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Our always popular speaker Lee Rainie discusses the Project's new research about those who use the library and those who do not: who they are, what their information needs are, what kinds of technology they use, and how libraries can meet the varying needs of their patrons. This keynote is filled with strategies and opportunities for libraries!
Libraries are all about creating know-how, know-that, and ahas! Increasing this impactful interaction with our communities happens digitally. Immerse yourself in this track about how libraries are creating digital services, information and processes.
Highly effective digital branch services are simpler, cheaper, and closer at hand than you think. This session lays the foundation for a less-is-more approach to launching your next web project and iterating through a continuous cycle of feedback and improvement. Fitzpatrick introduces some free or cheap tools as well as a proven process that will set up your web team for a successful product your patrons will love.
Hear about an all-electronic business branch library that has continually transformed itself and become an integral part of the Notre Dame business school's educational system. Speakers describe the library's services, working relationships with students and faculty, staffing model and staff competencies, funding and licensing approaches, and, perhaps most importantly, how they continuously strategize and evolve themselves to be true partners in the business faculty.
This session focuses on innovative approaches to dealing with copyright and student tutorials. Learn how SIPX's university pilots are using real-time copyright clearance, matching assigned readings to library holdings for maximum ROI and library recognition for subscribed content, and calculating the lowest pricing for access. Hear about UC Merced's use of Guide on the Side, open source tutorial software developed by the University of Arizona Libraries. Instead of screencasting, users get instructions on one side of the screen, and interact with the actual webpage, catalog or other search tool in another pane on the other side of the screen—authentic learning at its best!
Hennig begins this session with a look at various multi-touch, multimedia ebooks that create learning experiences for all types of readers, including people with disabilities. She examines the book as iPad app and the potential for use in innovative library programs and services. Kirker and Kerns demonstrate how librarians at a medium-sized private university developed, designed, and assessed the implementation of iPad kiosks as service points within the library. Wireless tablets are compact alternatives to the traditional computer, but there are some complications. Speakers highlight these complications as well as the solutions developed.
As budgets shrink, organizations must be creative to fund their programs. Menon and Koury discuss the world of crowd-funding. They explore funding websites, discuss the pros and cons on online fundraising, and share examples on how some libraries, individuals, or organizations have successfully used this tool.
Design and user experience reflect the relevancy and importance of whatever we do. This track is filled with ideas and insights for creating easier-to-use and more engaging user experiences.
Many libraries have institutionalized usability testing to improve their websites, but task-based testing, while extremely useful, only paints a partial picture. How do we know what tasks our users need and want to perform? We don't; we need to ask them, and ask them again and again. This session discusses the who, what, where, when, how, and why of using user interviews and personas, along with task-based testing, to provide the missing link in designing a site that's not only usable, but also useful, and maybe even desirable, for library users.
Website design as a field is still changing rapidly as new technologies and new design ideas are created to make websites more beautiful, functional, and user friendly. King takes you through the newest web design trends for optimizing user experience, illustrates with examples, lets you know what to incorporate, what to watch for, and what to ignore.
Usability testing is one of the most effective ways for libraries to connect with their user base while assessing and improving their online presence. At its best, usability testing is a highly collaborative process. The feedback, support, and time your colleagues contribute is key to even one round of successful testing, to say nothing of ongoing iterative testing. But how do you secure stake- holder buy-in and demonstrate that usability testing is a valuable undertaking? O'Donnell explores this question and offers practical guidance and strategies for implementing usability testing. The second presentation discusses how Webster University Library's web committee decided to conduct usability testing on their current website design to plan for a possible future redesign. After reviewing various testing models, they felt that observational task analysis would be the most cost-effective yet efficient model for a first round of testing. Hear how they utilized Adobe Connect to record and capture participants' actions, the pros and cons to using Adobe Connect for usability testing, and preliminary results of their findings. Future plans and lessons learned from usability testing are discussed by both speakers.
This presentation focuses on the experience of a multilibrary system as it seeks to collaborate on multiple initiatives to streamline the user experience by creating cohesive web design and a unified discovery framework. Topics of discussion include development of a unified brand, implementation of shared applications and services, and large-scale projects undertaken in support of an enhanced and improved user experience. This talk also addresses the leadership dynamics undertaken to facilitate this process and discusses the growing pains experienced during this transition. This presentation offers feedback to other library systems experiencing similar transitions.
As the rest of this track has demonstrated, the principles and practices of UX design are particularly pertinent when it comes to designing web interfaces and systems. But there are wide-ranging benefits to applying these same principles and practices to everything libraries design, from service desks to signage. Join us for the final presentation of the UX track as Etches and Schmidt explore ways to harness UX principles to improve virtual touch- points, as well as physical ones.
As enterprises are evolving, so are their information services and the competition to prove value and secure funding. Our speakers discuss digitization and social media, strategies and tech tools to engage communities, info pro skills for the future, and more.
How does a two-person library/archive manage 14 social media sites, get 2.5 million views on its Flickr photo site in less than 5 years, acquire thousands of Twitter followers, and become a leader in daily news publishing while supporting reference and other traditional library activities? Get strategies and tools to successfully implement integrated digitization and social media on a grand scale despite having a very small staff, a large service population, and limited resources. Hear about a proactive approach to deploying new technologies, including harvesting resources from within documents and manuscripts and using social media to promote higher interest in digital collections. How to leverage automated processes with social media and develop a digitization plan focused on the benefits for decision-makers and users are shared.
This session covers technology for connecting in new ways to your immediate library community and also reaching out to new and unknown communities. It discusses a process that can be adapted for any library, including a rare book library and a health sciences library. Hear from an outreach librarian who uses new strategies, services, and tools to allow the library to live beyond its bookshelves for more active promotion. The CAMH Library is actively engaging users outside of the library using web development tools and techniques including audio/video software such as GarageBand and iMovie, Web 2.0 tools such as Facebook, YouTube, Flickr, Pinterest, and Vine, and content management software such as Drupal. Barriers, challenges, pitfalls, and timelines for launching new projects using emerging technologies for the user experience are shared, including listening to your userbase and working with your corporate structure.
The first presentation discusses how info pros are well- positioned to help design metadata schema, apply governance principles, and understand end-user needs such as searching and delivery of content. All of these strengths are essential to the success of a digital asset management (DAM) project. It emphasizes the skills to enhance your professional toolkit for DAM project readiness and gives examples of DAM librarians (e.g., in corporate marketing departments, museums, creative services). Kneale discusses how she wears three different systems hats: systems administrator, systems engineer, and systems librarian. She shares information about these three jobs and shows how the tools and skills of librarianship are used to add value to all areas of responsibility.
Hear from two libraries in the same industry. Evans discusses engaging clients in a large corporation with no physical libraries, sites closing, and people exiting. During these turbulent times, Pfizer's Information & Library Services group has been successful by selecting specific client groups and formulating a targeted marketing plan; outcomes of the marketing plan and outreach activities are shared. In the second case study, speakers discuss how when Ironwood Pharmaceuticals expanded from a mostly R&D operation to include business development, medical scientific affairs, legal, commercial and pharma-covigilance, not only were more database and journal subscriptions needed, so were ways to stay within budget, engage the user population to inform them of available tools and services, and disseminate information through the company. They highlight various tools and techniques used to coordinate transcontinentally between one remote librarian and one onsite librarian.
Public librarians are fortunate in that there always seems to be a "next big thing" for their institutions to offer to engage and serve their constituents—ebooks, gaming, cutting-edge programming, clubs, unique lending, etc. For corporate and law firm librarians, the challenge to stay innovative is a bit more tricky. We know the value that we bring, and we know what we can do, but how do we remain vital, vibrant, and interesting to the people who we serve when it seems like we have nothing new to offer? How can we continually market our services to keep them fresh, constantly applicable, and responsive to our organization's challenges? This session explores several techniques to keep our current requestors as happy as ever while adding new requestors and users of our services; it also includes embedded librarianship, clips and alerts, rainmaking, and Pinterest for customizing library experiences to help customers prepare for practicing law in the information age; and ultimately transform the traditional law library into a 21st-century information hub.
Libraries are dynamic organizations which demand dynamic management practices and lots of planning. Hear how libraries are using appreciative inquiry to plan changes and project management to track progress, learn about building digital teams and moving staff from tech shy to tech savvy. Filled with tips and techniques for dealing with change.
Is your library contemplating reinventing itself in response to social, economic, and technology trends and searching for an effective process of self-discovery? This session explains how Howard County Library System and Somerset County Library System applied appreciative inquiry (AI), a philosophy of organizational change based on positive psychology and constructionist learning theory, to strategic planning to create an inclusive and participatory do-it- yourself process that transformed stakeholders from staff to customers to community leaders into strategic thinkers imagining new possibilities for their libraries. Belfont provides an overview of both theoretical foundations and action steps of Appreciative Strategic Planning, including the Discovery Stage, the Dream Stage, and the Design Stage, in a strategic plan. It is an autobiography, the next chapter in a library's history, co-written by the stakeholders, expressing who they are, what they do, and why the library is important to their communities. Appreciative Strategic Planning locates the forces that give life to libraries—stakeholder passion, intelligence, creativity, aspirations—do not become irrelevant, and are essential to their future adaptability, resilience, and success.
Projects, projects, projects! How do libraries manage, keep track of progress, and collaborate on projects? This talk provides a few different looks at current project management practices in a variety of libraries. Speakers focus on project management software options, and share some tips on selecting and implementing appropriate project management software to fit a library's needs. They report on findings from a survey of libraries currently using project management software or other tools to track projects. Survey results show a snapshot of which platforms libraries are currently using, and what types of library projects are a good fit for project management software. Presenters share standards and best practices from the project management industry and frame their analysis using these principles.
The first talk shares a how-to manual that will change the dynamics of your library regardless of your environment. It is based on four years of evidence of the library revitalization, the transformation of student success through library initiatives, and also the recent approval of a mandatory, library-led first year experience course. The journey began with the charge to assess the current state of the university library, create a library strategic plan, look at eliminating library services and/or identify a process to revitalize the library. It culminated in an approved learning outcome called "information literacy and technology" as a result of the library's success. Hear the step-by-step process for developing library stakeholders in the campus and area communities through proven high-impact practices. In the second presentation, hear how one librarian used techniques from Think and Grow Rich by Napoleon Hill and How to Win Friends and Influence People by Dale Carnegie to transform the Tyrone Bryant Branch, doubling reference stats, tripling summer reading program numbers, and cutting customer complaints. By requiring the staff to read Think and Grow Rich, answer questions about it, and scheduling self-improvement courses, he was able to lead his team to success. Get some tips & techniques from this talk.
This session covers the process VPL followed to develop a new digital services department focused on web projects, digital licensing, and community digital engagement. It covers key elements of the planning process (measuring the effort that was currently going toward digital projects, assessing current and future needs, and determining staffing numbers and roles) and implementation (developing training plans, team building, creating a sense of urgency and fostering creativity, and setting department norms). Hear about their first projects—the overhaul of VPL's corporate intranet and the creation of a city-wide informal learning calendar. Gain valuable insights and lessons learned, and leave with a template that can be modified to develop new digital centers in your organization.
Given the changing role of the librarian as provider of "tech support," this session looks at increasing the skills of staff in digital literacy and information technology, addresses the attitudes and flexibility of tech-shy staff members to increase their comfort level with today's rich and dynamic information landscape, and shares a partnership that provides additional support. Speakers share experiences from two public libraries providing training around ebook downloads, handheld devices, navigating web and mobile apps, and using social media to empower staff with the confidence patrons expect around technology at the information desk. They discuss assessing needs through surveys and interviews and designing training series according to results, new software and web applications, and system updates, as well as offering one-on- one sessions and tablet checkouts to staff for hands-on practice; providing "how-to" documentation; and taking the lead in collaborative social media projects such as readers' advisory on Facebook and the creation of a department Goodreads account. They describe community partnership with Best Buy, including their provision of tablets and e-readers to update their "Tech Petting Zoo," and co-trainings with Geek Squad experts. They discuss the importance of staff trainings in preparing librarians to ease patrons' tech-induced frustration and speak from a knowledgeable and confident perspective.
On Day 2 of the 2-day, K–12-focused Internet@Schools track, learn about the online badging movement, social action research, ebooks in schools, LibGuides, and open educational resources.
Do you yearn for a free and fun way to provide incentives for students and encourage positive work habits? Do you wish you could reward good citizenship and foster creativity and work that goes beyond the expected? Online badging is for you! This motivational practice is growing in popularity with students and educators at all levels. Badges are already in use with commercial applications such as Edmodo and Dojo, but creating your own can be even more fun and rewarding. And it's free! Bell and Weimar share their firsthand experiences with their students and also those of K–12 educators. They will offer steps for starting up a system and then maintaining it efficiently and effectively. Attendees leave the session with specific ideas that will help make such a program successful and effective.
What happens when middle school students are challenged to make a difference in their world? Learn how sixth-grade students researched a topic about a local or global problem, its causes and current solutions, and how they could personally get involved. The entire research was done without printing a single sheet of paper using Google Docs and online digital resources such as databases, the internet, and citation tools. The original project grew to include persuasive essays, a student presentation at a Nebraska State Legislature committee hearing, and a Make a Difference Share Fair, where groups of students presented their research findings to the general public and raised money for their causes. This project has led students to independently volunteer and to make a difference in their world.
Internet@Schools track co-moderator Foote provides an overview of recent news on the ebook front and discusses trends in the ebook market for schools. Then Arriaga and Simons offer detailed steps on their e-reader program and how they streamlined the process of device selection, cataloging, funding, promotion, support programs, and curriculum integration. They address the challenges their program encountered as they navigated through the newly evolving landscape of ebooks in the publishing and retail book industry, as well as how e-readers fit into the life of a library and within OPACS.
As education changes and people talk about online learning, blended classes, ebooks and tablets, there is one constant--teachers. Whether students are using technology in a classroom with face-to-face instruction, receiving instruction through a flipped classroom model, or taking a class that is entirely online, instruction is impacted by teachers. But has professional development kept up with the changes in the way instruction is delivered? As time demands increase and as "sit and get" professional development has less impact, some are exploring additional ways to meet the challenges and provide that professional development. Attendees will see a variety of ways that training can be provided either fully online or using a flipped model, explore platforms for presenting different options, and discuss ways to engage learners.
Join a well-known expert on the vital subject of finding free educational resources online. Veteran web resource locator Gary Price discusses discovery and finding tools, techniques, and even the necessary mind-set you need to unearth the best digital content for education—so you can serve up just what's needed for that social studies or history class, just when it's needed.
Be prepared to be excited and inspired by librarians who have engaged their communities in novel ways. This fast-paced, fun learning event can only be described as Cybertours meets Pecha Kucha meets Battledecks meets TED! Join us for an amazing session of insights and ideas that you will want to implement in your library immediately. Hear about the Story sail boat off the California coast, leveraging "techkknowledgie" by sharing skills in other countries, game based learning, interactive maps, and recommended apps from librarianAPProved.com! Leave the status quo behind and return to work inspired and ready to transform your world.


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Before Ol' Myrt here unceremoniously deleted a reader's valid email, along with the usual SPAM, I noted in the preview screen that the request went something like this:
"I am getting an old family bible rebound with a new cover. The first pages have lots of family notations in pencil, but some pages have deteriorated and are in pieces. The bookbinder suggests using contact paper to keep things from falling apart."
AAACK!!! I am thinking you mean that clear contact paper that is normally used to line cupboard shelves. CERTAINLY NOT!
PLEASE understand that a regular book binder isn't necessarily an archivist.
There IS a type of paper used by trained archivists that looks like very thin tissue paper. It is low acid, and requires skill to use without further damaging the pages in question.
1. MAKE SURE your book binder is a member of The AMERICAN SOCIETY OF ARCHIVISTS, or is recommended by your state's archivist. Each state HAS an archivist, and some counties, such as Sarasota County, Florida have archivists that work in historic preservation positions with the government.
2. CAREFULLY MAKE PHOTOCOPIES of these precious family pages so they won't need to be handled unnecessarily.
3. FIND OUT MORE ABOUT PRESERVATION of family heirlooms, including study at these sites:
-- Library of Congress' "Preparing, Protecting, Preserving Family Treasures" http://www.loc.gov/preserv/familytreasures
-- North East Document Conservation Center's "NEDCC Offers Hints for Preserving Family Collections"
-- A great Source for preservation materials (including an acid-free box for storing your family bible) see: http://www.lightimpressionsdirect.com
-- Northeast Document Conservation Center's "Supplier's List"
Happy family tree climbing!
Myrt :)
DearMYRTLE, your friend in genealogy
Snail Mail Address:
227 Bellevue Way NE PMB 544
Bellevue, WA 98004

subset: commoncrawl


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Welcome to my blog. As we had our first winter snow storm this week, I continued with my daily activities as Archbishop of Boston.
My friends John and Claire Bertucci, who are members of the board of trustees of the Isabella Stewart Gardner Museum, invited me to have a tour of the museum last week.
That's Anne Hawley, director of the museum,
pointing out a feature of the courtyard.
With us is Damien DeVasto, who works with us at the archdiocese,
and John and Claire Bertucci.
I enjoyed the tour, and it is wonderful to think that we have this grand resource here in Boston that does so much to promote knowledge and appreciation of the arts, particularly among students. Some of our Catholic schools are very tied into the programs of the museum.
Admiring a Raphael artwork titled Count Tommasso Inghirami
A beautiful crucifix from XVI century Venetian artist Francesco Terilli
Virgin and Child Enthroned with Saint from Giuliano da Rimini, XIV century,Italian
It was interesting to see how the interior courtyard had been made by bringing actual balconies from Venice.
The museum web site has a very nice animation of the Courtyard. Watch it here
I noticed that one of the balconies in the courtyard even had a coat of arms with a Franciscan symbol on it, as I have on my own — the crossed arms of St. Francis and Christ.
You can see the arms of St. Francis and Christ in my coat of arms
The Church has always been involved in promoting art, music and architecture as a way of manifesting for people a glimpse of God's beauty. The beauty of art helps people to understand God's beauty and His goodness. This can attract people to God.
Sandro Botticelli's Virgin and Child with an Angel, from the early 1470s
I enjoyed the visit very much
– – –
I attended the Catholic Charities Greater Boston annual Christmas Dinner that took place at the Fairmont Copley Plaza in Boston Dec. 7. It had a very good turnout. In fact I think it was one of the best turnouts the dinner has ever had, which is a very good sign.
A general view of the room
The work of Paulo De Barros and others at the Teen Center at St. Peter's in Dorchester was highlighted. A young lady from the center spoke, and there was a dance group of Cape Verdean youth that entertained the people at the dinner.
A cape Verdean dance group
The new Catholic Charities president, Tiziana Dearing, gave a very inspiring talk. It was her first dinner as president. And of course Vivian Soper, director of Catholic Charities Greater Boston, also spoke. She is doing a wonderful job in that important role at Catholic Charities.
From left Vivian Soper, director of Catholic Charities Greater Boston;
Michael Gilleran, chair of the Catholic Charities Greater Boston Advisory Board,
and Tiziana Dearing, president of Catholic Charities, Archdiocese of Boston
– – –
On Saturday, I installed Father Walter Carreiro as pastor of St. Anthony of Padua Parish in Cambridge.
A large contingent of priests and St. Anthony parishioners were there.
Most of the parishioners at the parish are Portuguese, but there is a growing Brazilian presence there.
Father Carreiro's mother and some of his relatives were also able to be present for the Mass.
With Father Walter Carreiro
Afterwards, there was a huge Portuguese dinner in the parish hall for everyone.
People had a wonderful time, and they were very enthused.
The outgoing pastor, Father Jose Ferreira, who had served the parish for so many years was present at the installation Mass. He received a big ovation from the people, and the good news is that he is able to continue to help out in the parish.
Father Ferreira greeting his "former" parishioners
– – –
On Sunday, I celebrated an Advent Mass at Holy Family Parish in Amesbury.
They had a very good turnout, and afterwards there was a reception in the hall.
– – –
On Wednesday, I met with the seminarians at St. John's for an evening of prayer. I meet with them occasionally and we always have a holy hour, dinner and then a conversation.
This time, I gave them a talk about Our Lady of Guadalupe — it was her feast day — and the role of the priest in building unity in the community. I spoke about how the apparition of Our Lady of Guadalupe, who came in the form of an indigenous woman, helped to break down the barriers that had stood in the way of the evangelization of America.
Today, we also face many barriers in our very secularized culture, but we have to know how to break those down and to build unity. I talked about the first great challenges in the Church. The first Council of Jerusalem is called in the Acts of the Apostles to confront the kinds of tensions that came about because of the ethnic differences in the community. The variety of seminarians we have here in Boston, I think helps the men to learn how to embrace the catholic — universal — nature of our Church.
After my talk, there were many interesting questions. The seminarians wanted to know about the new ministry to youth that is being organized in the archdiocese through a new department for the new evangelization of youth. They were enthusiastic about that. Some of them asked about the school 2010 Initiative and the implications for Catholic education as we go forward. Other seminarians talked about their upcoming trip to Peru to visit our men in the Missionary Society of St. James who are currently serving there.
This time, they did not take any pictures of the evening, but later they sent me the following photo, taken a couple of days later, as some of them were digging out after the first winter storm of the season that left around one foot of snow at St. John's.
We have a group of new seminarians from South East Asia at St. John's this year and, I am told, this was the first time they saw snow… and the first time they had to shovel it, lol.
– – –
On Thursday I addressed a group of people attending the Christ Speaks in the City Lecture Series. The event is hosted by the Vocation Office of the Archdiocese at the Old State House located in the heart of Downtown Boston's Financial Center.
The Old State House is a beautiful venue. It was the seat of government during the British colonial period in Boston and is now a museum.
The Vocations Office has been having a lecture series there for professionals and people who work in town as a way to try to be present to that population and as a way to increasing the Church's contact with young professionals in the downtown Boston.
I gave a conference on prayer an discipleship. In it, I tried to stress the fact that without prayer it is impossible to lead a life of faith and to really be faithful disciples. The people in the group we very receptive to the message and there were several questions afterwards
I talked to them about Jesus' example and teachings on prayer, particularly in the Gospels of Matthew and Luke.
I tried to give an explanation of the "Our Father" which the Church has always considered the model for prayer the one that Jesus Himself taught us. I tried to stress the fact that in prayer we are trying to achieve union with God and that in prayer we come to embrace God's will with great trust. I ended my conference by praying the so-called prayer of abandonment of Charles de Foucauld, the prayer that I have in my prayer card:
Father, I abandon myself into your hands;
do with me what you will.
Whatever you may do, I thank you:
I am ready for all, I accept all.
Let only your will be done in me,
and in all your creatures – I wish no more than this, O Lord.
Into your hands I commend my soul:
I offer it to you with all the love of my heart,
for I love you, Lord, and so need to give myself,
to surrender myself into your hands without reserve,
and with boundless confidence, for you are my Father.
The talk was very well attended even as we were expecting a winter storm to hit Boston at the same time. In fact, by the end of the event it was already snowing heavily.
It took us a long time to get home, which is less than 2 miles away from the Old State House. The snow caused great traffic jams in Boston as everybody started going home instead of going for lunch… so everyone tried to leave the city at the same time.
– – –
For the photo of the week I am sharing with you this photo of my visit to the Gardner Museum. I am impressed by the beauty of the place and the amount of art hosted in there.
God Bless,
Cardinal Seán.


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Vikings: War of Clans is an MMO strategy game that has taken over the planet! Join millions of players from all around the globe and fight for power against worthy opponents!
These harsh lands raise up true Vikings, ones who can survive all the hardships of warrior life and win glorious victories! Are you ready to rush into this bitter confrontation and gain the prized title of Konung of the Kingdom? A true warrior has but one answer: "Let the battle begin!"
Seize your chance to build a great Town that will make all approaching enemies tremble in fear! Create a mighty army by training the strongest infantrymen, killers, cavalry, ranged and siege troops, as ahead of you lie battles with other Jarls, struggles for the Place of Power, fights with fierce Invaders and the massive Kingdoms Battle — and let all result in your victory and your opponents' defeat! Don't forget about allies — join a powerful Clan or create your own: in your hour of need, loyal friends will lend a helping hand!
This universe of mighty warriors, bitter frost and savage struggle needs new heroes! Embrace your inner Viking and capture the riches of the North that are yours by right!
Additional Details
|Release Date
|January 16, 2017
System Requirements
|Internet Connection


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Academic Appointments
Assistant Professor, Pathology
Member, Bio-X
Member, Wu Tsai Neurosciences Institute
We are interested in addressing questions in neuronal development and function by a combination of genetic, cell biological, biochemical and chemical approaches.
The main focus of our lab is centered around two topics: 1) the interface of signaling and gene regulation in neuronal development, with a focus on calcineurin-NFAT signaling; 2) the development of small molecules, which interfere with pathogenic protein-protein interactions underlying neurodegenerative diseases.
The misassembly of soluble proteins into toxic aggregates, including amyloid fibrils, underlies a large number of human degenerative diseases. Cardiac amyloidoses, which are most commonly caused by aggregation of Ig light chains or transthyretin (TTR) in the cardiac interstitium and conducting system, represent an important and often underdiagnosed cause of heart failure. Two types of TTR-associated amyloid cardiomyopathies are clinically important. The Val122Ile (V122I) mutation, which alters the kinetic stability of TTR and affects 3% to 4% of African American subjects, can lead to development of familial amyloid cardiomyopathy. In addition, aggregation of WT TTR in individuals older than age 65 y causes senile systemic amyloidosis. TTR-mediated amyloid cardiomyopathies are chronic and progressive conditions that lead to arrhythmias, biventricular heart failure, and death. As no Food and Drug Administration-approved drugs are currently available for treatment of these diseases, the development of therapeutic agents that prevent TTR-mediated cardiotoxicity is desired. Here, we report the development of AG10, a potent and selective kinetic stabilizer of TTR. AG10 prevents dissociation of V122I-TTR in serum samples obtained from patients with familial amyloid cardiomyopathy. In contrast to other TTR stabilizers currently in clinical trials, AG10 stabilizes V122I- and WT-TTR equally well and also exceeds their efficacy to stabilize WT and mutant TTR in whole serum. Crystallographic studies of AG10 bound to V122I-TTR give valuable insights into how AG10 achieves such effective kinetic stabilization of TTR, which will also aid in designing better TTR stabilizers. The oral bioavailability of AG10, combined with additional desirable drug-like features, makes it a very promising candidate to treat TTR amyloid cardiomyopathy.
View details for DOI 10.1073/pnas.1300761110
View details for Web of Science ID 000320930100085
View details for PubMedID 23716704
Drug design studies targeting one of the primary toxic agents in Alzheimer's disease, soluble oligomers of amyloid ?-protein (A?), have been complicated by the rapid, heterogeneous aggregation of A? and the resulting difficulty to structurally characterize the peptide. To address this, we have developed [Nle(35), D-Pro(37)]A?(42), a substituted peptide inspired from molecular dynamics simulations which forms structures stable enough to be analyzed by NMR. We report herein that [Nle(35), D-Pro(37)]A?(42) stabilizes the trimer and prevents mature fibril and ?-sheet formation. Further, [Nle(35), D-Pro(37)]A?(42) interacts with WT A?(42) and reduces aggregation levels and fibril formation in mixtures. Using ligand-based drug design based on [Nle(35), D-Pro(37)]A?(42), a lead compound was identified with effects on inhibition similar to the peptide. The ability of [Nle(35), D-Pro(37)]A?(42) and the compound to inhibit the aggregation of A?(42) provides a novel tool to study the structure of A? oligomers. More broadly, our data demonstrate how molecular dynamics simulation can guide experiment for further research into AD.
View details for DOI 10.1021/jm201332p
View details for Web of Science ID 000302591100010
View details for PubMedID 22420626
A valine-to-isoleucine mutation at position 122 of the serum protein transthyretin (TTR), found in 3 to 4% of African Americans, alters its stability, leading to amyloidogenesis and cardiomyopathy. In addition, 10 to 15% of individuals older than 65 years develop senile systemic amyloidosis and cardiac TTR deposits because of wild-type TTR amyloidogenesis. Although several drugs are in development, no approved therapies for TTR amyloid cardiomyopathy are yet available, so the identification of additional compounds that prevent amyloid-mediated cardiotoxicity is needed. To this aim, we developed a fluorescence polarization-based high-throughput screen and used it to identify several new chemical scaffolds that target TTR. These compounds were potent kinetic stabilizers of TTR and prevented TTR tetramer dissociation, partial unfolding, and aggregation of both wild type and the most common cardiomyopathy-associated TTR mutant, V122I-TTR. High-resolution co-crystal structures and characterization of the binding energetics revealed how these diverse structures bound to tetrameric TTR. These compounds effectively inhibited the proteotoxicity of V122I-TTR toward human cardiomyocytes. Several of these ligands stabilized TTR in human serum more effectively than diflunisal, which is a well-studied inhibitor of TTR aggregation, and may be promising leads for the treatment or prevention of TTR-mediated cardiomyopathy.
View details for DOI 10.1126/scitranslmed.3002473
View details for Web of Science ID 000294207000005
View details for PubMedID 21865539
View details for PubMedCentralID PMC3227540
Schwann cells develop from multipotent neural crest cells and form myelin sheaths around axons that allow rapid transmission of action potentials. Neuregulin signaling through the ErbB receptor regulates Schwann cell development; however, the downstream pathways are not fully defined. We find that mice lacking calcineurin B1 in the neural crest have defects in Schwann cell differentiation and myelination. Neuregulin addition to Schwann cell precursors initiates an increase in cytoplasmic Ca2+, which activates calcineurin and the downstream transcription factors NFATc3 and c4. Purification of NFAT protein complexes shows that Sox10 is an NFAT nuclear partner and synergizes with NFATc4 to activate Krox20, which regulates genes necessary for myelination. Our studies demonstrate that calcineurin and NFAT are essential for neuregulin and ErbB signaling, neural crest diversification, and differentiation of Schwann cells.
View details for DOI 10.1126/science.1166562
View details for Web of Science ID 000262862800048
View details for PubMedID 19179536
View details for PubMedCentralID PMC2790385
An increase in extracellular Ca(2+) induces the nuclear localization of the Crz1 transcription factor and the activation of target genes in yeast. A recent study indicates that nuclear entry occurs in short stochastic bursts that are unsynchronized within the population of cells. The frequency but not the amplitude of the bursts is controlled by Ca(2+). Modulation of the frequency of the burst coordinates aspects of expression of Crz target genes.
View details for DOI 10.1126/scisignal.151pe54
View details for Web of Science ID 000207497900002
View details for PubMedID 19109237
View details for PubMedCentralID PMC2713346
The diversity of dendritic patterns is one of the fundamental characteristics of neurons and is in part regulated by transcriptional programs initiated by electrical activity. We show that dendritic outgrowth requires a family of combinatorially assembled, neuron-specific chromatin remodeling complexes (nBAF complexes) distinguished by the actin-related protein BAF53b and based on the Brg/Brm ATPases. nBAF complexes bind tightly to the Ca(2+)-responsive dendritic regulator CREST and directly regulate genes essential for dendritic outgrowth. BAF53b is not required for nBAF complex assembly or the interaction with CREST, yet is required for their recruitment to the promoters of specific target genes. The highly homologous BAF53a protein, which is a component of neural progenitor and nonneural BAF complexes, cannot replace BAF53b's role in dendritic development. Remarkably, we find that this functional specificity is conferred by the actin fold subdomain 2 of BAF53b. These studies suggest that the genes encoding the individual subunits of BAF complexes function like letters in a ten-letter word to produce biologically specific meanings (in this case dendritic outgrowth) by combinatorial assembly of their products.
View details for DOI 10.1016/j.neuron.2007.08.021
View details for Web of Science ID 000250289800013
View details for PubMedID 17920018
Mammalian neural stem cells (NSCs) have the capacity to both self-renew and to generate all the neuronal and glial cell-types of the adult nervous system. Global chromatin changes accompany the transition from proliferating NSCs to committed neuronal lineages, but the mechanisms involved have been unclear. Using a proteomics approach, we show that a switch in subunit composition of neural, ATP-dependent SWI/SNF-like chromatin remodeling complexes accompanies this developmental transition. Proliferating neural stem and progenitor cells express complexes in which BAF45a, a Kr�ppel/PHD domain protein and the actin-related protein BAF53a are quantitatively associated with the SWI2/SNF2-like ATPases, Brg and Brm. As neural progenitors exit the cell cycle, these subunits are replaced by the homologous BAF45b, BAF45c, and BAF53b. BAF45a/53a subunits are necessary and sufficient for neural progenitor proliferation. Preventing the subunit switch impairs neuronal differentiation, indicating that this molecular event is essential for the transition from neural stem/progenitors to postmitotic neurons. More broadly, these studies suggest that SWI/SNF-like complexes in vertebrates achieve biological specificity by combinatorial assembly of their subunits.
View details for DOI 10.1016/j.neuron.2007.06.019
View details for Web of Science ID 000248635800006
View details for PubMedID 17640523
View details for PubMedCentralID PMC2674110
The calcium/calcineurin-dependent NFATc family is thought to have arisen following the recombination of an ancient precursor with a Rel domain about 500 million years ago, producing a new group of signaling and transcription factors (the NFATc genes) found only in the genomes of vertebrates. Cell biological, genetic and biochemical evidence indicates that the circuitry of this pathway is well suited for intercalation with older pathways. We propose that this recombination enabled Ca(2+) signals to be redirected to a new transcriptional program, which provided part of the groundwork for vertebrate morphogenesis and organogenesis. This notion predicts that calcineurin-NFAT signaling would be essential for much of vertebrate development. We review recent evidence supporting this prediction and propose a systematic approach to explore aspects of vertebrate morphogenesis.
View details for DOI 10.1016/j.tcb.2007.04.006
View details for Web of Science ID 000247508200001
View details for PubMedID 17493814
The molecular mechanism and significance of endocytic processes involved in directional axon elongation are not well understood. The Unc-51 family of serine/threonine kinases was shown to be important for axon growth and was also linked to endocytosis, providing an entry point to study this problem. We found that mouse Unc-51-like kinase 1/2 (Ulk1/2) proteins are localized to vesicular structures in growth cones of mouse spinal sensory neurons. RNAi-mediated knockdown of Ulk1 and/or Ulk2 resulted in impaired endocytosis of nerve growth factor (NGF), excessive axon arborization, and severely stunted axon elongation. The evidence also indicates that Ulk1/2 mediates a non-clathrin-coated endocytosis in sensory growth cones. Interestingly, NGF can induce the interaction of Ulk1 with TrkA receptor complexes through promoting K63-polyubiquitination of Ulk1 and binding of Ulk1 to the scaffolding protein p62. These results and additional studies suggest that Ulk1/2 proteins regulate filopodia extension and neurite branching during sensory axon outgrowth, probably through regulating TrkA receptor trafficking and signaling.
View details for DOI 10.1073/pnas.0701402104
View details for Web of Science ID 000245657600027
View details for PubMedID 17389358
View details for PubMedCentralID PMC1851579
Compromised immunoregulation contributes to obesity and complications in metabolic pathogenesis. Here, we demonstrate that the nuclear factor of activated T cell (NFAT) group of transcription factors contributes to glucose and insulin homeostasis. Expression of two members of the NFAT family (NFATc2 and NFATc4) is induced upon adipogenesis and in obese mice. Mice with the Nfatc2-/- Nfatc4-/- compound disruption exhibit defects in fat accumulation and are lean. Nfatc2-/- Nfatc4-/- mice are also protected from diet-induced obesity. Ablation of NFATc2 and NFATc4 increases insulin sensitivity, in part, by sustained activation of the insulin signaling pathway. Nfatc2-/- Nfatc4-/- mice also exhibit an altered adipokine profile, with reduced resistin and leptin levels. Mechanistically, NFAT is recruited to the transcription loci and regulates resistin gene expression upon insulin stimulation. Together, these results establish a role for NFAT in glucose/insulin homeostasis and expand the repertoire of NFAT function to metabolic pathogenesis and adipokine gene transcription.
View details for DOI 10.1128/MCB.00580-06
View details for Web of Science ID 000241252300003
View details for PubMedID 16908540
View details for PubMedCentralID PMC1636854
Protein-protein interactions are a regulatory mechanism for a number of physiological and pathological cellular processes. Neurodegenerative diseases, such as AD (Alzheimer's disease), are associated with the accelerated production or delayed clearance of protein aggregates. Hence, inhibition of pathologic protein-protein interactions is a very attractive mechanism for drug development. This review focuses on a novel therapeutic strategy to inhibit the de novo formation of protein aggregates. Inspired by strategies used in Nature and optimized over millions of years of evolution, we have created a bifunctional molecule [SLF (synthetic ligand for FK506-binding protein)-CR (Congo Red)] that is able to block Abeta (amyloid beta) aggregation by borrowing the surface and steric bulk of a cellular chaperone.
View details for Web of Science ID 000231345700001
View details for PubMedID 16042540
Integration of protein kinases into transcription activation complexes influences the magnitude of gene expression. The nuclear factor of activated T cells (NFAT) group of proteins are critical transcription factors that direct gene expression in immune and nonimmune cells. A balance of phosphotransferase activity is necessary for optimal NFAT activation. Activation of NFAT requires dephosphorylation by the calcium-mediated calcineurin phosphatase to promote NFAT nuclear accumulation, and the Ras-activated extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase, which targets NFAT partners, to potentiate transcription. Whether protein kinases operate on NFAT and contribute positively to transcription activation is not clear. Here, we coupled DNA affinity isolation with in-gel kinase assays to avidly pull down the activated NFAT and identify its associated protein kinases. We demonstrate that p90 ribosomal S6 kinase (RSK) is recruited to the NFAT-DNA transcription complex upon activation. The formation of RSK-NFATc4-DNA transcription complex is also apparent upon adipogenesis. Bound RSK phosphorylates Ser(676) and potentiates NFATc4 DNA binding by escalating NFAT-DNA association. Ser(676) is also targeted by the ERK MAP kinase, which interacts with NFAT at a distinct region than RSK. Thus, integration of the ERK/RSK signaling pathway provides a mechanism to modulate NFATc4 transcription activity.
View details for DOI 10.1128/MCB.25.3.907-920.2005
View details for Web of Science ID 000226652900005
View details for PubMedID 15657420
View details for PubMedCentralID PMC544015
Protein aggregation is involved in the pathogenesis of neurodegenerative diseases and hence is considered an attractive target for therapeutic intervention. However, protein-protein interactions are exceedingly difficult to inhibit. Small molecules lack sufficient steric bulk to prevent interactions between large peptide surfaces. To yield potent inhibitors of beta-amyloid (Abeta) aggregation, we synthesized small molecules that increase their steric bulk by binding to chaperones but also have a moiety available for interaction with Abeta. This strategy yields potent inhibitors of Abeta aggregation and could lead to therapeutics for Alzheimer's disease and other forms of neurodegeneration.
View details for Web of Science ID 000224969400045
View details for PubMedID 15514157
The delicate leaflets that make up vertebrate heart valves are essential for our moment-to-moment existence. Abnormalities of valve formation are the most common serious human congenital defect. Despite their importance, relatively little is known about valve development. We show that the initiation of heart valve morphogenesis in mice requires calcineurin/NFAT to repress VEGF expression in the myocardium underlying the site of prospective valve formation. This repression of VEGF at E9 is essential for endocardial cells to transform into mesenchymal cells. Later, at E11, a second wave of calcineurin/NFAT signaling is required in the endocardium, adjacent to the earlier myocardial site of NFAT action, to direct valvular elongation and refinement. Thus, NFAT signaling functions sequentially from myocardium to endocardium within a valvular morphogenetic field to initiate and perpetuate embryonic valve formation. This mechanism also operates in zebrafish, indicating a conserved role for calcineurin/NFAT signaling in vertebrate heart valve morphogenesis.
View details for Web of Science ID 000223730300014
View details for PubMedID 15339668
Axon outgrowth is the first step in the formation of neuronal connections, but the pathways that regulate axon extension are still poorly understood. We find that mice deficient in calcineurin-NFAT signaling have dramatic defects in axonal outgrowth, yet have little or no defect in neuronal differentiation or survival. In vitro, sensory and commissural neurons lacking calcineurin function or NFATc2, c3, and c4 are unable to respond to neurotrophins or netrin-1 with efficient axonal outgrowth. Neurotrophins and netrins stimulate calcineurin-dependent nuclear localization of NFATc4 and activation of NFAT-mediated gene transcription in cultured primary neurons. These data indicate that the ability of these embryonic axons to respond to growth factors with rapid outgrowth requires activation of calcineurin/NFAT signaling by these factors. The precise parsing of signals for elongation turning and survival could allow independent control of these processes during development.
View details for Web of Science ID 000183397600015
View details for PubMedID 12787506
NFATc proteins transduce Ca(2+) signals to the nucleus and then pair with other proteins on DNA to generate NFAT complexes that activate transcription in response to both electrical and tyrosine kinase signaling. The four NFATc genes arose at the origin of vertebrates, implying that they have evolved for the development of vertebrate-specific functions, such as a complex nervous system, a recombinational immune system, and a vascular system with a complex heart. These speculations are borne out by studies of mice with null mutations in the different family members.
View details for Web of Science ID 000171477500003
View details for PubMedID 11532391
Vascular development requires an orderly exchange of signals between growing vessels and their supporting tissues, but little is known of the intracellular signaling pathways underlying this communication. We find that mice with disruptions of both NFATc4 and the related NFATc3 genes die around E11 with generalized defects in vessel assembly as well as excessive and disorganized growth of vessels into the neural tube and somites. Since calcineurin is thought to control nuclear localization of NFATc proteins, we introduced a mutation into the calcineurin B gene that prevents phosphatase activation by Ca(2+) signals. These CnB mutant mice exhibit vascular developmental abnormalities similar to the NFATc3/c4 null mice. We show that calcineurin function is transiently required between E7.5 and E8.5. Hence, early calcineurin/NFAT signaling initiates the later cross-talk between vessels and surrounding tissues that pattern the vasculature.
View details for Web of Science ID 000169664300007
View details for PubMedID 11439183
The recent sequencing of several complete genomes has made it possible to track the evolution of large gene families by their genomic structure. Following the large-scale association of exons encoding domains with well defined functions in invertebrates could be useful in predicting the function of complex multidomain proteins in mammals produced by accretion of domains. With this objective, we have determined the genomic structure of the 14 genes in invertebrates and vertebrates that contain rel domains. The sequence encoding the rel domain is defined by intronic boundaries and has been recombined with at least three structurally and functionally distinct genomic sequences to generate coding sequences for: (i) the rel/Dorsal/NFkappaB proteins that are retained in the cytoplasm by IkB-like proteins; (ii) the NFATc proteins that sense calcium signals and undergo cytoplasmic-to-nuclear translocation in response to dephosphorylation by calcineurin; and (iii) the TonEBP tonicity-responsive proteins. Remarkably, a single exon in each NFATc family member encodes the entire Ca(2+)/calcineurin sensing region, including nuclear import/export, calcineurin-binding, and substrate regions. The Rel/Dorsal proteins and the TonEBP proteins are present in Drosophila but not Caenorhabditis elegans. On the other hand, the calcium-responsive NFATc proteins are present only in vertebrates, suggesting that the NFATc family is dedicated to functions specific to vertebrates such as a recombinational immune response, cardiovascular development, and vertebrate-specific aspects of the development and function of the nervous system.
View details for Web of Science ID 000168623300067
View details for PubMedID 11344309
The Jun N-terminal kinases (JNKs) recently have been shown to be required for thymocyte apoptosis and T cell differentiation and/or proliferation. To investigate the molecular targets of JNK signaling in lymphoid cells, we used mice in which the serines phosphorylated by JNK in c-Jun were replaced by homologous recombination with alanines (junAA mice). Lymphocytes from these mice showed no phosphorylation of c-Jun in response to activation stimuli, whereas c-Jun was rapidly phosphorylated in wild-type cells. Despite the fact that c-jun is essential for early development, junAA mice develop normally; however, c-Jun N-terminal phosphorylation was required for efficient T cell receptor-induced and tumor necrosis factor-alpha-induced thymocyte apoptosis. In contrast, c-Jun phosphorylation by JNK is not required for T cell proliferation or differentiation. Because jnk2-/- T cells display a proliferation defect, we concluded that JNK2 must have other substrates required for lymphocyte function. Surprisingly, jnk2-/- T cells showed reduced NF-AT DNA-binding activity after activation. Furthermore, overexpression of JNK2 in Jurkat T cells strongly enhanced NF-AT-dependent transcription. These results demonstrate that JNK signaling differentially uses c-Jun and NF-AT as molecular effectors during thymocyte apoptosis and T cell proliferation.
View details for Web of Science ID 000166949200083
View details for PubMedID 11172026
View details for PubMedCentralID PMC29332
Apoptotic and mitogenic stimuli activate c-Jun NH2-terminal kinases (JNKs) in T cells. Although T cells express both JNK1 and JNK2 isozymes, the absence of JNK2 alone can result in resistance to anti-CD3-induced thymocyte apoptosis and defective mature T cell proliferation. Similar defects in thymocyte apoptosis and mature T cell proliferation, the latter due to reduced interleukin 2 production, are also caused by JNK1 deficiency. Importantly, T cell function was compromised in Jnk1(+/-)Jnk2(+/-) double heterozygous mice, indicating that JNK1 and JNK2 play similar roles in regulating T cell function. The reduced JNK dose results in defective c-Jun NH2-terminal phosphorylation in thymocytes but not in peripheral T cells, in which nuclear factors of activated T cells (NK-ATs)-DNA binding activity is affected. Thus, JNK1 and JNK2 control similar functions during T cell maturation through differential targeting of distinct substrates.
View details for Web of Science ID 000166902900005
View details for PubMedID 11157052
View details for PubMedCentralID PMC2195924
The molecular basis of learning and memory has been the object of several recent advances, which have focused attention on calcium-regulated pathways controlling transcription. One of the molecules implicated by pharmacological, biochemical and genetic approaches is the calcium/calmodulin-regulated phosphatase, calcineurin. In lymphocytes, calcineurin responds to specific calcium signals and regulates expression of several immediate early genes by controlling the nuclear import of the NF-ATc family of transcription factors. Here we show that NF-ATc4/NF-AT3 in hippocampal neurons can rapidly translocate from cytoplasm to nucleus and activate NF-AT-dependent transcription in response to electrical activity or potassium depolarization. The calcineurin-mediated translocation is critically dependent on calcium entry through L-type voltage-gated calcium channels. GSK-3 can phosphorylate NF-ATc4, promoting its export from the nucleus and antagonizing NF-ATc4-dependent transcription. Furthermore, we show that induction of the inositol 1,4,5-trisphosphate receptor type 1 is controlled by the calcium/calcineurin/NF-ATc pathway. This provides a new perspective on the function of calcineurin in the central nervous system and indicates that NF-AT-mediated gene expression may be involved in the induction of hippocampal synaptic plasticity and memory formation.
View details for Web of Science ID 000083207400058
View details for PubMedID 10537109
View details for Web of Science ID 000087225400061
View details for PubMedID 11232327
Antigen-receptor interactions on lymphocytes result in local clustering of actin, receptors and signaling molecules into an asymmetric membrane structure termed a cap. Although actin polymerization is known to be required, the mechanisms underlying cap formation are unclear. We have studied the events underlying cap formation using mice bearing a null mutation in vav (vav-/-), a gene that encodes a guanine-nucleotide exchange factor for the GTPase Rac.Lymphocytes from vav-/- mice failed to form T-cell receptor caps following activation and had a defective actin cytoskeleton. The vav-/- T cells were deficient in interleukin-2 (IL-2) production and proliferation, and the peak of Ca2+ mobilization was reduced although of normal duration. Activation of Jun N-terminal kinase or stress-activated kinase (JNK or SAPK) and mitogen-activated protein kinase (MAPK) and the induction of the transcription factor NF-ATc1 and egr-1 genes was normal. Despite the reduced Ca2+ mobilization, translocation of cytoplasmic NF-ATc to the nucleus was normal, reflecting that the lower levels of Ca2+ in vav-/- cells were still sufficient to activate calcineurin. Treatment of lymphocytes with cytochalasin D, which blocks actin polymerization, inhibited cap formation and produced defects in signaling and IL-2 transcriptional induction in response to antigen-receptor signaling that were nearly identical to those seen in vav-/- cells. In transfection studies, either constitutively active Vav or Rac could complement constitutively active calcineurin to activate NF-AT-dependent transcription.These results indicate that Vav is required for cap formation in lymphocytes. Furthermore, the correlation between cap formation, IL-2 production and proliferation supports the hypothesis that an actin-dependent pathway is a source of specialized growth regulatory signals.
View details for Web of Science ID 000073590300014
View details for PubMedID 9601640
Signaling by the antigen receptor of T lymphocytes initiates different developmental transitions, each of which require the tyrosine kinase ZAP70. Previous studies with agonist and antagonist peptides have indicated that ZAP70 might respond differently to different structures of the TCR-CD3 complex induced by bound peptides. The roles of membrane proximity and orientation in activation of ZAP70 signaling were explored using synthetic ligands and their binding proteins designed to produce different architectures of membrane-bound complexes composed of ZAP70 fusion proteins. Transient membrane recruitment of physiological levels of ZAP70 with the membrane-permeable synthetic ligand FK1012A leads to rapid phosphorylation of ZAP70 and activation of the ras/MAPK and Ca2+/calcineurin signaling pathways. ZAP70 SH2 domains are not required for signaling when the kinase is artifically recruited to the membrane, indicating that the SH2 domains function solely in recruitment and not in kinase activation. Using additional synthetic ligands and their binding proteins that recruit ZAP70 equally well but orient it at the cell membrane in different ways, we define a requirement for a specific presentation of ZAP70 to its downstream targets. These results provide a mechanism by which ZAP70, bound to the phosphorylated receptor, could discriminate between conformational changes induced by the binding of different MHC-peptide complexes to the antigen receptor and introduce an approach to exploring the role of spatial orientation of signaling complexes in living cells.
View details for Web of Science ID A1997XY11200015
View details for PubMedID 9312021
View details for Web of Science ID A1997XK41800030
View details for PubMedID 9235633
The immunosuppressants cyclosporin A (CsA), FK506, and rapamycin suppress the immune response by inhibiting evolutionary conserved signal transduction pathways. CsA, FK506, and rapamycin bind to their intracellular receptors, immunophilins, creating composite surfaces that block the activity of specific targets. For CsA/cyclophilin and FK506/FKBP the target is calcineurin. Because of the large surface area of interaction of the drug-immunophilin complex with calcineurin, FK506 and CsA have a specificity for their biologic targets that is equivalent to growth factor-receptor interactions. To date, all the therapeutic as well as toxic effects of these drugs have been shown to be due to inhibition of calcineurin. Inhibition of the action of calcineurin results in a complete block in the translocation of the cytosolic component of the nuclear factor of activated T cells (NF-AT), resulting in a failure to activate the genes regulated by the NF-AT transcription factor. These genes include those required for B-cell help such as interleukin (IL-4) and CD40 ligand as well as those necessary for T-cell proliferation such as IL-2. The purpose of this article is to illustrate the means by which these drugs produce immunosuppression.
View details for Web of Science ID A1996VG75000006
View details for PubMedID 8811062
The Src-like tyrosine kinases require membrane localization for transformation and probably for their normal role in signal transduction. We utilized this characteristic to prepare Src-like tyrosine kinases that can be readily activated with the rationally designed chemical inducer of dimerization FK1012. Dimerization of cytoplasmic Src-like tyrosine kinases was not sufficient for signaling, but their recruitment to the plasma membrane led to the rapid activation of transcription factors identical to those regulated by crosslinking the antigen receptor. Moreover, recruitment of activated Src-like kinases to the membrane replaced signaling by the T-lymphocyte antigen receptor complex, leading to the activation of both the Ras/protein kinase C and Ca2+/calcineurin pathways normally activated by antigen receptor signaling. Since these chemical inducers of dimerization are cell permeable, this approach permits the production of conditional alleles of any of the Src-like tyrosine kinases, thereby allowing a delineation of their developmental roles.
View details for PubMedID 7568222


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Canadian Film Centre's ideaBOOST Announces Cohort 4 Companies
Canadian Film Centre's ideaBOOST Announces Cohort 4 Companies
Stage TEN, changio, SlimCut Media, PerceptivSHIFT, MBLOK and Tunestars join the four-month accelerator program, with Vubble and One Story accepted as affiliate companies
Toronto, November 6, 2014 – The Canadian Film Centre (CFC), together with Corus Entertainment and Shaw Media, announced today the six companies selected to participate in the fourth cohort of ideaBOOST, Canada's only digital entertainment accelerator for companies focused on developing technologies and content platforms for the media and entertainment industry.
Set to begin on Monday, November 10, 2014, ideaBOOST cohort four received a record number of submissions from companies all over Canada. A panel of industry jurors reviewed and ranked the companies and narrowed the number of entrants down to 11 finalists.
"The breadth of companies we selected to be a part of the ideaBOOST portfolio speaks volumes about the talent and innovation that Canadians are bringing to the global digital entertainment industry," said Ana Serrano, Chief Digital Officer, CFC. "From robotic computer vision hardware solutions, to real time cloud-based production platforms for next generation news, these companies will redefine how we make, store, pay for and discover media and entertainment in the next decade."
ideaBOOST identifies the most promising companies that are developing next-generation technologies and products for the entertainment industry, and provides the support necessary for them to scale or become market- or investor-ready in today's competitive media market. Through an intensive four-month program, ideaBOOST offers entrepreneurs access to global mentorship and valuable insights in product development, audience acquisition, financial modeling, pitch and packaging, $15,000 in capital, and the potential for direct investments from Corus Entertainment and Shaw Media, among other investors. Graduating companies are considered eligible to join the ideaBOOST Portfolio program, which provides further opportunities for the startups to secure corporate partnerships or equity investment.
The fall 2014 ideaBOOST cohort is comprised of the following companies, selected out of a record number of applicants:
1. Stage TEN: a platform to create professional, live and interactive content; it is a TV control room web app that can preview, switch and mix live video feeds from any web-connected camera with pre-produced segments.
2. changio: the first next-generation coalition virtual currency media rewards program that has been created with in-store, second screen, on-the-go, social, location-aware, mobile technologies.
3. SlimCut Media: a platform for publishers to engage, better understand, and monetize their audiences.
4. PerceptivSHIFT: the SHIFT is a vision-guided camera motion control system to enable dynamic cinematography.
5. MBLOK: a smart memory device that aims to personalize VPN and Cloud for offline access.
6. Tune Stars: a game-changing new music app that is lined up to disrupt the way fans, artists and the industry connect online for music.
Out of the 11 companies shortlisted, two will also join ideaBOOST as affiliate companies who will receive support and mentorship to prepare them to potentially become full-fledged participants in the next ideaBOOST cohort. These two companies are:
1. Vubble: a unique discovery platform that brings users the best video they need to see now and shows them video they didn't know they needed to see.
2. OneStory: a platform to create and share video interviews.
Since its inception in 2012, ideaBOOST has accepted 19 early-stage startups and SMEs into their portfolio, including Bubl Technology, the creators of the Bublcam – the only fully spherical consumer camera in the world, whose current collaboration with Google allows anyone with a Bublcam to upload spherical photos directly to Google Maps, StreetView and Google+; ApprenticeA Productions, the largest online video production company in Canada with more than 280,880 subscribers on their network, and the founders of Canada's first YouTube festival Buffer Festival; AsapSCIENCE, a leading YouTube channel with more than 2,800,000 subscribers, who partnered with the CBC last winter for a series of Olympic-related shorts, and plan to release an AsapSCIENCE book in March (Simon and Shuster, 2014); and RAUR by Instaradio, an app to live stream and record audio from a mobile phone, which has received two rounds of seed funding from three investors to date; among many other successful companies.
Through the generous support of founding partners Corus Entertainment and Shaw Media, ideaBOOST has provided these 19 participants with $15,000 towards development costs, $15,000 of in-kind services and key program benefits, such as access to top mentors in the digital entertainment industry, hands-on support to build customized business strategies, the necessary tools to engage the market and pitching tips on how to attract angel and institutional investments.
About CFC
CFC accelerates the careers of the brightest talent in film, television, screen acting, music, and digital media. A charitable organization, CFC is committed to promoting and investing in Canada's diverse talent; providing exhibition, financial, and distribution opportunities, and fostering industry collaborations and creative partnerships. CFC makes a significant cultural and economic contribution to Canada by launching the country's most creative ideas and voices to the world. For more details, visit cfccreates.com.
About CFC Media Lab
Created in 1997, the Canadian Film Centre's Media Lab (CFC Media Lab) provides a unique training, research and production think-tank environment for digital media content developers, and practitioners, as well as acceleration programs and services for start-ups and SMEs in digital entertainment. An internationally acclaimed and award-winning facility, CFC Media Lab participating developers and start-ups emerge as leaders in the world of digital media, produce innovative projects, and sustain 21st century companies. www.cfccreates.com.
About ideaBOOST
ideaBOOST is a business accelerator with a difference – a bootcamp for companies that want to navigate an entertainment ecosystem that has been radically disrupted by new technologies and demanding audience expectations. Companies selected to participate in ideaBOOST get the budget, tools, training, and mentorship designed to help bring their product to market and improve their chances of success with audiences, investors, and partners. ideaBOOST is an initiative of the CFC Media Lab, with founding partners Corus Entertainment, Google and Shaw Media. www.ideaboost.ca
For media inquiries, please contact:
Cory Caverson-Angeletti
Communications Specialist, CFC
416.445.1446 x463


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City of Simi Valley, CAHome Menu
Task Force on Homelessness
The Task Force on Homelessness was established by the City Council in 1999 to address the issue of homelessness in Simi Valley. The Task Force provides policy recommendations to the City Council to assist in developing the community's response to homelessness. The Task Force is comprised of representatives from the City Council, regional and local services providers, and government agencies providing services to individuals experiencing and at risk of homelessness.
The Task Force meets quarterly. All Task Force meetings are open to the public. Information for upcoming meetings is available below. Those interested in receiving meeting and other information related to the Task Force's efforts can sign up to receive email notifications. For information provided at the meetings, please refer to the Resources and Referrals page.
Additionally, City staff represents the City through involvement with the Ventura County Continuum of Care to ensure that the City's efforts take into account regional efforts and federal policies to maximize effectiveness. The Continuum of Care coordinates the regional Point In Time Count and prepared a brief summary of the findings to detail the state of homelessness in Ventura County.
For more information regarding the Task Force on Homelessness, please call (805) 583-6759. Interested organizations and individuals are encouraged to sign up for e-notify to receive email information, variances in meeting dates, and to stay informed regarding current and future updates.
Upcoming Events
Task Force on Homelessness Meeting
- Date: 05/11/2017 3:30 PM - 5:00 PM
- Location: City Hall Community Room
2929 Tapo Canyon Road
Simi Valley, California 93063
The Task Force on Homelessness serves as an advisory board to the City Council to coordinate and strengthen efforts to address homelessness in Simi Valley. The public is invited to attend all meetings. For more information regarding the Task Force on Homelessness, please click here or call (805) 583-6759.
To view the meeting agenda packet, please click here.


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Mainers stranded in Boston
Can't leave until city lockdown lifted
Many Mainers are stranded in Boston due to the manhunt for the second suspect in the Boston Marathon bombings.
Chris Gurney is stranded at the Bulfinch Hotel with his 10-year-old son.
Gurney said he and his son can't leave until the Amtrak Downester resumes service from the city.
He described the city as eerie because it is so empty.
"It's kind of eerie seeing how dead the streets are and the amount of armed cars and police, but we're trying to make the most of it and have a good time together, hopefully get home soon," said Gurney.
Mike and Bertha Naylor of Damariscotta said they will stay at the Bulfinch for an unexpected second night and are treating it as an extended vacation.
"We've seen it all. They've been everywhere. Lots of sirens going off, but there's a good police presence here, and so we haven't been worried at all about where we've been," said Bertha Naylor.
The Naylors said they feel safe with the amount of police presence in Boston.


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According to a new report, the quest for the perfect body is putting more boys at risk than ever. Experts say that extreme weight-lifting and calorie-counting is on the rise in boys as young as 14, which could interfere with their development. NBC's Rehema Ellis reports.
All those glossy magazine ads showing men – and women – with bulging muscles may be having a big impact on America's youth. In a new study of 2,793 teens from 20 urban middle and high schools, more than 90 percent of boys and 80 percent of girls said they were exercising to become more buff.
If exercise was the only method kids were using to pump up their muscles, it wouldn't be a problem. But a large number of American teens are also using protein powders and other methods to help them bulk up, researchers reported. And even more concerning, almost 6 percent of boys and 5 percent of girls were turning to steroids to achieve the toned up look they craved, according to the study published Monday in Pediatrics.
What's troubling, the researchers say, is the possibility that as they grow older, more and more teens will turn to unhealthy methods to muscle up.
"If they're interested in developing muscle at 13, 14, and 15, what are they going to be doing at 18 or 20?" says the study's lead researcher Marla Eisenberg, an assistant professor in pediatrics in the division of Adolescent Health and Medicine at the University of Minnesota School of Medicine. "Are they going to be doing something more dangerous?"
The researchers were surprised at the number of girls who were hoping to bulk up. That certainly signals a change in what American teens see as the ideal female body.
"The ideal figure for women for a long time was very thin," Eisenberg says. "Now more and more we're seeing images of women who are not just slender, but also have toned shoulder and arms. They're very fit looking."
For the new study, Eisenberg and her colleagues surveyed adolescents from 20 middle schools and high schools in the St. Paul/Minneapolis area of Minnesota. The teens, whose average age was nearly 14 and a half (14.4), were asked to fill out a 235-item questionnaire.
The questionnaire looked at attitudes and behaviors relating to weight and appearance.
Particularly telling were the answers to this question:
"How often have you done each of the following things in order to increase your muscle size or tone in the past year? (a) Changed my eating (b) Exercised more (c) Used protein powder or shakes (d) Used steroids (e) Used another muscle building substance (such as creatine, amino acids, hydroxyl methylbutyrate, DHEA, or growth hormone)."
The possible answers were: never, rarely, sometimes, often.
More than two thirds of boys said they had changed the way they ate to muscle up, while more than 90 percent said they were exercising to add muscle, 40.9 percent saying they did this often. Similarly, nearly two thirds of girls said they'd changed their diets and more than 80 percent girls said they were exercising to tone their muscles.
Among the boys, 34.7 percent were consuming protein powders or shakes, 5.9 percent reported using steroids, and 10.5 percent said they were using some other muscle enhancing substance. That's compared to 21.2 percent of girls using protein powders or shakes, 4.6 percent taking steroids, and 5.5 using some other muscle enhancing substance.
Those numbers concern Dana Rofey, an assistant professor of pediatrics in the Division of Weight Management and Wellness at the Children's Hospital of Pittsburgh.
"I am quite surprised at the prevalence of protein powders and shakes and steroid use," Rofey says.
While it's good that young people are trying to get in shape, there could be a dark side to all this bulking up if kids take it too far, Rofey says.
A study like this should serve as a warning call to parents, she adds.
"I always tell my patients' parents, you can never underestimate your role in terms of role modeling," she explains. "I have two young daughters myself. Sometimes I have to stop and explain to them why I'm working out. Why I'm doing all those ab exercises.
"You need to talk openly with them about the importance of being healthy and of not doing fad kinds of things to look a certain way."
For her part, Eisenberg hopes that people will understand that fitness is a good thing, but you have to achieve it through healthy means.
"We definitely don't want to be taken as trying to send the message that exercise or eating in a certain way is bad," Eisenberg says. "There are many good things that go along with those behaviors, such as general fitness and health. We're concerned that when achieving a certain physical appearance is the driving force, those good behaviors might give way to less healthy ones in the future."


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Posted by Editoress on 05/9/08
Montivilliers Challenge May 8th, France
Courtesy Richardn Wooles
BC's Cody Campbell Finishes 6th in Normandy
Cody Campbell, riding for the Canadian National Team, had a great debut in Europe finishing 6th. He was in the front group of riders all day, on a windy 12km course with a 1.5km climb to the finish. It was a fast, active race, with lots of attacking from the gun. Cody reported that he was happy with his result, after being in the majority of the breaks for 80km.
The team is doing a stage race next weekend, the Tour de Bessin.
Montivilliers Junior Challenge, 106 Km
1. Renaut St Hilaire
2. Kevin Taillefer (E.S. Livarot)
3. Jeremie Cornu (E.S. Livarot)
6. Cody Campbell (Canadian National Team)
|Return to Canadian Cyclist homepage | Back to Top


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Fresh off their recent two-pronged European tour, NEUROSIS will congregate at a one-off performance in Providence, Rhode Island this Saturday, August 24th.
This special ceremony has been arranged as part of the city-wide NecronomiCon -- a four-day convention exploring the works of H.P. Lovecraft and other past and present writers as an exploration of the intersection of science and art that lays at the foundation of the "Cthulhu Mythos" genre. NEUROSIS will take the stage at Lupo's Heartbreak Hotel to perform a massive set as part of the festivities, with support from avant/crushing solo act LUSTMORD. The early show open with the 45-minute silent film, "The Call of Cthulhu," about the Strand Theater -- now Lupo's -- and how it was Lovecraft's favorite movie theater to attend.
NEUROSIS at NecronomiCon:
8/24/2013 Lupo's Heartbreak Hotel - Providence, RI w/ Lustmord [5pm doors]
8/24/2013 Lupo's Heartbreak Hotel - Providence, RI w/ Lustmord [5pm doors]
Since 1985 NEUROSIS surpassed the boundaries of any genre, never ceasing to mutate and progress their songwriting and sonic delivery, and never failing to mesmerize audiences both in the studio and onstage. In 2012 the unit released their monumental tenth studio album, Honor Found In Decay, which went on to receive countless plaudits from the press on a global scale, and was positioned highly in end of year polls, as always reaffirming why NEUROSIS remains one of the most significant heavy acts in existence.
Witness an array of live footage collected over the ongoing tour cycle for Honor Found In Decay HERE.
"Those who prefer their epics harrowing, their atmospheres apocalyptic and their metaphorical gut punches landed squarely on the emotional solar plexus will not be disappointed." - Decibel
"For 27 years, the members of Neurosis have demonstrated what metal can be and what it can aspire to: transcendent, cathartic, graceful, innovative." - National Public Radio
"...officially upped the ante for all the post-metal bands who ought to be paying these guys royalties for their patent on psychedelic purgation..." - Spin
"Another spiritual journey into the very heart of mankind. Completely and utterly mind-blowing." - Metal Hammer
"The most stunning aspects of Honor Found In Decay come from Neurosis' grasp of dynamics...as ever, in the hands of these uncompromising sorcerers, true heaviness can be as much about the directness as disorientation, and as much about the sinister rumble as an unearthly roar. 5/5" - Terrorizer
"...doesn't abandon the moody sprawl of the band's last few full-lengths, but it does help restore urgency to an aesthetic that seemed in danger of growing soporific... It's a record that proves these grizzled artisans still know how to flex their muscles." - Pitchfork


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Top flight deals to Edmonton (YEA)*
Fly to Edmonton with KLM
Together with our global network, we as KLM Royal Dutch Airlines offer flights to Edmonton, serving Edmonton International Airport (YEG) in Alberta, Canada. Browse over 1.000 hours of interactive media with our in-flight entertainment, available on intercontinental KLM flights. The most recent blockbuster films in multiple languages and exciting TV shows make flying to Edmonton with us a breeze.
KLM Destinations: Edmonton, Canada, in winter
Top Edmonton attractions
- Francis Winspear Centre for Music: a beautiful modern building and a performing arts centre located in the downtown core, home to the Edmonton Symphony Orchestra.
- Fort Edmonton Park: a living history museum located on the site of the first enduring European post in Edmonton, featuring original and rebuilt historical structures along with costumed historical interpreters.
- West Edmonton Mall: the largest shopping mall in North America and tenth largest in the world, offering visitors over 800 stores, an amusement park, a waterpark, a skating rink, and even a hotel!
- Alberta Legislature Building: a famous beaux-arts styled building and home to the Legislative Assembly and the Executive Council.
- Muttart Conservatory: a breath-taking botanical garden consisting of three city-operated greenhouses, public gardens, as well as four feature pyramids for display of plant species found across three biomes.
Edmonton is filled with interesting things to see, but you need an expert to help you get the most out of your visit! Why not check out our travel guide for an insider's take on the best Edmonton has to offer.
What's the best way to get around Edmonton?
Edmonton's Light Rail Transit (LRT) service is an excellent way to get around the city's key attractions. For CAN 9,50 you can buy a day pass, which allows unlimited travel on a single day by 1 adult and up to 4 children age 12 and under. Taxis are a good option and provide you with a great deal of flexibility, at an increased cost.
What's the weather like in Edmonton?
Whilst July might be the hottest month with an average temperature of 16°C (61°F), it is also the wettest. Therefore, make sure to pack an umbrella and an appropriate coat, but don't forget the sunscreen either as it can get very hot in the summer!
Weather in Edmonton
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16 °CThursday13/08/2020
18 °CFriday14/08/2020
19 °CSaturday15/08/2020
22 °CSunday16/08/2020
24 °CMonday17/08/2020
24 °CTuesday18/08/2020
23 °CWednesday19/08/2020
*Lowest available fares, incl. taxes and surcharges, excl. EUR 10 booking fee (credit card surcharge may apply). Prices shown may vary depending on fare availability. You will see the exact total price when selecting your payment method.


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Chronic Traumatic Encephalopathy (CTE)
Getting your bell rung was once a badge of honor in sports. The ability to shake it off and not miss a play was accepted and routine. But it had been known for almost a hundred years that repeated hits to the head had long-term consequences and "dementia pugilista" was the term used for a punch drunk old fighter who had been hit in the head one too many times. The realization was slow in coming that the same injury to the brain could occur in football players, and that the most popular sport in the country could be a potential cause of psychiatric disturbances and early dementia.
A new term was born: Chronic traumatic encephalopathy (CTE) describes a gradual degeneration in brain function due to repeated head injuries that causes both concussions with symptoms and concussions that are asymptomatic (do not cause symptoms). Once the initial symptoms of concussion have faded, months and years later, new symptoms occur. CTE symptoms start slowly and creep up on the patient. Initially, there may be concentration and memory problems with episodes of disorientation and confusion, dizziness, and headache. It is as if the concussion symptoms were starting to return even without a new head injury.


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Obama laments site's IT problems
President Barack Obama expects that the Affordable Care Act will succeed but would change some things about its rollout if he could do it all again, he said Tuesday.
"I am confident that the model that we built … is one that will succeed," he said in an interview at the Wall Street Journal CEO Council. But, given the troubled rollout of exchanges, "we obviously are going to have remarket and rebrand, and that will be challenging in this political environment."
In retrospect, Obama said in a question-and-answer session with Journal Washington bureau chief Gerald Seib, he would have "blow[n] up" the information-technology procurement to prevent the problems that have plagued HealthCare.gov. He and the administration "probably could have identified earlier the way the federal government does procurement and does IT just generally is not very efficient" and made changes to that process to put the health care website on more solid footing.
( Also on POLITICO: Obama to insurers: No bailout)
The construction of health care marketplaces was "very challenging, just mechanically" and those issues were exacerbated by political pressures and the federal government's rigidity on technology.
"There's probably no bigger gap between the public sector and the private sector than IT," he said.
Washington has been overtaken in recent months by the government shutdown and by "the fact that my website's not working as it's supposed to," Obama said, and that has translated into real frustration with Washington. He and lawmakers need to "break through the stubborn cycle of crisis politics and start working together" because "my understanding is nobody in this town is doing particularly well at the moment" when it comes to the views of the American people.
( Also on POLITICO: Bachmann weighing ACA lawsuit)
While Obama's agenda has stalled over the past few months, Obama is still optimistic that the House will move forward on immigration reform. "I am a congenital optimist. My name is Barack Obama and I ran for president," he joked.
It would be fine with him if House Republicans chopped up the Senate bill into "five pieces" so long as it meets the principles that he and Democrats support. "I don't care what it looks like," he said.
With another round of fiscal talks ongoing, Obama said he's hopeful for constructive progress and not another government shutdown. But, he said, the pressure level is always high, particularly when it comes to needing to raise the debt limit. "The way our system is set up is like a loaded gun," he said.


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Gerard Depardieu, one of France's best-known actors, has chastised his country's Socialist prime minister for insulting remarks over his decision to move to tax-friendly Belgium and said in an open letter published Sunday that he's turning in his passport.
The letter, which the weekly Le Journal du Dimanche said was penned by Depardieu, quickly propelled him into the spotlight, not for his acclaimed acting skills but for raising the sensitive issue of tax exiles as France looks to fill state coffers with a stiff tax on the rich.
"We no longer have the same country. I'm a true European, a citizen of the world," Depardieu wrote in the letter. He said his 2012 tax bill — 85 percent of his revenue — is fully paid.
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Depardieu, who turns 64 this month, said he has worked since the age of 14, first as a printer, and that in last 45 years he has paid €145 million ($190 million) in taxes.
"I hand over my passport to you and my social security card, which I have never used," the letter said, referring to Prime Minister Jean-Marc Ayrault.
Last week, Ayrault called Depardieu "pathetic" and "unpatriotic" for the actor's decision to move to Nechin, a Belgian village barely a mile (1.6 kilometers) across the border from Lille in northern France. Nechin has drawn other high-earning French residents.
The letter drew quick reaction but little sympathy.
Culture Minister Aurelie Filippetti said she was "scandalized" by Depardieu's decision to turn in his passport. "French citizenship, it's an honor," she said on BFM-TV. "It is rights and duties, too, among them to be able to pay taxes."
President Francois Hollande plans to levy a 75 percent tax on revenue over €1 million to reduce France's budget deficit and debt, and Filippetti said, "Gerard Depardieu is deserting the battle in the war against the crisis."
David Assouline, a spokesman for the governing Socialist Party, said of the actor: "He's playing his worst role."
But Depardieu said in the letter that he is leaving his country because the government "considers that success, creation, talent ... should be sanctioned."
Others have crossed the border before Depardieu, notably the man billed as France's richest, Bernard Arnault, chief of the luxury goods and fashion giant LVMH and worth an estimated $41 billion. He is seeking Belgian citizenship.
It's unclear whether Depardieu realizes his proclamation may in the end just be a symbolic gesture because it's hard to stop being a French citizen. The Civil Code says one must have another nationality in order to give up French citizenship because it is forbidden to be stateless.
Depardieu's burly presence is well-known in France.
He has made more than 150 films and is internationally acclaimed, including an Academy Award nomination for his portrayal of Cyrano de Bergerac in the 1990 film by the same name.
In an upcoming movie to be directed by Abel Ferrara, Depardieu will portray former International Monetary Fund chief Dominique Strauss-Kahn, who fell from power on claims by a New York hotel maid of sexual assault. Charges were dropped and a civil settlement was reached.
A French case that Strauss-Kahn seeks to dismiss is pending.


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RJ Smith's
RJ Smith's
Color: Blue and orange
Pet name: The Badger
Value: To me priceless
Under the hood: 358 Chevy
Origin: Built to race
Special features: Big tires, small seat
Favorite place to cruise: Orange County Fair Speedway
Favorite cruise music: They require we listen to the race control.
Dream car: This is it
Other ride: BMW 328i
What bugs you about other drivers? Drivers who will not let me pass them
Any bad experiences? Steering wheel came off in a race
On which make and model did you learn to drive, and did you pass your driver's test the first time? Go-kart and tractor on grandfather's farm; yes
Other: Every week we promote a different nonprofit organization on the car. Come out to the Orange County Fair Speedway on a Saturday night during racing season. Kids under 12 are admitted free.


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The Student Government Association, also referred to as SGA, works as a liaison between the student body, university, faculty and administration. The Student Government Association:
SGA also works with more than 50 chartered clubs to see that all SGA policies are being followed.
Elected annually by students and composed of more than 80 representatives of the student body, SGA is the official voice of student opinion.
The Student Government Association consists of three branches:
Application forms, procedures and additional information
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