做动物实验奠定基础。目的:通过研究转录因子c-fos/c-jun对小鼠成釉细胞基质金属蛋白酶20基因的调控作用,初步确定c-fos/c-jun在牙釉质发育中的作用。方法:首先构建 c-fos 真核表达载体重组质粒,分别利

  5. 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. (United States)

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


    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.

  6. 40 CFR 52.1162 - Regulation for bicycle use. (United States)


    ...: (i) For present bicycle riders, the origin, destination, frequency, travel time, distance and purpose... Section 52.1162 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS..., regional and local planning staffs, state, regional and local agencies, bicycle organizations and...

  7. Bicycling for transportation and health: the role of infrastructure. (United States)

    Dill, Jennifer


    This paper aims to provide insight on whether bicycling for everyday travel can help US adults meet the recommended levels of physical activity and what role public infrastructure may play in encouraging this activity. The study collected data on bicycling behavior from 166 regular cyclists in the Portland, Oregon metropolitan area using global positioning system (GPS) devices. Sixty percent of the cyclists rode for more than 150 minutes per week during the study and nearly all of the bicycling was for utilitarian purposes, not exercise. A disproportionate share of the bicycling occurred on streets with bicycle lanes, separate paths, or bicycle boulevards. The data support the need for well-connected neighborhood streets and a network of bicycle-specific infrastructure to encourage more bicycling among adults. This can be accomplished through comprehensive planning, regulation, and funding.

  8. Bicycling to school improves the cardiometabolic risk factor profile

    DEFF Research Database (Denmark)

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


    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....

  9. A Bicycle Safety Education Program for Parents of Young Children (United States)

    Lohse, Julie L.


    This study examined parental perceptions of the benefits and barriers to bicycle helmet use and their level of knowledge about bicycle safety issues. A school-based bicycle safety education program was taught to first- and second-grade students in a rural/suburban school district by a graduate nursing student. Pender's Health Promotion Model was…

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

    DEFF Research Database (Denmark)

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


    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)...

  11. On the Stability of a Bicycle on Rollers (United States)

    Cleary, Patricia A.; Mohazzabi, Pirooz


    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…

  12. An Analysis of Florida Physical Educators' Knowledge of Bicycle Laws (United States)

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


    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…

  13. Experiment study of effect of Valeriana officinalis var. latifolia on expression of C-Fos, C-Jun in hippocampus zone after focal cerebral ischemia%宽叶缬草对局灶性脑缺血后海马区C-Fos,C-Jun表达的实验研究

    Institute of Scientific and Technical Information of China (English)

    王云甫; 严洁; 黄朝芬; 何国厚


    AIM: To study influence of Valeriana officinalis var. latifolia(VOL) on expression of C-Fos, C-Jun after focal cerebral ischemia. METHODs: Inducing rat model of reversible middle cerebral artery occlusion(MCAO) using Koizumi' s intraluminal suture occlusion method. 48 male rats were divided into 5 groups randomly, pseudo-operation group, MCAO group, saline control group, VOL group. 2 hours after MCAO, we took gastric gavage with VOL and saline, 8 hour per time, and took out of brain to test C-Fos, C-Jun expression immunohistochemically at the 5th day after oper-ation. RESULTS: There was no positive cell in each hippocampus zone of ormal group; we observed C-Fos, C-Jun positive cells in each Hip-pocampus zone after MCAO; Density of C-Fos, C-Jun positive cells of VOL group were apparently lower than that of simple ischemia group. CON CLUSION: VOL can relieve histopathological lesions after cerebral is-chemia and promote protection function of rat through inhibiting the ex-pression of C-Fos, C-Jun expression.

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

    DEFF Research Database (Denmark)

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

    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...

  15. Bicyclic semigroups of left I-quotients

    CERN Document Server

    Ghroda, Nassraddin


    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.

  16. Safety effects of permanent running lights for bicycles

    DEFF Research Database (Denmark)

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


    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...

  17. 原癌基因c-jun在毒胡萝卜素内酯诱导小鼠胚胎成纤维细胞凋亡中的作用%The role of c-jun in thapsigargin-induced mouse fibroblast cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    张洁; 周方舟; 曹新冉; 任宏生; 楚玉峰; 王爱红; 董波; 赵鹏


    Objective To examine the impact of c-jun on thapsigargin-induced fibroblast cell apoptosis and address the mecha-nisms.Methods The thapsigargin was used to treat c-jun-/-mouse fibroblast cells,wild-type mouse fibroblasts and reconstitution of c-jun expression in c-jun-/-cells(c-jun Re).Cell viability was evaluated by trypan blue dye exclusion.Apoptosis was detected by fluorescence ac-tivated cell sorting(FACS)and DNA staining.c-jun,caspase-12,Grp78,Gadd153 and α-tubulin were analyzed by immunoblotting.Confocal images of cells loaded with the ER-Tracker and visualized by two-photon microscopy.Results Wild type(c-jun+/+),c-jun-/-and c-jun Re cells exhibited dramatic differences in sensitivity to TG.The c-jun-/-cells were the most sensitive,while c-jun Re cells were relatively resistant,to TG-induced cell death(P<0.05).TG treatment led to the activation of caspase-12,as indicated by the cleavage of procaspase-12, in c-jun-/-cells in a time-dependent manner.In contrast,caspase-12 activation was significantly attenuated in wild type fibroblast cells and abrogated in c-jun Re cells in response to TG treatment(P<0.05).c-jun-/-cells exhibited a large degree of apoptosis after treatment with TG,while c-jun Re cells demonstrated relative resistance to TG-induced apoptosis.c-jun-/-mouse fibroblast cells were more sensitive to TG-induced cell death compared to wild-type mouse fibroblasts,while reconstitution of c-jun expression in c-jun-/-cells(c-Jun Re)enhanced re-sistance to TG-induced cell death(P<0.05).The expression levels of ER chaperones Grp78 and Gadd153 induced by TG were lower in c-jun Re than those in c-jun-/-cells.ER-tracker found different patterns in the ER structure between c-jun-/-and c-jun Re cells.Conclusions Thapsigargin could cause mouse fibroblast cells apoptosis.c-jun gene expression changes of apoptosis degree,this change is mediated by endoplasmic reticulum stress.c-jun gene expression plays a protective role in thapsigargin-induced fibroblast cell

  18. 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


    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.

  19. 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


    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.

  20. 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. (United States)

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


    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.

  1. 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


    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

  2. The selective protein kinase C inhibitor, Ro-31-8220, inhibits mitogen-activated protein kinase phosphatase-1 (MKP-1) expression, induces c-Jun expression, and activates Jun N-terminal kinase. (United States)

    Beltman, J; McCormick, F; Cook, S J


    The role of protein kinase C (PKC) in inflammation, mitogenesis, and differentiation has been deduced in part through the use of a variety of PKC inhibitors. Two widely used inhibitors are the structurally related compounds GF109203X and Ro-31-8220, both of which potently inhibit PKC activity and are believed to be highly selective. While using GF109203X and Ro-31-8220 to address the role of PKC in immediate early gene expression, we observed striking differential effects by each of these two compounds. Growth factors induce the expression of the immediate early gene products MAP kinase phosphatase-1 (MKP-1), c-Fos and c-Jun. Ro-31-8220 inhibits growth factor-stimulated expression of MKP-1 and c-Fos but strongly stimulated c-Jun expression, even in the absence of growth factors. GF109203X displays none of these properties. These data suggest that Ro-31-8220 may have other pharmacological actions in addition to PKC inhibition. Indeed, Ro-31-8220 strongly stimulates the stress-activated protein kinase, JNK1. Furthermore, Ro-31-8220 apparently activates JNK in a PKC-independent manner. Neither the down-regulation of PKC by phorbol esters nor the inhibition of PKC by GF109203X affected the ability of Ro-31-8220 to activate JNK1. These data suggest that, in addition to potently inhibiting PKC, Ro-31-8220 exhibits novel pharmacological properties which are independent of its ability to inhibit PKC.

  3. 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.

  4. Estrogen receptor alpha, fos-related antigen-2, and c-Jun coordinately regulate human UDP glucuronosyltransferase 2B15 and 2B17 expression in response to 17beta-estradiol in MCF-7 cells. (United States)

    Hu, Dong Gui; Mackenzie, Peter I


    UDP-glucuronosyltransferase 2B15 and 2B17 expression is up-regulated by 17beta-estradiol in MCF-7 breast cancer cells, as assessed by quantitative real-time polymerase chain reaction. Using 5'-deletion mapping and site-directed mutagenesis, we demonstrate that 17beta-estradiol activation of UGT2B15 gene transcription is mediated by a 282-base pair fragment positioned -454 to -172 nucleotides from the translation start site. This region contains two putative activator protein-1 (AP-1) elements, one imperfect estrogen response element (ERE), and two consensus ERE half-sites. We propose that these five sites act as an estrogen response unit (ERU), because mutation in any site reduces activation of the UGT2B15 promoter by 17beta-estradiol. Despite the presence of two AP-1 elements, the UGT2B15 promoter is not responsive to the AP-1 activator phorbol 12-myristate 13-acetate. Although electrophoretic mobility shift assays (EMSA) indicate that the AP-1 proteins c-Jun and Fos-related antigen 2 (Fra-2) bound to the distal AP-1 site, binding of Jun or Fos family members to the proximal AP-1 site was not detected by EMSA. Chromatin immunoprecipitation assays showed a 17beta-estradiol-induced recruitment of estrogen receptor (ER) alpha, c-Jun, and Fra-2 to the 282-bp ERU. The involvement of these three transcription factors in the stimulation of UGT2B15 gene expression by 17beta-estradiol was confirmed by siRNA silencing experiments. Mutagenesis and siRNA experiments indicate that UGT2B17 expression is also regulated by 17beta-estradiol via the ERU, which is fully conserved in both promoters. Because UGT2B15 and UGT2B17 inactivate steroid hormones by glucuronidation, the regulation of their genes by 17beta-estradiol may maintain steroid hormone homeostasis and prevent excessive estrogen signaling activity.

  5. Dimerumic Acid Inhibits SW620 Cell Invasion by Attenuating H2O2-Mediated MMP-7 Expression via JNK/C-Jun and ERK/C-Fos Activation in an AP-1-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Bing-Ying Ho, Yao-Ming Wu, King-Jen Chang, Tzu-Ming Pan


    Full Text Available Reactive oxygen species (ROS such as hydrogen peroxide (H2O2 in the tumor microenvironment play important roles in tumor invasion and metastasis. Recently, ROS have been reported to cause a significant increase in the production and expression of matrix metalloproteinase (MMP-7, which is closely correlated with metastatic colorectal cancer. The present study was undertaken to evaluate the scavenging activity of dimerumic acid (DMA for H2O2 isolated from Monascus-fermented rice to investigate the inhibitory effects of DMA on the invasive potential of SW620 human colon cancer cells, and to explore the mechanisms underlying both these phenomena. Our results showed that increased MMP-7 expression due to H2O2 exposure was mediated by activation of mitogen-activated protein kinases (MAPKs such as Jun N-terminal kinase (JNK, extracellular-regulated kinase (ERK, and p38 kinase. DMA pretreatment suppressed activation of H2O2-mediated MAPK pathways and cell invasion. Moreover, H2O2-triggered MMP-7 production was demonstrated via JNK/c-Jun and ERK/c-Fos activation in an activating protein 1 (AP-1-dependent manner. Taken together, these results suggest that DMA suppresses H2O2-induced cell invasion by inhibiting AP-1-mediated MMP-7 gene transcription via the JNK/c-Jun and ERK/c-Fos signaling pathways in SW620 human colon cancer cells. Our data suggest that DMA may be useful in minimizing the development of colorectal metastasis. In the future, DMA supplementation may be a beneficial antioxidant to enhance surgical outcomes.

  6. The Effect of an All-Ages Bicycle Helmet Law on Bicycle-Related Trauma. (United States)

    Kett, Paula; Rivara, Frederick; Gomez, Anthony; Kirk, Annie Phare; Yantsides, Christina


    In 2003, Seattle implemented an all-ages bicycle helmet law; King County outside of Seattle had implemented a similar law since 1994. For the period 2000-2010, the effect of the helmet legislation on helmet use, helmet-preventable injuries, and bicycle-related fatalities was examined, comparing Seattle to the rest of King County. Data was retrieved from the Washington State Trauma Registry and the King County Medical Examiner. Results comparing the proportions of bicycle related head injuries before (2000-2002) and after (2004-2010) the law show no significant change in the proportion of bicyclists admitted to the hospital and treated for head injuries in either Seattle (37.9 vs 40.2 % p = 0.75) nor in the rest of King County (30.7 vs 31.4 %, p = 0.84) with the extension of the helmet law to Seattle in 2003. However, bicycle-related major head trauma as a proportion of all bicycle-related head trauma did decrease significantly in Seattle (83.9 vs 64.9 %, p = 0.04), while there was no significant change in King County (64.4 vs 57.6 %, p = 0.41). While the results do not show an overall decrease in head injuries, they do reveal a decrease in the severity of head injuries, as well as bicycle-related fatalities, suggesting that the helmet legislation was effective in reducing severe disability and death, contributing to injury prevention in Seattle and King County. The promotion of helmet use through an all ages helmet law is a vital preventative strategy for reducing major bicycle-related head trauma.

  7. 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.


    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

  8. System identification of the brompton bicycle (United States)

    Hladun, Monique Victoria Teresa

    The Brompton (a European folding design) bicycle was instrumented with a variety of sensors including acceleration, angular rate, speed, and steering sensors. A bicycle state estimator was designed to obtain additional information from this data including heading, turn rate, lean angle, steer rate, and positions of the wheels during a trajectory. The first part of the thesis describes the model setup for system identification including the Steer-to-Lean dynamics and Lean-to-Steer dynamics reduced models. CIFER software was used in the system identification process of these models. The second part describes the validation of the Empirical model by using the Rider Control model ([1]) and the Complete Rider/Vehicle model ([1]) to determine the feedback gains. The Theoretical model feedback gains were also determined by using the Rider Control model ([1]) and the Complete Rider/Vehicle model ([1]).

  9. Maximum Estrada Index of Bicyclic Graphs

    CERN Document Server

    Wang, Long; Wang, Yi


    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.

  10. Free Use of Bicycles at CERN

    CERN Multimedia


    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...

  11. 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


    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

  12. Estimating Bicycle and Pedestrian Demand in San Diego


    Jones, Michael; Buckland, Lauren


    This paper introduces the concepts behind estimating bicycle and pedestrian demand and provides an example of the development of a sketch-plan method for estimating bicycle and pedestrian demand from land use in San Diego County. The paper describes the methodology involved in collecting counts for the currently ongoing Seamless Travel project. The Seamless Travel project intends to develop a model for estimating bicycle and pedestrian demand within San Diego County. The project methodology i...

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

    Directory of Open Access Journals (Sweden)

    Lena eStorzer


    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

  14. Potential risk and its influencing factors for separated bicycle paths. (United States)

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


    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.

  15. Caffeine induces matrix metalloproteinase-2 (MMP-2) and MMP-9 down-regulation in human leukemia U937 cells via Ca2+/ROS-mediated suppression of ERK/c-fos pathway and activation of p38 MAPK/c-jun pathway. (United States)

    Liu, Wen-Hsin; Chang, Long-Sen


    Caffeine attenuated invasion of human leukemia U937 cells with characteristic of decreased protein expression and mRNA levels of matrix metalloproteinase-2 (MMP-2) and MMP-9. Down-regulation of MMP-2 and MMP-9 in U937 cells was abrogated by abolishment of caffeine-elicited increase in intracellular Ca(2+) concentration and ROS generation. Pretreatment with BAPTA-AM (Ca(2+) chelator) and N-acetylcysteine (ROS scavenger) abolished caffeine-induced ERK inactivation and p38 MPAK activation. Moreover, caffeine treatment led to MAPK phosphatase-1 (MKP-1) down-regulation and protein phosphatase 2A catalytic subunit (PP2Ac) up-regulation, which were involved in cross-talk between p38 MAPK and ERK. Transfection of constitutively active MEK1 or pretreatment with SB202190 (p38 MAPK inhibitor) restored MMP-2 and MMP-9 protein expression in caffeine-treated cells. Caffeine treatment repressed ERK-mediated c-Fos phosphorylation but evoked p38 MAPK-mediated c-Jun phosphorylation. Knock-down of c-Fos and c-Jun by siRNA reflected that c-Fos counteracted the effect of c-Jun on MMP-2/MMP-9 down-regulation. Taken together, our data indicate that MMP-2/MMP-9 down-regulation in caffeine-treated U937 cells is elicited by Ca(2+)/ROS-mediated suppression of ERK/c-Fos pathway and activation of p38 MAPK/c-Jun pathway.

  16. Solar Electric Bicycle Body Modeling and Simulation

    Directory of Open Access Journals (Sweden)

    Zhikun Wang


    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.

  17. On Wiener polarity index of bicyclic networks (United States)

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


    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.

  18. 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


    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.

  19. Activation of c-Jun N-terminal kinase (JNK) by widely used specific p38 MAPK inhibitors SB202190 and SB203580: a MLK-3-MKK7-dependent mechanism. (United States)

    Muniyappa, Harish; Das, Kumuda C


    Mitogen-activated protein kinases (MAPKs) are key signaling molecules that respond to mitogenic stimulation or environmental stress, resulting in the expression of target proteins. c-Jun N-terminal kinase (JNK) and p38 MAPKs are activated by inflammatory cytokines or environmental stress. Specific p38 MAPK inhibitors, such as SB202190 or SB203580, are widely used to dissect p38 MAPK-related signal transduction mechanisms. While using SB202190 to inhibit p38 MAPK-related signaling, we observed that SB202190 treatment could activate JNK. Further experiments showed that treatment of cells with SB202190 could phosphorylate JNK and activating transcription factor 2 (ATF-2), and increased AP-1 DNA binding. Using multiple cell lines and primary endothelial cells, we demonstrated that specific p38 MAPK inhibitors SB202190 or SB203580 induces the activation of the JNK pathway. Further, using with RNA interference and kinase-inactive expression of intermediates of the JNK pathway, we demonstrated SB202190- or SB203580-induced JNK activation is dependent on the MLK-3-MKK4/MKK7-dependent signal transduction pathway. Finally, we demonstrate that treatment of cells with SB202190 or SB203580 induces the phosphorylation and activation of MLK3.

  20. Retinoic acids acting through retinoid receptors protect hippocampal neurons from oxygen-glucose deprivation-mediated cell death by inhibition of c-jun-N-terminal kinase and p38 mitogen-activated protein kinase. (United States)

    Shinozaki, Y; Sato, Y; Koizumi, S; Ohno, Y; Nagao, T; Inoue, K


    Retinoic acids (RAs), including all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA), play fundamental roles in a variety of physiological events in vertebrates, through their specific nuclear receptors: retinoic acid receptor (RAR) and retinoid X receptor (RXR). Despite the physiological importance of RA, their functional significance under pathological conditions is not well understood. We examined the effect of ATRA on oxygen/glucose-deprivation/reperfusion (OGD/Rep)-induced neuronal damage in cultured rat hippocampal slices, and found that ATRA significantly reduced neuronal death. The cytoprotective effect of ATRA was observed not only in cornu ammonis (CA) 1 but also in CA2 and dentate gyrus (DG), and was attenuated by selective antagonists for RAR or RXR. By contrast, in the CA3 region, no protective effects of ATRA were observed. The OGD/Rep also increased phosphorylated forms of c-jun-N-terminal kinase (P-JNK) and p38 (P-p38) in hippocampus, and specific inhibitors for these kinases protected neurons. ATRA prevented the increases in P-JNK and P-p38 after OGD/Rep, as well as the decrease in NeuN and its shrinkage, all of which were inhibited by antagonists for RAR or RXR. These findings suggest that the ATRA signaling via retinoid receptors results in the inhibition of JNK and p38 activation, leading to the protection of neurons against OGD/Rep-induced damage in the rat hippocampus.

  1. c-Jun N-terminal kinase 2 prevents luminal cell commitment in normal mammary glands and tumors by inhibiting p53/Notch1 and breast cancer gene 1 expression. (United States)

    Cantrell, Michael A; Ebelt, Nancy D; Pfefferle, Adam D; Perou, Charles M; Van Den Berg, Carla Lynn


    Breast cancer is a heterogeneous disease with several subtypes carrying unique prognoses. Patients with differentiated luminal tumors experience better outcomes, while effective treatments are unavailable for poorly differentiated tumors, including the basal-like subtype. Mechanisms governing mammary tumor subtype generation could prove critical to developing better treatments. C-Jun N-terminal kinase 2 (JNK2) is important in mammary tumorigenesis and tumor progression. Using a variety of mouse models, human breast cancer cell lines and tumor expression data, studies herein support that JNK2 inhibits cell differentiation in normal and cancer-derived mammary cells. JNK2 prevents precocious pubertal mammary development and inhibits Notch-dependent expansion of luminal cell populations. Likewise, JNK2 suppresses luminal populations in a p53-competent Polyoma Middle T-antigen tumor model where jnk2 knockout causes p53-dependent upregulation of Notch1 transcription. In a p53 knockout model, JNK2 restricts luminal populations independently of Notch1, by suppressing Brca1 expression and promoting epithelial to mesenchymal transition. JNK2 also inhibits estrogen receptor (ER) expression and confers resistance to fulvestrant, an ER inhibitor, while stimulating tumor progression. These data suggest that therapies inhibiting JNK2 in breast cancer may promote tumor differentiation, improve endocrine therapy response, and inhibit metastasis.

  2. 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.


    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

  3. Bicycle-related maxillofacial injuries: a double-center study

    NARCIS (Netherlands)

    Boffano, P.; Roccia, F.; Gallesio, C.; Karagozoglu, K.H.; Forouzanfar, T.


    Objective Bicycle-related injuries account for an important proportion of road injuries all over the world. As only few reports have focused on the characteristics of maxillofacial fractures sustained in bicycle accidents, the purpose of this study was to present and compare epidemiological data abo

  4. 77 FR 39927 - Vehicles and Traffic Safety-Bicycles (United States)


    ... that, at a minimum, the plan: Evaluates the suitability of existing trail surface and soil condition for accommodating bicycle use, or prescribes a sustainable trail design for the construction of new... to look at whether to designate an existing trail or build a trail for bicycle use, but also as...

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

    NARCIS (Netherlands)


    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

  6. On Sum--Connectivity Index of Bicyclic Graphs

    CERN Document Server

    Du, Zhibin


    We determine the minimum sum--connectivity index of bicyclic graphs with $n$ vertices and matching number $m$, where $2\\le m\\le \\lfloor\\frac{n}{2}\\rfloor$, the minimum and the second minimum, as well as the maximum and the second maximum sum--connectivity indices of bicyclic graphs with $n\\ge 5$ vertices. The extremal graphs are characterized.

  7. Bicycle Freewheeling with Air Drag as a Physics Experiment (United States)

    Janssen, Paul; Janssens, Ewald


    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…

  8. Bicycle-related maxillofacial injuries : a double-center study

    NARCIS (Netherlands)

    Boffano, Paolo; Roccia, Fabio; Gallesio, Cesare; Karagozoglu, K. Hakki; Forouzanfar, Tymour


    Objective. Bicycle-related injuries account for an important proportion of road injuries all over the world. As only few reports have focused on the characteristics of maxillofacial fractures sustained in bicycle accidents, the purpose of this study was to present and compare epidemiological data ab

  9. Factors of the physical environment associated with walking and bicycling

    NARCIS (Netherlands)

    Wendel-Vos, G.C.W.; Schuit, A.J.; Niet, de R.; Boshuizen, H.C.; Saris, W.H.M.; Kromhout, D.


    PURPOSE: The purpose of this study was to identify factors of the physical environment that may influence time spent on walking and bicycling. METHODS: Demographic factors and time spent on walking and bicycling (during leisure time and for commuting purposes) were assessed with a self-administered

  10. Modeling of speed distribution for mixed bicycle traffic flow

    Directory of Open Access Journals (Sweden)

    Cheng Xu


    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.

  11. 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


    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.

  12. A mixed methods investigation of bicycle exposure in crash rates. (United States)

    Fournier, Nicholas; Christofa, Eleni; Knodler, Michael A


    Crash rates are an essential tool enabling researchers and practitioners to assess whether a location is truly more dangerous, or simply serves a higher volume of vehicles. Unfortunately, this simple crash rate is far more difficult to calculate for bicycles due to data challenges and the fact that they are uniquely exposed to both bicycle and automobile volumes on shared roadways. Bicycle count data, though increasingly more available, still represents a fraction of the available count data for automobiles. Further compounding on this, bicycle demand estimation methods often require more data than automobiles to account for the high variability that bicycle demand is subject to. This paper uses a combination of mixed methods to overcome these challenges and to perform an investigation of crash rates and exposure to different traffic volumes.

  13. Bicyclic Peptide Inhibitor of Urokinase-Type Plasminogen Activator

    DEFF Research Database (Denmark)

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


    The development of protease inhibitors for pharmacological intervention has taken a new turn with the use of peptidebased inhibitors. Here, we report the rational design of bicyclic peptide inhibitors of the serine protease urokinase-type plasminogen activator (uPA), based on the established...... monocyclic peptide, upain-2. It was successfully converted to a bicyclic peptide, without loss of inhibitory properties. The aim was to produce a peptide cyclised by an amide bond with an additional stabilising across-the-ring covalent bond. We expected this bicyclic peptide to exhibit a lower entropic...... burden upon binding. Two bicyclic peptides were synthesised with affinities similar to that of upain-2, and their binding energetics were evaluated by isothermal titration calorimetry. Indeed, compared to upain-2, the bicyclic peptides showed reduced loss of entropy upon binding to uPA. We also...

  14. Predicting bicycle setup for children based on anthropometrics and comfort. (United States)

    Grainger, Karl; Dodson, Zoe; Korff, Thomas


    Bicycling is a popular activity for children. In order for children to enjoy cycling and to minimize injury, it is important that they are positioned appropriately on the bicycle. The purpose of this study was therefore to identify a suitable bicycle setup for children aged between 7 and 16 years which accommodates developmental differences in anthropometrics, flexibility and perceptions of comfort. Using an adjustable bicycle fitting rig, we found the most comfortable position of 142 children aged 7 to 16. In addition, a number of anthropometric measures were recorded. Seat height and the horizontal distance between seat and handlebars were strongly predictable (R(2) > 0.999, p bicycle manufacturers.

  15. Dynamic Study of Bicycle Frame Structure (United States)

    Sani, M. S. M.; Nazri, N. A.; Zahari, S. N.; Abdullah, N. A. Z.; Priyandoko, G.


    Bicycle frames have to bear variety of loads and it is needed to ensure the frame can withstand dynamic loads to move. This paper focusing on dynamic study for bicycle frame structure with a purpose to avoid the problem regarding loads on the structure and to ensure the structure is safe when multiple loads are applied on it. The main objectives of dynamic study are to find the modal properties using two method; finite element analysis (FEA) and experimental modal analysis (EMA). The correlation between two studies will be obtained using percentage error. Firstly, 3D model of mountain bike frame structure has been draw using computer-aided design (CAD) software and normal mode analysis using MSC Nastran Patran was executed for numerical method meanwhile modal testing using impact hammer was performed for experimental counterpart. From the correlation result, it show that percentage error between FEA and EMA were below 10% due to noise, imperfect experiment setup during perform EMA and imperfect modeling of mountain bike frame structure in CAD software. Small percentage error differences makes both of the method can be applied to obtain the dynamic characteristic of structure. It is essential to determine whether the structure is safe or not. In conclusion, model updating method is required to reduce more percentage error between two results.

  16. Safe bicycling – Problems and solutions

    Directory of Open Access Journals (Sweden)

    Grecka M.


    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.

  17. The Design of Sport Bicycle Speed Odometer

    Directory of Open Access Journals (Sweden)

    Dongbing Liu


    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.

  18. Rates of bicycle helmet use in an affluent Michigan County. (United States)

    Jacques, L B


    Bicycle helmet use in the United States has remained low despite clear demonstration of its beneficial effect on reducing the incidence of serious head injury. Several interventions have been reported, with variable results and costs. Much of the recent literature has focused on child cyclists and on demographic factors associated with helmet use. This paper reports on helmet use by children and adults in a sample of 652 riders in an affluent southeast Michigan region, chosen to minimize the effect of previously recognized socioeconomic negative predictors that are not readily changed by intervention. Subjects were classified by age, sex, location, riding surface, type of bicycle, child bicycle seat use, child bicycle trailer use, and helmet use by companions. Overall helmet use was 24 percent; infants and toddlers had the highest rate of helmet use at 61 percent, followed by adults at 26 percent and school-aged children at 17 percent. The strongest predictor of helmet use in all age categories was the presence of a helmeted companion. Adult helmet use was also positively predicted by riding in the street and by riding a racing-type bicycle. The use of a city-type bicycle negatively predicted helmet use. For non-adults, female sex and the use of a child seat or trailer were positive predictors. Fostering peer pressure to increase helmet use may be an effective yet relatively inexpensive way to achieve the goal of widespread use of bicycle helmets.

  19. 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. (United States)

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


    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.

  20. Activation of c-Jun N-terminal kinase 1/2 regulated by nitric oxide is associated with neuronal survival in hippocampal neurons in a rat model of ischemia

    Institute of Scientific and Technical Information of China (English)

    ZENG Xian-wei; LI Ming-wei; PAN Jing; JI Tai-ling; YANG Bin; ZHANG Bo; WANG Xiao-qiang


    Background C-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in cerebral ischemia.Although the mechanistic basis for this activation of JNK1/2 is uncertain,oxidative stress may play a role.The purpose of this study was to investigate whether the activation of JNK1/2 is associated with the production of endogenous nitric oxide (NO).Methods Ischemia and reperfusion (I/R) was induced by cerebral four-vessel occlusion.Sprague-Dawley (SD) rats were divided into 6 groups:sham group,I/R group,neuronal nitric oxide synthase (nNOS) inhibitor (7-nitroindazole,7-NI)given group,inducible nitric oxide synthase (iNOS) inhibitor (2-amino-5,6-dihydro-methylthiazine,AMT) given group,sodium chloride control group,and 1% dimethyl sulfoxide (DMSO) control group.The levels of protein expression and phospho-JNK1/2 were detected by Western blotting and the survival hippocampus neurons in CA1 zone were observed by cresyl violet staining.Results The study illustrated two peaks of JNK1/2 activation occurred at 30 minutes and 3 days during reperfusion.7-NI inhibited JNK1/2 activation during the early reperfusion,whereas AMT preferably attenuated JNK1/2 activation during the later reperfusion.Administration of 7-NI and AMT can decrease I/R-induced neuronal loss in hippocampal CA1 region.Conclusion JNK1/2 activation is associated with endogenous NO in response to ischemic insult.

  1. 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. (United States)

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


    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.

  2. Pregnane X Receptor Activation Attenuates Inflammation-Associated Intestinal Epithelial Barrier Dysfunction by Inhibiting Cytokine-Induced Myosin Light-Chain Kinase Expression and c-Jun N-Terminal Kinase 1/2 Activation. (United States)

    Garg, Aditya; Zhao, Angela; Erickson, Sarah L; Mukherjee, Subhajit; Lau, Aik Jiang; Alston, Laurie; Chang, Thomas K H; Mani, Sridhar; Hirota, Simon A


    The inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a complex etiology. IBD is thought to arise in genetically susceptible individuals in the context of aberrant interactions with the intestinal microbiota and other environmental risk factors. Recently, the pregnane X receptor (PXR) was identified as a sensor for microbial metabolites, whose activation can regulate the intestinal epithelial barrier. Mutations in NR1I2, the gene that encodes the PXR, have been linked to IBD, and in animal models, PXR deletion leads to barrier dysfunction. In the current study, we sought to assess the mechanism(s) through which the PXR regulates barrier function during inflammation. In Caco-2 intestinal epithelial cell monolayers, tumor necrosis factor-α/interferon-γ exposure disrupted the barrier and triggered zonula occludens-1 relocalization, increased expression of myosin light-chain kinase (MLCK), and activation of c-Jun N-terminal kinase 1/2 (JNK1/2). Activation of the PXR [rifaximin and [[3,5-Bis(1,1-dimethylethyl)-4-hydroxyphenyl]ethenylidene]bis-phosphonic acid tetraethyl ester (SR12813); 10 μM] protected the barrier, an effect that was associated with attenuated MLCK expression and JNK1/2 activation. In vivo, activation of the PXR [pregnenolone 16α-carbonitrile (PCN)] attenuated barrier disruption induced by toll-like receptor 4 activation in wild-type, but not Pxr-/-, mice. Furthermore, PCN treatment protected the barrier in the dextran-sulfate sodium model of experimental colitis, an effect that was associated with reduced expression of mucosal MLCK and phosphorylated JNK1/2. Together, our data suggest that the PXR regulates the intestinal epithelial barrier during inflammation by modulating cytokine-induced MLCK expression and JNK1/2 activation. Thus, targeting the PXR may prove beneficial for the treatment of inflammation-associated barrier disruption in the context of IBD.

  3. 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


    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.

  4. Arrestin-3 binds c-Jun N-terminal kinase 1 (JNK1) and JNK2 and facilitates the activation of these ubiquitous JNK isoforms in cells via scaffolding. (United States)

    Kook, Seunghyi; Zhan, Xuanzhi; Kaoud, Tamer S; Dalby, Kevin N; Gurevich, Vsevolod V; Gurevich, Eugenia V


    Non-visual arrestins scaffold mitogen-activated protein kinase (MAPK) cascades. The c-Jun N-terminal kinases (JNKs) are members of MAPK family. Arrestin-3 has been shown to enhance the activation of JNK3, which is expressed mainly in neurons, heart, and testes, in contrast to ubiquitous JNK1 and JNK2. Although all JNKs are activated by MKK4 and MKK7, both of which bind arrestin-3, the ability of arrestin-3 to facilitate the activation of JNK1 and JNK2 has never been reported. Using purified proteins we found that arrestin-3 directly binds JNK1α1 and JNK2α2, interacting with the latter comparably to JNK3α2. Phosphorylation of purified JNK1α1 and JNK2α2 by MKK4 or MKK7 is increased by arrestin-3. Endogenous arrestin-3 interacted with endogenous JNK1/2 in different cell types. Arrestin-3 also enhanced phosphorylation of endogenous JNK1/2 in intact cells upon expression of upstream kinases ASK1, MKK4, or MKK7. We observed a biphasic effect of arrestin-3 concentrations on phosphorylation of JNK1α1 and JNK2α2 both in vitro and in vivo. Thus, arrestin-3 acts as a scaffold, facilitating JNK1α1 and JNK2α2 phosphorylation by MKK4 and MKK7 via bringing JNKs and their activators together. The data suggest that arrestin-3 modulates the activity of ubiquitous JNK1 and JNK2 in non-neuronal cells, impacting the signaling pathway that regulates their proliferation and survival.

  5. 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. (United States)

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


    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.

  6. 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.

  7. 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...

  8. Bicycle helmet ventilation and comfort angle dependence. (United States)

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


    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.

  9. Beijing Bicycle - Stories from a Transformative Space

    DEFF Research Database (Denmark)

    Bagger-Petersen, Mai Corlin


    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...... relevant in a new context – that of the Chinese mainland society in the 21st century. Doreen Massey (2005: 9) defines space as “a simultaneity of stories-so-far”, a space that is constantly exploding and imploding with the influx of new and old stories. Within this theoretical framework Wang Xiaoshuai...

  10. Bicyclic graphs with maximal revised Szeged index

    CERN Document Server

    Li, Xueliang


    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 $n \\geq 6$:

  11. Bamboo Bicycle – Past or Future?

    Directory of Open Access Journals (Sweden)

    Suzana Jakovljević


    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.

  12. 补益营卫方、TGFβ1及bFGF对衰老人皮肤成纤维细胞c-Jun基因表达的影响%c-Jun Gene Expression Of The Recipe Of Supplementing Ying-wei And TGF-β1 And bFGF In the aging Human Skin Fibroblasts

    Institute of Scientific and Technical Information of China (English)

    周小平; 司晓伟; 徐武清; 俞洋


    进c-Jun基因表达存在不依赖于TGF-β1和bFGF的途径.bFGF蛋白是TGF-β1信号调节途径的下游蛋白;是c-Jun基因表达的重要促进因子.%Objective To study the c-Jun gene expression influenced by the recipe of supplementing Ying-wei and transforming growth factor-β1(TGF-β1) and basic fibroblast growth factor(bFGF) in the aging human skin fibroblasts. Methods Firstly,to copy the aging model of human skin fibroblasts by continuous passage culturing.Secondly,to detect the c-Jun gene expression of the aging human skin fibroblasts through the fluorescent quantitative PCR method,after neutralizing antibody blocking TGF-β1 and bFGF. Results When the human skin fibroblasts aging,the expressive level of c-Jun gene,compared to that of young skin fibroblasts,falls by 70%and 71%in 24h and 48h.But theexpressive levels in 72h are both similar.As aging human skin fibroblasts treated by the recipe of supplementing Ying-wei,the c-Jun gene expression which has increased to 4.67 times and 2.12 times in 24h and 48h,has significantly improved,compared to the aging human skin fibroblasts.And the expressive levels of them are equivalent in 72h.After neutralizing TGF-β1 protein,c-Jun gene expressive level of the aging human skin fibroblasts is 2.4 times and 1.7 times as large as that of young skin fibroblasts in 24h and 72h.In 48h,the gene expressive level of young skin fibroblasts is 9.2 times as large as that of aging human skin fibroblasts.After using the recipe of supplementing Ying-wei,the c-Jun gene expression of aging human skin fibroblasts has improved obviously.The c-Jun gene expressive level of human skin fibroblasts raise by 2.3 times and 1.5 times in 48h and 72h.After neutralizing TGF-β1 protein and bFGF protein,c-Jun gene expressive level is decreased obviously with different time;Compared with the young skin fibroblasts,c-Jun gene expression of the aging human skin fibroblasts falls by 64.5%,94.2%and 73.7%in 24h,48h and 72h.As aging human skin

  13. 脑溢安对出血性中风大鼠脑内磷酸化蛋白激酶表达的影响%Effect of Nao Yi An on the Expression of P-C-Jun in the Brain of Experimental Intracerebral Hemorrhagic Rat

    Institute of Scientific and Technical Information of China (English)

    聂亚雄; 黎杏群; 袁梦石; 张花先; 张化彪; 唐涛


    To investigate the effect of traditional Chinese medicine Nao Yi An (NYA) on the expression of P-C-Jun in the brain of experimental intracerebral hemorrhagic rat.The rats were randomly divided into the normal control group,the model control group and NYA treatment group.By injecting collagenase type Ⅶ stereotaxically into the right globas pallidus,rat models with haemorrhagic stroke were made.We investigated the changes of the expression of P-CJun in the piriform cortex of the rats.Results:The expression of P-C-Jun in NYA group was weaker than that in the model control group(P<0.05).Conclusion:NYA interferes in the expression of P-C-Jun in the brain of rat models with haemorrhagic stroke,and affects the MAPK signal transduction.%探讨脑溢安对出血性中风大鼠脑内磷酸化蛋白激酶(P-C-Jun)表达的影响和治疗机理。根据Roserberg法复制大鼠脑出血模型,采用免疫组织化学方法观察脑出血后梨状皮质内P-C-Jun的表达变化,并用组织病理学方法分析脑皮质内神经元的损伤状况。结果:脑溢安治疗组较模型组脑内P-C-Jun蛋白表达弱,神经元受损状况轻。结论:脑溢安下调脑内P-C-Jun蛋白表达,从而干预了丝裂原活化的蛋白激酶(MAPK)信号转导通路。

  14. 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. (United States)

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


    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.

  15. Associations between bicycling and carotid arterial stiffness in adolescents

    DEFF Research Database (Denmark)

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


    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...... Youth Heart Study. Total frequency of bicycle usage was assessed by self-report, and carotid arterial stiffness was assessed using B-mode ultrasound. After adjusting for pubertal status, body height, and objectively measured physical activity and other personal lifestyle and demographic factors, boys...... 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. 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.

  17. On the Skill of Balancing While Riding a Bicycle. (United States)

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


    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.

  18. 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


    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.

  19. [Bicycle spoke-related injuries in children: emphasise prevention]. (United States)

    Kramer, William L M; Haaring, Gert-Jan


    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.

  20. Bicycle helmet use and non-use - recently published research. (United States)

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


    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.

  1. 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.


    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

  2. 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;


    Objectives To study cyclists’ share of transport modes (modal share) and single-bicycle crashes (SBCs) in different countries in order to investigate if the proportion of cyclist injuries resulting from SBCs is affected by variation in modal share. Methods A literature search identified figures...... (largely from western countries) on SBC casualties who are fatally injured, hospitalised or treated at an emergency department. Correlation and regression analyses were used to investigate how bicycle modal share is related to SBCs. Results On average, 17% of fatal injuries to cyclists are caused by SBCs...... 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...

  3. 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


    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

  4. 表达人JNK基因重组腺病毒的构建和鉴定%Construction and identification of expressing human c-Jun N-terminal kinase(JNK)recombinant adenovirus

    Institute of Scientific and Technical Information of China (English)

    陈金虎; 刘慧霞; 张佳妮; 郭敏; 全养雅; 谭莺


    Objective To construct replication deficient recombinant adenovirus expressing human c-Jun N-terminal kinase by homologous recombination.Methods The linearized recombinant shuttle vector pAdTrack-CMV-WT-JNK was co-transformed with backbone vector pAdEasy-1 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 adenovirus was detected by PCR and DNA sequencing.Results JNK recombinant adenoviral vector was effectively transfected into HEK 293 cells and was 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 animal experiment confirmed that Ad-WT-JNK was effectivety expressed in liver tissue. Conclusion The research successfully constructed recombinant adenoviral vector and recombinant adenoviral particle.And 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.方法 将重组穿梭载体pAdTrack-CMV-WT-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.将重组腺病毒载体转染入包装细胞HEK293内制备复制缺陷型重组腺病毒,并经PCR及DNA测序鉴定.结果 JNK重组腺病毒载体能有效转染HEK293细胞并在细胞内成功包装,5 d后可以观察到绿色荧光蛋白(GFP)明显表达,搜集的病毒经过PCR扩增得到特定JNK基因片段并测序鉴定.动物实验证实构建的Ad-WT-JNK能有效在肝组织表达.结论 该研究成功构建了JNK重组腺病毒载体及相应重组腺病毒颗粒,为进一步研究JNK的作用及应用JNK进行相关疾病的基因治疗奠定了基础.

  5. Independent repression of bile acid synthesis and activation of c-Jun N-terminal kinase (JNK) by activated hepatocyte fibroblast growth factor receptor 4 (FGFR4) and bile acids. (United States)

    Yu, Chundong; Wang, Fen; Jin, Chengliu; Huang, Xinqiang; McKeehan, Wallace L


    The fibroblast growth factor (FGF) receptor complex is a regulator of adult organ homeostasis in addition to its central role in embryonic development and wound healing. FGF receptor 4 (FGFR4) is the sole FGFR receptor kinase that is significantly expressed in mature hepatocytes. Previously, we showed that mice lacking mouse FGFR4 (mR4(-/-)) exhibited elevated fecal bile acids, bile acid pool size, and expression of liver cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme for canonical neutral bile acid synthesis. To prove that hepatocyte FGFR4 was a negative regulator of cholesterol metabolism and bile acid synthesis independent of background, we generated transgenic mice overexpressing a constitutively active human FGFR4 (CahR4) in hepatocytes and crossed them with the FGFR4-deficient mice to generate CahR4/mR4(-/-) mice. In mice expressing active FGFR4 in liver, fecal bile acid excretion was 64%, bile acid pool size was 47%, and Cyp7a1 expression was 10-30% of wild-type mice. The repressed level of Cyp7a1 expression was resistant to induction by a high cholesterol diet relative to wild-type mice. Expression of CahR4 in mR4(-/-) mouse livers depressed bile acid synthesis below wild-type levels from the elevated levels observed in mR4(-/-). Levels of phosphorylated c-Jun N-terminal kinase (JNK), which is part of a pathway implicated in bile acid-mediated repression of synthesis, was 30% of wild-type levels in mR4(-/-) livers, whereas CahR4 livers exhibited an average 2-fold increase. However, cholate still strongly induced phospho-JNK in mR4(-/-) livers. These results confirm that hepatocyte FGFR4 regulates bile acid synthesis by repression of Cyp7a1 expression. Hepatocyte FGFR4 may contribute to the repression of bile acid synthesis through JNK signaling but is not required for activation of JNK signaling by bile acids.


    Directory of Open Access Journals (Sweden)

    Mykea Mcknight


    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

  7. Analysis of EMG measurements during bicycle pedalling. (United States)

    Jorge, M; Hull, M L


    Activity of eight leg muscles has been monitored for six test subjects while pedalling a bicycle on rollers in the laboratory. Each electromyogram (EMG) data channel was digitized at a sampling rate of 2 kHz by a minicomputer. Data analysis entailed generating plots of both EMG activity regions and integrated EMG (IEMG). For each test subject, data were recorded for five cases of pedalling conditions. The different pedalling conditions were defined to explore a variety of research hypotheses. This exploration has led to the following conclusions: Muscular activity levels of the quadriceps are influenced by the type of shoes worn and activity levels increase with soft sole shoes as opposed to cycling shoes with cleats and toeclips. EMG activity patterns are not strongly related to pedalling conditions (i.e. load, seat height and shoe type). The level of muscle activity, however, is significantly affected by pedalling conditions. Muscular activity bears a complex relationship with seat height and quadriceps activity level decreases with greater seat height. Agonist (i.e. hamstrings) and antagonist (i.e. quadriceps) muscles of the hip/knee are active simultaneously during leg extension. Regions of peak activity levels, however, do not overlap. The lack of significant cocontraction of agonist/antagonist muscles enables muscle forces during pedalling action to be computed by solving a series of equilibrium problems over different regions of the crank cycle. Regions are defined and a solution procedure is outlined.

  8. Bicycle, city and education: search moves

    Directory of Open Access Journals (Sweden)

    Sheila Hempkemeyer


    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.

  9. Reviving a ghost in the history of technology: the social construction of the recumbent bicycle. (United States)

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


    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.

  10. Built environment influences on healthy transportation choices: bicycling versus driving. (United States)

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


    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.

  11. How similar are two-unit bicycle and motorcycle crashes? (United States)

    Haworth, Narelle; Debnath, Ashim Kumar


    This paper explores the similarities and differences between bicycle and motorcycle crashes with other motor vehicles. If similar treatments can be effective for both bicycle and motorcycle crashes, then greater benefits in terms of crash costs saved may be possible for the same investment in treatments. To reduce the biases associated with under-reporting of these crashes to police, property damage and minor injury crashes were excluded. The most common crash type for both bicycles (31.1%) and motorcycles (24.5%) was intersection from adjacent approaches. Drivers of other vehicles were coded most at fault in the majority of two-unit bicycle (57.0%) and motorcycle crashes (62.7%). The crash types, patterns of fault and factors affecting fault were generally similar for bicycle and motorcycle crashes. This confirms the need to combat the factors contributing to failure of other drivers to yield right of way to two-wheelers, and suggest that some of these actions should prove beneficial to the safety of both motorized and non-motorized two-wheelers. In contrast, child bicyclists were more often at fault, particularly in crashes involving a vehicle leaving the driveway or footpath. The greater reporting of violations by riders and drivers in motorcycle crashes also deserves further investigation.

  12. Predicting Public Bicycle Adoption Using the Technology Acceptance Model

    Directory of Open Access Journals (Sweden)

    Benjamin T. Hazen


    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.

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

    DEFF Research Database (Denmark)

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


    of interventions in bicycle infrastructure on travel choices, safety, design appreciation, and other factors. These clarify under which conditions certain measures are effective or not and inform about the effectiveness of improving a single route versus upgrading a whole network. The information from the studies...... to be still generally valid. In addition to studies that traditionally focus on dedicated bicycle infrastructure, two cases of shared space are discussed, a rather new type of intervention that assumes mixed use of infrastructure. One case is from Denmark, the other from the Netherlands. The paper will so...... uncover the valuable results of the possibly largest evaluations of interventions in bicycle infrastructure ever made, verify these by examining more recent studies, and contribute to the discussion of shared space....

  14. Bicycling to Work and Primordial Prevention of Cardiovascular Risk

    DEFF Research Database (Denmark)

    Grøntved, Anders; Koivula, Robert W; Johansson, Ingegerd


    BACKGROUND: Bicycling to work may be a viable approach for achieving physical activity that provides cardiovascular health benefits. In this study we investigated the relationship of bicycling to work with incidence of obesity, hypertension, hypertriglyceridemia, and impaired glucose tolerance...... across a decade of follow-up in middle-aged men and women. METHODS AND RESULTS: We followed 23 732 Swedish men and women with a mean age of 43.5 years at baseline who attended a health examination twice during a 10-year period (1990-2011). In multivariable adjusted models we calculated the odds......% CI 0.74-0.91) compared with participants not cycling to work at both times points or who switched from cycling to other modes of transport during follow-up. CONCLUSIONS: These data suggest that commuting by bicycle to work is an important strategy for primordial prevention of clinical cardiovascular...

  15. Use and activity levels on newly built bicycle playgrounds

    DEFF Research Database (Denmark)

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


    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 defence...... circle around the City of Copenhagen, the Copenhagen Fortifications. The concept of a bicycle playground is new, and to examine how the three areas were used, and explore how users experience the areas, this study was designed as a combination of systematic observations, using the System for Observing...... Play and Recreation in Communities (SOPARC), and short on-site interviews with ‘typical users’. Based on the structural observations and 12 short interviews it became clear that 63% of the users were active during their use. The bicycle playgrounds main users were teenagers and children, especially...

  16. 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


    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.

  17. 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...... and bicycling. The study shows that instruments that improve the cyclists’ speed and increase the car drivers’ time consumption and costs will influence the competition conditions significantly. The total transfer potential will be between 12 and 16 % of the car trips in case of short tours, equivalent to 1...

  18. Efficiency of choice set generation methods for bicycle routes

    DEFF Research Database (Denmark)

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


    The current study analyses the efficiency of choice set generation methods for bicycle routes and proposes the extension of cost functions to bicycle-oriented factors not limited to distance and time. Three choice set generation methods for route choice were examined in their ability to generate...... relevant and heterogeneous routes: doubly stochastic generation function, breadth first search on link elimination, and branch & bound algorithm. Efficiency of the methods was evaluated for a high-resolution network by comparing the performances with four multi-attribute cost functions accounting...... generated realistic routes, while the former outperformed in computation cost and the latter produced more heterogeneous routes....

  19. 16 CFR Figure 8 to Part 1512 - Reflectorized Bicycle Wheel Rim Abrasion Test Device (United States)


    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Reflectorized Bicycle Wheel Rim Abrasion... HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR BICYCLES Pt. 1512, Fig. 8 Figure 8 to Part 1512—Reflectorized Bicycle Wheel Rim Abrasion Test Device EC03OC91.074...

  20. 16 CFR Figure 1 to Part 1512 - Bicycle Front Fork Cantilever Bending Test Rig (United States)


    ... 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 SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR BICYCLES Pt. 1512, Fig. 1 Figure 1 to Part 1512—Bicycle...

  1. Bicycle Training for Youth with Down Syndrome and Autism Spectrum Disorders (United States)

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


    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…

  2. Head injuries and bicycle helmet laws. (United States)

    Robinson, D L


    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

  3. 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)


    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.

  4. Experimental and mathematical car-bicycle collision simulations.

    NARCIS (Netherlands)

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


    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

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

    CERN Document Server

    Guemez, Julio


    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.

  6. Nonfatal bicycle accident risk after an evening of alcohol consumption

    NARCIS (Netherlands)

    Verster, J.C.; van Herwijnen, J.; Volkerts, E.R.; Olivier, B.


    Introduction: After an evening of alcohol consumption, blood alcohol concentration (BAC) may reach intoxication levels above legal limits for operating a car or bicycle. In the Netherlands, legal limits for participating in traffic are 0.05% for experienced drivers and 0.02% for novice drivers. The

  7. The safety impact of a yellow bicycle jacket

    DEFF Research Database (Denmark)

    Lahrmann, Harry; Madsen, Tanja Kidholm Osmann; Olesen, Anne Vingaard


    The hypothesis of this project is that the safety of cyclists can be improved by increasing their visibility in traffic. This is explored by testing whether or not a high-visibility bicycle jacket (colour and reflectors) will increase the safety of cyclists. The project has been carried out...... as a randomized controlled trial with 6,800 volunteer cyclists. After random selection, half of the group – the test group – got the bicycle jacket at once and promised to wear it each time they biked during a year. The other half of the group composed a control group that got the bicycle jacket after the closing...... 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...

  8. "Walking" Along a Free Rotating Bicycle Wheel (Round and Round) (United States)

    Güémez, J.; Fiolhais, M.


    We describe the kinematics, dynamics, and also some energy issues related to Marta mouse's motion when she walks on top of a horizontal bicycle wheel, which is free to rotate like a merry-go-round, as presented recently by Paul Hewitt in the "Figuring Physics" section of this journal. The situation is represented in Fig. 1, which was…

  9. Bicyclic graphs with exactly two main signless Laplacian eigenvalues

    CERN Document Server

    Huang, He


    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.

  10. Embedding the bicyclic semigroup into countably compact topological semigroups

    CERN Document Server

    Banakh, Taras; Gutik, Oleg


    We study algebraic and topological properties of topological semigroups containing a copy of the bicyclic semigroup $C(p,q)$. We prove that each topological semigroup $S$ with pseudocompact square contains no dense copy of $C(p,q)$. On the other hand, we construct a consistent example of a Tychonov countably compact semigroup containing a copy of $C(p,q)$.

  11. Utilizing the Bicycle for Non-Traditional Activities (United States)

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


    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…

  12. Consequences of Underestimating Impalement Bicycle Handlebar Injuries in Children. (United States)

    Ramos-Irizarry, Carmen T; Swain, Shakeva; Troncoso-Munoz, Samantha; Duncan, Malvina

    Impalement bicycle handlebar trauma injuries are rare; however, on initial assessment, they have the potential of being underestimated. We reviewed our prospective trauma database of 3,894 patients for all bicycle injuries from January 2010 to May 2015. Isolated pedal bike injuries were reported in 2.6% (N = 101) of the patients who were admitted to the trauma service. Fifteen patients suffered direct handlebar trauma. Patients were grouped into blunt trauma (n = 12) and impalement trauma (n = 3). We examined gender, age, injury severity score (ISS), Glasgow Coma Scale score, use of protective devices, need for surgical intervention, need for intensive care (ICU), and hospital length of stay. Mean age was 9.6 years. All children with penetrating injuries were males. Mean ISS was less than 9 in both groups. None of the children were wearing bicycle helmets. Three patients who sustained blunt injuries required ICU care due to associated injuries. All of the children with impalement injuries required several surgical interventions. These injuries included a traumatic direct inguinal hernia, a medial groin and thigh laceration with resultant femoral hernia, and a lateral deep thigh laceration. Impalement bicycle handlebar injuries must be thoroughly evaluated, with a similar importance given to blunt injuries. A high index of suspicion must be maintained when examining children with handlebar impalement injuries, as they are at risk for missed or underestimation of their injuries.

  13. How Fast Can You Go on a Bicycle? (United States)

    Dunning, R. B.


    The bicycle provides a context-rich problem accessible to students in a first-year physics course, encircling several core physics principles such as conservation of total energy and angular momentum, dissipative forces, and vectors. In this article, I develop a simple numerical model that can be used by any first-year physics student to…

  14. Expedition Paris-Beijing by Bicycle 2008 Launched

    Institute of Scientific and Technical Information of China (English)


    <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.

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

    DEFF Research Database (Denmark)

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


    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...

  16. Power assist control of electric bicycle taking environment and rider's condition into account (United States)

    Niki, Hiroshi; Miyata, Junichi; Murakami, Toshiyuki


    Recently, bicycles are widely used as a convenient transportation tool. But from a viewpoint of wide use for the future aging society, it is problem to pedal on rider's own. As well known, power assistance bicycle has already been used. The power assistance bicycle helps the elderly people or the people who has weak legs to expand their field. However, existing power assistance bicycle doesn't take running environment and rider's condition into account. The new control algorithm for power assistance bicycle is proposed in this paper. Human input and running friction are estimated as a disturbance torque with a disturbance observer. By using high pass filter (HPF), human input is separated from running friction. This method realizes power assistance bicycle without torque sensor. Disturbance observer compensates running friction. Compliance control is applied to make the bicycle have desired compliance. The effectiveness of this control algorithm is verified by numerical and experimental results.

  17. 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


    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.

  18. Chest Traumas due to Bicycle accident in Childhood

    Directory of Open Access Journals (Sweden)

    Ufuk Cobanoglu


    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


    Toi, Satoshi; Kajita, Yoshitaka; Nishikawa, Shuichirou

    This study aims to find an effective removal method of illegal parking bicycles based on the analysis on the numerical change of illegal bicycles. And then, we built the time and space quantitative distribution model of illegal parking bicycles after removal, considering the logistic increase of illegal parking bicycles, several behaviors concerning of direct return or indirect return to the original parking place and avoidance of the original parking place, based on the investigation of real condition of illegal bicycle parking at TENJIN area in FUKUOKA city. Moreover, we built the simulation model including above-mentioned model, and calculated the number of illegal parking bicycles when we change the removal frequency and the number of removal at one time. The next interesting four results were obtained. (1) Recovery speed from removal the illegal parking bicycles differs by each zone. (2) Thorough removal is effective to keep the number of illegal parking bicycles lower level. (3) Removal at one zone causes the increase of bicycles at other zones where the level of illegal parking is lower. (4) The relationship between effects and costs of removing the illegal parking bicycles was clarified.

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

    Directory of Open Access Journals (Sweden)

    Marilson Kienteka


    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.

  1. 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.


    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

  2. BUGS at work : a bicycle user group guide

    Energy Technology Data Exchange (ETDEWEB)



    This guide provides practical advice to cyclists on how start a Bicycle User Group (BUG) at their workplace. It offers tools to encourage employers to be proactive in improving facilities in support of cycle commuting. Several BUGs across Canada have worked towards getting better bicycle parking, lockers and shower facilities at their workplace. Other incentives include policies such as flexible work hours for cyclist commuters; casual dress on Friday; reimbursement for the subsidized cost of free parking provided by employers; and, use of a company car if needed for company business during the work day. The advantages to employers include: reduced health care costs because cyclists are physically fit; decreased absenteeism; increased productivity; reduced parking costs; lower company transportation bills; and, a greener corporate image. BUGs provide cycling information ranging from cycling maps to pamphlets and they raise cycle awareness. This guide includes cycling survey samples and examples of successful BUG activities across Canada. refs., tabs., figs.

  3. 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


    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.

  4. Rates of bicycle helmet use in an affluent Michigan County.


    Jacques, L B


    Bicycle helmet use in the United States has remained low despite clear demonstration of its beneficial effect on reducing the incidence of serious head injury. Several interventions have been reported, with variable results and costs. Much of the recent literature has focused on child cyclists and on demographic factors associated with helmet use. This paper reports on helmet use by children and adults in a sample of 652 riders in an affluent southeast Michigan region, chosen to minimize the ...

  5. Optimal Design of Mountain Bicycle Based on Biomechanics

    Institute of Scientific and Technical Information of China (English)

    卜研; 黄田; 项忠霞; 吴小凡; 陈春


    To achieve better cycling performance and vibration comfort of mountain bicycle, the optimization of frame structural parameters and rear suspension scale parameters is investigated based on biomechanics.Firstly, the quadratic sum of rider lower limb muscles stresses is presented as the evaluation criterion of muscle fatigue.By taking the criterion as the objective function, the relative positions of three pivot points of frame are optimized to ensure that the frame structural parameters match the stature o...

  6. Traffic conflicts on bicycle paths: a systematic observation of behaviour from video. (United States)

    van der Horst, A Richard A; de Goede, Maartje; de Hair-Buijssen, Stefanie; Methorst, Rob


    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 traffic. As the usage of bicycle paths steadily increases, it is to be expected that safety on bicycle paths will become a major issue in the coming years in The Netherlands. A study was conducted into the behaviour of bicyclists and moped riders to improve traffic safety on bicycle paths. By behavioural observations with video, mutual conflicts and bicyclist behaviour on bicycle paths were recorded and analysed, among other things by means of the conflict observation method DOCTOR (Dutch Objective Conflict Technique for Operation and Research). The explorative phase of the study (phase 1), included two research locations, one in the city of Amsterdam and one in Eindhoven. The results gave guidance for a better understanding of the behaviour between different users of separate two-directional bicycle paths. An example includes the relationship between bicyclist-moped rider behaviour and the width of the bicycle path. For a condition with busy bicycle traffic in both directions the width of the bicycle path in Amsterdam (effectively 3.55m) is relatively narrow, whereas the bicycle path width in Eindhoven (>4.94m) appears to be sufficient to accommodate large flows of bicyclists. Because of a large flow of crossing pedestrians resulting in (severe) conflicts with bicyclists in Amsterdam, additional countermeasures to better control these interactions are needed. The DOCTOR conflict observation method from video appears to be applicable for conflicts between intersecting road users and for head-on conflicts on the bicycle path. Conflict situations between bicyclists in the same direction (constituting an important share of injury accidents on bicycle paths) require an

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


    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.

  8. Observational study of compliance with Queensland bicycle helmet laws. (United States)

    Debnath, Ashim Kumar; Haworth, Narelle; Schramm, Amy; Williamson, Amy


    Mandatory bicycle helmet laws have been found to increase helmet wearing rates in Australia and internationally. However, much of the research on factors influencing compliance with the Australian helmet laws is dated or focuses on commuters and city areas only. To address this gap, video recordings of bicycle riders were undertaken at 17 sites across Queensland, Australia, representing a mixture of on- and off-road locations, speed limits and regions. Helmet status was able to be determined for 98% of riders observed. The level of compliance with the laws was very high, with 98.3% of the more than 27,000 riders observed wearing helmets. Riders riding on roads were less compliant than those riding on bicycle paths, but no significant differences were observed between the school-holiday and school-term periods. Among the on-road riders, boys were less compliant than girls and overall children were less compliant than adults. Higher compliance levels were found for group riders, road bike riders, lycra-clad riders, during morning hours, and on 50km/h or lower speed limit roads. While the overall level of compliance was very high, certain subgroups were identified as a possible focus for interventions to further improve the compliance level, for example children (particularly boys) riding mountain bikes away from groups during the afternoon hours on 60km/h roads.

  9. Harvesting energy from the counterbalancing (weaving) movement in bicycle riding. (United States)

    Yang, Yoonseok; Yeo, Jeongjin; Priya, Shashank


    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.

  10. Design Analysis And Applications Of A Regenerative Bicycle Ergometer

    Directory of Open Access Journals (Sweden)

    Chukwuneke J. L.


    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. Electric motor assisted bicycle as an aerobic exercise machine. (United States)

    Nagata, T; Okada, S; Makikawa, M


    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.

  12. It's not just about speed: Reviewing the recumbent bicycle once more. (United States)

    Wieser, Bernhard


    Why did the recumbent bicycle never become a dominant design, despite the fact that it was faster than the safety bicycle on the racetrack? Hassaan Ahmed et al. argue in their recently published paper that the main reason for the marginalization of the recumbent bicycle was semiotic power deployed by the Union Cycliste Internationale (UCI). Here, I demonstrate that the authors drew their conclusions from an incomplete application of the Social Construction of Technology (SCOT) framework. Understanding the diffusion of alternative bicycle designs requires considering more than speed, and more than the UCI as a powerful actor. The recumbent bicycle was fast, but rather tricky to ride, and was not really feasible for the transport needs of the working classes, which constituted the most relevant social group of bicycle users during the 1930s.

  13. Effect of zinc on expression of c-fos and c-jun in spermatogenic cell in rats exposed to fluorine%锌对染氟大鼠生精细胞c-fos和c-jun蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    梁鸿镖; 侯俊; 冯亚静; 段丽菊; 程学敏; 巴月; 崔留欣


    Aim: To discuss the antagonism mechanism of zinc on reproductive toxicity of fluorine through observing the effects of appropriate amount zinc to the c-fos and c-jun protein expression level. Methods: Randomly divided fifty SD male rats into control group, fluorine treatment group, fluorine and low-dose zinc treatment group, fluorine and middle-dose zinc treatment group, fluorine and high-dose zinc treatment group. The content of NaF in testis was measured by using fluorine selective electrode. The levels of LDH were examined by the reagent box. The c-fos and c-jun protein expression level in germ cells are measured by immunohistochemistry. In addition, we observed the quality of spermatozoa and the micro-structure of testis. Results: The c-fos and c-jun protein expression in germ cells of every treatment groups was higher than that of control group,and the difference has the statistical significance,mid-dose zinc treatment group was lower than that of fluorine treatment groups, low-dose zinc and high-dose zinc treatment groups,and the difference has the statistical significance(F = 130. 251 ,P =0.031 ;F = 301. 141 , P = 0. 018 ). Conclusion: Middle-dose zinc can antagonize the reproductive toxicity of fluorine in male rats by lowering the fluorine burden, lowering the expression level of c-fos and c-jun protein expression in testis spermatogenic cell.%目的:观察锌对染氟大鼠生精细胞c-fos、c-jun蛋白表达水平的影响.方法:选用4周龄雄性SD大鼠50只,随机分为对照组、染氟组、氟加低锌组、氟加中锌组、氟加高锌组,灌胃染毒6周后处死动物,采用氟离子选择电极法测定各组大鼠睾丸组织中氟的含量,用试剂盒检测睾丸组织中的乳酸脱氢酶(LDH)活力,做精于质量分析及睾丸组织病理学镜检,免疫组化法检测生精细胞中c-fos、c-jun蛋白的表达水平.结果:氟加中锌组和氟加高锌组睾丸氟含量明显低于染氟组;氟加低锌组和氟加高锌组睾丸

  14. 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)


    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

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



    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...

  16. Modeling cyclist acceleration process for bicycle traffic simulation using naturalistic data


    Ma, Xiaoliang; Luo, Ding


    Cycling is a healthy and sustainable form of transportation. The recent increase of daily cyclists in Sweden has triggered broad interest in finding how policies and measures may facilitate the planning of bicycle traffic in the urban area. However, in comparison to car traffic, bicycle traffic is still far from well understood. This study is part of the research effort to investigate microscopic cyclist behavior, model bicycle traffic and finally build a simulation tool for applications in t...

  17. Bicycle-related injuries: a survey in a pediatric emergency department.


    Cushman, R; Down, J; MacMillan, N; Waclawik, H


    The number of bicycle-related injuries has risen significantly with the increased popularity of bicycle riding in Canada. The risk of injury is highest among children. To assess the magnitude of the problem and to identify the contributing factors we used a questionnaire, injury reports and patient charts to survey bicycle-related injuries among children brought to the emergency department of the Children's Hospital of Eastern Ontario, Ottawa, between May 1 and Sept. 30, 1988. The questionnai...

  18. Bicyclic graphs with maximum sum of the two largest Laplacian eigenvalues

    Directory of Open Access Journals (Sweden)

    Yirong Zheng


    Full Text Available Abstract Let G be a simple connected graph and S 2 ( G $S_{2}(G$ be the sum of the two largest Laplacian eigenvalues of G. In this paper, we determine the bicyclic graph with maximum S 2 ( G $S_{2}(G$ among all bicyclic graphs of order n, which confirms the conjecture of Guan et al. (J. Inequal. Appl. 2014:242, 2014 for the case of bicyclic graphs.

  19. Improvement of Freezing of Gait in Patients with Parkinson's Disease by Imagining Bicycling

    Directory of Open Access Journals (Sweden)

    Akio Kikuchi


    Full Text Available Freezing of gait (FOG is one of the factors that reduce the quality of life in patients with Parkinson's disease (PD. Imagining bicycling before gait start provided improvement in FOG in 2 PD patients. Imagining and mimicking bicycling after the initiation of gait allowed the rhythmic gait to continue without interruption. We suggest that imagining and mimicking bicycling, which are nonexternal cues, could serve as a helpful therapeutic approach for the intractable freezing and interruption of gait of PD patients.

  20. 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


    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.

  1. 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


    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.

  2. The Effect of Sharrows, Painted Bicycle Lanes and Physically Protected Paths on the Severity of Bicycle Injuries Caused by Motor Vehicles

    Directory of Open Access Journals (Sweden)

    Stephen P. Wall


    Full Text Available We conducted individual and ecologic analyses of prospectively collected data from 839 injured bicyclists who collided with motorized vehicles and presented to Bellevue Hospital, an urban Level-1 trauma center in New York City, from December 2008 to August 2014. Variables included demographics, scene information, rider behaviors, bicycle route availability, and whether the collision occurred before the road segment was converted to a bicycle route. We used negative binomial modeling to assess the risk of injury occurrence following bicycle path or lane implementation. We dichotomized U.S. National Trauma Data Bank Injury Severity Scores (ISS into none/mild (0–8 versus moderate, severe, or critical (>8 and used adjusted multivariable logistic regression to model the association of ISS with collision proximity to sharrows (i.e., bicycle lanes designated for sharing with cars, painted bicycle lanes, or physically protected paths. Negative binomial modeling of monthly counts, while adjusting for pedestrian activity, revealed that physically protected paths were associated with 23% fewer injuries. Painted bicycle lanes reduced injury risk by nearly 90% (IDR 0.09, 95% CI 0.02–0.33. Holding all else equal, compared to no bicycle route, a bicycle injury nearby sharrows was nearly twice as likely to be moderate, severe, or critical (adjusted odds ratio 1.94; 95% confidence interval (CI 0.91–4.15. Painted bicycle lanes and physically protected paths were 1.52 (95% CI 0.85–2.71 and 1.66 (95% CI 0.85–3.22 times as likely to be associated with more than mild injury respectively.

  3. Thermoregulation during prolonged actual and laboratory-simulated bicycling. (United States)

    Brown, S L; Banister, E W


    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)

  4. 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...... (notably chickens, ducks and guinea fowl) in the Republic of Benin. For this purpose, we applied the hedonic price method on field data collected from retailers in four urban and five rural markets. We found that meatier drake and meatier guinea fowl with white plumage are preferred by consumers who...

  5. 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...... (notably chickens, ducks and guinea fowl) in the Republic of Benin. For this purpose, we applied the hedonic price method on field data collected from retailers in four urban and five rural markets. We found that meatier drake and meatier guinea fowl with white plumage are preferred by consumers who...

  6. Exploring the Chemistry of Bicyclic Isoxazolidines for the Multicomponent Synthesis of Glycomimetic Building Blocks

    NARCIS (Netherlands)

    Hoogenboom, Jorin; Lutz, Martin; Zuilhof, Han; Wennekes, Tom


    Starting from a chiral furanone, the nitrone-olefin [3 + 2] cycloaddition can be used to obtain bicyclic isoxazolidines for which we report a set of reactions to selectively modify each functional position. These synthetically versatile bicyclic isoxazolidines allowed us to obtain complex glycomi

  7. 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.


    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

  8. 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.


    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

  9. The Bicycle Helmet Attitudes Scale: Using the Health Belief Model to Predict Helmet Use among Undergraduates (United States)

    Ross, Thomas P.; Ross, Lisa Thomson; Rahman, Annalise; Cataldo, Shayla


    Objective: This study examined bicycle helmet attitudes and practices of college undergraduates and developed the Bicycle Helmet Attitudes Scale, which was guided by the Health Belief Model (HBM; Rosenstock, 1974, in Becker MH, ed. "The Health Belief Model and Personal Health Behavior". Thorofare, NJ: Charles B. Slack; 1974:328-335) to predict…

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

    DEFF Research Database (Denmark)

    Jørgensen, Ulrik; Pedersen, Bjørn Brix


    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...

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

    NARCIS (Netherlands)

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


    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

  12. Envisioning Competence: Learning, Problem Solving, and Children at Work in the Exploratory Bicycle Shop (United States)

    Hammond, Charles Florian


    This study examines the conceptual learning and cognitive development processes of schoolchildren engaged in problem solving activities in a non-school, workplace setting known as the exploratory bicycle shop. The exploratory bike shop is a commercial bicycle shop: a) that has been adapted for combined retail and educational purposes and b) where…

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

    NARCIS (Netherlands)

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


    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

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

    Institute of Scientific and Technical Information of China (English)


    <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

  15. 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


    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.

  16. The spatio-temporal Development of Copenhagen's bicycle infrastructure 1912-2013

    DEFF Research Database (Denmark)

    Carstensen, Trine Agervig; Olafsson, Anton Stahl; Bech, Nynne Marie


    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......’s bicycle infrastructure and explores how the development corresponds to other processes of urban transformation. The study builds on historical maps of bicycle infrastructure that are digitised into geographical information, which allows for a comprehensive analysis of the formation of the network....... 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...

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

    Directory of Open Access Journals (Sweden)

    Hongyu Hu


    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.

  18. 76 FR 61266 - Special Regulations; Areas of the National Park System, Grand Teton National Park, Bicycle Routes... (United States)


    ..., Grand Teton National Park, Bicycle Routes, Fishing and Vessels AGENCY: National Park Service, Interior... (Park) as routes for bicycle use. National Park Service (NPS) regulations require issuance of a special regulation to designate bicycle routes that are located off park roads and outside developed areas. The...

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

    Directory of Open Access Journals (Sweden)

    Shashank Priya


    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.

  20. Effect of Salusin-β on the expression of c-fos, c-jun and proliferating cell nuclear antigen in vascular smooth muscle cells of thoracic aorta of rat%Salusin-β对大鼠胸主动脉血管平滑肌细胞c-fos、c-jun和增殖细胞核抗原表达的影响

    Institute of Scientific and Technical Information of China (English)

    马艳红; 王海昌


    Objective To observe the effect of Salusin-β on c-fos, c-jun and proliferating cell nuclear antigen (PCNA) in vascular smooth muscle cells (VSMCs) of thoracic aorta of rat. Methods Fifty male Wistar rats were randomly divided into normal saline (NS)group (n=25) and Salusin-β group (n= 25) . Rats in Salusin-β group were injected Salusin-β(5nmol/kg) uia the femoral vein, while in NS group were injected equal amount of NS. All the rats were infused with paraform at 0.5, 1, 2, 4 and 24h after the injection, and then the thoracic aortas were harvested. The expressions of c-fos, c-jun and PCNA in VSMCs of rats' thoracic aorta were detected by immunocytochemistry and analyzed by Image-Pro Plus 5.0 image software. Results Compared with NS group, in Salusin-β group, the expression of c-fos at 1h and 2h, of c-jun at 1h, 2h and 4h, and of PCNA at 24h were up-regulated significantly (P<0.0001). Conclusion Salusin-β may promote the proliferation of VSMCs.%目的 观察Salusin-β对大鼠胸主动脉血管平滑肌细胞(VSMCs)中c-fos、c-jun和增殖细胞核抗原(PCNA)表达的影响.方法 健康雄性Wiser大鼠50只,随机均分为生理盐水(NS)组(n=25)和Salusin-β组(n=25).经股静脉向Salusin-β组大鼠体内注射Salusin-β(5nmol/kg),NS组注射等量生理盐水.分别于0.5、1、2、4、24h后用多聚甲醛灌注大鼠,取其胸主动脉,采用免疫组织化学方法,检测两组大鼠胸主动脉VSMCs中c-fos、c-jun和PCNA的表达情况,使用Image-Pro Plus 5.0图像分析软件对结果进行面积密度分析.结果 Salusin-β组c-fos表达量在1、2h明显高于NS组(P<0.0001),c-jun表达量在1、2和4h Salusin-β组明显高于NS组(P<0.0001),PCNA表达量在24h明显高于NS组(P<0.0001).结论 Salusin-β可促进胸主动脉VSMCs的增殖.

  1. 上调c-Jun和抑制磷酸化p44/42的活性参与苯妥英诱导的培养的大鼠小脑颗粒神经元凋亡%Activation of c-Jun and suppression of phospho-p44/42 were involved in diphenylhydantoin-induced apoptosis of cultured rat cerebellar granule neurons

    Institute of Scientific and Technical Information of China (English)

    赵灵芝; 苏兴丈; 黄奕俊; 邱鹏新; 颜光美


    目的:研究苯妥英(diphenylhydantoin,DPH)(100 μmol/L)对体外培养的小脑颗粒神经元(CGN)毒性的细胞内信号机制.方法:比较DPH对体外培养的大脑皮质神经元(CN)和小脑颗粒神经元的作用;考查信号通路抑制剂对苯妥英诱导的小脑颗粒神经元存活的作用;采用相关信号通路中蛋白分子的抗体及其活性部位磷酸化特异性抗体蛋白质印迹法检测信号分子c-Jun,p44/42,JNK,p38的活性及表达;RT-PCR检测c-jun mRNA的表达.结果:DPH 100μmol/L可选择性诱导CGN凋亡,而对CN无明显毒性;JNK/p38抑制剂B203580 10 μmol/L和MLK抑制剂CEP-11004 1 μmol/L可明显抑制苯妥英诱导的小脑颗粒神经元的凋亡;DPH可诱导CGN中c-Jun的活性及表达,c-jun mRNA亦随之上调;SB203580 10μmol/L和CEP-11004 1μumol/L可抑制DPH引起的c-Jun活性的上调;DPH不影响JNK和p38的活性表达量;DPH不影响p44/42的表达,但可明显抑制p44/42的活性.结论:DPH对体外培养的CGN的神经毒性源于其介导的CGN的凋亡,在此过程中c-Jun的表达及活性被上调,p44/42活性被抑制.%AIM: To investigate possible intracellular signal molecules involved in diphenylhydantoin (DPH)-mediated apoptosisof cerebellar granule neurons (CGN) and explore possible molecular mechanisms of neurotoxicity of DPH.METHODS: Fluorescein diacetate (FDA) stain, hochest 33258 stain, and agar gel electrophoresis were used to testmorphological and biological characters of primary CGN and cortical neurons (CN) in the presence or absence of100 μmol/L DPH; Western blot and RT-PCR were employed to further investigate apoptotic/survival signal molecularsinvolved in the neuronal apoptotic signal transdution. RESULTS: DPH 100 μrnol/L induced a typical apoptosis ofCGN but had no toxicity on CN. Cerebellar granule neural apoptosis induced by 100 μmol/L DPH was significantlyinhibited by pre-treatment with SB203580 (10 μnol/L) or CEP-11004 (1 μrnol/L) for 1 h. DPH

  2. Predicting Free Flow Speed and Crash Risk of Bicycle Traffic Flow Using Artificial Neural Network Models

    Directory of Open Access Journals (Sweden)

    Cheng Xu


    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.

  3. 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: [Ocean College, Zhejiang University, Hangzhou, 310058 China (China); Wang, Dianhai [College of Civil Engineering and Architecture, Zhejiang University, Hangzhou, 310058 China (China)


    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.

  4. Cyclist safety on bicycle boulevards and parallel arterial routes in Berkeley, California. (United States)

    Minikel, Eric


    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.

  5. Enhanced recycling network for spent e-bicycle batteries: A case study in Xuzhou, China. (United States)

    Chen, Fu; Yang, Baodan; Zhang, Wangyuan; Ma, Jing; Lv, Jie; Yang, Yongjun


    Electric bicycles (e-bicycles) are a primary means of commuting in China because of their light weight, speed, and low maintenance costs. Owing to short service life and environmental pollution hazards, recycling and reuse of e-bicycle batteries has always been a focus of industry and academia. As a typical case of both production and use of large electric bicycles, 113 major sellers, 378 corporate and individual buyers, 147 large e-bicycle repair centers, and 1317 e-bicycle owners in Xuzhou City were investigated in order to understand the sales, use, recycling, and disposal of spent e-bicycle batteries. The findings show that the existing distempered recycling system is the main limitation of spent battery recovery, and the actual recovery rate of spent batteries is lower than the estimated output (QW) for the years 2011-2014. Electric bicycle sellers play a fundamental role in the collection of spent batteries in Xuzhou, accounting for 42.3±8.3% of all batteries recovered. The widespread use of lithium batteries in recent years has resulted in a reduction in spent battery recycling because of lower battery prices. Furthermore, consumer preferences are another important factor affecting the actual recovery rate according to survey results evaluated using canonical correspondence analysis. In this paper, we suggest that a reverse logistics network system for spent battery recycling should be established in the future; in addition, enhancing producer responsibility, increasing publicity, raising of public awareness, developing green public transport, and reducing dependence on e-bicycles also should be pursued. This study seeks to provide guidance for planning construction and management policies for an effective spent battery recycling system in China and other developing countries.

  6. Dual inhibitory roles of geldanamycin on the c-Jun NH2-terminal kinase 3 signal pathway through suppressing the expression of mixed-lineage kinase 3 and attenuating the activation of apoptosis signal-regulating kinase 1 via facilitating the activation of Akt in ischemic brain injury. (United States)

    Wen, X-R; Li, C; Zong, Y-Y; Yu, C-Z; Xu, J; Han, D; Zhang, G-Y


    It is well documented that heat-shock protein (hsp90) plays an essential role in maintaining stability and activity of its clients. Recent studies have shown that geldanamycin (GA), an inhibitor of hsp90, could decrease the protein of mixed-lineage kinase (MLK) 3 and activate Akt; our previous research documented that MLK3 and Akt and subsequent c-Jun N-terminal kinase (JNK) were involved in neuronal cell death in ischemic brain injury. Here, we investigated whether GA could decrease the protein of MLK3 and activate Akt in rat four-vessel occlusion ischemic model. Our results showed that global cerebral ischemia followed by reperfusion could enhance the association of hsp90 with MLK3, the association of hsp90 with Src, and JNK3 activation. As a result, GA decreased the protein of MLK3 and down-regulated JNK activation. On the other hand, Src kinase was activated and phosphorylated Cbl, which then recruited the p85 subunit of phosphatidylinositol 3-kinase (PI-3K), resulting in PI-3K activation, and as a consequence increased Akt activation, which inhibited ASK1 activation and down-regulated JNK3 activation. In summary, our results indicated that GA showed a dual inhibitory role on JNK3 activation and exerted strong neuroprotection in vivo and in vitro, which provides a new possible approach for stroke therapy.

  7. 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...

  8. Bicycle messengers: energy expenditure and exposure to air pollution. (United States)

    Bernmark, Eva; Wiktorin, Christina; Svartengren, Magnus; Lewné, Marie; Aberg, Samuel


    The purpose of the study was to determine the level of energy expenditure and exposure to air pollution for bicycle messengers. Relationships between heart rate (HR) and oxygen uptake, and between HR and pulmonary ventilation (VE) for each participant were established in laboratory tests. Air pollution and HR were measured during one working day. The total oxygen uptake was then described as the total energy expenditure in Joule (J) and in multiples of the energy expenditure at rest (MET). The mean energy expenditure during a working day (8 h) was 12 MJ, (4.8 MET). The level of air pollution exposure when cycling seemed to be comparable with the levels of exposure when sitting inside a vehicle. The VE during cycling was four times higher than resting value. Increased VE led to increased exposure to air pollution.

  9. Fatal truck-bicycle accident involving dragging for 45 km. (United States)

    Klintschar, M; Darok, M; Roll, P


    Vehicle-bicycle accidents with subsequent dragging of the rider over long distances are extremely rare. The case reported here is that of a 16-year-old mentally retarded bike rider who was run over by a truck whose driver failed to notice the accident. The legs of the victim became trapped by the rear axle of the trailer and the body was dragged over 45 km before being discovered under the parked truck. The autopsy revealed that the boy had died from the initial impact and not from the dragging injuries which had caused extensive mutilation. The reports of the technical expert and the forensic pathologist led the prosecutor to drop the case against the truck driver for manslaughter.

  10. Aromatic Esters of Bicyclic Amines as Antimicrobials against Streptococcus pneumoniae. (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


    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.

  11. Optimal Time-Trial Bicycle Racing with Headwinds and Tailwinds

    CERN Document Server

    Anton, A Brad


    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.

  12. [Prognostic significance of bicycle ergometry test in patients with myocarditis]. (United States)

    Gavalova, R F; Borodina, V I


    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.

  13. Optimal protruding node length of bicycle seats determined using cycling postures and subjective ratings. (United States)

    Chen, Yi-Lang; Liu, Yi-Nan


    This study examined body posture, subjective discomfort, and stability, requiring the participants to ride a stationary bicycle for 20 min (cadence: 60 rpm; workrate: 120 W), using various combinations of two handle heights and five seat-protruding node lengths (PNLs). The results indicated that bicycle handle height significantly influenced body posture, and that seat PNL caused differences in the riders' subjective discomfort and stability scores. The various PNLs affected only the trunk angle (approximately 6°), but had significantly positive (r = 0.994, p optimal reference for bicycle seat designs.

  14. Characteristics of bicyclic sesquiterpanes in crude oils and petroleum products. (United States)

    Yang, Chun; Wang, Zhendi; Hollebone, Bruce P; Brown, Carl E; Landriault, Mike


    This study presents a quantitative gas chromatography-mass spectrometry analysis of bicyclic sesquiterpanes (BSs) in numerous crude oils and refined petroleum products including light and mid-range distillate fuels, residual fuels, and lubricating oils collected from various sources. Ten commonly recognized bicyclic sesquiterpanes were determined in all the studied crude oils and diesel range fuels with principal dominance of BS3 (C(15)H(28)), BS5 (C(15)H(28)) and BS10 (C(16)H(30)), while they were generally not detected or in trace in light fuel oils like gasoline and kerosene and most lubricating oils. Laboratory distillation of crude oils demonstrated that sesquiterpanes were highly enriched in the medium distillation fractions of approximately 180 to 481 degrees C and were generally absent or very low in the light distillation fraction (boiling point to approximately 180 degrees C) and the heavy residual fraction (>481 degrees C). The effect of evaporative weathering on a series of diagnostic ratios of sesquiterpanes, n-alkanes, and biomarkers was evaluated with two suites of weathered oil samples. The change of abundance of sesquiterpanes was used to determine the extent of weathering of artificially evaporated crude oils and diesel. In addition to the pentacyclic biomarker C(29) and C(30) alphabeta-hopane, C(15) and C(16) sesquiterpanes might be alternative internal marker compounds to provide a direct way to estimate the depletion of oils, particularly diesels, in oil spill investigations. These findings may offer potential applications for both oil identification and oil-source correlation in cases where the tri- to pentacyclic biomarkers are absent due to refining or environmental weathering of oils.

  15. Evaluating the effectiveness of on-street bicycle lane and assessing risk to bicyclists in Charlotte, North Carolina. (United States)

    Pulugurtha, Srinivas S; Thakur, Vidya


    The objectives of this manuscript are (1) to evaluate the effectiveness of on-street bicycle lane in reducing crashes involving bicyclists on urban roads, (2) to quantify and compare risk to bicyclists on road segments with and without on-street bicycle lane, (3) to evaluate the effect of on-street bicycle lane on other road network users (all crashes), and, (4) to assess the role of on-network characteristics (speed limit, the number of lanes, the width of on-street bicycle lane, the width of the right-most travel lane, and, the numbers of driveways, unsignalized approaches and signalized intersections per unit distance) on risk to bicyclists. Data for thirty-six segments with on-street bicycle lane and twenty-six segments without on-street bicycle lane in the city of Charlotte, North Carolina were extracted to compute and compare measures such as the number of bicycle crashes per center-lane mile, the number of bicycle crashes per annual million vehicle miles traveled (MVMT), the number of all crashes per center-lane mile, and the number of all crashes per MVMT. The results obtained from analysis indicate that bicyclists are three to four times at higher risk (based on traffic conditions) on segments without on-street bicycle lane than when compared to segments with on-street bicycle lane. An analysis conducted considering all crashes showed that on-street bicycle lanes do not have a statistically significant negative effect on overall safety. An increase in annual MVMT (exposure) and the number of signalized intersections per mile increases the number of bicycle crashes, while an increase in on-street bicycle lane width or right-most travel lane width (if on-street bicycle lane cannot be provided) decreases the number of bicycle crashes. Installing wider on-street bicycle lanes, limiting driveways to less than 50 per mile and unsignalized approaches to less than 10 per mile, increasing spacing between signalized intersections, and, facilitating wider right

  16. Prioritization of Integrated Bicycle Network Clusters in Istanbul Using Analytic Hierarchy Process

    Directory of Open Access Journals (Sweden)

    Dilek Çol Yılmaz


    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.

  17. The relation between mechanical impact parameters and most frequent bicycle related head injuries

    NARCIS (Netherlands)

    Monea, A.G.; Perre, G. van der; Baeck, K.; Delye, H.H.; Verschueren, P.; Forausebergher, E.; Lierde, C. van; Verpoest, I.; Sloten, J. van der; Goffin, J.; Depreitere, B.


    The most frequent head injuries resulting from bicycle accidents include skull fracture acute subdural hematoma (ASDH), cerebral contusions, and diffuse axonal injury (DAI). This review includes epidemiological studies, cadaver experiments, in vivo imaging, image processing techniques, and computer

  18. Health in All Policies? The case of policies to promote bicycle use in the Netherlands. (United States)

    den Broeder, Lea; Scheepers, Eline; Wendel-Vos, Wanda; Schuit, Jantine


    To gather insight on how Health in All Policies (HiAP) is applied in practice, we carried out a case study on transport policies intended to stimulate a shift from car use to bicycling. We reviewed 3 years (2010, 2011, and 2012) of national budgets and policy documents in the Netherlands, followed by two focus group sessions and a second round of document analysis. We found to our surprise, given the country's history of bicycle promotion, that no HiAP approaches for bicycle promotion remain in place in national transport policies. The Netherlands may face serious challenges in the near future for facilitating bicycle use. Inclusion of health goals requires that the health sector work towards acquiring a better understanding of core values in other sector's policies.

  19. An Analyses of Bicycle Accidents in Ankara: Analyses of 5 Years

    Directory of Open Access Journals (Sweden)

    Muhittin Yilmaz


    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

  20. EU to Continue 48.5% Anti-dumping Duties on Chinese Bicycles

    Institute of Scientific and Technical Information of China (English)


    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.

  1. Formation of isoprostane bicyclic endoperoxides from the autoxidation of cholesteryl arachidonate. (United States)

    Yin, Huiyong; Havrilla, Christine M; Morrow, Jason D; Porter, Ned A


    Autoxidation of polyunsaturated fatty acids and esters leads to a complex mixture containing hydroperoxides and cyclic peroxides. Prostaglandin bicyclic endoperoxides have been detected from the autoxidation of cholesteryl arachidonate by LC-MS and GC-MS techniques. All four possible types (I-IV) of bicyclic endoperoxides have been found starting from different regioisomeric hydroperoxides of cholesteryl arachidonate. Furthermore, the stereochemistry of Type IV bicyclic endoperoxides has been determined by conversion to pentafluorobenzyl (PFB) ester, trimethylsilyl (TMS) derivatives, and comparison with synthetic standards by the use of GC-MS. All eight possible diastereomers of the derivatized isoprostanes were observed and were separated by gas chromatography. The bicyclic endoperoxides with the two alkyl chains syn on the cyclopentane ring were formed preferentially to those with anti configuration, a result anticipated from earlier work. Substantial amounts of the anti-substituted isoprostanes, including PGF(2)(alpha), were, however, observed in the product mixture.

  2. 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


    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.

  3. Teaching children about bicycle safety: an evaluation of the New Jersey Bike School program. (United States)

    Lachapelle, Ugo; Noland, Robert B; Von Hagen, Leigh Ann


    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.

  4. Association of Sociodemographic and Perceived Environmental Factors with Public Bicycle Use among Taiwanese Urban Adults

    Directory of Open Access Journals (Sweden)

    Yung Liao


    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.

  5. Lannea coromandelica (Houtt.) Merr. Induces Heme Oxygenase 1 (HO-1) Expression and Reduces Oxidative Stress via the p38/c-Jun N-Terminal Kinase–Nuclear Factor Erythroid 2-Related Factor 2 (p38/JNK–NRF2)-Mediated Antioxidant Pathway (United States)

    Alam, Md Badrul; Kwon, Kyoo-Ri; Lee, Seok-Hyun; Lee, Sang-Han


    The leaves of Lannea coromandelica (Houtt.) Merr. are used in the Garo, Pahan, and Teli tribal communities of Bangladesh as a traditional medicinal plant to treat hepatitis, diabetes, ulcers, heart disease, and dysentery. However, there have been limited phytochemical and biological studies on the bark of L. coromandelica. This study aimed to investigate the antioxidant activities of L. coromandelica bark extract (LCBE) and the underlying mechanism using RAW 264.7 cells. The LCBE was analysed by high-pressure liquid chromatography (HPLC) to detect its key polyphenolic compounds. Various in vitro antioxidant assays were performed using RAW 264.7 cells to assess the antioxidant effects of the LCBE and to understand the underlying molecular mechanism. HPLC revealed the presence of gallic acid, (−)-epigallocatechin-3-gallate, catechin, chlorogenic acid, and caffeic acid in the LCBE. The extract showed a very potent capacity to scavenge numerous free radicals through hydrogen atom transfer and/or electron donation and also quenched cellular reactive oxygen species (ROS) generation without showing any toxicity. The LCBE was found to combat the oxidative stress by enhancing the expression, at both transcriptional and translational levels, of primary antioxidant enzymes as well as phase II detoxifying enzymes, especially heme oxygenase 1, through the upregulation of the nuclear factor erythroid 2-related factor 2 (NRF2)-mediated pathway in RAW 264.7 cells via the phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK). The LCBE exhibited strong antioxidant activities and mitigated the cellular ROS production. These results provide scientific evidence of its potential as an ideal applicant for a cost-effective, readily available, and natural phytochemical, as well as a strategy for preventing diseases associated with oxidative stress and attenuating disease progress. PMID:28146074

  6. 鼠缺血肠癌基因c-jun活化碱性成纤维细胞生长因子受体表达的关系%Relationship between oncogene c-jun activation and fibroblast growth factor receptor expression of ischemia-reperfusion intestine in rats

    Institute of Scientific and Technical Information of China (English)

    蒋礼先; 付小兵; 孙同柱; 杨银辉; 顾小曼


    目的探讨在体条件下癌基因c-jun与碱性成纤维细胞生长因子受体(FGFR)的相互关系,以期阐明癌基因c-jun在创伤修复中的作用.方法利用免疫组织化学ABC法检测缺血再灌注肠道. 切片顺序与特异性一抗、生物素标记的二抗孵育,冲洗后滴加辣根过氧化物酶标记的链霉卵蛋白,DAB染色,苏木素复染,封片,镜检.结果正常肠道c-jun,FGFR均有恒定表达,其中Jun阳性信号主要在核内,少量在胞质,而FGFR阳性信号主要在细胞膜,少量于胞质,两者的分布具有一致性,主要位于肠绒毛固有层,为淋巴细胞、粒细胞;再灌注即刻,肠绒毛脱落、坏死,阳性信号减弱;再灌注6h,两者均达最高峰;而再灌注24h,两者阳性信号减弱,相关分析显示,c-jun与FGFR成直线相关.结论缺血再灌注后大鼠肠道癌基因c-jun与FGFR的表达两者之间可能存在内在联系.

  7. 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


    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.

  8. 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


    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

  9. Incidence and costs of bicycle-related traumatic brain injuries in the Netherlands. (United States)

    Scholten, Annemieke C; Polinder, Suzanne; Panneman, Martien J M; van Beeck, Ed F; Haagsma, Juanita A


    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

  10. The effects of surface-induced loads on forearm muscle activity during steering a bicycle. (United States)

    Arpinar-Avsar, Pinar; Birlik, Gülin; Sezgin, Onder C; Soylu, Abdullah R


    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

  11. Big Bicycle Data Processing: from Personal Data to Urban Applications (United States)

    Pettit, C. J.; Lieske, S. N.; Leao, S. Z.


    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.

  12. How does the edge height of curb ramps obstruct bicycles? (United States)

    Hayashi, Masahiro; Uetake, Teruo; Shimoda, Masahiro


    The aim of this study is to recommend revisions, based on empirical data, to the current curb ramp standards for keeping bicyclists safe. Four types of curb ramps were tested: (1) concrete with a 50 mm edge height, (2) concrete reinforced by a metal plate with a 50 mm edge height, (3) plastic with a 20 mm edge height, and (4) recycled rubber with a 10 mm edge height. Twenty subjects aged 20-60 years ascended the curbs on a bicycle under various conditions. The angles of approach were 15 degrees, 30 degrees, 45 degrees, 60 degrees, 75 degrees and 90 degrees. Experiments were executed under both wet and dry conditions. We found that when approaching from an angle of 45 degrees or more, all subjects could ascend all ramps under both conditions. From a 15 degrees approach under wet conditions, no subjects ascended the concrete ramps. Some could not ascend at a 15 degrees approach on the concrete ramps in dry conditions, and some could not ascend from a 30 degrees approach on the reinforced concrete ramp in wet conditions. Bicyclists riding on roadways cannot easily ascend a curb ramp with a 50 mm edge, even in dry conditions. We thus recommend that curb ramp edge heights be lower than 50 mm. Keywords: friction coefficient; approach angle

  13. Environmental Determinants of Bicycling Injuries in Alberta, Canada

    Directory of Open Access Journals (Sweden)

    Nicole T. R. Romanow


    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.

  14. Environmental Determinants of Bicycling Injuries in Alberta, Canada (United States)

    Romanow, Nicole T. R.; Couperthwaite, Amy B.; McCormack, Gavin R.; Nettel-Aguirre, Alberto; Rowe, Brian H.; Hagel, Brent E.


    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

  15. On the closure of the extended bicyclic semigroup

    CERN Document Server

    Fihel, Iryna


    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)\

  16. Optimization of electric bicycle for youths with disabilities. (United States)

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


    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.

  17. 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


    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.

  18. Latent segmentation based count models: Analysis of bicycle safety in Montreal and Toronto. (United States)

    Yasmin, Shamsunnahar; Eluru, Naveen


    The study contributes to literature on bicycle safety by building on the traditional count regression models to investigate factors affecting bicycle crashes at the Traffic Analysis Zone (TAZ) level. TAZ is a traffic related geographic entity which is most frequently used as spatial unit for macroscopic crash risk analysis. In conventional count models, the impact of exogenous factors is restricted to be the same across the entire region. However, it is possible that the influence of exogenous factors might vary across different TAZs. To accommodate for the potential variation in the impact of exogenous factors we formulate latent segmentation based count models. Specifically, we formulate and estimate latent segmentation based Poisson (LP) and latent segmentation based Negative Binomial (LNB) models to study bicycle crash counts. In our latent segmentation approach, we allow for more than two segments and also consider a large set of variables in segmentation and segment specific models. The formulated models are estimated using bicycle-motor vehicle crash data from the Island of Montreal and City of Toronto for the years 2006 through 2010. The TAZ level variables considered in our analysis include accessibility measures, exposure measures, sociodemographic characteristics, socioeconomic characteristics, road network characteristics and built environment. A policy analysis is also conducted to illustrate the applicability of the proposed model for planning purposes. This macro-level research would assist decision makers, transportation officials and community planners to make informed decisions to proactively improve bicycle safety - a prerequisite to promoting a culture of active transportation.

  19. Assessing the Bicycle Network in St. Louis: A PlaceBased User-Centered Approach

    Directory of Open Access Journals (Sweden)

    Bram Boettge


    Full Text Available To transition towards sustainability and increase low-impact transportation, city planners are integrating bicycle infrastructure in urban landscapes. Yet, this infrastructure only promotes cycling according to how well it is sited within a specific city. How to best site bicycle facilities is essential for sustainability planning. We review approaches to assessing and siting new bicycle facilities. Following sustainability science, we argue that active cyclists should be consulted to incorporate users’ site-specific knowledge into bicycle infrastructure assessments. We then pilot an approach that surveys cyclists concerning level of stress along routes ridden in St. Louis, MO, USA. Among the active cyclists surveyed (n = 89, we found stress correlates with speed limit, roadway classification, and number of lanes. Although cyclists surveyed in St. Louis prefer roads with bike lanes over roads with sharrows or no infrastructure, the presence of bicycle infrastructure had no correlation with reported levels of stress. The piloted survey and spatial analytic tool are transferable to other localities. For planners, the maps generated by this participant data approach identify high-stress routes as targets of new infrastructure or information to direct cyclists to safer routes. For bicyclists, the maps generated identify low-stress routes for recreation and commuting.

  20. Johnson Space Center's Free Range Bicycle Program.- Fall 2015 Intern Report (United States)

    Lee-Stockton, Willem


    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

  1. The impact response of traditional and BMX-style bicycle helmets at different impact severities. (United States)

    DeMarco, Alyssa L; Chimich, Dennis D; Gardiner, John C; Siegmund, Gunter P


    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.

  2. Investigation of Bicycle Travel Time Estimation Using Bluetooth Sensors for Low Sampling Rates

    Directory of Open Access Journals (Sweden)

    Zhenyu Mei


    Full Text Available Filtering the data for bicycle travel time using Bluetooth sensors is crucial to the estimation of link travel times on a corridor. The current paper describes an adaptive filtering algorithm for estimating bicycle travel times using Bluetooth data, with consideration of low sampling rates. The data for bicycle travel time using Bluetooth sensors has two characteristics. First, the bicycle flow contains stable and unstable conditions. Second, the collected data have low sampling rates (less than 1%. To avoid erroneous inference, filters are introduced to “purify” multiple time series. The valid data are identified within a dynamically varying validity window with the use of a robust data-filtering procedure. The size of the validity window varies based on the number of preceding sampling intervals without a Bluetooth record. Applications of the proposed algorithm to the dataset from Genshan East Road and Moganshan Road in Hangzhou demonstrate its ability to track typical variations in bicycle travel time efficiently, while suppressing high frequency noise signals.

  3. Tunicamycin inhibits Toll-like receptor-activated inflammation in RAW264.7 cells by suppression of NF-κB and c-Jun activity via a mechanism that is independent of ER-stress and N-glycosylation. (United States)

    Kim, Song-Yi; Hwang, Ji-Sun; Han, Inn-Oc


    In this study, we investigated the effect of tunicamycin on the production of pro-inflammatory molecules in RAW264.7 macrophage cells in response to lipopolysaccharide (LPS) and Toll-like receptor (TLR) agonists. Tunicamycin caused a reduction in LPS-induced nitric oxide (NO) production and expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α). In contrast, other ER stress-inducing chemicals, such as A23187 and thapsigargin (TG), increased LPS-induced COX-2 expression and had no effect on LPS-induced iNOS, TNF-α or IL-1β expression. Furthermore, the inhibitory effect of tunicamycin on LPS-induced inflammation was not influenced by salubrinal, an ER stress inhibitor, suggesting that the anti-inflammatory effect of tunicamycin is independent of ER stress. Tunicamycin also inhibited the expression of inflammatory molecule mRNAs induced by stimulation of TLR2 (with lipoteichoic acid) or TLR3 (with polyinosinic:polycytidylic acid), which do not require myeloid differentiation protein-2 (MD2) for their activation. Moreover, inhibition of LPS-induced iNOS expression was not inhibited by castanospermine, another N-glycosylation inhibitor, suggesting that the inhibitory effect of tunicamycin on LPS-induced iNOS induction is likely independent of MD2 N-glycosylation. Tunicamycin inhibited nuclear factor-kappaB (NF-κB) activity by suppressing LPS-induced nuclear translocation of p50 and subsequent DNA binding of p50 and p65 to the NF-κB site of the iNOS promoter. Tunicamycin also inhibited the transcriptional activity of a cAMP-response element (CRE) reporter, possibly by inhibiting c-Jun activation. Therefore, we conclude that tunicamycin represses TLR-induced inflammation through suppression of NF-κB and CRE activity via a mechanism that is independent of ER-stress and N-glycosylation.

  4. Get Wheelin' in Westlawn: Mounting a Bicycling Program in a Low-Income Minority Urban Community

    Directory of Open Access Journals (Sweden)

    Anne Dressel


    Full Text Available Located in Milwaukee, Wisconsin, USA, the Westlawn neighborhood is home to the State of Wisconsin’s largest public housing development. Westlawn is a low-income, African-American urban community that suffers from a wide range of health and environmental disparities. A community-based participatory action (CBPA team was formed to address environmental health issues in Westlawn, and found asthma rates there are among the highest in the State. Decreasing air pollution, and corresponding asthma triggers, became a priority for the community. The CBPA team developed a bicycling program to reduce trips made by car and improve air quality in the Westlawn neighborhood. Input from focus group meetings shaped the development, implementation and expansion of the bicycling program. While the program was originally conceived to address environmental health issues, it provided key findings about how to encourage bicycling in low-income minority urban communities.

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

    Directory of Open Access Journals (Sweden)

    Marius Janavičius


    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. 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


    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.

  7. Study of the health effects of bicycling in an urban atmosphere. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Waldman, M.; Weiss, S.; Articola, W.


    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.

  8. 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;


    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...

  9. Perceiving and Acting on Complex Affordances: How Children and Adults Bicycle across Two Lanes of Opposing Traffic (United States)

    Grechkin, Timofey Y.; Chihak, Benjamin J.; Cremer, James F.; Kearney, Joseph K.; Plumert, Jodie M.


    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…

  10. The role of bicycle sharing systems in normalising the image of cycling: An observational study of London cyclists. (United States)

    Goodman, Anna; Green, Judith; Woodcock, James


    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.

  11. 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


    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

  12. Evaluation of a pilot program in rural schools to increase bicycle and motor vehicle safety. (United States)

    Floerchinger-Franks, G; Machala, M; Goodale, K; Gerberding, S


    Concerned with high bicycle-and motor vehicle-related mortality rates among children, Idaho's South Central District Health Department provided a competition to increase use of 1) seat belts, 2) motor vehicle rear seating, and 3) bicycle helmets among children attending elementary schools in the eight rural counties it serves. Nine of the 44 elementary schools in the health district chose to participate in the contest. Eight schools addressed increasing helmet use, four schools also addressed increasing seat belt use and rear seating, and one school addressed safety in general. A $1,000 prize was awarded to each of four schools judged to have the highest levels of student and community involvement, outreach, creativity, and changes in safety behavior (based on perceptions of outside judges). In 1997, baseline observations were collected for 1) seat belt use and rear seating for children in 28 schools, and for 2) bicycle helmet use among children in 25 schools. In 1998, follow up data were collected for 1) seat belt and rear seating in 42 schools, and 2) bicycle helmet use in 35 schools. Data were analyzed using SAS. Adjusting for differences in baseline rates, regression analysis was used to compare 1997 and 1998 rates for seat belt use, rear seating, and bicycle helmet use for those schools having baseline data. Results showed that although there was no significant difference between participating and non-participating schools in rear-seating behaviors, there was an increase in seat belt and bicycle helmet use for participating schools. Since schools self-selected participation, it is unknown whether those schools were fundamentally different from nonparticipating schools.

  13. Relationship between Locations of Facial Injury and the Use of Bicycle Helmets: A Systematic Review. (United States)

    Hwang, Kun; Jeon, Yun Moon; Ko, Yeong Seung; Kim, Yeon Soo


    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.

  14. Mapping cyclist activity and injury risk in a network combining smartphone GPS data and bicycle counts. (United States)

    Strauss, Jillian; Miranda-Moreno, Luis F; Morency, Patrick


    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

  15. Aminocyclopentanols as sugar mimics. Synthesis from unsaturated bicyclic lactones by Overman rearrangement

    DEFF Research Database (Denmark)

    Bøjstrup, Marie; Fanefjord, Mette; Lundt, Inge


    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...

  16. 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;


    The inhibitory action of bicyclic isoxazole gamma-aminobutyric acid (GABA) analogues and their 4,4-diphenyl-3-butenyl (DPB) substituted derivatives has been investigated in cortical neurones and astrocytes as well as in human embryonic kidney (HEK 293) cells transiently expressing either mouse GABA...... 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....

  17. The Feasibility of Wood and its Derivatives as a Bicycle Frame Building Material




    [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. Risky riding: Naturalistic methods comparing safety behavior from conventional bicycle riders and electric bike riders. (United States)

    Langford, Brian Casey; Chen, Jiaoli; Cherry, Christopher R


    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

  19. Orthogonal ring-closing alkyne and olefin metathesis for the synthesis of small GTPase-targeting bicyclic peptides. (United States)

    Cromm, Philipp M; Schaubach, Sebastian; Spiegel, Jochen; Fürstner, Alois; Grossmann, Tom N; Waldmann, Herbert


    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.

  20. c-Jun氨基末端激酶信号转导途径在哮喘大鼠气道重塑过程中的作用%Role of c-Jun N-terminal kinase signal transduction pathway in the course of airway remodeling of asthma rat

    Institute of Scientific and Technical Information of China (English)

    李昌崇; 林立; 王晓丽; 管小俊; 苏苗赏; 项蔷薇; 韩晗; 张维溪; 李孟荣


    and group A8,the concentrations of IL-1β in BALF of group A12 significantly increased(P<0.01 or P<0.05).but the levels of IL-11β in serum were not significantly different among them(P>0.05).Mean absorbance values(by immunohistochemistry)of P-JNK and e-c-Jun in asthma groups were significantly higher than those in corresponding control groups(P<0.01,respectively),and compared with group A4 and group A8,those of group A12 significantly increased(P<0.01 or P<0.05).The absorbance(by Western Blot)of P-JNK in A4,A8,A12 group WaS significantly higher than that in C4,C8,C12 groups(P<0.01,respectively),and compared with group 3.4,that of P-JNK of A12 significantly increased(P<0.01),and compared with group A8,there was no significant difference(P>0.05).Strong positive correlatiom were found between Wat or Wam and P-JNK(r=0.823 and r=0.818,P<0.01,respectively,n=68)and between P-JNK and concentration of IL-1βin serum or BALF(r=0.717and,=0.803,P<0.01,respectively,n=68).Condusions The expression of P-JNK and its downstream P-c-Jun in rats of asthma airway remodeling is increased.which implicates that JNK signal transduetion pathway plays an important role in the course of asthma airway remodeling.IL-1β participates in asthma airway remodeling possibly partly through activating JNK signal traneduction pathway.%目的 探讨c-Jun氨基末端激酶(JNK)信号转导途径在哮喘气道重塑过程中的作用;IL-1β是否通过JNK信号途径参与哮喘气道重塑形成过程.方法 SD大鼠随机分为对照组(C)和哮喘组(A),以卵白蛋白致敏和激发复制哮喘气道重塑模型,A组根据激发时间不同,分为4、8、12周组(分别为A4、A8、A12组),同时设立相应C组(分别为C4、C8、C12组).电镜观察肺组织超微结构变化,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;免疫组化(IHC)检测肺内磷酸化JNK(P-JNK)及其下游

  1. Building the fastest bicycle in the world; a year with the Human Power Team Delft & Amsterdam

    NARCIS (Netherlands)

    Schuurman, M.; Roks, G.


    “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. Bicyclic and tricyclic heterocycle derivatives as histamine H3 receptor antagonists for the treatment of obesity. (United States)

    de Lera Ruiz, Manuel; Zheng, Junying; Berlin, Michael Y; McCormick, Kevin D; Aslanian, Robert G; West, Robert; Hwa, Joyce; Lachowicz, Jean; van Heek, Margaret


    A novel series of non-imidazole bicyclic and tricyclic histamine H3 receptor antagonists has been discovered. Compound 17 was identified as a centrally penetrant molecule with high receptor occupancy which demonstrates robust oral activity in rodent models of obesity. In addition compound 17 possesses clean CYP and hERG profiles and shows no behavioral changes in the Irwin test.

  3. Use of automated video analysis for the evaluation of bicycle movement and interaction (United States)

    Twaddle, Heather; Schendzielorz, Tobias; Fakler, Oliver; Amini, Sasan


    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.

  4. Bicycle fatalities : trends in crashes with and without motor vehicles in The Netherlands.

    NARCIS (Netherlands)

    Schepers, P. Stipdonk, H.L. Methorst, R. & Olivier, J.


    Boufous and Olivier (2015) recently found an increasing trend of police-reported cyclist deaths in single-vehicle crashes while a decreasing trend was found for fatal bicycle-motor vehicle crashes. This study sets out to conduct the same trend analyses for the Netherlands using causes of death stati

  5. Balance and control of a rear-wheel steered speed-record recumbent bicycle

    NARCIS (Netherlands)

    Schwab, A.L.; Kooijman, J.D.G.


    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

  6. Evaluation of a promotional strategy to increase bicycle helmet use by children. (United States)

    Parkin, P C; Spence, L J; Hu, X; Kranz, K E; Shortt, L G; Wesson, D E


    Bicycle-related head injuries are an important cause of death and disability, despite the availability of helmets. The objective of this study was to evaluate the effectiveness of a school-based bicycle helmet promotion program in increasing helmet use by children while controlling for secular trends. Two high-income and two low-income schools in an urban Canadian community were selected to receive a bicycle helmet promotion intervention, with the remaining 18 schools serving as controls. Approximately 1800 observations of bicycling children were made at randomly selected observational sites 2 to 5 months after the intervention to assess changes in behavior. Helmet use at all observation sites tripled from 3.4% (1990, preintervention) to 16% (1991, postintervention). In the high-income intervention area, observed helmet use rose dramatically from 4% to 36% in contrast to the more modest increase in the high-income control area from 4% to 15%. In the low-income intervention area, there was a modest increase from 1% to 7%, but it did not differ from the increase in the low-income control area from 3% to 13%. The program was highly successful in children of high-income families but not in children of low-income families. Developing strategies for low-income families remains a priority.

  7. Design of an aluminium bicycle path integrated in a steel bridge

    NARCIS (Netherlands)

    Maljaars, J.; Soetens, F.; Burggraaf, H.G.


    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

  8. Effect of Toe Clips During Bicycle Ergometry on VO2 max. (United States)

    Moffat, Roger S.; Sparling, Phillip B.


    Eight men participated in three randomized maximal oxygen uptake tests to investigate the hypothesis that the use of toe clips on bicycle ergometers produced a higher VO2 max. No significant difference in mean VO2 max or performance time was observed. (Author/MT)

  9. Environmental and social life cycle assessment of bamboo bicycle frames made in Ghana

    NARCIS (Netherlands)

    Agyekum, Eric Ofori; Fortuin, K.P.J.; Harst-Wintraecken, van der E.J.M.


    This case study assessed the environmental and social impact of bicycle frames made from wild Ghanaian bamboo. The environmental life cycle assessment (LCA) of the bamboo frame was compared to the LCA results of an aluminium frame and a steel frame. The results show that the overall environmental im

  10. Environmental and social life cycle assessment of bamboo bicycle frames made in Ghana

    NARCIS (Netherlands)

    Agyekum, Eric Ofori; Fortuin, K.P.J.; Harst-Wintraecken, van der E.J.M.


    This case study assessed the environmental and social impact of bicycle frames made from wild Ghanaian bamboo. The environmental life cycle assessment (LCA) of the bamboo frame was compared to the LCA results of an aluminium frame and a steel frame. The results show that the overall environmental im

  11. Responses to kayak ergometer performance after kayak and bicycle ergometer training. (United States)

    Ridge, B R; Pyke, F S; Roberts, A D


    Ten moderately active male volunteers, age 19-30 years, completed one month of training on either a kayak or a bicycle ergometer (five men in each group). The men completed sixteen 30 minute sessions of continuous work at an intensity which maintained their HR within 85-90% of its maximum, as previously determined on the kayak ergometer. After this training period the kayak group demonstrated significant decreases in VO2, VE, HR and blood lactate in submaximal kayak ergometer work and a significant increase in VO2 during maximal kayak ergometer work. These changes contributed to a significantly higher maximal kayaking work output. The bicycle-trained group did not make any of these improvements on the kayak ergometer. However in their last training session on the bicycle ergometer they were able to work at a higher submaximal load while maintaining the same heart rate as in the first training session. It was concluded that the circulatory and metabolic adjustments to kayak work are greater with kayak training than with bicycle training.

  12. Synthesis of bicyclic guanidines via cascade hydroamination/Michael additions of mono-N-acryloylpropargylguanidines. (United States)

    Kwon, Ki-Hyeok; Serrano, Catherine M; Koch, Michael; Barrows, Louis R; Looper, Ryan E


    A cascade silver(I)-catalyzed hydroamination/Michael addition sequence has been developed to deliver highly substituted bicyclic guanidines. This transformation gives rise to geometrically and constitutionally stable ene-guanidines and generates a remote stereocenter with moderate to high diastereoselectivity.

  13. Road safety and bicycle usage impacts of unbundling vehicular and cycle traffic in Dutch urban networks

    NARCIS (Netherlands)

    Schepers, Paul; Heinen, Eva; Methorst, Rob; Wegman, Fred


    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

  14. 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.


    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

  15. The Bicycle Illusion: Sidewalk Science Informs the Integration of Motion and Shape Perception (United States)

    Masson, Michael E. J.; Dodd, Michael D.; Enns, James T.


    The authors describe a new visual illusion first discovered in a natural setting. A cyclist riding beside a pair of sagging chains that connect fence posts appears to move up and down with the chains. In this illusion, a static shape (the chains) affects the perception of a moving shape (the bicycle), and this influence involves assimilation…

  16. On a finite group having a normal series whose factors have bicyclic Sylow subgroups

    CERN Document Server

    Monakhov, V S


    We consider the structure of a finite groups having a normal series whose factors have bicyclic Sylow subgroups. In particular, we investigated groups of odd order and $A_4$-free groups with this property. Exact estimations of the derived length and nilpotent length of such groups are obtained.

  17. A New Method for Computing the Centre of Mass of a Bicycle and Rider (United States)

    Yizhaq, Hezi; Baran, Gil


    For developing riding skills on mountain bikes, it is important to know how the centre of mass of a bicycle and its rider changes with ground inclination or with rider position. We show here a new method for finding the location of this point by measuring the normal forces acting on the wheels in two positions with a digital weight indicator. This…

  18. Tertiary Student Attitudes to Bicycle Commuting in a Regional Australian University (United States)

    Whannell, Patricia; Whannell, Robert; White, Richard


    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…

  19. Macroscopic modeling of pedestrian and bicycle crashes: A cross-comparison of estimation methods. (United States)

    Amoh-Gyimah, Richard; Saberi, Meead; Sarvi, Majid


    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.

  20. The Effects of Prompting and Reinforcement on Safe Behavior of Bicycle and Motorcycle Riders (United States)

    Okinaka, Takeru; Shimazaki, Tsuneo


    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…

  1. The Synthesis of cis- and trans-Fused Bicyclic Sugar Amino Acids

    NARCIS (Netherlands)

    Risseeuw, Martijn D.P.; Grotenbreg, Gijsbert M.; Witte, Martin D.; Tuin, Adriaan W.; Leeuwenburgh, Michiel A.; Marel, Gijsbert A. van der; Overkleeft, Herman S.; Overhand, Mark


    Four isomeric bicyclic sugar amino acids (SAAs) were prepared from an α-acetylenic-C-glucoside by employing a Petasis olefination and a ring-closing metathesis (RCM) as key steps. The applicability of the resulting SAAs in solid-phase peptide synthesis was demonstrated by the synthesis of a tetrapep

  2. A description of bicycle and moped rider accidents aimed to indicate priorities for injury prevention research.

    NARCIS (Netherlands)

    Huijbers, J.J.W.


    The aim of the study is to indicate priorities in the field of bicycle and moped injury prevention research, based on criteria given. The study is a part of a preparation for a SWOV accident investigation project that has to identify and to gratify factors influencing injuries of pedestrians, cyclis

  3. [Changes in ECG indicators during bicycle ergometry in patients having suffered myocardial infarction]. (United States)

    Kheifets, Z N


    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.

  4. Modeling Mixed Bicycle Traffic Flow: A Comparative Study on the Cellular Automata Approach

    Directory of Open Access Journals (Sweden)

    Dan Zhou


    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.

  5. Sandia bicycle commuters group -- pollution prevention at Sandia National Laboratories, New Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Wrons, R.


    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.


    Directory of Open Access Journals (Sweden)

    Pinar Arpinar-Avsar


    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. Identification of miRNomes reveals microRNA-199a-5p promoting the repairment of dosal column lesion through c-Jun N-terminal kinase pathway%微小RNA-199a-5p下调后通过c-jun氨基端激酶通路促进脊髓后索损伤修复的研究

    Institute of Scientific and Technical Information of China (English)

    王天仪; 刘勇; 原文琦; 张衍军; 王志杰; 张亮; 曹建刚; 冯世庆


    ).Thereby the upregulation of MKP2 inhibits the phosphorylation of c-Jun N-terminal kinase (JNK).Comparing with the simple dorsal column lesion group,the expression level of neurofilament protein significantly increased and the shape of nerve fiber bundle was more regular in caudal lesion site of sciatic nerve conditioning injury group.And simple sciatic nerve injury cannot alter the expression level of miR-199a-5p and MKP2 protein.Conclusion It is one of the repair mechanisms of dorsal column lesion which is promoted by sciatic nerve conditioning injury that the downregulation of miR-199a-5p inhibits the phosphorylation of JNK by upregulating MKP2 protein.

  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


    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. Using data mining techniques to predict the severity of bicycle crashes. (United States)

    Prati, Gabriele; Pietrantoni, Luca; Fraboni, Federico


    To investigate the factors predicting severity of bicycle crashes in Italy, we used an observational study of official statistics. We applied two of the most widely used data mining techniques, CHAID decision tree technique and Bayesian network analysis. We used data provided by the Italian National Institute of Statistics on road crashes that occurred on the Italian road network during the period ranging from 2011 to 2013. In the present study, the dataset contains information about road crashes occurred on the Italian road network during the period ranging from 2011 to 2013. We extracted 49,621 road accidents where at least one cyclist was injured or killed from the original database that comprised a total of 575,093 road accidents. CHAID decision tree technique was employed to establish the relationship between severity of bicycle crashes and factors related to crash characteristics (type of collision and opponent vehicle), infrastructure characteristics (type of carriageway, road type, road signage, pavement type, and type of road segment), cyclists (gender and age), and environmental factors (time of the day, day of the week, month, pavement condition, and weather). CHAID analysis revealed that the most important predictors were, in decreasing order of importance, road type (0.30), crash type (0.24), age of cyclist (0.19), road signage (0.08), gender of cyclist (0.07), type of opponent vehicle (0.05), month (0.04), and type of road segment (0.02). These eight most important predictors of the severity of bicycle crashes were included as predictors of the target (i.e., severity of bicycle crashes) in Bayesian network analysis. Bayesian network analysis identified crash type (0.31), road type (0.19), and type of opponent vehicle (0.18) as the most important predictors of severity of bicycle crashes.

  10. Bicyclic proline analogues as organocatalysts for stereoselective aldol reactions: an in silico DFT study. (United States)

    Shinisha, C B; Sunoj, Raghavan B


    Density functional theory has been employed in investigating the efficiency of a series of bicyclic analogues of proline as stereoselective organocatalysts for the aldol reaction. Three classes of conformationally restricted proline analogues, as part of either a [2.2.1] or [2.1.1] bicyclic framework, have been studied. Transition states for the stereoselective C-C bond formation between enamines derived from [2.2.1] and [2.1.1] bicyclic amino acids and p-nitrobenzaldehyde, leading to enantiomeric products, have been identified. Analysis of the transition state geometries revealed that the structural rigidity of catalysts, improved transition state organization as well as other weak interactions influence the relative stabilities of diastereomeric transition states and help contribute to the overall stereoselectivity in the aldol reaction. These bicyclic catalysts are predicted to be substantially more effective in improving the enantiomeric excess than the widely used organocatalyst proline. Enantiomeric excesses in the range 82-95% are predicted for these bicyclic catalysts when a sterically unbiased substrate such as p-nitrobenzaldehyde is employed for the asymmetric aldol reaction. More interestingly, introduction of substituents, as simple as a methyl group, at the ortho position of the aryl aldehyde bring about an increase in the enantiomeric excess to values greater than 98%. The reasons behind the vital energy separation between diastereomeric transition states has been rationalized with the help of a number of weak interactions such as intramolecular hydrogen bonding and Coulombic interactions operating on the transition states. These predictions could have wider implications for the rational design of improved organocatalysts for stereoselective carbon-carbon bond-forming reactions.

  11. 参芎化瘀胶囊预处理对脑缺血再灌注大鼠海马CA1区细胞凋亡及原癌基因c-fos、c-jun表达的影响%Effect of Shenxiong-Huayu capsule preconditioning on cell apoptosis and the expression of C-fos and C-jun in the hippocampal CA1 area of rats with cerebral ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    刘斌; 李爱华; 蔡梅芝; 王新宇


    目的 观察参芎化瘀胶囊预处理对脑缺血再灌注大鼠海马CA1区细胞凋亡及c-fos、c-jun 表达的影响.方法 将SD大鼠采用完全随机的方法分为假手术组(24只)、脑缺血再灌注组(模型组24只)和参芎化瘀胶囊预处理组(预处理组24只).假手术组、模型组给予生理盐水1 ml灌胃,预处理组给予参芎化瘀胶囊生理盐水混悬液1 ml (480mg)灌胃.均给药7d,1次/d.第7天给药2h后,用线栓法制作大脑中动脉阻断再灌注模型(MCAO).采用TUNEL法检测细胞凋亡,免疫组织化学法检测c-fos、c-jun的表达.结果 ①模型组6、24、48、72 h海马CA1区细胞凋亡数分别为(11.17±3.71、39.83±5.67、48.33±5.32、22.17±3.71)个/高倍视野,预处理组分别为(7.83±2.04、15.00±3.58、29.50±6.89和10.17±2.32)个/高倍视野.与模型组比较,预处理组不同时间点凋亡细胞减少(P<0.05或P<0.01).②模型组6、24、48、72h海马CA1区c-fos表达分别为(14.50±3.45、33.67±1.63、42.33±3.32、32.00±2.90)个/高倍视野,预处理组分别为(10.17±2.93、21.50±2.43、30.83±3.76、25.17±5.27)个/高倍视野.模型组6、24、48、72 h海马CA1区c-jun表达结果分别为(15.50±4.19、22.83±5.64、33.10±4.19、14.67±3.08)个/高倍视野,预处理组分别为(9.67±3.63、15.67±2.73、21.26±3.63和9.33±3.61个/高倍视野.与模型组比较,预处理组不同时间点c-fos、c-jun表达减少(P<0.05或P<0.01).结论 预处理组可通过抑制c-fos、c-jun表达,减少细胞凋亡,对大鼠脑缺血再灌注损伤具有保护作用.%Objective To observe the effect of Shenxiong-Huayu Capsule preconditioning on cell apoptosis and the expression of c-fos、c-jun in the hippocampal CA1 area of rats with acute cerebral ischemia reperfusion injury.Methods SD rats were divided into 3 groups by completely randomized method:sham operation group(n=6),ischemia reperfusion group (model group),and Shenxiong-Huayu Capsule preconditioning group

  12. Highly Constrained Bicyclic Scaffolds for the Discovery of Protease-Stable Peptides via mRNA Display. (United States)

    Hacker, David E; Hoinka, Jan; Iqbal, Emil S; Przytycka, Teresa M; Hartman, Matthew C T


    Highly constrained peptides such as the knotted peptide natural products are promising medicinal agents because of their impressive biostability and potent activity. Yet, libraries of highly constrained peptides are challenging to prepare. Here, we present a method which utilizes two robust, orthogonal chemical steps to create highly constrained bicyclic peptide libraries. This technology was optimized to be compatible with in vitro selections by mRNA display. We performed side-by-side monocyclic and bicyclic selections against a model protein (streptavidin). Both selections resulted in peptides with mid-nanomolar affinity, and the bicyclic selection yielded a peptide with remarkable protease resistance.

  13. Bicycle transport as an object of ecological marketing and innovations in urban transportations

    Directory of Open Access Journals (Sweden)

    O.S. Teletov


    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

  14. Angular Impact Mitigation system for bicycle helmets to reduce head acceleration and risk of traumatic brain injury. (United States)

    Hansen, Kirk; Dau, Nathan; Feist, Florian; Deck, Caroline; Willinger, Rémy; Madey, Steven M; Bottlang, Michael


    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 (pbicycle helmet, and may enhance prevention of bicycle-related TBI. Further research is required.

  15. "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.

  16. "Bicycles May Use Full Lane" Signage Communicates U.S. Roadway Rules and Increases Perception of Safety. (United States)

    Hess, George; Peterson, M Nils


    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.

  17. Development of an experimental methodology to evaluate the influence of a bamboo frame on the bicycle ride comfort (United States)

    Thite, A. N.; Gerguri, S.; Coleman, F.; Doody, M.; Fisher, N.


    In the current environment of increased emphasis on sustainable transport, there is manifold increase in the use of bicycles for urban transport. One concern which might restrict the use is the ride comfort and fatigue. There has been limited research in addressing the difficulty in bicycle ride comfort quantification. The current study aims to develop a methodology to quantify bicycle discomfort so that performance of bicycles constructed from bamboo and aluminium alloy can be compared. Experimentally obtained frequency response functions are used to establish a relation between the road input and the seat and rider response. A bicycle track input profile based on standard road profiles is created so as to estimate the acceleration responses. The whole-body-vibration frequency weighting is applied to quantify the perception of vibration intensity so that eventual discomfort ranking can be obtained. The measured frequency response functions provide an insight into the effect of frame dynamics on the overall resonant behaviour of the bicycles. The beneficial effect of frame compliance and damping on lower modes of vibration is very clear in the case of bamboo frame, in turn affecting seat and rider response. In the bamboo frame, because of multiple resonances, the frequency response of the handlebar is smaller at higher frequencies suggesting effective isolation. Further improvements may have come from the joints made from natural composites. Overall, based on the comparative analysis and the methodology developed, bamboo frame shows significant improvement in ride comfort performance compared with the aluminium frame.

  18. Optimal design parameters of the bicycle-rider system for maximal muscle power output. (United States)

    Yoshihuku, Y; Herzog, W


    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.

  19. The effect of cannabis on regular cannabis consumers' ability to ride a bicycle. (United States)

    Hartung, Benno; Schwender, Holger; Roth, Eckhard H; Hellen, Florence; Mindiashvili, Nona; Rickert, Annette; Ritz-Timme, Stefanie; Grieser, Almut; Monticelli, Fabio; Daldrup, Thomas


    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.

  20. 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


    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

  1. A sketch planning methodology for determining interventions for bicycle and pedestrian crashes: an ecological approach


    Thakuriah, P.; Cottrill, C.; Thomas, N.; Vaughn, S.


    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...

  2. Using Evolutionary Multiobjective Optimization Algorithms to Evolve Lacing Patterns for Bicycle Wheels


    Svensson, Mats Krüger


    This thesis investigates the use of evolutionary algorithms (EAs) to evolve and optimize lacing patterns of spokes for a bicycle wheel. There are multiple objectives and tradeoffs to be considered when evaluating a lacing pattern, for instance, strength versus balance. To handle this, an evolutionary multiobjective optimization (EMO) method has been used. Various EMO algorithms and approaches are tested. Among these, the new NSGA-III algorithm is used. Different representations of the lac...

  3. Synthesis and Structure of A Novel Caged Bicyclic Phosphate Flame Retardant

    Institute of Scientific and Technical Information of China (English)


    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.

  4. A holistic approach to the integration of bicycle traffic into the urban landscape


    Polonca Andrejčič Mušič; Ilka Čerpes


    Qualitative and quantitative indicators can be used to assess the quality of public space. The coherence of cycling infrastructure connectivity is an indicator of a public space's attractiveness as a basis for the quality of the bicycle traffic operation. We would like to find an optimal balance between the space's form and its image to provide good conditions for cycling as one of the most important forms of sustainable mobility, and consequently a factor facilitating a healthy lifestyle. Th...

  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. Product Variety, Supply Chain Structure, and Firm Performance: Analysis of the U.S. Bicycle Industry


    Taylor Randall; Karl Ulrich


    Using data from the U.S. bicycle industry, we examine the relation among product variety, supply chain structure, and firm performance. Variety imposes two types of costs on a supply chain: production costs and market mediation costs. Production costs include, among other costs, the incremental fixed investments associated with providing additional product variants. Market mediation costs arise because of uncertainty in product demand created by variety. In the presence of demand uncertainty,...

  7. Synthesis and Insecticidal Activity of Bicyclic Phosphorothionates and Related Monocyclic Phosphorothionates


    Wu, Shao-yong; Hirashima, Akinori; Takeya, Ryuko; Eto, Morifusa


    Some thiono-type bicyclic phosphorus esters (BPS) were synthesized and bioassayed for insecticidal activity against susceptible (SRS) houseflies. n-Propyl was most favorable as a substituent at position 4 for insecticidal activity. The introduction of substituents at position 3 did not improve the activity. Some functionized monocyclic phosphorothionates (MPs) were also synthesized as proBP candidates. Although some MPs were cyclized to the corresponding BPS by oxidation or by action of a bas...

  8. Factors of the safety in bicycle traffic in the City of Zagreb and its surrounding

    Directory of Open Access Journals (Sweden)

    Sindik Joško


    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.

  9. A Geo-Aware and VRP-Based Public Bicycle Redistribution System

    Directory of Open Access Journals (Sweden)

    J. H. Lin


    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.

  10. Changes in human cervical and lumbar spine curves while bicycling with different handlebar heights. (United States)

    Chen, Yi-Lang; He, Kuo-Chang


    Cycling is a daily activity that needs a high demand of human-bicycle fitness. However, studies into the fitness or ergonomic aspects are very little. In this study, the simulated 20 min bicycling test were performed by 26 male participants under 5 handle height conditions. Body joint angles and external cervical/lumbar spine lordosis were measured at the initial and cycling after 20 min. Results show that different handle heights did cause various trunk inclinations. Trunk inclination was negatively and positively correlated with lumbosacral angle (r = -0.620, p < 0.001) and cervical angle (r = 0.510, p < 0.001), respectively. In this study, regression models were also developed to predict the internal cervical and lumbar spine movements by external trunk inclination and head extension, respectively. The explanatory abilities for the variance of the models were 67.2% for LSA and 82.8% for CE prediction. This can be used to understand the cyclist's spine movements while field study of bicycling.

  11. A solid solution to a conjecture on the maximal energy of bipartite bicyclic graphs

    CERN Document Server

    Huo, Bofeng; Li, Xueliang; Shi, Yongtang


    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...

  12. The effect of alcohol hangover on the ability to ride a bicycle. (United States)

    Hartung, Benno; Schwender, Holger; Mindiashvili, Nona; Ritz-Timme, Stefanie; Malczyk, Axel; Daldrup, Thomas


    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.

  13. Built environment effects on cyclist injury severity in automobile-involved bicycle crashes. (United States)

    Chen, Peng; Shen, Qing


    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.

  14. Pedaling into high gear for bicycle policy in Canada : lessons from bike summit 2008 in Toronto

    Energy Technology Data Exchange (ETDEWEB)



    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.

  15. The impact of transportation infrastructure on bicycling injuries and crashes: a review of the literature

    Directory of Open Access Journals (Sweden)

    Cripton Peter A


    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

  16. 沙苑子总黄酮通过抑制内质网应激和JNK通路过度活化减轻百草枯中毒大鼠肺损伤%Total flavonoids from astragalus complanatus attenuates lung injury following paraquat poisoning in rats through inhibiting excessive endoplasmic reticulum stress and c-Jun N-terminal kinase pathway

    Institute of Scientific and Technical Information of China (English)

    张志坚; 董瑶瑶; 李晓萍; 彭礼波


    ) poisoning by inhibiting excessive endoplasmic reticulum stress (ERS) and c-Jun N-terminal kinase (JNK) pathway in rat.Methods Forty-eight Sprague-Dawley (SD) rats were randomly divided into six groups (n=8 in each group),including control group,model group,dimethyl sulfoxide (DMSO) vehicle control group,and FAC in low,medium,and high dosage groups.The model was reproduced by giving PQ 80 mg/kg orally to induce lung injury.The rats in control group were treated with saline by gavage.The rats in DMSO group were given 10% DMSO 20 mL/kg by gavage 2 hours before intraperitoneal injection of PQ,and those in FAC low,medium and high dosage groups received 40,80,160 mg·kg-1· d-1 of FAC solution intraperitoneally after the PQ administration.The rats were sacrificed 72 hours after giving PQ,and the left lung tissue was harvested 72 hours after the reproduction of experimental model.The ratio of wet/dry weight (W/D) and total lung water content (TLW) were determined.The pathohistological changes of the left lung was observed under light microscope,and scored with alveolar damage index of quantitative assessment (IQA).The mRNA expressions of JNK and glucose regulated protein 78 (GRP78) were determined by reverse transcription-polymerase chain reaction (RT-PCR),and the protein expression of JNK,phosphorylation-JNK (p-JNK),and GRP78 were determined by Western Blot.Results Compared with control group,the W/D ratio,TLW and IQA were increased significantly in model group and DMSO group,and the mRNA expressions of JNK and GRP78 and the protein expressions of JNK,p-JNK and GRP78 were markedly increased.Compared with the model group,the W/D ratio,TLW and IQA,and the expressions of JNK mRNA and p-JNK protein were significantly decreased in the FAC groups,especially in FAC high dosage group [W/D ratio:3.0 ± 0.3 vs.5.5 ± 0.5,TLW:2.2 ± 0.3 vs.4.7 ± 0.4,IQA:(15.4 ± 3.0)% vs.(40.0 ± 5.7)%,JNK mRNA:0.21 ± 0.08 vs.0.82 ±0.27,p-JNK protein:0.31 ±0.09 vs.0.78 ±0.25,all P<0.O1].The m

  17. The usefulness of GPS bicycle tracking data for evaluating the impact of infrastructure change on cycling behaviour. (United States)

    Heesch, Kristiann C; Langdon, Michael


    Issue addressed: A key strategy to increase active travel is the construction of bicycle infrastructure. Tools to evaluate this strategy are limited. This study assessed the usefulness of a smartphone GPS tracking system for evaluating the impact of this strategy on cycling behaviour.Methods: Cycling usage data were collected from Queenslanders who used a GPS tracking app on their smartphone from 2013-2014. 'Heat' and volume maps of the data were reviewed, and GPS bicycle counts were compared with surveillance data and bicycle counts from automatic traffic-monitoring devices.Results: Heat maps broadly indicated that changes in cycling occurred near infrastructure improvements. Volume maps provided changes in counts of cyclists due to these improvements although errors were noted in geographic information system (GIS) geo-coding of some GPS data. Large variations were evident in the number of cyclists using the app in different locations. These variations limited the usefulness of GPS data for assessing differences in cycling across locations.Conclusion: Smartphone GPS data are useful in evaluating the impact of improved bicycle infrastructure in one location. Using GPS data to evaluate differential changes in cycling across multiple locations is problematic when there is insufficient traffic-monitoring devices available to triangulate GPS data with bicycle traffic count data.So what?: The use of smartphone GPS data with other data sources is recommended for assessing how infrastructure improvements influence cycling behaviour.

  18. Factors associated with bicycle-helmet use among 8-16 years aged Turkish children: a questionnaire survey. (United States)

    Secginli, Selda; Cosansu, Gulhan; Nahcivan, Nursen O


    The purpose of this cross-sectional, descriptive study was to assess the rates of helmet and to examine variables related to bicycle helmet use in a sample of 8-16 year old Turkish children. Data were collected from a purposive sample of 1180 students who self-identified as cyclists and 1128 parents or guardians in two state primary schools in two urban municipalities in the northern part of Istanbul, Turkey. Results showed that self-reported helmet use was found prevalent in 4.4% of the children. The most cited reasons for not wearing a helmet were: 'don't own one', 'helmets are uncool', and 'uncomfortable'. Significant differences between helmet users and non-users correlated to gender, age, owning a bicycle helmet, wearing a friend's bicycle helmet and parents or guardian's bicycle helmet use while riding. Only three variables--helmet ownership (OR = 10.028, 95% CI 5.08, 19.79), parents' helmet use (OR = 2.62, 95% CI 1.22, 5.66) and friends' helmet use (OR = 0.16, 95% CI 0.07, 0.37) emerged as significant predictors of the likelihood of helmet use. The relatively low helmet use prevalence points to an urgent need for a multipronged campaign, including strategies such as raising awareness, educating primarly parents and friends, and distributing bicycle helmets for free or at a reduced cost.

  19. 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


    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.

  20. 盐酸戊乙奎醚对发育期大鼠学习记忆能力及海马c-Jun氨基末端激酶表达的影响%Effect of penehyclidine hydrochloride on learning-memory and expression of hippocampal c-Jun N-terminal kinase in developing rats

    Institute of Scientific and Technical Information of China (English)

    徐刚; 卢锡华


    Objective To investigate the effect of penehyclidine hydrochloride on learning-memory and expression of hippocampal c-Jun N-terminal kinase in developing rats.Methods Forty specific pathogen free (SPF) Sprague-Dawley (SD) rats,aged 7 days,were randomly allocated into two groups,20 rats per group.Rats were injected intraperitoneally with penehyclidine hydrochloride at the dose of 0.3 mg/(kg·d) or normal saline at the same dose for continuous seven days in Pen group or NS group.After drug administration,ten rats of each group were randomly euthanized and hippocampus was excised.The ratio of wet weight/dry weight (W/D) and total content of water (TCW) of hippocampus were tested.The expression of JNK mRNA and phosphorylated JNK (p-JNK) protein were detected respectively by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.Apoptosis index (AI) of hippocampus was determined by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method.The rest of rats underwent Morris water maze test when they were aged two months in the two groups.After Morris water maze test was finished,the rats were euthanized and hippocampus was excised.W/D and TCW of hippocampus were tested.The expressions of JNK mRNA and p-JNK protein were detected by RT-PCR and Western blotting,respectively.AI of hippocampus was determined by TUNEL method.Results Comparedto NSgroup [(17.67±7.94) s,(12.35±6.78) s;(2 122.67± 543.56) mm,(1 123.78± 369.22) mm],the escape latency [(54.58± 9.85) s,(56.73 ± 7.85) s] and swimming distance [(4 789.54 ± 677.83) mm,(4 987.34 ± 884.85) mm]were prolonged (both P < 0.05).Compared to rats aged 14 d at the same group,AI[(35.15 ± 5.97) %vs.(2.91 ± 0.98) %],W/D (4.94 ± 0.77 vs.3.43 ± 0.51) and TCW (3.94 ± 0.76 vs.2.43 ± 0.50)of hippocampus were all notably higher (P < 0.05) and the expression of JNK mRNA (0.97 ± 0.17 vs.0.45 ± 0.10) and p-JNK protein (2.78 ± 0.75 vs.1.08 ± 0.25) were

  1. The Physics of Motorcycles and Fast Bicycles : Lean, Stability and Counter-steering

    CERN Document Server

    Shayak, B


    In this work I will obtain the system of nonlinear equations that correctly describes the motion of motorcycles and fast bicycles (above 30 km/hr) for the first time in literature. I will use it to calculate the lean angle during a turn and prove that the motion of the vehicle is unconditionally stable at all operating speeds under consideration. I will then employ it to give a quantitative model of counter-steering - the phenomenon by which a turning mobike first goes the wrong way and then starts going the right way.

  2. 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)


    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.

  3. 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


    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.

  4. Synthesis and Antibacterial Activity of Novel Oxazolidinone Analogs Containing Substituted Thiazole/Fused-Bicyclic Groups

    Institute of Scientific and Technical Information of China (English)


    Sixteen novel oxazolidinone analogs containing substituted thiazole/fused-bicyclic(imidazo[1,2-b] pyridazine/imidazo[2,1-b]thiazole) groups were designed and synthesized. A new method for the preparation of the key intermediate compound 11 was proposed. The structures of the target compounds were confirmed by 1H NMR, IR and MS, and their in vitro antibacterial activities against staphylococcus aureus were evaluated. Among them, compound 16a displays a promising antibacterial activity comparable to that of linezolid.

  5. Synthesis of fused bicyclic piperidines: potential bioactive templates for medicinal chemistry. (United States)

    Zhou, Jinglan; Campbell-Conroy, Erica L; Silina, Alina; Uy, Johnny; Pierre, Fabrice; Hurley, Dennis J; Hilgraf, Nicole; Frieman, Bryan A; DeNinno, Michael P


    An array of six pyridyl-substituted fused bicyclic piperidines was prepared as novel cores for medicinal chemistry. For maximum diversity, the size of the fused ring varied from three to six atoms and contained up to two oxygen atoms. The pyridine ring was incorporated to improve physicochemical properties and to challenge the robustness of the chemistry. The presence of the pyridine did interfere with our initial approaches to these molecules, and in several instances, a blocking strategy had to be employed. These new scaffolds possess high sp3 character and may prove useful in multiple medicinal chemistry applications.

  6. Feasibility study on a perceived fatigue prediction dependent power control for an electrically assisted bicycle. (United States)

    Kiryu, T; Minagawa, H


    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.

  7. [The electrical stimulation bicycle: a neuroprosthesis for the everyday use of paraplegic patients]. (United States)

    Szecsi, J; Fiegel, M; Krafczyk, S; Straube, A; Quintern, J; Brandt, Th


    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.

  8. Long-Term Effects of Education and Legislation Enforcement on All-Age Bicycle Helmet Use: A Longitudinal Study. (United States)

    Huybers, Sherry; Fenerty, Lynne; Kureshi, Nelofar; Thibault-Halman, Ginette; LeBlanc, John C; Clarke, David B; Walling, Simon


    Bicycle-related injuries are a leading cause of child and youth hospitalizations in Canada. The use of helmets while bicycling reduces the risk of brain injuries. This study investigated the long-term effect of legislation coupled with enforcement to improve helmet use rates. We conducted a longitudinal observational study of helmet use at 9, 11, and 14 years after bicycle helmet legislation was enacted. Data were compared to baseline observations collected after legislation was passed in 1997. A comprehensive enforcement and educational diversion program, Operation Headway-Noggin Knowledge (OP-NK), was developed and implemented in partnership with regional police during the study period. Helmet use was sustained throughout the post-legislation period, from 75.3 % in the year legislation was enacted to 94.2 % 14 years post-legislation. The increase in helmet use was seen among all age groups and genders. Helmet legislation was not associated with changes in bicycle ridership over the study years. OP-NK was associated with improved enforcement efforts as evidenced by the number of tickets issued to noncompliant bicycle riders. This observational study spans a 16-year study period extending from pre-legislation to 14 years post all-age bicycle helmet legislation. Our study results demonstrate that a comprehensive approach that couples education and awareness with ongoing enforcement of helmet legislation is associated with long-term sustained helmet use rates. The diversion program described herein is listed among best practices by the Public Health Agency of Canada.

  9. Analysis of vehicle-bicycle interactions at unsignalized crossings: A probabilistic approach and application. (United States)

    Silvano, Ary P; Koutsopoulos, Haris N; Ma, Xiaoliang


    In the last decades, bicycle usage has been increasing in many countries due to the potential environmental and health benefits. Therefore, there is a need to better understand cyclists' interactions with vehicles, and to build models and tools for evaluating multimodal transportation infrastructure with respect to cycling safety, accessibility, and other planning aspects. This paper presents a modeling framework to describe driver-cyclist interactions when they are approaching a conflicting zone. In particular, the car driver yielding behavior is modeled as a function of a number of explanatory variables. A two-level hierarchical, probabilistic framework (based on discrete choice theory) is proposed to capture the driver's yielding decision process when interacting with a cyclist. The first level models the probability of the car driver perceiving a situation with a bicycle as a potential conflict whereas the second models the probability of yielding given that a conflict has been perceived by the driver. The framework also incorporates the randomness of the location of the drivers' decision point. The methodology is applied in a case study using observations at a typical Swedish roundabout. The results show that the conflict probability is affected differently depending on the user (cyclist or driver) who arrives at the interaction zone first. The yielding probability depends on the speed of the vehicle and the proximity of the cyclist.

  10. Antiproliferative activity of bicyclic benzimidazole nucleosides: synthesis, DNA-binding and cell cycle analysis. (United States)

    Sontakke, Vyankat A; Lawande, Pravin P; Kate, Anup N; Khan, Ayesha; Joshi, Rakesh; Kumbhar, Anupa A; Shinde, Vaishali S


    An efficient route was developed for synthesis of bicyclic benzimidazole nucleosides from readily available d-glucose. The key reactions were Vörbruggen glycosylation and ring closing metathesis (RCM). Primarily, to understand the mode of DNA binding, we performed a molecular docking study and the binding was found to be in the minor groove region. Based on the proposed binding model, UV-visible and fluorescence spectroscopic techniques using calf thymus DNA (CT-DNA) demonstrated a non-intercalative mode of binding. Antiproliferative activity of nucleosides was tested against MCF-7 and MDA-MB-231 breast cancer cell lines and found to be active at low micromolar concentrations. Compounds and displayed significant antiproliferative activity as compared to and with the reference anticancer drug, doxorubicin. Cell cycle analysis showed that nucleoside induced cell cycle arrest at the S-phase. Confocal microscopy has been performed to validate the induction of cellular apoptosis. Based on these findings, such modified bicyclic benzimidazole nucleosides will make a significant contribution to the development of anticancer drugs.

  11. Comparison between treadmill and bicycle ergometer exercise tests in mild-to-moderate hypertensive Nigerians

    Directory of Open Access Journals (Sweden)

    Abiodun OO


    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

  12. Solution and Structural Investigations of Ligand Preorganization in Trivalent Lanthanide Complexes of Bicyclic Malonamides

    Energy Technology Data Exchange (ETDEWEB)

    Parks, Bevin W.; Gilbertson, Robert D.; Hutchison, J. E.; Rather Healey, Elisabeth; Weakley, Timothy J R; Rapko, Brian M.; Hay, Benjamin P.; Sinkov, Sergei I.; Broker, Grant A.; Rogers, Robin D.


    This report describes an investigation into the coordination chemistry of trivalentlanthanides in solution and the solid state with acyclic and preorganized bicyclic malonamide ligands. Two experimental investigations were performed: solution bindingaffinities were determined through single-phase spectrophotometric titrations and the extent of conformational change upon binding was investigated with single-crystal X-raycrystallography. Both experimental methods compare the bicyclic malonamide (BMA), which is designed to be preorganized for binding trivalent lanthanides, to an analogousacyclic malonamide. Results from the spectrophotometric titrations indicate that BMA exhibits a 10-100 times increase in binding affinity to Ln(III) over acyclic malonamide.In addition, BMA forms compounds with high ligand-metal ratios, even when competing with water and nitrate ligands for binding sites. The crystal structures exhibit nosignificant differences in the nature of the binding between Ln(III) and the BMA or acyclic malonamide. These results support the conclusion that rational ligand design canlead to compounds that enhance the binding affinities within a ligand class.

  13. Cardiovascular and hormonal responses to bicycle exercise during lower body negative pressure (United States)

    Bonde-Petersen, F.; Suzuki, M.; Christensen, N. J.

    The purpose was to combine bicycle exercise and LBNP as a model to investigate the mechanisms regulating circulation during gravitatiobal stresses. METHODS: Cardiac Output (CO) by acetylene-, argon-, oxygen rebreathing; Heart Rate (HR) from ECG; Mean Arterial Pressure (MAP) by arm cuff; Plasma Nor-Epinephrine (NE), Epinephrine (E), and Lactate (HLa) by isotope and enzymatic techniques respectively. Total Peripheral Resistance (TPR)=MAP/CO and stroke volume (SV)=CO/HR. Six subjects exercised at 180-200 Watts in the upright position on a mechanically braked computer controlled small bicycle ergometer placed in a LBNP box. The above parameters were measured at rest and at 5 and 9 min of exercise without and with LBNP at -30 or -40 mmHg (depending on LBNP tolerance). RESULTS AND CONCLUSIONS: In the face of an increased sympathetic nervous activity (Ne+E, TPR, and HR increased) during exercise in LBNP, there was a decrease in CO and SV indicating that the venous return was insufficient. However, HLa was unchanged demonstrating that the blood flow to the working muscles did not suffer.

  14. A holistic approach to the integration of bicycle traffic into the urban landscape

    Directory of Open Access Journals (Sweden)

    Polonca Andrejčič Mušič


    Full Text Available Qualitative and quantitative indicators can be used to assess the quality of public space. The coherence of cycling infrastructure connectivity is an indicator of a public space's attractiveness as a basis for the quality of the bicycle traffic operation. We would like to find an optimal balance between the space's form and its image to provide good conditions for cycling as one of the most important forms of sustainable mobility, and consequently a factor facilitating a healthy lifestyle. The new approach brings a completely different view on planning cycling infrastructure, while rather than physical infrastructure characteristics, humans are placed at the forefront of the cycling infrastructure design as the most important measure of its quality. Since the complexity of human beings cannot be controlled with only one science or profession, solving the problem of bicycle traffic is not just a technical problem, but its design and management also lend a multidisciplinary character. From the perspective of different cycling infrastructure users, the study will define integrated multidisciplinary methodology for evaluating the quality of cycling infrastructure, which will equally include the criteria of sensing and perceiving of space. The new approach seeks a system of criteria, which enables the integrated planning of cycling infrastructure in all spatial, organizational, sectoral, and professional levels. All theoretical findings will be tested and demonstrated on the pilot case of the long-distance cycling connection in the area of four Slovenian coastal municipalities, namely Koper, Izola, Piran, and Ankaran.

  15. 150 bicycle injuries in children: a comparison with accidents due to other causes. (United States)

    Illingworth, C M; Noble, D; Bell, D; Kemn, I; Roche, C; Pascoe, J


    One hundred and fifty bicycle accidents seen at the Children's Hospital Sheffield over a 6-month period from mid-August 1979 were analysed and 9.3 per cent of the cases were admitted. Twenty-two per cent had fractures, 20 per cent had soft tissue injuries of face or scalp, 8 children having damaged their teeth. Of the accidents 17.3 per cent were due to hitting an obstruction, 30.7 per cent were due to loss of control on a hill or corner and 8 per cent were of mechanical origin. Eighty-eight per cent had cycling experience of a year or more, and 32.7 per cent had had previous cycling accidents. Comparison with other types of accidents previously studied at the hospital, involving skateboards, playground equipment or road traffic accidents affecting child pedestrians, showed that by far the most serious were those involving child pedestrians. The injuries from bicycle accidents were similar in severity to those involving skateboards.

  16. Energy cost and mechanical efficiency of riding a human-powered recumbent bicycle. (United States)

    Capelli, Carlo; Ardigo, Luca Paolo; Schena, Federico; Zamparo, Paola


    When dealing with human-powered vehicles, it is important to quantify the capability of converting metabolic energy in useful mechanical work by measuring mechanical efficiency. In this study, net mechanical efficiency (eta) of riding a recumbent bicycle on flat terrain and at constant speeds (v, 5.1-10.0 m/s) was calculated dividing mechanical work (w, J/m) by the corresponding energy cost (C(c), J/m). w and C(c) increased linearly with the speed squared: w = 9.41 + 0.156 . v(2); C(c) = 39.40 + 0.563 . v(2). eta was equal to 0.257 +/- 0.0245, i.e. identical to that of concentric muscular contraction. Hence, i) eta seems unaffected by the biomechanical arrangement of the human-vehicle system; ii) the efficiency of transmission seems to be close to 100%, suggesting that the particular biomechanical arrangement does not impair the transformation of metabolic energy in mechanical work. When dealing with human-powered vehicles, it is important to quantify mechanical efficiency (eta) of locomotion. eta of riding a recumbent bicycle was calculated dividing the mechanical work to the corresponding energy cost of locomotion; it was practically identical to that of concentric muscular contraction (0.257 +/- 0.0245), suggesting that the power transmission from muscles to pedals is unaffected by the biomechanical arrangement of the vehicle.

  17. Long-term use of computerized bicycle ergometry for spinal cord injured subjects. (United States)

    Sipski, M L; Alexander, C J; Harris, M


    Twenty-eight spinal cord injured subjects who participated in an electrical stimulation bicycle ergometry home program were surveyed to determine perceived benefits, home exercise adherence, and predictors of continued home exercise with electrical stimulation. Subjects were classified as users or nonusers depending upon if they used the electrical stimulation ergometry on a regular basis in the home during the past four months. Nineteen subjects qualified as users and nine were nonusers. Ninety-five percent of the users cycled at least twice per week whereas the majority of the nonusers stopped regular home exercise within one month postclinic discharge. All subjects generally perceived increases in muscle bulk and endurance. Users and nonusers perceived inconsistent results related to spasticity. Minimal effects were noted with neurogenic pain and swelling. Adherence to the home exercise program was significantly related to sex of subject and pre-injury exercise habits. Results are discussed in relation to the costs and benefits of electrical stimulation bicycle ergometry in the home.

  18. Bicycle helmets.

    NARCIS (Netherlands)


    One third of the cyclists who are admitted to hospital with serious injury after a road crash are diagnosed with head or brain injury. Approximately three-quarters of the head and brain injuries among cyclists are caused by crashes that do not involve motorized traffic; as many as nine out of ten yo

  19. A Balanced Scorecard of Sustainable Management in the Taiwanese Bicycle Industry: Development of Performance Indicators and Importance Analysis

    Directory of Open Access Journals (Sweden)

    Chih-Chao Chung


    Full Text Available The main purpose of this study is to investigate the development of the performance indicators of sustainable management in the Taiwanese bicycle industry and to perform an importance analysis. Based on the Balanced Scorecard concept, the framework of sustainable management is added. Ten experts evaluated the performance indicators of a sustainable Balanced Scorecard in the Taiwanese bicycle industry using five major categories: (1 Financial, (2 Customer, (3 Internal Business Processes, (4 Learning and Growth, and (5 Sustainable Development, and a total of 21 performance indicators were used. The analytic network process (ANP was used to perform an importance analysis of the various performance indicators. Most of the experts suggested that for the introduction of a sustainable management strategy into the bicycle industry in Taiwan, it is necessary to include the definition of sustainable management and to improve five performance indicators: innovation process, customer satisfaction, operations process, after-sales service, and market share. According to the analysis results, this study proposed relevant management definitions and suggestions to be used as important references for decision-makers to understand the introduction of sustainable management strategies to the current bicycle industry in Taiwan.

  20. Changes in VO2 Max. Resulting from Bicycle Training at Different Intensities Holding Total Mechanical Work Constant. (United States)

    Burke, Edmund A., Jr.; Franks, B. Don

    Effects of different training intensities on oxygen intake were determined in this study. Sixteen male subjects aged 16-18 were randomly assigned to one of three training groups or a control group. The training groups trained 3 days per week on bicycle ergometers at different intensities (85 percent, 75 percent, or 65 percent of heart rate…

  1. The effect of depressive symptomatology on plasma cortisol responses to acute bicycle exercise among post-menopausal women

    NARCIS (Netherlands)

    van der Pompe, G.; Bernards, N; Meijman, T.F.; Heijnen, C.J


    The present study was designed to elucidate the effect of depressive symptomatology on the cortisol response to strenuous exercise. Thirteen healthy, post-menopausal women participated in this study. The results show that acute bicycle exercise activates the hypothalamic-pituitary-adrenal (HPA) axis

  2. Examining the potential for modal change : motivators and barriers for bicycle commuting in Dar-es-Salaam

    NARCIS (Netherlands)

    Nkurunziza, A.; Zuidgeest, M.H.P.; Brussel, M.J.G.; Maarseveen, van M.F.A.M.


    The paper examines the effect of various motivators, barriers and policy related interventions (i.e., personal, social and physical–environmental factors) on bicycle commuting in Dares-Salaam, Tanzania. The research shows that these factors have different effects on people depending on the stage of

  3. Age Does Not Affect the Material Properties of Expanded Polystyrene Liners in Field-Used Bicycle Helmets. (United States)

    Kroeker, Shannon G; Bonin, Stephanie J; DeMarco, Alyssa L; Good, Craig A; Siegmund, Gunter P


    Bicycle helmet foam liners absorb energy during impacts. Our goal was to determine if the impact attenuation properties of expanded polystyrene (EPS) foam used in bicycle helmets change with age. Foam cores were extracted from 63 used and unused bicycle helmets from ten different models spanning an age range of 2-20 yrs. All cores were impact tested at a bulk strain rate of 195 s(-1). Six dependent variables were determined from the stress-strain curve derived from each impact (yield strain, yield stress, elastic modulus, plateau slope, energy at 65% compression, and stress at 65% compression), and a general linear model was used to assess the effect of age on each dependent variable with density as a covariate. Age did not affect any of the dependent variables; however, greater foam density, which varied from 58 to 100 kg/m(3), generated significant increases in all of the dependent variables except for yield strain. Higher density foam cores also exhibited lower strains at which densification began to occur, tended to stay within the plateau region of the stress-strain curve, and were not compressed as much compared with the lower density cores. Based on these data, the impact attenuation properties of EPS foam in field-used bicycle helmets do not degrade with the age.

  4. Synthesis of novel N1-substituted bicyclic pyrazole amino acids and evaluation of their interaction with glutamate receptors

    DEFF Research Database (Denmark)

    Conti, Paola; Grazioso, Giovanni; di Ventimiglia, Samuele Joppolo


    N1-substituted bicyclic pyrazole amino acids (S)-9a-9c and (R)-9a-9c, which are conformationally constrained analogues of glutamic acid, were prepared via a strategy based on a 1,3-dipolar cycloaddition. The new amino acids were tested for activity at ionotropic and metabotropic glutamate receptors...

  5. Solar battery powered bicycle lamp SKL050. Final report; Solar/Akkufahrradleuchte SKL050. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Lang, O.


    Up to now there are no functional or high quality mobile solar powered chargers and lamps available for the outdoor and bicycle consumer. Hence the project SKL050 was concerned with the development of a novel combination of battery powered multi-functional lamp and solar charger. All components such as solar module, bulb, electronics and housing were supposed to be involved in the development. The goal was a ready-for-production development well placed in the field of high quality bicycle, camping and household appliances by efficient, well matched components and an exclusive and functional design. Another issue in the development was a cost effective production by automated assembling in order to maintain the maximum customer price of 129,- DM (incl. VAT). Most of the stated goals were reached at the end of the project. Only the detailed construction of the housing parts and final approvals have to be carried out by a bicycle accessories company which is interested to produce and market the SKL050 in licence. Apart from the product SKL050 several important results regarding automation processes of small solar modules have been collected and are supposed to be integrated in future products of the SOLARC GmbH. (orig.) [German] Im Bereich mobiler solarbetriebener Ladegeraete und Leuchten fuer den Outdoor- und Fahrradkonsumenten sind bislang keine funktionell oder aesthetisch brauchbaren Produkte verfuegbar. Das Vorhaben SKL050 umfasste daher gezielt die Entwicklung einer neuartigen Kombination aus akkubetriebener Mehrzweckleuchte und Solar-Akkulader. Saemtliche Basiskomponenten wie Solarmodul, Leuchtmittel, Elektronik und Gehaeuse sollten mit in die Entwicklung einbezogen werden. Ziel des Vorhabens war ein zur Serienreife entwickeltes Produkt, welches durch leistungsfaehige, optimal aufeinander abgestimmte Komponenten sowie durch ein exklusives und funktionelles Design einen Platz im Bereich der hochwertigen Fahrrad-, Camping-, und Haushaltsaccessoires findet. Bei

  6. Conformational Preference and Donor Atom Interaction Leading to Hexacoordination vs Pentacoordination in Bicyclic Tetraoxyphosphoranes(1). (United States)

    Sherlock, David J.; Chandrasekaran, A.; Prakasha, T. K.; Day, Roberta O.; Holmes, Robert R.


    New bicyclic tetraoxyphosphoranes all containing a six-membered oxaphosphorinane ring, C(6)H(8)(CH(2)O)(2)P(OC(12)H(8))(OXyl) (1), (C(6)H(4)O)(2)P(OC(12)H(8))(OXyl) (2), CH(2)[(t-Bu)(2)C(6)H(2)O](2)P(OC(12)H(8))(OXyl) (3), O(2)S[(t-Bu)MeC(6)H(2)O](2)P(OC(12)H(8))(OXyl) (4), and S[(t-Bu)MeC(6)H(2)O](2)P(OC(12)H(8))(OXyl) (5), were synthesized by the oxidative addition reaction of the cyclic phosphine P(OC(12)H(8))(OXyl) (6) with an appropriate diol in the presence of N-chlorodiisopropylamine. X-ray analysis revealed trigonal bipyramidal (TBP) geometries for 1-4 where the dioxa ring varied in size from six- to eight-membered. With a sulfur donor atom as part of an eight-membered ring in place of a potential oxygen donor atom of a sulfone group as in 4, the X-ray study of 5 showed the formation of a hexacoordinated structure via a P-S interaction. Ring constraints are evaluated to give an order of conformational flexibility associated with the (TBP) tetraoxyphosphoranes 4 > 3 approximately 1 > 2 which parallels the degree of shielding from (31)P NMR chemical shifts: 4 > 3 > 1 > 2. The six- and seven-membered dioxa rings in 1 and 2, respectively, are positioned at axial-equatorial sites, whereas the eight-membered dioxa ring in 3 and 4 occupies diequatorial sites of a TBP. V-T (1)H NMR data give barriers to xylyl group rotation about the C-OXyl bond. The geometry of 5 is located along a coordinate from square pyramidal toward octahedral to the extent of 60.7%. Achieving hexacoordination in bicyclic tetraoxyphosphoranes of reduced electrophilicity relative to bicyclic pentaoxyphosphoranes appears to be dependent on the presence of a sufficiently strong donor atom.

  7. Procyanidin induces apoptosis of esophageal adenocarcinoma cells via JNK activation of c-Jun. : Procyanidin induces apoptosis of esophageal adenocarcinoma cells via JNK activation of c-Jun.

    NARCIS (Netherlands)

    Connor, Carol A; Adriaens, Michiel; Pierini, Roberto; Johnson, Ian T; Belshaw, Nigel J


    Procyanidins are polymeric flavanols found in fruits and vegetables and have shown anticarcinogenic/chemopreventive properties. We previously showed that oligomeric procyanidin extracted from apples induced cell cycle arrest and apoptosis in esophageal adenocarcinoma (OA) cells. To understand the me

  8. Universal flow-density relation of single-file bicycle, pedestrian and car motion (United States)

    Zhang, J.; Mehner, W.; Holl, S.; Boltes, M.; Andresen, E.; Schadschneider, A.; Seyfried, A.


    The relation between flow and density is an essential quantitative characteristic to describe the efficiency of traffic systems. We have performed experiments with single-file motion of bicycles and compared the results with previous studies for car and pedestrian motion in similar setups. In the space-time diagrams we observe three different states of motion (free flow state, jammed state and stop-and-go waves) in all these systems. Despite their obvious differences they are described by a universal fundamental diagram after proper rescaling of space and time which takes into account the size and free velocity of the three kinds of agents. This indicates that the similarities between the systems go deeper than expected.

  9. Commuter Transport Mode Choice and Typologies in the Bicycle City Copenhagen

    DEFF Research Database (Denmark)

    Olesen, Anne Vingaard; Kjems, Erik; Reinau, Kristian Hegner;


    Bicycle Cities” such as Copenhagen can serve as role models: how far can we push the commuter modal shares in the direction of more sustainable transport? This paper presents a study that aims to give a state-of-the-art picture of a Copenhagen that provides wide cycling highways and the politica...... restricted our analysis to commuters both living and working within the city center. The characterization of these commuter types was strikingly short of personal attitudes about environmental concerns....... transport and car use. Furthermore, we derived a typology of four commuter types: “cyclists because of short distances” (40 percent), ”commuters by car or public transport out of necessity” (35 percent), ”more eco-oriented cyclists and others” (16 percent) and ”passionate motorists” (8 percent) when we...

  10. Synthesis of bicyclic molecular scaffolds (BTAa): an investigation towards new selective MMP-12 inhibitors. (United States)

    Mannino, Claudia; Nievo, Marco; Machetti, Fabrizio; Papakyriakou, Athanasios; Calderone, Vito; Fragai, Marco; Guarna, Antonio


    Starting from 3-aza-6,8-dioxa-bicyclo[3.2.1]octane scaffold (BTAa) a virtual library of molecules was generated and screened in silico against the crystal structure of the Human Macrophage Metalloelastase (MMP-12). The molecules obtaining high score were synthesized and the affinity for the catalytic domain of MMP-12 was experimentally proved by NMR experiments. A BTAa scaffold 20 having a N-hydroxyurea group in position 3 and a p-phenylbenzylcarboxy amide in position 7 showed a fair inhibition potency (IC50 = 149 microM) for MMP-12 and some selectivity towards five different MMPs. These results, taken together with the X-ray structure of the adduct between MMP-12, the inhibitor 20 and the acetohydroxamic acid (AHA), suggest that bicyclic scaffold derivatives may be exploited for the design of new selective matrix metalloproteinase inhibitors (MMPIs).

  11. Laser dye stability. Pt. 4. Photodegradation relationships for bicyclic dyes in alcohol solutions

    Energy Technology Data Exchange (ETDEWEB)

    Fletcher, A.N. (Naval Weapons Center, China Lake, Calif. (USA). Research Dept.)


    Changes in the absorption of a dye laser solution are examined after excitation with a xenon flashlamp. It is found that the rate of bleaching as a function of the total input energy of coumarin or quinolone dyes in ethanol increases in direct proportion to the dye concentration. This relationship suggests that the dye reacts with a photoproduct of the solvent rather than being directly decomposed by the xenon flash. We have measured the conversion of the dye to form products, P, absorbing at the lasing wavelength. Results correspond to the dye reacting with a precursor of P to form either insoluble products or ones not absorbing at the lasing wavelength. Thus larger total amounts of bleached dye do not proportionately increase P, and hence do not proportionately inhibit lasing. Furthermore, we find that P increases with the total input energy fairly independent of the rate of bleaching for a given bicyclic dye in an alcohol solution.

  12. Universal flow-density relation of single-file bicycle, pedestrian and car motion

    CERN Document Server

    Zhang, Jun; Holl, Stefan; Boltes, Maik; Andresen, Erik; Schadschneider, Andreas; Seyfried, Armin


    The relation between flow and density, also known as the fundamental diagram, is an essential quantitative characteristic to describe the efficiency of traffic systems. We have performed experiments with single-file motion of bicycles and compare the results with previous studies for car and pedestrian motion in similar setups. In the space-time diagrams we observe three different states of motion (free flow state, jammed state and stop-and-go waves) in all these systems. Despite of their obvious differences they are described by a universal fundamental diagram after proper rescaling of space and time which takes into account the size and free velocity of the three kinds of agents. This indicates that the similarities between the systems go deeper than expected.

  13. Universal flow-density relation of single-file bicycle, pedestrian and car motion

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, J., E-mail: [Jülich Supercomputing Centre, Forschungszentrum Jülich GmbH, 52425 Jülich (Germany); Mehner, W., E-mail: [Jülich Supercomputing Centre, Forschungszentrum Jülich GmbH, 52425 Jülich (Germany); Holl, S., E-mail: [Jülich Supercomputing Centre, Forschungszentrum Jülich GmbH, 52425 Jülich (Germany); Boltes, M., E-mail: [Jülich Supercomputing Centre, Forschungszentrum Jülich GmbH, 52425 Jülich (Germany); Andresen, E., E-mail: [Department of Computer Simulation for Fire Safety and Pedestrian Traffic, Bergische Universität Wuppertal, 42285 Wuppertal (Germany); Schadschneider, A., E-mail: [Institut für Theoretische Physik, Universität zu Köln, 50937 Köln (Germany); Seyfried, A., E-mail: [Jülich Supercomputing Centre, Forschungszentrum Jülich GmbH, 52425 Jülich (Germany); Department of Computer Simulation for Fire Safety and Pedestrian Traffic, Bergische Universität Wuppertal, 42285 Wuppertal (Germany)


    The relation between flow and density is an essential quantitative characteristic to describe the efficiency of traffic systems. We have performed experiments with single-file motion of bicycles and compared the results with previous studies for car and pedestrian motion in similar setups. In the space–time diagrams we observe three different states of motion (free flow state, jammed state and stop-and-go waves) in all these systems. Despite their obvious differences they are described by a universal fundamental diagram after proper rescaling of space and time which takes into account the size and free velocity of the three kinds of agents. This indicates that the similarities between the systems go deeper than expected.

  14. Laplacian spectral characterization of products of complete graphs with trees, unicyclic graphs, and bicyclic graphs

    CERN Document Server

    Wang, Suijie


    In this paper, we give a Laplacian characterization of the product of the complete graphs $K_m$ with trees, unicyclic graphs, and bicyclic graphs. More precisely, let $G$ be a connected graph with at most two independent cycles. If $G$ is neither $C_{6}$ nor $\\Theta_{3,2,5}$ and determined by its Laplacain spectrum, then the product $G\\times K_{m}$ is also a graph determined by its Laplacian spectrum. In addition, we find the cosepctral graphs of $C_{6}\\times K_{m}$ and $\\Theta_{3,2,5}\\times K_{m}$, where the case $m=1$ is shown in Figure \\ref{F1} and \\ref{F2}.

  15. Deciphering characteristics of bicyclic aromatics--mediators for reductive decolorization and bioelectricity generation. (United States)

    Xu, Bin; Chen, Bor-Yann; Hsueh, Chung-Chuan; Qin, Lian-Jie; Chang, Chang-Tang


    This first-attempt study quantitatively assessed electron-mediating characteristics of bicyclic aromatics - 1-amino-2-naphthol, 4-amino-1-naphthol (i.e., decolorized intermediates of azo dyes - orange I and II) for color removal and power generation in MFCs. According to cyclic-voltammetric profiles, the presence of reduction and oxidation peak potentials clearly suggested a crucial role of these intermediates as electron-shuttling mediators. Shake-flask cultures also showed that appropriate accumulation of 1A2N, 4A1N apparently enhanced color-removal efficiencies of bacterial decolorization. This study clearly suggested that suitable supplementation of electrochemically active electron shuttle(s) to dye-bearing MFCs is a promising strategy to stimulate reductive decolorization and bioelectricity generation.

  16. Compliant mechanism road bicycle brake: a rigid-body replacement case study

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, Brian M [Los Alamos National Laboratory; Howell, Larry L [NON LANL; Magleby, Spencer P [NON LANL


    The design of high-performance bicycle brakes is complicated by the competing design objectives of increased performance and low weight. But this challenge also provides a good case study to demonstrate the design of compliant mechanisms to replace current rigid-link mechanisms. This paper briefly reviews current road brake designs, demonstrates the use of rigid-body replacement synthesis to design a compliant mechanism, and illustrates the combination of compliant mechanism design tools. The resulting concept was generated from the modified dual-pivot brake design and is a partially compliant mechanism where one pin has the dual role of a joint and a mounting pin. The pseudo-rigid-body model, finite element analysis, and optimization algorithms are used to generate design dimensions, and designs are considered for both titanium and E-glass flexures. The resulting design has the potential of reducing the part count and overall weight while maintaining a performance similar to the benchmark.

  17. 深圳市自行车交通系统发展策略%Development Strategies for Bicycle Transportation System in Shenzhen

    Institute of Scientific and Technical Information of China (English)



    The percentage of bicycle travel in Shenzhen has decreased 38%from early 1980s to 2010, indi-cating the urgent need for bicycle transportation system reconstruction. By analyzing the bicycle travel de-mand, characteristics and public opinions in Shenzhen, this paper reveals that the low percentage of bicy-cle travel is mainly caused by inadequate bicycle lanes and parking facilities. Based on analyses of influen-tial factors and future development of bicycle transportation, along with the comprehensive transportation system planning in Shenzhen, the paper proposes the functionalities and objectives of bicycle transporta-tion development. Development strategies for establishing a harmonious and friendly bicycle transporta-tion system are further elaborated from six aspects, including differentiating development for different re-gions, bicycle lane network, bicycle lanes, bicycle parking facilities, bike share system, and electric bicy-cles.%20世纪80年代初至2010年,深圳市自行车出行比例下降38%,未来如何构建自行车交通系统亟须探讨。首先通过对深圳市自行车交通出行需求与特征、公众意见调查等分析,指出自行车道、停放设施不完善是导致自行车出行比例低的主要原因。基于深圳市自行车交通发展影响因素及前景分析,结合深圳市综合交通体系规划,提出自行车交通发展的定位和目标。重点从区域差异化发展、自行车道网络、自行车道、自行车停放设施、公共自行车以及电动自行车六个方面阐述构建与公共交通和谐发展、骑行环境友好的深圳市自行车交通系统发展策略。

  18. Driver behavior during bicycle passing maneuvers in response to a Share the Road sign treatment. (United States)

    Kay, Jonathan J; Savolainen, Peter T; Gates, Timothy J; Datta, Tapan K


    The interaction of motorists and bicyclists, particularly during passing maneuvers, is an area of concern to the bicycle safety community as there is a general perception that motor vehicle drivers may not share the road effectively with bicyclists. This is a particular concern on road sections with centerline rumble strips where motorists are prone to crowd bicyclists during passing events. One potential countermeasure to address this concern is the use of a bicycle warning sign with a "Share the Road" plaque. This paper presents the results of a controlled field evaluation of this sign treatment, which involved an examination of driver behavior while overtaking bicyclists. A series of field studies were conducted concurrently on two segments of a high-speed, rural two-lane highway. These segments were similar in terms of roadway geometry, traffic volumes, and other relevant factors, except that one of the segments included centerline rumble strips while the other did not. A before-and-after study design was utilized to examine changes in motor vehicle lateral placement and speed at the time of the passing event as they relate to the presence of centerline rumble strips and the sign treatment. Centerline rumble strips generally shifted vehicles closer to the bicyclists during passing maneuvers, though the magnitude of this effect was marginal. The sign treatment was found to shift motor vehicles away from the rightmost lane positions, though the signs did not significantly affect the mean buffer distance between the bicyclists and passing motorists or the propensity of crowding events during passing. The sign treatment also resulted in a 2.5miles/h (4.0km/h) reduction in vehicle speeds. Vehicle type, bicyclist position, and the presence of opposing traffic were also found to affect lateral placement and speed selection during passing maneuvers.

  19. Prediction of oxygen uptake on a bicycle wind-loaded simulator. (United States)

    Dengel, D R; Graham, R E; Jones, M T; Norton, K I; Cureton, K J


    The primary purpose of this study was to determine the accuracy of estimating oxygen uptake (VO2) from the flywheel revolution rate of a bicycle wind-loaded simulator. VO2 at four different flywheel revolution rates was measured on a Findlay Road Machine (FRM). Ten male trained cyclists, 10 male untrained cyclists, 10 female trained cyclists and 10 female untrained cyclists served as subjects. Significant curvilinear relationships (P less than 0.01) were found between road speed estimated from flywheel revolution rate and VO2 expressed as 1.min-1,, 1.min-1.m-2 (r = 0.97, 0.96, 0.98, respectively). The absolute standard error of the mean VO2 was 0.21 l.min-1 (9.6%), 3.71 (11.5%) and 0.10 l.min-1.m-2 (7.9%), respectively. The relationship between VO2 and speed was similar to that reported during road cycling. To determine the magnitude of between-machine differences in VO2, six subjects randomly performed cycling using two different FMR. Significant (P less than 0.05) differences between machines were found at only the highest speed. The present study indicates that it is possible to accurately predict VO2 from flywheel revolution rate using a FRM. Since the FRM appears to approximate the resistance a cyclist experiences on the road and allows cyclists to use their own bicycle, it provides a good alternative to traditional laboratory ergometers.

  20. Analysis of the Influencing Factors of the Public Willingness to Participate in Public Bicycle Projects and Intervention Strategies—A Case Study of Jiangsu Province, China

    Directory of Open Access Journals (Sweden)

    Ranran Yang


    Full Text Available In this study, factors influencing the willingness to participate in public bicycle projects were analyzed using the binary logistic model. The study builds on a broad and practical conceptual framework that embraces four dimensions of influencing factors, including household demographic, psychological, external, and public bicycle variables. The empirical results are based on a questionnaire survey that was sent to 520 urban residents in Xuzhou, Taizhou, and Suzhou in Jiangsu province. The survey indicates that environmental responsibility, improvement of the public transport system, health and safety considerations in relation to public bicycles, and environmental crisis consciousness have appreciable impacts upon the willingness to participation in public bicycle projects. The first three of these have a positive impact, whereas the last (environmental crisis consciousness has a negative impact. Consequently, some policy suggestions are proposed.