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June 2007
APPENDIX B: Resources
BuildingChoice.org, a Web site funded by the U.S. Department of Education, provides tools and resources for educators who are working to expand choice options for families. The Web site includes many examples of how districts across the country are communicating choice options to parents and working to involve parents in their schools, along with sample materials from these districts and tools that have been developed to help facilitate parent involvement.
Harvard Family Research Project
Housed in the Harvard Graduate School of Education, the Harvard Family Research Project (HFRP) assists policymakers, practitioners, and philanthropic organizations in developing strategies to support more effective educational programs, practices, and policies for all children, especially those who are disadvantaged due to poverty and other challenging circumstances. In addition to featuring relevant research and information that the project has collected, analyzed, and synthesized, the organization's Web site also includes a link for joining the Family Involvement Network of Educators (FINE), its national network of over 5,000 people who are interested in promoting partnerships between children's families, educators, and their communities.
KSA-Plus Communications
The KSA-Plus Communications Web site offers training opportunities and a range of other services to help parents gain the skills, knowledge, and confidence to become advocates for better schools for their children. KSA also runs workshops and provides consulting services, and provides materials to help administrators and teachers better understand how they can tap into the underutilized resources that parents and families offer and can better meet the increasingly diverse needs of families.
National Network of Partnership Schools
The National Network of Partnership Schools (NNPS), at Johns Hopkins University, is an organization that helps to build parent involvement, family engagement, and community partnerships for elementary, middle, and high schools across the country by providing tools, guidelines, and a model for developing a school-based action team. Among the many resources offered on the Web site are information on how to join NNPS, research publications and products that support implementation of the NNPS model, training opportunities for school-, district-, and state-level participants, and myriad success stories from those who have used the model.
The Parent Teacher Association
The Parent Teacher Association (PTA) is a national organization with state and local offices around the country. Its national Web site offers a range of resources, including parent resources, relevant current event articles and stories, and information about training opportunities. It also provides a tool to help visitors find their local PTA. PTAs provide a forum at which parents, administrators, teachers, and other concerned adults discuss how to promote quality education and how to encourage community involvement in order to create a healthy environment and safe neighborhoods for all children.
Parents for Public Schools
Parents for Public Schools is a national organization with community-based chapters working in public schools to improve education. The Web site offers links to all of the local chapters, which offer a range of services, such as trainings, outreach events, and information on school enrollment. The Web sites for both the national organization and local chapters also include links to a range of other organizations that provide resources for advocacy, training, and many other types of assistance.
The Prichard Committee for Academic Excellence
The Prichard Committee for Academic Excellence is a nonprofit education advocacy organization serving the state of Kentucky. Among its key initiatives is the Commonwealth Institute for Parent Leadership, which trains Kentuckians to become advocates in their children's education. In response to requests for assistance from outside of Kentucky, in 2001, the Prichard Committee also initiated the Center for Parent Leadership to offer similar parent support and training in other states. The Prichard Committee and its multiple initiatives offer training, consulting services, and publications to support parents as education advocates.
The Right Question Project
The Right Question Project offers ideas and services intended to equip low- and moderate-income families and their communities with the skills to participate at all levels of democracy. The organization's Web site provides materials and publications, information on training sessions and consulting services, and stories of how other organizations and participants have used the organization's services.
The Southwest Educational Development Laboratory
The Southwest Educational Development Laboratory (SEDL) is a nonprofit education research, development, and dissemination corporation that works with professionals in schools, districts, states, and service agencies to improve education for all students. Its Web site provides a PDF version of A New Wave of Evidence: The Impact of School, Family, and Community Connections on Student Achievement (2002), a synthesis of 51 studies about the impact of family and community involvement on student achievement and -effective strategies to connect schools, families, and community. SEDL, in collaboration with the Harvard Family Research Project, is now providing technical assistance to the PIRCs through a 2006 award from the U.S. Department of Education.
U.S. Department of Education Parental Information and Resource Centers
The U.S. Department of Education's Web site provides a Parental Information and Resources Center section that includes a description of the program and links to additional information, including lists of current and former awardees and information on the grant process.
In addition, the home page of the Department Web site includes on its main navigation bar a parent link that serves as a portal to a section created exclusively for parents. Here parents and guardians can find information about how NCLB affects them and their children, how to help their children succeed in school, how to help their children learn to read, and other education issues.


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Difference between revisions of "User talk:Jpatokal"
Revision as of 07:18, 18 September 2012
What to do? --Stefan (sertmann) talk 09:28, 17 December 2009 (EST)
Discussions for you
Hey Jani, your opinion is desired at Talk:Singapore#New article for Pulau Ubin?. Also, I wondered if you might have any advice re this map of the Maldives—it was an unusually tricky map to create. --Peter Talk 13:54, 11 January 2010 (EST)
Any Bali feedback
I guess you got back safely :) Hope all went well. If you have any feedback on Bali listings (or new ones), please fire away. --Burmesedays 03:31, 13 January 2010 (EST)
It might have taken a while, but there is now a reply to your comment here. --Burmesedays 00:24, 19 January 2010 (EST)
(ja) バタム島
先日JpatokalさんがSharedにアップしたバタム島の画像を日本語版にも使わせていただきました。できればお時間があるときに"NagoyaHill FoodStreet"(「名古屋ヒル?」面白い名前ですね :-) )の簡単な解説を書いてもらえませんか?よろしくお願いします--Shoestring 15:53, 2 February 2010 (EST)
Make sure you are sitting down...
....when you read this. That Ubud won the award for top city in Asia is just about believable, but one hell of an achievement nonetheless. But this? If you take the top scores of all cities in the world, Ubud is fifth! I am stunned. Bali sadly lost (just) its perennial top island spot to The Maldives. --Burmesedays 02:50, 8 February 2010 (EST)
I never knew there was something like this on the wikia projects until I saw your profile on wiktionary :) I like it, it's pretty fun. Haven't you ever visited the Netherlands? We like to welcome you soon! 188.8.131.52 14:08, 15 February 2010 (EST)
Naming conventions
There's a lengthy discussion at Wikitravel talk:Naming conventions#Latin Characters, and a point was raised about why Vietnamese is an exception to the "use the Latin alphabet including accents/diacritics" rule. Since you wrote Wikitravel:Romanization#Vietnamese you would seem to be the expert on the matter, so can you add your thoughts? Thanks! -- Ryan • (talk) • 22:51, 16 February 2010 (EST)
Hi Jani. You might not be aware that Riverside has been up for Star Nomination for ages now? I thought you might want to comment.--Burmesedays 04:45, 17 February 2010 (EST)
As you are probably the only regular Wikitraveller who is not me that has been to Ubud this year, it would be great if you could comment on the starnom :). Cheers.
New admin
Globe-trotter's switch is ready to be flipped. --Peter Talk 12:29, 23 March 2010 (EDT)
Help with mapmaking
I've been trying to use the osmatravel scripts (I run Linux) to make a map of Riga, but I have a hard time understanding some of the instructions, namely where I'm supposed to draw the boundary and how I'm supposed to configure the tags.
Thanks, Rastapopulous 15:07, 15 April 2010 (EDT)
I want to serve the Chinese bureaucracy, the operator.
I want to serve the Chinese bureaucracy, the operator.
please give me Chinese sysop and bureaucrats Thanks you.
--用戶 03:21, 15 July 2010 (EDT)
see ZH
Enabling the Add Listing feature
Hi there. I've been trying to get the listing form editor working for pt:. I added the edit tools successfully and I've translated the labels for the listings editor and they show up fine in Portuguese when you access it from the edit button of a listing already in template format (example: pt:Viana do Castelo#Coma, but there is no section button to add a listing. Do you know how to enable that? Texugo 01:19, 7 September 2010 (EDT)
User:[email protected]
Hi, Jpatokal I noticed that "User:Msnhinet8" in Chinese wikitraval might be a vandalist who was blocked at Chinese wikipedia. I think adminins may have to watch him/her. Thanks. Mok 21:09, 10 September 2010 (EDT)
Hi. I wonder if you could tell me how to edit the main left-hand navigation box. Pt:'s navigation box doesn't have a link to its traveller's pub. Texugo 23:17, 16 September 2010 (EDT)
またお時間のあるときに日本語版にも遊びに来てください(よろしくお願いします)。--Shoestring 07:11, 13 November 2010 (EST)
Hi. Please clarify -> Talk:Delhi, thanks. Upamanyuwikitravel • ( Talk ) • ( Travel ) • 05:57, 26 November 2010 (EST)
mysterious letter
Hey Jani, there's this letter that looks like a p with the top poking out a little more than usual... I assume it's a Roman character since it is supported by my Nokia (the 9 wxyz key) while texting... Which letter is that exactly? upamanyu
Advice requested: Jeju page restructuring
Hey mate, last week I gave the Jeju page a roadtest -- without a car -- and found it just horrendously difficult to use. Ended up relying on a fistful of soulless brochures and browsing over odds and ends of Jeju Life on my phone. Sure, theres info missing and lacking in places, but that stuff comes with time. My concern was that some of the info actually there was lain out in such a jumbled and confused manner that I couldn't use all of what was there. Basic navigation info proved confusing and I think that's related to the article structure. I've thought about this a bit and come up with what I feel is a solution, albeit a bit unorthodox so I want a second opinion. A cross between splitting the article and following a Huge City template-esque structure. As you seem to have a fairly large interest in the South Korean articles I figured you'd be a good one to ask. I've detailed the proposal and the rationale behind it on the Talk page and I'm quite willing to play around with it myself whilst adding bits and bobs I've picked up. If you get a moment, could you please have a quick read and throw me some feedback or an opinion?
Also, any advice (or links to advice) on making consistent "Wikitravel-style" maps would be greatly appreciated as I can see a couple of articles begging for them. Cheers!
PS: Keep an eye out for snakes hey! I was living in Batchelor down beside Litchfield only a few years back for a few months. 4m python outside my door one night coming back from the pub. Harmless unlike the death adders I regularly spotted (have the photos to prove it too, my students scream if I pull them out). Snave 08:42, 31 January 2011 (EST)
Region and town quickbars
Hi there. How are you doing? A resurgent suggestion has come from a relatively new user about making quickbars for city and region articles, and I would really love to hear your opinion on it. When you get a chance, could you possibly join in this discussion? texugo 02:52, 21 May 2011 (EDT)
Suomen historiasta
Sinulle on täällä kommentti.
Bangkok Airport Bus
Hey Jpatokal, are you sure the Bangkok Airport Bus has stopped operations? That would be a tragic loss, I've used it not that long ago! :( I am looking for a source for more information on this, but I cannot find any. Do you have one? --globe-trotter 08:15, 13 June 2011 (EDT)
It started 10/06 last time. Digr 13:09, 15 July 2011 (EDT)
Inappropriate discussion
As should be obvious, especially in this case, fork discussions are not appropriate at WT. I have removed your two topics, as they amount to a backdoor method of undermining this community.--IBobi 16:14, 2 July 2012 (EDT)
Hi Jani, I have again reverted your changes to the fi: sitenotice. Please do not use the sitenotice feature to promote or discuss a fork of Wikitravel. You may see the discussion in the Pub for my reasons, of which I believe you are already aware. Thank you, --IBobi talk email 14:10, 23 July 2012 (EDT)
Hi, Jc, As I said, we'd prefer that you stay. But accusing IB technicians of being lazy based on absolutely no information other than that it took some time to fix a security hole built into the MW software that we just upgraded is irresponsible and unfair. There are a lot of emotions and accusations being bandied about lately due to the ongoing fork discussion; but that does not affect our duties as hosts of this site. I simply ask that we be given credit for the work that we are doing and have been doing for some time now, rather than blaming everything on past troubles. This is and has been an earnest effort, and I'm sorry if you can't see that. Hopefully it will become more apparent in time. Meanwhile, thank you for your contributions as always. If you have further comments on this or other issues that have nothing to do with Jani's page, I suggest we discuss them at my page or yours. Thank you,--IBobi talk email 14:00, 25 July 2012 (EDT)
Thanks, privileges, and inactivity
I realize you have not formally stated you have left Wikitravel, as Peter and Ryan have done, among others. And your work over the many years you've been a member and admin on WT is beyond reproach. I did notice that your contributions of late have been extremely minimal, almost entirely consisting of fork-related posts. You have not patrolled edits in a long time on EN, and I'm guessing you have not been doing so on FI or elsewhere either, though I'll check that.
You remain an Administrator on all versions where you previously had that title.
From December until July, you made no contributions at all on EN, and only resumed in order to talk about the fork. Since then, you've only made 21 edits, only 2 of which were non-fork related. One was a 5-word edit on a Japan page, the other was a vote on article templates. Neither of those required even Admin rights, let alone Bureaucrat rights. In fact I can't even find the last time you used your Bureaucrat privileges. Do you know?
Although you have technically been active again on the site since July, it's essentially been to promote the fork, which you have been doing very zealously, and which you are actively pursuing on WV and WM (where you will presumably move to if and when the fork is ever up and running).
Three months of inactivity occurred for your account March 5, 2012, which is when your bureaucrat privileges could have been switched off for site security. I'm open to a discussion about this, but I do not see your reasons for wanting bureaucrat privileges, other than the fact that you were given them in the first place. Please let me know if I'm wrong about this, as, again, I have no wish for you to feel badly about your excellent contributions to WT, and I'd love to see you resume constructive activity here.
Thank you Jani,
--IBobi talk email 16:06, 23 August 2012 (EDT)

subset: commoncrawl


text:
53,150pets' lives saved since becoming no-kill in January 2002
Hello! Woof! Meow! (not required to browse site)
LORA ROBINS GIFT SHOP Shop to save lives at our Robins-Starr Humane Center!
About Our Store
The best part about shopping at the Richmond SPCA? Your purchases directly benefit orphaned pets in our shelter. Named in honor of a wonderful person and benefactor, Lora Robins, our shop has many wonderful gifts for pets and pet lovers. We will also place special orders for our valued customers. Our prices are excellent, our staff are knowledgeable, and our selection of high-quality merchandise can't be beat!
Pets are welcome in our store. Please note that we recommend puppies be at least 6 months of age and up-to-date on their shots before visiting the Richmond SPCA."Like" us on Facebook for the latest deals and special offers!
Hours of Operation
Please visit the shop at our Robins-Starr Humane Center. Our hours of operation are:
Monday: 12 p.m. - 5 p.m.Tuesday through Friday: 12 p.m. - 7 p.m.Saturday: 11 a.m. - 6 p.m.Sunday: 12 p.m. - 5 p.m.Contact Us
Please give us a call at 804-521-1334 (shop manager) or 804-521-1301 (shop number), or email Christina Bird, our coordinator of retail, at email@example.com.
Accepted Forms of Payment
Cash, credit/debit cards, money orders, and Richmond SPCA gift cards are accepted forms of payment. No checks please. This policy applies to payments made for retail purchases, adoptions and clinic services.
Purchase a Gift Card
Looking for a gift for that special someone? Why not consider a Richmond SPCA gift card? Cards may be redeemed in our retail store, for pet adoptions or for training classes. You may purchase Richmond SPCA gift cards in our Lora Robins Gift Shop during normal operating hours.
Toy drive for homeless pets
The homeless pets at the Robins-Starr Humane Center are in need of extra tough toys for stimulation and play time while they await permanent homes. Help purchase a toy for a homeless pet in our care by donating $1 or more, and we'll add your name to our shop windows to show your support.
Some of Our Most Popular Items
Come see us soon!


text:
Watch 1980s video clip of WWUH in the News!
When the University of Hartford was incorporated just over 50 years ago by business and community leaders, they envisioned a center of education and culture for Greater Hartford. Read more...
Persons with disabilities who wish to access the WWUH Public File may contact John Ramsey at: firstname.lastname@example.com
Ambience News
Hi! Mark Time here.
Once upon a time (cir. 1978-1983), having 'graduated' from the Connecticut School of Broadcasting, my plan was to merge my passion (music) with my career. I simultaneously held positions at WHCN and WWUH. I always expected someone to tap me on the shoulder and say, "You gotta choose one or the other, buddy - commercial or non-commercial radio." It was nice getting paid to do radio, but that job wasn't 'about the music.' At 'UH, it was ALL about the music. I quickly graduated from The all Night Show and Gothic Blimp Works, to Midday Fuse (the show/bridge between Morning Jazz and Afternoon Roll). In order to fit Public Affairs in at noon, Fuse and Afternoon Roll were combined into a new show called Synthesis. Because I had the Monday slot, I actually premiered the very first Synthesis show. It was a great ride. We all explored this new world from jazz to rock, electronic, progressive, imports......almost anything goes. It was ALL about the music! My best musical 'high' was filling in for Dave DeMaw on the Greatest Show From Earth! Sadly, retail called, and I walked away from my non-realized career in radio. Though I always wished to find time to volunteer at WWUH again, the demands of retail afforded little time nor flexibility.
Fast forward 25 years to the WWUH 40th Anniversary Reunion, where I reconnected with Dave DeMaw and started hanging around the station, sitting in on shows, reacquainting myself with radio and the new equipment. Susan was fading from the Ambience line-up, and there was room for a fourth host. I said, "Pick me! Pick me!"
I love ambience music. It's a great musical-mood on Sunday mornings to accompany you in whatever you fare. Ambience is low-keyed. It doesn't require earnest listening, yet is good accompaniment, with a complexity that will entertain you, if you have the mind to listen.
As much as I like Ambience, I love stretching the definition of ambience music. Ambience can be a mellow one-note-drone-with-variance, or it can be a rhythmical picking on an acoustic guitar or sequenced synthesizer. Maybe a marimba or a sitar, a harp or even a saxophone will provide contrast between songs. The inclusion of drums is not typically ambient, but sometimes it works. There is Jazz Ambience, Ambient Space, Ambient Dance, Minimalist Ambience, Heavy-Metal-Ambience (maybe not!) and many other variations of ambient music. Mix in a bit of audio experiences from around the world, some spoken word, and consider yourself Ambience'd - Time-style. Personally, I like the Solo-Acoustic-Progressive-Classical-Guitar-With-Just-A-Hint-Of-Waltz Ambience category.
Join me, and the Ambient Apprentice, Time-Clock, on the first the Sunday of every month (and sometimes the fourth – when there are FIVE Sundays in the month), as we explore "Ambience Without Borders." Listen for 'something different'. It's ALL about the music to me.


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Cowboys Fall to the Giants 31-24
Dallas went to New York with high hopes and fell short, a touchdown short to be exact. Giants (7-5) walk away with the win and are only one "W" out of first place. The Cowboys (8-4) now share the division lead with the Eagles. Never a dull moment in the NFC East.
Early on the Cowboys seemed to be controlling the game with a score of 10-0 up until the two minute warning. Then all of a sudden the Giants scored two touchdowns in less than two minutes right before halftime.
Tony Romo put up good numbers, but that just proves that stats don't win games. Romo went 41/55, 392 yards, three touchdowns and ZERO interceptions. Romo's 41 receptions set a new franchise record.
Roy Williams collected two touchdowns and had six receptions for 60 yards. Jason Witten came away with a career high 156 yards on 14 carries. While, Miles Austin had 10 receptions, 104 yards and one touchdown.
Romo and the receiving corps played great but those numbers mean nothing though when you lose to a division rival. And, it certainly didn't help that the ground game never showed up. Between the three backs, Dallas only had 45 yards on the ground. All three lacked explosiveness and ran tentatively.
Nick Folk missed two field goals, and to be honest may not be a Cowboy for much longer. The Cowboys need a winner and Folk is definitely struggling lately. Many games come down to field goals and when you are in a run for the playoffs you need to be sure your kicker can make those shots.
On the defensive side of things, highlights include Jay Ratliff's forced fumble and recover, Mike Jenkins' interception and DeMarcus Ware had one sack. Other than that, mistakes, penalties and missed tackles were abundant.
This one is on the defense and special teams.
Jason Witten, who should have been celebrating a career best day and his 500th career catch said it best…
"We've got to challenge ourselves and find a way to play. We have to get back to it and forget all this December stuff. I'm not trying to avoid it or say it's not true. We've got to put it away. You let another one slip and you're really in trouble."
Things we kept waiting for but never happened:
1. Massive Sack Attack from DeMarcus Ware and Anthony Spencer
2. Deep Passes to Miles Austin
3. The Three-Headed Monster to Wake Up
4. Urgency From the Cowboys
Fans prepare yourself, because its going to be a long week of hearing about the Cowboys record in December. The schedule doesn't get any easier either. Coming up: Chargers, Saints, Redskins, Eagles.
I'm not saying that our season is over, I'm not saying we can't still win the division. All I'm saying is it won't be easy.
This loss pissed me off more than any of the others this season. Usually I get sad, but not necessarily mad. It's passion-driven anger. It's uncontrollable and I shouldn't let it get the best of me. I apologize to anyone who I offended or attacked during or after this game.
Don't worry, I will pull myself together. I'll get over it and look forward to the next game. The team should do the same thing. I hope they take this loss personally and take it out on the next team in line.


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Blue Cheese Crispies with Red Grapes
Blue Cheese Crispies with Red Grapes
- 1/2 cup (1 stick) butter, softened
- 8 ounces blue cheese, crumbled or 8 ounces white cheddar cheese, shredded
- 1 cup all-purpose flour
- 1/4 teaspoon salt
- 1/4 teaspoon cayenne pepper
- 1/2 teaspoon Worcestershire sauce
- 1/4 teaspoon lemon juice
- 1/4 teaspoon sugar
- 1 cup crisp rice cereal, slightly crushed
- 2 pounds red seedless grapes
In large mixing bowl beat butter and blue cheese with electric mixer until combined. Add all other ingredients except rice cereal and grapes. Beat until mixture just comes together. Add cereal. Stir by hand until combined.
Preheat oven to 350°F. Form cheese mixture into small 3/4 -inch balls. Place on ungreased baking sheets. Mash flat with fork dipped in flour; go back and mash in other direction to make crisscross pattern (tines of fork will make nice texture on top). Try to get as flat as possible so they will be crisp. ( 3/4 -inch balls will make bite-sized crackers)
Bake about 12 minutes or until browned on bottoms and around edges. Remove from baking sheet; cool on wire racks. To make crackers even crisper (like biscotti), return to baking sheet and bake 6 to 8 minutes more or until lightly golden brown. Remove from baking sheet and cool on wire racks. Delicious served with red grapes.
Tip: Can be baked and frozen ahead of time. Place in airtight container and freeze up to 3 months. Thaw and bring to room temperature before serving. Makes about 75 bite-sized crackers.
Return to: wildewood garden club progressive dinner menu [1]


text: Online video has become an invaluable tool for informing, entertaining and marketing. PARS can provide a custom interface or skin designed to extend your organization's branding and awareness campaigns. PARS offers a full array of solutions including streaming, hosting, and licensing designed to fit your needs and budget. We support a multitude of popular file formats including 3G2, 3GP, WMV, MOV, AVI, MPEG, MPEG4, FLV and HTML5.


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October 24, 2012 (BROOKFIELD, Ill.) --Animals at Brookfield Zoo were treated to some Halloween pumpkins Wednesday afternoon.
The African lions, sloth bears, meerkats, red river hogs, pygmy hippos, and rhinos seemed to thoroughly enjoy their treats. Some of the pumpkins were carved out and filled with other goodies such as grain, meal worms, meat, raisins, and grapes.
Through the end of the month, many of the zoo's other animals will be getting pumpkins too. This weekend, zoo guests can see the lions and sloth bears receiving pumpkins during the annual Boo! at the Zoo celebration on October 27 and 28.


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November 20, 2010
Wabash scored 20 fast break points and 48 points in the paint to cruise to a 96-55 win over Franklin College in the final game of the 2010 Little Giant Tipoff Classic Saturday afternoon.
View photos from the Little Giants' win here.
The victory was never in doubt with the Little Giants taking an early 12-3 lead after Franklin grabbed its only lead of the game at 3-2. Wabash continued to pound the ball inside to Wes Smith, Nick Curosh, Ben Burkett, and Derek Bailey. Twenty Franklin turnovers lead to 28 Little Giant points.
The Little Giants took a 52-22 halftime edge before outscoring the Grizzlies 44-33 in the final period.
Smith (left) led all scorers with 26 points to earn All-Classic MVP honors. He finished 10-of-15 from the field, 1-of-1 from beyond the three-point arc, and had four steals, one block, one assist, no turnovers, and two rebounds. Brian Shelbourne's tenacity led to eight rebounds for the junior, while he also contributed six points, three assists, and one steal to earn a spot on the All-Classic team. Bailey joined Smith and Shelbourne (below right) as an All-Classic selection, coming off the bench to score 10 points, hand out a career-high four assists, and grab four rebounds to go with one blocked shot and one steal.
Burkett and freshman Pete Nicksic each had nine rebounds. Nicksic enjoyed his best game of the season, shooting 5-of-7 from the field for a total of 13 points along with two blocked shots and an assist. Burkett added four points. AJ Sutherlin also reached double figures for the second consecutive game, scoring 10 points to go with two steals and an assist.
Nick Curosh and Aaron Zinnerman each finished with four assists as the Little Giants recorded the third-most assists in school history with 23 on Saturday. Wabash shot 37-of-70 from the field and a stellar 7-of-11 from three-point range, while outrebounding Franklin 54-28.
JT Barton scored 17 points for Franklin (1-2), while Will Conoley tossed in 13.
Wabash (3-0) travels to Hanover College on Tuesday night.


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Trick Daddy Disses Plies "Shouts Out To F*cker Ass, Fake a$$ Plies"
New Beef? Trick Daddy @ DJ Khaled video shoot. Watch as he shouts out everyone then gets at Plies for not showing up. Courtesy of Terniondc. Submitted by Johnny
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|Remove Year: 2011
|Publication type:
|Remove Publication type: Perspectives
|Energy topic:
|Remove Energy topic: Scenarios
Our ad hoc World Energy Perspectives reports and studies are based on the expert insights from our network of leaders and practitioners and provide a bottom up assessment of key issues and technologies impacting the energy sector.
World Energy Scenarios: Global Transport Scenarios 2050
Over the next four decades, the global transportation sector will face unprecedented challenges related to demographics, urbanization, pressure to minimize and dislocate emissions outside urban centres, congestion of aging transport infrastructure and growth in fuel demand. In light of these challenges and the levels of uncertainty, the World Energy Council (WEC) decided to re-examine the […]
Published in December 2011


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Snodeo 2012
February 13, 2012 by Judy Trull
Although it certainly hasn't seemed like winter here in our area, these last few days of bitter cold have reminded me that winter is just waiting in the wings to show itself yet again. The Northport Riders are ready to host Snodeo this weekend and pull off another fabulous event. Friday night will feature Vintage Oval racing under the lights, registration starts at 3 p.m. on Friday the 17th, practice from 4 to 6 and the event is from 7 to 9. Saturday is Lake Cross racing with registration starting at 7:30 a.m. There will be radar runs hosted by the Manawa Lions Club and lots of other things happening. There will be food and refreshments available on site as well. This will all be taking place at Bear Lake just a few miles South of Manawa. Come on down and check it out, this event is possible through generous sponsors and hard working volunteers. Check out http://www.northportsnowriders.com/index_files/Page371.htm for more information.


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Garbage cans belong to that group of mundane household items that have been around for so long that it seems there really isn't much that can be done to improve on their design. Or so we thought. Industrial designer Arnold Castro recently introduced us to the Nubagg, and at first glance, we could hardly tell that it was a trash receptacle at all. With no walls or sides, Castro's design basically consists of what he calls a "freakishly lightweight" metal frame that is used as a support for the plastic bags you bring home from the supermarket. We were very interested in the Nubagg's extremely minimalist design and the way it encourages reuse, so we decided to take it for a test drive to see how well it would stand up to our trash. Read on for our full review.
The beauty of the Nubagg is that it allows you to save money by substituting plastic bags you get at the store for garbage bags. But since we already do that (using regular trash cans), we weren't quite sure what the added benefits might be. Upon checking it out more carefully, we realized that its design, which features two protruding bars for you to sling your bag handles over, solves one of our biggest pet peeves – when the sides of our bags cave in and we have to reach into the muck to readjust them. We also noticed that we had to take the garbage out less with the Nubagg because it can be filled up to the full capacity of each bag and is not restricted by walls. If you've ever picked up a full-looking trash bag to go throw it out and realized that there was still a lot of room in the bag itself, you'll see why it's better to use each bag to its full capacity.
The one precaution we did have about the Nubagg was that it probably should not be used with just one bag unless you're only trashing dry goods. Double or triple bagging is a better idea, especially in the kitchen, but the upside to this is that the Nubagg can do double duty as a plastic bag storage unit. Just keep all of your bags on there and when the top few are full, throw them (and the trash) away to reveal clean bags underneath.
In addition to being a vehicle for the reuse and recycling of bags, the Nubagg is, itself, recycled. The body is made of 100% recycled metal and weighs about 1 lb., cutting down on the fuel needed to ship it. The box it's shipped in is also recycled.
If you're interested in getting your hands on your own modern Nubagg, they recently launched an Indiegogo campaign where your contribution of $20 will not only help you get this product off the ground, but also score you a Nubagg Classic (or a Nubagg mini for $15) just in time for the holidays.


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NOTE: 2018-19 Financial Aid data is expected to be viewable via Tulane's Gibson Online portal on or about December 1, 2018. During the week of December 4, 2018, we are currently scheduled to begin sending award notification e-mails to admitted Early Decision students who have applied for aid and who have been packaged with financial aid (in which the applicants are instructed to navigate to the Tulane Gibson Online portal to securely view their financial aid package).
We offer the following information to help full-time undergraduate division incoming freshmen students and their families with the financial aid process:
1. If seeking Tulane merit scholarship consideration
2. If seeking Federal student aid consideration
3. If seeking Tulane need-based scholarship consideration
1. If seeking Tulane merit scholarship consideration, please note that all merit scholarship decisions are determined by the Tulane Undergraduate Admission Office. While a few of Tulane's merit scholarship offerings require a separate special application, most of Tulane's merit scholarships DO NOT require any additional application, as students are evaluated solely on the applicant's admission application materials and appropriately assigned merit aid at the time of admission. All decisions of the Admission Office are final.
Below is a listing of Tulane merit scholarships requiring a special application or form process:
Dean's Honor Scholarship
Paul Tulane Award
Global Scholarship
Stamps-Tulane Scholarship
Community Service Scholarship
Legislative Scholarship (only available to Louisiana students)
Mayoral Scholarship (only available to New Orleans students)
Check the Undergraduate Admission website for respective deadline and application or form information.
Check with the school at which the employee works for the respective deadline and application information for:
Tuition Exchange Scholarship (only available to dependents of employees of Tuition Exchange schools)
All admitted students will be automatically considered for any of other partial tuition merit awards using the admission application materials.
2. If seeking Federal student aid consideration, then you must complete the 2019-2020 Free Application for Federal Student Aid (FAFSA) and provide any additional documentation that might be requested.
Below is a listing of Federal student aid available to qualifying undergraduate students/parents who successfully complete the FAFSA application process:
Federal Pell Grant
Federal Supplemental Educational Opportunity Grant (SEOG)
Federal TEACH Grant
Federal Work Study
Federal Direct Loan (Subsidized and Unsubsidized)
Federal PLUS Loan (for parents of an undergraduate student)
Below is a listing of State of Louisiana student aid available to qualifying undergraduate students from Louisiana who successfully complete the FAFSA application process:
Louisiana Tuition Opportunity Program for Students (TOPS)
Louisiana GO Grant
Aside from completing the 2019-2020 FAFSA, a student may be required to provide additional documentation (if requested). The U.S. Department of Education will randomly select FAFSA applicants for verification of the data reported on the FAFSA. Tulane will notify all students selected for federal verification as to the exact documentation needed: often this includes copies of 2017 IRS tax transcripts (for student and parents).
3. If seeking Tulane need-based scholarship consideration, then you must complete the 2019-2020 Free Application for Federal Student Aid (FAFSA) AND the 2019-2020 College Scholarship Service (CSS) PROFILE application (and provide any additional documentation that might be requested). Consideration for Tulane's NOLA (No Loan Assistance) Scholarship requires that the two aforementioned applications (2019-20 FAFSA & 2019-20 CSS PROFILE) be completed by our February 15, 2019 deadline! Absolutely no exceptions are made to this deadline!
Below is a listing of documents Tulane must receive for our initial review of a student's eligibility for Tulane need-based scholarship:
Please send any documentation related to your 2019-2020 financial aid application to:
Tulane University Financial Aid
6823 St. Charles Avenue
Room 205, Building 14
New Orleans, LA 70118
Below is a listing of some of the documents Tulane may identify as being needed prior to our initial review and that we must receive prior to our finalizing a student's eligibility for Tulane need-based scholarship (initial awards are often made without these documents, yet necessary award adjustments will occur if our review of these documents reflects discrepancies from the reported application data). The final deadline to complete a financial aid file is the last date of the student's attendance for the aid period or four weeks before the end of the aid period, whichever comes first.
After an award is made, this documentation is also required if applicable:
To be assured of consideration for Tulane institutional need-based financial aid as well as federal financial aid, full-time undergraduate students* must complete both the 2019-2020 Free Application for Federal Student Aid (FAFSA) and the 2019-2020 College Scholarship Services (CSS) Financial Aid Profile by February 15 (April 15 for continuing students) prior to the semester for which aid is sought, and must also complete all additional requirements (including requests that loans and other aid be processed) at least two weeks before the end of the semester for which aid is sought. Availability of limited institutional funding determines whether an applicant may be considered for need-based institutional aid in cases where the application deadline is not met; however, please note that applications not received at Tulane at least four weeks before the end of the semester for which aid is sought will not be reviewed.
The guaranteed-consideration deadline to complete FAFSA and CSS applications are as follows:
November 15, 2018: For incoming students applying Early Decision
Award notifications expected to start the week of 12/4/2018
December 15, 2018: For incoming students applying Early Action or Early Decision II
Award notifications expected to start the week of 1/22/2019
February 15, 2019: For incoming students
Award notifications expected to start the week of 3/5/2019
April 15, 2019: For all continuing students
Award notifications expected to start in late June 2019
Note: Applications will be considered on a funds-available basis for those applications completed after the aforementioned deadlines. Federal aid will still be available for those who 1.) complete a FAFSA sent to Tulane at least four weeks before the end of the semester for which aid is sought and 2.) complete all additional requirements (including requests that loans and other aid be processed) at least two weeks before the end of the semester for which aid is sought.
Students can complete the 2019-2020 FAFSA online at www.fafsa.ed.gov as early as October 1, 2018, and Tulane's school code for the FAFSA is 002029. Students can complete the 2019-2020 CSS Financial Aid Profile application online at www.collegeboard.com (select "Paying for College" on student's home page) also starting October 1, 2018, and Tulane's school code for the CSS Profile is 6832. Students who only file the FAFSA will be considered for federal aid only.
Students seeking and/or awarded Tulane need-based scholarship will be required to provide signed copies of parents' 2017 federal tax returns and the parents' 2017 W-2 forms. This documentation is used to validate the data reported on the CSS Profile. ALL VALIDATION DOCUMENTS MUST BE RECEIVED BY TULANE BEFORE WE CAN INITIATE A REVIEW FOR TULANE NEED-BASED SCHOLARSHIP!
The U.S. Department of Education randomly selects students for whom their FAFSA data must be verified. Generally, if selected for verification student's seeking need-based federal student aid will be required to provide copies of parents' 2017 IRS tax transcript, the student's 2017 IRS tax transcript, parents' 2017 W-2 forms, the student's 2017 W-2 forms, and a completed 2019-2020 Verification Worksheet. Again, this documentation is used to verify the data reported on the FAFSA. ALL VERIFICATION DOCUMENTS MUST BE RECEIVED BY TULANE BEFORE WE CAN INITIATE A REVIEW FOR FEDERAL NEED-BASED AID!
Note: Per federal regulation, copies of tax returns used for Tulane's validation of CSS Profile data CANNOT be used for federal verification of FAFSA data. IRS tax transcripts are needed to complete the federal verification process, thus we regret that there will be some situations whereby Tulane must collect both copies of tax returns as well as copies of IRS tax transcripts.
Other documents may also be required (for example, proof of citizenship, Social Security number or Social Security benefits) in some cases, and packaged aid must be accepted to be processed in virtually all cases. Certain other requirements must be completed fo reducational loans to be processed. Please note the student's name and identification number clearly on the documents and ensure that tax returns are signed; otherwise, a significant delay in processing may occur. Please note that the U.S. Internal Revenue Service website www.irs.gov provides copies of tax forms, instructions on obtaining copies of previously filed tax returns, and answers to frequently asked questions. Students and/or parents not required to file 2017 federal tax returns complete the appropriate Tulane 2019-2020 Non-Filer Worksheet.
*Please note: This page contains information for those applying for admission for or enrolled in a full-time division at Tulane University as a Freshman, Sophomore, Junior or Senior (undergraduate) during the fall-spring academic year in New Orleans.
Students who plan to study full-time in the part-time division (that is, who will be enrolled full or part-time in Tulane's School of Professional Advancement) should visit the link Aid for School of Professional Advancement Undergraduate Students for instructions. Students who are not undergraduates should visit the link Aid for Graduate and Professional Students.
Students who are planning to study abroad or take summer classes should visit the appropriate link for more information regarding the financial aid application process: Aid for Study Abroad Programs and/or Aid for Summer Session.
Page last modified on November 15, 2018.
University Financial Aid, New Orleans, LA 70118 504-865-5723 firstname.lastname@example.com


text: Challenger Signs On Two Nebraska Dealerships September 29, 2010 11:30 AM Tweet TAGS: Marketing, Overseas December 18, 2014 By MyMachinery.com Editors Email Manzer Equipment, Inc. and Osceola Implement & Supply, Inc. have expanded their offerings of AGCO brands as a provider of sales, parts and service for the full-line of Challenger ag equipment as a AGCO is working with Nebraska Machinery Company (NMC) to establish Challenger Alliance dealers throughout the state. Challenger Alliance dealers are AGCO Corporation dealers that are qualified by AGCO Corporation and NMC to sell and support Challenger Ag products in defined areas of Nebraska. Along with the addition of the Challenger line at the two Nebraska dealerships, a precision agriculture support technician will be added to the support team. Key parts, sales and service employees who will be working with the Challenger line will also be added. In addition, mobile service and parts capabilities are being expanded, and customers will receive additional information on that effort as future service and support capabilities are added. Manzer Equipment is located in Osmond, Nebraska and was founded in 1975 as an Allis-Chalmers dealership. It has represented AGCO Corporation brands for the past 35 years and today represents AGCO Tractors, Massey Ferguson, Gleaner, Sunflower and White Planters, in addition to Challenger. To learn more about Manzer Equipment visit: www.manzerequipment.com. Osceola Implement & Supply is located in Osceola, Nebraska. The company was founded in 1910 as a Minneapolis-Moline dealership and has been representing AGCO Corporation brands throughout its history. Osceola Implement & Supply represents AGCO brands, including AGCO Tractors, Massey Ferguson, Gleaner, Sunflower and White Planters, in addition to Challenger. To learn more about Osceola Implement & Supply visit www.osceolaimplement.com. Back to news


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Lack of TRPM2 Impaired Insulin Secretion and Glucose Metabolisms in Mice
OBJECTIVE TRPM2 is a Ca2+-permeable nonselective cation channel activated by adenosine dinucleotides. We previously demonstrated that TRPM2 is activated by coapplication of heat and intracellular cyclic adenosine 5′-diphosphoribose, which has been suggested to be involved in intracellular Ca2+ increase in immunocytes and pancreatic β-cells. To clarify the involvement of TRPM2 in insulin secretion, we analyzed TRPM2 knockout (TRPM2-KO) mice.
RESEARCH DESIGN AND METHODS Oral and intraperitoneal glucose tolerance tests (OGTT and IPGTT) were performed in TRPM2-KO and wild-type mice. We also measured cytosolic free Ca2+ in single pancreatic cells using fura-2 microfluorometry and insulin secretion from pancreatic islets.
RESULTS Basal blood glucose levels were higher in TRPM2-KO mice than in wild-type mice without any difference in plasma insulin levels. The OGTT and IPGTT demonstrated that blood glucose levels in TRPM2-KO mice were higher than those in wild-type mice, which was associated with an impairment in insulin secretion. In isolated β-cells, smaller intracellular Ca2+ increase was observed in response to high concentrations of glucose and incretin hormone in TRPM2-KO cells than in wild-type cells. Moreover, insulin secretion from the islets of TRPM2-KO mice in response to glucose and incretin hormone treatment was impaired, whereas the response to tolbutamide, an ATP-sensitive potassium channel inhibitor, was not different between the two groups.
CONCLUSIONS These results indicate that TRPM2 is involved in insulin secretion stimulated by glucose and that further potentiated by incretins. Thus, TRPM2 may be a new target for diabetes therapy.
Under physiological conditions, blood glucose levels are kept in a narrow range despite periods of food intake and fasting. Insulin secretion from pancreatic β-cells is the only efficient means to decrease blood glucose concentration. Accordingly, insulin secretion is strictly controlled by glucose, hormones, and autonomic nervous system activity. Glucose is the principal stimulator of insulin secretion from pancreatic β-cells. The primary and best-characterized pathway involved in glucose-stimulated insulin secretion is the ATP-sensitive potassium channel (KATP channel)-dependent pathway. ATP closes KATP channels, causing depolarization, resulting in Ca2+ influx from the extracellular space via l-type voltage-gated Ca2+ channels followed by exocytosis. Glucose-stimulated insulin secretion is potentiated by incretins such as glucagon-like peptide-1 (GLP-1).
Transient receptor potential melastatin 2 (TRPM2, previously named TRPC7 or LTRPC2) is a Ca2+-permeable nonselective cation channel, expressed predominantly in brain and also detected in bone marrow, spleen, heart, liver, lung, and immunocytes (1–3). This channel is activated by nicotinamide adenine dinucleotide (NAD), adenosine 5′-diphosphoribose (ADPR), and hydrogen peroxide (H2O2). Previously, we reported that TRPM2 is expressed in mouse pancreatic β-cells and is dramatically activated at body temperature by treatment with intracellular cyclic ADPR (cADPR) (4). Although some reports have shown that TRPM2 is involved in H2O2-mediated apoptosis in insulin-secreting cell lines (5,6), the physiological significance of TRPM2 in pancreas, especially at an in vivo level, has not been well characterized.
To clarify the involvement of TRPM2 in insulin secretion, we analyzed TRPM2 knockout (TRPM2-KO) mice. We found that lack of TRPM2 impairs insulin secretion not only stimulated by glucose but also potentiated by incretins.
The study was conducted in 9- to 12-week-old male and female C57BL/6Cr wild-type mice and TRPM2-KO mice (7). TRPM2-KO mice were backcrossed onto the C57BL/6Cr strain over eight generations. The animals were maintained on 12 h–12 h artificial light–dark cycles at 23 ± 1°C and allowed free access to food and water. The in vivo experiments were performed between December and April. All procedures involving the care and use of animals were approved by the National Institute for Physiological Sciences and carried out in accordance with the National Institutes of Health Guidelines for the care and use of laboratory animals (NIH publication no. 85-23; revised 1985).
Metabolic and biochemical measurements.
Measurement of food and water intake and body weight, and collection of blood samples were carried out every week. Blood glucose levels were measured using a glucose monitor (G sensor, GLUCOCARD DIA meter, Arkray, Kyoto, Japan), and plasma insulin, glucagon, and somatostatin levels were measured using ELISAs (Morinaga Institute of Biological Science, Inc., Yokohama, Japan; WAKO Pure Chemical Industries, Ltd., Osaka, Japan; and Phoenix Pharmaceuticals, Inc., CA, USA, respectively). Core body temperature and locomotor activity were monitored using transmitter devices (Mini Mitter Company, OR, USA) surgically implanted in the peritoneal cavity under anesthesia (50 mg/kg sodium pentobarbital, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan). After surgery, each animal was housed alone in a recording cage and allowed to recover from surgery for >1 week. Data were recorded by placing each cage containing an animal implanted with a radiotransmitter on a receiver plate (ER-4000, Mini Mitter Company). A Vital View data acquisition system (Mini Mitter Company) was used for data collection and analysis.
Isolation of pancreatic islets.
Islets of Langerhans were isolated from mouse pancreas by collagenase digestion as described previously (8) with minor modifications. Animals were anesthetized with sodium pentobarbital (80 mg/kg, i.p., Dainippon Sumitomo Pharma Co., Ltd.), followed by injection of 1.05 mg/ml collagenase (Sigma-Aldrich, St. Louis, MO, USA) into the common bile duct. The collagenase was dissolved in 5 mmol/l Ca2+-containing HEPES-added Krebs-Ringer bicarbonate buffer solution (HKRB, 129 mmol/l NaCl, 5 mmol/l NaHCO3, 4.7 mmol/l KCl, 1.2 mmol/l KH2PO4, 2 mmol/l CaCl2, 1.2 mmol/l MgSO4, 10 mmol/l HEPES, 0.1% BSA, pH 7.4). The pancreas was removed by dissection and incubated at 37°C for 20 min. The islets were then collected and used either for insulin release experiments or dispersed into single cells in Ca2+-free HKRB.
Single cells were plated sparsely on coverslips and cultured for 12–16 h at 37°C in an atmosphere of 5% CO2 and 95% air in Eagle's minimal essential medium containing 5.6 mmol/l glucose supplemented with 10% FBS, 100 μg/ml streptomycin, and 100 units/ml penicillin. Samples were fixed for 10 min at room temperature in ethanol, followed by washing (3 × 5 min) with PBS. Samples were then washed (3 × 5 min) in PBS supplemented with 0.1% Tween-20 (PBST) and blocked with PBST containing 3% BSA for 1 h at room temperature. Cells were incubated with primary antibodies (rabbit anti-TRPM2 antibody at 1:100, generous gift from Dr. Y. Mori, and guinea pig anti-insulin antibody at 1:700, Dako Japan, Tokyo, Japan) dissolved in PBST containing 3% BSA and then washed (3 × 10 min) with PBST for 1.5 h at room temperature. This was followed by incubation with secondary antibodies (Alexa Rb488 and Alexa GpCy3, Molecular Probes, Invitrogen Corp., CA, USA) for 1 h at room temperature. Images were then obtained with a fluorescence microscope (Olympus, Tokyo, Japan).
Glucose tolerance test.
Oral and intraperitoneal glucose tolerance tests (OGTT and IPGTT) were performed after 16–17-h fasting. Glucose (1 g/kg body wt, Otsuka Pharmaceutical, Tokyo, Japan) was administered orally or injected intraperitoneally. Blood glucose levels were measured before (0 min) and 15, 30, 45, 60, and 120 min after administration or injection. Blood samples were taken from the tail vein and blood glucose levels were measured using a glucose monitor. Plasma insulin levels were determined by ELISA. Area under the curve (AUC) of insulin secretion was calculated after subtraction of basal insulin levels (at time zero).
Insulin tolerance test.
An insulin tolerance test was performed after 4-h fasting. Porcine insulin (1 unit/kg body wt, Sigma-Aldrich) was injected into the intraperitoneal space and blood glucose levels were measured with a glucose monitor before (0 min) and 15, 30, 45, and 60 min after injection of insulin.
Measurement of cytosolic-free Ca2+ in single mouse β-cells.
Single cells were sparsely plated on coverslips and maintained in short-term culture for up to 2 days at 37°C in an atmosphere of 5% CO2 and 95% air in Eagle's minimal essential medium containing 5.6 mmol/l glucose supplemented with 10% FBS, 100 μg/ml streptomycin, and 100 units/ml penicillin. Single β-cells on coverslips were mounted in an open chamber and superfused in HKRB. Cytosolic-free Ca2+ ([Ca2+]i) in single β-cells was measured by dual-wavelength fura-2 (Molecular Probes, Invitrogen Corp.) microfluorometry with excitation at 340/380 nm and emission at 510 nm. The ratio image was calculated and acquired using an imaging processing system (IP-Lab, Scanalytic Inc., VA, USA). Cells showing an increase in the ratio of >0.3 from basal values in response to heat stimulation were defined as heat-sensitive cells. All glucose- and tolbutamide-positive cells were confirmed to be β-cells. AUC for changes in [Ca2+]i was calculated after subtraction of basal [Ca2+]i.
Measurement of insulin release in mouse islets.
Islets were collected in RPMI-1640 medium (WAKO Pure Chemical Industries, Ltd.) containing 10% FBS, 100 units/ml penicillin, and 100 μg/ml streptomycin, incubated in that medium for 3 h and then preincubated in Krebs-Ringer buffer (KRB, 129 mmol/l NaCl, 5 mmol/l NaHCO3, 5.2 mmol/l KCl, 1.3 mmol/l KH2PO4, 2.7 mmol/l CaCl2, 1.3 mmol/l MgSO4, 0.2% BSA, pH 7.4) containing 3.3 mmol/l glucose for 30 min at 37°C. The solution was then replaced with fresh KRB buffer containing glucose (3.3, 8.3, 11.2, or 16.7 mmol/l, Sigma-Aldrich) and islets were incubated for 10, 15, or 60 min at 37°C. In some experiments, GLP-1 (10 or 30 nmol/l, Sigma-Aldrich) or exendin-4 (Ex-4, 10 or 30 nmol/l, Sigma-Aldrich) was present throughout the incubation with 8.3 mmol/l glucose. In some experiments, tolbutamide (30 or 100 μmol/l, Sigma-Aldrich) was present throughout the incubation with basal glucose (3.3 mmol/l). To examine the contribution of TRPM2 to KATP channel-independent glucose-stimulated insulin release, islets were incubated at 37°C for 60 min in KRB containing glucose (3.3 or 16.7 mmol/l), 250 μmol/l diazoxide (Sigma-Aldrich), and 30 mmol/l K+. Insulin content in the supernatant was measured by ELISA. Second-phase insulin secretion (from 10 to 60 min) was calculated by subtracting first-phase secretion (from 0 to 10 min) from the total secretion.
Whole-cell patch-clamp recordings were performed 1 day after plating single pancreatic cells on coverslips. The standard bath solution contained (mM) 140 NaCl, 5 KCl, 2 MgCl2, 2 CaCl2, 10 HEPES, and 10 glucose, pH 7.4 (adjusted with NaOH). The pipette solution contained (mM) 140 CsCl or KCl, 5 EGTA, and 10 HEPES, pH 7.4 (adjusted with CsOH or KOH). Data from whole-cell voltage-clamp or current-clamp recordings were sampled at 10 kHz and filtered at 5 kHz for analysis (Axon 200B amplifier with pCLAMP software, Axon Instruments, CA, USA). Membrane potential was clamped at −60 mV in the voltage-clamp recordings. Heat stimulation was applied by increasing the bath temperature with a preheated solution through the inline heater (1°C/s, with a maximum of 45°C).
Statistical analysis.
Data are expressed as means ± SEM. Statistical analysis was performed using Student t test, two-factor repeated measures ANOVA, followed by Dunnett post hoc test, or ANOVA followed by the Bonferroni-type multiple t test. P values < 0.05 were considered significant.
Characterization of the TRPM2-KO mouse.
In cells isolated from pancreatic islets of wild-type mice, TRPM2 immunoreactive cells were also shown to be positive for insulin as described in a previous report (4) (Fig. 1A). In contrast, no TRPM2-like immunoreactivity was seen in TRPM2-KO cells (Fig. 1B). Heat stimulation increased cytosolic Ca2+ ([Ca2+]i) in wild-type cells (45% heat-sensitive cells, 25/56 cells) (Fig. 1C), whereas the majority of TRPM2-KO cells (92%, 48/52 cells) failed to respond to heat stimulation (Fig. 1D).
Table 1 depicts a comprehensive evaluation of the metabolic parameters of 12 week-old TRPM2-KO mice. Body weight, food intake, and water intake were similar in wild-type and TRPM2-KO mice. Under ad libitum feeding conditions, blood glucose levels were significantly higher in TRPM2-KO mice. Although plasma insulin levels measured between 10:00 and 11:00 a.m. tended to be lower in TRPM2-KO mice, this difference was not statistically significant. Plasma glucagon and somatostatin levels did not differ between wild-type and TRPM2-KO mice. The data from 9- to 11-week-old mice were similar to those from 12-week-old mice (data not shown). Core body temperature and locomotor activity also did not differ between wild-type and TRPM2-KO mice (Table 1).
Glucose and insulin tolerance tests.
To assess glucose metabolism and insulin secretion, OGTT and IPGTT were performed in fasted (16–17 h) male wild-type and TRPM2-KO mice. Basal fasting blood glucose and plasma insulin levels were similar between the two groups of mice. In the OGTT, TRPM2-KO mice exhibited significantly higher blood glucose levels (Fig. 2A) with significantly lower plasma insulin levels (Fig. 2C) 15 min after glucose administration. In the IPGTT, TRPM2-KO mice also exhibited significantly higher blood glucose levels (Fig. 2B) associated with significantly lower plasma insulin levels (Fig. 2D) after glucose administration. Lower plasma insulin levels in TRPM2-KO mice were also detected by another analysis with integrated insulin secretion expressed as the AUC (Fig. 2C and 2D). Impaired glucose tolerance with lower insulin secretion was also observed in female TRPM2-KO mice (supplementary Fig. 1, available in an online appendix at http://diabetes.diabetesjournals.org/cgi/content/full/db10-0276/DC1). Measurement of blood glucose levels during the insulin tolerance test showed only minor differences between wild-type and TRPM2-KO mice (supplementary Fig. 2, available in an online appendix).
Ca2+ imaging.
[Ca2+]i is considered to be the primary regulator of insulin secretion in pancreatic β-cells. To determine whether TRPM2 is involved in control of [Ca2+]i, fura-2 microfluorometry was used to measure [Ca2+]i in pancreatic β-cells isolated from wild-type and TRPM2-KO mice. Figure 3A and B shows representative changes in [Ca2+]i after application of increasing concentrations of glucose from 2.8 to 22.4 mmol/l. The increase in [Ca2+]i tended to be lower in pancreatic β-cells from TRPM2-KO mice than in those from wild-type mice during the first-phase. Moreover, the peak [Ca2+]i increases in TRPM2-deficient β-cells appeared to be lower than in wild-type cells, although Ca2+ oscillations were also observed in TRPM2-KO mice. We then analyzed the integrated [Ca2+]i increase in 20 min in each cell, expressed as the AUC. As shown in Fig. 3C, high glucose-stimulated (16.7 and 22.4 mmol/l) increases in [Ca2+]i were significantly blunted in β-cells from TRPM2-KO mice, whereas basal (2.8 mmol/l glucose) [Ca2+]i and moderate glucose-stimulated (8.3 mmol/l) increases in [Ca2+]i did not differ between the two groups of mice (Fig. 3C and D). In addition, analysis of first- and second-phase AUC revealed that [Ca2+]i response to 22.4 mmol/l glucose was significantly reduced in β-cells from TRPM2-KO mice in both phases (Fig. 3C). In contrast, the [Ca2+]i response to incubation with 300 μmol/l tolbutamide for 10 min, which causes membrane depolarization by inhibiting KATP channels, was not different in pancreatic β-cells from TRPM2-KO mice under basal glucose (2.8 mmol/l) conditions (Fig. 3E). We also measured [Ca2+]i increases potentiated by GLP-1 (10 nmol/l) with 8.3 mmol/l glucose for 2 min. Increases in [Ca2+]i were significantly reduced in β-cells from TRPM2-KO mice (Fig. 3F).
In vitro insulin secretion test.
To determine whether β-cells isolated from TRPM2-KO mice exhibited impaired insulin secretion, an insulin secretion test was carried out using islets obtained from TRPM2-KO mice. As shown in Fig. 4A, basal and moderate glucose-stimulated (3.3 and 8.3 mmol/l) insulin secretion did not differ in islets obtained from wild-type and TRPM2-KO mice. However, high glucose-stimulated (11.2 and 16.7 mmol/l) insulin secretion was significantly impaired in islets from TRPM2-KO mice. Next, to examine whether the impairment in glucose-stimulated insulin secretion observed in TRPM2-KO islets was time-dependent, we measured insulin secretion for 60 min, separating the values from the first 10 min (first phase) and the second 50 min (second phase). Insulin secretion stimulated by a high concentration of glucose (16.7 mmol/l) was significantly reduced in islets from TRPM2-KO mice in both the first and second phases (Fig. 4B). However, insulin secretion induced by either 30 or 100 μmol/l tolbutamide with basal glucose (3.3 mmol/l) was not different between wild-type and TRPM2-KO mice (Fig. 4C). We previously reported that TRPM2 may be involved in the potentiation of glucose-stimulated insulin secretion by Ex-4, a glucagon-like peptide analog (4). In this study, we examined insulin secretion induced by GLP-1 and Ex-4 and found that GLP-1 (10 and 30 nmol/l) and Ex-4 (10 and 30 nmol/l) significantly potentiated insulin secretion in wild-type islets exposed to 8.3 mmol/l glucose, whereas this potentiation was markedly reduced in islets from TRPM2-KO mice (Fig. 4D). To determine to what extent TRPM2 is involved in KATP channel-independent glucose-stimulated insulin release, we measured insulin release after stimulation with a high concentration of glucose (16.7 mmol/l) with diazoxide (250 μmol/l) and 30 mmol/l K+, as shown in another report (9), conditions that would be expected to completely inactivate KATP channel-mediated pathways. Under these conditions, glucose-stimulated insulin secretion was not observed in islets obtained from TRPM2-KO mice (Fig. 5).
In this study, we confirmed the expression of TRPM2 at both the protein and functional levels in mouse pancreatic β-cells, confirming previous reports (4,6,10), and also confirmed the deletion of TRPM2 in TRPM2-KO mice (Fig. 1). To date, many TRP channels (TRPC1, TRPC4, TRPC6, TRPV2, TRPV4, TRPV5, TRPM3, TRPM4, TRPM5, and TRPM7) have been shown to be expressed in pancreatic β-cells (11–14), with TRPV2, TRPM3, TRPM4, and TRPM5 reported to be involved in insulin secretion (13,15–18). Some of these TRP channels (TRPV2, TRPV4, TRPM4, and TRPM5) exhibit thermosensitivity. In this study, a temperature increase up to 42–43°C increased intracellular Ca2+ levels, an effect which was nearly abolished in pancreatic β-cells obtained from TRPM2-KO mice (Fig. 1C and D). This suggests that the functional expression of thermosensitive TRP channels other than TRPM2, except for TRPV2 (activated over 52°C), may be modest. Alternatively, TRPM2 might function in concert with other thermosensitive TRP channels in the pancreas.
In vivo experiments in TRPM2-KO mice showed that insulin secretion during an OGTT was significantly reduced in these mice 15 min after glucose administration (Fig. 2C). This early phase of insulin secretion is believed to involve the action of incretin hormones released from gut endocrine cells after absorption of nutrients (19). This reduction in insulin secretion during the OGTT is in agreement with the finding that incretin-potentiated [Ca2+]i increases were nearly abolished in β-cells from TRPM2-KO mice (Fig. 3F) and that incretin-potentiated insulin secretion was markedly impaired in islets from TRPM2-KO mice (Fig. 4D). These findings support the notion that TRPM2 is involved in incretin-potentiated insulin secretion. In the IPGTT, where the incretin-mediated component is thought not to predominate, TRPM2-KO mice showed impaired glucose tolerance with a lower insulin response (Fig. 2B and D). This impairment is similar to what was observed in the OGTT and is consistent with the reduction in glucose-stimulated [Ca2+]i increases and insulin secretion in TRPM2-KO β-cells and islets (Figs. 3C and 4A). These data indicate that TRPM2 is involved in insulin secretion stimulated by glucose and that further promoted by incretins. Insulin sensitivity was also found to be slightly impaired in TRPM2-KO mice (supplementary Fig. 2), suggesting that insulin resistance may also be partially involved in the impaired glucose tolerance observed in TRPM2-KO mice.
An increase in intracellular ATP concentration is one of the most important events in glucose-stimulated insulin secretion. In this study, the effects of tolbutamide, a KATP channel inhibitor, were not changed in TRPM2-KO mice (Figs. 3E and 4C), suggesting that the capacity for insulin secretion is intact in β-cells from TRPM2-KO mice. The results of our in vitro experiments suggest that impairment of glucose-stimulated insulin secretion in TRPM2-KO islets is caused by reduced increases in [Ca2+]i (Figs. 3C and 4A). We previously reported that cADPR activates TRPM2 at body temperature (4), and we observed heat-evoked inward currents in the presence of 100 μmol/l cADPR in the pipette in isolated pancreatic cells from wild-type but not TRPM2-KO mice (supplementary Fig. 3, available in an online appendix). Although the physiological significance of cADPR in β-cell function is still controversial (20), cADPR, synthesized from NAD by CD38, has been reported to be a second messenger that increases intracellular Ca2+ not only in lymphocytes (21) but also in pancreatic β-cells (22), and to be involved in insulin secretion. Given the fact that NAD also activates TRPM2, NAD and its metabolites may cooperatively activate TRPM2 at body temperature.
[Ca2+]i increases resulting from high concentrations of glucose were impaired in TRPM2-KO β-cells, suggesting that Ca2+ influx through TRPM2 can modulate [Ca2+]i levels. However, glucose-stimulated insulin secretion evoked under conditions of glucose, diazoxide, and high K+ was lost in TRPM2-KO islets, but changes in [Ca2+]i resulting from stimulation by glucose, diazoxide, and high K+ were not different in β-cells from wild-type and TRPM2-KO mice (Fig. 5 and supplementary Fig. 4, available in an online appendix). These results suggest that the TRPM2-mediated insulin secretion is KATP channel-independent to some extent and that it involves a pathway not related to changes in [Ca2+]i. The possible existence of a pathway not involving Ca2+ influx could explain the fact that glucose-stimulated insulin secretion from islets (Fig. 4A) was impaired to a greater extent than [Ca2+]i changes in isolated β-cells (Fig. 3C) from TRPM2-KO mice. Gene expression of signaling molecules for glucose-stimulated exocytotic machinery may also be changed by ablation of TRPM2. More experiments are necessary to clarify the detailed mechanism of TRPM2-mediated insulin secretion.
As shown in Figs. 3F and 4D, the responses to GLP-1 and Ex-4 in pancreatic β-cells and islets, respectively, were markedly reduced in TRPM2-KO mice. We have previously shown that potentiation of insulin secretion by forskolin, an adenylate cyclase activator, is mediated by TRPM2 activation. Furthermore, TRPM2 currents induced by cADPR at an elevated temperature were potentiated by forskolin, and this potentiation was blocked by H-89, a cAMP-dependent protein kinase (PKA) inhibitor (4). GLP-1 is known to cause a rise in intracellular Ca2+ concentration (23), and GLP-1 receptor is a G-protein coupled receptor coupled to Gs and involved in insulin secretion through PKA-dependent and -independent mechanisms (24). Thus, we hypothesize that TRPM2 potentiation by incretin may occur via the cAMP-PKA pathway, possibly through phosphorylation of TRPM2 by PKA. Moreover, it has been reported that TRPM2 is activated by intracellular Ca2+ through binding of Ca2+/calmodulin to the NH2 terminus of TRPM2 (25). In addition, the receptors for vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide are also G-protein coupled receptors coupled to Gs (26) and may modulate TRPM2 function. On the other hand, TRPM2 activation could evoke l-type voltage-gated Ca2+ channel-mediated Ca2+ influx to increase insulin secretion because activation of TRPM2 causes influx of Na+ as well as Ca2+, leading to the depolarization of pancreatic β-cells, followed by activation of the voltage-gated Ca2+ channel. Indeed, we observed generation of action potentials upon heating in the isolated pancreatic cells from wild-type mice (supplementary Fig. 5, available in an online appendix). Collectively, these findings support the notions that TRPM2 activity can be modulated in several ways and that TRPM2 activation can cause intracellular Ca2+ increase in different ways, which may, in turn, regulate insulin secretion.
In conclusion, endogenous TRPM2 in pancreatic β-cells plays a key role in insulin secretion induced by glucose and incretins. This indicates that TRPM2 is a sensor not only for signals from the gut but also for glucose metabolism and that TRPM2 integrates this information to control insulin secretion by modulating intracellular Ca2+ levels and by another mechanism not involving changes in intracellular Ca2+ levels. Pharmacological activation of TRPM2 channels may therefore be useful for enhancing insulin secretion and may potentially lead to the development of effective drugs for the treatment of diabetes.
This work was supported by grants to M.T. and Y.Mi. from the Ministry of Education, Culture, Sports, Science and Technology in Japan, and to M.T. from Hayama Center for Advanced Studies Projects. No potential conflicts of interest relevant to this article were reported.
K.U. performed the experiments and wrote the manuscript. K.D. performed the experiments and contributed to discussion of the results. B.D. performed the experiments. H.I., T.S., Y.Mo., T.Y., and Y.Mi. contributed to discussion of the results. M.T. wrote the manuscript.
We thank N. Fukuta and A. Fukuda at the National Institute for Physiological Sciences for technical assistance.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
See accompanying commentary, p. 28.
- Received February 25, 2010.
- Accepted September 24, 2010.
- © 2011 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.


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by Tom Utescher
Mount St. Joseph Academy's 2012 tennis team will have a tough act to follow. Last fall, the Magic finished up as the champions in the Athletic Association of Catholic Academies, and posted an overall record of 13-1.
As coach Ron Mutchnik embarks on his eighth season at the helm, Mount St. Joe looks to be ready for action in the singles area, with the only graduation loss coming on the last of the three rungs on the ladder. Pairs play is more of a work in progress; among the Magic's 2012 graduates were three of the four members of the first and second doubles teams, both of which went undefeated for two years in a row.
Back at number one singles is sophomore Morgan Weiss, who was out of action with a minor injury during the Mount's lone loss last fall. Second singles stalwart Mary Gorman, now a senior, also returns.
Gorman's classmate Jessica Bonet had been the MSJ number one back in the 2010 campaign, but she suffered a season-ending injury last year, and unfortunately she won't be able to come back for a senior season, either.
Nevertheless, Coach Mutchnik has been pleased with the way that sophomore Betsy Napolitano has stepped up to claim the third singles spot.
Senior Allison Murray is the returning member of the former first doubles combo, and this year she'll be joined by classmate Morgan Devine. They're also serving as team captains this season along with a third senior, Sarina Carr. Carr will appear at second doubles alongside sophomore Emily Christine. Another tenth-grader, Belin Mirabile, had also been in the mix for second doubles, but she's recuperating from a pre-season injury.
Mount St. Joe plays in a three-singles, two-doubles configuration within the AACA, but the Magic usually line up some non-league bouts against schools that employ a four/three or four/four format, giving other players a chance to see some varsity action.
After the top seven, there are a number of players of roughly equal ability, according to Mutchnik, who will be watching to observe who emerges from the pack.
The junior reinforcements are Máiread Glowacki, Krista Goebel, and Katie Moses, and the legion of sophomores includes Colleen Burns, Katie Meister, Serena Romanelli, and Nicolette Sommar.
The Magic will kick off the 2012 campaign with a tri-scrimmage involving Wissahickon High School and Germantown Academy, and another practice bout against Springfield High.


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David Beckham said a dinner date with pals Katie Holmes and Tom Cruise turned into his worst nightmare.
"We were at dinner once with Tom and Katie ... and we sat there and everyone was like, 'Ok, let's play a music game, let's start a singing game!" Beckham said last night on "Lopez Tonight."
Singing is "my worst nightmare," he said.
The soccer stud said he hates when Eva Longoria Parker and Tony Parker play after-dinner party games following their dinner soirees in Hollywood and felt no differently when Cruise insisted on a singalong.
Beckham said he spotted a friend at a nearby table.
"So I was texting my friend, 'Oh, please, invite me to your table," he said. "I kind of get uncomfortable with that."
Despite their party habits, Beckham said Cruise and Holmes are "amazing parents and really good people."
"You say there's good looking people, and you look at Tom, and he's one of the most handsome men I've ever met."