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Frederik Dagnaes-Hansen
Aarhus University, Aarhus, Central Jutland, Denmark
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Available from: Marie S Ostenfeld
Cellular Disposal of miR23b by RAB27-Dependent Exosome Release Is Linked to Acquisition of Metastatic Properties.
Marie Stampe Ostenfeld
Dennis K Jeppesen
Jens R Laurberg
Anders T Boysen
Jesper B Bramsen
Bjarke Primdal-Bengtson
An Hendrix
Philippe Lamy
, Frederik Dagnaes-Hansen,
Mads H Rasmussen
, [......],
Iver Nordentoft
Jens P Morth
Jørgen B Jensen
Jakob S Pedersen
Martin Beck
Dan Theodorescu
Michael Borre
Kenneth A Howard
Lars Dyrskjøt
Torben Falck Orntoft
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Exosomes are small secreted vesicles that can transfer their content to recipient cells. In cancer, exosome secretion has been implicated in tumor growth and metastatic spread. In this study, we explored the possibility that exosomal pathways might discard tumor-suppressor miRNA that restricts metastatic progression. Secreted miRNA characterized from isogenic bladder carcinoma cell lines with differing metastatic potential were uncoupled from binding to target transcripts or the AGO2-miRISC complex. In metastatic cells, we observed a relative increase in secretion of miRNA with tumor-suppressor functions, including miR23b, miR224, and miR921. Ectopic expression of miR23b inhibited invasion, anoikis, angiogenesis, and pulmonary metastasis. Silencing of the exocytotic RAB family members RAB27A or RAB27B halted miR23b and miR921 secretion and reduced cellular invasion. Clinically, elevated levels of RAB27B expression were linked to poor prognosis in two independent cohorts of patients with bladder cancer. Moreover, highly exocytosed miRNA from metastatic cells, such as miR23b, were reduced in lymph node metastases compared with patient-matched primary tumors and were correlated with increments in miRNA-targeted RNA. Taken together, our results suggested that exosome-mediated secretion of tumor-suppressor miRNA is selected during tumor progression as a mechanism to coordinate activation of a metastatic cascade. Cancer Res; 74(20); 1-14. ©2014 AACR.
Cancer research. 09/2014;
Available from: Marie S Ostenfeld
Functional Screening Identifies miRNAs Influencing Apoptosis and Proliferation in Colorectal Cancer.
Lise Lotte Christensen
Anja Holm
Juha Rantala
Olli Kallioniemi
Mads H Rasmussen
Marie S Ostenfeld
, Frederik Dagnaes-Hansen,
Bodil Oster
Troels Schepeler
Heidi Tobiasen
, [......],
Philippe Lamy
Torben F Hansen
Anders Jakobsen
Eva M Riising
Kristian Helin
Jan Lubinski
Rikke Hagemann-Madsen
Søren Laurberg
Torben F Orntoft
Claus L Andersen
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MicroRNAs (miRNAs) play a critical role in many biological processes and are aberrantly expressed in human cancers. Particular miRNAs function either as tumor suppressors or oncogenes and appear to have diagnostic and prognostic significance. Although numerous miRNAs are dys-regulated in colorectal cancer (CRC) only a small fraction has been characterized functionally. Using high-throughput functional screening and miRNA profiling of clinical samples the present study aims at identifying miRNAs important for the control of cellular growth and/or apoptosis in CRC. The high-throughput functional screening was carried out in six CRC cell lines transfected with a pre-miR library including 319 synthetic human pre-miRs. Phenotypic alterations were evaluated by immunostaining of cleaved cPARP (apoptosis) or MKI67 (proliferation). Additionally, TaqMan Human MicroRNA Array Set v2.0 was used to profile the expression of 667 miRNAs in 14 normal colon mucosa and 46 microsatellite stable stage II CRC patients. Among the miRNAs that induced growth arrest and apoptosis in the CRC cell lines, and at same time were dys-regulated in the clinical samples, miR-375 was selected for further analysis. Independent in vitro analysis of transient and stable transfected CRC cell lines confirmed that miR-375 reduces cell viability through the induction of apoptotic death. We identified YAP1 as a direct miR-375 target in CRC and show that HELLS and NOLC1 are down-stream targets. Knock-down of YAP1 mimicked the phenotype induced by miR-375 over-expression indicating that miR-375 most likely exerts its pro-apoptotic role through YAP1 and its anti-apoptotic down-stream targets BIRC5 and BCL2L1. Finally, in vivo analysis of mouse xenograft tumors showed that miR-375 expression significantly reduced tumor growth. We conclude that the high-throughput screening successfully identified miRNAs that induce apoptosis and/or inhibit proliferation in CRC cells. Finally, combining the functional screening with profiling of CRC tissue samples we identified clinically relevant miRNAs and miRNA targets in CRC.
PLoS ONE 01/2014; 9(6):e96767.
· 3.53 Impact Factor
Available from: PubMed Central
Megalin-Mediated Specific Uptake of Chitosan/siRNA Nanoparticles in Mouse Kidney Proximal Tubule Epithelial Cells Enables AQP1 Gene Silencing.
Shan Gao
San Hein
, Frederik Dagnæs-Hansen,
Kathrin Weyer
Chuanxu Yang
Rikke Nielsen
Erik I Christensen
Robert A Fenton
Jørgen Kjems
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RNAi-based strategies provide a great therapeutic potential for treatment of various human diseases including kidney disorders, but face the challenge of in vivo delivery and specific targeting. The chitosan delivery system has previously been shown to target siRNA specifically to the kidneys in mice when administered intravenously. Here we confirm by 2D and 3D bioimaging that chitosan formulated siRNA is retained in the kidney for more than 48 hours where it accumulates in proximal tubule epithelial cells (PTECs), a process that was strongly dependent on the molecular weight of chitosan. Chitosan/siRNA nanoparticles, administered to chimeric mice with conditional knockout of the megalin gene, distributed almost exclusively in cells that expressed megalin, implying that the chitosan/siRNA particle uptake was mediated by a megalin-dependent endocytotic pathway. Knockdown of the water channel aquaporin 1 (AQP1) by up to 50% in PTECs was achieved utilizing the systemic i.v. delivery of chitosan/AQP1 siRNA in mice. In conclusion, specific targeting PTECs with the chitosan nanoparticle system may prove to be a useful strategy for knockdown of specific genes in PTECs, and provides a potential therapeutic strategy for treating various kidney diseases.
Theranostics 01/2014; 4(10):1039-51.
· 7.81 Impact Factor
Available from: PubMed Central
A Modified Chronic Infection Model for Testing Treatment of Staphylococcus aureus Biofilms on Implants.
Nis Pedersen Jørgensen
Rikke Meyer
, Frederik Dagnæs-Hansen,
Kurt Fuursted
Eskild Petersen
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Bacterial biofilms causing implant-associated osteomyelitis is a severe complication with limited antimicrobial therapy options. We designed an animal model, in which implant associated osteomyelitis arise from a Staphylococcus aureus biofilm on a tibia implant. Two bioluminescently engineered (luxA-E transformed), strains of S. aureus were utilized, Xen29 and Xen31. Biofilm formation was assessed with epifluorescence microscopy. Quantitative measurements were performed day 4, 6, 8, 11 and 15 post-surgery. Bacteria were extracted from the biofilm by sonication and the bacterial load quantified by culturing. Biofilm formation was evident from day 6 post-implantation. Mean bacterial load from implants was ∼1×104 CFU/implant, while mean bacterial load from infected tibias were 1×106 CFU/bone. Bioluminesence imaging revealed decreasing activity throughout the 15-day observation period, with signal intensity for both strains reaching that of the negative control by day 15 while there was no significant reduction in bacterial load. The model is suitable for testing antimicrobial treatment options for implant associated OM, as treatment efficacy on both biofilm and viable counts can be assessed.
PLoS ONE 01/2014; 9(10):e103688.
· 3.53 Impact Factor
The inflammatory response in blood and in remote organs following acute kidney injury.
Anne Craveiro Brøchner
, Frederik Dagnaes-Hansen,
Jimmy Højberg-Holm
Palle Toft
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In patients with acute kidney injury (AKI) mortality remains high, despite the fact that the patients are treated with continuous renal replacement therapy. The interaction between the kidney and the immune system might explain the high mortality observed in AKI. In order to elucidate the interaction between the kidney and immune system we developed a two-hit model of AKI and endotoxemia. Our hypothesis was that ischemia/reperfusion (I/R) of the kidney simultaneously with endotoxemia would generate a more extensive inflammatory response compared to I/R of the hind legs. Our expectation was that elevated levels of cytokines would be found in both blood and in organs distant to the kidneys. Forty mice were divided into five groups. The mice were subjected to the following operations: A: Sham only, no lipopolysaccharide (LPS); B: I/R of both kidneys + LPS; C: LPS only; D: Nephrectomy + LPS; E: I/R of both hind legs + LPS. In groups B and E, I/R times were identical. All mice were kept alive for 24 h and then sacrificed. Levels of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α were measured in the blood. The activity of myeloperoxidase (MPO) in lungs, kidneys, and liver was evaluated as an indirect measurement of accumulation of granulocytes. In this study, significantly higher amount of IL-6 and IL-10 in the plasma was observed following renal I/R compared to hind leg I/R. The elevated levels of cytokine in plasma were observed following nephrectomy and endotoxemia. The neutrophil infiltration of distant organs measured by the levels of MPO in the lung and liver also showed a significantly higher level in renal I/R compared to hind leg I/R. Renal I/R is associated with a more pronounced inflammatory response in blood and distant organs. The high cytokine levels measured following nephrectomy might be explained by compromised elimination of cytokines by the kidney in AKI.
Apmis 09/2013;
· 2.07 Impact Factor
Available from: Yonglun Luo
A simple method for deriving functional MSCs and applied for osteogenesis in 3D scaffolds.
Lijin Zou
Yonglun Luo
Muwan Chen
Gang Wang
Ming Ding
Charlotte Christie Petersen
Ran Kang
, Frederik Dagnaes-Hansen,
Yuanlin Zeng
Nonghua Lv
Qing Ma
Dang Q S Le
Flemming Besenbacher
Lars Bolund
Thomas G Jensen
Jørgen Kjems
William T Pu
Cody Bünger
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We describe a simple method for bone engineering using biodegradable scaffolds with mesenchymal stem cells derived from human induced-pluripotent stem cells (hiPS-MSCs). The hiPS-MSCs expressed mesenchymal markers (CD90, CD73, and CD105), possessed multipotency characterized by tri-lineages differentiation: osteogenic, adipogenic, and chondrogenic, and lost pluripotency - as seen with the loss of markers OCT3/4 and TRA-1-81 - and tumorigenicity. However, these iPS-MSCs are still positive for marker NANOG. We further explored the osteogenic potential of the hiPS-MSCs in synthetic polymer polycaprolactone (PCL) scaffolds or PCL scaffolds functionalized with natural polymer hyaluronan and ceramic TCP (PHT) both in vitro and in vivo. Our results showed that these iPS-MSCs are functionally compatible with the two 3D scaffolds tested and formed typically calcified structure in the scaffolds. Overall, our results suggest the iPS-MSCs derived by this simple method retain fully osteogenic function and provide a new solution towards personalized orthopedic therapy in the future.
Scientific Reports 07/2013; 3:2243.
· 5.08 Impact Factor
Available from: PubMed Central
Directing HER4 mRNA expression towards the CYT2 isoform by antisense oligonucleotide decreases growth of breast cancer cells in vitro and in vivo.
T O Nielsen
S Sorensen
, F Dagnæs-Hansen,
J Kjems
B S Sorensen
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Background:The tyrosine kinase receptor HER4 is a member of the epidermal growth factor receptor (EGFR) family. It plays diverse roles in cancer development and cancer progression and can both exert oncogenic and tumour-suppressive activities. Alternatively spliced isoforms of HER4 are critical to the different signalling possibilities of HER4.Methods:We use a splice-switching oligonucleotide (SSO) to direct the alternative splicing of HER4 from the CYT1 to the CYT2 isoform in HER4-expressing breast cancer cells.Results:Treatment with a target-specific SSO was accompanied by a decreased growth of the cells (P<0.0001). In addition, the SSO treatment induced a decreased activity of Akt. We confirmed the SSO-dependent switching of the HER4 isoform CYT1 to CYT2 expression in a xenografted mouse tumour model driven by subcutaneously injected MCF7 cells. We hence demonstrated the feasibility of SSO-directed splice-switching activity in vivo. Furthermore, the SSO treatment efficiently decreased the growth of the xenografted tumour (P=0.0014).Conclusion:An SSO directing the splicing of HER4 towards the CYT2 isoform has an inhibitory effect of cancer cell growth in vitro and in vivo. These results may pave the way for the development of new anticancer drugs in HER4-deregulated cancers in humans.British Journal of Cancer advance online publication, 21 May 2013; doi:10.1038/bjc.2013.247 www.bjcancer.com.
British Journal of Cancer 05/2013;
· 5.08 Impact Factor
Mitochondria and the lectin pathway of complement.
Christel R Brinkmann
Lisbeth Jensen
, Frederik Dagnaes-Hansen,
Ida E Holm
Yuichi Endo
Teizo Fujita
Steffen Thiel
Jens C Jensenius
Søren E Degn
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Mitochondria, the powerhouses of our cells, are remnants of a eubacterial endosymbiont. Notwithstanding the evolutionary time that has passed since the initial endosymbiotic event, mitochondria have retained many hallmarks of their eubacterial origin. Recent studies have indicated that during perturbations of normal homeostasis, such as following acute trauma leading to massive necrosis and release of mitochondria, the immune system might mistake symbiont for enemy and initiate an inappropriate immune response. The innate immune system is the first line of defense against invading microbial pathogens, and as such is the primary suspect in the recognition of mitochondria-derived danger-associated molecular patterns (DAMPs) and initiation of an aberrant response. Conversely, innate immune mechanisms are also central to non-inflammatory clearance of innocuous agents. Here we investigated the role of a central humoral component of innate immunity, the lectin pathway of complement, in recognition of mitochondria in vitro and in vivo. We found that the soluble pattern-recognition molecules (PRMs), mannan-binding lectin (MBL), L-ficolin and M-ficolin were able to recognize mitochondria. Furthermore, MBL in complex with MBL-associated serine protease 2 (MASP-2) was able to activate the lectin pathway and deposit C4 onto mitochondria, suggesting that these molecules are either involved in homeostatic clearance of mitochondria or induction of untoward inflammatory reactions. We found that following mitochondrial challenge, C3 was consumed in vivo in the absence of overt inflammation, indicating a potential role of complement in non-inflammatory clearance of mitochondria. Thus, we report here the first indication of involvement of the lectin pathway in mitochondrial immune handling.
Journal of Biological Chemistry 02/2013;
· 4.65 Impact Factor
Diabetes-induced changes in mannan-binding lectin levels and complement activation in a mouse model of type 1 diabetes.
Jakob Appel Ostergaard
Mette Bjerre
, Frederik Dagnaes-Hansen,
Troels Krarup Hansen
Steffen Thiel
Allan Flyvbjerg
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Circulating mannan-binding lectin (MBL) levels are elevated in type 1 diabetes. Further, high MBL levels are associated with the development of diabetic nephropathy. In animals, a direct effect of MBL on diabetic kidney changes is observed. We hypothesized that MBL levels and detrimental complement activation increase as a consequence of diabetes. We measured plasma MBL before and seven weeks after inducing diabetes by streptozotocin. Mice have two MBLs, MBL-A and MBL-C. Diabetes-induction led to an increase in MBL-C concentration whereas no change during the study was found in the control group. The increase in MBL-C was associated with the increasing plasma glucose levels. In accordance with the observed changes in circulating MBL levels, liver expression of Mbl2 mRNA (encoding MBL-C) was increased in diabetes. Mbl1 expression (encoding MBL-A) did not differ between diabetic and control animals. The estimated half-life of recombinant human MBL was significantly prolonged in mice with diabetes compared with control mice. Complement activation in plasma and glomeruli did not differ between groups. We demonstrate for the first time that MBL levels increase after induction of diabetes and in parallel with increasing plasma glucose. Our findings support the previous clinical observations of increased MBL in type 1 diabetes. This change may be explained by alternations both in MBL production and turnover.
Scandinavian Journal of Immunology 01/2013;
· 2.20 Impact Factor
Available from: Shan Gao
Protection and Systemic Translocation of siRNA Following Oral Administration of Chitosan/siRNA Nanoparticles.
Borja Ballarín-González
, Frederik Dagnaes-Hansen,
Robert A Fenton
Shan Gao
San Hein
Mingdong Dong
Jørgen Kjems
Kenneth A Howard
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Harnessing the RNA interference pathway offers a new therapeutic modality; however, solutions to overcome biological barriers to small interfering RNA (siRNA) delivery are required for clinical translation. This work demonstrates, by direct northern and quantitative PCR (qPCR) detection, stability, gastrointestinal (GI) deposition, and translocation into peripheral tissue of nonmodified siRNA after oral gavage of chitosan/siRNA nanoparticles in mice. In contrast to naked siRNA, retained structural integrity and deposition in the stomach, proximal and distal small intestine, and colon was observed at 1 and 5 hours for siRNA within nanoparticles. Furthermore, histological detection of fluorescent siRNA at the apical regions of the intestinal epithelium suggests mucoadhesion provided by chitosan. Detection of intact siRNA in the liver, spleen, and kidney was observed 1 hour after oral gavage, with an organ distribution pattern influenced by nanoparticle N:P ratio that could reflect differences in particle stability. This proof-of-concept work presents an oral delivery platform that could have the potential to treat local and systemic disorders by siRNA.Molecular Therapy - Nucleic Acids (2013) 2, e76; doi:10.1038/mtna.2013.2; published online 5 March 2013.
Molecular therapy. Nucleic acids. 01/2013; 2:e76.
Available from: Shan Gao
Optimized siRNA-PEG Conjugates for Extended Blood Circulation and Reduced Urine Excretion in Mice.
Frank Iversen
Chuanxu Yang
, Frederik Dagnæs-Hansen,
David H Schaffert
Jørgen Kjems
Shan Gao
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Some of the main concerns with application of naked small interfering RNA are rapid degradation and urinary excretion resulting in a short plasma half-life. In this study we investigated how conjugation of polyethylene glycol (PEG) with variable chain length affects siRNA pharmacokinetics and biodistribution. The PEG chains were conjugated to chemically stabilized siRNA at the 5' terminal end of the passenger strand using click chemistry. The siRNA conjugate remained functionally active and showed significantly prolonged circulation in the blood stream after intravenous injection. siRNA conjugated with 20kDa PEG (PEG20k-siRNA) was most persistent, approximately 50% PEG20k-siRNA remained 1h post-injection, while the uncoupled siRNA was rapidly removed >90% at 15min. fluorescent imaging of the living animal showed increased concentration of siRNA in peripheral tissue and delayed urine excretion when coupled to PEG 20k. Biodistribution studies by northern blotting revealed equal distribution of conjugated siRNA in liver, kidney, spleen and lung without significant degradation 24 h post-injection. Our study demonstrates that PEG conjugated siRNA can be applied as a delivery system to improve siRNA bioavailability and may potentially increase the efficiency of siRNA in therapeutic applications.
Theranostics 01/2013; 3(3):201-9.
· 7.81 Impact Factor
Available from: Hanne Gissel
Spatial distribution of transgenic protein after gene electrotransfer to porcine muscle.
Iben Spanggaard
Thomas Juhl Corydon
Pernille Hojman
Hanne Gissel
, Frederik Dagnæs-Hansen,
Thomas G. Jensen
Julie Gehl
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Gene electrotransfer is an effective non-viral technique for delivery of plasmid DNA into tissues. From a clinical perspective muscle is an attractive target tissue as long-term high-level transgenic expression can be achieved. Spatial distribution of the transgenic protein following gene electrotransfer to muscle in a large animal model has not yet been investigated. In this study 17 different doses of plasmid DNA (1-1500 µg firefly luciferase pCMV-Luc) were delivered in vivo to porcine gluteal muscle using electroporation. Forty-eight hours post treatment several biopsies were obtained from each transfection site in order to examine the spatial distribution of the transgenic product. We found a significantly higher luciferase activity in biopsies from the center of the transfection site compared to biopsies taken adjacent to the center 1 and 2 cm along muscle fibre orientation (p<0.05 and p<0.0001, respectively). On average, 43 % of the total luciferase activity was localized in the center biopsy. In conclusion, we found that gene electrotransfer to muscle in a large animal model led to localized gene expression corresponding to the area delineated by the electrodes. High doses of plasmid DNA did not lead to a larger area of the muscle expressing the transgenic protein.
Human Gene Therapy Methods 11/2012;
· 1.64 Impact Factor
Available from: Rong Li
Generation of minipigs with targeted transgene insertion by recombinase-mediated cassette exchange (RMCE) and somatic cell nuclear transfer (SCNT).
Jannik Ejnar Jakobsen
Marianne G Johansen
Mette Schmidt
, Frederik Dagnæs-Hansen,
Karen Dam
Anders Gunnarsson
Ying Liu
Peter M Kragh
Rong Li
Ida E Holm
Henrik Callesen
Jacob Giehm Mikkelsen
Anders Lade Nielsen
Arne Lund Jørgensen
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Targeted transgenesis using site-specific recombinases is an attractive method to create genetically modified animals as it allows for integration of the transgene in a pre-selected transcriptionally active genomic site. Here we describe the application of recombinase-mediated cassette exchange (RMCE) in cells from a Göttingen minipig with four RMCE acceptor loci, each containing a green fluorescence protein (GFP) marker gene driven by a human UbiC promoter. The four RMCE acceptor loci segregated independent of each other, and expression profiles could be determined in various tissues. Using minicircles in RMCE in fibroblasts with all four acceptor loci and followed by SCNT, we produced piglets with a single copy of a transgene incorporated into one of the transcriptionally active acceptor loci. The transgene, consisting of a cDNA of the Alzheimer's disease-causing gene PSEN1M146I driven by an enhanced human UbiC promoter, had an expression profile in various tissues similar to that of the GFP marker gene. The results show that RMCE can be done in a pre-selected transcriptionally active acceptor locus for targeted transgenesis in pigs.
Transgenic Research 10/2012;
· 2.61 Impact Factor
Available from: Shan Gao
Peritoneal macrophages mediated delivery of chitosan/siRNA nanoparticle to the lesion site in a murine radiation-induced fibrosis model.
Nawroth I
Alsner J
Deleuran BW
, Dagnaes-Hansen F,
Yang C
Horsman MR
Overgaard J
Howard KA
Kjems J
Gao S
Acta Oncologica 10/2012;
· 2.87 Impact Factor
Available from: Bent Deleuran
Peritoneal macrophages mediated delivery of chitosan/siRNA nanoparticle to the lesion site in a murine radiation-induced fibrosis model.
Isabel Nawroth
Jan Alsner
Bent W Deleuran
, Frederik Dagnaes-Hansen,
Chuanxu Yang
Michael R Horsman
Jens Overgaard
Kenneth A Howard
Jørgen Kjems
Shan Gao
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Background. Radiation-induced fibrosis (RIF) is a dose-limiting complication of cancer radiotherapy and causes serious problems, i.e. restricted tissue flexibility, pain, ulceration or necrosis. Recently, we have successfully treated RIF in a mouse model by intraperitoneal administration of chitosan/siRNA nanoparticles directed towards silencing TNF alpha in local macrophage populations, but the mechanism for the therapeutic effect at the lesion site remains unclear. Methods. Using the same murine RIF model we utilized an optical imaging technique and fluorescence microscopy to investigate the uptake of chitosan/fluorescently labeled siRNA nanoparticles by peritoneal macrophages and their subsequent migration to the inflamed tissue in the RIF model. Results. We observed strong accumulation of the fluorescent signal in the lesion site of the irradiated leg up to 24 hours using the optical imaging system. We further confirm by immunohistochemical staining that Cy3 labeled siRNA resides in macrophages of the irradiated leg. Conclusion. We provide a proof-of-concept for host macrophage trafficking towards the inflamed region in a murine RIF model, which thereby suggests that the chitosan/siRNA nanoparticle may constitute a general treatment for inflammatory diseases using the natural homing potential of macrophages to inflammatory sites.
Acta oncologica (Stockholm, Sweden) 10/2012;
· 2.27 Impact Factor
SKG arthritis as a model for evaluating therapies in rheumatoid arthritis with special focus on bone changes.
Kresten Krarup Keller
Lisa Mejlvang Lindgaard
Lise Wogensen
, Frederik Dagnæs-Hansen,
Jesper Skovhus Thomsen
Shimon Sakaguchi
Kristian Stengaard-Pedersen
Ellen-Margrethe Hauge
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The aim was to further characterize the SKG model of rheumatoid arthritis (RA) and its potential for studying intervention treatments, with special focus on bone targeting therapies. Three individual studies were conducted, using a total of 71 SKG mice, comparing arthritis induction with mannan versus zymosan A, female versus male mice, and the effect of dexamethasone intervention treatment initiated at different time points after arthritis induction. Hind paws were embedded undecalcified in methyl methacrylate, and sections were stained with Masson-Goldner trichrome. Areal Bone Mineral Density (aBMD) of the femora was determined with pDXA. RNA was extracted from the hind paws followed by the quantification by reverse transcriptase PCR. SKG mice stimulated with mannan presented a higher arthritis score than mice stimulated with zymosan A. Female SKG mice developed a more severe arthritis than male SKG mice. Dexamethasone inhibited arthritis clinically as well as histologically when the treatment was initiated prophylactically or within the first week of arthritis. Femoral aBMD was lower in animals with arthritis than in control animals. The RANKL RNA expression was elevated in arthritic mice, whereas OPG RNA expression was unchanged. The results suggest mannan as arthritis inductor and female instead of male mice in experiments as well as an optimal time window for the initiation of treatment. Systemic bone loss as well as local up regulation of RANKL was present early in SKG arthritis. These results demonstrate that SKG arthritis is a suitable new model for evaluating therapies in RA.
Rheumatology International 09/2012;
· 2.21 Impact Factor
Object recognition as a measure of memory in 1-2 years old transgenic minipigs carrying the APPsw mutation for Alzheimer's disease.
Lene Vammen Søndergaard
Jan Ladewig
, Frederik Dagnæs-Hansen,
Mette S Herskin
Ida Elisabeth Holm
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Alzheimer's disease (AD) is a disabling, fatal disease, where animal models potentially can enable investigation of aetiology and treatment. The first litter of Göttingen minipigs carrying a mutation for human AD was born in 2007, showing transgene expression. In human AD patients, memory impairment is the most striking and consistent feature. The aim of the present study was to examine effects of the APPsw transgene on memory of AD minipigs compared with non-transgenic controls at two ages (1-2 years) using the spontaneous object recognition test (SORT), which is based on behavioural discrimination of familiar and novel objects. No significant difference between AD minipigs and controls was found when comparing object recognition as a measure of memory. The minipigs did explore the novel object significantly more than the familiar, indicating the expected recognition of the familiar object. Two different inter-phase intervals were used (IPI: 10-40 min). For both ages, object recognition was evident using 10 min IPI. When using 40 min IPI, object recognition was evident only at age 1 year. Comparing memory of a relatively small group of AD minipigs and controls at two rather young ages using the SORT, we were not able to show memory impairment in APPsw carrying minipigs. Being an age-dependent disease, the transgene is expected to cause AD-like symptoms in this porcine model, and the SORT should be repeated at older ages.
Transgenic Research 06/2012;
· 2.61 Impact Factor
Available from: Holger Jon Møller
Targeting the hemoglobin scavenger receptor CD163 in macrophages highly increases the anti-inflammatory potency of dexamethasone.
Jonas H Graversen
Pia Svendsen
, Frederik Dagnæs-Hansen,
Jakob Dal
Gabriele Anton
Anders Etzerodt
Mikkel D Petersen
Peter A Christensen
Holger J Møller
Søren K Moestrup
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Synthetic glucocorticoids are potent anti-inflammatory drugs but serious side effects such as bone mobilization, muscle mass loss, immunosuppression, and metabolic alterations make glucocorticoid therapy a difficult balance. The therapeutic anti-inflammatory effect of glucocorticoids relies largely on the suppressed release of tumor-necrosis factor-α and other cytokines by macrophages at the sites of inflammation. We have now developed a new biodegradable anti-CD163 antibody-drug conjugate that specifically targets the glucocorticoid, dexamethasone to the hemoglobin scavenger receptor CD163 in macrophages. The conjugate, that in average contains four dexamethasone molecules per antibody, exhibits retained high functional affinity for CD163. In vitro studies in rat macrophages and in vivo studies of Lewis rats showed a strong anti-inflammatory effect of the conjugate measured as reduced lipopolysaccharide-induced secretion of tumor-necrosis factor-α. The in vivo potency of conjugated dexamethasone was about 50-fold that of nonconjugated dexamethasone. In contrast to a strong systemic effect of nonconjugated dexamethasone, the equipotent dose of the conjugate had no such effect, measured as thymus lymphocytes apoptosis, body weight loss, and suppression of endogenous cortisol levels. In conclusion, the study shows antibody-drug conjugates as a future approach in anti-inflammatory macrophage-directed therapy. Furthermore, the data demonstrate CD163 as an excellent macrophage target for anti-inflammatory drug delivery.
Molecular Therapy 05/2012; 20(8):1550-8.
· 7.04 Impact Factor
Available from: Lars Aagaard
Adeno-associated virus-delivered polycistronic microRNA-clusters for knockdown of vascular endothelial growth factor in vivo.
Maria Pihlmann
Anne Louise Askou
Lars Aagaard
Gitte Hoffmann Bruun
Jesper Dyrendom Svalgaard
Marie Hebsgaard Holm-Nielsen
, Frederik Dagnaes-Hansen,
Toke Bek
Jacob Giehm Mikkelsen
Thomas Gryesten Jensen
Thomas Juhl Corydon
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Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that plays a critical role in several diseases, including cancer, rheumatoid arthritis and diseases of the eye. Persistent regulation of VEGF by expression of small interfering RNAs targeting VEGF represents a potential future strategy for treatment of such diseases. As a step toward this goal, the present study combines the potency of VEGF-targeted miRNA mimics, produced from a miRNA cluster, with delivery by adeno-associated virus (AAV)-based vectors. Nine different engineered tri-cistronic miRNA clusters encoding anti-VEGF effectors were generated and tested in adult human retinal pigment epithelial (ARPE-19) cells using Renilla luciferase screening, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), western blotting and immunostaining analysis. In vivo efficacy was tested by the injection of scAAV2/8 vectors expressing the most effective miRNA cluster into murine hindlimb muscles, followed by quantitative RT-PCR. Plasmids containing anti-VEGF miRNA clusters showed efficient silencing of VEGF and demonstrated a combined gene silencing effect for miRNA clusters composed of multiple miRNA-mimicked RNA interference effectors. The most potent molecule, miR-5,10,7, resulted in a knockdown of VEGF by approximately 75%. Injection of scAAV2/8 vectors expressing miR-5,10,7 into murine hindlimb muscles, resulted in a 44% reduction of endogenous VEGF. We have developed miRNA clusters encoding anti-VEGF effectors and shown, in a mouse model, that VEGF is efficiently down-regulated by scAAV2/8-delivered miRNA clusters, allowing potent attenuation of VEGF. These findings may contribute to the development of gene therapy based on AAV-mediated delivery of miRNA clusters.
The Journal of Gene Medicine 03/2012; 14(5):328-38.
· 2.16 Impact Factor
Available from: Allan Randrup Thomsen
TLR3 deficiency renders astrocytes permissive to herpes simplex virus infection and facilitates establishment of CNS infection in mice.
Line S Reinert
Louis Harder
Christian K Holm
Marie B Iversen
Kristy A Horan
, Frederik Dagnæs-Hansen,
Benedicte P Ulhøi
Thomas H Holm
Trine H Mogensen
Trevor Owens
Jens R Nyengaard
Allan R Thomsen
Søren R Paludan
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Herpes simplex viruses (HSVs) are highly prevalent neurotropic viruses. While they can replicate lytically in cells of the epithelial lineage, causing lesions on mucocutaneous surfaces, HSVs also establish latent infections in neurons, which act as reservoirs of virus for subsequent reactivation events. Immunological control of HSV involves activation of innate immune pattern-recognition receptors such as TLR3, which detects double-stranded RNA and induces type I IFN expression. Humans with defects in the TLR3/IFN pathway have an elevated susceptibility to HSV infections of the CNS. However, it is not known what cell type mediates the role of TLR3 in the immunological control of HSV, and it is not known whether TLR3 sensing occurs prior to or after CNS entry. Here, we show that in mice TLR3 provides early control of HSV-2 infection immediately after entry into the CNS by mediating type I IFN responses in astrocytes. Tlr3-/- mice were hypersusceptible to HSV-2 infection in the CNS after vaginal inoculation. HSV-2 exhibited broader neurotropism in Tlr3-/- mice than it did in WT mice, with astrocytes being most abundantly infected. Tlr3-/- mice did not exhibit a global defect in innate immune responses to HSV, but astrocytes were defective in HSV-induced type I IFN production. Thus, TLR3 acts in astrocytes to sense HSV-2 infection immediately after entry into the CNS, possibly preventing HSV from spreading beyond the neurons mediating entry into the CNS.
The Journal of clinical investigation 03/2012; 122(4):1368-76.
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Odense University Hospital
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text:
Editor's note: The plan has been released. Read our updated story here.
The long-awaited digital strategy from the Office of Management and Budget may be announced as early as May 23, sources say. Officials have been previewing the plan for several weeks, and FCW got a sneak preview of draft version of the plan. Some elements of the draft version could be different in the final release.
Titled "Building a Future-Ready Digital Government", the plan expands on the efforts of the 25-point plan to reform federal IT and management. Its main objective is to help agencies create an architecture that promotes openness and interoperability. The end goal: Ensure citizens can access government information and services "anywhere, anytime, on any device," according to an April 2012 draft version FCW was shown.
OMB officials have kept mum about the plan's details and the release date, avoiding spilling much information about its overarching goal. U.S. CIO Steven VanRoekel only in recent weeks disclosed tidbits of information, without revealing any concrete deliverables, and noted that mobile technologies will play a major part.
"We're not very far from you taking the device sitting in front of you and just plugging that in -- it just becomes a conversation about screen size, not about where you are and how you're accessing the network," he said at a May 11 technology forum. "It's 'anytime, anywhere, any device' and make that government experience exist for federal employees and for citizens interacting with government. It needs to be a necessity. "
Haley van Dyck, a policy analyst at the Office of Management and Budget, who spoke at a May 3 event, said the strategy is the culmination of the federal government's work to improve its use of mobile technology and rethink its service delivery model.
Developed in conjunction with federal CIOs, chief acquisition officers, the Federal CIO Council and other groups, the strategy foremost focuses on making machine-readable connections to government data and service so citizens have better access to high-quality government information .
The framework also stresses building a modern infrastructure to support the digital government's efforts to leverage its buying power to slash costs. It also calls for the procurement and management of mobile devices, apps, and data in a smart, cost-efficient and secure way.
The plan calls for the creation of a digital services innovation center within the General Services Administration, as well as the establishment of an advisory group that will work with agencies to promote shared services, best practices and training. The center will function as a cooperative enterprise, drawing on resources across government to leverage expertise from "forward-leaning" agencies.
Under the new strategy, agencies will drive the use of emerging technology. Each agency will have to identify at least two major customer-facing systems that contain high-value data and content and expose this into "responsive web design."
GSA will set up a governmentwide contract vehicle for mobile devices and wireless services, as well as a governmentwide mobile device management platform. The plan is to also develop models for fast and secure delivery of commercial mobile apps into the federal space.
The strategy's four key principles:
About the Author
Camille Tuutti is a former FCW staff writer who covered federal oversight and the workforce.
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In an interview with FCW, the Department of Veterans Affairs' chief technology officer talks about overhauling the digital experience for VA customers.
The National Information Exchange Model's usefulness extends far beyond its origins in justice and law enforcement.
ACT-IAC'S Rick Holgate and Dan Chenok look ahead to what's next for federal IT in 2015.
A bill that will allow DHS to hire cybersecurity professionals faster and pay them more now heads to the president for his signature.
How NASA and other agencies are using contests to bring better ideas into acquisition.
ONC will focus more on data interoperability and the use of health IT to improve patient outcomes.
A new report from the DOD CIO offers soup-to-nuts guidance on security for commercial cloud providers and Defense Department customers.
Steve Kelman considers the costs of corruption in Mexico, China, and most developing countries -- and argues that Americans should keep their own government troubles in perspective.
Agency leaders must proactively invest time, energy and resources to shape the future rather than reactively wait for change to happen.
8609 Westwood Center Drive, Suite 500Vienna, VA 22182-2215 703-876-5100
© 1996-2013 1105 Media, Inc. All Rights Reserved. This copy is for your personal, non-commercial use only.To order presentation-ready copies for distribution to colleagues, clients or customers, visit: www.1105Reprints.com

subset: commoncrawl


text:
Side Navigation:
- Shop by brand
- Shop all apparel
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- Denim
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- Tops
- Skirts
- Pants
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Women's dresses
Elizabeth and JamesVivi Dress
Rebecca MinkoffLorelelei Dress
LanstonV-Neck Mini Dress
Eight SixtyPrint Wrap Dress
Eight SixtyFaded Plaid Shift
The Fifth LabelYou 'n Me Dress
ZimmermannFloral Choker Dress
Ella MossTempe Romper
ParkerEllery Jumpsuit
Piperlime women's dresses
Discover the women's dresses featured at Piperlime from top designers in the industry such as Joie, French Connection and Splendid.
Women's dresses Piperlime Collection
Our brand name womens dresses offer a range of styles for any casual or formal occasion. Find a selection of party dresses, day dresses, maxi dresses, work dresses and more for your day at the office or your evening on the town. The luxurious rich colors and prints combined with the flattering cuts will upgrade your image to a new level of fashion.
Women's dresses Features
The softest materials comprise every item in this collection. The sophisticated color and pattern combinations ensure designs filled with visual appeal and elegance. The impeccable tailoring and attention to detail mark the dresses with couture fashion to highlight your curvaceous figure. From A-line skirts to ruffle accents, enjoy all the unique elements sure to elevate your look to the next level.
Piperlime Women's dresses Style Tips
Find the womens dress perfect for your next cocktail party or business meeting with this collection from Piperlime. Look your best at a posh charity event with our line of elegant black dresses. Add colorful jewelry accents to a solid dress for visual contrast and appeal. Try on a printed maxi dress with sandals for an easy, laid-back outfit. Discover an array of casual dresses you can wear with chic flats, wedges, sneakers and more. Pair a dress with fitted blazers or jackets to take your style from day to night in minutes. These strong, stand-alone dresses need only your favorite accessories and footwear for you to complete a hip, polished image. Discover all the hip-hugging and loose fit designs that will get you noticed.
The women's dress collection at Piperlime features intricate details, rich colors and prints and impeccable tailoring for unique modern looks.
womens clothes sale | soft shirts for women | women's perfect trouser pants | womens print shirts | women's vests
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bra sized tankini tops | summer beach dresses | women's ski clothing | bra size bikini | women's sports apparel


text:
50% Off Already Reduced Prices
mouse over photo to zoom click for larger image
Metallic Crinkle Blazer
It is your time to shine in our intentionally crinkled blazer. We made it extra shimmery and ruched the sleeves for a gorgeous, gathered effect.
- Fabric-covered buttons set in metal.
- Elastic insert at the back waist.
- Hand pockets.
- Length: 24" to 25".
- 73% cotton, 17% nylon, 10% metallic.
- Machine wash. Imported.


text:
guided imagerySyllabification: guid·ed im·age·ry
Definition of guided imagery in English:
The use of words and music to evoke positive imaginary scenarios in a subject with a view to bringing about some beneficial effect.
Example sentences
- Patients were chosen at random to be given standard care or an alternative therapy - guided imagery, stress relaxation, healing touch or intercessory prayer sent from various denominations from all over the world.
- Many patients have found relaxation therapy, guided imagery, and other methods of relieving tension helpful.
- Many patients have found relaxation therapy, guided imagery, or other methods of relieving tension helpful.
Definition of guided imagery in:
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Pronunciation: nōˈel


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Slave cylinder is a Lockheed, the master is missing so I don't have much to go on. The mounting bolts are 3/8" diameter on a 3" center mounted in the horizontel position. It uses a Dodge slant 6 engine with 4 speed manual trans. The truck is about the size of a Subaru SW for use in a shop. Anyone got any ideas. Thanks Jeff
Dodge » W150 » 1990 Dodge W150 » Questions
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1990 Dodge W150 Question: Need to locate a clutch master cylinder for my 1985 Task Master Fire truck.
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text:
Apr 18, 2014 at 12:27 pm
ST. PAUL, Minn. (AP) — A teacher who spoke out for gay students during a bullying debate in the state's largest school district says he's running for a state House seat.
Jefferson Fietek will challenge Rep. Mark Uglem, a Champlin Republican, the St. Paul Pioneer Press reported.
Fietek advocated for gay students in 2010 when the Anoka-Hennepin school district struggled with several student suicides and federal lawsuits from students who said they were bullied over real or perceived sexual orientation.
Staff Writer
Temp: 12°F (-11°C)
Dewpoint: 7
Wind: 4 NE
Weather: Clear
Thu December 18, 2014
Thu December 18, 2014
Thu December 18, 2014
Sat December 20, 2014
Wed December 24, 2014


text:
A slot machine 40, of the type having a video display screen which displays a plurality of rotatable reels 42 carrying symbols 43, is arranged to pay a prize on the occurrence of a predetermined symbol or combination of symbols.
The game includes a special feature which is invoked when a special triggering combination of symbols occurs. Once the special feature is triggered a wild symbol moves around the screen progressively replacing each symbol in the display with a dye symbol and the prize generated is multiplied by the value shown on the die.
1. A gaming machine including display means, and game control means arranged to control images displayed on the display means, the game control means being arranged to play a game wherein a plurality of symbols are randomly selected and displayed on the display means and, if a winning combination results, the machine awards a prize, the game being characterised in that upon the occurrence of a predetermined triggering event, a wild card symbol is displayed, the wild card symbol having associated with it, a prize multiplier display icon indicating a value of a selected integer value within a predetermined range and the prize awarded for the combination formed with the wild card symbol being equal to a predetermined prize for the combination multiplied by the randomly selected integer value.
2. The gaming machine as claimed in
3. The gaming machine of
4. The gaming machine of
5. The gaming machine of
6. The gaming machine of
7. The gaming machine as claimed in
8. The gaming machine of as claimed in
9. The gaming machine as claimed in
10. The gaming machine as claimed in
11. The gaming machine of
12. The gaming machine as claimed in
[0001] The present invention relates to gaming machines of the type arranged to play a game of poker and in particular the invention provides an improvement to a game played on such a machine.
[0002] Players who regularly play gaming machines quickly tire of particular games and therefore it is necessary for manufacturers of these machines to come up with innovative game features that add interest to the games provided on such machines in order to keep the players amused and therefore willing to continue playing the game.
[0003] Gaming or poker machines have been well known in the state of New South Wales for many years and have more recently gained considerable popularity throughout Australia, with quite substantial amounts of money wagered on these machines. There is a growing tendency for State Governments to legalise the use of gaming machines by licensing operators, with resulting revenue gains through licence fees and taxation of monies invested. The licensed operation of gaming machines is the subject of State legislation and regulation. This regulation almost always dictates a minimum percentage payout for a gaming machine. For example, a minimum of 85% of monies invested must be returned as winnings, and manufacturers of gaming machines therefore must design their machines around these regulatory controls.
[0004] With the growth that has occurred in the gaming machine market there is intense competition between manufacturers to supply the various existing and new venues. When selecting a supplier of gaming machines, the operator of a venue will often pay close attention to the popularity of various games with their patrons. Therefore, gaming machine manufacturers are keen to devise games which are popular with players, as a mechanism for improving sales.
[0005] Many various strategies have been tried in the past to make games more enticing to players, including the commonly known double-up feature whereby, if a player wins a particular game, they can then risk the winnings of that game in a double-or-nothing mode in which they gamble on a subsequent, and often different, game such as whether a red or black card will be the next card drawn.
[0006] Other techniques adopted in the past have been to provide complexity in the numbering and combinations of indicia which would result in a win, thereby hoping to convince the player that there is a greater chance of winning and to keep their interest in a particular game.
[0007] The present invention provides a game feature in which in response to a trigger condition a wild card substitutes for a symbol in the outcome and a randomly generated number is used to multiply a prize awarded for winning combinations created while the wild card is displayed.
[0008] The present invention consists in a gaming machine having display means, and game control means arranged to control images displayed on the display means, the game control means being arranged to play a game wherein a plurality of symbols are randomly selected and displayed on the display means and, if a winning combination results, the machine pays a prize, the game being characterised in that upon the occurrence of a predetermined triggering event, a wild card symbol is displayed in at least one display location, a prize being awarded for winning combinations formed with the wild card symbol when the wild card symbol is displayed, the wild card symbol having associated with it a prize multiplier display icon indicating a value of a randomly selected integer within a predetermined range and the prize awarded for the combination formed with the wild card symbol being equal to a predetermined prize for the combination multiplied by the randomly selected integer value.
[0009] Preferably, the wild card symbol contains one or more dice and the randomly selected integer is indicated as the total value displayed on the dice. In one preferred embodiment, a single die is displayed and the predetermined range for the integer value is 1-6. In another embodiment, two dice are displayed and the integer range is 1-6n. In another embodiment, two dice are displayed and the integer range is 2-12. In yet another embodiment the number of dice is also variable such that the integer range is 1-6n where n is the maximum number of dice.
[0010] In a particularly preferred embodiment of the invention, the wild card symbol is displayed in a first display location, and then progressively moved to each of a predetermined number of display locations, a prize being awarded for winning combinations formed with the wild card symbol for each location in which the wild card symbol is displayed.
[0011] In the preferred embodiment, the wild card symbol is one or more dice which travelled from location to location in the display by an animated rolling motion.
[0012] The present invention is applicable to video gaming machines of the traditional poker machine style (also known as slot machines or fruit machines) in which the display means comprises a video simulation of a set of rotatable reels, each carrying a plurality of symbols. The invention is equally applicable to video draw poker machines in which a poker hand is displayed on the screen, the cards of the hand being selected from a standard 52 or 53 card deck and to keno and bingo machines in which a ball with a wildcard value is displayed and its occurrence is associated with a random odds multiplier. The ball may also be replaced by a DIE which displays the prize multiplication factor (or odds multiplier).
[0013] Preferably, the feature of the present invention will be triggered by the occurrence of a special symbol or a combination of special symbols displayed in a particular arrangement. In the preferred embodiment the feature is triggered by a first special symbol appearing in the first (or left hand) column of the display and a second special symbol appearing in the last (or right hand) column of the display.
[0014] Preferably, the wild card symbol is first displayed at a location at one end of the display and is progressively moved from location to adjacent location until it has been displayed in each and every location of the display.
[0015] An embodiment of the invention will now be described, by way of example with reference to the accompanying drawings, in which:
[0016]FIG. 1 illustrates a gaming machine with a video simulation of a rotating reel display incorporating a first embodiment of the invention;
[0017]FIG. 2 illustrates a video draw poker machine incorporating a second embodiment of the invention;
[0018]FIG. 3 diagrammatically illustrates a wild card symbol display progression path for the embodiment of FIG. 1; and
[0019]FIG. 4 is a schematic diagram of a slot machine control circuit.
[0020] In the following detailed description the methodology of the embodiments will be described, and it is to be understood that it is within the capabilities of the non-inventive worker in the art to introduce the methodology on any standard microprocessor-based gaming machine by means of appropriate programming.
[0021] Referring to FIG. 1 of the drawings, the first embodiment of the invention is illustrated in which a slot machine 40, of the type having a video display screen which displays a plurality of rotatable reels 42 carrying symbols 43, is arranged to pay a prize on the occurrence of a predetermined symbol or combination of symbols.
[0022] In the slot machine 40 illustrated in FIG. 1, the game is initiated by a push button 44, however, it will be recognised by persons skilled in the art that this operating mechanism might be replaced by a pull handle or other type of actuator in other embodiments of the invention. The top box 45 on top of the slot machine 40 carries the artwork panel 35 which displays the various winning combinations for which a prize is paid on this machine.
[0023] The game played on this machine is a relatively standard game which includes a 3 by 5 symbol display and allows multiple pay lines. The game also includes a special feature embodying the invention, the special feature being invoked when a first special symbol appears in the left hand column and a second special symbol appears in the right hand column of the display. The second special symbol might, for example, be a background coin symbol comprising any standard symbol of the game superimposed over a background image of a coin.
[0024] When the special feature is triggered, a spinning DIE will appear on the screen and can be stopped from spinning by the player pressing a button. Alternatively, the DIE will stop spinning after a predetermined time if the button is not pressed. When the DIE stops spinning, it will display a number which will be the factor by which the prizes will be multiplied for this feature. The DIE will then move around the display as described below.
[0025] In the following description of the feature embodying the invention, game symbols will be abbreviated as listed below.
[0026] When the feature is invoked, a special DIEWALKER sound associated with the feature is heard and an animated DIE symbol and sounds are to accompany the animation. At each win during the feature, normal winning tunes are to be heard as the win meter increments in the same manner as for the base game to which the feature has been added, These tunes last for the length of time that the win meter is incrementing.
[0027] The sequence of the features in this embodiment are as follows:
[0028] 1. When an ICEBERG appears anywhere on Reel 1 together with a background COIN anywhere on Reel 5, the DIEWALKER FEATURE begins.
[0029] 2. The number of lines and the credits bet per line played before the feature starts is the same for the feature.
[0030] 3. When the feature begins, feature DIEWALKER SOUNDS will occur and a message centred in the display area above the symbols �DIEWALKER FEATURE� is to be displayed.
[0031] 4. The animated spinning DIE symbol will appear on the screen as described above, on top of the top left hand symbol on Reel 1. The DIE will then be stopped by the player or by timing out and the prize multiplication factor will be displayed.
[0032] 5. The DIE will move to each symbol in the window (Animation from Video Graphics). As the DIE moves to each of the symbols the symbol changes to a DIE then changes back to the original symbol as the DIE moves on to the next symbol and pays each winning combination in which the DIE substitutes. For each paying combination the DIE animation will be extended (that is, a DIE bouncing and bobbing as the meter increments (See examples). The win meter increment speed for each partial feature pay will be �as if� the win meter started at zero.
[0034] A combination of an ICEBERG displayed on the first reel, and a Jack with background coin on the last reel starts the feature.
[0035] When the feature begins the Die appears on the top symbol on Reel 1.
[0036] The Die then moves to the second position and the top symbol changes back to the original symbol.
[0037] The Die moves to the third position and the second symbol changes back to its original symbol.
[0038] The Die then moves on to the fourth position and the third symbol changes back to its original symbol and so on. The path followed by the Die is illustrated diagrammatically in FIG. 3.
[0039] 6. As the DIE moves from symbol to symbol, special sounds created for �walking� die will be heard.
[0040] 7. At each win during the feature, a �win� sound, as in the base game, will be heard as the win meter increments. Sounds are to last for the length of time as win meter increments. The prize paid, will be the normal prize paid for the combination credited by substituting the wild symbol multiplied by the factor shown on the DIE.
[0041] 8. When the DIE reaches the last position in the window, the DIE disappears and a message displaying �END OF DIEWALKER FEATURE� is to be centred in the display area above the symbols.
[0042] Of the 15 positions the DIE moves to, this example shows just some of the winning combinations.
[0043] This combination starts the feature and pays 3 of a kind SEAL, 2 of a kind POLAR and 3 of a kind scattered WHALE.
[0044] The DIE moves to the second position of the walk and pays the 3 of a kind SEAL only.
[0045] When the DIE reaches the second column, on the centre line it pays 3 of a kind SEAL and 2 of a kind POLAR.
[0046] When the DIE reaches this position it will pay 3 of a kind QUEEN.
[0047] When the DIE reaches this position it will pay 3 of a kind SEAL, 2 of a kind POLAR and 3 of a kind QUEEN.
[0048] When the DIE reaches this position it will pay 4 of a kind SEAL and 2 of a kind POLAR and 3 of a kind JACK.
[0049] When the DIE Teaches this position it will pay 2 of a kind POLAR.
[0050] When applied to a draw poker machine, the feature might be invoked, for example by an ACE in the first card position and a club suit in the last card position.
[0051] The special feature symbol (preferably the DIE as in the previous embodiment) would then be displayed sequentially in each card position and act as a wild card in combination with the remaining cards of the hand. A prize is awarded for each new winning combination created by the wild card.
[0052] Referring to FIG. 4, embodiments of the present invention are incorporated into a gaming machine including a standard gaming machine control processor 31 as illustrated schematically in FIG. 4. This processor forms part of a controller 30 which drives the display screen 11 and receives touch input signals from touch sensors 32 as well as receiving coin input pulses from a coin chute mechanism 33 and driving a coin payout mechanism 34.
[0053] It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.
Referenced by
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text:
Xbox 360
This page contains Rock Revolution Unlockables for Xbox 360 called "Normal Achievements" and has been posted or updated on Sep 16, 2008 by vhayste. Let us know what you think of this Unlockable by thumbs voting.
- Developer: Zoe Mode
- Publisher: Konami
- Genre: Miscellaneous Rhythm Music
- Release Date: Oct 15, 2008
- ESRB: Teen
Normal Achievements
Complete the following achievements to unlock Xbox Live Gamerscore points.
|How to Unlock:
|250 Combo (10 GP)
|Earn a 250 hit combo.
|500 Combo (10 GP)
|Earn a 500 hit combo.
|999 Combo (20 GP)
|Max out the Combo Meter.
|Back from the Brink (10 GP)
|Recover a song performance from the red warning level in Career or Quickplay.
|Band Together (10 GP)
|Compete in a six player Band Battle and be in the winning band!.
|Birth of a Legend (10 GP)
|Finish a song performance on expert difficulty in Career or Quickplay.
|Calmly Done (30 GP)
|Complete all Crank It Up challenges at expert difficulty for an instrument.
|Career Complete (20 GP)
|Complete Career mode for an instrument.
|Centurion (10 GP)
|Earn a 100 hit combo.
|Class Act (20 GP)
|Play a total of 50 online games.
|Distinguished Career (30 GP)
|Reach a cumulative 'career points' total of 50,000,000 for an instrument.
|Dominator (10 GP)
|Win 3 ranked Versus online games in a row.
|Expert Complete (80 GP)
|Complete all songs on Expert Difficulty for an instrument in Career or Quickplay .
|Expert Song Aced (30 GP)
|100% any song on expert difficulty.
|Get Out of My House (10 GP)
|Win 5 local multiplayer VS sessions in a row.
|Gig Complete (20 GP)
|Complete a poster gig at any difficulty level for an instrument.
|Going for Gold (10 GP)
|Achieve a Gold rating for a Disc in Career Mode.
|Grudge match (10 GP)
|Beat an online opponent on your friends list.
|Heard 'em All (30 GP)
|Try out all the instrument sounds in Studio Mode.
|Hold it Together (30 GP)
|Complete all Poison Note challenges at expert difficulty for an instrument.
|Illustrious Drum Career (20 GP)
|Complete all album and gig events in the drum career at Expert difficulty.
|Illustrious Guitar Career (20 GP)
|Complete all album and gig events in the guitar career at Expert difficulty.
|Industry Veteran (20 GP)
|Play a total of 100 online games.
|Internship (20 GP)
|Create a song using the song generator in Studio Mode.
|It's Gone Platinum (20 GP)
|Complete all events on a Disc in Career Mode at any difficulty.
|King of the Castle (10 GP)
|Win 10 local multiplayer VS sessions.
|Long Distance Relationship (10 GP)
|Complete a song in an online co-op game.
|Look and Learn (10 GP)
|Complete all tutorials for either instrument.
|Lucky 7's (10 GP)
|Earn a 777 hit combo.
|More Tracks Please (20 GP)
|Record on all 8 tracks in Studio Mode.
|Multi-talented Musician (20 GP)
|Complete all Discs to at least Gold standard for both instrument Careers.
|Multiple Identities (25 GP)
|Complete at least one song performance with each of the characters in Career or Quickplay.
|Multiplier Max (10 GP)
|Reach the maximum multiplier (x8).
|On the Career Path (10 GP)
|Complete your first event in Career mode.
|Party On (10 GP)
|Complete a song in a local co-op session.
|Platinum Career (50 GP)
|Complete all Discs to Platinum standard for an instrument.
|Power Surge (10 GP)
|Activate the Power Meter 3 times in a song.
|Producer (10 GP)
|Save a song you have created in Studio Mode.
|Professional Musician (20 GP)
|Complete all discs to Platinum standard for both instrument Careers.
|Session Player (30 GP)
|Complete all Studio Recording challenges at expert difficulty for an instrument.
|Show Off (10 GP)
|Hit 100% notes in any online game.
|Slick Player (20 GP)
|Win a total of 10 ranked online games.
|Song Aced (20 GP)
|Complete a song to 100% on any difficulty.
|Songs Complete (50 GP)
|Complete all songs for an instrument in Career or Quickplay.
|Super-Dominator (20 GP)
|Win 5 ranked Versus online games in a row.
|Taking It Slow (10 GP)
|Hit all notes in an expert song at 50% speed in rehearsal.
|Thanks for the Memory (30 GP)
|Complete all Band Practice challenges at expert difficulty for an instrument.
|Virtuoso (20 GP)
|Win a total of 50 ranked online games.
|Your First Million (25 GP)
|Score 1,000,000 points for a song in Career or Quickplay.
|Zoned Out (30 GP)
|Complete all In The Zone challenges at expert difficulty for an instrument.
More Unlockables
Back to all Cheats
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I am almost 20, living at home still and trying to finish college. My boyfriend and i never used protection because we do want a baby. I have been feeling super tired, stomach pains and cramps all day long. headaches last for days and back pain is longer. I found that my pants are getting tighter and my lower abdomen feels really hard at times. My "period" (if you want to call it that) was two days long than brown discharge. sorry if tmi. I cant eat my favorite foods with out throwing up when i smell them. I took a test, it had a faint line. I got a blood test yesterday and am waiting for a call. Scared what they will say honestly.
19 and feeling pregnant! But am i?
Posted 02/07/2013
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The University of Sydney has a range of University-wide core research facilities. These platforms for collaboration provide access to high-end research infrastructure and services, to internal and external researchers. Each core facility has expert staff who provide training and can advise on research design, equipment use and data analysis.
Core facilities now open
- Mass Spectrometry Core Facility (MSCF)
- Sydney Microscopy and Microanalysis (SMM)
- Advanced Cytometry Facility (ACF)
- Vibrational Spectroscopy Core Facility (VSCF)
Core facilities coming soon:
- Preclinical (Small Animal) Imaging Core Facility (PICF) – available from early 2015
Research Computing Core Facility (RCCF) – available from early 2015
The University is also looking to develop a clinical imaging core facility and a research and prototype foundry, both scheduled to open in 2016.
Core Facilities Program
The University of Sydney Research Portfolio enables our research strategies by delivering high-end research infrastructure through the Core Facilities Program. Core facilities are funded through a combination of user fees and contributions from user faculties.
This initiative is the first step in the University's broader strategy to establish, manage and govern high-end research infrastructure in whole-of-university core research facilities, representing an exciting new phase in the University's approach to enabling advanced research.
For further information about the Core Facility Program, please contact:
Professor Simon Ringer
Director, Core Research Facilities


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Join the green movement today with this environmentally responsible,
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Protect the environment without sacrificing the level of cleaning you've
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Simoniz Green Scene HE Powdered Laundry Detergent, Lemon Fresh, 35-lb. Box, Each
CleanItSupply.com - The wholesale janitorial supply company buyers trust.
Clean It Supply is your top spot for wholesale cleaning supplies online. We offer janitorial, home and office cleaning supplies to keep your surroundings clean and comfortable. You can be confident we'll have the wholesale cleaning products you need with our selection of tens of thousands of cleaning products available 24/7 on our website. If you shop for bulk cleaning supplies you can take advantage of our free shipping offer as all orders over $1,200 qualify for free shipping. We have the widest selections of industrial cleaning supplies on the internet at the lowest prices.


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Quality Inn
100A East Seright St.
Harrisburg, IL 62946
Phone: (618) 252-2442
Fax: (618) 252-2442
100A East Seright St., Harrisburg, IL, US, 62946
- Phone: (618) 252-2442
- Fax: (618) 252-2442
Practical Information
»Treetop Productions
Treetop Productions provides professional videography including: commercials, promotional DVD's, video editing, photo montage and special event videography services in the Southern Illinios region.
»Klein & Cook Orthodontics
This orthodonic office offers SureSmile, Invisalign, traditional braces, self-ligating braces, laser recontouring, temporary implants & more.
»Enterprise Rent-A-Car
Nationally known car rental company that provides a variety of quality vehicles plus free pickup and delivery services.
»Carbondale Chamber of Commerce
Provides visitor and relocation information.
»Regions Bank
Both locations are full service banks that provide checking accounts, debt consolidation, loans, investment services, certificate of deposits, trusts, and online banking. They also offer mortgage, commercial, treasury and management.
»Vine Community Church
Vine Community Church has live worship services: Sunday 9:30, 11a.m., & 5:30 p.m.
America's only express train serving destinations nationwide.
»Greyhound Lines
Provides bus transportation to most cities across the United States.
Offering the largest variety of locations and services in the truck and trailer rental industry. Seventeen other locations available in Carbondale.
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Offering news from the Carbondale area and more.
»First Christian Church
Sunday School classes at 9:45 a.m. Worship Service at 10:30 a.m. Before Sunday school enjoy refreshments and fellowship. Wednesday night services begin with supper 5:30 p.m., small group discussions 6:00 - 7:00p.m, and 6:45 choir practice. Nursery provided.
»The View First Baptist Church
A couple of years ago the people of the First Baptist Church of Carbondale began a season of fervent prayer, asking that God would lead them in a way that would bless the people of the Carbondale area and would build on the church's legacy of service to God and to humankind.


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Tech Helproom
It's free to register, to post a question or to start / join a discussion
SP1 update fail
Likes # 0
Posted April 11, 2011 at 8:02PM
I updated my home and laptop pcs today with SP1, the laptop was all ok but the pc locked up at the start screen on the first 'new boot', restarting it and then trying to go into safe mode produced a warning that SP1 did not configure correctly and it was reversing the installation - which it is doing as I write this. I intend trying to download it and install it again but I just wanted to ask if anyone else has had or heard of other people with similar problems. Both machines are running win7 professional 64bit.
Likes # 0
Posted April 12, 2011 at 8:13AM
If anyone's interested, it appears that it was my anti-virus causing the problem, I have McAfee Total Protection. All installed after turning the real-time scanning off and re-installing the updates.
I know that the install instructions say to switch off the AV (as do a lot of programs) but I am not too happy about that especially when downloading the program from the net so always leave it on!
What I don't understand is that the installation on my laptop went ok and that is running the exact same OS and AV.
Likes # 0
Posted April 12, 2011 at 9:17AM
I had same on 6 yr old desktop, but newish laptop was fine. Even with AV off.
An error message suggested System Update Readiness Tool http://support.microsoft.com/kb/947821 and it worked after running that.
But others have reported success on 2nd attempt anyway, so who knows.
Reply to this topic
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Rejoice, Miley Cyrus' 'Can't Be Tamed' Video Is Here!
The long wait it over! Miley Cyrus 2.0 has finally arrived!
Behold, Miley's new video "Can't Be Tamed," which emphasizes the transformation that the Hannah Montana star is undergoing with such force that it'll probably cause bruising.
She's a bird! She's a vixen! She's Super Miley! And in case you haven't figured it out already, she CAN'T BE TAMED, people!
Check out the video below and let us know in the comments section: What do you think?
Source: E! Online


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Family Fun at Pigeon Forge
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The EarthRoamer
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City Under the Sea (released as War-Gods of the Deep in USA) is a 1965 science fiction film. It was directed by Jacques Tourneur (his final film) and starred Vincent Price, Tab Hunter and David Tomlinson.
List of links to City in the Sea fansites:
Register to update information, save favorites, post photos, news stories and comments.


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You are using an outdated browser. Please upgrade your browser to improve your ReverbNation experience.
Label: Hicemiester Music
Manager: Hicemiester Entertainment
Linnie Hice started playing guitar in his early teens after being turned on to Alcatraz (Steve Vai)
by a friend. With his main inspirations taken from Vai and Racer X guitarist, Paul Gilbert, Linnie
took his guitar and ran with it! By the age of eighteen he was in his second Berkeley theory
prog... See Full Bio
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Copesetic will be opening for Jonathan Tyler and the Northern Lights.
Be the first to ask Linnie Hice Band a question!
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- Filed Under
The Michigan Educator Survey was a 19-item questionnaire about the prevalence of grade-fixing and cheating on standardized tests in Michigan public schools. The Free Press survey was voluntary, so results cannot be generalized to all educators in Michigan.
The survey was based, in part, on a survey administered to Arizona educators and published last year in the scholarly research journal Education Policy Analysis Archives. The results are similar: In both surveys, educators reported that among the top methods for cheating on standardized tests are encouraging students to redo problems and copying key information to teach students the next year.
"While I would expect small fluctuations, especially with the low response rate, the very fact that such similar results have been yielded suggests there is some underlying correlation yielding at some level an underlying truth," said Audrey Amrein-Beardsley, an Arizona State University professor and co-author of the study.
The Free Press survey was administered in May and June with the help of the Michigan Education Association, the American Federation of Teachers-Michigan and the Detroit Federation of Teachers. The AFT and MEA e-mailed the survey to about 51,000 educators statewide. The DFT posted a link on its Web site. The number of respondents who completed the entire survey was 3,083. The participation rate was about 6%. The Arizona study had a participation rate of about 5%.
About the participants
• More than half of the responses came from the metro Detroit tri-county area: Macomb (13%), Oakland (15%) and Wayne (25%).
• About 82% are teachers, from all grade levels; 24% are veterans with at least 26 years of experience.
• About 62% of respondents work in a school that receives Title I federal grants for low-income students
• About 12% reported their school was not meeting a federal academic standard called Annual Yearly Progress (AYP).


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Posted on March 25, 2014 – 11:05 am | Author: Susan Lulgjuraj
Baseball, Basketball, Beckett Updates, Football, Hockey, News Categories, Pop Culture News, World Of Sports | 2014 Goodwin Champions, 2014 Upper Deck Goodwin Champions, Byron Buxton, Eric Dickerson, Goodwin Masterpieces, Joe Montana, Ken Griffey Jr, Museum Relics, Peyton Manning, Upper Deck, World War I | Comments (7)
By Susan Lulgjuraj | Beckett Sports Card Monthly Editor
Goodwin Champions is coming back with new patches, World War I relics and slew of new signers.
Each box of 2014 Goodwin Champions will come with 20 packs and five cards in each pack. There will be three hits per box that range from a number of different elements such as autographs, memorabilia cards, manufactured patch cards, Museum Relics and Goodwin Masterpieces.
Each box will contain 10 mini cards with the chance at getting Magician Back or Presidential Back parallels. Each pack will have a mini, short-print or insert.
On the case level, collectors will find five Origin of Species Patch cards, four Monster 3-D cards, one dual-swatch memorabilia short-print and one Sport Royalty memorabilia card.
Some of the hits are new to Goodwin Champions.
The manufactured patch cards are Origin of Species, and start a new three-year program for Upper Deck. The 2014 set will begin with The Dawn of Complex Life with six tiers of collectability: Reptiles, Fish, Cambrian Explosion, Arthropods, Tetrapods and Cephalopods. The checklist will include 100 cards of different degrees of rarity.
The 3-D Monster cards are a new addition to Goodwin Champions, and will be tough pulls. There are four subsets within the 3-D Monster cards: Bizarre Beasts (1 in 120 packs), Classic Creatures (1:360), The Giants (1:870) and Alien Menaces (1:4,160).
Goodwin Masterpieces Art of the Ages continues with 300 new paintings. Some of the additions include Vincent Van Gogh's Café Terrace at Night, Picasso's Old Guitarist and Cezanne's The Card Players.
There are also Museum Relics from World War I, which Upper Deck recently displayed at the 2014 Industry Summit.
When it comes to autographs, Upper Deck has added some new, recognizable names such as Joe Montana, Peyton Manning, Lindsey Vonn, Ken Griffey Jr., Eric Dickerson, LaDainian Tomlinson and Byron Buxton. It also added a number of Winter Olympians including Shani Davis, Ashley Caldwell, Steve Holcomb, Julie Chu and Hayley Wickenheiser.
Goodwin Champions is set to come out in July.
Susan Lulgjuraj is an editor at Beckett Media. You can email her here with questions, comments or ideas. Follow her on Twitter here. Follow Beckett Media on Facebook and Twitter.
A mummy? Ghosts? C'mon!
Remember when Goodwin Champions was basically a baseball set? I miss that. I like the look of their cards but could care less about any card depicting anything other than baseball. I guess this product is not for me. I will have to search and trade for the singles I want. I certainly won't be buying it.
Considering they don't really have a MLB license, making a baseball set is totally pointless. Not everyone's a baseball fan anyway.
C'Mon Now!!!
Licences or not.
This looks like some left-over products from various issues that you (not me) would pick up (1,000 cards in a box) at the swap meet for a $1.00
People really buy this stuff ?
Always bust some of this product, for the price its beats hitting more repetive garbage auto from overpriced Topps Baseball product.
this product is great. never know what your going to get. i landed a redemption last year of michael jordan auto. this year a museum collection redemption.
Bought my first pack; pulled a Julie Krone autograph.She is a horse racer.Nice signature, with a happy face!
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Breastfeeding check in
View Single Post
April 29th, 2014, 09:35 AM
Mega Super Mommy
Join Date: Jan 2007
Location: Alberta, Canada
Posts: 3,014
We are still hanging in there. My left nipple is finally healed enough that I tried nurses off it once yesterday. I did again today and it was still fine. I am hoping to stop with the pumping on that side. It still burns on either side... Im not used to this feeling at all and I dont like it. I have to have a fan on me while I nurse because I get very hot and uncomfortable. I really hope that initial shock of pain stops happening soon
He constantly is falling asleep while he nurses. He doesnt when he takes a bottle, only when I nurse him. Its trying because I know he can eat faster and put me outta my misery but he likes to just hang out there.
So i guess overall we are doing good since I am still at it. Just waiting and hoping that it stops hurting so freaking much.
View Public Profile
Find all posts by Nel


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State's breeding duck population increases
Breeding waterfowl populations have increased from 2010 estimates for eight of the ten duck species surveyed; and overall, duck estimates increased 11 percent from last year to just over 45 million birds. The U. S. Fish and Wildlife Service and Canadian Wildlife Service conduct annual waterfowl population surveys on the breeding grounds to monitor waterfowl populations and help set hunting season frameworks.
The 2011 May pond count was 8.1 million ponds, an increase of 22 percent over the 2010 count of 6.6 million ponds.
"Last year's May pond counts held steady with recent years, which were very good. This year's counts were significantly higher" said Houston Havens, Waterfowl Program Biologist for the MDWFP.
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Home » NewHampshire.com
Mont Vernon's Preston makes it to final 'Idol' seven
Preston, whose real name is Alex Preston Philbrick, confirmed with a Tweet that he will be back for the next round as he continues to try and win season 13 of the singing competition.
"Thanks y'all, another week" Preston wrote on Twitter.
Preston and six others advance to next week's rounds.
|Tweets by @newhampshirecom
Most Read
'Interview' buzz spreads to NH
Most Shared
Bedford pizza shop gets a visit from a famous former employee
Nature Talks: Taking a closer look at the red-bellied woodpecker
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'Interview' buzz spreads to NH
Lyndeborough official would not give up on tree


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VxD to monitor File I/O in Windows 95/98
Spy Windows 95/98 File I/O
Published 12/07/1999
VxD to monitor File I/O in Windows 95/98
Discover Code::Blocks, an open source IDE for C/C++.
Explore the basics of accessing a Twitter account and look at the ways we can search and interact with the data available to you.
Over the past 10 years, Facebook use has become pervasive in our everyday lives. Use VB to tame your feeds.
Arun Karthick introduces you to the state machine model and shows you how to create a simple working state machine sample using the .NET framework in the C# language.


text:
44th Street Theatre
From Wikipedia, the free encyclopedia
(Redirected from Nora Bayes Theatre)
The 44th Street Theatre was a Broadway theatre located at 216 W. 44th St in New York City from 1912 to 1945.[1] The architect was William A. Swansea. Built by the Shubert Organization, and first named Weber and Fields' Music Hall, the theatre was renamed in 1915 when the comedy duo Weber & Fields split with the Shuberts.[2]
The Nora Bayes Theatre was located on the roof of the 44th Street Theatre[3] and club space in the theatre's basement was operated as the Stage Door Canteen during World War II. The building was demolished in 1945 to make way for an expansion to the New York Times offices and printing plant.
Notable productions[edit]
- 1913: The Girl on the Film
- 1914: The Lilac Domino
- 1915: Katinka
- 1916: The Blue Paradise
- 1917: Maytime (musical)
- 1919: Take It From Me
- 1927: The Five O'Clock Girl
- 1927: A Night in Spain
- 1933: Face the Music (musical)
- 1943: Die Fledermaus as Rosalinda (total 521 perfs)
- ^ Internet Broadway Database: 44th Street Theatre
- ^ Weber—Fields Partnership
- ^ What the Summer Promises
|This United States theatre-related article is a stub. You can help Wikipedia by expanding it.
|This article about a building or structure in Manhattan is a stub. You can help Wikipedia by expanding it.


text:
For Sale: Like New -Loaded RZR over $20,000. Invested
152 miles-28.5 hours
Ad #182253135 Posted:2014-07-29 13:29:45
This ad expired 57 days ago.
These are current photos, I have put a hard top on it. It has never been wrecked or damaged. Only has normal wear from the minimal use. 28.5 hours. Thanks08 RZR loaded--extra red body in box , factory nets and has hard top on it. Fresh service only 152 miles on unit, stored in heated/ ac garage. Carbon fiber scooped hood, aftermarket rims & tires. Drink cooler w/ mount, shock covers, full skid plate, u-joint protectors, side tube slider bars, front & rear tube bumpers, hard & soft tops, driving lights on top bar & driving lights on front bumper bar, 1/2 windshield, rear view mirror, Marine HD am/fm/ cd player w/ speakers & mounting boxes, trailer hitch bar, aftermarket air filter. Four stroke dual cyl. 760cc engine that's rated @ 58mph or remove the factory clutch sleeve and its 63 mph. Unit is fast and dependable never wrecked only been in the woods three times. Everything factory installed and wired. This unit is in excellent condition!! Buy for less than 1/2 of the cost of a new one equipt like this. My loss your gain. Make an offer-Thanks
Above Added: Fri August 22, 2014, 7:48 am EST
Seller Phone Number: 704-938-2608
This item is USED
Trades NOT ACCEPTED
Item Location: KANNAPOLIS, NC Get Directions To This City
This item is USED
Trades NOT ACCEPTED
Item Location: KANNAPOLIS, NC Get Directions To This City
Seller Information
Ad posted by:
Ad posted by:
blueblod (#168554)
Member Since: 2007-01-08
Phone Number: 704-938-2608
Member Feedback
Number of Honor Payments: 0
Average Accepted Sale Price: $70.00
Average Honor Payment: $0.00
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I don't really know what to write here so... I love anime and I love to cosplay. I also really like yaoi. I'm a part of Purple Cosplayers Productions! Favorite Animes/Manga series Black Butler Alice IN The Country Of Hearts Fullmetal Alchemist Hetalia Soul Eater Black Rock Shooter XXXHolic Angel Beats Ouran High school Host Club Trinity Blood Junjou Romantica Hell Girl I am mainly a reader so I won't update my stories very much. My favorite bands are: Black Veil Brides My Chemical Romance Panic! At the Disco Escape The Fate Vocaloid Breaking Benjamin Evanescence Rise Against Refused System of a Down The Offspring Billy Talent Foo Fighters Green Day Attack Attack! Ludo Thursday Hawthorne Heights Silverstein From First To Last Enter Shikari Mindless Self Indulgence I am in love with Kingdom Hearts and am a member of Organization Awesome! I love Demyx Time and The Sora Show they're amazing!!! 0%Normal (since there's no such thing it's only a setting on a dryer) █ 10% Bad Singer ██ 20% Depressed ███ 30% Funny ████ 40% Shy █████ 50% Cosplayer ██████ 60% Bass Player ███████ 70% Yaoi Fangirl ████████ 80% Anime Lover █████████ 90% Music Lover ██████████ 100% ME ╔╗ ║║ ║║ ╚╝ ╔╗ ║║╔═╦╦╦═╗ ║╚╣║║║║╩╣ ╚═╩═╩═╩═╝ ╔══╗ ╔╗ ╔╗ ║╔╗║ ╚╝ ║║ ║╚╝╠══╦╦══╦═╗╚╝ ║╔╗║╔╗║║║║║╩╣╔╗ ╚╝╚╩╝╚╩╩╩╩╩═╝╚╝ l...............| |...............| Put this on your |...............| page if you have |............O| ever pushed a |...............| door that said pull |...............| ╔╦╦╦╦═╗Put this on your page ║╩║║║╔╗if you love giving away ╚╩╩═╩═╝ hugs.♥♥♥ ╔══╗♫ ║██║♫ Paste this on ║██║♫ your page if♫ ║(O)║ ♫you love♫ ╚══╝♫ music♫ You say Pink I Say Black You Say Zac Efron I Say WTH! You Say Pop I Say Rock You Say I'm Weird I Say I'm Different XP You Say Justin Bieber I Say WTF!?! Andy Six all the way!!!! I suport LBGT ♀+♀= ♥ GENDER ♂+♂= ♥ DOESN'T ♂+♀= ♥ MATTER BECAUSE LOVE HAS NO BOUNDARIES Why can't people understand that!
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