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Shout! Holiday Employment
What do Play Workers do? Job Description, Person Specification and Wages
Recruitment for Summer 2016 is now open. (Applications for Easter 2016 has closed)
For more information, please see the job descriptions below, or call the Play Development Officer on 01372 474 544
Shout! Holiday Activities aim to provide a supervised, happy environment during the school holidays for children and young people aged between 5 and 13 years living in the Elmbridge area. Shout! aims to offer new experiences and to promote physical and social development.
The role of a Play Worker, Deputy Leader and Site Leader is to facilitate a varied programme of play opportunities such as games, arts and crafts, sports, dance and drama and above all free choice. This creates a safe and exciting environment in which children can explore their creative potential and try out new experiences. To find out more detailed information about specific duties please see the Job Descriptions below. Qualified Playworkers are expected to hold a minimum Level 2 in Child Care. Qualified Deputy Leaders and Site Leaders are expected to have a minimum Level 3 in Child Care. If you are over 18 years old find out what sort of person makes a good Shout! Worker, please see the Person Specification below.
- |Qualified Playworker: Job Description and Person Specification £7.00 per hour
- |Play Worker: Job Description and Person Specification £6.50 per hour
- |Qualified Deputy Leader: Job Description and Person Specification £8.00 per hour
- |Qualified Site Leader: Job Description and Person Specification £9.00 per hour
If you are a particularly sporty person, we also employ Multi-Sports Assistants to work on our sports courses. If you think this role would be more suitable for you, complete an application for this post.
Multi-Sports Assistant: £6.49 per hour
|Multi-Sports Assistant Job Description and Person Specification
Please be aware that both Play Workers and Multi-Sports Assistants should be prepared to be flexible in their approach to working in different environments and settings.
All rates of pay are exclusive of holiday pay which is paid on top of your basic rate of pay.
You can apply for positions by downloading a |Shout! Holiday Employment Application form.
Please post your application form to the Play Development Officer, Elmbridge Borough Council, Leisure and Cultural Services, Civic Centre, High Street, Esher, Surrey, KT10 9SD or if you would prefer you can |email your form.
If your application is successful we will invite you for an interview. If you are unsuccessful we will write to inform you.
|Information for attending interviews


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IMDb > Zorgon (Character)
Top Linksmain detailsbiographyby votesphoto galleryquotes
Filmographiesby yearby typeby ratingsby votesby TV seriesby genreby keyword
Did You Know?photo galleryquotes
Zorgon (Character)
from Zathura: A Space Adventure (2005)
The content of this page was created by users. It has not been screened or verified by IMDb staff.
Alternate Names:
Lead Zorgon
FilmographyEdit Credits
There may be more credits available for this character. To edit the credits displayed or to add more credits to this character's filmography, click the Edit Credits link.
- Zathura: A Space Adventure (2005) Played by Douglas Tait / Joe Bucaro III / Jeff Wolfe / Derek Mears (as Lead Zorgon)
... aka "Zathura" - International (English title) (short title), USA (short title)
Additional Details
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subset: commoncrawl


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Eva Longoria just dented any hopes that the Apple Company had of getting consumers to believe that they are protected with the privacy concerns surrounding all Apple projects. And it only took 45 seconds to shock users of the iPad, iPhone and even the iCloud. According to Access Hollywood on Wednesday, the actress was has issues with privacy concerns as the employees of the stores get her profile details. In one case an employee even called her directly.
Eva Longoria is a sexy woman in Hollywood and there is no doubt that people would want to see compromising pictures, but the star is too smart to be a victim. Apparently, she has already been a victim to the idea of people getting into her email and phone, but it isn't some international hacker. Nope, allegedly it was an Apple employee. Knowing her information might be compromised, she has hired a team to make sure her privacy is protected.
According to Buzzfeed, her allegation comes just a day after Apple denied there had been an iCloud security breach in relation to the Hollywood naked photo scandal. And it also puts a damper on any damage control that Apple might have done to reflect the privacy concerns of their products.
Eva Longoria has shocked the country with her allegations of privacy issues and what's worse is that it appears the profile access can be obtained from anywhere. This makes everyone wonder if the hacker who stole pictures from celebrities is an average person or someone who has a connection with profiles to get details not available to the public.


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Willie Nelson has a new book out, Roll Me Up and Smoke Me When I Die: Musings from the Road, bringing his total to four, including one autobiography. Roll Me Up follows along with The Tao of Willie: A Guide to the Happiness in Your Heart and The Facts of Life: and Other Dirty Jokes in form and lives up to the subtitle, "Musings from the Road." It's an interesting amalgam of song lyrics, autobiographic bits, jokes (dirty and otherwise), and journal entries. There are some funny stories and some touching stories. and there are a few rants concerning the killing of family farms, legalizing marijuana, and God.
Two parts that stood out to me were when he talked about his bass players, Bee Spears and Chris Ethridge, who both played with him separately and for a brief time, together. Both pickers passed as he was writing the book and he talks about each and shares a little about their life on the road. At nearly 80 years old, Willie has seen several of his friends pass. Even though the humor continues in the book to the end, I continued the book with a more somber reading that was reinforced by the short passages written by his family and close friends. The final chapter of the book is filled with writings by his children and I couldn't help but to read it as almost like a memorial. I wish Willie many more years, though.
But don't get me wrong, the book's not one big downer after another. Maybe it was just my mood on that day, I don't know. There are several stories in the book that made me laugh out loud. Though some of the stories have been recounted elsewhere, I still enjoy hearing him tell about hanging out with Roger Miller, or playing in Ray Prices band, or being in the Highwaymen. He does a fair bit of bragging on his kids, as might be expected of a proud papa and grandpapa with talented offspring.
If you are a Willie fan, and I don't know why you'd be reading the book if you weren't, he does mention two projects that are slated for release. One is a double album with Leon Russell and the other is an album with Ray Price. Of course he has recorded with both of them in the past, but both sound like promising releases.


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Red Chapel (Det rode kapel) Movie Reviews
Red Chapel (Det rode kapel)
Release Date: Dec 29, 2010
Genre: DocumentaryComedy
Rating: (NR)
User reviews on Red Chapel (Det rode kapel)
Red Chapel is a doc**entary about two Danish comics Simon and Jacob and the movie director Mads Brugger going to North Korea and exposing how evil it is. I honestly had a hard time believing that the doc**entary is real. I do not understand how they got away alive and managed to film it all. I was fascinated by this film. I truly do not know if I loved it or hated it, but I was definitely intrigued. Mrs. Pak, who was assigned to be a caretaker for the group, is the most interesting and the saddest individual in this film. I could not believe that someone could love their country so blindly. I know that North Korea is not a good place to live, but after this movie I think it is literally hell. I can not believe what is happening in there and that it is made to be legal. It is truly terrifying and mind blowing that people in North Kortea are being killed and starved by their own government. I do not know how Simon, Jacob and Mads succeded in filming this and not getting killed, all I know is that this doc**entary blew me away and I am going back to see it again.
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Middlebury Community Schools educator Gerald Rasler is retiring this year after 43 years and a local group will honor him.
A local principal is being recognized for his achievements.
The Crystal Valley Exchange Club of Middlebury has selected Northridge High School Principal Gerald Rasler for its Book of Golden Deeds award.
"Mr. Rasler is being recognized for his outstanding service and contribution to the local community and Middlebury Community Schools during his years as an educator and administrator in the local school system," the group said in a statement.
Rasler is retiring at the end of this year after 43 years with Middlebury schools, the statement said.
The club will present the principal with the award at a banquet at 6:30 p.m. on Thursday, May 1 at Essenhaus Inn and Conference Center in Middlebury.
The event is open to the community for $20 per ticket.
Tickets can be purchased from any Crystal Valley Exchange Club member, or from Lake City Bank, Hawkins Water Tech, or First State Bank in Middlebury.
For more information, contact Bill Leedy at 825-5320 or Dave Hawkins at 536-7359 or by email firstname.lastname@example.com.


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Very Chocolate Chip Brownies RecipeRead Reviews Be the first to add a review
5 12 14
Chocolate chips and melted chocolate make these doubly delicious. They're a treat I love to bake and share. — Jan Mock, Dillon, Montana
- 1-1/2 cups sugar
- 2/3 cup butter, cubed
- 1/4 cup water
- 4 cups (24 ounces) semisweet chocolate chips, divided
- 4 eggs
- 2 teaspoons vanilla extract
- 1-1/2 cups all-purpose flour
- 1/2 teaspoon baking soda
- 1/2 teaspoon salt
- Confectioners' sugar
- In a large heavy saucepan, combine the sugar, butter and water; bring to a boil, stirring constantly. Remove from the heat; stir in 2 cups chocolate chips until melted. Cool slightly.
- In a large bowl, beat eggs and vanilla; stir in chocolate mixture. In another bowl, mix the flour, baking soda and salt; gradually add to chocolate mixture, mixing well. Stir in remaining chocolate chips.
- Spread into a greased 13-in. x 9-in. baking pan. Bake at 325° for 35-40 minutes or until a toothpick inserted in center comes out clean. Cool completely in pan on a wire rack.
- Sprinkle with confectioners' sugar. Cut into bars. Store in an airtight container. Yield: 3 dozen.
Originally published as Very Chocolate Chip Brownies in Best of Country Cookies 1999, p77
Reviews for Very Chocolate Chip Brownies
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Any changes to your rating or review will appear where you originally posted your review
Reviewed Sep. 20, 2015
"Very moist, decadent with chocolate....absolutely the BEST brownies I have ever made!"
Reviewed May. 15, 2015
"These are simply spectacular! They came out huge, thick, chewy and chocalatey! Have made them three times so far, and they're definitely worth the extra work and dishes."
Reviewed Jan. 24, 2015
"I made these yesterday. My husband loved them, and so do I! These are definitely a keeper for sure! I'll be making these for sure in the future for a church potluck!!"
Reviewed Apr. 29, 2014
"Everybody loved this one! We have LOTS of brownie recipes in this household and this recipe held its own! My son even copied down the recipe! We love the extra chocolate chips in the brownie!"
Reviewed Apr. 8, 2014
"These are simply the best brownies ever! They are a hit anywhere I bring them."


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Another revelation: Matt Walsh claims he was at a game in Foxboro filming the signals, and that there was a guy from another team who was doing the same. He told Goodell the story, and the name of the team.
Goodell never mentioned that (of course), but was asked about it this week during a press conference. He said he wasn't told the name of the team, then backpedaled and said maybe he had, but there was no evidence to support the claim, so he didn't pursue it.
Just like he didn't pursue anything with the Patriots at first, until some media pressure forced his hand.
I know you don't want the money to suffer. But, this is disingenuos. You are not acting in the best interest of the sport, and this will come back to haunt you. TELL THE FREAKIN' TRUTH, already!
Incidentally, the story also says that the team was going to meet New England again, so it was likely to be the Dolphins, Colts, Jets, or Bills that he was talking about.
If it did turn out to be the Dolphins, my stance would not change. Cheating is cheating. Period.
Dave Wannstedt (coach at the time) declined comment, and Harvey Greene had to meet with Bryan Weidmeir before providing a no comment. How's that for humor?
Home » Unlabelled » What is wrong with this guy?
Saturday, May 24, 2008
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A brief note on a few clinical experiences I've had with Monotropa uniflora (Indian Pipe/Ghost Pipe/Fairy Smoke) since my first encounters with the plant this summer:
-- A client had a panic attack while visiting a friend. She found him doubled over and only able to say "The pain! The pain!" She assumed that he was in excruciating physical pain and reached for the Monontropa uniflora tincture she had on the shelf and gave him a moderate dose (I don't know for certain but I suspect 10-20 drops).
He came to see me a few days later and told me that "The Indian Pipe took everything I was worried about and put it outside me, in front of me, where I could work on it." I told him that was almost exactly how people described the plant's effect on physical pain. (Tommy Priester says that it puts you "beside your pain" where you are aware of it without feeling it.)
Over the next two weeks or so, he continued using the tincture for acute panic attacks that were coming almost daily. When I saw him next he told me that one day he began having a panic attack and began thinking about the plant and remembered the way it worked inside him. He said he realized then that he didn't need to take the tincture anymore. Despite dealing with some large setbacks in his life since then, his emotional health has remained excellent.
-- A client had been experiencing severe migraines since sustaining a Traumatic Brain Injury in the first Gulf War. As he described his experiences, I immediately saw Monotropa uniflora, its form resembling the brainstem. I told him to take 3 drops for acute migraine pain. He came back to me the next day and told me it was the first medicine that had ever touched the pain of his headaches. (I also gave him a formula including Ashwagandha, Wood Betony, Oat Milky Seed, and Clematis for daily use but have not heard back about the effectiveness of that formula.)
-- On two occasions, I have used Monotropa uniflora with people experiencing acute psychotic episodes brought on after taking large doses of psychedelics. (As Jim McDonald and others have pointed out, psychedelics don't cause psychosis, but they can bring out an underlying psychosis.)
In the first instance, I gave 30 drops of Monotropa uniflora and 30 drops of Monotropa uniflora to a man who was disoriented and very verbally agressive. After a short time he became much more subdued though still severely disoriented, and a little while later fell asleep. He was lucid when he eventually woke up.
In the second instance, I was part of a team working with a man who had gone into a full scale dissociative state after taking 5 hits of LSD and had become extremely physically and verbally violent. We initially gave him 10 drops of Monotropa uniflora tincture with no response. Over the course of the next hour we gave him two 30 drop doses of the tincture. (In addition to Mimulus to address his panic.) After the second dose his pupils became less dilated and his eyes became more responsive and he began to respond more directly to outside stimuli. Our sense was that the Monotropa uniflora had brought him "down" from the trip at a physical level.
However, it didn't touch the underlying psychosis. He remained physically violent, emotionally agitated, and verbally incoherent for the following four hours. Eventually he became physically exhausted enough for friends to take him to a hospital at which point we lost touch with him.
(We had avoided calling 911 because we knew there was little that an Emergency Room could do in this instance that we couldn't and that an ambulance would have required police assistance. Given the near certainty that he would have assaulted the officers trying to help him, we erred on the side of sparing him from facing felony charges.)


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Eddie Wayne Hill
Position: RB
Height: 6-2 Weight: 205 lbs.
Born: May 13, 1957 in Nashville, TN
High School: Hillsboro
College: Memphis (school history) (Hill college stats)
Drafted by the Los Angeles Rams in the 2nd round (54th overall) of the 1979 NFL Draft.
Weighted Career AV (100-95-...): 5 (9377th overall since 1950)
Other SR Links: College Football at Sports-Reference.com
Promote your website or business by sponsoring this page for $5 on Pro-Football-Reference.com. Your message will replace this ad.
Output includes all games from 1920 to 2015.


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370 Linwood Avenue, Buffalo, NY 14209
24-Hour Crisis Help Line: 716.886.0935
Fax: 716.886.8386
1451 Main Street, Buffalo, NY 14209
Client Services: 716.884.3066
Administrative Offices: 716.886.1351
Fax: 716.886.8387
Staff Contacts
Executive Director: Lisa Freeman
Development Director: Candice Fletcher-Pacheco
Operations and Communications Director: Rachel Wozniak
Youth Services Director: John Ferby
Shelter Director: Thom Piniewski
Questions and Comments:
Questions or comments about Compass House? Contact 716.886.1351 or email [email protected] for more information.
Thank You for Caring About Our Kids.


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ORLANDO, Fla. (AP) -- Want a free house? Talk to officials in Orlando who are trying to get rid of five semi-historic houses as they prepare to expand Lake Eola Park.
The Orlando City Council decided Monday to the $8.5 million purchase of 1.36 acres of property to expand the downtown park.
The Orlando Sentinel reports the prospective owners of the houses will have to foot the bill to move them.
If there are no takers, the buildings will be demolished.
Orlando Mayor Buddy Dyer says it was a "once-a-generation opportunity" to expand the park.
The houses were built between 1915 and 1930. Three are two-story houses and the other two are single-story.
Officials say they hope to close on the property by the end of the year


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It has been almost three years since we learned the name Amber Cole, a fourteen year old blackgirl who was secretly recorded while performing fellatio on a former boyfriend. Images and taunts spread quickly as the video went viral and commentary about Amber's agency, privacy and sexuality sparked controversy across the interwebs. There was slut-shaming, blaming, and judgment of Amber and her family (especially her mother) with little mention of the three boys involved (the boy receiving oral sex, the boy recording it on his phone, and a third who watched in the background). In my gender class we discussed …Read more »
Category Archives: Body
Unbreakable or The Problem with Praising Blackgirl Strength
Time for the Supremes: Hobby Lobby and Your Boss in Your Bedroom
Sometime between now and July 4th, the Supreme Court is set to rule on two cases that will affect our access to birth control, Sebelius v. Hobby Lobby Stores, Inc. and Conestoga Wood Specialties v. Sebelius. In both these cases for-profit companies are using the Religious Freedom Restoration Act (RFRA) to challenge the Affordable Care Act's (ACA) guarantee that health insurance plans include coverage of contraceptives. Since the ACA policy went into effect, 24 million more prescriptions for oral contraceptives were filled with no co-pay in 2013 than in 2012 and has saved women $483 million in out-of-pocket costs for …Read more »
Dear Gabby
Dear Gabby, Hey, girl! It's me, Crunkadelic. I've been a fan for a long time, but I just wanted to drop you a line and send you a bit of love. Things seem to be going really well for you, but I see that you've experienced a fair bit of shade this past weekend for your outfit at the Golden Globes. Well, it's a truth universally acknowledged that haters gonna hate. Folks were up in arms about your cream colored ensemble. Some said it wasn't flattering and, of course, there were the comments on your weight that varied from …Read more »
De-Tangling Racism: On White Women and Black Hair
Pictures from a new exhibit by photographer Endia Beal called "Can I Touch It?" showcase several white women, all corporate execs, who agreed to get a "Black hairstyle" and then have their portrait taken. Apparently, this very quotidian fixation with Black women's bodies and Black women's hair is now the stuff of art exhibits. This project started when Beal began permitting many of her white corporate colleagues to touch her big red 'fro, to pull it even, while she photographed them doing it. Over the summer, a friend and I happened upon the "You Can Touch My Hair" exhibit that …Read more »
Somebody, Anybody? It's Hard Out Here for a Sista
Trigger warning: Violent language "Somebody, anybody sing a Black girl song" Ntozake Shange, For Colored Girls Who Considered Suicide When the Rainbow was Enuf Being a Black woman or girl in the United States has never been easy. That much seems clear. We are Black, so we're not Latina enough. And we are certainly not beauty queens. We are not perfect victims. We get what we deserve. We are trans* so we're not "woman enough." Violence and imprisonment are par …Read more »
To Rachel Jeantel, With Love
If you've been following the George Zimmerman Trial, the name Rachel Jeantel probably rings a bell. Rachel is 19 years old and was one of the last people to speak with Trayvon Martin before his murder. Brought on as a witness for the prosecution, this brave young person has been ridiculed in the mainstream media and social media for her size, her complexion, her speech, and her mannerisms in ways that betray how unsafe, and yet how necessary, it is for a Black woman to unapologetically speak truth to power. Rachel has been fierce and steadfast through it all. We …Read more »
Atlanta Harm Reduction: Prevention as the First Response
Dear CFC Community, There are some places where people are warned never to go, known for violence, drug traffic, and poverty. For those who have not grown up in these environments we are taught to fear and/or condemn people who live there. This is not true of everyone. There are some s/heroes who "see the faces at the bottom of the well," and offer a rope AND a bucket of food and water. Atlanta Harm Reduction Coalition (AHRC) is the rescue organization where prevention is key and care is unconditional. This week the CFC will spotlight AHRC because they need …Read more »
Not that Kind of Dr.
She has a substance abuse issue, she has anxiety disorder, she had an abortion during the semester (did not tell parents), she experienced sexual abuse by older female family members, she experienced being homeless (on her on) before coming to college, she is escaping a dangerous neighborhood and has lost several friends to gun violence, she has been on anti-depressant medication, she experienced physical abuse by her father, she is having major financial trouble, he is struggling and caring for his mother, he has gone without meals and shelter during college, she has struggled with peers pressuring her about weight, …Read more »
Like Riding a Bike? Dry Spell Dilemmas
I have spent this Valentine's Day season wrapped in the loving embrace of feminist friends and family who have expressed their care and affection through thoughtful cards, shared meals, and copious amounts of cocktails. I have been reminded numerous times how bootleg a holiday is that celebrates heterosexual coupledom at the expense of all other kinds of love, and I have felt blessed to be reminded of all the other kinds of love and care I experience routinely. But can I talk about how sometimes a sister just wants to get laid? I mention this not because it goes …Read more »
A Crunk Take on the Latest Anti-Choice Legislation
Check out CFC member Eesha on GRITtv. She's dropping knowledge on some of the latest anti-choice tactics. [vodpod id=ExternalVideo.935215&w=425&h=350&fv=] more about "A Crunk Take on the Latest Anti-Choic…", posted with vodpod Source
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A blog by Bryn Keller about simplicity - in software design, and in life
As I wrote in my previous post, I recently started working on a Mac. This is a collection of my notes on the problems and surprises I ran into. Maybe it will be useful for you, too.Read more
I recently switched to a MacBook Pro. I have customers that use Linux and Mac, and I wanted to work in a similar environment. Also recently (a few months before the MacBook) I started working with C++ again after a long hiatus.
I had thought that the Mac, being a Unix, would be relatively close to Linux, and that things I was building for Linux would be much more likely to work there than on Windows. That might still be true, but it turns out that there are several things on Mac that are not obvious, and seriously complicate native code development compared with Linux. These are my notes on those differences and how to deal with them. Hopefully, it may be useful for other migrants to Mac as well.Read more
Recently there's been an outpouring of useful resources folks have found for learning Homotopy Type Theory (aka HoTT). These have come mainly from the HoTT Cafe Google Group.
The main resource is of course, the book, but these videos and other resources seem useful enough that I want a consolidated list of them for myself. So I thought maybe you might, too.Read more
WordPress was nice for some time. There were lots of nice themes to choose from, installation was easy, things mostly worked. However, the need to keep updating it with security patches, and the need to keep sifting through comment spam, became tiresome.
I always wish I had time to work on something in Haskell, so I decided to put the need for a new blog platform together with that: I've switched to Hakyll, at least for now.Read more
…or you can find more in the archives.


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WAM 655 Spotted dolphin (Stenella frontalis)
The UNCW stranding team received a call from a Bald Head Island about a dead dolphin in the surf on November 11, 2010. The fresh, robust carcass of an adult male spotted dolphin was located and transported back to UNCW to be necropsied. Adhesion of both lungs to the rib cage, scarring of the heart, active lymph nodes, and possible bruising of the brain were all noted. The most significant finding was severe abdominal peritonitis, which was a likely contributor to the death of the animal.


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Fall 2010 Workshops
All workshops are in room 7324 of the Sewell Social Science Building at 3:45 p.m. unless otherwise noted.
September 6 - 10
- Tuesday, Sept. 7
Organizational meeting
- Thursday, Sept. 9
JAMES FEYRER, Dartmouth
"Distance, Trade, and Income -- The 1967 to 1975 Closing of the Suez Canal as a Natural Experiment" pdf
- Friday, Sept. 10
AKIHIKO MATSUI, University of Tokyo
"A Social Foundation of Nash Bargaining Solution With Endogenous Bargaining Protocols" with In-Koo Cho. pdf


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The studio projects she turned down didn't "touch my heart," she says. "I never had an aversion to doing something commercial. The question for me always was, 'Can I offer it anything?' If I can't, what's the point?" She gravitated instead to independent film, and in 1990 she was cast opposite Sean Penn, then newly divorced from Madonna, in the gangland drama State of Grace. A month after their wedding in 1996, Wright Penn was carjacked outside the couple's L.A. home with her son and daughter, then ages five and three, in the backseat. She calmly (and successfully) negotiated with the thieves to release the children before they took the car, but deeply traumatized by the incident, the family moved to Marin County, north of San Francisco.
For Wright Penn, the highest priority in those years was raising her children. She limited her roles to films that shot during the summer or didn't require her to be away for more than 10 days during the school year. She says, convincingly, that she doesn't wish she'd agreed to more films. "Everything I would have wanted to do had already been done by Meryl Streep," she says. "Sophie's Choice. Kramer vs. Kramer. Silkwood. Done."
Now, after years of making choices based on what she didn't want, Wright Penn is ready to be driven by what she does want: "Joy. Decisiveness. Travel." Offscreen, she has become an advocate for The Greatest Silence, a documentary about violence against women in the Congo, and she's working with the EcoMom Alliance to raise money to aid women and children in that country. Soon she plans to return to L.A., where her daughter will be attending film school and where her brother and other family members live. To bolster her confidence, she's been working with the renowned stage director J Ranelli. Despite her talent, Wright Penn says she feels insecure because she never attended college or had formal training to be an actor. "I have no foundation other than instinct," she says. "If I had to sail a boat, I would figure it out. That's kind of what I've felt like as an actress."
Wright Penn's fans in the industry say she possesses qualities that can't be taught: perfect mimicry and the ability to disappear into a role. "I have this whole theory on her," says writer/director Erin Dignam, who has worked with the actress on a number of projects, including Loved. "She's extremely intelligent, and she's not intellectual: It's a great combination for an actress who has to inhabit all these people who think in different ways. She really embraces the words in an egoless way." Dignam also cites Sean Penn as an admirer of Robin's work. "He told me early on that she was much more the natural actor than him," she says.
After years of playing tormented women, Wright Penn is now shopping for a comedy that will display the funny side that her friends know well. She has a wicked, self-deprecating wit, they say, and a perfect sense of timing. "If she can get a comedy role, people are going to be shocked," Dignam says. "She could just explode." Wright Penn also hopes to direct and produce, and she is in discussions about a Broadway play. "If you don't have passion for things, you don't get up in the morning," she says. Whatever direction she chooses, this much is clear: Robin Wright Penn will deliver an uncompromising performance.
Karen Breslau has profiled Jodie Foster and Maria Shriver for MORE.
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The multi-disciplinary team at GSI specializes in the older-adult market. We work with clients to assess consumer demand, position new and existing product lines, and develop strategies and programs for successful implementation. Our professional backgrounds include gerontology, research, administration, planning, design and marketing, and data systems architecture.
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Molecular Motors
Last Updated: January 10, 2008
Important Link: Stunning illustrations of these motors (and other features and processes within the cell) can be seen in the 8-minute animated video The Inner Life of a Cell, available on Studio Daily.
Hume vs. Paley: These "Motors" Settle the Debate, By Dr. Fazale Rana and Micah Lott
* Note: The sources quoted below attribute the details of these scientific discoveries to naturalistic evolution.
"Organisms, from human beings to bacteria, move to adapt to changes in their environments, navigating toward food and away from danger. Cells, themselves, are not static but are bustling assemblies of moving proteins, nucleic acids, and organelles (Figure 34.1). Remarkably, the fundamental biochemical mechanisms that produce contractions in our muscles are the same as those that propel organelles along defined paths inside cells. In fact, many of the proteins that play key roles in converting chemical energy in the form of ATP into kinetic energy, the energy of motion, are members of the same protein family, the P-loop NTPases. These molecular motors are homologous to proteins that we have encountered in other contexts, including the G proteins in protein synthesis, signaling, and other processes. Once again we see the economy of evolution in adapting an existing protein to perform new functions.
Molecular motors operate by small increments, converting changes in protein conformation into directed motion. Orderly motion across distances requires a track that steers the motion of the motor assembly. Indeed, we have previously encountered a class of molecular motors that utilize mechanisms that we will examine herenamely, the helicases that move along DNA and RNA tracks (Section 28.1.7). The proteins on which we will focus in this chapter move along actin and microtubules protein filaments composed of repeating identical subunits. The motor proteins cycle between forms having high or low affinity for the filament tracks in response to ATP binding and hydrolysis, enabling a bind, pull, and release mechanism that generates motion.
We will also consider a completely different strategy for generating motion, one used by bacteria such as E. coli. A set of flagella act as propellers, rotated by a motor in the bacterial cell membrane. This rotary motor is driven by a proton gradient across the membrane, rather than by ATP hydrolysis. The mechanism for coupling the proton gradient to rotatory motion is analogous to that used by the F0 subunit of ATP synthase (Section 18.4.2). Thus, both of the major modes for storing biochemical energy namely, ATP and ion gradients have been harnessed by evolution to drive organized molecular motion." (34. Molecular Motors)."
Molecular motors cooperate in moving cellular cargo, study shows
Functional coordination of intraflagellar transport motors
Nature 436, 583-587 (28 July 2005) | doi: 10.1038/nature03818
Functional coordination of intraflagellar transport motors
Guangshuo Ou1, Oliver E. Blacque2, Joshua J. Snow1, Michel R. Leroux2 and Jonathan M. Scholey1
"Top of pageCilia have diverse roles in motility and sensory reception, and defects in cilia function contribute to ciliary diseases such as Bardet−Biedl syndrome (BBS). Intraflagellar transport (IFT) motors assemble and maintain cilia by transporting ciliary precursors, bound to protein complexes called IFT particles, from the base of the cilium to their site of incorporation at the distal tip1, 2, 3. In Caenorhabditis elegans, this is accomplished by two IFT motors, kinesin-II and osmotic avoidance defective (OSM)-3 kinesin, which cooperate to form two sequential anterograde IFT pathways that build distinct parts of cilia4, 5, 6, 7. By observing the movement of fluorescent IFT motors and IFT particles along the cilia of numerous ciliary mutants, we identified three genes whose protein products mediate the functional coordination of these motors. The BBS proteins BBS-7 and BBS-8 are required to stabilize complexes of IFT particles containing both of the IFT motors, because IFT particles in bbs-7 and bbs-8 mutants break down into two subcomplexes, IFT-A and IFT-B, which are moved separately by kinesin-II and OSM-3 kinesin, respectively. A conserved ciliary protein, DYF-1, is specifically required for OSM-3 kinesin to dock onto and move IFT particles, because OSM-3 kinesin is inactive and intact IFT particles are moved by kinesin-II alone in dyf-1 mutants. These findings implicate BBS ciliary disease proteins and an OSM-3 kinesin activator in the formation of two IFT pathways that build functional cilia.
Top of page Center for Genetics and Development, Section of Molecular and Cellular Biology, University of California, Davis, California 95616, USA
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada
Correspondence to: Jonathan M. Scholey1 Correspondence and requests for materials should be addressed to J.M.S. (Email: firstname.lastname@example.com).
Received 16 April 2005; Accepted 9 May 2005"
Molecular engineering of a backwards-moving myosin motor
Nature 427, 558-561 (5 February 2004)
"Georgios Tsiavaliaris1,2, Setsuko Fujita-Becker2 and Dietmar J. Manstein1,2
Top of pageAll members of the diverse myosin superfamily have a highly conserved globular motor domain that contains the actin- and nucleotide-binding sites and produces force and movement1, 2. The light-chain-binding domain connects the motor domain to a variety of functionally specialized tail domains and amplifies small structural changes in the motor domain through rotation of a lever arm 3, 4. Myosins move on polarized actin filaments either forwards to the barbed (+ ) or backwards to the pointed (- ) end 5, 6. Here, we describe the engineering of an artificial backwards-moving myosin from three pre-existing molecular building blocks. These blocks are: a forward-moving class I myosin motor domain, a directional inverter formed by a four-helix bundle segment of human guanylate-binding protein-1 and an artificial lever arm formed by two -actinin repeats. Our results prove that reverse-direction movement of myosins can be achieved simply by rotating the direction of the lever arm 180°.
Top of pageInstitut für Biophysikalische Chemie, Medizinische Hochschule Hannover, OE 4350, Carl-Neuberg-Strasse 1, D-30623 Hannover, Germany
Abteilung Biophysik, Max-Planck-Institut für Medizinische Forschung, Jahnstrasse 29, D-69120 Heidelberg, Germany
Correspondence to: Dietmar J. Manstein1,2 Correspondence and requests for materials should be addressed to D.J.M. (Email: firstname.lastname@example.com).
Received 3 September 2003; Accepted 19 December 2003"
Marathon of Nano-Sprinters
November 14th, 2005
"Max Planck scientists show that the cooperation of a small number of molecular motors yields cargo transport over large distances
Processive bio-molecular motors, which move actively along cytoskeletal filaments, drive the cargo traffic in cells and in biomimetic systems. A single motor molecule is sufficient for continuous transport of cargoes such as vesicles or latex beads over a few micrometers. To achieve transport over larger distances, several motor mole-cules have to cooperate. Scientists from the Max Planck Institute of Colloids and In-terfaces in Potsdam have now developed a new theory that only seven or eight mo-tor molecules are sufficient for directed transport over centimeters or even meters. They also show that an applied load force, which is shared by the pulling motors, strongly reduces the cargo velocity and leads to a highly nonlinear force-velocity relationship (PNAS, Advanced Online Publication, November 14-18, 2005).
Image: Different bound states of a cargo particle, with several molecular motors which move along a filament. Each motor can unbind from and rebind to the filament, which implies that the number of motors that actually pull the cargo varies with time.
Image: Max Planck Institute of Colloids and Interfaces
Molecular motors are nano-tractors for all kinds of cargo within the cells of living beings. They move in a stepwise manner along filaments of the cytoskeleton, consuming energy provided by the hydrolysis of ATP, which can be considered the fuel of the cell. Kinesin and dynein motors move along microtubules and myosins move along actin filaments. The step sizes of these motors are of the order of 10 nm. By stepping in a directed fashion along filaments, the motors pull cargo particles which are much larger than the mo-tors themselves. In addition to their importance for the functioning of cells, molecular motors have many possible applications as biomimetic transport systems and are likely to become a key component in the emerging bio-nanotechnology.
Active transport driven by molecular motors is particularly important for nerve cells, or neurons. These cells have extended compartments, axons, which connect the cell body with the synapse, where the nerve signals are transmitted from one neuron to another. The length of axons is in the centimeter or even meter range; examples of relatively long axons are those that connect our spinal cord with the tips of our fingers and toes. Within such an axon, microtubules provide the tracks along which molecular motors transport their cargo, such as vesicles filled with neurotransmitters.
During the last decade, our knowledge about molecular motors has increased rapidly. This was mainly due to the development of powerful single molecule experiments and biomimetic model systems which permit the study of molecular motors outside cells in a systematic fashion. One example is the bead assay, where filaments are immobilized on a surface. Molecular motors pull latex beads along these filaments, and the movement of the beads is observed under the microscope.
One important result of these experiments is that molecular motors, unlike railways or cars, have a strong tendency to fall off their track and diffuse away into the surrounding aqueous solution. This is a direct consequence of their nanoscale size which makes them rather susceptible to thermal noise. Thus, a single molecular motor can only 'grab' onto the filament for a relatively short time, on the order of one second. During this time, a single motor covers about one micrometer, which represents only a tiny fraction, about 1/10000, of the long transport distances for cargo particles in axons. In other words, a single motor behaves much like a sprinter, whereas the whole cargo performs a marathon.
Scientists of the Max Planck Institute of Colloids and Interfaces in Potsdam have now provided a simple solution to this puzzle. If the cargo is pulled by several motors as shown in Fig.1, any motor that unbinds from the filament will stay close to that filament as long as the cargo and filament are still cross-linked by at least one bound motor. In such a situation, the unbound motor can rebind to the filament and then continue to pull the cargo - in contrast to human sprinters, molecular motors don't get tired.
This mechanism has been derived from a new theoretical model, which distinguishes the different bound states of the cargo particle and describes the transitions between these states. Using this model, the Max Planck scientists have been able to calculate several transport properties, such as the average velocity and the average walking distance of the cargo particle as a function of the maximum number of motors that can pull this par-ticle. For kinesin motors, for example, calculations show that only seven or eight motors are sufficient for the transport over centimeter distances and that a cargo particle pulled by 10 motors has an average walking distance of about 1 meter.
If molecular motors move against an external load force, this force is shared among the pulling motors. One obvious consequence is that the movement of the cargo is slowed down. In addition, the force felt by each pulling motor strongly increases the unbinding probability for such a motor. Furthermore, as more motors unbind, each of the remaining pulling motors has to sustain a larger force, which would mean that their unbinding probability increases even further. This leads to a cascade of unbinding processes and to a strongly nonlinear dependence of the cargo velocity on the external load force. Simi-lar cascade processes are expected in more complex situations, in which the cargo transport is performed by different types of molecular motors.
All transport properties predicted by the new theory can be investigated in experiments using techniques which have been developed for single motors. In fact, preliminary ex-periments at the Max Planck Institute in Potsdam agree with the theoretical predictions. Likewise, the quantitative theory should also be useful in order to design biomimetic transport systems for lab-on-a-chip applications -- in which, for example, molecular mo-tors transport certain molecules to specific reaction sites. Depending on the arrange-ment of the filaments in these systems, varying the travel distance provides a strategy to control either the localization of the reagents to their target sites or, alternatively, their diffusion, which is enhanced by motor-driven active transport."
Purdue biologists clarify how a cellular 'spacecraft' opens its airlock
December 2, 2005
"WEST LAFAYETTE, Ind. – Scientists have a tough time visualizing the tiny hatchways that allow nutrients to pass into our cells, but a group of Purdue University biologists may have found the next best thing: a glimpse into the workings of the "motor" that opens and closes them.
A research team led by Jue Chen has clarified the connection between these minuscule gates – which are called membrane transport proteins – and the steps by which they use a cell's energy to permit or deny materials entry into the interior of the cell from the outside world.
In what the team perceives to be a three-step process, cells feed chemical energy to a tiny machine called an ABC protein, which is the part of the membrane protein that connects it to the interior of the cell. These ABC proteins use the energy to bend the membrane protein into its open and closed positions, allowing the cell both to bring in nutrients and to flush out waste.
"We think we have a better handle on a process fundamental to life in creatures from bacteria to humans," said Chen, who is an assistant professor of biology in Purdue's College of Science. "This is the first time the entire cycle has been visualized, and this could enhance our understanding of how the process of metabolism unfolds."
The team's paper appears in this week's issue of Proceedings of the National Academy of Sciences. Chen's group also includes her Purdue colleagues Gang Lu and James M. Westbrooks, as well as Amy L. Davidson, who recently relocated to Purdue from the Baylor College of Medicine. The team used X-ray crystallography and other advanced imaging techniques to obtain a clear picture of the ABC protein, a method which has only had limited success in revealing secrets of the membrane proteins themselves.
Membrane proteins in cells have been likened to spacecraft airlocks, which ensure that only the astronauts gain entry and no air is lost. Where spacecraft have metal walls, cells have membranes that surround their inner protoplasm, and their airlock proteins are highly complex individual molecules that allow nutrients to enter cells and waste products to leave them.
Of the thousands of membrane proteins that exist, scientists only know the structure of a few dozen. They are of great interest to biologists because, as the regulators of intercellular commerce, they essentially permit metabolism – and, thus, life itself – to continue. However, while most proteins dissolve in water and can be easily crystallized and examined, membrane proteins dissolve only in fatty substances, making it difficult to isolate them for study.
"If we had a better understanding of this class of proteins, we might know more about how our bodies use and transfer energy," Chen said. "It's an unfortunate gap in our knowledge of how living things work. But in this study, we looked at a protein that is a bit of a hybrid: one part of it is fat-soluble, and the other is water-soluble."
Because the entire membrane protein would not submit to crystallization, Chen's team focused their efforts on the ATP-binding cassette proteins, or ABC proteins for short, that connect the membrane proteins with the cell's interior. This portion of the protein is of the more study-friendly, water-soluble variety, and also plays a critical role in cellular commerce: It is the motor that drives a membrane protein's motion.
"We isolated the ABC proteins from an E. coli bacterium, which is a very common research subject," Chen said. "Different as these single-celled organisms are, their ABC proteins are structurally very similar to those in human cells, so studying them could help our knowledge of our own metabolism."
ABC proteins function like tiny tweezers and are powered by ATP, a chemical that animal cells use for energy. When ATP causes the tweezers to squeeze shut, the membrane proteins open to reveal a small cavity that can hold a nutrient or other substance the cell requires from the outside. Once the nutrient is in place, the cell uses water to break down the ATP, signaling the "tweezers" to relax, closing the membrane protein gate and capturing the nutrient. Lastly, the membrane protein releases the nutrient into the cell's interior.
"The ABC protein is like the inner door of the airlock; that's what we were able to see in operation in this study," Chen said. "If you opened both it and the membrane protein simultaneously, nothing would stop the interior of the cell from getting sucked out."
Chen admits that the team is not yet certain that the description of the process is complete, though it does seem compelling based on what science already knows about the workings of membrane proteins.
"We need to look closer at our information and try to find out more," Davidson said. "We will be applying several tests to our data in the near future to determine if our image of these proteins accurately describes their behavior."
Chen said the work might have long-term payoffs in the fight against cancer, though it was too soon to make more than general statements as to how.
"Many cancer cells are resistant to anticancer drugs because the ABC proteins are overabundant and get too good at pumping the drugs out before they can work," she said. "Future therapies might exploit what we are finding out about these proteins' operation. It's too soon to talk about specific therapies, but because there are so many kinds of cancer out there, every piece of knowledge helps."
This research was sponsored in part by the National Institutes of Health and the Pew Charitable Trusts.
Members of Chen's research group are associated with the Purdue Cancer Center. One of just seven National Cancer Institute-designated basic-research facilities in the United States, the center attempts to help cancer patients by identifying new molecular targets and designing future agents and drugs for effectively detecting and treating cancer. The Cancer Center is part of the Oncological Sciences Center in Purdue's Discovery Park.
Writer: Chad Boutin, (765) 494-2081, firstname.lastname@example.com
Sources: Jue Chen, (765) 496-3113, email@example.com
Amy Davidson, (765) 494-5291, firstname.lastname@example.com
Purdue News Service: (765) 494-2096; email@example.com"
Direct observation of steps in rotation of the bacterial flagellar motor
"Nature 437, 916-919 (6 October 2005) | doi: 10.1038/nature04003
Direct observation of steps in rotation of the bacterial flagellar motor
Yoshiyuki Sowa1,5, Alexander D. Rowe2,5, Mark C. Leake2, Toshiharu Yakushi3, Michio Homma3, Akihiko Ishijima1,4 and Richard M. Berry2
Top of page
The bacterial flagellar motor is a rotary molecular machine that rotates the helical filaments that propel many species of swimming bacteria1, 2. The rotor is a set of rings up to 45 nm in diameter in the cytoplasmic membrane3; the stator contains about ten torque-generating units anchored to the cell wall at the perimeter of the rotor4, 5. The free-energy source for the motor is an inward-directed electrochemical gradient of ions across the cytoplasmic membrane, the protonmotive force or sodium-motive force for H+-driven and Na+-driven motors, respectively. Here we demonstrate a stepping motion of a Na+-driven chimaeric flagellar motor in Escherichia coli6 at low sodium-motive force and with controlled expression of a small number of torque-generating units. We observe 26 steps per revolution, which is consistent with the periodicity of the ring of FliG protein, the proposed site of torque generation on the rotor7, 8. Backwards steps despite the absence of the flagellar switching protein CheY indicate a small change in free energy per step, similar to that of a single ion transit.
Top of page
1. Department of Applied Physics, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8603, Japan
2. The Clarendon Laboratory, Department of Physics, Oxford University, Parks Road, Oxford OX1 3PU, UK
3. Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8602, Japan
4. PRESTO, Japan Science and Technology Corporation (JST) 4-1-8, Honmachi, Kawagoe, Saitama 332-0012, Japan
5. *These authors contributed equally to this work
Correspondence to: Richard M. Berry2 Correspondence and requests for materials should be addressed to R.M.B. (Email: firstname.lastname@example.com).
Received 1 April 2005; Accepted 11 July 2005"
Cooperative cargo transport by several molecular motors
( active transport | bionanosystems | load force | run length | walking distance )
Stefan Klumpp and Reinhard Lipowsky *
Max Planck Institute of Colloids and Interfaces, Science Park Golm, 14424 Potsdam, Germany
Edited by David R. Nelson, Harvard University, Cambridge, MA, and approved October 3, 2005 (received for review August 26, 2005)
"The transport of cargo particles that are pulled by several molecular motors in a cooperative manner is studied theoretically in this article. The transport properties depend primarily on the maximal number N of motor molecules that may pull simultaneously on the cargo particle. Because each motor must unbind from the filament after a finite number of steps but can also rebind to it again, the actual number of pulling motors is not constant but varies with time between zero and N. An increase in the maximal number N leads to a strong increase of the average walking distance (or run length) of the cargo particle. If the cargo is pulled by up to N kinesin motors, for example, the walking distance is estimated to be 5N-1/N micrometers, which implies that seven or eight kinesin molecules are sufficient to attain an average walking distance in the centimeter range. If the cargo particle is pulled against an external load force, this force is shared between the motors, which provides a nontrivial motor-motor coupling and a generic mechanism for nonlinear force-velocity relationships. With increasing load force, the probability distribution of the instantaneous velocity is shifted toward smaller values, becomes broader, and develops several peaks. Our theory is consistent with available experimental data and makes quantitative predictions that are accessible to systematic in vitro experiments.
Author contributions: S.K. and R.L. designed research, performed research, and wrote the paper.
Conflict of interest statement: No conflicts declared.
Freely available online through the PNAS open access option.
*To whom correspondence should be addressed.
Reinhard Lipowsky, E-mail: email@example.com
Biological motors sort molecules one by one on a chip
12 May 2006 by M&C
"Researchers from Delft University of Technology's Kavli Institute of Nanoscience have discovered how to use the motors of biological cells in extremely small channels on a chip. Based on this, they built a transport system that uses electrical charges to direct the molecules individually. To demonstrate this, the Delft researchers sorted the individual molecules according to their color. Professor Hess of the University of Florida has called the Delft discovery "the first traffic control system in biomolecular motor nanotechnology". The research findings will be published in Science on May 12.
The biological cell is a complex of many different small protein factories. The necessary transportation of materials within the cell occurs across a network of microtubules: long, tubular-shaped proteins that extend in a star-shaped formation from the nucleus of the cell to the walls of the cell. Molecular bio-motors, such as the enzyme kinesin, can walk in small steps (of 8 nanometers) with a load of material along these microtubule-networks and thus provide transport within the cell.
Fascinated by these biological motors, the researchers at Delft University of Technology's Kavli Institute of Nanoscience are currently exploring the possibility of inserting these kinesin-motors and microtubules in an electrically directed transport system that is made by the researchers using nano-fabrication techniques.
The researchers turned the system around: the kinesin-motors are fastened in large quantities on a surface with their 'feet' up; the microtubules (measuring approximately 1 to 15 micrometers in length) were then transported over the 'carpet' of motors. The microtubules are, as it were, 'crowd surfing' over the sea of small kinesin motors. A particular challenge of the research was to ensure beforehand that the microtubule tubes could be transported in a determined direction and were not dislodged by collisions of the motor carpet.
PhD student Martin van den Heuvel, master student Martijn de Graaff and groupleader Professor Cees Dekker have for the first time achieved to control and address individual microtubules. An important step in this was to allow microtubule-transport to occur in small closed liquid channels. This made it possible to apply a strong electrical field locally at the Y-junction in the channels. Because of this, the electrical force could be exerted on the individual microtubules. The researchers discovered that by using this electrical force they could push the front of the microtubule into the determined direction.
To demonstrate this, the researchers allowed a mixture of green and red fluorescent microtubules to arrive at a Y-junction. By changing the direction of the electrical force, depending on the color of the microtubule, the Delft researchers were able to collect the green and red microtubules in different reservoirs.
With their approach to the nano-channels, the researchers killed two birds with one stone. In addition to the possibility of steering individual microtubules, they were able to prevent the microtubules from derailing from their tracks. Incidentally, the Delft researchers discovered that their work contained a third interesting aspect. The closed channels offered the possibility to observe the electrical transport of freely suspended microtubules, thus proving that the speed of the microtubules under an external electrical field is largely dependent on the orientation of the cylinder-shaped molecules. This was the first time that this orientation-dependency of the electrophoretic mobility was observed.
In an accompanying Perspective article in Science, Professor Hess of the University of Florida wrote that the Delft researchers had developed the first traffic control system in biomolecular motor nanotechnology.
For additional information:
* Cees Dekker
E: firstname.lastname@example.com.
* Frank Nuijens, science information officer,
E: email@example.com."
Myosin-V is a mechanical ratchet
"( backward movement | molecular motor | optical tweezers | asymmetry | kinesin )
J. Christof M. Gebhardt, Anabel E.-M. Clemen, Johann Jaud, and Matthias Rief *
Physics Department E22, Technical University of Munich, James-Franck-Strasse, D-85748 Garching, Germany
Edited by Ronald D. Vale, University of California, San Francisco, CA, and approved April 6, 2006 (received for review November 24, 2005)
Myosin-V is a linear molecular motor that hydrolyzes ATP to move processively toward the plus end of actin filaments. Motion of this motor under low forces has been studied recently in various single-molecule assays. In this paper we show that myosin-V reacts to high forces as a mechanical ratchet. High backward loads can induce rapid and processive backward steps along the actin filament. This motion is completely independent of ATP binding and hydrolysis. In contrast, forward forces cannot induce ATP-independent forward steps. We can explain this pronounced mechanical asymmetry by a model in which the strength of actin binding of a motor head is modulated by the lever arm conformation. Knowledge of the complete force-velocity dependence of molecular motors is important to understand their function in the cellular environment.
Author contributions: M.R., A.E.-M.C., and J.J. designed research; J.C.M.G. performed research; J.C.M.G. analyzed data; and M.R. and J.C.M.G. wrote the paper.
Conflict of interest statement: No conflicts declared.
*To whom correspondence should be addressed.
Matthias Rief, E-mail: email@example.com
On the hand-over-hand mechanism of kinesin
"Qiang Shao, and Yi Qin Gao
Department of Chemistry, Texas A&M University, College Station, TX 77843
Communicated by Rudolph A. Marcus, California Institute of Technology, Pasadena, CA, April 6, 2006 (received for review December 8, 2005)
We present here a simple theoretical model for conventional kinesin. The model reproduces the hand-over-hand mechanism for kinesin walking to the plus end of a microtubule. A large hindering force induces kinesin to walk slowly to the minus end, again by a hand-over-hand mechanism. Good agreement is obtained between the calculated and experimental results on the external force dependence of the walking speed, the forward/backward step ratio, and dwell times for both forward and backward steps. The model predicts that both forward and backward motions of kinesin take place at the same chemical state of the motor heads, with the front head being occupied by an ATP (or ADP,Pi) and the rear being occupied by an ADP. The direction of motion is a result of the competition between the power stroke produced by the front head and the external load. The other predictions include the external force dependence of the chemomechanical coupling ratio (e.g., the stepping distance/ATP ratio) and the walking speed of kinesin at force ranges that have not been tested by experiments. The model predicts that the chemomechanical coupling remains tight in a large force range. However, when the external force is very large (e.g., {approx}18 pN), kinesin slides in an inchworm fashion, and the translocation of kinesin becomes loosely coupled to ATP turnovers."
Researchers probe the machinery of cellular protein factories
September 13, 2006
Contact: Tim Stephens (831) 459-2495; email@example.com
"Proteins of all sizes and shapes do most of the work in living cells, and the DNA sequences in genes spell out the instructions for making those proteins. The crucial job of reading the genetic instructions and synthesizing the specified proteins is carried out by ribosomes, tiny protein factories humming away inside the cells of all living things.
Harry Noller, the Sinsheimer Professor of Molecular Biology at the University of California, Santa Cruz, has been studying the ribosome for more than 30 years. His main goal is to understand how the ribosome works and how it evolved, but there are also practical reasons to pursue this research. Many of the most effective antibiotics work by targeting bacterial ribosomes, and findings by Noller and others have led to the development of novel antibiotics that hold promise for use against germs that have developed resistance to current drugs. Drug-resistant staph infections, for example, are a serious problem in hospitals.
Noller's laboratory achieved breakthroughs in 1999 and 2001, producing the first high-resolution images of the molecular structure of a complete ribosome. Now, his team has made another major advance with an even higher-resolution image that enables them to construct an atom-by-atom model of the ribosome.
The new picture shows details never seen before and suggests how certain parts of the ribosome move during protein synthesis. A paper describing the new findings will be published in the September 22 issue of the journal Cell and is currently available online.
"We can now explain a lot of the results from biochemical and genetic studies carried out over the past several decades," Noller said. "This structure gives us another frame in the movie that will eventually show us the whole process of the ribosome in action."
The ribosome is a complex molecular machine made up of proteins and RNA molecules. The bacterial ribosomes studied in Noller's lab (obtained from the bacterium Thermus thermophilus) are made up of three different RNA molecules and more than 50 different proteins.
Noller proposed in the early 1970s that the RNA component was responsible for carrying out the ribosome's key functions. At the time it was considered a "crackpot idea," but subsequent findings by Noller and others proved he was right.
"It was a completely heterodox view when we first proposed it, but it is now the accepted paradigm," said Noller, who directs the Center for Molecular Biology of RNA at UCSC. "Our latest results confirm that the ribosomal RNA is really the key to ribosome function. The proteins are also involved, but more peripherally," he said.
To make a new protein, the genetic instructions are first copied from the DNA sequence of the gene into a messenger RNA molecule. The ribosome then reads the genetic code from the messenger RNA and translates it into the structure of a protein.
Proteins are linear molecules that fold into complex three-dimensional shapes to carry out their functions. They are made from amino acid building blocks, and the sequence of amino acids determines the protein's structure. Amino acids are carried to the ribosome by transfer RNA molecules. On the ribosome, the transfer RNAs recognize specific sequences of genetic code on the messenger RNA, and the amino acids are then joined together in the proper order.
The images from Noller's group not only show the complete ribosome, they show it with a messenger RNA and two full-length transfer RNAs bound to it. "We can now see the details of most of the interactions between the ribosome, the messenger RNA, and the transfer RNAs," Noller said.
The results provide a snapshot of the molecular machine in action. By comparing his images with those obtained by other groups that have caught the ribosome or its subunits in different positions, Noller is finding clues to the molecular motions with which the ribosome does its work.
"Our next goal is to trap the ribosome in other functional states to get more frames of the movie," he said.
The authors of the paper, in addition to Noller, are postdoctoral researcher Andrei Korostelev, senior scientist Sergei Trakhanov, and postdoctoral researcher Martin Laurberg. The researchers used a technique called x-ray crystallography, which involves growing crystals of purified ribosomes, shining a focused beam of x-rays through the crystals, and analyzing the resulting diffraction pattern. Trakhanov prepared the crystals and Korostelev and Laurberg performed the crystallography and solved the structure, Noller said.
This research was supported by grants from the National Institutes of Health and the Agouron Institute."
Molecular Motors and Brakes Work Together in Cells
January 30, 2007
"Interaction sheds light on how cells inner skeleton is organized
Researchers at the University of Pennsylvania School of Medicine have discovered that microtubules – components responsible for shape, movement, and replication within cells – use proteins that act as molecular motors and brakes to organize into their correct structure. If microtubules are not formed properly such basic functions as cell division and transport can go wrong, which may have implications in such disease processes as cancer and dementia. The study, published in the January issue of Cell, is featured on the cover of that issue.
"Up until now motors and brakes were studied separately from microtubules," says senior author Phong Tran, PhD, Assistant Professor of Cell and Developmental Biology. "This study lets us have a more complete picture."
Microtubules are structures that help give shape to many types of cells, form the spindle – a structure important in cell division – and act as a railroad, of sorts, upon which molecular motors move protein packages for waste removal and nerve transmission.
In the Cell study, the investigators, working with fission yeast cells, showed that stable end-to-end arrays of microtubules can be achieved by a balance between the sliding by a molecular motor called klp2p and the braking of a microtubule-associated protein (MAP) called ase1p. Specifically, they showed that a preexisting "mother" microtubule acts as a platform on which a new microtubule can be formed. The new "daughter" microtubule grows and moves along the mother microtubule. In time, the daughter grows beyond the end of the mother to ultimately produce two microtubules, connected by the cross-linking MAP ase1p.
"Imagine that the daughter microtubule is a short train on the track of the mother microtubule," explains Tran. "The molecular motor is the train's engine, but the problem is that the cargo – the molecular brakes – gets longer, slowing down the daughter train. But when the train gets to the end of the track it remains attached to the end of mother microtubule. At the tail end, it stops moving and that defines the region of overlap. Our work shows that the cell can make microtubule structures of defined lengths stable by coordinating the sliding of the motors and the slowing of the brakes."
If microtubule-based structures are not formed properly because of failures in brakes or motors, such basic functions as cell division and cell transport can go awry, with such diseases as cancer and dementia possibly resulting. "For the first time we have shown how MAPs and motors work together in a mechanistic way," says Tran. "This is important and it will make other people who study microtubules rethink how they study the cell."


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Download UUT Forms in Adobe PDF Format:
This Section imposes a tax upon every person using electricity, water, gas, or telephone
service in the City. The taxes imposed by this Section will be at the rate of six (6) percent
of all charges made for such services. The maximum annual tax payable by any service user for
an individual service will be one thousand five-hundred dollars ($1,500.00) for each twelve (12)
month period commencing January 1 and ending December 31 of the same calendar year. The tax will
be collected from the service user by the person providing the service and remitted to the Finance
Director on or before the last day of the following month.
Tax Maximum:
The annual tax payable by any service user for an individual service is one-thousand-five-hundred
dollars ($1,500.00) for each twelve (12) month period. An "individual service" refers to each
individual utility location with a separate meter and separate billing. The regulation of this
maximum is the responsibility of the service supplier.
You may elect to prepay the utility tax maximum if you believe you will exceed the cap. The city
would then notify each utility company that payment has been made and they will cease collection of
the tax for the following year. In order to allow utility companies enough time to adjust their billing,
prepayments should be made by December 15th.
Refer to the City
of Modesto Municipal Code:
Chapter 2 TAXATION
Article 9. Utility Users' Tax
8-2.905 Electricity User Tax
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Most of the time, when you think of benches, you imagine
those in a baseball dugout, or in a park. However, benches are so much more versatile than
A bench can add personality and much needed seating to
any living area, and because they aren't as heavy as a love seat or a couch, they are easier to
move around. Indoor bench cushions are a way to add style and comfort to that
Many people put benches in the kitchen, near a bay
window or in a breakfast nook. An indoor bench with a
cushion provides instant window seating, with no remodeling required.
benches with cushions provide a relaxing place to enjoy a cup of coffee and read the morning paper before you
rush off to work, and they provide the extra seating you need when you're entertaining a crowd. Dining tables with benches are also gaining in
popularity in many homes.
There's no better place to put an indoor bench with a cushion than your
entryway or your foyer. This is the first area most people see when they enter your home, so why not make it
warm and inviting? Plus, people will be more likely to stop and take off their muddy shoes if there's a
comfortable place to sit. A teak bench would work especially well here.
Many also bring a bench into their bedroom, placing it at the foot of
the bed. Indoor bench cushions to match your drapes will add a stylish touch to your room, and a wrought iron
bench would look great in front of a vanity or beside a garden tub. Indoor benches with cushions can be
especially useful in homes where the elderly live.
In preparing to order bench cushions, the video above provides
tips in preparing measurements.
Sunrooms and other places can be made more inviting with cushioned
indoor benches. Use them in place of a traditional sofa and love seat
to make your space seem more open and airy. Wooden benches can lend a
more down-home look to your front porch. Benches can be so much more
than just extra seating, they can be a comforting place for family and friends to
benches and cushions can be used in any
room in your home, and you can re-upholster the cushions to match any décor, or go out and buy new indoor bench
cushions. Whether the look you are going for is fun, light and airy, or elegant and sophisticated, there is an
indoor bench and cushion set that will be a perfect fit for your home.
We've highlighted a few pictures of different indoor bench cushion
options on this site for your convenience.
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Cushions. All Rights
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Weeds (2005–2012)
Episode List
Season 8
1 Jul. 2012Messy
The victim is rushed to the hospital after being shot, with the family following close behind. They grapple with the tragedy, and hypothesize on the shooter's identity.
8 Jul. 2012A Beam of Sunshine
Andy and Jill are interrupted by Jill's husband. Silas maintains an unconventional affair with Kiku, while Shane makes new friends. Meanwhile, Doug and Whit are pitched new business ideas.
15 Jul. 2012See Blue and Smell Cheese and Die
Nancy and Silas chase after Shane, who has discovered the identity of the shooter. Andy attempts to bond with Jill's daughters. Meanwhile, Doug and Whit come up with a new plan.
22 Jul. 2012Only Judy Can Judge
Nancy plans a family dinner. Andy and Jill agree to watch over Stevie throughout the day. Meanwhile, Silas befriends a local pot grower while Shane invites Angela, his classmate, over to their family dinner. Back at the house, Doug makes enemies with the neighbor's dog.
29 Jul. 2012Red in Tooth and Claw
Nancy enrolls Stevie in soccer and, after seeing how happy he is, makes a life-altering decision. Jill becomes addicted to extreme couponing while Andy skates into the arms of another woman. Later, Silas learns a hard lesson and Shane takes it to the next level with Angela.
5 Aug. 2012Allosaurus Crush Castle
Nancy is ready to get her life back on track, and starts anew with a job search. Jill drops a bomb on Andy and Doug. Silas must track down the location of his stolen plants. Shane uses his superior intellect to make some extra cash at the police academy.
12 Aug. 2012Unfreeze
Nancy and Silas start their new, legit and highly competitive jobs. After graduating from the police academy, Shane gets an assignment. Andy seeks employment at the local Jewish temple. Meanwhile, Doug's reckless spending comes to a complete halt.
19 Aug. 2012Five Miles From Yetzer Hara
Nancy gets promoted and takes on new responsibilities. Silas and Shane both start their new jobs. Doug recruits homeless people in an attempt to legitimize his scam charity, while Jill breaks some upsetting news to Andy.
26 Aug. 2012Saplings
Nancy and Silas are approached with a new job opportunity. Shane does something reckless to impress Angela. A dejected Andy offers love advice to Rabbi Dave and his students. Doug tries to keep his fake charity -- and restless homeless group -- from disbanding.
2 Sep. 2012Threshold
Nancy meets Rabbi Dave's friends during an awkward Shabbos dinner. Andy brings home a very special guest to meet the family. Silas prepares for his new business venture. Shane and Angela attempt to retrieve some stolen property. Meanwhile, Doug's homeless group threatens to leave him if he doesn't begin catering to their needs.
9 Sep. 2012God Willing and the Creek Don't Rise
Nancy, Andy, and Silas take a trip. Shane is busted for stealing property off the impound lot. Doug gives up on his charity and decides to pursue a bigger, more lucrative scheme.
16 Sep. 2012It's Time, Part 1
It's Part 1 of the WEEDS series finale. The Botwins (and Doug!) are at a crossroads. How will it all end?
16 Sep. 2012It's Time, Part 2
It's Part 2 of the WEEDS series finale. The Botwins (and Doug!) are at a crossroads. How will it all end?
« Season 7 | Season 8


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In search of a drug-free Ohio
State Rep. Robert F. Hagan knows that his latest proposal has as much chance of passing the General Assembly as Gov. John Kasich has of being invited by AFSCME to lead a Labor Day parade.
Some legislators are playing to their constituencies with legislation that would require drug testing for anyone receiving public assistance or unemplyment benefits from the state. Hagan is playing to his with a what's-good-for-the-goose-is-good-for-the-gander counterproposal.
Hagan says that he won't vote for state Sen. Tim Grendell's legislation aimed at mandatory drug testing applicants for benefits at Job and Family Services unless legislators and other elected officials, including Supreme Court justices, are also subject to mandatory drug and alcohol testing.
The Hagan and Grendell proposals each raise questions of constitutionality — and not only in requiring people to pay for their own tests up front. But those millions of people who are subject to entry-level or mandatory random testing to get or keep their jobs, should be inclined to support both Hagan, D-Youngstown, and Grendell, R-Chesterton.
All Hagan and Grendell have to do is demonstrate that the law would be constitutional, fair and cost-effective.
If people receiving welfare, state or federal should be drug tested to protect the tax payer then priorities should be set. We should get the most bang for our buck. The oil companies like Chevron who avoid paying taxes altogether and in fact receive billions in tax credits payed for by the middle class should be at the top of the list due to the corporate welfare they and others receive. I've worked on projects for Chevron and every construction worker must pass a drug test before working on a project.
I've had to pass drug test to work on many other construction projects. I don't see a problem with people receiving welfare or the legislators passing the laws having to pass the same test but those companies on corporate welfare should be at the top of the list.
Dreamers can always dream!
To me its about more then cost saving in welfare programs its about fighting the destruction of our way of life by drugs.
I have seen drugs turn good women in to prostitute that sell there body. Next time you see a cop ask him if drugs are the major driver of prostitution? I have seen it turn men that i have known all my life that would never steal or lie in to someone that i would shoot on site if they came to my front door.
There are those that say look at Florida only 2% failed isnt that enough what is a percentage we worry about 5, 10 or 50 how bad does it have to get before we care. I though our nations drug problem was bad enough already but i guess not.
Well, to be honest, the urine test is only really going to detect marijuana users, the rest of the drugs all are quickly metabolized and won't show up in a urine sample after 2-3 days. So those spending welfare checks on more expensive addictions such as heroin, crack, and meth are going to be able to get off more easily than those who use marijuana (which can be detected in urine up to a month after using) which doesn't cost all that much to buy and is so much gentler and less harmful than other drugs, and also has therapeutic benefits. So, I see this proposal as sort of flawed. I do agree that those receiving government aid should not buy any form of drugs, but this is only going to punish the least we need to worry about of the offenders.
Drugs have been around for centuries and they aren't going to just disappear anytime soon.
Preliminary results from Florida show that it is costing the state more to reimburse for drug tests for those that pass, than is recovered by not paying benefits to those that fail. It will be interesting to see how that plays out in the long term.
I have decided Mexico cannot solve their internal drug cartel issues, so we should concentrate our efforts to using CIA drones flying over Mexican cartel bosses, just as we did with Al Qaida leaders and supporters. Mexican cartel bosses are worse terrorists against our country than any other group in our history and we need to begin putting pressure on them.


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After apologizing to shareholders during a press conference today in Osaka, Japan, Nintendo president Satoru Iwata said he would not resign despite a bleak financial forecast, according to a report today from GameSpot.
Nintendo announced today that it would be operating for the third straight annual operating loss after slashing sales projects of the Wii U by 70 percent and the 3DS by 25 percent.
"There will be no major management shake-up in the short term," Iwata told Reuters, along with a group of other news outlets, today.
Because of the bleak sales forecasts, Nintendo expects to operate a loss come the end of its financial year in March to the tune of 35 billion yet, or roughly $335 million.
The flop of the Wii sucessor, according to one analyst, likely will trigger a sell off of Nintendo shares. You can read that full Examiner report by clicking here.
The dreary news comes just a day after market research firm NPD Group said Nintendo's 3DS console outperformed all other consoles globally in 2013.


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Every spring break Cocoa Beach, Fla. is invaded by college students on a last hiatus before settling down to take final exams. Finishing college is a milestone in a persons life, and graduations are about to begin. High school graduations on the other hand, launch young adults into a world where they must decide whether or not attending college is for them. As the class of 2014 heads out into the world, hopefully they have already chosen the next rung in the ladder of their education. Selection of a college should have begun before they entered their senior year in high school. So, now is the time for the class of 2015 to start thinking about it.
The following list compares five outstanding Christian schools. They are not necessarily the best in the nation and are not ranked accordingly. Selection of them to include in this list is simply based on the fact that they have already established a good reputation in the field of academics. Taken into consideration, among other things, are curricula, class size, and athletics. The list includes three universities and two seminaries. All of them offer financial aid to students. And, since they all have a visitation policy, during the summer would be a good time to check them out.
1. Columbia International University – To Know Him and to Make Him Known
Founded: 1923
Location: Columbia, South Carolina
Campus Population: 1,284 with 17-1 student-teacher ratio
Curricula: Undergraduate, Graduate and Seminary programs available for Bachelor's Degree; Master or Arts; Master of Divinity; Master of Education; and, Doctor of Education
Athletics: Yes
2. Dallas Theological Seminary – Teach Truth. Love Well.
Founded: 1924
Location: Dallas, Texas
Campus Population: 2,024
Masters Programs – Biblical Counseling; Biblical Exegesis & Linguistics; Christian Education; Christian Leadership; Cross-cultural Ministry; Media Arts & Worship; Master of Theology (ThM); Master of Divinity (MDiv); and, Master of Sacred Theology (STM)
Doctoral Programs – Doctor of Philosophy (PhD); Doctor of Ministry (DMin) – in English and Spanish; and, Doctor of Education Ministry (DEdMin)
Athletics: No
3. Liberty University – Training Champions for Christ Since 1971 (Largest Christian University in the world; 7th largest university in America)
Founded: 1971
Location: Lynchburg, Virginia
Class Size: 19-1 student-teacher ratio
Curricula: Over 315 programs including religion, psychology, education, business, and nursing
Athletics: Yes
4. Oral Roberts University – Make no Little Plans Here
Founded: 1963
Location: Tulsa, Oklahoma
Campus Population: 3,403 students with 16-1 student-teacher ratio
Curricula: College of Arts & Cultural Studies; College of Business; College of Education; College of Nursing; College of Science & Engineering; College of Theology & Ministry
Athletics: Yes
5. Southeastern Baptist Theological Seminary
Founded: 1950
Location: Wake Forest, North Carolina
Campus Population: 3,000+
Curricula: 38 different programs with degrees ranging from Associate of Divinity to Doctor of Philosophy, including our flagship degree, the Master of Divinity.
Athletics: No
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The website for Another Anime Convention has announced their first round of guests for the upcoming 2014 convention, which will be held in Manchester in October.
Matt Myers is most well known as being a member of otaku music group The LeetStreet Boys, and has been a frequent guest of the convention. Along with performing with The LeetStreet Boys, Myers also composes music for video games, wtih some of his work being heard in games such s "Always Remember Me," "The Royal Trap," and "Date Warp."
J. Michael Tatum is a familiar name among anime fans. Most well known for doing the voice of Sebastian in "Black Butler," Tatum has also voiced characters in animes such as "Sgt. Frog," "Black Blood Brothers," "Hetalia," and "Ouran High School Host Club," among others. Recently, it was announced that Tatum would voice the character of Erwin in megahit anime "Attack on Titan." This is Tatum;s third appearance at Another Anime Convention.
Chris Cason is a familiar guest at Another Anime Convention. Cason is most well known as the voice of Gluttony from "Fullmetal Alchemist," and has been heard in such projects as "Borderlands 2," Negima!," "Hell Girl," and "Shin-Chan."
Christopher Smith is another familiar face for convention goers. Smith has voiced such characters as Spandam in "One Piece," Raizer Phoenix in "High School DxD," and various characters including Bren and Jon Ace in "Monsuno."
Another Anime Convention will be held October 17 to 19 at the Radisson Hotel in Manchester.


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BITS Pilani-Hyderabad campus in association with Unseen Underground presents JUNKYARD GROOVE live at
Pearl2013 -the annual cultural fest.
Junkyard Groove was formed in the year 2005 and have become a main stay in the Indian Independent music scene. A band that has seen every high and low of being in a band, from being signed to an international label, opening for some of the biggest bands in the world like Iron maiden, Incubus, Prodigy, Robert Plant and more, to being dropped from their label, and going through line up changes. Thei
Date: 8th March 2013 (Friday)
Venu: BITS Pilani Hyderabad Campus.
More Details about the festival: http://bits-pearl.


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Ranked among the nation's most integrated healthcare systems, Community Health Network is Central Indiana's leader in providing convenient access to exceptional healthcare services, where and when patients need them—in hospitals, health pavilions, workplaces, schools and homes.
Food and drink must be changed into smaller molecules of nutrients to be absorbed into the blood and carried to cells throughout the body. Digestion is the process by which food and liquid are broken down into smaller parts so that the body can use them to build and nourish cells, and to provide energy.
Digestion involves:
Digestion begins in the mouth, where food and liquids are taken in, and is completed in the small intestine.
The digestive system is made up of the digestive tract and other organs that aid in digestion.
The digestive tract is a series of hollow organs joined in a long, twisting tube from the mouth to the anus, consisting of the following:
Organs that help with digestion, but are not part of the digestive tract, include the following:
Parts of other organ systems, such as nerves and blood, also play a major role in the digestive process.
In a wave-like movement, called peristalsis, muscles propel food and liquid along the digestive tract. In general, there are six steps in the process of moving food and liquid through the digestive system:
Click here to view the
Online Resources of Digestive Disorders
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