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Inadequate blood circulation to tissues caused by obstruction of arterioles and/or capillaries results in ischemic injuries – these injuries can range from moderate (eg leg ischemia) to severe conditions (eg myocardial infarction stroke). disease an ischemic condition impacting the low extremities summarizing different facets of vascular regeneration and talking about which and exactly how stem cells restore the blood circulation. The writers also present a synopsis of encouraging outcomes from early-phase scientific studies using stem cells to take care of peripheral arterial disease. The writers believe that extra analysis initiatives ought to be undertaken to raised identify the type of stem cells and an extensive co-operation between laboratory and scientific investigators is required to optimize the look of cell therapy studies and to increase their technological rigor. Just this allows the outcomes of the investigations to build up best clinical practices. Additionally although a number of stem cell therapies exist many treatments are performed outside international and national regulations and many clinical trials have been not registered on databases such as ClinicalTrials.gov or EudraCT. Therefore more demanding clinical trials are required to confirm the first hopeful results and to address the challenging issues. Keywords: adult stem cells crucial limb ischemia bone marrow transplantation therapeutic angiogenesis What is peripheral arterial disease? Peripheral arterial disease (PAD) is usually a common circulatory problem in which narrowed arteries reduce blood Acolbifene (EM 652, SCH57068) flow to the limbs especially the legs. The most common causes of PAD are atherosclerosis obliterans (ASO) and thromboangiitis obliterans (TAO).1 Two major classification systems are currently used to evaluate the spectral range of symptoms: (1) the Fontaine classification not found in Acolbifene (EM 652, SCH57068) everyday clinical Acolbifene (EM 652, SCH57068) practice but helpful for analysis reasons and (2) the Rutherford classification additionally cited in recent magazines in neuro-scientific vascular medication (Desk 1). The American University of Cardiology/American Center Association 2005 suggestions noted the effectiveness from the Rutherford classification for standardized conversation between clinicians.1 Disease classification and staging systems are essential for clinical administration of the sufferers. Based on the severe nature of symptoms generally two distinct scientific presentations are recognized in PAD sufferers: (1) intermittent claudication seen as a intermittent discomfort in quads when the individual strolls and (2) important limb ischemia (CLI) a far more severe type of PAD seen as a discomfort at rest nonhealing wounds and gangrene. After 12 months 30 of sufferers with CLI will eventually lose their knee and 25% will expire.2 Desk 1 Two Acolbifene (EM 652, SCH57068) classifications of peripheral arterial disease (PAD): Fontaine and Rutherford The incidence of CLI in American societies is approximately 220 brand-new situations per million people each year and with an aging inhabitants the population in danger is likely to increase due to persistent prices of cigarette abuse and a rise in diabetes.2 50 percent of diabetics (7% from the globe inhabitants this year 2010) have problems with PAD which might result in amputation because of CLI.3 Moreover smoking cigarettes hypertension dyslipidemia a sedentary way of living and a genetic predisposition all donate to Acolbifene (EM 652, SCH57068) the introduction of PAD.4 5 Current remedies for PAD Revascularization either surgical or endovascular may be the silver regular treatment for sufferers with severe PAD. Nevertheless despite developments in operative and endovascular methods 6 a lot more than 30% of sufferers do not meet the criteria as applicants for revascularization due to extreme operative risk or undesirable vascular participation. Furthermore the current presence of comprehensive atherosclerotic LILRA1 antibody plaques in the tibial and/or peroneal arteries renders revascularization unsuccessful. These patients are left to medical therapy which may only slow disease progression and the only remaining alternate for relief of rest pain or gangrene is usually amputation of the affected lower leg. An estimated 120-500 amputations are performed per million people per year and one-quarter of these patients require long-term institutional care or professional assistance at home.2 Medical therapy is limited to antithrombotic therapy 7 the prostaglandin analogue iloprost 8 or recently to cilostazol. Cilostazol has been.
Category Archives: Adenosine Kinase
Laminins are heterotrimeric glycoproteins belonging to the extracellular matrix that are
Laminins are heterotrimeric glycoproteins belonging to the extracellular matrix that are released by epithelial cells and which are vital for the regular structure and performance of the basements membrane. Alternatively the loss of ?3 HST-1 laminin was associated with a tremendous increase in the collagen articles of the lung area. We deduce that the reduction in ?3 laminin in the sonant epithelium ends up in an increase in chest collagen which in turn confers capacity mechanical harm. floxed rats We made a vector targeting exon 42 of your mouse gene (the murine comparable of exon 41 belonging to the human gene) by ranking sequences two to three kb upstream and some kb downstream of exon 42 (Fig. 1A). Removal of this exon will result in reduction in the two key splice isoforms encoded by gene (the ?3a and ?3b laminin subunits) (Ryan et 's. 1999 This kind of vector was introduced in embryonic come cells (ESCs) through electroporation and the skin cells were picked and processed through security Piragliatin for homologous recombination by simply southern blotting. These skin cells were being injected into Piragliatin blastocysts which were afterward Piragliatin implanted in mice. The chimeric children were combined to C57BL/6 mice and ESC-derived progeny were sequentially bred to generate mice homozygous for the floxed ?3 laminin subunit allele. In order to avoid the possibility that the Neo cassette which is made up of strong regulating regions could influence reflection of the targeted gene or perhaps it friends and neighbors we taken off it by simply mating the homozygous floxed mice to mice. Rats bearing a homozygous floxed ?3 laminin subunit allele in the a shortage of the Neo cassette had been further carefully bred to remove the transgene. GENETICS isolated in the tails of 5 littermates as a result of crossing pets or animals exhibiting germline transmission belonging to the floxed allele was broken down with sites (Fig. 1B). The predicted size with regards to the wild-type (wt) explode is dua puluh enam kb and then for the flox fragment is certainly 9. almost 8 kb. Genomic DNA was isolated in the lungs of wild-type rats infected with null contamination and rats infected with null contamination or Cre-encoding virus. PCR primers had been designed to boost within intron 40 through intron 40 a region flanking the built sites. We all amplified the expected 950-bp product in the wild-type chest genomic GENETICS and a great 1100-bp merchandise from the chest genomic GENETICS from rats treated with control contamination indicating inserting the the sites. Making use of the same primers we increased an additional 500-bp product out of lung genomic DNA in the mice medicated with Cre virus implying excision belonging to the targeted string (Fig. 1C). To ensure that the knockdown would not result in the development of an N-terminal fragment we all designed special primer sequences to amplify brief regions especially within the and regions and within a location common to equally downstream belonging to the deleted exon (supplementary materials Fig. S1). In RNA obtained from sonant type 2 cells separated from rats treated with Ad-Null or perhaps Ad-Cre sixty days earlier all products had been significantly lowered confirming a knockdown of and and suggesting that Piragliatin no N-terminal laminin explode is generated (Fig. 1D). Fig. 1 ) Generation of your mouse. (A) Picture of portion of the vector that targets exon 42 of your mouse gene. (B) DNA separated from tails of five littermates resulting from bridging animals demonstrating germline indication of the floxed allele was… Lung-specific knockdown of ?3 laminin rats were medicated with Ad-Cre or Ad-Null and thirty days 60 days or perhaps 6 months subsequently the lung area were collected homogenized plus the abundance belonging to the ?3 laminin subunit was detected by simply immunoblotting. Employing ?-galactosidase Cre reporter rats we have recently shown that it dose of adenovirus ends up in widespread recombination in the breathing passages and sonant space belonging to the lung (Budinger et 's. 2010 Weinberg et 's. 2010 Nominal knockdown of ?3 laminin protein was observed thirty days after the treatment of adenoviral Cre recombinase (Fig. 2A B). For 60 days following your administration of Ad-Cre a great ~60% knockdown of the ?3 laminin subunit was noticed in mouse chest homogenates (Fig. 2A B). This knockdown persisted in mice looked after for six months time after irritation with adenoviral Piragliatin Cre (Fig. 2C). Furthermore there was a strong reduction in discoloration of parts of the lung area of the Cre-virus-treated animals weighed against that noticed in the control (Fig. 2D). These.
Accurately describing synaptic interactions between neurons and how interactions change over
Accurately describing synaptic interactions between neurons and how interactions change over time are key difficulties for systems neuroscience. inferred from spikes relate to simulated synaptic input? and 2) What are the limitations of connectivity inference? We find that individual current-based synaptic inputs are detectable over a broad range of amplitudes and conditions. Detectability depends on input amplitude and output firing rate and excitatory inputs are detected more readily than inhibitory. Moreover as we model increasing numbers of presynaptic inputs we are able to estimate connection strengths Alogliptin more accurately and detect the presence of connections more quickly. These results illustrate the possibilities and outline the limits of inferring synaptic input from spikes. Author Summary Synapses play a central role in neural information processing – weighting individual inputs in different ways allows neurons to perform a range of computations and the changing of synaptic weights over time allows learning and recovery from injury. Intracellular recordings provide the most detailed view of the properties and dynamics of individual synapses but studying many synapses simultaneously during natural behavior is not feasible with current methods. In contrast extracellular recordings allow many neurons to be observed simultaneously but the details of their synaptic interactions have to be inferred from spiking alone. By modeling how spikes from one neuron statistically affect the spiking of Alogliptin another neuron statistical inference methods can reveal "functional" connections between neurons. Here we examine these methods using neuronal spiking evoked by intracellular injection of a defined artificial Alogliptin current that simulates input from a single presynaptic neuron or a large population of presynaptic neurons. We study how well functional connectivity methods are able to reconstruct the simulated inputs and assess the validity and limitations of functional connectivity inference. We find that with a sufficient amount of data accurate inference is often possible and can become more accurate as more of the presynaptic inputs are observed. Introduction Neural computation requires fast structured transformations from presynaptic input to postsynaptic spiking [1-3]. Changes in these Alogliptin transformations underlie learning memory and recovery from injury [4 5 Tools for identifying synaptic weights and tracking their changes thus play a key role in understanding neural information processing. Traditionally synaptic integration and plasticity are studied using intracellular recordings [6-8] recording intracellularly from connected neurons is technically prohibitive. Rabbit polyclonal to AQP9. On the other hand methods for recording extracellular spike trains are advancing at a rapid pace [9 10 and allowing the simultaneous recording of hundreds of neurons. Estimation of synaptic interactions from extracellularly recorded spike trains requires development of sensitive data analysis tools. Although strong synapses are usually readily detectable using cross-correlation analysis [11-17] where they appear as asymmetric short latency peaks on cross-correlograms [18 19 in general it is difficult to link the statistical relationships between spike trains to specific Alogliptin synaptic processes [20 21 Here we provide empirical tests of statistical tools for such analysis using current injection where the true synaptic input is known. As techniques for large-scale electrical [22] and optical [23] neural recordings continue to improve methods for inferring interactions between the recorded neurons are needed to provide insight into the connectivity and information processing of neural circuits. Although correlational methods have long been used to study interactions between pairs of neurons [18 19 recent work has shown that statistical inference methods may be able to substantially improve our ability to detect neuronal connectivity and predict neural activity [24-26]. These model-based methods [22 27 28 are important in removing the confounds that occur with simultaneous recordings [20 29 and have revealed highly structured functional interactions that Alogliptin accurately reflect the known circuit architecture in the retina [30] and invertebrate systems [31]. However it has proven difficult to relate functional connectivity reconstructed from spikes to the known anatomy and physiology of cortical connectivity [26 32 Sparse sampling of neurons and large electrode spacing may contribute somewhat to the difficulty in interpreting the results of functional connectivity analyses of cortical.
(E. layed out in System 1. Despite comprehensive research of the
(E. layed out in System 1. Despite comprehensive research of the system of inhibition by these substances questions still stay regarding the character and need for the many intermediates (7-19). SHV-1 a course A ?-lactamase is situated in K primarily. pneumoniae and it is of significant scientific importance since expanded range and inhibitor resistant variations have been defined in this family members (20). buy A-419259 Furthermore structural and buy A-419259 analytical research established that SHV is a superb model for mechanistic research of course A ?-lactamase inhibition. Lately we have proven the fact that monitoring and trapping of intermediates in SHV ?-lactamase crystals could be achieved using an interplay of two methods X-ray and Raman crystallography (21-23). These initiatives were aided with a deacylation lacking variant of the SHV-1 enzyme E166A. We have shown that in three inhibitor bound crystal structures a trans-enamine intermediate is usually formed an indication that all these inhibitors could follow a common buy A-419259 pathway to inhibition (22 23 Both from Raman and X-ray crystallographic data it was obvious that buy A-419259 tazobactam forms the most conformationally stable trans-enamine while sulbactam and clavulanate form less stable trans-enamine intermediates. These observations could in part explain their clinical efficacy. The crystallographic observations of these inhibitor reaction intermediates units the stage to further our understanding how resistance to ?-lactamase inhibitors can occur. Alterations at M69 have been described in many TEM-type inhibitor resistant variants and recently an M69I variant in SHV (SHV-49) was observed clinically (24). This SHV variant experienced previously been shown to increase resistance to clavulanic acid and to a lesser degree resistance to sulbactam and tazobactam in laboratory constructs of SHV and the 94% sequence identical OHIO-1 (25-27). Helfand et al. have also studied the role of substitution at M69 by site-saturation mutagenesis (25). The findings indicated that substitution of -Ile -Leu or -Val significantly increased the MICs and IC50s for all those three inhibitors; while -Lys -Tyr and -Phe substitution leads to cephalosporinase activity. These results indicate that this size and nature of the residue at the M69 position impacts the substrate specificity. An overall pattern for OHIO-1 M69I was an apparent slower turnover rate and a significant reduction in the affinity for inhibitors. Although the Ki and kinact of the inhibitors are affected by the M69 mutation ?-lactam substrates are still amazingly well hydrolyzed since there is no obvious overall pattern in either kcat or Km in SHV and TEM ?-lactamases (26-28). Crystallographic analyses of such mutations have been carried out previously in related ?-lactamases TEM-32 (M69I/M182T) and TEM-34 (M69V) (29) and found the mutations expose subtle active site changes that result in an effect on enzyme catalysis and inhibitor acknowledgement. This study pointed to a possible role for the local environment of S130 for the inhibitor resistance trait of M69 PLA2G5 variants. This effect was also postulated to be mediated via S70 changes that were observed in the uncomplexed TEM variant structures (29). In the wt SHV and TEM buy A-419259 ?-lactamases S130 is usually shown to act as a second nucleophile for irreversible inhibition by ?-lactamase inhibitors (30) so the changes observed in the orientation of the S130 side chain in the M69V and M69I TEM structures could negatively impact irreversible inhibition (29). In a different crystallographic study including TEM-33 (M69L) (28) structural changes were not observed however molecular dynamics simulations hinted at simple adjustments in enzyme dynamics. In cases like this it was figured the system of inhibitor level of resistance for the M69L mutation in TEM may be the decreased affinity for the inhibitors which most likely affects the speed of the forming of the original acyl inhibitor complicated. In today's research we survey the Raman and X-ray crystallographic analyses from the SHV-1 variant M69V-E166A complexed with all three inhibitors..
. absence of platelet-reactive antibodies circulate up to 48h [8]. After
. absence of platelet-reactive antibodies circulate up to 48h [8]. After estimating a baseline value (100%) of human platelets platelet-reactive antibodies Methazathioprine (with or without drug administration) can be infused. The Methazathioprine impact of these antibodies on the survival of human platelets can then be analyzed by taking bloodstream samples as time passes through the mouse [8]. Methodological information that require interest within this Methazathioprine model consist of: platelet planning and resuspension in plasma or 'artificial plasma' the concentrations and level of used analytes (platelet antibody or medication) the path of platelet shot (retro-orbital shot or tail vein shot) and antibody shot (intravenous intra-peritoneal). The technique of data catch including time factors of bloodstream sampling and following sample planning for evaluation percentage of circulating individual platelets and software program details also needs to end up being reported at length. Additional steps necessary for responding to the scientific queries for instance platelet preincubation using a drug appealing or an antibody in pooled plasma or 'artificial plasma' also needs to end up being reported [2 9 Amazingly application techniques and the quantity of injected platelets and antibodies possess just been loosely described and standardization ought to be carried out to be able to enhance the reproducibility from the procedures also to enable dependable evaluation of the outcomes. This report isn't didactic with regards to how to gauge the success of individual platelets utilizing the NOD/SCID mouse model. Its purpose would be to recommend standardized techniques and define factors that needs to be regarded when presenting technique in published reviews. The shown procedures were released and discussed through the meetings from the Subcommittee of Platelet Immunology from the Scientific and Standardization Committee Liverpool 2012 and Milwaukee 2014. Recommendations were released to the SSC people and the shown recommendations got unanimous agreement. Implementing these recommendations is going to be of benefit for researchers and laboratories to lessen imprecision and harmonize outcomes and will enable various other laboratories to easily reproduce reported strategies and results and interpret outcomes appropriately. Suggestions Platelet planning from individual bloodstream It is strongly recommended that bloodstream ought to be used under soft suction (not really vacuum suction) by way of a 21 G needle using a light tourniquet or no tourniquet using the donor within a seated position. The very first 2-3 mL of bloodstream which could possibly be contaminated by tissue factor present in skin or vascular cells should be discarded. Blood should be collected from healthy donors of blood group 0 (no medication) into acid-citrated dextrose. Prostaglandine E1 (PGE1) should be added to blood samples at 50 ng/mL immediately after collection. Before any Tbx1 further manipulation samples should rest for at least 10 min but no longer than 60 min after collection to avoid activation. Platelet isolation should be performed Methazathioprine using gentle protocols (first centrifugation 200×g second one 700×g). Platelet pellets should be resuspended very gently after addition of PGE1 and adjusted to 2×109/mL using platelet poor plasma from the same donor (or in citrated patient plasma for drug-induced thrombocytopenia cases). Adjusted platelets should rest for 30 min before injection. Platelet injection into mice It is recommended to inject 200 ?L of platelet suspension (+PGE1). Platelet injection can be performed either via lateral tail vein injection (warming mice prior to the injection may help dilate the veins) or via retro-orbital injection (under general anesthesia). Animals It is recommended to use Non-Obese Diabetic Severe Combined Immune Deficiency mice (NOD/SCID Strain name: NOD.CB17-Prkdcscid/J Stock number 001303; The Jackson Laboratory Bar Harbor Maine); age: 8-16 weeks weight: 20-25 g. Mice should be age- and sex-matched in each experimental setting. It is our recommendation to include both genders and our experience indicates there are no differences Methazathioprine between the genders for this protocol. For pilot studies at least three animals should be tested per experimental group. The real amount of animals ought to be motivated predicated on power calculation if statistical analysis.
The signal transducers and activators of transcription 3 (STAT3) signaling pathway
The signal transducers and activators of transcription 3 (STAT3) signaling pathway plays critical roles in the pathogenesis and progression of varied human cancers including non-small cell lung cancer (NSCLC). NSCLC cells with constitutively activated STAT3; it also suppressed both constitutive and induced STAT3 activity by modulating the phosphorylation of JAK2 and JAK3. Furthermore physalin A abrogated the nuclear translocation and transcriptional activity of STAT3 thereby decreasing the appearance degrees of STAT3 its focus on genes such as for example Bcl-2 and XIAP. Knockdown of STAT3 appearance by little interfering RNA (siRNA) considerably improved the pro-apoptotic ramifications of physalin A in NSCLC cells. Furthermore physalin A suppressed tumor xenograft development. Hence as an inhibitor of JAK2/3-STAT3 signaling physalin A provides potent anti-tumor actions which might facilitate the introduction MGC5370 of a healing strategy for dealing with NSCLC. var. franchetii (Solanaceae) continues to be trusted in traditional Chinese language medicine for the treating sore throat coughing dermatitis hepatitis urinary complications and tumors [13]. We've previously confirmed that physalin A a significant bioactive steroidal element of var. franchetii possesses anti-inflammatory activity by changing IKK? through a Michael addition response [14]. Furthermore physalin A can activate mitochondrial apoptotic pathways through p53-Noxa-mediated ROS era in individual melanoma A375-S2 cells [15]. In addition it activates the loss of life receptor-associated extrinsic apoptotic pathways via the upregulation of Fas appearance [16]. Nevertheless the molecular system root its anti-tumor actions is not completely elucidated. Constitutive activation of sign transducers and activators of transcription 3 (STAT3) has a critical function in the tumorigenesis and development of various individual malignances [17-20]. Notably persistently turned on STAT3 was seen in around 50% of late-stage NSCLC tumors examined [21]. STAT3 activation is certainly highly governed by intracellular kinases such as for example Janus kinases (JAKs) and Src that are hyperactivated in an array of individual malignancies including NSCLC [22-24]. As a result inhibition of STAT3 signaling continues to be suggested to be always a guaranteeing healing strategy for the treating this malignancy. Within this research we investigated PI-103 Hydrochloride the result of physalin A in the proliferation apoptosis and JAK/STAT3 signaling pathway in NSCLC cell lines. Furthermore the anti-tumor activity of physalin A was examined within an xenograft model. Our outcomes indicate that physalin A is usually a promising anti-cancer agent with potential clinical application in the treatment of NSCLC. RESULTS Physalin A inhibits cell viability in human NSCLC cells with constitutively activated STAT3 To determine the anti-proliferative effects of physalin A (structure shown in Physique PI-103 Hydrochloride ?Physique1A)1A) in NSCLC cells five human cell lines (H292 H358 H1975 H460 and A549 cells) were treated with various dosages of physalin A for 24 h. In addition adenovirus-12 SV40 hybrid virus transformed non-tumorigenic human bronchial epithelial (BEAS-2B) cells PI-103 Hydrochloride were also included as normal control epithelial cells. As shown in Physique ?Physique1B 1 physalin A at 15 ?M slightly suppressed the viability of BEAS-2B cells by approximate 10-15%. Similarly H460 and A549 cells were relatively resistant to physalin A. Compared to BEAS-2B H460 and A549 cells H292 H358 and H1975 cells at 5 10 and 15 ?M of physalin A were significantly sensitive to the inhibitory effect of physalin A (all ? 0.002). Interestingly physalin A induced higher growth inhibition PI-103 Hydrochloride in TKI-resistant H1975 cells than PI-103 Hydrochloride in H292 and PI-103 Hydrochloride H358 cells (10 and 15 ?M ? 0.005 Determine ?Physique1B1B). Physique 1 Physalin A exerts anti-proliferative effects in human NSCLC cells with activated STAT3 The levels of phosphorylated STAT3 at Tyr705 (Tyr705-p-STAT3) and total protein were next examined in all five NSCLC cell lines. p-STAT3 levels were high in H292 H358 and H1975 cells (Physique ?(Figure1C) 1 which were shown to be sensitive to physalin A (Figure ?(Figure1B).1B). In contrast H460 and A549 cells which were relatively resistant to physalin A had almost undetectable levels of p-STAT3 (Physique ?(Physique1C).1C). Therefore we hypothesized that this growth inhibitory effect of physalin A was mediated through its repression on STAT3 activation. Physalin A induces apoptosis of human NSCLC cells We next decided whether physalin.
Background Medical morbidity and mortality (M&M) for individuals with disseminated malignancy
Background Medical morbidity and mortality (M&M) for individuals with disseminated malignancy (DMa) is high plus some possess questioned the part of surgery. regression were used to judge temporal predictors and developments of M&M. Outcomes The prevalence of surgical treatment for DMa declined on the time frame from 1 slightly.9% to at least one 1.6% of most procedures (p<0.01). Among DMa sufferers the most regular functions performed were colon resection various other gastrointestinal techniques and multivisceral resections all of these showed little statistically significant reduces as time passes (p<0.01). The speed of emergency functions also reduced (p<0.01). On the other hand the speed of preoperative unbiased functional status increased while the price of preoperative weight reduction and sepsis reduced (p<0.01). Prices of 30-time morbidity (33.7 vs 26.6%) serious morbidity (19.8 vs 14.2%) and mortality (10.4 vs 9.3%) all decreased on DLL3 the research period (p<0.05). Multivariate evaluation identified regular predictors (e.g. impaired useful status pre-operative weight reduction pre-operative sepsis and hypoalbuminemia) of worse 30-time M&M. Bottom line 30 morbidity critical morbidity and mortality possess reduced incrementally for sufferers with DMa going through surgical involvement but surgical involvement remains widespread. These data additional highlight the significance of careful individual selection and goal-directed therapy in sufferers with incurable malignancy.
Anti-factor VIII (FVIII) antibodies is a significant complication of FVIII replacement
Anti-factor VIII (FVIII) antibodies is a significant complication of FVIII replacement therapy for hemophilia A. T-cells a lower percentage of pro-inflammatory splenic T-cells and up-regulation of tolerogenic cytokines and markers. Disruption of Fc interactions with either FcRn or Fc? receptors diminished tolerance induction suggesting the involvement of these pathways. These results indicate that rFVIIIFc reduces immunogenicity and imparts tolerance to rFVIII demonstrating that recombinant therapeutic proteins may be modified to influence immunogenicity and facilitate tolerance. and activated with 10 nM of rFVIII in X-VIVO 15 Rabbit Polyclonal to RPS6KC1. medium (Lonza) containing co-stimulatory antibodies namely anti-CD28 and anti-CD49d (BD Biosciences) for 96 h at 37 °C. IFN? levels in the culture supernatant were measured using an ELISA kit WF 11899A from Meso Scale Devices (MSD). 2.1 Statistical analysis Statistical analyses of results were carried out either using unpaired 2-tailed student's in the presence of rFVIII compared to that observed with T cells from control treated mice (Fig. 2E) with no induction of IFN-? secretion (Fig. 2F). In contrast T-cells from the 250 IU/kg rFVIIIFc treatment group showed a solid dose-dependent upsurge in proliferation (Fig. 2E) and secretion of IFN-? in response to rFVIII publicity (Fig. 2F). Furthermore Tregs isolated from mice treated with 5 every week dosages of 50 IU/kg rFVIIIFc could suppress IFN? creation from effector Compact disc4 + T-cells isolated from mice getting two weekly dosages of 250 IU/kg rFVIIIFc (Fig. 2G). This suggests the lifestyle of Treg cells in spleen of mice getting 50 IU/kg of rFVIIIFc that may take part in the suppression of T-cell reactions to rFVIII. In conclusion these outcomes from research support the observations through the splenic leukocyte profiling and claim that rFVIIIFc treatment led to suppression of T-cell reactions to rFVIII. 3.3 rFVIIIFc activates multiple molecular determinants to advertise tolerance To recognize the main pathways mixed up in tolerance induced by rFVIIIFc we performed transcriptional profiling of splenocytes from mice treated with vehicle 50 IU/kg rFVIIIFc and 250 IU/kg rFVIIIFc the second option being a dosage that was not connected with functional proof tolerance (Fig. 3A). The outcomes proven the induction of many genes that are regarded as involved with multiple pathways of tolerance and anergy in mice treated with 50 IU/kg rFVIIIFc (Fig. 3B). Outcomes had been validated with qPCR. As well as the tolerance particular genes such as WF 11899A for example Foxp3 CTLA-4 and IL-10 (Fig. 3C-E) anergy connected genes such as for example Egr2 Dgka and CBL-B (Fig. 3F-H) prostaglandin synthase 2 (PTGS2) and prostaglandin E2 receptor (PTGER2) (Fig. 3B) were all up-regulated in the splenocytes from mice treated with 50 IU/kg rFVIIIFc in comparison to automobile and 250 IU/kg rFVIIIFc treated mice. Conversely pro-inflammatory substances such as for example CCL3 and STAT3 (Fig. 3B) were down-regulated in the 50 IU/kg rFVIIIFc group. Extra qPCR evaluation also exposed up-regulation of TGF-? (Fig. 3I). The up-regulation of tolerogenic substances such as for example IL-10 TGF-? IL-35 and IDO-1 (Suppl.) and down-regulation of pro-inflammatory cytokines such as for example IL-17 (Suppl.) can be consistent with the induction of a tolerogenic microenvironment in response to 50 IU/kg rFVIIIFc that is conducive to the suppression of antibody responses to rFVIII. Fig. 3 Tolerogenic mechanisms activated by rFVIIIFc: (A) heat map depicting the expression profiles of all the genes in the real time PCR array among the three tested groups: vehicle WF 11899A 50 IU/kg and 250 IU/kg of rFVIIIFc. cDNA from each of the total splenocyte … 3.4 Role of FcRn and Fc? receptors in rFVIIIFc-mediated immune tolerance Because of the presence of the Fc moiety the gain of immune tolerance function of rFVIIIFc may be attributed to the interaction of rFVIIIFc with either FcRn or Fc? receptors some of which are associated with immunosuppression (namely the Fc? RIIb receptor) WF 11899A (Fig. 4A). To dissect the receptor-mediated effect of rFVIIIFc we constructed two mutants – rFVIIIFc-N297A and rFVIIIFc-IHH (I253A H310A H435A) which abrogate Fc.
The renin-angiotensin-aldosterone system (RAAS) is an integral mediator of blood pressure
The renin-angiotensin-aldosterone system (RAAS) is an integral mediator of blood pressure (BP) and volume regulation in both normotensive and hypertensive persons. role of this novel class of antihypertensive medication in preventing cardiovascular disease morbidity and mortality. Keywords: hypertension renin inhibitors renin-angiotensin-aldosterone system Renin-angiotensin-aldosterone system Blood pressure (BP) and extracellular fluid volume are regulated by the renin-angiotensin-aldosterone system (RAAS) in both normotensive and hypertensive persons. Renin is an aspartyl protease that is synthesized as a preprohormone cleaved and stored in an inactive (prorenin) form in the juxtaglomerular cells surrounding the afferent arterioles in the kidney.1 Prorenin is rendered enzymatically active by both proteolytic and nonproteolytic processes. Most proteolytic activation of prorenin occurs within the juxtaglomerular cells BMS-708163 by cleavage of its 43 amino acid N-terminal pro-segment.1 While both prorenin and active renin are secreted in the juxtaglomerular cells in to the flow in response to reductions in glomerular afferent arteriolar pressure sympathetic nerve arousal or reduced sodium delivery towards the macula densa prorenin may be the predominant circulating form accounting for about 90% of total renin in regular human plasma as well as for a much greater portion of the full total in diabetics.2 3 Great things about the renin-angiotensin-aldosterone program inhibition Increased RAAS activity particularly increased angiotensin (Ang) II and aldosterone amounts contribute to focus on organ harm and enhance cardiovascular risk both by elevating BP and through direct results on vascular endothelium and cardiac and renal tissue.4 Ang II promotes focus on organ harm through BP elevation and by mediating constriction and remodeling of level of resistance vessels aldosterone synthesis and discharge enhancement BMS-708163 of sympathetic outflow from the mind and facilitation of cathecolamine release from your adrenals and peripheral sympathetic nerve terminals.5 6 Various antihypertensive medications including beta blockers angiotensin-converting enzyme (ACE) inhibitors Ang II receptor blockers (ARBs) and aldosterone antagonists antagonize the RAAS at different steps. RAAS blockers have been used effectively to lower BP limit or reverse various forms of target organ damage and improve BMS-708163 outcomes in patients with hypertension and/or chronic kidney disease coronary artery disease left ventricular (LV) hypertrophy and heart failure. Direct renin inhibitors (DRIs) the newest class of antihypertensive brokers block the RAAS at its point of origin the renin-angiotensinogen reaction and offer a novel approach to the prevention or reversal of target organ damage and cardiovascular events.4 Aliskiren Aliskiren is the only orally active DRI that has been approved for the treatment of hypertension in humans and has been shown to have favorable effects on target organ damage (Determine 1).7 Aliskiren is a competitive transition state analog and selective inhibitor of human renin and has a therapeutic potential comparable to that of other antagonists of the RAAS.8 In humans the plasma concentration of aliskiren increases dose-dependently after oral administration in doses of 40-640 mg/day peaking after 3-6 h. 9 The oral bioavailability Rabbit Polyclonal to IFIT5. of aliskiren in humans is limited (2.7%) and the average plasma half-life is 23.7 h varying from 20 to 45 h producing suitable for once-daily administration aliskiren.9 Aliskiren is 47% to 51% protein-bound as well as the steady-state plasma concentration is reached after 5-8 times of treatment. The primary elimination route of is via biliary excretion as unmetabolized medication aliskiren. 9 Amount 1 Organs and protective effects aliskiren showed with. Although aliskiren suppresses plasma renin activity (PRA) it causes main reactive boosts in plasma renin focus. It has led some to hypothesize that reactive renin and prorenin secretion may limit the potency of DRIs and will cause focus on organ damage unbiased of BP.10-12 They cause that if the RAAS reaches all leaky allowing a good little percentage of the surplus prorenin generated during DRI treatment to become activated the antihypertensive aftereffect of the DRI could be offset limiting its tool seeing that an antihypertensive agent. This theory is normally controversial and has been questioned. 13 Recently a BMS-708163 study.
Abnormal expression or mutations in Ras proteins has been found in
Abnormal expression or mutations in Ras proteins has been found in up to 30% of cancer cell types making them excellent protein models to probe structure-function relationships of cell-signaling processes that mediate cell transformtion. be directly targeted to Ras using Structure-Based Drug Design (SBDD) and Fragment-Based Lead Discovery (FBLD) methods. The inactivation of Ras oncogenic signaling by small molecules is currently an attractive hurdle to try to and leap over in order to attack the oncogenic state. In this regard important features LX-4211 of previously characterized properties of small molecule Ras targets as well as a current understanding of conformational and dynamics changes seen for Ras-related mutants relative to wild type must be taken into account as newer small molecule design strategies towards Ras LX-4211 are developed. [9] who designed a glycosylated derivative of SCH 54292 that exhibited significant water solubility and LX-4211 could bind to Ras. Through multi-dimensional NMR spectroscopy and biochemical characterization studies this compound showed inhibitory activity towards nucleotide-exchange of GTP for GDP on Ras; however the binding affinity for the compound was low [?M] [9]. While the low affinity of this ligand was disappointing the generation of a water-soluble compound that was able to target Ras showed the promise of this approach. Targeting small molecules to regulate protein-protein interactions has also proven to be challenging. However Waldmann study. Additionally our increased knowledge of the conformational and dynamics changes seen for Ras-related mutant proteins should also be exploited in subsequent design strategies to target small molecules to adjacent regions on Ras proteins. Although the state of knowledge and the tangible applications are at an early stage small molecule drug candidates nevertheless show promise for disturbing disease-causing Ras-related protein-protein interactions. 4 Acknowledgements We thank Drs. Roger Koeppe II and Robert Oswald for providing critical feedback and suggestions on the content and scope of this LX-4211 manuscript and Mrs. Kyla Morris and Mr. Hans Wang with Figure design. This publication was supported by Grant Number 1K-01-CA113753 to P.D.A. from the National Cancer Institute of the National Institutes of Health (NIH) Grant Number P30 GM1034-50 Rabbit Polyclonal to PNPLA8. from the National Institute of General Medical Sciences of the NIH and the Arkansas Biosciences Institute. REFERENCES [1] Bos JL. Ras Oncogenes in Human Cancer: A Review. Cancer Research. 1989;Vol. 49(No. 17):4682-4689. [PubMed] [2] Baines AT Xu D Der CJ. Inhibition of Ras for Cancer Treatment: The Search Continues. Future Medicinal Chemistry. 2011;Vol. 3(No. 14):1787-1808. http://dx.doi.org/10.4155/fmc.11.121. [PMC free article] [PubMed] [3] Gysin S Salt M Young A McCormick F. Therapeutic strategies for Targeting Ras Proteins. Genes & Cancer. 2011;Vol. 2(No. 3):359-372. http://dx.doi.org/10.1177/1947601911412376. [PMC free article] [PubMed] [4] Guo W Sutcliffe MJ Cerione RA Oswald RE. Identification of the Binding Surface on Cdc42Hs for p21-Activated Kinase. Biochemistry. 1998;Vol. 37(No. 40):14030-14037. http://dx.doi.org/10.1021/bi981352+ [PubMed] [5] Adams PD Loh AP Oswald RE. Backbone Dynamics of an Oncogenic Mutant of Cdc42Hs Shows Increased Flexibility at the Nucleotide-Binding Site. Biochemistry. 2004;Vol. 43(No. 31):9968-9977. http://dx.doi.org/10.1021/bi0490901. [PubMed] [6] Lin R Bagrodia S Cerione R Manor D. A Novel Cdc42Hs Mutant Induces Cellular Transformation. Current Biology. 1997;Vol. 7(No. 10):794-797. http://dx.doi.org/10.1016/S0960-9822(06)00338-1. [PubMed] [7] Taveras AG Remiszewski SW Doll RJ Cesarz D Huang EC Kirschmeier P Pramanik BN Snow ME Wang YS del Rosario JD Vibulbhan B Bauer BB Brown JE Carr D Catino J Evans CA Girijavallabhan V Heimark L James L Liberles S Nash C Perkins L Senior MM Tsarbopoulos A Webber SE LX-4211 et al. Ras Oncoprotein Inhibitors: The Discovery of Potent Ras Nucleotide Exchange Inhibitors and the Structural Determination of a Drug-Protein Complex. Bioorganic & Medicinal Chemistry. 1997;Vol. 5(No. 1):125-133. http://dx.doi.org/10.1016/S0968-0896(96)00202-7. [PubMed] [8] Ahmadian MR Zor T Vogt D Kabsch W Selinger Z Wittinghofer A Scheffzek K. Guanosine Triphosphatase Stimulation of Oncogenic Ras Mutants. Proceedings of the National Academy Sciences of the USA. 1999;Vol. 96(No. 12):7065-7070. http://dx.doi.org/10.1073/pnas.96.12.7065. [PMC free article] [PubMed].


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|Top 200
The economy, explained, with stories and surprises. Imagine you could call up a friend and say, "Meet me at the bar and tell me what's going on with the economy." Now imagine that's actually a fun evening. That's what we're going for at Planet Money. People seem to like it.
February 17th, 2012
Episode 451 of 960 episodes
When you walk around a big city in China, it feels like an entrepreneurial free-for-all — guys selling stuff on street corners, lots of little shops, everybody hustling.But when you pull back the curtain on the country's economy, you find the government everywhere. The government owns, among other things, the country's biggest cell phone carrier, the three biggest airlines and the four biggest banks.Those state-owned banks in particular play a central role in the country's economy.Chinese people have one of the highest savings rates in the world, and they don't have many options for investing the money they save. So they put lots of their money in ordinary savings accounts at those state-owned banks.The banks, in turn, lend a lot of that money out to other government-owned companies, typically at very low interest rates. Those companies go out and build lots of new stuff. All that building contributes a huge chunk of China's growth.But the building can't go on forever. In fact, China may already have built too much stuff with borrowed money.
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In a time where we're all threatened by a rhetoric of hate from the people in power; A Gay And A NonGay challenges many of our differences head on and promises that no matter who you are, or what you're into (Bruce Springsteen or Britney), love is love and gay and nongays can be friends.

An independent podcast from James Barr (@imjamesbarr) and Dan Hudson (@DanHudson). Contact us on Twitter, IG or Facebook @gaynongay

subset: commoncrawl


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Governor John Hickenlooper outlined his five-point plan to address what he calls Colorado's budget "contradictions" in an April 16 letter to lawmakers. The governor's proposal lays out options to free up more state money for areas such as education and transportation, including reclassifying the Hospital Provider Fee.
But it didn't meet with universal approval, especially coming just weeks before the end of the legislative session. Sen. Pat Steadman (D) dismissed it as a "Hail Mary."
The Denver Post's editorial board responded more favorably, saying that action is needed and the governor deserves "credit for trying." With limited time remaining in the session, however, it seems unlikely the governor's plan will result in immediate changes.
While the governor advocates for full TABOR rebates for taxpayers in fiscal years 2014-15 and 2015-16, he believes that the refund mechanism should be addressed after that. Of special interest: he wants to grant the Hospital Provider Fee enterprise status. For an explanation or refresher on that topic, see Joe's blog on the "magic" of converting the provider fee to an enterprise fund. However, the apparently simple process may be more difficult to accomplish than it seems.
In health care legislation news: the much-watched House Bill 1194, which would allocate $5 million in state funding to continue a long-acting reversible contraception (LARC) program for low-income women, seems poised to fail. The bill, championed by Rep. Don Coram (R), passed the House by a vote of 37-26 but was assigned by Senate President Bill Cadman (R) to the Committee on State, Veterans and Military Affairs – traditionally viewed as the "kill committee."
It's unlikely HB 1194 will pass the five-member group at its April 29 scheduled hearing. State funding for LARC could also have been granted through an amendment to the budget bill, which was added during budget discussions but did not make the final cut. If the bill somehow does manage to pass, it would be the only notably controversial health care bill to make it through this session.
Similarly, Rep. Dianne Primavera (D) saw her House Bill 1083, which originally sought to make rehabilitation services more affordable by prohibiting their classification as "specialty services," quickly pass its first chamber after a long-delayed vote in the House Health, Insurance and Environment Committee. But Speaker Cadman then assigned it to the same Senate committee, State, Veterans and Military Affairs.
The copayment for a rehabilitation visit – including physical therapy, occupational therapy, and chiropractic services – would have been limited to half of what an insurance company pays the provider for the visit. However, the bill was amended to instead require a study on patient cost-sharing for rehab services by the Colorado Commission on Affordable Health Care, with a report due by November 1, 2015. It remains to be seen if the weakened version of the bill can pass State Affairs; a hearing date has not been set.
After months of lead-up, an anticipated bill to provide a universal health care system for all Coloradans fell short before it could begin. The legislation, drafted by Rep. Joann Ginal (D) and Sen. Irene Aguilar (D), will not be introduced this session. The group created to support the effort reported that House Speaker Dickey Lee Hullinghorst (D) has decided not to allow its introduction.
Instead, advocates will continue their work to get a citizens' initiative on the November 2016 ballot. CHI will continue to monitor the issue and the voter campaign, to be called ColoradoCareYES.
Meanwhile, Sen. David Balmer (R) surprised many with his Senate Bill 274, which would reinstate a sales tax exemption for soft drinks sold in Colorado. The exemption was removed in 2010 to discourage soda purchases, but Balmer's bill argues that "singling out soft drinks" when most food and drinks are exempt from state sales tax is "arbitrary and unfair." It has been assigned to the Senate Finance and Appropriations Committees.
House Bill 1367, introduced by the Joint Budget Committee along with the Speaker of the House and Senate President, refers a ballot issue to voters in November asking their permission (again) for the state to keep retail marijuana tax revenue. If the ballot measure is defeated, the bill lays out how the money will be spent. The bill passed the Appropriations Committee and needs a final affirmative vote on the House floor to pass the chamber. For a helpful explanation of retail marijuana policy and the tax issue in Colorado, check out CHI's newest report – released, appropriately, on 4/20.
Senate Bill 259, introduced by Sen. Aguilar, sought to protect consumers from some out-of-network charges, but it went down on a party-line vote in the Senate Business, Labor and Technology Committee. Consumers, insurers and advocacy groups spoke in favor of the bill, which Aguilar branded as "Know Before you Owe," while physician and hospital groups opposed it. Physicians believe that they already lack bargaining power when up against insurers and said this bill would remove more of their limited agency.
During the bill's hearing, several changes were suggested that ultimately made the legislation more about the need for transparency so consumers wouldn't be shocked by high price tags. While several opponents agreed with the need for better information disclosure, they said they could not support the bill as written. The committee's five Republican members voted to kill it after several hours of testimony.
Senate Bill 197, though, fared much better. The bill, which would expand the abilities of advanced practice nurses (APNs) by making it easier for them to write prescriptions, passed the House without any amendments and is ready to be signed by the governor. It continues a streak of success for health professional scope-of-practice bills, which have appealed to legislators from both sides of the aisle. SB197 allows APNs to write prescriptions after 1,000 practice hours (down from 3,600 hours) as long as they have at least three years of clinical experience.
A quick roundup of other bill developments:
In the Senate, the Health and Human Services Committee passed five bills we're watching. House Bill 1242, requiring patients to have the opportunity to designate a caregiver during their first day in the hospital, passed the committee 5-0 and then easily passed the full Senate. It is heading to the governor for signature. Senate Bill 256, concerning the Colorado Health Insurance Exchange Oversight Committee, passed Health and Human Services, the Appropriations Committee and then the full Senate. The House Health, Insurance and Environment Committee sent the bill forward on a unanimous vote to the Legislative Council Committee, where it now stands. Senate Health and Human Services also voted 5-0 in favor of House Bill 1232, which would expand the availability of emergency epinephrine auto-injectors. The bill goes next to Appropriations.
The committee voted unanimously to pass House Bill 1186, which would expand the age limit for autistic children to receive health care services and remove the set cap on annual per-child spending. The bill then passed Senate Appropriations and is awaiting its final vote on the Senate floor. House Bill 1097 passed Health and Human Services 4-1, but was then voted down (3-2) in State, Veterans and Military Affairs. The bill would have revived a commission on fetal alcohol spectrum disorders under the Department of Human Services.
In the House, the two health committees sent several bills forward. House Bill 1297, which aims to prohibit insurance carriers from limiting the fees that optometrists may charge or requiring optometrists to participate in specific plans or networks, passed the House Health, Insurance and Environment Committee on a vote of 7-6. The bill's next reading on the House floor has been postponed until May 11, after the end of the session – meaning that it will not move forward. The same committee approved House Bill 1318, which would create a single Medicaid waiver for home- and community-based services for adults with intellectual and developmental disabilities, on a margin of 10-3. The bill subsequently passed the Appropriations Committee and is waiting for third reading on the House floor.
The House Public Health Care and Human Services Committee gave the nod (11-2) to House Bill 1226, a bill that is of great interest to the public health community. It seeks to increase funding for inspections of retail food establishments and reduce the payment burden on county governments and local public health agencies (LPHAs). Currently, the LPHAs must contribute food inspection funding out of their limited budgets because the annual licensing fees paid by restaurants are not adequate to foot the bill. HB 1226 later passed House Finance and is ready for a floor vote.
Governor Hickenlooper has signed several more bills into law as the end of the session nears. They include Senate Bill 15 (requiring benefit parity for autism services), House Bill 1067 (requiring continuing professional development for licensed psychologists) and House Bill 1164 (allowing women who are breast-feeding to postpone jury duty).


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Drag Racing's Glory Days, Part 1
This documentary, hosted by Dave Despain, features incredible footage from the 1971 NHRA SuperNationals in Ontario, Ca. There are neat interviews with Dick Landy and classic footage of Top Fuelers and Funny Cars. This two-parter is 30 minutes in length.
Drag racing's 1st live TV show Lions Drag Strip KTTV 1961.mov
On September 16, 1961, history was made at Lions Drag Strip (Wilmington/Long Beach, CA), when local Los Angeles television station KTTV (Channel 11) aired the first-ever "live" drag racing TV program. Hosted by Bill Welch, plus the legendary track's first manager and iconic hot rodder, Mickey Thompson. Clip is from Part 1 of the three-disk DVD trilogy "Lions - The Greatest Drag Strip", by Don Gillespie. Early day film clips include Tom McEwen, Dode Martin, Zane Shubert, Bob Muravez and Gary Cagle. TV show was the result of manager Thompson's second job, as a pressman for the Los Angeles Times, and friendship with its owners, the Chandler Family, whom also owned KTTV. Each "Lions - The Greatest Drag Strip" DVD is nearly two hours in length, and chronicles the track's incredible history from its opening in October 1955 thru "The Last Drag Race", held on December 2, 1972.
Sportsman Drag Racing in the '70s and '80s
The grass roots of Drag Racing, the weekend warriors, my old racin' buddies, as we were 25 or 30 years ago. Includes some exhibition cars too. These are pictures and video that I took at US 131 Dragway in Martin, MI, Central Michigan Dragway in Stanton MI, Brainerd International Raceway in Brainerd Minnesota, and Indianapolis Raceway Park in Indianapolis IN. The soundtrack is just me jammin' on some Foreigner and Police.


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Pebbled Champagne Leather Earrings - Medium Teardrop (2.25")
These beautiful black feathered leather earrings are a dramatic statement piece and light as a feather. The unique quilted design and soft texture make these earrings a perfect accessory to dress up any outfit. All handmade by Sweet P & Fi owner Molly.


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The effects of temperature on host plant resistance responses have been reported in several pathosystems but there is little information on the effect of leaf wetness. The tobacco N gene-mediated resistance to tobacco mosaic virus (TMV) is temperature-sensitive. Below 27°C, the N resistance gene mediates a hypersensitive response (HR); above 27°C, there is no HR and the virus is able to infect the plant systemically (Wright et al., 2000). Wheat cultivars with the resistance gene Sr6 are resistant to the fungal pathogen Puccinia graminis f.sp. tritici when grown at 18°C, but are susceptible at 27°C (Moerschbacher et al., 1989). Tomato Cf-4 gene-mediated resistance to Cladosporium fulvum is also sensitive to temperature. Transformed tomato seedlings expressing both the Cf-4 gene and the corresponding effector (formerly termed avirulence) gene Avr4 died rapidly as a result of systemic HR at 20°C but grew normally at 33°C (de Jong et al., 2002). The HR is commonly associated with a gene-for-gene interaction. Leptosphaeria maculans, causing phoma stem canker of oilseed rape, has a gene-for-gene interaction with Brassica napus (Ansan-Melayah et al., 1998; Balesdent et al., 2001). Several single locus resistance genes (e.g. Rlm1, Rlm3, Rlm7, Rlm9) (Ansan-Melayah et al., 1998; Delourme et al., 2004) and the corresponding effector genes (AvrLm1, AvrLm3, AvrLm7, AvrLm9) (Ansan-Melayah et al., 1995; Balesdent et al., 2002) have been identified and AvrLm1 has recently been cloned (Gout et al., 2006). However, little is known about the influence of temperature and leaf wetness duration on the interactions between B. napus resistance genes and L. maculans effector genes.
Phoma stem canker epidemics are initiated by airborne L. maculans ascospores (West et al., 1999; Huang et al., 2005), which infect leaf laminas and produce leaf lesions from which the pathogen grows systemically down the petiole into the stem to cause stem canker (Hammond et al., 1985). However, most previous studies on resistance to L. maculans operating at the leaf infection stage have been done with L. maculans conidia. When cotyledons (cv. Quinta) were inoculated with L. maculans conidia (race A2 isolates), the response was resistant at 18°C but susceptible at 27°C (Badawy et al., 1992). The interaction between Quinta and the A2 isolates of L. maculans has now been characterised as a specific Rlm1/AvrLm1 interaction (Ansan-Melayah et al., 1995; Balesdent et al., 2001). In these experiments using a conidial inoculum, the leaves had to be wounded before inoculation. This methodology is not ideal for studying the interactions between a pathogen and its host, since wounding alone can induce plant defence responses. The development of an ascospore inoculation method (i.e. simulating natural infection; Huang et al., 2006) now provides an appropriate method for investigating the effects of temperature and leaf wetness duration on the interaction between L. maculans and B. napus. Studies on the development of phoma leaf lesions on oilseed rape plants inoculated with L. maculans ascospores suggest that temperature and leaf wetness duration both affect the number of leaf lesions and incubation period (time from inoculation to the appearance of lesions) (Toscano-Underwood et al., 2001). Work is now needed to examine the effects of temperature and wetness on the expression of resistance to L. maculans in B. napus leaves.
As phoma stem canker is monocyclic, and the timing of leaf infection on young plants in autumn affects the severity of phoma stem canker before harvest in the following summer, the systemic growth of L. maculans from leaf lesions to stems is a crucial phase in the development of epidemics. However, it has been difficult to study such growth because this phase is symptomless (Hammond et al., 1985). There is now the opportunity to study this symptomless growth using green fluorescent protein (GFP)-expressing isolates of L. maculans (Sexton & Howlett, 2001; Eckert et al., 2005). Such GFP-expressing isolates can be used to investigate whether the expression of resistance in B. napus leaves can prevent the subsequent symptomless spread of L. maculans to stems. This paper describes a series of experiments using near-isogenic B. napus lines carrying/lacking a resistance gene Rlm6, which was introduced into the B. napus genome from B. juncea (Chèvre et al., 1997) but has not been used in commercial cultivars, to investigate effects of temperature and leaf wetness on the phenotypic expression of Rlm6-mediated resistance to L. maculans in B. napus leaves and the use of GFP to observe the symptomless growth of L. maculans from a leaf lesion down the petiole to the stem.


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How to make a R/C boat for under $20by TigrisLi
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In May 2014, Carol Huttner, RN, BSN, MA, found a new way to share her passion for supporting nurses at Abbott Northwestern Hospital.
As the former vice president for Patient Care and a current Foundation board member, she established a new giving society called Nursing Champions of Care.
The new program is for current and past Abbott Northwestern nurses to support the Foundation's Nursing Excellence fund. Dollars to this fund support nursing scholarships, attendance at conferences, and evidence-based practice and research fellowships to advance the nursing practice.
"Changes in health care mean that only the sickest of patients are hospitalized. In caring for patients who are sicker, nurses need to rely on the knowledge they gain through advanced education and other experiences. We need to ensure that our nurses are prepared for the future," said Huttner.
Donations to the Nursing Excellence fund help ease the financial barriers that nurses can face in pursuing education. That frees them up to focus on exploring their ambitions, fulfilling their greatest potential and transforming the future of patient care.
Huttner contends that advanced training and education for nurses leads to innovation in patient care and is directly related to a hospital achieving Magnet status. "This is what helps Abbott Northwestern maintain its cutting edge," she said.
Give in support of nursing education by designating your gift to the "Nursing Excellence Fund."


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Mazda CX-9 Repair and Maintenance Costs
A guide to repairs, service, and maintenance costs for your Mazda CX-9
The national average repair and maintenance cost for a Mazda CX-9 is between $414 and $506 per year. Repair and maintenance costs vary depending on age, mileage, location and service provider.
Repair Cost Index Score
Mazda CX-9scores in the least expensive range of all car models for average repair and maintenance costs
- average of all models
What does this score mean?
Annual Repair Cost
on average
Brake Pad Replacement
$176 to $316
Brake Rotor Replacement
$380 to $736
Wheel Bearing Replacement - Front
$210 to $577
Power Steering Pressure Hose Replacement
$366 to $467
Strut/Shock Absorber Replacement - Front
$254 to $577
The Mazda CX-9 is known to have issues with hard shifts and transmission slippage on models equipped with the six speed automatic transmission. When the transmission gets warm, the issues is most n...
the airbag light on the dash started blinking and continues to blink off and on while driving
My car is throwing the code that this O2 sensor needs replacement.
How expensive is it to paint a 2007 CX9 Mazda?
Mazda North America Operations (Mazda) is recalling certain 2012 CX-7, CX-9 and Mazda6 vehicles s...
Mazda North America Operations (Mazda) is recalling certain model year 2009-2011 Mazda6, 2007-201...
Mazda North American Operations (Mazda) is recalling certain model year 2016 CX-3 vehicles manufa...
2007 Mazda CX-9 Location: Front
Brake Pad Replacement
$199 - $262
2007 Mazda CX-9 Location: One Side
Strut/Shock Absorber Replacement - Front
$176 - $216
2007 Mazda CX-9 Location: One Side
Wheel Bearing Replacement - Front
$231 - $291
2007 Mazda CX-9 Location: Front
Brake Rotor Replacement
$427 - $694
2007 Mazda CX-9
Power Steering Pressure Hose Replacement
$360 - $419
Overall Score (8 Reviews)
September 13, 2013
2008 Mazda CX-9
Purchased our CX-9 Grand Touring in December 2007 (new). Have 65,000 miles and I must say this car drives / rides / handles like new. Only had one minor problem of the interior fan for the air-co...
March 02, 2013
2012 Mazda CX-9
The CX-9 is as close to perfect as an SUV/Crossover can get! It is superior to my former Explorers and Grand Cherokee in every way! The interior could pass for a Lexus. Handling, acceleration ...
August 02, 2012
2007 Mazda CX-9
Major problems I have had 1) faulty front wheel bearing @ 92500 miles 2) a horrible interior noise not easily traceable. It sounds like there is a air leak into cabin at high speeds. 3) In all...


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Clarksville TN Online is the voice of the people of Clarksville Tennessee.Clarksville Online takes you beyond the ordinary in local news and gives the Extras: political coverage, opinion pieces and editorial work, local and regional arts and theater, municipal and county news and events, and more.
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To submit Clarksville Tennessee area news, story leads, tips, or press releases send us an email
Sunday, June 25th, 2017, 10:00pm
Clarksville, TN – Clarksville Gas and Water has planned a water outage on a section of Trenton Road and Tylertown Road on Sunday evening, June 25th, 2017 at 10:00pm for new water main line connection work.
The water outage will affect Trenton Road from Tylertown Road to the state line, Tylertown Road from Trenton Road to Sage Meadow Lane, Connemara Way, Castile Bar, Anthony Court, Drawbridge Court, Roscommon Way, Travis Place, Meshaw Trail, Waterford Circle, Waterford Court, New Grange Circle, New Grange Court, Challis Drive, Snoopy Drive, North Woodstock Way, North Woodstock Drive, Woodstock Court, Spring Water Drive and Sage Meadow Lane.
«Read the rest of this article»
Wednesday, June 21st, 2017
Clarksville, TN – Clarksville Gas and Water has closed approximately 100 feet of the outer eastbound lane of North Riverside Drive at 631 North Riverside Drive to repair a natural gas main.
The inside lane of Riverside Drive will be open to motorists; however, traffic may become congested and motorists may wish to choose an alternate route.
Clarksville, TN – Clarksville Gas and Water has turned off water service on Porters Bluff Road from Madison Street to the intersection of Trahern Lane and Commerce Street and on Trahern Lane to repair a water main leak.
Both roads will be passable; however, traffic congestion may be possible during the work.
Clarksville, TN – Clarksville Gas and Water is continuing sewer main installation on Madison Street closing 400 feet of the outer eastbound lane of Madison Street from Crossland Avenue to 1604 Madison Street.
Clarksville, TN – Clarksville Gas and Water's Annual Drinking Water Quality Report confirms the City's water treatment plant continues to deliver safe and reliable drinking water to Clarksville residents that exceeds federal and state standards.
The report, also known as the "Consumer Confidence Report," allows water consumers to see the results achieved by the Clarksville water system from January 1st to December 31st, 2016, in its efforts to monitor water quality and to prevent health risks.
Gas and Water annual report shows water supply is safe, reliable.
Monday, June 19th, 2017
Clarksville, TN – Clarksville Gas and Water has closed approximately 500 feet of the outer westbound lane of Madison Street from 1807 Madison Street to Memorial Drive for contract pavement work.
Motorists will be directed to the inside lane to bypass the work zone.
Friday, June 16th, 2017
Clarksville, TN – Clarksville Gas and Water is repairing a water main leak on Fort Campbell Boulevard causing low water pressure between 1200 Fort Campbell Boulevard and Fountainbleau Road.
The road is open to traffic.
Clarksville Gas and Water Department Administration and Engineering
Thursday, June 15th, 2017
Clarksville, TN – Clarksville Gas and Water Department reports Madison Street has been reopened to traffic and the sewer installation work has been postponed due to inclement weather.
The work will resume when weather permits.
Clarksville, TN – Clarksville Gas and Water has closed Tyler Street and Martin Street from Greenwood Avenue to East Union Street for water service line maintenance work.
Motorists will be detoured to Greenwood Avenue and East Union Street during the work
Madison Street will be passable and motorists will be directed to the inside lane during the work.


text: Posted January 10, 2010 Except Holliday beat him in the 300meter or somethin, they were showing it during LSU's bowl game a week ago. Plus, Holliday runs a faster UNOFFICIAL 40 but Ford is a better PLAYER. Can you post a link supporting your claim? http://www.independentmail.com/news/2007/aug/24/clemsons-jacoby-ford-turning-blazing-speed-receivi/ A 4.126!!! That is insane. Share this post Link to post Share on other sites


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Part One: What Every Employer Needs to Know About Workplace Instant Messaging
Chapter List
- Introduction: Why Instant Messaging Management?
- Chapter 1: Instant Messaging Is Used by Someone in Nearly Every U.S. Company
- Chapter 2: Uncovering Unauthorized Instant Messaging Use in Your Office
- Chapter 3: What's the Best Way to Manage Employees' Instant Messaging Use?
- Chapter 4: Establishing an E-Risk Management, Compliance, and Litigation Response Team
- Chapter 5: Instant Messaging Pros and Cons
Introduction: Why Instant Messaging Management?
This book addresses the potentially costly business and legal challenges instant messaging (IM) brings to the workplace. Thanks to IM, employers (many of whom remain challenged by e-mail rules and risks) now face even greater electronic communications' problems, as IM brings to the workplace new legal and regulatory issues, and challenges management to reevaluate security, technology, and employee productivity.
Long popular with Internet-savvy American teenagers, one-fifth of whom use IM as the primary means of communicating with friends, [1] and widely used by businesspeople abroad, instant messaging is now gaining a solid foothold in the U.S. workplace. It is estimated that about 40 percent of organizations now authorize IMuse for business, with another 9 percent planning to begin using IM in the future. [2]
As IM gains popularity as the best way to communicate urgent messages, industry analyst Gartner Group predicts e-mail usage will drop 40 percent by 2006.[3]
[1]Jake Wagman, ''Instant Mess,'' St. Louis Post-Dispatch (May 25, 2003), B1, citing a 2001 Pew Internet and American Life Project report.
[2]Michael Osterman, ''More IT Departments Turning Against IM,'' Network World Messaging Newsletter (April 1, 2003), www.nwfusion.com/newsletters/gwm/2003/0331msg1.html.
[3]Brian Deagon, ''Top Brass Slow to Embrace InstantMessaging Technology—Explaining IM Benefits,'' Investor's Business Daily (July 2, 2003).
Exactly What Is Instant Messaging? Business Struggles to Define Instant Messaging
As instant messaging sweeps through the American workplace, employers, lawyers, compliance officers, and information technology professionals wrestle to define and manage it in light of myriad business, legal, and regulatory concerns.
Think of instant messaging as a combination of the telephone, which facilitates conversations with multiple people in real time, and of e-mail, which combines the speed of online communication with a written record of your conversation.
The hybrid nature of IM has created confusion among organizations that can't decide whether to interpret IM traffic as e-mail or phone chat. Some organizations and industries prefer to think of IM chat as an extension of a casual telephone call—a conversation that ends when all parties hang up. Others define IM more formally as a type of e-mail—an electronic communication that produces a written record that may be discoverable in the course of an audit, an investigation, or a litigation.
When the National Association of Securities Dealers (NASD) in 2003 joined the Securities and Exchange Commission (SEC) and New York Stock Exchange (NYSE) in announcing new IM retention regulations, the definition of instant messaging was clarified for broker-dealers, investment bankers, and those who choose to follow the lead of the financial services industry—arguably the earliest, most enthusiastic adopter of IM technology. Industry and government regulators helped the financial services industry clarify that, from the standpoint of content and retention, IM is a form of written correspondence that creates a written business record, just as e-mail does.
IM Rule # 1: Instant messaging is a form of e-mail—written correspondence that creates a written record.


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With every new Han Solo revelation, Lord & Miller keep looking worse
It's looking like Lucasfilm dodged a blaster bolt by firing these two.
It's looking like Lucasfilm dodged a blaster bolt by firing these two.
A dam that killed more than 500 people.
No wireless, though.
We're in deep waters.
'The Boy Who Lived' just entered another decade.
The history of Nintendo's lost SNES classic, explained.
We go down the rabbit hole so you don't have to.
He didn't hold back.
A reminder that good things can still happen in 2017.
Classic magic!
There's good news and bad news for would-be Super NES Classic buyers.
"Wonder Woman," "The Big Sick" and more.
Some of them even made it into 'Cursed Child.'
Too many people believe these.
And as usual, there's a man with an opinion.
When 'Flight Sim X' role-playing sessions go horribly, hilariously awry.
"Everyone go back to your homes. Nothing to see here, folks. #Iwasthere".
Series inspiration Sophia Amoruso addressed the cancellation in an Instagram Story.
30 Seconds to Themyscira
Will Pete Campbell make cameo?
And you thought park tickets were expensive.
They covered anything from chimpan-A to chimpan-Z!
Fan theories do come true!
A look back at the relationship between a creator and her fans that would define a generation.
Humanitarian award 24. No pressure.
Get ready to get punched.
"Ah, shut up, Dursley, you great prune."
Talk about going out with a bang.
Nailed it.


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As a homeowner you've greater option in suburban roofing materials than you had ever before. Items vary from conventional wood shake to state-of-the-art aluminum and offer just the appearance preferred, even as offering desirable protection. A straight comparison of aluminum and wood shake roofing is able to supply you with …Read More »
Home / Tag Archives: hard-wearing
Why Composite Roof Shingles a great choice
Building the ideal residence with the whole lot absolutely right is a monotonous chore. The most vital part of your residence is definitely the roof. Pocking the apt material for its roofing can be a rather delicate job once in a while. Making use of composite shingles for your roof …Read More »


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- Home
- Scented Candles
- Paddywax Vetiver & Cardamom Hygge Candle
Product Description
Manufacture Description
"Hygge" is the Danish word for coxiness. Whether it's curling up with a good book, or having a long dinner with friends, you know the feeling. Introduce Hygge into your daily life with this new Scandi-inspired collection. Five fragrances in matte ceramic vessels with copper lids really bring home the warm minimalism trend.
Our signature soy wax blend paired with notes of Vetiver & Cardamom; hand-poured in a 15 oz. Scandi-inspired matte ceramic vessel with a copper lid.
Approximate Burn Time: 120 Hours
Net Weight: 15 oz.
Wick Type: Cotton Wick
Wax Type: Soy Wax
Fragrance Notes: Vetiver, Cardamom
Fragrance Family: Exotic


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On Sunday April 9th at 3:00 p.m. the Salisbury Symphony will be performing Verdi's Requiem with a 200 community member choir and four seat-gripping soloists; this performance will be at Keppel Auditorium located at Catawba College.
The 200 member chorus consists of 7 different choirs from the Salisbury community and surrounding counties. They consist of the Concert Choir which is directed by Ms. Kay Peeler; Catawba College Singers directed by Dr. Phillip Burgess; The Livingstone College Concert Choir directed by Dr. DaVaughn L. Miller; Mr. Joseph Judge conducts both the Piedmont Choral Society and The Pfeiffer University Concert Choir; the Stanly County Chorale; and the Wake Forest University Concert Choir directed by Dr. Brian Gorelick.
Maestro David Hagy has engaged four wonderful soloists for this concert! Our Soprano Jasmina Halimic had a triumphant debut with the Charleston Symphony as the soprano soloist in Verdi's Requiem and is was most recently Hanna Giawari in Lehar's The Merry Widow with Minnesota's North Nights Music Festival. Jasmina is sponsored by Mrs. Teresa Moore-Mitchell for this concert. Our Mezzo-Soprano Cristy Brown has toured extensively in the Unites States and in Europe; she also sang the world premiere of composer Steven Landis's Songs of Love and Immolation. Cristy is sponsored by Dr. Phillip Burgess. James Allbritten, our Tenor for the performance, is beginning his third season as General Director for the Piedmont Opera after serving ten years as its Artistic Director. James is sponsored by Bud & Betty Mickle. Finally, Bass-Baritone Richard Ollarsaba has recently finished his residency with the Patrick G. and Shirley W. Ryan Opera Center at the Lyric Opera of Chicago, where he stepped into the title role in their 2014 production of Don Giovanni as well as the Majo-Domo in Capriccio. He is anonymously sponsored. For the full biographies of these wonderful soloists, please refer to the Symphony's website.
Our Concert Sponsor, Dr. W. Gerald Cochran invites you to come, enjoy the Salisbury Symphony perform Verdi's Requiem with a vocal ensemble you will not want to miss! Tickets to the April 9th concert are $23.75 for adults, $6.50 for students, and $4.25 for children ages 8 and younger. Concert tickets are available at Rowan County Convention & Visitors Bureau, Sidewalk Deli, Pinocchio's (Spencer), and Crescent Pharmacy (Rockwell). Tickets may be purchased also through PayPal on the Symphony's website or by credit card by calling the Symphony office at 704.637.4314. The box office will open at 2:00 p.m. the afternoon of the performance.
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Season Calendar
Pops at the Post
Sat June 3, 2017 -
Martin Luther's Quincetennial
Sat Sept 23, 2017 -
The 3 Bs' 3s!
Sat Oct 21, 2017 -
The Nutcracker
Sat Dec 16, 2017 -
Sun Dec 17, 2017 -
The 4th and Fiedler's Finest
Thurs Jan 18, 2018 -
Bernstein and Prodigies
Sun Feb 18, 2018 -
Diverse Dvořák
Sat Mar 24, 2018 -
Country &
Western Wit
Sat May 5, 2018 -
Past Performances
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Museum L-A will be hosting a book signing event with David A. Sargent on Saturday, August 21st from 1:00 pm. to 4:00 pm with a brief presentation of his book, "Remembering Lewiston-Auburn on the Mighty Androscoggin", at 2:00 pm. Sargent's remarks will include how people from many countries have been drawn to the Twin Cities. The museum will be open free of charge from 10:00 to 4:00 as part of the annual Lewiston-Auburn Balloon Festival Celebration. Complimentary tours of the museum will also be available.
The event is being sponsored by Androscoggin Bank as the final "Voices" lecture in a three-part series held in conjunction with the Museum's Rivers Immigration: Peoples of the Androscoggin exhibit.
David A. Sargent is a native of Auburn, Maine. He has pursued a lifelong interest in writing and history which was built on the Maine-flavored poetry and journalism of his father, brother, and aunt. In the 1960's he was a general assignment reporter for the Lewiston Daily Sun. In recent years, he founded, edited and published Business Focus, a monthly newspaper. Sargent has carefully chronicled the history of Maine communities in his "River Views" columns which have appeared twice monthly in the Lewiston Sun Journal since 2005. He presents this collection from the early industrial days to the modern splendor of the balloon festival in "Remembering Lewiston-Auburn on the Mighty Androscoggin."
Sargent lives with his wife, Judy, on historic family farm built by his great-grandfather after the Civil War. They have two daughters and six grandchildren.
For further information contact Museum L-A at 207-333-3881.


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The war is over............ what now? Dipper and Mable blew out the candles to their cake making a small wish. There was a burst of light from the sky and meteor fell from the sky landing a few miles away.
The question is what was it.
garnetcat999 Mar 23
baby bill is cute if anyone thought gideon was cute when they first met him they see bill and they be like "wtf is a gideon
ambi2006 Dec 23, 2016
Pie tree hahahhahahahha , lets eat. The PIES which fell from a PINETREE
CleoBrinnCipher Apr 07, 2016
Fangirl squeals eeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeee .... So cute
troylerr5ever Oct 17, 2016
I started laughing out of no where and now everyone is looking at me weird. Lol


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A very good Japo restaurant, the food was excellent and the staff also. Just a small problem, the place is very small and the tables are very close.
1 - 10 of 80 reviews
A very good Japo restaurant, the food was excellent and the staff also. Just a small problem, the place is very small and the tables are very close.
We really appreciated the restaurant and the food was very very good. The atmosphere was excellent. We went there, me, my husband and friends and we were all satistified . We would go back there whenever it's possible. I recommend that restaurant beacause of its...More
A little newer than the established restaurants on the seafront, Sitthai is not just thai food (though they have a thai curry I'm yet to try), but also a wide variety of sushi and sashimi in amazing form and presentation. Try the "dragon" one... amazing...More
We had a very nice evening at this restaurant. The food was really delicious with unusual food mixes which we loved. We had the salmon tartar and salmon sashimi. The fish was really fresh and tasty. We then tried the steak tartar with grapefruit mixed...More
My friend was excited to go becuase of the good reviews of the sushi, but said it was only ok, and has had much better elsewhere, and that it was a bit pricey. I enjoyed the cooked pork cheeks, but i didnt feel that it...More
Went there with a couple of friends last night and it was absolutely delicious, the food was amazing and so was the service. We ordered a bunch of plates from the menu and all shared. Each dish was better than the last one, even the...More
We were on vacation in Sitges and decided we wanted asian food. people recommended Sitthai and we really enjoyed the experience. Very nice cozy restaurant. The food and the service were beyond our expectations. I highly recommend it to anyone visiting Barcelona, it's worth the...More
This was our second visit to sitthai, the first visit was really amazing, food service atmosphere almost faultless, on this occasion we were sadly disappointed, I rang and left a message and requested a certain table, which was not available, fair enough, but no explanation...More
Cannot recommend this little gem of a restaurant enough. the decor is beautiful, the vibe very modern and chilled (great ambient music in the background) and the service is great. The sushi is just about the best I've had anywhere. I had the chef's special...More
We had Dinner Last Night. Very calm, only very few People... Friendly Staff and Nice food. The coco Soup and vegetables with Sedan were very tasty, Main course duck and Green chicken Curry which was VERY hot. But TOP has Been the Dessert: Heaven... A...More
Thank you very much Olaf15 !! It is a pleasure for us to know that our customers enjoy our gastronomy and service. We continue to work for it !!!


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In the process of setting objectives for your business goals, you should always think SMART – as management guru Peter Drucker applies this expression. To make your objectives easy to understand and monitor, they need to be specific, measurable, assignable, realistic and time-related. This mnemonic can be useful when establishing innovation challenges.
Are you building your innovation challenges right?
Having identified your key innovation challenges – aligned with your company's higher purpose and strategic goals and made attainable, useful and targeted – it's time to focus on describing them plainly and completely, to guarantee you'll get meaningful content.
How to mobilise the right audiences for innovation challenges
When putting your innovation challenges together, make sure you have a complete plan with clearly defined, targeted audiences, across cultures and business units, as well as key messages, frequency expectations, a communication and incentives strategy.
Fighting for your audience? Take on the right incentives
Your customers will always be glad to share with you insights on how to improve your product. They're probably doing it now in some way, though irregularly and outside any structured framework.
Finally, your 7th innovation journey must-have
Last but not least, when launching your innovation management effort, remember to find a way to communicate why the initiative is bigger than just a simple project with a set of processes and tools. A strategic intent that shows the … Read More
Is it clear enough? Your innovation journey 6th must-have
From the beginning of your innovation efforts, people need to clearly understand the journey ahead and to feel they have a voice in the process. At Exago, we are strong believers in the power of collective intelligence to envision new … Read More
10 best practices for cross-border innovation. Number 9 makes this a shared journey
People need to understand clearly the common journey ahead (purpose-driven communication in action), and to have a voice in the process. Besides, they need to trust the process.
10 best practices for cross-border innovation. Number 6 assures community awareness
If people don't come, your innovation efforts stand no chance. Active and clear communication is fundamental to maximising engagement, guaranteeing adequate participation. It also assures community awareness. Building a witty communication plan – one that lives and breathes innovation – is paramount for the success of your idea management programme across borders.
TIP: The innovation keystone you may be missing
When launching your innovation management effort, you must find a way to communicate that the initiative is bigger than just a simple project. We're talking about the opportunity to define the company's future. The opportunity to out-differentiate your competition and, more importantly, to write history together.
TIP: Is your innovation effort transparent enough?
Today the traditional model of 'top management decides' and 'everyone else unquestioningly executes' is less likely to succeed, namely in your innovation efforts. Leaders need to define strategy based upon established fundamentals and then clearly communicate that strategy throughout their organisation. Transparency is paramount in the twenty-first century enterprise.
TIP: How to duck the innovation implementation void
Say you've run the front-end process and have successfully identified the ideas and opportunities that make the most sense to implement, but now you lack resources. As a result, the opportunity falls into an implementation void and you get the blame for the low return of your innovation management programme.
TIP: Are top leaders tuned in?
If you have already started your innovation programme, you most likely have a mandate from top management. But do you have their attention? These days you rarely find an organisation where innovation is not a part of leadership's mandate. Yet … Read More
Roche Latin America deploys Exago's transformation services
Roche, a global leader in healthcare, has decided to deploy Exago's transformation services to develop a rich culture of innovation among its employees. Roche will extend the programme to Brazil, Chile, Colombia, Costa Rica and Ecuador. Roche seeks to launch … Read More


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1. Customer is responsible for owning the copyright or having permission from the copyright holder for all images uploaded to this website. Customer agrees to hold Beau-coup harmless from any claim arising out of the use of copyrighted material.
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By Anonymous on 04/09/12
A:2 1/4" x 1" h- 24 tags per sheet. 2 1/4" w x 3 1/2" h- 8 tags per sheet.
By Jessica on 04/10/12
Staff Reviewer
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text: One of the most beautiful faces in the world right there, as far as I'm concerned. Emily Blunt was at the premiere of a rather bizarrely-titled film called SALMON FISHING IN THE YEMEN in Los Angeles, looking radiant in that hot English girl manner with her big ball gown dress. I love Emily however I can get her, but when I really enjoy her the most is when she's got on those tight, black pants she wears everywhere, which make a fantastic spectacle of that fine ass of hers. She literally wears those all the time. I see all kinds of candids of her and she's always got those on. I find that fascinating, because I thought it was only guys who subscribed to the "forever clean" concept in pant-wearing, which dictates that pants can be worn several times in between washes with no personal grooming penalties. Could it be that I've suddenly found a way to love Emily even more? I didn't think it was possible, but yes, I think so.


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The view Place was cluttered, expected us to pay in cash. Room was small and cluttered with personal effects. Breakfast was undesirable and the same breakfast each day.


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Latest News
Come join us at Breithaupt Park on August 27th for the 'Big Breithaupt Campout'! Bring your own picnic dinner, a tent, and some marshmallows for the camp fire as well.
The fun will start at 6pm. We have arranged that the splash pad will stay open later than usual.
It has been almost a year and we are working on getting our second annual MHBPNA soapbox derby race ready to go!
If you missed the last one, it was held at the end of the summer on the Louisa Street hill, just off Margaret Ave. We had four, enthusiastic racers. We ran several test runs, test races and a couple heats. A winner was crowned before noon. Good times were had by all!
This year we are doing things mostly the same -- cart specs are the same, registration process it the same, rules are mostly the same. The big change is that we are going to use a different hill. More details once everything is confirmed. The race will be held on August 20th, 2016.
Other News
Central Fresh and Driving on KingSubmitted by Anonymous (not verified) on Thu, 03/09/2017 - 18:25
I like Central because it is large enough to have most food you want yet small enough to be easy to navigate. They seem to always put on more staff when customers start to line up at the checkout and they have a great supply of cardboard boxes if you want to avoid using tons of plastic bags and forgot to bring your own bags.
KENA Festival InvitationSubmitted by Anonymous (not verified) on Wed, 02/15/2017 - 15:42
Our friends at the King East Neighbourhood Association have invited everyone to their winter festival on February 26.
Here is their message and poster:
152 Shanley Update, February 2017Submitted by Anonymous (not verified) on Thu, 02/09/2017 - 13:00
In 2012 the City of Kitchener claimed it would put this property up for a tax sale. That did not happen.
Save the dateSubmitted by Anonymous (not verified) on Thu, 01/12/2017 - 09:22
Now is an excellent time to enter this into your calendar. Click on the image to make the date larger and more vibrant!
PARTS-walkSubmitted by Anonymous (not verified) on Mon, 10/17/2016 - 10:37
MHBPNA-2016AGMSubmitted by Anonymous (not verified) on Thu, 10/13/2016 - 19:02
Octoberfest on a budget.....Submitted by Anonymous (not verified) on Thu, 09/22/2016 - 13:11
You are invited to: OKTOBERFESTHAUS
AGM and Constitutional ChangesSubmitted by Anonymous (not verified) on Sun, 09/18/2016 - 23:00
What's in a Name?Submitted by Anonymous (not verified) on Fri, 09/16/2016 - 22:52