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Book your room at NH Milano Machiavelli
Standard Room, 1 Double or 2 Single BedsMax Occupancy: 2 guests (up to 1 child)
Superior Room, 1 Double or 2 Single BedsMax Occupancy: 2 guests (up to 1 child)
Standard Room, 1 Single BedMax Occupancy: 1 guest
Standard Double Room Single Use, 1 Double or 2 Single BedsMax Occupancy: 1 guest
Superior Double Room Single Use, 1 Double or 2 Single BedsMax Occupancy: 1 guest
4-star family-friendly hotel in Milan with a restaurant
Located in the heart of Milan, this family-friendly hotel is within walking distance of Indro Montanelli Public Gardens, Spazio Oberdan, and Planetario di Milano. Also nearby are Via della Spiga and Contemporary Arts Pavillion.
Hotel Features
In addition to a restaurant, NH Milano Machiavelli features a bar/lounge. Other amenities include a coffee shop/café and complimentary wireless Internet access.
Room Amenities
Televisions come with satellite channels. Guestrooms also feature complimentary wireless Internet access, air conditioning, and safes.Information missing or incorrect? Tell us!
Hotel Amenities
Hotel Amenities
The hotel offers a restaurant and a coffee shop/café. A bar/lounge is on site where guests can unwind with a drink. A complimentary breakfast is offered each morning. High-speed wireless Internet access is complimentary.
This 4-star property offers access to a business center and meeting rooms. 6 meeting rooms are available. This family-friendly hotel also offers multilingual staff, concierge services, and complimentary newspapers in the lobby.
- Babysitting or childcare (surcharge)
- Luggage storage
- Free WiFi
- 24-hour front desk
- Total number of rooms - 103
- Number of floors - 4
- Bar/lounge
- Business center
- Coffee shop or café
- Free newspapers in lobby
- Free breakfast
- Conference space
- Dry cleaning/laundry service
- Elevator/lift
- Laundry facilities
- Meeting rooms
- Multilingual staff
- Restaurant
- Safe-deposit box at front desk
- Number of meeting rooms - 6
- Number of buildings/towers - 1
- Concierge services
Available in all rooms: Free WiFi
Available in some public areas: Free WiFi
Room Amenities
- Television
- Satellite TV service
- Free WiFi
- Free cribs/infant beds
- Bathtub or shower
- Connecting/adjoining rooms available
- Soundproofed rooms
- Air conditioning
- Minibar
- Daily housekeeping
- Private bathroom
- Free toiletries
- Hair dryer
- Bidet
- Desk
- In-room safe
- Room service
Where to Eat
A complimentary buffet breakfast is served each morning between 7 AM and 10 AM.
Caffe Niccolo - This restaurant serves breakfast only. Reservations are required.
Room service is available.
To make requests for specific accessibility needs, complete the "Special or Accessibility Requests" section of "Trip Preferences" when you book your hotel.
- Accessible path of travel
- Accessible bathroom
- In-room accessibility
Hotel Policies
Check-in time starts at 3 PM
Minimum check-in age is 18
Check-out time is noon
Payment types
Pets allowed
You need to know
Extra-person charges may apply and vary depending on hotel policy.
Government-issued photo identification and a credit card or cash deposit are required at check-in for incidental charges.
Special requests are subject to availability upon check-in and may incur additional charges. Special requests cannot be guaranteed.
- A tax is imposed by the city: EUR 5 per person, per night, up to 14 nights. This tax does not apply to children under 18 years of age.
- Pet deposit: EUR 20.00
We should mention
Cash transactions at this property cannot exceed EUR 999.99, due to national regulations. For further details, please contact the property using information in the booking confirmation. Children 11 years old and younger stay free when occupying the parent or guardian's room, using existing bedding. The property has connecting/adjoining rooms, which are subject to availability and can be requested by contacting the property using the number on the booking confirmation.

subset: commoncrawl


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The District of Columbia is implementing provisions of the Affordable Care Act that increase payment rates for certain primary care services. To qualify for the increased rates, physicians must have a specialty designation of family medicine, general internal medicine or pediatric medicine and complete the Medicaid Primary Care Practitioners Self-Attestation Form.
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The Piano Music of Mendelssohn
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The Piano Music of Mendelssohn composed by Felix Bartholdy Mendelssohn (1809-1847). For piano. Piano Collections. Classic. Intermediate. Book. Published by Kevin Mayhew Publishers (KV.3611186).
A beautiful Kevin Mayhew publication which features 11 favorite pieces by Felix Mendelssohn. This outstanding edition includes Algretto; Opus 72, No.3; Andante Sostenuto; Opus 19, No.4; Barcarolle; Meditation; Opus 30, No.3; Romance; Opus 102, No.2; Scherzo; Opus 102, No.3 and more. This book will surely become one of your favorites!
- Pastorale Op 62 No 4 Performed by Felix Bartholdy Mendelssohn
- Andante Sostenuto Op 19 No 4 Performed by Felix Bartholdy Mendelssohn
- Scherzo Op 102 No 3 Performed by Felix Bartholdy Mendelssohn
- Barcarolle Performed by Felix Bartholdy Mendelssohn
- Allegretto Op 72 No 3 Performed by Felix Bartholdy Mendelssohn
- Meditation Op 30 No 3 Performed by Felix Bartholdy Mendelssohn
- Adagio Performed by Felix Bartholdy Mendelssohn
- Canzona Op 19 No 2 Performed by Felix Bartholdy Mendelssohn
- Andante Con Moto Op 72 No 4 Performed by Felix Bartholdy Mendelssohn
- Cavatina Op 102 No 6 Performed by Felix Bartholdy Mendelssohn
- Romance Op 102 No 2 Performed by Felix Bartholdy Mendelssohn
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Tenders and TurntablesComments2
this wiki
|This article is about the episode. You may be looking for the magazine story or the VHS.
- "Take care. You might stick too!"
"No fear! I'm not so fat as you!"
- — Gordon and James
|Tenders and Turntables
David Mitton
Britt Allcroft
Reverend W. Awdry
Ringo Starr (UK/US)
|Air date
November 27th,
|Previous episode
|Next episode
Tenders and Turntables is the fifteenth episode of the first season. In the US, this episode aired on the Shining Time Station episodes Whistle While You Work and Schemer's Robot.
Life is harder at the yard since Thomas left to run his branch line. With no tank engine to shunt or be the station pilot, Henry, James, and Gordon must shunt in the sidings and fetch their own coaches.
One blustery day, Gordon arrives at the other end of the line with his train and heads for the turntable. The turntable is by the sea, so the wind is very strong and unless an engine is perfectly balanced on the turntable, it becomes difficult to turn. Gordon is in a bad mood and is unable to get perfectly balanced. Neither his driver nor his fireman can get him to cooperate. After trying again and again, they give up and are forced to pull his next train tender first.
When Gordon arrives at the junction, a group of boys joke around and taunt Gordon by calling him a tank engine. Thomas, who is waiting at the junction, laughs and suggests that Gordon "scrap his tender and get a nice bunker". James flies by with his train and laughs at Gordon. Gordon warns James that he may stick as well, but James claims that he won't stick because he's not as fat as Gordon.
When James gets to the sheds, he carefully lines up on the turntable and his crew slowly rotates the turntable. But the strong wind has other ideas and begins to spin James around uncontrollably. Gordon arrives just in time to see the whole thing. When the turntable finally stops, James backs into the shed and says nothing, looking rather sick, dizzy and humiliated.
That night, Gordon, James, and Henry hold an indignation meeting. They decide it would be best, after the day's events, to go on strike.
- Thomas
- Henry
- Gordon
- James
- Annie and Clarabel (do not speak)
- Sir Topham Hatt (does not speak)
- Bertie (cameo)
- This episode is based on the story of the same name from The Railway Series book, Troublesome Engines with the opening dialogue from Henry and the Elephant.
- James' whistle after being spun on the turntable is absent in both Ringo Starr versions, but can be heard in all other versions.
- In the Railway Series, Henry has a mishap with a circus elephant and that, along with the problems in this episode, causes Gordon, Henry, and James to go on strike. In the television series, Henry's mishap occurred in the fourth season.
- Two freeze frames are used when Thomas talks to Gordon about pulling his train backwards and when James is in the shed by himself.
- A behind the scene photo from this episode shows that the Marklin engine was used.
- The episode may have been filmed alongside Troublesome Trucks, as Thomas can be seen in a behind the scenes photo, with the same trucks he was pulling in the opening shot of the latter. Also when the turntable stops spinning, it's pointed to the right end berth where James was seen in when the Fat Controller had shut him up.
- When the engines say, "We get no rest! We get no rest!", there are two orange coaches behind Henry. But in the next scene when the coaches say, "You're lazy and slack! You're lazy and slack!" Henry is coupled up to three coaches.
- When the narrator says, "The big stations at both ends of the line...", Henry is shunting the same coaches as he was when James came past shunting his.
- James' brake coach is backwards when he rushes through Elsbridge.
- Gordon' left buffer is crooked when he is talking with Thomas at Elsbridge.
- In the close-up of James spinning on the turntable a crewmember's face is reflected in his paintwork.
- When the turntable stops spinning it connects the last berth on the right, but when James reverses the turntable leads to the middle line.
- When Thomas and Gordon are at Elsbridge, Clarabel is facing forwards.
- When James spins on the turntable, the trees in the background are not blowing even when the narrator says there is wind.
In Other Languages
|Kohlewagen und Drehscheiben
|Coal Wagons and Turntables
|Store tog og snuplasser
|Big Trains and Turning Places
|Brazilian Portuguese
|O Descontentamento dos grandes
|The Discontent of the Large
|Vagones Y Plataformas
|Wagons and Platforms
|Troi mewn Cylchoedd
|Turning in Circles
|Big Engines and Turntables
|Parowozy i Obrotnice
|Locomotives and Rotors
|A rakoncátlan mozdony
|The Unruly Engine
|Kolen Wagons en draaitafels
|Coal Wagons and Turntables
|Locomotive Arrabbiate
|Angry Locomotive
|Tarjous Moottorit "Merry-Go-Round
|Tender Engines' Merry-Go-Round
|Tenderi i okretaljke
|Tenders and Turners


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The following is an abstract for the selected article. A PDF download of the full text of this article is available here. Members may download full texts at no charge. Non-members may be charged a small fee for certain articles.
Thermal Processing of o-Terphenyl: A Raman Study
Volume 47, Number 4 (April 1993) Page 458-462
Biswas, A.
Raman spectra from o-terphenyl sealed in glass capillary tubes were acquired over temperatures ranging from 233 K to 343 K. Over this temperature range, o-terphenyl can exist in the solid-crystalline, molten, supercooled-liquid, and amorphous-glassy states. Representative structure-sensitive spectra are presented along with a qualitative description. The lattice spectral feature occurring at a Raman shift of 123 cm−1 displays abrupt changes in profile and intensity as melting and glass transition occur. The intensity ratio of the C-C stretching 996-cm−1 line and C-H stretching line at 1008 cm−1 displays a change related to the transformation of the ordered-crystalline phase to the disordered-liquid or glassy state. At a Raman shift of 1162 cm−1 the solid-crystalline state shows a splitting due to the effect of the crystal field. The possibility of using these structure-sensitive Raman characteristics for in situ diagnostics during materials processing is discussed.


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Bulldogs sweep Dickinson State, end Blue Hawks season at conference tourney
GREAT FALLS, Mont., — The Dickinson State volleyball team's season ended as it began, on a loss.
The Blue a fell to Western Montana 25-20, 27-25, 25-13 Thursday night in the play-in match of the Frontier Conference Volleyball Tournament.
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This is not the most recent version of the article. View current version (8 OCT 2013)
Intervention Review
Hyaluronate for temporomandibular joint disorders
Editorial Group: Cochrane Oral Health Group
Published Online: 20 JAN 2003
Assessed as up-to-date: 13 NOV 2002
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Database Title
Additional Information
How to Cite
Shi Z, Guo C, Awad M. Hyaluronate for temporomandibular joint disorders. Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD002970. DOI: 10.1002/14651858.CD002970.
Publication History
- Publication Status: Edited (no change to conclusions)
- Published Online: 20 JAN 2003
This is not the most recent version of the article. View current version (08 OCT 2013)
Temporomandibular joint disorders (TMD) refer to a group of heterogeneous pain and dysfunction conditions involving the masticatory system, reducing life quality of the sufferers. Intra-articular injection of hyaluronate for TMD has been used for nearly 2 decades but the clinical effectiveness of the agent has not been summarized in the form of a systematic review.
To assess the effectiveness of intra-articular injection of hyaluronate both alone and in combination with other remedies on temporomandibular joint disorders.
Search methods
Intensive electronic and handsearches were carried out. The Cochrane Oral Health Group's Trials Register (September 2001), CENTRAL (The Cochrane Library 2001, Issue 3), MEDLINE (1966 to May 2001), PubMed (up to March 2002), EMBASE (1980 to August 2001), SIGLE (1980 to December 2001), CBMdisc (1983 to July 2001, in Chinese) and Chinese Medical Library were searched. All the Chinese professional journals in the oral health field were handsearched and conference proceedings consulted. There was no language restriction.
Selection criteria
Randomized or quasi-randomized controlled trials (RCTs), with single or double blind design, testing the effectiveness of hyaluronate for patients with temporomandibular joint disorders.
Data collection and analysis
Two review authors independently extracted data, and three review authors independently assessed the quality of included studies. The first authors of the selected articles were contacted for additional information.
Main results
Seven studies were included in the review. Three studies, including 109 patients with temporomandibular disorders, compared hyaluronate with placebo. Long term effects (3 months or longer) are in favour of hyaluronate for the improvement of clinical signs/overall improvement of TMD (RR = 1.71, 95% CI: 1.05, 2.77) from two of the studies (n = 71). However, this conclusion was not stable enough at sensitivity analysis.
Three studies provided data from 124 patients for the comparison of hyaluronate with glucocorticoids (one study also included a placebo group). Hyaluronate had the same short term and long term effects on the improvement of symptoms, clinical signs or overall conditions of the disorders as glucocorticoids.
When comparing the effect of arthroscopy or arthrocentesis with and without hyaluronate, results were inconsistent. Hyaluronate had a potential in improving arthroscopic evaluation scores.
Mild and transient adverse reactions such as discomfort or pain at the injection site were reported in the hyaluronate groups. No quality of life data were reported
Authors' conclusions
There is insufficient, consistent evidence to either support or refute the use of hyaluronate for treating patients with TMD. Further high quality RCTs of hyaluronate need to be conducted before firm conclusions with regard to its effectiveness can be drawn.
Plain language summary
Hyaluronate for temporomandibular joint disorders
There is insufficient evidence to either support or refute the use of hyaluronate for treating patients with temporomandibular joint disorders.
When the joint between lower jaw and the base of the skull is not working well it can led to movement problems, noises (clicking or grating), muscle spasms or pain (temporomandibular joint disorders (TMD)). Arthritis can also affect the joint. A range of treatment options are available including the injection of substances such as glucocorticoids or hyaluronate into the joint. Hyaluronate is sometimes used for osteoarthritis of the knees or hips. The review found that there is not enough evidence to judge whether hyaluronate injections into the joint are helpful for people with TMD. Reported side-effects were mild and transient. No data on quality of life were reported.
進階電子搜尋和手動搜尋資料庫。搜尋了The Oral Health Group's Trials Register (September 2001)、The Cochrane Library CENTRAL database (Issue 3, 2001)、MEDLINE (1966~2001.05)、PubMed (2002.03)、EMBASE (1974~2001.08), SIGLE (1980 – 2001.12), CBMdisc (1983 – 2001.07;中文)和中文醫學圖書資料庫。並手動搜尋所有口腔保健領域的中文專業期刊與相關的研討會議論文集。沒有語言限制。
回顧性文獻篩選取得7篇研究。其中3篇研究含109位顳顎關節障礙症患者,為玻尿酸治療和安慰劑的比較。在2篇研究中,評估長期效果時(3個月或更長時間), 顯示玻尿酸有助於改善顳顎關節障礙症的臨床徵候/全面改善。(RR = 1.71, 95%CI: 1.05, 2.77)(n = 71)。然而,此結論對於敏感度分析而言還不夠穩定。有3篇研究提供124位患者來比較玻尿酸與糖化皮質類固醇的效果。(其中一篇研究甚至包含安慰劑群組)。對於改善症狀、臨床徵候或障礙症的整體狀況,玻尿酸的短期和長期效果都與糖化皮質類固醇相似。當比較有無玻尿酸合併治療的關節內視鏡檢查或關節穿刺時,其結果並不一致。玻尿酸治療能改善關節鏡的評估指標。玻尿酸群組在注射區域會有輕度和短暫不良反應,如不舒服或疼痛。無文獻提供有關生活品質的資料。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。


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We just stayed for a night while on a cross border shopping trip and the TownPlace didn't fail to live up to our expectations. It was again conveinent, quiet and check in was friendly and quick. Two small things with regards to cleanliness one being there was some black gunk in part of our shower, it didn't really make it unusable but it was a little unsightly and here were a couple of stains on the sofa in the room.
One thing that really stood out was the service as we had a small issue in the middle of the night and needed a 24 hour pharmacy. Regan at the front desk was great and when I called down he said he would have directions and maps for me if I can to the desk. I went down and he had it all printed off and even gave me directions to avoid some overnight construction that as going on. I felt he really went above an beyond.
Thanks again TownPlace for a great stay.
- Reservation Options:
- TripAdvisor is proud to partner with Expedia, Orbitz, Travelocity, Booking.com, Marriott, Priceline, Hotels.com, TripOnline SA, Odigeo and Tingo so you can book your TownePlace Suites Seattle Everett/Mukilteo reservations with confidence. We help millions of travelers each month to find the perfect hotel for both vacation and business trips, always with the best discounts and special offers.
- Also Known As:
- Towneplace Suites Seattle North/Mukilteo Hotel Mukilteo
- Towneplace Suites Mukilteo


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|View all free ACCA lectures >>
|This P2 lecture is based on OpenTuition course notes, view or download here>>
Technical ProblemsIf you have technical problems with downloading notes or watching lectures etc.. please visit the support page>>
MikeLittle says
The opening inventory is DEBITED to statement of profit or loss – whatever makes you think that it's credited?
The figure for the statement of financial position is the one on the debit side below the total lines
fahim231 says
sorry I meant is the closing* inventory credited to the profit and loss?
MikeLittle says
Correct, closing inventory is a deduction made within the cost of sales calculation. Effectively therefore it is credited to statement of profit or loss
fahim231 says
hello sir – in relation to your inventory T account – is opening inventory credited to the income statement? and which figure of the account would you put in the balance sheet?
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LONDON (Reuters) - People given cholesterol-fighting statin drugs before heart surgery are far less likely to die or suffer complications afterwards, German researchers said on Wednesday.
The analysis of more than 31,000 patients provides some of the strongest evidence yet of the benefits of statins before heart surgery but it also found that too few doctors are prescribing them, they said in the European Heart Journal.
"This is the first big summary of all the existing studies about people undergoing cardiac surgery," said Oliver Liakopoulos, a researcher at the University of Cologne, who led the study.
"What our study underscores is the need to increase statin therapy."
Statins are the world's top-selling drugs and are highly effective at cutting the risk of heart attack and stroke.
The medicines have also made fortunes for drug companies like Pfizer, which sells the market leader Lipitor, and AstraZeneca, which makes Crestor. Cheaper generic versions are now increasingly available.
The review of 19 studies found that the odds of dying after heart surgery were 43 percent lower for people who had been on statins. The drugs also lowered the post-operative risk of irregular heartbeats by 33 percent and stroke by 26 percent.
But only a little more than half of the 31,000 people in the studies got statins before surgery.
"More patients should receive statins," Liakopoulos said in a telephone interview.
The researchers could not say what the right dose should be or how long people should take statins because patients in the studies were on the drugs anywhere from a few days to a few months.
The study also showed the drugs did not seem to make any difference when it came to post-operative heart attacks or kidney failure.
"We can't say how much or how long is optimal but these are things that need to be looked at in further studies," Liakopoulos said.
(Reporting by Michael Kahn; Editing by Maggie Fox, Paul Bolding)
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Healthy, high-fat diet may be a pipedream
A much-hyped new study, conducted with just 150 participants, calls for us to "embrace fat" — even the saturated kind. The alleged benefits? Weight loss and, most incredibly, healthier hearts. But the truth is the jury is still out. Commentary


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Home Creek Elegant Chrome Table Lamp
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Counterfeit bill passed; police ask for assistance identifying suspect
WORTHINGTON -- The Worthington Police Department is asking for assistance from the public in identifying a woman in a surveillance photo.
According to authorities, the woman was involved in allegedly passing a counterfeit bill March 3.
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The Multi Commodity Exchange Ltd (MCX), India's premier commodity exchange, has set a price band of Rs.860-1,032 a share for its initial public offering (IPO) to raise around Rs.660 crore.
MCX is offering about 6.4 million shares, which will open on February 22 and close on February 24.
With this IPO, MCX will become the first Indian bourse to list its shares on an exchange.
MCX's majority shareholder, Financial Technologies India Ltd, and other stakeholders, including state-owned State Bank of India and Bank of Baroda, will sell part of their holdings through the IPO. Morgan Stanley, Citigroup and Edelweiss Capital are the book-runners for the share sale.
Keywords: Multi Commodity Exchange Ltd


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Possible Answer
Mark Jeffries was the guest on Monday, February 23, on 12 News at Noon. Jefferies was speaking on the play, "What the Bellhop Saw" at the Friendlander's Center in ... - read more
Destiny's servers will go live on Monday, September 8, at 12 noon GMT / 7am EDT / 4am PDT. Anyone who gets hold of the game early – including press reviewing ... - read more
Please vote if the answer you were given helped you or not, thats the best way to improve our algorithm. You can also submit an answer or search documents about 12 noon edt to gmt.


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September 2013, TruckingInfo.com - Test Drives
By Tom Berg
Time is money, and that's the essence of a front-discharge mixer. It drives right up to where concrete's needed and, after the driver adds chute extensions, starts offloading. Terex/Advance Mixer in Fort Wayne, Ind., makes rear-discharge drums for mounting on conventional truck chassis, but its heart is in the front-discharge version that it builds all-new and as glider kits.
Tags: Terex, Test Drive, Vocational, Mixer
We offer e-newsletters that deliver targeted news and information for the entire fleet industry.
The expert, Mark Betner from CITGO, will answer your questions
The expert, Rence Oliphant from Hendrickson, will answer your questions
Drones And the Future of Package Delivery
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Ultimate Test Drive Video: Brain and Brawn
Ultimate Test Drive Video: Small Block, Big Load
Webasto Releases Advanced Heater Controls
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Yee Haw...guess what....???!!!!!!
Our Walmart is reopening the fabric dept....
One of the girls who worked the fabric dept before told me it's coming back.
Keep your fingers crossed that it will be nation wide.
Hope it's true. I hate the Porter Ranch Walmart as they are now a sporting goods,pet goods,scrapbooking goods,etc. Trying to force all those stores out of business. It was a nice store when it opened but I rarely go there now. Joanne's is nearby & Sporting Goods store & Pet shop,how mean to try to get rid of them & so have bunch of empty stores & yours is only 1 left. I'm not for ghost town shopping centers. We have plenty of those already. Just hope they don't force out Joanne's, only yardage store around these days. Got to drive miles to get spool of thread.(where the thread is good stuff & doesn't break constantly)! Jan


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Description from the manager
- Studio
- 1 bathrooms
- Sleeps 3
- Apartment
Bedrooms: 0
Bathrooms: 1
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Type: Apt. / Condo00116SREB A2(3) - Srebreno
Description from the manager
BASIC INFORMATION: Type of property: apartments. Number of studio apartments and their capacity is 2XSA(3), SA(2).
FACILITIES AND EQUIPMENT: free parking within the property, courtyard.
DISTANCES: The distance to the sea is 300 metar. The distance to the town center is 300 metar. Grocery store - 150 m. Closest restaurant - 150 m. Closest infirmary/hospital - 150 m. Airport - 14 km.
BASIC FEATURES: Type of studio apartment: SA2. 3 bed/s for adults. Capacity of the studio apartment (adults) (3). The category is 3 star/s. Size of the studio apartment is: 30 m2. The studio apartment is on the first floor. Kitchen, living room and beds are in the same ...Read more
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00116SREB A2(3) - Srebreno
Srebreno, Southern Dalmatia, Croatia
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Croatia - Riviera Dubrovnik - Srebreno - 00116SREB A2(3)
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is it compatible with D7000 ?
does the cable work with Nikon D7000 model ?
- Asked by Eisa A from Sharjah
- 11-Dec-2012
ioShutterSLR Controller for Nikon Cameras
Product No Longer Available
2 Answers from the Community
Yes it does. ioShutterSLR for Nikon has two connectors, the 10pin for pro-spec Nikon cameras and the rectangular -DC2 connector that your D7000 has.
- Answered by James M
- 11-Feb-2013
Yes, my Nikon version came supplied with cable terminated in MC-DC2 type plug - small rectangular USB looking thing...
- Answered by Bob M
- 27-Dec-2012


text: We visited in January 2015 and found great food in very comfortable surroundings & at a reasonable price. The Ramen was excellent, filling enough in itself but we also tried the tempura sushi. Thanks to the chef, Akira and our welcoming waitress Reeta. We will certainly visit again on our next... read more


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Nearly a decade in and "Harry Potter" filmgoers can't get enough — a fact which was proved by the massive box-office showing of the latest flick in the franchise, "Harry Potter and the Deathly Hallows – Part 1."
Powered by a $24 million haul from the movie's midnight showings, which was the third highest midnight-screening debut of all time, the film netted $61.1 million on Friday. Fans sporting "Potter" garb and brandishing pretend wands have swarmed theaters, and experts predict that the penultimate installment in the series could ring up over $100 million its debut weekend.
Action junkies were still able to get their fix at theaters with "Unstoppable," which arrived in second place on Friday. Denzel Washington and Chris Pine's locomotive-themed adventure pulled down a little over $4 million dollars. The film's haul now stands at around $33 million as the thriller kicks off its second weekend on screens.
Third-place flick "Megamind" was hot on the heels of "Unstoppable." The comedian-packed animated hit scored $3.7 million as the flick, which stars Will Ferrell and Tina Fey, headed into the weekend. The movie's total estimated haul is skyrocketing toward $100 million, with $97 million picked up since its debut in early November.
Zach Galifianakis and Robert Downey Jr.'s cross-country trek "Due Date" continued to cruise along in the top five. Audiences handed over $2.9 million Friday to check out the odd couple's journey to deliver Downey's character in time for the birth of his child. The Friday figure kicks the movie's estimated haul to around $66 million.
"The Next Three Days" opened in fifth place on Friday. Russell Crowe's turn as a determined husband who plots to spring his wife — played by Elizabeth Banks — from jail scored $2.2 million on screens.
Check out everything we've got on "Harry Potter and the Deathly Hallows – Part 1," "Unstoppable" and "Megamind."
For breaking news, celebrity columns, humor and more — updated around the clock — visit MTVMoviesBlog.com.


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Tomoko Hayashi1, Lucinda Beck1, Cyprian Rossetto1, Xing Gong1, Osamu Takikawa2, Kenji Takabayashi1, David H. Broide1, Dennis A. Carson1 and Eyal Raz1
1University of California, San Diego, Department of Medicine, La Jolla, California, USA. 2Central Research Institute, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Address correspondence to: Eyal Raz, University of California, San Diego, Department of Medicine, 9500 Gilman Drive, La Jolla, California 92093-0663, USA. Phone: (858) 534-5444; Fax: (858) 534-5399; E-mail: firstname.lastname@example.com.
Published July 15, 2004Submitted: February 9,
2004; Accepted: May 18,
Epidemiological evidence points to the inverse relationship between microbial exposure and the prevalence of allergic asthma and autoimmune diseases in Westernized countries. The molecular basis for this observation has not yet been completely delineated. Here we report that the administration of certain toll-like receptor (TLR) ligands, via the activation of innate immunity, induces high levels of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of tryptophan catabolism in various organs. TLR9 ligand–induced pulmonary IDO activity inhibits Th2-driven experimental asthma. IDO activity expressed by resident lung cells rather than by pulmonary DCs suppressed lung inflammation and airway hyperreactivity. Our results provide a mechanistic insight into the various formulations of the hygiene hypothesis and underscore the notion that activation of innate immunity can inhibit adaptive Th cell responses.
The dramatic increase in the prevalence of allergic and autoimmune diseases over the last 30 years suggests an important contributory role for environmental factors (1). The so-called hygiene hypothesis, first suggested by Strachan (2), proposes that a major source of microbial, Th1-like immune provocations has been lost with the decreased incidence of many infectious diseases due to vaccinations, the use of antibiotics, and other modern public health practices. The deficiency in Th1-like provocations leads to an increase in Th2-biased immune responses toward environmental allergens (3–6) and consequently to an increase in allergic asthma. While the evidence for a role of certain viral and bacterial exposure in protecting against allergic asthma is fairly strong (7, 8), the hygiene hypothesis in its Th1/Th2 formulation is unable to explain the protective role of helminth infection (a Th2-biased condition) in the development of allergic asthma (9). Furthermore, it also ignores the increase in the prevalence of Th1-mediated organ-specific autoimmune diseases that has been observed in affluent Westernized societies (10). These mechanistic inconsistencies of the hygiene hypothesis have been recently challenged by the "counter-regulation hypothesis." This hypothesis proposes that microbial infections induce regulatory T cell (Treg) responses, which display tolerogenic activities and therefore inhibit both Th2- and Th1-immune-mediated immunopathologies (10). Although the counter-regulation hypothesis provides an attractive explanation, the molecular pathways induced by microbial exposure and tolerogenic responses in the host have not yet been identified.
Toll-like receptors (TLRs) are expressed mainly on macrophages and DCs and recognize signature microbial products. Although the interaction of TLRs with their microbial ligands activates innate immunity to mount a defense mechanism, i.e., upregulation of costimulatory molecules and the production of chemokines and cytokines (11), it also elicits a counter-regulatory response. In particular, others and we have demonstrated that bacterial DNA, its synthetic immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) analogs (TLR9 ligands), and LPS (TLR4 ligand) induce indoleamine 2,3-dioxygenase (IDO) expression in vivo and in vitro (12, 13).
IDO, the rate-limiting tryptophan-catabolizing (trp-catabolizing) enzyme, is induced by IFNs (14) and enhanced by IL-10 but is suppressed by IL-4 and IL-13 (15). IDO is expressed in various cell types, including fibroblasts, macrophages, DCs, trophoblasts (14), and epithelial cells (16). DCs expressing IDO contribute to the generation and maintenance of peripheral tolerance by depleting autoreactive T cells (17–19) and by inducing Treg responses (20). The IDO-specific inhibitor 1-methyl-DL-tryptophan (M-trp) reverses these effects (20, 21).
As IDO inhibits T cell reactivity (22) and induces a Treg response (20), we hypothesized that the induction of IDO by certain TLR ligands could provide the missing link between microbial exposure and the inhibition of allergic asthma and organ-specific autoimmunity. Our studies presented below indicate the inhibitory role of TLR ligand–induced IDO in both Th2-mediated and Th1-mediated lung inflammation.
Differential induction of IDO by ISS-ODN in various organs. We initially evaluated IDO enzymatic activity in various organs after i.v. ISS-ODN administration. Increased IDO enzymatic activity was observed in the lung, small intestine, colon, uterus, and heart. In contrast, we did not detect a statistically significant increase in IDO activity in the spleen, kidney, pancreas, or brain (Table 1). The kinetics of IDO activity in the lung and the spleen are presented in Figure 1A. Although we did not detect an increase in IDO activity in spleen homogenates, when we fractionated the splenocytes into subpopulations we clearly detected induction of IDO activity by ISS-ODN in CD11c+ cells (<1% of total splenocytes) (Table 2). The induction of IDO in the lungs was similarly provoked by subcutaneous, intraperitoneal, or intratracheal administration of ISS-ODN (Figure 1B). IDO expression in the lung tissue was detected in alveolar and bronchial epithelial cells as well as in cells with macrophage and/or DC features, as shown by immunohistochemical staining (Figure 1, C–J).
Differential induction of IDO by ISS-ODN. (A) BALB/c mice were injected i.v. with ISS-ODN (20 μg) or mutated ODN (M-ODN) (20 μg), and the lungs and spleen were harvested on days 1, 2, 3, 4, 7, 10, 14, and 21. The kinetics of IDO enzymatic activity in the lung and spleen homogenates were determined (KYN assay) and plotted. *P > 0.05 vs. PBS-treated or M-ODN–treated mice. (B) ISS-ODN (20 μg/mouse) was delivered to BALB/c mice via different routes: subcutaneously (s.c.), intraperitoneally (i.p.), i.v., or intratracheally (i.t.). Four days later, IDO enzymatic activity in the lung and spleen homogenates was assessed (KYN assay). Data are means ± SEM of results from four mice per group and represent one of three independent experiments that yielded similar results. (C–J) Immunohistochemistry of lung tissue. Naive mice (C, E, G, and I) and mice that were injected with ISS-ODN (D, F, H, and J) were sacrificed 4 days after injection. (C and D) Staining with rabbit anti-IDO Ab. Arrows indicate IDO-positive cells (D). (E and F) Staining with F4/80 and anti-IDO Ab. *F4/80–positive single cell (blue) or IDO-positive single cell (brown) (E). Arrows indicate double-positive cells (F). (G–J) Staining with anti-keratin Ab and anti-IDO Ab. *Anti-keratin–positive single cell (brown) or anti-IDO–positive single cell (blue) (G and I). Arrows indicate double-positive cells (H and J). Original magnification: C, ×100; D, ×200; E–J, ×400.
Differential induction of IDO by ISS-ODN in various organs
Induction of IDO by ISS-ODN in splenic CDD11c+ cells
Induction of IDO activity is mediated by IFN-γ and IL-12. ISS-ODN is known to induce TNF-α, IL-6, IL-12, and IFNs in mice (23). To elucidate the role of ISS-ODN–induced cytokines in IDO expression, we analyzed IDO activity in TNF-α, IL-6, IL-12p40, IFN-γ, IFN-α/β receptor (IFN-α/βR), or IL-1β receptor (IL-1βR) KO mice after ISS-ODN administration. An induction of IDO enzymatic activity in the lungs was detected in TNF-α, IL-6, IFN-α/βR, and IL-1βR KO mice but was absent in IL-12p40 and IFN-γ KO mice (Table 3 and Figure 2A).
The impact of ISS-ODN–induced cytokines on IDO expression levels. (A) Western blot of lung homogenates (40 μg protein) from TNF-α, IL-12p40, and IFN-γ KO mice and WT mice that were injected i.v. with ISS-ODN (20 μg). (B–D) Lung CD11c+ cells were isolated from WT or IFN-γ KO (γ-KO) mice (five mice per group) that were injected i.v. with ISS-ODN (ISS) (20 μg/mouse). IDO expression was assessed by RT-PCR (B), Western blot (C), and measurements of enzymatic activity (KYN assay) (D). *P < 0.05, ISS-ODN–treated vs. PBS-treated group.
Induction of IDO in lungs by ISS-ODN in various cytokine KO mice
The above results indicate that IL-12p40 and/or IFN-γ are necessary for IDO induction. The induction of IDO by IL-12 is mediated by IFN-γ, and IFN-γ was shown to directly induce IDO expression in the lung tissue (24). In contrast to those observations, ISS-ODN induced IDO transcript in bone marrow–derived DCs (BMDCs) from IFN-γ KO mice similar to that induced in BMDCs from WT mice (Figure 2B). Furthermore, lung CD11c+ cells isolated from IFN-γ KO mice after in vivo ISS-ODN administration display a comparable level of IDO expression and enzymatic activity, as was detected in lung CD11c+ cells isolated from WT mice under the same conditions (Figure 2, C and D) (<1% of total pulmonary IDO activity). These data indicate that the induction of IDO in pulmonary DCs (CD11c+ cells) by ISS-ODN is independent of IFN-γ. In contrast, induction of high levels of IDO enzymatic activity in whole lung tissue, which is composed mainly of alveolar and bronchial epithelial cells (CD11c+), is dependent on IFN-γ.
We next assessed the relationship between low levels of pulmonary IDO activity and the ability of ISS-ODN to inhibit experimental asthma in OVA/alum–sensitized, OVA-challenged, ISS-ODN–treated IL-12p40 or IFN-γ KO mice. These KO mice, unlike their WT controls, were resistant to ISS-ODN treatment and developed airway hyperreactivity (AHR; provocative concentration of methacholine200 [PC200], or the concentration of MCh needed to induce a 200% increase of enhanced pause [Penh] from baseline measurements]) and eosinophilic inflammation (Table 4).
Inhibition of experimental asthma by ISS-ODN in IFN-g and IL-12 KO mice
IDO inhibits experimental asthma. The data above could suggest that ISS-ODN–induced pulmonary IDO plays a role in the inhibition of experimental asthma. To validate this assumption, we administered the IDO inhibitor M-trp to OVA/alum–sensitized, ISS-ODN–treated WT (BALB/c) mice. M-trp implantation competitively inhibited in vivo IDO activity as assessed by kynurenine (KYN) level in the lungs (Figure 3A). Furthermore, M-trp significantly reduced the effects of ISS-ODN on experimental asthma as shown by increases in AHR (measurements of %Penh and airway resistance in Figure 3, B and C, respectively), eosinophilic infiltration (Figure 3D), and levels of IL-5 and IL-13 in the bronchoalveolar lavage (BAL) fluid (Table 5). In contrast, M-trp did not interfere with the Th2-mediated pulmonary inflammation (Figures 3 and 4 and Table 5), suggesting that the M-trp effects are not due to some nonspecific antiinflammatory activities of this compound.
Reversal of ISS-ODN–induced inhibition of experimental asthma by M-trp. BALB/c mice (five mice per group) were sensitized by subcutaneous OVA/alum on day 0 and day 7. On days 16 and 21, mice were challenged intranasally with 5 μg OVA. ISS-ODN (50 μg) was given intraperitoneally on day 16. AHR was measured on day 22. M-trp or placebo (pb) pellets were implanted (day 15). Naive mice and OVA-immunized, PBS-challenged mice served as controls. (A) In vivo KYN levels in lung homogenates. (B) AHR measurements (%Penh). (C) Measurement of airway resistance. (D) Total cell number of eosinophils, lymphocytes, neutrophils, and macrophages in the BAL fluid. *P < 0.05, ISS-ODN–treated (50 μg/mouse) vs. PBS-treated group. **P < 0.05, ISS-ODN–treated mice with M-trp pellets vs. ISS-ODN–treated mice with placebo (pb) pellets.
IDO induces cell death of a Th2 cell line and inhibits experimental asthma in an adoptively transferred SCID mouse model. SCID mice (six mice per group) were implanted with M-trp pellets, adoptively transferred with 5 × 106 cells of a Tg Th2 cell line (DO11.10) per mouse, challenged with OVA (50 μg), and treated with ISS-ODN (50 μg/mouse). (A) IDO enzymatic activity in the lung homogenates. (B and C) The numbers of adoptively transferred Th2 cells in the lungs (B) and spleens (C) were calculated by staining with anti-CD4 and anti–T cell receptor Ab (KJ 1-26; FACS). (D and E) The percentage of cell death of the Th2 cell line in lungs (D) and in spleens (E) was determined by staining with 7-AAD (FACS). The total number of cells in the organ was calculated by multiplication of the total number of live cells by the percentage of CD4+/DO11.10 TCR+ cells in the cell suspension. The percentage of 7-AAD+ cells was determined in the CD4+/DO11.10 TCR+ gate (30). *P < 0.05, OVA-challenged, PBS-treated mice (with placebo and M-trp pellets) vs. nonchallenged group. **P < 0.05, ISS-ODN–treated mice with placebo pellets vs. PBS-treated mice with placebo pellets. ***P < 0.05, ISS-ODN–treated mice with M-trp pellets vs. ISS-ODN–treated mice with placebo pellets.
Th2 cytokine levels in the BAL fluid in experimental asthma
IDO controls the pulmonary survival of an OVA-specific Th2 cell line in vivo. To explore whether the inhibition of experimental asthma by ISS-ODN is mediated by IDO-induced cell death of a Th2 cell line, we adoptively transferred an in vitro–differentiated, OVA-specific transgenic (Tg) Th2 cell line (DO11.10) to SCID mice that were treated with ISS-ODN, or with ISS-ODN and M-trp, and then challenged with intranasal OVA. Increased IDO activity was observed in the lung homogenates of ISS-ODN–treated SCID mice (Figure 4A). The administration of ISS-ODN, with or without M-trp, inhibited antigen-specific (OVA-specific) T cell trafficking into the lung (Figure 4B) but not into the spleen (Figure 4C). ISS-ODN administration enhanced cell death of this Th2 cell line in the lungs, and this enhancement was reversed by M-trp (Figure 4D). The induction of cell death of the Th2 cell line was organ-specific, since no difference in cell death of the transferred Tg Th2 cell line was observed in the spleens of recipient mice (Figure 4E). Figure 4, D and E, represent a snapshot of the cell death seen on day 5 after ISS-ODN administration. In addition, the administration of ISS-ODN reduced the levels of Th2 cytokines (IL-4, IL-5, and IL-13) in the BAL fluid, and this reduction was partially reversed by the IDO inhibitor M-trp (Table 6).
Th2 cytokine levels in the BAL fluid of adoptively transferred SCID mice
IDO controls the pulmonary survival of an OVA-specific Th1 cell line but not of B cells in vivo. IDO activity has already been demonstrated to inhibit activated Th1 cells via the induction of apoptosis (14, 25). Furthermore, IDO activity was recently shown to inhibit the rejection of pulmonary allografts by recipient T cells (26). To explore whether ISS-ODN–induced IDO also controls pulmonary Th1 cell survival, we adoptively transferred in vitro–differentiated, OVA-specific Tg Th1 cell line (DO11.10) or WT B cells to SCID mice (Figure 5). In contrast to the Th2 transfer, OVA challenge in these mice significantly increased IDO activity in the lungs, and the administration of ISS-ODN further enhanced this activity (Figure 5A). The in vivo administration of ISS-ODN did not further increase the direct KYN measurement in the lung homogenate; this reflects that the actual in vivo KYN levels were determined by the in vivo trp availability (Figure 5B). As expected, M-trp implantation significantly reduced in vivo KYN levels in the lungs (Figure 5B). Neutrophil infiltration in the BAL fluid, an indicator of a Th1 lung inflammation (27), was significantly enhanced by M-trp implantation (Figure 5C). In addition, OVA challenge significantly enhanced cell death of the Th1 cell line in the lung (Figure 5D), but not in the spleen (Figure 5E), and the implantation of M-trp reversed this effect (Figure 5D). In contrast, the survival of B cells transferred to SCID mice was not affected in the lungs (Figure 5F) or in the spleen (Figure 5G) after OVA challenge and ISS-ODN administration. Similar data were obtained in experiments designed to evaluate B cell death in an antigen-specific model using OVA-immunized BALB/c mice (data not shown).
IDO induces cell death of a Th1 cell line, but not B cell death, in the lungs of adoptively transferred SCID mice. SCID mice (six mice per group) were implanted with M-trp pellets, adoptively transferred with 5 × 106 cells of a Tg Th1 cells line (DO11.10) per mouse, challenged with OVA (50 μg), and treated with ISS-ODN (50 μg/mouse). (A and B) IDO activity (A) and in vivo KYN levels (B) in the lung homogenates. (C) Neutrophil infiltrates in BAL fluid. (D and E) The percentage of cell death of the Th1 line in lungs (D) and in spleens (E) was assessed. *P < 0.05 vs. nonchallenged group. **P < 0.05, PBS-treated vs. ISS-ODN–treated mice. ***P < 0.05, mice with M-trp pellets vs. mice with placebo pellets. (F and G) B cells (5 × 106 per mouse) were transferred i.v. to SCID mice treated with ISS-ODN or PBS and challenged with OVA for 4 days (six mice per group). The percentage of B cell death in lungs (F) and in spleens (G) was determined by 7-AAD staining.
Induction of IDO and inhibition of experimental asthma by certain TLR ligands. Inhibition of experimental asthma has been documented for ISS-ODN (28) and for high but not for low doses of LPS (29). To determine the relationship between IDO induction by various microbial TLR ligands and the inhibition of experimental asthma, we first measured pulmonary IDO activity after administration of TLR ligands. As shown in Figure 6, only ISS-ODN and high-dose LPS (50 μg) induced IDO enzymatic activity in the lungs. However, the high dose of LPS was associated with 70% mortality. We attributed this effect to LPS toxicity mainly in the lung tissue. IDO enzymatic activity correlated with reduced AHR (i.e., increased PC200) and with reduced eosinophil infiltration in the BAL fluid (Table 7).
Induction of IDO by various TLR ligands. BALB/c mice (four mice per group) were injected i.v. with ISS-ODN (20 μg), LPS (50 or 1 μg), poly I:C (pI:C, 20 μg), Pam3Cys-Ser-(Lys)-4-3HCl (P3C, 25 μg), or flagellin (Flag, 50 μg). IDO activity in lung homogenates was assessed 4 days after injection by KYN assay. IDO activity is expressed as fold induction over the activity measured in PBS-injected mice (100%). *P < 0.05 vs. OVA-immunized and PBS-treated mice.
Inhibition of experimental asthma by TLR ligands
Our results indicate that the induction of pulmonary IDO by ISS-ODN protects the lung from Th2-driven lung inflammation and experimental asthma. Likewise, the induction of IDO in the SCID/Th1 transfer model attenuated Th1-driven lung inflammation. However, in this case, in contrast to the Th2 transfer model, the inhibition of lung inflammation by ISS-ODN administration was buffered by the intrinsic ability of Th1 cells to induce pulmonary IDO activity after OVA challenge, most probably via the production of IFN-γ, a potent transcriptional activator of IDO (24). In fact, our data suggest that the induction of pulmonary IDO by antigen-specific Th1 cell lines negatively controls their own survival and their inflammatory response, i.e., M-trp implantation reduced Th1 cell death (Figure 5D) and increased neutrophil infiltration, a marker of pulmonary inflammation (Figure 5C).
IDO can inhibit Th-mediated lung inflammation in multiple ways: (a) it depletes trp availability in the microenvironment (22); (b) it promotes the generation of various toxic trp metabolites, which induce Th cell death (30, 31); (c) it generates other compounds, e.g., formylkynurenine, through a reaction that removes oxygen radicals at inflammatory sites (32); and (d) in the case of Th2-mediated lung inflammation, it inhibits the generation of 5-hydroxytryptamine, a potent airway constrictor (33). These unique and synergistic activities of IDO likely collaborate to inhibit Th2-mediated experimental asthma and to attenuate Th1-mediated pulmonary inflammation. These effects were organ-specific and cell type–specific, since IDO did not affect the survival of adoptively transferred Tg Th cell lines in the spleen (Figures 4 and 5) and did not alter B cell survival in the lung or the spleen (Figure 5). The cell death seen in Figure 4, D and E, and Figure 5, D–G, represents only a fraction of the total cell death resulting from ISS-ODN–induced IDO, since these numbers reflect only a snapshot of the cell death seen on day 5 after ISS-ODN administration.
The induction of IDO by ISS-ODN in BMDCs and lung CD11c+ cells did not depend on IFN-γ (Figure 2). In contrast, the high level of IDO enzymatic activity observed in the lung tissue (i.e., epithelial cells) (Figure 1) after ISS-ODN administration was dependent on IFN-γ (Figure 2). Indeed, in other studies we confirmed that IFN-γ induced IDO expression and IDO enzymatic activity in the murine respiratory epithelial cell line MLE-15 (data not shown). This high enzymatic activity of IDO in the lung epithelial cells rather than in the lung DCs appears necessary to inhibit the Th2-mediated lung inflammation (Figures 3 and 4, Tables 4 and 5). A similar mechanism has been observed in the placenta (34), where high tissue levels of IDO inhibit maternal T cell responses against the developing fetus (21).
Our results also indicate that activation of innate immunity by ISS-ODN, via the induction of IDO, suppresses lung inflammation in the adoptive transfer models. These models rule out the generation of CD4+CD25+ Treg or of Tr1 cells, thereby eliminating their contribution to the inhibition of lung inflammation via cognate interaction or via their secretion of IL-10 (35). The transfer models, therefore, establish the fundamental contribution of activated innate immunity to the inhibition of Th2- and Th1-mediated lung inflammation. We have previously demonstrated that this protective effect is transient (36) and therefore may require a periodic exposure to immunostimulatory DNA (ISS-DNA; i.e., bacterial DNA) in order to maintain the inhibition of allergic phenotype in a sensitized host. However, epidemiological evidence indicates that the exposure to microbial agents in early childhood provides long-term protection against allergic asthma, suggesting that there is an induction of a memory, adaptive immune response. Treg cells were recently proposed to mediate this protection (10). In this respect, recent studies have also demonstrated a crucial role for IDO-producing DCs in the induction of a Treg response (19). Thus, the exposure to certain microbial agents or to their signature compounds (e.g., TLR ligands) can provide an immediate and/or long-term, IDO-related protective effect against Th2- and Th1-driven inflammation. The immediate protective effect is mediated by innate immunity; is organ-specific, i.e., in the lung, placenta, and most probably other organs, as shown in Table 1; and is driven by high levels of IDO enzymatic activity in nonimmune cells. This high level of IDO activity generates a hostile and cytopathic microenvironment for the infiltrating Th cells. In contrast, the long-term protective effect induced by microbial agents (including helminths) or their signature compounds is mediated by adaptive immunity (10). It is initiated by low levels of IDO enzymatic activity in DCs, which elicit effector and memory Treg responses that counter-regulate proinflammatory T cell responses.
Our results also provide insight into recent data documenting the differential effects of LPS on the induction of experimental asthma. While administration of low doses of LPS did not prevent the induction of experimental asthma, administration of high doses inhibited its development (29). As is presented here, high doses but not low doses of LPS induced pulmonary IDO enzymatic activity. Likewise, other TLR ligands, such as Pam3Cys-Ser-(Lys)-4-3HCl (P3C; TLR2 ligand), poly I:C (pI:C; TLR3 ligand), and flagellin (Flag; TLR5 ligand), did not induce pulmonary IDO activity and did not provide an immediate protection against experimental asthma (Figure 6 and Table 7).
Why do the lungs have a special ability to produce high levels of IDO upon stimulation with microbial products such as bacterial DNA? A potential answer is based on the unique physiological role of the lung. This organ has evolved to maintain its gas-exchange function while interacting with airborne microorganisms. The lung can develop strong, organ-specific antimicrobial activity while at the same time limiting the potential damage inflicted on the lung parenchyma by subsequent inflammatory processes. IDO has antimicrobial properties against a variety of intracellular pathogens, such as parasites (e.g., Toxoplasma gondii) (37), bacteria (e.g., Listeria monocytogenes) (38), mycobacteria (e.g., Mycobacterium avium) (12), and viruses (e.g., cytomegalovirus) (39). The inhibition of intracellular growth of these microorganisms can occur (a) by depletion of intracellular levels of the rarest amino acid, trp, which is essential for their growth, and/or (b) by the generation of antimicrobial trp metabolites. Interestingly, by the very same mechanisms, IDO inhibits Th cell–mediated inflammatory responses and therefore limits the potential damage to lung function. A similar rationale can be applied to IDO induction in the small intestine and the colon (Table 1).
In summary, the induction of IDO by certain microbial TLR ligands results in immediate and long-term immunoregulatory activities. In certain aspects this induction of IDO provides a biochemical and an immunological basis for the hygiene and the counter-regulatory hypotheses. However, additional pathways of innate immunity are activated by other microbial products and could promote immunoregulatory functions in the host. One such innate pathway is via DC-SIGN, a C-type lectin expressed on DCs (40), which, upon ligation with viral, bacterial, mycobacterial, fungal, or helminth-derived carbohydrate structures, induced the secretion of IL-10, an immunosuppressive cytokine, which also promotes a Treg cell response (41). Thus, the activation of other pathways of innate immunity may also contribute to the inverse association between microbial exposure and the prevalence of allergic and autoimmune diseases. The identification of such novel microbial products allows for the application to modern medicine of lessons initially learned through the hygiene hypothesis.
Animals. Mice were purchased from The Jackson Laboratory (Bar Harbor, Maine, USA). IFN-α/βR KO mice were purchased from B&K Universal Ltd. (East Yorkshire, United Kingdom). All animal procedures followed the University of California, San Diego, animal-care guidelines.
Reagents. ISS-ODN (5′-TGACTGTGAACGTTCGAGATGA-3′) and mutated ODN (M-ODN) (5′-TGACTGTGAAGGTTAGAGATGA-3′) were purchased from Trilink Biotechnologies (San Diego, California, USA). P3C was purchased from EMC Microcollections GmbH (Tübingen, Germany), Flag was kindly provided by J. DiDonato (Cleveland Clinic Foundation, Cleveland, Ohio, USA) (42), and LPS and pI:C were purchased from Sigma-Aldrich (St. Louis, Missouri, USA). OVA and various trp metabolites were purchased from Sigma-Aldrich.
Measurement of IDO mRNA levels and enzymatic activity. IDO mRNA levels were measured by RT-PCR using the sense primer 5′-TTATGCAGACTGTGTCYTGGCAACTG-3′ and the antisense primer 5′-TTTCCAGCCAGACARATATATGCGRAG-3′, as previously described (12). We used two measurements to evaluate IDO activity. First, maximal IDO activity was indirectly determined by incubation of various organ homogenates with an excess of exogenous trp (780 μM) as a substrate in the reaction buffer for 30 minutes in vitro (43). The resulting KYN levels in the reaction homogenates were measured colorimetrically, and the IDO activity was expressed as nanograms KYN per milligrams protein per 30 minutes (43). Second, to determine the impact of the IDO-competitive inhibitor M-trp on IDO activity in vivo, we directly assessed KYN levels in lung homogenates. The resulting IDO activity in these organs was expressed as nanograms KYN per milligrams protein. Protein concentrations were determined using a BCA protein assay kit (Pierce Chemical Co., Rockford, Illinois, USA).
Culture of BMDCs and isolation of pulmonary and splenic CD11c+ DCs. BMDCs were prepared from BALB/c or IFN-γ KO mice as previously described (42). Single-cell suspensions of lung or spleen were prepared by collagenase digestion as previously described (44). The DC population was initially enriched by discontinuous density gradient centrifugation using OptiPrep (Axis-Shield PoC AS, Oslo, Norway) according to the manufacturer's instruction. Low-density cells in the interface were harvested, and CD11c+ cells were positively isolated using anti-CD11c magnetic beads (Miltenyi Biotec Inc., Auburn, California, USA). The CD11c+ population was greater than 90% of the total cells as determined by FACS analysis. High-density cells were collected and served as a CD11c– cell population.
Experimental asthma. Airway inflammation was induced by a protocol previously described (45) with minor modifications. In brief, mice (BALB/c, IFN-γ KO, and IL-12 KO) were sensitized by subcutaneous injection of 20 μg OVA absorbed with 500 μg alum (Alhydrogel; Brenntag Biosector AS, Federikssund, Denmark) per mouse in saline on day 0 and day 7. On days 16 and 21, mice were challenged intranasally with 5 μg OVA per mouse. In some groups, ISS-ODN (50 μg/mouse) or one of various TLR ligands was given intraperitoneally 1 day before OVA challenge (day 16). Twenty-four hours after the last challenge (day 22), mice were subjected to measurements of airway responsiveness and sacrificed by CO2 asphyxiation. In experiments using M-trp, pellets containing either M-trp (80 mg, 10 mg/d release; Innovative Research of America, Sarasota, Florida, USA) or placebo were surgically implanted under the dorsal skin 1 day before ISS-ODN treatment (day 15). Naive mice and OVA/alum–sensitized, PBS-challenged mice served as controls.
After the mice were sacrificed, BAL cells, lungs, and spleen were recovered. The total number of cells in BAL were counted, and BAL cells were stained with Wright-Giemsa stain for the differential count. Percentages of eosinophils, lymphocytes, neutrophils, and macrophages were determined microscopically using standard morphological criteria (36). The total cell number of each cell type was calculated from the total cell number and the percentage of each cell type in the differential cell count. The level of each cytokine (IL-4, IL-5, and IL-13) in the BAL fluid was determined by ELISA (BD Biosciences - Pharmingen, San Diego, California, USA).
Airway responsiveness to methacholine (MCh) was assessed 24 hours after the final OVA challenge using a single-chamber, whole-body plethysmograph obtained from Buxco Electronics Inc. (Wilmington, North Carolina, USA), as previously described (45). The Penh, a dimensionless value, which correlates well with pulmonary resistance measured by conventional two-chamber plethysmography in ventilated mice (45), was used to monitor airway responsiveness. In the plethysmograph, mice were exposed for 3 minutes to nebulized PBS to establish base-line Penh values and were subsequently exposed to increasing concentrations of nebulized MCh (Sigma-Aldrich) in PBS using an Aerosonic ultrasonic nebulizer (DeVilbiss Health Care Inc., Somerset, Pennsylvania, USA). Following each nebulization, recordings were taken for 3 minutes. The Penh values measured during each 3-minute sequence were averaged and are expressed for each MCh concentration as the percentage of base-line Penh values following PBS exposure (45). The PC200 concentration of MCh describes the provocative concentration of MCh that induced a 200% increase of Penh from base-line measurements (36).
To determine airway resistance, mice were anesthetized and a midcervical skin incision was made to expose the trachea, which was cannulated with an 18-gauge blunt needle. The airway resistance was measured with an in-line pressure transducer and software program (SCIREQ Inc., Montreal, Quebec, Canada) in intubated and ventilated mice connected to a rodent ventilator, as previously described (46). Airway resistance measurements were taken at base line, after nebulized PBS, and after each increasing concentration of nebulized MCh (46, 47).
Preparation of OVA-specific Th1 and Th2 cell lines. CD4+ T cells were positively selected from splenocytes of Tg DO11.10 mice using a MACS CD4+ T cell isolation kit (Miltenyi Biotec Inc.). Naive CD4+ T cells (5 × 105) were cultured with 5 × 106 irradiated splenocytes in RPMI 1640 supplemented with 0.3 μM OVA-specific peptide (OVA323–339) for 7 days (48). For in vitro Th1 differentiation, recombinant IL-12 (40 ng/ml; BD Biosciences - Pharmingen) and neutralizing anti–IL-4 mAb (11B11, 10 μg/ml; BD Biosciences - Pharmingen) were added to the culture media. For in vitro Th2 differentiation, recombinant IL-4 (25 ng/ml; BD Biosciences - Pharmingen) and anti–IL-12 mAb (C17.8, 10 μg/ml; BD Biosciences - Pharmingen) were added to the culture media. The commitment to a Th1 or Th2 phenotype was confirmed by CFSE labeling of the T cells after the initial OVA stimulation (more than five cell divisions as determined by FACS) and by measurement of their cytokine profile in the supernatants after OVA stimulation (49): in vitro–differentiated Th1 cell lines secreted high IFN-γ (2.83 ± 0.09 ng/ml) and undetectable IL-4, IL-5, and IL-13 (<50 pg/ml), whereas in vitro–differentiated Th2 cell lines secreted high IL-4 (79.5 ± 7.7 ng/ml), IL-5 (10.7 ± 1.0 ng/ml), and IL-13 (21.7 ± 1.7 ng/ml) and undetectable IFN-γ (<50 pg/ml).
Adoptive transfers and induction of Th1- and Th2-mediated lung inflammation. In vitro–differentiated OVA-specific Th1 or Th2 cell lines (5 × 106) were transferred i.v. to SCID mice on day 0 as previously described (48). Mice that received the Th2 cell line were given intranasal OVA (50 μg) daily for 4 days (days 1–4) before being analyzed, whereas mice that received the Th1 cell line were given intranasal OVA (50 μg) twice, once on day 3 and once on day 4. On day 5, mice were sacrificed, BAL fluid was collected, and the lungs were perfused with PBS and harvested for further studies. BAL cells were Wright-Giemsa–stained (36), and single-cell suspensions of spleen and lung were prepared by being passed through a sterile cell strainer.
In some experiments, B cells were isolated from the spleens of BALB/c mice using MACS CD19 microbeads (Miltenyi Biotec Inc.), and 5 × 106 purified B cells were then transferred i.v. into SCID mice treated with or without ISS-ODN and then intranasally challenged with OVA as described for Th2 transfer. To study antigen-specific B cell death, BALB/c mice were immunized four times, on days 0, 7, 14, and 21, with OVA (20 μg) absorbed with alum (500 μg). Mice were challenged with OVA twice, once on day 26 and once on day 31. Mice were then sacrificed 24 hours after the last challenge. Lung cells and splenocytes were prepared and stained for FACS analysis (see below).
FACS analysis, Western blot, and histological examination. Cells were stained for CD4 (BD Biosciences - Pharmingen) and DO11.10 T cell receptor (Caltag Laboratories, Burlingame, California, USA). B cells were identified with anti-B220 Ab (BD Biosciences - Pharmingen). Staining with 7-amino-actinomycin D (7-AAD; BD Biosciences - Pharmingen) was performed according to the manufacturer's instructions. The stained cells were analyzed using a FACSCalibur flow cytometer (BD Biosciences - Immunocytometry Systems, San Jose, California, USA). Western blot was performed using rabbit anti-IDO antiserum (43) following standard methods.
Ten-micrometer cryosectioned lung tissues were stained with anti–F4/80 (Serotec Inc., Raleigh, North Carolina, USA) followed by biotin anti-rat Ab (BD Biosciences - Pharmingen), and visualized by alkaline phosphatase–streptavidin (Jackson ImmunoResearch Laboratories Inc., West Grove, Pennsylvania, USA) and Vector Blue (Vector Laboratories Inc., Burlingame, California, USA). These sections were subsequently stained with rabbit anti-IDO Ab (50) followed by HRP–anti-rabbit Ab (Jackson ImmunoResearch Laboratories Inc.) and then developed with NovaRed (Vector Laboratories Inc.). Sections were also stained with rabbit anti-keratin Ab (DakoCytomation California Inc., Carpinteria, California, USA) followed by DAKO EnVision System HRP–anti-rabbit Ab (Dakocytomation California Inc.) and then visualized with NovaRed. These sections were subsequently stained with anti-IDO Ab, followed by alkaline phosphatase–anti-rabbit Ab, and then developed with Vector Blue (Vector Laboratories Inc.).
Statistics. Data were compared using the Student's t test. A P value of less than or equal to 0.05 was considered statistically significant.
We thank Nissi Varki (University of California, San Diego) for histological evaluation and Robert Coffman (Dynavax Technologies Corp.) for helpful comments. This work was supported by NIH grants AI40682, DK35108, AR47360 (to E. Raz), and AI56453 (to D. Carson). E. Raz is supported by a grant from Dynavax Technologies Corp.
Nonstandard abbreviations used: airway hyperreactivity (AHR); 7-amino actinomycin D (7-AAD); bone marrow–derived DC (BMDC); enhanced pause (Penh); flagellin (Flag); IFN-α/β receptor (IFN-α/βR); IL-1β receptor (IL-1βR); immunostimulatory sequence oligodeoxynucleotide (ISS-ODN); indoleamine 2,3 dioxygenase (IDO); kynurenine (KYN); methacholine (MCh); 1-methyl-dl-tryptophan (M-trp); Pam3Cys-Ser-(Lys)-4-3HCl (P3C); poly I:C (pI:C); regulatory T cell (Treg); transgenic (Tg); tryptophan (trp).
Conflict of interest: The authors have declared that no conflict of interest exists.
Copyright © 2015
American Society for Clinical Investigation


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No. You need to use the Play To application to select pictures for sharing.
Nokia Lumia 625 - Can I share pictures with Play To from the Picture hub?
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Posted August 6, 2006
Lamar Herrin (Professor of Creative Writing and Contemporary Literature, Cornell University) presents Romancing Spain, a memoir and love story about his relationship with the Spanish woman whom he married 30 years ago. Obstructed by a church and bureaucracy, Lamar nevertheless pursued her, earning her love and trust even as he adjusted to the complexities of an Iberian nation steeped in centuries of tradition. Enthusiastically recommended reading, Romancing Spain is a simply beautiful and inspiring true-life story of love, romance, perseverance and eventual triumph which is brilliantly presented with emotion and empathy.Was this review helpful? Yes NoThank you for your feedback. Report this reviewThank you, this review has been flagged.
Posted June 5, 2006
He looks back thirty years to when he first met the woman he married and thinks how romantic he was (and still is) as he informed her that she is his Sancho Panza. Aparo reminded Lamar that Panza was squat (she is not he swears) and dumber than Quixote for following his lead. Now three decades later, three offspring later he ponders whether he fell in love with the Spanish culture as epitomized by his beloved Aparo or by falling in love with Aparo he fell in love with the Spanish culture. He knows even now the clash between his in your face Kentucky Protestant upbringing and her a gentile Catholic Spaniard. Thus as a sort of second honeymoon, the pair retrace the roots of their love by traveling the countryside together while the author ponders whether he was ROMANCING SPAIN when he courted Aparo or romancing Aparo and found Spain either way Lamar Herrin knows that three decades ago he found his soulmate. --- This terrific lyrical biography combines a beautiful declaration of love with a wonderful look at Spain from an American expatriate and the wife he still cherishes. Readers will appreciate the travelogue on three levels: a true love story and salute to his wife, a guide to Spain, and a deep philosophical debate. Mr. Herrin¿s thought provoking question as to whether it is Spain, which shaped his beloved, or Aparo is delicately and eloquently developed so that the audience will ponder what dynamics shaped the roots of those they cherish. ROMANCING SPAIN is an insightful romantic philosophical treasure. --- Harriet KlausnerWas this review helpful? Yes NoThank you for your feedback. Report this reviewThank you, this review has been flagged.


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A lot of Colombians are learning to invest in the New York exchange Market. They want to learn all about it, but most of the local traders do not how to teach them how to become real good at it.
Mar 22, 2013. 02:43 AM | 0 Likes |Link to Comment
It is real hard to perform scalping trading at local exchange Bolsa De Valores de Colombia (BVC), because of the voumen.
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I am a Colombian and it is real painful for me to see people from other countries coming to Colombia to start a business here. i have helped a lot of people to do that. Most of them were deceived. For instance they were not told about those big lines at the Dian ( taxes and customs department) Any time you have to updated the nit ( your company ID number) you have to do a long line and sometimes you do not have the proper documentation, because you did not know about, then you have to go and bring the proper documentation. Mostly all the papers have to be authenticated by a notary, this means that you are wasting a lot of time. There is another fact: crime, mot of the businesses have to pay an amount of money to criminal bands supposedly by protection and you cannot go to the police because there are a lot policemen who are crooked.
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Friedrich Broadens Seasonal Lineup With Air Purifier Launch
Tuesday March 18th, 2014 - 3:43PM
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Toyota Sequoia
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SUM UP: Superfast guilty pleasure. RATING: ***1/2


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Experimental off dock drop yard at the Port of Los Angeles could help speed containers.
The federal agency alleges shipments did not include relevant documents and were improperly packaged and labeled.
Violations outlined in the report include copyright piracy and trademark counterfeiting.
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I had Contact Check working well. However I just found today that the "Other" output was not routing to the next stage.
Are you maybe saying that I should fabricate a John Doe entry with an empty as you show? My accidentally-empty entry should have filled that function if that is the case. However that entry had a phone number. I could make one with no phone number, but I doubt that is what you are suggesting.I have been thinking that the "Other" output of the CONTACT CHECK call control would be used when there was no match of a number to the Contacts list. I thought I tested for that.
To test I suggest you add a contact with your own cellphone number, the name doesn't matter but set the Contact Type to blank.Route the Other tab to a voicemail and call your Anveo phone number from your cellphone. You should hit the voicemail.The Other tab works fine for me, both with Contacts having the Contact Type blank and for callers not in my Contacts.
It appears to be working well....
Am I accurate ?


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Mom's Someone Like You Personalized Heart Jewelry Box
Mother Personalized Photo Box
Personalized Mirror Trinket Box for Mom
Wood Italian Angel Music Box
Harmonious 22 Note Double Heart & Roses Musical Jewelry Box
Personalized Silver-Plated Heart Box
Personalized Photo Jewelry Box with Poem
Personalized Unique Grandma Jewelry Box
Burl Walnut Flower Musical Jewelry Box
Pink Rose Romantic Music Jewelry Box
Majestic Silver Musical Egg Trinket Box
Dad's Personalized Keepsake Box
Lavender Heart Shaped Music Jewelry Box with Floral Inlay
Perfect Gifts, Music boxes and Jewelry boxes, many, many songs!


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Archinect - News 2015-03-29T05:41:21-04:00 http://archinect.com/news/article/80596440/bolles-wilson-transforms-historic-hanomag-u-boat-hall-into-stylish-retail-outlet BOLLES+WILSON transforms historic Hanomag 'U-Boat Hall' into stylish retail outlet Justine Testado 2013-08-29T14:45:00-04:00 >2013-09-02T19:47:18-04:00
 Bolles+Wilson was commissioned to redesign the historic Hanomag "U-Boat Hall" into an RS+Yellow Furniture Outlet in Hanover, Germany—yet another example in the repurposing of unused industrial spaces and fusing the past with the present.

 The contemporary furniture pieces and the U-Boat Hall's warehouse atmosphere are an interesting juxtaposition, and both vie for visitors' attention. Wooden flooring and bright-colored accents contrast against the rusty columns of the structure, an intended U-boat production site that halted construction in 1944. A brick wall on one side of the building's interior adds hip appeal that complements the outlet store's colorful inventory. On the other hand, the structure's original components—in addition to its enormous size—are hard to ignore, almost to the point where it becomes the main showpiece.

 What do you think of B+W's redesign? Scroll down to see some images and more details.

 ↑ Interior of the U-Boat Hall. Photo by Olaf Mahlstedt. © ...
 http://archinect.com/news/article/79854198/architecture-student-converts-school-bus-into-cozy-home Architecture Student Converts School Bus Into Cozy Home Archinect 2013-08-19T19:36:00-04:00 >2013-08-26T20:15:38-04:00
School buses are so much fun. The springy seats, the awkward-to-open windows [..]—it all hearkens back to a time in your life when you were younger, happier and worry-free. But did you ever imagine living in one? Hank Butitta did. By his last semester at architecture school, Butitta had grown weary of doing projects that only existed on paper, ones that were destined to be filed away and forgotten. He got sick of making things that nobody cared about. So what did he do? He bought a school bus.

<!DOCTYPE html PUBLIC "-//W3C//DTD HTML 4.0 Transitional//EN" "http://www.w3.org/TR/REC-html40/loose.dtd"> <meta> http://archinect.com/news/article/65023089/winner-of-the-2012-sleep-european-hotel-design-award-hotel-valentiner-hof-by-noa Winner of the 2012 SLEEP European Hotel Design Award: Hotel Valentiner Hof by noa* Alexander Walter 2013-01-07T15:44:00-05:00 >2013-01-08T08:28:42-05:00
At the annual SLEEP European Hotel Design Awards, the project "Hotel Valentiner Hof" in Castelrotto, Italy was recently named the 2012 winner in the category "Conversion And/Or Extension Of An Existing Hotel Building." Architects of the hotel conversion was the young firm noa*, based in Bolzano in Northern Italy.

<!DOCTYPE html PUBLIC "-//W3C//DTD HTML 4.0 Transitional//EN" "http://www.w3.org/TR/REC-html40/loose.dtd"> <meta>


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First - Does subroutines require GLSL 4.0+? So it unavailable in GLSL version of OpenGL ES 2.0?
I quite understand what multi-pass shaders are.
Well what is my picture:
- Draw group of something (e.g. sprites) to FBO using some shader.
- Think of FBO as big texture for big screen sized quad and use another shader, which, for example, turn texture colors to grayscale.
- Draw FBO textured quad to screen with grayscaled colors.
Or is this called else?
So multi-pass = use another shader output to another shader input? So we render one object twice or more? How shader output get to another shader input?
For example
glUseProgram(shader_prog_1);//Just plain sprite draw
glBindTexture(GL_TEXTURE_2D, /*some texture_id*/);
//Setting input for shader_prog_1
glDrawArrays(GL_TRIANGLE_STRIP, 0, 4);
//Disabling arrays, buffers
glUseProgram(shader_prog_1);//Uses same vertex, but different fragment shader program
//Setting input for shader_prog_2
glDrawArrays(GL_TRIANGLE_STRIP, 0, 4);
Can anyone provide simple example of this in basic way?