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Two Lancaster cardiologists are up on the latest trend when it comes to heart catheterization.
Drs. Taral Patel and Paul Slota of Carolina Heart Specialists, who are affiliated with Springs Memorial Hospital, are among the first cardiologists in the area to offer radial artery cardiac catheterization as a first option for patients.
A cardiac catheterization typically involves inserting a small tube or sheath into a major artery, most commonly the femoral artery in the groin, and snaking a small catheter to the heart.
A new business catering to attorneys, real estate agents and other professionals with a taste for coffee has opened in the shadow of the Lancaster County courthouses.
Justice Java Coffee House and Meeting Place opened on Dec. 31, said owner Rosanne Lenderman, who runs the business with her daughter, Samantha Cauthen.
Lenderman and her husband, Rob, live in Charlotte but own the building that houses the new business, at 104 N. Catawba St.
With all the fast food restaurants around, hamburgers and chicken sandwiches are available in abundance in Lancaster County.
But what if you just want to sit back and enjoy a fresh chicken salad sandwich along with a piping hot bowl of homemade soup?
Not as many choices available for that.
One such choice may be in an unexpected place – Hercheks Convenience Store and Sandwich Shop on Meeting Street.
Over the last year, many businesses have been struggling to keep their heads above water. And some haven't made it.
It's a risk to open a new small business, even during good economic times.
But despite the current downturn in the economy, the owners of Wing King Cafe in Lancaster have been pleasantly overwhelmed at the response to its newest restaurant.
Wing King Cafe, 426 S.C. 9 Bypass East, opened Dec. 14, and the restaurant has been busy since Day 1, say owners Kim and Bobby Jones and Lori and Brad Hartley.
"Busy is a good thing," Lori Hartley said.
INDIAN LAND – The name of Indian Land's first brick-oven pizza restaurant means "friends" in Italian, which is fitting since its owners are childhood pals.
Rob Ross and Jimmy Warner opened Amici Italian Lovin' Oven in September to offer the area something unique.
The restaurant is located next to Carolina Bistro, which is also run by the pair. The restaurants share kitchen space and staff to reduce overhead costs.
"It's a friendly, fun, family place," said Gloria Ross, Rob's wife and daytime manager.
Santa brought a mixed bag of gifts for area jewelry and pawn shops this holiday season.
Through December, several store owners reported a shift in the spending habits of customers.
Sales of electronics at pawn shops were better than expected, while silver replaced gold as the precious metal of choice for customers at several jewelry stores.
But due to the recession, several pawn shops have seen an influx in people selling goods to them, getting cash to stay afloat.
Springs Memorial Hospital is recognizing three of its employees with honors for the work they've done at the hospital in Lancaster.
Debra Izzard has been named the 2009 Springs Memorial Hospital Employee of the Year.
Izzard is a member of the Environmental Services Department and has been employed with the hospital since 2002.
Living on the river doesn't have to be expensive.
Just ask Molinda Goforth, Realtor for Pinnacle Homes, which is selling lots in the Edgewater development along the Catawba River in western Lancaster County.
Pinnacle Homes is set to construct about 200 custom homes in Edgewater, by builders Ben Russell and Crystal Hollingsworth. Goforth lives in the community herself in Pinnacle Homes' model home.
Indian Land's newest pizzeria is already attracting a steady stream of customers.
Donatos Pizza, located at 9931 Charlotte Highway, opened its doors Oct. 27 for a grand opening bash and has been serving up piping hot pizzas ever since.
Donatos, as a franchise partner, Siler Chapman said business at the newly opened pizza parlor has been impressive.
"It's going fantastic," Chapman said. "It's all been really, really good."
Despite a slumping economy and a significant dip in vehicle sales nationwide, local automotive dealers say they are in good standing and are excited about what the next year may bring.
Annette Gause, owner of H&H Chevrolet in Kershaw, said over the last year, she's had to cut expenses at the dealership to offset the 20 percent decline in sales.
However, sales are picking up and Gause believes the worst of the economic recession has passed. The dealership has not downsized at all and is at no risk to close, she said.
Copyright © 2019
The Lancaster News is your source for local news, sports, events, and information in Lancaster County and Lancaster, South Carolina, and the surrounding area..


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Just a last second notice to everyone that you can drink beers and support the Japan relief effort, tonight. Two of Ballard's watering holes will be donating their proceeds to tsunami victims.
If you have a moment, stop by King's Hardware or Sunset Tavern tonight to pitch in. King's will be donating 100% of their proceeds from tonight's sales of beer, burgers and more to victims. The Sunset is putting on a special show this evening, featuring 3 bands. All proceeds will be donated the relief effort, as well.
While you are visiting King's Hardware, be sure to tell them to stop charging $8.50 (seriously) for their cans of Oscar Blues Gubna. That way you can drink more and help the cause.
Below, check out the more specific news from My Ballard, a neigborhood blog:
Updated: The Sunset Tavern (5433 Ballard Ave NW) will also be raising money on Tuesday. Tonight, all door proceeds will go to relief funds for Japan.
Show starts at 9:30. $6 cover (for Japan relief) 21+
9:30p – Danielle Henry
10:30p – Wind-Up Bird
11:30p – Barry Sebastian
Earlier: Although the Japan earthquake and tsunami were half way around the world, people right here in Ballard are doing what they can to help. Mike Leifur, the general manager at King's Hardware emailed us about their fundraiser. On Tuesday, March 15th, 100 percent of the proceeds from King's (5225 Ballard Ave NW) will be donated to the International Medical Corps.
If you know of other businesses raising money for Japan earthquake and tsunami relief, post it in comments below.
Filed under: Seattle, US, The Events Tagged: help Japan, japan relief, Kings Hardware, seattle japan bar, seattle japan relief, Sunset Tavern

subset: commoncrawl


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2100 E Spring St
Directions Signal Hill, CA 90755
When it comes to your automotive needs, choosing the right dealership is absolutely crucial! At Glenn E. Thomas Dodge Chrysler Jeep, our friendly team of experts is here to help you every step of the way.
You'll find the vehicles that you love at our Chrysler, Jeep, RAM, and Dodge dealership serving Huntington Beach. We're thrilled to offer all of the latest models for you to explore in our showroom. A test drive with our team is sure to help you find the perfect vehicle for your needs and style!
If you're looking for the perfect pre-owned vehicle, we're still your prime destination. With a sprawling selection of used cars from a wide array of different automakers, we take pride in the quality of all the vehicles that we sell. Let our team help you find a used car that fits you just right.
Our Los Angeles area Jeep dealership is in your corner when it's time to finance your vehicle, as well. Whether you're looking to lease or finance your new vehicle, our experts can walk you through the process and help you find the competitive financing rates that you deserve.
As the miles fly by, you'll find the expert maintenance that you need at our car repair center. With access to all of the latest equipment in our state-of-the-art facility, our expert technicians can keep your car running right long into the future!
No matter what your automotive needs are, we look forward to exceeding your expectations at Glenn E. Thomas Dodge Chrysler Jeep. To learn more about our current inventory and the many services we provide, be sure to call us directly at (888) 884-8130 or to contact us online today!


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As recommended by the Committee on Campus Life 11/1/01
This policy was formulated in response to complaints that signs from campus groups are often removed almost immediately after they have been posted. In trying to understand why this happens, CCL became aware that there are considerable differences of opinion as to where it is appropriate to post signs, as well as the nature of what may be posted. Because of these differences of opinion, Earlham community members have sometimes felt they were justified in removing signs that students had posted. The aim of this policy is to establish criteria for posting signs in public places, so that when individuals or campus organizations follow these criteria, they can feel confident that the signs they post will not be removed prematurely.
Postings that follow the guidelines of this policy should not be removed before their designated "removal date." If signs have been posted consistent with this policy, the premature removal of those signs may be deemed to be a violation of the Principles and Practices document, and therefore may result in disciplinary action.
The content of all postings in public spaces on the Earlham College Campus should be consistent with the nature and spirit of The Earlham College Principles and Practices. All such postings (including banners) posted by members of the Earlham community should include:
As noted above, individual buildings may specify additional areas that are unavailable for general posting.


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Observe your blinking rate while looking (or is it staring?) at the
monitor. Train yourself to gently blink at the end of every paragraph or
with every mouse click. Blink at least once or twice a minute.
Measure the height of the monitor. The top of the screen should be equal
to or lower than the height of your eyebrows. When you look slightly down,
your lids will usually sweep down the whole eyeball when you blink. This
moistens the cornea instead of only the upper eyeball, which is what
occurs when you are looking straight ahead or slightly up.
Check the humidity in the room. Often the humidity is less than 20% with
air conditioning and heating. Eyes dry out much more quickly when the
humidity is low, especially when you wear contacts. Bring moisture to
your office with a humidifier or plants. Plants not only increase
humidity, they also absorb irritating volatile organic chemicals and
encourage relaxation when we look at their green color.
Copyright 2003 Erik Peper, Ph.D. and Katherine Hughes Gibney
Permission to copy and distribute Healthy Computing Email Tips for
personal use is granted. Distribution or copying of Healthy Computing
Email Tips for commercial purposes is prohibited without prior written
consent of the copyright holders


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CD-i's seamless branching technique used in modern DVD
>> Friday, January 18, 2008
Devin surprised us with some remarkable use of the old CD-i technology in todays DVD standard. Jean-Pierre Abello described the technique as follows: "The seamless branching mechanism allows a CD-i player with the Digital Video cartridge to play non-linear interactive Digital Video. Seamless branching provides the ability to play MPEG data from different streams or different portions of streams without breaking the delivery and presentation continuity of video or audio."
Now, let's have a look at the DVD release of 'Blade Runner: The Final Cut - Ultimate Collector's Edition'. Devin: "Composed of 5 Discs some of which hold 3 different versions of the same film, not even mentioning all the extra content, we began to ask how this was done! The average DVD can only hold 2 hours of video footage, double that for Dual-Layer. Quoted on the boxset itself, 'All Seamlessly Branched and Seperately Available on one Disc'. A relative obscure technique originally used on CD-i applied to a modern problem. Combining common elements of footage between each version this effectively eliminates the need to duplicate film on the DVD thus reducing the storage capacity required from the DVD. So that's how they got 3 versions of the same film onto one DVD! Maybe the technique was re-invented as an original concept, however we'd like to believe it was poached from the vaults of creative design within Philips Media!"
More? Check The Black Moon Project! Credits: Devin


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I had the great pleasure of speaking to an amazing crowd of students on campus at ASU on Tuesday, November 29th 2011 (my anniversary date with Microsoft). The response and feedback from the students in attendance has been overwhelming. As promised, here are some resources requested from the session:
Here are a few insightful tweets that followed the presentation and Q&A session:
The highly popular HTML5 Web Camp events sponsored by Microsoft are typically filled to capacity when delivered at any location. In my humble opinion, the best HTML5 Web Camp delivered to date was in my hometown of Phoenix, AZ. Fortunately, the team at EventDay showed up that day to record every session. With great pleasure, I announce the availability of these videos for you to watch at your convenience – for free!
Each video provides a simple user interface that allows you to see the presenter, the content on the screen, and navigation controls to the topic you are most interested in. When the screen in maximized, you will truly be immersed into the experience as if you attended live!
The link for all these videos is found below. Please share with your community!!!
My latest article published by DevProConnections is dealing with a fundamental yet very misunderstood topic – semantics. If you would like to learn why semantics matter, I encourage you to read the online article – "HTML5 Syntax and Semantics: Why they Matter"
The article demonstrates the use of semantics by building a simple web site using Visual Studio 2010.
For the serious tech traveller – one who take 2 or more notebook computers on the road – this tip is for you. Having said that, this tip truly applies to anyone who works with multiple PCs at a time.
Recently, my boss (Scott Kerfoot) showcased (via video conference) his multi-computer setup in his home office. When he demonstrated how all the computers could be managed by any of the computers in the setup, I am thinking it must be a KVM switch. NOT! In fact, his setup was all linked together via Mouse Without Borders – a software solution for allowing seamless mouse & keyboard control to any computer in the setup by any computer in the setup (see picture below).
After I installed Mouse Without Borders, I did run into a technical difficulty. Every time I tried to connect a certain PC, it "timed out". After going down multiple rabbit holes, I came across an unrelated post dealing with network issues setting up HomeGroup. In that post, there was a suggestion that having a dash in the computer name could cause an issue. It just happened to be that the name of the PC having the issue was mpalermo-s9. I renamed the PC, restarted, and Mouse Without Borders worked like a charm!
The main advantage of this tech travel tip is the need to only pack one mouse while you are on the road. Even if you don't use it for travel, Mouse Without Borders can allow you to use your favorite mouse (and keyboard) across multiple computers at your home or office!


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Temperature for March 1960
In March 1960 the average high temperature in Meridian, MS was 0.0°F, and this was 71.7°F cooler than the average of 71.7°F. The hottest day in March 1960 was 0 March when the temperature reached 0.0°F. Overnight the average temperature in March is 44.2°F and in 1960 the average overnight temperature was 44.2°F cooler at 0.0°F.


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Alumni Chapter Awards
Alumni Chapter Excellence Award
Established in 1999, this award recognizes the accomplishments of an entire alumni chapter to improve the alumni experience. This biennial award is presented at Grand Chapter to all alumni chapters selected on the basis of excellence in membership fulfillment, undergraduate support and community involvement.
Dr. Donald B. Ward Alumni Chapter Community Service Award
Named for Order of Constantine Sig Dr. Donald B. Ward, NORTHWESTERN 1942, this award was created in 1957 to recognize the alumni chapter that makes the most significant contribution to the welfare of its community or to a worthy regional, national or international charity.
James E. Montgomery Alumni Chapter Publications Award
The Fraternity annually recognizes the most outstanding alumni chapter publications with the Montgomery Award, named for the late Indiana newspaper publisher James E.


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I am looking for tennis academy with scholarship! I speak English and Japanese, but I will be very glad to train at any tennis academy with scholarship. I hope you can help me. You can watch video of my game with this links
Part 1 http://www.eatlime.com/play_372BE465...F-8AD14F62D533
Part 2 http://www.eatlime.com/video/Eldar-B...4-9EE17503069D
Part 3 http://www.eatlime.com/play_B4410C43...3-CDA7E295C758
What do u think? my email is firstname.lastname@example.com


text: Essential Resources for Managing Career Change During the last 25 years there has been a complete shift in the world of work. People used to start work for an employer in their 20's, performing largely the same job, with a few promotions, until they retired in their 60's. Current economic conditions have all but eliminated predictability. It has become routine for people to find themselves at a crossroads in their career path. The average American changes careers 4 to 5 times in the course of her or his working life. People change jobs or career paths for a wide range of reasons. Many people look for a new challenge after working a career path for a number of years or which no longer seems like a good match for their interests. For others, economic problems within companies, regions and industries and off-shoring jobs can motivate a job or career change before a person would otherwise start looking for a new direction. You may find yourself looking at career change for these or other reasons. This workshop will address some tools to navigate rapid changes in your career path. I want to discuss with you some of the essential elements of tracking your career development over the life-span to further progress toward your career goals. All these elements can be discussed with a career counselor whom you would consult periodically, much as you would a doctor, accountant or other consultant. Issues we will cover: Purpose and Vision Life-long Learning Adaptability Information Community Purpose and Vision We are used to attaching much of our sense of identity to our jobs and places of residence - things that used to be somewhat stable, but are now subject to frequent change. Learning how to make the most of change is a life-long process. As your interests evolve and values deepen over time, you may find ways to enjoy the process of change by using it to explore new activities or pursue interests. In order to take best advantage of changes in career opportunities, personal goals and vision are more important than ever as an anchor to stay on track with your development. You may find the worksheet for writing your own Professional Motivation Statement helpful. We will revisit the concept of motivation throughout the workshop. This will give you an easy formula for creating a first draft of your own motivation statement from this worksheet, which has been used by a number of counselors and authors. Step 1. To use Personal Motivation Statement worksheet, start first by identifying 2 or 3 of your key skills you most want to use. The list provided is there as suggestions to generate ideas. You are not limited to the words on the list. The hard part of this exercise is focusing in on the particular skills you get the most satisfaction out of using. Step 2. Next you will want to select the groups of people (or animals) or causes you most want to serve using these skills. Again, The list is there to generate ideas. Step 3. From here you have the concepts to write a first draft of your own Personal Motivation Statement. You may find that you refine this statement over a period of time as you clarify your goals. How closely do your current activities (work and others) support the ideas in your statement? Are you off track or burned out and need a change or are you on the right track but needing to refuel your career momentum? Think about what you want to do, where you want to be, and how you want to get there. It's often helpful to discuss all this with a career counselor who can help with assessment, decision-making and life direction planning. Life Long Learning Building learning into your life is one of the best ways to to keep your career options open. Continued learning builds the skills to keep life and work interesting and growing. Naturally, as a Regis student or alumnus, you have engaged in interactive and experiential learning which you may have experience in a classroom setting, an online setting or some of each to complete your degree. One of the first things you may have learned at Regis is that learning how to learn is the key. People informally update their skills all the time, often without knowing it. For example, you update your skills in using the Internet almost every time you search for information online. Everything you read, each challenge at home or on the job that you face teaches you something new. Our focus for this section is on transferable skills. Effective learning builds on skills that transfer from job to job and industry to industry. Transferable skills usually fit into three main categories. Management / Organizational (supervise, plan, budget, compile) Communication / Interpersonal (listen, educate, negotiate, sell) Problem Solving / Innovation (design, adapt, simplify, reorganize, program) Many of us take for granted the things we do well. You may want to ask people you work with or know you well about the skills they see in you, as well as the skills you see in yourself. Using the Transferable Skills Checklist, circle skills on this sheet, ask yourself which of these skills match those needed for the vision from the Motivation Statement. As you use this worksheet, as yourself: Which do you need to build on? Are there other skills not included on the sheet that you would identify? Which skills do I want to acquire? Circle them in a different color. Are there skills that you are very good at, but have little interest in using again? Even these capabilities may serve you well in a different setting. Meeting new challenges with new skills and knowledge helps you adjust to the fact that many jobs require a different range of skills. If it seems like the rules of career progress have changed in the middle of the game, it's because they have, but you can make it work to your advantage. Continuing formal education is an investment of time and money. If you have a lot of new material to learn, you'll want to prioritize and choose which skills to learn first. Tackling new learning one skill or class at a time makes your goals more attainable. A Regis University Center for Career and Professional Development Career Counselor can help you plan your continuing education strategy to help you pursue your goals and track your career development. Adaptability This is a challenging area because change is often externally imposed. We rarely have as much control over change as we'd like. Learning to manage frequent transitions keeps us flexible and adaptable. This is a tremendous skill to develop in an evolving economy. It's helpful to remember that transition is a process that takes place over time; it's not a momentary event. I'm going to draw from a few authors for help here. Mark Twain once said "Habit is habit and not to be flung out the window … but coaxed downstairs a step at a time." William Bridges, author of Transitions writes about change as an external event or catalyst that triggers transition which is the process people go though to adjust to change. Productive change takes time. Bridges describes transition as a neutral zone between the ending of something old and the beginning of something new when creativity and experimentation can flourish, during this time organizations and jobs develop into new shapes and sizes—they become more fluid and less mechanical - harder to put on a flow chart. Organizational mergers are a good example of this. Predictability will not always be desirable in the search for progress. Making the most of new opportunities in a fluid workplace becomes an important and meaningful challenge. Becoming portable, being able to change jobs, career, locations, companies, works best if we remember our transferable skills. Morale Curve for Adjustment to Change from the Menninger Leadership Center Arrival: Change has happened. Mix of shock, disbelief, numbness, false hope. "Nothing will really change and if it does, it won't affect me." Realization: Impact hits. Anger, frustration, confusion, anxiety or depression dominate people's thoughts as they see the negative possibilities. Acceptance: Reorganizing thoughts around resources, decisions, planning and actions. Seeing the positive possibilities, act on new opportunities improves morale and performance. Reentry: Moving in a new direction with a sense of what they learned and gained from the change. Making friends with change helps you see it as a catalyst for new opportunities. Where do you find yourself in this process? What changes might you want to initiate to promote your goals from your Motivation Statement? Information Gathering and using Information to the fullest is another tool in managing change and fueling career success. Having facts and new ideas from a variety of reliable sources helps you map out the next part of your career path. Arm yourself with information from all sources includes: Electronic - Information that helps you find, sort, store and update information at a speed that keeps pace with the changing world. Examples: Internet, tv, radio, video media, online magazines, databases, directories and journals Print - Hard copy information resources are still around and useful. They haven't been replaced because they are portable and cannot be easily altered. Examples: Books, legal documents, printed magazines, directories and journals Personal There is no substitute for person-to-person information. Nothing you read can tell you what a person can convey, especially when it comes to career information. Information interviewing and networking are still the most useful tools in any successful job search or career transition. With all information formats, consider the source.Investigate the credentials of anyone giving any format of information just as you'd read the label on a food product before buying it. Sources will not just come from your field. Community Your personal and professional network can act as an anchor during times of change, making the process of transition more comfortable. There is no need to face constant change alone when you can be part of a team. Keeping track of your network helps you discover that you have more good contacts than you may think. Your Professional Circle can include a personal board of advisors that you organize as well as people you mentor. This is a concept found in a variety of sources including Gregg Levoy's book, Callings. Determine whom you trust to have your best interests at heart. Your advisors will not just come from your field. Solicit feedback and ideas from your board of advisors individually or in a group over coffee, lunch, golf, hiking or some other activity. Consider also those people whom you advise formally and informally. Remember that some important contacts will fall into neither category, but may be listed as personal information sources. Foster your own development by mentoring others. Close connections with someone new to your field benefits both parties. Helping others negotiate change keeps your own perspective fresh. You'll be more aware of this if you track your mentoring. The competitive paradigm is being softened with a renewed sense of collaboration and teamwork. Synergy of work teams and collaborative efforts creates vitality for people and organizations. Productive collaboration is a fine art, but when it's mastered, the results increase energy to help keep your career change moving. Part of your community connection includes checking in with career counselor as you would with your coach or physician. Just as a good physician can track healthy development, a career counselor can help you track progress toward your goals by helping you define your issues, identify resources, develop solutions and move toward implementing those solutions as part of an overall strategy with your life mission as the focal point. You may fill out these exercises and, after looking at the results, think you'd like to plan a change or shift in your career path. Or you might look for a new approach to maintaining vitality on your current path. Either way, your support community, including periodic check-ins with a career counselor provides encouragement and new ideas. Putting it all Together Making a career change takes time, planning, patience and support. The Career Counselors at Regis University Center for Career and Professional Development are available to assist with in-person and telephone appointments, as well as email assistance to help you determine a course of action and implement your next career move. Job seekers find that writing a resume, conducting an effective job search campaign, or developing a career plan will progress more easily by clarifying the core mission and tapping into the other elements we discussed: education, information, adaptability and community. Career Counselors in Regis University Center for Career and Professional Development can help you with your career development needs, including helping you navigate and manage a career change. Call 303-458-3508 (800-388-2366 x3508) to make an in-person, phone or Skype appointment.


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Joseph had covered a few language apps over two posts last year (see part 1 and part 2). Here's a new one.
Midori is a Japanese/English dictionary useful if you are studying Japanese or if you find yourself lost in translation. This app is especially convenient for students, mainly for the following key features when studying Japanese:
- Fast searching for translation terms. Whereas a lack of speed exists in many Japanese dictionaries, this app performs very well;
- Kanji details are shown with an animation for the correct strokes drawing order;
- A large number of examples using the searched word, which is great for learning purposes;
- finally: bookmarks, kanji lists based on JLPT and a translation mode that automatically separates searchable words from particles.
In a nutshell, the strong point of this app is its speed and an easy, clean and minimalistic interface. Added bonus for the translation mode, really helpful to do searches of terms from an article.


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Ferrari won't be building Italy's newest high speed train, but the company's chair is holding the reigns on the sleek "Italo" train. You think it's a coincidence it's bright red with a prancing animal — a hare — on the side?
The French-built train actually has more in common with a Renault than a Ferrari — Luca Cordero di Montezemolo's train monopoly-busting startup is part owned by French national railway SNCP — but that seems to be the way of things for Italian companies these days.
The always impeccably dressed Montezemolo said that the locomotiveless Italo, officially dubbed NTV, can travel as fast as 220 MPH, but Italy's existing high speed rails can only support speeds of up to 185 MPH. Able to travel from Rome to Milan in about three hours, Montezemolo has his sights set upon loosening Trenitalia's long running hold over Italian rail travel. By the end of this week, the new trains will offer service between Rome and eight other cities.
Montezemolo's started NTV — Nuovo Trasporto Viaggiatori — four years ago, and has his sights set on garnering 25 percent of Italy's high speed train ridership (some 8-9 million passengers per year) by 2014. To do this, his team has employed that most Ferrariesque feature: Style.
(Hat tip to AntiSpeed!)
Photo Credit: Getty Images


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Canadian appeals his Guantánamo 'child soldier' conviction
Omar Khadr, the Canadian "child soldier" who pleaded guilty to hurling a grenade that killed a U.S. soldier in a 2002 firefight in Afghanistan, is appealing his Guantánamo war crimes conviction.
Pentagon lawyers for Khadr, captured in a firefight at age 15, filed the appeal at the U.S. Court of Military Commissions Review on Friday. They argued both that he was abused in U.S. custody and that throwing a grenade in combat or planting land mines are not war crimes because American soldiers do it.
"Even considering the seriousness of his charges, the punishment inflicted on Khadr since his capture would be atypical for adults in the American justice system, let alone juveniles," his U.S. military and Canadian lawyers wrote in a 44-page brief that invoked episodes of his mistreatment brought up in pretrial hearings.
He was held in isolation, according to the brief, terrorized by barking dogs, threatened with rape, subjected to sleep deprivation, and shackled painfully.
It added: "The government's decision to treat Khadr as an adult war criminal, rather than a trafficked child soldier, resulted in unjust and unreasonably punitive conditions of confinement."
Khadr's father moved the family from his son's native Toronto to Afghanistan before the Sept. 11, 2001, attacks that spawned the Guantánamo tribunals.
The teen was captured, near dead, after a July 2002 battle at a suspected al-Qaida compound in which Army Sgt. 1st Class Christopher Speer, 28, was killed by a grenade.
The U.S. said Khadr, now 27, threw it and separately also planted land mines meant to kill U.S. forces. Three years ago Khadr agreed. He pleaded guilty at Guantánamo under a U.S.-Canadian diplomatic deal to serve the majority of an eight-year sentence in his native Canada, where he is now in a federal prison.
The appeal comes days after a former Australian prisoner at Guantánamo, David Hicks, appealed his war crimes conviction on grounds that he was coerced and that his charges of providing material support for terror were not legitimate war crimes.
Now Khadr's appeal argues that the acts he admitted doing did not constitute internationally recognized war crimes — an argument a U.S. military judge rejected in pretrial hearings.
The brief was signed by Pentagon-paid appellate attorneys, including an Air Force Capt. Justin Swick, who argue that grenades and "command-controlled land mines" are not only allowed "against a lawful military target" but that "U.S. service members routinely use these types of weapons in combat."
Pentagon prosecutors had argued at various times that Khadr was obliged to surrender and not resist the U.S. invasion in the aftermath of the 9/11 attacks.
Swick said Friday that although Khadr gave up his right to appeal the conviction in his 2010 plea agreement, "there are certain things you cannot waive. Jurisdiction can never be waived. In other words you can never be found guilty of something that is not a crime."
At the Pentagon, a spokesman said the prosecution had no immediate comment.
"We believe it's premature to respond," said Army Lt. Col. Todd Breasseale. "The response to Mr. Khadr's arguments will come when the government files its brief."


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In the event of an oil spill, Pirtek offers a range of absorbent, containment products and spill kits to help contain and clean up oil spills and minimise the environmental impact
Select a specific type of item using the dropdown list below to view the relevant PDF page:
© Copyright Pirtek 2019 | Intranet Log-in | Privacy Policy | Terms and Conditions | Contact Us | The Pirtek App | Website by Verto
Pirtek UK Ltd. Registered in England and Wales: 2301810 Registered office: 199 The Vale, Acton, London, W3 7QS. VAT no. 701872940.


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Brands Across
the United States
Platform Strategy helps remarkable people achieve new heights in visibility, credibility, recognition, and income. The Platform Strategy team packages your expertise with an award winning personal branding process, fueled by sharp effective publicity, to make you the recognized leading voice of your profession.
Platform Strategy clients are media trained and speech coached while we build brand-supporting websites, arrange book deals, capture the media spotlight, arrange speaking engagements, and use tools, techniques, and technologies from the entertainment, publishing and corporate worlds to promote the best authentic you.
The result is a very visible high-value professional brand that catapults you to the elite 1% of your field and keeps you there.
Jay Jessup & Maggie Jessup
Every field has its Alpha Celebrities; they all follow a similar playbook to join the elite one percent of their industry. Now anyone can learn and apply the same personal branding and publicity formula used by Donald Trump, Martha Stewart, Suze Orman, the Dalai Lama and other notables.
Fame 101 shows you how as authors Jay Jessup and Maggie Jessup share the radical branding strategies they use to create and maximize brands for lawyers, authors, business leaders, scientists, and others who want to harness the power of personal branding.


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There is no "real time" camera or Web cam on board the telescope for live relay links. The images that the Hubble takes are digital pictures and spectra released to the public after one year (to allow the investigators time to do their research).
The data, which are transmitted from the telescope in digital form, needs to be converted from this digitized information by computers into black-and-white photos. These are then enhanced to discern details in the images.
For more detailed information on how the telescope and its instruments operate, visit HubbleSite's Nuts & Bolts.
HubbleSite and STScI are not responsible for content found outside of hubblesite.org and stsci.edu
Next question: Does Hubble withhold information from the public?
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See all questions and answers on one big page.
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A single column system can be used with a webcam connected to Bluehill Universal to track the force needed to tear flexible plastic film in accordance with ASTM D1004-13.
The lap shear strength of metal specimens depends on the bonding process; to minimize variations in the process and testing results, follow the ASTM D1002 standard.
For testing polymer hydrogels, use an electromechanical test system with a low force load cell, pneumatic or manual screw action grips, and a BioPuls™ Bath for realistic testing conditions.
For ASTM D1876, a T-Peel test with a correct and uniform data sampling rate is important to understanding the peel characteristics of adhesives.
By moving a sled across a stationary plane, one can determine the coefficient of friction of plastic film and sheeting while following ASTM D1894.
ASTM D413 recommends creating an artificial tear in rubber attached to other materials and then pulling apart the layers placed into the grips.
When testing adhesion between rubber and rigid materials, use a tension or peel procedure and follow ASTM D429 standards.
ASTM D5587 is used to determine the tearing strength fabrics using the trapezoid procedure.
For testing the peel or stripping strength of adhesive bonds, use manual screw or pneumatic action grips with rubber coated or smooth flat faces.
BioPuls Submersible Pneumatic Grips and a Temperature-Controlled Bath can imitate the behavior of human tissue in order to test the strength of tissue adhesives.
The 5940 Series Testing System with pneumatic side-action grips can test the adhesive strength of medical packaging for pre-packaged devices and instruments.
Following ASTM F88, a test with the 3345 system determined the strength of a seal on packaging for disposable medical devices to secure the sterilization.
EN 12242 is used to determine peel strength of touch and close fasteners.
A loop tack test can be used to understand the adhesive strength of an adhesive impacted by the pressure of its application by following the EN 1719 method.
The EN 1939 method can illustrate the peel adhesion and average load of self-adhesive tapes by applying the tape and using a tensile machine to find the peel force.
EN 868-5 is meant to find out the peel characteristics of laminate products, including the heat seal joints in self-sealable pouches for sterilized medical products.
With a CEAST 9350, wedge impact fixtures used can test the bond strength of FRP composites and epoxy vinyl ester resins used on Jet Bubbling Reactors.
The peel strength of a T-shaped bond of two flexible substances can be determined in following ISO 11339 method for self-adhesive tape.
Following ISO 11897 to determine tear propagation of thin films using Instron pneumatic side acting grips with rubber coated faces.
To determine the tear strength of vulcanized or thermoplastic rubber, ISO 34-1 characterizes standards for tests including trouser, angle, and crescent test pieces.
ISO 36 provides the way to measure the peak force and adhesion strength of either fabric bonded with rubber or rubber and fabric bonded together.
To follow ISO 6383-1, test the resistance to tearing for thin, plastic films and sheets of rigid and flexible specimens in a trouser-shape.
ISO 8067 gives guidelines for analyzing the peak force and tear strength of flexible cellular polymeric materials with a particular thickness.
ISO 813 gives a method to test the adhesion strength of rubber attached to rigid materials by stripping a layer from the bond to determine the strength.
Non-sticky film and sheet plastics can be tested for static and dynamic frictional characteristics with a tensile testing machine and coefficient of friction table.
ISO 9073-4 is used to determine the tear strength of nonwoven specimens.
Instron's multi-needle and single-needle test fixtures reduce time in testing needle insertion force in the development and quality control of needles.
Lid packaging needs to be checked for barrier properties, seal strength, shelf life, and peel strength to determine is usability and security.
With a FINAT test roller and a tensile testing machine, the peel adhesion properties of laminates can be determined, following FINAT Test Method 2.
Solar cell manufacturers create mechanical tests to evaluate thin films and substrates to improve energy output, quality, and reliability as well as minimizing cost.
Instron's syringe testing figure assists pharmaceutical manufacturers in determining the force needed to eject medications from needles and syringes.
With a variable angle peel fixture to stimulate real conditions, technicians can test the adhesive strength of tissue adhesives of the biomedical industry.
Universal testing machines can pull off a layer with a tensile force to test adhesion strength between rubber and flexible substrates.
ISO 2411 tests the coating adhesion strength of wet and dry fabrics coated with natural rubber, plastics, or synthetic rubber and works best with pneumatic grips.
In following ASTM D1335 for tuft bind testing of artificial turf, the short tufts are challenging to grip in testing the durability of the surface.


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This question already has an answer here:
- How do I improve my coding skills? [closed] 19 answers
From my experience in the current working environment, one's professional development is definitely in the hands of the individual.
As I see it there are several routes to the same objective based on cost, time and availability
- External Offsite training Online
- Training providers (itunes U,Pluralsight etc)
- Books
- Specialist /user groups
- Specialist web sites (Channel9, stackoverflow,dnrtv,codeplex etc)
What would you consider to be the best approach (blend) to continued learning and maintaining a professional standard of work?


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WESTCHESTER COUNTY, N.Y. - An online petition supporting a Port Chester father who is facing deportation has garnered nearly 250 signatures as his family attempts to keep him stateside.
The Hudson Valley Community Coalition is circulating the petition on behalf of Aroldo Soto-Contreras, who was detained last month during a routine check with Immigration and Customs Enforcement and is now facing deportation
According to the petition, Soto-Contreras came to America from Guatemala in 1989, when he fled the war-torn country. He was arrested for driving while intoxicated three times during his early years in the country, though he "has since reformed himself, married and is now the father of three children."
Soto-Contreras has worked at a Stamford, Conn. pizza place for nearly two decades and he has been a resident at the same house in Port Chester for several years. He is currently being held at the Bergen County Homeland Detention Center in New Jersey.
In just two days, the petition received 240 signatures from well-wishers supporting Soto-Contreras. His family has also been in contact with New York Sen. Chuck Schumer's office regarding his deportation, according to a lohud report .
Another Port Chester father, Noel Lopez-Reyes, received an eight-month stay of execution from ICE last month.
"My father is a crucial and needed part of our family unit. He is not only the most devoted and loyal father a family could ever hope to claim as their own, he is also the hardest working man I have ever known," his son, Ronald Fernando Contreras said.
"He leads by example in our household by upholding values and enforcing strong character in me and my two younger brothers. My entire life, he has put the needs of us - his family - first. He instead of worrying about himself, he always asks first about our needs and what he can do to help us in any way possible."
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Perl Module Monday: namespace::autoclean
This week, I'm writing from the relative comfort of my hotel room in Portland, as I am attending the 2011 O'Reilly's Open Source Convention. I always enjoy the hell out of this conference, as it's great to see people in person that I only correspond with via email the rest of the year. And the caliber of the tech talks seems to go up and up each year.
For this week's PMM, I've chosen a pragma: namespace::autoclean*. This pragma solves a problem that I'm embarrassed to admit I didn't even know existed— the problem of those functions you import being left laying around in your namespace.
See, the reason I'm embarrassed is that it's actually quite obvious: when you import a symbol into your namespace, it's there until/unless you get rid of it. Maybe in some cases you want this to happen, but what about when you're writing a class? You don't import methods from other classes, you inherit them. So nothing that you imported is necessary for the user-facing interface your class provides. And if you leave things laying around, your users can call them as methods, though the result might be a mess. Worse, is when the result isn't a mess, but is something you didn't want them to be able to do, such as calling
has as a method on your Moose-based class, and thus adding to the class attributes at run-time. You probably don't want that to happen. Indeed, that is how I came to hear about this module; during RJBS's Moose tutorial today, he stressed the importance of ending your Moose-based class with "
no Moose;", but then as an aside mentioned that he preferred to use namespace::autoclean.
That sort of clean-up is where namespace::autoclean steps in. At the end of a lexical scope, it cleans up everything you've imported. Where you used these symbols, they're still properly bound. But to the outside world (read: clueless and/or nosy users) it's as if those symbols were never there. And it has options as well, letting you specify additional symbols to clean: have some helper functions that you used, but don't want users who've read your code to call them directly? You can tell namespace::autoclean to take those out of the picture, as well.
It's a simple module, with a simple purpose. And it solves a non-simple problem. So this week, I recommend giving namespace::autoclean a good look.
* Starting with this week's PMM, I am linking modules to MetaCPAN.org. I'm really impressed with the new search interface, and the ability to link it to my PAUSE ID, to my GitHub account, PerlMonks, etc. I think it is showing a lot of potential.


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Climate change and its consequences, ranging from increasingly destructive storms to rising sea levels, have become prominent features in the international news.
Climate change is having an impact on the water cycle, raising the issue of whether we should be investing in adapting to these impacts or focusing on more pressing water resource issues, such as providing water and sanitation for increasing populations? If investment in adapting to climate change is a priority, then is it best to invest in protecting natural ecosystems or developing engineered infrastructure?
"The traditional way of handling extreme events such as floods and droughts, with engineering works should be complemented with the ecosystems approach which integrates the management of land and water that promotes conservation and sustainable use in an equitable way", says Dr. Max Campos, Review Editor for the Latin American Chapter for IPCC Impacts and Adaptation Report .
"Climate change is indeed an important issue, but it needs to be seen in context of the many other global challenges affecting water resources such as population growth, urbanization and land use change. Adaptation is vital – but we need to adapt to the full range of factors that are stressing water resources, and not focus on human-forced climate change to the exclusion of everything else", says Oliver Brown from the International Institute for Sustainable Development (IISD).
"It should be a must for vulnerable communities whether in the developed or developing world to ensure that their development ambitions are prepared for climate change. Adaptation should not be limited to the rich", said Dr. Henk Van Schaik, Deputy Programme Coordinator UNESCO-IHE. He argued that vulnerable communities in the developed world are preparing and investing to protect their societies, economies and environments to the impacts of climate change. This is not so in transition economies nor in developing countries.
Going beyond the issue of investment in pressing development issues or adaptation measures, is the question of looking at natural versus engineered solutions.
"Conventional approaches to climate change adaptation range from water conservation and efficient use to new operational techonologies", says Dr Mark Smith, Head of the IUCN Water Programme. "Dams and reservoirs are still considered as the most effective structural means of risk management. But we need to start thinking of the environment as infrastructure for adaptation as well. Health and intact river basins, wetlands and floodplains make us less vulnerable to climate change. Lowering risk is a good reason for investing in watersheds and the environment."
Darren Saywell from the International Water Association (IWA) stressed that "we need to work with different approaches, selecting locally tailored solutions for demand and supply. In order to maintain or improve access to water and sanitation in light of climate change, these ecological solutions or 'green infrastructure' stand out as cost-effective measures adding a range of ecological benefits, such as reducing the damage of extreme weather events."


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Ellaroo baby carriers are designed by parents, for parents. The styles are inspired by traditional baby carriers from around the world, while keeping the modern parent in mind.
Ellaroo was founded in 2003 as a reliable source of superior baby carriers, and to be an economically, socially, and environmentally sustainable business. The product list has grown gradually, always focused on well-crafted designs that are practical and convenient for parents.
It is essential to the Ellaroo team that our work contributes something meaningful to other people's lives. Ellaroo has a mission to improve people's lives – farmers, crafts people who make the products, staff, resellers, parents and babies – at every level of business interactions.
We've made it easier for you to search for available products in your area. Browser through our product selection to find the perfect Ellaroo Baby Carrier for you and your little one. Then find the nearest reatailer carrying your selection.
Let's explore the various ways to wear your Ellaroo. Here are some easy to follow instructions for wearing your Ellaroo. Browse through our selection of wearing instructions and videos.
Find additional resourses from other mothers that enjoy Ellaroo baby carriers. See the video clips for custom wearing options and techniques.


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'Excellent' Vintage in Rioja 2004
Fri 13 May 2005
The 2004 vintage from Rioja has been rated at 'excellent' by the governing body, the Consejo Regulador. Overall, the weather was ideal for the vintage and has produced full, ripe, aromatic wines. A spokeswoman for the Consejo Regulador said the 'extraordinary' growth cycle will make for an historic harvest.


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Popular Lecture Series on Topics of Chemistry Prem Mohan Mishra | added on Feb 03, 2011 | India Aimed at arranging innovative lectures on different topics of modern Chemistry. The topics are selected from the level of graduate & post graduate students of Indian Universities.
|students of b.sc. (hons) of 3 years degree course, post- graduate students persuing chemistry & physics as main subjects, research scholars, teachers of junior & senior colleges


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The Game (Feat. Clyde Carson & The CMC) - 911 Is A Joke
The video to "911 is a Joke". Just hanging out at the studio, BWS decided to shoot a hood video to this song dedicated to Sean Bell.
Please click the "Report" button below if the video on this page is not working properly.
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The Expert at the Card Table 7 DVD Set Plus Bonus Book (205 pages) The Expert At The Card Table
The Expert at the Card Table , is considered the bible by many card experts. For many readers the material is difficult to understand. Now for the first time you can see exactly how the moves should look and, more importantly, how to perform them correctly.
Underground card expert, Wesley James, is finally releasing the real work on Erdnase, and so much more! On this seven DVD set you will not only see everything from the book, but also learn to perfect it from a master teacher. In addition, Wesley gives you his own handlings and insights on the moves; with co-host, Simon Lovell, he will guide you step by step through the ground-breaking text that made Erdnase a legend.
Esteemed sleight-of-hand artiste, Wesley James, is proud to release the full details...
Do you own this product? Write a review.


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What Is the New Covenant Church?
A churchless Christian is an oxymoron. As John Calvin famously said, echoing the church father Cyprian, "For those to whom God is Father the church may also be Mother." While the notion of "mother church" may jolt some readers, a …Read More
A Dwelling Place for God
In the Old Testament, God's presence with His people was most vividly manifested in the earthly symbols of Israel's tabernacle and temple. As symbols or types, these institutions pointed to a future fulfillment. That fulfillment is found in …Read More
The Power of the Broken Body
Mention the word church and a vast array of images enter the mind. A steepled building housing a congregation; a movement of God across the centuries and the world; "one, holy, catholic, and Apostolic"; "visible and invisible"; "militant and triumphant …Read More
Kids These Days
It's a funny thing about slippery slopes—you can slide down them slowly. The principle behind the concept isn't that you must move swiftly from here down to there if you have no moral brakes, but that you will …Read More
One Family Under God
He was asking a question that I had heard multiple times during my years as a pastor: "Do you have children's church?" This time, instead of giving an extensive explanation for our practice of not segregating our church worship …Read More
Knowledge Without Zeal
When Paul, under the inspiration of the Holy Spirit, describes the church as the body of Christ, he speaks more wisely than we fools tend to hear. As is the habit of the modern evangelical church, we take the full …Read More
Who Draws the Line?
As Jesus ascended into heaven, He delegated His authority to the Apostles to make disciples: "Go therefore and make disciples of all nations, baptizing them in the name of the Father and of the Son and of the Holy Spirit …Read More
Your Church and Your Life Planning
A friend recently emailed me asking how he should weigh leaving his church to take a job in another city. I told him that he was "free in Christ" to stay or go but that I loved his factoring his …Read More
An Appetizer for the Feast
Go ahead. Ask me what would make me happiest if I had a totally free day. I'd tell you that during such a dream day I'd be by myself, probably with a book. Right at the front of …Read More
Band of Brothers
Real men don't eat quiche, and real men don't do church. For a variety of cultural and sociological reasons, it has become an accepted fact that the majority of people in most churches are women. It is now …Read More
The Bonds of Brotherhood
Fraternity … what does this word mean? It can refer to several distinct types of associations or relationships, and the church can learn valuable lessons by exploring these in more depth. The term fraternity may prompt us to recall the motto …Read More
The Church Gathered
In ancient Athens, Aristotle, a Greek philosopher of the fourth century BC, wrote about a custom in which, at age eighteen, young men submitted to an examination by fellow citizens and subsequently started physical and military training. Three fathers from …Read More
A Generation of Heroes
Satan watches for those vessels that sail without a convoy," wrote Puritan pastor George Swinnock (1627–1673). Every individual knows he was created for community. Isolation is the Devil's playground, and our Enemy is on the lookout for the Christian …Read More
Who Is My Brother?
Conservative Christians seeking a way to encapsulate our most fundamental political commitments came up with "family values." We vote "family values." We support "family values" candidates. Even the left has noticed, countering our language with this bit of …Read More
The Crown of Thorns Club
When was the last time you went to a private social club? If you think that kind of thing is for the elite members of our society alone, guess again. The Yellow Pages are filled with lists of social clubs …Read More


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Hardware EngineeringApril 17, 2003
I find it pretty easy to take for granted the amazing feats computer engineers pull off these days, mainly because they're too small to be visible. It often helps my understanding to have an analogy on a larger scale.
For example, according to this article, a new portable storage device for digital cameras / MP3 players has improved efficiency by shrinking the space between the reader and the media. Their analogy is that this increased shrinkage is akin to a Boeing 747 flying a millimeter above the earth's surface.
Think about the control here. A device moving quickly enough to read data is so amazingly close to the actual media that the slightest deviation would be enough to cause the two to collide and probably destroy them both. But instead, the technique is reliable enough to allow for consistent data storage.
A 747 flying a millimeter above the ground. Now that's pretty amazing.


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Our unique and comprehensive approach leverages industry experience and a nonprofit mission - focused 100% on ALS research.
Scroll to Learn More
We are the world's foremost drug discovery center focused solely on ALS. Pioneering the 'nonprofit biotech' model, we have
placed the person with ALS at the center of every decision made in our labs.
With preclinical, clinical, and translational research all happening under our one roof, we rapidly pursue the best ideas for slowing,
stopping, and ending ALS. We will not stop until there is a treatment for every person living with ALS.
There are too few potential treatments in clinical trials for ALS. We need a robust, good quality drug pipeline to ultimately treat every
person living with ALS. More treatments mean more hope.
ALS is extremely complex involving a myriad of biological pathways. To test drugs more rigorously, we need a variety of both cell and animal
models to capture all of the complexities of ALS.
Clinical trials for ALS currently require too many participants. That slows the studies down and makes them very costly. Using emerging
technologies, we hope to make clinical trials more efficient to reveal the most promising treatments faster.
In recent years, we've learned a lot about ALS, but there is still much that we don't know. We believe that best way to learn more is to
partner with people living with ALS. Through our Precision Medicine Program, we combine medical histories, family histories, genetics,
biomarkers, and patient cell biology to better understand the processes that drive and influence ALS.
Since its incorporation, ALS TDI has seen major expansion of all our research programs, making progress toward our mission to end ALS.
Meet the team
Schedule a tour
View all trials
This program seeks to gain critical new insight into the discovery and clinical development of treatments for ALS through the
integration of genomic, molecular, and patient reported data.
Learn More
In my opinion, the research ALS TDI is doing will bring us closer to a cure than anything else going on.
Bob Hebron
We have met the people who work at ALS TDI and their passion shines through, their personal connections to this disease drive them. We believe they are one of the most progressive and effective insitutes around, and they will be part of the cure.
Jeremy Truman
Jose supported ALS TDI because "of the Institute's single-minded focus on finding a solution for ALS, and doing so as a nonprofit biotech company with top-tier talent. Clear Objective + Solid Strategy + Stellar People = Desired Results."
José Cofiño (PALS, Died 2017)
A hallmark of chronic neurodegenerative diseases such as Alzheimer's, Parkinsons disease, and Huntington's is the abnormal accumulation of toxic, misfolded cellular proteins. In ALS genetic, biochemical and pathology data from animal models and patients have demonstrated that the accumulation of misfolded proteins causes neuronal stress and the activation of the unfolded protein response (UPR) is a protective mechanism.
The translation and processing of proteins is a highly regulated cellular function. Proteins that are destined for secretion or insertion into cellular membranes are translocated to a specific sub cellular organelle called the endoplasmic reticulum (ER). Under normal physiologic conditions the endoplasmic reticulum associated degradation (ERAD) system in the ER is designed to shuttle improperly folded proteins from the ER to the cytosol for degradation via the ubiquitin-proteosome system. The homeostasis of properly folding proteins in the ER, glycosylating secreted proteins, and properly inserting them into membranes prior to secretion or subcellular organelles is orchestrated by dozens of protein chaperones and enzymes. One of the must abundant and critical ER chaperones that maintains this homeostasis is the chaperone BiP/Grp78.
BiP associates with three ER transmembrane proteins ATF6, Ire1, and PERK that mediate distinct downstream UPR signaling events. Initial evidence suggested that the accumulation of unfolded proteins in the lumen of the ER disrupted a stoichiometry that exists between binding of BiP to these signaling molecules on the ER membrane versus its association with unfolded proteins. Under normal physiological conditions BiP associates with these signaling molecules keeping them tethered to the ER membrane but when the concentration of unfolded proteins in the ER increases BiP is pulled away from these molecules allowing them to be cleaved from the ER membrane and mediate downstream UPR signaling. It is now more evident that BiP does play this role to some extent but that the signaling molecules themselves are capable binding to misfolded proteins in the ER and initiating downstream UPR signaling in the absence of BiP binding.
These three regulatory proteins (ATF6, Ire1, and PERK) work together to decrease cellular stress under condition of protein misfolding by increasing the protein chaperone machinery, increasing the protein degradation machinery, and decreasing protein synthesis until cellular stress is relieved.
IRE1 is a type I ER transmembrane protein with a cytoplasmic kinase and RNAse domains. IRE1 forms oligomers under conditions of UPR activation resulting in the functional activation of its RNAse functionality. IRE1 homo oligomers dissociate from the ER plasma membrane into the cytosol. The activation of IRE1's RNAse activity in the cytosol results in the splicing of the Xbp1 mRNA transcript into an alternatively spliced form that is recognized by the protein translational machinery which now translates Xbp1 into a functional transcription factor that enters the nucleus and changes the expression of UPR associated target genes.
PERK is a type I transmembrane protein of the ER whose cytosolic domain has a kinase domain. Under conditions of ER stress PERK dissociated from the ER membrane and its kinase activity phosphorylates the translation initiation factor EIF2A. Phosphorylation of EIF2A results in an overall reduction in protein translation in an attempt to alleviate the accumulation of misfolded proteins. A subset of RNAs are preferentially recognized by phosphortylated EIF2A however and become translated into functional proteins. These include the transcription factors CHOP and ATF4 as well as GADD34 which is a phosphatase the provides a negative feedback loop dephosphorylating EIF2A. Under prolonged conditions of ER stress the downstream targets of the transcription factor CHOP become activated and are proapoptotic genes that result in cell death.
ATF6 is a type II transmembrane protein that under conditions of ER stress translocates to the Golgi where the amino terminus is cleaved releasing an active transcription factor that enters the nucleus upregulating UPR associated genes.
In addition to its role in cleaving Xbp1 prolonged activation of the UPR results in IRE1 mediated activation of ASK1 kinase. ASK1 is a critical component of two cellular stress pathways the Jun N Terminal Kinase (JNK) Pathway and the p38 Map kinase pathway both of which activate downstream apoptotic signaling.
Several conflicting reports have suggested that either activation or inhibition of the UPR can ameliorate apoptosis and improve disease progression and improve survival in murine models of ALS. In addition several studies have demonstrated that the UPR is up regulated in post mortem spinal cords from ALS patients. Modulation of this critical pathway has shown therapeutic potential in models of prion disease, and Alzheimers disease.
At the ALS TDI we are exploring multiple ways to mediate down stream apoptotic signaling by controlling long term UPR activation. These approaches are focused on small molecule inhibitors of critical regulators of the pathway.
ALS is a progressive neuromuscular disease characterized by muscle atrophy and paralysis. One of the hallmarks of ALS that differentiates the disorder from muscular dystrophis, which primarily effects muscle fiber formation and integrity, is progressive degeneration of the synaptic connection between the motor neuron and the specific sites on muscle fibers. These highly specialized synapses are called the neuromuscular junctions (NMJs).
In ALS patients is has been demonstrated that at the time of symptom onset more than 50% of the NMJs are lost in an affected muscle group. These data have been validated in animal models of ALS where loss of NMJs occur at least thirty days prior to symptom onset.
The formation of NMJs occurs during embryogenesis and later developmental stages as the fetus actively moves in utero. It is during this period that motor units on the muscle fibers become innervated from multiple motor neurons. Postnatally a normal process of synaptic pruning occurs eliminating "weaker" connections such that by adulthood a motor unit is innervated by a single motor neuron.
In the context of injury to the muscle or nerve, the synaptic connection at the NMJ can be transiently lost. Yet the system demonstrates plasticity allowing for reinnervation by the previous motor neuron or even adjacent motor neurons. It is currently unclear how this plasticity is maintained and what signals dictate the reinnervation process.
The formation of NMJs is dependent on a complex signalling cascade that coordinates the formation of a mature synaptic cleft between muscle and the nerve terminus. A key regulator of signalling on the muscle (postsynaptic) side is the receptor tyrosine kinase MuSK. MuSK expression is pre patterned in the motor unit and is regulated by Wnt signaling and the expression of the MuSK ligand LPR4. On the nerve (presynaptic) side the expression of the LRP4 receptor Agrin by the incoming nerve terminal of the motor neuron results in the binding of Agrin to LRP4 enhancing its association with its ligand MuSK resulting in MuSK phosphorylation and clustering of MuSK-LRP4-Agrin. Phosphorylated MuSK results in the intracellular recruitment of DOK-7. In the presence of Agrin Dok-7 becomes phosphorylated resulting in further phosphorylation of MuSK and MuSK dimerization. Dimerization events result in the recruitment of adapter and anchoring proteins Rho, Rac, and rapysin all of which are required for NMJ formation and stabilization. The recruitment of the adapter proteins causes the recruitment and clustering of acetylcholine receptors. The subsequent clustering of the acetylcholine receptors results in the establishment of a highly synchronized neurotransmitter release mechanism at the NMJ synapse that converts the intracellular signaling into electrical action potential and ultimately kinetic muscle movement.
Though it is an active area of research the cellular mechanisms underlying the repair and plasticity in the context of injury and neurodegeneration such as in ALS is currently unclear. However several neurotrophic factors (IGF1, GDNF), microRNAs (mir-206), and Schwann cell derived factors (NOGO-A, Sema3A) appear to play both positive and negative roles in repair and stabilization of the NMJ. ALS TDI has several small molecule and protein therapeutic strategies targeting these key mediators of NMJ repair in the context of neurodengeration.
Recent evidence suggests that Amyotrophic Lateral Sclerosis is a non cell autonomous disease whose onset and progression are influenced by the immune system.
Microglial activation, astrocytosis and the presence of infiltrating inflammatory cells from the periphery have been well described. There is accumulation of IgG immunoreactive deposits in the spinal cord of ALS, infiltration of lymphocytes, dendritic cells, monocytes, and macrophages into the spinal cord in ALS.
Although the role of infiltrating is poorly understood recent work would suggest that type I macrophages are localized to neurons that have "died" back from their appropriate connections on muscle fibers, and pro inflammatory lymphocytes are present in the periphery both of which infiltrate into central nervous system tissues. The infiltration of pro inflammatory cell types results in astrocyte and microglial activation with ensuing neuroinflammatory cascades.
It is generally accepted that two signals are required for maximal T cell activation. The engagement of the T Cell Receptor (TCR) on T cells with antigen bound Major Histocompatibility Complex (MHC) on antigen presenting cells (APCs) and binding of CD28 on T cells to B7 receptors on APCs. With the development of knock out mice and blocking antibodies it became apparent that there were multiple CD28 homologues capable of binding B7 receptors on APCs and that multiple B7 receptors existed with different affinities for CD28 ligands/receptors. CTLA4 a homologue of CD28, is expressed on activated T cells, has 20 times higher affinity than CD28 for binding to B7 on APCs, and blocks T cell activation. A soluble form of CTLA4 (CTLA4-Ig is capable of binding B7 receptors and blocking T cell activation. Expression cloning identified two distinct B7 receptors on APSs, B7-1 (CD80) and B7-2 (CD86) both of which are capable of binding CD28 and CTLA4.
In addition to the B7 receptors the Tumor Necrosis Factor (TNF) family member CD40 is up regulated on APCs after activation by foreign antigens. In CD40 knockout mice the activation of APCs by foreign antigen up regulates CD80, CD86, and MHC expression on APCs but fails to activate T cells or elicit a humoral response. CD40 is expressed on mature B cells, macrophages, and dendritic cells. The receptor for Cd40, CD40L (CD154, gp39) is a Type I membrane receptor and a member of the TNFR superfamily. CD40L expressed on activated T cells as a result of antigen presentation. CD40 ligation induces expression of adhesion molecules and costimulatory molecules on APCs such as CD44, ICAM1, ITGAX (CD11c ), CCL3 (Mip1a); Fcgr2b (CD32); ITGAM (CD11b); ITGB2 (LFA1/CD18) and MHC class II molecules.
Induction of CD40L expression on T cells activates B cells which can be blocked by antiCD40L Abs (MR1). Administration of anti CD40L Ab MR1 blocks primary humoral responses in vivo induced by the immunization of SRBC (Sheep red blood cells) as assessed by the number of plaque forming units in the spleen of treated mice. Transient treatment with MR1 results in prolonged inhibition of primary humoral response in vivo including the expression of immunoglobulin isotypes.
A significant body of work has demonstrated the immunomodulatory effects of blocking CD40L, CD80 and CD86, or both in preclinical models of transplantation and autoimmunity. Blocking CD40L function with blocking antibodies or adenoviral expression of CD40L-Ig improves allograft transplant by 30 to 90 days. Similar studies blocking CD80/CD86 on APCs with CTLA4-Ig or adenoviral expression of CTLA4-Ig transiently improves allograft transplant survival. Transplant rejection in these models is transient and graft rejection ensues over time. Longer term repression of transplant rejection can be accomplished by blocking both the costimulatory pathway with CTLA4-Ig and blocking CD40L activation of APCs with aCD40L antibodies. However secondary induced tolerance and the acceptance of a second graft has not been successful. Blocking antibodies to CD40L or genetic deletion of CD40L in mice has demonstrated that CD40L ameliorates disease progression, survival, and surrogate markers of disease in preclinical models of experimental allergic encephalomyelitis (EAE) a model of multiple sclerosis, collagen induced arthritis, and systemic lupus erythematosus.
We have recently characterized the activation of the costimulatory pathway in the spinal cord, sciatic nerve, and skeletal muscle of SOD1G93A mice using whole genome transcriptional profiling . We further demonstrated that in the periphery the costimulatory signature is associated with the accumulation of CD68+ monocytes in sciatic nerve and focal activation in the central nervous system . The activation of the costimulatory pathways was also evident in the peripheral blood in 47% of ALS patients analyzed. In an effort to determine whether anti-CD40L would impact disease progression in the SOD1G93A mouse model, we administered an anti-CD40L monoclonal antibody, MR1, to SOD1G93A mice. Treatment with anti-CD40L delayed disease onset, improved body weight maintenance, and extended survival in this murine model of ALS. MR1 treatment reduced the number of CD68+ cells in sciatic nerve by 42%, reduced astrocyte activation in the spinal cord, improved motor neuron survival, and decreased the activation of the costimulatory pathway in spinal cord and peripheral blood.
In summary, there is considerable evidence indicating that neuroinflammation and break down of the blood brain barrier are associated with disease progression in ALS. The modulation of the costimulatory and humoral response has proven to be efficacious in preclinical models of allograft transplant, experimental allergic encephalomyelitis, collagen induced arthritis, and systems lupus erythematosis. We have previously demonstrated that modulation of the costimulatory pathway is also efficacious in ALS. Our current immune modulatory portfolio consists of several protein biologics as well as antisense oligonucleotide that should modulate the activation of the pro inflammatory cascade and provide neuroprotective benefit.
Superoxide Dismutase 1 (SOD1) is a 16kd protein which acts as an enzyme whose primary function is to scavenge and convert damaging superoxide free radicals to less damaging chemicals. SOD1 is predominantly found in the cytoplasm, but can also be detected in mitochondria and cellular nuclei. Normal SOD1 forms a 32 kd homodimer forming an 8 key beta barrel that binds a catalytic copper ion and structural zinc ion. SOD1 is an abundant and ubiquitous protein, however its cellular concentration is significantly higher in metabolic tissues and in the central nervous system. The half life of wild-type SOD1 protein is long, notably in motor neurons. The longer half-life increases the likelihood that SOD1 protein may be subjected to post translational modifications oxidation.
Mutations in the gene encoding SOD1 are associated with familial ALS. Much evidence suggests that mutant SOD1 mediated toxicity resulting in neurodegeneration is caused by some unknown gain of function by the protein. Biochemical studies have suggested that under physiological conditions even wild-type SOD1 can become oxidized and misfolded and that mutant forms of SOD1 have a higher propensity for oxidation. Further, mutant SOD1, and to a lesser extent, wild-type SOD1 has been demonstrated to oligomerize and aggregate.
It remains unclear what elements of misfolded SOD1 are deleterious. There is evidence to believe that misfolded monomeric SOD1 are damaging to cells. Alternately there is evidence that aggregated SOD1 may be toxic. The presence of both could arise from mutations or post translational modifications that promote disulfide reduction, alter the dimer interface, or adversely affect copper and zinc loading.
The shortened cellular half-life of the monomeric SOD1 when compared to the homodimer offers the basis for the hypothesis that mutant SOD1 or monomeric wild-type SOD1 are taxing to the cellular protein quality control systems resulting in less efficient cellular housekeeping by protein chaperones and protein degradation mechanisms.
There is accumulating evidence that SOD1 misfolding occurs not only in patients with mutations in the SOD1 gene but also in sporadic ALS cases. Wildtype SOD can acquire biochemical properties of mutant SOD1 via oxidative damage and several studies have detected a unique 32 kd band in post mortem spinal cord extracts from patients containing SOD1 mutations as well as sporadic ALS patients but not healthy controls or other neurodegenerative diseases.
Monoclonal antibodies and Fab fragments have also been generated that are specific for unfolded SOD1 and do not bind SOD1 dimer. These antibodies were generated using either apo SOD1 or on internal epitopes (aa 141-151) on the dimer interface of wild type SOD1 that they predicted would only be exposed on misfolded SOD1 monomers and oligomers. In SOD1 animal models these antibodies suggest that only a small percentage of total SOD1 is misfolded during disease course (less than 5%) and that misfolded SOD1 was not apparent presymptomatically. ALS TDI has worked with several of these antibodies and have shown that at least one of these antibodies does indeed slow down disease and improve survival in the SOD1G93A transgenic animal model (NI-204B, Neurimmune). ALS TDI is partnering with Neurimmune on a clinical development strategy for this antibody and investigating the ability of this antibody to detect misfolded SOD1 in sporadic ALS tissue samples.
Mutant forms of SOD1 when bound to zinc form stable dimers under physiological conditions which are stable for months and contain no oligomers. The apo (metal free) form of both WT and mutant forms of SOD1 behave very differently under normal physiological conditions across a wide temperature range. At low temperatures oligomerization occurs fairly slowly over the course of 12 months however at physiological conditions oligomerization occurs rapidly and even small increases in temperature above 15 degrees Celsius enhances this rate up to physiological temperatures. Intermolecular disulfide bonds are formed during oligomerization and that Cys-6 and Cys-111 are implicated in this bonding. The addition of reducing agents such as DTT eliminated oligomers suggesting the formation of covalent disulfide bonds during the oligomerization process. Its interesting to note that once metalated both mutant and WT SOD1 dimers are very stable and thus non toxic.
It is also interesting that in an oxidative environment the process of disulfide bond formation will be driven more aggressively under physiological conditions and that in the mitochondria which favors a more oxidative environment that the process could be greatly accelerated and favored towards oligomerization. Elevated levels of noxious monomers could arise from mutations that promote disulfide reduction, weaken the dimer interface, decrease the global stability or folding cooperativity of either the monomeric or dimeric species, or adversely affect metal loading through the copper chaperone. The low stability of the reduced monomer provides also an explanation for sporadic ALS. In these cases, impaired function of the cellular ''housekeeping'' system, i.e., chaperones, quality control, and degradation mechanisms, might cause the reduced form of wild-type SOD to enter the same cytotoxic pathway as the ALS associated mutants, consistent with observations of cytosolic SOD containing aggregates in both familial and sporadic ALS.
Proof of concept experiments have shown that a mutated multiprotein homodimer can be stabilized by the binding of a small molecule at the subunit interface. This is exemplified by that of transthyreitin. Mutations in TTR cause familial amyloid polyneuropathy (FAP). Mutations in TTR cause destabilization of the TTR homotetramer resulting in dissociation of the tetramer, monomer mis folding and protein aggregation (Connolly, 2010). The natural ligand of TTR, thyroxine, can bind to the tetramer and stabilize the tetramer. Studies identified that the destabilized tetramer creates two binding sites that when occupied by thyroxine stabilize the tetramer. A structure based design identified several small molecule scaffolds that were capable of binding to the tetramer at the T4 binding sites and stabilizing the tetramer much like the natural ligand.
Similar proof of concept experiments have shown that small molecules can stabilize the mutant SOD1 dimer driving equilibrium away from a toxic misfolded SDO1 monomer. These small molecules lack pharmacological properties for in vivo testing thus requiring medicinal chemistry for further validation in vivo. One program we are pursuing at ALS TDI is to expand on this approach and screen for small molecules that eliminate the toxicity of misfolded SOD1 via interactions with crtical epitopes on the SOD1 dimer.
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My best Tartine bread attempt to date
I made two loaves of Tartine bread starting with Christmas eve overnight fermentation and baking on Christmas day. I thought this was not going to work because the dough had really started to rise at room temperature and in my proofing box (microwave oven) to double it's size. I thought that I was going to have a problem with over proofing and hence, get a gassed out final loaf. But it ended up being my best bread to date. I gave one loaf to my mom and the other was ours for eating. My, this is a great recipe (Chad Robertson's) and if you are patient and learn from mistakes, I'm confident anyone can achieve similar results.


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A cozy corner for moms & expecting mothers. The Den is a socializing area for members who are interested in or experiencing pregnancy, childbirth, and parenting.
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- People per Site: 50
Contact the park directly to reserve this facility; a minimum of three campsites in the Pin Oak Campground must also be reserved for the same dates.
- Picnic tables
- Outdoor grill
- Water nearby
- Electricity
- Restrooms nearby
- Open air pavilion
Plus daily
entrance fee
Note: Information and prices are subject to change. Please call the park or park information (1-800-792-1112) for the latest updates. The daily entrance fee is charged in addition to any facility fees, unless otherwise stated. A Texas State Park Pass will allow you and your guests to enjoy unlimited visits for 1-year to more than 90 State Parks, without paying the daily entrance fee, in addition to other benefits.
Pets are not allowed in any Texas State Park buildings. For other general pet restrictions check the Texas State Park Regulations. For park specific pet restrictions contact the park.
Call the park or park information (1-800-792-1112) for more information.