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While the political adage holds that to the winner go the spoils, under Democratic Gov. Pat Quinn, even some losers have done very well.
Take Dan Seals. He failed three times to win a North Shore congressional seat, and his tax returns showed he mostly spent his time campaigning instead of working.
Following November's defeat, Quinn hired him as a $121,029-a-year assistant director in the Department of Commerce and Economic Opportunity.
Seals joined a host of other Democratic castaways who've landed on the state payroll after losing bids for Congress and the General Assembly. Friends and family of Democrats with clout also have found themselves with paid appointments to state panels.
Hiring the connected is not new. But for Quinn, embracing legal political patronage contrasts with his long-running message of populist reform that attacks the way insiders do the people's business.
And with Quinn complaining that lawmakers haven't given him enough money and Illinois still billions of dollars behind in paying its bills, questions linger over whether the governor even needs to fill some highly paid administrative positions — let alone with political allies.
"It really (raises) the question of, Is there something in the nature of elected office that makes you so sequestered from the rest of the public that you don't see appointments beyond your nose?" said Cindi Canary, the former executive director of the Illinois Campaign for Political Reform.
"I mean, none of this is to say that at least some of these appointees don't bring talents to the table," Canary said. "But when the governor is giving appointments to highly positioned political colleagues, Democrats, winners or losers, it really does sort of beg for a greater level of disclosure and what it is about these particular people that made them qualified for this position."
Quinn spokeswoman Brooke Anderson said that the governor "rejects patronage" and that his goal "is to recruit the very best people for the job."
"The governor's approach to appointments is to seek out people who exemplify his philosophy of integrity, competence and public service," Anderson said. "On an ongoing basis, he recruits dedicated public servants who are honest and produce results, and who comply with the requirements and extensive criteria that are in place for appointments."
Shortly after taking office from his disgraced predecessor in January 2009, Quinn pledged to "fumigate" Rod Blagojevich appointees in an effort to restore integrity in state government.
That never happened. Then in April, Quinn vetoed legislation aimed at cleaning house among hundreds of people picked by Blagojevich and imprisoned Republican ex-Gov. George Ryan.
Quinn argues he has made the appointment process more transparent by posting vacancies for boards and commissions online and allowing regular citizens to apply.
More recently, Quinn has been criticized for hiring former Democratic lawmakers who voted as lame ducks for a massive income tax increase in January.
Quinn named former Rep. Careen Gordon, a Democrat formerly of Morris, to the Illinois Prisoner Review Board only days after she voted for a 67 percent increase in the personal income tax rate.
Gordon, defeated in her November re-election bid, had campaigned against raising the state income tax. When her Senate confirmation ran into opposition, Quinn moved Gordon into a job as lawyer for the state Department of Financial and Professional Regulation at $84,000 a year.
Last month, Quinn named former Rep. Mike Smith, a Democrat from Canton, to the state's Educational Labor Relations Board at a salary of $93,926, a raise from his legislative pay. Unlike Gordon, Smith, who chaired the House Elementary and Secondary Education Committee, had supported the income tax increase prior to his re-election defeat.
Sen. Tim Bivins of Dixon, the ranking Republican on the Democrat-led Senate Executive Appointments Committee, said that while Smith is "a nice guy, the statute is very clear that you have to have five years' collective bargaining experience, which he doesn't have."
"I think if you look around, there's plenty of qualified people who would love to have these positions," Bivins said. "Political appointees, if they're qualified and do a good job, he's got a right to appoint who he wants. He's made some good choices and a whole lot of bad ones."
In the case of Seals' hiring and others, Quinn's awarding of jobs resembles a consolation prize for falling short in a bid for Congress.
Seals won the 10th Congressional District Democratic nomination last year by defeating veteran state Rep. Julie Hamos of Wilmette. Hamos quit her $78,163 job in the Legislature to seek the congressional seat. Two months after losing the primary, Quinn appointed Hamos director of the Department of Healthcare and Family Services, where she now makes $142,338.
Liberal political activist Christine Cegelis, of Rolling Meadows, a member of the Democratic State Central Committee, twice ran and lost for Congress from the west suburban 6th Congressional District.
After losing to Tammy Duckworth in the 2006 Democratic primary, Cegelis worked as Midwest campaign field director for Americans for Democratic Action. After becoming governor, Quinn tapped Cegelis as deputy director of the state Department of Central Management Services for $121,029 a year.
Last fall, in the midst of Quinn's election campaign, the still politically active Cegelis hosted an Elk Grove Township Democrats' door-to-door canvass of voters on behalf of her boss. The Quinn administration said Thursday that Cegelis is no longer at the agency.
Anderson, the Quinn spokeswoman, said each of the former congressional candidates offered "strong" backgrounds and experience.
Friends and family of Democratic insiders also have benefited under Quinn with paid appointments to boards and commissions. One place they've landed is the 13-member Human Rights Commission, a longtime source of political nepotism.
Earlier this year, Quinn came under fire for his appointment of Terry Cosgrove, the head of an abortion rights political action committee that spent more than $400,000 backing the governor's election. Cosgrove is paid $49,960 for serving on the board, which adjudicates civil rights complaints involving housing and employment.
Quinn also reappointed four holdovers from the Blagojevich era: Marylee Freeman, who is married to Illinois Supreme Court Justice Charles Freeman; Marti Baricevic, who is married to former St. Clair County Board Chairman John Baricevic, now a circuit judge; Rozanne Ronen, sister of former Sen. Carol Ronen, a Blagojevich friend who remains on the Democratic State Central Committee; and Diane Viverito, the daughter of former Sen. Lou Viverito, D-Burbank.
Another controversial appointment by Quinn was naming Carrie Zalewski, who is married to Rep. Michael Zalewski, D-Chicago, to a $117,043 annual position on the Pollution Control Board. She had spent three years as a $61,200-a-year lawyer for the Illinois Department of Transportation.
While Republicans are contesting Quinn's appointment of former Rep. Smith to the Illinois Educational Labor Relations Board, Lynne Sered chairs the five-member panel that considers labor disputes involving local school districts. Sered, who earns $104,358 per year, is a former staff lawyer for the National Labor Relations Board appointed by Blagojevich and reappointed by Quinn. She is married to Sen. Jeff Schoenberg, D-Evanston.
The Quinn administration said Zalewski and Sered were both "well-qualified" for the jobs.
"It's one thing to say we've got to fill this slot, this person brings 'X' skill set, we've talked to 18 other people and this is the one," Canary said of the governor's appointments. "But without illuminating that process, you've got a population that — while it finds Quinn to be an honest man — is scandal-weary and budget-panicked."


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Muskingum County Now Under Level One Snow Emergency
Muskingum County has been placed under a level one snow emergency. A level one snow emergency means that roads are hazardous with blowing and drifting snow. Roads are icy and drivers are warned to be cautious.
Please continue to be aware of weather conditions, and stay up to date with all the current snow emergency levels by checking in at the Muskingum County Sheriff Office website.


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Avast Cleanup Pro is an optimization tool for Mac that includes a range of scans which detect unnecessary items and performance issues to free up disk space and improve the speed of your system.
Install Avast Cleanup Pro
- Click the button below to download the Avast Cleanup Pro setup file, and save it in a familiar location on your Mac (by default, all files are saved to your Downloads folder). Download Avast Cleanup Pro
- Double-click the downloaded file
- In the Avast Cleanup Pro dialog that appears, double-click the Install Avast Cleanup Pro icon.
- In the setup wizard, click Continue.
- Review the End User License Agreement and click Continue, then click Agree.
- Click Change install location to select a destination for installation, then click Continue.
- Click Install.
- Use your Touch ID to grant permission for the installation, or click Use Password..., then enter your password and click Install Software.
- Click Close to exit setup.
- Click Move to Trash to remove the installer.
Avast Cleanup Pro is now installed on your Mac and can be used in scan-only mode. To unlock all features, you need to activate Avast Cleanup Pro using your valid activation code from an order confirmation email. For instructions, refer to the following article:
If you experience any installation issues:
- Ensure your Mac meets the minimum system requirements and your operating system is up to date.
- Apple macOS 10.15.x (Catalina), Apple macOS 10.14.x (Mojave), Apple macOS 10.13.x (High Sierra), Apple macOS 10.12.x (Sierra), Apple Mac OS X 10.11.x (El Capitan), Apple Mac OS X 10.10.x (Yosemite).
- Intel based Mac with 64-bit processor.
- 512 MB RAM or above (1 GB RAM or higher preferred).
- 68 MB minimum hard disk free space.
- An internet connection is needed to download, activate, and use the program.
- Optimally standard screen resolution not less than 1024 x 768 pixels.
- Restart your Mac and try to install Avast Cleanup Pro again by following the instructions in this article.
- Avast Cleanup Pro 1.x for Mac
- Apple macOS 10.15.x (Catalina)
- Apple macOS 10.14.x (Mojave)
- Apple macOS 10.13.x (High Sierra)
- Apple macOS 10.12.x (Sierra)
- Apple Mac OS X 10.11.x (El Capitan)
- Apple Mac OS X 10.10.x (Yosemite)


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Montero hurls eight innings of one-hit ball for Vegas
Righty pitching prospect delivers second straight scoreless outing, strikes out 11
Right-hander Rafael Montero, the Mets' No. 6 prospect, threw eight scoreless innings Tuesday to lead Triple-A Las Vegas to a 3-0 victory at Sacramento.
Montero struck out a season-high 11 batters and held the River Cats to one hit and two walks while throwing 105 pitches, 73 for strikes.
Montero began the game with four hitless innings before Nick Buss led off the fifth with a single. It would be the last baserunner Montero allowed. He retired the final 12 batters he faced to complete his second straight scoreless outing. He threw 6 2/3 scoreless innings against El Paso in his last start.
Right-hander Chase Bradford struck out the side on 10 pitches in the ninth to complete the combined one-hitter and earn his third save of the season.
Center fielder Matt den Dekker, the Mets' No. 19 prospect, went 2-for-4 with a run scored and a walk to lead the offense. He now has six multihit games in his last nine starts.
Montero began the season with Las Vegas and made his Major League debut May 14. He made four starts for the Mets, posting a 5.40 ERA in 20 innings, before getting sent back to Triple-A. After returning to the Minor Leagues, he strained his left oblique and spent a few weeks on the disabled list.
Now healthy once again, Montero is 6-3 with a 3.28 ERA in 15 starts with Las Vegas this season. He has struck out 75 batters and walked 32 in 74 innings.


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The Alaskan Arctic Expedition highlights the need to save the Arctic from attempts by oil companies to exploit the regions resources for short term profit. The MY Esperanza will document whats at stake in the region whilst creating a sanctuary around the North Pole.
To help Save The Arctic click here.
Pilots Shannon Lo Ricco (L) of Australia and John Hocevar of the USA get ready for their first dive in a two-seater submersible craft, on loan from the Waitt Institute is prepared on board the Greenpeace ship Esperanza for its first dive exploring the deep sea canyons of the Bering Sea, Alaska.The Greenpeace ship Esperanza is on an Arctic expedition to study unexplored ocean habitats threatened by offshore oil drilling, as well as industrial fishing fleets. 07/11/2012
© Jiri Rezac/Greenpeace
1 - 12 of 900 results.


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There can be only one fan-favorite character from the Highlander TV series: Methos, played by Peter Wingfield. And now you can ask Wingfield your burning Highlander questions — and win Highlander on Blu-ray, or a replica of Duncan MacLeod's katana!
It's pretty simple: Post your questions for Wingfield in the comments below. And then, in mid-August, Wingfield will answer five of your questions in a video posted at io9.
And the people who ask the best questions will be eligible to win prizes, which including this awesome replica katana and Highlander (Season 1) on Blu-ray. (Free shipping only within the United States.)
Right now Highlander Seasons 1-6 episodes are just 99 cents on iTunes. Check it out at iTunes.com/TV/Highlander.


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|Instrument: MSS : Multispectral Scanner
Instrument Category:
Earth Remote Sensing Instruments
Instrument Class: Passive Remote Sensing
Instrument Type: Spectrometers/Radiometers
Instrument Subtype: Imaging Spectrometers/Radiometers
Associated Platforms
Spectral/Frequency Information
Wavelength Keyword: Visible
Spectral/Frequency Coverage/Range: 0.5 ?m -0.6 ?m
Wavelength Keyword: Visible
Spectral/Frequency Coverage/Range: 0.6 ?m -0.7 ?m
Wavelength Keyword: Near Infrared
Spectral/Frequency Coverage/Range: 0.7 -0.8 ?m
Wavelength Keyword: Near Infrared
Spectral/Frequency Coverage/Range: 0.8 ?m -1.1 ?m
Related Data Sets
View all records related to this instrument
The Multispectral Scanner (MSS) sensors were line scanning devices observing the Earth perpendicular to the orbital track. The cross-track scanning was accomplished by an oscillating mirror; six lines were scanned simultaneously in each of the four spectral bands for each mirror sweep. The forward motion of the satellite provided the along-track scan line progression.
The first five Landsats carried the MSS sensor which responded to Earth-reflected sunlight in four spectral bands. Landsat 3 carried an MSS sensor with an additional band, designated band 8, that responded to thermal (heat) infrared radiation.
An MSS scene had an Instantaneous Field Of View (IFOV) of 68 meters in the cross-track direction by 83 meters in the along-track direction (223.0 by 272.3 feet respectively). To understand this concept consider a ground scene composed of a single 83 by 83 meter area. The scan monitor sensor ensures that the cross-track optical scan is 185 km at nominal altitude regardless of mirror scan nonlinearity or other perturbations of mirror velocity.
Cross- track image velocity was nominally 6.82 meters per microsecond. After 9.958 microseconds, the 83 by 83 meter image has moved 67.9 meters. The sample taken at this instant represented 15 meters of previous information and 68 meters of new information.
Therefore, the effective IFOV of the MSS detector in the cross-track direction was considered to be 68 meters which corresponds to a nominal picture element (pixel) ground area of 68 by 83 meters at the satellite nadir point. Using the effective IFOV in area calculation eliminates the overlap in area between adjacent pixels.
[Summary provided by NASA.]
Online Resources
Instrument Logistics
Instrument Start Date: 1972-07-23
Instrument Owner: NASA


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France suggests arming Syrian rebels
PARIS (AP) — France raised the possibility Thursday of sending "defensive weapons" to Syria's rebels, but Russia warned that such a move would violate international law.
French Foreign Minister Laurent Fabius said his country will ask the European Union to consider lifting the Syrian arms embargo, which prevents weapons from being sent to either side.
"We must not militarize the conflict ... but it's obviously unacceptable that there are liberated zones and they're bombed" by President Bashar Assad's regime, Fabius said in an interview with RTL radio. "We have to find a good balance."
The civil war in Syria, which began as an uprising against Assad's regime, has killed more than 36,000 Syrians since March 2011, according to anti-government activists. The fighting and flood of refugees seeking safety have also spilled over into several of Syria's neighbors, including Israel, Lebanon, Turkey and Jordan.
The fighting has descended into a bloody stalemate, and rebels say they desperately need weapons to turn the tide.
"The question of defensive arms will be raised," Fabius said, without providing details about what such arms would be. "This cannot be done without coordination between Europeans."
The topic of Syria is sure to be on the agenda at the EU foreign ministers meeting Monday in Brussels.
France has taken a leading role among Western countries in supporting Syria's rebels. On Tuesday, it became the first Western nation to formally recognize Syria's newly formed opposition coalition as the sole legitimate representative of the Syrian people.
On Saturday, the president of the new opposition coalition, the 52-year-old preacher-turned activist Mouaz al-Khatib, is to visit Paris and meet with President Francois Hollande. Al-Khatib is scheduled to hold talks a day earlier in London with British officials, who have said they will urge the opposition to set out a strategy to halt the conflict.
Syria's splintered rebel factions agreed to a U.S.-backed plan to unite last weekend under the new umbrella group, which seeks a common voice and strategy against the regime.
A French diplomatic official said Thursday that Paris sees quick recognition as a primary way to assure success for the opposition.
"There won't be many other occasions like this," said the official who was not authorized to speak publicly on the matter and asked not to be named. "We have a collective responsibility, to the Syrians and ourselves, to make this live."
Turkey, which shares a long border with Syria and is a major backer of the opposition, followed suit on Thursday, with Foreign Minister Ahmet Davutoglu saying Ankara recognized the Syrian National Coalition as "the only legal representative" of Syria, the Anadolu news agency reported.
The six-nation Gulf Cooperation Council already has recognized the new broad-based Syrian opposition group. The GCC includes Qatar and regional power Saudi Arabia, both of whom have been some of the strongest supporters of the rebels fighting to oust Assad.
The U.S. also recognized the leadership body announced in Qatar on Sunday as a legitimate representative, but stopped short of describing it as the sole representative, saying the group must first demonstrate its ability to represent Syrians inside the country.
President Obama on Wednesday reiterated that the U.S. isn't considering sending weapons to the opposition because of concerns the arms might end up in the hands of extremists.
Although Assad remains isolated internationally, he still has the backing of key allies Russia, China and Iran.
On Thursday, Russian Foreign Ministry spokesman Alexander Lukashevich warned that providing assistance to Syrian opposition fighters would breach international law.
He specifically cited a 1970 United Nations document saying that no country should help or finance military action aimed at the violent overthrow of a foreign government. He also said the opposition's refusal to hold talks with Assad would "strengthen positions of extremists."
Lukashevich said Russia will continue its contacts with both the government and the opposition to encourage them to sit down for talks. "There is no alternative to an inclusive dialogue without any foreign interference," he said.
Despite myriad attempts over the past year to reach a diplomatic solution to the crisis, violence has continued unabated on the ground.
Syrian activists said regime warplanes carried out airstrikes Thursday on an eastern town bordering Iraq after rebels seized a security headquarters following days of heavy fighting.
Rebels had been making advances in the town of al-Boukamal in the oil-rich province of Deir el-Zour for weeks. On Thursday, they seized control of the military security building and a military checkpoint at the edge of the town.
The Britain-based Syrian Observatory for Human Rights and a local activist who gave only his first name, Omar, said Syrian regime forces retaliated with air raids on al-Boukamal. It was not immediately clear whether there were any casualties.
The Observatory also said it received a report from Aleppo, Syria's largest city and the epicenter of some of the worst fighting, that dozens of soldiers' bodies were being held at the international airport. The men apparently had been killed in fighting, but authorities were delaying returning the soldiers' bodies to their families.
It was impossible to independently confirm the report.
Associated Press writers Vladimir Isachenkov in Moscow, Christopher Torchia in Istanbul, David Stringer in London, and Zeina Karam in Beirut contributed to this report.
Copyright 2012 Associated Press. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.


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Davenport - the largest city and economic engine of the bi-state Quad-Cities area - is a premier place to start or grow your business. Our economic development staff is ready to connect businesses with the resources they need to create jobs and improve the quality of life in Davenport. Let us know your plans and we can help guide you to the resources available. Anything goes! From urban cafes in the heart of downtown to large industrial facilities located in the Eastern Iowa Industrial Center, we are saving a seat in Davenport for you.
For more information on Economic Development Programs
Please call 563.326.7765


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We thought we would discuss Dragon Age and League of Legends among other things in the Kotaku podcast today. But you called in about other things. Including: How to do the Prince of Persia rewinding thing in a movie.
Co-hosts Brian Crecente and I take your calls every Wednesday at 11am Mountain Time, 1pm Eastern. If you missed us this time, call in next week!
Kotaku Talk Radio: GTA At A Crossroads [Blog Talk Radio]
Kotaku Talk Radio: Modern Warfare 2, Dragon Age, LoL [iTunes]


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FreakScore is a weighted average of all aggregated professional and user review scores.
Leer Más
This product has a FreakScore of 8.2*
de 10 based on 2 scores.
*Score is uncertain and deviates toward category average due to low number of scores.
This product has a FreakScore of 6.0
de 10 based on 122 scores.


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Julie van der Poel began her career in the IT industry, where over the course of a decade she wrote user documentation and training programs, developed and managed an educational services department, and eventually headed up a marketing team for an internet startup. Her somewhat accidental career shift towards special education came about during her six-year stint as an expat in Europe. Out of necessity, she became a full-time advocate and teaching support for her young son while they lived in Amsterdam. A move to London found Julie working with high school seniors in her son's special needs school. It was this experience that fueled Julie's passion for transition issues facing students with developmental and learning disabilities. Upon returning to the United States, Julie became an Independent Living Skills Instructor for postsecondary students. In this role, Julie developed curriculum and taught students everything from money handling and budgeting, to nutrition and household management.
Julie attended Georgia Tech where she earned a B.S. in Management. Julie now resides in Washington, DC with her family and two labradoodles. When she is not writing for Autism After 16, she spends most of her time ensuring that her 16-year-old son with Autism Spectrum Disorder and his exceptionally bright 8-year-old sister are getting appropriate educations.


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Football Club
Serving the Parish of Marston Moreteyne including Lower Shelton, Upper Shelton, Wood End and part of Wootton Green.
Our privacy notice can be found here
Any errors or omissions should be reported via the Contact Us link.
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The script has been written, but there's still one thing missing from the potentialFridayNight Lightsmovie: Coach Taylor himself.
During her appearance on Monday'sWatch What Happens: Live,Connie Brittonrevealed that her former co-starKyle Chandlerisn't so keen on doing the film. "There's been a ...
The script has been written, but there's still one thing missing from the potential Friday Night Lights movie: Coach Taylor himself.
During her appearance on Monday's Watch What Happens: Live, Connie Britton revealed that her former co-star Kyle Chandler isn't so keen on doing the film. "There's been a lot of talk about a lot of things. Some people are really excited about it and some people aren't," Britton said, adding that she personally loves the idea.
17 cult shows that deserve a movie
The actress explains that Chandler is hesitant to do the film because it's already been done before (the series Friday Night Lights was based on the 2004 movie, which was based on a book). "And he has a point," Britton noted.
FNL star Scott Porter, who played Jason Street on the series, has also expressed concerns about the film, telling Entertainment Weekly: "I'd put 50/50 odds on it. I'm so scared we would never be able to top the show. And I wouldn't want what we did together tarnished in any way."
Watch Britton discuss the prospect of a FNL movie below.
View original Connie Britton: Kyle Chandler Doesn't Want to Make a Friday Night Lights Movie at TVGuide.com
Other Links From TVGuide.com Friday Night LightsConnie BrittonKyle ChandlerScott PorterWatch What Happens: LiveTV Guide iPhone App TV Listings New Tonight on TV


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By: 14th January 2013 at 16:28-
Embraer Picks Pratt & Whitney Engine For New E-Jet
January 08, 2013
Embraer has selected Pratt & Whitney's PW1000G geared turbofan to power its soon-to-be-launched, second-generation E-Jet family, which is scheduled to enter service in 2018.
The engine decision marks a key milestone in Embraer's plan to formally launch the second-generation E-Jet family later this year. Provisionally outlined with 78- to 122-seats, the new aircraft will succeed the current E-170 and E-190 lines. The new family will be reconfigured with an all-new wing, full fly-by-wire flight control systems and extended main landing gear to provide more clearance for the higher bypass engines.
Embraer's award is a significant victory for Pratt's campaign to penetrate the single-aisle market, and is a major blow for General Electric (GE) which was believed to be in pole-position with a mix of the next-generation NG34 and de-rated CFM Leap.
The NG34 is based on the common 'eCore' design used in the CFM Leap engine and is earmarked as a successor to the CF34 that powers the current-generation of E-Jets.
Rolls-Royce, which hoped to build on a relationship established with Embraer with the AE3007-powered ERJ-145 regional jet family, also competed with a new two-shaft engine design.
Two new versions of the PW1000 family will be developed for the Embraer program, which is unofficially dubbed the 'G2'. Covering a thrust range of 15,000-22,000 lb thrust they include the PW1700G and the PW1900G, which will power the second-generation E-170/175 and larger E-190/195, respectively.
Embraer commercial aviation president Paulo Cesar Silva says the engine decision was made on technical and commercial considerations. "We do appreciate the relationship with GE, but the proposition that Pratt is offering seems to us [to be the] one that brings more value to our customers based on the fuel burn and maintenance costs. So we believe it is the best option."
Despite the busy development schedule now facing Pratt, Silva says Embraer is "very comfortable in that regard. [Parent company] United Technology [Corp.] and Pratt & Whitney is a big organization."
Silva adds that Pratt's on-going progress to-date with development of geared turbofans for Bombardier's CSeries, the Mitsubishi Regional Jet (MRJ), Airbus A320NEO and Irkut MS-21 has reassured the Brazilian manufacturer that the Pratt "engine will deliver the savings our customers are looking for. The decision we are making today is the most credible and we are comfortable with it."
Part of Embraer's comfort level is based on the fact the PW1700G will be configured with a 56-in. diameter fan, while the PW1900G will have a 73-in. fan. The smaller engine is a virtual clone of the PW1200G in advanced development for the MRJ, while the PW1900G is the same size as the PW1500G now poised to power the first flight of the CSeries.
First engine test is expected early in 2015 to provide ample margin for the planned first flight of the new Embraer jet in 2016.
Pratt Next Generation Product Family VP Bob Saia says commonality with the MRJ and CSeries engines eases the engine maker's workload. "These will be newly certificated by model, but a lot of the reports will be based on initial certification tests already conducted on the other engines such as fan blade out and so on."
Saia adds the selection by Embraer represents "a good fit" for Pratt's overall market penetration strategy.
More good news for PW, after years of languishing.
I didn't even know Embraer had committed to a new generation 170/190.


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Of the brace of bands to spring out of Omaha, Nebraska in recent years, there are probably few more Omaha than Tilly and the Wall; two of them used to be in a band with Conor Oberst, they're signed to his Team Love_ label and he even produced their first album. Time moves on though and album number three, helmed by Bright Eyes regular Mike Mogis, finds them clutching a set of songs that may make network TV spots, such as their recent _Letterman _performance, the norm rather than the exception.
'O', so called because that's the shape of the band's name on the cover (officially it's self-titled), is that best of third albums – the kind a band makes when they've become truly comfortable in their skin, and are confident enough to rough up their recordings with some interesting ideas. Hence strummy and melodic 'Tall Tall Grass' which tails into a discordant guitar solo befitting a song about "falling in deep love with your rock and roll," while fearsome stomp-a-long and current single 'Pot Kettle Black', with its themes of high school bitchiness, was apparently recorded in a school gymnasium.
'Dust Me Off' meanwhile performs the age old trick of teaming a relatively melancholy vocal with a fun-filled melody, making it the perfect thing to put on repeat when the darkness creeps in and you really can't get out of bed. The vocals become incredibly cheery, winding up in a set of doo-doo-dee-doos which find the band sitting on the shoulders of their doo-oohing peers.
It's probably obligatory in a Tilly review to mention that they don't have a drummer, they have a tap dancer, and Jamie Pressnall's footwork lends a sense of almost flamenco drama to proceedings, driving things forward rather than detracting. She even gets to wig out properly in the intro to 'Too Excited', a point where a drum solo would have seemed incongruous, but her capable feet serve as a great revving up. You wonder how she keeps it up for a whole live show but then they do whip out the drum machine for a couple of songs here, which probably gives her a chance to take the weight off and apply some Deep Heat.
One of those songs is of course the Radio 1 play-listed 'Beat Control', absent on the US version of this album released earlier this year but tacked on the end here. Pretty much the definition of a floor filler, indie or otherwise, it taps into a timeless pop aesthetic that it conjures up elements of 'ABC' and the great days of disco. It makes it literally impossible not to smile and jig around a bit, even if you're sitting completely alone in a dimly lit room. Like I am now.
Clever, joyous and never patronising, 'O' is a half hour bite of summer that's perfect for fending off the darkening nights.
8John Winters's Score


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"It is critical that people attend the meeting and then make written comment on the proposals," said San Juan County Planner Nick Sandberg.
Sandberg added that unless residents make a written comment on the proposal at this time, they may not have standing to make statements in the future regarding the sage grouse issue.
The U.S. Fish and Wildlife Service is proposing the endangered species designation, along with declaring millions of acres of land as critical habitat.
County officials state that the endangered species designation may be difficult to stop, as it part of a court settlement. However, they hope to derail the designation of large swaths of land as critical habitat.
The critical habitat designation would spread across portions of Colorado and Utah, including 70,595 acres of land in San Juan County. Approximately 95 percent of the acreage in San Juan County is private and represents nearly 20 percent of the total private land in the county.
San Juan County government is "aggressively trying to find ways to help land owners and mineral rights owners" on the issue, said Commissioner Bruce Adams. Adams called the possible designation the most important issue facing the county.
Adams outlined a number of ideas under consideration after Sandberg completed an exhaustive review of federal law, stating, "We want the Federal government to follow their own rules."
The county is planning opposition to the designation based on exclusions approved in the Endangered Species Act, the Regulatory Flexibility Act, the National Environmental Policy Act (NEPA), and Executive Orders regarding impacts of federal actions on the energy supply and the taking of private property rights.
County officials explain that the economic impact of federal action must be taken into account and losing 20 percent of the private property in the county could have a dramatic impact on the economy.
Commissioner Phil Lyman said, "If you take out everything else, it boils down to private property rights. Those laws are unconstitutional because they don't support state or individual sovereignty. This is not a public lands issue, it is a private property rights issue."
Lyman encouraged participation and added, "Whatever they can do to those land owners they can do to the rest of us."
Commissioners announced that a resolution before the Utah State legislature would oppose the designation of critical habitat on private property in San Juan County.
At the February 4 meeting of the San Juan County Commission, members of the Mexican Hat community approached the Commission with a request that the county help subsidize the expenses to run the Special Service District that provides services to the small community.
Danny Fleming, who manages the Special Service District, said that a $22,000 subsidy from the county government would help the district avoid an increase in fees.
Fleming said that over the past several years, the district has seen a 169 percent increase in Transient Room Tax collections, a 90 percent increase in sales tax collections and an entirely new tax on restaurants.
In total, the district collects about $105,000 in annual revenues, but additional increases may be needed because of increased costs.
Commissioners said that they support the community of Mexican Hat and would like to see local residents more involved in the governing decisions.
Approximately eight years ago, the local board that governed the district was dissolved and the Commission became the board.
Commissions asked the Mexican Hat community to reestablish a board or an advisory committee and help develop options of how the county can be of assistance.
In other matters at the February 4 Commission meeting, Burton Black, Allan Barry, Gail Johnson, and Doug Allen were each appointed to a third term on the San Juan Health Service Board. The reappointments required a resolution by the Commission since the service district initially restricted board members to two terms.
County Administrator Rick Bailey explained the board members were willing to serve another term and added, "Finding people willing to serve is at times difficult."
Commissioners appointed Lee Bennett to serve on the San Juan County Library Board.
Commissioners approved a request by the Hole in the Rock Foundation to seek a $8,000 state history grant for work on the Kumen Jones home in Bluff.
The home is on the National Registry. The Hole in the Rock Foundation will provide a matching grant to the state funding.
A project to explore economic development options on the Navajo Reservation was outlined by William Guevara, Director of programs at First Nations Oweesta Corporation
The group is partnering with American Express in a goal to expand Community Development Financial Institutions.


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JNBridge has sharpened up its interoperability tools for Java and .NET with the 3.0 version release of its JMS Adapters. The tools themselves are designed for developers to access JMS (Java Messaging Service) directly from BizTalk Server or from .NET-based applications themselves. The lengthily named JNBridge JMS Adapter for BizTalk Server V3.0 has now added support for JMS Map Messages, and this is intended to automatically convert received map messages to XML documents based on user provided schemas.
The JNBridge JMS Adapter for .NET adds full support for Visual Studio 2010 and Microsoft Windows Communication Foundation (WCF) Line-of-Business (LOB) SDK. The company says that the adapters enable the integration of any existing JMS (Java Message Service) infrastructure with BizTalk Server or with Microsoft .NET Framework-based desktop applications, server solutions, and cloud deployments. With the adapters, developers are able to configure transports and integrate applications, simplifying the complexity and therefore allowing development teams to reduce risk and focus on automating other businesses processes.
"This latest release of the adapters is another step forward in our vision of interoperability, allowing users to deploy interoperable solutions anywhere," said Wayne Citrin, CTO of JNBridge. "The latest version of each adapter allows enterprises to purchase and deploy according to their business needs: from conventional perpetual machine-based licensing to annual licenses on virtual machines, or even to instances in the cloud."


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SHOW: Calvin Klein
WHEN: Sept 13
FASHION: The show was attended by celebrities, like Emma Stone, who were excited for the collection. The colors overall were neutral lots of black, beige, off white, and white. The dresses featured lots of low cut necks, v-neck sweetheart and plunging were all seen. There were also lots of pant and skirt suits. All the pieces seemed to focus on emphasizing the small waist of the woman and led out to full skirts. Overall very wearable with lots of sleek designs.
BEAUTY: The make up was simple, a very nude face with a light pink lip. The hair was down with a side part.


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"Bush would be able tell you, right here in Texas," Bob Vander Plaats was saying over a La Quinta cup of coffee in The Woodlands Friday morning, "that when the conservative base is motivated and energized, you will win the presidency. If the conservative base is not motivated and energized — John McCain can tell you that story."
Head of the Iowa-based Family Leader organization and one of the nation's most influential conservative Christian activists, Vander Plaats had Mitt Romney in mind when he made that comment. If the former Massachusetts governor is the nominee, he warned, conservatives may vote for him, reluctantly — because they don't want another four years of Barack Obama — but they won't be knocking on doors, making the calls and driving people to the polls to vote for a candidate they enthusiastically believe in. And Obama will be re-elected.
Vander Plaats, in Houston for a couple of meetings, is a Rick Santorum man and is in regular contact with the former Pennsylvania senator whose staunch Catholic faith is at the core of his campaign. "I really thought and I still do believe that there's an opportunity for him to be our nominee," he said.
He anticipates a brokered convention.
"Two weeks ago, I would have said Gingrich ought to get out," he said. "Had Gingrich gotten out earlier, Ohio is in Santorum's column, Michigan is in Santorum's column and the narrative's completely different today. But now that Gingrich has stayed in, the polling I've seen, 57 percent of Gingrich's support would go to Santorum, 43 percent of Gingrich support would go to Romney, so by Gingrich staying in he does keep some delegates from going to Romney. Now, you can also argue that he's keeping some delegates from Santorum, but right now probably Santorum's best shot is going into a convention. We go into a convention, I'll guarantee those delegates are not going to Romney."
Under that scenario, Texas with its May 29 primary would be something more than an afterthought.
"Romney can't get to 1144 (delegates) by June 5, unless everybody else drops out other than Ron Paul," Vander Plaats said. "So Texas is going to be a player. And if Texans rally around the alternative to Romney, it's Santorum. I think that's what Louisiana's doing right now. Looking at some polls right now, it looks like Santorum's going to have a huge day in Louisiana. If Texas does the same thing, it sets the stage – we're going to a brokered convention. And that's Romney's worst nightmare."
The biggest problem that conservative Christian voters have with Romney, in Vander Plaats' view, is not necessarily his relatively moderate positions in years past or his Mormon faith, but their lack of trust in his core beliefs.
I remember Darla (Vander Plaats) and I having dinner with Mitt and Ann Romney in 2006," he said. "Very impressive guy, very impressive couple. But the more you're around him and the more you understand his policies and his changes and his flips, you just wonder, 'Who am I dealing with?' It's like you'll morph yourself to be whatever candidate you need to be for the campaign you're in. . . . What Romney has – and I'm not sure how he's going to shore it up – is a huge trust gap with conservatives."
Vander Plaats, known as the Iowa Caucus kingmaker, was Mike Huckabee's Iowa campaign manager in 2008, and the former Arkansas governor and Baptist preacher won the Iowa caucuses. Vander Plaats tried to persuade him to run this time. He also thinks Huckabee would have made a good McCain running mate.
It's different this time. Vander Plaats says no one should expect a Romney-Santorum ticket or a Romney-Gingrich ticket.
"Huckabee and McCain at least liked each other," he said. "With Santorum and Gingrich and Romney, Santorum and Gingrich intuitively believe that Romney is the most disingenuous person. And Gingrich would probably say, dishonest."


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7 Valentine's Menus are coming your way this week -- for every scenario, whether you're wooing a first date or boycotting romance altogether.
No heart-shaped desserts allowed. Follow the action and share your stories at #NoMoreBadValentines.
Sometimes you want to put on your swankiest outfit and go out for a fancy meal. Sometimes you want bottles of wine and boxes of chocolate. Other times, you just want Mexican food.
Don't let anybody tell you that you can't eat queso on Valentine's day. Make it a meal by pairing it with some super-simple carnitas, an exotic drink, and a chocolate-dipped dessert. As an extra consideration for your mate, we've even got a guacamole recipe with no raw garlic in sight. Now that's what we call romance.
Diana Kennedy's Carnitas from Genius Recipes
Roberto Santibañez' Classic Guacamole from Genius Recipes
El Presidente from Erika Kotite
Nacho Cheese Sauce from Lara
Coconut Cajeta & Chocolate Fondue from hardlikearmour
More Valentine's Menus:
The Swanky Steakhouse Dinner
The Anti-Valentine's Dinner
See what other Food52 readers are saying.


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PEEK cages
Exceptional performance capabilities
Perfect for compressorsPEEK cages are extremely well suited for oil-flooded compressors, as the bearings operating within them require chemical resistance to gases and the ability to run under difficult lubrication and temperature conditions.
SKF PEEK cages are often used in bearings with ceramic rolling elements or super-tough stainless steel rings. The combination offers excellent protection from damage caused by poor lubrication and exposure to chemicals, enabling reliable, robust, low-energy compressor designs that are virtually leak-free.


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As snow continues to fall around the country, Yorkshire is an area which continues to be affected with hundreds of schools being shut and transport being disrupted. Although Yorkshire is often affected by snow, is there a reason for this and why do some parts of this county always seem to receive greater snowfall than others?
Grahame Madge from the Met Office states that the current weather setup revolves around snow showers which "can develop in some areas rather than others", but that the random nature of these showers "makes it harder to pinpoint exact areas". Mr Madge says that the "eastern parts of Britain are a showery region", which is why Yorkshire is usually affected by the snow.
The East Coast receives a very strong easterly flow of winds from the North Sea and as the moisture rises and reacts with the cold air, these showers are formed. This explains why the country as a whole is seeing an influx of snow, as the moisture is rising from the sea and meeting the extremely cold air generated from the 'Beast from the East'.
Read more: When Storm Emma will arrive in Yorkshire and the amount of snow it could drop
North Yorkshire in particular is an area which usually receives a large amount of snowfall and areas such as Harrogate and Skipton are almost always affected by cold-weather fronts. This is due to its geographical location as it is more upland than West and South Yorkshire, which makes it more likely to receive a greater amount of snow.
Mr Madge explains that in regards to general weather principles, "elevation sees more snow" as more "snow jets" occur in upland areas. This is why the elevated areas of the North York Moors and Yorkshire Dales always seem to receive a large amount of snow, as the higher up and more exposed a place is generally gets more snow on the ground.
Coastal sites are also more prone to these snow showers due to the moisture from the sea, which makes seaside resorts such as Bridlington and Whitby more likely to receive snow.
Read more: Spectacular drone footage shows off beautiful snow-covered Yorkshire
As the snow showers then run out of moisture as they retreat further inland, general weather principles makes other parts of Yorkshire less likely to receive as much snowfall as its coastal and highland counterparts.
However, the recent influx of widespread snow over all parts of Yorkshire reiterates Mr Madge's notion of the random nature of these snow showers.
Mr Madge hopes that as the Met Office continues to make developments in regards to weather predictions, it will become easier to see exactly where snow should fall, as currently "forecasting showers is one of the biggest challenges of meteorology".
Read more: Yorkshire farmer shares incredible photos of snow in Swaledale


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Displaying 1 to 2 of 2Search Help
USDA. Animal and Plant Health Inspection Service.
On October 10, 2019, the U.S. Department of Agriculture's (USDA) Animal and Plant Health Inspection Service (APHIS) in coordination with the New York State Department of Agriculture and Markets, New York State Department of Environmental Conservation, and New York City Department of Parks and Recreation announced that they have eliminated the Asian longhorned beetle (ALB) from the New York City boroughs of Brooklyn and Queens. "I am proud to say that we have eradicated Asian longhorned beetle from Brooklyn and Queens," said Greg Ibach, USDA's Under Secretary for Marketing and Regulatory Programs. "This officially marks the end of our 23-year long battle with this pest in New York City."


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Music is a huge part of my everyday life. I am always listening to music and I decided that it would be fun to make monthly playlists! Each playlist will feature some new songs, some old songs and a random mix of genres.
Please share this playlist with your friends and link me to your own monthly playlists!
Check out the playlist below or click here. Check out November's playlist here.


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|Phaidon International
US-NC, Clinical Research Associate 452431244145-MZ
|Position - Contract Clinical Research Associate
Therapeutic Area: CNS
Industry: Biotech
Length: 2 years
Site Locations: Florida, North Carolina, South Carolina, Alabama
A leading biotech company is looking to add a contract Clinical Research Associate (CRA) to its already prestigious workforce. This is a 2-year, home-based position responsible for monitoring sites in Florida, North Carolina, South Carolina and Alabama.
The position is 1.0 FTE and requires previous experience in the CNS therapeutic area, as well as an extensive Late Phase (Phase IV) background.
Contract CRA's Required Locations
Key Requirements for Contract Clinical Research Associate (CRA)
Please visit our website at www.phaidoninternational.com


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Anales de la Asociación Química Argentina
Print version ISSN 0365-0375
An. Asoc. Quím. Argent. vol.94 no.1-3 Buenos Aires Jan./July 2006
Molecular recognition and binding mechanism of N-aralkyl substituted 2-aminoindans and the dopamine D2 receptor. A theoretical study
1 Andujar, S. A.; 1Garibotto, F. M.; 1Enriz, R. D.; 2Migliore de Angel, B.; 3Angel-Guío, J.; 4Charris, J.
1 Departamento de Química, Universidad Nacional de San Luis, Chacabuco 917, 5700 San Luis, Argentina. FAX: +54-2652-431301, E-Mail: firstname.lastname@example.com.
2 Laboratorio de Síntesis Orgánica y Diseño de Fármacos. Departamento de Química, Facultad de Ciencias. Universidad del Zulia, Apartado N 526, Maracaibo. Venezuela.
3 Sección de Farmacología. Instituto de Investigaciones Clínicas. Dr. Américo Negrette, Facultad de Medicina. Universidad del Zulia, Apartado N 526, Maracaibo. Venezuela.
4 Laboratorio de Síntesis Orgánica. Facultad de Farmacia. Universidad Central de Venezuela. Caracas. Venezuela.
Received March 1st, 2006. In final form April 24th, 2006
Dedicated to Prof. Imre G. Csizmadia on the occasion of his 75th birthday
In order to better understand, at submolecular level, the minimal structural requirements for the recognition process in the inhibitor activity, N-aralkylsubstituted 2-aminoindans were examined as D2 dopamine receptor antagonist variants. Semiempirical (AM1) and ab-initio (RHF/3-21G and RHF/6-31G(d)) calculations were performed for a better understanding of the recognition process at submolecular level. Using the above-mentioned computational model, we were able to interpret the basic behavior and predict some additional features of N-aralkyl substituted 2-aminoindans-Dopamine D2 receptor interaction.
Se estudiaron N-aralquil-2-substituidos-aminoindanos como variantes de inhibidores del receptor D2 de dopamina con el objeto de mejorar el entendimiento, a nivel molecular, de los requerimientos mínimos estructurales para el proceso de reconocimiento en la actividad inhibitoria. Se utilizaron cálculos semiempiricos (AM1) y ab initio (RHF/3-21G y RHF/6-31G(d)) para entender el proceso de reconocimiento a nivel sub-molecular. Utilizando el mencionado modelo computacional fue posible interpretar el comportamiento básico y predecir algunas características adicionales de la interacción entre los N-aralquil-2-substituidos-aminoindanos y el receptor D2 de dopamina.
The brain dopaminergic system has a crucial role in the etiology of several neuropsychiatric disorders, including Parkinson's disease, depression and schizophrenia [1,2].
Since the introduction of chlorpromazine, a known dopamine (DA) antagonist, DA-ergic drugs have been widely used in medicinal practice. Thus, several dopaminergic drugs are used to treat these pathologies, but many problems are attributed to these therapies [1,2]. For these reasons the search for new, more efficient dopaminergic agents with lower adverse effects is still an extremely active research field. Scientific literature in this field is numerous and can be found summarized in relatively recent review articles [3,4].
During the last decades, a large amount of N-substituted 2-aminoindan (compound 2 in Figure 1) and 2-aminotetraline analogs (compound 3) with peripheral and central nervous system action have been reported [5-8]. Recently we reported the synthesis and dopaminergic profile of N-aralkyl substituted (compound 1), which displayed an interesting dopaminergic activity [9]. Now, we are interested to evaluate at submolecular level the minimal structural requirements for the recognition process between compound 1 and its biological receptor. Thus, in the present theoretical study we simulate the electrostatic interactions between compound 1 with its biological receptor in terms of a reduced molecular model. In an attempt to better understand the biological profile reported for compound 1, we present here an exhaustive conformational and electronic study of compound 1. We also discuss a possible molecular recognition and binding mechanism for this compound and the stereoelectronic requirements to elicit the dopaminergic activity.
Figure 1. General structure feature of N-substituted 2-aminoindan (2) and 2-aminotetraline analogs (3). Chemical structure of compound 1 showing the different torsional angles (f1,f2, f3 and f4).
Methods of calculation
Conformational and electronic study
To determine the minima on the conformational potential energy hipersurface (PEHS) of compound 1, fully relaxed semiempirical (AM1) and ab-initio (RHF/3-21G and RHF/6-31G(d)) calculations were performed.
An extensive search for low energy conformation on the PEHS of compound 1 was carried out by using 54 input files obtained from multidimensional conformational analysis (MDCA)[10-12] in connection with AM1 semiempirical calculations. Subsequently, several distinct trial atomic spatial arrangements were used in the geometry optimization jobs using ab-initio (RHF/3-21G and RHF/6-31G(d)) calculations to locate the possible equilibrium structures present on the multidimensional energy surfaces. Minima were characterized through harmonic frequency analysis employing RHF/6-31G(d) calculations. Rotational energy profiles around torsional angles have been determined using RHF/3-21G calculations. The energy has been calculated at 30º intervals of the dihedral angles.
All calculations reported here were performed using Gaussian 03 [13]. The electronic study of compound 1 was performed using molecular electrostatic potentials (MEPs). MEPs have been shown to provide reliable information, both on the interaction sites of molecules with point charges and on the comparative reactivities of these sites [14-16]. These MEPs were calculated using RHF/6-31++G(d,p) wave functions. RHF/6-31G(d) coordinates were imported to generate the wave functions; thus, RHF/6-31++G(d,p) single-point calculations were performed from Gaussian 03 program. All MEPs graphical presentations were created using Molekel [17].
Construction of the receptor model
A reduced 3D model of the human dopamine D2 receptor was constructed, based on the theoretical model structure of bacteriorhodopsin [18]. Binding pocket of the D2 DAR (dopamine receptor) was defined according to M. M. Teeter et al. In our reduced model, only 22 aminoacids were included for the molecular simulations. The size of the molecular system simulated and the complexity of the structures under investigation restricted the choice of the quantum mechanical method to be used. Consequently the semiempirical AM1 method [19] was selected. The torsional angles of the ligands and the flexible side-chains of the amino acids as well as the bond angles and bond lengths of the moieties involved in the potential intermolecular interactions were optimized. In contrast, the torsional angles of backbones as well as the bond angles and bond lengths of non-interacting residues were kept frozen during the calculations.
Results and Discussion
Conformational and electronic study of compound 1
The postulate that a molecule has to assume a particular conformation in order to function as a receptor implies that the ability of a molecule to achieve the required conformation would affect its activity. This is usually interpreted in the sense that activity will be impaired unless a molecule can assume the active form. However, it must be pointed out that to relate the biological activity of an antagonist to its conformational properties possess considerable problems since it is difficult to devise molecules of a given conformation without also changing some other physico-chemical properties.
In the first step of our work we performed an exhaustive conformational study of compound 1 because it is essential to know the conformational behavior of this compound in order to understand the drug-receptor interaction; not only in terms of its preferred conformations but also in terms of conformer interconversions. According to Fig 1, the flexible aspects of the molecular conformation of 1 is governed by four torsional angles f1, f2, f3 and f4. Consequently, the potential energy hypersurface (PEHS) of four independent variables
E = f (f1, f2, f3, f4 ) (1)
contains all the conformations as minima. Thus, this compound is, in principle, a quadruple rotor. Multidimensional Conformational Analysis (MDCA) [10-12] predicts the existence of 3 x 3 x 3 x 2 = 54 legitimate minima for a quadruple rotor with these multiplicities. Using MDCA predicted 54 geometries as input, we located a total of 43 conformers on the PEHS (eq. 1) at the AM1 level of theory, instead of the expected 54 structures (Table 1). Next, using the 43 AM1 geometries as input files, we performed RHF/3-21G calculations. Only 33 different conformers were obtained from RHF/3-21G computations (Table 2). To categorize the different structures obtained for this compound, we introduced intuitively rather than by a precise definition, four forms: Fully Folded (FF), Partially Folded (PF), Partially Extended (PE) and Fully Extended (FE). By the FF form, we mean a closed structure with relatively short distances between the aromatic rings. By the FE form, we mean a form with a linearized connecting chain. By PF and PE forms we denote a intermediate conformation between folded and extended. In these two forms the catecol ring can adopt two different spatial orderings: closed in the PF forms and open for the PE conformations.
Table 1.Torsional angles and energy gap obtained for the different conformations of compound 1 from AM1 calculations.
Table1 (continued)
Table 2. Torsional angles and energy gap obtained for the different conformations of compound 1 from RHF/3-21G calculations.
Table2 (continued)
Table 3. Torsional angles and energy gap obtained for the preferred conformations of compound 1 from RHF/6-31G(d) calculations.
The conformational analysis of compound 1 requires at this point the evaluation of its flexibility i.e.; the energy determination of the transitional barriers between the predicted conformers. This is of crucial importance because, if the barriers display low, energy during the molecular recognition this molecule could be converted, with a low energy cost, to a preferred geometry in the binding site within the receptor.
The energy profiles showing the influence of the torsional angles f1 - f4 on the potential energy of the rotamers are given in Figures 2(a) – 2(d), respectively.
The curves of Figures 2(a), 2(b) and 2(c) show that these rotations possess three preferred conformations (gauche +, anti and gauche -). However, the barriers that separate these conformations are somewhat different. The energy barrier for f2 is ≈ 5.5 kcal/mol, whereas the barriers for f1 and f3 are relatively high (≈ 7 kcal/mol) at RHF/3-21G level. Looking at the torsional angle f4 (Fig 3(d)) the preferred conformations were found to be those in which the catecol ring was located perpendicular to the C–C bond (f4≈ ± 90º). The barriers at f4 = 0º and 180º are ≈ 5.5 kcal/mol. This result could explain that practically all the conformations obtained for compound 1 possess the torsional angle f4 in a perpendicular or antiperpendicular position (see Tables 1-3).
Figure 2. Rotational energy barrier profiles computed at the RHF/3-21G level. a) torsional angle f1, starting with f2, f3 and f4 in -76.00°; 173.00°; -75.00°, respectively. b) Torsional angle f2, starting with f1, f3 and f4 in -150.00°; 173.00°; -75.00°, respectively. c) Torsional angle f3, starting with f1, f2 and f4 in -150.00°; -76.00°; -75.00°, respectively. d) Torsional angle f4, starting with f1, f2 and f3 in -150.00°; -76.00°; 173.00°, respectively.
Figure 3. Spatial view of the preferred low-energy conformations (17, 2, 3, 19, 16, 26 and 10) of compound 1 obtained from RHF/6-31G(d) calculations.
In order to confirm the conformations obtained from RHF/3-21G calculations, we optimize the energetically preferred forms using RHF/6-31G(d) calculations (Table 3); these conformations were confirmed through harmonic frequency analysis.
It is interesting to note that RHF/3-21G calculations found one FE conformation (conformer 19) and one FF form (conformer 16). However, these conformations were not found at RHF/6-31G(d) level. Conformation 19 changes the torsional angle f1 from anti to gauche+ and conformation 16 changes the torsional angle f2 from gauche- to anti; therefore RHF/6-31G(d) calculations predict that all the energetically preferred conformations of compound 1 can adopt PF or PE forms. Also, it is interesting to note that the four preferred forms (conformations 1, 17, 2 and 3) possess a closely related spatial ordering indicating that this type of conformations are highly preferred for compound 1. Figure 3 gives a spatial view for the energetically preferred conformations obtained for compound 1 obtained from RHF/6-31G(d) computations.
The energy differences between the most stable conformation and the other forms, and also the barriers that separate them (predicted by ab-initio calculations) are large enough to suggest that the transition between the different forms is somewhat restricted. Thus, ab-initio calculations predict only a moderate molecular flexibility for compound 1.
Once the preferred conformations of compound 1 were obtained, in an attempt to find the potentially reactive sites for this compound, we evaluate the electronic aspects of this molecule using MEPs. MEPs are of particular value because they permit visualization and assessment of the capacity of a molecule to interact electrostatically with a binding site. MEPs can be interpreted in terms of a stereoelectronic pharmacophore condensing all available information on the electrostatic forces underlying affinity and specificity.
Figure 4 shows the MEPs obtained for compound 1. The MEPs of dopamine is also included in this figure for comparison. It should be noted that both MEPs show a remarkable similarity. In fact the MEPs obtained for compound 1(figure 4a) looks like "two joined dopamine molecules". The close electronic similarity between compound 1 and dopamine could account for their common affinity for the D2-dopamine receptor. This assumption is supported by a qualitative comparison of the isopotential maps obtained through ab-initio calculations.
Figure 4. Electrostatic potential-encoded electron density surfaces of the core structures of compounds 1 (a) and dopamine (b). The surfaces were generated with Gaussian 03 after ab-initio minimizations with a 6-31++G(d,p) basis set. The coloring electrostatic potential in red is indicating the strongest attraction to a positive point charge whereas blue is indicating the strongest repulsion. The electrostatic potential is the energy of interaction of the positive point charge with the nuclei and electron of a molecule. It provides a representative measure of overall molecular charge distribution
The analysis of MEPs showed three characteristic regions, two with negative potential (red and orange zones) and another with positive potential (blue zone). The negative regions are generated by the presence of OH groups on the aromatic rings; while the positive region corresponds to the large positive potential around the nitrogen cationic head.
In the case of compound 1, the electrostatic potentials surrounding both aromatic rings displayed an adequate electronic profile to produce electrostatic interactions. The questions which arise are: a) which of the catecol rings of 1 is mimetizing the catecol ring of dopamine and b) which is the role (if any) of the other catecol ring of compound 1. This problem will be discussed in the next section.
A molecular model for the binding mechanism of compound 1
The recent cloning [20-25] of dopamine receptor (D1-D5) suggests that they are members of a large family of G-protein coupled, seven transmembrane receptors [26]. These receptors are similar to the better-characterized rhodopsin protein [27], which spans the plasma membrane seven times, with the transmembrane (TM) domains forming a binding pocket. Based on the amino acid sequence of the dopamine D2-receptor and computer modeling, Sukalovic et al. [28] suggest that dopamine may interact with aspartate86 and the serines (141 and 144). Consistent with the D2 receptor model proposed by Sukalovic et al. [28], the experimental results of Mansour et al. [29] clearly demonstrate the importance of the negatively charged aspartate86 for both dopaminergic agonist and antagonist binding. Elimination of the negative charge by mutating this critical amino acid to either asparagine or glycine markedly reduced the affinity of both agonists and antagonists to the D2 receptors.
The structure of bacteriorhodopsin reported by M. M. Teeter et al. [18] was plotted using the Chimera program [30] (Figure 5). Binding pocket of the D2 DAR was defined according to Sukalovic et al. [28]; while molecular interaction calculations were carried out using semiempirical AM1 computations. The binding pocket used for theoretical calculation is denoted by a circle in Figure 5. The main features of the D2 DAR model shown in Figure 6 using dopamine as the ligand are:
a- salt bridge between protonated nitrogen atom of the flexible side-chain and negatively charged Asp86 (calculated distance 2.34 Å).
b- hydrogen bonds between the OH of catecol ring and Ser144 and Ser141, calculated distance 1.84 and 2.45 Å, respectively.
Figure 5. Spatial view of the dopamine D2 receptor model from reference [18] using the Chimera program as graphic interface.
Figure 6. Interactions of dopamine (ligand) with the D2 dopamine receptor. Schematic representation of two interactions: salt bridge to the left and catecol ring with Ser144 and Ser141 to the right. All the heteroatoms involved in the intermolecular interactions are shown in the figure
Our results indicate that the aspartate residue86 serves as a possible anchoring point. Previously, we reported that R-NH+-Asp interactions would be the driving force for the N-alkyl-benzyltethrahydroisoquinolines/D1DAR complex [31]. Those calculations were performed using B3LYP/6-31++G (d,p) calculations and taking into account the solvent effects. Thus it appears that semiempirical AM1 calculations are in agreement with experimental [19] as well as theoretical [31] results using more accurate computations.
Given that the amino group of dopamine is likely anchored at aspartate86, the meta- and para-hydroxyls of the catecol moiety are free to form hydrogen bonds with either serine141 or serine144. The calculated interatomic distances for these interactions are shown in Figure 6.
Examination of the structure of compound 1 and computer modeling of the D2 receptor suggest that unlike dopamine, compound 1 could form hydrogen bonds with serine144 using ring A or ring B. Both situations are shown in Figures 7 and 8, respectively.
Figure 7. Interactions of compound 1 (ligand) with the D2 dopamine receptor. Schematic representation of the salt bridge (down), the catecol ring A with Ser144 and Ser141 to the right and catecol ring B with His189 and Phe185 (denoted by a circle). All the heteroatoms involved in the intermolecular interactions are shown in the figure.
Figure 8. Interactions of compound 1 (ligand) with the D2 dopamine receptor. Schematic representation of the salt bridge (down), the catecol ring B with Ser144 and Ser141 to the right and catecol ring A with His189 and Phe185 (denoted by a circle). All the heteroatoms involved in the intermolecular interactions are shown in the figure.
Figure 7 gives a spatial view of the molecular interaction between compound 1 and D2 DA receptor in which the ring A is interacting with Ser144 and Ser141. The salt bridge between protonated N of the flexible connecting chain and the negatively charged Asp86 displayed a distance of 2.69 Å, whereas the hydrogen bonds between the OH of catecol ring A and Ser144 and Ser141, displayed a calculated distance of 1.68 and 2.63 Å, respectively. The total energy of this complex is –0.896605 hartree.
Figure 8 gives a spatial view of the molecular interaction between compound 1 and D2 DA receptor in which the ring B is interacting with Ser144 and Ser141. In this case, the salt bridge between protonated N of the flexible connecting chain and the negatively charged Asp86 displayed a distance of 3.73 Å, whereas the hydrogen bonds between the OH of catecol ring A with Ser144 and Ser141 , displayed a calculated distance of 2.14 and 2.78 Å, respectively. The total energy of this complex is –0.825268 hartree. Thus, the energy gap between these complexes is 44.76 Kcal/mol. On the other hand, the interatomic distances obtained in the first complex are shorter than those attained in the second one. These results indicate that the complex in which catecol ring A is interacting with both serines is energetically preferred with respect to the other complex.
Finally, we wish to discuss some details about the role in compound 1 of the catecol ring which is not interacting with Ser144 and Ser141 (ring B). It is clear that in order to obtain a clear profile of the overall recognition process it is necessary to underline the role of this moiety in the binding mechanism of compound 1. If it is assumed, as it seems highly probable, the ligand will have only a single conformation in its complex with the receptor; thus, the conformation of this complex must involve a process of conformational selection (or alternatively, the ability of the ligand to achieve the required conformation) which will influence the kinetics and energetic of complex formation.
In principle, at least three different roles might be attributed to catecol ring B, i.e:
(i) conformational restriction
(ii) steric hindrance
(iii) a third possibility is that this ring could contribute to its own interaction through a van der Waals interaction
Although these concepts are independently formulated, they might be interdependent.
Our theoretical calculations predict that His189 in TM VI as well as Phe185 could be also involved in van der Waals interactions (zone denoted with a circle in Figure 6). Thus, AM1 computations indicate that the catecol ring B is positioned in the ancillary pocket spanned by two conserved aromatic residues, i.e Phe185 and His189 (Figure 9). It appears that an additional hydrogen bond can be built with His189. However, more accurate calculations considering the electronic correlation are required to confirm this assumption.
Figure 9. Spatial view of the molecular interaction of catecol ring B with the ancillary pocket (His189 and Phe185). Non-interacting atoms have been deleted in this figure to better appreciate the intermolecular interactions. All the heteroatoms involved in the intermolecular interactions are shown in the figure.
The results of AM1 calculations presented here show that the molecular mechanism for the recognition process of the dopamine D2-receptor is energetically feasible. The general picture is that both the salt bridge interaction and the hydrogen bonds between the catecol ring A with Ser144 and Ser141 play a key role in the molecular recognition process. In addition, an appropriate ring orientation of the other catecol moiety (ring B) may be operative stabilizing this process. Thus, a kind of stepwise binding involving first the salt bridge followed by the rest of the molecule seems a reasonable possibility and there is some strongly suggestive evidence that this phenomenon takes place.
To better understand how N-aralkylsubstituted 2-aminoindans interact with dopamine D2 receptors, the conformational and electronic properties of compound 1 have been studied using ab-initio calculations. A putative binding mechanism of compound 1 to dopamine D2 receptor has been prepared on theoretical calculations grounds. The results of molecular interaction simulations on compound 1-D2DAR complexes revealed that this ligand interacts through protonated N of the connecting flexible chain with Asp86 (salt bridge) as well as hydrogen bonds between one of the catecol (ring A) of the ligand with Ser144 and Ser141. In addition, an appropriate ring orientation of the other catecol moiety (ring B) may be operative stabilizing this process. The results presented here provide a basis for further rational design of DA-ergic compounds structurally related to N-aralkylsubstituted 2-aminoindans.
This work was supported by grants from the National University of San Luis, Argentina. R.D. Enriz is a member of CONICET-Argentina. S.A. Andujar thanks CONICET and F.M. Garibotto thanks ANPCyT for Research Fellowships.
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[17] Flükiger, P.; Lüthi, H.P.; Portmann, S.; Weber, J MOLEKEL 4.0; Swiss Center for Scientific Computing: Manno, Switzerland, 2000. [ Links ]
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Audio: High Country Views, episode 2
HCN editors dissect the news
In this episode of High Country Views, editor in chief Jonathan Thompson and multimedia fellow Cally Carswell talk about why the Interior Department's decision not to put the sage grouse on the endangered species list was smart politics, the flurry of states' rights bills being passed by Western legislatures, and how federal health care reform might impact the West.
For our next podcast, we want to hear what's happening in your neck of the West! Call High Country Views anytime at (970) 497-1310 to leave us a short voicemail postcard. Tell us what's making news in your area or just how the landscape is changing this time of year. Whatever is happening where you are, we'd like to know about it.
You can now catch High Country Views every other week. Available for download soon!


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text:
The Evil Spawn just turned 12.
She's a nerd and I use this term with respect.
She's a great nerd (she prefers geek).
For her birthday, she wanted a QR code cake and a QR coded scavenger hunt that led her and her friends all over town.
They went to all of her old haunts. From her first babysitter to the dentist's office where she lost her first tooth.
The clues led them to the grocery store where they had to figure out how much money we have spent on Buddy the Dog's food in the last four years.
They even visited their 2nd grade teacher where they had to recall the order of the planets from their very first big school project and recite them to her in order (funny what they forget).
They had a blast even though they have evidently forgotten everything they learned in 2nd grade.
It's good to have a school technology coordinator as a mom.
Go ahead, scan the cake with your reader. It works.


text:
(visited by Joseph Kerski)
02-Mar-2013 -- As I was in the area to give presentations and meet with students and faculty at Kansas State University, Haskell Indian Nations University, and the University of Kansas, a confluence visit seemed like the perfect capstone, the last thing to do before heading for the airport and leaving the region. It required driving a bit north of the Kansas City airport to reach, but I had a small window of time in which to do it and was hopeful that I would reach my goal.
I suppose the lack of a road name on most online maps should have clued me in to the fact that the road I would be passing over was not in an ideal condition for a rental car. Compounding the situation was the fact that the area had received two significant snowfalls over the past week. I passed St Joseph Missouri and exited I-29 just north of the Honey Creek Recreation Area, intending to take the frontage road to the northwest. The road was completely snowed under and had not been plowed. Therefore, I struck out due north on a very hilly road, which fortunately at least had been driven on since the snow had fallen. It was quite muddy and slippery, but I made my way without mishap to the next section line road running east-west, also unnamed. I headed west on it until it curved to the north at the next section line. So far, all was well, though I was losing precious time by driving so slowly. After a few snowy but scenic miles, I descended a steep hill into the Lincoln Creek valley, hoping I would be able to drive up and out of the valley a short time later.
I parked just south of the bridge over Lincoln Creek and made haste to gather necessary supplies: GPS receiver, camera, batteries, confluence sign. Fortunately I had remembered to wear my non-work shoes. I had just begun to walk north along the road when a truck approached from the south, coming down the hill. A nice fellow leaned out the window and asked if I was having car trouble and if I needed any help. I explained my mission and asked if he owned the field to the west. He said no but that the owner wouldn't mind me walking out there. He then became quite interested in what I was doing. I showed him the GPS, with its reading so close to 40 North. As we talked, I began to walk north, explaining that we would soon be at 40 North, and he followed at my side. It would have been kind of amusing to someone observing us right then, with me walking along and approaching 40 North latitude with him right beside me, driving slowly. We reached 40, he drove off and waved, and I walked back south to the trail paralleling the creek. The reason was that I thought my footing would be better on the trail rather than in the middle of the field. It would require a bit more walking, but I thought it would save time in the end. It turned out that I was right.
After about 20 minutes walking west and west-southwest along the north side of the creek, with snowdrifts up to my knees in places, I reached the west end of the field, and had crossed the 95th Meridian. I then descended off of the embankment into the field and experienced more snow and mud, but the day was just breaking out of a high cloud cover and it was not too cold; about 25 F (-4 C). In five minutes, I was at the confluence site. The field had been sown with corn in the past, and a few old cobs were poking through the snow, which was only about 6 inches (15 cm) high where the wind had been blowing on it. I was on the confluence site for 10 minutes, marveling at how just west of me, this line of latitude marked the Kansas-Nebraska border. The confluence lies in the middle of the valley north of Lincoln Creek. The longest view was to the northwest and to the east, with the shortest to the south and the embankment and trees in the riparian zone beyond. I saw no people or wildlife.
I had stood on 40 North from California on the west to New Jersey on the east. I had stood on 95 west fewer times over the past 11 years, just twice before, in Iowa one degree north of here, and in Kansas one degree south of here. I was glad to be here, and as is typical on these visits, the sun came out just as I had finished photographing the area. No time to retake these; I tried to skip over the snow as fast as I could back to the embankment and back to the road and vehicle. My total round trip hiking time came in at about an hour. I made it out of the area without incident, the way I had come in, and did not stop until I was at the Kansas City airport. It was indeed a great day to be out in the field, and I hoped that I would return to Missouri someday.


text: Those of us who've been eying the Kingston Wi-Drive but have been disappointed with the iOS-first emphasis can rejoice, as a new firmware update is expanding access in a big way. At a minimum, anyone with a web browser can now stream music, photos and videos to their heart's content once they're linked to the drive over WiFi. And if you'd rather use a native app, any Android 2.2 or later device is now an option instead of having to turn to one of Apple's gadgets or the Amazon Kindle Fire. Future Wi-Drives should have the firmware loaded from the get-go. The apps as always remain free, although you'll need to spend a minimum of $50 to join the club with a drive of your own.


text:
Franklin High School students accused of selling Adderall at school
7 students accused, 3 facing expulsion
Seven Franklin High School students are being questioned for their involvement in selling and using Adderall inside the High School.
Police and administrators were tipped off that pill dealing was going on after a girl got sick last Friday.
"When you take someone else's medication, that is not prescribed to you, it may mix with something you've already taken or that you are prescribed and can put your life in danger," Franklin Police Chief Russ Whitman said.
Drug-sniffing dogs went through the school Wednesday and found no drugs.
Safety is one of the reasons administrators are taking this seriously.
Three students could face expulsion. They could all be criminally charged.
Students said they've heard some students talk about popping the pills.
"Just to get high, feel good, just to get through school easier," one student said.
But many said it's not often you hear students using it in school.
"No it's not going around. You're not hearing about it in class like dude, I smoked a bunch of this. You're not hearing about a bunch of Adderall being popped," student James Haines said.
Administrators agree, but they don't believe this is the new drug of choice for teens.
"The school is only a microcosm of the entire community so whatever is out in the community is also going to be in the schools," Superintendent Mike Sander said.
Sander said it's important that parents with children who are prescribed the drugs take an active role in how the drug is kept and how it is taken.
At school, he encourages students to report drug abuse even if it's anonymously.
"Silence is acceptance. If you know this is going on in the school and you don't do anything about it, you accept this is OK and it's not," Sander said.
He told WLWT News 5 he believes this was a one-time problem.


text:
Ever feel bad about throwing away plastic cups? And during the summer, with all the birthdays, pool parties, BBQ and picnics-- well, that's a whole lot of cups! Since most events that we are attending this summer are pot-luck, I volunteer to bring the cups. That way, I can buy the right ones (wink!) and use them for this awesome project!
*****UPDATE***** My sister made this project during her time in the UAE. When she showed me, I found some small transparent cups and was able to melt those, but I haven't done any since, so I am not sure where to get them. I have seen some transparent cups at the dollar store but now sure if they are #6 or not. I hope you can find some cups since this is such a cute project. If you do find some cups, please let us know where you got them. Thanks :)


text:
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A full house ?
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Joined: 23 May 2006
Posts: 13510
Posted: Thu Jul 14, 16 5:00 am Post subject: A full house ?
Right now it's just coming up to six o'clock in the morning and I'm just about to go out into the farmyard to check on Gladys. I took this photo last night.
Hopefully I'll have some more photos for you later on today. The old girl should have farrowed a few days ago, so she's taking her time.
Joined: 23 May 2006
Posts: 13510
Posted: Thu Jul 14, 16 5:11 am Post subject:
News up date.
It's a nice morning out
I've just tripped the light fantastic in wellies and dressing gown to check her. Everything looks peaceful and I'm pleased to report that she has seven healthy looking Gloucester Old Spot piglets suckling on her.
The piglets look very clean and contented, so they were probably born late last night rather than early this morning. Gladys still looks very big, so there maybe some more to come but I'd be more than happy to stick at the seven.
Joined: 28 Oct 2004
Posts: 44319
Location: Essex
Posted: Thu Jul 14, 16 6:13 am Post subject:
Downsizer Moderator
Joined: 28 Oct 2004
Posts: 41992
Location: North Devon
Posted: Thu Jul 14, 16 6:38 am Post subject:
Good oh.
Joined: 23 May 2006
Posts: 13510
Posted: Thu Jul 14, 16 6:50 am Post subject:
The good things in life really are worth waiting for.
Joined: 23 May 2006
Posts: 13510
Posted: Thu Jul 14, 16 7:24 am Post subject:
She had eleven in total. I've just fed her and when she got up, I could see that there was a still born piglet beneath her and a nice boar crushed in the corner where her bottom is in the picture. At the moment, that leaves me with nine healthy piglets but I do hate this next few days until they get a bit more agile and can avoid mum when she lies down. She's passed her afterbirth, so that should be it.
Downsizer Moderator
Joined: 28 Oct 2004
Posts: 41992
Location: North Devon
Posted: Thu Jul 14, 16 10:20 am Post subject:
Fingers crossed the rest of them make it.
Joined: 02 Jul 2005
Posts: 36278
Location: yes
Posted: Thu Jul 14, 16 10:59 am Post subject:
well done gladys ,accidents are sad but they happen and she seems like a good mum.
well done mr midpig ,the first few days are a bit tense but those moments when you you sit there sniffing warm piggy smells and watching them feed or snooze or discover the fun of life does give a chance for being very calm and knowing everything is well with the world.
iv'e just gone all pig broody
Joined: 21 Sep 2006
Posts: 2315
Location: Away with the fairies
Posted: Thu Jul 14, 16 11:08 am Post subject:
Awwww - piglets
Joined: 24 Jun 2010
Posts: 2111
Location: Llanfyllin area
Posted: Thu Jul 14, 16 1:18 pm Post subject:
They look a good healthy bunch, Bodger. You could save a few piglets from the 'crush' if you had farrowing rails round the outside walls (screwed to the walls rather than the floor), as in the Solari type farrowing pens. They will save a high percentage of crushed little ones, but obviously not all. I had the mis-fortune to work with Solari houses as they are not pigman friendly, being so low at the back with a mother after you as you try to add creep feed and so on or adjust a lamp. However the farrowing rails were a definite saving in piglets lives at birth. On the college farm where I worked we also had pig arks, a remnant from a former outdoor enterprise, and as they were on concrete they were called "crarks"! These too had farrowing rails fitted inside, but the added advantage of a piglet creep area with access from outside so no involvement with mother when doing the various pig early operations, iron, teeth, ear notching and castration-all carried out at three days old-quick and easy ay that age rather than the traditional 8 weeks with the associated growth set back. I am not sure if castration is even carried out now, but I guess that iron injection, ear notching or tattooing is still done for pedigree purposes.
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