text:
Registration takes less than 1 minute.
Chinese carriers COSCO and China Shipping told the Federal Maritime Commission they are in the beginning stages of a merger, while Bloomberg reported CMA CGM has entered into talks to buy APL parent Neptune Orient Lines.
With a lack of preference cargo, carriers that move international cargo are exiting the U.S. flag; fleet has shrunk from 106 to 78 in past four years.
French ocean carrier CMA CGM and its subsidiary line Delmas will begin purchasing slots on the transpacific CEN loop, on which COSCO and CSCL provide vessels.


text:
Stuffed Loin Roast with Beer Sauce
Source: Pork.org
Sweet brown sugar, fresh herbs, and beer are the backbone of hearty flavors surrounding this lean pork roast.
3 lb top loin pork roast
15 each wheat crackers
0.3333 cup fresh chopped onion
2 tbsp Horseradish, cream
1 1/2 tsp caraway seeds
2 tsp brown sugar
10 tbsp beer
0.6667 cup cold water
1 tbsp cornstarch
0 1/4 oz Bouillon, chicken, sodium free, instant packet
1 tsp Worcestershire sauce
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subset: commoncrawl


text:
Cafe Spiaggia Map
980 N. Michigan Ave. (Oak St.)
312-280-2750 | Make Restaurant Reservations | Menu
The location of Cafe Spiaggia is marked on the map below with a green arrow. Click on it to get directions if you don't see a pop-up. Enjoy your meal at Cafe Spiaggia!
Check out the 2015 edition of GAYOT's Annual Restaurant Issue, which features the Top 40 Restaurants in the US and more.


text:
Find your next commercial space in Tysons Corner
The easiest way to find the right real estate professionals and commercial properties based on your needs. Schedule property tours. Get accurate pricing. Discover unlisted properties.
Tysons Corner, VA Office Space for Rent, Warehouses, and Retail Locations
Useful Links for Tysons Corner:Commercial real estate agents (13) Commercial real estate companies (2) Tenant leasing requirements (2) Lease and sale comps (0)
Showing 1 - 14 of 14 buildings with 23 total listings
8245 Boone Blvd., Tysons Corner, VA 22182
Suites range from 371 square feet to 5,856 square feet.
Tysons Corporate Center consists of approximately 270,000 square feet in two eight-story Class B office buildings in the heart of Tysons Corner....
PS Business Parks
7921 Jones Branch Dr., Tysons Corner, VA 22102
Suites range from 166 square feet to 8,719 square feet.
Westpark Business Campus is an seven building park in the heart of Tysons Corner totaling 751,279 square feet. It is ideally located at the intersection...
PS Business Parks
8206 Leesburg Pike, Tysons Corner, VA 22182
Suites range from 804 square feet to 2,488 square feet.
Sperry Van Ness, as exclusive representative for the Owner, is pleased to present this great office leasing opportunity. Very well maintained...
Sperry Van Ness
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8614 Westwood Center Drive, Tysons Corner, VA 22182
Suites range from 1,985 square feet to 6,507 square feet.
Off-white precast 12 story office building with smoked grey windows.. . On-site Deli. Ample Parking Available (3.6 per 1,000SF leased). Abundant...
1950 Old Gallows Road, Tysons Corner, VA 22180
Suites ranging to 4,246 square feet.
Tycon Frederick is a gray precast 8-story office building with bands of black windows. The lobby includes a three-story atrium with gray marble...
7900A Westpark Drive, Tysons Corner, VA 22102
Suites ranging to 17,863 square feet.
Tysons Space Center is two integrated buildings of thirteen and six floors. Inside the building contains vaulted glass ceilings with the outer...
7926 Jones Branch Drive, Tysons Corner, VA 22102
Suites range from 641 square feet to 23,348 square feet.
Park Place I is a tan precast 11-story building adjacent to the McLean Hilton Hotel. The building offers a deli and travel agency.
2070 Chain Bridge Road, Tysons Corner, VA 22180
Suites range from 1,270 square feet to 2,439 square feet.
Grey precast building with a arching entranceway. Features TGI Fridays and Hunan Lion. Spectacular views from upper floors.
8230 Old Courthouse Road, Tysons Corner, VA 22182
Suites range from 2,158 square feet to 4,725 square feet.
Tycon V is a five-story contemporary office building with an oval, paved-floor lobby and a facade of granite horizontals with shimmering bands...
1945 Old Gallows Road, Tysons Corner, VA 22180
Suites range from 4,031 square feet to 71,030 square feet.
Dark brick seven story office building with dark tinted windows. The building wil, new lobby/entrance, elevators. Renovation to be completed...
7915 Jones Branch Dr., Tysons Corner, VA 22102
Suites range from 499 square feet to 20,799 square feet.
2236 Gallows Road, Tysons Corner, VA 22182
- Current Approved Occupancy 300 persons - First Floor Area 4,250sf - Second Floor Area 4,107sf - Full Commercial Kitchen, Smoking Lounge with...
2236 Gallows Road, Tysons Corner, VA 22182
- Current Approved Occupancy 300 persons - First Floor Area 4,250sf - Second Floor Area 4,107sf - Full Commercial Kitchen, Smoking Lounge with...
Rofo researches and displays commercial real estate listings from top brokerage firms and landlords in Tysons Corner, VA making it easier to find available commercial space and compare current asking rental rates. In Tysons Corner, VA there are currently 23 office spaces for lease, and 1 shared office spaces (also known as co-working spaces and executive suites) with 2 real estate professionals to help you find the right space for you. Filter your search below and get free advice from recommended brokers in Tysons Corner, VA.


text:
The ACP Advocate Blog
by Bob Doherty
Wednesday, July 29, 2009
What's the deal with the deals?
The late-breaking news from Washington is that deals have been made in both the House and Senate to trim the cost of health care reform. Not a lot of details yet, but the Washington Post reports that House Democrats have reached a tentative deal with conservative "Blue Dog" Democrats to cut "$100 billion from the cost of the legislation and would not pay health-care providers [under a public plan option] based on Medicare reimbursement rates." A final vote on the bill will be put off until after the August recess. In return, the Blue Dogs agreed to allow the final committee of jurisdiction, the House Energy and Commerce Committee, to complete the process of considering amendments to the bill so it can be voted out before the House recesses on Friday.
On the Senate side, Senator Max Baucus (D-MT), chair of the Senate Finance Committee, has reached a preliminary deal with three Republican Senators to lower the cost of the bill by $900 billion over ten years. The Washington Post says the deal will substitute non-profit regional health care cooperatives for a public plan and make additional cuts in Medicare, including provisions to "scale back Medicare payments to physicians, a long-promised but costly provision." (I think what the Post writer meant to say is that the bill will scale back relief from the Medicare SGR payment cuts, not pile on more cuts in addition to the SGR.) The deal reportedly will also replace broad based tax increases on upper income earners with "targeted" tax increases and to create "incentives" for employers to provide coverage instead of taxing those who do not.
From one standpoint, the deals will help move the legislation forward by winning support from conservative Democrats and at least a few Republicans. Rising public opposition to broad-based tax increases may be ameliorated.
The risk is that the changes will lose the support of liberal Democrats and their progressive allies who will recoil at the process of "watering down" health reform by removing a public plan option and employer mandate. How far will the cost-trimming move back the goal posts from providing the vast majority of Americans with affordable coverage? (The Washington Post says that the Baucus deal would cover 95% of Americans, compared to 97% in the current version of the House bill. But this has not been verified.) Taking more money out of Medicare could lose the support of beneficiaries (where will the AARP come down?) and on providers who likely will bear the brunt of the cuts. Going back on plans to fund long-term relief from Medicare physician payment cuts could cost physician support. And you have to wonder if plans to spend billions of Medicare dollars to fund payment increases to primary care physicians are at risk of being dropped to meet the cost-saving targets. (Nothing specific to this effect has been reported, but one has to assume that any additional Medicare spending on physicians is vulnerable.)
The give and take of legislation inevitably leads to compromise, and some of the changes - like eliminating a requirement that a public plan pay doctors and hospitals based on the Medicare rates - are likely to win support from more doctors and hospitals. But at what point will the cost-trimming unacceptably compromise some of the principal goals of health reform, including providing everyone with access to affordable coverage and reversing the shortage of primary care physicians?
I expect that there will be later deals to change these deals, many of which will take place over the August recess, so this is hardly the end of the process. We will all have a chance to make our cases for an even better deal. For ACP, maintaining funding for primary care, stopping the SGR payment cuts, and ensuring that the legislation provides enough help to the uninsured remain critical objectives that must not be dealt away.
Today's question: Do you like what you hear about the deals being made to trim the cost of health reform?
4 Comments :
- Jay Larson MD said...
Ah, the politicking begins. So far most of the emphasis is on health insurance reform. Will have to wait and see what deals are struck in regards to delivery reform, HIT, and primary care.
- Christie said...
Here is an article that discusses co-op plans. Our patients best interests should remain paramount.
Health Care Co-ops
- Steve Lucas said...
What I like is the focus on cost and the review of the true winners and losers in the process. The July 30th Akron Beacon Journal highlights lab cost at a 24 doctor practice as it opens up its internal lab for outside use in Low-cost lab aids patients.
This practice serves a large number of "self-pay" patients and the difference in cost are astounding between this lab and other services. One example is "for five of the most commonly ordered test range from $34 to $347 at area hospitals and major labs.
Pioneer charges $14 to $32 for those same test..."
We are also seeing those with a vested interest in the current system lining up against change in such July 29 WSJ articles as Doctors Oppose Giving Commission Power Over Medicare Payments. Such a commission would be open to public scrutiny and subject to public record laws.
If we are truly going to see positive change the process will be neither slow or without pain. We must be able to afford the final product.
Steve Lucas
- Robert J. Sobel, M.D. said...
Where is the true reform? If you want to protect patients, you need to support cognitive services and provide some margins for necessary ancillaries. If you want to control costs, you need to get more than the limited pharmaceutical rebates that make Medicaid and Medicare work like a charm for big companies and stick it to the health care providers.
As yesterday's bust in Texas illustrates, fraud that exists can be found and punished. We don't need the inefficiency of a quality bureaucracy to help us provide appropriate care for our patients. We need sane financing.
Why in God's name are my type 1 diabetics fighting for their strips and insulin? Why are my patients stopping meds they can't afford? It is because the system is broken. Do not focus on behavior modification. Instead, make the system work. Reform the Hatch-Waxman Act or the industry/physician financial ratio will get even worse and we'll all suffer. Get the perverse games out of health care.
Fair fee-for-serice and Regulated Royalties. If you don't address the exorbitant cost of the new, then it won't matter what financing scheme you create.
Subscribe to Post Comments [Atom]
About the Author
Bob Doherty is Senior Vice President, American College of Physicians Government Affairs and Public Policy; Author of the ACP Advocate Blog
Email Bob Doherty: email@example.com @BobDohertyACP
Previous Posts
- Singing the health reform blues
- "Don't tax him. Don't tax me. Tax that man behin...
- Winners and losers under the House's health reform...
- The battle for doctors' hearts and minds (day thre...
- The battle for physicians' hearts and minds (part ...
- A battle for physicians' hearts and minds
- Are doctors and non-physicians speaking the same l...
- The summer of internists' discontent
- Hospitals to Obama: Deal us in!
- Obama uses regulatory authority to give raise to p...
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text:
- Equipment World - http://www.equipmentworld.com -
Pyott-Boone names marketing manager, sales manager
Posted By Equipment World Staff On February 14, 2011 @ 1:47 am In Industry Briefs | No Comments
Pyott-Boone Electronics has promoted Gary L. Sergent to marketing manager and Dave Childress to sales manager at the company's North Tazewell, Va., operation.
Sergent has been promoted to marketing manager. He joined PBE in 2000 as a sales engineer after graduating from Bluefield State College with a BS in Electrical/Electronics Engineering Technology. He was promoted to project manager in January 2009 over the Minecom Leaky Feeder Radio Systems and PBE Tracking Boss personnel tagging systems. His concentration will now be expanding Pyott-Boone's product lines and to grow the business with new market opportunities. Sergent resides in Tazewell with his wife and three children.
Childress has been promoted to sales manager. He joined PBE in January of 2009 as a sales engineer. He has a BS from Bluefield State College in Mining Engineering Technology and Business Administration as well as a Masters in Business Administration from Averett College.
Childress has experience in underground mining and management, and as a previous business owner. His concentration will be to increase the company's service support and direct the entire PBE sales team. Childress resides in the Gratton area of Tazewell with his wife and two children.
Pyott-Boone Electronics is owned by The Fetterolf Group in Somerset, Pa., and is celebrating its 40th anniversary in 2011. The company has 230 employees and provide advanced communication and atmospheric monitoring products for the U.S. and International mining industry. It also has a contract manufacturing division which produces sophisticated assemblies for some of the largest defense contractors in the U.S.
Article printed from Equipment World: http://www.equipmentworld.com
URL to article: http://www.equipmentworld.com/pyott-boone-names-marketing-manager-sales-manager/
URLs in this post:
[1] Image: http://betterroads.randallreillycms.com/files/2011/02/gary.jpg
[2] Image: http://betterroads.randallreillycms.com/files/2011/02/dave.jpg
Click here to print.
Copyright © 2012 Equipment World -- Development. All rights reserved.


text:
Spoiler whore's thread! (enter at your own risk)
View Single Post
September 5 2005, 12:06 AM
Location: Yukon Ho!
Re: Spoiler whore's thread! (enter at your own ris
Posted by mac:
Posted by Hobs202:
Posted by Babaganoosh:
Posted by insert_name_here:
Here is the link for the script:
It's similar to the script that was leaked before, just with more details this time. The script however doesn't mention any use of stem cells so I don't know where that fits in. But the link I originally gave at the top is from some interview so all the spoiler hounds will have to follow that up for me.
Even still not all the facts are in yet so we really don't know for sure how this story will play out on screen and what they might add or take out before filming.
Okay, I've been out of touch for awhile, but I gotta ask:
Spoiler:

"Admiral" Adama? Has this happened on the actual show? When is he supposed to be promoted?
Also, what is the Prometheus? Yet another battlestar they manage to stumble across? Or just another ship in the fleet?

Here's my theory:
After the Pegasus episode(s) it becomes obvious that Adama is a better at commanding the fleet than Evil-Admiral-From-Hell Cain is/was. So Roslin promotes him to Admiral, thus ensuring that he stays in command if they encounter any more surviving battlestars with Evil Admirals/Commanders From Hell.
It makes sense - but IMHO "Commander Adama" sounds a lot cooler than "Admiral Adama." But that's just my opinion.
Does he get busted back down to Commander for trying to save Tigh from a ...ummm..lets say a ...Genesis Planet?
Yes, but first, he has to time travel back to Kobol in a stolen Cylon Basestar to pick up a pair of humpback whales.
Why humans are here: Tiger food.
--- Hobbes
From now on, I will not try to reason with the idiots I encounter. I will dismiss them by waving my paw and saying "Bah"
--- Dogbert
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text:
Sen. Patrick Leahy, D-Vt. / AP FILE
WASHINGTON — The National Security Agencys bulk collection of American phone records is not making Americans safer and must end, Sen. Patrick Leahy says.
Leahy, chairman of the Senate Judiciary Committee, called for new limits on the governments surveillance powers, particularly when directed at Americans, and greater oversight of the NSA.
Speaking Tuesday at the Georgetown University Law Center, the Vermont Democrat said hes working with House and Senate Republicans to reform provisions of the Patriot Act and Foreign Intelligence Surveillance Act.
The Obama administration has used those laws to justify gathering data on Americans phone records and personal data on foreigners from U.S. Internet firms servers, according to leaked information from former NSA contractor Edward Snowden.
Its not an either-or thing, your privacy or national security, Leahy said, speaking before a panel discussion on foreign surveillance.
Leahys committee will continue its oversight of government surveillance programs this week, beginning with a classified briefing for committee members Wednesday with Justice Department and intelligence officials.
On Oct. 2, the committee will hold its second public hearing in less than three months on the surveillance programs. That hearing will include testimony from Director of National Intelligence James Clapper and Gen. Keith Alexander, director of the NSA.
In June, Leahy introduced legislation designed to end the bulk collection of phone records by requiring the government to show the information is relevant to an investigation and linked to a foreign terrorist group or power.
He also co-sponsored a bill to declassify portions of significant FISA court opinions that show how the government interprets FISA and the Patriot Act in granting surveillance requests.
During his Tuesday speech, Leahy said he is working on a bill with GOP Rep. Jim Sensenbrenner of Wisconsin, chairman of the House Judiciary subcommittee on crime and terrorism, and Sen. Mike Lee, a Utah Republican and member of the Senate Judiciary Committee. Leahys staff could not say when the bill would be released.
This is not a liberal or conservative issue, Democrat or Republican, Leahy said. Were going to have a bipartisan response.
Leahy said the country has reached a watershed moment in which the system set up in the 1970s to regulate surveillance is no longer working.
We must recalibrate, he said.
He also said greater oversight for the NSA, including increased use of inspectors general, should be considered, along with possible structural changes to the secret FISA courts that review surveillance requests.
Monday, Leahys office released a bipartisan letter he wrote with other Judiciary Committee members calling for the inspector general of the intelligence community to review the use of surveillance authority under the Patriot Act and FISA and to make the findings public.
Sen. Bernie Sanders, I-Vt., and Rep. Peter Welch, D-Vt., also have called for limits on the governments surveillance powers. Sanders introduced legislation in June to curtail government tracking of American phone calls. The bill was referred to the Senate Judiciary Committee.
Sanders said he would work with other members of Congress to rein in the surveillance programs run by NSA and other agencies.
Their job is to protect us against terrorists, but in a way that is consistent with the Constitution of the United States, Sanders said in a statement.
Contact Nicole Gaudiano at email@example.com. Follow her on Twitter at www.twitter.com/ngaudiano.


text:
For mooring the many ropes of technology.
What use is an electrical plug when you're not plugged in? Two simple tabs on the ends of a standard cover plate increase its function.
Please visit the website for details & pricing.
- Product: Wall Cleat
- Brand: Boiler Design
- Retailer: Oboiler.com
- Designer: Karl Zahn
- Color: White
Have an opinion? Care to comment? We'd love to hear what you have to say.


text:
|A transfer function method for the continuous assessment of baroreflex control of renal sympathetic nerve activity in rats.
MedLine Citation:
|PMID: 17804584 Owner: NLM Status: MEDLINE
|The present study examined whether the gain of the transfer function relating cardiac-related rhythm of renal sympathetic nerve activity (RSNA) to arterial pressure (AP) pulse might serve as a spontaneous index of sympathetic baroreflex sensitivity (BRS). AP and RSNA were simultaneously recorded in conscious rats, either baroreceptor-intact (control, n = 11) or with partial denervation of baroreflex afferents [aortic baroreceptor denervated (ABD; n = 10)] during 1-h periods of spontaneous activity. Transfer gain was calculated over 58 adjacent 61.4-s periods (segmented into 10.2-s periods). Coherence between AP and RSNA was statistically (P < 0.05) significant in 90 +/- 3% and 56 +/- 10% of cases in control and ABD rats, respectively. Transfer gain was higher (P = 0.0049) in control [2.39 +/- 0.13 normalized units (NU)/mmHg] than in ABD (1.48 +/- 0.22 NU/mmHg) rats. In the pooled study sample, transfer gain correlated with sympathetic BRS estimated by the vasoactive drug injection technique (R = 0.75; P < 0.0001) and was inversely related to both time- (standard deviation; R = -0.74; P = 0.0001) and frequency-domain [total spectral power (0.00028-2.5 Hz); R = -0.82; P < 0.0001] indices of AP variability. In control rats, transfer gain exhibited large fluctuations (coefficient of variation: 34 +/- 3%) that were not consistently related to changes in the mean level of AP, heart rate, or RSNA. In conclusion, the transfer function method provides a continuous, functionally relevant index of sympathetic BRS and reveals that the latter fluctuates widely over time.
|Roy Kanbar; Valérie Oréa; Bruno Chapuis; Christian Barrès; Claude Julien
Related Documents :
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Publication Detail:
|Type: Journal Article Date: 2007-09-05
Journal Detail:
|Title: American journal of physiology. Regulatory, integrative and comparative physiology Volume: 293 ISSN: 0363-6119 ISO Abbreviation: Am. J. Physiol. Regul. Integr. Comp. Physiol. Publication Date: 2007 Nov
Date Detail:
|Created Date: 2007-11-05 Completed Date: 2007-12-26 Revised Date: -
Medline Journal Info:
|Nlm Unique ID: 100901230 Medline TA: Am J Physiol Regul Integr Comp Physiol Country: United States
Other Details:
|Languages: eng Pagination: R1938-46 Citation Subset: IM
|Université de Lyon, France. email@example.com
Export Citation:
|APA/MLA Format Download EndNote Download BibTex
|MeSH Terms
Baroreflex / physiology*
Blood Pressure / physiology
Data Interpretation, Statistical
Heart Rate / physiology
Kidney / innervation*, physiology*
Kidney Function Tests
Rats, Sprague-Dawley
Sympathetic Nervous System / physiology*
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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text:
Marie Petigny is the owner of Grace Hair Studio, a stylish and welcoming hair salon specializing in the world of black hair, wigs, weaves and related hair care products. Fostering her love of hair since the early age of 12, Marie has studied in both Montreal and New York, working with industry professionals to master her craft. With unwavering ambition, Marie's commitment to her work has sparked the drive and confidence to not only open her own salon, but create a line of all natural hair care products that "fly off the shelf." Determined to make her dream into a full-time job, Marie engaged in local self-employment programs and committed to building a marketing strategy that she would later bring to ACCESS.
With a determination to give back to her community, Marie is currently a trainee of the Children's AID Society, in addition to being a self-proclaimed "therapist and psychologist" to her sometimes 8-hour hair appointments. Marie is thankful for what ACCESS has allowed her to do, but with all the current and future help Marie is giving her community, we can't help but thank her in return.


text:
Paris transport plans paves way for Rogers' city-wide vision
Rogers Stirk Harbour + Partners' (RSHP) vision for Paris in 2030 has taken a step nearer realisation with news that a pivotal transport scheme has been approved
The UK architect was part of a 10-strong team that drew up ambitious city-wide plans for the then Sarkozy government in 2009 known as the Grand Paris vision.
Now the new French government has announced the approval of the Paris Metropolitan Transportation Plan (PMTP) which includes several new Grand Paris Express Stations, or 'polycentres' as well as other major road and rail links.
RSHP senior partner Mike Davies said the green light for the PMTP was the first stage 'in the provision of major new housing stock in the French capital.'
With just two million of the nine million Parisians living in the city's centre, RSHP proposed dramatic measures including building over the railway lines that split up large tracts of the city (see AJ 19.03.2009).
Meanwhile the practice is continuing work on its Bercy-Charenton masterplan, also in the centre of Paris (see AJ 01.07.2010).
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text:
Clarity, Technology, and Solving Problems | PracticeThis.com
WP7 App with Key Windows Azure resources – Slides, Videos, How-To's, and T-shooting – for quick consumption on the go.
by glennharper
The customer complained about potential memory leak. Following the procedure described in Identifying Memory Leak With Process Explorer And Windbg we realized that we are dealing with static variable that grows in unlimited way. This assumption is based on the fact that after running !gcroot on the leaking type we get the following:
After reviewing Tess' .NET Debugging Demos Lab 7: Memory Leak - Review we found the following which made us believe we are dealing with static variable:
DOMAIN(001CCE68):HANDLE(Strong) - Strong reference, Typically a static variable
DOMAIN(001CCE68):HANDLE(Strong) - Strong reference, Typically a static variable
To identify what this static variable is we needed to dump its values. The variable was a DataTable. I have not found a straightforward way of dumping contents of DataTable. This is the walkthrough that does the job.
The objective of this step is identify all DataTable object and pick the one of the interest
0:000> !dumpdatatables DataTable Rows Columns DataSet nextRowID ColumnCount ----------------------------------------------------------------------------------------------- 0x024dc948 0x024dcbc8 0x024dcdec 0x064f2400 1 2 0x025156b8 0x02515938 0x02515b5c 0x02515478 1 7 ...
0x0e5b9ce4 0x0e5b9f64 0x0e5ba138 0x0e55a338 428 5 0x06510e54 0x065110d4 0x065112a8 0x064f2400 1,359 7 0x0e5778f0 0x0e577b70 0x0e577d44 0x0e55a338 1,359 7 0x0a55d270 0x0a55d4f0 0x0a55d6c4 0x06a62620 4,194,305 10 Total 61 DataTable objects
The objective of this step is identifying the address of columnCollection of the DataTable.
0:000> !do 0x0a55d270 Name: System.Data.DataTable ... 0x176c1560 0x40003f2 0x18 CLASS instance 0x0a55d6c4 columnCollection ...
The objective of this step is identifying the address of list object of the columnCollection.
0:000> !do 0x0a55d6c4 Name: System.Data.DataColumnCollection ... 0x176c5ffc 0x4000377 0x8 CLASS instance 0x0a55d6f8 list ...
The objective of this step is identifying the address of _items object.
0:000> !do 0x0a55d6f8 Name: System.Collections.ArrayList ... 0x79ba75ec 0x4000362 0x4 CLASS instance 0x0a55d710 _items ...
The objective of this step is identifying addresses of DataColumn objects.
0:000> dd 0x0a55d710 0a55d710 01e5209c 00000010 79b92eec 0a55d854 0a55d720 0a55d8d4 0a55d954 0a55d9d4 0a55da54 0a55d730 0a55dad4 0a55db54 0a55dbd4 0a55dd74
The objective of this step is identifying the address of storage object.
!do 0a55d854 Name: System.Data.DataColumn ... 0x176c69e8 0x400036b 0x48 CLASS instance 0x0a55df40 storage ...
The objective of this step is identifying address of value object.
0:000> !do 0x0a55df40 Name: System.Data.Common.Int32Storage ... 0x176ecc8c 0x4000729 0x10 CLASS instance 0x4dbd0030 values ...
The objective of this step is dumping the actual values, finally...
0:000> !do 0x4dbd0030 Name: System.Int32[] ... Content: 8,388,608 items
Ouch, it is array.... !do -v will dump its values, but I am afraid it is not a good idea doing it for 8 million items here ;)
The objective of this step is automate the process of dumping values (Step 8):
This post is made with PracticeThis.com plugin for Windows Live Writer
!dumpdatatables isn't available with SOS.dll for .net 2.0 externally as yet. I guess we need to do a
!dumpheap -type System.Data.DataTable
to get started
Good catch AtulGupta!
Thanks for calling this out.
.NET NP .NET Profiler – a tool is designed to assist in troubleshooting issues such as slow performance


text:
Continuity of Functions
Continuity on Closed and Half-Closed Intervals
When looking at continuity on an open interval, we only care about the function values within that interval.
If we're looking at the continuity of a function on the open interval (a,b), we don't include a at b, they aren't invited. No value of x less than a or greater than b is invited, either. This is an exclusive club.
In a closed interval, denoted [a,b], we also must also invite our friends a and b to the pool party. Half-closed intervals either invite a, [a,b), or b, (a,b]. To talk about continuity on closed or half-closed intervals, we will see what this means from a continuity perspective. Start with a half-closed interval of the form [a,b). What does it mean for a function to be continuous on this interval?
Since we can only approach a from the right, we use the continuity definition for a right-sided limit instead of a two sided limit. We say f is continuous on [a,b) if f is continuous on (a,b) and
- f(a) exists
- exists
- f(a) and agree
Sample Problem
This function is continuous on the interval [a,b):
This function is continuous on (a,b). f(a) is defined, is defined, and the function value at a agrees with the right-sided limit at a.
Sample Problem
The following functions are not continuous on the interval [a,b).
This function is not continuous on [a,b) because f(a) is undefined. We could also say this function is not continuous on [a,b) because does not exist.
This function is not continuous on the interval [a,b) because .
This function is not continuous on the interval [a,b) because it is not continuous on the open interval (a,b).


text:
Mark Godsey, faculty director of the Ohio Innocence Project at the University of Cincinnati, speaks to law students. At his right is City Councilman John Cranley, administrative director.
- Filed Under
One thousand hours of work.
At least.
That's what it took to get Clarence Elkins released in December from prison. He had served 7½ years of a life sentence. ...


text:
A Girl Scouts of America pin.
- Filed Under
It's one thing for Barbie to strut her stuff on the Sports Illustrated swimsuit issue in a sexy one-piece. But it's another thing entirely for world's most famous doll to show up on a Girl Scout patch.
A consumer advocacy group wants the patch - and the commercial tie-in with Girl Scouts - nixed. While the patch does not show a Barbie doll, it shows the familiar Barbie logo.
"Holding Barbie, the quintessential fashion doll, up as a role model for Girl Scouts simultaneously sexualizes young girls, idealizes an impossible body type and undermines the Girl Scouts' vital mission," says Susan Linn, ...


text:
Currently, opioid-based drugs are the most effective pain relievers that are widely used in the treatment of pain. However, the analgesic efficacy of opioids is significantly limited by the development of tolerance after repeated opioid administration. Glutamate receptors have been reported to critically participate in the development and maintenance of opioid tolerance, but the underlying mechanisms remain unclear. Using whole-cell voltage-clamp recordings in brainstem slices, the present study investigated chronic morphine-induced adaptations in glutamatergic synaptic transmission in neurons of the nucleus raphe magnus (NRM), a key supraspinal relay for pain modulation and opioid analgesia. Chronic morphine significantly increased glutamate synaptic transmission exclusively in one class of NRM cells that contains μ-opioid receptors in a morphine-tolerant state. The adenylyl cyclase activator forskolin and the cAMP analog 8-bromo-cAMP mimicked the chronic morphine effect in control neurons and their potency in enhancing the glutamate synaptic current was significantly increased in neurons from morphine-tolerant rats. MDL12330a, an adenylyl cyclase inhibitor, and H89, a protein kinase A (PKA) inhibitor, reversed the increase in glutamate synaptic transmission induced by chronic morphine. In addition, PMA, a phorbol ester activator of protein kinase C (PKC), also showed an increased potency in enhancing the glutamate synaptic current in these morphine-tolerant cells. The PKC inhibitor GF109203X attenuated the chronic morphine effect. Taken together, these results suggest that chronic morphine increases presynaptic glutamate release in μ receptor-containing NRM neurons in a morphine-tolerant state, and that the increased glutamate synaptic transmission appears to involve an upregulation of both the cAMP/PKA pathway and the PKC pathway. This glutamate-mediated activation of these NRM neurons that are thought to facilitate spinal pain transmission may contribute to the reduced opioid analgesia during opioid tolerance.
Opioid analgesics, such as morphine, currently are the most effective and frequently used pain reliever for moderate to severe pain. However, long-term administration of opioids can alter the central pain-related systems and results in opioid tolerance (decreased analgesic effect of opioids) and opioid dependence (a behavioral state requiring continued opioids to avoid a series of aversive withdrawal syndromes). Opioid tolerance and dependence significantly hamper the effective treatment of chronic pain with opioid analgesics [1]. Numerous agonists and antagonists of various receptors and inhibitors of second messenger pathways have been reported to block or reduce morphine tolerance and/or dependence [2]. It has been well established that glutamate receptors are critical in the development and maintenance of opioid tolerance [3-6]. However, the underlying mechanisms by which glutamate receptors mediate opioid tolerance and dependence remain unclear. An upregulation of the cAMP/PKA signaling pathway has been characterized as a typical molecular adaptation in several brain regions following chronic morphine treatment [1], but the detailed role of the cAMP pathway in analgesic tolerance to chronic opioids has yet to be demonstrated.
Nucleus raphe magnus (NRM), a key medullary relay for descending pain modulation, is critically involved in opioid-induced analgesia [7]. According to their electrophysiological characters and opioid responses, NRM neurons in an in vitro preparation have been divided into two general types, primary cells that lack the μ-opioid receptor and secondary cells that contain the μ receptor [8]. Based on the observation that acute opioids inhibit GABA synaptic transmission in primary cells, we have proposed that opioids produce analgesia in the NRM by disinhibiting or activating those primary cells that send descending projections to the spinal dorsal horn and inhibit spinal pain transmission [8,9]. Several lines of evidence suggests that some NRM cells that are directly inhibited by opioids or contain μ receptors have a facilitating action on spinal pain transmission through their descending projections [7,10,11]. Thus, both activation of pain-inhibiting primary cells and inhibition of pain-facilitating secondary cells in the NRM may be involved in acute opioid-induced analgesia. The synaptic connections between primary cells and secondary cells and the neurotransmitter they release are currently unknown. Accumulating evidence has clearly demonstrated that the μ receptor-containing cells in the NRM are activated in many chronic pain conditions with pain sensitization [11-13], but the activation mechanisms remain unclear. The present study was aimed to investigate chronic morphine-induced adaptation of glutamate synaptic transmission in NRM neurons from morphine-tolerant rats and the intracellular signaling pathways involved in the synaptic adaptation.
Chronic morphine selectively increases presynaptic glutamate release
Glutamate-mediated excitatory postsynaptic currents (EPSCs) were recorded under whole-cell voltage-clamp in NRM slices in vitro. The EPSCs were compared between NRM slices from saline-treated control rats and those from morphine-treated tolerant rats. Both groups of slices (control and tolerant) were maintained in 5 μM morphine throughout recording experiment in vitro to prevent morphine withdrawal (Ingram et al., 1998). A separate group of control slices kept in a morphine-free solution (normal group) was used as controls for the acute morphine added. We used the paired-pulse ratio (PPR) to assess chronic morphine-induced changes in glutamate synaptic transmission in the two types of NRM neurons, primary cells and secondary cells. In the μ receptor-containing secondary cells in control slices, the average PPR was 1.76 ± 0.05 (n = 16), indicating a common synaptic facilitation (PPR>1) by the two stimuli. However, in secondary cells from morphine-tolerant rats, the PPR was significantly smaller than that in controls (1.43 ± 0.07, n = 41, P < 0.01, Fig. 1A,C), indicating an increased probability of presynaptic glutamate release in these secondary cells in a morphine-tolerant state. The PPR in secondary cells in the normal group without 5 μM morphine was 1.89 ± 0.13 (n = 33), which was not statistically different from that in control cells kept in 5 μM morphine (p > 0.05), excluding possible effect of the acute morphine on the PPR. In contrast to secondary cells, there was no significant difference between the EPSC PPRs in μ receptor-lacking primary cells from control and from morphine-tolerant rats (control, 1.43 ± 0.11, n = 10; tolerant, 1.44 ± 0.08, n = 17; P > 0.05, Fig 1B,C). These data indicate that chronic morphine increases glutamate synaptic transmission selectively in the μ receptor-containing secondary cells in a morphine-tolerant state.
Figure 1. Chronic morphine decreases the paired-pulse ratio (PPR) of glutamate EPSCs in μ-opioid receptor-containing cells (termed secondary cells) in the NRM from morphine-tolerant rats. A, Representative EPSC pairs in secondary cells from a saline-treated rat, a morphine-treated tolerant rat and the same two EPSC pairs normalized to the first EPSC. B, Representative EPSC pairs in the other type of NRM cells (termed primary cells) lacking the μ receptor from two similar groups of rats. C, Group data of the PPR in the two cell types from saline control and morphine-tolerant rats. Stimulus artifacts are blanketed. Numbers in columns indicate cell numbers. ** p < 0.01.
EPSC-enhancing effect of activators of cAMP pathway is increased
In control secondary cells, bath application of the adenylyl cyclase (AC) activator forskolin (10 μM) significantly increased the amplitude of evoked EPSCs (eEPSCs) by 53.9 ± 4.1% (control, 95.1 ± 7.3 pA, forskolin, 144.1 ± 14.2 pA, n = 12, P < 0.01). Forskolin produced a comparable EPSC increase in secondary cells in normal slices without 5 μM morphine (57.4 ± 11.4%, n = 6, p < 0.01, p > 0.05 when compared to its effect in control slices with 5 μM morphine). However, in tolerant secondary cells, the EPSC-enhancing effect of forskolin was significantly increased to 95.3 ± 5.3% (p < 0.01, compared to its effect in control group) (control, 88.9 ± 7.8 pA, forskolin, 174.3 ± 13.9 pA, n = 7, P < 0.01, Fig. 2A,B). Similar to the effect of chronic morphine, forskolin (10 μM) also significantly decreased the PPR of glutamate EPSCs in secondary cells from both saline-treated and morphine-tolerant rats (saline: control, 1.73 ± 0.21, forskolin, 1.03 ± 0.14, n = 5, P < 0.01; tolerant: control, 1.43 ± 0.14, forskolin, 0.90 ± 0.03, n = 5, P < 0.01, Fig 2C). Due to a significant decrease in the basal PPR, direct comparison in percentage term of the forskolin effects between the two groups was not feasible. In primary cells, by contrast, although forskolin increased the eEPSC amplitude in both control and tolerant groups, the magnitude of its effects in the two groups was not changed (control, 72.8 ± 17.6%, n = 7, tolerant, 67.0 ± 14.9%, n = 5, P > 0.05).
Figure 2. EPSC-enhancing effect of Forskolin is increased in secondary cells from morphine-tolerant rats. A, Glutamate EPSCs before (control) and during bath application of forskolin (10 μM) in cells from saline control and tolerant rats. B, Time course for the forskolin enhancement of EPSC amplitudes in saline control (n = 12) and tolerant cells (n = 7). The horizontal bar indicates application time for forskolin. C, Normalized EPSC pairs in the absence (control) and presence of forskolin in saline control and tolerant cells. Note forskolin-induced decrease in the PPR of both groups. Forsk, forskolin. * p < 0.05, ** p < 0.01.
To further confirm the forskolin effect on presynaptic glutamate release, we examined forskolin action on miniature EPSCs (mEPSCs) in NRM neurons. In control secondary cells, forskolin (10 μM) increased the frequency, but not the amplitude, of glutamate mEPSCs (frequency: control, 5.70 ± 1.03 Hz, forskolin, 8.46 ± 1.07 Hz, n = 5, P < 0.05; amplitude: control, 20.8 ± 2.0 pA, forskolin, 20.6 ± 2.4 pA, n = 5, P > 0.05). This forskolin effect was also observed in secondary cells from tolerant rats (frequency: control, 7.64 ± 0.96 Hz, forskolin, 15.18 ± 0.98 Hz, n = 5, P < 0.01; amplitude: control, 21.3 ± 2.4 pA, forskolin, 20.5 ± 2.23 pA, n = 5, P > 0.05). By comparison, the forskolin-induced increase in the mEPSC frequency was significantly greater in tolerant secondary cells (control, 54.2 ± 9.8%, tolerant, 104.3 ± 11.5%, n = 5, P < 0.05, Fig 3 & Fig. 4D). The forskolin-induced increase in mEPSC frequency in tolerant primary cells was not altered (control, 62.6 ± 17.4%, n = 4, tolerant, 72.2 ± 36.4%, n = 5, P > 0.05).
Figure 3. Forskolin enhancement of miniature EPSC (mEPSC) frequency is greater in secondary cells from morphine-tolerant rats. A,B,C, Representative current traces with miniature synaptic events (A) and plots of cumulative distribution of mEPSC frequency (B) and amplitude (C) before and during application of forskolin (10 μM) in the same saline control cell. D,E,F, Current traces (D) and plots of mEPSC distribution data (E,F) from a tolerant cell.
Figure 4. EPSC-enhancing effect of 8-bromo-cAMP is increased in secondary cells from morphine-tolerant rats. A, Normalized EPSC pairs in control and in 8-broma-cAMP (8-br-cAMP, 1 mM) in a saline control cell and a tolerant cell. B, Group data of 8-br-cAMP-induced decrease in the PPR in saline control (n = 4) and tolerant cells (n = 5). C, Distribution data of mEPSC frequency before and during application of 8-br-cAMP in a saline control (left) and a tolerant cell (right). D, Percent increase by 8-br-cAMP and forskolin in mEPSC frequency in saline control and tolerant cells.
The cAMP analog 8-bromo-cAMP (8-br-cAMP) produced similar effects to those of forskolin. Bath application of 8-br-cAMP (1 mM) increased the eEPSC amplitude in secondary cells from both saline control and morphine-tolerant rats (saline: control, 110.9 ± 14.8 pA, 8-br-cAMP, 166.6 ± 9.2 pA, n = 4, P < 0.01; tolerant: control, 130.1 ± 1.4 pA, 8-br-cAMP, 260.2 ± 28.5 pA, n = 7, P < 0.001). This cAMP effect was significantly enhanced by chronic morphine treatment (saline, 52.1 ± 9.4%, tolerant, 103.6 ± 10.1%, p < 0.05). 8-br-cAMP also decreased the PPR in secondary cells from both saline control and tolerant rats (saline: control, 1.70 ± 0.08, 8-br-cAMP, 1.10 ± 0.07, n = 4, P < 0.01; tolerant: control, 1.49 ± 0.17, 8-br-cAMP, 1.14 ± 0.10, n = 5, P < 0.05, Fig 4A,B).
Bath application of 8-br-cAMP (1 mM) also significantly increased the frequency of mEPSC in secondary cells from both saline control and tolerant rats (saline: control, 4.72 ± 0.47 Hz, 8-br-cAMP, 6.85 ± 0.70 Hz, n = 8, p < 0.01; tolerant: control, 6.62 ± 0.88 Hz, 8-br-cAMP, 12.46 ± 1.25 Hz, n = 7, p < 0.01, Fig. 4C). However, similar to the forskolin effect, this effect of 8-br-cAMP was also significantly enhanced in the slices from morphine-tolerant rats (saline, 46.9 ± 7.9%, n = 8, tolerant, 97.5 ± 21.2%, n = 7, p < 0.05, Fig. 4D). 8-br-cAMP did not change the amplitudes of mEPSCs in either group (saline: control, 15.9 ± 0.6 pA, 8-br-cAMP, 15.9 ± 1.3 pA, n = 8, P > 0.05; tolerant: control, 18.8 ± 1.2 pA, 8-br-cAMP, 18.9 ± 1.6 pA, n = 7, P > 0.05).
The enhanced forskolin and 8-br-cAMP effects on eEPSC amplitude and mEPSC frequency in morphine-tolerant rats indicate a sensitized or upregulated AC system in a morphine-tolerant state.
Chronic morphine-induced EPSC increase involves cAMP pathway
To determine the involvement of the AC pathway in the chronic morphine-induced increase of glutamate release in NRM secondary cells, NRM slices were treated with MDL12330a, a selective AC inhibitor. While pre-incubation with MDL12330a (100 μM) did not change the EPSC PPR in secondary cells from control rats (control, 1.71 ± 0.06, MDL, 1.76 ± 0.03, n = 5, p > 0.05), it largely reversed the chronic morphine-induced PPR decrease in secondary cells from morphine-tolerant rats (tolerant, 1.43 ± 0.07, +MDL, 1.74 ± 0.07, n = 16, P < 0.01, Fig. 5A,B,C). Bath application of MDL12330a (100 μM) also significantly decreased the frequency of mEPSCs in tolerant secondary cells (tolerant, 10.17 ± 0.89 Hz, +MDL, 5.86 ± 0.66 Hz, n = 5, P < 0.01, Fig. 5D,E,F) whereas it did not alter the mEPSC amplitude (tolerant, 16.9 ± 1.1 pA, +MDL, 18.1 ± 1.2 pA, n = 5, P > 0.05). MDL had no effect on either the frequency or the amplitude of mEPSCs in secondary cells from saline control rats (frequency: control, 4.39 ± 0.45 Hz, +MDL, 4.71 ± 0.50 Hz, n = 5, P > 0.05; amplitude: control, 16.9 ± 2.0 pA, +MDL, 17.5 ± 1.5 pA, n = 5, P > 0.05, Fig. 5F). Next, we used a PKA inhibitor to determine whether PKA was involved in the enhanced glutamate transmission in secondary cells induced by chronic morphine. Pre-incubation with H89 (10 μM) largely inhibited the chronic morphine-induced decrease of the EPSC PPR in secondary cells from morphine-tolerant rats (tolerant, 1.43 ± 0.07, +H89, 1.71 ± 0.06, n = 13, P < 0.01, Fig. 6A,B). H89 was without effect on the EPSC PPR in secondary cells from control rats (tolerant, 1.76 ± 0.06, +H89, 1.90 ± 0.08, n = 6, P > 0.05, Fig. 6B). Similarly, bath application of H89 (10 μM) significantly decreased the frequencies, but not the amplitude, of mEPSCs in tolerant secondary cells (frequency: tolerant, 8.55 ± 2.42 Hz, +H89, 4.66 ± 2.11 Hz, n = 5, P < 0.05; amplitude: tolerant, 15.1 ± 0.9 pA, +H89, 14.3 ± 0.7 pA, n = 5, P > 0.05, Fig 6C,D). In control secondary cells, H89 did not change either the frequency or the amplitude of mEPSCs (frequency: control, 3.96 ± 0.44 Hz, +H89, 3.43 ± 0.62 Hz, n = 5, P > 0.05; amplitude: control, 20.5 ± 3.8 pA, +H89, 20.2 ± 3.0 pA, n = 5, P > 0.05, Fig. 6D).
Figure 5. MDL12330a reverses the chronic morphine effect on glutamate EPSCs in tolerant secondary cells. A, Representative EPSC pairs in tolerant cells without (tolerant) and after treatment with the adenylyl cyclase (AC) inhibitor MDL12330a (MDL, 100 μM). B, Normalized EPSC pairs from A. C, Group data of the MDL effect on the PPR in cells from morphine-tolerant (n = 16) and saline control rats (n = 5). D,E, Representative current traces (D) and a plot of mEPSC frequency distribution (E) in a tolerant cell before and during application of MDL (100 μM). F, Group data of the MDL effect on mEPSC frequency in tolerant and saline control cells (n = 5 in each group).
Figure 6. H89 reverses the chronic morphine effect on glutamate EPSCs in tolerant secondary cells. A, Normalized EPSC pairs in tolerant cells without and after treatment with H89 (10 μM), a protein kinase A inhibitor. B, Group data of the H89 effect on PPR in tolerant (n = 13) and saline control cells (n = 6). C, A plot of mEPSC frequency distribution in tolerant cells with or without H89 treatment. D, Group data of the H89 effect on mEPSC frequency in tolerant and saline control cells (n = 5 in each group).
These data obtained with both MDL12330a and H89 suggest that the cAMP/PKA pathway is critically involved in the chronic morphine-induced enhancement of glutamate synaptic transmission in NRM secondary cells.
Chronic morphine-induced EPSC increase involves PKC pathway
Finally, we examined whether the PKC pathway was also involved in the chronic morphine effect on glutamate EPSCs. Phorbol 12-myristate 13-acetate (PMA, 1 μM), a phorbol ester activator of PKC, increased the amplitude of eEPSCs in NRM secondary cells from both saline control and morphine-tolerant rats (saline: control, 109.9 ± 15.8 pA, PMA, 180.4 ± 22.2 pA, n = 7, P < 0.001; tolerant: control, 134.8 ± 12.9 pA, PMA, 284.7 ± 25.8 pA, n = 7, P < 0.01, Fig. 7A). However, when the PMA effects were compared between the two groups, the EPSC-enhancing effect of PMA was significantly larger in cells from tolerant rats than that in control cells (control, 67.7 ± 6.9%, n = 7, tolerant, 126.6 ± 16.4%, n = 7, p < 0.01, Fig. 7B), indicating a likely upregulated PKC pathway. GF109203X (2 μM), a selective PKC inhibitor, had no significant effect on the EPSC PPR in control secondary cells (control, 1.76 ± 0.14, GF109203X, 1.76 ± 0.05, n = 6, P > 0.05), but it reversed the chronic morphine-induced decrease of the EPSC PPR in secondary cells from morphine-tolerant rats (tolerant, 1.43 ± 0.07, +GF109203X, 1.79 ± 0.10, n = 8, P < 0.05, Fig. 7C,D,E).
Figure 7. Chronic morphine-induced EPSC augmentation involves the protein kinase C pathway. A, Representative EPSCs in the absence and presence of the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA, 1 μM) in a saline control cell and a tolerant cell. B, PMA effect on the peak amplitude of eEPSCs in saline control and tolerance cells. C,D, Representative EPSC pairs (C) and the same pairs after normalization (D) in tolerant cells with or without treatment with the PKC inhibitor GF109203X. E, Group data of the GF109203X effect on PPR in tolerant (n = 8) and saline control cells (n = 6).
The present study has illustrated that chronic morphine increases presynaptic release of glutamate in the μ receptor-containing secondary cells in a morphine-tolerant state. It also provides evidence that both cAMP/PKA and PKC signaling pathways are critically involved in this chronic morphine-induced synaptic adaptation during morphine tolerance.
Upregulation of the cAMP pathway and glutamate release
In the present study, the effect of chronic morphine on glutamate synaptic transmission was primarily assessed by using the paradigm of EPSC PPR in NRM neurons kept in a tolerant state from morphine-tolerant rats [14]. The PPR has been widely used to determine the involvement of a presynaptic site in the mechanism of neurotransmitter release [15-21]. A change in the PPR is inversely related to the probability of transmitter release and thus, a manipulation that increases the probability of transmitter release results in a reduction in the PPR and vise versa. Since the PPR in a cell under a certain condition is relatively stable, the advantage of using the PPR is to avoid large variance usually present in eEPSC amplitudes and mEPSC frequencies among individual cells, making it possible to compare EPSCs in two separate groups of slices, such as those from saline-treated control rats and those from morphine-tolerant rats. Our current results obtained with the PPR analysis suggest that glutamate synaptic transmission is enhanced through a presynaptic mechanism in NRM secondary cells from morphine-tolerant rats. This conclusion is further supported by the effects of activators and inhibitors of the cAMP/PKA or PKC pathway, which mimicked and reversed the effect of chronic morphine, respectively. It is interesting to note that the chronic morphine-induced EPSC enhancement occurred exclusively in μ receptor-containing secondary cells. This may implicate a functional activation of these μ receptor-expressing NRM cells by glutamate inputs during morphine tolerance (see below). The source of these glutamate inputs is currently unclear.
Presynaptic glutamate release is modulated by many complex and interacting proteins and processes, including components of the cAMP/PKA pathway, in presynaptic terminals [22,23]. It has been demonstrated that in vitro application of activators of the cAMP/PKA pathway enhances presynaptic release of glutamate in many types of central neurons [23-27]. In vivo administration of chronic morphine induces adaptive hyperactivation of the cAMP/PKA signaling pathway in several brain regions [1,27,28]. The hyperactivated cAMP/PKA pathway induced by chronic morphine may induce a series of cellular adaptations, including enhanced transmitter release. However, cAMP-dependent synaptic adaptation induced by in vivo administration of chronic morphine has been reported only in GABAergic synapses in central neurons during morphine withdrawal [21,28,29]. The current study provides direct evidence that chronic morphine enhances glutamate synaptic transmission also in a cAMP-dependent way in NRM neurons from morphine-tolerant rats.
Several observations in the current study support a critical role of an upregulated cAMP/PKA pathway in the enhanced glutamate neurotransmission in secondary cells from morphine-tolerant rats. First, the AC activator and cAMP analog mimic the effect of chronic morphine on EPSC PPR. Second, the potency of cAMP activators in enhancing eEPSC amplitude and mEPSC frequency is significantly augmented in neurons from morphine-tolerant rats. Such an augmented effect has been interpreted as the result of a sensitized or upregulated cAMP pathway [21,27,29]. Finally, inhibitors of both AC and PKA reverse the chronic morphine-induced EPSC enhancement. This effect of AC/PKA inhibitors observed in tolerant cells, but not in control cells, indicates an elevated basal activity of the cAMP/PKA pathway induced by chronic morphine. Such an upregulation of basal and stimulated PKA activity has been shown in other brain areas [1,30].
Upregulation of the PKC pathway and glutamate release
It has been shown that activation of PKC either by the intracellular messenger diacylglycerol or by phorbol esters produces an enhancement of neurotransmitter release including glutamate release in central neurons [23,31,32]. Activated PKC may phosporylate a number of proteins in nerve terminal and increase neurotransmitter release by calcium influx through voltage-gated calcium channels or by direct effects on exocytosis or on vesicle-recycling pathways [33]. Chronic morphine increases PKC activity in the rat brain and spinal cord [34,35]. The increased PKC activity, which may be mediated through opioid activation of the phospholipase C pathway coupled to opioid receptors, can phosphorylate AC and increase its adaptive responses to chronic opioids [27,30]. In the present study, the PKC activator, similar to activators of the cAMP/PKA pathway, exhibited an augmented potency in enhancing glutamate EPSCs in NRM neurons from morphine-tolerant rats, and the PKC inhibitor reversed the effect of chronic morphine. Although non-specific effects of these PKA and PKC inhibitors cannot be completely ruled out, these data indicate a likely upregulated PKC and PKA activity, which is at least partially responsible for the enhanced glutamate synaptic transmission in NRM secondary cells from morphine-tolerant rats.
Functional implications in morphine tolerance
Extensive evidence has shown that some NRM cells inhibited by μ opioids have a facilitating action on spinal pain transmission through their descending projections [7,10]. Recent pain research shows that those brainstem cells expressing μ-opioid receptors are commonly activated in various chronic pain conditions, including chronic opioid-induced abnormal pain, and contribute to the sensitized pain or hyperalgesia observed during these conditions [11-13,36]. It remains unclear what mediates the activation of these μ receptor-containing cells in those pain conditions. Data from the current study indicate that excessive activity of glutamate synaptic inputs after chronic exposure to opioids may contribute to the activation of these cells during morphine tolerance. An overall effect of this enhanced glutamate synaptic activity in driving these cells needs to be evaluated by taking into account other synaptic inputs such as GABA synaptic transmission.
It has been proposed that the chronic opioid-induced activation of those presumably pain-facilitating cells and consequently, abnormal pain, constitute part of the mechanisms underlying opioid tolerance characterized by a reduced analgesic effect of opioids [36]. For example, microinjection of lidocaine into the NRM area to inactivate cell activity reverses the tactile allodynia and thermal hyperalgesia induced by prolonged exposure to morphine, and attenuates morphine tolerance [37,38]. A critical role of glutamate receptors in the development of opioid tolerance and dependence has been established [3-6]. The present study illustrates an example of the mechanisms by which glutamate receptors and synapses participate in the development of opioid tolerance. An important role of PKC in opioid tolerance has also been demonstrated in previous studies. For instance, PKC inhibition reduces opioid tolerance [34,35,39,40], and PKCγ mutant mice display alleviated morphine tolerance [41].
In summary, the current study shows that chronic morphine enhances glutamate synaptic transmission in μ receptor-containing NRM neurons. This synaptic adaptation appears to be mediated by an upregulated cAMP/PKA and PKC pathway in morphine-tolerant rats. These results may provide key information for pain therapies aiming at inhibiting those brainstem neurons and their descending pain facilitation, which is responsible for the pain sensitization in several chronic pain conditions.
All procedures involving the use of animals conformed to the guidelines set by the University of Texas-MD Anderson Cancer Center Animal Care and Use Committee. Chronic morphine treatment Male, Wistar neonatal rats were injected (i.p.) twice daily with morphine solutions for 6 days. The dose of the morphine was 10 mg/kg on the first day, and increased by 5 mg/kg each day to reach a maximum dose of 30 mg/kg on day 5. On day 7, the rats were euthanized for brain slice preparation. Saline was injected at the same volume and schedule in a separate group of rats for controls. Morphine tolerance in these neonatal rats has been described previously [42].
Whole-cell voltage-clamp recording The methods for NRM brain slice preparations, visualized whole-cell recordings, cell classification and analysis of glutamate EPSCs have been published previously [15]. The brain of a rat (10–14 days old) was cut in a vibratome in cold (4°C) physiological saline to obtain brainstem slices (220–250 μm thick) containing the NRM. A single slice was submerged in a shallow recording chamber and perfused with preheated (35°C) physiological saline (in mM: NaCl, 126; KCl, 2.5; NaH2PO4, 1.2; MgCl2, 1.2; CaCl2, 2.4; glucose, 11; NaHCO3, 25, saturated with 95% O2 and 5% CO2, pH 7.2–7.4). Slices were maintained at around 35°C throughout the recording experiment. Neonatal rats were used for better visualization of neurons in brain slices with an infrared Nomarski microscope. It has been demonstrated that the physiological and pharmacological properties of neurons from these young rats are indistinguishable from those of adult rats[9,15]. Visualized whole-cell voltage-clamp recordings were made from identified neurons held at -60 mV with a glass pipette (resistance 3–5 MΩ) filled with a solution containing (mM): potassium gluconate, 126; NaCl, 10; MgCl2, 1; EGTA, 11; Hepes, 10; ATP, 2; GTP, 0.25; pH adjusted to 7.3 with KOH; osmolarity 280–290 mosmol/L. An AxoPatch 1-D amplifier and AxoGraph software 4.7 (Axon Instruments, Inc.) were used for data acquisition and on-line/off-line data analyses. A seal resistance of 2 GΩ or above and an access resistance of 15 MΩ or less were considered acceptable. Series resistance was optimally compensated. The access resistance was monitored throughout the experiment. Electrical stimuli of constant current (0.25 ms, 0.2–0.4 mA) were used to evoke EPSCs with bipolar stimulating electrodes placed lateral (200–400 μm) to the recording pipette within the NRM. The difference in glutamate synaptic transmission between control and morphine-tolerant slices was assessed by the paradigm of paired-pulse ratio (PPR). A pair of EPSCs was evoked by two stimuli with an interval of 40 ms. The PPR was determined by dividing the second EPSC amplitude by the first one. Miniature EPSCs were obtained in 60-sec epochs in the presence of tetrodotoxin (1 μM). The AxoGraph software was used to detect and measure the amplitude and intervals of the synaptic events, and to analyze their distribution data. All NRM cells recorded were classified into either a μ-containing secondary cell or a μ-lacking primary cell according to the criteria described in our previous study [8]. NRM slices from both morphine- and saline-treated rats were kept in 5 μM morphine throughout the recording experiment to maintain the slices in a morphine-tolerant state and prevent withdrawal [14]. Another group of slices from saline-treated rats kept in a morphine-free solution was used as controls for the acute morphine. Statistic analysis of mEPSCs were performed with the Mann-Whitney U test or the Kolmogorov-Smirnov test using the Statview software. Other numeral data were statistically analyzed with Students' t tests and presented as mean ± S.E.M. Some slices were incubated in MDL12330a (100 μM), or H89 (10 μM) or GF109203X (2 μM) for at least 1 hour. Drugs were generally applied through the bath solution unless otherwise specified. Morphine sulfate was kindly supplied by the National Institute on Drug Abuse. All other drugs were purchased either from Sigma-Aldrich Co. or from Tocris Cookson Inc. (Ellisville, MO).
Competing interests
The author(s) declare that they have no competing interests.
This work was supported by the National Institute on Drug Abuse grant DA14524 and by an institutional fund of MD Anderson Cancer Center.
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Pan ZZ: Opioid Tolerance in Adult and Neonatal Rats. In Opioid Research: Methods and Protocols. Edited by Pan ZZ. Totowa, NJ: Humana Press; 2003:223-232. [ (Series Editor): Methods in Molecular Medicine]


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Randy Owen
Singer, guitarist, and songwriter Randy Owen is best known for being the lead singer in Alabama, the most successful group in the history of country music. Born on December 14, 1949, Owen and his cousin, Teddy Gentry, grew up on cotton farms on Lookout Mountain in Alabama, sharing a passion for singing and guitar. The duo played in a number of different bands during the '60s, teaming with another ...more


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Welcome to Citizens Bank. This site is screen reader friendly.
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Full- or half-time undergraduate and graduate students are eligible for Perkins Loans, based on financial need. These loans are made through your school, and are repaid to the school. The interest rate on these loans varies, and the repayment term is generally ten years. The amounts available for any one student depend on their financial need, the amount of other aid they're being given, and the funds available at their school. These loans carry a nine-month student loan repayment grace period after graduation. Similar to the Stafford Loan, students must complete the FAFSA to apply for a Perkins Loan.
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The Mercedes Benz C320 floor mat of your vehicle is designed to be able to protect your ride's floor well. Created from grime-resistant substances, car floor mats are practical when you happen to spill the beverage you are drinking on your ride's floor or when you hop on your auto with mud on your shoes.
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- Filed Under
An off-duty Rapides Parish Sheriff's Office deputy working at a Cleco storage area because of recent thefts nabbed two Boyce men Sunday who allegedly were trying to steal copper, according to a release.
David Andries, 52, of 50 Herring Road, and Steven Stickell, 46, of 4847 La. Highway 121, both were arrested and booked into the Rapides Parish Detention Center.
The deputy found the two men ...


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A diverse and constantly updating source of astrology-themed content, Astrodispatch is edited by Elsa P, astrologer and author of ElsaElsa - The Astrology Blog.
To reach the editor, please visit our contact page.
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"In your mind, you are psycho and insecure. In my mind, you're a knowledgeable person who is fantasizing and denying. Big difference!
In your model, you're a victim of circumstance. In my model, you have choices – lots of them!"
I wrote that for a client. I am a card player from way back. I've seen too many games turn on a dime, to think that people and things can't change, radically.
When is the last time you asked for an outside perspective?
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When I started writing science fiction, I had a few "general" first readers who would read what I wrote, and very few, if any "in-community" readers steeped in the language and tropes of science fiction. I was very glad that "regular" or "general" readers could understand the stories I was writing, and that I was putting together conflicts and characters that regular people could relate to.
Time passed. Some of my "regular" readers have themselves, passed on. Others, I wouldn't impose work upon them, taking time away from their busy schedules.
I'm novelizing "To Kiss the Star" and I thought it would be a good idea to take the first part of it to a more "general" audience to see their reaction. So, I signed up for the Critiquenic of the Los Angeles-area Society of Children's Book Writers and Illustrators (SCBWI) that was held last weekend. This is an annual event, and small critique groups break up and read each others' work for picture books, middle grade, and YA books.
So, I got my general readers at this event, although the entire group was writing something with an element of the fantastic (light fantasy, urban fantasy, etc.), with the single exception of a really cool historical story for older teens.
The picture, by the way, is an illustration of Sarcosuchus, a 40-foot long Triassic crocodile - the infamous "supercroc." Point being, this beast isn't a direct ancestor of today's crocodilians, it's an ancient similar animal. Nature has recreated certain body plans over and over . . . even the clumsy reptilian side-leg arrangement has its benefits.
In my opinion, the average person is going to see this as a giant crocodile, end of story.
What were the advantages of presenting "To Kiss the Star" to a group of general readers? Well, none of them said it was like "The Ship Who Sang" - advantage #1. Also, they thought that the idea was original, and liked Melodie. However, some of them missed things that are clearly explicated in the text, suitable for "in genre" readers. For example, the story clearly states that Melodie has the opportunity to become a probe controller because she won the cripple lottery. That didn't register with some readers. Others didn't know how her voiceboard worked, even though she explained its workings in the story.
Her voiceboard is similar to the one used by Stephen Hawking:
" . . .David Mason, of Cambridge Adaptive Communication, fitted a small portable computer and a speech synthesizer to my wheel chair. This system allowed me to communicate much better than I could before. I can manage up to 15 words a minute. I can either speak what I have written, or save it to disk. I can then print it out, or call it back and speak it sentence by sentence. Using this system, I have written a book, and dozens of scientific papers. I have also given many scientific and popular talks. They have all been well received. I think that is in a large part due to the quality of the speech synthesiser, which is made by Speech Plus. One's voice is very important. If you have a slurred voice, people are likely to treat you as mentally deficient: Does he take sugar? This synthesiser is by far the best I have heard, because it varies the intonation, and doesn't speak like a Dalek. The only trouble is that it gives me an American accent."
So, the moral of this story is - the "reality" of the science in a story isn't as important as what the reader perceives as reality. This is basic storytelling 101, and I find this cognitive dissonance between in-genre SF and "regular" SF for general audiences fascinating. In-genre explanations usually focus on language - i.e. "special" sci fi terms that are "offputting" to the general reader and so-on. I have a feeling that I've hit on something that is much more a cause of SF not being picked up for general audiences than I've heard from others. Readers will accept almost any SFnal premise as long as it fits with the story and makes sense within the story. However, the story needs to make sense on a character and conflict basis - the characters have to be the right ones for the story, and the conflict needs to fit who those characters are. Above all, readers want to be able to relate to the characters, and the overall conflict needs to be something comprehensible - with "stakes" that the readers can understand.
That, I think, is why some of the very successful SF for young people in recent years, such as Suzanne Collins' Hunger Games, which is a post-apocalyptic story with a simple, yet frightening premise, have proven so popular.


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John Wick, Senior Vice President and General Manager, Mobile Transaction Services, discusses the latest developments with the innovative expansion of Syniverse's Real-Time Intelligence platform and LTE.
Line of Business leaders John Wick and Mary Clark discuss the advantages of Real-Time Intelligence for operators, addressing important needs such as managing bill shock and providing a seamless experience for end users.
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November 27, 2015
Knoxville (WVLT) - Rural Metro says they've added ambulances across Knox County to help speed up their response time.
They're posting one extra unit in Karns and Seymour, 24 hours a day.
They say they are also adding an advance life support unit in Gibbs during peak hours.
The new plan is their way to move toward better compliance with their contract with Knox County.
In May, they were penalized $97,500 over slow response times.
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North Fayette to start using new recycling carts April 21April 8, 2014 10:34 PM
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North Fayette has distributed new recycling carts to more than 5,000 homes and will begin accepting recyclables in the blue containers the week of April 21, township officials said tonight.
The public works department has a new truck with an automated arm for picking up and emptying the special carts.
All recyclables may be placed in the same container, including paper, glass, plastic and metal.
Details are available online at www.north-fayette.com/public-works/trash-recycling/recycling.
Andrea Iglar, freelance writer: email@example.com.


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General Climbing : Where in the Caribbean to g... : Post
Jan 21, 2010
our wedding at Torrent Falls, photo by Wes Allen
General Climbing : Climber Wedding Locations??... : Post
Jan 12, 2010
View of T-Wall westward in late December
TN : The Tennessee Wall
Mar 10, 2008
Close-up of second roof. I placed a TCU under the first roof and then got a little sketched pulling the moves for the second roof. I put a #3 stopper in a little seam, but it only fit halfway in. I do
TN : The Tennessee Wall : ... : Passages (5.8)
Feb 11, 2008
Great 8.
Peter L K : T-Wall December 07
Passages - a great 8. Pretty straight forward pro until the second roof.
View of wall looking west
Peter L K : personal
Feb 7, 2008


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Singapore to host India's international Academy Awards
Singapore is to host the fifth International Indian Film Academy (IIFA) Awards on May 22.
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PA301 - Ultra-high performance photoacoustic detector for solid, semi-solid, and liquid samples
PA301 - Ultra-high performance photoacoustic detector for solid, semi-solid, and liquid samples
The PA301 photoacoustic FTIR accessory improves laboratory productivity and safety by enabling extremely versatile and rapid analysis of solid, semi-solid, and liquid samples in any form without sample preparation.
Due to the ultra-high sensitivity of the Gasera novel cantilever sensor, high quality spectra can be obtained in just seconds unlike in other available photoacoustic accessories. In fact the PA301 is over 100x faster that other competing PA solutions in the market. Furthermore, ambient air can be used as the carrier gas to obtain a signal-to-noise ratio (SNR) that is still significantly better compared to other commercial photoacoustic detectors used with helium carrier gas.
The quickness and the ease of use make the PA301 a must-have accessory for every lab!
PA301 photoacoustic FTIR accessory consists of:
Technical notes
Application notes
Digital brochure
Application NoteS


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great bar clamp
By wooly
from hazlehurst ga
About Me Avid Do-It-Yourselfer
Comments about Pittsburgh 48 in. Aluminum Bar Clamp:
great for straight cuts and rip cuts
Bottom Line Yes, I would recommend this to a friend
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Performed like a champ
By home brews
from Temecula, Ca
worked great.....used 4 of them to clamp a 3'X 10' bar top together...
(3 of 3 customers found this review helpful)
LOVE these clamps!!!
By Wil's woodshop
from NYC
I own several sizes and I love them all. They're strong, they fit very well and the slide is smooth. Highly RECOMMEND!!
(1 of 1 customers found this review helpful)
Excellent Clamps
By Rayne
from Mount Dora, FL
I've had a couple of these for a few years and I have to say, these things are solid. They hold under pressure very well. I also agree on how HF is making money on these due to the quality. Keep it up!
(2 of 2 customers found this review helpful)
good clamps
By lui
from san jose ,CA
Good clamps.I hate and usually stay away from cheap stuff but clamps can get very expensive,specially if you need a lot of them.These clamps work great,they seam strong enough,light an easy to use,I dont see anything going wrong with them in the future,they look like they are well built.I dont understand how can they possibly make money selling this so cheap,it blows me away.Really good clamps.
(5 of 5 customers found this review helpful)
Very strong,light and easy to adjust.
By Old war horse
from Longview,Wa
Have 2 of these clamps and have had for a few years.Definitely have needed this length a few times over the years and these have always filled the bill.I got mine on a sale and also used a % off offer so they were really cheap.They are really light and easy to use and don't twist and warp under stress.Would tell anyone that these would be a great addition to any handymans tool cache.
Great value
By Gregjkm
from Charlotte NC
This clamp is great value for the money compares to competitors priced 3x's more. I for added rigidity fill the aluminum with a piece of wood
These work
By clamper
from austin
The clamp works well if it slips I drill a 1/4 inch hole so the catch would have more to catch on.
(1 of 2 customers found this review helpful)
By RX007
from Lakeland, Florida
it is a great value, but for fit ups where the pressure is great the head breaks.I glued up some boards for a project and clamped them together. One broke while going together and two more broke when I checked on it the next morning. I have a bunch of these and other styles in various sizes. They really let me down this time. I am going to get them warrantied tomorrow. I hope it was just a bad batch. Other than that I have had very good use from them.
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Date: 5 years ago
Runtime: 4:04
Views: 6,449
a day alone :)
am so horny right now!!!
masturbation, wet, tits, nipples, nippleclamps
Categories: Amateur, Big Boobs, Miscellaneous
All Comments
you sound so wet
You have such an awesome body. I hope you will post more hot video footage.
What in the Hell are you doing home alone, with a body like that, the door should always be openinggo
I love your sexy nipples.You make me cum so good.
Hope you get alot more days alone you are great
what a dirty little girl. you got my load.
delicious pinched silence -- deep sighing wet breath.
Sexy nipples and breasts!!!
I'm v horny too. Sexy nipples and breasts. Very nice
Sexy nipples and breasts! Very nice...
nice tits mami
more plz more
Beautiful video!
Very hot vid, looks like you had fun, can't wait for more
omg what an amazing video! you have SUCH PERFECT BREASTS!! fking delicious baby! and I love your tummy, and that smooth pretty pussy, all shaven like a good girl, LOVE IT! u make me want my cum in you So Bad!!
Delightfully eatible
Love to replace those fingers with my mouth & tongue!!
Omg you are so hot... i cant wait to see more
Those nipples are freakin' awesome !!! Wow, I want to satisfy you
You need your pussy sucked while the clamps are tight on your nipples!
Your very erotic~~~
Your nipples are so Hawt! The clamps make them so hard!
You need your pussy sucked while the clamps are tight on your nipples!
Your very erotic~~~
Wow!!!! What an exceptionally hot, hot video honey.... hope you post some more soon! Love hearing that heavy breathing, your sighs, seeing your hands play with your sweet gorgeous boobies and nipples... the clothespins were a hot extra treat... hearing the slippery noises as you played with your puss.... having you show off your wet fingers... mmmm... wished you had licked them for us.... please, please, post more! You're sooooo sexy!
that was hot!
OH my! That was a great video.