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The Americans Season 2 Podcast Exclusive
A Slate Plus exclusive: Listen to The Americans showrunners Joe Weisberg and Joel Fields talk about the Season 2 finale with Slate's Willa Paskin.
As a member of Slate Plus, you'll get access to exclusive podcasts—including the audio of this special conversation about the second season The Americans.
Slate's television critic Willa Paskin chats with showrunners Joe Weisberg (brother of Slate's own Jacob) and Joel Fields about the show's Season 2 finale as well as what might come in Season 3.
This podcast contains spoilers, so listen after you watch the Season 2 finale.
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Access to the New England Law Library
The library is open to New England Law | Boston students, faculty, staff, and alumni; local law students; active members of the Massachusetts Bar; Tufts Health and Sciences faculty, students, and staff; and New England Law Library Permit holders.
Current students and Alumni must bring their valid school ID with them in order to access the library through the turnstiles. Other qualified users must present proper identification to security and sign the visitor's log prior to entering the library. Except during the reading and exam period, a current New England Law student may bring one guest into the library on an occasional basis. Guests must sign the visitor's log. If you have special needs and require assistance, please see a Librarian or Desk Assistant.
Access is restricted during New England's reading and exam period. Only students, faculty, staff and alumni may use the library at this time.
Access to the Law Library's electronic databases may be limited to current students, faculty, and staff due to licensing restrictions. For more information on specific databases, see our Databases A-Z page.
Access to Boston Public Library
Access to Boston Public Libraries
The Boston Public Library is, as the name implies, open to all.
Of particular interest to law students is the fact that it is both a Government Depository Library and a United Nations Depository Library.
Many of the BPL's databases are accessible via our database list; other databases are available to those students with a BPL library card. Massachusetts residents can get an e-card online, allowing them access to many of the BPL databases.
Local & NELLCO Law Libraries: All You Need to Know Before You Visit
Boston College Law School Library
885 Centre Street
Newton, MA 02459
Hours: 8am-Midnight, M-Th; 8am-10pm, F; 9am-10pm, Sat; 10am-midnight, Sun.
Circulation Desk: (617) 552-4434
NEL students have library access with their ID for study and research purposes except during reading and exam periods.
Boston University - Pappas Law Library
765 Commonwealth Ave.
Boston, MA 02215
Hours: 8am-11:30pm, M-Th; 8am-10pm, F; 9am-9pm, Sat; 10am-11:30pm, Sun. (Annex hours are different.)
Phone: (617) 353-3151
NEL students have access to the library for specific research projects that require materials in the Pappas collection, except during reading and exam periods (at which time please see a NEL reference librarian if you need access to a unique item in the collection). Be sure to bring a NEL ID. Students will have to sign in the visitor's register at the circulation desk and indicate the purpose of their research.
Harvard Law School Library
1545 Massachusetts Ave. (Langdell Hall)
Cambridge, MA 02138
Hours: 8:30am-midnight, M-Th; 8:30am-9pm, F, Sat.; noon-midnight, Sun.
Phone: (617) 495-3174
NEL students must present a NEL ID and a letter from a reference librarian stating that they are conducting research unique to the Harvard Law Library Collection. There is limited access during exam periods.
Massachusetts Trial Court Law Libraries
2 Center Plaza, 9th Floor
Boston, MA 02108 (mailing address)
Hours: 8:30am-4:30pm, M-F
Administrative Office Phone: (800) 572-5027 x338
For more information, including locations of the various courts, see the Trial Court webpage.
All 17 Massachusetts Trial Court Law Libraries (located in Barnstable, Brockton, Cambridge, Dedham, Fall River, Fitchburg, Greenfield, Lawrence, Lowell, Norwood, New Bedford, Northampton, Pittsfield, Plymoth, Salem, Springfield, Taunton, Worcester) are open to the public without restrictions.
Northeastern University School of Law Library
400 Huntington Library 300 KN
Boston, MA 02115
Hours: 7:30am-10pm, M-Th; 7:30am-9pm, F; 9am-5pm, Sat.; 2pm-10pm, Sun.
Circulation Desk: (617) 373-3332
NEL students have free library access with their student ID.
Social Law Library
1200 Court House
Boston, MA 02108
NOTE: The Social Law Library is on the 12th floor of the New Suffolk County Court House.
Hours: 8am-8pm, M-F
Phone: (617) 523-0018
NEL students will be allowed limited access with a NEL ID and a letter from a reference librarian identifying their specific need, times and dates. For interlibrary loans, please see the New England Law Library interlibrary loan staff.
Suffolk University Law School
120 Tremont St., 6th Floor
Boston, MA 02108
Hours: 8am-11pm, M-F; 9am-11pm, Sat. and Sun.
NOTE: Any changes in hours will be posted on the library door, in the online catalog and on the library web site. Reserve/Circulation Desk: (617) 573-8177. NEL students need to bring a NEL ID and a letter from a reference librarian specifying the materials that they need. Because of space concerns, Suffolk cannot allow use of their computer terminals to non-Suffolk law students.
Access to Tufts Health Sciences Library
A valuable resource-sharing partnership has been forged between New England Law library and the library associated with Tufts medical, dental and veterinary schools. Current students, faculty and staff of each institution have on-site access to each other's collections, which in the case of Tufts means an extensive medical journal collection and a reference collection of basic works, including such things as medical dictionaries, general textbooks, and narrowly subject-specific monographs.
The Tufts Health Sciences Library is located in the Arthur M. Sackler Center for Health Communications at 145 Harrison Ave., approximately two blocks from New England Law. See the map below.

subset: commoncrawl


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Living Room Drapes Ideas
Living Room Drapes Ideas
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|Music by
|Joe Raposo
|Lyrics by
|Raposo, Jon Stone, Bruce Hart
"One of These Things" was a song regularly used on Sesame Street for sketches where viewers would be shown a group of four items, one of which was different from the other three, and they would have to identify the item which didn't belong. In a 1999 episode, in which the Dingers plan on having a ding-a-long, the cast sang a variation called "One of These Dings".
A similar game was played to two different songs written by Joe Raposo and Jeff Moss in 1970 and called "Three of These Things Belong Together", with variations such as "Two of These Things", "Here Are Some Things", and "Three of These Kids Belong Together". (The last version involved a four-way split screen with three children performing one activity, plus a fourth child "doing his own thing". Sometimes it was called "One of These Kids".) In some instances of the game, kids were encouraged to find more than one different answer, depending on how the things could be categorized.
This game has been used in segments starring William Wegman's dogs, and in animated form, melody only, with footprints. It was also the basis for a game in one "Journey to Ernie" segment. A line of the song is included in the theme for the "This is the Game Today" segments, and some of the games from "This is the Game Today" include this song.
|Earliest Known Appearance
|Episode 0001
|W and three Twos
|One of These Things
|Susan and Oscar the Grouch
|Episode 0013
|Ice cream cone sizes
|One of These Things
|Episode 0043
|Shoe sizes
|Episode 0054
|Episode 0083
|Silverware and a clock
|Episode 0123
|Capital and lower-case R's.
|Susan, Bob and Grover
|Episode 0131
|One of These Things
|Oscar the Grouch
|Episode 0135
|Rancid sneaker, tattered glove, messed up sock, and nice hat.
|Three of These Things
|Episode 0136
|Hot dog, mustard, bun, and flower.
|Three of These Things
|Episode 0158
|Some of These Fruit
|Episode 0158
|Some of This Stuff
|Cookie Monster
|Episode 0174
|Number of cookies on each plate
|One of These Things
|Mr. Hooper
|Episode 0179
|Groups of candy
|Three of These Groups
|Episode 0267
|Plates full of cookies
|One of These Things Belongs with the Others
|Kermit the Frog and Susan
|Episode 0276
|Hammer, shoe, pliers, and a saw
|Three of These Things
|Kermit the Frog and Susan
|Episode 0276
|Three birds and a frog
|Big Bird and Mr. Snuffleupagus
|Episode 0298
|Three cut-out drawings of Snuffleupaguses and a cup
|Grover and Susan
|Episode 0406
|Car and three animals
|Episode 0408
|Three Policemen, one fireman. (all Kids)
|Three of These Kids
|Episode 0413
|Upside-down kids, right side up kids
|Three of These Kids
|Episode 0418
|Basketball and Baseball
|Three of These Kids
|Episode 0463
|Three kids wearing winter clothes, and one kid not in winter clothes
|Three of These Kids
|Episode 0536
|Three starfish and one crab
|Episode 0536
|Football and Baseball
|Three of These Kids
|Bob and Maria
|Episode 0592
|Three triangles and 23
|One of These Things
|Bob and the kids
|Episode 0597
|Three of These Things
|Bob, Luis and David
|Episode 0598
|A scarf, hat, glove and book
|One of These Things
|The kids
|Episode 0825
|Three kids riding one seat bicycle, and two kids riding two seat bicycle
|Three of These Things
|Episode 0901
|Fruit and a shoe
|Three of These Things
|The adults, Gladys the Cow, and the kids
|Episode 1056
|People and a cow
|One of Us Here
|Episode 1733
|Three kids are jumping rope, but the fourth one is sitting down and reading a book.
|Three of These Kids
|Episode 2238
|Three kids holding umbrellas, and one kid not holding an umbrella
|Three of These Kids
|Edith Prickley (Andrea Martin)
|Episode 2459
|Boots and Pumps
|Three of These Things
|Snuffy and Alice
|Episode 2477
|Brussels Sprouts and Balls
|One of These Things
|The Big Bad Wolf, The Three Little Pigs, and Kermit the Frog - Sesame Street News Flash
|Episode 2567
|Three pigs and one frog
|Three of These Things
|Uncle Wally, horses
|Episode 2578
|Uncle Wally and a singing group of horses.
|One of Us Here is Not Like The Others
|Maria, Gina, and Telly Monster
|Episode 2746
|When Oscar shows up while Maria, Gina, and Telly are making Oscar's favorite dish - a hat with ice cream and a fish inside - they play an impromptu game of this, featuring a hat, fish, ice cream, and apple.
|Three of These Things
|Big Bird and the adults
|Episode 2747
|Big Bird, Susan, Luis, and Linda.
|Three of These Things
|Big Bird, Bob, Luis, Maria, and Gabriella
|Episode 2747
|Three adults and a child
|Three of These Things
|Big Bird and the adults
|Episode 2747
|One bird and six adults
|Six of These Things
|Episode 2755
|Three cans, one cup
|One of These Things
|Telly, Savion, and Kids
|Episode 2953
|A toy rocket ship, a pair of tap-shoes, a toy airplane, and a toy helicopter.
|Three of These Things
|A penguin
|Episode 3145
|Four penguins - one of which has a clown nose on its beak, and one of which is Wolfgang in disguise.
|One of These Things
|Ruthie, Telly Monster, Merry Monster, and The Kids
|Episode 3164
|A roller skate, towel, soap, and a Rubber Duckie.
|Three of These Things
|Gina, Kids, Elmo and Baby Bear
|Episode 3410
|A blue ball, a yellow ball, a blue pull-duck, and a blue block.
|One of These Things
|Big Bird and Gordon
|Episode 3540
|The Squirrelles and a rabbit.
|One of These Things
|Gina, Zoe, Alice, and kids
|Episode 3757
|A squirrel, a teddy bear, a penguin, and a drum.
|Three of These Things
|Elmo and Zoe
|Episode 3872
|A number 1 and three socks.
|One of These Things
|Cookie Monster and Ernie
|Episode 3943
|A hamburger, a cookie, pizza and a fajita
|Three of These Things
|Elmo and viewer
|Episode 3967
|A soccer ball, a jump rope, jacks and Stinky the Stinkweed
|Three of These Things Belong Here
|Big Bird and Cookie Monster
|Episode 3981
|A cookie, a hat, a t-shirt, and a shoe
|Three of These Things
|Big Bird and Snuffy
|Episode 3992
|Oscar, a hat, a mat, and a cat (Little Murray Sparkles)
|Three of These Things
|Maria and Kids
|Episode 3993
|A kangaroo, a rabbit, a fish and a grasshopper
|Three of These Things
|Big Bird, Elmo, Zoe, Luis, Maria, H-Man
|Episode 4115
|A helicopter, a hippopotamus, a ball and a hexagon
|Three of These Things
|Oscar the Grouch and Alan
|Episode 4118
|Food scraps and a button
|Three of These Things
|Episode 4809
|Vegetables and meat
|One of These Things
|Jay Leno and Big Bird
|Three triangles and one circle
|Bob (pretending to be John-John) and John-John (pretending to be Bob)[1]
Versions (animated)
A series of animated segments from season 4 featured an instrumental of the song over visuals of footprints or shoes in a graph.
- Audio
- The Sesame Street Book & Record (1970)
- One of These Things/Up and Down (single, 1970)
- Susan Sings Songs from Sesame Street (1970)
- Somebody Come and Play (1974)
- 60 Favorite Songs from Sesame Street (1975)
- 25 Greatest Hits (1975)
- Susan and Bob Sing: One of These Things/What Are Kids Called (single, 1976)
- 10th Anniversary Album (1978)
- Platinum Too (1997)
- Video
- Play-Along Games and Songs (Cookie Monster version)
- Old School: Volume 1 (in episodes 0001, 0131, 0276, 0406, and 0536)
- Old School: Volume 2 (in episode 1056)
- Let's Play Games (kids with umbrellas version) (on bonus CD-ROM)
- 40 Years of Sunny Days (Cookie Monster version)
- Publications
- Sesame Street Songbook Vol. 1
- The Sesame Street Songbook (1971, 1992 and 2007 editions)
- Online
- YouTube (Cookie Monster version) (YouTube)
- This song was included in a 2004 Subway commercial, where it was called "One of These Subs".
- Dave Grohl, from the Foo Fighters, admits that he was influenced by "One of These Things" while writing the song "The Pretender". (YouTube)
- The Mindless Self-Indulgence song "Unsociable" has the line: "One of these shapes is not like the other holes," which is very similar to this song.
- In the tour Jeff Dunham: Spark of Insanity, Peanut comments on Jose Jalapeno calling Jeff "Senor Heff" and then "Senor Cheff". Jeff Dunham says it's the same thing and Peanut replies "No it's not! Didn't you watch Sesame Street?" Then he sings a short clip of "One of These Things" singing "One of these things just doesn't belong here". Then he parodies the end of the show by saying that "this show was sponsored by the sound CH."
- Taylor Swift's song "ME!" references the song in the lyrics. (YouTube)


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Here's to the Loud
Previous / Next
Chrome Editor Hal Honigsberg, working with Joneses Director Vincent Laforet via Motive, recently edited a 30-second for Mountain Dew to introduce its new Mountain Dew White Out drink. Here's to the Loud is a 30-second, nationwide celebration of youth and energy that marks the launch of the latest Mountain Dew flavor: Mountain Dew White Out. The characters are portrayed in a black-and-white montage spiked with a colorful Mountain Dew bottle, and appear alone and in groups, stoic and shouting, dancing and standing confidently still. The winning flavor was chosen through the DEWmocracy 2 campaign during which fans led in all aspects of the creation of the Mountain Dew White Out, including the color, name, design and even the advertising. The footage conveys a raw, fan-driven feel - consistent with brand's approach of relying on the collective intelligence of its fans to design and choose the newest member of the Mountain Dew family. Honigsberg stitched this varied footage with a rocking backbeat and a voiceover celebrating the soft-drink democracy. "In keeping with the Mountain Dew brand, this is an energetic spot," noted Honigsberg. "We had to pack a tremendous amount of footage into a 30-second without sacrificing the quality, a tough assignment, but the final product looks great and made the challenge worthwhile." Read more: http://www.trustcollective.com/portfolio/content/chrome_mountaindew.php#ixzz14E7rtB5Z Attribution: Written content created by TRUST: http://www.trustcollective.com Under Creative Commons License: Attribution Share Alike
Client: Mountain Dew Spot Title: Here's to the Loud Air Date: October 2010 Agency: Motive CD: Matt Statman AD: Spencer Trierweiler Copy: Glenn Morey Producer: Carol Williams Prod Co: Joneses Director: Vincent Laforet DP: Vincent LaForet EP: Annie Hanlon Producer: Beth Aranda Editorial Co: chrome Editor: Hal Honigsberg EP: Betsy Beale Producer: Rebecca Baker Post/Effects Co: Elephant Lead Artist: Rob Doolittle Producer: Aaron Leichter Shoot Location: Across the US and Denver


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I am a relaxed girl, I like sport and music, those men and women who are taken for the moment, stripping their insecurities to find their fantasies and fetishes and enjoy them with me.I love the people who come with me to share their craziest and weird ideas, I adore obey 100% and offer an unforgettable time, I am an insatiable person of fun and eroticism, just tell me what you want, I will do everything possible to satisfy you.To be with me you have to be clear and respectful, I hate who abuses my trust and forget that I am a human being, people always receive what they offer, do not expect a good attention, if as first impression you are an indifferent person, I want to In my room there is always good attitude for me and the other users.
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Trumpet and I Exchange numerous messages a week discussing our team. It's quite therapeutic for me. I get to blow off some steam about what's pissing me off, and on the flip get to talk about what's going well. Some good stuff comes from our "talks". He sees stuff I don't and vice versa. I have tons of steelers buddies, but trumpet digs into the fine details like I do about the team. I look forward to my steelers talks with trumpet more than anyone else.
Like Scott shares his views about the bills, we'll share our private convos for all to see. Scotts stuff on the bills has been awesome. Stuff you can't read online. A juxtaposition of all the local media, national media, as interpreted by a hardcore fan. I don't think I've commented much in any of scotts threads, since I'm just there to absorb knowledge.
Perhaps the bengals, pack, and bears fans could do the same. Let's get the forums active again. They're more dead than the offseason.. let's face it, none of us like to do anything more as it applies about football, than talk about our teams. {Unless you're a browns fan, then I can understand} even still pruitt and 6 could fire it up, however Andy may need a team doctor to give us a group prozac script...
Here's the last message I sent trumpet, talking about the game vs the bengals and the upcoming one vs the skins and rg3.
I think all said the line did well. Legursky is a gamer. Tough kid, and the exact kind of swing lineman we need to keep around a long time. I love colon's aggression (and him not getting dumbass penalties), and he's picking up the position well, but damn he's slow in pass block situations. He got killed by atkins 1 on 1.
I know so does every other guard, by I'm being a hyper critical steelers fan.
While legursky played well, having pouncey would have helped there. Doug isn't strong enough to pick up a house like atkins when he's coming in late to help. Pouncey is finally back, and I'm not sure what to think of Adams yet. He looked pretty good on runs, but had crazy help from heath on most passing downs.. Gilbert is going to miss some time, so I guess we will see what we've got in him.
Decastro has been running, and is eligible to practice next week. We might see him back in time for the ravens game. He definitely will by December, and just in time for the weather change. With how mean pouncey, colon, and decastro are inside I think its fair to say we could have a pretty awesome run game late this year. Not shift the focus from what we do, but make those runs much more productive. In turn that makes the pass game all the more productive. Just what we need for a late playoff run.
As far as the skins go, I'm perplexed as to what to think.. which d comes out? The d we had in every game and the 1st half of the bengals game, or the one from the second half of the bengals game? Does it follow suit, as its always done, and overwhelm a rookie qb (lebeau is 13-1 vs rook qbs)? And all of that KNOWING rg isn't a normal rook qb. And he has a damn good rb.
The key again will be our offense. We need the murderously long methodical drives we destroyed the jets with. Keep rg off the field entirely. I think the offense does. This skins d sucks, and is already missing 2 of their 3 best guys, and now might not have fletcher either.
Ultimately I think rg shows well, but makes some mistakes. He's never seen the exotic blitzes and combo coverages we use. Accordingly Ben and co possess the ball for 38 minutes and QUIT settling for field goals so much. Steelers 41-28 with 2 of those skins tds in garbage time. Unless we continue to get a penalty on every single kick and punt like we've done the last 2 weeks. Then the score is more likely to be 35-31.


text:
{These are in no particular order, and the links are below the graphic}
1. Pottery Barn Burlap Table Runner Tutorial {click here}
2. Simplified Chalkboard Drawing Tutorial {click here}
3. Our Living Room {click here}
4. 6 DIY Fall Decorations under $6 {click here} & Autumn Sign Tutorial {click here}
5. Handmade Vintage Snowflake Ornament {click here}
6. Our Dining Room {click here}
7. My Top Favorite Fonts {click here} & Valentine Fonts {click here}
8. Halloween Chalkboard Template {click here}
9. Vintage Napkin Pennant Banner Tutorial {click here}
10. Washing and Cutting Burlap Tutorial {click here}
Truly, from the bottom of my heart, thank you for sharing in this adventure with me.
I look forward to 2013 in all of its vintage inspired loveliness here on Ella Claire 🙂
Linking up at Stone Gable!


text:
Pepe's: Coming to a College Town Near You?
According to the Yale Daily News, the legendary Pepe's Pizza, in New Haven, Connecticut, is contemplating opening more branches in college towns across the country. But I wonder: Is it possible to clone high-quality, family-owned and operated pizzerias across state lines?
Pepe's, a Slice favorite beloved by just about everyone, including Michael Stern of Roadfood, and me. Pepe's, which I named one of pizzadom's "keepers of the flame" in my book Pizza: A Slice of Heaven, had previously opened a branch in Fairfield, Connecticut, in 2005 and another in Mansfield, Connecticut, last month. I tried to go to the Fairfield branch but was repelled by the long line.
College town expansion sounds like a sound business strategy. College kids love pizza (actually, who doesn't), ditto for professors living on academic salaries, and Pepe's would be a cost-effective way for parents visiting their kids to take them out for some non-dorm food.
But is the pizza going to be any good? Is it going to do justice to Frank Pepe's name and legacy as one of the true pizza giants in this country? Can you make a good coal-fired oven tomato pie beyond the Connecticut state line? I have my doubts.
High-quality burger chains? Not really a problem. In-N-Out is beloved by burger afficionados. Want a pretty damn fine burrito anywhere in the country? You can get it at Chipotle Grill. There's a Chipotle Grill near the Slice/Serious Eats office that I eat in once a week (I get a salad with half barbacoa, half pork, back beans, two kinds of salsa, no sour cream, and just a sprinkling of cheese), and it's mighty tasty.
Turning out good burgers and fine burritos and tacos in multiple locations is one thing, but cloning Pepe's is another. Why? Because pizza is hard. Famous chefs have told me, "Cooking is easy. Pizza is hard." Turning out great pizza day in and day out, when changes in temperature and humidity force the pizzaiolo to make many split-second decisions, is a challenge to even the best pizza-makers like Chris Bianco of Phoenix's Pizzeria Bianco and Anthony Mangieri of New York's Una Pizza Napoletana. Bianco once told me, "I could teach a monkey to make one great pizza." At a high-volume pizzeria like Pepe's, the pie men and women are going to be making hundreds of pies a day, and I just wonder if they're going to be up to snuff. Making great pizza, consistently, every day for years takes passion, dedication, and know-how, and usually requires an obsessive owner to be there every day presiding over the pies and getting his or her hands in the dough.
Maybe I'm wrong. If the Fairfield and Mansfield Pepe's are turning out consistently good piesand I would welcome any Slice correspondent's reportmaybe this foray by Frank Pepe's heirs, in concert with a Yale alumnus turned financier, will work. It would be one small step for pizzakind.
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- Research article
- Open Access
The population genetics of cooperative gene regulation
- Alexander J Stewart1, 2,
- Robert M Seymour2, 3,
- Andrew Pomiankowski2, 4Email author and
- Joshua B Plotkin1Email author
© Stewart et al.; licensee BioMed Central Ltd. 2012
- Received: 13 April 2012
- Accepted: 31 August 2012
- Published: 6 September 2012
Changes in gene regulatory networks drive the evolution of phenotypic diversity both within and between species. Rewiring of transcriptional networks is achieved either by changes to transcription factor binding sites or by changes to the physical interactions among transcription factor proteins. It has been suggested that the evolution of cooperative binding among factors can facilitate the adaptive rewiring of a regulatory network.
We use a population-genetic model to explore when cooperative binding of transcription factors is favored by evolution, and what effects cooperativity then has on the adaptive re-writing of regulatory networks. We consider a pair of transcription factors that regulate multiple targets and overlap in the sets of target genes they regulate. We show that, under stabilising selection, cooperative binding between the transcription factors is favoured provided the amount of overlap between their target genes exceeds a threshold. The value of this threshold depends on several population-genetic factors: strength of selection on binding sites, cost of pleiotropy associated with protein-protein interactions, rates of mutation and population size. Once it is established, we find that cooperative binding of transcription factors significantly accelerates the adaptive rewiring of transcriptional networks under positive selection. We compare our qualitative predictions to systematic data on Saccharomyces cerevisiae transcription factors, their binding sites, and their protein-protein interactions.
Our study reveals a rich set of evolutionary dynamics driven by a tradeoff between the beneficial effects of cooperative binding at targets shared by a pair of factors, and the detrimental effects of cooperative binding for non-shared targets. We find that cooperative regulation will evolve when transcription factors share a sufficient proportion of their target genes. These findings help to explain empirical pattens in datasets of transcription factors in Saccharomyces cerevisiae and, they suggest that changes to physical interactions between transcription factors can play a critical role in the evolution of gene regulatory networks.
- Transcription Factor Binding Site
- Deleterious Mutation
- Fitness Landscape
- Selective Coefficient
- Cooperative Regulation
It is often difficult for a population to acquire an adaptive phenotype that requires simultaneous changes in the co-expression of multiple genes [1–10]. If selection favours a change in the way a group of genes are regulated, then each of the target genes must independently gain novel binding sites and/or lose existing ones [8, 9, 11, 12]. This has led to the proposal that adaptive rewiring of a regulatory network can be accelerated if pairs of transcription factors bind their targets cooperatively, through a physical interaction between the transcription factor proteins themselves [8, 9, 11].
A number of previous studies have explored the mechanistic details of cooperative transcription factor binding at a given target gene [13–15]. Such biophysical studies focus on transcription factor binding at a single target gene and are able, with remarkable accuracy, to account for a number of the physical properties of binding sites [14, 16, 17]. However, the evolution of cooperative binding occurs through mutations at transcription factor proteins, and such mutations can alter transcription factor binding at every binding site across the genome. To understand the fitness effects of such a mutation therefore requires that we understand the evolution of the whole ensemble of binding sites for a transcription factor. The population genetics of such an ensemble cannot be understood in a simple way just by focusing on the details of a single member of the ensemble. They depend critically on the population-genetic parameters of the ensemble, such as number of target genes, overall mutation rates and selection coefficients, and population size. Therefore in this paper, we do not focus on the details of a cooperative binding at a single target gene. Instead our analysis is in terms of these population-genetic parameters, and whilst we estimate selective coefficients from biophysical studies, we do not specify the mechanistic details of protein-DNA interactions that give rise to them.
We use a mathematical model to study the conditions under which cooperative binding between pairs of transcription factors is favoured. We first determine the evolutionary conditions that favour cooperative binding under stabilising selection, in terms of the basic evolutionary parameters of the population: the strength of selection on binding sites, the rate of mutation, and the population size. We then study the influence of cooperative regulation on the capacity for a transcriptional circuit to adapt under positive selection. We calculate the time required for a target gene to gain a new, adaptive transcription factor binding site, in the presence or absence of cooperative interactions among its regulators. We confirm our analytical results on the evolution of cooperative regulation by comparison to Monte-Carlo simulations of the Wright-Fisher process associated with our system, and we compare our qualitative conclusions to systematic empirical data.
Our population-genetic model describes a pair of transcription factors, each with its own set of target genes, with some degree of overlap between these sets (Figure 1). According to our model, which is specified in detail below, a target gene that is regulated by both factors has two corresponding binding sites, while a target gene that is regulated by only one of the factors has a single binding site. We assume that mutations that result in loss of function can occur at any binding site, and that non-functional binding sites can also undergo gain of function mutations. When there is no cooperative regulation between the two transcription factors, binding to each of their targets is determined solely by their binding sites. If a binding site is not functional, this results in reduced fitness. When cooperative binding is present, two conflicting effects occur: On the one hand, cooperative binding partially compensates for the deleterious effects of loss of function mutations to the binding sites at shared targets. On the other hand, cooperative binding results in some degree of mis-regulation at each of the targets that are not shared, and this has a deleterious impact on fitness. By constructing our model in terms of these fitness benefits and costs we are able to study the evolutionary dynamics of the system, and determine the effects of varying different population-genetic parameters on the evolution of cooperative gene regulation. This approach therefore complements the detailed mechanistic models of gene regulation that have been studied elsewhere [13–15].
Results and discussion
Stabilising selection without cooperative binding
We consider a pair of transcription factors, labelled 1 and 2, that have K1 and K2 targets, respectively. A fraction β of the binding sites are at shared target genes, so that the number of binding sites at genes that are co-regulated by the pair is β(K1 + K2), as illustrated in Figure 1. Loss of function mutations occur at binding sites at a rate u l , and back mutations, which result in a functional binding site being gained at a target, occur at rate u g . An individual incurs a fitness penalty s, where 0≤s < 1, for each non-functional binding site, and fitness is assumed to be multiplicative across loci. Therefore the fitness of an individual that lacks i≤K1 + K2 of its required binding sites is w i =(1−s) i . The fitness landscape associated with our model thus has a single peak at i=0; and for each transcription factor binding site that is lost, fitness is reduced by an additional factor (1−s). Empirical estimates of the strength of selection on transcription factor binding sites suggest that typically Ns∼10 [18], suggesting that s is small. We assume that s is the same for all binding sites, an assumption which we relax in the Methods section.
where , and P ij is the probability a genotype lacking j functional binding sites mutates to a genotype lacking i functional binding sites (see Methods). Previous work [19–21] has shown that at equilibrium, when rates of forward and back mutations are identical (u l =u g ), the solution to Equation 1 is a binomial distribution. In the more general case of a finite population, with u l ≠u g , we find that the equilibrium continues to be well approximated by a binomial distribution, with mean (K1 + K2)a s . The term a s is the probability that a binding site will be non-functional in a randomly chosen individual at equilibrium. The probability a s depends on the strength of selection against non-functional binding sites, s, population size, N, and the rates of forward and back mutation, u l and u g (see Methods and [20, 21]).
(see Methods). These equations have an intuitive interpretation: When 2Ns > 1 the first term describes the effect of genetic drift which tends to push the system towards its neutral equilibrium, a0=u l /(u l + u g ), and the second term describes the effect of selection. In the limit N→∞, a s equals u l /s, which is the standard result for the frequency of a deleterious allele in an infinite population under mutation-selection balance. When 2Ns < 1, evolution is nearly neutral and drift dominates, so the system is close to the neutral equilibrium a0.
Stabilising selection with cooperative binding
Here we modify our model to account for cooperative regulation by a pair of factors. This allows us to ask when cooperative regulation is favored by evolution. A mutation that results in cooperative binding between a pair of transcription factors has two effects on the fitness of a transcriptional circuit. For a target that is regulated by both transcription factors, we assume that cooperative binding mitigates the effects of deleterious mutations at transcription factor binding sites [7–9]. This results in a reduced fitness penalty for a mutation at the β(K1 + K2) shared targets, so that (1−s) is replaced by (1−hs) for some constant 0≤h≤1. Nonetheless, there are also (1−β)(K1 + K2) targets that are regulated by only one or the other of the transcription factors. We assume that the cooperative binding of the transcription factors causes pleiotropic mis-regulation at these targets (since the other transcription factor, which does not have a binding site at such sites, now binds to the first transcription factor through a physical interaction). This results in a fitness penalty t at each of the (1−β)(K1 + K2) targets that are not co-regulated. Fitness is again assumed to be multiplicative, so that the cost of pleiotropy associated with cooperative binding is .
Provided u l ,u g ≪ 1, genes that are co-regulated and genes that are not co-regulated have equilibrium distributions described by independent binomial distributions with means a hs and a s respectively, which are approximated by Equation 2 (substituting hs for s appropriately, see Methods). We can now specify the conditions for the invasion of cooperative gene regulation. A mutation resulting in cooperative binding between a pair of factors will be favoured if the expected fitness of the mutant is greater than the equilibrium mean fitness. Using the expressions for mean fitness given above, this occurs when . Assuming t,s ≪ 1, this expression can be simplified to give . This means that, when the fraction of binding sites at shared targets, β, is greater than a threshold depending on s, h, t and a s , a mutation that results in cooperative binding can invade a population at equilibrium.
Similarly, a mutation that results in the loss of cooperative binding in a population where it is present will be favoured when . Again assuming t,s ≪ 1, this expression can be simplified to give so that, when the fraction of binding sites at shared targets, β, is less than a threshold depending on s, h, t and a hs , a mutation that results in loss of cooperative binding can invade a population at equilibrium.
Since the first expression in Equation 2 is monotonically decreasing in s, and the second expression is independent of s, it is always true that a hs ≤a s , i.e populations that have cooperative binding accumulate more deleterious mutations, that result in weaker transcription factor binding sites, than populations that lack it. As a result there is a range of β for which both a population that lacks cooperative binding, and a population that has cooperative binding are not invadable by mutations that gain or remove cooperative binding respectively. In this range, the evolutionary dynamics of the system are bi-stable. In this range, we expect to find some genes that are regulated by pairs of transcription factors that act cooperatively and some that don't.
Similarly, from Equation 4 for a population with cooperative binding, we see that when N and/or hs is large, so that 2Nhs > 1, the threshold number of shared targets βbelow which cooperative binding becomes disadvantageous is independent of the strength of selection s (Figure 2a). As before, the threshold decreases as the mutation buffering effect of cooperative binding increases (i.e. as h decreases, Figure 2b) and the threshold increases with population size N (Figure 2c), and the cost of pleiotropy t (Figure 2d). In contrast, when N and/or hs is small, so that 2Nhs < 1, drift dominates and the threshold number of shared targets βis independent of population size N (Figure 2c), but decreases with the strength of selection s (Figure 2a). The size of the bistable region is largest when s is large and h is small, and for intermediate values of N and t, as shown in Figure 2. As this analysis demonstrates, there is a broad range of possible evolutionary outcomes and, crucially, cooperative binding can evolve under a wide range of circumstances despite the deleterious pleiotropic effects associated with physical interactions among transcription factors.
Adaptation of transcriptional circuits under positive selection
We study adaptive change that involves replacement of an existing transcription factor by a new one that confers higher fitness. We assume that the target gene must first suffer an initially deleterious mutation at its existing binding site before a newly adaptive binding site can be acquired (Figure 3) [8, 9, 11]. The newly adaptive binding site is produced from binding sites that have already mutated at a rate u r . The expected waiting time for such a gene to produce a newly adaptive binding site therefore depends on the number of binding sites in the population that harbor a deleterious mutation, which is proportional to a s when cooperativity is absent and a hs when it is present. Since a hs > a s , this number is greater when cooperative binding is present than when it is absent.
Cooperative binding and the fraction of shared targets in yeast
Cooperative binding in the yeast sex determination network
The ability of cooperative transcription factors to facilitate adaptation also has empirical support, from observations in the sex determination networks of different yeast species [7–9]. The acquisition of a protein-protein interaction between the mating factor MATα2 and Mcm1 was able to buffer the deleterious effects of mutations that strengthened Mcm1 binding sites [7]. Prior to the emergence of a protein-protein interaction, sex determining genes were activated only in the presence of Mcm1 and MATa2 together [7]. The buffering effects of the protein-protein interaction allowed Mcm1 binding sites to acquire strengthening mutations such that sex determining genes became activated by Mcm1 alone. As a result, MATa2 became redundant and was lost [7]. The result was a significant upstream reorganization of the yeast sex determination network without the need for any parallel changes to the downstream output of the network. Similar patterns, in which acquisition of cooperative binding between transcription factors is followed by changes to the regulation of their shared targets, are observed across the yeast transcriptome [8], and support the prediction of our analysis of positive selection on transcriptional networks.
We have shown that cooperative binding between a pair of transcription factors is favoured under stabilising selection, provided the overlap between their targets is sufficiently large. The threshold fraction of shared targets depends upon the strength of selection on binding sites, the cost of pleiotropy associated with protein-protein interactions, and the rates of mutations. It also depends on the population size. Just as in models that consider the evolution of redundancy [20, 29], we find that greater redundancy (i.e. cooperative regulation) is more strongly favoured in smaller populations; and that for intermediate population sizes the evolutionary dynamics are bistable, such that cooperative binding is maintained if it is already present, but cannot evolve if it is absent. Finally, we found that cooperative binding facilitates the rewiring of transcriptional circuits under positive selection.
This study shows that, even when the deleterious effects of pleiotropy are taken into account, mutations that change transcription factor function can play an important role in the evolution of gene expression. Taking account of mutations both to regulatory binding sites and to the transcription factors themselves reveals a rich set of evolutionary dynamics that helps explain how complex transcriptional networks can rapidly rewire large sets of genes in order to adapt to new environments.
Equilibrium distribution
To find the equilibrium relative abundances of the hamming classes x i that give the solution to Equation 1, we follow [20, 21] and look for a solution of the form . Given this assumed form, the mean fitness of the population at equilibrium is . Since ∑ i x i =1 it is easy to show that . Taking p=a(1−s)/(1−a), this gives a mean fitness of , which is the form given in the main text.
and at equilibrium . Because we are assuming that w ij is just the product of the two independent fitness landscapes associated with the different selective coefficients, i.e w ij =(1−hs) i (1−s) j using our assumed form of x ij results in values of a s and a hs as given by Equation 5 for the independent distributions with the appropriate selective coefficients.
Assuming u l ,u g ≪ s, we obtain the Taylor expansion of a s to first order, in terms of 1/(2Ns) (which is relevant when 2Ns > 1) and in terms of 2Ns (relevant when 2Ns < 1) to obtain Equation 2.
According to this inequality, cooperative binding is advantageous only when the fraction of targets shared by the pair of transcription factors is greater than a threshold. Since by definition β≤1, Equation 7 says that cooperative binding can only increase population mean fitness when 2Nhs < 1 and 2Ns > 1, i.e if the benefit of cooperativity, h, is sufficient to make mutations at transcription factor binding sites that are deleterious in the absence of cooperativity nearly neutral when it is present.
Rewiring time
Therefore the ratio of expected waiting times with and without cooperative binding is independent of the number of genes to be rewired, and depends only on the ratio a hs /a s .
Variation in selection strength across sites
Up to this point we have assumed that the selective coefficients, s and h, are constant across binding sites. However it is obviously possible that these parameters may vary between binding sites. Such a generalization of our model represents a significant complication, and a full treatment is outside the scope of this paper. However, it can be analyzed in the simple case that the coefficients associated with each binding site i satisfy s i ≪ 1, such that the fitness landscape is approximately additive.
We assume that there are a finite set of selective coefficients, s α and h γ , where the super-scripts αand γindex the different sets, and that the number of binding sites with a given coefficient s α or h γ are distributed according to some function F(s) and G(h). We also assume that the coefficients s and h are distributed independently of one another. Each binding site i has a value s i associated with it, drawn according to F(s). In the quasi-species regime the probability that binding site i has a mutation is simply given by , as given by Equation 5. In this case the distribution of hamming classes, rather than being binomial, is poisson binomial, paramaterized by . Similarly, when cooperative binding is present, the distribution is poisson binomial with the modification that shared targets have a mutation with probability where h i is drawn independently from the distribution G(h). The system is easiest to analyse if we separate binding sites into sub-classes, α, of binding sites with the same selective coefficients, where the size of each sub-class, n α is given by n α =F(s α )(K1 + K2). The number of mutations in each subclass is then given by a binomial distribution.
When the fitness landscape is close to additive, the method of [19] can be applied independently to each sub-class to determine the expected number of mutations in the sub-class. This is only true in an additive fitness landscape, or in a multiplicative fitness landscape in which cross terms between subclasses are sufficiently small that they can be neglected. When this condition holds, the value of associated with each sub-class is given by Equation 6.
From these the invasion probabilities and threshold values of βcan be calculated in the same way as in the case of constant s and h above. The only difference in the case with variable selective coefficients is that the invisibility criteria for a mutation resulting in gain or loss of cooperative biding dependants on the average of a s s across the distribution F(s), and on the average a hs hsacross the joint distribution F(s)G(h). Investigating different forms of the functions F(s) and G(h) represents an interesting avenue for further work.
JBP and AJS acknowledge funding from the Burroughs Wellcome Fund, the David and Lucile Packard Foundation, the James S. McDonnell Foundation, the Alfred P. Sloan Foundation, grant #D12AP00025 from the U.S. Department of the Interior and Defense Advanced Research Projects Agency, and grant RFP-12-16 from the Foundational Questions in Evolutionary Biology Fund. AP acknowledges grants from the Natural Environment Research Council (NE/G00563X/1) and the Engineering and Physical Sciences Research Council (EP/F500351/1, EP/I017909/1). AJS also acknowledges an EPSRC PhD Plus fellowship.
Authors' Affiliations
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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Tennessee Gov. Bill Haslam called it a "third option" as he turned down an expansion of Medicaid funding at least for now with the federal government paying 100 percent of the cost in the first three years.
The goal he is pursuing is an expansion of TennCare, the state's version of Medicaid, to include more of who are now uninsured but a use of the federal funding to allow those added to buy private health insurance.
The Medicaid decision is the second and arguably the more important of two Affordable Care Act decisions Haslam has made. His first was the decision not to set up a state exchange for health care insurance and instead rely on a federal exchange.
While Haslam said the two decisions involved different factors, they have in common his insistence that he couldn't get detailed answers from federal health care regulators at the Department of Health and Human Services and he was unwilling to accept federal conditions.
"There are a lot of federal requirements that come with Medicaid that make it difficult to provide quality care in the most cost-effective way possible," Haslam told legislators Wednesday, March 28, in announcing his decision. "Instead of insuring more people through an inherently flawed system, we'd hoped to purchase private insurance to insure as many as 175,000 more Tennesseans. To do that HHS says we have to provide additional benefits, above and beyond what everyone else in the exchange will receive."
There would also have been Medicaid guidelines on copays and an appeals process that were unlike those in private insurance plans.
Haslam acknowledged his decision on the federal funding and expansion for now will be hard on hospitals across the state.
In Shelby County's case, the hospital is The Regional Medical Center at Memphis and the estimate of people affected by the Medicaid expansion decision is 60,000 to 80,000, according to Shelby County Mayor Mark Luttrell's March 14 letter to Haslam. Luttrell urged Haslam to expand TennCare with the federal funding.
"Some low income residents may find affordable coverage now in the federal Health Insurance Exchange, but we estimate that most will be eligible for the Medicaid expansion," Luttrell wrote. "Unfortunately in Shelby County, we are keenly aware of the implications of non-insurance. This includes the uncompensated costs of delayed care for low-income persons who simply do not have the resources to seek care at earlier, less acute and less costly points in their illness."
Luttrell told Haslam he had "no doubt" a decision by the state not to participate in the Medicaid expansion "would be damaging to The Med, if not devastating."
Haslam acknowledged that possibility in January when he set the political parameters for his decision to come on Medicaid expansion.
"There are hospitals across this state, many of them in rural communities, that are going to struggle if not close under the health care law without expansion, and that's not something to take lightly," he told the Tennessee legislature in his state of the state address that month. "Most of us in this room don't like the Affordable Care Act, but the decision to expand Medicaid isn't as basic as saying, 'No ObamaCare, no expansion.'"
Haslam's consideration is also rooted in the decisions of his Democratic predecessor as governor seven years ago.
That's when Phil Bredesen, a health care executive and Nashville mayor before becoming governor, cut a large number of people from the TennCare program. It was one of the most controversial acts of Bredesen's two terms in office.
Without a Medicaid expansion, Haslam's budget, delivered to the Tennessee legislature in January, anticipated a $350 million increase in TennCare costs over last year. That includes "the higher cost of medical care, more people who qualify for Medicaid in tough economic times and primarily the impact of the Affordable Care Act," Haslam said in his state of the state address.
Copyright 1995 -
by The Daily News Publishing Co. Inc. - All Rights Reserved


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Enter a dark world filled with despair and threaded by hope where your ability to creatively strategize, learn and overcome unpredictable and unique challenges determines your fate. Dark Souls will demand your absolute concentration, unflinchingly punish your mistakes, but reward your ability to learn from death. Each challenge is a mind game met with endless combinations that will test your ability to creatively strategize a way to conquer unimaginable monsters and progress deeper into this bleak and forbidding environment filled with the un-dead.
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SAN ANTONIO — It was the kind of night when you expected Tim Duncan to take the court wearing flip-flops, Tony Parker in straw hat and sunglasses and that annoying Manu Ginobili to be squirting SPF-50 in the eyes of the Grizzlies.
After all, the Spurs were coming off the most infamous vacation since Mitt Romney's dog took a road trip strapped to the roof of the family car.
But in the end, it was hardly a day at the beach.
The Spurs had to come from 14 down in the fourth quarter and get through five more minutes of overtime to deliver the kind of 99-95 drama that commissioner David Stern had wanted for the TNT audience on Thursday night from Miami.
When the Big Three plus Danny Green didn't stick around for that affair and, under the orders of coach Gregg Popovich, flew home for a few extra days of R&R, it touched off the kind of up-from-the-ground fire that used to send out a call to Red Adair.
So perhaps it was only natural that the players at the center of the controversy were motivated to provide and extra spark of their own to defend their coach after the $250,000 fine.
Call it "Win One For the Tripper."
"We definitely have always got Pop's back," said Parker, who had eight of his 30 points in the overtime. "I felt like it was for Pop. I wanted to be super aggressive and make sure we win the game."
Though none of them would say it, this was their way of sticking a thumb in eye of the commissioner for meddling in their team business, a quarter-million-dollar zinger, so to speak.
It was the Grizzlies, playing the second night of a back-to-back, who looked frazzled, worn out and just plain gassed coming down the stretch.
Prior to the game, Popovich spoke about the fine for the first time and said he was "disappointed" in the league's action, but did nothing else to ruffle the feathers of the league office.
"What I do from my perspective is a coaching perspective," Popovich said. "I think the league operates from a business perspective, and that's reflected in the action they took.
"That's that, and we move on."
Memphis still has the best record in league, but the fresher down the stretch Spurs proved their point. That they made their biggest move by climbing out of such a fourth-quarter hole only made the whole thing more delicious.
"I really just tried to come out and play hard," said the 36-year-old Duncan, who had 27 points and 15 rebounds and his highest-scoring first half since 2004. "I got some shots going early and continued to attack."
"I felt good in overtime," said Parker with an extra twinkle in his eye. "I had two days off. So I felt like I had a lot of energy."
Win One For the Tripper. Message delivered.


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2013 National Car Rental Assistant PGA Championship presented by Cobra Puma Golf
When: Oct. 31-Nov. 3
Where: PGA Golf Club (Wanamaker Course), Port St. Lucie, Fla.
Defending Champion: Jake Scott, Strongsville, Ohio
Format: 72 holes of stroke play. Following the first 36 holes, the field will be reduced to the lowest 70 scorers and ties. In the event of a tie for first place after 72 holes, there will be a hole-by-hole playoff.
What's at Stake: $100,000 will be distributed to the 2013 field of 126 competitors. The champion will receive $9,000 and a spot in the 2014 PGA Professional National Championship next summer in Myrtle Beach, S.C.
Official scoring
Championship field (.pdf) | Official media guide
Last Year: Relive Jake Scott's 2012 victory
PHOTO GALLERIES: Thursday | Friday | Saturday | Sunday
INTERVIEWS: Audio and video interviews
TWITTER: Join the conversation at #AssistantChamp
Jeff Schmid of Columbia, Mo., and Charles Frost of Charlotte, N.C., are tied for the lead heading into Sunday's final round. Frost, who trailed Schmid by five strokes entering the third round, eagled the par-5 16th hole en route to a 69. Schmid, who owned a four-stroke lead through 36 holes, bogeyed his final two holes for a 74.
--Watts makes hole-in-one, wins $25,000
Muttitt and Rhind, fresh off PGA Championship, seek more success
David Muttitt and Lee Rhind both finished in the top 20 of the 2013 PGA Professional National Championship, then competed in the PGA Championship. With those memorable experiences in their pockets, both now have their sights set on excelling in the PGA Assistant Championship.
--Pre-tournament Notebook: McCorkle preparing for plenty of championship golf
Greg Bisconti was the Low Club Professional at the 2005 PGA Championship, where he stood with Y.E. Yang after Yang's historic victory over Tiger Woods. Bisconti thinks of that moment frequently, and hopes to use it for inspiration this week as he tries for another prize.
For the 18th consecutive year, PGA Golf Club in Port St. Lucie, Fla., will host the 2013 National Car Rental PGA Assistant Championship presented by Cobra Puma Golf, a national championship for 126 PGA assistant professionals and apprentices. The 2012 field will feature three of the top four finishers from last year's Championship as well as 123 players who advanced through their PGA Section Championships.
For nearly 40 years, tournament has produced outstanding PGA Professionals who have gone onto successful careers in teaching and administering the game, as well as competing at the highest level. Past competitors or champions include: Loren Roberts (Champion, 1979); Fred Funk (Champion, 1984); Rich Beem (Third, 1998); and Tim Thelen (Champion, 2009).


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The Black One
The black goggle cover.
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Two plastic clips on either side clip over your goggle strap to insure the Proggle sits snugly over your lenses, protecting your goggles from all the elements of mountain life!
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Handmade in Scotland.


text: Mark, I will let others step forward individually. I was one of the last employees to leave Quadrics , so I do know who had support contracts at that time, plus the even larger set of sites that had expired support contracts but still were actively running their QsNet clusters. You know that a company called Vega took on the ongoing support? : here is the website I set up at the time: https://support.hpc.vega.co.uk/ I agree too though that there should be a community of QsNet-owning enthusiasts, who could provide mutual support in this legacy era. Also off the record, I know that there is a lot of Elan4 stock sitting in a warehouse. As long as you are not looking for long term vendor support, I expect you could acquire cards, cables and switches for a bargain price. Daniel > Are you still using Quadrics Elan4-based clusters? > > We would like to continue using Quadrics on one of our clusters, since it > is still quite good in latency. Maintaining the Quadrics drivers, though, > is a bit of a pain going forward - would be nice to avoid duplicating effort, > if there are other groups also doing so. > > please follow up or email me if you are using Elan4, or know anything > relevant. > > thanks, > Mark Hahn | SHARCnet Sysadmin | hahn at sharcnet.ca | http://www.sharcnet.ca > | McMaster RHPCS | hahn at mcmaster.ca | 905 525 9140 x24687 > | Compute/Calcul Canada | http://www.computecanada.org > _______________________________________________ > Beowulf mailing list, Beowulf at beowulf.org sponsored by Penguin Computing > To change your subscription (digest mode or unsubscribe) visit http://www.beowulf.org/mailman/listinfo/beowulf > > -- Bull, Architect of an Open World TM Dr. Daniel Kidger, HPC Technical Consultant daniel.kidger at bull.co.uk +44 (0) 7966822177


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MODELING NANODEVICES: FROM SEMICONDUCTOR HETEROSTRUCTURES TO JOSEPHSON JUNCTION ARRAYS Copyright 2012 by Bruna Pereira Wanderley de Oliveira A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (PHYSICS) May 2012 Bruna Pereira Wanderley de Oliveira
Object Description
|Modeling nanodevices: from semiconductor heterostructures to Josephson junction arrays
|de Oliveira, Bruna Pereira Wanderley
|Author email
|Doctor of Philosophy
|Document type
|Degree program
|College of Letters, Arts And Sciences
|Date defended/completed
|Date submitted
|Date approved
|Restricted until
|Date published
|Advisor (committee chair)
|Haas, Stephan
|Advisor (committee member)
Dappen, Werner
Däppen, Werner
Daeppen, Werner
Roscilde, Tommaso
Bickers, Nelson Eugene
El-Naggar, Mohamed Y.
Cronin, Stephen B.
|In this thesis we study the physical properties of two distinct physical systems. First, a generalized propagation matrix method is used to study how scattering off local Einstein phonons affects resonant electron transmission through quantum wells. In particular, the parity and the number of the phonon mediated satellite resonances are found to depend on the available scattering channels. For a large number of phonon channels, the formation of low-energy impurity bands is observed. Furthermore, an effective theory is developed which accurately describes the phonon generated sidebands for sufficiently small electron-phonon coupling. Finally, the current-voltage characteristics caused by phonon assisted transmission satellites are discussed for a specific double barrier geometry. In the second part of this thesis we numerically investigate the complex interplay between frustration and disorder in a magnetically frustrated Josephson junction array on the square lattice with site dilution, modeled by the fully frustrated classical XY model on the same lattice. This system has a superconducting ground state featuring a vortex crystal induced by frustration. In absence of dilution this system is known to exhibit two thermal transitions: a Kosterlitz- Thouless transition at which superconductivity and quasi-long-range phase order disappear, and a higher-temperature transition at which the vortex crystal melts - the two critical temperatures delimit a chiral phase. We find that dilution enhances the width of the chiral phase, and that at a critical dilution superconductivity is suppressed down to zero temperature, while chiral order survives - the corresponding ground state of the system becomes therefore a chiral phase glass. At an even higher dilution chiral order disappears in the ground state, leaving the system in a vortex and phase glass state. We reconstruct the complex phase diagram via extensive Monte Carlo simulations, and we investigate the main signatures of the various phases in the transport properties (I-V characteristics).
|Josephson junction arrays; electronic transport; phase transitions
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|University of Southern California dissertations and theses
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|University of Southern California
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|Los Angeles, California
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|de Oliveira, Bruna Pereira Wanderley
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|MODELING NANODEVICES: FROM SEMICONDUCTOR HETEROSTRUCTURES TO JOSEPHSON JUNCTION ARRAYS Copyright 2012 by Bruna Pereira Wanderley de Oliveira A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (PHYSICS) May 2012 Bruna Pereira Wanderley de Oliveira


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Martin Oppermann
Chapter 1: Introduction
Martin Oppermann
- Sex Tourism and Prostitution
- The Sex Tourist
- The Prostitutes
- The Place
- Summary
Martin Oppermann, Shawna McKinley, and Kye-Sung Chon
- Tourism Destination Images
- Nudity and Innuendo in Advertising
- Sexual Imagery and Tourism Marketing
- Sex and Marketing of Tourism Destinations
- The Case of Marketing Pacific Tourism Destinations
- Conclusion
Heidi Dahles
- Tourism Development in Indonesia and Yogyakarta
- Street Guides in Yogyakarta
- Prostitution, the Pasar Economy, and Tourism
Christine Beddoe
- Tourism and Child Prostitution
- Culture Contact and Culture Change: Theory and Context
- Who Are the Beachboys?
- Tourism in Sri Lanka
- The Beachboys and Child Prostitution in Sri Lanka
- Conclusion
Jody Hanson
- Historical and Contemporary Accounts
- Middle-Class Accounts and Proposed Solutions
- The "It's a Job'' Perspective
- More Questions and Further Considerations
Joan Phillip and Graham Dann
- Open-Ended Prostitution in Bangkok
- The Setting
- Understanding the Phenomenon: Prostitution as Work
- The Bar Girl as Entrepreneur
- Beguiling the Farang
- The No Face Business
Armin Gunther
- The Case of R.
- "The Edge of Ambiguity'' Revisited
- Sex Tourism and Monetary Exchange
- Sex Tourism Settings in Thailand: Massage Parlors and Bars
- Temporal Dimension
- Conclusions
Thomas J. Iverson and John C. Dierking
- Locational Context
- The Legal Framework
- Regulation Through Health Code Enforcement
- Ethical Considerations
- Policy Recommendations
- Conclusion
C. Michael Hall
- The Politics of Sex Tourism
- The Australian Crimes (Child Sex Tourism) Amendment Act 1994
- The Significance and Success of the Act
- The Politics of Reason? Lobbying, International Relations, Health, and External Affairs
- Conclusions
Chris Ryan, Helen Murphy, and Rachel Kinder
- Agencies and Parlors
- Economics and Demand
- Registration and Legality
- Changing Times
- Street Workers
- Conclusion
Asuncion Suren and Robert Stiefvater
- Leisure Services Industry
- Topless Dancing as a Spectator Sport
- Manipulating Leisure Environments
- The Interview: A Case Study
- Six Elements of Place
- Conclusion
Jon Griffin Donlon
- Elements of Typicality
- Regulating Adult Play
- Performance Styles and Types
- Does the Jafari Model Explain Part of the Club Experience?
Steven Kohm and John Selwood
- Authenticity
- Virtual Reality
- Virtual Sex Markets
- Virtual Sex Tourism Destinations
- The Drive for Reality
- Virtual Sex and the Law
- Conclusion
J. S. Perry Hobson and Vincent Heung
- Marriage, the Family, and Concubines
- Hong Kong-Its Changing Social Norms
- Hong Kong and China: The New Economic Relationship
- Business Travel to China From Hong Kong
- Internal Migration Patterns in China
- Increasing Availability of Sexual Services in Southern China
- The Emergency of the Modern Chinese Concubine
- Effects on the Family in Hong Kong
- Action Taken by the Authorities and Wives
- Conclusion
Malcolm Cooper and Jody Hanson
- Economy, Tourism, and the Development Debate
- Vietnamese Tourism: An Alternative Sex Tourism Plan
- The Sex Industry in Vietnam: A Case Study of the Brothels and on the Streets of Ho Chi Minh City
- Considerations and Recommendations
Martin Oppermann
- Power and Politics
- Who Benefits?
- Who Exploits Whom?
- Marriage and the Prostitution Trade
- Final Thoughts
List of Figures
1.1. Dimensions of sex tourism and prostitution
List of Tables
1.1. Number of local sexual partners and number of sexual contacts
1.2. Intention to engage in sex with local women
1.3. Would you call yourself a sex tourist?
1.4. Australian Thailand tourists' intentions for sexual contacts
1.5. Have you paid your sexual partner(s) with money?
1.6. Length of time with last prostitute in the destination
1.7. Intention to revisit same sex partner
1.8. Sexual practices engaged in by heterosexual male tourists
5.1. Juxtaposition of the literature
6.1. Estimated number of prostitutes in Bangkok and Thailand
10.1. Distribution of escort agencies and massage parlors in New Zealand
13.1. Top twenty ranked sites
14.1. Hong Kong divorce statistics
14.2. China's special economic zones
14.3. Trips to China through Hong Kong
14.4. Survey on attitudes of Hong Kong residents to concubines
15.1. Estimated number and qualifications of tourism employees
16.1. Type of prostitute and interaction with society
Book Review
The following excerpts are from a book review by Vincent J. Del Casino Jr., Department of Geography, University of Kentucky, Lexington, KY, appearing in the Annals of the Association of American Geographers (1999, pp. 566-568):
Sex Tourism and Prostitution: Aspects of Leisure, Recreation, and Work. Martin Oppermann, ed. New York: Cognizant Communication Corp., 1998.
The goal of this edited volume is to address a lacuna in the field of tourism studies through a more detailed examination of the relationship between sex tourism and prostitution. In so doing, the editor and his contributing authors hope to expand the narrowly defined parameters of sex-tourism and prostitution studies and to provide a framework for future research. To do this, the editor has brought together a multidisciplinary set of international scholars, journalists, and activists, who make contributions to our understanding of, among other issues, child prostitution, motivations of sex tourists, the organization of sex-tourism places, international law and pedophilia, the economic dimensions of prostitution, and the role of the internet as sex-tourism site.
The intention of this volume is an important one: to expand the ways in which we think about the relationships between sex tourism and prostitution. There are some interesting chapters and some valuable insights made by several of the contributors.
...while this volume might offer something to undergraduates with limited knowledge of the subject, it has little for the scholar seeking to understand how to theorize and conduct research on sex tourism and prostitution.


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Power Electronics
Technology research and development for the control and conversion of electric power.
Research Projects
- UM Electron Ring
The University of Maryland Electron Ring (UMER) is a world-class research facility in beam and accelerator physics at the Institute for Research in Electronics and Applied Physics, on the University of Maryland, College Park campus. Using a scaled low-energy electron beam, UMER cleverly accesses the intense, high-brightness, regime of beam operation in accelerators, at a much lower cost than larger and more energetic machines. UMER therefore makes an ideal testbed for experimenting in pushing up the brightness of existing and future accelerators.


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NCPreps.com is a web site that focuses on all of the top high school football players and schools from across the state.
NCPreps.com is a web site that focuses on all of the top high school football players and schools from across the state.
The web site recognized three Craven County football stars this season on its all-state team.
New Bern wide receiver and defensive back Bra�lon Cherry, along with Havelock�s duo of quarterback/athlete Pharoh Cooper and wide receiver/defensive back A.J. Coplon were selected to be on the squad.
Cooper was picked as a special team�s athlete for his interception and kick-return talent, Cherry and Coplon were tabbed to the team as defensive backs.
Cooper will be playing at the next level in the SEC for South Carolina. Cherry is committed to play at N.C. State, of the ACC, and Coplon will play up the road at East Carolina, from Conference USA.
The team features a ton of Division-I commits in addition to Craven County�s stars.
On the defensive side, with Cherry and Coplon, NCPreps named defensive end Tyquan Lewis, of Tarboro (Ohio State), defensive end Lewis Neal, of Wilson Hunt (LSU), linebacker Sean Wiggins, of Butler (Ball State), linebacker Peter Kalambayi, of Butler (Stanford), and defensive back Chris Duffy, of Porter Ridge (UNC-Charlotte).
Cooper�s future college teammate at South Carolina, Connor Mitch of Wakefield was named the quarterback. A duo of running backs in T.J. Logan, of Northern Guilford (UNC), and Elijah Hood, of Charlotte Catholic, were picked to be the teams� backfield.
Coplon was among the most feared return men in North Carolina to go along with his ball-hawking skills.
Coplon racked up 270 return yards on 12 punt returns with four touchdowns, and had six interceptions with two returned for touchdowns.
�It feels really good to be on there with these guys. It was a bit of a shock� Coplon said.
�It showed me that all of my hard work in the spring and summer paid off, and I think having three of us from Craven County is great.�
Coplon, Cooper and Cherry are still enjoying basking in the spotlight from winning a state championship.
New Bern and Havelock were crowned state champs last weekend.
Bra�lon Cherry posted statistics this season including 795 receiving yards with nine touchdowns, two rushing touchdowns, five interceptions, a punt return for a touchdown and two kick returns for scores.
�It feels great and it is a big accomplishment,� Cherry said.
�I just wanted to go out there this year and do what I could to help my team win a state championship, which we did. I wanted to do better this year than the year before.�
Cooper, Havelock�s quarterback and MVP of the state title game, is no stranger to accolades.
This season, the Rams� senior leader accounted for 2,895 passing yards and 25 touchdowns and 1,267 rushing yards and 15 touchdowns.
�It�s a great honor to be recognized as one of the best players in the state and I have to give all of the glory to God,� Cooper said.
�It doesn�t matter to me what position they picked me for either, it�s just great to be on the team. With three of us on there, it speaks a lot to the talent in Craven County and we are putting it on the map.�
Jordan Honeycutt can be reached at 252-635-5670 or at firstname.lastname@example.com. Follow Jordan on Twitter @JHONEYnbsj29.


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360 Gold Laine Saint-Pierre embroidery floss
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Made from half wool, half polyamide fibre, Laine Saint-Pierre is very solid and the colours remain fast.
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