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commercial property for rent or lease in Sugar Grove (PA), Industrial Space For Lease.
Sugar Grove commercial real estate for lease, rent, and leased investments.
Find Sugar Grove industrial buildings for lease, retail rentals, & Sugar Grove shops. Locate a Sugar Grove warehouse lease and any real estate for lease / investment, including industrial properties to rent and sale.
Any Sugar Grove commercial lease is simply an agreement between the parties that sets out the parameters for the business arrangement. The potential for future adversity is more than real if the terms are not fully understood and considered at the time of signing. A standard lease will have been prepared that will naturally protect the landlords interest in most eventualities. A successful leasing agreement should reflect the issues faced by both landlord and tenant and should consider the needs and requirements of each party.
commercial space listings
Tionesta (Forest), Youngsville (Warren), East Springfield (Erie), Utica (Venango), Lamartine (Clarion), Saegertown (Crawford), Lake City, Riceville, Wattsburg
in Sugar Grove Pennsylvania (PA) (Warren)


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subset: commoncrawl


text:
After a rousing $41 million Friday, universally praised Pixar sequel Toy Story 3 racked up an estimated $109 million three-day weekend, a record, reports Anthony D'Alessandro. That makes Pixar's unbroken string of blockbusters 11 for 11. The western Jonah Hex was dead on arrival.Read More »
film review: Toy Story 3Read More »
"I refuse to say the sky is falling," declared Sony chairman Amy Pascal, when I asked her about the grim summer box office so far. She was observing the Sony 3D show-and-tell Wednesday on the Sony lot. Clearly, not only is the studio earmarking a number of 3D features for 2010 and beyond--including ...Read More »
I had lunch today with Matt Atchity, the LA-based editor-in-chief of critics aggregator Rotten Tomatoes, which Flixster acquired from Fox/IGN in January. The marriage is a happy one--Flixster's mobile phone app and other efforts are tripling RT's traffic, which is back on the rise. The film that sat...Read More »
Last weekend's horrific box office numbers continued into this weekend, which returned animated family film Shrek Forever After--in its third week--to the top of the fray, the only film to crack the $20-million mark! The lucrative summer season is when the studios send their surefire top guns to do ...Read More »
James Sims reviews Nicole LaPorte's new book The Men Who Would Be King: An almost epic tale of moguls, movies, and a company called DreamWorks and agrees with me that of the founding troica, Steven Spielberg, David Geffen and Jeffrey Katzenberg, LaPorte gives the latter the worst appraisal of the th...Read More »
- Nobody knows more about deep-sea robotic technology than filmmaker/tech head James Cameron, who has taken submersibles and his own robotic cameras down to the ocean floor to shoot documentaries on the Titanic and Bismarck. So it makes sense that he was part of a brainstorming session with U.S. officials, scientists and academics who are trying to come up with a solution to the BP oil spill in the Gulf of Mexico. Since BP's efforts have failed, the Federal government is opening its ears to a wider knowledge database. The Huffington Post lists other parties involved in the session: the Woods Hole Oceanographic Institute; Oceanographic Institu...Read More »
Are you a John Lasseter or Brad Bird wannabe? Check this out. The place I have always fantasized about working--assuming that I had the necessary skill-set, which I don't--is Pixar, in Emeryville, in the Bay Area. I actually applied for a long-shot marketing job there once. Not only do they make the best movies on the planet, year in year out--ten for ten blockbusters to date, and I'll lay odds that Toy Story 3 beats How to Train Your Dragon and takes this year's number one summer spot--but I've visited the campus, and it's fabulous. It's the kind of place where bicycles line the hallways and folks like Lasseter use their offices to display t...Read More »
Holdover family film Shrek 4 carried the anemic four-day Memorial Day Weekend holiday; its estimated $55.7 million gross bested two weak openers in the high-to-low $37-million range, Disney's Prince of Persia: The Sands of Time and R-rated Sex and the City 2, reports Anthony D'Alessandro:Read More »
-Disney's Alice in Wonderland will cross the $1 billion worldwide box-office threshold tomorrow, marking the sixth movie to do so and a record for a springtime release. With over $332 million domestic and $667 million foreign, Alice in Wonderland is Disney's second-highest grosser behind Pirates of ...Read More »


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Therapists: 1 to 20
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Depression Therapists in Elizabeth - Charlotte, NC 28204
Verified by Psychology Today
Brandi Ledbetter
Counselor, MA, NCC, LPCA
"Thank you for taking the time to view my profile! Congratulations, you have taken the first step in the therapeutic process, seeking help. The step you have taken can often to be the scariest part of the process. I believe you are the expert of your life, and I will collaborate with you to help you find the life you desire. I will work with you to identify patterns or life choices that have held you back from displaying your full potential or having the life you desire. We can work together to assist you in achieving your goals.
Verified by Psychology Today
Laura H. Frohboese
Clinical Social Work/Therapist, MSW, LCSW
"You come to therapy to face hard truths in your life and learn better ways to handle them. Maybe you find yourself repeating the same patterns, having the same interactions, or feeling a certain way about yourself. I balance truth and tact, giving genuine feedback. I have 15 years of experience helping adults overcome depression, anxiety, and life stress. Sometimes you're depressed & sometimes your life is depressing-usually it's some of both. I address both, helping you change the way you think, act, & feel, while also looking at your whole life situation, environment, lifestyle, friends & stressors.
(704) 312-1854
Verified by Psychology Today
Jenna Wilson
Clinical Social Work/Therapist, MSW, LCSW
"Throughout our life's journey, we encounter a multitude of transitions - some filled with positivity and joy, and others colored with uncertainty and heartache. Traversing these bridges of our path requires the courage to explore challenging questions and the willingness to listen to the answers that emerge.
(704) 729-7588
Verified by Psychology Today
Mary Tota-Faucette
Psychologist, PhD
"I have worked for Presbyterian Hospital in an outpatient clinic for nearly 20 years. There I see a variety of outpatients who have difficulties with depression, anxiety and marital/couples issues. I also help patients with chronic medical issues cope better and manage stress more effectively. I coordinate the Novant Health Pain Rehabilitation Program which helps patients effectively cope, manage and reduce chronic pain due to a variety of medical problems, including fibromyalgia, back pain, headaches/migraines and other types of chronic pain. My general therapeutic approach is cognitive-behavioral. Finally, I do pre-surgical screens for bariatric and SCS patients.
(704) 684-4989
Verified by Psychology Today
Kasandra Wheeler
Clinical Social Work/Therapist, LPC
"I help people feel better by learning new ways to cope and manage. Moving beyond difficult moments is what I would like to help you conquer. I offer convenient day and late evening appointments.
(704) 504-7991
Verified by Psychology Today
Jenny N. Poston
Psychologist, PhD
"As a psychologist with nearly 20 years' experience, I work with people who are struggling with diverse challenges, from temporarily overwhelming stressors to life-altering losses or burdens. Complicated or unsatisfactory relationships, difficult life transitions, health concerns, and significant losses are common problems that, if left unresolved, can lead to depression, anxiety, and feelings of inadequacy, helplessness, or hopelessness. My goal is to provide you with a safe, non-judgmental environment to explore your concerns. I offer insight, support, and guidance, while helping you develop strategies to navigate life's challenges and cope effectively with the difficulties you are facing.
(704) 288-0495
Verified by Psychology Today
Nicole Saunders
Clinical Social Work/Therapist, LCSW
"Come to terms with the past & change your life for the better.
(704) 233-3371
Verified by Psychology Today
Caroline M Biber
Clinical Social Work/Therapist, MSW, LCSW
"I enjoy working with people to help them overcome and cope with life challenges. I have a relaxed and supportive approach and utilize a variety of treatment modalities including cognitive-behavioral, psychodynamic, supportive and educational. I believe that all people have the capacity for change and healing. I create a safe and non-judgmental environment for you to explore your concerns and establish goals. My skills allow me to establish rapport and focus on a range of issues that are important to you.
(704) 750-8279
"I am a pastoral psychotherapist, and like to use a collaborative approach in working with individual and couples. My experience is in working with clients with depression, anxiety, grief and bereavement, relationship and marital problems, divorce recovery, women's concerns, critical illness, and end-of-life issues. I have a special care for those who have experienced traumatic events such as rape, abuse, accidents, disasters, or critical illness.
(919) 887-2888
Verified by Psychology Today
Lauren Foxworth Hall
Counselor, LPCA, LCASA, NCC
"To work with those struggling with addiction issues is one of my deepest passions. Addiction is an insidious and complex bio-psycho-social disease that can be a mind boggling challenge. I believe it requires many avenues of help, most importantly a non-judgmental and compassionate therapist. I approach every client with a person centered perspective and according to their individual needs. I seek to meet clients where they uniquely reside on the developmental/change continuum.
(704) 594-3057
Verified by Psychology Today
Hannelore K Bragg
Psychological Associate, MS, SSP
"When the intensity of painful feelings, the persistent chatter and/or stories in our minds become paralyzing; when worry or rumination interferes with sleep or functioning; when the depression and/or anxieties constrict life; when disempowerment and feeling overwhelmed drain energies and self-esteem; when feeling stuck, miserable and/or afraid is too familiar; when fears and uncertainties rob you of a vital life, it is important to know that you may expect from me radical acceptance, full attention, compassionate listening, active participation, extensive knowledge plus experience, to assist, support and facilitate the creative journey for renewed passion for life.
(828) 333-7553 x3
Verified by Psychology Today
Vivian M. Peralta-Mesa
Marriage & Family Therapist, MS, LMFT
"Counseling can help you understand your relationships at a deeper level & increase intimacy & trust. I am bilingual & provide therapy in English / Spanish. Children do better in school, home & out in the community when parents communicate effectively with each other & agree on how to respond to their children's negative behavior. Sometimes we just get stuck, have too many stressors & don't know how to move forward, even though we want to & wish for it everyday. Counseling can help you become more resilient in coping & embraces life not as a problem to be solved, but an experiment to be lived.
(704) 445-7629
Verified by Psychology Today
Progress and Peace Counseling Services, PLLC
Clinical Social Work/Therapist
"Progress and Peace Counseling Services offers individual, family, and group therapy. We work with children, teenagers, and adults. We specialize in helping families who are dealing with issues such as behavior problems, depression, marital discord, mistrust, anxiety, separation/divorce, problems with peer groups, grief/loss, sibling rivalry, trauma, and life transitions. We also work with many adults on an individual basis.
(980) 272-8213
"We are a group of highly qualified, caring professionals dedicated to helping people achieve their goals for personal growth and emotional well being. All of our clinicians are licensed professionals.
(704) 312-4394 x201
"The Stone Center For Counseling & Leadership is a private practice dedicated to providing professional counseling, consulting & coaching services. We provide services for children, adolescents, adults, couples and families. We offer our "4Kids Sake Parenting Programs" which are designed to support you as you face the various challenges of raising healthy children. We also provide Trainings, Seminars, Workshops and Consultation Services related to Leadership, Self-Growth & Development, Family Life Issues (including parenting, marriage and other family related issues) to organizations and Corporations. Our trainings and workshops assist individuals to be more productive in both their work and home life.
(704) 209-7442
Verified by Psychology Today
Elvita Kondili
Counselor, LPC, MEd
"Opening up to a complete stranger can be difficult but if you are thinking about talking to a therapist there is a part of you that wants to be happier and live to your full potential. Listen to it. I'm a Licensed Professional Counselor and I help people make real change and transform their lives. I provide counseling for anxiety, depression, low self-esteem, stress, life transitions, relationship issues,addictions (alcohol and drug use, sexual addiction, gambling, over-spending, etc), affairs and infidelity, codependency, adult children of dysfunctional families, gay and lesbian issues, etc.
(704) 966-2914
Verified by Psychology Today
Maria Guidetti
"*I AM NOT CURRENTLY ACCEPTING NEW CLIENTS AT THIS TIME* My goal is to support my clients while they identify the changes they want to make and collaborate with them to reach these goals. I think that developing good rapport with my clients is the key to making progress when discussing potentially painful and difficult topics, so I take the time to get to know each individual while being open, honest, and warm. Using such modalities as cognitive behavioral therapy (CBT), motivational interviewing, and solution-focused brief therapy, I team up with my client to create positive change.
(336) 791-0538
Verified by Psychology Today
Jennifer Ratajczak
Counselor, MA, LPC, NCC
"I provide discrete and non-judgmental professional counseling services focused on identifying and resolving underlying and often unconscious influences. Everything we experience shapes us in ways we are often not even aware of and for many of us today's problems stem from the struggles of yesterday. Many of my clients have experienced emotional problems they just couldn't seem to escape including stress, anger, anxiety, depression, and difficulty with families, partners and parenting. Often these problems show up as insecurities about ourselves and our relationships or a loss of control over our behaviors or mood.
(704) 812-5347
Verified by Psychology Today
Andrea Miller
Counselor, MS, EdS, LPC, RPT
"Are you struggling to parent your child on a regular basis? Do you feel overwhelmed in parenting your child? Or do you have twins or triplets and need help navigating the parenting world of multiples? Let me help you! I can help with daily parenting struggles that you face and support your child in overcoming obstacles. Or are you feeling anxious, depressed, and struggling in relationships? I can help with this too! I also work with individuals and can help give you the support you need for healing and living a happier and healthier life
(980) 404-2055 x22
Verified by Psychology Today
Melissa Mosca Fabeny
Counselor, LPC, MA
"Please Note: I will be out of the office from June 30th until October 30th, 2014 on maternity leave. I am passionate about providing a safe, nurturing and non-judgmental environment for all who come to see me. I value each person or family and provide care that is professional and compassionate. I find it a privilege to walk with those who are hurting or want to grow personally, spiritually or relationally. If you are seeking guidance and long lasting change, I encourage you to take the first step.
(704) 980-2723
Not enough Depression Therapists in Mecklenburg County, North Carolina (NC), 28204 to choose from?
Try expanding your search for Therapists in 28204 to a larger area (e.g. click the plus sign or 28204+ .)
Depression Therapists
If you're looking for help with depression in 28204 or for a 28204 depression Therapist, these Therapists provide depression therapy (and depression therapies), depression treatment and depression help in 28204. They include depression Therapists, depression psychologists, depression psychotherapists and depression counselors in 28204. They can help with relationship Therapist in 28204. A Therapist can help with post partum depression, feeling depressed, depression anxiety as well as teen depression. Therapists provide 28204 depression counseling, depression support, referrals to depression support groups in 28204 and 28204 depression groups. If you're depressed in 28204, get help from one of these depression specialists.
How can I tell if a therapist is right for me?
Therapists in Elizabeth - Charlotte have broad skills and are able to work with a wide range of issues.
For example, if you're seeking a marriage counselor in 28204 you'll find that most therapists are trained in marriage counseling or couples counseling in 28204 and couples therapy. And they welcome families for family counseling in 28204 or family therapy in Elizabeth - Charlotte.


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'Die Hard 6′ to Reunite Bruce Willis and Samuel L. Jackson?
Let's be honest: the last two 'Die Hard' movies were almost unwatchable. There's little Fox could do to get us excited for a 'Die Hard 6' at this point, but what little there is to do, they're at least trying to do. Early reports suggest that Fox is working on a 'Die Hard 6' story that would reunite John McClane (Bruce Willis) and Zeus Carver (Samuel L. Jackson), the co-stars of the last good 'Die Hard' movie.
'Star Wars: Episode 7′ Will Take Place 30 Years After 'Return of the Jedi'; Will Follow a Trio of New Characters
'Star Wars: Episode 7' hasn't been very forthcoming when it comes to details. We sorta knew what was happening, but then J.J. Abrams completely scrapped the existing script by Michael Arndt to start fresh with Lawrence Kasdan ('The Empire Strikes Back'), calling into question everything we thought we knew. But, now we actually have some confirmed story facts for the upcoming sequel. 'Star Wars: Episode 7' will take place 30 years after the events of 'Return of the Jedi' and will follow a trio of young characters.
Legendary Movie Trailer Voice-Over Guy, Hal Douglas, Dies at 89
Hal Douglas, the voice-over artist who popularized the "In a world..." line and whose voice could be heard in movie trailers for 'Forrest Gump,' 'Meet the Parents' and 'Lethal Weapon' has died at the age of 89 from complications of pancreatic cancer.
Ellen's Oscar Selfie Was Part of a $20 Million Samsung Ad Buy With ABC
Did you think that bit at the Oscars where host Ellen DeGeneres wandered into the audience to tweet a selfie with A-listers like Brad Pitt, Julia Roberts, Meryl Streep, Jennifer Lawrence and Bradley Cooper was a refreshing moment of spontaneity in an otherwise scripted affair? Wrong. The viral photo was actually part of a $20 million Samsung advertising campaign designed to promote the Galaxy Note 3, the phone that took the picture.
2014 Super Bowl Trailers: What to Expect During the Big Game
Football fans are no doubt excited for the 2014 Super Bowl, but even non-sports fans can find something to enjoy. No, we're not talking about Bruno Mars, we're talking about the Super Bowl movie trailers that will be airing during the commercial breaks. With the 2014 Super Bowl set to air on FOX at 6pm on February 2, we thought now would be the perfect time to run through what we know is going to debut during the big game and what surprises could still be in store.
Seth Rogen and James Franco's Shot-for-Shot Recreation of Kanye West's "Bound 2″ Video
The world collectively chuckled last week as Kanye West revealed his ludicrous "Bound 2" music video, which co-starred his fiancee Kim Kardashian, who rode topless on a motorcycle. Get ready to laugh even harder as Seth Rogen and James Franco made a shot-for-shot remake of the "Bound 2" video on the set of their new movie, which gives new meaning to the lyric, "I wanna f--- you hard on the sink."
Listen All Y'All, It's a First Look at Arnold Schwarzenegger in 'Sabotage'
Arnold Schwarzenegger has yet to star in a breakout hit since stepping down as governor of California. 'The Last Stand' and 'Escape Plan' were mostly disappointments, but Arnold has his best chance of success coming up with the action-thriller 'Sabotage' (formerly known as 'The Ten'). In fact, Arnold compares this movie to one of his best ever - 'Predator.' Get a first look at 'Sabotage' with a set of new photos below.
Will Ferrell and John C. Reilly to Reunite For Halloween Comedy 'Devil's Night'
Huff and Doback are back. Will Ferrell and John C. Reilly will once again reunite for the upcoming Halloween-themed comedy titled 'Devil's Night.' Hey, it's no 'Step Brothers 2' but it's a start.


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A theological seminary is not guilty of subjecting two female students to a hostile work environment, according to the Supreme Court of New Jersey. The students claimed that the school failed to reign in a 60-year-old seminary resident who romantically pursued the two women. The resident asked the students out for dates but did not touch them or make inappropriate comments.
See all the latest links and resources that supplement the current issue of Security Management magazine.


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Reason #50 Why Readers Love Widescreen Review:
Your magazine was the only one available to me that not only provided forward-looking articles (such as reports on the development of the HDTV standard), but also provided information on equipment and offered the only reviews I could find on Laser Discs. Thanks to your publication, most of my video library is letterboxed. I am now prepared for my dream HDTV. Thanks for the information that allows me to prepare for the future!Donald C. Williams


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Bayazid Bastami Quotes (3 quotes)
Quoted in James Fadiman and Robert Frager, eds., Essential Sufism (Castle Books, 1998, ISBN 0-7858-0906-6), p. 37.
"I grow a white rose
In July just as in January
For the sincere friend
Who gives me his frank hand.
And for the cruel man who pulls out of me
the heart with which I live,
I grow neither nettles nor thorns:
I grow a white rose."
―Jose Marti
Cultivo una rosa blanca / En julio como en enero, / Para el amigo sincero / Que me da su mano franca. Y para el cruel que me arranca / El corazon con que vivo, / Cardo ni ortiga cultivo, / Cultivo una rosa blanca. - Simple Verses (1891)
"Perhaps the most valuable result of all education is the ability to make yourself do the thing you have to do, when it ought to be done, whether you like it or not; it is the first lesson that ought to be learned; and however early a man's training begins, it is probably the last lesson that he learns thoroughly."
―Thomas Henry Huxley
Select Works of Thomas H. Huxley (J. B. Alden, Publisher, 1886 ), p. 339
"Every Indian outbreak that I have ever known has resulted from broken promises and broken treaties by the government."
―Buffalo Bill
Buffalo Bill Museum (1995 edition)
"Did perpetual happiness in the Garden of Eden maybe get so boring that eating the apple was justified?"
―Chuck Palahniuk
Survivor: A Novel (2010 edition), p. 92
As quoted in: "The New York Times Book Review" (1985), p. 47
Picture Source: Wikimedia CommonsBayazid Bastami
Bio: Bayazid Bastami, also known as Abu Yazid Bistami or Tayfur Abu Yazid al-Bustami, was a Persian Sufi born in Bastam, Iran.
Quote of the day
"Cosimo: It is only a play... with music? Does God say the same at every death? It is only a play... with music? When I die, will someone say the same? He was only a prince. He died. It was only a play... with music."


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Looking at - and into - Trowbridge Street School
Trowbridge Street School of Great Lakes Studies, 1943 E. Trowbridge St., in Bay View has been staring me in the face for years. Living in Bay View for six years, I walked past it regularly. But I never really looked at it.
I saw it, certainly. How could anyone miss the sea of concrete behind the school? I even looked at a house for sale directly across the street. But I never really did more than give it a passing glance.
So, it came as something of a revelation last week when I decided to drive down to Bay View and take photos of current and former elementary schools in the neighborhood, including this one, which was originally District 17 Primary and then, in 1905, designated as District 17-2 (Nearby Dover Street was District 17-1) and was renamed Trowbridge Street in 1912.
The school – which currently runs from K4 through eighth grade – originally housed first through sixth grade classes. Kids then went to Dover for seventh and eighth grades until Trowbridge was expanded to include seventh and eighth grades in 1905. Likely its most famous alumnus is Oscar-winning Hollywood actor Spencer Tracy.
I realized I'd let the sprawling schoolyard distract me from what might be the loveliest vintage building in MPS. Principal Tom Matthews invited me down for a tour, so I returned this week to see the inside and he told me that he believes it is the only vintage cream city brick schoolhouse that has never had a painted exterior.
Most of the schools burned coal for heat and the soot was more easily painted over than sandblasted off the buildings. Somehow, this 1894 Queen Anne building, with its stunning Romanesque portal and pleasing details escaped that fate.
However, the interior of the building – designed by architect Walter A. Holbrook – couldn't boast the same success over the years.
"When I got the building it was somewhat in disrepair," he says, noting that he's since replaced all the windows and doors and opened up the windows in the Romanesque arch above the main entrance, which had been boarded up.
Matthews says when he took over, the main hallway was painted a sort of "Pepto Bismol pink" that can still been seen in some parts of the building and the second floor corridor was "macho muscle car purple. I had Marquette's rugby team come in and paint the first weekend I was here because I couldn't handle it.
"None of the rooms had been painted in over 30 years," he says. "So we've systematically gone about a plan of continuous improvement, just aesthetically and the way the building looks."
He spent a year renovating a disaster of a library, too.
But Matthews has also taken what was a struggling school with declining enrollment that was on the verge of being closed and nearly doubled the number of students – two-thirds of whom come from the Bay View area – and created partnerships with First Stage, the Coast Guard, the Milwaukee Symphony, the MMSD and other local businesses and groups. The student body is roughly a third African-American, a third Latino and a third white, making it among the most diverse schools in the district.
Matthews had been principal at Roosevelt Middle School and was about at the end of his rope there, he says, when he expressed his frustration to then-superintendent William Andrekopoulos, who offered Matthews Trowbridge.
"He said, 'I've got a problem in Bay View. I've got a school that only has 180 kids in it. We should close it, but the community won't allow it because it's been there since 1894. Do you think you'd be interested in that?'
"I said, 'I'll take it'," remembers Matthews. "'Sight unseen?' Sight unseen."
And now?
Now Trowbridge's reading and math scores are on the rise and walking through the building, the hallways are empty and quiet, the classrooms orderly but lively with learning and Matthews clearly earns the respect of his teachers – many of whom have transferred to Trowbridge to be a part of the rebirth – and his students, who don't hesitate to ask him questions, express concerns and joke with him good-naturedly. And, he appears to know the names of each and every one of his 320 kids.
Matthews says it took some time to adjust to the new environment. At his old school, kids would swear at him in the halls. "Here, they break out of line, hug my knees and say, 'We love you, Mr. Matthews'."
Having known Tom Matthews in a previous Milwaukee rock and roll life, during which we often shared a stage further up KK Avenue at the Odd Rock Cafe, I'm thoroughly impressed by Principal Matthews, who seems the perfect balance of engaged, stern, friendly, fair, concerned.
According to a 1991 historic designation study report, Trowbridge was built in two phases. The three easternmost sections, including the main entry, and a classroom section on either side of it, were constructed in the first phase. In 1909, two more classroom sections were added to the western side.
The school was built in 1894 – four years after Dover Street was constructed west of Kinnickinnic Avenue – to replace a much smaller school that was located on Wentworth, just south of Russell Avenue. The playground behind the building was added in the 1920s and expanded in the '70s.
The top floor of the building has just about the tiniest gym I've ever seen, so that outdoor expansion must have been welcomed.
The report notes that, "The Trowbridge Street School is architecturally significant as a fine example of a Victorian era schoolhouse by a noted Milwaukee architect. It is historically significant for its associations with the development of the Bay View neighborhood."
Holbrook was a partner of important Milwaukee architect Edward Townsend Mix in the 1880s. Born in Sacketts Harbor, N.Y., in 1849, Holbrook arrived in Oshkosh and then, in 1869, in Milwaukee, where he began working with Mix, rising up from his role as a draftsman to becoming Mix's partner in 1881.
Holbrook designed the former Sentinel building at 225 E. Mason St. and a number of local residences, and also worked on many famous local Mix projects, like the Mackie Building, the Mitchell Building and St. Paul's Episcopal Church on Knapp Street.
Holbrook died riding his bicycle on State Street in 1910.
Luckily, for fans of Milwaukee history and architecture – as well as for the Trowbridge community of staff, students and families – his gorgeous schoolhouse endures.
hardgeminiguy | May 19, 2011 at 7:01 p.m. (report)
Sandblasting was referred to in the article. Cream city brick must NEVER be sand blasted. That removes the protective layer of the brick which ruins the brick over time as the brick then flakes away, especially in freezing weather. Only water blasting with chemicals can, appropriately, be used in cleaning cream city brick. Years ago, i cleaned several cream city brick buildings in the downtown area and in Brewers' Hill. thank-you
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The NLRB has launched a new website as part of an effort to beef up employee rights. But how many workers who need to know their rights can read and understand it?
According to a new report, Native-American children ''face unprecedented challenges'' of violence and extreme poverty.
Bill Quigley is legal director at the Center for Constitutional Rights and a law professor at Loyola University New Orleans. He is a Katrina survivor and has been active in human rights in Haiti for years with the Institute for Justice and Democracy in Haiti. He can be reached at email@example.com


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If you need additional space to store seasonal items, the Outdoor Living Today Partnership 3 ft. 1/2 in. 6 ft. 2-1/2 in. Western red cedar wood Grand Garden Chalet is a great solution. Big enough for a bicycle, garbage cans and sporting equipment, this versatile chalet features a cedar shingle roof that offers extra strength and a handsome appearance. The chalet is made entirely with renewable resources and accepts a wide range of finishes to help you create a personalized look. Manufacturer will call to offer site preparation information and discuss delivery before shipping.
|Approximate Shed Depth (ft.)
|Approximate Shed Width (ft.)
|Assembled Depth (in.)
|36.5 in
|Assembled Height (in.)
|72 in
|Assembled Width (in.)
|74.5 in
|Assembly Required
|Door Opening Width (ft.)
|Floor Options
|With Floor
|Lockable Door/Gate Latch
|Manufacturer Warranty
|Structures are covered for one year for defects in manufacturing and workmanship. Costs incurred for customer installations are not included. For missing or broken piece, call Outdoor Living Today at 888-658-1658 within 30 days of the delivery. Replacement parts are free of charge within 10 business days of notification and will not be provided free of charge after 30 days
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Multi-coloured dress from SONIA BY SONIA RYKIEL. Sleeveless and hidden zip in the back. Ruffled in the front. Dry clean only.
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Dr. Mouhammed K. Sheikha, MD
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Dr. Mouhammed K. Sheikha has been practicing medicine for 28 years. Dr. Sheikha graduated from the University of Damascus - Faculty of Medicine, Damascus, Syria in 1986. He practices medicine in Fort Smith, AR and specializes in Internal Medicine.
Gender: Male
Years in Practice: 28 Years
Languages Spoken: English
Medical School: University of Damascus - Faculty of Medicine, Damascus, Syria
Graduation Date: 1986
Hospital Affiliations: Not Available
Specialties: Internal Medicine


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Nijmegen, Netherlands-based ReSnap offered its own take on physical photo albums made up of images from Facebook, Instagram, and Twitter, using its popularity algorithm to automatically select the most popular photos and updates from those social networks for inclusion in the photo books.
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Krug Grande Cuvee
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375ml Bottle $911.89
Case of 12
375ml Bottle $911.89
Case of 12
Item #255614
Size: 375ml
Type: Sparkling Wine
Country: France
Region: Champagne
"This is all about balance and the integration of power and finesse, with finely honed acidity supporting flavors of quince paste, dried black cherry, spun honey and candied orange zest, while rich notes of roasted walnut, coffee liqueur and toasted cardamom resonate on the finish. Hard to stop sipping."
Reviewed by: Wine Spectator - 97pts
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Moet & Chandon Imperial Brut
"The minerally undertow imparts a subtle, smoky note that blends with flavors of dried pineapple, biscuit, salted almond and white peach. A balanced version, with a fine bead and well-honed acidity."
$27.99 / 375ml Bottle
$319.09 / Case of 12
$319.09 / Case of 12
Bollinger Special Cuvee Brut
"This is firm and tightly knit, with a backbone of steely acidity, showing a fine, creamy texture that imparts an overall sense of finesse to the layers of poached apple, mille-feuille, black currant, kumquat and honey, showing hints of ground spice and smoky mineral."
$69.99 / 750ml Bottle
$398.94 / Case of 6
$398.94 / Case of 6
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Jabil Circuit Implosion Not Negative For ApplePaulo Santos • Dec. 18, 2013 • 45 Comments
Cisco: What Happened And What's NextNikos Theodosopoulos • Nov. 22, 2013 • 5 Comments
Thu, Nov. 13, 11:02 AM
- Goldman has downgraded contract manufacturer Jabil (JBL -3.1%) to Neutral, and IT hardware/chip distributor Avnet (AVT -3.4%) to Sell.
- Regarding Jabil, Goldman still sees upside to analyst EPS estimates, but considers this "offset by customer concentration and valuation." It's also worried on Jabil's dependence on Apple (seeing strong iPhone 6 demand, from all indications) to drive growth.
- As for Avnet, the firm is worried 1H15 sales could be soft, and that this could lead to multiple contraction.
- Jabil is up over 20% YTD, while Avnet is nearly flat.
Wed, Oct. 29, 5:30 PM
- Level 3 (NYSE:LVLT) will take Jabil's (NYSE:JBL) place in the S&P 500 following the Nov. 4 close.
- The announcement comes a day after Level 3 and TW Telecom (NASDAQ:TWTC) shareholders each approved the companies' cash/stock merger. The merger is expected to close before Level 3's Nov. 5 Q3 report.
- Jabil will take TW's place in the S&P MidCap 400.
- LVLT +3.1% AH. JBL hasn't moved yet.
Thu, Oct. 16, 4:40 PM
- Jabil Circuit (NYSE:JBL) declares $0.08/share quarterly dividend, in line with previous.
- Forward yield 1.73%
- Payable Dec. 1; for shareholders of record Nov. 14; ex-div Nov. 12.
Tue, Oct. 14, 3:31 PM
- Global growth, foreign-exchange, oil, and small caps are the subject of every client inquiry, says David Kostin. His team's recommendation: Buy "American exceptionalism."
- In Kostin's view, U.S. economy and corporate fundamentals are still strong, with economic growth expected by Goldman economists to be 3.2% next year, the fastest expansion since 2005. Europe is expected to grow just 1%.
- What his team likes are those stocks of companies which have a high proportion of domestic sales, plus sectors like Consumer Staples (XLP -0.1%) and Discretionary (XLY +0.7%) which stand to benefit from lower oil prices (plunging again today).
- As for small caps (IWM +0.9%), Kostin is wary, noting downward earnings revisions have boosted small cap P/E ratios even as prices have declined.
- The list of S&P 500 names capturing two or more of Kostin's themes: GT, GM, PCLN, AMZN, CMCSA, LOW, DG, TSN, ADM, CVS, AVP, WAG, PXD, HAL, JPM, BAC, SCHW, PNC, MS, C, GNW, LNC, MET, THC, AET, UNH, ESRX, HUM, WLP, BIIB, GILD, DAL, CMI, FLR, CRM, JBL, MA, FB, MU, FSLR, VMC, MON, T.
Fri, Oct. 10, 1:42 PM
- Following Microchip's warning and related prediction of a chip industry correction, Goldman's James Covello thinks there's 15%-20% downside in industry names.
- Covello, who lowered his industry view to Cautious in August: "The last time Microchip negatively preannounced was October 15, 2012 (3% sales miss). Between October 1 and December 31, Street 2013 sales estimates for the Semi group were revised down 6% on average."
- He adds several datapoints suggest the industry has been overheating. Among them: Semi revenue growth has outpaced end-market growth, and supply chain inventory dollars rose 3% more than their 3-year average in Q2.
- "Nobody will be spared," predicts Hedgeye's Craig Berger. Benchmark's Gary Mobley observes 5 of the 6 chip stocks to have made Q3 pre-announcements have thus done so to the downside.
- Worth noting: Mobile chipmaker Silicon Motion (SIMO -8.9%) is the one chipmaker to have positively pre-announced. It might not be a coincidence that Microchip has relatively low mobile exposure.
- Observing U.S. macro data remains positive even as China and Europe soften, Longbow's JoAnne Feeney remains bullish long-term on select names. However, she has cut her short-term rating on Linear (LLTC -3.8%) to Sell, and removed IDT (IDTI -7.1%) from her trading long list.
- In addition to the names previously mentioned, the following chip stocks are seeing steep losses: AMD -5.1%. FCS -13.6%. NXPI -11.2%. CODE -11%. LSCC -9.6%. SIMG -8.1%. IPHI -7.7%. ISIL -9.5%. CY -6.9%. RMBS -7.1%. QUIK -5.7%. SQNS -5.1%. IMOS -6.5%.
- Foundries and contract manufacturers are also selling off: TSM -3.9%. UMC -2%. SMI -2.4%. SANM -11.7%. FLEX -6.8%. JBL -4%.
- Chip ETFs: SOXX, SMH, XSD, PSI, SOXL, USD, SOXS, SSG
Wed, Sep. 24, 5:35 PM
Wed, Sep. 24, 4:24 PM
- Jabil (NYSE:JBL) expects FQ1 revenue of $4.2B-$4.4B and EPS of $0.41-$0.53, mostly above a consensus of $4.11B and $0.41. However, FY15 (ends Aug. '15) guidance of $1.65-$1.95 is reiterated; consensus is at $1.74.
- Diversified manufacturing revenue rose $300M Y/Y to $2.1B; enterprise & infrastructure was $1.4B; high-velocity systems (still affected by the loss of BlackBerry sales) fell $400M to $900M.
- Gross margin fell 40 bps Y/Y to 6.5%. SG&A spend rose 3% to $177.9M.
- FQ4 results, PR
Wed, Sep. 24, 4:07 PM
- Jabil Circuit (NYSE:JBL): FQ4 EPS of $0.05 beats by $0.05.
- Revenue of $4.1B (-14.8% Y/Y) beats by $270M.
- Shares +7.87% AH.
- Press Release
Tue, Sep. 23, 5:35 PM
Fri, Jul. 25, 9:27 AM
- With the company's current $200M buyback expected to be used up by the end of August, Jabil (NYSE:JBL) is creating a new $100M buyback that's good until Aug. 31, 2015.
- At current levels, Jabil's buyback is good for repurchasing 2.3% of outstanding shares.
Wed, Jul. 23, 6:11 PM
- Jabil Circuit (NYSE:JBL) declares $0.08/share quarterly dividend, in line with previous.
- Forward yield 1.52%
- Payable Sept. 2; for shareholders of record Aug. 15; ex-div Aug. 13.
Wed, Jun. 18, 4:44 PM
- Jabil (JBL) expects FQ4 revenue of $3.7B-$3.9B and EPS of -$0.10 to $0.10 vs. a consensus of $3.78B and $0.02. FY15 (ends Aug. '15) guidance for EPS of $1.65-$1.95 has been reiterated; consensus is at $1.72.
- Diversified manufacturing revenue totaled $1.6B in FQ3, enterprise & infrastructure $1.3B, and high-velocity systems (hurt by the loss of BlackBerry) $0.9B.
- FQ4 segment guidance: Diversified manufacturing -6% Y/Y, enterprise & infrastructure -7%; high-velocity systems -38%.
- Thanks to lower sales, gross margin fell to 5.7% from 7.1% a year ago. Jabil ended FQ3 with $1.3B in cash, and $1.7B in debt.
- FQ3 results, PR
Wed, Jun. 18, 4:04 PM
- Jabil Circuit (JBL): FQ3 EPS of -$0.06 beats by $0.02.
- Revenue of $3.8B (-15.0% Y/Y) beats by $200M.
- Shares +5.42% AH.
- Press Release
Tue, Jun. 17, 5:35 PM
Wed, May. 14, 5:44 PM
- Cisco's FQ3 beat, above-consensus FQ4 guidance,, and positive CC commentary are providing a lift to networking equipment rivals and component suppliers.
- Up AH: ALU +1%. JNPR +1.6%. FFIV +0.8%. FNSR +2%. JDSU +1.5%. RVBD +0.9%. JBL (a major Cisco contract manufacturer) +0.8%.
- Cisco's product orders were nearly flat Y/Y in FQ3 after falling 4% in FQ2. U.S. orders (+7%, with 10%+ increases in enterprise/SMB orders) provided a boost, as did a 4% increase in Northern European orders.
- The company's service provider orders fell another 5% Y/Y (router/set-top share loss), but that was better than FQ2's 12% drop. Emerging markets (-7% vs -3% in FQ2) also remained weak.
Mon, Apr. 21, 9:39 AM
- Jabil (JBL -1.5%) has been cut to Sector Perform by RBC.
- Plexus (PLXS +2.9%) has been upgraded to Buy by Needham five days after posting an FQ2 revenue beat.
- A10 Networks (ATEN +2.3%) has been started at Buy by Citi. IPO underwriters launched coverage last Wednesday. Shares are right near their $15 March 21 IPO price.
- 2U (TWOU +1.8%) has been started at Buy by Compass Point. Shares are slightly above their $13 March 28 IPO price.
JBL vs. ETF Alternatives
Company Description
Jabil Circuit Inc, together with its subsidiaries is a provider of electronic manufacturing services and solutions. It provides electronic design, production &product management services to companies in the aerospace, automotive, & among others.
Sector: Technology
Industry: Printed Circuit Boards
Country: United States
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Printable Area
By NcMysteryShopper on September 26, 2006
Photo by NcMysteryShopper
Photo by NcMysteryShopper
"We really enjoyed this recipe. The Chambord really lends itself well to this dish and creates a nice fruity sweet that contrasts well with the heat of the jalapeno. The original recipe called for 5-6 ounces of olive oil, but we felt that 2 ounce was plenty. The sauce is really good so make sure you have some crusty bread to soak it up with. I served it on a bed of Hawaiian Rice (Hawaiian Rice) by Chabear01, but it would be equally good on plain white rice."
Serving Size: 1 (59 g)
Servings Per Recipe: 4
"I had this for dinner last night and it was delicious! I never considered chambord to cook with but it is a great flavor with the garlic. I had it with some garlic rice and it was a great match!"
"Excellent and very easy! Thanks for a great recipe."
"i love this"
"This is superb. The reviewers are right, have plenty of crusty bread on hand to sop up the sauce. We will be doing this one again!"
"This shrimp dish was a little wierd and too sweet in my opinion. My husband thought it was great as he tends to enjoy unusual flavors. If you like odd combinations...this is for you."
"Nice combination...but would remove the seeds from the jalapeno next time...found it too dominant."
"Yummy shrimp....I definitely enjoyed this for my dinner tonight. I like the taste of raspberries with jalapeno, reminds me of pepper jelly. Very good!"
"This was very good! Super quick and easy to make. Due to not having any raw shrimp or Chambord, I used precooked frozen shrimp thawed and 2 Tbs of Sugar free Raspberry Preserves that I had on hand. Note: if preserves are chilled stand back when you add to hot oil...lol. The shrimp was wonderful like this and only 10gm of carbs. Next time I'm going to try this with orange marmalade or orange liquer such as Grand Marnier. Everyone was right, the bread is perfect for getting every last wonderful bit of sauce!"
"Sweet and Spicy- much different than any shrimp recipe I have tried. I wanted to drink the sauce!"
"i tried this last valentine's day and my fiance loved it!!! it was super easy to do plus very very tasty!"
"Absolutely amazing! I made this as the appetizer for my Valentine's Day dinner. My bf could hardly speak. He was thrilled with the flavor and said he wanted to burst from all that he was tasting! Thanks so much!"
"Incredibly delicious. Wished I had made more, these were just so good. The sauce is a bit sweet & a bit spicy and made us grab for more bread to dip up every last bit. A keeper, and will be a true favorite."
"My DH and friend loved this, easy, simple and oh so good! thanks Cheryl!...Kitz:)"
"Fantasmic! The sweetness of the Chambord hits you first and you are like... hmmm...This is pretty good. Then the bite from the jalapeno tingles your tongue and you are like... VERY good! I cant really repeat what dh said, but here is the censored version "MMMM, This is some good #*%#" We both agreed that 2 ounces of olive oil was more than enough and could probably be reduced even more. The sauce was amazing so definitely follow NCM's advice and have some crusty bread waiting. Next time I will play with the amount of oil and maybe increase the garlic just a touch. For those who really like heat you may want to use a bit more hot pepper. We thought this was perfect. Just tingles on the tongue doesnt over power or burn. I served this with my Rice Verde and it was a great accompaniment. I did not take a pic bc mine would never come as pretty as the one already here. Perfection NCM! Thanks for sharing this great dish!"


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Are you Tom Burdon?Claim your profile
Publications (16)82.35 Total impact
Article: Tuning Differentiation Signals for Efficient Propagation and In Vitro Validation of Rat Embryonic Stem Cell Cultures.[Show abstract] [Hide abstract]
ABSTRACT: The rat is one of the most commonly used laboratory animals in biomedical research and the recent isolation of genuine pluripotent rat embryonic stem (ES) cell lines has provided new opportunities for applying contemporary genetic engineering techniques to the rat and enhancing the use of this rodent in scientific research. Technical refinements that improve the stability of the rat ES cell cultures will undoubtedly further strengthen and broaden the use of these stem cells in biomedical research. Here, we describe a relatively simple and robust protocol that supports the propagation of germ line competent rat ES cells, and outline how tuning stem cell signaling using small molecule inhibitors can be used to both stabilize self-renewal of rat ES cell cultures and aid evaluation of their differentiation potential in vitro.Methods in molecular biology (Clifton, N.J.) 09/2014; · 1.29 Impact Factor
Article: Tuning of β-catenin Activity is Required to Stabilise Self-renewal of Rat Embryonic Stem Cells.[Show abstract] [Hide abstract]
ABSTRACT: Stabilisation of β-catenin, through inhibition of Glycogen synthase kinase 3 (GSK3) activity, in conjunction with inhibition of the enzyme MEK, promotes self-renewal of naïve-type mouse embryonic stem cells (ESC). In developmentally more advanced, primed-type, epiblast stem cells (EpiSC), however, β-catenin activity induces differentiation. We investigated the response of rat ESCs to β-catenin signalling and found that when maintained on feeder-support cells in the presence of a MEK inhibitor alone (1i culture), the derivation efficiency, growth, karyotypic stability, transcriptional profile, and differentiation potential of rat ESC cultures was similar to that of cell lines established using both MEK and GSK3 inhibitors (2i culture). Equivalent mouse ESCs, by comparison, differentiated in identical 1i conditions, consistent with insufficient β-catenin activity. This interspecies difference in reliance on GSK3 inhibition corresponded with higher overall levels of β-catenin activity in rat ESCs. Indeed, rat ESCs displayed widespread expression of the mesendoderm-associated β-catenin targets, Brachyury and Cdx2 in 2i medium, and overt differentiation upon further increases in β-catenin activity. In contrast, mouse ESC were resistant to differentiation at similarly elevated doses of GSK3 inhibitor. Interestingly, without feeder support, moderate levels of GSK3 inhibition were necessary to support effective growth of rat ESC, confirming the conserved role for β-catenin in ESC self-renewal. This work identifies β-catenin signalling as a molecular rheostat in rat ESC, regulating self-renewal in a dose-dependent manner, and highlights the potential importance of controlling flux in this signalling pathway to achieve effective stabilisation of naïve pluripotency.Stem Cells 07/2013; · 7.70 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Distinct signaling pathways are reported to maintain pluripotency in embryo-derived stem cells. Mouse embryonic stem cells (ESCs) respond to leukemia inhibitory factor (LIF) and bone morphogenetic protein (BMP)-mediated activity, whereas human ESCs depend upon Fibroblast growth factor (FGF) and activin signaling. In the majority of mammals investigated, however, the signals that support stem cell pluripotency are not well defined, as is evident by the persistent difficulties in maintaining authentic stable ESC lines. Induction of pluripotency by transcription factor-mediated reprogramming could provide an alternative way to produce ESC-like cells from nonpermissive species, and facilitate identification of core ESC signaling requirements. To evaluate the effectiveness of this approach in pigs, we transduced porcine foetal fibroblasts with retroviruses expressing Oct4, Sox2, Klf4, and c-Myc, and maintained the resulting cultures in medium containing either LIF or FGF2. Alkaline phosphatase positive colonies with compact, mouse ESC-like morphology were preferentially recovered using serum-free medium supplemented with LIF. These cell lines expressed the endogenous stem cell transcription factors, OCT4, NANOG, and SOX2, and the cell surface marker SSEA-4, consistent with acquisition of an undifferentiated state. However, restricted differentiation potential, and persistent expression of retroviral transgenes indicated that reprogramming was incomplete. Interestingly, LIF activated both the transcription factor STAT3 and its target gene SOCS3, and stimulated cell growth, indicating functional coupling of the signaling pathway in these cells. This demonstration of LIF-dependence in reprogrammed pig cells supports the notion that the connection between LIF/STAT3 signaling and the core regulatory network of pluripotent stem cells is a conserved pathway in mammals.Cellular reprogramming. 02/2012; 14(2):112-22.
- [Show abstract] [Hide abstract]
ABSTRACT: Pluripotential stem cells from livestock offer an exciting prospect for the biotechnology industry. Applying strategies established for the derivation of murine induced pluripotential stem cells (iPSCs), we have isolated ovine iPSCs that can give rise to cells characteristic of all three germ cell layers both in vitro from embryoid bodies and in teratomas in vivo. Furthermore, although at a low level, these ovine iPS cells can contribute to live-born chimeric lambs. Colonies derived from ovine embryonic fibroblasts transfected with murine cMyc, Klf4, Oct4, and Sox2 displayed smooth domes with sharp edges when grown in human embryonic stem cell (ESC) medium but not in mouse ESC medium. These ovine iPSCs were alkaline phosphatase positive, expressed Nanog, and had a normal karyotype. These cells represent an important step in the understanding of mechanistic nature of pluripotency in ungulates.Cellular reprogramming. 01/2012; 14(1):8-19.
Article: An interspecies analysis reveals a key role for unmethylated CpG dinucleotides in vertebrate Polycomb complex recruitment.[Show abstract] [Hide abstract]
ABSTRACT: The role of DNA sequence in determining chromatin state is incompletely understood. We have previously demonstrated that large chromosomal segments from human cells recapitulate their native chromatin state in mouse cells, but the relative contribution of local sequences versus their genomic context remains unknown. In this study, we compare orthologous chromosomal regions for which the human locus establishes prominent sites of Polycomb complex recruitment in pluripotent stem cells, whereas the corresponding mouse locus does not. Using recombination-mediated cassette exchange at the mouse locus, we establish the primacy of local sequences in the encoding of chromatin state. We show that the signal for chromatin bivalency is redundantly encoded across a bivalent domain and that this reflects competition between Polycomb complex recruitment and transcriptional activation. Furthermore, our results suggest that a high density of unmethylated CpG dinucleotides is sufficient for vertebrate Polycomb recruitment. This model is supported by analysis of DNA methyltransferase-deficient embryonic stem cells.The EMBO Journal 11/2011; 31(2):317-29. · 9.82 Impact Factor
Article: Parkinson's disease induced pluripotent stem cells with triplication of the α-synuclein locus.[Show abstract] [Hide abstract]
ABSTRACT: A major barrier to research on Parkinson's disease is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells from patients and differentiate them into neurons affected by disease. Triplication of SNCA, encoding α-synuclein, causes a fully penetrant, aggressive form of Parkinson's disease with dementia. α-Synuclein dysfunction is the critical pathogenic event in Parkinson's disease, multiple system atrophy and dementia with Lewy bodies. Here we produce multiple induced pluripotent stem cell lines from an SNCA triplication patient and an unaffected first-degree relative. When these cells are differentiated into midbrain dopaminergic neurons, those from the patient produce double the amount of α-synuclein protein as neurons from the unaffected relative, precisely recapitulating the cause of Parkinson's disease in these individuals. This model represents a new experimental system to identify compounds that reduce levels of α-synuclein, and to investigate the mechanistic basis of neurodegeneration caused by α-synuclein dysfunction.Nature Communications 01/2011; 2:440. · 10.74 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The rat is the preferred experimental animal in many biological studies. With the recent derivation of authentic rat embryonic stem (ES) cells it is now feasible to apply state-of-the art genetic engineering in this species using homologous recombination. To establish whether rat ES cells are amenable to in vivo recombination, we tested targeted disruption of the hypoxanthine phosphoribosyltransferase (hprt) locus in ES cells derived from both inbred and outbred strains of rats. Targeting vectors that replace exons 7 and 8 of the hprt gene with neomycinR/thymidine kinase selection cassettes were electroporated into male Fisher F344 and Sprague Dawley rat ES cells. Approximately 2% of the G418 resistant colonies also tolerated selection with 6-thioguanine, indicating inactivation of the hprt gene. PCR and Southern blot analysis confirmed correct site-specific targeting of the hprt locus in these clones. Embryoid body and monolayer differentiation of targeted cell lines established that they retained differentiation potential following targeting and selection. This report demonstrates that gene modification via homologous recombination in rat ES cells is efficient, and should facilitate implementation of targeted, genetic manipulation in the rat.PLoS ONE 01/2010; 5(12):e14225. · 3.53 Impact Factor
- Mechanisms of Development - MECH DEVELOP. 01/2009; 126.
Article: Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells.[Show abstract] [Hide abstract]
ABSTRACT: The POU domain transcription factor OCT4 is a key regulator of pluripotency in the early mammalian embryo and is highly expressed in the inner cell mass of the blastocyst. Consistent with its essential role in maintaining pluripotency, Oct4 expression is rapidly downregulated during formation of the trophoblast lineage. To enhance our understanding of the molecular basis of this differentiation event in humans, we used a functional genomics approach involving RNA interference-mediated suppression of OCT4 function in a human ESC line and analysis of the resulting transcriptional profiles to identify OCT4-dependent genes in human cells. We detected altered expression of >1,000 genes, including targets regulated directly by OCT4 either positively (NANOG, SOX2, REX1, LEFTB, LEFTA/EBAF DPPA4, THY1, and TDGF1) or negatively (CDX2, EOMES, BMP4, TBX18, Brachyury [T], DKK1, HLX1, GATA6, ID2, and DLX5), as well as targets for the OCT4-associated stem cell regulators SOX2 and NANOG. Our data set includes regulators of ACTIVIN, BMP, fibroblast growth factor, and WNT signaling. These pathways are implicated in regulating human ESC differentiation and therefore further validate the results of our analysis. In addition, we identified a number of differentially expressed genes that are involved in epigenetics, chromatin remodeling, apoptosis, and metabolism that may point to underlying molecular mechanisms that regulate pluripotency and trophoblast differentiation in humans. Significant concordance between this data set and previous comparisons between inner cell mass and trophectoderm in human embryos indicates that the study of human ESC differentiation in vitro represents a useful model of early embryonic differentiation in humans.Stem Cells 03/2007; 25(2):500-10. · 7.70 Impact Factor
Article: Oct-4 knockdown induces similar patterns of endoderm and trophoblast differentiation markers in human and mouse embryonic stem cells.[Show abstract] [Hide abstract]
ABSTRACT: The transcription factor Oct-4 is a marker of pluripotency in mouse and human embryonic stem (ES) cells. Previous studies using a tetracycline-regulated Oct-4 transgene in the ZHBTc4 cell line demonstrated that downregulation of Oct-4 expression induced dedifferentiation into trophoblast, a lineage mouse ES cells do not normally generate. We found that transfection of Oct-4-specific short interfering RNA significantly reduced expression and functional activity of Oct-4 in mouse and human ES cells, enabling its role to be compared in both cell types. In mouse ES cells, Oct-4 knockdown produced a pattern of morphological differentiation and increase in expression of the trophoblast-associated transcription factor Cdx2, similar to that triggered by suppressing the Oct-4 transgene in the ZHBTc4 cell line. In addition, downregulation of Oct-4 was accompanied by increased expression of the endoderm-associated genes Gata6 and alpha-fetoprotein, and a gene trap associated with primitive liver/yolk sac differentiation. In human ES cells, Oct-4 knockdown also induced morphological differentiation coincident with the upregulation of Gata6. The induction of Cdx2 and other trophoblast-associated genes, however, was dependent on the culture conditions. These results establish the general requirement for Oct-4 in maintaining pluripotency in ES cells. Moreover, the upregulation of endoderm-associated markers in both mouse and human ES cells points to overlap between development of trophoblast and endoderm differentiation.Stem Cells 02/2004; 22(2):225-35. · 7.70 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Pluripotent mouse embryonic stem (ES) cells can be expanded in large numbers in vitro owing to a process of symmetrical self-renewal. Self-renewal entails proliferation with a concomitant suppression of differentiation. Here we describe how the cytokine leukaemia inhibitory factor (LIF) sustains self-renewal through activation of the transcription factor STAT3, and how two other signals - extracellular-signal-related kinase (ERK) and phosphatidylinositol-3-OH kinase (PI3K) - can influence differentiation and propagation, respectively. We relate these observations to the unusual cell-cycle properties of ES cells and speculate on the role of the cell cycle in maintaining pluripotency.Trends in Cell Biology 10/2002; 12(9):432-8. · 11.72 Impact Factor
Article: Suppression of SHP-2 and ERK signalling promotes self-renewal of mouse embryonic stem cells.[Show abstract] [Hide abstract]
ABSTRACT: The propagation of pluripotent mouse embryonic stem (ES) cells depends on signals transduced through the cytokine receptor subunit gp130. Signalling molecules activated downstream of gp130 in ES cells include STAT3, the protein tyrosine phosphatase SHP-2, and the mitogen-activated protein kinases, ERK1 and ERK2. A chimaeric receptor in which tyrosine 118 in the gp130 cytoplasmic domain was mutated did not engage SHP-2 and failed to activate ERKs. However, this receptor did support ES cell self-renewal. In fact, stem cell colonies formed at 100-fold lower concentrations of cytokine than the unmodified receptor. Moreover, altered ES cell morphology and growth were observed at high cytokine concentrations. These indications of deregulated signalling in the absence of tyrosine 118 were substantiated by sustained activation of STAT3. Confirmation that ERK activation is not required for self-renewal was obtained by propagation of pluripotent ES cells in the presence of the MEK inhibitor PD098059. In fact, the growth of undifferentiated ES cells was enhanced by culture in PD098059. Thus activation of ERKs appears actively to impair self-renewal. These data imply that the self-renewal signal from gp130 is a finely tuned balance of positive and negative effectors.Developmental Biology 07/1999; 210(1):30-43. · 3.87 Impact Factor
Article: Signaling mechanisms regulating self-renewal and differentiation of pluripotent embryonic stem cells.[Show abstract] [Hide abstract]
ABSTRACT: An ability to propagate pluripotent embryonic cells in culture is the foundation both for defined germline modification in experimental rodents and for future possibilities for broad-based cellular transplantation therapies in humans. Yet, the molecular basis of the self-renewing pluripotent phenotype remains ill-defined. The relationship between factors that influence embryonic stem cell propagation in vitro and mechanisms of stem cell regulation operative in the embryo is also uncertain. In this article we discuss the role of intracellular signalling pathways in the maintenance of pluripotency and induction of differentiation in embryonic stem cell cultures and the mammalian embryo.Cells Tissues Organs 02/1999; 165(3-4):131-43. · 1.96 Impact Factor
Article: Paracrine induction of stem cell renewal by LIF-deficient cells: a new ES cell regulatory pathway.[Show abstract] [Hide abstract]
ABSTRACT: The propagation of pluripotential mouse embryonic stem (ES) cells is sustained by leukemia inhibitory factor (LIF) or related cytokines that act through a common receptor complex comprising the LIF receptor subunit (LIF-R) and the signal transducer gp130. However, the findings that embryos lacking LIF-R or gp130 can develop beyond gastrulation argue for the existence of an alternative pathway(s) governing the maintenance of pluripotency in vivo. In order to define those factors that contribute to self-renewal in ES cell cultures, we have generated ES cells in which both copies of the lif gene are deleted. These cells showed a significantly reduced capacity for regeneration of stem cell colonies when induced to differentiate, confirming that LIF is the major endogenous regulatory cytokine in ES cell cultures. However, self-renewal was not abolished and undifferentiated ES cell colonies were still obtained in the complete absence of LIF. A differentiated, LIF-deficient, parietal endoderm-like cell line was derived and shown to support ES cell propagation via production of a soluble, macromolecular, trypsin-sensitive activity. This activity, which we name ES cell renewal factor (ESRF), is distinct from members of the IL-6/LIF family because (i) it is effective on ES cells lacking LIF-R; (ii) it is not blocked by anti-gp130 neutralizing antibodies; and (iii) it acts without activation of STAT3. ES cells propagated clonally using ESRF alone can contribute fully to chimaeras and engender germline transmission. These findings establish that ES cell pluripotency can be sustained via a LIF-R/gp130-independent, STAT-3 independent, signaling pathway. Operation of this pathway in vivo could play an important role in the regulation of pluripotency in the epiblast and account for the viability of lifr -/- and gp130 -/- embryos.Developmental Biology 12/1998; 203(1):149-62. · 3.87 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The propagation of embryonic stem (ES) cells in an undifferentiated pluripotent state is dependent on leukemia inhibitory factor (LIF) or related cytokines. These factors act through receptor complexes containing the signal transducer gp130. The downstream mechanisms that lead to ES cell self-renewal have not been delineated, however. In this study, chimeric receptors were introduced into ES cells. Biochemical and functional studies of transfected cells demonstrated a requirement for engagement and activation of the latent trancription factor STAT3. Detailed mutational analyses unexpectedly revealed that the four STAT3 docking sites in gp130 are not functionally equivalent. The role of STAT3 was then investigated using the dominant interfering mutant, STAT3F. ES cells that expressed this molecule constitutively could not be isolated. An episomal supertransfection strategy was therefore used to enable the consequences of STAT3F expression to be examined. In addition, an inducible STAT3F transgene was generated. In both cases, expression of STAT3F in ES cells growing in the presence of LIF specifically abrogated self-renewal and promoted differentiation. These complementary approaches establish that STAT3 plays a central role in the maintenance of the pluripotential stem cell phenotype. This contrasts with the involvement of STAT3 in the induction of differentiation in somatic cell types. Cell type-specific interpretation of STAT3 activation thus appears to be pivotal to the diverse developmental effects of the LIF family of cytokines. Identification of STAT3 as a key transcriptional determinant of ES cell self-renewal represents a first step in the molecular characterization of pluripotency.Genes & Development 08/1998; 12(13):2048-60. · 12.44 Impact Factor
Top Journals
The University of Edinburgh
Edinburgh, SCT, United Kingdom
- • Roslin Institute
- • Royal (Dick) School of Veterinary Studies
- • Credit Research Centre
The Roslin InstituteEdinburgh, Scotland, United Kingdom


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Tuesday, February 7, 2012
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The issue features an interview with ANOC president Sheikh Ahmad, a look...
October 29, 2014
(ATR) The head of the Committee to Protect Journalists says the IOC is facing a "crisis" in its search for a 2022 Winter Olympics host.
CPJ executive director Joel Simon to...
October 28, 2014
(Getty Images)
(ATR) Adam Vaccaro, writer for Boston.com, features a group that could try to block the 2024 Summer Olympics from coming to Boston. If the U.S. Olympic Committ...
October 23, 2014
The set of NBC's Today Show during the Sochi Olympics (Getty Images)
(ATR) Thomas Bach said on Thursday that the IOC will move deliberately in its efforts to set up an Olympi...
(ATLANTA) -- War and civil strife, health crises, economics, natural disasters, and government interference -- all in a day's work for the world's 200+ national Olympic Commit...
October 21, 2014
Oscar Pistorius in court prior to his sentencing on Tuesday (Getty Images)
(ATR) Gushwell Brooks, a radio talk show host and columnist in South Africa, tells Around the Rings...
October 13, 2014
(Getty Images)
(ATR) Reporter Steve Blakely, who covered the 1980 Winter Olympics, says that as Washington vies to bid for the 2024 Games, it can learn from previous hosts. "...
October 10, 2014
The announcement was made at Sportel Monaco. (SPORTELMonaco)
(ATR) German network Sport1 has agreed to broadcast 17 days of 2015 European Games coverage, the biggest network ...


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Astoria fishery is transforming the anchovy from bait to foodie treat
Whiting fishers have volunteered to tie up their boats until July 20 due to intermingling with overfished canary rockfish.
A sewer system that has been in the works since 1999 finally opened in the Miles Crossing Sanitary Sewer District, near Astoria.
Seafood Watch guide says to "avoid" wild-caught salmon, despite Oregon's first commercial salmon fishing season in three years.