text:
The pro-inflammatory cytokine interferon gamma (IFNγ), a key player in various neurological diseases, was recently shown to induce a dysregulated phenotype in neural stem/precursor cells (NSPCs) that is characterized by the simultaneous expression of glial and neuronal markers and irregular electrophysiological properties. Thus far, the mechanisms of this phenomenon have remained unclear.
Methodology/Principal Findings
To determine if binding of the signal transducers and activators of transcription (Stat 1) to the sonic hedgehog (SHH) promoter is important for this phenomenon to occur, chromatin immunoprecipitation and pharmacological inhibition studies were performed. We report here that the activation of both the Stat 1 and SHH pathways is necessary to elicit the dysregulated phenotype.
Thus, blocking these pathways might preserve functional differentiation of NSPCs under inflammatory conditions leading to more effective regeneration.
Citation: Walter J, Hartung H-P, Dihné M (2012) Interferon Gamma and Sonic Hedgehog Signaling Are Required to Dysregulate Murine Neural Stem/Precursor Cells. PLoS ONE 7(8): e43338. doi:10.1371/journal.pone.0043338
Editor: Andreas Androutsellis-Theotokis, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Germany
Received: February 23, 2012; Accepted: July 19, 2012; Published: August 29, 2012
Copyright: © Walter et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: These authors have no support or funding to report.
Competing interests: The authors have declared that no competing interests exist.
The pro-inflammatory cytokine IFNγ is mainly produced by cytotoxic CD8+ T-cells, natural killer cells [1], astrocytes, fibroblasts and endothelial cells [2], [3], [4] under normal or pathological conditions after stroke, cerebral traumata or in the course of inflammatory brain diseases [5]. As previously reported, IFNγ affects murine NSPCs in vitro leading to a dysregulated phenotype [6]. This phenotype is characterized by reduced proliferative activity and a synchronous up-regulation of mature neuronal and glial markers also in the presence of growth factors. The IFNγ-induced phenotype bears electrophysiological properties that are indiscernible from undifferentiated NSPCs. The mechanisms involved in IFNγ-induced NSPC dysregulation are unknown. Up-regulation of Stat 1 after IFNγ exposure suggested one of the common down-stream pathways of IFNγ to be involved in NSPC dysregulation. Interestingly, also SHH was considerably up-regulated pointing to a possible crosstalk of IFNγ signaling and SHH production during formation of the dysregulated NSPC phenotype. Similar mechanisms were observed during the differentiation of granular neuron precursor cells of postnatal mice [7] or primary mouse and human pre-adipocytes [8] under IFNγ influence.
Genotypic and Phenotypic Dysregulation of NSPCs and Effects of SHH Antagonism
To verify if SHH signaling is involved in generating the IFNγ-induced phenotype in NSPCs, we antagonized SHH signaling with cyclopamine during IFNγ exposure. Cyclopamine is known to inhibit SHH signaling due to binding, inactivation and change in protein conformation of smoothened [9]. Smoothened is a seven-pass membrane protein and G Protein coupled receptor that regulates the translocation of Gli transcription factor to the nucleus [9]. In a first set of experiments, we verified the induction of the dysregulated GFAP+/βIII-tubulin+ phenotype by IFNγ treatment of NSPCs under the influence of growth factors. As previously reported, we could reliably induce the GFAP+/βIII-tubulin+ phenotype by 1000 U/ml IFNγ (Figure 1a). Also, on mRNA level we demonstrated an up-regulation of both, GFAP and βIII-tubulin after IFNγ exposure (Figure 1b). We then inhibited the SHH pathway during IFNγ-induced dysregulation. For this purpose, we simultaneously applied cyclopamine and IFNγ. And indeed, cyclopamine nearly completely prevented the generation of GFAP+/βIII-tubulin+ cells. These findings were confirmed on protein and on mRNA level by means of immunocytochemistry and real-time quantitative PCR (Figure 1a+b). To investigate effects of SHH antagonism on proliferating, non-dysregulated NSPCs, we also applied cyclopamine without IFNγ. We found no significant differences in the expression of βIII-tubulin or GFAP in the non-treated control or the cyclopamine-treated group (Figure 1a+b).
γ in NSPCs are blocked by cyclopamine. In Figure a: Photomicrographs of undifferentiated murine NSPCs are given. The left panel shows an immunocytochemical staining for GFAP, the middle panel for βIII-tubulin and the right panel shows both. The first row represents the control, and the second row represents the IFNγ-treated cells. The third row shows cells that are treated with cyclopamine alone, and the fourth row shows cells treated with both substances. In Figure b: The results of the real-time quantitative PCR experiments for GFAP, βIII-tubulin, Stat 1 and SHH gene expression are depicted. Delta CT values are means +/− standard error of mean (SEM). Independent experiments were repeated for three times in triplicate.
We monitored the expression levels of Stat 1 and SHH in all 4 experimental groups by real-time quantitative PCR, since we postulate a crosstalk of IFNγ signaling and SHH pathway, probably mediated by phosphorylated Stat 1 leading to the establishment of the dysregulated phenotype of NSPCs. We found Stat 1 and SHH to be up-regulated after IFNγ exposure in comparison to the control group. Cyclopamine inhibited this IFNγ-induced up-regulation and no significant changes in Stat 1 and SHH expression in comparison to control were observed when cultures were treated with cyclopamine alone (Figure 1b).
Gen-expression Levels of SHH and Stat 1 and Population Size of NSPCs Correlate to the Concentration of IFNγ
To detect a possible concentration threshold from where IFNγ induces SHH and/or Stat 1 up-regulation, we performed experiments with different concentrations of IFNγ. We found a significant up-regulation of SHH and Stat 1 at an IFNγ concentration of 100 Units per ml and higher (Figure 2 a+b). We then investigated the population size of undifferentiated NSPCs under the influence of different concentrations of IFNγ since we speculate, that the above mentioned concentrations of 100 Units per ml or higher will also influence their proliferation. Undifferentiated NSPC populations treated for 72 hours with the indicated concentrations of IFNγ showed a significant decrease in optical density, which represents the measuring value in the MTT assay indicative for a reduced population size due to reduced proliferation or induced apoptosis. As the MTT assay measures metabolic activity, a bias towards lower values in differentiated cultures after IFNγ-treatment cannot completely be excluded. Again, these findings were significant with concentrations of 100 Units per ml or higher (Figure 2c).
γ treatment in NSPCs are dose-dependent. In Figure 2 a, b, c: Gene expression of SHH and Stat 1 or the population sizes of the NSPCs are shown in relation to illustrated concentrations of IFNγ. Values are means +/− standard error of mean (SEM). Independent experiments were repeated for three times in triplicate. For concentration dependent gene expression and proliferation studies, NSPCs were seeded at an equal density at day 0, than incubated with different amounts of IFNγ as indicated in the figure. The experimental read out took place three days after the start of the experiment.
Administration of Recombinant SHH alone does not Lead to a Dysregulated Phenotype in NSPCs
As SHH antagonism diminished the generation of IFNγ-induced GFAP+/βIII-tubulin+ phenotypes, we investigated if SHH alone is sufficient to induce this phenotype which would implicate a linear down-stream signaling IFNγ – SHH – GFAP+/βIII-tubulin+ phenotype. For this purpose, we applied 300 ng/ml recombinant murine SHH to undifferentiated NSPCs under the influence of growth factors. However, neither an increase in numbers of GFAP+/βIII-tubulin- or GFAP−/βIII-tubulin+ cells nor the appearance of dysregulated GFAP+/βIII-tubulin+ cells was detectable. These findings were confirmed by immunocytochemistry and on gene expression level by real-time quantitative PCR (Figure 3a+b). Also, no alteration in Stat 1 gene-expression was detectable after SHH treatment. Instead, we found SHH gene-expression to be significantly up-regulated after administration of recombinant SHH to undifferentiated NSPCs implying a positive autoregulatory loop. These results suggest, that the dysregulated phenotype of NSPCs is not inducible by SHH alone, even when applied at higher concentrations.
In Figure 3a: Immunocytochemical photomicrographs of undifferentiated murine NSPCs are presented under the illustrated conditions. In Figure 3b: The results of real-time quantitative PCR are depicted. The values represent delta CT values. Delta CT values are means +/− standard error of mean (SEM). Independent experiments were repeated for three times in triplicate.
Stat 1 Interaction with the SHH Promoter
To further investigate the up-regulation of SHH after IFNγ treatment and to clarify if Stat 1 binds to an IFNγ-activated side (GAS) sequence in the promoter region of the SHH promoter, we performed chromatin immunoprecipitation. For this purpose NSPCs were treated with IFNγ or cultured under control conditions and afterwards chromatin immunoprecipitation (with Stat 1 antibody, normal rabbit IgG antibody or Histon H3 antibody as positive control) was performed. After immunoprecipitation, real-time quantitative PCR against a GAS Sequence in the SHH promoter and a reference gene sequence was used to analyze possible binding of Stat 1 in the SHH promoter region. We chose primer sequences that were specifically designed to amplify GAS sequences in the SHH promoter [7]. We could show a 1.5 fold increase in the chromatin immunoprecipitation sample of IFNγ treated cells for the SHH promoter. Our findings suggest, that a phosphorylated dimer of Stat 1 is able to enter the nucleus, and then binds to a GAS sequence in the SHH promoter (Figure 4a) and therefore leads to the up-regulation of SHH after IFNγ treatment. A possible mechanism for this interaction is visualized in Figure 4b.
γ-mediated dysregulation of NSPCs. In Figure 4a: The results of the chromatin immunoprecipitation of the SHH promoter region with a Stat 1 antibody are shown. In Figure 4b: A schematic drawing of potential pathways that might be involved in IFNγ-induced NSPC dysregulation. CP: Cyclopamine, SMO: smoothened, PTCH: patched, GAS: interferon-gamma-activated site (GAS), ICAM-1: intercellular adhesion molecule 1, MHC-1: major histocompatibility complex 1, i-NOS: inducible nitric oxide synthase, JAK2: janus kinase 2, Stat 1: signal transducers and activators of transcription 1.
In the last few years various studies were aimed at elucidating the role of the pro- inflammatory cytokine IFNγ during neurodegenerative or neuroinflammatory conditions and its impact on NSPCs. In those reports Janus-faced properties of IFNγ were described. On the one hand, pro neurogenic effects of IFNγ on neural stem cell differentiation were described [10], [11], [12], [13], [14]. On the other, a number of publications report a negative effect on neuronal differentiation and neurite outgrowth [15], [16], [17], [18], [19], [20], [21]. A dualistic role of IFNγ was also seen when proliferation and differentiation of astrocytes was investigated [5], [22], [23].
We recently reported that IFNγ leads to phenotypic and genotypic dysregulation in a substantial portion of murine E14 neurosphere-derived stem/precursor cells. This dysregulation is characterized by a simultaneous expression of neuronal and glial markers in immature NSPCs as soon as 3 to 6 hours after application of IFNγ. Furthermore, it was shown that IFNγ causes an up-regulation of SHH and Stat 1 mRNA and a decrease in the population size.
We now extended those investigations and found that the IFNγ-induced decrease in the population size is concentration dependent beginning with 100 Units per ml. Although there might be a bias towards lower population sizes in differentiated cultures that bear a lower metabolic activity, the IFNγ-induced reduced values in the MTT assay are best explained by anti-proliferative and/or pro-apoptotic effects. This is substantiated by the observation that the IFNγ-induced dysregulation was accompanied by an up-regulation of caspase 3/7 and a decrease in BrdU uptake, suggesting IFNγ-related anti-proliferative effects and enhanced apoptosis [6].
We found that also the IFNγ-induced up-regulation of SHH and Stat 1 is concentration dependent beginning with 100 Units per ml. We speculated that SHH, as one of the major morphogenes in brain development, is involved in the formation of GFAP+/βIII-tubulin+ cells and that Stat 1 might be involved in SHH up-regulation. To substantiate this hypothesis, we first investigated if Stat 1 can bind to the SHH promoter. For this, we performed a chromatin immunoprecipitation assay and confirmed that a phosphorylated dimer of Stat 1 is capable to enter the nucleus in order to bind to a GAS sequence in the SHH promoter region and therefore leads to an up-regulation of SHH. This shows that IFNγ-related Stat 1 up-regulation is directly linked to the induced SHH pathway since its known, that the phosphorylated dimers of Stat 1 enter the nucleus and function as transcription factors [24], [25], [26].
To investigate if an activated SHH pathway is directly involved in generating the IFNγ-induced phenotype, we antagonized the SHH pathway by administration of cyclopamine. Cyclopamine is known to inhibit the activity and down-stream-signaling of smoothened by a binding-induced conformational change in the smoothened protein [9]. We were able to show that the IFNγ-induced dysregulation of NSPCs is significantly ameliorated after antagonizing SHH signaling indicating that SHH signaling is necessary to induce the dysregulated phenotype. This finding was confirmed by immunocytochemistry and real-time quantitative PCR. Notably, we were not able to completely block IFNγ-induced NSPC dysregulation by cyclopamine. This could probably be due to the low concentration of cyclopamine as it was used in our study to prevent toxicity. After identification of SHH as mediator for NSPC dysregulation, we added recombinant murine SHH in high doses to undifferentiated NSPCs, to clarify if the dysregulated phenotype can be induced solely via SHH signaling downstream from IFNγ. However, SHH alone was not able to induce NSPC dysregulation. This indicates that the IFNγ-induced dysregulated phenotype is depending on activation of the SHH pathway and simultaneously on other IFNγ-related effects. Thus, the dysregulated phenotype could either be induced via a simultaneous SHH- and Stat 1-activation of the SHH promoter or, for instance, via simultaneous SHH-activation of the SHH promoter and activation of common [27], [28], [29] IFN-regulated genes (IRGs) or IFN-stimulated genes (ISGs) by the JAK/Stat cytokine pathway. We summarized this in the schematic drawing. The IFNγ-activated site (GAS) element in the SHH promoter region might therefore be involved in SHH up-regulation or in a direct co-activation of the dysregulated phenotype.
The binding of phosphorylated Stat 1 to the SHH promoter after IFNγ exposure was previously shown by Sun et al. [7]. Interestingly, Sun and colleagues did not find a dysregulated phenotype or a reduced proliferation, but they described a clear up-regulation of SHH after IFNγ administration and they also describe a binding of Stat 1 to the SHH-promoter region. Notably, the cells used by Sun and colleagues were granular neural precursor cells from postnatal mice, in contrast to NSPCs or the murine ES cell-derived neural stem cells used in our study. This suggests that effects mediated by IFNγ exposure seem not only to depend on the examined brain region but also on the developmental stage and the cell type investigated. It is even more surprising that Todoric and colleagues described a cross-talk of IFNγ and SHH in human and murine pre-adipocytes as well [8]. This leads to the hypothesis, that crosstalk of IFNγ and SHH is an important genetically conserved factor in cellular response to inflammatory signals, since this pathway is not limited to the murine species or a special cell type. Further experiments to elucidate this hypothesis could be I) the application of JAK inhibitors, to block IFNγ signaling to the nucleus and studying the SHH expression afterwards, II) the administration of exogenous SHH together with IFNγ, to see if the amount of dysregulated cells increases by exogenously applied SHH, as well as III) a Stat 1 phosphorylation assay to measure the increase of phosphorylated Stat 1 molecules in a dependency to the used Units of IFNγ. This experiment would further confirm a direct receptor mediated phosphorylation of Stat 1 in NSPCs.
Taken together these findings provide new evidence for the importance of pro-inflammatory signals in cell fade- and differentiation-decisions since SHH is an important morphogene in brain development and the neural stem cells niche [30].
Therefore, we claim a complex and diverse role of IFNγ as mediator of dysregulation in NSPCs.
Materials and Methods
Neurosphere Cultures
Neurospheres were generated from fourteen-day-old wild type C57BL/6J mouse embryos. Cell preparation and animal care were performed in compliance with the German Animal Protection law (State Office, Environmental and Consumer Protection of North Rhine-Westphalia). Ganglionic eminences were removed, mechanically dissociated and seeded in DMEM/F12 culture medium (1∶1; Invitrogen, Karlsruhe, Germany) containing 0.6% Glucose (Sigma-Aldrich, Hamburg, Germany), glutamine (2 mM; Invitrogen), sodium bicarbonate (3 mM; Invitrogen), Hepes buffer (5 mM; Invitrogen) and B27 (20 µl per ml; Invitrogen). For generation and expansion of neurosphere cells, epidermal growth factor (EGF) (Tebu-bio, Le Perray en Yvelines Cedex, France) and basic fibroblast growth factor-2 (FGF-2) (Tebu-bio) were added to a final concentration of 20 ng per ml each.
IFNγ Treatment and Immunocytochemistry
For immunocytochemistry, neurosphere cells were dissociated to a single cell suspension and plated on poly-L-ornithine (PLO; 0.001%; Sigma-Aldrich) and fibronectin (5 µg/ml; Tebu-bio) coated cover slips (VWR International, Darmstadt, Germany) at a density of 125,000 cells per cm2. After 3 days under the influence of EGF and FGF-2 (20 ng/ml both Tebu-bio), cells were assigned to the different experimental groups. To verify the marker expression of undifferentiated (proliferating) neural populations under control or IFNγ treated conditions, cultures were kept under the influence of EGF/FGF-2 without or with IFNγ (1000 U/ml; Millipore) until fixation for further 3 days (NSPC-p -IFNγ/+IFNγ). For control experiments, only phosphate-buffered saline solution (PBS; 1X; Invitrogen) was added to the medium. Primary antibodies used at 4°C overnight were the monoclonal mouse antibody against βIII-tubulin (Tuj1; 1∶500; R&D Systems, Minneapolis, USA or 1∶800, Abcam, Cambridge, UK) and the polyclonal rabbit antibody against glial fibrillaric acid protein (GFAP) (1∶500; Dako, Hamburg, Germany or 1∶1000; Abcam). For detection of primary antibodies, fluoresceine-isothiocyanate (FITC; 1∶500; Millipore) and indocarbocyanine (Cy3; 1∶800; or Cy5; 1∶200; Millipore) coupled secondary antibodies were used. For negative controls, primary antibodies were omitted in each experiment. To measure the total population of cells, Dapi positive cell nuclei were counted. On every cover slip, at least 100 cells were counted.
To analyze the population size of NSPCs, the optical density, indicative of conversion of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT; Sigma-Aldrich) into formazan crystals which takes place in live cells only, was determined after IFNγ treatment at indicated concentrations. An OD value of 0.5 represents approximately 50,000, and an OD value of 1.0 represents approximately 100,000 live NSPCs. The population size was measured after 72 hours of IFNγ treatment. Therefore cells were incubated with MTT (final concentration 0.5 mg/ml) and media one half each and incubated for 3–5 hours at 37°C afterwards the supernatant was discarded and a lysis with DMSO was performed.
Real-time Quantitative PCR
RNeasy Kit (Qiagen) was used for RNA isolation of cultured NSPCs. Then a reverse transcription into cDNA (ABI, Darmstadt, Germany) was performed. Real-time quantitative PCR was carried out by the usage of the 7500 fast or 7500 real-time quantitative PCR cycler (ABI, Darmstadt, Germany). Either SYBR green master mix (Qiagen) or equivalent chemistry from another supplier (Quantace, London, UK) was used. The specific primers for genes of interest or the housekeeping gene (glyceraldehyde- 3-phosphate dehydrogenase, GAPDH) were either purchased (QuantiTect primer assays, Qiagen) or self designed (BioTEZ, Berlin, Germany). The genes of interest (target gene) in IFNγ-treated groups or control groups (PBS-treated) were analyzed in at least 3 independent cultures in triplicate each. Every experiment in IFNγ-treated or control (PBS-treated) groups provided delta CT values (ΔCT: gene of interest minus reference gene). NSPCs were cultivated for 72 hours with IFNγ at the indicated concentrations before the RNA was harvested.
Chromatin Immunoprecipitation Assay
Chromatin immunoprecipitation (CHIP-Assay) was performed by using the simpeCHIP IP Kit (cell signaling) according to the manufacturers instruction, with chip grade antibodies against Stat 1 (cell signaling). Briefly, NSPCs were seeded on PDL and fibronectin coated dished and treated with IFNγ or PBS as control for three days and then fixed with 1% PFA for 10 minutes, harvested and lysed. Chromatin was digested by sonification and incubation with micrococcal nuclease. For chromatin immunoprecipitation the isolated chromatin was incubated with normal rabbit IgG antibody as negative control, Histon H3 antibody as positive control and Stat 1 antibody over night at 4°C. Afterwards the chromatin/antibody mixture was incubated with protein G agarose beads for 2 hours at 4°C. The chromatin was washed and eluted from the protein g agarose beads, the DNA was reverse cross linked to single strand formation and purified over silica membranes. After purification, the isolated DNA was used for real-time quantitative PCR using primers against the SHH promoter regions and the histon H3 complex.
Statistical Analyses
Experiments were repeated with independent cultures at least three times in triplicate each. The resulting data sets were statistically analyzed und illustrated using the GraphPad Prism 4 (GraphPad Software Inc., San Diego,CA, USA, 2003) software. For approval of statistical significance between groups, a two-tailed unpaired t-test was performed. P values <0.05 were considered to indicate significant differences.
We are grateful to Christine Holland for excellent technical assistance, animal care and laboratory support.
Author Contributions
Conceived and designed the experiments: JW MD. Performed the experiments: JW. Analyzed the data: JW MD. Contributed reagents/materials/analysis tools: JW MD HPH. Wrote the paper: JW MD.
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Your primary focus as a musician may be on the sound, but if you want to put on a great show, you'll need some great visuals to go along with it. Color changers and wash lights help you shine when you're onstage. With a wide variety of effects options, this stage lighting can add the visual impact to put on a show the whole audience will remember. Color changers and wash lights are great for DJs and bands alike. Most of these units give you the option of setting them up on the stage or mounting them on a truss, so you can direct their effects exactly where you want them. Take your pick between traditional bulb-powered units for a more classic feel and warmer look, or modern LED stage lighting that's lightweight and runs cool so you won't be sweating it out while you perform. These accent lights come in a few different forms. Bar-shaped wall wash lights will give you a wide curtain of light that's perfect for shining on your backdrops, lining the front of the stage or under-lighting a drum set. Spot-type wash lights work well as overhead lighting, so they're a great addition to an elevated truss. To really dial up the energy of a show, add an effects light such as a flame, fan beam, moonflower, asteroid or projector—these types of lighting are a must-have for DJs. Most LED wash lights and bars are color changers, loaded with RGB LEDs that either come with dozens of color presets, or allow you to program in your own hues by changing the levels of red, green and blue. If you're looking for a wash light that can give you softer colors or pastel effects, take a look at some "RGBA" models. These units have additional amber LEDs that give you control over the warmth of the light as well as the color. When you're choosing your color changers and wash lights, consider the features to make sure you're getting lighting that can do everything you want it to. Some lights come with built-in macros and strobe effects, some can be daisy-chained together to share the same effect across the stage and some can take advantage of sound-activated effects to respond in real time to your music. Thanks to the low power draw of LEDs, you can even get lighting that's battery-powered and wirelessly controlled, making setup and teardown virtually instant. To make your gigs look as great as they sound, color changers and wash lights are an important part of your gear. Even though some venues may provide lighting for you, bringing your own along gives you the advantage of having consistent effects for every show.

subset: commoncrawl


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MINNEAPOLIS -- Minnesota Vikings quarterback Brett Favre extended his record streak of consecutive games started to 290 on Sunday.
Favre was listed as questionable this week because of tendinitis in his throwing elbow, but was under center as the Vikings took on the Cowboys.
The Vikings also put rookie cornerback Chris Cook on the inactive list for Sunday's game against Dallas. Cook was listed as questionable, recovering from a torn meniscus in his left knee.
The Vikings put rookie running back Toby Gerhart the active list and fullback Naufahu Tahi on the inactive list. Center John Sullivan was active, but Jon Cooper was listed as the starter. Sullivan was questionable because of a calf injury.
Dallas rookie wide receiver Dez Bryant was on the active list. He was listed as questionable because of rib and ankle injuries.
Information from The Associated Press contributed to this report.


text:
Dude Climbs 1,500 Feet to Change Light Bulb, Conquer Fear of Heights
Changing a light bulb is not hard. Doing it 1,500 feet high in the sky is.
Changing a light bulb is not hard. Doing it 1,500 feet high in the sky is.
Watch a man solve the 17x17x17 rubiks cube in less than 7 hours.
Everyone loves a boneheaded game show contestant, but sometimes you gotta give it up for a contestant who's actually really, really good. Like this guy.
Well, it took until the end of the year, but we have finally found the best Jenga move, perhaps of all-time.
Oh, Holy Night, indeed!
Buying a house comes with plenty of ups and downs.
The ability to communicate with anyone at any time is nothing new, but now it's going to a whole new level.
Mother Nature never ceases to amaze.
Thanks to new experimental treatments, doctors may have found a cure for leukemia.
As far as birthdays go, they don't get much better than this. This boy is suffering from a brain tumor that leaves him with months to live, so his dad (of the year) dressed up as Spider-Man to surprise him on his 5th birthday.
A San Angelo dog hitched a ride on the side of an ambulance as his owner was taken to the hospital nearly 20 miles away.
If you thought you'd seen it all, prepare to have your mind blown.


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CHENNAI: Narsingh Yadav's Rio hopes are all but over as the NADA committee, hearing the appeal on his positive dope test, decided to defer their... ...http://www.newindianexpress.com/sport/olympics/Narsingh-reiterates-conspiracy-theory-panel-to-decide-today/2016/07/28/article3550499.ece
Cornered by the Supreme Court's acceptance of the Lodha Committee recommendations on sweeping reforms, the BCCI is set for a revamp as some of its... ...http://www.outlookindia.com/newswire/story/bcci-shake-up-on-cards-as-sc-approves-lodha-recommendations/947077
The Board of Control for Cricket in India respects the Supreme Court's verdict on sweeping reforms in the cricket body and it will work towards... ...http://www.rediff.com/cricket/report/we-respect-supreme-court-verdict-rajeev-shukla-lodha-bcci-bedi-kirti-azad/20160718.htm
Feroz Shah Kotla. () Justice Mukul Mudgal is the most sought after man in the world of sport. The former chief justice of the Punjab and... ...http://www.news18.com/cricketnext/news/who-will-act-on-justice-mukul-mudgals-report-on-ddca-1270633.html
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13 years old girl looks like she 40 years old.
A 13 years old Girl has avery rare disease called Lipodystrophy that makes her skin grow fast and makes her look older than her age too much , she is only 13 but she looks like she is 40 also, her mom has the same disease.
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President's costly vacationDecember 26,2012Presidents costly vacation
While President Obama set a fine example (both as President and as a father) by his words/actions in consoling families in Connecticut recently, he fails to set a good example for families in financial difficulty. Its been reported that a vacation in Hawaii will cost $4 million to $5 million.
I wonder what Calvin Coolidge would have done. I wonder what George Akin would think of such expense during this time.
While our President is a great family man in one sense, he falls terribly short in the manner noted above.
Fair HavenMORE IN LettersVoters won big last week. Full StoryWith Aug. Full StoryI am writing to express my support for solar in Vermont. Full Story
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The Coalwood Way: A Memoir Mass Market Paperback – Sep 4 2001
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In this follow-up to his bestselling autobiography Rocket Boys, Homer Hickam chronicles the eventful autumn of 1959 in his hometown, the West Virginia mining town of Coalwood. Sixteen-year-old Homer and his pals in the Big Creek Missile Agency are high school seniors, still building homemade rockets and hoping that science will provide them with a ticket into the wider world of college and white-collar jobs. Such dreams make them suspect in a conservative small town where "getting above yourself" is the ultimate sin and where Homer's father, superintendent of the Coalwood mines, is stingy with praise and dubious about his son's ambitions. Homer's mother remains supportive, but bluntly reminds him, "You can't expect everything to go your way. Sometimes life just has another plan." Indeed, Hickam's unvarnished portrait of Coalwood covers class warfare (union miners battling with his authoritarian father), provincial narrow-mindedness (the local ladies scorn a young woman living outside wedlock with a man who abuses her), and endless gossiping along the picket "fence line." These sharp details make the unabashed sentiment of the book's closing chapters feel earned rather than easy. Hickam can spin a gripping yarn and keep multiple underlying themes and metaphors going at the same time. His tender but gritty memoir will touch readers' hearts and minds. --Wendy Smith --This text refers to the Hardcover edition.
From Publishers Weekly
Not really a sequel to Hickam's first memoir, Rocket Boys (which was made into the successful movie, October Sky, and dealt primarily with his gang of misfit friends and their inventive, adventurous exploits) this book, set around Christmas 1959, is a study of the town of Coalwood and how a fast-moving world affects a small community resistant to change and the introspective teenage boy in its midst. Hickman's reading is flawless. His voice and perspectiveAas a man looking back on his childhoodAconvincingly conveys experience and a reminiscent tone, while at the same time sounding so full of youthful exuberance that listeners will be certain they hear the voice of teenage Homer himself. Coalwood, W.Va., is a coal-mining town. Homer Hickam Sr., the author's father, is the superintendent of the mine and resented by the workers. To his children, he is a formidable man, and his imaginative second son, Homer Jr., aka "Sonny," obsessed with the 1950s space race, does not want to follow in his father's black, dusty footprints. With Christmas fast approaching, the tension in the town grows as layoffs threaten miners' jobs, until Sonny's father takes a huge risk to save them and the town's livelihood. Simultaneous release with the Dell hardcover (Forecasts, Sept. 18). (Oct.)
Copyright 2000 Reed Business Information, Inc. --This text refers to the Audio Cassette edition.
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Where you love the "return to the fullness of [Sonny's] senior high school year," I find it boring, and often confusing. The timeframe keeps switching throughout the memoir. Sometimes Hickam refers to things that he had already discussed in "Rocket Boys," and sometimes he introduces new material. It is constantly hard to tell exactly what's going on, and where the story is taking place. Especially towards the beginning, I find this to be far from the great novel that you describe. Maybe the difference in opinion comes because you enjoy the detail that Hickam uses in this second book, and I find it tedious. It seems fairly obvious to me that all the action was used up in the first book, and nothing "good" was left for the sequel. This story is made up of filler material that was (rightfully) omitted from "Rocket Boys."
I, too, see the message you write of (what it's like to fight through the hard times), but I don't find the story as emotionally intense as you do. In this sequel, we learn only about some of Sonny's schoolboy crushes, but we don't discover anything more that really lets us come to a better understanding of Sonny as a person. It is true that the ending of the book is far superior to the opening. However, Win Idle, you are over exaggerating the amount that the reader will learn about himself by discovering Coalwood. You also over emphasize Hickam's use of emotion.Read more ›
For one thing, i was a bit disappointed about the author's foreword. He swears that even though the events in the book passed so long ago (1959), he remembers everything in tremendous detail. If he hadn't said that, i wouldn't have even thought about it. As a person with very bad memory, i don't believe him.
Some of the characters are described to a point that they almost seem caricatures. I couldn't help think of Martin on The Simpsons when reading about Quentin. Roy Lee reminded me of Elvis Presley in one of his cheesy movies.
The memoir almost redeemed itself in page 267 (chapter 27), when Sonny finally realizes what has been bugging him all along (here's something i wish i had done: jot down the items on Sonny's list as you read along). That discovery makes the book worthwhile. However, the memoir ends with the Christmas Pageant, and that image really ruined the moment for me.
Not only did I now have a chance to get more familiar with the "Rocket Boys" story and characters, but I also had a whole other novel with which to do it. For, you see, this memoir isn't really a sequel to the aforementioned book, but actually an expansion of a section of the original story; a kind of story within a story. Think of it as zooming in on just one section of a fractal image to see all of the intricate details within the new image.
The scope of the first memoir was pretty much the entire high school career of Homer (Sonny) and the Rocket Boys and focused predominantly on their exploits with amateur rocketry. But, the real charm of the original story came from the background setting and people of Coalwood, West (by God) Virginia. The boys of the Big Creek Missile Agency (BCMA) still play a big part in this story that spans basically only one year of high school from roughly Christmas of their junior year through Christmas of their senior year.Read more ›
Most recent customer reviews
I wished there was more to the story. Loved Rocket Boys but this was too slow and a bit boring.Published 15 months ago by Ari B.
How many wonderful works of literature were we denied by Homer Hickam (not Hickham or Hickman) going into Industrial Engineering? Read morePublished on May 12 2004 by Michael in Helena, Alabama
There is something about Mr. Hickam's writing that draws you in immediately. It seems that each and every word that he writes is meaningful not just as a word in a sentence, but... Read morePublished on May 7 2003 by Jennings Xu
Brilliant, I took me only 2 days to finish this book, a great book to follow Rocket Boys (aka October Sky). Read morePublished on Jan. 5 2003
I love Christmas stories and this is one of the best ever written. It is the only Christmas book that has made me truly appreciate the miracles that can only happen at Christmas. Read morePublished on Oct. 9 2002
The Coalwood Way, by Homer Hickam, is the sequel to October Sky. It is 1959 and the
Rocket Boys are still making their handmade rockets. Read more
This book is not about rockets. But then, neither was Rocket Boys, when you think about it. Rockets happen to be the glue that held the vignettes in the first story together, but... Read morePublished on July 1 2002 by Bruce Pierson
The book The Coalwood Way by Homer Hickam is an excellent read. Out of a five scale rating, I give it a five. It was truly, an incredible book. Read morePublished on May 16 2002
I have lived in West Virginia all my life. I know how hard life is, to find a job and raise a family. I also know how proud most West Virginia's are of the state. Read morePublished on Feb. 8 2002


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Paper goods from outer space. Cosmic wonder made with love in Seattle, Washington.
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Paper goods from outer space. Cosmic wonder made with love in Seattle, Washington.
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lostrom01 on Jul 24, 2016
This light garland is ABSOLUTELY GORGEOUS! I am so excited to find the perfect place to use it at my cactus themed wedding and then in my home! Thank you so much!
Sharon Ellery on Jul 18, 2016
jamhill18 on Jul 8, 2016
The lights look so good in my sons new big boy room. He loves them!
paper goods from outer space
The Society of National Industry is a collaboration between Katey Rissi and Chris Campbell.
We've been working together and making things since we met in college at Western Michigan University, where Katey studied design and Chris studied journalism. Chris's interest in writing about the strange and uncanny and Katey's interest in making objects and weird imagery made for a good combination. The Society of National Industry started when Katey, who was working a computer-heavy design job, found herself looking an outlet to do more things with her hands. We started doing little pop-up shows and eventually found our way to Etsy, which is now the main hub for our business.
Our work explores the intersection of the conceptual and the craft-driven. The mediums we are currently exploring include illustration, collage, various printmaking techniques, assemblage, and paper folding/cutwork, and we're always looking for new techniques and materials to bring into the fold. Conceptually, we are interested in the tension between different ideas of what the future will be like, geometry and color, and objects where form interacts with light. Together, we figure out new color palettes for lanterns, concepts for zines, and images for our print work.
All of our work is made by hand, by us. We try to maintain processes that are socially responsible and sustainable, which means buying environmentally friendly, sweatshop free supplies whenever possible, reusing materials, and using sustainable packaging. We hope that our pieces become long-living objects of love in the homes they end up in, and try to make things that are timeless, delicate but sturdy, and made to last.
Sometimes we also sell vintage at our sister shop, Decay Rate:
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We make paper goods, prints and other jazzy stuff with culty magic and cosmic chutzpa.
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This also means that it takes about 2 weeks for some items to ship. Please be patient. Take note that depending on the volume of orders we have, it may be a bit longer. The creation of much of our work is a labor-intensive process, but rest assured that we try and make and ship them in as timely a manner as possible.
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If you order more than one item (excluding print-only orders), you will receive a discount on shipping. You will be refunded the difference after your order has been completed.
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All domestic items are shipped with tracking information. If your package is lost, but the USPS has recorded that it was delivered, we unfortunately cannot offer a refund/exchange. Please contact us if this happens, and we will try our best to track down your package. (we're very good at it!) If your package is lost and you are outside the states, our ability to work with the postal service to find lost packages is extremely limited, since USPS does not track international packages. Please contact us if this applies to you, and we can help talk you through the steps you can take to contact your postal service/local post office. We do not offer refunds for lost international packages, so if you live somewhere with an unreliable postal system, it might be a good idea to purchase insurance or upgrade to a different carrier that does offer tracking.
We try to present our work in the most accurate way possible. Please read the listing carefully before you make your purchase, and please keep in mind that with our lights, color will look different at different times of day, when lit/not lit, etc. Since each piece is made to order, we do not offer refunds or exchanges unless your item is in some way defective.
If you have any specific questions concerning refunds/returns, contact us. Every situation is different and we want to honor that.
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*Can the lanterns be hung outside?
Sure, but since they're made of paper, you'll want to bring them in when it rains more than a drizzle or snows. Leaving them outside will significantly shorten their lifespan depending on your climate. But if you live in Arizona or Tunisia, leave 'em out!
*Are your lanterns safe?
Of course! We would never sell you anything that posed even the smallest bit of danger. The lights we use have been fire-tested for use on Christmas trees (aka dead, dry wood), and we went through a lengthy product testing phase as we developed these lanterns. They can be left on 24-7 if you feel so inclined. That being said, please practice common sense when you use our lanterns. Don't plug them into shotty electrical outlets, don't hang them near open flames, don't use the extendable plugs to plug in high-voltage electrical items, etc.
*How long do they last?
That depends on how long you choose to plug them in. As mentioned above, it is perfectly safe to leave them plugged in all day, every day, but doing so will reduce the lifespan of your lights. If you have them on for a few hours each day, and turn them off when you go to bed, they can last for years. And, if they do die, you've got options (see next Q)
*What happens if my lights burn out?
If your lights breathe their last breath and go out for good, we are happy to sell you a replacement (between $5-$10, depending on the garland length). You can then pop the lanterns off of the dead strand and put them on the new strand. If your lights die, please send us a message - oftentimes replacing a fuse will make them work again, and we can walk you through that process.
*I live in Europe/Africa/Asia. Can I plug your lanterns straight into the wall?
NOPE. Please read below:
As mentioned in each listing, our lighting is made for the outlets/electrical systems used throughout most of the Western Hemisphere. If you aren't in this region, you will likely need an adapter and/or convertor to plug them in. You may need one or the other, or both, depending on the electrical system in use in your country. If you are in Europe, Asia, or Australia, chances are you will need a device that converts current as well as adapts the plug, as the voltage used in these regions is higher than the voltage used in North America. There are lots of power converters that do both, so look for those. For more info on the different electrical systems used around the world, please visit this link: http://wikitravel.org/en/Electrical_systems
This information is provided here, in every listing, and in the email you receive when you place an order. If you have any questions regarding plugs, adapters, transformers/converters, voltage, etc, please message us and we'll help you out. We cannot offer returns or exchanges based on misunderstandings about electrical systems/plugs, because we provide this info to you like 5 million times, so please make sure you follow these instructions.
Several of our items are made from recycled or repurposed materials, are hand painted or drawn. Everything is hand-assembled. Because of this, there are subtle differences in appearance between listing and reality. These differences are small enough to go unnoticed, but please take this into consideration when purchasing anyway. We like to think of it as a bonus/surprise, and invite you to do the same.
Everything can be customized and altered to your liking. If you have any modifications in mind, please message us! We'll do our best to make it happen.
For wholesale inquiries, please email us at society.national.industry [!at] gmail.com or check us out on Etsy Wholesale.
We also occasionally sell vintage clothing at our sister Etsy shop, Decay Rate.


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Done Deals: Venture Capitalists Tell Their Stories Hardcover – September, 2000
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Where is the industry going? Again, no real insights here...
As someone stated earlier, if I wanted a historical perspective on the VC industry or a who's who in the industry, there are many, many sources on the internet for this information.
Try Ruth Ann Quindlan's book for better insights into the decision making that goes into dealmaking.
The book begins with a very short summary of the growth of the VC industry after WWII and then presents the VCs in five groups. It begins with the "Fast Forward" or the hot Internet and computer based VCs. Then come the "Beginnings" - the group after WWII that built the industry. A contrast is made with the next two groups, the East Coast versus the West Coast VCs. Finally, a group is presented in Visions.
Each of the VCs is presented with a little drawing in the WSJ style. I think this book is worthwhile just to get to know some of the big names, where they work - or used to work (there have been some changes since 2000) - and what projects these firms and people did. It can help in building professional associations let alone dinner conversation.
Is it a must read? I don't think so. However, if you are interested in the venture capital industry I think this would be a very good way to get some understanding of the terrain the industry has occupied and who some of the movers and shakers are (and were).
Organized into five parts (Fast Forward, Beginnings, West Coast, East Coast and Visions), the book examines the industry's humble beginnings to its extraordinary present (ok, very very recent past and hopefully a recent future). For a non-US reader such as myself, it also contains a priceless critique on the differences between West Coast and East Coast investing, which is unique because you'll recognize that a relatively nascent industry such as VC can sport widely varying investment philosophies as well. As investment spreads out to Europe, Australia and China, this becomes even more useful.
The book packs info about the hottest deals we had heard about - from Yahoo to www.Amazon.com - which makes for a gripping read in of itself. But beyond that, there are invaluable insights and discussions at length about how the VCs set up their partnerships and hand pick top management teams. Much better than reading a "VC 101" text book because it presents a hands-on glimpse at the industry's past and future from the veterans' point of view.Read more ›
Most Recent Customer Reviews
These interviews are really good insights into the people and the flavor of their firms. Some better than others, but they help you understand how firms have evolved differently. Read morePublished on May 13, 2009 by W. Danco
I opened this book with anticipation that I would be presented with an insightful examination of how the greats of the venture capital world worked with thier investments. Read morePublished on May 21, 2002
As a VC myself, I found this book to be very inspirational. What struck me as a common theme among the great VCs was that there was a sense of vision and purpose. Read morePublished on February 10, 2001 by James Altucher
I was disappointed with this book. Rather than a behind the scenes look into the strategy and excitement of today's dealmaking, it is a look into the past (poorly edited)of several... Read morePublished on January 6, 2001 by jason tomms
The stories of the pioneers of the industry were captivating and showed the "pure" spirit of the early VC world. Read morePublished on December 27, 2000 by Henry Ligot
you can find the information found in this book via the internet... the only thing i found this book good for is to convince the obvious: venture capital business is big... Read morePublished on November 28, 2000
As the Dot Coms become Dot Gones...its hilariously obvious that the modern VC is the equivalent of the Junk Bond Trader of the 80's. Read morePublished on November 7, 2000


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Updated Apr 24, 2015 - 8:06 pm
Graduate student tries out violin solo on pair of elephants
University of Wisconsin graduate student Eleanor Bartsch went searching high and low earlier this month for a genuine audience she could test her violin rendition of Bach's 'Concerto for Two Violins' on before a performance at the Circus World Museum in Baraboo, Wisc.
She settled on two elephants — 44 and 45-year-old Kelly and Viola — and began to play.
As it turns out, they were huge fans of Bach — swinging to and fro to the sounds of Bartsch's violin.
"I had no idea this would be the response," Bartsch said to the Baraboo News Republic.
And according to their trainer, Chip Arthurs, the music choice was a bit of change from the normal rock lyrics of Lynard Skynard.
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Global Warming May Change The Way Your French Wine Tastes
CREDIT: AP Photo/Bob Edme
If life is too short to drink bad wine, then climate change is messing with our options.
Rising temperatures associated with human-caused climate change are pushing grape harvesting in France earlier than growers have experienced in centuries, possibly changing wine quality for years to come, according to a new study in Nature Climate Change. "We don't need to talk about how climate change will affect wine in the future, we can see that it's affecting it right now," said Benjamin Cook, lead author and a climate scientist at Columbia University's Lamont-Doherty Earth Observatory.
The study published Monday comes as grapes, one of the most valuable cash crops in the world, have been at the forefront of climate change worries. That's because the caliber of a wine bottle is the sum of complicated environmental factors — what vintners call terroir — at play during grape growth. Terroir and grapes are sensitive, so if rain or temperature patterns change, grapes may grow too slow or not enough, producing undesirable sugar levels that produce low alcohol content. On the other hand, the weather can also induce quicker growth, which tends to improve grapes' sugar content, increase alcohol levels, and reduce acidity.
For more than 30 years now, wine grape harvest in France has happened on average two weeks earlier than it has in the past 400 years, all without the aid of a drought, according to the study. And while an early harvest is generally associated with higher wine quality, researchers say French viticulture has unprecedented growing conditions that may exert unknown tipping points in the future. "One of the things that we noticed is that before about 1980, to get an early harvest, or to get a summer hot enough to get an early harvest, you needed a drought," Cook told ThinkProgress. "After 1980, because of climate change, it can get hot enough for an early harvest without a drought."
CREDIT: AP Photo/Bob Edme
To reach their conclusions, Cook and Harvard biologist Elizabeth Wolkovich analyzed data from the last four centuries. They had wine harvest data from across France, including those from major wine growing regions of Bordeaux and Burgundy. They also had independent sources of climate information, including tree-ring studies and historical documents like trade archives, church documents, and local weather observations. "So what we were able to do is look at climate and wine over a much longer time period than people have typically done and [see] how exceptional the most recent decades are compared to the last 400 years of climate and wine variability," Cook said.
The most dramatic case of an early wine harvest happened in 2003, following a European heat wave that in France killed more than 15,000 people. Harvest that year happened in August, about a month early, said Cook, adding this was the earliest harvest recorded since the 1600s. "You might expect that with such an early harvest you will really get good wine. But if you look at the wine quality for that particular year, there is nothing really exceptional."
Jimena Rábago, a viticultural agronomist, doesn't seem surprised. In a phone interview, she said not all grapes benefit from an early harvest. "For the white [grapes] an early harvest is fine because white grapes don't need to develop flavors, aromas or colors in the skin," said Rábago, who works for prestigious vineyards in the ballooning wine industry of Baja California, Mexico. "Red grapes do."
France could thus experience different benefits and costs depending on the region. In Burgundy, for instance, 61 percent of wine produced is white, while 30 percent is red. But in Bordeaux, the world's most popular wine region, close to 90 percent of its wine production is red, according to the Wine Cellar Insider.
"The bad news is that if we keep warming the globe we will reach a tipping point," Wolkovich said in a statement. "The trend, in general, is that earlier harvests lead to higher-quality wine, but you can connect the dots here … we have several data points that tell us there is a threshold we will probably cross in the future where higher temperatures will not produce higher quality."
CREDIT: AP Photo/Bob Edme
The threshold remains unclear for researchers, but in late 2015 Euromonitor International reported that French wine has been suffering from poor crops already. "Disastrous" climatic conditions caused the grape harvest to be limited in 2013, according to the report, affecting wine volume in 2014, creating low stocks and higher prices. Production has recuperated since then, however.
Still, climate change is a comprehensive problem that extends beyond French borders and needs answers that appropriate local conditions, Rábago explained. "Some areas will have more water, others will have less," she said, pointing to just one example of a problem climate change brings. In California's Napa Valley and Baja California, Rábago said, drought seems to the norm while in Bordeaux — on top of higher temperatures — it may be varying humidity. In response, vineyards need to adapt to the current effects of global warming. One way to do so is by changing soil composition so that it holds more — or less — water, or by creating weather resisting grapes. "That implies changing how we plant vineyards," Rábago said in Spanish, "but also having less of a carbon footprint by moving away from tractor and pesticide use."
As impacts of global warming have accelerated in recent years, the $200 billion wine industry has responded, though. In Australia, winemakers are moving south to the island of Tasmania, Reuters reported. In Chile, the world's fourth-largest wine exporter, vineyards are moving to cooler, wetter climates farther south. Others are moving their production uphill or changing the type of vines they grow. In England, for example, some have planted "champagne" vineyards more common in southern, milder climes. But while appropriating new "terroir" may be a new opportunity, a massive move of vineyards could encroach on wildlife. According to a 2013 study published in the Proceedings of the National Academy of Sciences, areas that could become prime for viticulture in the United States or China house endangered animals like bears.
What's more, climate change may affect wine flavors through factors that have nothing to do with the grapes and vineyards can't control. Scientists are now reporting a shift in cork trees, the source of wine's often overlooked companion that regulates the oxygen intake that makes wine evolve over time. In the past two decades, cork bark has become thinner, according to a 2014 study. Researchers said this lower quality cork tree likely stems from a warming weather and increased exposure to ultraviolet light brought on by climate change, which in turn affects tree chemistry.
"Our studies and other studies are really just starting to [show] how climate is really affecting these vineyards and the wine grapes and wine in general," said Cook. "There's still a lot we don't know and a lot of details that we need to start working out.
Bryan Dewan contributed reporting to this article.


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Hi there i'm trying to output custom field values in my meta's but instead of getting the custom field name i get the value.
The code im using is: %%title%% %%cf_city%%
output: Elysium 674
the number is suppose to correspond to the city, i would like to use some more of my field but have the same problem ie, age, sex, language.
Im using a custom theme, any help would be appreciated.


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Will smart traders/investors continue buying now that company is showing the world they are serious about this business? Looking for new highs this month!
<<...now that company is showing the world they are serious about this busines..>>Not that I disagree with you but which breaking news are you talking about? The hiring of Ken Ord? That is the only news other than the news of the frivilous lawsuit by the 24 retards.
I can vouch for the 24 retards. The information given to potential medical students included that at the cumulation of their training they will be fully prepared and qualified to take the certified medical assistant exam. Seems like the effects of LAX management has turned shareholders into the retards. As I have said before in previous postings this is not the last or most serious suit to be served.
ithink some of these funds should sue the 24 students if their suit is foun baseless for actin irresponibly


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Hotel St. Pierre, Ahr - Middle Rhine (region)
- Free WiFi and free parking
Main amenities
- 19 guestrooms
- Breakfast available
- Room service
- Area shuttle
- Daily housekeeping
- Garden
- Front desk safe
- Laundry service
- Hair salon
- Multilingual staff
- Free newspapers in the lobby
- Luggage storage
What's around
- Wiedtalbad (6.6 mi / 10.7 km)
- Neuerburg Castle Ruins (9.2 mi / 14.8 km)
- Neuwied Castle (10.2 mi / 16.4 km)
- Oil Mill (10.5 mi / 16.8 km)
- Deichwelle Neuwied (10.5 mi / 17 km)
For families
- Rollaway/extra beds available
- Private bathroom
- Free toiletries
- Garden
- Daily housekeeping
- Laundry facilities
Hotel St. Pierre, Ahr - Middle Rhine (region)
Hotel Info: 866-539-8117from $58
- Double Room Single Use, Smoking, Garden View
- Double Room, Non Smoking, Garden View
- Family-"Sweet" Single use
- Family-"Sweet" Single use
- Double Room Single Use, Non Smoking (Sunny Side)
- Double Room
- Double Room Single Use, Non Smoking, Garden View
- Standard Apartment
- Double Room Single Occupancy Fair Rate
- Double Room Fair Rate
- Double Room Single Use
- Family-"Sweet" Double Use
- Double Room, Non Smoking (Sunny Side)
- Double Room, Smoking, Garden View
- Apartment Fair Rate
- Family-"Sweet" for 3 persons
Also popular with travelers from the USA
At a glance
Key facts
Hotel size
- This hotel has 19 rooms
- This hotel is arranged over 2 floors
- Check-in time 3 PM-9 PM
- Check-out time is noon
Required at check in
- Credit card or cash deposit required
- Government-issued photo ID required
Travelling with others
- Pets allowed (dogs only) *
- Specific rooms only *
Extra people
- Roll-away beds available, charges may apply*
- Free WiFi in public areas
- Free WiFi in rooms
- Free self parking
- Area shuttle *
Other information
- Resort fee included
Nearby Three Star Ahr - Middle Rhine (region) hotels
In the hotel
- Breakfast (surcharge)
- Room service (during limited hours)
- Bicycle rentals on site
- Hiking/biking trails nearby
- Tours/ticket assistance
- Dry cleaning/laundry service
- Laundry facilities
- Hair salon
- Free newspapers in lobby
- Luggage storage
- Multilingual staff
- Number of buildings/towers - 1
- Safe-deposit box at front desk
- Garden
In the room
- Minibar
- Iron/ironing board (on request)
- Pillow menu
- Private bathroom
- Shower only
- Free toiletries
- Hair dryer
- Flat-screen TV
- Digital TV channels
- Desk
- Free newspaper
- Free WiFi
- Phone
- Daily housekeeping
- In-room safe (laptop compatible)
Top Ahr - Middle Rhine (region) hotels
Recently reviewed hotels in Ahr - Middle Rhine (region)
- Hotel Haus HindenburgFrom
"Quite impressed with the hotel and the room! Very close to the Jewish cemetery, which we specifically came for to visit family. The evening's storm made the WiFi inaccessible in…"Jun 9, 2016
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"The Hotel is outside of town (you need a car) in a Park setting, high on top of a hill(great views) the rooms are nicely furnished but ours was VERY small and there was no Tee/…"May 25, 2016
- Hotel zum AdlerFrom
"Friendly staff, Nice hotel. Good breakfast buffet. Would stay there again."May 20, 2016
- Park Hotel Bad GodesbergFrom
"The hotel has an excellent location, in front of a park and one block away from the subway station, which makes it very convenient for a business trip."May 19, 2016
Nearby hotels
Hotel St. Pierre, Ahr - Middle Rhine (region)'s small print
Also known as
- Hotel St. Pierre Bad Hoenningen
- St. Pierre Bad Hoenningen
Pet-friendly rooms can be requested by contacting the property at the number on the booking confirmation.
Mandatory fees
The charges below are included in the total price displayed:
- Resort fee
Optional extras
Rollaway beds are available for an additional charge
Breakfast is offered for an extra charge of EUR 6 per person (approximately)
Cribs/Infant beds are available for EUR 30 per night
Pets are allowed for an extra charge of EUR 5 per pet, per night
Area shuttle service is offered for an extra charge
We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.
Recent reviews
Good 3.8 /5 from 18 reviews
Stayed a few nights to spectate the 24 Hours of Nurburgring race, which is about an hour away by car. Hotel St Pierre was one of the few hotels available within this distance when I booked it. Check-in was quick and easy and breakfast was inexpensive and great. Clean rooms, nice new bathrooms, but the mattresses and pillows are a bit hard and thin. Still a great experience! Most importantly, the room was quiet!
This hotel was a very tired place in a terrible town. There was very little choice in restaurants in the vicinity and most businesses had closed their doors permanently. The entire town had the feeling og being abandoned. The price of the hotel is expensive considering what you get and the location. Much, much nicer towns in nearby Klotten and Cochem.
Marcus and staff were the best---computer help----history lesson---dining options---could not have been better----Thanks
Stayed en route down the Rhine. Staff friendly and helpful, good breakfast selection, good location
The St Pierre was well located. Clean, comfortable and functional with a great breakfast
Is the description of this hotel not correct? Tell us


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OK, I think I've heard something about that last one, but the fact is that Tales of the Cocktail is a great place to learn new, if arguably trivial, facts about your favorite drinks, as well as get a glimpse of the latest trends in mixology and taste the newest products, often months before you see them on the shelf of your local package store.
For instance, the recent explosion of Italian amaros (amari?) — the bitter liqueur made by Averno, Cynar, Fernet and, one of my favorites, Montenegro — was so well represented at Tales that a seminar on the subject had filled before I could sign up. Also, the Italian and French love of aperitifs, such as Lillet, Campari and Aperol, a relative newcomer here, was also duly noted. Pisco, the mild Peruvian brandy, continues to make inroads in the national cocktail scene, while I didn't see as much attention paid to "white dog," the un-aged bourbon or "silver whiskey" as it is sometimes called, as I had two years ago. Both of those are good trends as far as I'm concerned.
Another trend I noticed is a perennial, namely, that rum is the Roger Dangerfield of spirits (for you millennials out there, that means it don't get no respect). I've been hearing predictions for years no at Tales that premium rum will soon enjoy the popular renaissance that high-end vodkas and tequilas have enjoyed, but so far it hasn't happened. This year, probably the best seminar I attended was a guided tasting by master spirit taster (how's that for a job?) Paul Pacult. The nearly 200 people who filled a ballroom at the Monteleone Hotel were each greeted by a placemat set with 14 1-oz pours of various rums made in the Caribbean, Central and South America of both sugar cane and molasses.
Pacult, the proprietor of the subscription-only Spirit Journal, is my favorite seminar leader at Tales, not just because he's typically animated and funny, but because he offers insightful tasting notes that have allowed me to better appreciate whatever it is I'm sampling. For instance, when you give your beverage an initial sniff, inhale deeply with with your mouth slightly open so the fumes can reach your taste buds. Believe it or not, there are master distillers who learn more from smelling their product than from tasting it.
Anyway, here are some of my tasting notes from the rum session:
* I was surprised by how smooth and caramelly the 10 Cane was, given that it's fairly cheap.
* Diplomatico Reserva Exclusiva, a new rum from Venezuela, is pleasantly reminiscent of vanilla frosting.
* Ron Abuelo 12, a Panamanian entry, was quite popular with the audience, but I thought it too coconutty. I don't like coconuts.
* Shellback Silver, a new light rum from Barbados, has a nice vanilla flavor. BUt don't look for it yet because it hasn't made it's way stateside yet.
* My personal favorites were the Zapaca 23-year-old from Guatemala , which was drier and more complex than most we tasted; Depaz Blue Cane, a rhum agricole from Martinique made from... you guessed it, that was surprisingly delicate; and the Banks 7, a blended rum for which the "7" doesn't indicate the age, but how many countries and islands are represented in the blend.
While at Tales, I bumped into Holeman & Finch barkeep Greg Best, who said the Banks 7 was the most interesting new product he tasted over the weekend. So, wouldn't you know it, this particular rum also hasn't made its way to Atlanta yet.
Speaking of local bartenders, I also ran into the celebrated Miles Macquarrie of Leon's Full Service and Kevin Bragg of 4th & Swift, who's coming off some bartending wins this year.
Every year, I hear complaints about how overly ginormous and industry-driven Tales has become, and it's true. When you have tasting rooms dedicated to Midori and Amaretto Disaronno, and pool parties centered around Jagermeister, you know that no self-respecting bartender put these events together.
And yet, it's relatively easy to sidestep the cheesy stuff — such as, say, yet another sweet tea-flavored vodka handed out in the street by swimsuit-clad pin-up girls — as seen above, while you keep yourself open to new discoveries. My own moment of surprise came at a VIP tasting (for which someone gifted us with tickets) where folks were pouring Johnnie Walker Blue and high-end cognacs. At one unassuming booth, I sampled something calledBalcones Texas Single Malt Whisky, a fruity, woody potion that has much of the complexity of a Scotch.
It's that kind of spirited serendipity that keeps me coming back to Tales. That and four days of free booze.
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Hotels in Marseille, France
Hotel search
Trending now in Marseille
- Most bookedRadisson Blu Hotel, Marseille Vieux Port
354 people looked at this hotel in the last hour
Most recent review
"From check-in to check out, the staff were friendly, helpful and spoke excellent English. Great rooms, a nice pool and pool bar and a great location looking out to the port."
A Traveller, Jun 2016, GB
269 people looked at this hotel in the last hour
Most recent review
"Although listed as modern and clean in my guide, it was a little tired and needs a little care - for example to shower/bath was not great - the bath panel had been kept in by mastic as it had become damp and swollen over the years. Spa bath a bit lame. Otherwise overall good. Good breakfasts and..."
A Traveller, May 2016, GB
260 people looked at this hotel in the last hour
Most recent review
"The hotel is well located near the port and the subway. It's been fully renovated and it's cozy."
A Traveller, May 2016, US
252 people looked at this hotel in the last hour
Most recent review
"We luckily got a last minut reservation. This hotel was ver convienient and the staff was great"
A Traveller, Jun 2016, US
251 people looked at this hotel in the last hour
Most recent review
"Very nice hotel trying hard to be a premium hotel without the price. Free minibar, and standalone shower were a welcome addition. Coffee machine its in hallway which can be cumbersome. Location close to train station and short walk to the old city."
A Traveller, Jun 2016, AU
239 people looked at this hotel in the last hour
Most recent review
"Very good service, friendly staf with good English skills. Good looking lobby, lounge bar and outdoor area. Very comfy beds. Nice shower gel. Small but clean and nice gym with sauna. Hotel is next to a natural lake where one can go for a run when it's not muddy outside."
A Traveller, Feb 2016, GB
223 people looked at this hotel in the last hour
Most recent review
"A very enjoyable stay in a good location. Being able to sit out on the balcony really added to the experience. Friendly and helpful staff with good service. As a solo traveller, I felt at ease and safe."
A Traveller, May 2016, GB
215 people looked at this hotel in the last hour
Most recent review
"Wonderful hotel with excellent grounds, staff, and rooms. The perfect place to relax and not worry about anything. Location in Aix is great, close to downtown but secluded enough to not hear or get bothered by any kind of noise."
A Traveller, Jun 2016, US
214 people looked at this hotel in the last hour
Most recent review
"Stayed overnight waiting for my friends to arrive from Stansted the next day so we could all travel to our holiday villa together. I really enjoyed my short stay - staff couldn't have been more helpful and I had a delicious salad in the restaurant and good breakfast in the morning. My room was ..."
A Traveller, Jun 2016, GB
172 people looked at this hotel in the last hour
Most recent review
"It's expensive but luxurious. The service is excellent and on the more formal side. View from the patio was spectacular."
A Traveller, Jun 2016, US
Map of Marseille hotels
- Calanques
- Museum of Civilizations in Europe and the Mediterranean
- Cassis Beach
- Prado Beach
- Palais des Sports de Marseille
- Cathedral la Major (Cathedral of Sainte-Marie-Majeure)
- Chateau d'If
- Timone Hospital
- Les Lecques Beach
- Palais Longchamps
- Sormiou de Calanque
- Parc Chanot Convention and Exhibition Center
- Marseille Opera House
- La Ciotat Beach
- Pharo Palace
- Iles du Frioul
- Calanque de Figuerolles
- Radiant City
- Place Castellane
- Bandol Beach
Best hotels in Marseille
If you are looking for Marseille hotels in a particular area, you can use the search feature at the top of the page to search by neighborhood, landmark, address or zip code, or you can search by using the built-in map feature. You can also browse hotels in Marseille by type, amenities, and star-rating so that you can find the best hotel. Currently, top rated hotels in Marseille are:
- Relais de la Magdeleine
- C2 hôtel
- Hotel 96
- InterContinental Marseille - Hotel Dieu
- Sofitel Marseille Vieux Port
The location of your Marseille hotel is important. If you are traveling to Marseille, &StateorCountry for business, you may want to consider getting a hotel close to the airport or near your meeting venue. By doing so, you can really cut down on transportation costs and time. You may also want to book a hotel that offers free wifi just in case you need to get some work done.
If you are traveling for vacation, figure out which attractions or landmarks you want to see and book a hotel that is within close proximity. Although hotels near attractions might cost a little more, you may find that spending those extra few dollars is worth the convenience. You can even find hotels that align with your interests. For example, if you are looking for a relaxing vacation, a spa hotel may be the perfect choice for you.
You'll also want to determine which type of accommodations will suit your needs before booking a hotel in Marseille. If you're traveling with the kiddos, a family friendly hotel will offer larger rooms and more sleeping arrangements. For those traveling for an extended period of time, booking a hotel suite with a kitchenette is a smart move and will feel a little more like home. If you are budget conscience and just need a place to rest your head, a hostel or motel may be all you need.
If you are looking to score the best discounts and deals, use the filter to sort by price from low to high. You can book a hotel in Marseille for as low as $21 per night. If you are looking to cut down on expenses, look for hotels that include free breakfast and parking. Some hotels even offer free shuttle service to and from nearby places. You can also sort by star rating, proximity, and guest rating.
Before you book, check out user reviews. Hotels.com has 19603 reviews in Marseille. We show reviews from Expedia and TripAdvisor so you know that you are reading genuine, reliable reviews. Be sure to download the Hotels.com app so you can book your reservations on the go, view amenities, and save the hotels you want to view and compare later.
Marseille travel guides
A Provence travel guide – dry sunlit hills, historic towns and dining at shaded outdoor tables
Holidays in Provence mean relaxed sunlit days and long warm evenings. Explore Roman towns, colourful...


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Richmond, VAUSA
August 20, 2014
BOMB and the Meetup site.
Advanced beginner.
I am relatively new to the area and have only ridden at Pocahontas.
Hello! My name is Jim and I enjoy mountain biking. I would like to meet other bikers and ride more.
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It is said that the average human has between 60,000 – 70,000 thoughts each day. Why not make them positive?
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