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Andromeda–Milky Way collision
The Andromeda–Milky Way collision is a galaxy collision predicted to occur in about 4 billion years between the two largest galaxies in the Local Group—the Milky Way (which contains our Solar System and Earth) and the Andromeda Galaxy.[1][2][3]
Stellar collisions[edit]
While the Andromeda Galaxy contains about 1 trillion (1012) stars and the Milky Way contains about 300 billion (3×1011), the chance of even two stars colliding is negligible because of the huge distances between the stars. For example, the nearest star to the Sun is Proxima Centauri, about 4.2 light-years (4.0×1013 km; 2.5×1013 mi) or 30 million (3×107) solar diameters away. If the Sun were a ping-pong ball, Proxima Centauri would be a pea about 1,100 km (680 mi) away, and the Milky Way would be about 30 million km (19 million mi) wide, about 1⁄5 the distance from the Earth to the Sun. Although stars are more common near the centres of each galaxy, the average distance between stars is still 160 billion (1.6×1011) km (100 billion mi). That is analogous to one ping-pong ball every 3.2 km (2.0 mi). Thus, it is extremely unlikely that any two stars would collide.[4]
Black hole collisions[edit]
The Milky Way and Andromeda galaxies each contain a central supermassive black hole, these being Sagittarius A* (ca. 3.6 x 106 solar masses) and an object within the P2 concentration of Andromeda's nucleus (1-2 x 108 solar masses). These black holes will converge near the center of the newly formed galaxy, transferring orbital energy to stars that will be moved to higher orbits by gravitationally interacting with them, in a process that may take millions of years. When they come within one light year of one another, they will emit gravitational waves that will radiate further orbital energy until they merge completely. Gas taken up by the combined black hole could create a luminous quasar or an active galactic nucleus. As of 2006, simulations indicated that the future Earth might be brought near the center of the combined galaxy, potentially coming near one of the black holes before being ejected entirely out of the galaxy.[5]
The quasar, if it were to be created at the center of the Andromeda Galaxy, would be visible from Earth, and would be as bright as the full moon despite being 10,000 light years away.[citation needed] Its accretion disk would not be visible and it would appear as a blinking star due to atmospheric fluctuations.[citation needed] However, if a quasar were to be created at the center of the Milky Way, it would not be visible due to the dust between Earth and the galactic center. A quasar at the center of the Andromeda Galaxy would be brighter than one at the center of the Milky Way since the black hole at the center of Andromeda is larger than the Milky Way galactic center black hole.[6][7][8]
Up until 2012, there was no way to know whether the possible collision was definitely going to happen or not.[9] In 2012, researchers came to the conclusion that the collision is definite after using the Hubble Space Telescope between 2002 and 2010 to track the motion of Andromeda.[1] Such collisions are relatively common. Andromeda, for example, is believed to have collided with at least one other galaxy in the past,[10] and several dwarf galaxies such as SagDEG are currently colliding with the Milky Way and being merged into it.
These studies also suggest that M33, the Triangulum Galaxy – the third largest and brightest galaxy of the Local Group – will participate in this event. Its most likely fate is to end up orbiting the merger remnant of the Milky Way and Andromeda galaxies to merge with it in an even farther future, but a collision with the Milky Way before our galaxy collides with M31 or being ejected from the Local Group cannot be ruled out.[11]
The fate of the Solar System[edit]
Two scientists with the Harvard–Smithsonian Center for Astrophysics stated that when, and even whether, the two galaxies collide will depend on Andromeda's transverse velocity.[2] Based on current calculations they predict a 50% chance that in a merged galaxy the solar system will be swept out three times farther from the galactic core than it is currently located.[2] They also predict a 12% chance that the Solar System will be ejected from the new galaxy some time during the collision.[12] Such an event would have no adverse effect on the system and the chances of any sort of disturbance to the Sun or planets themselves may be remote.[12][13]
Without intervention, by the time that the two galaxies collide, the surface of the Earth will have already become far too hot for liquid water to exist, ending all terrestrial life, which is currently estimated to occur in about 3.75 billion years due to gradually increasing luminosity of the Sun.[14][15]
Possible triggered stellar events[edit]
When two spiral galaxies collide, the hydrogen present on their disks is compressed producing strong star formation as can be seen on interacting systems like the Antennae Galaxies. In the case of the Andromeda–Milky Way collision, it is believed that there will be little gas remaining in the disks of both galaxies, so the mentioned starburst will be relatively weak, though it still may be enough to form a quasar.[13]
Merger remnant[edit]
The galaxy product of the collision has been nicknamed Milkomeda or Milkdromeda. According to simulations, this object will look like a giant elliptical galaxy, but with a center showing less stellar density than current elliptical galaxies.[13]
In the far future the remaining galaxies of the Local Group will coalesce into this object, being the final evolutionary stage of our group of galaxies.[16]
See also[edit]
- ^ a b Cowen, R. (31 May 2012). "Andromeda on collision course with the Milky Way". Nature. doi:10.1038/nature.2012.10765.
- ^ a b c Muir, Hazel. (4 May 2007) "Galactic merger to 'evict' Sun and Earth". New Scientist.
- ^ Loeb, Abraham; Cox, TJ. (June 2008). Astronomy. p. 28.
- ^ NASA (2012-05-31). "NASA's Hubble Shows Milky Way is Destined for Head-On Collision". NASA. Retrieved 2012-10-13.
- ^ John Dubinski (October 2006). "The Great Milky Way-Andromeda Collision". Sky & Telescope.
- ^ Thomsen, D. E. (Jun 20, 1987). "End of the World: You Won't Feel a Thing". Science News (Society for Science & the Public) 131 (25): 391. doi:10.2307/3971408. JSTOR 3971408.
- ^ https://www.cfa.harvard.edu/~tcox/localgroup/lg.pdf
- ^ Alex Filippenko (University of California, Berkeley) on The Universe Season 4 Episode 10.
- ^ van der Marel, G. et al. (2012). "The M31 Velocity Vector. III. Future Milky Way M31-M33 Orbital Evolution, Merging, and Fate of the Sun". The Astrophysical Journal 753: 9. arXiv:1205.6865. Bibcode:2012ApJ...753....9V. doi:10.1088/0004-637X/753/1/9.
- ^ "Andromeda involved in galactic collision" MSNBC 10:38 a.m. PT 29 January 2007.
- ^ The M31 Velocity Vector. III. Future Milky Way-M31-M33 Orbital Evolution, Merging, and Fate of the Sun
- ^ a b Cain, Fraser (2007). "When Our Galaxy Smashes Into Andromeda, What Happens to the Sun?". Universe Today. Archived from the original on 17 May 2007. Retrieved 2007-05-16.
- ^ a b c Cox, T. J.; Loeb, Abraham (2007). "The Collision Between The Milky Way And Andromeda". Monthly Notices of the Royal Astronomical Society 386: 461. arXiv:0705.1170. Bibcode:2008MNRAS.tmp..333C. doi:10.1111/j.1365-2966.2008.13048.x.
- ^ Schröder, K.-P.; Smith, R. C. (2008). "Distant future of the Sun and Earth revisited". Monthly Notices of the Royal Astronomical Society 386 (1): 155. arXiv:0801.4031. Bibcode:2008MNRAS.386..155S. doi:10.1111/j.1365-2966.2008.13022.x.
- ^ Carrington, D. (2000-02-21). "Date set for desert Earth". BBC News. Retrieved 2007-03-31.
- ^ A dying universe: the long-term fate and evolution of astrophysical objects, Fred C. Adams and Gregory Laughlin, Reviews of Modern Physics 69, #2 (April 1997), pp. 337–372. Bibcode: 1997RvMP...69..337A. doi:10.1103/RevModPhys.69.337 arXiv:astro-ph/9701131.
External links[edit]
- Merrifield, Michael. "Milky Way vs Andromeda: The ultimate head-on crash". Deep Space Videos. Brady Haran.


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text: PokeBase Battle Subway Meta-PokeBase Q&A Login Register All Activity Questions Unanswered Tags Users Ask a Question Rules Chat How do you create your own website or a pokemon website? 0 votes How do you create a pokemon website? pokemon asked Aug 16, 2011 by Phanpy22 Please log in or register to add a comment. Please log in or register to answer this question. 1 Answer 1 vote If you want to make a pokemon site you usually have to pay money but her is a web site so you can make your web site for free http://www.weebly.com/?footer Hope i helped answered Aug 16, 2011 by Flying Flygon Oh, weebly is free? Please log in or register to add a comment. Related questions how do you start a pokemon data base how do you get to the Pokemon Events page Why not create a page with Pokemon with the highest stats till the lowest? How did you create a website that allowed users to create an account? How about a POKEMON FACTS page ? Is there a time limit to how long before you can't delete your own posts of another user's wall? Will the pokemon Db app be on the android market place anytime soon or in the future? How do you delete your Pokemon Database account? Useful Posts How to change your username How to add a user avatar Why was my post hidden? The points system Question etiquette Flags vs Downvotes Anime FAQ PokemonDb Tournaments PokemonDb Showdown server Help out Report users Name Origins corrections Location guide corrections Spelling/Grammar mistakes New X&Y info


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' ISBIS.ER & CO., LIMIT JD. good words. " _ " isbister's 15 & 16, Tavistock Street, sunday magazine. school books. Covent Garden, TELEGRAPHIC ADDRESS] LONDON, W.C. •CONTEMPORARY, LONDON." Office of MANAGING DIRECTOR, PRIZE BOOKS, Ac. April I7th, ^2 Dear Sir, I am sending you herewith soma of the more iis^ortant clippings from London Papers, which I think you will find interesting reading. I have accidental! become aware of a fact* which I did not know before, namely, that in other cases Messrs Macmillar; have taken only the American, or in some cases, only the English rights, the books in question being published by other firms on one side or the other. Under these circumstances I hope that you can arrange 30 that we can have the English rights of whatever book.you may give to them, in accordance with your former promise. I did not suggest this to you before, because I was not aware that there were cases in which that house only published on one side. Under the circumstances, however, (unless you have pacifically agreed that they shall have the English publication as well as the American)there is no reason at all why you should not Inform them that you desire the English publication of all your works to be in our hands. Please believe that I em not speaking in my own interest, or the interest of thi3 house only,when I say that I believe It will be immansely more to your advantage to avoid,
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You are in... Forums > Discuss This > MotoGP > Nicky Hayden confident Ducati can cure understeer issue
Matthew Birt says:
Nicky Hayden remains confident Ducati can solve a persistent understeer issue that has dogged the Desmosedici MotoGP project in recent years. The understeer issue was a constant complaint of Valentino Rossi during his disastrous two-year stint with Ducati, which ended in him walking out to sign a new deal with Yamaha for 2013 and 2014. Hayden believes Ducati made some progress in...
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Oct 11
Posts: 225
redracer46 says:
I really hope your right Benny, I think there is a new confidence at Ducati now with new hands at the helm.... In reality the factory prototypes should all be at the top of the pile, not finishing behind satellites every weekend and even CRT's on bad days.... Project seems to have gone consitently backward or stagnated since their early promise in class debut, which is strange compared to a WSBK project that has gone the other direction... Time for change :P
Nov 09
Posts: 230
diceman23 says:
We need more competitive bikes. But actually I just want them to sort it for Nickys sake. He's always been patient and professional about the Duc he deserves to be given a decent bike he can show some class on. Say what you like about how he won his championship but he is an Ex world champion and I belive he's still fast.
Apr 09
Posts: 1298
Richard1967 says:
I hope so , but i'll believe it when i see Dovin on the rostrum in the Dry when they all finish
Nov 03
Posts: 1526
saturn392 says:
heralds Ducati's second coming ? Nah - can't see it myself where is their expertise in prototype motorcycle development ?
Mar 09
Posts: 4361
Nostrodamus says:
When a frankly mediocre rider (in this company, it's not 2006 anymore when Nicky was the third best rider out there) like Hayden can on occasion run with the fast boys you'd have to say the bike is pretty damn close. The Duke probably is not as good as either of the Japanese bikes, but it's a damn sight closer than most of the fools on here, or the media in general profess.
Whilst I'm sure understeer has been an issue for them in the past two years, it hasn't been nearly as big an issue as overrated riders.
It shall be interesting to follow to combined progess of Ducati (with some engineering muscle behind them) and Dovi who should bring some clarity of direction missing in the last couple of years. I'm picking a lot more podiums for Ducati 2013 than this season. Shouldn't be difficult!
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May 09
Posts: 695
CH987 says:
Funniest post yet Benny. Just for a minute I thought you was being serious. I think you'll find the futures bright, the futures Repsol orange.
I agree that the Ducati isn't far off. But it's that last few tenths that are the hardest to find. If you take Casey out of the equation in ten years what have they won. Loris a couple, Bayliss one I think, and thats it. Personally I just can't see them ever catching the Japanese and beating them on a regular basis.
Apr 11
Posts: 1514
ow01fogno1 says:
its all too late for hayden now,new guns are in the same boat now and im sure will get better results, not taking anything away form nicki here tho as i do recall his honda days very good rides indeed against a very fast then rossi, ducati need new meat, and they have it.roll on 2013,no more excuses.
Jul 12
Posts: 2512
wosihound says:
When serial under achiever and repsol rent boy wins more races than the crowned WC..you know the bike he's riding is head & shoulders..
Don't forget, Nicky spanked Dani last time they were riding the same big bikes, as opposed to the corgi toy 800 designed for midgets.
Fk me..Bautista finished fifth?
Put Dovi, Hayden and Spies on an RCV like Alvaro's and they'd beat him and Bradl every weekend..
The Ducati has a multitude of issues..understeer, a light switch power delivery, limited front and rear traction, it eats tyres etc. etc.
Rossi has turned the bike around as far as is possible with that fkin great dinosaur of an engine shoe-horned into a makeshift chassis. The DNA is all wrong. As is..it's nowhere near being a title contender, despite the limited progress. The Japs have left Ducati scratching their heads.
Unfortunately for the current crop of riders, Ducati will gather reams of useless data next year and nothing will change..until they expunge all remnants of Prezels design to the bin and start again from the ground up.
May 12
Posts: 857
cornbowl says:
cash that Audi bring to Ducati, they don't have development skills for two wheels. If Ducati found, and that's a big if, the pace of the Yamaha, they still wouldn't do any good, because there's no-one riding the Ducati's that's capable of taking wins, and at the end of the year, that's all that matters. If Audi hit a brick wall, by mid season, they'll loose interest, it's no more to them than buying a 'take-away' on the way home.
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What may have been just another typical Saturday for animal residents at The Montgomery Zoo, guests experienced a side of the animals that they normally do not see.
The Montgomery Zoo hosted it's the annual public Animal Enrichment Day. Animals were given new toys, foods, treats. and other items to stimulate them in their various environments. The idea is to stimulate behavior that is typical of the animals in the wild and to exercise them both physically and mentally. Different items are specifically selected for the individual animals.
The Montgomery Zoo says that Animal Enrichment Day is really more for zoo visitors than the animals. Zoo officials say they try to make every day animal enrichment day for the animals.
For more information on The Montgomery Zoo visit www.montgomeryzoo.com/
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The True American Dream
For most Americans in the United States, home ownership is the fulfillment of a lifelong dream, as well as an essential way to achieve long-term financial security, for themselves and for future generations. But over the past few years, the U.S. has faced a "subprime" lending crisis, in which a flood of high-cost loans has jeopardized home ownership and future prospects for tens of thousands of Americans across the country...Go to page >
Lending Lessons
In June 2009, the National Council of Negro Women and the National Community Reinvestment Coalition partnered to produce a report titled "Assessing the Double Burden: Examining Racial and Gender Disparities in Mortgage Lending." The report explored race and gender disparities in mortgage lending. The following essay is a modified version of the report's cover letter, and is authored by Dr...Go to page >
Shut Out of Wealth
In the current subprime mortgage crisis, women and minorities are losing their homes at a disproportionate rate, disrupting their circumstances and daily lives. But foreclosures also have a significant impact on wealth building and long-term prospects. Without a home, women and people of color can't build equity, they have no safety net, they have limited access to loans for their children's tuition and fees, and they have nothing to pass on to the next generation...Go to page >
Not an Equal Opportunity Disaster
The subprime mortgage crisis has affected millions of Americans--but women were hit the hardest...Go to page >
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Cell Reports, Volume 2, Issue 4, 766-773, 04 October 2012
The KRAB-ZFP/KAP1 System Contributes to the Early Embryonic Establishment of Site-Specific DNA Methylation Patterns Maintained during Development
Simon Quenneville1, Priscilla Turelli1, Karolina Bojkowska1, Charlène Raclot1, Sandra Offner1, Adamandia Kapopoulou1, 2 and Didier Trono1, ,
1 School of Life Sciences and Frontiers in Genetics Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
2 Swiss Institute of Bioinformatics (SIB), Quartier Sorge - Bâtiment Génopode, 1015 Lausanne, Switzerland
Graphical Abstract
► KAP1 mediates DNA methylation in ESCs ► DNA methylation is G9a and NP95 independent ► DNA methylation does not occur in somatic cells ► DNA methylation follows heterochromatin formation
- De novo DNA methylation is an essential aspect of the epigenetic reprogramming that takes place during early development, yet factors responsible for its instatement at particular genomic loci are poorly defined. Here, we demonstrate that the KRAB-ZFP-mediated recruitment of KAP1 to DNA in embryonic stem cells (ESCs) induces cytosine methylation. This process is preceded by H3K9 trimethylation, and genome-wide analyses reveal that it spreads over short distances from KAP1-binding sites so as to involve nearby CpG islands. In sharp contrast, in differentiated cells, KRAB/KAP1-induced heterochromatin formation does not lead to DNA methylation. Correspondingly, the methylation status of CpG islands in the adult mouse liver correlates with their proximity to KAP1-binding sites in ESCs, not in hepatocytes. Therefore, KRAB-ZFPs and their cofactor KAP1 are in part responsible for the establishment during early embryogenesis of site-specific DNA methylation patterns that are maintained through development.
The genome-wide site-specific methylation of cytosine residues is a key epigenetic contributor to the identity, fate, and transcriptional activity of a cell. This process is tightly regulated during development (Reik, 2007; Saitou et al., 2012). A set of enzymes partakes in the deposition and maintenance of the 5-methylcytosine (5mC) mark. DNA methyltransferase (DNMT) 3a and DNMT3b, in conjunction with DNMT3L, recognize nonmethylated DNA and catalyze de novo cytosine methylation, while DNMT1, recruited at the replication fork by PCNA and NP95 (also known as UHRF1), is responsible for the maintenance of this modification during cell division (Sharif et al., 2007). In contrast, what tethers de novo DNMTs to specific genomic loci remains ill defined, although an association with chromatin changes, notably methylation of histone 3 at lysine 9 (H3K9), has been noted in some circumstances. For instance, the H3K9 mono- and dimethyltransferase G9a appears to be important for de novo DNA methylation of the OCT4 promoter (Feldman et al., 2006) and of murine leukemia virus (MLV)-derived retroviral vectors in embryonic stem cells (ESCs) (Leung et al., 2011), the H3K9 trimethyltransferase SETDB1 was found to recruit DNMT3a at tumor suppressor genes in cancer cells (Li et al., 2006), and the H3K36me3 mark was observed to foster DNA methylation (Dhayalan et al., 2010). This is reminiscent of the interplay between chromatin changes and DNA methylation that has been documented in plants and fungi (Jackson et al., 2002; Tamaru and Selker, 2001).
The first four days of embryonic development are characterized by a genome-wide wave of demethylation. However, this reprogramming spares imprinted loci and is incomplete over sequences derived from retrotransposons such as endogenous retroviruses (ERVs) and long interspersed nuclear elements (LINEs). DNA methylation is then rapidly re-established by the time of implantation. During this window of epigenetic instability, both DNA demethylating and de novo methylating activities are expressed. How their opposite influences lead to specific methylation patterns remains unclear, although the role of cis-acting elements that autonomously determine DNA methylation states during this period was recently revealed (Lienert et al., 2011b; Saitou et al., 2012).
Recent evidence implicates the KRAB/KAP1 epigenetic regulation system in the early embryonic control of DNA methylation. With almost 400 members in both human and mouse, KRAB-containing zinc finger proteins (KRAB-ZFPs) constitute the largest family of transcriptional regulators encoded by higher vertebrates (Emerson and Thomas, 2009). Using their C-terminal array of C2H2 zinc fingers for DNA binding, KRAB-ZFPs recruit their universal cofactor KAP1 (also known as TRIM28 or TIF1beta) via their N-terminal KRAB domain. KAP1 then acts as a scaffold for chromatin-modifying complexes that, notably, comprise histone deacetylases and the histone methyltransferase SETDB1, leading to histone deacetylation, deposition of H3K9me3, binding of HP1, formation of heterochromatin, and transcriptional silencing (Friedman et al., 1996; Moosmann et al., 1997). KAP1 and KRAB-ZFPs were recently shown to silence ERVs and murine leukemia virus in ESCs (Rowe et al., 2010; Wolf and Goff, 2007), and this system was implicated in DNA methylation maintenance of imprints during early development. (Li et al., 2008; Quenneville et al., 2011). Finally, artificial tethering of KAP1 to the body of a lentiviral vector leads to DNA methylation and permanent silencing of an adjacent promoter when allowed to occur during the first few days of embryogenesis (Wiznerowicz et al., 2007).
In this study, we provide formal evidence that the KRAB/KAP1-mediated sequence-specific recognition of thousands of genomic loci in ESCs leads to their DNA methylation, thus ensuring the genome-wide establishment of site-specific epigenetic marks that are subsequently maintained during development.
KRAB/KAP1-Induced De Novo DNA Methylation in ESCs
In order to investigate the role of KRAB-ZFPs and KAP1 in de novo methylation, we first used a lentiviral vector-based system suitable for monitoring both DNA methylation and epigenetic silencing in either mouse or human ESCs. A first set of vectors expressed a Tet repressor (tTR) fused to different parts of ZFP57, the KRAB-ZFP involved in the maintenance of imprinting (Li et al., 2008; Quenneville et al., 2011). The second set contained a PGK.GFP expression cassette downstream of TetO repeats, with or without a 2 kb KvDMR1 imprinted control region (ICR) as intervening sequence. We previously demonstrated that, in this configuration, tTR fusion proteins bind TetO in a doxycycline-preventable manner (Wiznerowicz and Trono, 2003). We first engineered murine ESC lines to produce the various tTR derivatives, before transduction with the TetO.ICR.PGK.GFP vector in the presence or absence of Dox. Three weeks later, we examined GFP expression and ICR DNA methylation, respectively, by fluorescence-activated cell sorting (FACS) (Figure 1A) and pyrosequencing (Figure 1B). In the presence of Dox, all cell lines exhibited high levels of GFP and the ICR displayed low rates (<20%) of CpG methylation. In contrast, when doxycycline was omitted; hence, when tTR.ZFP57 or tTR.KRAB was allowed to bind its TetO target, GFP production was silenced and the ICR was methylated to about 60%. Both GFP repression and tTR-induced ICR methylation were absent in tTR.ZNF-expressing cells, irrespective of Dox exposure, consistent with the KAP1-docking dependence of these processes.
In mouse ESCs, KAP1 deletion leads to growth arrest, differentiation, and ultimately cell death (Rowe et al., 2010). However, human ESCs can maintain pluripotent self renewal after shRNA-mediated knockdown of the master regulator (D.T., unpublished data). We thus tranduced a human ESC line expressing tTR.KRAB with either a control (shEMPTY) or a Kap1-specific (shKAP1) shRNA lentiviral vector that reduced the Kap1 mRNA level to less than 10% that of wild-type (data not shown). We then introduced TetO.ICR.PGK.GFP in these cells, in the presence or absence of Dox. Without the drug, shEMPTY-transduced human ESCs efficiently repressed GFP expression, while this phenotype was almost completely abrogated in the Kap1 knockdown cells (Figure 1C). As a corollary, methylation of the lentivector-contained ICR occurred in control cells, but was prevented by KAP1 depletion (Figure 1C). Together, these results demonstrate that human ESCs support KRAB-induced de novo DNA methylation and confirm the KAP1 dependence of this process on the PGK promoter and KvDMR1 ICR.
To assess the possible impacts of the ICR sequence and of the distance between the KAP1-docking site and the promoter, we examined in parallel an ICR-devoid TetO.PGK.GFP vector, in which the transcription start site is about 2 kb closer to the TetO motif. Pyrosequencing-based examination of six CpGs situated within the PGK promoter revealed that these readily underwent KAP1-recruitment-dependent de novo DNA methylation, whether or not the ICR was present (Figure 1D). If anything, 5mC deposition at the PGK promoter was higher in the presence of the intervening sequence, demonstrating not only that DNA methylation could spread at some distance from the KAP1-docking site, but also that the KvDMR1 ICR may contain methylation-promoting elements.
Differential Kinetics of KRAB/KAP1-Induced Transcriptional Repression and De Novo DNA Methylation
With a similar system, we previously demonstrated that transcriptional repression is driven by the deposition of repressive histone marks at the promoter and initially does not reflect DNA methylation, which only later establishes a secondary state of irreversible silencing (Wiznerowicz et al., 2007; Wiznerowicz and Trono, 2003). KAP1-mediated GFP silencing was immediately apparent in our system (Figure 2A), confirming that histone-mediated transcriptional repression proceeds very rapidly. To determine the underlying kinetics of KRAB/KAP1-induced DNA methylation, we examined 5mC deposition at the CpG dinucleotides contained in both the ICR and PGK promoter in murine ESCs at a series of time points after transduction with the TetO.ICR.PGK.GFP vector (Figures 2B and 2C). At day 3, levels of DNA methylation were extremely low over both sequences. By 1 week, they raised to about 20%, and they stayed at this level if Dox was present in the culture. If tTR.KRAB was allowed to bind the TetO motif, CpG methylation progressively increased to reach more than 80% at both the ICR and the PGK promoter within 3 weeks.
G9a and NP95 Independence of KRAB/KAP1-Induced De Novo DNA Methylation
It has been reported that G9a histone methyltransferase is needed for methylation of an MLV-derived retroviral vector in murine ESCs (Leung et al., 2011), and it was proposed that NP95 plays a similar role for the CMV immediate early promoter (Meilinger et al., 2009). To find out whether these findings related to KRAB/KAP1-dependent events, we stably expressed tTR.KRAB into murine ESCs knocked out for either one of these factors (Dong et al., 2008; Sharif et al., 2007) and transduced the resulting cell lines with the TetO.ICR.PGK.GFP lentiviral vector. In both settings, KAP1-induced GFP repression was fully preserved and Dox-controllable ICR methylation was maintained. Indeed, both baseline and induced ICR methylation levels were higher in G9a knockout than in control ESCs, whereas both were lower in NP95−/− cells, as anticipated from a defect in the maintenance of this modification (Figure 2D). Because the deletion of SETDB1 rapidly leads to ESC growth arrest and death, we could not test the importance of this known partner of KAP1 (Matsui et al., 2010) in KAP1-induced DNA methylation.
Spreading of KAP1-Induced DNA Methylation to Nearby CpG Islands
In order to assess the impact of KAP1 genomic recruitment and patterns of DNA methylation in ESCs, we used a combination of publically available and in-house ChiP-seq and CpG methylation data, for both murine and human ESCs (Lienert et al., 2011a; Meissner et al., 2008; Stadler et al., 2011). Considering the very strong levels of overall DNA methylation of the genome, we concentrated our analysis on so-called CpG islands, which are highly enriched in CpG dinucleotides and are typically hypomethylated. We first classified CpG islands in three subsets according to their DNA methylation status in murine ESCs: low (less than 20% methylation), intermediate (between 20% and 80%) and high (more than 80%) (Figure 3A). Of the total CpG island pool, 89% was found in the low methylation subset, whereas only 8% and 3% exhibited intermediate and high levels of this modification, respectively. However, when CpG islands located less than 5 kb (591) or less than 1 kb (324) from a KAP1-binding site were examined, the fraction with low methylation levels decreased to 70% and 60%, respectively Correspondingly, the proportion of CpG islands with intermediate and high levels of DNA methylation increased, reaching 27% in intermediate and 12% in highly methylated categories for islands situated within 1 kb of a KAP1-binding site (p < 10−15). To further examine the distance at which KAP1 can promote the methylation of a CpG island, we performed a reverse analysis, in which the average methylation levels of CpG islands located at given distances from a KAP1-binding site were determined (Figure 3B). CpG islands coinciding precisely with a KAP1 site (0 kb) had the highest average methylation score, while a relatively rapid decrease was noted afterward, CpG islands situated between 8 and 10 kb from a KAP1 site displaying profiles no different from a random pool of these sequence elements. These results, obtained on the basis of the analysis of CpG-rich sequences, were confirmed when elements identified as CpG islands were examined in the mouse genome through biochemical purification (Figure S1). In human ESCs, we used reduced representation bisulfite sequencing (RRBS) data (Meissner et al., 2008) and similarly found that levels of methylation of CpG islands were inversely proportional to their distance to a KAP1-binding site (Figure 3C). Remarkably, in both murine and human ESCs, a strong enrichment in CTCF-binding sites was seen in the space separating KAP1 landing sites and unmethylated KAP1-close CpG islands, compared with their methylated counterparts (Figure 3D). In this setting, CTCF may thus act as a barrier element, or directly counteract the deposition of methylation marks, as previously suggested (Stadler et al., 2011).
KRAB/KAP1-Induced Repression and DNA Methylation Patterns in Adult Tissues
We previously observed that KRAB/KAP1-induced transcriptional repression is reversible when triggered in somatic cells (Wiznerowicz and Trono, 2003). This suggested that, in this setting, docking of the silencing complex does not lead to DNA methylation. To ascertain this point, we introduced the TetO.ICR.PGK.GFP vector in tTR.KRAB-expressing NIH 3T3 cells and primary mouse embryonic fibroblasts (MEFs). In either cell type, Dox-controllable GFP repression was fully operational, but no significant methylation of the ICR could be detected (Figure 4A). DNMT3a, DNMT3b, or DNMT3L overexpression in NIH 3T3 (Figure S2) did not trigger any increase in KRAB/KAP1-induced DNA methylation, indicating that other factors account for the ESC specificity of this process. To confirm the general implications of this finding, we examined a possible relationship between the methylation status of CpG islands in the mouse liver, as previously determined by RRBS (Meissner et al., 2008), with that of KAP1-binding sites mapped in this organ by ChIP-seq (Bojkowska et al., 2012). There was no correlation between these two parameters (Figure 4B). Instead, the likelihood that a CpG island was found to be methylated in the liver was conditioned by its proximity to a KAP1-binding site in ESCs, a relationship that was also observed in three other somatic cell types (Figure 4C). Thus, whereas KRAB and KAP1 do not govern DNA methylation in differentiated tissues, site-specific methylation marks established by this system in early embryogenesis are maintained through development.
While KRAB/KAP1-induced DNA methylation is expected to be functionally beneficial at ERVs and ICRs, the resulting permanent inactivation of its other targets, such as promoters or enhancers of cellular genes, could be problematic. In that respect, our genome-wide exploration revealed interesting features. Methylated CpG islands were on average positioned farther from transcriptional start sites (TSSs) than their unmethylated counterparts, suggesting that they functioned in their majority as enhancers rather than promoters (Figure 4D), while the few TSSs (26) close to these CpG islands were transcriptionally inactive (Figure S3). Also, KAP1-close CpG islands were often linked to genes active during the earliest phases of embryogenesis and in extraembryonic tissues; that is, not likely to suffer from the functional inactivation of cis-acting transcriptional activators in inner cell-mass- or epiblast-derived ESCs (Figure 4E).
The present study demonstrates that the site-specific KRAB/KAP1-mediated induction of heterochromatin in ESCs can lead to de novo DNA methylation and suggests a mechanism for the establishment of this epigenetic mark during early embryogenesis at many genomic loci found to be methylated in adult tissues. Our data support a model in which, at KRAB-ZFP-targeted sites, KAP1 and associated chromatin modifiers, including DNA methyltransferases, directly counter the DNA-demethylating forces that are active across the genome during this period. This process is particularly relevant for endogenous retroviruses, which constitute primary targets of KRAB/KAP1-mediated silencing and most likely drove the positive selection undergone by KRAB-ZFP genes during evolution. Our data suggest that the sequence-specific recognition of ERVs by KRAB-ZFPs, most of which are expressed in ESCs but shut down shortly thereafter (unpublished data), leads to their permanent silencing by DNA methylation, alleviating the need for continuous expression of their cognate trans-repressors. Although emanating from the same general mechanism, the control of imprinted loci represents an interesting variant, since the responsible KRAB-ZFP, ZFP57, recognizes only the methylated version of a motif present in all ICRs (Quenneville et al., 2011). This elegantly ensures that methyl marks are preserved on the imprinted allele during the wave of reprogramming that takes place after fertilization, while avoiding their instatement on the nonimprinted allele.
On the basis of the analysis of CpG islands at least, the spreading of KAP1-induced DNA methylation was limited in ESCs, averaging no more than 3 to 5 kb from the KAP1-docking sites. While this could reflect the rapid exhaustion of a putative heterochromatin-propagating activity, the local recruitment of counteracting factors such as CTCF may play a role. Our observation of limited KAP1-induced heterochromatin spreading is also consistent with the description of DNA methylation occurring in mouse ESCs over the 5′ long terminal repeat and genomic flanking sequences of a retroviral vector, but not over its 3′ regions (Berwin and Barklis, 1993). Such short-range propagation also explains how KRAB/KAP1 might be involved in controlling tens of thousands of endogenous retroelements during early embryogenesis without triggering the complete methylation-mediated blockade of the host genome.
In 3T3 or primary murine embryonic fibroblasts, KRAB/KAP1-mediated induction of heterochromatin was not followed by DNA methylation. This is in agreement with our previous observation that the repression of a promoter through the doxycycline-controllable nearby docking of KRAB/KAP1 is fully reversible in a wide variety of somatic cells, whether in tissue culture or in vivo (Wiznerowicz and Trono, 2003). These data are also consistent with our finding that the methylation status of CpG islands in the mouse liver is conditioned by their proximity to KAP1-binding sites in ESCs, not in hepatocytes. That epigenetic changes triggered in differentiated tissues by the recruitment of KRAB/KAP1 at specific loci be histone- rather than DNA-based explains how this system can regulate such highly dynamic processes as lymphohematopoietic differentiation, B cell activation, hepatic metabolism, and management of behavioral stress (Bojkowska et al., 2012; Santoni de Sio et al., 2012; Jakobsson et al., 2008). Nevertheless, our finding of such a fundamental difference in the outcome of KRAB/KAP1-mediated repression between ESCs and differentiated tissues warrants a characterization of the molecular complexes recruited at KAP1-binding sites in either setting. This effort may not only shed light on the mechanisms involved in conditioning the establishment of permanent epigenetic marks at specific loci under physiological circumstances, but also point to the kind of dysregulation driving their aberrant instatement in pathologies such as cancer.
Experimental Procedures
Cell-Based Assays
All cell lines were cultured under standard conditions. Lentiviral vector was used with a mutiplicity of infection (MOI) of 50 and 10, respectively, for tTR-fusion expression vectors and 36 and 10 for TetO-containing reporter vectors, into mouse (ES, MEF, and NIH 3T3) and human (ES) cells. Human ESCs transduced with control or Kap1 shRNA lentiviral vectors were selected with hygromycin (see Extended Experimental Procedures). DNA was extracted and bisulfite conversion was performed, followed by PCR (primers are available in Extended Experimental Procedures) and pyrosequencing performed according to standard protocols.
In Silico Analyses
Data from different public data sets (GEO IDs GSE28247GSE11034GSE30280GSE31183) were used to examine whole-genome bisulfite sequencing, RRBS-, and CTCF-binding sites in mouse ESCs. Mouse and human CpG islands and human RRBS data were obtained from the ENCODE project (ENCODE Project Consortium, 2011). KAP1 ChIP-seq data were from our previous work (Bojkowska et al., 2012; Rowe et al., 2010). Data were analyzed with the use of the "ChIP-seq on-line analysis tools" package (http://ccg.vital-it.ch/chipseq/), the GREAT website (http://bejerano.stanford.edu/great/public/html/) (McLean et al., 2010), and in-house shell scripts using h19 and mm9 assemblies. Fisher's exact test was used to determine statistical significance.
The ICR sequence was first PCR amplified using 5′-GATTTTTATGGTGAGGTTTTA-3′ and 5′-CAAAACCACCCCTACTTCTAT-3′ and blunt cloned into pRRL.TetO_PGK_GFP vector between TetO repeats and PGK promoter in a EcoRV site. The sequence 5′-GAGTATTTAGGAGGTATAAGAATT-3′ was then added between the TetO and ICR to facilitate the vector specific bisulfite PCR. The shRNA vectors were generated from a pLKO backbone. The puro resistance gene was replaced for a hygromycin resistance gene. The hairpin targeting human KAP1 gene (targeting: GACCACCAGUACCAGUUCUUA) was cloned in EcoRI/AgeI sites. All the lentiviral vectors were produced and tittered as previously described (Barde et al., 2010).
Extendend Human ESC Cultures and Experimentations
Undifferentiated H1 human ES cells (Thomson et al., 1998) were used following the Swiss Federal guidelines and maintained on BD Matrigel (BD Biosciences, as recommended by the manufacturer) in mTeSR1 medium (Stemcell technologies). For transduction, hES were detached with TrypLE Express (Invitrogen) and maintained for 24hrs with the Rho-associated kinase (ROCK) inhibitor Y-27632 (Ascent Scientific) (Watanabe et al., 2007). Cells were transduced with pLV.ttrKRAB and pLV.TetO.GFP or pLV.ICR .TetO.GFP vectors (Quenneville et al., 2011) at a multiplicity of infection of 36 and 10 respectively. When indicated cells were previously transduced with a control pLKO.1.empty or a pLKO.1.shKAP1 lentivector (SIGMA, TRCN0000018002). The KAP1 knock-down was verified, after hygromycin selection, by quantitative RT.PCR during the experiment. Maintenance of the pluripotent state of the transduced cells was verified by FACS analysis using the BD human pluripotent Stem Cell Transcription Factor Analysis kit.
DNA was extracted using from approximately 100 000 cells using DNeasy Blood & Tissue Kit (QIAGEN). 1ug of DNA was then used for bisulfite conversion using EpiTect Bisulfite kit (QIAGEN). Pyrosequencing was performed using Pyro Gold reagent (QIAGEN). The ICR PCR product was obtained by nested PCR. First, a vector specific PCR was performed using 5′-GAGTATTTAGGAGGTATAAGAATT-3′and 5′-CTACCTCAACAATTAAATCACTTCC-3′.primers. The 600 bp product was gel purified and second PCR was produced using 5′-GGGAAAAGAAGAGTGTTGAAGAAAAATTG-3′ and 5′-biot-CTACCTCAACAATTAAATCACTTCC-3′ followed by gel purification. Sequencing was then performed with 5′-TTAAAAAAAAATGTTGAGAAGTTAA-3′ sequencing primer. PGK methylation was evaluated by amplification with 5′-AGATTAGGATGGGTATTATTT-3′ and 5′-biotAATATAAACCCTATTCCTACCC-3′. DNA was gel extracted and sequencing was performed with 5′-GTGGATTTTTTTGGGGAGAGAGG-3′ sequencing primer.
We thank Dirk Schuebeler (Friedrich Miescher Institute) for helpful discussions, and Matthew Lorincz (University of British Columbia) and Haruhiko Koseki (Riken Center for Allergy and Immunology), for the gift of the G9a and NP95 knockout ES cells, respectively. Part of the computations were performed in the Vital-IT facility (www.vital-it.ch) of the Swiss Institute of Bioinformatics. This work was supported by grants from the Swiss national Science Foundation and the European Research Council.
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Publication Information
Received: April 18, 2012
Revised: July 18, 2012
Accepted: August 14, 2012
Published online: October 4, 2012


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CINCINNATI, OH (FOX19) - The University of Cincinnati has reached the halfway point in its most ambitious campaign ever - raising $1 billion by the year 2013.
Proudly Cincinnati: Tower of Strength, Rock of Truth is UC's vision to become the finest urban research university in the United States.
Through Proudly Cincinnati, alumni, faculty, staff and friends of UC provide essential monetary support. Their gifts support private scholarships, fellowships, co-op opportunities and more to help transform students' lives and enable them to do great things for their communities and the people they serve after graduation. UC has passed the halfway point of its fund-raising goal, but it still has a challenging road ahead.
Only two percent of public universities have even attempted such a feat – and UC launched the public phase of its campaign in 2009, in one of the worst economic periods this country has ever known.
The university has already used Proudly Cincinnati funds to build facilities designed by signature architects, build nationally and internationally ranked programs and record record-breaking support for UC's research.
According to U.S. News and World Report, there was an estimated 22.5 percent drop in endowment funds between July 2008 and Dec. 2008. These private gifts are used for funding scholarships, keeping college costs low, improving facilities and strengthening ties to student life and surrounding communities.
UC's new president, Dr. Gregory Williams, has taken over campaign after former president Nancy Zimpher, who launched the campaign, left to become chancellor of the State University of New York (SUNY). Williams holds the record for the largest individual gift ever received by Ohio State University and attracted a number of high-profile donations during his tenure at City College of New York.
"President Williams has a bold vision for the future of higher education," said UC Trustees Chair H.C. Buck Niehoff, who led the effort to appoint UC's newest president. "He is a noted scholar with a remarkable record for building enrollment while ensuring academic excellence and diversity. He also has a substantial background in leading successful fundraising efforts. We were looking for that kind of symbiosis between vision and proven excellence, to inspire university leadership and help meet the aggressive goals established by the Proudly Cincinnati campaign."
Williams helped launch a celebration of Proudly Cincinnati on Tuesday by announcing the campaign has officially passed the halfway point with approximately $638 million in donations to-date. In addition, he shared his vision of the future of the campaign by issuing a challenge to the UC community that aims to make Proudly Cincinnati an indelible part of the fabric of the university's campus.
The university's student community took Williams' challenge seriously by introducing a new component to the Proudly Cincinnati campaign, Proudly Pennies. UC students pledged to make every penny count by instituting a campus-wide effort to raise 1 billion pennies – the equivalent of $10 million.
"We as students are an integral part of the University of Cincinnati community, and we believe it is our responsibility to help mobilize support of this great university," said Tim Lolli, UC Student Body President. "Proudly Pennies is the student body's contribution to making this great university even better."
The addition of Proudly Pennies to the university's $1 billion campaign isn't the only new idea the foundation recently brought to the table. The foundation's leadership has launched a new Web site that makes it easy for participants to invite personal and professional networks to contribute to the campaign; and faculty and staff volunteers who encourage participation among their colleagues. The results have been impressive: in 2009, the campaign saw a 22 percent increase in the number of faculty/staff contributors, and more than $1.3 million in contributions over the previous year.
Visit http://www.uc.edu/proudlycincinnati/default.html for more information.
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text: Changes: Template:Future game Edit Back to page Revision as of 02:17, May 10, 2006 (view source)Thai420 (Talk | contribs)m← Older edit Latest revision as of 19:46, June 13, 2006 (view source)Thai420 (Talk | contribs) m Line 7: Line 7: |} |} <noinclude> <noinclude> − [[Category: Templates]] + [[Category: Templates|Future Game]] </noinclude> </noinclude> ---- ---- Latest revision as of 19:46, June 13, 2006 This article or section contains information about a computer or video game under development. It is likely to contain information of a speculative nature, and the content may change dramatically as the game's release approaches and more information becomes available. Related Categories Category: Templates


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marvingal 5pts What's the deal? Lots of games will not come up. Some have no hint or clue as to what you are to do. Give us a break!
kathy_schoen 5pts I too am getting a black box with 100% at the bottom and Shape Sifter won't load. Help!
Sunckr55 5pts I've been playing this game for a long time and all of a sudden I can't get it to advance any further then when 100% comes up at the bottom of a black screen. Are others having problems? Shape Shifter.
crllbrown 5pts This new set up is ridiculous. Please go back to the side listings of games by names. i do not need pictures of recently played or favorites. Too confusing
HafidMomni 5pts I cannot log in to candy crush. There is a screen blocking my log in screen العاب بن 10 جديدة ben 10 bike
vickiew1998 5pts Did you ever find out why Shape Shifter will not advance passed the 100% at the bottom of the screen? It just started happening to me yesterday.


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Watch It TODAY
On DVD
Superb drama of resistance fighters in Denmark going against the occupying Nazis in WW II.
What a thriller! Complex; well acted; more realistic war movie. Loved the stylized version with the news reals; the shadows; the look on a little boy's face; the fear on all. Trying for the truth isn't always easy. Really showed the complexiteis of war.
Netflix - Try for Free
Instantly watch TV episodes and movies via the Internet on your computer or TV. 1 month FREE!


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Rainbow Brite! Lydia Hearst for Vixen Magazine
Loving the hair
The hair!
Would LOVE TO MAKE THAT HAPPEN! #Colors #awesomeness
rainbow brite
I just found this photo fascinating. It intrigued me, and I'd like to see if I could use this as inspiration
Look At This -____- Maybe Its FIT On Me LOL =))
wow I would love to have her hair for one day.


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The Walking Dead
Series: Image Comics The Walking Dead
artist : Charlie Adlard
scenario : Robert Kirkman
volume: 96
publisher: Image Comics
publish date: 02-02-2012
coloring: black/white
product type: digital comic/eComic (Ongoing Series)
"THE ROAD TO ISSUE ONE HUNDRED STARTS HERE AS ""A LARGER WORLD"" CONCLUDES! Will Rick's community join the network? Will they enter into an era of unprecedented peace and prosperity - or has Rick ruined that for everyone? Has he now made more, deadlier enemies for them to deal with?"


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It is a good and clean hotel. They offer very good price for Anacapri. The location is ok - it is not the best, but not bad at all. Rooms were ok - everything was working, but it is quite outdated. Breakfast is terrible. Juice are not juice, there is no choice, some dry cheap pastries.... Coffee is awful. If... More
- Also Known As:
- Bussola Di Hermes Hotel
- Bussola Di Hermes Anacapri
- Hotel Bussola Island Of Capri/Anacapri, Italy
- Official Description (provided by the hotel):
- A wonderful welcoming hotel, in neo classic style, rooms are furnished with all comfort, some with private terrace overlooking the sea. ... more less
- Reservation Options:
- TripAdvisor is proud to partner with Booking.com, HostelWorld, Otel, Travelocity, HostelBookers, TripOnline SA and Expedia so you can book your Hotel Bussola reservations with confidence. We help millions of travelers each month to find the perfect hotel for both vacation and business trips, always with the best discounts and special offers.


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Marketing and Consumer Research
Market ResearchUSDA. Foreign Agricultural Service.
Supplies U.S. exporters with a number of resources and tools to obtain up-to-date market information, including an array of resources regarding market research and a database of U.S. agricultural exports and imports.
Economic Research Service TopicsUSDA. Economic Research Service.
Analyzes and collects authoritative resources on a variety of agricultural topics that have become the focus of study at the Economic Research Service. Provides links to recent ERS research developments, readings, data, questions and answers, and an assortment of other ERS products and services addressing the issues. Presents resources by topic, including by country and commodity.
Quality StandardsUSDA. Agricultural Marketing Service.
Provides full-text access to the quality standards for cotton, dairy products, fresh fruits and vegetables, livestock, nuts and speciality crops, poultry and eggs, processed fruits and vegetables, and tobacco.
Global Agricultural Information NetworkUSDA. Foreign Agricultural Service.
Provides access to a searchable database of reports by FAS agricultural attachés stationed around the world. Includes a wide range of reports covering foreign import regulations, agricultural commodities, current agricultural production, and country-specific exporter guidance.
Amber WavesUSDA. Economic Research Service.
A print and online publication covering the economics of food, farming, natural resources, and rural America. Published five times a year since February 2003. Includes access to all back issues.
AgEcon SearchUniversity of Minnesota.
A searchable database of full text copies of reports from over 100 U.S. and international organizations and universities on agribusiness, food supply, policy issues, agricultural trade, and economic development.
Checkoff Programs Reading RoomUniversity of Arkansas. National Agricultural Law Center.
Links to statutes, regulations, case law, and congressional reports on the research and promotion programs tied to various agricultural commodities, and several commodity boards.
Market Research LibraryUSDOC. U.S. Commercial Service.
A searchable database of research and reports addressing business in more than 120 countries and 110 industry sectors. Register for e-Alerts from the Commercial Service.
University of Wisconsin Center for CooperativesUniversity of Wisconsin.
Studies, promotes, and researches cooperative action as a means of meeting people's economic and social needs. Provides links to current co-op news, to agricultural co-ops, and to related resources by topic and sector.
Access links to Web sites with guides for small businesses, information on advertising and marketing, information on international trade and more.
Market ResearchExport.gov.
Provides guidance on how and where to conduct market research in a step-by-step approach. Includes Webcasts on business exporting, and links to a range of reports, studies, statistics, and resources.
Marketing and Trade -- Market ResearchUnited States Department of Agriculture.
Links to comprehensive market and trade data research and reports and supplies numerous databases searchable by product or country.


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Is this you?
Claim profile
Claim profile
Dr. Douglas Richard Nelson DDS is a male dentist and practices in Family Dentistry.
Dr. Douglas Nelson has
1 office location.
3521 Commerce Ct
Appleton, WI 54911
Phone Number
Locations and availability (1)
3521 Commerce Ct
Appleton, WI 54911
Phone Number
Locations and availability (1)
License & Identifications
A medical license is required for a doctor to practice medicine in a particular state. Requirements vary by state but most require, at a minimum, post-graduate training in the doctor's specific specialty. An NPI number is a national identifier unique to an individual health care provider and is managed by the Center for Medicare & Medicaid Services (CMS).
Learn more about Dr. Douglas Nelson:
View the full profile to get information on:
- Qualifications
- What's important to you
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Patient Reviews
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be the first!
Accepted Insurance Plans
Dr. Nelson accepts these dental insurances in at least one office:
- Delta Dental - 1 plan
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- Additional Information
- Where does Dr. Douglas R. Nelson practice?
Dr. Douglas Nelson practices Family Dentistry near Appleton, WI.
See Appleton Dentists.


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We spent two wonderful nights in this lovely home high above Russell. The rooms was impeccable, the deck was inviting and comfortable and the hostess was so gracious. She not only offered us a fantastic breakfast but also filled us in on some local history about the Maori people. We left feeling very pampered!
- Also Known As:
- Pukematu Hotel Russell
- Pukematu Lodge Russell, New Zealand - Bay Of Islands


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Beautifully said, Wes (as is the case with virtually everything you write). Thank you.jason
Not an Amusing Post
However, when I was just downstairs attempting to photograph said throngs, a red-faced man tried to grab my camera out of my hands, while screaming (I swear), "Have you no decency, sir?"
It seems GuangZhou is a destination for American families adopting Chinese babies and a just-minted grandpapa thought I was intruding on his newly-forged family's privacy. Well, if I thought he was red-faced before the camera-grabbing incident, I didn't know the half of it.
Just for the record, I believe that happy families are the ones that choose one another. Sometimes you even pick the one you were born into—but it's far from your only choice. And every time you make the choice to include someone in your group of loved ones, you've changed the world for the better. Good luck, folks.
Loudspeakers Amplification Digital Sources | Analog Sources Accessories Featured | Music Columns Features | Show Reports | Show Reports |
Recommended Components Blogs Latest News Community |
Shop Resources Subscriptions |


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Nominations are in for the 2014 MTV Movie Awards
Watch Sunday, April 13
5 Things to Know About Nathan For You's Nathan Fielder
Watch now!
Achy Breaky Part 2 is a thing and now the world makes sense
Watch now!
Add these new songs to your playlist ASAP
Miley, Charlie and more!
January 25th, 2013
After tweeting about his involvement in the Scream and Shout Remix, Waka Flocka Flame's verse, along with Lil Wayne and Diddy, has now leaked online. The original line up, including Will.i.Am and Britney Spears, still appear on the revamped release of the track, though this time the song features a much darker feel to it. The track was produced by Hit Boy, who is rumoured to be one of the main producers on Britney's upcoming album.
PerezHilton.com is reporting that the remix of Scream and Shout will soon be heard on TV screens across North America with plans to feature the track on a commercial for Beats By Dre Headphones to air during next month's Super Bowl. Britney and Destiny's Child in one Super Bowl? Fine. I'll watch the dang football game.
Tags: Britney Spears, diddy, lil wayne, Waka Flocka Flame, Will.i.Am.
Posted on Friday, January 25th, 2013 at 4:47 pm by Allison and is filed under MuchRadar, Music & Videos.


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"Today is Ken birthday and also Simon's birthday.
Let's sing!!
Social Networking for Fashion Doll Lovers
Outfits made based on the traditional Panamanian outfit called Pollera.
The cross-stitched embroidery is done by hand and I also made the "jewelry" and the head ornaments based on the traditional ones used in Panama.
Add a Comment
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Certified Environmental, Safety and Health Trainer
Quick Jumps: Eligibility and Examination + Review and Study Sources
The Certified Environmental, Safety and Health Trainer
The Certified Environmental, Safety & Health Trainer (CET) is a certification held by those with experience and expertise in the developing, designing, and delivering safety, health and environmental training.
The CET:
- Measures an individual's knowledge of the theory and practice of basic adult education
- Confirms knowledge and experience in the SH&E specialty area(s) in which they teach
To retain the CET certification, individuals must:
- Pay an annual renewal fee
- Meet Recertification requirements
The Certified Environmental, Safety and Health Trainer (CET) certification is accredited by the Council of Engineering and Scientific Specialty Boards (CESB).
Eligibility and Examination
To be eligible for the CET, candidates must have a high school diploma or GED, hold a BCSP-approved SH&E credential, and have conducted at least 270 delivery hours of teaching or training in any SH&E specialty.
To achieve the CET certification a candidate must meet all of the eligibility requirements and pass the examination.
The eligibility period to take the CET examination is one (1) year from the application approval date.
CET Review and Study Sources
Candidates preparing for the CET examination may use information about the examination's build as a guide to study material. Of particular interest are the CET Examination Blueprint and the CET Examination References. Additionally, BCSP has created a Library of Safety Practice containing the most up-to-date source material for every domain on the exams.


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Mama, I Want to Sing illustrates the story of many great performers who learned their craft in the church choir. The Doris in Mama, I Want to Sing (fashioned after Vy's own sister Doris Troy) stepped out the church choir, performed during Amateur Night at the Apollo, migrated to London where she performed and provided a gospel and soul underpinning for groups such as the Beatles, and eventually performed in Mama, I Want to Sing in the role of her own mother. In Mama, I Want to Sing: The Next Generation, Ahmaya Knoelle Higginson (the daughter of Vy Higginsen and Ken Wydro) performs in the role of her aunt, Doris Troy. Mama, I Want to Sing: The Next Generation also features selected performers from Vy Higginsen's Gospel for Teens Choir. Gospel for Teens is the award-winning choir recently featured on CBS' 60 Minutes, Good Morning America, and ABC's World News. Higginsen created Gospel for Teens to pass the legacy of gospel music on from generation to generation.
Proceeds benefit the groundbreaking, award winning Mama Foundation program, Gospel for Teens. |
MAMA, I WANT TO SING: Saturdays at 5:00 p.m. TICKET PRICES $35 general admission Individual tickets, theater parties, group sales and discounts. BOX OFFICE Purchase your tickets at The Mama Foundation for the Arts at 149 West 126th between Adam Clayton Powell, Jr. and Malcolm X Boulevards (Lenox and Seventh Avenues) weekdays between 10 a.m. and 7 p.m. THEATER Dempsey Theater The new Dempsey Theater is centrally located in Harlem between Adam Clayton Powell, Jr. and Malcolm X Boulevards (Lenox and Seventh Avenues). The theater has been renovated with state-of-the-art technology for light and sound. Handicapped accessible


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Jeremy Arlo Lincoln
Position: DB
Height: 5-10 Weight: 180 lbs.
Born: April 7, 1969 in Toledo, OH
College: Tennessee (school history)
Drafted by the Chicago Bears in the 3rd round (80th overall) of the 1992 NFL Draft.
Weighted Career AV (100-95-...): 22 (4287th overall since 1950)
Our primary support comes from users like you. Sponsor this page for $5. Your message will replace this ad.


text:
Computing Services is pleased to announce training opportunities for
the Microsoft Office 2010 program suite. These training workshops will
address Word, Excel, PowerPoint, and Outlook.
Each program will be broken down into an "Introductory" class and
a "Advanced" class. The introductory class will cover the fundamentals
of each program along with new changes. The advanced class will extend
the introductory class to cover more complex features. The training
classes will be provided as a half day course with the introductory
classes on one day and the advanced classes on a separate day.
Special Note: For Fall 2012 we will be offering the 'Advanced' classes
only due to high requests for the more advanced classes
versus the introductory. However, if you desire the
introductory material please reference the documentation
we have developed for you on our Microsoft Office website
or contact the HelpDesk requesting what introductory class
you are interested in and a technician will contact you.
If you are still running Office 2007 and are interested in upgrading to
Office 2010, please send a request to the Help Desk (and include your
CSID# in the request).
In addition to these workshops, please note that our Microsoft Office web
site (http://www.clarion.edu/260188/) includes a variety of self-paced
training resources. The full training manuals from the workshops and
associated quick reference guides are also available on the site.
If you are interested in registering for one or more
of the below classes please fill out the Registration Form
Clarion Campus
Still 103 - LTC Lab
Course ID |
Course Name |
Date |
Time |
CL-Word II-F12-01 |
Microsoft Word II |
November 05, 2012 |
9:00am - 12:00pm |
CL-Excel II-F12-01 |
Microsoft Excel II |
November 07, 2012 |
9:00am - 12:00pm |
CL-Outlook II-F12-01 |
Microsoft Outlook II |
November 09, 2012 |
9:00am - 12:00pm |
Microsoft PowerPoint II |
November 15, 2012 |
9:00am - 12:00pm |


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The most I've stayed so far is 5 days.
I'll be there 7 Days for Mousefest time.
As soon as I pass under that Walt Disney World entrance sign, the outside world to me is gone
In Sept. I went on a really long Honeymoon surrounded by Disney Magic. My Wife and I spent 8 days in the parks followed by a 3-day Cruise followed by 1 more day to catch Mickey's Not So Scary and the reopened Haunted Mansion. About 6 days in I had lost all sense of time and place. The outside world no longer existed.
It was a couple of screaming babies away from perfect.
What I want to know is what's the longest YOU ever stayed? Did you experience the same wonderful disconnect from reality? Is there a point where you realized you booked TOO LONG a trip and find yourself just going through the motions?
BTW, by the end of my trip I was already planning our return.
The most I've stayed so far is 5 days.
I'll be there 7 Days for Mousefest time.
As soon as I pass under that Walt Disney World entrance sign, the outside world to me is gone
Next WDW Trip? Who knows, things are tough all over.
The longest we stayed at Disney was 16 days in December 2005. Actually, for us, as soon as we get on the plane (one of many traveling from Asia this last trip...before that it was South America) the outside world is gone. Not once did we feel we overstayed our time. I would have loved to have stayed another 16 days on top of that. We can never get enough of Disney! And we are always planning our next trip. We went in July this year and it will be quite a long time before we get back there again...December 2008/January 2009. 438 more days!
Our longest stay has been 13 days/12 nights staying at ASMo! This last trip we were only there for 8 days/7 nights at the Wilderness Lodge and I have to say it was very difficult fitting in everything we wanted to do!
the longest we've ever been was 8 days.
Tiffany~ºoº ~ D23 member
Sufferer of Disney Vacation Depression
97'~French Quarter, 99'~CBR, 01'~Movies, 03'~Music/PORriverside/DCL, 05'~POP, 06'~Movies, 08'~Movies, 09'~Disneyland/ Embassy Suites Irvine/ 10'~Music, 12'~LBV Best Western Disney View
my first time was 2 days... sad i know..
this time will be at disney from monday to saturday but who knows other than that
All Star Sports July 2006
All Star Movies October 2007
Coronado Spring February 2010
Pop Century October 2010
All Star Movies September 2011
Pop Century September 2012Chrissy
We stayed for 11 days at teh carribean beach back in 2003. One of the best vacations I ever had. Just wandred around, park hopped, slept late stayed out late, the world disappeared. it was Bliss.
Veri S&B LLC WHAFTFCOL
SITTM, No Retreat, No Surrender!
Our Highly Trained Experts Are Always Prepared To "Assist" You.
5 days has been the longest
Summer '83-Off Site
Dec '95- Shades Of Green
March '03-All Star Movies
March '06-All Star Movies
October '07-POFQ
March '10-POFQ
March '13 POFQ
June/July '14-not sure where yet!
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Last updated on 03/12/14 UTC
Branchville Overview
Coldwell Banker Helps You Learn More About Branchville, New Jersey Real Estate
Branchville, New Jersey is located in Sussex. Nearby cities and towns include Crandon Lakes, Lake Mohawk, Newton, Ross Corner and Sussex. Branchville is a rural community with a population of 840. The median household income in Branchville is $63,181. 58% of residents are married and families with children reside in 28% of Branchville households. Half the population of Branchville commutes 19 minutes or more to work, with 86% of residents holding white collar jobs and 14% residents holding blue collar jobs.
The median age of homes in Branchville, NJ is 63 years, with 58% of those homes owned, 35% rented and 5% not occupied. In the previous year, 0 Branchville properties were sold. The median sale price of a home in Branchville in the previous year was $194,950. Find a Coldwell Banker real estate agent in Branchville, New Jersey today.
Homes for Sale around Branchville
26 Broad Street
Branchville, NJ 07826
3 Beds, 1 Baths -
16 Mattison Rd
Branchville Boro, NJ 07826
3 Beds, 2 Baths -
2 Holly Dr
Hampton Twp., NJ 07860
4 Beds, 2 Baths -
64 E Shore Culver Rd
Frankford Twp., NJ 07826
4 Beds, 2 Baths -
54 Church Rd
Hampton Twp., NJ 07860
16 Mattison Rd
Branchville Boro, NJ 07826
3 Beds, 1 Baths -
198 Hwy 206
Frankford Twp., NJ 07826
3 Beds, 2 Baths -
66 Phillips Rd
Frankford Twp., NJ 07826
2 Beds, 1 Baths
New Jersey Demographics Data
Branchville Demographics Data
New Jersey Real Estate Statistics
Branchville Real Estate Statistics
Branchville Real Estate Offices
Real Estate Careers Near Branchville
Looking for a change?,
Coldwell Banker Pinnacle Realty |
Milford, PA
Coldwell Banker Pinnacle Realty, located in Milford, PA Looking for a change? We are looking for licensed sales associates in our busy office.
Sales Associate,
Coldwell Banker Susani Realty, Inc. |
Paterson, NJ
Coldwell Banker Susani Realty, Inc., located in Paterson, NJ A career as a real estate agent can provide both personal and financial rewards to self-directed individuals who are entrepreneurial, technologically resource...
Branchville Real Estate Agents


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Simply confirm your registered email address below and click "Reset Password." We will immediately email you a link back to the site where you can enter a new password for this account.
We've found your existing Atlanta magazine account. Please login below to complete the Facebook login process.
Tennis fans rejoice: the BB&T Atlanta Open is in full force this week. The tournament began Saturday and the first round of the main draw started yesterday. Both the singles and doubles championship matches will be played on Sunday, July 28.
Catch some of the area's rising stars as well as beloved players such as Mardy Fish, James Blake, and UGA alum John Isner. But don't expect the infamous Bryan brothers—they pulled at out the last minute due to injury.
Atlanta has hosted the tournament since 2010, but BB&T signed on only last year as the title sponsor. This is also the second year the tournament's home has been in Atlantic Station. Although the courts are temporary, the tournament has a great setup. Between matches, fans can play cornhole in the food court, buy freshly squeezed lemonade, and wander Vendor Row—a street where fans can meet players and sponsors have set up tents.
Like clockwork, our daily thunderstorm raged Monday afternoon, causing an almost hour-long rain delay. However, the tournament crew dried off the courts as quickly as possible and play resumed in what felt like 110-degree heat. Luckily, some of the sponsors handed out racket-shaped cardboard paddles so people could fan themselves. Note, if you plan to attend: WEAR SUNSCREEN.
After a day of intense qualifying and first-round matches, organizers staged an exhibition match, the "Bro Down Showdown," a doubles round-robin mini-tournament, that featured the Blake brothers, the Sock brothers, the Harrison brothers, and Kevin King and Juan Spir (doubles partners from Georgia Tech who filled in for the Bryans). The informal, low-key matches allowed the players to roam freely and trash talk. During the final, the Socks and the Blakes let four ball boys play a few points as the "host" caught up with the Harrison brothers and the Yellow Jackets duo. Ryan Harrison even got pantsed by his younger brother, Christian, at one point.
Monday's results: Singles, first round: R. Williams (USA) def. D. Kudla (USA) 7-5 6-4 R. Harrison (USA) def. M. Matosevic (AUS) 6-2 2-6 6-3
Doubles, first round: [3] C. Fleming (GRB) / J. Marray (GRB) def. E. Donskoy (RUS) / D. Istomin (UZB) 6-3 7-6(5)
Qualifying Singles, third round: M. Ebden (AUS) def. C. Guccione (AUS) 6-4 7-6(2) T. Smyczek (USA) def. D. Young (USA) 7-5 7-6(3) M. Zverev (GER) def. P. Amritraj (IND) 6-4 6-2 K. King (USA) def. R. Ginepri (USA) 2-6 6-4 6-4
The Atlanta Braves RelocationTrack the latest developments in the team's move from Turner Field to Cobb County.
Big StormsFrom a Polar Vortex to the Icepocalypse, the crazy weather of Winter 2014.
The Walking Dead All things TWD—including our weekly haiku recaps now that Season 4 has resumed.


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Top page New!!ü@ü@18th Feb. 2014 ü@ü@Sale
To Japanese
Karakuri Creation Group
Sep. 2013 OPENüI
This web page is Japanese only.
English page is coming soon. ü@
"Karakuri Club"ü@Invitation
Click Photos
Hiroshi Iwahara
Hiroyuki Oka
Yoh Kakuda
Osamu Kasho
Akio Kamei
Hideaki Kawashima
Kanae Saito
Shiro Tajima
Kazuyuki Tanaka
Fumio Tsuburai
Kyoko Hoshino
Yoshiyuki Ninomiya
Tatsuo Miyamoto
Kagen Schaefer (a friend of KCG)
the late Yoshio Okiyama
Karakuri Small Box
Chotto Karakuri
New Secret box
Creative Secret Box
Remade Products
Electric Secret Box
Karakuri Event
Book & Booklet
Exhibition Room
Karakuri Museum
Karakuri Report
<Notice Board>
Odawra Hakone Association of Karakuri-Puzzle and throughout Japan
Click here! ü½ü½
*We introduce other excellent products.
Please Check here. Sale of Other Excellent Products
*We have begun Karakuri Club 2009 acceptance already.
*Karakuri Craft Museum Tanaka was closed. Thanks for your patronage.
*A book was published in Nov. 2006. Contemporary Japanese mechanical puzzles are shown. Karakuri Small Box also appears. (Japanese only.) "The Mechanical Puzzle 130" ISBN 4-06-317164-7 ü@


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My dad came to visit for the weekend and we went out to eat for every meal and I didn't exercise at all. I am having a hard time getting motivated again. Any suggestions? I know "just do it", but I am not in the mood to think about eating at all, let alone six meals a day. Today is the start of week three for me and I did great for the first week and a half. But now I am feeling depressed. Motivation, please. :-) Thanks. Christie
Here's a gem from a low carb forum I'm a part of:
Go look at yourself in the mirror. naked.
That does it for most of us.
dont beat yourself up its all good just get back on track and believe you are worth the changes you are going to be seeing. your worth it
lipirata thats so funny, the mirror thing, it takes 28 days to form a habit, and bad habits are overcome by creating new habits, believe in yourself, because the battle is in the mind, if you say you cant do it, you cant, but let me say this i believe you can, your only limitations are those you impose on yourself, and if all else fails look in the mirror naked,
LOL... Um, yeah Rodie thats what I MEANT to say :)
to echo what has been said:
Do not beat yourself up over it.
Believe in yourself
Look at yourself in the mirror naked
and then know that deep down inside you have the strength to get back on track.
You can not get those lost days back, but you can get started again.
Once you start again, do not lament where you are versus where you would have been, that will just make you feel worse.
Like it says in the book, focus on progress not perfection
You can do this. Think about how you felt during the first week and a half. Wasn't it better than how you feel now? It only gets better when you stay with it. Look forward and take it one day (one workout... one meal) at a time. You can't change what is in the past but you can create the future! I'm starting week 3 also... we can do this!
You guys are going to think I'm a hard@$$ for posting this, but in my opinion you either want to do this or you don't.
That's what makes the difference in getting back at it when you have a long weekend of down time.
It's not the end of anything, it's the beginning of discovering what you really want for yourself. In my opinion you should kick yourself right in the seat of the pants until you are in the gym doing what you know you should be doing and until you are in that kitchen eating what you should be. Sugar coating screw ups in some way says it's ok for that to happen over and over and in the long run, you'll be stringing together 3 day free days again and again.
Wallowing in the things you can't change doesn't prepare you for the next time you are tempted to go on hiatus.
Get your head on straight and decide what YOU WANT and commit to yourself that this is what you want to do.
Whether you think you can or you think you can't, you're right ~ Henry Ford
Michelle Simpson ~2009 Body-for-LIFE Champion 46+ Catagory
Christie, I did the exact same thing and I am going into week 7, so like Champster said don't beat your self up, just get back in the gym. I did this morning, missed two workouts, ran on Saturday, and picked up today. Felt good too. I did however look in the mirror and said "I can do this" and "I don't want this" gave me some motivation.
Just keep going, don't stop. I said I was going to complete this challenge even though I messed up, surely I will still see some results.


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2009 Lexus IS
More Lexus IS News and Reviews
Lexus RC F GT3 Racing Concept is green-flag ready
March 04,2014
Lexus is hardly the first brand that comes to mind when comes to motorsports. In fact, it's not even the first Japanese brand. But Toyota's premium marque is showing new signs of understanding...
Read Full Review -
Lexus RC F GT3 Racing Concept threatens to go racing
February 28,2014
In case you needed more proof that the Lexus RC F is a statement car intended to scream "This is not your father's brand" (yes, we're paraphrasing the tagline of another automaker), ...
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Lexus Eco Challenge rewards schools for clean water, briquette press projects
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Teams from one New Jersey high school and one Michigan middle school reversed the old adage by thinking locally and acting globally. And that strategy won them the grand prizes in the most recent edit...
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Lexus RC 350 F Sport ready to take on Europe's coupes
February 28,2014
Rumbling into the slot between the Lexus RC 350 Sport Coupe and the RC F is this, the RC 350 F Sport. Debuting at the Geneva Motor Show next week, the intergalactic malevolence of that spindle grille ...
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Krysti Mikkonen
Age: 42
Home: Rural Frederick
Party: Democrat
Education: Bachelor's degree in political science from Northern State University
Occupation: Owner of WSI, an Internet marketing and consulting franchise, and part-time wind energy consultant
Krysti Mikkonen wants to be elected to the Brown County Commission to provide more rural representation.
"There is not a candidate or a current commissioner who lives in northern Brown County," she said. "That is 1,731 square miles. We need to make sure there is a voice from that area."
Mikkonen, who lives in rural Frederick, said road maintenance is the biggest problem for the county.
"I went to a couple of road meetings in April, and there was a study released from a company from Bismarck," she said. "Living in northern Brown County, I noticed that area was not established as a priority."
Northern Brown County has been hit especially hard the last three years with high-water levels that damaged roads, she said.
The study was flawed because traffic counts were used that did not reflect the importance of certain roads, she said. Many of the preferred roads had lower traffic totals because drivers avoided them. If the roads were in better shape, the traffic counts would have been higher, she said.
"Clearly there is an education process that needs to take place," she said. "If people understood the depth and breadth of the problem, there would be more urgency. Farmers need to have roads to get crops to where they need to go and to keep the money flowing into Aberdeen."
Mikkonen said there are ways to get more money for roads. One way is to expand the wheel tax by taxing all wheels, not just four wheels. Large trucks and agricultural equipment could be taxed by each wheel with the money going to roads, she said.
There could also be a grain check-off that could go to roads, she said.
An increase in fuel tax is a last resort but should not be ruled out, she said.
Mikkonen has served in a variety of leadership positions, including nine years on the Frederick School Board. She has also served on the Avera Community Health board, NSU Alumni board, Brown County Extension board and as an Aberdeen Area Chamber of Commerce diplomat. Additionally she was the state director of Kids Voting for eight years.
She said she sees her strength as a communicator. She is not afraid to speak out but is willing to listen to others, she said. She said she asks a lot of questions to give people a chance to share their thoughts. Through communication, ideas and plans take shape, she said.
"I want things to be better, and not just be satisfied with the status quo," she said.
In addition to roads, the county will need to address the updating the sheriff's office, Brown County Jail and Juvenile Detention Center, she said.