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Identification of cocaine adulterants plays a critical role in identifying sources, dealers, and routes of distribution. Both GC and LC methods can be used to "fingerprint" cocaine samples. Shown in this note is the analysis of simulated cocaine samples by both techniques.
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The credits for this production have not yet been completed or verified.
His Honor: Abe Potash
Bijou Theatre , (10/14/1919 - circa. 4/1920)
Category: Play, Comedy, Original, Broadway
Description: A three-act play
Setting: The living room of Potash home and the Mayor's office in City Hall in Damascus, New York

subset: commoncrawl


text: Hi, Andrew Cunningham wrote: > Hi, I am struggling with the most efficient way to render > "finite-element" models with the best speed/memory tradeoff. These > models may have milllions of "nodes" and "elements" ( triangles and > quads), with usually simple shading. I am replacing some custom > OpenGL code (hard to maintain, not clean C++) with OSG ( easy to > maintain, well written C++) > > For example, with one particular model, the old custom code which > basically just held a vertex array and sent the primitives down the > pipeline used about 650M of memory. The OSG version with no > optimization of the primitives and using display lists used 1.3G of > memory. Turning on optimization, and turning off display lists > brought that down to 850M. Turning display lists back on, cost about > 200M. The big problem with optimizing the geometry , is that one > loses the ability to pick as all association of the primitive index > with the original geometry is lost... Have you tried VBOs instead of display lists? I understand your picking problem and would first try to optimise everything that does not throw away vertices, i.e. try to share as much as possible. The picking code in osgmovie gives an example of how you can get back indices. jp > > Obviously there is always a memory/speed trade-off here, but perhaps > someone has been this way before and has some best practices advice. > > Thanks > > Andrew > > ------------------ Read this topic online here: > http://forum.openscenegraph.org/viewtopic.php?p=19712#19712 > > > > > > _______________________________________________ osg-users mailing > list osg-users at lists.openscenegraph.org > http://lists.openscenegraph.org/listinfo.cgi/osg-users-openscenegraph.org > > -- This message is subject to the CSIR's copyright terms and conditions, e-mail legal notice, and implemented Open Document Format (ODF) standard. The full disclaimer details can be found at http://www.csir.co.za/disclaimer.html. This message has been scanned for viruses and dangerous content by MailScanner, and is believed to be clean. MailScanner thanks Transtec Computers for their support.


text:
au revoir
04.05.2013 - 04.05.2013
My life has been interesting of late, plenty to talk about, nothing I want to say. That's always been the problem with this blog, that I avoid interesting gossip and end up talking about negative TIC stuff like oh...I don't know, like the taxi driver last night who had a rigged his meter that charged about twice the going rate. Maybe not something people notice too much round town but when you're doing 35km it's impossible to disguise. (I've done the route at night metered several times before, it should be a little above or below 40, we were heading towards 80 but I got out the taxi early). I could have scared him by asking for a receipt, his ID number and so on but I'd rather let the universal forces deal with him. And the ratio of time to write and stuff happening has been tipped in favour of stuff happening to the extent that there's been no time to write about it as well. So I think it's time to let the keys sleep. I've got a lot of bitching out my system and any that's left will have to be sung in the shower. I'll post the odd comment and photo but I'm too busy to keep this going...
Thank you to my four subscribers for their support.
Posted by safemouse 19:51 Archived in China Comments (2)


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Take a fall class at Fluent City! Fall is an awesome time to study a new language. Here are some reasons why = http://fluentcityblog.com/5-reasons-fall-is-the-best-season-to-study-a-language/
101 things to do in New York City in the fall
Thu Sep 1 2011
CommentsAdd +
Photograph: Courtesy of Lomography
Weekend Workshops at the Lomography Gallery Store
Photograph: Alex Strada
Chat among the Mute Swans at Jamaica Bay wildlife refuge
Lose your head over a visit Sleepy Hollow
Photograph: Paul Kolnik
Say hello, say goodbye, at the New York City Ballet. Pictured: Anthony Huxley...
Photograph: Courtesy of Lomography
Weekend Workshops at the Lomography Gallery Store
51. Flip the bird to pixels and shoot some film
Today, everyone has some manner of digital photographic device—why not distinguish yourself as a photographer by going back to film? Lomography cameras are an affordable and creative way to express yourself on celluloid; the Lomography Gallery Store has regular classes on how to make the most of its throwback photographic technology. Recent offerings include "Lubitel Lovers Workshop," which introduced shooters to working with the iconic twin-lense camera, and "Analog in an Instant," covering techniques for working with instant film. On Thursdays, "Lomography's Blue Hour" (at the 23rd Street location; 6pm; free) attracts analog enthusiasts to sip free drinks and sway to music on vinyl. 106 E 23rd St at Park Ave * 41 W 8th St between MacDougal St and Sixth Ave (212-529-4353) * lomography.com/nyc
52. Chat among the mute swans at Jamaica Bay wildlife refuge
Some may be surprised to learn that there is a huge nature preserve located in the middle of all this urban sprawl. The 9,155-acre Queens park is a birdwatcher's dream and boasts well-marked trails. In the fall, head over to the West Pond, where you can expect to see ducks, mute swans, snow geese and other birds that haven't joined their cowardly brethren in warmer seasonal climes. Crossbay Blvd at Broad Channel, Jamaica, Queens (718-318-4340, nps.gov). Daily dawn--dusk; free.
53. A revived orchestra grows in Brooklyn
The Brooklyn Philharmonic makes a triumphant return since cutting back on concert offerings two years ago for financial reasons. With new leader Alan Pierson (who also directs the avant-garde ensemble Alarm Will Sound) at the helm, the ensemble has adopted a more contemporary repertoire that it's taking to all corners of the borough. The first full orchestra concert (Nov 3 at 7:30pm; $10--$55) features a program of Russian cartoons to be presented in Brighton Beach. The orchestra will explore 70 years of Russian and Soviet animation with scores from composers such as Shostakovich. Millennium Theater, 1029 Brighton Beach Ave between Brighton 11th and 12th Sts, Brighton Beach, Brooklyn (718-488-5700, bphil.org)
54. Lose your head during a visit to Sleepy Hollow
Those seeking a spooky experience at any time of year can find it here. Immortalized in Washington Irving's story (and later Tim Burton's film) about the murderous Headless Horseman, Sleepy Hollow is proud of its exceptionally creepy lore (to wit: the local high school's athletics team is the Horsemen). The Sleepy Hollow Cemetery (540 N Broadway; 914-631-0081, sleepyhollowcemetery.org; free) is open daily from 8:30am to 4pm, giving day-trippers plenty of time to explore the 90-acre grounds. You'll find almost as many famous New Yorkers there as at Brooklyn's famed Green-Wood: Take your own self-guided tour (free maps are available), and look out for the graves of Elizabeth Arden, Brook Astor and Irving himself. Travel: Metro-North's Hudson line to Philipse Manor. Off-peak $3.80--$16.50, peak hours $5.23--$22.50.
55. Walk the East River Waterfront Esplanade
Opened in July, this rehabilitated stretch of waterfront, wedged neatly between FDR Drive and the East River, includes new benches and seating (such as lunch-counter-style barstools that face the river with a little ledge to put your meal or book), a dog run and a down-into-the-water staircase. While it's not exactly an ideal location for a relaxing chill-out session (under the highway can get a bit noisy), it's still worth your time for the riverside view, if you're in the area. These renovations are one link in the ongoing project to connect Battery and East River Parks via a continuous walking-and-biking path, which should be completed by 2013. East River between Maiden Ln and Wall St (nyc.gov)
56. Say hello, say goodbye, at the New York City Ballet
The company's season opens with the return of Ballet Master in Chief Peter Martins' full-length staging of Swan Lake, before welcoming Paul McCartney to the world of dance. Macca penned the orchestral score to Ocean's Kingdom (Sept 22), which receives its world premiere at NYCB's fall gala. (McCartney's daughter Stella also designed the costumes for the production.) The final performance of the season bids farewell to principal dancer Charles Askegard, but fear not, the ballet has new talent on the rise: meet new soloist Anthony Huxley. David H. Koch Theater, 20 Lincoln Center Plaza at 63rd St (212-870-5570, nycballet.com). Time and price vary; Sept 13—Oct 9.
57. Mark the "discovery" of America at the Columbus Day parade
Well, he's still one of the most popular failures in history, but 35,000 marchers and nearly 1 million spectators are expected along Fifth Avenue, to mark the day in history when Christopher Columbus landed in the Americas and to celebrate the heritage of the Italian-American community. It may not be the glitziest of New York's parades, but where else can you catch the tarantella (a frenzied Italian folk dance)? Fifth Ave from 47th St to 72nd St (columbuscitizensfd.org). Oct 10 11:30am--3pm; free.
58. Ride in a hot-air balloon
You won't be going around the world like Phileas Fogg, but you will get a fairly excellent view of the lands around Orange County, NY, with Above the Clouds, Inc. Bonus points if you start singing the lyrics to John Parr's classic '80s track "St. Elmo's Fire" while airborne. That right there is worth the price of admission alone. Rides go out at early morning and twilight, and can last a half hour or full hour. Randall Airport, 100 Airport Rd, New Hampton, NY (845-692-2556, abovethecloudsinc.com). Through November; $169--$250.
59. Learn how to toss watercolors like Edward Hopper
The 92nd Street Y hosts a number of outdoor watercolor classes this fall. On Sept 21 there's a session in Central Park; on Sept 22, students will be painting near the High Line. On Oct 6, there's an indoor offering titled "Approaches to Abstraction with Watercolor," at which everyone can pretend they're Kandinsky for a day. For those less advanced, there is a beginners course on Nov 29. Instructors include former NEA and Yaddo fellows; materials aren't provided, but at this time of year, who doesn't fantasize about raiding Pearl Paint (308 Canal St between Church St and Broadway; 212-431-7932, pearlpaint.com) to stock up on tubes of cerulean blue and cadmium red? 1395 Lexington Ave between 91st and 92nd Sts (212-415-5500, 92y.org). Multiple sessions $185--$490; see website.
60. Check out some artists of the floating world
In a room filled with silver speech-bubble balloons, a poem that begins "The Truth Is I Am You" is written on the gallery walls. It's a message of unity, linguistics and antigravity that's worth checking out before Governors Island closes for the season at the end of September. And, if you're so moved, you can write your own aphorism on the balloons. The Gallery at Building 110, Governors Island (mocada.org). Fri--Sun noon--5pm, through Sept 25; free.
Users say
in autumn, we all like go out for picnic,go travelling and begin to get ready for thanksgiving and christmas,lol. http://www.geminideal.com/Topics/Christmas.shtml
Church of the Covenant at 310 East 42nd Street@ 2nd Avenue, welcomes guest preacher, Mary Barrett Speers! Come one, come all! Take this very exciting opportunity to hear one of NY's best preachers in Manhattan this and next Sunday!Stay for Fellowship Hour & refreshments after the service. Also, Mon. Oct., 25th(UN Day, join us for tributes to Civil Rights leaders, Rosa Parks and Rev. Fred Shuttlesworth, 8:30AM - 2PM. Additionally, come to our free Staged Theater Readings Mondays from 6-10PM, free Art Group every Tuesday from 10AM- 3PM,and Bible Study on Thursdays 7-8PM, public Advent Workshops Nov. 27th - Dec. 18, Sundays 2PM, and play: Thornton Wilder's "The Long Christmas Dinner",Sundays Dec. 8,9, 10, 11, 15, 16, 17, and 18th 5PM and Holiday Bazaar all day Sat., Dec. 3!
The information about the floating jack o' lanterns in central park was too vague w/ no DIRECT link in the parks website. I tried looking at central park's site and there was no information about this on their calender or the site.
Thanks for sharing these things to do in New York in fall. People definitely must have supported this cause as to burn some calories.
Nice to very useful info for me.Because I am new in blogging and I need good tutorial like your post.
#102: Leave New York City
is #50 supposed to list the 4 retreats time out new york recommends?
The bike MS link is wrong.


text:
AirTalk for July 6, 2012
The ethnoarchaeology of the American home
J. Arnold and CELF
Image from UCLA's study of American homes. Only 25 percent of garages could be used to store cars because they were so packed with household overflow. Family members said they were parking their stuff while deciding what to do with it. Plans to recoup the cost of unused items by selling them on eBay or Craigslist or at a garage sale rarely materialized.
J. Arnold and CELF
Only 3.1 percent of the world's children live in the United States, but U.S. families buy more than 40 percent of the toys consumed globally. The Los Angeles homes were no exception. Several homes had at least 250 toys on display, and most had at least 100. Untold numbers of other toys were tucked away in closets and under beds.
J. Arnold and CELF
Image from UCLA's study of American homes. Upgrading the master bedroom — often with the addition of an adjoining bathroom — was the single most common remodeling project among the families. At the time of the study, the cost of expanding a master bedroom or constructing a suite of modest proportions was a little more than $80,000.
What does the number of magnets on your refrigerator say about the clutter in your home? What's the most common, the most costly, yet the most underused home renovation? How many American garages actually house a car?
What we buy, where we store it and how much we use it inform the way we live, and our houses tell the story all too well. In a four-year study, UCLA researchers invaded the homes of 32 middle-class, dual-income Los Angeles families, videotaping their interactions, photographing their rooms and yards, and tracking their comings and goings.
What did they find?
Stacks of clutter, from bathrooms to kitchens to hallways. Freezers, closets and garages stockpiled with Gatorade, frozen pizzas, Ziplock bags. Desks drowning in papers; kids' rooms knee-deep in toys, precarious piles of laundry, magazines and CDs around every corner.
What emerges is a fascinating snapshot of America's material culture — a culture of acquiring, but not experiencing; of filling up space instead of using it; of hours spent shifting the messes we've created from corner to corner, instead of enjoying our leisure time. If you revel in the well-ordered worlds imagined in Martha Stewart Living and Dwell, this book is sure to give you a scare — yet it's hard to look away.
What's your clutter quotient? Do you bring more stuff into your house than you take out? To what extent does managing your possessions interfere with actually living your life?
Jeanne Arnold, lead author of "Life at Home in the Twenty-First Century: 32 Families Open Their Doors"; professor of anthropology at the University of California, Los Angeles
Anthony Graesch, co-author of "Life at Home in the Twenty-First Century: 32 Families Open Their Doors"; assistant professor of anthropology at Connecticut College


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Adjustable Stool
Customers Also Bought
Exclusive | Sturdy Swivel Stool has Vintage Appeal
- Versatile stool resembles a prized antique market find
- Height-adjustable to accommodate multiple uses
- Solid mango wood seat and stable steel base
Like a prized antique market find, this versatile stool goes from breakfast bar to potting shed to the dining table when a last-minute guest arrives. Designed with a nod to traditional industrial drafting stools, it's solid and sturdy, holding up to 300 pounds. Swivel the seat to adjust the stool's height from 24" to 32" . The 14" diameter seat is solid waxed mango wood, and the stable, 3-legged base is powder-coated steel with a dark gray anthracite finish.
- Mango wood, powder-coated steel
- Seat is 14" in diameter x 1-1/8" thick
- Seat height adjusts from 24" to 32"
- 3-legged base has 16" diameter footprint
- Weight capacity is 300 lbs.
- Gardener's Supply Exclusive
Reviewed by 9 customers
Sort by
- Simple design
- Poor construction
Best Uses
I ordered two stools; one was great, just as I expected. The other was scratched on the top and was wobbly. It seemed like the metal component was too large for the giant screw that is part of the structure of the stool. For the money I did not think it was worth the purchase and since it was a present we found out when the couple was opening the gift. I was very let down with the quality.
- Was this a gift?:
- Yes
I have just remodled my farmhouse kitchen and they look stunning in it. I bought 3 for my island counter and think I need 1 more. The wooden stool matches my hardwood floors and the metal stand matches my woodstove perfectly
Nice product. Sleek and edgy. Looks good with other black metal in the kitchen.
- Attractive Well Built
- Comfort For Long Periods
Best Uses
- Kitchen Counter Desk
I use this at my kitchen counter and can slide it under the counter when not in use. Nicely built, solid, well designed. Not so great for long periods because of the flat, hard seat, but that's ok for my use.
- Great Design
- High Quality
- Looks great
- Quality materials
- Slightly Wiggly Seat
Best Uses
- Craft table
- Kitchen counter
I bought 2 of these stools for my daughter to use in her fashion design studio. She loves them because she has to work at several tables that are different heights so the adjustability is important. The wooden seat has a beautiful natural grain pattern and the simple sturdy metal legs give it a cool industrial style. The seat can be raised up to a bar height if needed. The only slight problem is that the seat wiggles when it is fully extended, otherwise it is perfect.
these are wonderful kitchen bar stools...........love the way the wood and metal mix with our antique decor. they are sturdy,adjustable and have a beautiful wood finish. we've had many compliments on them!
- Nice Wooden Seat
- Solid frame
Best Uses
- Playing music
- Sitting High
Very nice stool ... in my previous review I mentioned a wobble in the adjustable screw shaft when at middle positions ... I retract that negative comment ... after further review, unbeknownst to me, there is a lock nut under the seat that upon tightening will remove any wobble ... so there you have it ... nice stool made in India ... I purchased 2.
- Nice Wood Seat
- Solid frame
Best Uses
- Playing music
- Sitting High
This stool is well built ... it has a very very small wobble in the adjustable screw shaft when it is at any middle height ... at full up or full down position it has no wobble ... after using this stool for awhile, the wobble doesn't bother me ... it is just something I noticed when I first sat on the stool. By the way, I purchased 2 stools and the report is identical on both. This stool is made in India.
- Adjustable
- Comfortable
- Great style
Best Uses
Style matches our kitchen very well. Very comfortable. Be sure to tighten well if putting seat at a higher position otherwise the seat will wobble. We have at ours at the lowest setting and love it.
Product InstructionsDownload instructions for Adjustable Stool as a PDF
There are no special shipping restrictions or charges associated with this item. For detailed information about our delivery methods and charges, click here.
We're proud of the fact that this item is shipped to you directly from our warehouse in Vermont, by one of our 250 employee-owners. In-stock items are packed with care and shipped within the next business day to ensure prompt delivery to your home and garden!


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China > News > Workshop on the Conservation and reintroduction of the endangered species Bretschneidera sinensis Hemsl.
Workshop on the Conservation and reintroduction of the endangered species Bretschneidera sinensis Hemsl.
7 October 2008
One of the BGCI China projects 'Conservation and reintroduction of the endangered species Bretschneidera sinensis Hemsl.' workshop was held in Nankunshan Provincial Nature Reserve, Longmen County, Guangdong on 23-24 September. About 60 people attended this workshop including BGCI China programme officer Xiangying Wen, specially invited experts from South China Agriculture University (SCAU) Prof. Bingtao Li and Prof. Xueying Zhuang , Prof. Fuwu Xing, Prof. Qingwen Zeng and Dr. Hongfeng Chen from SCBG, graduate students from SCBG and SCAU, leaders from Nankunshan Provincial Nature Reserve, leaders of local community and local residents.
Participants explored the species Bretschneidera sinensis Hemsl. in Nankunshan Nature Reserve in the afternoon of 23rd, to further understand its natural distribution, habitat, and conservation status.
The workshop officially opened in the morning of 24th. In the opening ceremony, Mr. Yingyang Zhang, the director of Nankunshan Nature Reserve, welcome the participant and committed to try to support this project. Xiangying wen briefly introduced BGCI and this project.
The workshop was held with the form of presentation and discussion. Dr. Hongfeng Chen, the leader of this project, reported the progress of this project and participants discussed how to effectively conserve this species.
During the workshop, participants mainly discussed on how to cooperate with local community to protect this species. The participants from local community told us that the local residents have strong sense of protecting plants, not only for Bretschneidera sinensis but also for all plants especially rare and endangered plants in this area.
Please read Chinese version here.
More News
26 August 2010
3 September 2008
13 July 2006


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Obstructed reView: 30 for 30–The Schedule Makers
"Grit" is an awful word when applied to sports. Superman III is an awful movie, when applied to eyes. I often conflate the word with the movie. Simply can't tell them apart, in a practical sense. Like Bills Pullman and Paxton, they're interchangeable concepts. "Onix Concepcion has Superman III coming out his ears" was neither a confusing nor untrue statement in 1983. Still, if I were tasked with making an e ...Read more ›


text:
Dr. Bentley has one office in Ohio.
Specializing in the field of Psychiatry, Dr. Bentley is prepared to diagnose and treat the various types of mental illness, which may include depression, eating disorders, bipolar disorder and anxiety disorders, among other psychiatric illnesses and disorders. Dr. Bentley is trained to provide various treatments, including the prescription of medications, different forms of psychotherapy and cognitive-behavioral therapy, among other techniques.
Dr. Bentley works with two doctors including Dr. Victor Moneme and Dr. Joseph Spare.
Provides care for the mental health in patients, sometimes referred to as "primary care for the mind."


text:
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On Fri, 2006-03-17 at 15:59 +0100, Sebastiaan wrote:
> Does anyone have an idea what the problem can be? I am unsure if the
> problem lies within VTK or Blackdown. Sun-jdk does not have a 64 bit
> version available, so I cannot compare with that.
FYI: Sun DOES have a JDK for 64-bit Linux. It is in Portage, too,
although it is currently masked (please see the list archives[1] if you
don't know why). The 64-bit sun-jdk is a "server VM", so it doesn't
include things like Web Start or applet support. However, it works just
I'm not sure what might be causing the rest of your build problems, but
wanted to at least provide the above.
Greg T.
Footnote [1]:
List archives:
Updated Jun 17, 2009
Archive of the gentoo-java mailing list.
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Post-inspection Compliance Assistance
This Web page contains documents and guidance developed for the Post Inspection Constrcution Stormwater Pilot Project. These web resources can help any EPA region or state that wants to implement a post inspection compliance assistance initiative.
The pilot project was a compliance assistance effort to provide owners and/or operators of construction sites with essential Stormwater Web resources at a central location, to help address any non-compliance issues after an inspection, and to encourage these entities to go beyond compliance. The pilot showed that the post inspection compliance assistance concept is a useful one and it is recommended as a possible element of an integrated strategy when the following conditions exist:
- compliance assistance materials already exist and can be easily compiled and organized into a post inspection Web site;
- the facilities to be inspected should have a permanent address with management personnel on site;
- the environmental management practice changes can easily be understood and implemented; and
- actions taken to improve environmental practices or achieve pollution reduction can be implemented at relatively low cost.
The Post Inspection Construction Stormwater Compliance Assistance Web Site provides "how-to" information for the construction industry to comply with stormwater requirements. This site can serve as a model for other post inspection efforts.


text:
December 28, 2014
PARIS, TX-- While residents were out and about finishing their last minute holiday shopping, some stopped and shared with us their holiday family traditions.
"We all pick a charity and then we have a drawing we all write a check for $25 or bring cash for whoever has cash during this time," said Paris resident Matt Coyle." Then we put it in a hat and whatever charity gets drawn gets all the money in the pot."
Other residents spend time with family and play games.
"We usually have lunch or dinner around 2 and then after that we sit around and play cards and different games and by 10 everyone is tired and ready to go home," said Virginia Taylor.
"We play bingo and through the year I'll collect silly stuff and they can pick the prize that they want," said Donna Boutwell.
If you'd like to share your family's holiday traditions, just comment on our Facebook page at News 12 Paris.
Click Here to access the online Public Inspection File
Viewers with disabilities can get assistance accessing this station's FCC Public Inspection File by contacting the station with the information listed below. Questions or concerns relating to the accessibility of the FCC's online public file system should be directed to the FCC at 888-225-5322, 888-835-5322 (TTY), or email@example.com.


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Outsourcing Guide
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Detoxification and decontamination using nanotechnology therapy
United States Patent: 7,563,613
Issued: July 21, 2009
Inventors: Dennis; Donn M.
(Gainesville, FL), Martin; Charles R. (Gainesville, FL), Morey; Timothy E.
(Gainesville, FL), Partch; Richard E. (Potsdam, NY), Shah; Dinesh O
(Gainesville, FL), Varshney; Manoj (Gainesville, FL)
Assignee: University of
Florida (Gainesville, FL)
Appl. No.: 11/195,046
Filed: August 1, 2005
Pharm/Biotech Jobs
A method of removing a toxic compound
comprising contacting the toxic compound with a particle having two
regions, the first region containing a detoxifying enzyme and the second
region containing a material selected to partition the toxic compound into
the second region. The particle may be a nanoparticle.
Description of the
A method for removal of at least one target chemical from a region
includes the steps of adding a nanoparticle size bioparticle to the region
and partitioning at least a portion of the target chemical into or onto
the bioparticle. The method results in reducing the active concentration
of the target chemical. The region can be a solution. Partitioning can
result from differences in physicochemical properties between the
bioparticle and the target chemical and/or from adsorption of the target
chemical on a surface of the bioparticle.
A method for removal of at least one target chemical from a region
includes the steps of adding a nanoparticle size bioparticle having at
least enzyme incorporated therein to the region and biotransforming at
least a portion of the target chemical into at least one substantially
inactive metabolite. The region can be a solution. The enzyme can
preferably be a genetically cloned enzyme.
A method for removal of at least one target chemical from a region
includes the steps of adding a bioparticle having at least one enzyme
incorporated therein and partitioning at least a portion of the at least
one target chemical into or onto the bioparticle. The method results in a
portion of the target chemicals being transformed into at least one
substantially inactive metabolite. The region can be a solution. The
bioparticle can be a nanoparticle. In one embodiment, the nanoparticle can
include a silica nanotube having an alkyl compound attached to the silica
nanotube. The bioparticle can have a size from approximately 1 to 100 nm
or preferably from approximately 1 to 5 nm. Enzymes can include
genetically cloned enzymes.
A method for treating a patient exposed to a toxic drug includes the steps
of providing a plurality of nanosized bioparticles capable of mitigating
the effects of the toxic drug through at least one mechanism selected from
the group consisting of partitioning the toxic drug into or onto the
bioparticle and transforming the toxic drug into at least one
substantially inactive metabolite, and introducing the plurality of
bioparticles and then introduced into the patient. This method can also be
applied to animals in the practice of veterinary medicine.
A composition for detoxification includes a plurality of nanoparticles.
The nanoparticles have at least one surface adapted for toxic drug
attachment. The nanoparticles are selected from the group consisting of
microemulsions with nanoscale oil cores having soft surface films,
hydrophobic cores having porous or soft shells and hard surfaces for
selective binding of toxins. The nanoparticles can include attached
enzymes for chemically degrading toxins. Preferably, the attached enzymes
include genetically cloned enzymes.
Bioparticles have been discovered which provide effective and generally
complementary mechanisms for reducing the free concentration and
biological effects of a broad range of toxins including drugs. Recent
advances in particle science engineering combined with developing
molecular medicine have been found to provide highly effective therapeutic
strategies aimed at effectively treating a wide variety of toxic
poisonings, including drug poisonings. Previously, applications for
particle technology were limited by the size of available particles. For
example, particles available for use had been too large to be effectively
used with living organisms.
With a reduction in size of available particles to less than 100 nm, or
even as small as typical molecular dimensions (1-5 nm), the invention has
created bioparticles having nanoparticle sizes which are small enough to
effectively interact with living organisms. It is noted that molecules may
be less than 1 nm in diameter or larger than 5 nm in diameter. For
example, proteins which are polymers or macromolecules can be 5 nm or
larger in diameter. As used herein, the term nanoparticles refer to
particles having sizes less than approximately 100 nm. These bioparticles
can act to bind with targeted drugs and other toxic substances and/or to
quickly degrade these drugs and toxins into largely inactive reaction
products. The invention can have valuable applications for a wide variety
of uses such as drug detoxification (e.g., drug overdose), military (e.g.,
toxic warfare agents), industrial (e.g., manufacturing processes),
environmental (chemical spill clean up), as well as many other purposes.
Drug poisonings may be treated by bioparticles which can use any or all of
the following mechanisms:
1) partitioning a targeted drug onto the bioparticles by exploiting
differences in physicochemical properties and/or using molecular
templating to adsorb the drug onto functionalized surfaces of bioparticles;
2) biotransforming a targeted drug into an inactive metabolite(s). For
example, an enzyme, such as a human purified and genetically cloned high
activity enzyme, may be incorporated into a bioparticle to provide
biotransformation effects on a targeted drug or toxin, or
3) preferably, providing a bioparticle which combines both approaches (1)
and (2).
These above methods are not limited to oral or intravenous use, but could
also be employed to remove toxins from biological surfaces such as skin or
non-biological surfaces such as metal, wood or plastic. Moreover, the
above methods can be used to detoxify a broad range of toxins.
The invention allows the synthesis of bioparticles that can directly
reduce the free drug concentration in the blood, either by exclusively
partitioning it inside the bioparticle, or more preferably, by
partitioning and biotransforming the drug into an inactive metabolite
within the bioparticle and ultimately promoting excretion from the body.
With this approach, the principles of lipid partitioning and/or adsorption
(via molecular templating) may act in a highly synergistic manner with
those of biotransformation to provide drug detoxification systems with
complementary detoxification mechanisms to provide added effectiveness.
Thus, by providing a very high local concentration of toxic drug
(substrate), partitioning and/or adsorption can dramatically increase the
rate of enzymatic degradation depending upon the KM of the enzyme and its
enzymatic efficiency in the bioparticle.
Nanoparticles (such as those shown in FIG. 1) have been created for
treating a broad range of toxins. For example, "soft particles" such as
microemulsions with nanoscale oil cores and "soft/hard" particles with
hydrophobic cores for lipophilic drugs and various shells each permit
relatively selective drug penetration. "Templated particles" allow for
toxins to be selectively fitted into pores in their surface generally with
1 or 2 point binding of the toxin to the nanoparticle. The above
nanoparticle types can preferably also include an attached enzyme for even
more rapid degradation of the target drug and/or toxin.
Soft/hard particles are ones consisting of a core composed of a liquid or
a (softer) polymeric organic material surrounded by or encapsulated in a
shell composed of an inorganic or (harder) polymeric organic material. The
example of a liquid encapsulated in a shell of metal oxide or metal
carbonate can be prepared by making a solution of the metal oxide
precursor in an oil and exposing droplets of the solution to water or
carbonate ion, respectively. This could be accomplished in aerosol or
microemulsion apparatus. The example of a liquid encapsulated in a shell
of organic polymer can be prepared by making a microemulsion stabilized by
surfactant having reactive vinyl functionality, followed by initiating
polymerization of the surfactant molecules around the surface of
individual oil droplets in the system. The example of a (soft) polymeric
organic core encapsulated in a (hard) polymeric shell can be prepared by
dispersing a polymer gel in a solution of organic monomer precursor to a
highly crosslinked or crystalline polymer, followed by initiation of
polymerization of the dissolved monomer.
Templated particles are ones consisting of material, either as the core or
shell component, that incorporates molecularly-sized and shaped pores into
its structure. These materials can be prepared by including in the
synthesis mixture suitably derivatized molecules or mimics (the templates)
of the chemicals (in this application the toxins) of interest to be
captured by the bioparticles. After the particles are formed and
collected, the templating species are removed from the particles by
dialysis or pyrolysis, leaving the desired pores as selective sites in
which toxic molecules to be removed can be trapped. Examples are various
metal oxides or solid organic polymers that have pores templated for
neural amines, aromatic compounds or terpenes.
A shell containing pores can provide significant improve the effectiveness
of nanoparticle-mediated drug detoxification. There are a number of
potential design benefits of encapsulating either a hydrophilic or a
hydrophobic environment with a solid shell containing nanopores. First, it
could act to stabilize a nanoemulsion injected into the blood to prevent a
dilutional effect on emulsion function. Second, it could act as a highly
selective molecular filter by allowing only molecules of certain physical
dimensions access to the bioparticle interior. Therefore, bioparticles
could be targeted against at toxic molecules with molecular weights (MWs)
at or below the selected cutoff points of molecular size. Third, by
"trapping" locally high concentrations of coenzymes and cofactors
important to CYP activity such as oxidoreductase (MW=75,000) and
cytochrome b5 (MW=17,500) within the bioparticle interior and preventing
their escape, a bioparticle with a shell incorporating nanopores would
potentially enhance (or at least help preserve) optimal P450 enzymatic
The reconstitution of P450 enzymes, especially the CYP 3A4 fraction, may
be technically challenging with regards to preserving its catalytic
activity, especially in blood. Inclusion of a shell can greatly aid this
process. Fourth, a bioparticle shell with nanopores could prevent
proteolytic degradation of CYP fractions while in the blood (i.e., armor
the enzymes). It will allow ingress of smaller sized toxic drug molecules
and easy egress of more water-soluble metabolites, but exclude those
molecules greater than the pore size cutoff. In contrast, CYP fractions
incorporated into soft bioparticles may not only be susceptible to
degradation in blood, but their local concentrations of cofactors and
coenzymes may not be preserved (see the second point given above). Fifth,
a solid shell with nanopores could be designed to provide a biodegradable
platform where the functional activity of the bioparticle is determined by
the blood half-life of biodegradable shell. That is, once the job of
biotransformation is complete, the biodegradable particle can slowly
disintegrate and releases the CYP fractions into the blood where they are
degraded. Sixth, design of the shell and its surface characteristics
(e.g., ionicity, lipophilicity) may be critical to prevent (or minimize)
uptake into RBCs or the reticuloendothelial system (RES), or eliminate the
risk of hemolysis. The goal of bioparticle design is to keep the
bioparticles within the vascular compartment. Seventh, if the shell of the
nanobioparticle is sized small enough to be directly excreted via the
kidney, it may be possible to directly sequester a highly lipophilic drug
within the bioparticle via partitioning and/or adsorption, or to attach it
to even smaller sized nanoparticles by adsorption onto its surface.
In a manner similar to what is observed clinically when the Fab antibody
Digibind.RTM. is used to treat digoxin toxicity, if the size of the "nanoparticulobody"
(a bioparticle acting functionally like an antibody) is less than a
50,000-60,000 MW molecule, it may be directly excreted from the body by
the kidneys, particularly if its surface has a neutral or positive charge.
Using molecular templating, highly selective adsorption of various
molecules (and members among their chemical class) can be achieved. In
this scenario, the P450 element of the bioparticle would not be needed. In
essence, the nanoparticle is accomplishing Phase I and II
biotransformation without the actual need for enzyme modification. That
is, it renders the toxic drug molecule more polar by complexing it to a
nanoparticle, which in turn allows excretion from the body. This type of
adsorption would be highly selective and would most likely be applicable
only to those molecules (or class of drugs sharing a common chemical
moiety) it was originally designed for. In contrast, if a lipid
partitioning system could be incorporated into a bioparticle, while
keeping its size less than 50-60 kDa, it would be useful for most
lipophilic drugs.
One approach for preparing such nanoparticles entails using the
template-synthesis method. In this method, the pores in a microporous
membrane or other solid are used as templates to prepare the nanoparticle.
The membranes employed contain cylindrical pores with monodisperse
diameters. The pore diameter can be controlled at will over a range from
iess than 1 nm to as large as tens of micrometers. A correspondingly large
range of nanoparticle sizes can be prepared. The template method is very
versatile. It has been used to prepare nanoparticles composed of metals,
semiconductors, other inorganic materials, carbons, etc. Nearly any method
used to prepare bulk materials can be adapted to allow for synthesis of
nanoparticles within the pores of a microporous template membrane.
Significantly, a hollow tubular nanostructures can be obtained.
Membranes that have been used to prepare nanoparticles via the template
method are shown in FIG. 3. These are microporous aluminas prepared
electrochemically from aluminum metal. The upper set of micrographs shows
an in-house prepared membrane of this type. In this case the pores are
approximately 60 nm in diameter. The lower micrograph in FIG. 3 shows a
commercially-available membrane of this type. In this case the pores are
200 nm in diameter. These micrographs illustrate the important point
discussed above that the pore diameter in such membranes (and
correspondingly the diameter of the nanoparticle obtained) can be
controlled at will. For these microporous alumina template membranes, the
pore diameter is varied by varying the potential used during the
electrochemical formation of the membrane.
Toxins can be adsorbed onto specialized nanoparticles to achieve drug
detoxification. Nanoemulsions have been synthesized for acutely reducing
the free concentration of potentially toxic molecules. FIG. 2 shows the
effect of Pluronic.RTM. L-44 Micelles and microemulsions in reducing the
concentration of the drug amitriptyline. A micelle may be defined as a
colloidal aggregate of amphipathic (surfactant) molecules, which occurs at
a well-defined concentration known as the critical micelle concentration.
The typical number of aggregated molecules in a micelle (aggregation
number) is from approximately 50 to 100.
Poloxamer, or Pluronic.RTM. gels are made from selected forms of
polyoxyethylene-polyoxypropylene copolymers in concentrations ranging from
15 to 50 weight %. Poloxamers generally are white, waxy, free-flowing
granules that are practically odorless and tasteless. Aqueous solutions of
poloxamers are stable in the presence of acids, alkalis and metal ions.
Commonly used poloxamers include the 124 (L-44 grade) used above as well
as 188 (F-68 grade), 237 (F-87 grade), 338 (F-108 grade) and 407 (F-127
grade) types, which are freely soluble in water. The trade name "Pluronic.RTM."
is used in the US by BASF Corp., of Mount Olive, N.J., for pharmaceutical
and industrial grade poloxamers.
In the example shown in FIG. 2, a nanoemulsion was produced using
Pluronic.RTM. L-44 (micelles) with or without addition of ethylbutyrate
ester. Ethylbutyrate ester was added at a low (ME-I) and high (ME-II)
concentration. As seen in FIG. 2, the emulsion effectively sequestered
significant quantities of amitriptyline, a tricyclic antidepressant agent
with potential cardiotoxic effects, when compared to the saline control
shown. The system labeled "Micelles" did not possess the oil core of
ethylbutyrate ester which was possessed by both ME-1 and ME-II. By
comparing the Micelles system to ME-1 and ME-2, it can be seen that the
oil core significantly increased the amount of amitripyline adsorbed, the
higher oil concentration (ME-II) adsorbing significantly more amitripyline
than the lower oil concentration (ME-I). Drugs that may be amenable to
this type of detoxification are not limited to tricyclic antidepressant
agents such as amitriptyline, but may include drugs and toxins from all
drug classes that have an affinity for, tend to combine with, or are
capable of dissolving in lipids (lipophilic drugs).
Many types of oils, surfactants, and cosurfactants may be used to produce
bioparticles based on nanoemulsion technology. The bioparticle composition
can be varied depending on the goal of the therapy and the specific
properties of the target toxin. For example, a particle system prepared
for intravenous use would, be preferably varied in composition compared to
a similar system prepared for skin or metal decontamination.
Another type of bioparticle that can be used to detoxify drugs can be
prepared using the template-synthesis method. Template-synthesized
nanoparticles can be either hollow nanotubules or solid nanoparticles and
they can remove the toxic substance by either adsorption on their surfaces
or extraction into the hollow part of the nanotubule. Such
template-synthesized nanoparticles can be composed of a wide variety of
materials including metals, polymers. semiconductors, other inorganic
materials, carbons, etc. The size of these nanoparticles (both the
diameter and the length) can be controlled at will from the nm regime to
the micrometer regime.
One embodiment of this technology is to use the template method to prepare
hollow cylindrical silica nanoparticles. These nanoparticles are
preferably prepared by using sol-gel template synthesis of silica within
the pores of a microporous alumina template membrane. The silica tubules
in this case were prepared using tetraethylorthosilicate as the starting
material; however, other precursors are available for preparing silica via
the sol-gel method. Sol-gel silica nanotubules of this type have been
prepared in the pores of various microporous alumina template of the type
shown in FIG. 3. It has been shown that both the inside and outside
diameters and the length of the silica nanostructures can be controlled by
varying the diameter of the pores and the thickness of the template used.
The tubular silica nanostructures prepared in this way can be derivatized
both on their outside and inside surfaces with chemical and/or biochemical
reagents. One approach for doing this is to use well-known silane
chemistry. Hundreds of silanes are available commercially, so this is a
very versatile route for chemically and biochemically derivatizing these
silica nanostructures. This is important because such derivatization
allows these nanotubules to extract or adsorb specific chemical reagents
and allows them to catalyze specific biochemical reactions. In addition
because the inside and outside of the tubules can be derivatized with
different reagents, the inside and outside chemistry/biochemistry can be
different. This is important because, for example, it might be desirable
to have the interior of the nanotubules hydrophobic so that they will
extract specific molecules but the outside hydrophilic so that the
nanotubules can be dispersed in an aqueous-based medium (e.g. blood).
Two embodiments of this concept are discussed herein. The first embodiment
derivatizes the inside surfaces of the silica nanocylinders with a
hydrophobic 18 carbon alkyl silane. In this case the outside surface is
left underivatized so that the outside surface retains the hydrophilic
character of silica. The second case entails derivatizing both the inside
and outside surfaces with trimethoxybutyl aldehyde to introduce the
aldehyde functionality to the surfaces. This aldehyde functionality can
then be reacted with terminal amino sites on a protein molecule to
covalently attach the protein to the nanotubules. Attachment of the
protein glucose oxidase (GOD) can be performed in this way. Many other
proteins have been attached using this general method. Accordingly, it is
a versatile way to attach proteins to the surfaces of these nanotubules.
Scanning electron micrographs of an alumina template membrane having a
plurality of open pores which can be filled with silica nanotubes are
shown in FIGS. 3(a)-3(c). FIG. 3(a) shows a surface image of an alumina
template membrane demonstrating a high packing density of pores, the pores
having diameters of approximately 60 nm. FIG. 3(b) shows a cross sectional
image of the template membrane shown in FIG. 3(a) while FIG. 3(c) shows a
perspective view of the template membrane. Although 60 nm nominal pore
diameters are shown, pore diameters of the template membrane can be
readily controlled.
In an embodiment of the invention, a long chain alkyl carbon (such as
C.sub.18) is added to silica nanotubes positioned within a template
membrane for the purpose of adsorbing a target molecule. It is noted that
the field of protein and enzyme attachment to particles, otherwise
referred to prolifically in the literature as "enzyme immobilization", is
a mature science, and that the methodologies described in this portion of
the application are similar to ones described earlier but that the
selection of which enzymes used and the overall particle composition is
The 18-carbon alkyl (C.sub.18) silane was chosen because this renders the
insides of the nanotubules hydrophobic. The nanotubules with the C.sub.18
groups inside can then be used to extract hydrophobic molecules from a
contacting solution phase. Again, in this case the outsides of the
nanotubules remain hydrophilic silica and this allows these tubules to be
dispersed into solutions containing polar solvents. The most obvious
example is water, but the same principle applies for other polar solvents.
Obviously, the outside could also be derivatized with the hydrophobic
silane and such tubules could then be dispersed into solutions containing
nonpolar solvents. Other alkyl silanes could be used to tune the
extraction selectivity of the derivatized nanotubules. Examples include
using shorter chain (e.g. C.sub.8) alkyl silanes to make the tubules less
hydrophobic on the inside, using aromatic silanes, using silanes with
specific chemical functionalities (e.g., acidic or basic), etc.
The hydrophobic C.sub.18 silane-containing tubules were used to extract a
hydrophobic target molecule (7,8-benzoqunoline or BQ) from a dilute
aqueous solution. Extraction was accomplished in two ways. In the first
method the hydrophobic nanotubules were left embedded within the pores of
the template membrane, and a piece of the membrane was simply immersed
into and then removed from the solution of the target molecule. Removing
the membrane also accomplished the removal of the target molecule BQ
sequestered inside. In the second method, the nanotubuies were liberated
from the template membrane, by dissolving the membrane in phosphoric acid
solution. The liberated tubules were then collected by filtration. The
tubules were then dispersed into a solution of the target molecule. The
solution was then filtered to remove the tubules as well as the target
molecule BQ sequestered inside.
FIG. 4 (see Original Patent) shows an example of the second method,
dispersion of the liberated nanotubules. This figure shows first the UV
absorption spectrum of a solution that was 1.times.10.sup.-5 M 7,8
benzoquinoline solution (BQ). To this solution was first added silica
nanotubules that did not contain the hydrophobic C.sub.18 silane inside.
(10 mg of tubules added per 100 mL of solution.) The solution was then
filtered to remove these tubules and the solution spectrum was remeasured.
Note that there is essentially no change in the BQ absorbance. This
experiment showed that silica tubules that were hydrophilic on the inside
did not extract the hydrophobic BQ.
An identical quantity of the C.sub.18 derivatized tubules was then added
to the solution. The solution was then filtered to remove the tubules and
the spectrum was remeasured. As indicated by the lower absorbance, these
tubules extracted 82% of the BQ from the solution. FIG. 5 shows analogous
data after addition of a second 10 mg of tubules per 100 mL of solution.
After the second extraction 92% of the BQ was removed from the solution.
In another embodiment of the invention, reactive molecules such as enzymes
can be incorporated into nanoparticles to improve the drug detoxification
ability of the nanoparticles. Although enzymes are described herein,
incorporation of any molecule capable of generating a chemical reaction or
aiding in the rate of a chemical reaction with a target molecule can also
be incorporated in nanoparticles to produce enhanced detoxification
results. This approach detoxifies substances and surfaces by using
nanoparticles as a platform to incorporate molecules such as enzymes for
catalyzing the conversion of toxic substances into inactive substances (or
for generating chemical reactions with toxic substances).
Protein (i.e., enzyme) attachment to SiO.sub.2 nanotubules was achieved
using 2 steps. A tubule wall was functionalized with an aldehyde-terminated
silane. A protein was then coupled to the aldehyde through primary amino
sites on the protein. The enzyme used, glucose oxidase (GOD), was the
first protein tested. GOD effectively catalyzes the oxidation of glucose
to glucono-1,5-lactone. In the presence of glucono-1,5-lactone, electrons
shuttle to O.sub.2, creating hydrogen peroxide. In the presence of
peroxidase (POD), hydrogen peroxide oxidizes o-dianisidine from a
colorless to red form, which then can be assayed by monitoring its
absorbance (See FIG. 6).
For preliminary experiments performed, an intact alumina template membrane
with the SiO.sub.2/GOD nanotubules in the pores was utilized. The
absorbance of a solution of glucose, o-dianisidine and POD immersed in a
"blank membrane" (without nanotube incorporation of GOD) was determined to
establish a baseline absorbance. Al.sub.2O.sub.3/SiO.sub.2/GOD membranes
were then immersed into the glucose solution. The time dependent changes
in the absorbance (concentration) of glucose (assayed indirectly via
oxidation of o-dianisidine) were determined. The results are depicted in
FIG. 6. Based on the absorbance spectra shown, it is apparent that GOD
incorporated into pores of the nanotubules converted much of the glucose
in the solution to glucono-1,5-lactone upon immersion of the membrane (at
approximately 140 seconds). As shown in FIG. 6, at approximately 400
seconds the membrane was removed from the solution. No further oxidation
of glucose is observed because in removing the membrane the GOD
incorporated inside is removed.
The nanotubes are important because they are new morphologies of
particulate material. They are also important, being newly available, for
evaluation and use in biomedical applications either by themselves or
modified as described in this application. However, the nanotube is not
the only shape carrier/core particle that can be derivatized as is
described in this application. Many other shapes are useful, such as
derivatized polyhedral-shaped porous (templated or not) nanoparticles.
Based on this observation, it was concluded that enzymes incorporated into
nanoparticles can be used to degrade drugs. The linkage of enzymes to the
inner surface of pores, can be achieved without losing the enzyme's
reactivity. Although nanotubes having inner cavities for enzyme attachment
was used, any shaped particle, whether tubular or not, having pores
adapted for this purpose can have enzymes inside the pores. Thus, any
nanoparticles having pores, whether the pores are tubular or any other
shape may be used with the invention.
An identical approach (i.e., linking a cytochrome P-450 (CYP) enzyme
system) to the inner surface of a nanoparticle) can also be used to
efficiently reduce the free concentration of lipophilic agents in human
plasma and blood by a biotransformation dominated mechanism.
Analogous experiments have been done with nanotubules that were liberated
from the template membrane, and substantially identical results were
obtained. In this case the GOD was on both the inner and outer surfaces of
the membrane. This is an advantage of the hollow nanotubule approach.
Having available inner and outer surfaces increases the surface area
available for biocatalysis. As before, it might also be advantageous to
separately derivatize the inner and outer surfaces. For example, the inner
surface could be derivatized with a specific dye and the outer surface
could be derivatized with a specific enzyme or other protein. In a second
set of tubules, a second specific dye could be attached to the inside and
a second specific protein to the outside. This could be continued for n
tubules that contain specific dyes and specific proteins on the insides
and outsides. The dye could then be used to identify the tubules. For
example, green tubules could contain protein #1, blue tubules could
contain protein #2, etc. In this way, in a mixture of tubules one could
identify which tubules are catalyzing which biochemical process.
Hollow and solid nanoparticles can also be used for removal of lipophilic
toxins. For example, nanoparticles, whether hollow or solid, having
substantially polyhedral or spherical morphologies can be used for this
purpose. Studies were performed to establish whether the benzene ring
moiety of the prototypical amide local anesthetic, bupivacaine, possessed
sufficient electron enrichment to enable .pi.-.pi. electron bonding to an
electron deficient molecular moiety attached to a solid nanoparticle.
Specifically, when a mimic of bupivacaine was mixed with the
dinitrobenzamide moiety, a number of changes in spectral values occurred.
Specifically, the UV-VIS diffuse shoulder from 280-320 nm moved to a
diffuse shoulder from 340-400 nm.
Complexation of the pi-pi type between bupivacaine and its mimics, and
several electron deficient aromatics, including a dinitrobenzamide
(designed for convenient subsequent attachment to nanoparticles), has been
proven using proton NMR spectrometry. Tables 1 and 2 (see Original Patent)
show the chemical shift values observed for test systems relevant to this
This data is consistent with the ranges published (Dust, 1992) for other
.pi. complexed electron deficient and electron rich benzene rings. Thus,
the dinitrobenzamide moiety can be attached to carrier nanoparticles
during synthesis for use treating local anesthetic detoxification
primarily by .pi.-.pi. complexation which can take place on solid or
soft/hard nanoparticles, and with or without two-point binding or
templated cores or shells.
Further experiments were performed to determine the effectiveness of
various emulsions to reduce the free concentration and toxic effects of
other drugs. As shown in FIGS. 7-9, the cardiotoxic effects of bupivacaine,
a local anesthetic, were significantly reduced using a macroemulsion of
FIG. 7 (see Original Patent) shows a macroemulsion of Intralipid.
Intralipid attenuates bupivacaine-induced sodium current (I.sub.ns) in
guinea pig ventricular myocytes. Panel A shows examples of current traces
in response to depolarization to -20 mV from a holding potential of -100
mV during interventions shown near cach records. Panel B shows the change
in current peaking as a function of time. Horizontal bars above panel B
denote the duration of drug administration. Panel C summarizes the effect
of bupivacaine (5, 10 and 20 .mu.M) and Intralipid (1.5%) on I.sub.ns. All
data was normalized to a control current. Bars represent the mean.+-.SEM
of 5-7 myocytes.
FIG. 8 (see Original Patent)shows concentration-dependent in vitro
attenuation of bupivacaine (1 .mu.M). Bupivacaine induces QRS prolongation
in guinea pig isolated hearts, paced at 200 beats per minute (BPM) as
shown in FIG. 8. FIG. 8 shows the mean.+-.SEM of 4 experiments (P<0.05).
As shown in FIG. 8, increasing Intralipid concentations reduce QRS
prolongation caused by bupivacaine 1%.
FIG. 9 (see Original Patent) shows the attenuation of in-vivo cardiotoxic
effects of bupivacaine in isofluanc-anesthetized rates. Specifically, the
effect of an IV bolus of bupivacaine (8 mg/kg over 10 scc) on the QRS
interval is shown. Compared to time matched controls, Intralipid (3
ml/kg/min over 2 min) more rapidly attenuated bupivacaine induced
prolongation of the QRS interval. Two additional experiments were also
carried out, both yielding similar results.
Therefore, compared to available methods, bioparticles which may be
produced using the invention have numerous advantages over current methods
for treating drug toxicity. Advantages from the invention are enhanced
through use of complementary approaches including lipid partitioning,
adsorption and xenobiotic biotransformation.
Bioparticles using lipid partitioning and/or drug biotransformation
produced using the invention not only scavenge most toxic drugs that are
more lipophilic (active drug state normally) but also offer broader
substrate usage. For example, various soft bioparticles can effectively
reduce the free blood concentration of all virtually lipophilic drugs.
Moreover, appropriately chosen enzymes incorporated into bioparticles can
further improve the bioparticle's therapeutic performance and
applicability by adding metabolization effects applicable to a broad range
of drugs. If desired, the feature of chemical selectivity inherent in
immunotoxicotherapy can be incorporated into bioparticles by using the
processes of molecular templating and/or adsorption onto functionalized
Using bioparticles, large lipid-water partition coefficients for highly
lipid soluble substances such as amiodarone indicate that the free
concentration of this antiarrhythmic agent can be effectively reduced by
using a concentration of soft bioparticles in the bloodstream that should
not be detrimental to cell function (approximately 1.5% maximum). A
bioparticle having a large lipid-water partition coefficient (e.g.
10,000), where the lipid component of the bioparticle is either liquid
solid core, or lipophilic molecular entities attached to the surface of an
inorganic core can bind a large fraction of highly lipophilic drugs. Thus,
a drug's free blood concentration can be effectively reduced in a small
volume of soft bioparticles.
In a preferred embodiment of the invention, bioparticles containing P450
cytochrome components such as a CYP 3A4 fraction are used to not only
offer broad substrate detoxification, but also to produce rapid
elimination of toxins from the blood. CYP3A4 and CYP2D6 hepatic microsomal
fractions of the P450 system can biotransform approximately 55% and 25%,
respectively, of virtually all xenobiotics [Benet L Z, Kroetz D L and
Sheiner L B, Pharmacokinetics in Goodman and Gilman's, Pharmacological
Basis of Therapeutics (1996) eds Hardman JG and Limbird LE, 9th Edition,
McGraw Hill, pp 3-27.] Cytochrome results in an enhanced drug elimination
rate by either increasing the quantity or quality of enzyme (e.g.,
selecting high activity enzyme systems using genetic polymorphisms or
molecular cloning) and/or optimizing the environment of the enzyme
(substrate concentration, cofactor levels, hydrophilicity for optimal
enzyme functioning).
Bioparticles can provide partitioning and a biotransformation to take
advantage of the potential synergistic actions which can result from
initially partitioning a drug at high local concentrations in an
environment containing high concentrations of an enzyme. This synergy can
dramatically increase the efficiency of the substrate degradation if the
toxic drug concentration occurs well below the KM value.
For example, partitioning a toxic drug from the bloodstream into the lipid
environment of a bioparticle containing a genetically engineered P450
enzyme designed for super high efficiency (e.g., supersomes) should not
only effectively and promptly reduce the free blood concentration of
xenobiotics in the blood but also concentrate the toxic drug in an area
adjacent to the active enzyme. This can promote extremely efficient
catalysis and degradation of target molecules.
The beneficial effects of bioparticles formed using the invention are
expected to be greatly enhanced by concentrating a large enzyme mass, such
as genetically engineering P450 fractions selected for super high activity
within the biocompatible particle. Preferably, the bioparticle should have
a large internal surface area whose efficiency of catalyzing its substrate
to its metabolite is marked augmented by the concentrating effect of the
soft bioparticle component (e.g., exposes the enzyme to a high
concentration of its substrate). In addition to its substrate
concentrating effect, another advantage gained by incorporating a lipid
matrix within the bioparticle is that this structure may dramatically
increase the intrinsic biocatalytic efficiency of an enzyme.
Salt-immobilized hydrolytic and co-factor requiring enzymes (lyophilizates
of enzyme in a salt matrix) in organic solvents have been shown to have
100-3000 times more activity than that observed in aqueous mediums (U.S.
Pat. No. 5,449,613 to Dordick, et al.). This technology applied to CYP
fractions located within bioparticles can produce extremely efficient
biocatalytical tools for drug detoxification, particularly when preferred
high efficiently molecular cloned supersomes are used.
Numerous products can be produced from the invention including those
composed of multiple types of nanoparticles for in-vivo detoxification of
drugs and toxins from humans or animals. For example, nanoparticles can be
synthesized for attenuating acute cardiotoxic effects of tricyclic
antidepressant drugs (e.g., amitriptyline). However, the invention is not
limited only to tricyclic antidepressants, but encompasses all drug
classes that may cause toxicity. In addition, biological toxins (e.g.,
snake and insect envenomation) may also be detoxified using the invention.
This can ensure human and animal safety and welfare. Furthermore,
endogenous toxins produced during organ dysfunction or failure (e.g.,
hepatic or renal failure) may also be removable using the invention to
create "circulating hepatocytes" or "circulation nephons."
Another potential product which can be produced from the invention is a
product for detoxification of poison warfare agents that are used for
military purposes (e.g., nerve gas). It is noted that warfare agents may
be solids, liquids or gases. Warfare agents can cause massive
intoxification of substances such as acetylcholine or tissue necrosis from
direct toxicity (e.g., mustard gases). Rapid and simultaneous removal of
both the warfare agent and molecules causing injury may prove to be
effective therapy to mitigate the dangers of these weapons of mass
destruction. For example, bioparticles produced using the invention could
be used intravenously to reduce the concentration of both the toxin (e.g.,
sarin) and acetylcholine. Alternatively, the invention can be used for
skin or metal decontamination for other types of toxic warfare agents such
as mustard gas.
Claim 1 of 13 Claims
1. A method comprising: contacting a
toxic compound with a particle comprising a hollow tube open at least at
one end, the hollow tube comprising a polymer or silica, an enzyme and a
hydrophobic compound that partitions the toxic compound to produce a high
local concentration of the toxic compound in contact with the enzyme,
wherein the hydrophobic compound and the enzyme are attached to a surface
of the hollow tube, whereby the enzyme transforms the toxic compound into
a substantially inactive compound.
If you want to learn more
about this patent, please go directly to the U.S.
Patent and Trademark Office Web site to access the full


text:
Swordfish with Roasted Vegetables
From Good Housekeeping
triple-tested at the Good Housekeeping Research Institute
Roasting vegetables is the "no-fuss" way to cook them and an appetizing way to get vitamins and fiber. Use two pans for roasting the eggplant, peppers, and potatoes -- if you crowd them all into one pan, they may "steam" instead of roast.
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Nutritional Information
(per serving)
|Total Fat
|Saturated Fat
|Total Carbohydrate
|Dietary Fiber
Serves: 6
Total Time: 1 hr
Oven Temp: 425
|Conversion chart
- 3 large limes
- 1 tablespoon(s) brown sugar
- 2 tablespoon(s) soy sauce
- 2 tablespoon(s) gingerroot, grated and peeled
- 2 (about 2 pounds) swordfish steaks, each 1 inch thick
- 8 clove(s) garlic
- 3 large red peppers
- 2 large yellow peppers
- 6 (about 1 1/4 pounds) medium-size red potatoes
- 1 (about 1 1/2 pounds) medium-size eggplant
- 1 teaspoon(s) salt
- 1/2 teaspoon(s) dried thyme leaves
- 1/4 ground black pepper
- 1 tablespoon(s) olive oil, substitute salad oil
- fresh thyme sprigs (optional)
- Squeeze enough juice from limes to equal 2 tablespoons juice; slice remaining limes into thin slices.
- In 11-inch by 7-inch glass baking dish, mix lime juice, brown sugar, soy sauce, and ginger. Add swordfish, turning to coat both sides. Set aside.
- While swordfish is marinating, preheat oven to 425 degrees F. Leave skin on garlic cloves. Cut red and yellow peppers into bite-size pieces; cut each potato in half; cut eggplant into 3-inch by 1-inch strips.
- In large bowl, mix salt, thyme, black pepper, and 1/4 cup olive or salad oil. Add garlic, red and yellow peppers, potatoes, eggplant strips, half of lime slices, and a few sprigs of fresh thyme; toss to coat well.
- Spoon half of vegetables into 17-inch by 11 1/2-inch roasting pan and remaining vegetables into 15 1/2-inch by 10 1/2-inch jelly-roll pan. Place pans in oven on 2 racks, and roast, switching pans halfway through cooking and stirring vegetables occasionally, until potatoes are fork-tender, about 30 minutes.
- After vegetables have roasted 20 minutes, cook swordfish: In nonstick 12-inch skillet over medium-high heat, in 1 tablespoon hot olive or salad oil, cook swordfish until it just loses its pink color throughout, about 10 minutes, turning fish once. (Or, when vegetables are done, broil swordfish in oven at closest position to source of heat, about 10 minutes.)
- To serve, arrange vegetables on large platter. Cut swordfish into 3-inch by 1-inch strips and tuck swordfish among vegetables. Garnish with remaining lime slices and fresh thyme.
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The long-sought dream of using lasers to defend against an enemy on a battlefield may be closer to realization, if recent tests in the New Mexico desert can be transitioned successfully into a tactical system. The U.S. Army is aiming to begin development next year of a prototype that would be ready in 2007 to defend against targets ranging from cruise missiles to incoming artillery shells.
The command in charge of the U.S. Army's information systems is refocusing the way it provides services to its 1.3 million users. For the first time, Army personnel will receive a negotiated level of support that is based on service-level objectives and performance indicators. This effort, information managers say, will lead to measurable improvements in the quality of information processes the Army uses in its missions. In addition, this new service-level management process is scalable to the entire Army, they warrant.
The future infantry soldier, who already is looking at new personal armor and communications systems, also may be equipped with a multisensor system that can provide him with a range of spectral views that can be changed with the flip of a switch. Helmet-mounted sensors would comprise both infrared and image intensifiers, and rifle sights would provide multispectral capability. Information gleaned from these sensors would fuel network-centric operations.
The U.S. Coast Guard is undertaking a massive upgrade of its command and control with an eye toward improving situational awareness. Digitized information will alleviate some of the tasks currently performed manually by crew members actively engaged in operations at sea, and it also will provide a clearer picture of both missions and options.
The U.S. Defense Department is bringing its expertise on the battlefield to the home front. Under the direction of an organization that was chartered less than eight months ago, the department is taking aim at those who would do the nation harm, assisting law enforcement and federal agencies with technical capabilities and proficiency in tactics, techniques and procedures. Although this is not a new mission for the military, it is an indication of the department's resolve to win the war against terrorism.
Military leaders are developing a vision of the tactical operations future where adversaries will have to decide if they should send flesh and blood troops to fight nuts, bolts, circuits and sensors. The implications of this battlefield revolution are far-reaching, and initial technical capabilities exist today. Military experts agree that it is only a matter of time before nations send sophisticated machines to augment well-trained troops. They also assert that it is in the United States' best interest to be the leader in this inevitable transformation of combat.
Effectively standing watch over 3.5 million square miles of ocean area and 98,000 miles of coastline calls for careful planning, and the U.S. Coast Guard is taking a layered approach to carrying out this mission. Ever-expanding homeland security demands have prompted the sentinel of the seas to create maritime domain awareness plans that extend from international to local borders and from industry to the federal government. Assessing, addressing and reducing risk is at the core of the strategy.
The changing composition of the semiconductor industry, combined with foreign government action that has leveraged market forces, has resulted in the shift of chip manufacturing from the United States to offshore locations, particularly China and East Asia. This migration has substantial national security ramifications, as the transformation of this nation's military into a network-centric force requires high-end semiconductor chips to provide the processing power for numerous defense applications.
In the near future, U.S. Army units will benefit from high-speed, high-capacity data networks that will connect every unit, from individual infantrymen to headquarters units. However, to realize this vision, hurdles such as managing mobile ad hoc networks and providing beyond-line-of-sight communications in a fluid combat environment must be addressed.
A major U.S. Defense Department research program is developing lightweight, miniaturized, low-power radios for dismounted infantry and support equipment. The program, which is part of an initiative to replace the current generation of military radios, has drawn competing design teams from across the defense industry.
Interoperability is a key issue in the move toward advanced software definable radio systems. Lessons learned from operation Desert Storm indicated a need for greater communications between the services during combat, necessitating the development of radios sharing common waveforms usable by all the services and that can be rapidly reprogrammed in the field.


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Creata's Play Search market research facility is ready to welcome your participants in a warm, modern, and kid-friendly environment.Read more about Creata Play Search »
"Top Rated by Impulse" marketing research support services organization providing face-to-face and online qualitative research expertise.Read more about National Data Research, Inc. »
Full-service custom qualitative & quantitative consumer product research, with facilities in Chi, LA, NY and Dallas, and a staff of 275.Read more about P&K Research »
Luxurious focus group facilities conveniently located only minutes from O'Hare. Magnificent three-room client suites, fully equipped test kitchens.Read more about Plaza Research-Chicago »
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Located in Chicago's West Loop, R5 Research is designed to provide key qualitative results for creative methodologies in a chic, versatile space.Read more about R5 Research »
New Facility on 26th floor. High quality recruitment for any methodology. We embrace the most challenging projects and hard-to-reach respondents.Read more about Schlesinger Associates Chicago »
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text: Cheese is one of the foods we miss the most after being in the backcountry for a few days, so we were happy to find this shelf stable cheddar cheese. Despite being shelf stable this cheese slices and tastes like a nice cheddar. Enjoy sliced with salami, melt into pasta, stir into refried beans or eat all on its own!


text:
How do people with vision disabilities use computers? How can you make your documents suitable for them? This lesson covers how computers are used by people with vision disabilities and what you can do to make your documents accessible for people who are blind, have low vision, or are color blind. Some of the areas we will look at are adding text descriptions to images, hyperlinks, font size, and color settings.
The first part of this lesson covers people who are blind, then the lesson moves on to other vision disabilities. To continue reading this lesson on your own, click the Next button.


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(Go to Listing by Title)
Abbott, E.A.Flatland:A Romance of Many Dimensions. Alley, R.B.The Two-Mile Time Machine:Ice Cores, Abrupt Climate Change, and Our Future. Zimmer, C.T. rex and the Crater of Doom. Ball, P.Designing the Molecular World:Chemistry at the Frontier. Bonner, J.T.The Evolution of Culture in Animals. Changeux, J.; Garey, L., trans.Neuronal Man:The Biology of Mind. Colinvaux, P.A.Why Big Fierce Animals Are Rare:An Ecologist's Perspective. de Waal, F.; Macedo, S. and Ober, J., eds.Primates and Philosophers:How Morality Evolved. Diacu, F. and Holmes, P.Celestial Encounters:The Origins of Chaos and Stability. Duhem, P.M.M.; Wiener, P.P., trans.The Aim and Structure of Physical Theory. Eigen, M. and Winkler, R.; Kimber, R.B. and Kimber, R., trans.Laws of the Game:How the Principles of Nature Govern Chance. Greene, B.The Meaning of Relativity:Including the Relativistic Theory of the Non-Symmetric Field (Fifth Edition). Eldredge, N.The Miner's Canary:Unraveling the Mysteries of Extinction. Emmeche, C.; Sampson, S., trans.The Garden in the Machine:The Emerging Science of Artificial Life. Feynman, R.P.QED:The Strange Theory of Light and Matter. Golomb, S.W.Polyominoes:Puzzles, Patterns, Problems, and Packings. Goodwin, B.How the Leopard Changed Its Spots:The Evolution of Complexity. Gordon, J.The New Science of Strong Materials or Why You Don't Fall through the Floor. Gregory, R.L.Eye and Brain:The Psychology of Seeing (Fifth edition). Hadamard, J.The Mathematician's Mind:The Psychology of Invention in the Mathematical Field. Haldane, J.B.The Causes of Evolution. Havil, J.Gamma:Exploring Euler's Constant. Hawking, S. and Penrose, R.The Nature of Space and Time. Heisenberg, W.Encounters with Einstein:And Other Essays on People, Places, and Particles. Holmes, P. and Diacu, F.Celestial Encounters:The Origins of Chaos and Stability. Jacob, F.; Spillmann, B.E., trans.The Logic of Life:A History of Heredity. Kirshner, R.P.The Extravagant Universe:Exploding Stars, Dark Energy, and the Accelerating Cosmos. Knoll, A.H.Life on a Young Planet:The First Three Billion Years of Evolution on Earth. Lauwerier, H.; Gill-Hoffstadt, S., trans.Fractals:Endlessly Repeated Geometrical Figures. Maor, E.e: The Story of a Number. Maor, E.The Pythagorean Theorem:A 4,000-Year History (PSL Edition). Maor, E.Trigonometric Delights. Marschall, L.The Supernova Story. Nahin, P.J.An Imaginary Tale:The Story of i [the square root of minus one] (Princeton Library Science Edition). Napier, J.; Tuttle, R.H., ed.Hands. Penrose, R. and Hawking, S.The Nature of Space and Time. Polkinghorne, J.C.The Quantum World. Polya, G.How to Solve It:A New Aspect of Mathematical Method. Rademacher, H. and Toeplitz, O.The Enjoyment of Math. Rossotti, H.Colour:Why the World Isn't Grey. Rucker, R.Infinity and the Mind:The Science and Philosophy of the Infinite. Ruddiman, W.F.Plows, Plagues, and Petroleum:How Humans Took Control of Climate. Ruelle, D.Chance and Chaos. Toeplitz, O. and Rademacher, H.The Enjoyment of Math. Vermeij, G.J.A Natural History of Shells. Weyl, H.Symmetry. Williams, G.C.Adaptation and Natural Selection:A Critique of Some Current Evolutionary Thought. Wilson, R.Four Colors Suffice:How the Map Problem Was Solved. Winkler, R. and Eigen, M.; Kimber, R.B. and Kimber, R., trans.Laws of the Game:How the Principles of Nature Govern Chance. Zee, A.Fearful Symmetry:The Search for Beauty in Modern Physics.
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Common simple phobias are those involving animals or insects, a fear of high places, a fear of lightning, a fear of flying, or other fears. These are very common in young children, and do not represent an abnormality.
Mercy Medical Clinton | 1410 N. Fourth Street Clinton, Iowa 52732 | 563-244-5555


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Gary Fry back playing ... at 47 years of age
Category: Sport Published Date
Gary Fry first played senior football at 14, yes, 14. Against grown men. And back in the day when Darwin football was renowned across the borders for its toughness and unforgiving nature. That was in 1978.
Now 47, Fry can be found running around for Jabiru Bombers, the club founded by his good mate, Garry Lindner.
It was the chance to keep active and join his mate that saw Fry lace up the boots...
More of this story can be read in the Print Edition, or subscribe online now. Receive full access to this article and also a years subscription to the Print Edition.
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Issue 389
Rally call goes out for an Invasion Day protest in Canberra
The multi-award winning National Indigenous Times is an independent newspaper and receives no government funding whatsoever. Thus, we rely entirely on advertising and subscriptions to survive, and hope you'll consider subscribing to NIT's print edition as well as the online version of our paper. Our new and improved website now contains stories and photos, you can even interact by providing feed back on articles in the your say section. We have a new video module where you can watch relevant videos sourced from all over Australia.
There is also the option of advertising online with high impact positions on the various pages and the ability to "click through" to the advertisers website. Our new website is fast and effective and as always if you advertise in the print edition you will be uploaded to our online jobs section as an added bonus. So contact our sales team now via our website or give us a call on 1300 786 611, we will be happy to structure a package that meets your advertising needs and budget.


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Forgot About My Journal For Awhile.Lots To Catch Up On.
Well After Alicias Party We Havn't Spoken At All.Danny And I Have Kinda Drifted Away From Each Other Since The Last Time I Wrote In Here.Partly Because Of The New People Me And Kim Have Started To Hang Around With.They Dont Like Him Really At All And Tend To Put Him Down Alot.Kim And I Stay Out Of It But I Guess He Feels Uncomfortable.Him And Kim Were Seeing Each Other For Awhile But Danny Being Danny Fuked Her Around And That Ended Nearly As Fast As It Started.
She Was Seeing Matt,The Guy From Her Sisters 18th Not Long Before That Happened.Didn't Last Because He Lives So Far Away.Then She Finally Hooked Up With John.John Thinks Hes A Player So He Also Fucked Her Around.Then She Was Seeing Tim.What Can I Say,All Guys Are The Same.
While All This Was Going On With Kim I Was Seeing This Really Nice Guy Matt.He Had A Bad Brake Up With His Last Girlfriend Which He Calms He Still Loves.So Me And Matt Didn't Last Long.Him And His Girlfriend Are Going Back Out But We Have Stayed Really Close Friends.I Still Have Feelings For Him But It Didn't Seem Right To Stay With Someone Who Had Feelings For Another Person.I've Met His Girlfriend,Kylie.Shes A Goth.Really Nice Girl,You Could Say Abit To Nice But I Like Her For What Its Worth.
Tom Has Asked Me Out About 3 Times Now Which Really Spun Me Out.Hes Like My Bestfriend,I Couldn't Being Myself To Go Out With Him.Plus Hes Not My Type.
Amela And Lanie Have Split From The Group,Thankgod.I Love Amela Still Because I Know Shes A Good Person At Heart Although I Dislike What She Has Chosen To Become,Up Tight And Self Centered.
Kim And I Have Had Some Rough Times Recently,Although Everything Seems To Be Going Back To Normal Again.She Was Getting Very Selfish And Controling At One Stage But I Let My Veiws Be Heared And She Woke Up To Herself.
I Hadn't Seen My Dad For About 3 Months Until Today.He Came Around To Pick Up My Little Sister.He Said Hello And Goodbye.Not Much Talking,There Never Really Is.I Dont Have Much To Say To Him.Its My Birthday On Sunday And I Wonder If He Will Remember And Call.He Probably Wont.He Never Calls Unless He Wants To Take Me,Bridie And Jesse Out Because There Is A Family Gathering.A Family Gathering To My Dad Is,Lets Drag My Children Down To Some Bowling Club Down The Road From My Mothers And Pretend Like Were All One Happy Loving Family.Its Depressing Growing Up Knowing That In Your Dads Eyes Your Just For Show.When Iam Forced To Go To Things Like This He Probably Speaks To Me Once The Whole Night.That One Sentance Being "Rhiannon,Smile And Act Happy.Ok?".Though These Days He Dosen't Even Ring To Invite Me To These Family Gatherings.I Think Its Because I've Facial Peircings I'm Not The Eye Candy I Used To Be.
Oh Well,Bridie Is Still 12.He Can Use Her For Awhile Now,Give Me A Rest.
Its Only Been 15 Years.
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For the 13th year in a row, SYLVANIA will sponsor the fall Cup race at NHMS in the form of the SYLVANIA 300. The race will again serve as the second race in the Chase for the Sprint Cup, where it functions as a stepping stone for aspiring champions. The playoff-style NASCAR Chase Grid will feature 16 championship hopefuls in the second race of the Challenger (First) Round of the Chase.
The ticket process is currently in the renewal stage for 2015. Anyone with tickets for the 2014 race will have the opportunity to renew their seats through the extended renewal deadline.
After the deadline, all unsold seats will be released to the public, and fans may call at that time to inquire about changing or acquiring new seats.
Tickets may be renewed by calling Guest Services at (603) 783-4931.
New Hampshire Motor Speedway race fans can rev up their race-day experience by purchasing a pre-race pit pass for Sunday of race weekends.
Pre-race pit passes are $75 per person and include infield admission only (grandstand seating must be purchased separately). Passes for children 14-and-under are $25.
With a pre-race pit pass, fans can experience pit road from a crew member's perspective before the NASCAR Sprint Cup Series races. Fans may roam the pit area in the morning before the race, where they can check out pit boxes and many of the race cars, as well as get a front row view of the pre-race festivities.
The access does not guarantee driver interaction, but many fans have been seen snapping a quick photo or grabbing an autograph from a driver on his way through the infield. It does not give access to the Sprint Cup garage area. Please see the "Pre-Race Pit Pass Policy" for more.
|Gift of Lights
|Sta-Green 200
|New Hampshire 301


text:
A collection of relevant and timely media clips and resources.
Posted on April 13, 2010
The Maryland General Assembly has adjourned for the 2010 session and Maryland's firearm owners were able to defeat three tyrannical gun bills, Senate Bill 516, Senate Bill 645 and House Bill 820, designed to cede more of your Second Amendment rights to vehement anti-gun politicians.
Senate Bill 516, sponsored by State Senator Mike Lenett (D-19), would have designated certain firearms as "assault weapons" and would have prohibited the possession, transfer or receipt of these firearms by law-abiding Maryland residents.
Under his proposed legislation, Maryland would have been forced to adopt policies broader than those imposed under the now defunct Federal Assault Weapons ban of 1994. SB516 would have allowed you to keep any preexisting "assault weapon" as long as you agree to register it with the State Police prior to October 1, 2010. A registration system that could have been used to wrongly target law-abiding citizens that own a firearm similar to one used in a crime.
Facing serious opposition and pressure from gun owners, Senator Lenett chose to withdraw his legislation shortly after introduction.
Senate Bill 645 and House Bill 820 could be considered the most egregious attempt to limit your Second Amendment rights and might be a harbinger of things to come if anti-gun politicians are able to gain further clout in Maryland.
As proposed, SB 645 and HB 820, introduced by State Senator Brian Frosh (D-16) and Delegate Sandy Rosenberg (D-41), would have required anyone wanting to purchase a handgun to possess a "Handgun Permit to Purchase". The permits, which could be denied by the Maryland State Police, would be required before a federally licensed dealer could transfer a handgun to a purchaser. The State Police would have as long as 30 days to review the permit application and applicants would have to pay an unspecified nonrefundable fee and demonstrate "satisfactory" completion of an approved firearm safety course.
Of course, since the legislation didn't repeal Maryland's existing purchase requirements, prospective handgun purchasers would still have to fill out the Maryland State Police purchaser form, pay another $10 fee, wait at least 7 business days and undergo another background check.
After gun owners packed the Committee rooms, the House Judiciary Committee defeated HB 820 and the Senate Judicial Proceedings Committee never brought SB 645 up for a vote.
Advocates of self-defense have good reason to cheer, the Maryland General Assembly passed Senate Bill 411, sponsored by State Senator Mac Middleton (D-28). The bill provides civil immunity from damages when force, including deadly force, is used and reasonable under the circumstances to repel an attack in the person's dwelling or place of business. SB 411 passed the House unanimously, 140-0 and passed the Senate 45-2. The bill now awaits Governor Martin O'Malley (D) for his signature or veto.
Additionally, four bills expanding Sunday hunting have been passed by both chambers and are currently awaiting the Governor's consideration:
House Bill 245- Authorizing a person to hunt turkey in Allegany County and Garrett County on the last Sunday in April and the first Sunday in May, except on Easter Sunday.
House Bill 246- Authorizing a person in Allegany County or Garrett County to hunt for deer on private property with a bow and arrow during open season on the last three Sundays in October and the second Sunday in November.
House Bill 301- Authorizing a person in Calvert County to hunt deer on private property with a bow and arrow during open season on the last three Sundays in October and the second Sunday in November; and authorizing a person in Calvert County and St. Mary's County to hunt deer on private property on the first Sunday of bow hunting season in November and each Sunday during the deer firearms season.
House Bill 851- Authorizing a person in Talbot County to hunt deer on private property with a bow and arrow during open season on the last three Sundays in October and the second Sunday in November.
Please contact Governor O'Malley by phone at 1-800-811-8336 and respectfully urge him to sign SB 411 and the Sunday hunting bills.
Established in 1975, the Institute for Legislative Action (ILA) is the "lobbying" arm of the National Rifle Association of America. ILA is responsible for preserving the right of all law-abiding individuals in the legislative, political, and legal arenas, to purchase, possess and use firearms for legitimate purposes as guaranteed by the Second Amendment to the U.S. Constitution.READ MORE
© 2014 National Rifle Association of America. Institute for Legislative Action. This may be reproduced. It may not be reproduced for commercial purposes.11250 Waples Mill Rd. Fairfax, VA 22030 1800-392-8683(VOTE)