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The Russians invade a neighboring nation and annex new territory. The outraged Americans responds with financial sanctions and chest thumping. Moscow tips the conflict toward a boiling point by upping its military presence in Cuba, just a few hundred miles from Florida's borders. Nope, it's not 19 ... More >>
Local campaign strategist Michael Caputo likes to employ some fowl play in his election day tactics. In the mid-1990s, Caputo busted out his patent-pending tactic of using a man-in-a-chicken-suit-to-tail-opponents when he worked for Russian President Boris Yeltsin's campaign. Back when ... More >>
MiMo 2000
When Cuba's top students were sent to the Soviet Union, no one could have guessed they would change from revolutionaries to refugees.

subset: commoncrawl


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226 results for "michael smith"
Matthew Berry's sleepers, busts from his Week 5 fantasy football ...Matthew Berry
Matthew Berry talks about some of the happenings in his favorite, most competitive league, as he reveals his loves and hates for Week 5.Story | Conversation | October 04, 2012
ESPN Fantasy Football deep sleepers: Kellen Davis of Chicago Bear...Christopher Harris
Christopher Harris lists 10 players who could emerge at some point this season as fantasy contributors despite a lack of experience or a clear role entering the season.Story | Conversation | August 22, 2012
Around the NFC SouthPat Yasinskas
Let's take a run through the afternoon headlines from around the NFC South. Here's an off-beat story. Before the Louisiana House passed a law to continue a tax break for the New Orleans Hornets, one lawmaker proposed an amendment that would have r...Blog | May 01, 2012
New York Jets Mark Sanchez and wide receivers Santonio Holmes, Pl...Christopher Harris
Christopher Harris looks at the historical probability that Mark Sanchez can improve his accuracy and that his wide receivers can thrive as fantasy weapons.Story | Conversation | August 19, 2011
Ty Law tells Jets how to defend SteelersTim Graham
Former New England Patriots and New York Jets cornerback Ty Law sat down with ESPN reporter Michael Smith to preview Sunday's championship games. Law gave extra emphasis to the Jets and Pittsburgh Steelers matchup because he and Revis graduated fr...Blog | January 20, 2011
Video: Jets at Steelers pregame reportTim Graham
ESPN reporter Michael Smith delivers pregame insights from Heinz Field, where the New York Jets will play the Pittsburgh Steelers at 4:15 p.m. Smith discusses Jets quarterback Mark Sanchez's mindset entering the game and the impact absent safety T...Blog | December 19, 2010
Henne, Jets DBs in Friday night spotlightTim Graham
"NFL Live" host Michael Smith and analysts Marcellus Wiley and Eric Allen broke down the matchups of Friday night's four preseason games, including the New York Jets versus Washington Redskins at the Meadowlands and the Miami Dolphins versus Atlanta ...Blog | August 27, 2010
Eric Mangini agrees to deal to coach Cleveland Browns
The Cleveland Browns will hire former Jets head coach Eric Mangini as their new head coach, a source told ESPN.Story | Conversation | January 07, 2009
Woody gives Jets four former first-round draft picks on O-lineMichael Smith
Having already solidified the left side of their offensive line with the addition of Alan Faneca, the Jets have now bolstered their right side, agreeing to terms with former Pats and Lions lineman Damien Woody to play right tackle according to sources.Story | Conversation | March 03, 2008
Bengals can't work out deal with Robertson so trade on holdMichael Smith
Sources say the Bengals have acquired Dewayne Robertson from the Jets.Story | Conversation | March 02, 2008
Faneca, Jets tentatively agree to four-year, $32M deal
The New York Jets and guard Alan Faneca have agreed in principle to a four-year, $32 million deal that includes roughly $23 million in guarantees, ESPN's Michael Smith reports.Story | Conversation | February 29, 2008
A few reasons we should let the spy game dieMichael Smith
When Bill Belichick and Eric Mangini exchange halfhearted pleasantries as they leave Gillette Stadium's field Sunday, let's hope we can close the book on the spy episode, writes Michael Smith.Story | Conversation | December 15, 2007
Bears swap Jones, pick for Jets draft pickMichael Smith
Tthe Bears have agreed to trade RB Thomas Jones and a 2007 second-round pick to the Jets for a 2007 second-round pick.Story | Conversation | March 05, 2007
Belichick has 7-2 record against MVPsMichael Smith
There's nothing easy about stopping LT and the Chargers' offense, but if anyone can devise the game plan to do it, it's Bill Belichick, writes Michael Smith.Story | Conversation | January 07, 2007
Power Rankings: Chargers finish on top
This week's Power Rankings show how far off our preseason rankings were.Power Ranking | Conversation | January 02, 2007
Patriots won't intimidate Mangini's JetsMichael Smith
Expect a cold reception when the Jets and Eric Mangini visit New England, Michael Smith writes. • '06 predictions: How did we pick 'em?Story | Conversation | December 31, 2006


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D H MacLennan
University of Toronto, Toronto, Ontario, Canada
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Exome analysis identifies Brody myopathy in a family diagnosed with malignant hyperthermia susceptibility
Nyamkhishig Sambuughin
Elena Zvaritch
Natasha Kraeva
Olga Sizova
Erica Sivak
Kelley Dickson
Margaret Weglinski
John Capacchione
Sheila Muldoon
Sheila Riazi
Susan Hamilton
Barbara Brandom
, David H. MacLennan
[Show abstract]
[Hide abstract]
Whole exome sequencing (WES) was used to determine the primary cause of muscle disorder in a family diagnosed with a mild, undetermined myopathy and malignant hyperthermia (MH) susceptibility (MHS). WES revealed the compound heterozygous mutations, p.Ile235Asn and p.Glu982Lys, in ATP2A1, encoding the sarco(endo)plasmic reticulum Ca2+ ATPase type 1 (SERCA1), a calcium pump, expressed in fast-twitch muscles. Recessive mutations in ATP2A1 are known to cause Brody myopathy, a rare muscle disorder characterized by exercise-induced impairment of muscle relaxation and stiffness. Analyses of affected muscles showed the absence of SERCA1, but SERCA2 upregulation in slow and fast myofibers, suggesting a compensatory mechanism that partially restores the diminished Ca2+ transport in Brody myopathy. This compensatory adaptation to the lack of SERCA1 Ca2+ pumping activity within the muscle explains, in part, the mild course of disease in our patient. Diagnosis of MHS in this family was secondary to a loss of SERCA1 due to disease-associated mutations. Although there are obvious differences in clinical expression and molecular mechanisms between MH and Brody myopathy, a feature common to both conditions is elevated myoplasmic Ca2+ content. Prolonged intracellular Ca2+ elevation is likely to have led to MHS diagnosis in vitro and postoperative MH-like symptoms in Brody patient.
Molecular Genetics & Genomic Medicine. 06/2014;
Type 2 Ryanodine Receptor Domain A Contains a Unique and Dynamic α-helix that Transitions to a β-strand in a Mutant Linked with a Heritable Cardiomyopathy.
Fernando J Amador
Lynn Kimlicka
Peter B Stathopulos
Geneviève M C Gasmi-Seabrook
, David H Maclennan,
Filip Van Petegem
Mitsuhiko Ikura
[Show abstract]
[Hide abstract]
Ryanodine receptors (RyRs) are large tetrameric calcium (Ca(2+)) release channels found on the sarcoplasmic reticulum (SR) which respond to dihydropyridine receptor activity through a direct conformational interaction and/or indirect Ca(2+) sensitivity, propagating SR luminal Ca(2+) release in the process of excitation-contraction coupling. There are three human RyR subtypes, and several debilitating diseases are linked to heritable mutations in RyR1 and RyR2 including malignant hypothermia (MH), central core disease (CCD), catecholaminergic polymorphic ventricular tachycardia (CPVT) and arrhythmogenic right ventricular dysplasia type 2 (ARVD2). Despite the recent appreciation that many disease-associated mutations within the N-terminal RyRABC domains (i.e. residues 1-559) are located in the putative interfaces mediating tetrameric channel assembly, the precise structural and dynamical consequences of the mutations are not well-understood. We used solution nuclear magnetic resonance (NMR) spectroscopy and x-ray crystallography to examine the effect of ARVD2- (i.e. R176Q) and CPVT- [i.e. P164S, R169Q and delta exon 3 (Δ3)] associated mutations on the structure and dynamics of RyR2A. Our solution NMR data exposed a mobile α-helix, unique to type 2; further, this α2-helix rescues the β-strand lost in RyR2A Δ3, but remains dynamic in the hot-spot (HS)-loop P164S, R169Q and R176Q mutant proteins. Docking of our x-ray crystal-NMR hybrid structure into the RyR1 cryo-electron microscopy map revealed that this RyR2A α2-helix is in close proximity to dense "columns" projecting toward the channel pore. This is in contrast to the HS-loop mutations that cause structural changes largely localized to the intersubunit interface between adjacent ABC domains. Taken together, our data suggest that ARVD2 and CPVT mutations have at least two distinct structural consequences linked to channel dysfunction: perturbation of the HS-loop (i.e. domain A):domain B inter-subunit interface, and disruption of the communication between the N-terminal region and the channel domain.
Journal of Molecular Biology 08/2013;
· 3.91 Impact Factor
CASQ1 gene is an unlikely candidate for malignant hyperthermia susceptibility in the North American population.
Natalia Kraeva
Elena Zvaritch
Wanda Frodis
Olga Sizova
Alexander Kraev
, David H MacLennan,
Sheila Riazi
[Show abstract]
[Hide abstract]
Malignant hyperthermia (MH, MIM# 145600) is a complex pharmacogenetic disorder that is manifested in predisposed individuals as a potentially lethal reaction to volatile anesthetics and depolarizing muscle relaxants. Studies of CASQ1-null mice have shown that CASQ1, encoding calsequestrin 1, the major Ca2+ binding protein in the lumen of the sarcoplasmic reticulum, is a candidate gene for MH in mice. The aim of this study was to establish whether the CASQ1 gene is associated with MH in the North American population. The entire coding region of CASQ1 in 75 unrelated patients diagnosed by caffeine-halothane contracture test as MH susceptible (MHS) was analyzed by DNA sequencing. Subsequently, three groups of unrelated individuals (130 MHS, 100 MH negative, and 192 normal controls) were genotyped for a variant that was identified by sequencing. Levels of CASQ1 expression in the muscle from unrelated MHS and MH negative individuals were estimated by Western blotting. Screening of the entire coding sequence of the CASQ1 gene in 75 MHS patients revealed a single variant c.260T > C (p.Met87Thr) in exon 1. This variant is unlikely to be pathogenic, because its allele frequency in the MHS group was not significantly different from that of controls. There was also no difference in calsequestrin 1 protein levels between muscle samples from MHS and controls, including those carrying the p.Met87Thr variant. This study revealed a low level of protein coding sequence variability within the human CASQ1 gene, indicating that CASQ1 is not a major MHS locus in the North American population.
Anesthesiology 02/2013; 118(2):344-9.
· 5.16 Impact Factor
Novel excitation-contraction uncoupled RYR1 mutations in patients with central core disease.
Natalia Kraeva
Elena Zvaritch
Ann E Rossi
Sanjeewa A Goonasekera
Hilal Zaid
Wanda Frodis
Alexander Kraev
Robert T Dirksen
, David H Maclennan,
Sheila Riazi
[Show abstract]
[Hide abstract]
Central core disease, one of the most common congenital myopathies in humans, has been linked to mutations in the RYR1 gene encoding the Ca(2+) release channel of the sarcoplasmic reticulum (RyR1). Functional analyses showed that disease-associated RYR1 mutations led to impairment of skeletal muscle Ca(2+) homeostasis; however, thorough understanding of the molecular mechanisms underlying central core disease and other RyR1-related conditions is still lacking. We screened by sequencing the complete RYR1 transcripts in ten unrelated patients with central core disease and identified five novel, p.M4640R, p.L4647P, p.F4808L, p.D4918N and p.F4941C, and four recurrent mutations. Four of the novel mutations involved amino acid residues that were positioned within putative transmembrane segments of the RyR1. The pathogenic character of the identified mutations was demonstrated by bioinformatic analyses and by the in vitro functional studies in HEK293 cells and RYR1-null (dyspedic) myotubes. Characterization of Ca(2+) channel properties of RyR1s carrying one recurrent and two novel mutations upholds the view that diminished intracellular Ca(2+) release caused by impaired Ca(2+) channel gating and/or Ca(2+) permeability is an important component of central core disease etiology. This study expands the list of functionally characterized disease-associated RyR1 mutations, increasing the value of genetic diagnosis for RyR1-related disorders.
Neuromuscular Disorders 11/2012;
· 3.46 Impact Factor
Available from: Thomas Kislinger
Structural determination of the phosphorylation domain of the ryanodine receptor.
Parveen Sharma
Noboru Ishiyama
Usha Nair
Wenping Li
Aiping Dong
Tetsuaki Miyake
Aaron Wilson
Tim Ryan
, David H Maclennan,
Thomas Kislinger
Mitsuhiko Ikura
Sirano Dhe-Paganon
Anthony O Gramolini
[Show abstract]
[Hide abstract]
The ryanodine receptor (RyR) is a large, homotetrameric sarcoplasmic reticulum membrane protein that is essential for Ca(2+) cycling in both skeletal and cardiac muscle. Genetic mutations in RyR1 are associated with severe conditions including malignant hyperthermia (MH) and central core disease. One phosphorylation site (Ser 2843) has been identified in a segment of RyR1 flanked by two RyR motifs, which are found exclusively in all RyR isoforms as closely associated tandem (or paired) motifs, and are named after the protein itself. These motifs also contain six known MH mutations. In this study, we designed, expressed and purified the tandem RyR motifs, and show that this domain contains a putative binding site for the Ca(2+) /calmodulin-dependent protein kinase β isoform. We present a 2.2 Å resolution crystal structure of the RyR domain revealing a two-fold, symmetric, extended four-helix bundle stabilized by a β sheet. Using mathematical modelling, we fit our crystal structure within a tetrameric electron microscopy (EM) structure of native RyR1, and propose that this domain is localized in the RyR clamp region, which is absent in its cousin protein inositol 1,4,5-trisphosphate receptor. DATABASE: The crystal structure of the RyR1 phosphorylation domain (amino acid residues 2734-2940) has been submitted to the Protein Data Bank under accession number 3RQR. STRUCTURED DIGITAL ABSTRACT: RyR1 C3 physically interacts with CaMKIIβ by pull down (View interaction) RyR1 C3 binds to CaMKIIβ by pull down (View interaction) CaMKIIβ physically interacts with RyR1 C3 by anti tag coimmunoprecipitation (View Interaction: 1, 2).
FEBS Journal 08/2012; 279(20):3952-64.
· 4.25 Impact Factor
Available from: Kevin Fogarty
Type 1 ryanodine receptor knock-in mutation causing central core disease of skeletal muscle also displays a neuronal phenotype.
Valerie De Crescenzo
Kevin E Fogarty
Jason J Lefkowitz
Karl D Bellve
Elena Zvaritch
, David H MacLennan,
John V Walsh
[Show abstract]
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The type 1 ryanodine receptor (RyR1) is expressed widely in the brain, with high levels in the cerebellum, hippocampus, and hypothalamus. We have shown that L-type Ca(2+) channels in terminals of hypothalamic magnocellular neurons are coupled to RyRs, as they are in skeletal muscle, allowing voltage-induced Ca(2+) release (VICaR) from internal Ca(2+) stores without Ca(2+) influx. Here we demonstrate that RyR1 plays a role in VICaR in nerve terminals. Furthermore, in heterozygotes from the Ryr1(I4895T/WT) (IT/+) mouse line, carrying a knock-in mutation corresponding to one that causes a severe form of human central core disease, VICaR is absent, demonstrating that type 1 RyR mediates VICaR and that these mice have a neuronal phenotype. The absence of VICaR was shown in two ways: first, depolarization in the absence of Ca(2+) influx elicited Ca(2+)syntillas (scintilla, spark, in a nerve terminal, a SYNaptic structure) in WT, but not in mutant terminals; second, in the presence of extracellular Ca(2+), IT/+ terminals showed a twofold decrease in global Ca(2+) transients, with no change in plasmalemmal Ca(2+) current. From these studies we draw two conclusions: (i) RyR1 plays a role in VICaR in hypothalamic nerve terminals; and (ii) a neuronal alteration accompanies the myopathy in IT/+ mice, and, possibly in humans carrying the corresponding RyR1 mutation.
Proceedings of the National Academy of Sciences 12/2011; 109(2):610-5.
· 9.81 Impact Factor
Available from: Elena I. Zvaritch
Response to "Malignant Hyperthermia - human stress triggering" in reference to original article "Mechanistic models for muscle diseases and disorders originating in the sarcoplasmic reticulum" http://dx.doi.org/10.1016/j.bbamcr.2010.11.009.
David H Maclennan,
Elena Zvaritch
Biochimica et Biophysica Acta 08/2011; 1813(12):2193-4.
· 4.66 Impact Factor
Enhanced Ca2+ transport and muscle relaxation in skeletal muscle from sarcolipin-null mice.
A Russell Tupling
Eric Bombardier
Subash C Gupta
Dawar Hussain
Chris Vigna
Darin Bloemberg
Joe Quadrilatero
Maria G Trivieri
Gopal J Babu
Peter H Backx
Muthu Periasamy
, David H MacLennan,
Anthony O Gramolini
[Show abstract]
[Hide abstract]
Sarcolipin (SLN) inhibits sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) pumps. To evaluate the physiological significance of SLN in skeletal muscle, we compared muscle contractility and SERCA activity between Sln-null and wild-type mice. SLN protein expression in wild-type mice was abundant in soleus and red gastrocnemius (RG), low in extensor digitorum longus (EDL), and absent from white gastrocnemius (WG). SERCA activity rates were increased in soleus and RG, but not in EDL or WG, from Sln-null muscles, compared with wild type. No differences were seen between wild-type and Sln-null EDL muscles in force-frequency curves or maximum rates of force development (+dF/dt). Maximum relaxation rates (-dF/dt) of EDL were higher in Sln-null than wild type across a range of submaximal stimulation frequencies, but not during a twitch or peak tetanic contraction. For soleus, no differences were seen between wild type and Sln-null in peak tetanic force or +dF/dt; however, force-frequency curves showed that peak force during a twitch and 10-Hz contraction was lower in Sln-null. Changes in the soleus force-frequency curve corresponded with faster rates of force relaxation at nearly all stimulation frequencies in Sln-null compared with wild type. Repeated tetanic stimulation of soleus caused increased (-dF/dt) in wild type, but not in Sln-null. No compensatory responses were detected in analysis of other Ca(2+) regulatory proteins using Western blotting and immunohistochemistry or myosin heavy chain expression using immunofluorescence. These results show that 1) SLN regulates Ca(2+)-ATPase activity thereby regulating contractile kinetics in at least some skeletal muscles, 2) the functional significance of SLN is graded to the endogenous SLN expression level, and 3) SLN inhibitory effects on SERCA function are relieved in response to repeated contractions thus enhancing relaxation rates.
AJP Cell Physiology 06/2011; 301(4):C841-9.
· 3.71 Impact Factor
Available from: Thomas Kislinger
Identification of novel ryanodine receptor 1 (RyR1) protein interaction with calcium homeostasis endoplasmic reticulum protein (CHERP).
Timothy Ryan
Parveen Sharma
Alex Ignatchenko
, David H MacLennan,
Thomas Kislinger
Anthony O Gramolini
[Show abstract]
[Hide abstract]
The ryanodine receptor type 1 (RyR1) is a homotetrameric Ca(2+) release channel located in the sarcoplasmic reticulum of skeletal muscle where it plays a role in the initiation of skeletal muscle contraction. A soluble, 6×-histidine affinity-tagged cytosolic fragment of RyR1 (amino acids 1-4243) was expressed in HEK-293 cells, and metal affinity chromatography under native conditions was used to purify the peptide together with interacting proteins. When analyzed by gel-free liquid chromatography mass spectrometry (LC-MS), 703 proteins were identified under all conditions. This group of proteins was filtered to identify putative RyR interacting proteins by removing those proteins found in only 1 RyR purification and proteins for which average spectral counts were enriched by less than 4-fold over control values. This resulted in 49 potential RyR1 interacting proteins, and 4 were selected for additional interaction studies: calcium homeostasis endoplasmic reticulum protein (CHERP), endoplasmic reticulum-Golgi intermediate compartment 53-kDa protein (LMAN1), T-complex protein, and phosphorylase kinase. Western blotting showed that only CHERP co-purified with affinity-tagged RyR1 and was eluted with imidazole. Immunofluorescence showed that endogenous CHERP co-localizes with endogenous RyR1 in the sarcoplasmic reticulum of rat soleus muscle. A combination of overexpression of RyR1 in HEK-293 cells with siRNA-mediated suppression of CHERP showed that CHERP affects Ca(2+) release from the ER via RyR1. Thus, we propose that CHERP is an RyR1 interacting protein that may be involved in the regulation of excitation-contraction coupling.
Journal of Biological Chemistry 03/2011; 286(19):17060-8.
· 4.65 Impact Factor
Available from: Kevin Nolan
Ryanodine receptor type 1 gene mutations found in the Canadian malignant hyperthermia population.
Natasha Kraeva
Sheila Riazi
Julian Loke
Wanda Frodis
Mary Lou Crossan
Kevin Nolan
Alexander Kraev
, David H Maclennan
[Show abstract]
[Hide abstract]
Malignant hyperthermia (MH) is an autosomal dominant pharmacogenetic disorder that is manifested on exposure of susceptible individuals to halogenated anesthetics or succinylcholine. Since MH is associated primarily with mutations in the ryanodine receptor type 1 (RYR1) gene, the purpose of this study was to determine the distribution and frequency of MH causative RyR1 mutations in the Canadian MH susceptible (MHS) population. In this study, we screened a representative cohort of 36 unrelated Canadian MHS individuals for RYR1 mutations by sequencing complete RYR1 transcripts and selected regions of CACNA1S transcripts. We then analyzed the correlation between caffeine-halothane contracture test (CHCT) results and RYR1 genotypes within MH families. Eighty-six percent of patients had at least one RyR1 mutation (31 out of 36), five of which were unrelated individuals who were double-variant carriers. Fifteen of the 27 mutations identified in RYR1 were novel. Eight novel mutations, involving highly conserved amino acid residues, were predicted to be causal. Two of the mutations co-segregated with the MHS phenotype within two large independent families (a total of 79 individuals). Fourteen percent of MHS individuals (five out of 36) carried neither RYR1 nor known CACNA1S mutations. The distribution and frequency of MH causative RyR1 mutations in the Canadian MHS population are close to those of European MHS populations. Novel mutations described in this study will contribute to the worldwide pool of MH-associated mutations in the RYR1 gene, ultimately increasing the value of MH genetic diagnostic testing.
Canadian Anaesthetists? Society Journal 03/2011; 58(6):504-13.
· 2.31 Impact Factor
Available from: Zoita Andronache
Muscle weakness in Ryr1I4895T/WT knock-in mice as a result of reduced ryanodine receptor Ca2+ ion permeation and release from the sarcoplasmic reticulum.
Ryan E Loy
Murat Orynbayev
Le Xu
Zoita Andronache
Simona Apostol
Elena Zvaritch
, David H MacLennan,
Gerhard Meissner
Werner Melzer
Robert T Dirksen
[Show abstract]
[Hide abstract]
The type 1 isoform of the ryanodine receptor (RYR1) is the Ca(2+) release channel of the sarcoplasmic reticulum (SR) that is activated during skeletal muscle excitation-contraction (EC) coupling. Mutations in the RYR1 gene cause several rare inherited skeletal muscle disorders, including malignant hyperthermia and central core disease (CCD). The human RYR1(I4898T) mutation is one of the most common CCD mutations. To elucidate the mechanism by which RYR1 function is altered by this mutation, we characterized in vivo muscle strength, EC coupling, SR Ca(2+) content, and RYR1 Ca(2+) release channel function using adult heterozygous Ryr1(I4895T/+) knock-in mice (IT/+). Compared with age-matched wild-type (WT) mice, IT/+ mice exhibited significantly reduced upper body and grip strength. In spite of normal total SR Ca(2+) content, both electrically evoked and 4-chloro-m-cresol-induced Ca(2+) release were significantly reduced and slowed in single intact flexor digitorum brevis fibers isolated from 4-6-mo-old IT/+ mice. The sensitivity of the SR Ca(2+) release mechanism to activation was not enhanced in fibers of IT/+ mice. Single-channel measurements of purified recombinant channels incorporated in planar lipid bilayers revealed that Ca(2+) permeation was abolished for homotetrameric IT channels and significantly reduced for heterotetrameric WT:IT channels. Collectively, these findings indicate that in vivo muscle weakness observed in IT/+ knock-in mice arises from a reduction in the magnitude and rate of RYR1 Ca(2+) release during EC coupling that results from the mutation producing a dominant-negative suppression of RYR1 channel Ca(2+) ion permeation.
The Journal of General Physiology 01/2011; 137(1):43-57.
· 4.73 Impact Factor
Available from: Elena I. Zvaritch
Mechanistic models for muscle diseases and disorders originating in the sarcoplasmic reticulum.
David H Maclennan,
Elena Zvaritch
[Show abstract]
[Hide abstract]
This review focuses on muscle disorders and diseases caused by defects in the Ca(2+) release channels of the sarcoplasmic reticulum, the ryanodine receptors, and in the luminal, low affinity, high capacity Ca(2+)-binding proteins, calsequestrins. It provides a time line over the past half century of the highlights of research on malignant hyperthermia (MH), central core disease (CCD) and catecholaminergic polymorphic ventricular tachycardia (CPVT), that resulted in the identification of the ryanodine receptor (RYR), calsequestrin (CASQ) and dihydropyridine receptor (CACNA1S) genes as sites of disease-causing mutations. This is followed by a description of approaches to functional analysis of the effects of disease-causing mutations on protein function, focusing on studies of how mutations affect spontaneous (store overload-induced) Ca(2+)-release from the sarcoplasmic reticulum, the underlying cause of MH and CPVT. Subsequent sections describe results obtained by analysis of knockin mouse lines carrying MH- and CCD-causing mutations, including a Casq1 knockout. The review concludes with the presentation of two mechanistic models. The first shows how dysregulation of Ca(2+) homeostasis can lead to muscle diseases involving both RyR and Casq proteins. The second describes a theory of central core formation wherein non-uniformity of Ca(2+) release, resulting in non-uniformity of muscle contraction, is presented as an intrinsic property of the specific tertiary structure of mutant heterotetrameric ryanodine receptors and as the underlying cause of core formation in skeletal muscle. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
Biochimica et Biophysica Acta 11/2010; 1813(5):948-64.
· 4.66 Impact Factor
Available from: Peter H Backx
Constitutively active calcineurin induces cardiac endoplasmic reticulum stress and protects against apoptosis that is mediated by alpha-crystallin-B.
Nicolas Bousette
Shaan Chugh
Vincent Fong
Ruth Isserlin
Kyoung-Han Kim
Allen Volchuk
Peter H Backx
Peter Liu
Thomas Kislinger
, David H MacLennan,
Andrew Emili
Anthony O Gramolini
[Show abstract]
[Hide abstract]
Cardiac-specific overexpression of a constitutively active form of calcineurin A (CNA) leads directly to cardiac hypertrophy in the CNA mouse model. Because cardiac hypertrophy is a prominent characteristic of many cardiomyopathies, we deduced that delineating the proteomic profile of ventricular tissue from this model might identify novel, widely applicable therapeutic targets. Proteomic analysis was carried out by subjecting fractionated cardiac samples from CNA mice and their WT littermates to gel-free liquid chromatography linked to shotgun tandem mass spectrometry. We identified 1,918 proteins with high confidence, of which 290 were differentially expressed. Microarray analysis of the same tissue provided us with alterations in the ventricular transcriptome. Because bioinformatic analyses of both the proteome and transcriptome demonstrated the up-regulation of endoplasmic reticulum stress, we validated its occurrence in adult CNA hearts through a series of immunoblots and RT-PCR analyses. Endoplasmic reticulum stress often leads to increased apoptosis, but apoptosis was minimal in CNA hearts, suggesting that activated calcineurin might protect against apoptosis. Indeed, the viability of cultured neonatal mouse cardiomyocytes (NCMs) from CNA mice was higher than WT after serum starvation, an apoptotic trigger. Proteomic data identified α-crystallin B (Cryab) as a potential mediator of this protective effect and we showed that silencing of Cryab via lentivector-mediated transduction of shRNAs in NCMs led to a significant reduction in NCM viability and loss of protection against apoptosis. The identification of Cryab as a downstream effector of calcineurin-induced protection against apoptosis will permit elucidation of its role in cardiac apoptosis and its potential as a therapeutic target.
Proceedings of the National Academy of Sciences 10/2010; 107(43):18481-6.
· 9.81 Impact Factor
Does Central Core Disease have a Neuronal Component?
Valerie De Crescenzo
Kevin E. Fogarty
Karl D. Bellvé
Elena Zvaritch
, David H. Maclennan,
John V. Walsh
Biophysical Journal 01/2010; 98(3).
· 3.67 Impact Factor
Available from: Douglas Holmyard
Ca2+ dysregulation in Ryr1(I4895T/wt) mice causes congenital myopathy with progressive formation of minicores, cores, and nemaline rods.
Elena Zvaritch
Natasha Kraeva
Eric Bombardier
Robert A McCloy
Frederic Depreux
Douglas Holmyard
Alexander Kraev
Christine E Seidman
J G Seidman
A Russell Tupling
, David H MacLennan
[Show abstract]
[Hide abstract]
Ryr1(I4895T/wt) (IT/+) mice express a knockin mutation corresponding to the human I4898T EC-uncoupling mutation in the type 1 ryanodine receptor/Ca(2+) release channel (RyR1), which causes a severe form of central core disease (CCD). IT/+ mice exhibit a slowly progressive congenital myopathy, with neonatal respiratory stress, skeletal muscle weakness, impaired mobility, dorsal kyphosis, and hind limb paralysis. Lesions observed in myofibers from diseased mice undergo age-dependent transformation from minicores to cores and nemaline rods. Early ultrastructural abnormalities include sarcomeric misalignment, Z-line streaming, focal loss of cross-striations, and myofibrillar splitting and intermingling that may arise from defective myofibrillogenesis. However, manifestation of the disease phenotype is highly variable on a Sv129 genomic background. Quantitative RT-PCR shows an equimolar ratio of WT and mutant Ryr1 transcripts within IT/+ myofibers and total RyR1 protein expression levels are normal. We propose a unifying theory in which the cause of core formation lies in functional heterogeneity among RyR1 tetramers. Random combinations of normal and either leaky or EC-uncoupled RyR subunits would lead to spatial differences in Ca(2+) transients; the resulting heterogeneity of contraction among myofibrils would lead to focal, irreversible tearing and shearing, which would, over time, enlarge to form minicores, cores, and nemaline rods. The IT/+ mouse line is proposed to be a valid model of RyR1-related congenital myopathy, offering high potential for elucidation of the pathogenesis of skeletal muscle disorders arising from impaired EC coupling.
Proceedings of the National Academy of Sciences 12/2009; 106(51):21813-8.
· 9.81 Impact Factor
Available from: ncbi.nlm.nih.gov
Store overload-induced Ca2+ release as a triggering mechanism for CPVT and MH episodes caused by mutations in RYR and CASQ genes.
David H MacLennan,
S R Wayne Chen
The Journal of Physiology 08/2009; 587(Pt 13):3113-5.
· 4.38 Impact Factor
Deficits in Ca2+ Release and invivo Muscle Strength in Heterozygous I4895T RyR1 Knock-In Mice
Ryan E. Loy
Simona Apostol
Murat Orynbayev
Zoita Andronache
Elena Zvaritch
, David H. Maclennan,
Werner Melzer
Robert T. Dirksen
Biophysical Journal 02/2009; 96(3):236-.
· 3.67 Impact Factor
Available from: Michio Asahi
Alterations of phospholamban function can exhibit cardiotoxic effects independent of excessive sarcoplasmic reticulum Ca2+-ATPase inhibition.
Joachim P Schmitt
Ferhaan Ahmad
Kristina Lorenz
Lutz Hein
Stefan Schulz
Michio Asahi
, David H Maclennan,
Christine E Seidman
J G Seidman
Martin J Lohse
[Show abstract]
[Hide abstract]
Low activity of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a) resulting from strong inhibition by phospholamban (PLN) can depress cardiac contractility and lead to dilated cardiomyopathy and heart failure. Here, we investigated whether PLN exhibits cardiotoxic effects via mechanisms other than chronic inhibition of SERCA2a by studying a PLN mutant, PLN(R9C), that triggers cardiac failure in humans and mice. Because PLN(R9C) inhibits SERCA2a mainly by preventing deactivation of wild-type PLN, SERCA2a activity could be increased stepwise by generating mice that carry a PLN(R9C) transgene and 2, 1, or 0 endogenous PLN alleles (PLN(+/+)+TgPLN(R9C), PLN(+/-)+TgPLN(R9C), and PLN(-/-)+TgPLN(R9C), respectively). PLN(-/-) +TgPLN(R9C) hearts demonstrated accelerated sarcoplasmic reticulum Ca(2+) uptake rates and improved hemodynamics compared with PLN(+/+)+TgPLN(R9C) mice but still responded poorly to beta-adrenergic stimulation because PLN(R9C) impairs protein kinase A-mediated phosphorylation of both wild-type and mutant PLN. PLN(+/+)+TgPLN(R9C) mice died of heart failure at 21+/-6 weeks, whereas heterozygous PLN(+/-)+TgPLN(R9C) mice survived to 48+/-11 weeks, PLN(-/-)+TgPLN(R9C) mice to 66+/-19 weeks, and wild-type mice to 94+/-27 weeks (P<0.001). Although Ca(2+) reuptake kinetics in young PLN(-/-)+TgPLN(R9C) mice exceeded those measured in wild-type control animals, this parameter alone was not sufficient to prevent the eventual development of dilated cardiomyopathy. The data demonstrate an association between the dose-dependent inhibition of SERCA2a activity by PLN(wt) and the time of onset of heart failure and show that a weak inhibitor of SERCA2a, PLN(R9C), which is diminished in its ability to modify the level of SERCA2a activity, leads to heart failure despite fast sarcoplasmic reticulum Ca(2+) reuptake.
Circulation 01/2009; 119(3):436-44.
· 15.20 Impact Factor
A new role for type 1 ryanodine receptor
Valerie De Crescenzo
Elena Zvaritch
Kevin E. Fogarty
, David H. MacLennan,
Paul D. Allen
John V. Walsh
Biophysical Journal 01/2009; 96(3).
· 3.67 Impact Factor
Available from: ncbi.nlm.nih.gov
Crystal structure of type I ryanodine receptor amino-terminal -trefoil domain reveals a disease-associated mutation
F. J. Amador
S. Liu
N. Ishiyama
M. J. Plevin
A. Wilson
, D. H. Maclennan,
M. Ikura
[Show abstract]
[Hide abstract]
Muscle contraction and relaxation is regulated by transient elevations of myoplasmic Ca(2+). Ca(2+) is released from stores in the lumen of the sarco(endo)plasmic reticulum (SER) to initiate formation of the Ca(2+) transient by activation of a class of Ca(2+) release channels referred to as ryanodine receptors (RyRs) and is pumped back into the SER lumen by Ca(2+)-ATPases (SERCAs) to terminate the Ca(2+) transient. Mutations in the type 1 ryanodine receptor gene, RYR1, are associated with 2 skeletal muscle disorders, malignant hyperthermia (MH), and central core disease (CCD). The evaluation of proposed mechanisms by which RyR1 mutations cause MH and CCD is hindered by the lack of high-resolution structural information. Here, we report the crystal structure of the N-terminal 210 residues of RyR1 (RyR(NTD)) at 2.5 A. The RyR(NTD) structure is similar to that of the suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor (IP(3)Rsup), but lacks most of the long helix-turn-helix segment of the "arm" domain in IP(3)Rsup. The N-terminal beta-trefoil fold, found in both RyR and IP(3)R, is likely to play a critical role in regulatory mechanisms in this channel family. A disease-associated mutation "hot spot" loop was identified between strands 8 and 9 in a highly basic region of RyR1. Biophysical studies showed that 3 MH-associated mutations (C36R, R164C, and R178C) do not adversely affect the global stability or fold of RyR(NTD), supporting previously described mechanisms whereby mutations perturb protein-protein interactions.
Proceedings of the National Academy of Sciences 01/2009; 106(27):11040-11044.
· 9.81 Impact Factor
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Michio Asahi
Osaka Medical College
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Kevin P Campbell
University of Iowa
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Kazimierz Kurzydlowski
University of Toronto
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Elena I. Zvaritch
University of Toronto
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University of Toronto
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Monaco Government Tourist and Convention Office
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Tel : +44 (0)207 491 4264
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On Wednesday 27 November 2013, the Association is holding a charity dinner. The money raised will be donated to the Tresta girls' school in India
The aim of the Child CARE Monaco Association is to promote and support the education of disadvantaged children all over the world. It organises charitable events throughout the year in the Principality to raise the money needed to carry out its projects.
The profits from the charity evening on Wednesday 27 November at the New Indian restaurant will be donated to the girls' school in the village of Tresta, near Udaipur, in India, which was founded in 2013 thanks to the support of Child CARE Monaco.
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Further information is available on the web site: www.childcaremonaco.com
Number of views : 152
15th "No Finish Line" – A Special Anniversary Event in Monaco
All Aboard – A Night of Elegance in Monaco in Aid of Children in Brazil
The Princess Charlene of Monaco Foundation and the Royal National Lifeboat Institution Join Forces to Help Prevent Deaths from Drowning in Africa
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Jesse Landon Rayburn, 17, of Stafford County passed away Monday, April 28, 2014, at his home.
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Showing faster with the second pregnancy?
I am 5 weeks prgnant and I am showing so much faster than I did if my first one. I know you that you usually show faster with the second one but I didn't think it was this fast. I have already grown into a new bra size and my pants are snug. Could I be further along?
Posted: 10/15/2007 by laurabeth31
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441 - 450 of 455 answers
I have calculated that I am about 6 weeks preg and feeling so much different this time. This is my second, too and I already feel like I am bloated and nothing fits right. I am a big girl anyway so I actually lost weight with my first and didn't start showing until I was about 6 or 7 months with the first. Even now, when I try to sleep on my stomach it is already uncomfortable.posted 02/11/2009 by BekaBlu
I am almost 10 weeks pregnant and this is my third child. My waistline has pooched out pretty quick also. I am already wearing maternity pants. I have been weighing and haven't gained hardly any weight, so I know it's not from excessive weight gain.posted 02/04/2009 by a BabyCenter Member
Wow! All these answers are comforting. I am 5 weeks pregnant and I am all bloated. I did not gain and single pound for my 1st until my 5th month. I have gained weight already and also look 3-4 months pregnant already. Good to know I am not alone.posted 01/05/2009 by a BabyCenter Member
I am just seven weeks pregnant with my second child and have asked other mom's about this because my clothes were getting snugger and I just feel more pregnant than I did with my first child...I was kinda wondering if I was just eating too much or if it was possible the second time around to just start showing earlier and am glad to hear that this is just normal...Whew....Now if I could just get a good nights sleep...!!!posted 01/01/2009 by a BabyCenter Member
omg! this post is a god send! i am less than 5 weeks pregnant and my first son is almost 7 months but i feelm pregnant already! i feel the pressure in my lower abdoman/ uterus and i can suck my belly in! i've also lost weight but my pants are tighter in the waist! my husband also told me it's all in my head! thank god i'm not just a crazo!posted 12/29/2008 by ArmyWifeL06
This website makes me feel so much better. I am 6 weeks pregnant with my second. I have been in denial the last few days that I am already pooching out. My pants are too snug, but I haven't gained any weight. I knew it would happen sooner the second time, but not that quick! Anyway, I love showing so I am glad I'm getting bigger sooner this time.posted 09/02/2008 by a BabyCenter Member
jmouney-its not the baby thats bulging, its the swollen uterus, hints your 'bloatedness".posted 10/03/2011 by a BabyCenter Member
No need to be so rude. I don't think that it is the baby's actual size that matters. I think the body is just more prepared. Everything that I have read on pregnancy says to expect showing sooner with your second child. Just because you aren't doesn't mean that its not normal.posted 03/19/2013 by a BabyCenter Member
Umm, I am so happy I FINALLY found a site where a bunch of women are having same problem I am. I started out at very thin and happy with my weight. I gained a bunch of weight in about a month...so tried doing a few things differently. Nothing worked...Breasts were hurting so I took preg test...to my shock, was positive. My daughter is 11 and i had no idea i could even get pregnant again. Anyway, I am at 9 wks and i am bigger than I was with my daughter at 5 months, and I'm seriously freaking out!! I'm down to two pairs of jeans that were huge on me normally. I've had severe morning sickness and can only keep down the carbs. I am hungry all the time, and crave sweets. I am wanting to start working out to see if i can prevent too much weight can altogether. I feel like a heffer!! But I guess, since i'm not alone, i'll relax (just a little)posted 11/24/2008 by a BabyCenter Member
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This small hotel just 5 minutes in a taxi from the Langkawi Ferry Terminal is small and rooms on two floors only. We took a first floor Deluxe Room for 128 Ringit nightly - when available we could have save more by taking a standard room at 98 Ringit. Our Room had a third bed also and very comfortable, LCD TV, Hot Shower, Air Con and WiFi. Spotlessly clean.
Very polite and helpful Reception - a Clean sandy beach is about 5 mins walk. Taxis around Kuah cost 6 Ringits (about £1.50) including back to the Ferry Terminal. don't order from the Hotel though as that results in paying an additional 4 Ringits - their cut!
There are plenty of cheap breakfast places around. Try the Roti Channai (a kind of pancake) served with a small bowl of curry sauce. Goes down nicely with the local coffee. The Hotel has no catering facilities.
We used this as an alternative to the Thai Visa run of cramming into a mini bus and do the round trip at the Land Border. We left the Car in the free Car park on the Thai side at Satun then the 1 hour Jet Foil (300 Baht OW) Staying longer on Langkawi we would recommend Cennang Beach, a 25 minute taxi ride from the Ferry but just 5 minutes from the Airport. Worth renting a motor Cycle to explore the Island - unlike Thailand full insure is mandatory. The is a very good cable car with wonderful views. All in all a very nice Island, not quite as shambolic as Thailand but without the entertainment.
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Chris Barrett Google+
Chris Barrett is a Sports Writer with The Sydney Morning Herald.
Sheffield Shield debutant Nick Larkin can press Irish Cricket World Cup claims
Chris Barrett Nick Larkin has spent the past two winters in Ireland auditioning for a World Cup berth.
Players cash in as Cricket Australia reports record $300 million revenue
Chris Barrett The rivers of gold are flowing into the Australian game and into the pockets of leading players at an unprecendented level, with Cricket Australia to this week report record revenue of nearly $300...
Matador Cup: Shane Watson hits form but Western Australia beat NSW
Chris Barrett The good news is that Shane Watson has found form and fitness. The bad is that it wasn't enough to propel NSW to victory at the SCG.
Taste of top flight inspires Sean Abbott to greater heights
Chris Barrett From Shane Watson to Mitch Marsh, and James Faulkner to Glenn Maxwell, Australia are not suffering from an absence of quality all-rounders.
Pat Cummins leads NSW Blues to thrilling Matador Cup semi-final victory
Chris Barrett With bat rather than ball Pat Cummins has played the hero to edge NSW into Sunday's Matador Cup final at the SCG, combining with fellow Blues young gun Ryan Carters to clinch a nailbiting win over...
Trent Copeland injury adds to Blues' headaches ahead of Sheffield Shield season
Chris Barrett A mass player shortage confronting the NSW Blues has been exacerbated by former Test seamer Trent Copeland succummbing to stress fractures of the back.
NSW Blues paceman Josh Hazlewood a serious contender for Test debut, says Mark Waugh
Chris Barrett National selector Mark Waugh has confirmed Josh Hazlewood is a serious contender to make a Test debut this summer.
Ben Dunk selected for Australia despite Darren Lehmann snubbing two years ago
Chris Barrett The irony is obvious to Ben Dunk. Unwanted by Darren Lehmann in Queensland two years ago the wicketkeeper-batsman took the road less travelled to national selection, but found himself very much back...
Cricket Australia urges players to report match-fixing suspicions during amnesty period
Chris Barrett Australian cricket has announced an unprecedented effort to weed out match-fixing and zero in on shady characters.
Shane Watson returns from injury in Sydney club cricket, scores 37 runs
Chris Barrett Nearly five months after he last raised a bat in anger, Shane Watson made his return to competitive cricket on Sunday, although the presence of the Australian all-rounder was not enough to propel his...
West Indies' future looks grim after Indian board hits them with $74 million damages bill
Chris Barrett Cricket Australia chairman Wally Edwards has described as "deeply concerning" the crisis that has seen the West Indies abandon their tour of India over a pay dispute, resulting in fears about their...
NSW Blues facing drastic player shortage as international duty bites hard
Chris Barrett Defending champions NSW face being gutted for the first two rounds of their Sheffield Shield defence due to a clash with Australia's Twenty20 series against South Africa, a dilemma that has left...
Forgotten star Ashton Agar on mission to return to Australian cricket team
Chris Barrett Ashton Agar turned 21 this week, a milestone that went by largely unnoticed outside the quiet dinner he shared with his family and girlfriend in Sydney.
Prodigal son Bollinger signs with Sydney Sixers
Chris Barrett In a week in which Cricket Australia has raised the possibility of shipping players around the country, one of NSW's favourite sons is returning home.
Steve Smith is lead candidate to be Australia's next captain, says selector Mark Waugh
Chris Barrett He's already had the tick of approval by Ricky Ponting. Now the case for Steve Smith to be Australia's next long-term captain has been rubber-stamped by a selector, with Mark Waugh saying the NSW...
Shane Watson says Kevin Pietersen is a loss to international cricket
Chris Barrett Shane Watson believes England cricket authorities should have done more to accommodate Kevin Pietersen, saying the revelations of discontent in his explosive autobiography provided a fresh reminder...
Cricket Australia contemplates player draft in bid to spread the wealth
Chris Barrett A rookie draft would likely be met by strong opposition from big states like NSW, who would bristle at the idea of losing players that have been produced inside their borders.
Darrell Hair says chucking crackdown is 20 years too late
Chris Barrett Darrell Hair, the umpire who famously no-balled Muttiah Muralitharan in a Boxing Day Test, says cricket's crackdown on illegal bowling actions has come 20 years too late, leaving the game with "a...
Moises Henriques puts hand up for World Cup with maiden ton against Victoria
Chris Barrett Nine years in the making, Moises Henriques' maiden one-day century was worth the wait.
SCG and ANZ fighting to host international cricket matches
Chris Barrett A tug of war for international cricket in Sydney is under way with Cricket Australia in talks with staff from the Sydney Cricket Ground and ANZ Stadium about deals to stage Australian games for the...


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New Rush Limbaugh Parody Song has Obama Singing, "Leaving on a Jet Plane" – Audio 7/1/11
Here is audio of a new Rush Limbaugh parody song done by Paul Shanklin. The parody has President Obama singing, "Leaving on a Jet Plane," thanks to his mention of raising taxes on people with "c
By: star53 | Comments: 9 | Views: 8207 | Votes: 1 | Shared: 0
Leaked: Jul-1-2011 in Other Entertainment
Rush Limbaugh: You Can't Call Obama D-word on MSNBC
Rush Limbaugh: You Can't Call Obama D-word on MSNBC...But You Can Call Conservatives 'Racist, Sexist, Bigot Homophobes'.
By: souljah45 | Comments: 7 | Views: 5139 | Votes: 1 | Shared: 1
Leaked: Jul-1-2011 in Politics
Rush Limbaugh Comments on Mark Halperin Saying Obama Behaved Like a "D*ck" Yesterday – Audio 6/30/11
Rush Limbaugh today giving his take on reporter Mark Halperin saying Resident Barack Obama behaved like a 'Äúdick'Äù during his Press Conference yesterday. Halperin has been 'Äúsuspended indefinitely'
By: star53 | Comments: 27 | Views: 5005 | Votes: 5 | Shared: 2
Leaked: Jun-30-2011 in Politics
Chris Matthews' Wild Rant: Beck & Limbaugh Are 'Evil' Liars for Denying Climate Change
Chris Matthews' Wild Rant: Beck & Limbaugh Are 'Evil' Liars for Denying Cl If you're a fan of wild rants, this is your story. If you are easily angered by the liberal media and people who t
By: aranger45 | Comments: 12 | Views: 7332 | Votes: 3 | Shared: 0
Location: New York, New York, United States | Leaked: Jun-22-2011 in Regional News
Rush Limbaugh Launches Own Line of Conservative…Iced Tea
Limbaugh Launches Own Line of Conservative…Iced Tea Rush Limbaugh has a reach that extends to many political circles. In fact, his daily reach into America's homes, cars, and workplaces is unq
By: aranger45 | Comments: 43 | Views: 6812 | Votes: 0 | Shared: 0
Location: Florida, United States | Leaked: Jun-15-2011 in Regional News
Rush Limbaugh Congratulates Barack Obama on Osama bin Ladens Death
For the first time in the history of the world, Rush Limbaugh actually Congratulates...a democrat!!!!!!!!
By: star53 | Comments: 51 | Views: 6137 | Votes: 2 | Shared: 8
Leaked: May-2-2011 in Other Entertainment
Limbaugh interviews Trump/Trump offered free $100 M ballroom to White House, no reply.
http://www.therightscoop.com/rush-limbaugh-interviews-donald-trump/ Rush Limbaugh interviews Donald Trump Posted by The Right Scoop on Mar 2, 2011 in Politics | View Comments Rush had Trump on
By: HydrogenEconomy | Comments: 38 | Views: 6190 | Votes: 1 | Shared: 0
Leaked: Mar-3-2011 in LiveLeaks
Colbert does the Limbaugh
After Rush Limbaugh decided to mock Chinese President Hu Jintao on his radio show for his "untranslated speech", Stephen Colbert decided to do a bit of translating of his own. He also took Limbaug
By: joalexan | Comments: 54 | Views: 8092 | Votes: 6 | Shared: 0
Leaked: Jan-21-2011 in Arts and Entertainment
Limbaugh's race-baiting continues
Rev. Al Sharpton talks about Rush Limbaugh's latest attack on the Obama administration using a Photoshopped image of Mount Rushmore and calling it "graffiti on the walls of American history
By: The_Illuminati | Comments: 22 | Views: 5799 | Votes: 2 | Shared: 0
Leaked: Nov-17-2010 in News
Rush Limbaugh: "The Poison Is The Democratic Party"
"You and I are the antidote," Rush Limbaugh tells his listeners. Limbaugh explains what would happen if he would "just shut up." "Just stop opposing this stuff, Rush. If you would stop opposing
By: star53 | Comments: 19 | Views: 5074 | Votes: 1 | Shared: 0
Leaked: Nov-16-2010 in News, Arts and Entertainment
Rush Limbaugh Interviews President Bush On "Decision Points"Two Of The Best
"I am happy seeing people go out and showing that democracy has won," former President George W. Bush told Rush Limbaugh. President Bush also tells Rush that he is absolutely not secretly against S
By: star53 | Comments: 50 | Views: 6890 | Votes: 3 | Shared: 0
Leaked: Nov-9-2010 in News, Arts and Entertainment
Rush Limbaugh: Democrats Covering Up For Obama After "Drubbing"
Rush Limbaugh on how Democrats are trying to explain their historic loss last week.Liberals want to debate his message? or just do what you do best? bash the messenger...LOL
By: star53 | Comments: 49 | Views: 6577 | Votes: 1 | Shared: 0
Leaked: Nov-8-2010 in News
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The Cosmo Field Report: July, Part II
Actionable intelligence from Cosmopolitan magazine about simultaneous orgasms, cleanliness, and vibrators.
Byon July 15, 2013
In each issue of the Esquire Weekly, we provide a collection of actionable intelligence culled from the pages of Cosmopolitan. Here is the second part of what we found in the magazine's July issue:
You were urged to be aware of the objects in your pockets. Meaning to offer his date a wet nap, David, 25, instead handed her a condom. If in this position, one can try some variation of the Always be prepared! jokewhich worked for Davidthough, generally, its best just to hand her the right thing in the first place.
To achieve a simultaneous orgasm, it was suggested you communicate verbally to match up pacing. She will likely take longer, so you may need to stop thrusting as she continues to touch herself (or you continue to touch her).
When dancing, it was strongly recommended that you do not grab your crotch and make a thrusting motion.
Cleanliness was said to generally work in your favor. Showering before sex will make you soft and smell good. Not doing so will make for sweat-smelling sheets, which, it was said, is a turn-off. Also: surprise chores makes one woman so relieved that I cant help but jump him!
It was stated that getting into something more comfortable does not always translate into Follow me into my room and have sex with me. One male interpreted it as such, and the woman threw a shoe at his face. Be cautious.
A note to any female readers: If you wish to imply your non-sexual intent, we might suggest that you do not use that exact phrasing, given its history. Instead, say something like I am going to go throw on some flannel. That will have the intended effect.
Should a woman desire to use her vibrator on you, there are three locations she was advised to explore: between your thighs (because the vibrations will awaken the nerve endings throughout [your] entire pelvic region), beneath the head of the penis, or between your balls and ass. A sexologist called the last of these the million-dollar point, which is probably preferable to taint. But feel free to experiment with the terminology.
Follow Esquire Magazine on RSS and on Twitter at @Esquiremag.
What To Read Next
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02A Few Billion Dollars, Over 400 NBA Players, And The One Woman Who Can Bring Them Together
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06There's A New Technology That Encourages You To Scream At Your TV To Skip Commercials
07The State of The American Dog
08The 50 Best Manly Movie Quotes
0910 Things Men Need to Stop Wearing to the Gym Immediately


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Retrieving JMX information for a Java process is very easy when using a tool such as JConsole or JVisualVM. These provide an interface that allows viewing of information such as CPU usage, memory usage, threads active and more. This blog post gives an example of how to retrieve such information programmatically.
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Jul 16 2014 / 06:47


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Make 100% CSS Vertical Navigation Menu in a Few Clicks for Free!
PureCSSMenu.com is a FREE web-based service that generates pure css drop down menus with minimum efforts!
You need just 3 easy steps to generate your CSS menu:
1. Open PureCSSMenu.com and select the menu template you like.
2. Setup the menu item link and appearance.
3. Download the result as a zip file.
That's all! No complicated HTML and CSS coding. No drawing. Easy and Free!
* Super small size ~ 4Kb.
* Immediate loading.
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* Horizontal css menu & Vertical css menu.
Tutorial: How To Create CSS Rollover Menu Nav in Minutes Online!
See Also
Pure CSS Menu is an excellent tool that gives you the possibility of creating desplegable menu in CSS without any knowledge of the design, and in a couple of clicks. We may from predefined templates, we choose to 8, are not very nice to say, but it is ideal that you personalicemos a gusto en instead of using a template. Tutorial Submenu Swmenufree PureCSSMenu.com provides the amateur or pro webmaster with tools to create custom, cross browser compatible, pure css drop down menus. PureCSSMenu.com menu generator makes it easy to create custom CSS menus w/o knowledge of HTML and CSS. If you are a more experienced web developer PureCSSMenu.com provides the sources code for all CSS menus so that you can download, tune, and integrate as much as you want.


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New Ulm Brothers head into HOF
A popular polka brother duo is headed into a hall of fame. Peter and Paul Wendinger have been announced as inductees into the International Polka Association Hall of Fame. Paul passed away in 2010 and …20 Jul 12
Local News, Multimedia, Sports - The Local Connection
Wheeler Dealer
A popular polka brother duo is headed into a hall of fame. Peter and Paul Wendinger have been announced as inductees into the International Polka Association Hall of Fame. Paul passed away in 2010 and …20 Jul 12
WILLMAR, Minn. – Motorists near Kingston will encounter delays as crews begin replacing a bridge barrier on Highway 15 Monday, July 23. Stop signs will be installed and traffic will be reduced to a single …20 Jul 12
The Minnesota Department of Natural Resources (DNR) is investigating a report that a zebra mussel was found in Lake Minnewaska in Pope County near Glenwood. While removing trash blown into the lake from a severe …20 Jul 12
Motorists should expect delays while traveling on Highway 4 from Cosmos to Fairfax beginning Monday as crews begin resurfacing the road. According to the Minnesota Department of Transportation Flaggers and a pilot car will control …19 Jul 12
A group of 53 Minnesota National Guard soldiers will leave Friday from St. Cloud to support Operation Enduring Freedom. The St. Cloud Times reports Members of C Company 2-211th General Support Aviation Battalion will leave …19 Jul 12
A 25 year old Wisconsin man is in custody today in connection with a Bank Robbery in Hutchinson Tuesday. Hutchinson police reported a man walked into the Citizens Bank building on Highway 15 shortly after 3 …18 Jul 12
A 45-year-old Raymond woman was sentenced Monday to nearly 5 years in prison for a 2010 crash south of Litchfield that claimed the lives of two people. The sentence was stayed for 180 days in …18 Jul 12
A Watkins man was in critical condition Tuesday after the motorcycle he was driving rear-ended a vehicle in Meeker County. According to the State Patrol the crash happened just after 4 pm Monday at Minnesota …18 Jul 12
Check out our Sports Broadcast Schedule! From the Twins, Wild, and Vikings to your local High Schools or Amateur Baseball teams, we've got you covered right here!


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DLA Piper: Still in "Growth Mode", Seeking "Escape Velocity"
Harley Lewin of McCarter & English discusses the leading issues facing global brands today
Emerging Markets: Opportunity, Risk, and What it Means for Brand Protection
gTLD Update for September 2013
What is Licensed Property? By Richard Hsu
What is a domain name? Is it the same as a company name?
Trademark Licensing: What You Need to Know
Trademark Series: Protecting your mark from becoming generic
Trademark Series: Matching your commercial strategy
Trademark Series: Building a global brand
Love the recent holiday billboard ad for the beloved Coca-Cola brand!
Having said that, whenever I see branding around the sound Mmm, for food and beverage products, even if it is only one Mmm, and not back-to-back...more
Designed to appeal and speak to the customers of a specific time and place, trademarks can become hallmarks of a bygone era.
The controversy surrounding the use of the REDSKINS trademark and logo shows just how much...more
A trademark is the legal term for what is commonly known as a brand. It is a word, phrase, symbol or design (or any combination of these) that identifies and distinguishes the source of the goods of one party from those of...more
On this especially cold day in the Northeast, my thoughts are on the coming winter. And winter reminds me of the cold, and of feeling frozen. And the word frozen reminds me of Disney's Frozen, the highest-grossing animated...more
In the past decade or so, manufacturers in the developed world that would previously have created their entire product in their own country now outsource manufacture to other parts of the world. This has had significant...more
We brand geeks at MarkIt to Market occasionally like to explore the history of interesting trademarks. A recent visit to Germany inspired a look into the history of the Störtebeker beer brand, which derives its name from one...more
We're fans here of saying that we aren't Dr. Nos; we try to create a symbiotic relationship between creatives and their lawyer counterparts. But more often then we realize, the advertising world affects the legal one. I may...more
The October issue of Sterne Kessler's MarkIt to MarketTM newsletter reviews some highlights from the new USPTO Service Mark Specimens Examination Guide, considers the colorful history of the Störtebeker beer brand name, and...more
Metaphors are a good choice for trademarks. A metaphor typically requires some thought, imagination or perception to understand the connection between the mark and what's for sale....more
Internet liability are increasingly tested with the growth of social media. And we receive a large number of requests of advice from clients running a fan page, a group or a list on social networks dedicated to either their...more
Nelson Bunker 'Bunkie' Hunt died last week. In a state filled with oversized egos and personalities (i.e. 'Texas-Rich'), Bunkie was one of the true giants. He was a son from the first marriage of the famous Texas...more
Q: I am in charge of risk management for a global organisation and have been asked to investigate product risk. What suggestions can you offer on managing global supply and distribution?
A: in the past decade or so,...more
Oct. 23, 2014 (Mimesis Law) -- Roger Meltzer, partner and incoming global co-chair for DLA Piper, talks with Lee Pacchia about how his firm has grown to one of the world's largest BigLaw brands in just under ten years....more
Whether you love, hate, or are indifferent to the Kardashian franchise, the Kardashian sisters undeniably know how to market and brand themselves and their products. In December 2012, the Kardashian sisters hoped to...more
Hashtags and Ads: Top 10 Legal Considerations for Brands Involved in Digital and Social Media Advertising -
In today's competitive marketplace, brands are relying heavily on social media and other digital methods to...more
Now more than ever, it is important to understand brand standards: why they are set; how they affect franchisors, franchisees, and customers; and what the boundaries of brand enforcement policies should be....more
The Atlantic's recent article, Buy Experiences, Not Things, addresses the fact that while, as consumers, we tend to think we want more material things, what really makes us happy are experiences. Anticipating experiences,...more
ICANN's new Generic Top-Level Domain (gTLD) program has been in full swing for over a year now, so it seems an apt time to examine some statistics as to how brands are engaging with new gTLDs, utilizing the Trademark...more
The recent criminal prosecution of several 7-Eleven franchisees, which arose out of a criminal alien employment investigation, as well as efforts by government agencies to treat franchisors and franchisees as joint employers...more
Harley Lewin a partner at McCarter & English discusses the leading issues facing global brands today....more
Coca-Cola just announced it is introducing Coke Zero in India, which will make it the sub-brand's 149th market in the world, a truly remarkable reach.
As the popular Coke Zero brand is approaching its tenth anniversary...more
In This Issue:
- Features
..Investors in Africa Benefit from Regional Trading Blocs
..Understanding the COMESA Merger Control Regime
..Protecting Your UK Business Against Departing...more
What a Trademark is and What it Does.
A trademark is any word, name, symbol, or device, or combination thereof, used to identify and distinguish the goods (i.e., products) of one supplier from those of others. A...more
The Worker Adjustment and Retraining Notification Act (WARN Act) was enacted in 1988 to allow workers to adjust to the prospective loss of employment from a plant closing or mass layoff. It requires employers to give affected...more
Counterfeiting is the practice of manufacturing and/or selling goods, usually of inferior quality, under a brand name without the brand owner's permission. The damage from counterfeiting is extensive and far-reaching and...more
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Copyright ©


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Showing All "Amanda Palmer" Posts
Nov 18th 1 Comment
Eddie Vedder played an intimate benefit show for EB Research, the charity he's been vocally supporting lately, last month at Microsoft's Seattle headquarters. The Pearl Jam frontman played songs by…   Read Story »
Oct 31st 13 Comments
Early this week, the Canadian broadcast network CBC announced that it had severed its relationship with the broadcaster Jian Ghomeshi, amidst allegations that Ghomeshi had non-consensually beat up…   Read Story »
Oct 28th 54 Comments
Over the weekend CBC announced that they'd ended their relationship with longtime broadcaster Jian Ghomeshi, former Moxy Früvous member and longtime pillar of the Canadian indie music scene. The…   Read Story »
Jul 19th 3 Comments
The weekend may be here but "Weird Al" week marches on. His latest video is a Pixies pastiche and sees him ranting about "First World Problems," like not being able to fast forward commercials during…   Read Story »
Dec 20th, 2013 13 Comments
The literary giant Alexis Krauss said it best: It was the best of times, it was the worst of times. From big-budget campaigns to no-budget crowdfunding, the haves and have-nots alike made selling…   Read Story »
Apr 29th, 2013 23 Comments
There are no words, really. Are there? The headline says it all. The subtext? I, Amanda Palmer, am trolling the fuck out of you, Stereogum. But let's put aside our own narcissism for a moment!…   Read Story »
Apr 22nd, 2013 85 Comments
These days, Amanda Palmer lives with her husband, author Neil Gaiman, near Minneapolis, but as you might know, Palmer's formative years were spent on the streets of Boston, working as a "living…   Read Story »
Mar 4th, 2013 53 Comments
Last week, Amanda Palmer was one of the speakers at the TED2013 conference, and she delivered an affecting 13-and-a-half-minute speech titled "The Art Of Asking," in which she detailed her rise from…   Read Story »
Nov 9th, 2012 9 Comments
Another week, like last week, when people had other things going on and weren't cranking out music videos with the consistently that they might otherwise. It makes sense. After watching the grand…   Read Story »
Nov 9th, 2012 18 Comments
Wayne Coyne co-directed Amanda Palmer's new NSFW video, for the track "Do It With A Rockstar," in which porn star Stoya does it with rockstar Palmer. (Stoya is the redhead in the above pic.) The clip…   Read Story »


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- Publisher: Global Star Software
- Release Date: Oct 21, 2004
- Critic Score
- Most active
- Publication
- Most clicked
The only people we can imagine buying this are confused parents who do not understand the world of the mystical home entertainment that is the videogame.
User Score
Generally favorable reviews- based on 16 Ratings
User score distribution:
Positive: 9 out of 10
Mixed: 1 out of 10
Negative: 0 out of 10
ShayaG.Jun 6, 2006I love this game, it's great, but I kinda came on this site to see if there was any cheats. I mean I know it's more challenging without them, but I can't seem to get passed the big lobster thing, the thing that follows you in the air and it shoots those things at you and stuff so if you have any cheats you could send me an email and stuff. But ya I love this game it's like my favorite game even better than grand theft auto San Andreas.… Full Review »
FilipR.Oct 23, 2004I could'nt believe it ... for that price I had more fun than any game that came out this year.
Nov 2, 2014This game doesnt know what it wants to be. Ratch and clank? Jak and Daxter? Crash Bandicoot? Spyro? This is clearly a platformer that came out too late to succeed. With many elements featured in other games this is probably something youve already played hundreds of times over. But, that doesnt make it bad. By the time this was out we already had, Jak and daxter and Ratchet and Clank, 2 far superior games that were big in scale and received more ettention as a result.
Scaler suffored from being the last born, the black sheep, the last sip of juice at the bottom of the glass that you dont bother to consume.
This games nothing new, but it sure is better than it seems. Probably one of the most hidden of gems ive come across.… Full Review »


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CNH Industrial N.V.
"Good "
I worked at CNH Industrial N.V.
great package. Nice work environement
not much growth possible in the company.
181 Other Employee Reviews for CNH Industrial N.V. (View Most Recent)Sort: Rating Date
1 person found this helpful
"cnh review "
- Comp & Benefits
- Work/Life Balance
- Senior Management
- Culture & Values
- Career Opportunities
I have been working at CNH Industrial N.V. full-time (more than 3 years)Pros
Big company, salary pays the bills, but is not fast paced and is not challenging professionally and is good for average people who are looking for a safe place before retirement.Cons
Rewards not by performance and promotes average folks with average professional skills but good networkers (unfortunately "brown nosing" is rewarded)Advice to ManagementAdvice
Pay more attention to regular folks who keep their heads down doing real work, not those who sit in your office half of the day talking tennis and golf. Change PLM, which is very subjective.Doesn't RecommendNegative OutlookNo opinion of CEO
"Not a great place to work for in manufacturing plant "
- Comp & Benefits
- Work/Life Balance
- Senior Management
- Culture & Values
- Career Opportunities
I have been working at CNH Industrial N.V.Pros
Flexible in working hours
If you are interested, there are lots of manufacturing processes you can get familiar with
Some experienced manufacturing engineering were helpfulCons
Salary not good
Old way of management
They start a project, without knowing why? and how?
Do not believe in young people and follow the old rules of management
Not a good place to growDoesn't RecommendNeutral Outlook


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More Fantasy
The Latest
Player Updates
Jesse Biddle (Phi-SP)
Jesse Biddle added to 40-man roster
Biddle had a rough 2014, holding a 5.03 ERA over 16 Double-A outings. He remains one of the Phillies' best pitching prospects, however, and is now protected from the Rule 5 Draft.
Juan Gutierrez (SF-RP)
J.C. Gutierrez designated for assignment
Gutierrez put up a 3.96 ERA with 44 strikeouts over 63 2/3 innings for the World Champs this season. He'll likely have to settle for a minor league deal this winter.
Norris Cole (Mia-PG)
Norris Cole goes to the locker room
He is back on the bench and chances are X-rays were negative. If Cole does miss time, rookie Shabazz Napier could be looking at a major bump in minutes. -- Heat on Twitter
Reymond Fuentes (SD-CF)
Royals acquire Reymond Fuentes from Padres
A former first-round pick, Fuentes batted .294/.363/.416 with five homers and 25 steals between Double- and Triple-A this season. The Royals have added him to their 40-man roster.


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Psychedelicatessen: Lifted Lemon Ginger Tarts
Lifted creates all organic, vegan edibles infused with cold-water hash for a pure high that even the most enlightened yogi could appreciate. "We wanted to use cannabis as a way to promote a healthier lifestyle," says marketing director Matthew, "and we d...
South Park Music Festival: Cannabis and Music Extravaganza
The South Park Music Festival is just around the corner and we're as excited as ever! With the advent of legalized marijuana in Colorado, cannabis is the hot, new feature at local events, and each innovation quickly draws national attention -- the next big thing is th...
Stoner Sex: Domination, Clean Sex, Flirting & Boozy Mates
Hyapatia Lee answers all of your questions regarding cannabis and sexuality.
5 Videos to Watch When Baked XXVI
In this weekly segment, the staff here at HIGH TIMES brings you the best vids to watch after indulging.


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Posts tagged finland
Rumor: New Alan Wake trailer to debut before Max Payne -- in Finland
Remedy is making Alan Wake; Remedy made Max Payne; Remedy is Finnish. The website Pelaajalehti is – along with being nigh-impossible to pronounce – also Finnish, and reports that a new trailer for the long lost Xbox 360 adventure of Mr. Wake will debut before a special preview screeni...
The DS not big enough for Tetris? How about a dorm building?
The Russians may have done it first (definitively proving that they have won the Tetris arms race), but that doesn't make this accomplishment by some Finnish students any less impressive. The goal behind the project known as MIKONTALOLIGHTS (Mikontalo being the name of the dorm building that was u...
Splinter Cell conViction featured in Finnish gaming mag
See what they've done with the "V"? Clever ... sorta. Finnish gaming mag Pelaaja ("Player") has the scoop on Xbox 360's console-exclusive, Splinter Cell V -- er, Splinter Cell Conviction (the title remains unchanged since it was leaked last September). GamersReports has compiled the first Conviction...
Breaking News
Dying Light cancelled on Xbox 360, PS3
Featured Stories
Games we love and hate
Posted on Nov 21st 2014 3:00PM
Super Joystiq Podcast 122: Far Cry 4, GTA V, Assassin's Creed Rogue, WWE 15
Posted on Nov 21st 2014 1:30PM
Hatsune Miku: Project Diva F 2nd review - Pretty punisher
Posted on Nov 21st 2014 9:00AM


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Guy Fieri Will Be Eating a 'Turketta' This Thanksgiving, In Case You Were Wondering
Can we add turkey-based food hybrids to the list of things we just don't want to eat this Thanksgiving?
The Worst Thanksgiving Stock Photos
So your day is not going to well, huh? Sh*t's already hitting the fan a little? We get it. That's what stock photos are here for: to put your life into perspective.
Albert Adrià On His Own Definition of Fear
Fear is a, well, scary thing. And if anyone should be afraid, it should be Albert "the brother of him, who shall not be named" Adrià. He's a world-renowned chef, brother to Ferran Adrià (oops, we named him) with plenty of expectations and pressure riding on him. Yet in a new video released this week from MAD4, Adrià admits that fear isn't all so bad -- and that young chefs should be especially afraid.
You Can Now Use Emojis to Search the New York Times' Food Section
Who knew that Sam Sifton was so into emojis?
the helpers
Miss Cakehead Creates Edible Murder Scene, Forces Us To Wonder Who The Real Cake Boss Is
Sometimes, in spite of the fact that we specialize in celebrity chef coverage, we just have to throw our hands up and accept that any given day is murder-and-dismemberment day. Today is that day.Read on...


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NSO Pops and Roberta Flack: Roberta's Back in Town
* Additional fees apply.
The last date listed for NSO Pops and Roberta Flack: Roberta's Back in Town was Friday October 26, 2012 / 8:00pm.
Currently at The Kennedy Center - Concert Hall
NSO: Pianist Angela Hewitt Plays Mozart, David Zinman Conducts
- Full Price:
- $59.00
- Our Price:
- $29.50
Canadian pianist and former child prodigy Angela Hewitt may be best known for her nine-year recor...Learn More
Venue Details
I wore sports coat, slacks.NSO: Parsifal in Concert dress • Nov 25 2014 star this tip starred
When you go to an event at the Kennedy Center, make certain to see what is playing at the Millenium Stage. A free performance is offered at 6:00 every night. I saw a wonderful set of Broadway show tune sung by very talented students from Catholic University.NSO: Koh Plays Barber info • Nov 01 2013 star this tip starred
Reviews & Ratings
Featured review from maddawg6713
view more less of this review
I have never been to a bad concert at the Kennedy Center but this one was among the best. Roberta Flack has such a unique voice and her stage voice is truly captivating. The first half of the night was just the NSO Pops playing the likes of Barry White and a melody of Diana Ross hits. It is great to see such music played on classical interestes.
But when Roberta came out in her sparkling attire it was an amazing experience. Her band blended seamlessly with the orchestra and her interaction with the audience was impressive. It was just well done from head to toe and she even got the orchestra director to assist her at the grand piano in singing Hey Jude. Remarkable talent.
star this review starred report as inappropriate
It was absolutely wonderful!
About the Ticket Supplier: The John F. Kennedy Center for the Performing Arts
The John F. Kennedy Center for the Performing Arts, located on 17 acres overlooking the Potomac River in Washington, D.C., is America's living memorial to President Kennedy as well as the nation's busiest arts facility, presenting more than 2,000 performances each year. The Center is home to seven theaters: the Concert Hall, the Opera House, the Eisenhower Theater, the Family Theater, the Terrace Theater, the Theater Lab, and the Terrace Gallery. In addition, as part of the Kennedy Center's Performing Arts for Everyone outreach program, free performances take place each evening at 6 p.m. on the Millennium Stage. In addition to offering annual series of the National Symphony Orchestra, Washington National Opera, theater, ballet, dance, chamber music, jazz, and performances for young audiences, the Kennedy Center presents festivals celebrating the arts and culture of countries and regions around the world.