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New Braunfels Herald Zeitung (Newspaper) - February 6, 2004, New Braunfels, Texas FRID/"' *###**##***** J*4:1: FOR ftOC ?80 a pm? !,\ I?9 iu,I,ll HUI ..... SPORTS RINGLEADERS Amateur boxing match comes to New Braunfels Saturday. The 25-bout event features 5 local athletes. Page SA FORUM | ANN COULTER | | Democrats didn't invent war I heroes. They invented the scam I | of deploying war heroes to I argue for surrender. Page AA COMING ZeitungIndictment alleges woman stole from PIA By Dylan Jim6nez and Ron Maloney Staff Writers A former Memorial Primary School PTA treasurer who allegedly stole money school children raised was indicted Wednesday on a felony theft charge. Assistant District Attorney Joe Soane said the Comal County grand jury indicted Angela Bielke, 30, on a charge of theft between $1,500 and $20,000. lf convicted, the allegation is punishable by six months to two years in a state jail and a $10,000 fine. New Braunfels Police Det. Mike Penshom said the thefts, totaling about $9,000, occurred in 2003 and were reported after school began this past fall. The theft was discovered in an audit when this year's PTA officers took over, Penshom said. Penshom said the majority of the missing money came from childrens' fund-raisers. Bielke cooperated in the investigation and paid back half the money, he said. The PTA is a parent-teacher organization that raises money to help educate children. At Memorial Primary, PTA-generated funds bought the school's reading materials this year. New Braunfels Independent School District spokeswoman Stephanie Ferguson said the district nor the school would comment on the incident. "We support what they do, and they support us through fund-raising, but it's not the same entity,'' Ferguson said. Memorial Primary PTA President Jana Evola said she could not comment on the incident, although she did confirm it involved last year's PTA and not this year's officers. Texas PTA officials did not return calls for comment Thursday. TAKS FACTS TESTING DATES ■ Fab. 24 Grades 4 & 7, writing Grade 4, Spanish writing Grade 9. reading Grades 10 & 11, English/language arts * March 3 Grade 3, reading, Spanish reading ■ April 27 Grades 3-8 and 11, math Grade 10, social studies Grades 3-6, Spanish math ■* April 28 Grades 4-8. reading Grades 4-6, Spanish reading Grade 10, math Grade 11, science Grades 3-8, reading Grade 3, reading retest Grade 3. Spanish reading retest ■ April 29 Grade 9. math Grades 8 and 11, social studies Grade 5. science Grade 5, Spanish science Grade 10, science PARENTS TAKE THE TAKS Want to know how tough the TAKS is? • Sample tests from 2003 are downloadable on the Texas Education Agency Web site. tea state.tx.us/, under the TAKS Released Tests* link. * Take the test at any grade level and check the answers. By Dylan Jimtnaz Staff Writer Misty Klein's second grade class at Lone Star Elementary is learning essential test-taking skills. They are learning to estimate the weight, length and diameter of classroom objects. By learning to estimate, they learn to identify and eliminate unreasonable multiple-choice answers on the Texas Assessment of Knowl edge and Skills test. "That's a big deal on the test because, if they come up with an answer that's not even close to what they should be looking for, they need to know that," Klein said. Critical-thinking skills like judging the "reasonableness" of answers will help her students next year when they take the I AKS the first time. School districts across Texas are preparing for the second year of TAKS testing, which begins later this month. The test is said to be a more rigorous assessment, and educators are preparing accordingly. Passing standards were to be phased in over two years and fully implemented by the 2004-05 school year, so test scores are more important this year. Last year, third-graders had to pass their TAKS reading sections to be promoted to Bulverde Baptist Church Although relatively young, Bulverde Baptist grew fast By Leigh Jones Staff Writer For Baptists living in Bulverde, there was a problem. "In 1973, there were only Lutheran and Catholic churches in Bulverde," recalled Gay Morgan. The solution? Start a new church. "That summer," Morgan said, "Bonnie Cejka held a vacation Bible school in her home for the children in her neighborhood." The children filled every room in Cej-ka's home, spilling out to the back porch for activities. Encouraged by the positive response, congregants of Dellview Baptist Church in San Antonio, where Cejka and Morgan were members, decided to sponsor a mission church in Bulverde. Eventually, Bulverde Baptist Church grew enough to stand on its own. Their first meetings were held in Morgan's home until the chapel at Singing Hill Ranch was offered. In 1975, they moved into their current location off Bulverde Road. Children, the impetus for starting the church, are still an important focus of activities. The most popular children's program is also the most successful community outreach. The Upward Basketball league, which consists of 32 teams of 311 first- through sixth-graders, is popular among members and also provides a fun activity for friends who do not attend church. After practicing one night every week, the teams play in all-day Saturday competitions. IWo basketball camps continue play through the summer months. The Youth Group is also active in outreach mission work. Once a month, members have a collection drive to support a food bank in San Antonio. Periodic trips to Mexican border towns allow See CNURCN. Page 3A Serving New Braunfels and Comal County since 1852. kids gear up for SA stock show the fourth grade. In 2004-05, fifth-graders will have to pass the reading and math tests to be promoted. This year, I lth-graders will have to pass all four assessment areas to graduate. "This is the first group of students who will have to pass TAKS rather than TAAS," said Vicki Pursch, CISD executive director of instruction and curriculum. Taking the TAKS each year See TANS. Page 3ADam progress With studies out of the way, county progresses on flood control dam projects. Bulverde Community Rahe Primary Center E Amman Road Fridays, the Herald-Zeitung will feature a different house of worship. BULVERDE BAPTIST CHURCH ■ Pastor Dick Loser • Mission Statement To lead people to faith in Christ and growth in Christlikeness 4 Denominational affiliation: Baptist • Current attendance 250 9 Meeting times: Sundays — 9:30 am Sunday School. 10:45 a m. worship. 6 p m. Break Out (for youth) and adult fellowship • Location: 1331 Bulverde Road ■ Phone (830) 980-7577 • Web Site www bulverdebap-tist com ■ Worship style Contemporary to blended Pl DEAR ABBY 3B CLASSIFIEDS 5-8B COMICS 2B CROSSWORD 2B FORUM 4A Partly cloudy High Low i OBITUARIES 2A I SPORTS MA De,aUs.^TB I"GRIDS SS FRONTand Center200 local By Dylan Jimtnez Staff Writer Vol. 153, No. 75 14 pages, 2 sections CK L herald-zeitung.com 500 a "56825 00001 DAVID INGRAM/Herald-Zeitung Meghan McCarthy, left, and James Felle use different kinds of dried beans and a scale to learn about weight and mass in their second grade class at Lone Star Elementary. Learning reasoning skills will help them on the TAKS test.TARS, TAKE TWOStakes are higher in second year of state-mandated test Drew Garrison, Canyon High School junior, has another week to make sure his hog is well-fed and well-behaved for the San Antonio Stock Show and Rodeo. "He's looking pretty good," Garrison said. Garrison will show a lamb and a hog representing CHS Future Farmers of America in the livestock judging contest. Although Garrison already has participated in area shows this year, for many agriculture students, the San Antonio show will be the beginning of the showing season and their chance to show and sell their animals before the Comal County lunior Livestock Show later this month. "This is really the one that gets us going," Garrison said. See STOCK SHOW Page 3A A ■ 55th Annual San Antonio Stock Show & Rodeo >■ Opens Friday and continues through Feb. 22 ■ SBC Center, San Antonio ■ Tickets: Call 1-877-637-6336 or log onto the Web. ticketmaster.com DAVID WKMtAM/HerakJ-Zertun Bulverde Baptist Church Pastor Dick Loser. ;
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A great choice for a stay in Livingstone, Oriental Swan Hotel Livingstone features a free airport shuttle. Guests looking for a bite to eat can check out Chinese Restaurant, which serves Chinese cuisine. Rooms offer up nice touches like bathrobes and slippers, along with flat-screen TVs and room service.

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When I decided to turn this into an Online Retreat Day, I confess I had not thought much about it ending on the vigil of the Feast of the Annunciation, one of the most important feast days of the church. But it always good to complete a day of prayer with meditation on this particular moment. Without Mary's fiat to set the whole mysterious pageant of salvation into its culminating track, where would we be?Our good friends, the Dominican Nuns of Summit, NJ celebrate this vigil with a special … [Read more...]
The Vigil of "Yes"
The Dark Light of Time, Memory & Meaning
"Nature abhors a vacuum."Had a conversation with young atheist who has trouble accepting that there might be things both natural and supernatural.Supernaturalism is, to him, unprovable, and therefore impossible.They always amaze me, these "wide open" minds who put so many limits on what can be believed, and rely so heavily on science, which is -at its core- a trying to understand all, because in truth we understand so little. Science itself -like all understanding- is ever-evolving.Why, … [Read more...]
Retreat 1 PM: The Difference God Makes
H/T"He who loves God loves everybody. He who hates God hates everybody." -- Mother AngelicaThe only hate worth fearing is the hate within our own hearts, which can destroy us. The rest? Pfffft! … [Read more...]
Retreat Day 10 AM: The Cross that Heals
Photo: Gregory A. Shemitz "When the dire venom of beasts came upon them, and they were dying from the bite of the crooked serpents, your anger endured not to the end. But as a warning, for a short time they were terrorized, though they had a sign of salvation, to remind them of the precept of your law. For he who turned toward it was saved, not by what he saw, but by you, the savior of all. And by this also you convinced our foes that you are he who delivers from all evil." - Widsom … [Read more...]
Lenten Retreat Day 6 AM
Bare arms of Advent reached out in supplication toward an empty sky and prayed "open up O earth and let the savior bud forth"Budding arms at Lent's closing hail the promise of new life hint at resurrectionBeyond the sky-dust gloom the palest -so pale!- of lights penetration dense barriers rolled back with mustard-seed strengthPiercing light is key the True light pierced poured forth radiant beams five-point illumination light for the world making all things newIn your light we see light … [Read more...]


text: Overview Discussion topics Read Activity Members 1–1 of 1 comment Interested in fantasy? Take a look, give me some feedback on how I'm doing. Posted by Drizzt on March 14, 2014 Add reply Share Send to a fan or friend Short link: Drizzt posted March 14, 2014 http://www.protagonize.com/story/the-vengeful-drow Back to top


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Deployment fails with new FMS12.0v6 installer
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By MikeKD
Hi Folks,
I've broken a pdf saving script which used to work. The filename itself hasn't changed so I don't think that's the problem (there are no /s for instance) - I'm pretty sure it's the file path and Mac OS re-organising itself to sync with iCloud.
I'm trying to save PDFs to Dropbox and I think that the Dropbox folder on my my has changed location. According to info, the location is /Users/mikekentdavies/Dropbox/KJA Music Library.
The calculation I'm using to set the location variable is below; can anyone see where I'm going wrong? (I've also tried various combinations of filemac: / file: / .. / : etc having read the FM creating file paths webpage.)
"filemac:../Users/mikekentdavies/Dropbox/KJA Music Library/Set Lists/" & Gig::Gig Name & " - " & Gig::Version & " Set List.pdf"
By LelandLong
I read that the new 3.01 version does not require Java.
When I run FMPAv16 on my Mac (10.11.6) and use the sample Email database it works just fine and I see nothing related to Java. I had the older v2.12 plugin installed on here and have just updated to v3.01 today.
When I run FMPAv16 on a different Mac (10.11.6) and install the v3.01 plugin (never had the plugin installed on this machine before today) and run the sample database a Java App runs without any windows, Just visible in the lower right dock and its single menu is titled "Java"
Any ideas as to this oddity?
Leland Long
By Mr. B
We are Americans who are a non-profit and have a school for squatter children in the slums of the Philippines and would like to create student attendance database that provides various rewards.
Our goal is to encourage the kids to attend school who otherwise wouldn't and provide them with a reward point type of system. Each day they attend school, they get 5pts. If they remembered to wear their school uniform they get additional 5 pts. At the end of the day or the end of the week, they can use their points and trade them in for rice, milk, things that will help them feed their family, get school supplies etc.
We would like to account for how often they come to track their daily attendance. We are hoping to include other fields that would be helpful to medical assistance, needs, etc.
As of now, we print and laminte, cutout little paper coins we give them and it is a lot of work. We have around 400-600 kids who attend class. Annually we have several large community events where we track the daily attendance during summer of up to 3,000 students who attend. This is all done by hand so a digital type system would really benefit, save time, manpower, and streamline what we are doing.
To Summarize:
- track attendance
- reward attendance and such by point system
- can use their student card points at cafeteria for snacks or for extra stuff as incentive to help their families.
If you know of something that would help us, or have some ideas, please let us know.
~ Mark
By calebruth
I tried to install MirrorSync 3.17 today on a MacOS with 10.12.3 and FMS 126.96.36.1998. The installer is hanging at about 80% progress at "Running package scripts..."
Is there an installer log file that I can examine?
In addition I noted in the docs the restriction against multiple users sharing the same file on the same device:
I am wondering about the details of this restriction and is it possible for multiple users to share the same db file on the same device if there is no record filtering or record-level access features enabled?
By BugsyOhar
Over the past ten years our organization have been using a PO database solution to store all purchasing information. Each year
the layout would change to illustrate which year it represents. We would like to merge each of these databases into one for better
searching capabilities. Is there an easy way to accomplish this task while still maintaining data integrity? Thank you!


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The SZC June/July newsletter is now available for download: szc-newsletter-april-may-2017
Applications are now open for our winter sesshin from June 10-17, 2017. Download flyer: flyer2 winter sesshin 2017 Down…
7:00 pm - 9:00 pm
Regular Zazen, Check newsletter for Dokusan.
7:00 pm - 9:00 pm
Regular Zazen and Dokusan. Check newsletter for Dokusan.
Robert Aitken Roshi (1917-2010), SZC's founding teacher, was introduced to Zen Buddhism while detained in a Japanese internment camp during World War 11. In 1959, he and his wife Anne established the Diamond Sangha, a Zen Buddhist society. A student of Nakagawa Soen Roshi, Yasutani Hakuun Roshi and Yamada Roshi, Aitken was authorised to teach in l974. He led sesshin in Sydney from 1979.
The author of thirteen books, Aitken was writing up to his death, and this final book is currently in the process of publication. Aitken Roshi was a pioneer in establishing Zen Buddhism in the West, never finding any separation between his vision of justice and the Zen teachings of complete interdependence, He co-founded the Buddhist Peace Fellowship in l978. You can learn more about Robert Aitken at RobertAitken.net.
Subhana Barzaghi, the senior resident teacher of the Sydney Zen Centre, has been practising meditation for over 20 years. She has studied in Australia and California with John Tarrant, in Japan with Yamada Koun Roshi, and in Australia and Hawaii with Robert Aitken Roshi, the founder of the Diamond Sangha. Subhana received Dharma transmission from Aitken Roshi and John Tarrant in 1996 at the Gorrick's Run Zendo.
Subhana Barzaghi is a qualified and experienced psychotherapist, a mother of two children, and a grandmother. She was a founding member of the 'Bodhi Farm' community in the Northern Rivers, where she lived for 20 years. She was also the founder of the Kuan Yin Zen Centre in Lismore. Subhana presently lives in Sydney with her partner. Subhana is a Registered Religious Marriage Celebrant, and also teaches in the Vipassana Insight Meditation tradition. She leads workshops, Zen sesshins and Vipassana retreats at a variety of centres in Australia, New Zealand, and India.
Gillian Coote, co-ordinating teacher of the Sydney Zen Centre, met Robert Aitken Roshi in l980, regularly attending his annual sesshin in Sydney as well as training periods and sesshin in Hawai'i. She also studied with John Tarrant and Subhana Barzaghi, from whom she received dharma transmission in June 2004 at Kodoji, Temple of the Ancient Ground.
Gillian has been involved with developing sangha at Sydney Zen Centre since the early '80's, organising sesshin, editing SZC's journal, Mind Moon Circle, and building Kodoji at Gorricks Run with her husband, architect/builder Tony Coote, over many years, inspired by their experience of sangha building at the Ring of Bone Zendo in California in l982. She trained with Joanna Macy and for fifteen years was the co-ordinator of the Sydney branch of the Buddhist Peace Fellowship. She has practised with Thich Nhat Hanh, attending his artists' retreat in Ojai, CA and joining his pilgrimage to Buddhist sites in India and Nepal; she directed and produced 'The Awakening Bell', a documentary film made during his visit to Sydney.
Gillian is a social documentary filmmaker, writer, grandmother and bush regenerator.
Paul Maloney began his Zen studies in the late 1950s, and formal zazen in 1966. He went to Japan in 1968 and attended his first sesshin under the direction of Nakagawa Soen Roshi in December 1968. He continued his Zen daily zen practice while studying Aikido and the classical Japanese martial art of Shindo Muso Ryu Jodo, and attended weekend zazenkai at Engakuji in Kita Kamakura. Returning to Australia in 1973 he, together with Leigh Davison and others, formed a sitting group that evolved into the Sydney Zen Centre sangha. He began formal koan study with Robert Aitken Roshi in 1979, and after continued with John Tarrant Roshi and Subhana Barzaghi Roshi. He is the teacher of the SZC Blue Mountains group, and the SZC Canberra Group.
He retired, in 2008, from the Faculty of Engineering, University of Technology Sydney, where he had been a Senior Lecturer and Director of the International Engineering Program since 1995. Prior to that, he had held the position of Assistant Director of the Japan Information and Culture Centre of the Consulate-General of Japan in Sydney since returning from Japan in 1973.
He has degrees in Asian history and Western philosophy. He has been a student of classical Japanese martial arts for over forty years. He now teaches Shindo Muso Ryu Jodo, Kasumi Shinto Ryu Kenjutsu and related weapon systems in Sydney and Canberra. His wife, Yayoi, is a teacher of the Japanese Tea Ceremony, chanoyu, which she has been practicing for over fifty years.
Maggie Gluek was appointed an apprentice teacher in the Diamond Sangha in 2003. Since that time she has been part of the collegial teaching team at the Sydney Zen Centre. She has co-taught sesshin with Subhana and Gillian Coote, offers dokusan at Annandale when the opportunity presents itself and gives dharma talks at zazenkai, including with the Canberra Zen Group. In April 2015 Maggie received Dharma transmission from Subhana Barzaghi Roshi.
She began Zen practise in 1983 at the Minnesota Zen Meditation Centre, while on leave in her home town. Upon returning to Australia, she found the Sydney Zen Centre and took up formal koan study with Robert Aitken Roshi. She continued her study with John Tarrant and completed it with Subhana Barzaghi. She has long experience of leadership in the sangha. Maggie has degrees in literature and psychology. Currently she works as a bush regenerator. She is married with two adult children.
SZC teachers offer dokusan (interviews) and teisho (dharma talks) and conduct jukai (Precept) ceremonies. They teach at Annandale, in the Blue Mountains, Canberra and Kodoji in sesshin (retreats). The two resident teachers. Subhana and Gillian, are financially supported in this work by members of the group.
In 1999 the Diamond Sangha Teachers Circle created and publicly released an Ethics Agreement. In it they established a clear and specific set of minimum expectations to which they would hold ourselves accountable now and in the future. See also the SZC Collegiate Teaching Model.
Allan Marett was appointed an apprentice teacher in the Diamond Sangha in 2011. He has co-taught sesshin with Subhana Barzaghi, Paul Maloney and Maggie Gluek. He also offers dokusan at Annandale from time to time and gives dharma talks at zazenkai. He also hosts a regular early morning sitting group at his home in Ashfield.
Allan began his formal Zen training under Yamada Koun Roshi in 1976. Shortly after the establishment of the SZC, he became a student of Robert Aitken. Subsequently he has studied with John Tarrant, Subhana Barzaghi and other Diamond Sangha teachers. He has a particular interest in pilgrimage and regularly walks the Henro pilgrimage in Shikoku, Japan.
In 2007, Allan retired from the post of Professor of Musicology at the University of Sydney, where apart from a period as Professor of Music at the University of Hong Kong in the 1990s, he had taught since 1978. His areas of academic interest include Sino-Japanese music history, Australian Aboriginal music and Japanese Noh theatre.


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Upcoming Conferences and Events
May 31 - Jun 1
Jun 15-16
Sep 14
Oct 11-13
SBD/1/Sports Industrialists
Published November 1, 1994
JOHN KOSNER has been named VP/Program Planning and Development of Sports Illustrated TV. Kosner, 34, had been VP/Broadcasting of the NBA since '91 (SITV)....MARGO HALLE has been named Director/Production, CBS Sports. Halle will oversee budgets for CBS Sports broadcasts and act as liaison to CBS Sports production and operations departments. She will continue as planner/coordinator for CBS' coverage of the '98 Winter Olympics in Nagano. BOB MATINA is the new Coordinating Dir of CBS Sports. Matina will also continue as Coordinating Dir for the '98 Winter Olympics in Nagano (CBS Sports)....GARY STEVENSON has been named COO of The Golf Channel. Stevenson was formerly Executive VP of Business Affairs for the PGA Tour (PGA Tour).


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Employment law 2014 preview: holiday pay - .PDF file.
Calculating the correct amount of holiday pay owed to a worker can prove to be a tricky task for an employer as it is dependent upon various factors. Does the worker have normal working hours or not? If they do, does their pay vary with the amount of work done? Do they work overtime and is that overtime guaranteed or non-guaranteed?
Traditionally, UK legislation has been interpreted so that guaranteed contractual overtime (obligatory on the part of the employer and the worker) was considered to count towards 'normal working hours'. However, non-guaranteed overtime did not count for workers with normal contractual hours: instead statutory holiday pay was calculated with reference to the contractual hours only.
But in 2012, the Court of Justice of the European Union (CJEU) and subsequent Supreme Court judgment in British Airways plc v Williams cast doubt on this. The Williams litigation established that a worker must be no worse off financially during annual leave than if he/she had continued working…
If you are registered and logged in to the site, click on the link below to read the rest of the Wragge & Co briefing. If not, please register or sign in with your details below.


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Kukla's Korner Hockey
Shanahan Done In New Jersey
by Paul on 10/01/09 at 02:02 PM ET
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from Tom Gulitti of Fire & Ice,
Future Hall of Famer Brendan Shanahan has left the Devils and will not be on the team this season.
Devils general manager Lou Lamoriello said Shanahan remains on the team's 23-player roster for now, but a decision will be made on that later today.
Lamoriello said that because of the emergence of young players on the team such as Niclas Bergfors, Matt Halischuk. Rod Pelley and Ilkka Pikkarainen, there was no place for Shanahan on the team's top three lines, which was a role that Shanahan desired. Lamoriello didn't rule out completely that Shanahan won't return to the team at some point this season, but it appears highly unlikely.
added 1:36pm, Tom has more information on this in a new blog post.
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When your pets don't listen, wishing they came with a remote control is not the craziest thought in the world. Remote controlled animals are much easier to deal with and happen to listen (not by choice) to everything you tell them to do.
This list of remote controlled animals serves a greater purpose than just plain domestic leisure. These animals are for research and they fulfill the duties they were intended to fulfill when created. I definitely want one.
13 Remote Controlled Animals
More Stats +/-
Remote Control Your Cat / Dog / Horse / Kid?
Remote Controlled Sharks
Remote Control Creepy Crawlers
Canine Robots
Leg Spines = Super Spider Robots
From Creepy Crawlers to Robotic Sharks
Aug 12, 2009By: Andrew Robichaud -


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Lots going on... Mark Morgan's opted out of the September tour. He's got some gnarly schedule conflicts to deal with, not the least of which is Sightings bassist Richard Hoffman's upcoming nuptials... It's a bummer, but as we're a collective (blah blah, etc.) we must absorb the blow and deal. Mark is much beloved here, and I'll definitely miss him on the cross-country jaunt. As we've not begun to exhaust the possibilities inherent in our collaboration, I consider MM an active, albeit non-participating (at least for the autumnal trek), member of the group. Tears are being shed, old bean.
His performances on Noon are wonderfully sinuous and evocative. (Constant readers have likely surmised as much.) He possesses a near-faultless sense of intuition.
Sightings fanatics can relate, right?
(Mark Morg'n and Benji W ruling at the Bug Jar, Rochester, NY, September 2004. Snap by CG.)
What else? Still assembling the interior sleeve art - that's the final obstacle to be cleared. Ben Wolcott and Syd Garon are racing against the clock to deliver the goods. After it's been approved, off to the plant.
The tour dates are being reconfigured again; now it looks as though we'll begin west of NYC, zigzag around the heartland, zoom through Detroit into Canada, and drive east from there. After Montreal, we'll drop south and finish the tour in Manhattan/Brooklyn/etc. I'll post updated info as soon as I have it...
We're pushing hard to finalize the itinerary; this shit has taken too long, and I'm as agitated as a purveyor of sweetness and light can be.
Fanny has answered the call! He's going to be participating in the Noon remix project we plan to release in 2007. If you haven't heard his new album, Shoebomb Hurricane, you're sleeping. I suggest you run out and grab it immediately. ('Cos it rips.)
Other 2007 news: TLASILA will be releasing new (and maybe archival) music via labels based in France (Savage Land) and Israel (Ron-Zed). Naturally, we're stoked.
That's all for now.
Yrz Internally,


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Fang: Explanation of what creates your powers.Mature
"No matter how many cesnia stones you have in your body, you will always have the same power. It will just be enhanced and upgraded, so to speak. For example, one of my marine buddies, Lucretia, in rank 1 she got her first cesnia stone, she had the ability to move fast. With 1 stone, she moved twice as fast, the more cesnia stones she got, the faster she could move. 1 stone, twice as fast; 2 stones, four times as fast; 3 stones, eight times as fast; 4 stones, sixteen times as fast. Now with 12 stones, she moves four thousand ninety-six times as fast.
"As a second example, me. With my first cesnia stone I gained the ability to turn into a wolf, for five minutes, my hide could resist 25 kpa of force, and I could run 4 times as fast as if I were a human. Now, with 12 stones, I have the ability to turn into a wolf for one hour, my hide can resist 300 kpa of force, and I can run 48 times as fast as if I were a human. These are the most significant among other attribute changes. My teeth and claws are also more sharper and more durable now that I have 12 stones.
"So, since you all started with such a large amount of stones, you're powers will be extremely strong. And so, I caution you with sparring with your friends, as you don't know what could happen."
Then I speak to Alex.
"In about three weeks is my Cesniamitva, that's when I gain my 13th rank and my 13th cesnia stone. Since chances are I won't be able to make it there, can we do it here? Because of Marine Corps technology, my badge will upgrade anyways, I would like if I could too."


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|Publication number
|Publication type
|Application number
|Publication date
|Jan 3, 2006
|Filing date
|Mar 17, 2003
|Priority date
|Mar 15, 2002
|Fee status
|Also published as
|Publication number
|Nicholas W. Warne, Rebecca L. Koval, John Carpenter, Theodore W. Randolph, Suchart Chongpraset
|Original Assignee
|Wyeth, The Regents Of The University Of Colorado
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (28), Non-Patent Citations (2), Referenced by (7), Classifications (26), Legal Events (3)
|External Links: USPTO, USPTO Assignment, Espacenet
This application claims priority to U.S. Ser. No. 60/365,044, filed Mar. 15, 2002. The contents of that application are incorporated herein by reference in their entirety.
This work was supported by grants by the National Institutes of Health Grant Nos. PHS-T32 CA 79446-02. (original claim) The government has certain rights in this invention.
The invention relates to compositions containing polypeptides, including therapeutic polypeptides such as interleukin-11, that provide for enhanced stability of the polypeptide following storage at room temperature or at elevated temperatures.
Recombinant human interleukin-11 (rhIL-11) is a non-glycosylated polypeptide of 177 amino acids. The polypeptide lacks cysteine residues and is highly basic (pI>10.5). rhIL-11 is used as a chemotherapeutic support agent, and is administered in conjunction with other cancer treatments to increase platelet levels. rhIL-11 has also been demonstrated to have anti-inflammatory effects and to be useful in treating conditions such as Crohn's disease. rhIL-11 is a member of a family of human growth factors that includes human growth hormone (hGH) and granulocyte colony-stimulating factor (G-CSF).
To minimize degradation, and to maintain the bioactivity of the polypeptide, preparations containing rhIL-11 and related polypeptides are typically provided as chilled preparations in either a liquid or lyophilized state. Preparing, storing, and transporting the chilled preparations can be labor-intensive, costly and inconvenient for patients and health-care providers.
The invention is based in part on the discovery of compositions that provide for enhanced stability of polypeptides such as rhIL-11. Combining rhIL-11 with hydroxyethyl starch and either of the disaccharides sucrose or trehalose has been found to result in a composition in which the rhIL-11 is stable following prolonged storage at room temperature. Unless otherwise noted, "room temperature" means 25�5� C.
Any polypeptide for which prolonged storage at or near room temperature is desired can be used in the compositions and methods described herein. In some embodiments, the polypeptide is non-glycosylated, lacks a cysteine residue, and/or has a basic pI.
In one aspect, the invention provides a composition that includes a polypeptide, a disaccharide, and an amylopectin derivative. A preferred amylopectin derivative is a branched amylopectin such as hydroxyethyl starch (HES).
Stability of the polypeptide in the composition can be assessed by storing the composition at elevated temperatures for extended periods of time. For example, the composition is preferably formulated so that the polypeptide is stable for one or more months (e.g., 1, 2, 3, 5, 6, 7, 8, or 9 or more months) when the composition is stored at 60� C.
Preferred disaccharides are trehalose or sucrose. In preferred embodiments, the disaccharide is present in the composition at a concentration of 1.5 to 6.0%. For example, the disaccharide can be present at a concentration of 2.5–5.0%.
The hydroxyethyl starch is preferably present in the composition at a concentration of 0.5 to 3.5%, e.g., the hydroxyethyl starch may be present at a concentration of 2.5%.
In one embodiment, the invention provides a composition that includes rhIL-11, sucrose, and hydroxyethyl starch. The sucrose is present in the composition at a concentration of 2.5% to 5.0%, and the hydroxyethyl starch is present in the composition at a concentration of about 2.5%.
Also provided by the invention is a composition that includes rhIL-11, trehalose, and hydroxyethyl starch. The trehalose is present in the composition at a concentration of 2.5% to 5.0%, and the hydroxyethyl starch is present in the composition at a concentration of about 2.5%.
In a further aspect, the method provides a method of treating or preventing inflammation in a subject by administering to the subject a composition that includes rhIL-11, a disaccharide, and hydroxyethyl starch. In some embodiments, the inflammation is associated with inflammatory bowel disease, such as Crohn's disease.
In one embodiment, the invention includes a method of treating or preventing inflammation in a subject by administering to a subject a composition that includes rhIL-11, sucrose, and hydroxyethyl starch. The sucrose is present in the composition at a concentration of 2.5% to 5.0%, and the hydroxyethyl starch is present in the composition at a concentration of about 2.5%.
Also within the invention is a method of treating or preventing inflammation in a subject by administering to a subject a composition that includes rhIL-11, trehalose, and hydroxyethyl starch, wherein the trehalose is present at a concentration of 2.5% to 5.0%, and the hydroxyethyl starch is present at a concentration of about 2.5%.
The invention further provides a method of enhancing an immune response in, or increasing platelet levels of, a subject by administering to the subject a composition that includes rhIL-11, a disaccharide, and hydroxyethyl starch.
In a further embodiment, the method includes a method of enhancing an immune response in a subject by administering to a subject a composition that includes rhIL-11, sucrose, and hydroxyethyl starch. The sucrose is present in the composition at a concentration of 2.5% to 5.0%, and the hydroxyethyl starch is present in the composition at a concentration of about 2.5%.
In a further aspect the invention includes a method of increasing platelet levels in a subject by administering to the subject a composition that includes rhIL-11, a disaccharide (e.g., sucrose or trehalose), and hydroxyethyl starch. The disaccharide is present in the composition at a concentration of 2.5% to 5.0%, and the hydroxyethyl starch is present in the composition at a concentration of about 2.5%.
The subject used in the herein described methods can be, e.g., a human, a non-human primate, a dog, a cat, horse, cow, pig, sheep, rabbit, rat, or mouse.
Also provided by the invention is a method of making a stable rhIL-11-containing composition. The method includes providing an rhIL-11 polypeptide and contacting the rhIL-11 with a disaccharide and hydroxyethyl starch, thereby making a stable rhIL-11-containing composition. Preferably, the rhIL-11 polypeptide is stable in the composition for at least 1 month when the composition is stored at 60� C. In preferred embodiments, the rhIL-11 polypeptide is stable in the composition for at least 2, 3, 4, 5, 6, 7, 8 or 9 or more months when the composition is stored at 60� C. The disaccharide in the composition is preferably sucrose or trehalose, and is preferably present in the composition at a concentration of 2.5% to 5.0%. The hydroxyethyl starch is preferably present in the composition at a concentration of about 2.5%.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In the case of conflict, the present Specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
Other features and advantages of the invention will be apparent from the following detailed description and claims.
The invention provides compositions that include a polypeptide (e.g., a therapeutically useful polypeptide), a disaccharide and an amylopectin derivative, including branched amylopectins such as hydroxyethyl starch (HES).
Without being limited by any particular mechanism, it is likely that the combination of a hydroxyethyl starch (HES) with a disaccharide, such as sucrose or trehalose, increases the glass transition temperature, Tg, of the dried polypeptide compositions of the invention, compared to protein dried with disaccharides alone, and results in improved protein stability during storage.
The invention also provides methods of treating or preventing various disorders, such as inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis, indeterminate colitis, and infectious colitis), mucositis (e.g., oral mucositis, gastrointestinal mucositis, nasal mucositis, and proctitis), necrotizing enterocolitis, aphthous ulcers, psoriasis, pharyngitis, esophagitis, peptic ulcers, gingivitis, periodontitis, and ocular diseases (e.g., conjunctivitis, retinitis, and uveitis) in a subject by administering to the subject a composition that includes rhIL-11, a disaccharide, and hydroxyethyl starch.
Interleukin 11 (IL-11) is a pleiotropic cytokine that stimulates primitive lymphohematopoietic progenitor cells and acts in synergy with other hematopoietic growth factors to stimulate the proliferation and maturation of megakaryocytes. IL-11 is described in detail in International Application PCT/US90/06803, published May 30, 1991; as well as in U.S. Pat. No. 5,215,895; issued Jun. 1, 1993. A cloned human IL-11 was previously deposited with the ATCC, 10801 University Boulevard, Manassas, Va. 20110-2209, on Mar. 30, 1990 under ATCC No. 68284. Moreover, as described in U.S. Pat. No. 5,270,181; issued Dec. 14, 1993; and U.S. Pat. No. 5,292,646; issued Mar. 8, 1994; IL-11 may also be produced recombinantly as a fusion protein with another protein. IL-11 can be produced in a variety of host cells by resort to now conventional genetic engineering techniques. In addition, IL-11 can be obtained from various cell lines, for example, the human lung fibroblast cell line, MRC-5 (ATCC Accession No. CCL 171) and Paul et al., the human trophoblastic cell line, TPA30-1 (ATCC Accession No. CRL 1583). Described in Proc Natl Acad Sci USA 87:7512 (1990) is a cDNA encoding human IL-11 as well as the deduced amino acid sequence (amino acids 1 to 199). U.S. Pat. No. 5,292,646, supra, describes a des-Pro form of IL-11 in which the N-terminal proline of the mature form of IL-11 (amino acids 22-199) has been removed (amino acids 23-199). As is appreciated by one skilled in the art, any form of IL-11 that retains IL-11 activity is useful according to the present invention.
In addition to recombinant techniques, IL-11 can also be produced by known conventional chemical synthesis. Methods for constructing the polypeptides useful in the present invention by synthetic means are known to those of skill in the art. The synthetically constructed cytokine polypeptide sequences, by virtue of sharing primary, secondary, or tertiary structural and conformational characteristics with the natural cytokine polypeptides are anticipated to possess biological activities in common therewith. Such synthetically constructed cytokine polypeptide sequences or fragments thereof, which duplicate or partially duplicate the functionality thereof may also be used in the method of this invention. Thus, they may be employed as biologically active or immunological substitutes for the natural, purified cytokines useful in the present invention.
Modifications in the protein, peptide or DNA sequences of these cytokines or active fragments thereof may also produce proteins that may be employed in the compositions and methods of this invention. Such modified cytokines can be made by one skilled in the art using known techniques. Modifications of interest in the cytokine sequences, e.g., the IL-11 sequence, may include the replacement, insertion or deletion of one or more selected amino acid residues in the coding sequences. Mutagenic techniques for such replacement, insertion or deletion are well known to one skilled in the art. (See, e.g., U.S. Pat. No. 4,518,584.)
Other specific mutations of the sequences of the cytokine polypeptides which may be useful therapeutically as described herein may involve, e.g., the insertion of one or more glycosylation sites. An asparagine-linked glycosylation recognition site can be inserted into the sequence by the deletion, substitution or addition of amino acids into the peptide sequence or nucleotides into the DNA sequence. Such changes may be made at any site of the molecule that is modified by addition of O-linked carbohydrate. Expression of such altered nucleotide or peptide sequences produces variants which may be glycosylated at those sites.
Additional analogs and derivatives of the sequence of the selected cytokine which would be expected to retain or prolong its activity in whole or in part, and which are expected to be useful in the present method, may also be easily made by one of skill in the art. One such modification may be the attachment of polyethylene glycol (PEG) onto existing lysine residues in the cytokine sequence or the insertion of one or more lysine residues or other amino acid residues that can react with PEG or PEG derivatives into the sequence by conventional techniques to enable the attachment of PEG moieties.
Additional analogs of these selected cytokines may also be characterized by allelic variations in the DNA sequences encoding them, or induced variations in the DNA sequences encoding them. It is anticipated that all analogs disclosed in the above-referenced publications, including those characterized by DNA sequences capable of hybridizing to the disclosed cytokine sequences under stringent hybridization conditions or non-stringent conditions (Sambrook et al., Molecular Cloning. A Laboratory Manual, 2d edit., Cold Spring Harbor Laboratory, New York (1989)) will be similarly useful in this invention.
Also considered useful in the compositions and methods disclosed herein are fusion molecules, prepared by fusing the sequence or a biologically active fragment of the sequence of one cytokine to another cytokine or proteinaceous therapeutic agent, e.g., IL-11 fused to IL-6 (see, e.g., methods for fusion described in PCT/US91/06186 (WO92/04455), published Mar. 19, 1992). Alternatively, combinations of the cytokines may be administered together according to the method.
Thus, where in the description of the methods of this invention IL-11 is mentioned by name, it is understood by those of skill in the art that IL-11 encompasses the protein produced by the sequences presently disclosed in the art, as well as proteins characterized by the modifications described above yet which retain substantially similar activity.
Hydroxyethyl Starch (HES)
While any branched polysaccharide (e.g., an amylopectin) can be used in the compositions and methods described herein, HES is a preferred stabilizer because it is non-toxic, is biodegradable, has excellent glass-forming properties, and is clinically approved for therapeutic uses.
Hydroxyethyl starch is a derivative of amylopectin, which is a highly branched compound of about 250–300 K that is soluble in water and virtually insoluble in organic solvents. HES includes about 0.4 to about 0.5 hydroxyethyl units per component glucose monomer. In humans and other animals, amylopectin is rapidly hydrolyzed by alpha-amylase. The activity of alpha-amylase depends on the position of the hydroxyethyl groups at positions C2, C3, and C6 on the glucose molecule. HES can be obtained from a variety of vendors.
Preferred disaccharides are sucrose and trehalose. Disaccharides can be obtained from a variety of vendors.
Preparing Compositions that Include a Polypeptide, Disaccharide, and Hydroxyethyl Starch
Compositions containing a polypeptide, disaccharide and hydroxyethyl starch can be prepared by buffer exchanging the polypeptide into the appropriate solution. This process can be accomplished, by one skilled in the art, by diafiltration, dialysis, chromatography, crystallization followed by reconstitution or some combination of freeze-drying or spray-drying followed by reconstitution with water or a combination of water and disaccharides and/or hydroxyethyl starch. Once the solution containing the polypeptide, disaccharide and hydroxyethyl starch has been prepared, it is dehydrated by means of freeze-drying, spray-drying, vacuum drying or by the use of supercritical fluid based dehydration. The resultant lyophilized powder represents the stable composition of the polypeptide, disaccharide and hydroxyethyl starch.
Methods of Treatment with IL-11
A suitable treatment regimen for patients undergoing treatment, including for example prophylactic treatment, may be determined by the attending physician based upon such factors as the patient's age, sex, weight, and general health. Generally, a suitable dose of IL-11 ranges broadly, preferably between 1 and 100 μg/kg body weight, e.g., 5 to 90 μg/kg body weight. 10 to 80 μg/kg body weight, 20 to 70 μg/kg body weight, or 30 to 65 μg/kg body weight. Another suitable dose is in the range of about 25 to 50 μg/kg body weight. If desired, these doses can be adjusted to units. A unit is conventionally described as the concentration of polypeptide which leads to half-maximal stimulation in a suitable assay, e.g., for IL-11, the T1165 assay described in PCT/US90/06803. Doses may be administered daily for between one day and six months, or for as long as is deemed necessary and safe, as is readily ascertained by standard tests by the attending physician, depending upon the nature of the disorder being treated. Where appropriate, the dosages may be adjusted upward or downward, for example, a dosing regimen requiring administration of IL-11 at a dose of 25 μg/kg, daily for one week, or fewer days, or multiple weeks if indicated. The progress of treatment is appropriately monitored by measurement of markers associated with the disorder being treated to determine if such a dose results in a decrease of, for example, TNFα levels (or corresponding marker) and if not, increasing the dose two-fold for an additional time period of treatment and measurement of marker levels until an effective dosing regimen is reached.
Compositions of the invention may be administered rectally, parenterally, intracistemally, intravaginally, intraperitoneally, bucally, or as a nasal spray. The term "parenteral" as used herein refers to modes of administration that include intravenous, intramuscular, intraperitoneal, intrastemal, subcutaneous and intraarticular injection and infusion.
The invention will be further illustrated in the following non-limiting examples. The examples describe the prediction of protein stability in a dried solid after formulation and lyophilization of composition that includes the polypeptide, hydroxyethyl starch (HES), and sucrose or trehalose (Example 1). Also shown are examples describing IL-11 properties in compositions after short-term storage (Example 2), and long-term storage nine months at three different temperatures (Example 3).
In some examples, protein stability was predicted by measuring the Tg of the lyophilized cake. The Tg, or glass transition temperature, is a temperature range over which a material undergoes a transformation from a glass state to rubbery texture state and undergoes a change in mobility. The Tg-glass transition is a useful indicator of the stability of a lyophilized polypeptide-containing composition: a low Tg-glass transition temperature indicates a relatively unstable lyophilized composition. The Tg temperature was determined using differential scanning calorimetry (DSC).
Protein structure was determined using infrared spectroscopy, size exclusion high performance liquid chromatography (SEC-HPLC) and reversed phase high performance liquid chromatography (RP-HPLC).
Materials and Methods
Recombinant Human Interleukin-11 (rhIL-11) was produced at Wyeth BioPharma (Andover, Mass.). The protein was expressed in Escherichia coli as a part of a fusion protein with a thioredoxin, from which it was cleaved and purified to homogeneity using conventional chromatography as previously reported. (Czupryn et al., J Biol Chem. 270, 978–985 (1995)). Sucrose and trehalose were purchased from Pfanstiehl laboratories (Waukegan, Ill.). Hydroxyethyl starch HES (Viastarch) was purchase from Fresenius, Austria, and had a mean molecular weight of 200 kD. (Searles et al., J Pharm Sci. 90, 860–871 (2001)). All other reagents were obtained from Sigma Chemicals Co. (St. Louis, Mo.).
Samples were freeze-dried with a FTS Durastop lyophilizer equipped with a Dura dry MP condenser unit (Stone Ridge, N.Y.). (Allison et al., J. Pharm. Sci. 89,199–214 (2000)). Formulations of rhIL-11 were prepared in 10 mM Tris buffer pH 7.0 to a final protein concentration of 3.9 mg/mL, with sucrose (1.0, 2.5, 5.0 or 10.0% wt/vol), trehalose (1.0, 2.5, 5.0 or 10.0%) or HES (2.5%). Formulations containing 2.5% HES with 1.0, 2.5, 5.0 or 10.0% disaccharide were also prepared. Samples aliquots (1 mL) were transferred into 5 mL lyophilization vials (West Co.) and placed on the lyophilizer shelf, which was at room temperature.
Samples were frozen by cooling the shelves to −40� C. at a rate of 2.5� C./min. After the samples were at this temperature for 4 hours, primary drying was started by reducing chamber pressure to 100 μmHg, and continued by maintaining the shelf temperature at −40� C. for 48 hours. Secondary drying (100 μmHg chamber pressure) was initiated by increasing shelf temperature to 25� C. at a rate of 2� C./min. This temperature was maintained for 12 hours. This lyophilization conservative cycle was designed to assure that the formulations containing disaccharides alone as excipients did not collapse during processing. All formulations formed pharmaceutically elegant cakes. The residual water content of all formulations were 0.5–0.9% by mass as determined by Karl-Fisher titration. (Allison et al., J. Pharm. Sci. 89,199–214 (2000)).
Storage Stability
After lyophilization, the vials were sealed under vacuum and placed in incubators at 40 and 60� C. Samples of each formulation were removed at the indicated time points and stored at −20� C. until analyzed.
Differential Scanning Calorimetry
Thermal analysis of dried Interleukin-11 formulations was performed using a Perkin-Elmer DSC-7 differential scanning calorimeter (Norwalk, Conn.). Dried samples (5 mg) were sealed in aluminum sample pans in a dry nitrogen-purged glove box, and analyzed with an empty pan in the reference oven. Samples were warmed at 5� C./min, and thermal data were obtained. Samples were scanned twice. (Hatley, Develop Biol Standard. 74, 105–122 (1991)). During the first scan, samples were heated to the onset of the Tg and cooled to 0� C. During the second scan the sample was heated to 190� C., and the Tg value was determined. Glass transition temperatures were reported as the midpoint in the second-order transition in the baseline. The results are presented as approximate average values for triplicate samples as shown in Table 1.
Percent Hydroxyl Ethyl Starch
Amorphous Component
140� C.a
1% sucrose
2.5% sucrose
5% sucrose
10% sucrose
1% trehalose
2.5% trehalose
5% trehalose
10% trehalose
atemperature calculated was a melting temperature, not a Tg.
ND = no glass transition detectable.
The thermograms for the lyophilized formulations containing either disaccharides alone or disaccharide/HES mixtures had a single observable glass transition (
For the lyophilized rhIL-11 formulation with 2.5% HES alone a glass transition could not be detected in the thermogram. HES is a relatively large carbohydrate polymer (mean molecular weight of 200 kD) and is expected to have a Tg near that of similarly sized unmodified starches (e.g., >120� C.) that is substantially greater than that for sucrose or trehalose. (Hageman, Water sorption and solid state stability of protein. In stability of protein pharmaceutical. Part A. Chemical and physical pathways of protein degradation; Aher, T. J. Manning, M. C., Eds.; Plenum press: New York: pp 273–309 (1992) and To and Flink, J Food Technol. 13, 567–581 (1978)). With both sucrose and trehalose formulations, the presence of 2.5% HES raised the formulations' Tg about 15–20� C., to well above the highest storage temperature of 60� C. The increased Tg in disaccharide formulations prepared in HES is because the Tg of a large polymer such as HES is substantially higher than that of a disaccharide. Because these formulations also preserved the native protein secondary structure after lyophilization, it is predicted that they will provide the greatest stability, of the formulations tested, to rhIL-11 during storage at both 40 and 60� C.
Infrared Spectroscopy
Infrared spectroscopy was used to study protein secondary structure in the dried formulations immediately after lyophilization and as a function of storage in the dried solid at 40 and 60� C. In a dry nitrogen-purged glove box, dry protein samples (approximately 0.5 mg protein) were mixed with 300 mg KBr. The mixture was ground and then pressed into a pellet at 12,500 PSI. This procedure for preparing KBr pellets does not alter the structure of proteins in the dry solid. (Prestrelski et al., Biophys J. 65, 661–671 (1993)). Aqueous solutions of native rhIL-11 (20 mg/mL) were placed into a cell fitted with CaF2 windows and path length of 6 μm (Biotools, IL). Spectra were acquired with a Bomem MB series spectrometer and processed as previously described. (Prestrelski et al., Biophys J. 65, 661–671 (1993); Allison et al., J. Pharm. Sci. 89,199–214 (2000); Chang et al., Arch Biochem Biophys. 331, 249–258 (1996); Kreilgaard et al., J Pharm Sci. 8, 281–290 (1999); Allison et al., Arch Biochem Biophys. 358,171–181 (1998); and Allison et al., Arch Biochem Biophy. 365, 289–298 (1999)). Second-derivative spectra in the conformationally sensitive amide I region were normalized for area and overlaid. (Kendrick et al., J Pharm Sci. 85, 155–158 (1996)).
Infrared spectroscopy was used to assess the effects of the excipients on lyophilization-induced protein unfolding. The second derivative spectrum for native rhIL-11 in the conformationally-sensitive amide I region is dominated by a band at 1656 cm−1 for α-helix (
Compositions containing 2.5% HES and 0, 1, 2.5, 5, or 10% sucrose or trehalose were prepared. The percentage of multimer formation and Met58OX was determined after one or two weeks of storage of the formulations at 60� C.
Stored samples were rehydrated in 10 mM Tris buffer (pH 7.0) to a final protein concentration of approximately 4.0 mg/ml. Size exclusion chromatography (SEC) was used to measure the levels of soluble aggregates. Analysis was performed using a Waters HPLC system equipped with a TosoHaas TSK-2000 SWXL column maintained at 5� C. Isocratic elution was performed for 20 minutes at 1.0 mL/min. The mobile phase was 50 mM MES, 0.1 mM Glycine, and 0.5M NaCl (pH 6.0). UV detection was performed at 225 nm. Peak areas in the chromatogram were used to quantify the amounts of soluble aggregates in rehydrated samples
For 2.5 and 5% trehalose and sucrose formulations, protein aggregates and cleavage products were not detected after storage at 40� C. and rehydration (
Oxidation of Met-58 did not occur in 2.5 or 5% trehalose and sucrose formulations during storage at 40� C. (
Proteins reconstituted from 10% sucrose or 10% trehalose were found to be unstable. Proteins reconstituted from 10% sucrose showed higher levels of multimers (had lower Tg).
Formulations were prepared using the ingredients described below and protein structure was analyzed after lyophilization and storage for up to nine months at different temperatures (5� C., 40� C., and 60� C.) with infrared spectroscopy, DSC, and after rehydration by SEC-HPLC and RP-HPLC.
Determination of Tg of Compositions Including IL-11, a Disaccharide and Hydroxyethyl Starch Using Differential Scanning Calorimetry.
DSC was performed on IL-11 containing formulations with the excipients indicated in Table 2. Tg is taken as the midpoint of a glass transition region, and was determined by measuring the change in heat flow Tg is taken as the mid-point temperature of a glass transition region (mW) at increasing temperatures. The texture (glassy or non-glassy) of the formulation was also noted.
Excipient Added to
2.5% Sucrose
2.5% Sucrose
2.5% Trehalose
5.0% Trehalose
2.5% Hydroxyethyl Starch
2.5% Sucrose/2.5% HES
5.0% Sucrose/2.5% HES
2.5% Trehalose/2.5% HES
5.0% Trehalose/2.5% HES
All freeze-dried formulations tested were observed to be in a glassy state. The Tg range extended from 60� C. in pure sucrose systems, to about 120� C.–125� C. in IL-11 that was lyophilized in the presence of trehalose. No Tg was observed in IL-11 lyophilized in the presence of only HES. The presence of HES along with a disaccharide increased the Tg of the dried power relative to that measured for a formulation lyophilized with only disaccharides (sucrose or trehalose). The Tg for all formulations did not change on storage for 9 months relative to Tg measured immediately after lyophilization (Table I), with two exceptions. Glass transitions for the formulations containing 2.5% and 5.0% sucrose at 60� C. were not observed during storage and the cakes collapsed completely. DSC analysis of the collapsed cakes showed a melting peak for crystalline sucrose. Storage of the sucrose formulations at a temperature above Tg resulted in crystallization of the sugar.
Determination of IR-Spectra of Compositions Including IL-11, a Disaccharide and Hydroxyethyl Starch
The structure of rhIL-11 in various compositions containing a disaccharide and/or the carbohydrate polymer hydroxyethyl starch (HES) was determined by examining the amide I band at 1600–1700 cm−1. Samples whose spectra were measured, and the temperatures at which they were stored, included the following: 2.5% sucrose (40� C. and 60� C.); 2.5% trehalose (40� C. and 60� C.); and 2.5% HES (40� C.).
Storage Stability of rhIL-11 Dried with HES Alone
rhIL-11 was freeze-dried with 2.5% (w/v) HES alone to test the hypothesis that even if a polymeric carbohydrate excipient has a high glass transition temperature it will not provide optimal storage stability to a dried protein, if it does not also prevent protein unfolding during lyophilization. First, to determine if alterations in the protein's secondary structure were occurring during storage in the dried solid, infrared spectra for rhIL-11 in the dried formulations stored at 40 and 60� C. were compared to the spectrum for the formulation immediately after lyophilization. Spectra of the protein in the samples stored for 3 months at both temperatures had a small decrease in the intensity of the α-helix band, indicating a minor, further structural perturbation of the protein during storage in the dried solid (
In contrast to the minor secondary structural changes arising during storage, there was great degradation of the stored protein detected after rehydration. Soluble aggregates and cleavage product levels slowly increased in samples stored at 40� C. In samples stored at 60� C., these degradation products reached high levels after only one month of storage. Smaller increases were noted with up to six months of storage, after which degradation appeared to reach a plateau. Levels of oxidized methionine-68 did not increase in samples stored at 40� C., but did increase linearly with time in samples stored at 60� C.
The failure of HES alone to provide storage stability to lyophilized rhIL-11 is consistent with earlier studies that showed that dextran (another high molecular carbohydrate polymer) also did not inhibit lyophilization-induced unfolding (Allison et al., J Pharm Sci. 89, 199–214 (2000); Kreilgaard et al., J Pharm Sci. 8, 281–290 (1999); Prestrelski et al., Pharm Res. 12, 1250–1259 (1995) and Kreilgaard et al., Arch Biochem Biophys. 360,121–134 (1998)) and protein degradation reactions during storage in the dried solid. (Allison et al., J Pharm Sci. 89, 199–214 (2000); Kreilgaard et al., J Pharm Sci. 8, 281–290 (1999); Prestrelski et al., Pharm Res. 12, 1250–1259 (1995); Kreilgaard et al., Arch Biochem Biophys. 360,121–134 (1998) and Pikal et al., Pharm. Res. 8, 427–436 (1991)). Overall, the results of the current and previous studies document that storage of an unfolded protein in a glassy polymeric carbohydrate matrix alone is not sufficient to assure inhibition of degradation in the dried solid.
Storage Stability of rhIL-11 Dried with Sucrose or Trehalose Alone
Infrared spectra of rhIL-11 lyophilized in the presence of either concentration (2.5% or 5%) of trehalose showed only trivial changes during 9 months of storage at 40 or 60� C. (
In contrast, during storage of the sucrose formulations at 60� C. there was a significant perturbation of secondary structure (
Storage Stability of rhIL-11 Dried with Mixtures of Disaccharides and HES
In the formulations with HES and trehalose, there was not a detectable change in rhIL-11 secondary structure during storage at either 40 or 60� C. This result is expected because the formulations with trehalose alone were also stable during storage at these temperatures. The formulations with sucrose and HES were also resistant to protein structural perturbations during storage at 40 or 60� C. HES increased the formulation Tg sufficiently high that sucrose crystallization did not occur during storage at 60� C., and protein structural perturbation was avoided.
During storage of disaccharide/HES formulations at 40� C., aggregates, oxidized Met-58 and cleavage products did not increase. During storage at 60� C., aggregate formation was almost completely inhibited and oxidation of Met-68 was greatly reduced. The formation of cleavage products was also low during storage of these formulations at 60� C.
Determination of Soluble Aggregates and Degradation Products
The ability of a disaccharide and/or HES to prevent rhIL-11 aggregate formation following long-term storage was determined. Also examined was the ability of a disaccharide and/or HES to prevent oxidation of the methionine residue at position 58 of rhIL-11 and degradation of the rhIL-11 polypeptide. Compositions were prepared containing rhIL-11 and either 2.5% HES, 2.5% sucrose, 5% sucrose, 2.5% trehalose, or 5% trehalose. Compositions were also prepared containing rhIL-11 along with 2.5% HES and 2.5% sucrose, 5% sucrose, 2.5% trehalose, or 5% trehalose. Samples were stored at 40� C. or 60� C., and the percentage of aggregate formation was examined after 1, 3, 6, and 9 months. The percent of soluble aggregates and breakdown products was determined using size exclusion high performance liquid chromatography (SEC-HPLC) and reverse phase high performance liquid chromatography (RP-HPLC).
Soluble aggregates accounted for less than 4% of all protein, with the exception of the rhIL-11 protein stored in 2.5% HES alone at 60� C. These results demonstrate that formulations of rhIL-11 lyophilized with the disaccharides alone or combined with HES showed a protective effect against soluble aggregates formation at either storage temperature.
The chemical stability of rhIL-11 during long-term storage of the proteins was examined by measuring the level of Met-58 oxidation in the preparations at the indicated temperatures. At 40� C., less than 4% of the methionine residues were oxidized for all formulations tested. At 60� C., sucrose formulations were not found to protect against Met-58 oxidation. Formulations prepared with trehalose and HES showed reduced Met-58 oxidation as compared to sucrose. Formulations of rhIL-11 lyophilized with sucrose and HES showed lower levels of Met-58 oxidation than rhIL-11 formulated with trehalose-HES formulations. HES by itself was not found to prevent Met-58 oxidation. Met-58 oxidation in HES-only formulations was higher in samples stored at 60� C. than in samples stored at 40� C.
The chemical stability of rhIL-11 during long-term storage was also examined by assaying the level of IL-11-related cleavage products. Levels of IL-11-related species were less than 3% and 10% for the disaccharide formulations stored at 40� C. or 60� C., respectively. The levels of cleavage products were slightly higher in rhIL-11 from trehalose-HES formulations as compared to cleavage products from rhIL-11 from sucrose-HES formulations. rhIL-11 formulated in 2.5% HES alone showed 12.0% and 45.0% related species after nine months storage at 40� C. and 60� C., respectively.
These data demonstrate that optimal stability was found with formulations that included both HES and either sucrose or trehalose. Including HES along with the disaccharides did not affect protein structure, but its presence did prevent aggregate formation. The disaccharides alone were more effective than HES alone at inhibiting lyophilization-induced protein unfolding.
Other embodiments are within the claims.
|Cited Patent
|Filing date
|Publication date
|Dec 20, 1983
|May 21, 1985
|Cetus Corporation
|Human recombinant interleukin-2 muteins
|Jan 22, 1985
|Dec 22, 1987
|Takeda Chemical Industries, Ltd.
|Stable composition of gamma-interferon
|May 21, 1990
|Jun 1, 1993
|Genetics Institute, Inc.
|Dna encoding a mammalian cytokine, interleukin-11
|Aug 14, 1991
|Dec 14, 1993
|Genetics Institute, Inc.
|Peptide and protein fusions to thioredoxin and thioredoxin-like molecules
|Jul 28, 1992
|Mar 8, 1994
|Genetics Institute, Inc.
|Peptide and protein fusions to thioredoxin and thioredoxin-like molecules
|Sep 14, 1994
|Mar 5, 1996
|Johns Hopkins University
|Inhibition of hemoflagellates by camptothecin compounds
|Mar 8, 1994
|May 20, 1997
|Somatogen, Inc.
|Method of stimulating hematopoiesis with hemoglobin
|Jun 27, 1995
|Oct 21, 1997
|Keith; James
|Method of using IL-11 for treating spondyloarthropies
|Feb 10, 1997
|May 26, 1998
|Fraunhofer-Gesellschaft Zur Forderung Der Angewandten Forschung E. V.
|Method for synthesizing soluble recombiant proteins from bacteria cells
|Feb 17, 1995
|Dec 8, 1998
|U.S. Bioscience, Inc.
|Methods of using aminothiols to promote hematopoietic progenitor cell growth
|Jun 18, 1999
|Jun 20, 2000
|Andrx Pharmaceuticals, Inc.
|Omeprazole formulation
|Oct 26, 1998
|Oct 3, 2000
|Genetics Institute
|Methods of treating inflammatory bowel diseases by administering IL-11
|Aug 28, 1998
|Jan 16, 2001
|Andrx Pharmaceuticals, Inc.
|Omeprazole formulation
|Dec 21, 1999
|Mar 27, 2001
|Novo Nordisk A/S
|Modified release formulations containing (R)-1-(10,11-dihydro-5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1propyl)-3-piperidinecarboxylic acid
|Apr 14, 2000
|Dec 18, 2001
|Bristol-Myers Squibb Company
|Enteric coated pharmaceutical tablet and method of manufacturing
|Nov 3, 1999
|Aug 6, 2002
|Astrazeneca Ab
|Pharmaceutical formulation comprising omeprazole
|Sep 15, 2000
|Apr 1, 2003
|Method of treating inflammatory bowel disease using a topical formulation of IL-11
|Feb 22, 2000
|Jul 1, 2003
|Baxter International Inc.
|Albumin-free Factor VIII formulations
|Oct 5, 2001
|Mar 25, 2004
|American Home Products Corp.
|Formulations for IL-11
|Nov 20, 1990
|May 30, 1991
|Genetics Institute, Inc.
|A mammalian cytokine, il-11
|Aug 29, 1991
|Mar 19, 1992
|Genetics Institute, Inc.
|Multidomain hematopoiesis stimulators
|Jul 2, 1992
|Jan 21, 1993
|Cryolife, Inc.
|Method for stabilization of biomaterials
|Nov 27, 1995
|Jun 27, 1996
|Genetics Institute, Inc.
|Human interleukin-11 receptor
|Jan 12, 1999
|Jul 29, 1999
|Genetics Institute, Inc.
|Method of using il-11 to enhance cell mediated immunity for treating various viral and parasitic infections and cancer
|Jun 8, 2000
|Dec 14, 2000
|Genetics Institute, Inc.
|Use of interleukin-11 to treat hemorrhagic shock
|Jul 14, 2000
|Jan 25, 2001
|Genetics Institute, Inc.
|Formulations for il-11
|Sep 17, 2001
|Mar 21, 2002
|Genetics Institute Llc.
|Topical formulations for delivery of interleukin-11
|Oct 18, 2002
|May 22, 2003
|Centocor, Inc.
|Lyophilized monoclonal antibody compositions
|Garzon-Rodriguez et al. Use Of Polymer/Sugar Mixtures To Optimize Storage Stability Of Freeze-Dried Recombinant Human Interleukin-11. Abstracts of Papers American Chemical Society. vol. 221 (1-2):pBIOT, Abstract #14 (2001).
|Paul, et al., "Molecular Cloning of a cDNA Encoding Interleukin 11, a Stromal Cell-Derived Lymphopoietic and Hematopoietic Cytokine", Proc. Natl. Acad. Sci. USA, 87:7512-7516 (1990).
|Citing Patent
|Filing date
|Publication date
|Sep 27, 2005
|Nov 11, 2008
|Hydroxyethyl starch-containing polypeptide compositions
|Jan 24, 2011
|Nov 17, 2015
|Alphavax, Inc.
|Alphavirus and alphavirus replicon particle formulations and methods
|Sep 27, 2005
|Apr 13, 2006
|Warne Nicholas W
|Hydroxyethyl starch-containing polypeptide compositions
|Nov 2, 2007
|Feb 19, 2009
|Alphavax, Inc.
|Alphavirus and Alphavirus Replicon Particle Formulations and Methods
|Aug 19, 2008
|Jul 23, 2009
|Warne Nicholas W
|Hydroxyethyl starch-containing polypeptide compositions
|Nov 8, 2010
|Apr 21, 2011
|Hydroxyethyl Starch-Containing Polypeptide Compositions
|Jan 24, 2011
|Jul 28, 2011
|Alphavax, Inc.
|Alphavirus and Alphavirus Replicon Particle Formulations and Methods
|U.S. Classification
|424/85.2, 514/777, 514/778, 514/19.3
|International Classification
|Cooperative Classification
|European Classification
|Aug 19, 2003
Owner name: REGENTS OF THE UNIVERSITY OF COLORADO, THE, COLORA
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text:
$1,441—$1,781 1—3 bed 11700 SW 26th St, Miramar FL, 33025
from $1,441 1—3 bed
11700 SW 26th St, Miramar, 33025
Commute to Downtown Miramar
The rent at Solano at Miramar Apartments ranges from $1,441 for a one bedroom to a $1,781 three bedroom. Apartments in this building are about 6% less expensive than the Miramar average. This is a pet-friendly apartment.
This apartment is in Miramar.
Solano at Miramar Apartments has a Walk Score of 38 out of 100. This location is a Car-Dependent neighborhood so most errands require a car.
A community of Mediterranean-style residences and townhomes designed for luxury living.Solano at Miramar apartment homes are centrally located in beautiful Miramar, Florida, a premier city in the fastest-growing metropolitan community in South Florida. Solano at Miramar is also conveniently located just minutes from downtown Fort Lauderdale and Miami, where you'll find fantastic dining, exclusive retail shopping, and the area's top employers, and you'll be within a quick drive of South Florida's major airports for those weekend getaways.
Pets allowed:
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Miramar, Florida, 33025
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Solano at Miramar Apartments is in the city of Miramar, FL. Miramar has an average Walk Score of 30 and has 122,041 residents.Learn More About Miramar


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maintenance free battery back up
What is the reason for not using a maintnenance free battery in the watchdog back up sump pump
So when you loose your normal AC power, the backup battery can keep the sump pump running....I'm sure you would really understand why if you had a power failure....and your basement started to fill up with water......
If the question is why not use a mantance free battery instead of a wet cell there is no good reason other then the higher cost of the battery.
I'm confused now.....
Is the question "Why use a battery"
or "Why not use a maint free battery"
or "It should have been a maint free battery"
or ???????????????
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Since it was first sold in 1935, the B72 has offered versatility, durability, and a dash of classic style to customer's bikes the world over. Billed as a light duty touring saddle, the B72 uses loop springs to cushion riders from rough city streets, and the wide, supportive shape is ideally suited to an upright riding posture. And, of course, the B72 features Brooks' full-grain, premium leather and trademark rivets for the ultimate in comfort and style.
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Phoenix, AZ
Patient, Caring and Compassionate Maestro40/hour
...office as a client or in your home as your tutor. It is important to understand that we all have different abilities and gifts but most importantly that we all learn in different ways. I take the time to... read moreSee Tutors Like This


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Odin water mapping in the Orion KL regionA. O. H. Olofsson1, G. Olofsson2, Å. Hjalmarson1, P. Bergman1, J. H. Black1, R. S. Booth1, V. Buat3, C. L. Curry4, P. J. Encrenaz5, E. Falgarone6, P. Feldman7, M. Fich4, H. G. Florén2, U. Frisk8, M. Gerin6, E. M. Gregersen9, J. Harju10, T. Hasegawa11, L. E. B. Johansson1, S. Kwok11, B. Larsson2, A. Lecacheux12, T. Liljeström13, R. Liseau2, K. Mattila10, G. F. Mitchell14, H. L. Nordh15, M. Olberg1, H. Olofsson2, L. Pagani5, R. Plume11, I. Ristorcelli16, G. Rydbeck1, Aa. Sandqvist2, F. von Schéele8, G. Serra16, N. F. Tothill14, K. Volk11 and C. D. Wilson9
1 Onsala Space Observatory (OSO), 439 92 Onsala, Sweden
2 Stockholm Observatory, SCFAB, Roslagstullsbacken 21, 106 91 Stockholm, Sweden
3 Laboratoire d'Astronomie Spatiale, BP 8, 13376 Marseille Cedex 12, France
4 Department of Physics, University of Waterloo, Waterloo, ON N2L 3G1, Canada
5 LERMA & FRE 2460 du CNRS, Observatoire de Paris, 61 Av. de l'Observatoire, 75140 Paris, France
6 LERMA & FRE 2460 du CNRS, École Normale Supérieure, 24 rue Lhomond, 75005 Paris, France
7 NRC-HIA, Herzberg Institute of Astrophysics, 5071 West Saanich Road, Victoria, BC V9E 2E7, Canada
8 Swedish Space Corporation, PO Box 4207, 171 04 Solna, Sweden
9 Department of Physics and Astronomy, McMaster University, Hamilton, ON L8S 4M1, Canada
10 Observatory, PO Box 14, University of Helsinki, 00014 Helsinki, Finland
11 Department of Physics and Astronomy. University of Calgary, Calgary, ABT 2N 1N4, Canada
12 LESIA, Observatoire de Paris, Section de Meudon, 5 place Jules Janssen, 92195 Meudon Cedex, France
13 Metsähovi Radio Observatory, Helsinki University of Technology, Otakaari 5A, 02150 Espoo, Finland
14 Department of Astronomy and Physics, Saint Mary's University, Halifax, NS B3H 3C3, Canada
15 Swedish National Space Board, Box 4006, 171 04 Solna, Sweden
16 CESR, 9 avenue du Colonel Roche, BP 4346, 31029 Toulouse, France
(Received 3 December 2002 / Accepted 14 February 2003)
New results from water mapping observations of the Orion KL region using the submm/mm wave satellite Odin (2.1´beam size at 557 GHz), are presented. The ortho-H 2O ground state transition was observed in a rectangular grid with a spacing of 1´, while the same line of H 218Owas measured in two positions, Orion KL itself and 2´ south of Orion KL. In the main water species, the KL molecular outflow is largely resolved from the ambient cloud and it is found to have an extension of 60´´-110´´. The H 2O outflow profile exhibits a rather striking absorption-like asymmetry at the line centre. Self-absorption in the near (or "blue") part of the outflow (and possibly in foreground quiescent halo gas) is tentatively suggested to play a role here. We argue that the dominant part of the KL H 218Ooutflow emission emanates from the compact (size ~15´´) low-velocity flow and here estimate an H 2Oabundance of circa 10 -5 compared to all H 2 in the flow - an order of magnitude below earlier estimates of the H 2O abundance in the shocked gas of the high-velocity flow. The narrow ambient cloud lines show weak velocity trends, both in the N-S and E-W directions. H 218Ois detected for the first time in the southern position at a level of ~0.15 K and we here estimate an H 2Oabundance of (1-8) .
Key words: ISM: abundances -- ISM: individual objects: Orion KL -- ISM: molecules -- submillimeter
Offprint request: A. O. H. Olofsson, firstname.lastname@example.com
SIMBAD Objects


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Fairfield Inn & Suites Marianna
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Merry Marianna
... 2014 I drove ol Charlie up thru Birmingham, so I guess I was somewhat familiar with the place and I had no trouble getting thru the town this time either. I didn't get much of a chance to gander around because it was bumper to bumper traffic. I'm wondering, "doesn't anybody work anymore". Jeez we got about a 5% unemployment rate and they all must be on the highways and byways..Yikes....OK, OK, OK, I'm done with my ******ety stuff now.
I kept ...
Today we went canoeing down Ecofina creek. There were 7+ miles and it took about 5 hours. Very fun!! Still really windy with high waves and jellyfish at beach, so good day to go inland. Daddy's fav was the Turtle springs and Kyler catching a fish. The kids ...
Didn't pay the electric bill!!
... boys had seen was surrounded by water so they just checked it out from a distance.
The campground was small but nice. Our spot was the only empty site when we arrived and we had to do some close maneuvering to get in.
Sa**************ed up to the visitors center to check out the museum and take the cave tour.
We had just paid for our tour and gone outside to get in the departure line when I noticed the visitors center looked closed. The lights ...
Driving east.
... the Caribbean is just out there beyond the horizon, I think.
We rolled on and pitched up at a rural campsite, at a farm homestead - this is horse country. Have just eaten more gumbo at their Mustang grill, but the only music playing was James Blunt unfortunately. Now the bullfrogs are competing loudly for attention and will continue all night. Very warm and humid here.
A piece of the panhandle
... Rivers State Park; children whined and grumbled, sleepy bodies shocked by the cold as we carried them into the cabin. We noticed the astounding number of stars visible overhead (none of those cozy warm clouds to keep in some heat) but little else before we all collapsed thankfully into the pre-heated cabin.
We awoke the next morning to a beautiful and tranquil sight. Where Florida meets the southwest corner of Georgia, ...


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Hotel Amahoro is one of the best hotels of international class in Burundi. Located deeply downtown the capital city Bujumbura, the Hotel offers well services at best prices. It is more known for its perfectionism as well as organizational and practical skills. We have 33 rooms self contained divide...
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On the 16th– 18th September, many members of the BABSEACLE team from throughout the region (including Australia) came together for the Strategic Planning Weekend in Chiang Mai, Thailand. During the weekend there were numerous team-building sessions that required collaboration and discussion about BABSEACLE's future and expanding role within the Asia region. The sessions also created an environment conducive to strengthening bonds and relationships within the organization. It was extremely fortunate to have the participation of Helen Yandell, one of BABSEACLE's board directors, and other team members from the Laos, Vietnam and Myanmar offices, who travelled to Thailand to attend the event.
View more: https://www.babseacle.org/articles/a-babseacle-weekend-for-strategic-planning-in-chiang-mai-thailand/


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Perak Tours
Lost World of Tambun - 6th Mile Tunnel
Tours Beyond KL
Need more of an adrenaline rush? Opt for the three-hour cave exploration experience at the Six Mile Tunnel. Eco-enthusiasts are guided by experienced guides through the 700 meter long cave tunnel; walking through knee-deep mud, swimming across a shallow pool, before continuing to walk through chest-deep water inside the tunnel. Along the way, you'll get to experience a bout of history where you'll get to learn about mining artifacts as well as stalactites in the making.Read More
- Batu Caves, Royal Selangor & Batik Half-Day Tour
- Sunway Lagoon Theme Park Admission with RM10 Meal Voucher
- Nature & Elephant Sanctuary Tour
- Historical City of Malacca Full-Day Tour
- Traditional English Afternoon Tea at the Eastern & Oriental Hotel
- Glittering Fireflies Night Tour with Dinner
- City Half-Day Tour
- Aquaria KLCC Admission
- Dining in the Clouds at the KL Tower with Transfer
- Kuala Lumpur Tower Observation Deck
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