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What Are The Means That Will Advice An Individual Survive The Agrarian And Become A Survivalist
It is already a accustomed actuality that camping trips and hiking are just some of the best and a lot of agitative means that humans are agreeable themselves into these days, so as to amuse and allay the appetite that they accept with commendations to accepting accustomed experiences. The acceptable affair about this amount is that about all of the hiking trails that are absolute in this present day and time, which includes campsites that are so famous, accept already become accepted day-tripper atom which afresh improves the all-embracing assurance of the action due to the breadth acceptable known. However, even admitting the said territories or areas are apparent actual anxiously and well, we still do not apperceive what ability appear as there ability be aberrant contest and affairs that may al of a sudden appear which may advance to humans accepting absent or abnormality off the aisle that could be abeyant crisis for them. We all apperceive that ability is ability that is why all the advice that we will be presenting beneath will altercate about the abundant allowances that you can possibly get with commendations to actual the agrarian and these advice are aggregate from a aboveboard source, a survivalist forum.
Accepting a focused apperception and blockage calm are advised as one of the a lot of basic and a lot of analytical elements in agreement of actual in the agrarian back if you are able of acceptable like this, it will be accessible for you to anticipate of a plan and appropriately laid that plan out so that you can break as safe as accessible in any alarming situations you ability be in. If we get absent in the agrarian or if we devious off the trail, these are the times if we al of a sudden feel the claret hasty through our veins, creating two monsters that we do not wish to meet: cutting abhorrence and anger. But afresh again, there is no charge for you to be afraid or be mad about the bearings you are in back you accept aural you the best and a lot of capital apparatus anyone can anytime accept if it comes to actual and that is your mind. That is why it is actual important for you to accept a bright apperception and be calm all the time in adjustment for you to appropriately accouter the cerebration abilities that you accept and also, in adjustment for you to anticipate of an able way of accepting our from the alarming bearings you ability be in.
Aside from befitting a focused apperception and blockage calm, addition actual important affair that you charge to do in this affectionate of bearings is to attending for a safe abode or area that you can use to cautiously and patiently delay for any help.


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In the middle of Manhattan lies the city's green heart: Central Park. This gigantic park offers picnic areas, playgrounds, ponds and sports fields. This is the place, in the middle of the busy city, where New Yorkers come to blow off steam. On Sunday, the roads in the park are closed and skaters, cyclists and joggers have the place to themselves.
Between 1821 and 1855, the number of inhabitants in New York quadrupled and there became a need for a large public park. It took another 16 years before Central Park was inaugurated 1871, but today this is one of the most pleasant areas in the city. Throughout all 4 seasons of the year, Central Park is a popular attraction for tourists and locals.
The park is used extensively year round. In summer, the park hosts many concerts (Summerstage) and plays (Shakespeare in the Park). The film festivals also draw crowds who watch movies on large outdoor screens. Bring a blanket and some snacks and enjoy a warm summer evening. In winter, thousands of New Yorkers don their ice skates for a spin on one of the two skating rinks in the park: the Wollman Rink and Lasker Rink. The Wollman Rink has been used as a set in many movies. There is nothing more romantic than skating with a view of the New York City skyline.
One of the best known and most visited places in the park is Strawberry Fields, the monument in memory of Beatles musician John Lennon. The mosaic with the lyrics of 'Imagine' (one of Lennon's greatest solo hits) is directly across from the Dakota building on West 72nd Street. Lennon had an apartment here and was shot in the doorway of the building in 1980.
The bronze statue of Alice in Wonderland also attracts many (young) visitors. It shows Alice and a number of other characters from the well-known fairy tale, such as the White Rabbit and the Mad Hatter. The statue was designed in 1959 to let children experience the enchanting story of Lewis Carol. Unlike other monuments, children are allowed to climb and explore this sculpture to their heart's content. Looking for more romance? Reserve a gondola and paddle around the lake with your loved one.
Once inside the park it is difficult to fathom how big Central Park really is. Anyone who is not staying at the Plaza Hotel on the edge of the park can visit the Top of the Rock for a great view of the park. A fast lift whisks visitors to the viewing platform on the roof of the Rockefeller Center. Visit the lookout during the day; at night, the park is one big black hole among the twinkling lights of Manhattan.

subset: commoncrawl


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i had a great time picking out the perfect one for each them.
on the inside page you can add another image
or a little book plate design.
i ordered one for me too...forgot to photograph that one. shoot.
was out christmas shopping & they even called to make sure one of the words/phrases was correct.
excellent customer service too!


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by George Zamora
SEATTLE – Several New Mexico Tech geoscientists will travel to Seattle next week to present talks and posters about their current research at the 115th annual meeting of the Geological Society of America (GSA), which is being held November 2-5 at the Washington State Convention and Trade Center.
Approximately 7,200 geoscientists from throughout the world are expected to attend this year's conference, making it the largest annual meeting ever held in GSA history. In all, 17 New Mexico Tech professors, researchers, and graduate students will give scientific presentations at the annual convention.
The New Mexico Tech geoscientists scheduled to make presentations at the GSA meeting in Seattle (along with the title of their presentations) are:
- Dylan G. Canales, The Akwatia Diamond Field, Ghana, West Africa: Source Rocks;"
- M. Bavani Cardenas, "Three-Dimensional Modeling of Hyporheic Flow through a Hetergenous Streambed;"
- Steven M. Cather, "Early Oligocene Global Cooling, Volcanic Iron Fertilization, and the Ignimbrite Flare-Up of Southwestern North America;"
- Sam Earman, "Groundwater Recharge and Movement in the Central Chiricahua Mountains, Arizona;"
- Laurel B. Goodwin, "Field-Based Analysis of Intrinsic and Extrinsic Controls on Fault-Zone Deformation Processes in Poorly Lithified Materials, with Implications for Hydrologic Studies" and "The Impact of Transient Brittle Failure on Deformation and Metamorphism at Middle and Lower Crustal Levels:"
- Huade Guan, "Modeling Investigation of Water Partitioning at a Semi-Arid Hillslope;"
- Shari Kelley, "Laramide Exhumation History of the Zuni Mountains, West-Central New Mexico,"
- Peter S. Mozley, "Calcite Cementation in Sandstone: From Concretions to Cemented Formations:"
- Samuel A. Ndur, "Sorption of Arsenic onto Laterite—A New Technology for Filtering Rural Water;"
- David I. Norman, "Involvement as a Geology Professor in Ghana Geology and Development;"
- Geoffrey Rawling, "Geologic Mapping for Characterization of Spring Hydrogeology on the Sevilleta and San Andres National Wildlife Refuges, New Mexico;"
- Adam S. Read, "Geologic and Hydrostratigraphic Mapping of the Santa Fe Region, New Mexico: Applications for Assessing and Managing Groundwater Resources;"
- Amanda Rowe, "The Goat Hill Orebody, Questa Porphyry Mo System, New Mexico—A Geochemical Study of Stratified Magmatic-Hydrothermal Breccia and Stockwork Veinlets;"
- Steven Scholle, "Investigations of Pre- and Intra-Bandelier Tuff Sediment Deposits in the Ponderosa and Jemez Springs 7.5 Minute Quadrangles, Sandoval County, New Mexico;"
- Remke L. Van Dam, "How Petrophysics can Contribute to Sedimentological and Stratigraphic Ground-Penetrating Radar Studies;"
- John L. Wilson, "Revolution in Observation-Driven Hydrologic Science—Then and Now" and "Twenty Years of Prejudice toward Contaminant Hydrology;" and
- Jennifer E. Wilson, "Deformation Bands in Nonwelded Ignimbrites: Petrophysical Controls on Fault-Zone Deformation and Evidence of Preferential Fluid Flow."


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Our strongest form of oil this Surepure premium CBD 500 (5% CBD) – 1500mg oil (15% CBD) is a very concentrated liquid hemp oil created using C02, the gentlest method of raw hemp extraction. That way the most important active molecules in the plant remain intact, applying gentle heat under filtration. our mild tasting oils are easily taken in drop form from the pipette under the tongue. this method ensures the product enters your system in the quickest possible way.


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A firewall is a security feature designed to help protect your computer and personal data from unauthorized external access and alert you to immediate threats. A firewall examines all incoming and outgoing Internet traffic and allows only traffic that meets the security policies that were set up. Internet traffic that does not meet these security policies is blocked by the firewall and never reaches your computer.
FiOS Internet has two things hackers love: high-speed access and dedicated connections. High-speed access allows data to move between the hacker and your computer very quickly. The hacker can more easily load malicious programs onto your computer or interact with the information on your computer.Dedicated connections make it easier for hackers to hijack your computer and use it for a server to distribute their illegal or unethical programs and spam. They commonly attempt to take control of your computer in the middle of the night when you are less likely to notice their activities.
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Obama on 'The Avengers,' Kardashians, 'Fifty Shades of Grey'
Perhaps he is actually the first pop culture president. President Obama appeared on ABC's "The View" Tuesday for an interview in which he discussed Wall Street, gay marriage and the Hulk.
Co-host Joy Behar administered a zeitgeist quiz to the president during the show, taped Monday, asking him to name three characters from "The Avengers." "I just saw it, so this is easy," Obama said. "You've got the Hulk, Captain America, Iron Man."
Asked which Kardashian was married for 72 days, the president answered correctly, "That would be Kim." Obama quickly explained his knowledge of the reality star as accidental. "Because he was a ballplayer," he said, referring to Kardashian's ex-husband, NBA player Kris Humphries. "That's how I know, from watching basketball."
Obama has made entertainment programs an increasingly important venue for his public appearances. In 2010 he became the first sitting president to appear on a daytime talk show when he visited "The View," and last month he talked about student loans on "Late Night with Jimmy Fallon." Such shows are a way to reach demographic groups key to the president's re-election campaign — women and young people.
A record-setting fundraiser at George Clooney's Studio City home last week also relied on the president's Hollywood ties: Organizers used the joint star power of Obama and Clooney to lure campaign donations from tens of thousands of participants in an online contest vying to attend.
On "The View" episode that aired Tuesday, the commander in chief seemed pretty pop culture savvy for a man with a country to run and a hotly contested campaign underway — he said he DVRs the shows "Mad Men" and "Homeland" for viewing on his long flights.
But the president did miss some questions. He didn't know that Jessica Simpson had recently had a baby, and he deflected a query on the hot-selling erotic novel "Fifty Shades of Grey." When asked "What's the controversial sex book that's on millions of women's bedside tables?" the president said: "I don't know that. I'll ask Michelle when I get home."
Obama's dinner guests at Clooney's: Details on lucky winners
George Clooney's Obama fundraiser uses star power with a twist
Steve Lopez: Clooney's Obama party full of 'Hollywood hypocrites'
— Rebecca Keegan
Photo: Barbara Walters, left, President Obama and Joy Behar on "The View." Credit: ABC.


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Despite temperatures in the high 90s, we had a capacity turnout at the Phoenix stop of our Come Up Tour presented by WeSC. The glue of Phoenix skateboarding, Cowtown, went above and beyond in its hospitality, helping us set up, judge, and they threw a premiere of Cliché's Bon Voyage Saturday night. Big ups to Trent, Andrew, JR, Sick Nick, and everyone else at the shop! Young Jackson Ellis won our Prime C.U.T. award by sticking the steeziest 360 flip down the ten just as the Best Trick contest ended. He ended up rolling his ankle just a few minutes later, so get well soon Jackson! You rip! Our top three came down to Michael Eddy, Jalen Noel in second, and first place was Greg Dunagan with too many tricks on the rail to mention. See all these guys in the video and photos below.
See you on May 11 New York City! Skaters, submit your footy tapes now to be pre-qualified for the finals!
Photos by Brandon Steed and Brandon Roggeman, Video By Brandon Steed
Music: Witchcraft, Schyssta Logner
Special thanks to our C.U.T. sponsors: WESC, Independent, Deathwish, Shake Junt, Olloclip, Fred Water, House Of Marley, I Ride I Recycle, Coal Headwear


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Showalter has thriving O's focused on task at hand
BALTIMORE -- Buck Showalter's agile baseball mind roams freely. At any given moment, seemingly out of nowhere, he may express an opinion about expanded September rosters, observe that Ty Cobb once stole first base before a rule change disallowed the tactic, wonder about another team's managerial plans or ponder the impact of a casino that recently opened near Oriole Park at Camden Yards.
There is one subject, however, that the Orioles' manager doesn't want to touch with a 10-foot fungo bat. And that is the enviable spot that Showalter's team is in, holding the second-best record in baseball and the biggest lead of any division leader, with just 3 1/2 weeks remaining in the regular season.
BALTIMORE -- Buck Showalter's agile baseball mind roams freely. At any given moment, seemingly out of nowhere, he may express an opinion about expanded September rosters, observe that Ty Cobb once stole first base before a rule change disallowed the tactic, wonder about another team's managerial plans or ponder the impact of a casino that recently opened near Oriole Park at Camden Yards.
There is one subject, however, that the Orioles' manager doesn't want to touch with a 10-foot fungo bat. And that is the enviable spot that Showalter's team is in, holding the second-best record in baseball and the biggest lead of any division leader, with just 3 1/2 weeks remaining in the regular season.
Part of that discomfiture is natural. No champagne has been uncorked yet, and the O's still have many goals to reach.
"I know how fleeting it all can be," Showalter explained. "When I hear a GM say he's on a five-year plan? I want day-to-day, hour-to-hour. 'What can we do this hour to get better?' And then see where it takes you."
That's the only way to approach the longest season, of course. Never get too high, never get too low, and all of that. But it's also a topic Showalter is going to be asked about a lot in the upcoming weeks.
Because the Orioles are one of the best stories in baseball and Showalter -- who took over a club in July 2010 that would end up losing 96 games -- is deservedly getting much of the credit.
"He's the most prepared person I've ever met. I feel like he knows everything that's going to happen before it happens," said shortstop J.J. Hardy. "All the guys in this clubhouse respect him. I think that's a huge thing. And on top of all that, he's really smart and knows how to manage the game."
"Buck instills that work ethic in his players by the way he goes about his job on a day-to-day basis," added executive vice president of baseball operations Dan Duquette. "And he demands good defense at every position. So the players know that to play for this ballclub, they have to be alert and they have to bring their gloves and do their job in the field."
There is a perception out there, which Showalter disputes, that he is responsible for everything from the more than 120 roster moves the O's have made this year to the stadium club menu.
"There are things that the front office brings that I can't and won't," Showalter said. "I just don't possess the skills. And there are things down there that have got to be [done by the uniformed personnel]. All the good organizations are able to mesh those two things. And both parties feel comfortable with what they bring. I embrace all the numbers and everything. But at some point, [the players are] human beings, too. And the good organizations are able to bridge those two factions.
"We sit in a room and we bang it around. And when we come out of the door with a decision, it's the organization's decision. At the end of the day, we make decisions as a group, and I think the players respect that. We know we're dealing with human beings and we don't just callously come to a decision. Whether it be scouts, whether it be player development people, whether it be that [coaches] room in there, whether it be everybody upstairs, I think the greatest accolade you can pay a man or woman is to ask their opinion.
"Since I've been here, whether it's me or Dan or [former general manager Andy MacPhail], nobody has [said], 'This is what we're doing, and I don't want to hear about it.' It's more, 'What do you think?' I don't know how everybody else does it, but that's the way we do it. You know if you come to this organization, you're going to get your opinion asked. And it's going to matter."
Showalter is also quick to credit those who came before him -- guys like MacPhail and former manager Dave Trembley -- for the groundwork that was done before he arrived, probably understandable since the 1996 Yankees and the 2001 D-backs both won the World Series the year after Showalter left.
"You can always look back at a situation that gets better and see some people who took some bullets along the way," he said. "It took a lot of work, and some of it was done before I got here. We're not there yet. We've had a winning club now, won more than we've lost, but is that good enough? There's only one team happy at the end of the year."
Baltimore's payroll of $105 million ranks in the middle of the pack. The Orioles embrace the reality that they're not going to be bidding up the price of the top free agents each winter, and they have even managed to turn that into an advantage.
"There's a good morale here because [Double-A] Bowie and [Triple-A] Norfolk and [Class A] Frederick, they know that's where we're going," Showalter explained. "When we go after six-year [Minor League] free agents, we can out-opportunity some of the higher-payroll teams. And we're proud of that. There's a reputation in the game that if you sign with the Orioles, you're going to get an opportunity. Because we're not always going to be looking in somebody else's back yard. We're going to look in our own first, and shame on us if the answers aren't there."
Showalter managed the Yankees when he was 36 years old. He's now 58 and in his 15th season managing in the big leagues. Showalter has won the Manager of the Year Award twice and has been runner-up two other times. But he's never been to the World Series, another understandable caution for not getting carried away.
Baseball can be a difficult game, a maddening game, a frustrating game, a humbling game even for teams that seem to be on cruise control. That's why Showalter is so adamant about staying focused, sticking to the basics.
"We ain't reinventing the wheel. We ain't got all the answers," Showalter said. "People talk about the 'Baltimore Way' or this and that. No. It's the 'baseball way,' and everybody's trying to do it. It's not just us. It's pretty simple. It's not complicated.
"I don't think there's ever been an increment put together that's better than 90 feet. It's about figuring out ways to get 90 feet and ways to keep them from getting 90 feet. If a guy hits 30 home runs a year, what percentage of his at-bats are they? Games are decided over the long haul by the ability to stop 90 feet and gain 90 feet, however it may be -- holding runners, defending the ball, turning double plays, bunting, foot speed."
And the O's have done that often enough and consistently enough this season to be in a position that Showalter really doesn't want to talk about.
Paul Hagen is a reporter for MLB.com.


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John McGovern, executive vice president, Resolute Consulting
John McGovern was promoted from Vice President to Executive Vice President at Resolute Consulting, the company said this week. Prior to joining Resolute, John was a senior advisor to J. Dennis Hastert, former Speaker of the United States House of Representatives. During his eight years with Speaker Hastert, John worked as a press secretary, national campaign spokesperson and executive director of Keep Our Majority PAC, Speaker Hastert's national political action committee. He holds a J.D. from Northwestern University School of Law and an A.B. in history and American studies from Princeton University. He is admitted to the Illinois Bar.
Copyright © 2019, Chicago Tribune


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Leftover notes, quotes from Laney-North Brunswick
I was in Leland last night as Laney visited North Brunswick for some high school hoops. The full story is here, but there were also plenty of notes and quotes that couldn't make it into the story. -Program building – Laney and North Brunswick's boys programs have a lot in common. Both teams lack a true post player and both have a bevy of athletic wings who can attack off the dribble. Both like to play with speed, and both… Read More »


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were made because of the candy in the photo below and her desire to eat it before I knew what I wanted to do with it. It was sitting in what we call the "don't touch Grandma's stuff" area. She told me to please hurry up and design a rainbow cloud cookie because she really needed to eat those rainbows. Okay, so I admit they've been there for over a month, waiting for a design inspiration to hit me. You hit a bullseye Danielle. You have again come up with a fun design idea for me to figure out how to make into cookie form.
Here is the rainbow candy Danielle really needed to eat. I found it at Party City. As you can see it's flexible enough to use for a rainbow.
I don't have a cloud cookie cutter, so I drew two cloud patterns with slots marked large enough for the rainbow candy to slide through. I scanned the drawing to my computer, cleaned it up in my paint program and printed it onto card stock for templates.
Using the template I cut out my clouds. I then marked where I wanted the rainbow candy to slide through and cut a slot large enough. I used a small cutter I found in a mini alphabet set (upper left cookie), but I also show how you can get the same result using a round icing tip to cut the ends (lower left cookie), and an offset spatula to cut out the middle (middle right cookie). A knife might have been better, but I had the spatula handy.
Note: If your cookie dough spreads you might need to make the hole for the candy rainbow larger and/or wider so it doesn't spread together and close up while it bakes.
Once the cookies were baked and cooled I did a wet on wet technique starting with white icing and then adding swirls of sky blue, light blue, and pink. (middle left cookie). I let this dry overnight. The next day I outlined in white icing (upper right cookie) and sprinkled white sanding sugar over the outline and let dry. (bottom right cookie).
Here they are all done with the rainbow candy threaded through the hole in the cookie. Now Danielle has a cookie to eat with her rainbow.
♥ Happy Decorating ♥


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AP photo
George W. Bush: His popularity was higher — and his campaign schedule more rigorous — in his first midterm election.
For a man who once appeared to derive some much energy from pumping up his audience at a political pep rally, President Obama has spent most of the election cycle anywhere but major rallies.
Indeed, he's attended fewer than half the political rallies attended by former President George W. Bush during his first midterm election.
With his popularity shrinking and Democrats in need of a cash infusion, President Obama has largely devoted his political efforts to big-money events, appearing at 69 political fundraisers, many of them hosted by longtime Democratic donors. His appearances paid off big for Democrats, who hauled in more than $73 million at presidential fundraisers, said CBS Radio's Mark Knoller, a longtime tracker of such statistics.
Though Obama's schedule has placed a heavy emphasis on fundraising, the president has continued to appear at some public rallies. On Sunday, which the White House planned as the president's final day of campaigning, Obama joined Vice President Joe Biden at an arena in Cleveland. Sunday's rally, Obama's 17th rally since assuming the presidency, followed a weekend of such events in Bridgeport, Conn., Chicago and Philadelphia.
Knoller, who also keeps tabs on presidential travel, added that aside from Maryland and Virginia, Obama has most often visited Florida, Illinois, New York, Ohio and Pennsylvania since he took office. Three of those states — Florida, Illinois and Pennsylvania — have been the sites of particularly tight Senate races during the midterm cycle.
In 2002, President George W. Bush traveled to such an extent that some in the media took to describing the presidential aircraft, Air Force One, as "Air Force Won." Democracy in Action, a website sponsored by the George Washington University, says Bush appeared at 17 rallies in 15 states during the final five days of the 2002 election cycle, which was the first midterm of the Bush presidency. Knoller said that in total, Bush notched attendance at 36 rallies in 2002.
Knoller also said Bush attended at 68 political fundraisers leading up to the 2002 elections, during which Republicans gained eight seats in the House and two in the Senate, giving the GOP control of both houses of Congress. Bush's appearances raised more than $145 million for the Republican Party.
Obama appeared to follow a more traditional style than Bush adopted in 2002.
"The usual behavior of a president in midterm elections is to raise money… then make occasional appearances in September and October for favored nominees, avoiding too close identification with candidates who may lose," said Larry Sabato of the University of Virginia. "George Bush decided to set a new precedent."
The contrasting degrees of political activity have at least some of their roots in the political climates of the two cycles. In 2002, less than 14 months removed from the terrorist attacks of Sept. 11, 2001, Bush enjoyed a better than 60 percent approval rating. Obama, who inherited a recession and two wars, had a 47 percent approval rating in two recent polls.
Taxpayers pick up much of the tab for the president's travel, even if a trip is mostly political in nature. The White House uses a formula created during the Reagan administration to calculate the expenses of political activity during a trip and if any factors, such as the presence of an official event on the president's calendar, mitigate the extent of partisan political activity on the trip.
The benefiting campaign or political group, such as the Democratic National Committee, is responsible for those expenses deemed partisan in nature. Some costs, like Secret Service protection and the transportation of essential equipment, are always borne by the federal government because they would be necessary whether the president was engaging in political activity or not.


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- Vintage 1950s
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Label: NA
Condition: Great. This hat is ready to wear, and freshly steamed. This hat presents beautifully and is ready to enjoy!
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Please note: Model in photo has a 21" head.
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Facebook: https://www.facebook.com/polishedraven
Twitter: https://twitter.com/polishedraven


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Lisa Cutler necesitaba un nuevo diseño de logotipo y lanzó un concurso de diseño en 99designs.
Un ganador ha sido elegido entre 33 diseños de 16 diseñadores freelance.
I require a unique, eye-catching and creative logo to establish my new brand for a life coaching company appealing to both individuals and corporates.
Cutler Coaching
I'm looking for a logo for Cutler Coaching that is simple, effective and reflects some of the essence of the Cutler Coaching Company. Cutler Coaching is life coaching for individuals and companies, and business and executive coaching. Cutler Coaching also holds workshops and seminars targeted to specific groups (such as women, teenagers, working mums), or specific agendas (such as the art of positive communication & turning goals into reality). Coaching is about motivating and inspiring people to live their lives to their full potential. It's about guiding them to personal empowerment through igniting the tools and strategies within them to achieve extraordinary results in all areas of their lives.
The values of Cutler Coaching are: Courage, Spirit, Heart, Learning, Passion, Happiness and Inspiration.
Some metaphors to generate ideas include: Expanding your horizons; Tour guide to your journey of self discovery; Finding the real you; Walking in the footsteps of your dreams; Widening the focus on your torch of life.
- Symbol, design or picture that can also be separated from the written Cutler Coaching
- Simple and effective
- Like purple and silver, but also open to other colour suggestions
- Winning design in Adobe Photoshop
- Anything too complex, detailed or busy
Descubre cómo funciona un concurso de diseño u obtén más información sobre nuestros servicios de diseño de logo.


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Search terms
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A cool 5.1 cm (2") high resolution display on your GoGear player offers excellent video quality and crisp, vivid images. Together with a full color menu, the large screen allows easy navigation of media files to complete the package for a all-round multimedia experience on the go.
Charge your GoGear player battery quickly and easily from your PC via USB. By connecting your player to your PC with the cable provided and following the necessary prompts, your PC will provide the power for charging your player within a few seconds. Enjoy the convenience of doing away with a separate recharger.
Folder view is an optional directory view of the GoGear player that lets you view all the files on your player as if it were a computer. Once you select Folder view, opening any supported file (i.e. music, pictures or videos) is as easy as selecting the file and hitting Play.
View videos on the go with Internet Video Download, an easy-to-use feature that lets you download videos from video sharing sites (YouTube, MySpace or Google Video) to your GoGear. Install the PC application provided, connect your GoGear to your PC and use Internet Explorer to visit your favorite video sharing site. Choose a video and click the Download button that appears when you hover the mouse cursor over the video. No need to wait, just move on to other videos and start downloading more.
RDS (Radio Data System) is a communications protocol standard that allows digital information to be transmitted over FM radio broadcasts. RDS-enabled FM radio receivers can display this useful information that includes station identity, program details and song title and artist, etc. At anytime, you can store a desired station as a preset channel on your GoGear player. With 20 preset radio stations that can be stored, you can quickly access your favorite radio station without having to manually tune the frequencies each time.
GoGear's easy and intuitive user interface is powered by an advanced navigation technology. It not only helps to ensure quick and smooth navigation but also an enjoyable multimedia experience that doesn't take long to master. Smart features like Album Art – which displays album artwork embedded in music files – enables you to have a richer experience, just like in the good old days when you would view the cover of a CD or LP while enjoying your music.
Voice recording converts your GoGear player into a handy dictation machine. Besides playing music or listening to radio, you can also record notes or reminders for work or school, record shopping lists and phone numbers – even song lyrics. By pressing the recording button and speaking into the built-in microphone, voice messages are compressed and stored in the built-in internal memory. Voice recording gives you a highly portable voice recorder allowing you to record anything, anytime and anywhere!
Audible.com is your destination for the widest selection of digital audiobooks, magazines, radio shows, stand-up comedy, and more available for download. Enjoy books in the car, at the gym, or around the house. Authors and icons read their own works, and famous actors narrate your favorite titles. At Audible.com you can browse and sample over 75,000 selections, including the latest best sellers and timeless classics.
Forget about the hassle of having to recharge your GoGear player battery constantly. This longlasting player allows you to savor your favorite tunes for up to a whopping 30 hours of continuous music playback or up to 6 hours of video playback - all on a single charge. Now you can sit back and listen to music all day long or watch the equivalent of 3 movies back-to-back wherever you go.


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secondwind wrote:Strom....... Build of a senior already. Absolute pure stroke. Needs to work plenty on taking defender off the dribble as he will be crowded defensively and also his defense. Has luxury of sitting on perimeter and spotting up for now as is surrounded with terrific talent.
T$$ wrote:I have never heard of either of these players. It seems like in the east individual stats are more important than how your team does. Any thoughts?
T$$ wrote:Nothing against either player with this question, but do they play varsity because their team lacks talent or in shanley case depth? I think calling any freshman "the future" of an entire confernce is unfair to that player. Are you going to measure success by their stats and pt or by how their teams do?
Ndbaseball999 wrote:Yes i have heard strom would maybe transfer, but its just a rumor, there also is a kid from kindred i believe who is really good and wants to play, and 2 to 3 players from south that would like to remain nameless until they make their choice.
Ndbaseball999 wrote:Well it's just a rumor I heard, but they both could help.
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ReleasesBack to
Eric Dolphy
The 1999 discovery of a previously unknown 1963 concert by Eric Dolphy makes it one of the finds of the decade. Taped for broadcast at the University of Illinois at Champaign, it was mentioned in an Eric Dolphy Internet chat room and eventually relayed to producer Michael Cuscuna. The sound is very good, except for overly prominent drums throughout the concert and an under-miked flute on "South Street Exit." Dolphy's playing is consistently rewarding, including a lengthy workout of "Softly, As in a Morning Sunrise," a miniature of "Something Sweet, Something Tender," and his always superb solo feature of "God Bless the Child." He switches to alto sax for an adventurous new work, "Iron Man" (which he would record a few months later for Douglas International), also inserting a hilarious quote of "Comin' Through the Rye." A 23-year-old Herbie Hancock on piano, Eddie Locke on bass, and drummer J. C. Moses make up the solid rhythm section. The last two tracks, "Red Planet" and Dolphy's "G.W.," add the support of the University of Illinois Brass Ensemble, which included a young Cecil Bridgewater on trumpet. Highly recommended!- ~ Ken Dryden


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David Skipper needed a new logo design and created a contest on 99designs.
A winner was selected from 156 designs submitted by 37 freelance designers.
I SMOKE - Electronic Cigarettes
We are a company working with end-user sales. We are on the way to startup a new product line selling E-cigarette product.
Our audience is male and female smokers who are looking to quit smoking or for a smoking alternative to reduce their smoking.
We need a loyal and trusted logo design, we prefer to get the file in .ai, so we can use it in several size variations.
Brand name: I SMOKE
Subtitles: Electronic Cigarette
Background: Black / White
Main Colors: Black/White and Silver
Design ideas: Luxury, Club, Lounge, High-End products.
Find out how a design contest works or learn more about our logo design services.


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The United States Court of Appeals for the Federal Circuit was established under Article III of the Constitution on October 1, 1982. The court was formed by the merger of the United States Court of Customs and Patent Appeals and the appellate division of the United States Court of Claims. The court is located in the Howard T. Markey National Courts Building on historic Lafayette Square in Washington, D.C.
The Federal Circuit is unique among the thirteen Circuit Courts of Appeals. It has nationwide jurisdiction in a variety of subject areas, including international trade, government contracts, patents, trademarks, certain money claims against the United States government, federal personnel, veterans' benefits, and public safety officers' benefits claims. Appeals to the court come from all federal district courts, the United States Court of Federal Claims, the United States Court of International Trade, and the United States Court of Appeals for Veterans Claims. The court also takes appeals of certain administrative agencies' decisions, including the United States Merit Systems Protection Board, the Boards of Contract Appeals, the Patent Trial and Appeal Board, and the Trademark Trial and Appeal Board. Decisions of the United States International Trade Commission, the Office of Compliance, an independent agency in the legislative branch, and the Government Accountability Office Personnel Appeals Board, and the Department of Justice Bureau of Justice Assistance also are reviewed by the court. Many of the administrative law cases consist of personnel and veterans claims. Nearly all of the intellectual property cases involve patents. Suits for money damages against the United States government include government contract cases, tax refund appeals, unlawful takings, and civilian and military pay cases.
The judges of the court are appointed by the President, with the advice and consent of the Senate. Judges are appointed to the court for life under Article III of the Constitution of the United States. There are twelve judges in active service. When eligible, judges may elect to take senior status, which permits them to continue to serve on the court while handling fewer cases than a judge in active service. Each judge in active service employs a judicial assistant and up to four law clerks, while each judge in senior status employs a judicial assistant and one law clerk.
Title 28 of the United States Code, the Federal Rules of Appellate Procedure and the court's Rules of Practice and Internal Operating Procedures govern procedure in the Federal Circuit. Appeals are heard by panels comprised of three judges who are selected randomly for assignment to the panels. Losing parties may seek review of a decision of the Federal Circuit in the Supreme Court of the United States.
Court sessions generally are held during the first week of each month in Washington, D.C. The court also is authorized to hear cases in other cities throughout the United States to meet the needs of litigants in other parts of the country. The court has sat in many other cities during its existence.
The court's work begins when an appeal is docketed by the Clerk of the Court, and is assigned a docket number. The parties to the cases then prepare and file written briefs setting forth their arguments. Parties also may submit materials such as transcripts of testimony and other relevant parts of the record made in the lower tribunal from which the appeal originated. Once all the briefs have been received, the case may be scheduled for oral argument before the court. Each side usually is allotted between 15 and 30 minutes for argument, depending on the nature of the case. During oral argument, the lawyers for the parties present their arguments and answer questions of the judges concerning the issues presented. If the court determines that oral argument is unnecessary, the case is decided by a panel of judges based on the arguments presented in the briefs. In each appeal, the presiding judge of the panel assigns a member of the panel to prepare the court's opinion. The opinion sets out the decision of the court and the reasons for the decision. If the panel determines that its decision will add significantly to a body of law, it issues a precedential opinion. Decisions that do not add significantly to the body of law are issued as nonprecedential. All opinions are made available to the public, and may be obtained from the court's home page on the Internet, the Federal Reporter 3rd Series, Westlaw® and Lexis®.
The senior staff of the court consists of the Circuit Executive and Clerk of Court, Chief Deputy Clerk, Deputy Circuit Executive and Operations Office, General Counsel, Circuit Librarian, and Director of Information Technology.
United States
Court of Appeals
for the
Federal Circuit


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Thirty-two years have passed since the Lucifer was destroyed. Its reactors were breached causing it go nova as it exited the SOL jump node. Since then the Earth has been cutoff from the rest of the galaxy. A group of rebels, the Neo Terran Front (NTF), have been putting a huge strain on the Terran-Vasudan relations and the new Galactic Terran-Vasudan Alliance (GTVA). Due to a discovery made by the NTF, an ancient device created by the "Ancients," a portal has been opened leading directly into Shivan space. The Shivans from "The Great War" are back and they are pissed off. You, a member of the human "Lost Generation", will have to answer the call to war.
Only registered members can share their thoughts. So come on! Join the community today (totally free - or sign in with your social account on the right) and join in the conversation.


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Winter is finally in full swing in Colorado and the powder is calling. But, with so many resorts to choose from – 26 in total – which one will give you maximum fun for the whole family without all the hassle? Winter Park Resort, Colorado's Favorite, is where it's at.
For starters, Winter Park is the closest major destination resort to Denver International Airport – just 67 miles northwest of Denver. It took my family a little less than two hours to drive there from the East side of Denver. We arrived at The Vintage Hotel just before 8am and even though check-in wasn't until that afternoon, the front desk showed us to the locker rooms in the hotel where we could change into our gear and head out onto the mountain. The Vintage is just one of three premier properties available for lodging at the resort, and the most economical for those on a budget. However, there is no skimping on quality. The Vintage just outfitted all 118 rooms with brand new high quality mattresses, pillows, linens and towels this month. After a long day on the mountain, the importance of a comfortable night's sleep can't
be overstated.
From the Vintage, a complimentary gondola ride takes you to the base of The Village at Winter Park. Our five-year-old daughter, Reagan loves the gondola ride and the little red wagons found at the entrance to The Village and at specially designated wagon drop-off stations throughout for hauling your gear… and your kids. In addition to lots of great shops, cafes and restaurants, there are play areas for the kids and metal xylophone-like instruments/sculptures everywhere in The Village to keep them entertained.
By 9am we were signing Reagan up for her very first ski lesson at the Kid's Ski & Ride School. The super-friendly staff and organization of check-in made the experience much less daunting than it could've been. Part of it is the all new system of kid's ski rentals by Head, called BYS, designed to get them (and you) on the slopes faster, that the resort has just invested in. It was the most painless rental experience we've ever had.
After seeing Reagan safely off to ski school, Danny and I met with a mountain guide for a free tour of the mountain – a great way to familiarize yourself with the terrain. We learned a lot about what makes Winter Park such a popular destination, including the fact that it is home to the National Sports Center for the Disabled, and where many winter Olympians choose to train.
What a treat we were in for at the end of our tour when we caught Reagan and the rest of her ski school buddies being carted up the mountain in a wagon, pulled by a snowmobile. No more magic carpet, they were on their way to their first green run! The wagon transport versus ski lift is just one of the unique ways Winter Park's ski school caters to new skiers not quite ready for the often tricky process of de-boarding a lift their first time up the mountain.
After lunch in the village at the popular Doc's Roadhouse Bar and Grille, we picked up Reagan and received a glowing report on her first day. It wouldn't be long before I wouldn't be able to keep up with her.
That evening, Danny and I enjoyed a romantic, five-course, gourmet meal two miles high at The Lodge at Sunspot. The Zephyr chairlift is converted into a gondola to carry diners to the top of the mountain where they will have a unique dining experience of authentic and award-winning Colorado cuisine.
We ended our weekend with a fun-filled, family afternoon of tubing at Colorado Adventure Park and then the hot tub, water slide and lazy river at the Grand Park Community Recreation Center. Had we had one more night, we definitely would've make the short, 15 minute drive to Devil's Thumb Ranch for their sleigh ride and dinner at either Heck's Tavern or The Ranch House Restaurant. Ski Magazine listed Devil's Thumb Ranch as one of their top 5 Favorite Sleigh Rides.
Next time.
Chris is a designer, WAHM and pilot's wife living in Colorado. She writes as Standby Traveling Mom as well as at MamaBirdsBlog.com. Follow her on Twitter as @BirdBanter.
Disclosure: Winter Park Resort hosted us for the purposes of writing this review. No other compensation was provided. All opinions expressed are my own and without influence by Winter Park Resort.


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When Roubini speaks one must listen.
When Roubini speaks one must listen.
Hmmmm. i seem to remember the errors of your ways. Blaming Obama for everything even when it didnt start on his watch and he has been busy trying to reform the financial system as the banks and Republicans try to block him every step of the way. You do know who Paul Volcker is correct. Do a little reading about him and what he is recommending. If you want i can post some articles for you.
No doubt there are major problems in the worlds financial system. Read the 2 articles on the political thread and try again to throw away those silly Republican talking points and then maybe we can have a serious discussion.


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For the third year, aspiring TV writers will flock to Woods Hole this February 22-24 to learn more about the craft of script writing from veteran television writer, P.K. Simonds.
Kicking off with a wine and cheese reception at the Woods Hole Inn on Friday night, writers will meet for two sessions on Saturday (2/23) plus a wrap up session on Sunday morning (2/24) making for a packed and fun-filled weekend of learning and excitement.
A vivid introduction to the inner workings of dramatic network television, this two-day Symposium will dissect all the pieces of success in hour-long drama writing.
Meet TV drama veteran P.K. Simonds (executive producer of "Ghost Whisperer" and "Party of Five") who will lead your journey. Film writing gets more attention in teaching programs and in the media, but the majority of jobs and income are derived writing for network and cable TV. Simonds has spent over 25 years in the network TV trenches and he will share his experience with you!
The Symposium will go from macro to micro, beginning with an overview of the industry, exploring the differing roles of the writer in TV versus film, then deconstructing the process of writing and producing a single TV episode. Says Simonds, "I want to break the business down and make it more understandable. How does a writers room work? How are stories developed and seasons planned? Who is responsible for a single script? What is the balance of power between the players? Is it possible to do your job in Hollywood without selling your soul?"
To illustrate the creative process in action, participants will be invited to share their stories with the group. Simonds will lead a story discussion, the same way it happens in professional writers rooms, to try to help writers develop their ideas. We'll conclude by discussing important first steps for writers to take to break into the industry. Writers will network, share ideas and enjoy the stark beauty of Cape Cod in winter.
Applications are currently being accepted via the Woods Hole Film Festival website and include submitting a writing sample. Fee to attend is $150 per writer. Accepted attendees will be offered a discounted lodging package at the Woods Hole Inn in Woods Hole. Book the Woods Hole Inn by calling (508) 495-0248, based on availability.


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We would love to hear from you! Simply fill up the form below to send us a message.
You may also email [email protected] Thank you!
UPAA as a broad-based, united, and strong body of fully supportive alumni members willing to commit their resources towards the attainment of its objectives.
To lead the alumni of the University of the Philippine in concerted support of the alma mater's mandate as the national university.
1. Provide organized alumni assistance to U.P. in its role as the country's premier academic institution
• Raise funds
• Establish scholarships
• Engage expert services and advice on U.P.'s
• various activities
2. Contribute to a more effective participation of U.P. in the development of Philippine society.
• Sponsor interactive programs and fora to tackle
• issues of national concern
3. Establish a placement assistance for U.P. graduates and other alumni
• Compile a directory of organizations led by
• U.P. alumni
• Build and maintain an alumni profiling system
4. Acquire competence on various areas of social activity outside the U.P. System
• Establish a needs analysis system


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(417)813-6654 Phone Number Reports
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If you have a huge sweet tooth like I do, then the chocolate art supplies by design firm Nendo are probably whetting your appetite. These tubes of paint and pencils are completely edible, and the paint tubes are full of different sweet fillings. You can sharpen the "pencils" and use the shavings to enhance other desserts.
Nendo originally created the chocolate pencils in 2007 for patissier Tsujiguchi Hironobu. Art and cooking (especially the art of plating food) go hand in hand, and the designers considered this with their initial idea. They write:
We wanted our plates to show off the beauty of meals and desserts like a painting on a canvas. Based on this idea, our "chocolate pencils" come in a number of cocoa blends that vary in intensity, and chocophiles can use the special "pencil sharpener" that comes with our plate to grate chocolate onto their dessert. Pencil filings are usually the unwanted remains of sharpening a pencil, but in this case, they're the star!
The paint tubes have an edible label that tell you what flavored syrup to expect. They range from green tea to honey to caramel. Nendo describes their new creation as "…design that combines the childhood excitement of opening a new box of paints and the thrill of opening a box of chocolates you've been given unexpectedly." What a perfect gift for someone who is both a sweets and artist. Yum! (Via This Is Colossal and Yatzer)


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Publications of ???
Genome-Wide Association Interaction Analysis for Alzheimer's Disease
Gusareva, Elena ; ; et al
in Neurobiology of Aging (2014)
We propose a minimal protocol for exhaustive genome-wide association interaction analysis that involves screening for epistasis over large-scale genomic data combining strengths of different methods and ... [more ▼]
We propose a minimal protocol for exhaustive genome-wide association interaction analysis that involves screening for epistasis over large-scale genomic data combining strengths of different methods and statistical tools. The different steps of this protocol are illustrated on a real-life data application for Alzheimer's disease (AD) (2259 patients and 6017 controls from France). Particularly, in the exhaustive genome-wide epistasis screening we identified AD-associated interacting SNPs-pair from chromosome 6q11.1 (rs6455128, the KHDRBS2 gene) and 13q12.11 (rs7989332, the CRYL1 gene) (p = 0.006, corrected for multiple testing). A replication analysis in the independent AD cohort from Germany (555 patients and 824 controls) confirmed the discovered epistasis signal (p = 0.036). This signal was also supported by a meta-analysis approach in 5 independent AD cohorts that was applied in the context of epistasis for the first time. Transcriptome analysis revealed negative correlation between expression levels of KHDRBS2 and CRYL1 in both the temporal cortex (β = -0.19, p = 0.0006) and cerebellum (β = -0.23, p < 0.0001) brain regions. This is the first time a replicable epistasis associated with AD was identified using a hypothesis free screening approach. [less ▲]Detailed reference viewed: 59 (14 ULiège)
Association of IL33-IL-1 receptor-like 1 (IL1RL1) pathway polymorphisms with wheezing phenotypes and asthma in childhood.
; Mahachie John, Jestinah ; et al
in Journal of Allergy and Clinical Immunology (2014)
BACKGROUND: Genome-wide association studies identified IL33 and IL-1 receptor-like 1 (IL1RL1)/IL18R1 as asthma susceptibility loci. IL33 and IL1RL1 constitute a single ligand-receptor pathway. OBJECTIVE ... [more ▼]
BACKGROUND: Genome-wide association studies identified IL33 and IL-1 receptor-like 1 (IL1RL1)/IL18R1 as asthma susceptibility loci. IL33 and IL1RL1 constitute a single ligand-receptor pathway. OBJECTIVE: In 2 birth cohorts, the Prevalence and Incidence of Asthma and Mite Allergy (PIAMA) study and Avon Longitudinal Study of Parents and Children (ALSPAC), we analyzed associations of longitudinal wheezing phenotypes and asthma with single nucleotide polymorphisms (SNPs) of 8 genes encoding IL-33, IL1RL1, its coreceptor IL1RAcP, its adaptors myeloid differentiation primary response gene 88 (MyD88) and Toll-IL-11 receptor domain containing adaptor protein (TIRAP), and the downstream IL-1 receptor-associated kinase 1, IL-1 receptor-associated kinase 4, and TNF receptor-associated factor 6 (TRAF6). Furthermore, we investigated whether SNPs in this pathway show replicable evidence of gene-gene interaction. METHODS: Ninety-four SNPs were investigated in 2007 children in the PIAMA study and 7247 children in ALSPAC. Associations with wheezing phenotypes and asthma at 8 years of age were analyzed in each cohort and subsequently meta-analyzed. Gene-gene interactions were assessed through model-based multifactor dimensionality reduction in the PIAMA study, and gene-gene interactions of 10 SNP pairs were further evaluated. RESULTS: Intermediate-onset wheeze was associated with SNPs in several genes in the IL33-IL1RL1 pathway after applying multiple testing correction in the meta-analysis: 2 IL33 SNPs (rs4742170 and rs7037276), 1 IL-1 receptor accessory protein (IL1RAP) SNP (rs10513854), and 1 TRAF6 SNP (rs5030411). Late-onset wheeze was associated with 2 IL1RL1 SNPs (rs10208293 and rs13424006), and persistent wheeze was associated with 1 IL33 SNP (rs1342326) and 1 IL1RAP SNP (rs9290936). IL33 and IL1RL1 SNPs were nominally associated with asthma. Three SNP pairs showed interaction for asthma in the PIAMA study but not in ALSPAC. CONCLUSIONS: IL33-IL1RL1 pathway polymorphisms are associated with asthma and specific wheezing phenotypes; that is, most SNPs are associated with intermediate-onset wheeze, a phenotype closely associated with sensitization. We speculate that IL33-IL1RL1 pathway polymorphisms affect development of wheeze and subsequent asthma through sensitization in early childhood. [less ▲]Detailed reference viewed: 64 (7 ULiège)
Genome-wide environmental interaction analysis using multidimensional data reduction principles to identify asthma pharmacogenetic loci in relation to corticosteroid therapy
Van Lishout, François ; Bessonov, Kyrylo ; et al
Poster (2013, October 25)
Genome-wide gene-environment (GxE) and gene-gene (GxG) interaction studies share a lot of challenges via the common genetic component they involve. GWEI studies may therefore benefit from the abundance of ... [more ▼]
Genome-wide gene-environment (GxE) and gene-gene (GxG) interaction studies share a lot of challenges via the common genetic component they involve. GWEI studies may therefore benefit from the abundance of methodologies that are available in the context of genome-wide epistasis detection methods. One of these is Model-Based Multifactor Dimensionality Reduction (MB-MDR), which does not make any assumption about the genetic inheritance model. MB-MDR involves reducing a high-dimensional GxE space to GxE factor levels that either exhibit high or low or no evidence for their association to disease outcome. In contrast to logistic regression and random forests, MB-MDR can be used to detect GxE interactions in the absence of any main effects or when sample sizes are too small to be able to model all main and GxE interaction effects. In this ongoing study, we demonstrate the opportunities and challenges of MB-MDR for genome-wide GxE interaction analysis and analyzed the difference in prebronchodilator FEV1 following 8 weeks of inhaled corticosteroid therapy, for 565 pediatric Caucasian CAMP (ages 5-12) from the SHARE project. [less ▲]Detailed reference viewed: 87 (17 ULiège)
Therapeutic Strategy and Patient Outcome during the First 2 Years of Pediatric Crohn's Disease
; Mahachie John, Jestinah ; et al
in Journal of Pediatric Gastroenterology and Nutrition (2013, May)Detailed reference viewed: 39 (7 ULiège)
An efficient algorithm to perform multiple testing in epistasis screening
Van Lishout, François ; Mahachie John, Jestinah ; Gusareva, Elena et al
in BMC Bioinformatics (2013), 14
Background: Research in epistasis or gene-gene interaction detection for human complex traits has grown over the last few years. It has been marked by promising methodological developments, improved ... [more ▼]
Background: Research in epistasis or gene-gene interaction detection for human complex traits has grown over the last few years. It has been marked by promising methodological developments, improved translation efforts of statistical epistasis to biological epistasis and attempts to integrate different omics information sources into the epistasis screening to enhance power. The quest for gene-gene interactions poses severe multiple-testing problems. In this context, the maxT algorithm is one technique to control the false-positive rate. However, the memory needed by this algorithm rises linearly with the amount of hypothesis tests. Gene-gene interaction studies will require a memory proportional to the squared number of SNPs. A genome-wide epistasis search would therefore require terabytes of memory. Hence, cache problems are likely to occur, increasing the computation time. In this work we present a new version of maxT, requiring an amount of memory independent from the number of genetic effects to be investigated. This algorithm was implemented in C++ in our epistasis screening software MBMDR-3.0.3. We evaluate the new implementation in terms of memory efficiency and speed using simulated data. The software is illustrated on real-life data for Crohn's disease. Results: In the case of a binary (affected/unaffected) trait, the parallel workflow of MBMDR-3.0.3 analyzes all gene-gene interactions with a dataset of 100,000 SNPs typed on 1000 individuals within 4 days and 9 hours, using 999 permutations of the trait to assess statistical significance, on a cluster composed of 10 blades, containing each four Quad-Core AMD Opteron Processor 2352 2.1 GHz. In the case of a continuous trait, a similar run takes 9 days. Our program found 14 SNP-SNP interactions with a multiple-testing corrected p-value of less than 0.05 on real-life Crohn's disease data. Conclusions: Our software is the first implementation of the MB-MDR methodology able to solve large-scale SNP-SNP interactions problems within a few days, without using much memory, while adequately controlling the type I error rates. A new implementation to reach genome-wide epistasis screening is under construction. In the context of Crohn's disease, MBMDR-3.0.3 could identify epistasis involving regions that are well known in the field and could be explained from a biological point of view. This demonstrates the power of our software to find relevant phenotype-genotype higher-order associations. [less ▲]Detailed reference viewed: 83 (22 ULiège)
Therapeutic Strategy and Patient Outcome during the First 2 Years of Pediatric Crohn's Disease
; Mahachie John, Jestinah ; et al
in Acta Gastro-Enterologica Belgica (2013)Detailed reference viewed: 22 (2 ULiège)
A robustness study to investigate the performance of parametric and non-parametric tests used in Model-Based Multifactor Dimensionality Reduction Epistasis Detection
Mahachie John, Jestinah ; Gusareva, Elena ; Van Lishout, François et al
in BioData Mining (2013)Detailed reference viewed: 19 (6 ULiège)
Molecular reclassification of Crohn's disease: a cautionary note on population stratification.
; ; Mahachie John, Jestinah et al
in PLoS ONE (2013), 8(10), 77720
Complex human diseases commonly differ in their phenotypic characteristics, e.g., Crohn's disease (CD) patients are heterogeneous with regard to disease location and disease extent. The genetic ... [more ▼]
Complex human diseases commonly differ in their phenotypic characteristics, e.g., Crohn's disease (CD) patients are heterogeneous with regard to disease location and disease extent. The genetic susceptibility to Crohn's disease is widely acknowledged and has been demonstrated by identification of over 100 CD associated genetic loci. However, relating CD subphenotypes to disease susceptible loci has proven to be a difficult task. In this paper we discuss the use of cluster analysis on genetic markers to identify genetic-based subgroups while taking into account possible confounding by population stratification. We show that it is highly relevant to consider the confounding nature of population stratification in order to avoid that detected clusters are strongly related to population groups instead of disease-specific groups. Therefore, we explain the use of principal components to correct for population stratification while clustering affected individuals into genetic-based subgroups. The principal components are obtained using 30 ancestry informative markers (AIM), and the first two PCs are determined to discriminate between continental origins of the affected individuals. Genotypes on 51 CD associated single nucleotide polymorphisms (SNPs) are used to perform latent class analysis, hierarchical and Partitioning Around Medoids (PAM) cluster analysis within a sample of affected individuals with and without the use of principal components to adjust for population stratification. It is seen that without correction for population stratification clusters seem to be influenced by population stratification while with correction clusters are unrelated to continental origin of individuals. [less ▲]Detailed reference viewed: 28 (2 ULiège)
Crohn's disease susceptibility genes involved in microbial sensing, autophagy and endoplasmic reticulum (er) stress and their interaction
; Mahachie John, Jestinah ; Van Steen, Kristel et al
in Autophagy (2013)Detailed reference viewed: 41 (5 ULiège)
Genetic variations in toll-like receptor pathway and lung function decline in Cystic fibrosis patients.
; Mahachie John, Jestinah ; Van Steen, Kristel et al
in Human Immunology (2013), 74(12), 1649-55
The toll-like receptor (TLR) family maintains pulmonary homeostasis by pathogen recognition, clearance and regulation of inflammation. Genes affecting inflammation response play a key role in modifying ... [more ▼]
The toll-like receptor (TLR) family maintains pulmonary homeostasis by pathogen recognition, clearance and regulation of inflammation. Genes affecting inflammation response play a key role in modifying Cystic fibrosis (CF) lung disease severity. We assessed the impact of single nucleotide polymorphisms (SNPs) of TLR genes (TLR1 to TLR10, CD14, lipopolyssacharide-binding protein (LBP)) on lung function in CF patients. Each SNP was tested for time-dependent effect on FEV1, using six genetic models. In addition, we investigated associations between SNP genotypes and extreme subject specific slopes of FEV1 decline. Variant alleles of polymorphisms of TLR2 rs1898830, rs5743708, and rs3804100 demonstrated a consistent association with lung disease severity (p = 0.008, p = 0.006 and p = 0.029 respectively). Patients homozygous for variant C allele of TLR5 polymorphism rs5744174 are more frequently associated with extreme fast FEV1 decline (OR: 20 (95% Confidence Interval:1.85-216.18)). Patients homozygous AA for TLR1 polymorphism rs5743551 are more frequently associated with faster decline of FEV1 compared to heterozygous genotype (OR:7.33 (95% CI:1.63-33.11). Our findings indicate that variations in TLR1, TLR2 and TLR5 genes may influence CF lung function decline. Further functional analysis is required to provide new insights into the pathogenesis of TLRs in CF lung disease severity. [less ▲]Detailed reference viewed: 26 (4 ULiège)
Genetic and microbial factors modulating the ubiquitin proteasome system in inflammatory bowel disease.
; ; et al
in Gut (2013)
OBJECTIVE: Altered microbiota composition, changes in immune responses and impaired intestinal barrier functions are observed in IBD. Most of these features are controlled by proteases and their ... [more ▼]
OBJECTIVE: Altered microbiota composition, changes in immune responses and impaired intestinal barrier functions are observed in IBD. Most of these features are controlled by proteases and their inhibitors to maintain gut homeostasis. Unrestrained or excessive proteolysis can lead to pathological gastrointestinal conditions. The aim was to validate the identified protease IBD candidates from a previously performed systematic review through a genetic association study and functional follow-up. DESIGN: We performed a genetic association study in a large multicentre cohort of patients with Crohn's disease (CD) and UC from five European IBD referral centres in a total of 2320 CD patients, 2112 UC patients and 1796 healthy controls. Subsequently, we did an extensive functional assessment of the candidate genes to explore their causality in IBD pathogenesis. RESULTS: Ten single nucleotide polymorphisms (SNPs) in four genes were significantly associated with CD: CYLD, USP40, APEH and USP3. CYLD was the most significant gene with the intronically located rs12324931 the strongest associated SNP (pFDR=1.74e-17, OR=2.24 (1.83 to 2.74)). Five SNPs in four genes were significantly associated with UC: USP40, APEH, DAG1 and USP3. CYLD, as well as some of the other associated genes, is part of the ubiquitin proteasome system (UPS). We therefore determined if the IBD-associated adherent-invasive Escherichia coli (AIEC) can modulate the UPS functioning. Infection of intestinal epithelial cells with the AIEC LF82 reference strain modulated the UPS turnover by reducing poly-ubiquitin conjugate accumulation, increasing 26S proteasome activities and decreasing protein levels of the NF-kappaB regulator CYLD. This resulted in IkappaB-alpha degradation and NF-kappaB activation. This activity was very important for the pathogenicity of AIEC since decreased CYLD resulted in increased ability of AIEC LF82 to replicate intracellularly. CONCLUSIONS: Our results reveal the UPS, and CYLD specifically, as an important contributor to IBD pathogenesis, which is favoured by both genetic and microbial factors. [less ▲]Detailed reference viewed: 36 (2 ULiège)
Profile of pediatric Crohn's disease in Belgium.
; Mahachie John, Jestinah ; et al
in Journal of Crohn's and Colitis (2013), 7(11), 588-98
AIM: A Belgian registry for pediatric Crohn's disease, BELCRO, was created. This first report aims at describing disease presentation and phenotype and determining associations between variables at ... [more ▼]
AIM: A Belgian registry for pediatric Crohn's disease, BELCRO, was created. This first report aims at describing disease presentation and phenotype and determining associations between variables at diagnosis and registration in the database. METHODS: Through a collaborative network, children with previously established Crohn's disease and newly diagnosed children and adolescents (under 18 y of age) were recruited over a 2 year period. Data were collected by 23 centers and entered in a database. Statistical association tests analyzed relationships between variables of interest at diagnosis. RESULTS: Two hundred fifty-five patients were included. Median age at diagnosis was 12.5 y (range: 1.6-18 y); median duration of symptoms prior to diagnosis was 3 m (range: 1-12 m). Neonatal history and previous medical history did not influence disease onset nor disease behavior. Fifty three % of these patients presented with a BMI z-score < -1. CRP was an independent predictor of disease severity. Steroids were widely used as initial treatment in moderate to severe and extensive disease. Over time, immunomodulators and biological were prescribed more frequently, reflecting a lower prescription rate for steroids and 5-ASA. A positive family history was the sole significant determinant for earlier use of immunosuppression. CONCLUSION: In Belgium, the median age of children presenting with Crohn's disease is 12.5 y. Faltering growth, extensive disease and upper GI involvement are frequent. CRP is an independent predictive factor of disease activity. A positive family history appears to be the main determinant for initial treatment choice. [less ▲]Detailed reference viewed: 134 (25 ULiège)
Genomic Association Screening Methodology for High-Dimensional and Complex Data Structures: Detecting n-Order Interactions
Mahachie John, Jestinah
Doctoral thesis (2012)
We developed a data-mining method, Model-Based Multifactor Dimensionality Reduction (MB-MDR) to detect epistatic interactions for different types of traits. MB-MDR enables the fast identification of gene ... [more ▼]
We developed a data-mining method, Model-Based Multifactor Dimensionality Reduction (MB-MDR) to detect epistatic interactions for different types of traits. MB-MDR enables the fast identification of gene-gene interactions among 1000nds of SNPs, without the need to make restrictive assumptions about the genetic modes of inheritance. This thesis primarily focused on applying Model-Based Multifactor Dimensionality Reduction for quantitative traits, its performance and application to a variety of data problems. We carried out several simulation studies to evaluate quantitative MB-MDR in terms of power and type I error, when data are noisy, non-normal or skewed and when important main effects are present. Firstly, we assessed the performance of MB-MDR in the presence of noisy data. The error sources considered were missing genotypes, genotyping error, phenotypic mixtures and genetic heterogeneity. Results from this study showed that MB-MDR is least affected by presence of small percentages of missing data and genotyping errors but much affected in the presence of phenotypic mixtures and genetic heterogeneity. This is in line with a similar study performed for binary traits. Although both Multifactor Dimensionality Reduction (MDR) and MB-MDR are data reduction techniques with a common basis, their ways of deriving significant interactions are substantially different. Nevertheless, effects on power of introducing error sources were quite similar. Irrespective of the trait under consideration, epistasis screening methodologies such as MB-MDR and MDR mainly suffer from the presence of phenotypic mixtures and genetic heterogeneity. Secondly, we extensively addressed the issue of adjusting for lower-order genetic effects during epistasis screening, using different adjustment strategies for SNPs in the functional SNP-SNP interaction pair, and/or for additional important SNPs. Since, in this thesis, we restrict attention to 2-locus interactions only, adjustment for lower-order effects always (and only) implies adjustment for main genetic effects. Unfortunately most data dimensionality reduction techniques based on MDR do not explicitly require that lower-order effects are included in the 'model' when investigating higher-order effects (a prerequisite for most traditional, especially regression-based, methods). However, epistasis results may be hampered by the presence of significant lower-order effects. Results from this study showed hugely increased type I errors when main effects were not taken into account or were not properly accounted for. We observed that additive coding (the most commonly used coding in practice) in main effects adjustment does not remove all of the potential main effects that deviate from additive genetic variance. In addition, also adjusting for main effects prior to MB-MDR (via a regression framework), whatever coding is adopted, does not control type I error in all scenarios. From this study, we concluded that correction for lower-order effects should preferentially be done via codominant coding, to reduce the chance of false positive epistasis findings. The recommended way of performing an MB-MDR epistasis screening is to always adjust the analysis for lower-order effects of the SNPs under investigation, "on-the-fly". This correction avoids overcorrection for other SNPs, which are not part of the interacting SNP pair under study. Thirdly, we assessed the cumulative effect of trait deviations from normality and homoscedasticity on the overall performance of quantitative MB-MDR to detect 2-locus epistasis signals in the absence of main effects. Although MB-MDR itself is a non-parametric method, in the sense that no assumptions are made regarding genetic modes of inheritance, the data reduction part in MB-MDR relies on association tests. In particular, for quantitative traits, the default MB-MDR way is to use the Student's t-test (steps 1 and 2 of MB-MDR). Also when correcting for lower-order effects during quantitative MB-MDR analysis, we intrinsically maneuver within a regression framework. Since the Student's t-statistic is the square root of the ANOVA F-statistic. Hence, along these lines, for MB-MDR to give valid results, ANOVA assumptions have to be met. Therefore, we simulated data from normal and non-normal distributions, with constant and non-constant variances, and performed association tests via the student's t-test as well as the unequal variance t-test, commonly known as the Welch's t-test. At first somewhat surprising, the results of this study showed that MB-MDR maintains adequate type I errors, irrespective of data distribution or association test used. On the other hand, MB-MDR give rise to lower power results for non-normal data compared to normal data. With respect to the association tests used within MB-MDR, in most cases, Welch's t-test led to lower power compared to student's t-test. To maintain the balance between power and type I error, we concluded that when performing MB-MDR analysis with quantitative traits, one ideally first rank-transforms traits to normality and then applies MB-MDR modeling with Student's t-test as choice of association test. Clearly, before embarking on using a method in practice, there is a need to extensively check the applicability of the method to the data at hand. This is a common practice in biostatistics, but often a forgotten standard operating procedure in genetic epidemiology, in particular in GWAI studies. In addition to the presentation of extensive simulation studies, we also presented some MB-MDR applications to real-life data problems. These analyses involved MB-MDR analyses on quantitative as well as binary complex disease traits, primarily in the context of asthma/allergy and Crohn's disease. In two of the presented analyses, MB-MDR confirmed logistic regression and transmission disequilibrium test (TDT) results. Part of the aforementioned methodological developments was initiated on the basis of observations of MB-MDR behavior on real-life data. Both the practical and theoretical components of this thesis confirm our belief in the potential of MB-MDR as a promising and versatile tool for the identification of epistatic effects, irrespective of the design (family-based or unrelated individuals) and irrespective of the targeted disease trait (binary, continuous, censored, categorical, multivariate). A thorough characterization of the different faces of MB-MDR this versatility gives rise to is work in progress. [less ▲]Detailed reference viewed: 238 (21 ULiège)
A robustness study to investigate the performance of parametric and non-parametric tests used in Model-Based Multifactor Dimensionality Reduction Epistasis Detection.
Mahachie John, Jestinah ; ; et al
Conference (2012, June 01)Detailed reference viewed: 33 (8 ULiège)
Factors determining therapeutic strategy at diagnosis and evolution of disease severity in a cohort of Belgian pediatric Crohn's disease patients (BELCRO)
; Mahachie John, Jestinah ; et al
in Gastroenterology (2012)Detailed reference viewed: 30 (7 ULiège)
Application of mixed polygenic model to control for cryptic/genuine relatedness and population stratification.
Gusareva, Elena ; Mahachie John, Jestinah ; et al
Poster (2012, March 12)
In genome-wide association studies (GWAs), population stratification may cause inflated type I errors and overly-optimistic test results, when not properly corrected for. During the past decade, several ... [more ▼]
In genome-wide association studies (GWAs), population stratification may cause inflated type I errors and overly-optimistic test results, when not properly corrected for. During the past decade, several methods have been proposed for association testing in the presence of population stratification. Among these, principal components-based approaches are the most popular. Principal component analysis (PCA) allows data transformation to a new coordinate system such that the projection of the data along the first new coordinate (called the PC1) has the largest variance; the second PC has the second largest variance, and so on. In practice, two components are usually enough to adjust or to control for population stratification. They can easily be included in parametric association models as covariates. Despite the success of this strategy, there are still some caveats which need further attention. Among these are that principal component-based methods generally do not account for cryptic relatedness (kinship) between supposedly unrelated individuals, are not straightforwardly adapted to accommodate family-based designs or mixtures of families and unrelated individuals, and do not always take proper account of the trait under investigation. In this work, we present an easy-to-use alternative that addresses the aforementioned issues. For quantitative traits, we propose to first use the mixed polygenic model (possibly taking into account important non-genetic confounders as covariates), second to derive "polygenic" residuals from this model – hereby removing genomic kinship relationships, and third to consider these residuals as new traits in a classical genome-wide QTL analysis for "unrelated individuals". The polygenic component of the aforementioned mixed polygenic model describes the contribution from multiple independently segregating genes, all having a small additive effect on the trait under investigation. Via an extensive simulation study, with various settings of population stratification and admixture, we show that this approach not only removes most of the "relatedness" between individuals (cryptic relatedness or known relatedness), but also removes most of the remaining substructures caused by population stratification or admixture. As a proof of concept, we demonstrate the efficiency of this robust method to control for population stratification on real-life genome-scale data from the SNP Health Association Resource (SHARe) Asthma Resource project (SHARP) (dbGaP accession number phs000166.v2.p1). We also provide leads to extend this method to dichotomous traits. [less ▲]Detailed reference viewed: 62 (18 ULiège)
A robustness study to investigate the performance of parametric and non-parametric tests used in Model-Based Multifactor Dimensionality Reduction Epistasis Detection
Mahachie John, Jestinah ; ; et al
Poster (2012, March)Detailed reference viewed: 38 (2 ULiège)
Lower-Order Effects Adjustment in Quantitative Traits Model-Based Multifactor Dimensionality Reduction
Mahachie John, Jestinah ; Cattaert, Tom ; Van Lishout, François et al
in PLoS ONE (2012)
Identifying gene-gene interactions or gene-environment interactions in studies of human complex diseases remains a big challenge in genetic epidemiology. An additional challenge, often forgotten, is to ... [more ▼]
Identifying gene-gene interactions or gene-environment interactions in studies of human complex diseases remains a big challenge in genetic epidemiology. An additional challenge, often forgotten, is to account for important lower-order genetic effects. These may hamper the identification of genuine epistasis. If lower-order genetic effects contribute to the genetic variance of a trait, identified statistical interactions may simply be due to a signal boost of these effects. In this study, we restrict attention to quantitative traits and bi-allelic SNPs as genetic markers. Moreover, our interaction study focuses on 2- way SNP-SNP interactions. Via simulations, we assess the performance of different corrective measures for lower-order genetic effects in Model-Based Multifactor Dimensionality Reduction epistasis detection, using additive and co-dominant coding schemes. Performance is evaluated in terms of power and familywise error rate. Our simulations indicate that empirical power estimates are reduced with correction of lower-order effects, likewise familywise error rates. Easy-to-use automatic SNP selection procedures, SNP selection based on ''top'' findings, or SNP selection based on p-value criterion for interesting main effects result in reduced power but also almost zero false positive rates. Always accounting for main effects in the SNP-SNP pair under investigation during Model-Based Multifactor Dimensionality Reduction analysis adequately controls false positive epistasis findings. This is particularly true when adopting a co-dominant corrective coding scheme. In conclusion, automatic search procedures to identify lower-order effects to correct for during epistasis screening should be avoided. The same is true for procedures that adjust for lower-order effects prior to Model-Based Multifactor Dimensionality Reduction and involve using residuals as the new trait. We advocate using ''on-the-fly'' lower-order effects adjusting when screening for SNP-SNP interactions using Model-Based Multifactor Dimensionality Reduction analysis. [less ▲]Detailed reference viewed: 76 (35 ULiège)
Inference and comparison of different genetic stratification techniques
Maus, Bärbel ; ; Mahachie John, Jestinah et al
Conference (2012)Detailed reference viewed: 9 (2 ULiège)
Clustering of Crohn's disease patients: Identification of sub-phenotypes and population stratification
Maus, Bärbel ; ; Mahachie John, Jestinah et al
in Genetic Epidemiology (2012), 36(7), 729Detailed reference viewed: 22 (4 ULiège)


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Student Stories: Environmental major prefers work in field, labs
Student Stories: Environmental major prefers work in field, labs
Your time at Penn State can be what you make it. Jenna Mitchell has spent a lot of her college time in the lab and doing field research -- and that's the way she likes it.
Penn State's College of Agricultural Sciences can offer unique experiences that many students don't have access to until graduate school. "You can go to class, but research is what makes it really come alive," Mitchell said. "It keeps me inspired."
For her, research is also an insight into her future. "I'd like to get a master's degree, and I am in the process of figuring out what to get into, but I definitely want it to be related to environmental science."
A native of Lancaster, Pa., Mitchell was inspired to pursue environmental research when she saw firsthand the effects of climate change on puffin populations during her time as a volunteer on an Icelandic ecotourism farm.
"It's real, it's happening," she said. "I need to do what I can do in research and help make it known."
After meeting with an adviser in the Environmental Resource Management major, she knew she had found everything she wanted to do just that. "It's a great foundational program, and it helps me continue with environmental science."
Mitchell has worked in three research labs on campus. One lab was looking at insect and plant interactions to mitigate the need for pesticide use and develop better pest-management strategies. Another was studying the effects of climate change in soils, forestry and vegetation.
Last summer she traveled to Spain to continue this research. By controlling heat and rainfall on various research plots, scientists hoped to pinpoint how the vegetation changes under different variables and predict the potential effects of climate change on the environment.
The researchers with whom she worked are analyzing tree core samples and measuring roots they collected from arid areas to study ecological growth in a region where climate varies considerably.
"I feel really comfortable here and love the culture of the College of Agricultural Sciences," Mitchell said. "I have access to great research opportunities."
For students interested in similar opportunities, she suggests keeping your eyes open and making connections. "One of my experiences I found on a flyer in the Tyson Building," she said. "There are options everywhere."
(Get information about the Environmental Resource Management major.


text:
cairnswk wrote:Victor Sullivan wrote:...
I currently have the starting positions coded to include each tribe's adjacent territory, and I'll probably edit the XML so that tribes start with more than 3 troops. No neutrals necessary
Mmmm, OK did we discuss that...it's been so long i don't remember.
So what value should the tribes start with?
I was thinking around 6.
cairnswk wrote:And what is your view on the probability criteria Sully?
I like to keep it as low as possible. Ideally, >2%.


text:
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