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Daily State of the Markets
Friday Morning - March 25, 2011
Good morning. As traders reached for some caffeinated assistance in perusing the early morning headlines on Thursday, they probably were thinking that it might be best to play the game from the short side. Once again the news flow bordered on depressing as Moody's had downgraded 30 Spanish banks, Portuguese 2-year bonds yields were soaring to their highest level since 1999, CDS spreads were blowing out, there were opposing tanks lined up in the streets of Yemen, there was steam coming out of a couple reactor buildings at Dai-ichi, and the mess in Libya continued unabated - this despite NATO forces announcing that the Libyan military had been all but destroyed.
So, what was the response to all of that bad news? Apparently it was, "Buy 'em!" For the second day in a row, traders simply shrugged their shoulders in response to the headlines and focused on the good stuff such as some strong earnings (Red Hat and Micron led the charge here) and continued improvement in initial unemployment claims. And by the time the closing bell rang at the corner of Broad and Wall, the question of the day was: Bad news? What bad news?
I know I've given our friends in the bear camp a hard time this week, but you've got to figure that it has been tough to be short lately. You see, just when it looked like the bulls were in trouble and most technical indicators were snapping like toothpicks, the bulls found a way to rebound when nothing horrific happened in Fukishima, Japan. And while the glass-is-half-empty gang didn't mind the quick pop, they probably are none too happy that the much ballyhooed "retest" of the lows has failed to materialize so far.
But since we all live in glass houses in this business, that's probably quite enough of the stone throwing for this morning. Our primary point is that the last six trading days has been a prime example of why it is soooo important to stay in tune with what the market IS doing as opposed to what you think it ought to be doing. I know I've said this more times than anyone cares to count, but it is vital to understand that this game isn't about being right - it's about making money. And the best way I've found to consistently make money in the stock market is to check your ego at the door and try to figure out what is driving prices each and every day.
While it would be easy to suggest that the recent tape action as well as Thursday's close above an important resistance zone is likely to lead to higher prices (and that the end-of-quarter window dressing may also lend a hand next week), we would be remiss if we didn't point out that the banks have been a real drag on the market lately. And the bottom line is if the BKX doesn't perk up pretty soon and join the party, our furry friends might just have something to hang their hats in the near future.
From a chart standpoint, it is clearly positive that the S&P, Dow, and NASDAQ all managed to break through their respective lines in the sand Thursday. But let's also keep in mind that the volume hasn't been stellar, that many of our internal momentum indicators aren't exactly singing a happy tune at the moment, and that the recent highs would be a logical point for the bears to try and get back in the game. So, while it has been enjoyable to see some green on the screens over the past week and a half, we would advise holding off on ordering the party favors for a while longer.
Sticking with the technical theme for a moment longer, the boys in the bull camp have been pointing out this week that the sentiment indicators have backed off of their extreme readings recently and that the market is no longer overbought. In short, this means that if traders decide to continue shrugging their shoulders and mumbling "what bad news?" these indicators suggest that there might be some room to run.
Turning to this morning... Despite more steam/smoke coming out of reactors at Dai-ichi, word that Portugal will need an €80 billion bailout, and reports that Ireland's banks need €27.5 billion as early as next week, earnings from Oracle and perhaps some momentum from the recent sessions has the futures pointing modestly higher in the early going.
On the Economic front... The government's final revision of the nation's fourth quarter GDP shows the economy grew at an annualized rate of +3.1% during the quarter, which was above the consensus expectations for a growth rate of +2.8%.
Thought for the day: Best of luck on this Friday and be sure to enjoy the weekend!
Pre-Game Indicators
Here are the Pre-Market indicators we review each morning before the opening bell...
- Major Foreign Markets:
- Australia: +0.96%
- Shanghai: +1.07%
- Hong Kong: +1.06%
- Japan: +1.07%
- France: +0.09%
- Germany: +0.15%
- London: +0.11%
- Crude Oil Futures: +$0.02 (May contract) to $105.62
- Gold: +$1.60 to $1436.50
- Dollar: higher against the Yen, Euro and Pound
- 10-Year Bond Yield: Currently trading at 3.403%
- Stocks Futures Ahead of Open in U.S. (relative to fair value):
- Dow Jones Industrial Average: +41
- NASDAQ Composite: +5.66
Wall Street Research Summary
- Holly Corp (HOC) - BAC/ML
- Mednax (MD) - BAC/ML
- Imax (IMAX) - Canaccord Genuity
- Priceline.com (PCLN) - Estimates and target increased at Citi
- Altera (ALTR) - Citi
- Seaspan (SSW) - Deutsche Bank
- Colonial Properties (CLP) - Goldman Sachs
- Zebra Technologies (ZBRA) - JPMorgan
- Aetna (AET) - Leerink Swann
- Alexion Pharmaceuticals (ALXN) - Target increased at Oppenheimer
- Akamai (AKAM) - Piper Jaffray
- CarMax (KMX) - RW Baird
- JetBlue Airways (JBLU) - Soleil Securities
- Charming Shoppes (CHRS) - Soleil Securities
- Las Vegas Sands (LVS) - UBS
- Lorillard (LO) - Target increased at UBS
- Research In Motion (RIMM) - BAC/ML, Deutsche Bank, RW Baird
- Best Buy (BBY) - Citi
- SAIC (SAI) - Credit Suisse
- Urban Outfitters (URBN) - Citi, Janney
- Harmony Gold (HMY) - HSBC
- United Health (UNH) - Leerink Swann
- ADTRAN (ADTN) - Morgan Keegan
- Devon Energy (DVN) - Morgan Stanley
- Qualcomm (QCOM) - Estimates reduced at Oppenheimer
Long positions in stocks mentioned: UHS
For more "top stock" portfolios and research, visit TopStockPortfolios.com
The opinions and forecasts expressed herein are those of Mr. David Moenning and may not actually come to pass. Mr. Moenning's opinions and viewpoints regarding the future of the markets should not be construed as recommendations. The analysis and information in this report and on our website is for informational purposes only. No part of the material presented in this report or on our websites is intended as an investment recommendation or investment advice. Neither the information nor any opinion expressed nor any Portfolio constitutes a solicitation to purchase or sell securities or any investment program. The opinions and forecasts expressed are those of the editors of TopStockPortfolios and may not actually come to pass. The opinions and viewpoints regarding the future of the markets should not be construed as recommendations of any specific security nor specific investment advice. Stocks should always consult an investment professional before making any investment.
Any investment decisions must in all cases be made by the reader or by his or her investment adviser. Do NOT ever purchase any security without doing sufficient research. There is no guarantee that the investment objectives outlined will actually come to pass. All opinions expressed herein are subject to change without notice. Neither the editor, employees, nor any of their affiliates shall have any liability for any loss sustained by anyone who has relied on the information provided.
The analysis provided is based on both technical and fundamental research and is provided "as is" without warranty of any kind, either expressed or implied. Although the information contained is derived from sources which are believed to be reliable, they cannot be guaranteed.
The information contained in this report is provided by Ridge Publishing Co. Inc. (Ridge). One of the principals of Ridge, Mr. David Moenning, is also President and majority shareholder of Heritage Capital Management, Inc. (HCM) a Chicago-based money management firm. HCM is registered with the U.S. Securities and Exchange Commission as an investment adviser. HCM also serves as a sub-advisor to other investment advisory firms. Ridge is a publisher and has not registered as an investment adviser. Neither HCM nor Ridge is registered as a broker-dealer.
Employees and affiliates of HCM and Ridge may at times have positions in the securities referred to and may make purchases or sales of these securities while publications are in circulation. Editors will indicate whether they or HCM has a position in stocks or other securities mentioned in any publication. The disclosures will be accurate as of the time of publication and may change thereafter without notice.
Investments in equities carry an inherent element of risk including the potential for significant loss of principal. Past performance is not an indication of future results.


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If you live in Collins, MO and you're in need of a home appliance repair, call us now at 844-257-6609 to speak with a technician that can handle your appliance repair, service and maintenance demands, no matter what type of appliance or brand. Don't be inconvenienced by malfunctioning or broken appliances. Call now, we make it easy to connect to a Collins, MO appliance repair tech that can help. Covering cities in St. Clair county and surrounding areas.
Dishwasher Repair
We rely on kitchen dishwashers to thoroughly clean our dishes, pots and pans while we spend our time on more enjoyable things like getting outside and enjoying the fresh Missouri air. But if your dishwasher leaves cloudy residue on your glassware or fails to completely remove food from dishes, you could be putting your family's health at risk. Dishwashers also may have extended wash cycles resulting from a faulty timer or thermostat. Or a malfunctioning float or float switch could prevent the wash cycle from ending properly. Either way, it may be a good idea to call us to schedule an appointment with a Collins, Missouri dishwasher repair tech to assess the situation.
St. Clair County Refrigerator Repair Techs
A refrigerator may be the most important appliance in your St. Clair county home. It keeps food fresh and edible, protecting our health and saving us money. When your refrigerator maintains an interior temperature between 37° and 41° Fahrenheit, it retards the formation of bacteria in your food. If your refrigerator isn't working properly, call us to schedule a service call by a qualified and able Collins, MO appliance repair tech. Some common refrigerator repairs in Collins, Missouri are :
· Thermostats
· Seals around the door
· Condenser
· Compressor
· Solenoids
Collins Washer & Dryer Repair
All too often we take the convenience of our home's washer and dryer for granted. Should you ever carry a week's worth of household laundry to a Collins laundromat you'll know how exhausting and time-consuming that chore is. If leaks, excessive vibration/agitation or drainage/spinning problems keep you from washing laundry at home, you are in need of a washer and dryer repair man in Collins, Missouri. Call us at 844-257-6609 will connect you with an Collins, MO appliance repair tech who will be able visit your home and examine your washer and dryer to provide a solution to the problem. Common issues that can be fixed by a tech are -
· Belts
· Agitator
· Water Pump
· Motor & Transmission
· Dryer Blower
· Heating Element
· Pulleys and Rollers
Oven And Range Repairs in Collins, Missouri
Have you ever been forced to dine in restaurants because you couldn't cook in your kitchen? If so, you know how expensive it is to eat out and how much money you save by eating at home. Not only is a malfunctioning oven, stove top or range inconvenient, precious family time together is often diminished and unhealthy dietary habits can result. If you need prompt service to get your kitchen operating again, call us now to be connected an appliance repair tech in Collins, Missouri. Technicians can service most brands and types of stoves and ovens, including both electric and gas. Don't go another night without a home cooked meal, call now - 844-257-6609!
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subset: commoncrawl


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Translink directors paid double standard rates
A CTV comparison with other boards shows Translink directors are among the most highly paid public officials -- higher than amounts recommended by the provincial government.
In fact, Translink board members are paid more than double the recommended salaries, and the board's new chair takes home more than triple his recommended income.
Victoria recommends board chairs be paid a maximum yearly retainer of $30,000. And the fee for taking part in board meetings should be no greater than $500, the recommendations say.
That's well below the $1200 being doled out to Translink directors -- even if they only phone their presence in.
And the recommended maximum of $30,000 is less than a third of the $100,000 being paid to Translink Chair Dale Parker.
In January, Translink board members voted in favour of a 500 per cent pay raise for themselves in their first board meeting.
Their first board meeting was also the first one closed to the public.
Last year, Translink directors made an average of about $7000. Now, they will start at $25,000 and depending on how many meetings they attend, a director could earn as much as $45,000 per year.
Assurances from the chair aren't cutting it with critics still upset about the pay hikes and the way they were implemented.
Some say taxpayers should keep this issue top of mind as we head towards elections in the fall and next spring.


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Casa Malaparte
|Alternative names
|Villa Malaparte, Malaparte House
|General information
|Private house
|Architectural style
|Modern architecture
|Isle of Capri
|40°32′49″N14°15′33″ECoordinates: 40°32′49″N 14°15′33″E
|Current tenants
|Foundation Giorgio Ronchi [1]
|Construction started
|Curzio Malaparte
|Design and construction
|Adalberto Libera
Casa Malaparte (also Villa Malaparte) is a house on Punta Massullo, on the eastern side of the Isle of Capri, Italy. It is one of the best examples of Italian modern and contemporary architecture.
The house was conceived around 1937 by the well-known Italian architect Adalberto Libera for Curzio Malaparte. Malaparte actually rejected Libera's design and built the home himself with the help of Adolfo Amitrano, a local stonemason.
Casa Malaparte is a red masonry box with reverse pyramidal stairs leading to the roof patio. On the roof is a freestanding curving white wall of increasing height. It sits on a dangerous cliff 32 metres above the sea overlooking the Gulf of Salerno. Access to this private property is either by foot from the Town of Capri or by boat and a staircase cut into the cliff. Casa Malaparte's interior and exterior (particularly the rooftop patio) are prominently featured in Jean-Luc Godard's 1963 film, Contempt (Le Mépris).
Casa Malaparte was abandoned and neglected after the death of Curzio Malaparte in 1957. It suffered from vandalism and natural elements for many years and was seriously damaged, including the desecration of a beautiful tiled stove, before the first serious renovation started in the late 1980s and early 1990s. The building was donated to the Foundation Giorgio Ronchi in 1972.
Malaparte's great-nephew, Niccolò Rositani, is primarily responsible for restoring the house to a livable state. Much of the original furniture is still there, because it is too large to remove. The marble sunken tub in the bedroom of his mistress still exists and functions. His bedroom and book lined study are still intact. Many Italian industrialists have donated materials for the preservation.
Today the house is used for serious study and certain cultural events in Italy and is admired and hated by many architecture enthusiasts worldwide.
The house can only be reached by traversing the island. The last twenty minute walk is over private property, belonging to The Ronchi Foundation. It takes an hour and a half to walk there from Capri's Piazzetta at the summit of the funiculare from the Marina Grande. The house can be reached by sea, on calm days only, as the waves are cast upon treacherous rocks and there has not been an official pier for many years. From the sea, one must climb 99 steps to reach the house. Malaparte gave his friend and boatman money to open a restaurant which is run by the boatman's son today. It is the only restaurant one would pass on the path from the Piazzetta to the promontory where Tiberius built his palace, Villa Jovis.
The book Malaparte: Casa Come Me (A House Like Me) edited by Michael McDonough, includes drawings and essays by many prominent artists and architects, such as James Wines,Tom Wolfe, Robert Venturi, Emilio Ambasz, Ettore Sottsass, Michael Graves, Willem Dafoe, Peter Eisenman, Wiel Arets and many other luminaries of arts and letters. Casa Malaparte was also prominently featured in the Jean-Luc Godard film, Contempt (1963).
Transition of a Fortified Italian Farmhouse
Once upon a time, Arrighi was a watchtower peering over Tuscany and all along the Niccone Valley, with an adjoining fortified farmhouse. In recent years, the dwelling known as Castello di Reschio, in Umbria, Italy, is the result of a meticulous restoration that resulted in a luxurious L-shaped main house, and a standalone guest cottage.
Once the fortified farmhouse and watchtower, the impressive five bedroom main house is approached via a large paved courtyard beyond the entrance gates, past the sweet guest cottage that contains a double bedroom, en-suite bathroom, library and fully-fledged kitchen.
A glass encased external staircase tower is flooded with sunlight, and soaks in the extensive view over the very private and unspoiled 2,700 acre Reschio Estate, filled with rolling hills, vineyards, olive groves, chestnut and oak trees, extensive infinity pool and pool house. (HOUSE TOURS)
HOUSE TOURS, . "Transition of a Fortified Italian Farmhouse." home Designing. N.p., 18 Jul 2012. Web. 18 Jul. 2012. <http://www.home-designing.com/2012/07/transition-of-a-fortified-italian-farmhouse?utm_source=feedburner&utm_medium=email&utm_campaign=Feed: home-designing (Home Design Ideas)&utm_content=Yahoo! Mail>.
Casa O Teolo, 2008
Andrea Tognon Architect, Initials. (n.d.). Residance o teolo, 2008/10. Retrieved from http://translate.google.com/translate?hl=en&sl=it&tl=en&u=http%3A%2F%2Fwww.atognon.com%2F&anno=2


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Irene Prochazka
Irene Prochazka
JACKSON — Mass of Christian Burial for Irene Mary Prochazka, 92, of Jackson, will be 11 a.m. Saturday at Good Shepherd Catholic Church in Jackson. Burial will follow the service in Good Shepherd Catholic Cemetery.
Prochazka died Thursday, Sept. 5, 2019, at Temperance Lake Ridge in Sherburn. Visitation will be 5-7 p.m. Friday at Good Shepherd Catholic Church in Jackson, with a rosary service at 7 p.m. Visitation will also be held one hour prior to the service Saturday at the church in Jackson.
Osterberg Funeral Home in Jackson is in charge of arrangements.


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Matthew 9:3-6 Living Bible (TLB)
3 "Blasphemy! This man is saying he is God!" exclaimed some of the religious leaders to themselves.
4 Jesus knew what they were thinking and asked them, "Why are you thinking such evil thoughts? 5-6 I, the Messiah,[a] have the authority on earth to forgive sins. But talk is cheap—anybody could say that. So I'll prove it to you by healing this man." Then, turning to the paralyzed man, he commanded, "Pick up your stretcher and go on home, for you are healed."
Living Bible (TLB)
The Living Bible copyright © 1971 by Tyndale House Foundation. Used by permission of Tyndale House Publishers Inc., Carol Stream, Illinois 60188. All rights reserved.
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1 Apple 1 Banana 1/3 cup Red seedless grapes 1/3 cup green seedless grapes 2/3 cup pineapple chunks 1 cup nonfat yogurt 1/4 cup dried shredded coconut
1. Wash all the fruits and cut into slices. Put on one plate. 2. Spread coconut onto another large plate. 3. Slide pieces of fruits onto a skewer or craft stick. Do this until the stick is almost covered from end to end. 4.Hold the fruit kabob at the ends and roll it in yogurt , so the fruits kabob is covered. 5. Roll the yogurt covered fruit kabob in the coconut. Repeat these steps with other skewers too.


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Most back 2 school information right now is all about the kids...which it should be! BUT what about us?! What about us mamas?! Us parents?!🤷♀🤷♂ we need a little something too right?? Well this podcast has a great focus that I thought I'd share, check it out ⬇ podcasts.apple.com/us/podcast/self-made-podcast/id1458565638
Tag: mom tip
Bike Safety
Bike Safety Tips and Articles https://healthbeat.spectrumhealth.org/bicycle-safety/ Top 10 Bike Helmets for Kids https://healthbeat.spectrumhealth.org/bicycle-safety/ https://healthbeat.spectrumhealth.org/bicycle-safety/ These are some great ideas! Safety always first! Please make your kiddos and YOU wear a helmet! I was always so concerned about my kids but then one night I was riding in a park after it rained and I had… Continue reading Bike Safety
Mom Tip #112
Seriously, I cannot believe I have waited this long to try a robot vacuum, I absolutely love it! It does a great job and no, it has not fallen down the stairs (this was my fear)! It is so convenient and efficient! I can work on other things while letting the vacuum go - I… Continue reading Mom Tip #112
My Amazon Travel List
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Mom Tip #111
AMAZON PRIME!! This mom STRONGLY suggests getting Amazon Prime! This is probably my most important mom tip 😉 Seriously, I use Prime every week, every day! I know the price has gone up this year to $119. Which is alot upfront, but in the long run, this has saved me $ and reduced my stress!… Continue reading Mom Tip #111
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Cosrx Oil-Free Ultra-Moisturising Lotion (With Birch Sap) is a lightweight formula enriched with 70% Birch Sap to hydrate, calm and soothe sensitive, irritated skin.
It is easily absorbed with no greasy residue, making it perfect to use under make-up. The oil-free formulation helps prevent acne breakouts while also quenching dry skin.
Directions: Apply 1-2 pumps evenly after cleansing, toning and treatments. Follow with SPF (daytime) or as a last step at night.
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Essential selection of UI, whooshes, alarms, keyboard, clicks, coins and errors sounds.
Enhance your vision through sound in explainer videos, motion graphics, commercials, videogames, infographics, mobile apps, websites, YouTube videos, and animations. This original library is from sound designer Matias Vidal Saavedra.
Number of Files: 150 High Quality WAVS (00:05:42)
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Sample Rate: 96kHz/24bit
Gear Used: Zoom H5, Ableton Live 9
Other Info: Meta-Tagged


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Applying to this job will open a new window on the employer's web site to apply there.
Care Manager - RN - South West Office * Days - 40hrs/wk
Requisition #: req1945
Shift: Days FTE status: 1 On-call: No Weekends: No
General Summary:
The Care Manager - RN provides care management services to adult and pediatric patients in an ambulatory setting. The Care Manager - RN performs clinical assessments and therapeutic interventions for complex patients with multiple chronic conditions and comorbidities. In addition, this position serves as community resource expert and care coordinator across the continuum of care. Furthermore, the Care Manager - RN optimizes care by engaging patients in the principles of self-management, goal setting and continuous improvement. This integral role expands primary care's scope of practice by focusing on patient's biopsychosocial needs to ensure the delivery of comprehensive, efficient and quality care. Requirements:
Essential Functions and Responsibilities:


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Safina v Jankovic
Rankings are 1 and 5 and head to head is 3-1 to Safina. The market has Safina as strong fave at 1.44 .
Both women have been impressive this week but I think it will be Safina's day. Her performance against Clijsters is probably the best indicator for me.
Jankovic will make a game of it but can make a few too many mistakes.
15-40 and scalping are the safer options as whenever I back Safina from the start she forgets how to play.
Safina to win in 2.
Update: See what i mean? Safina never stood a chance once i had tipped her to win!
Didn't manage to trade this myself but there will have been great price movements in the first set when jankovic broke and in the second when she broke for the first time 🙂
Jankovic won 6-4, 6-2


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Japan's Princess Kako Attends Dinner in Budapest
Newsfrom JapanSociety
- English
- 日本語
- 简体字
- 繁體字
- Français
- Español
- العربية
- Русский
Budapest, Sept. 21 (Jiji Press)--Japanese Princess Kako, niece of Emperor Naruhito, attended a dinner in Budapest on Saturday to mark the 150th anniversary this year of diplomatic ties between Japan and Hungary.
"I pay my respect to your efforts from the bottom of my heart," the princess told 12 guests who were invited to mark their contributions to bilateral relations.
The princess, the second daughter of Crown Prince Akishino and Crown Princess Kiko, was visiting Hungary as part of her first official overseas trip that also brought her to Austria earlier this week.
The dinner was held at Central Cafe, a restaurant known as a symbol of friendly ties between Japan and Hungary. It has connections with the late Juichiro Imaoka, a Japanese citizen who lived in Hungary in the 1920s and later edited the first Hungarian dictionary in Japan.
[Copyright The Jiji Press, Ltd.]


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Photo: Pixabay/MGN
Photo: Pixabay/MGN
Updated: August 13, 2019 11:59 AM
Troopers issued more than 700 citations and warnings for the hands-free law in just the first 10 days since the law went into effect.
The Minnesota State Patrol said troopers issued 740 citations and warnings for violations of the hands-free law in the first 10 days of August.
In addition to those citations and warnings, troopers also issued 88 citations and warnings for left lane violations during the same time period, according to the State Patrol.
Related stories:
New hands-free law now in effect
Get ready for the new laws going into effect in Minnesota on August 1
Updated: August 13, 2019 11:59 AM
Published: August 13, 2019 12:00 AM
Copyright 2019 - KSTP-TV, LLC A Hubbard Broadcasting Company


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Things to do in Jevnaker Municipality
Top recommendations from locals
From sightseeing to hidden gems, find out what makes the city unique with the help of the locals who know it best.
General Entertainment
"Glass factory with a lot of art and a great to visit both summer and winter. A Lovele place at Christmas"
- 10 locals recommend
Historic Site
"Kistefossmuseet is a famous and beautiful sculpture park which is about 20 minutes by car - here you can easily spend a whole day."
- 7 locals recommend
Bus Station
"Old glass factory with nice buildings and shops where you might find a souvenir you won't find elswhere. Nice surroundings too by the lake Randsfjorden."
- 4 locals recommend
"Fantastisk flott sted med mye historie! Kafe finnes også her. Besøk også Glassblåserlåven - atelier for unge kunstnere."
- 5 locals recommend
Beer Garden
"Wednesday and Thursday 18:00–23:00. Friday 18:00–02:30. Saturday 14:00–02:30. Sunday 18:00–23:00. Quiz and concerts"
- 4 locals recommend
" VEIEN CULTURAL HERITAGE PARK Veien Cultural Heritage Park is located approximately one hour north-west of Oslo by car. The area consists of over 100 grave mounds from the Early Iron Age, a reconstructed longhouse and a museum. The museum is open most of the year. During the summer the longhouse and the museum are open every day except Monday. The Longhouse In the field just south of the burial ground, archaeologists have uncovered the remains of four longhouses. They are all dated to the Early Iron Age. The longest of these houses has been reconstructed where the original was uncovered. Guiding in the longhouse is available in Norwegian and English, but we also have an audi"
- 5 locals recommend
Natural Feature
"Sølvsberget er en markert topp i det ellers småkuperte terrenget mellom Gran og Tingelstad på Hadeland i Oppland. Sølvsberget ligger ca. to kilometer vest for Granavollen og Søsterkirkene på Gran. Den karakteristiske profilen kommer av at det er et gammelt vulkanrør som en gang presset seg opp gjennom de sedimentære bergartene i området. Toppen ligger på 493 moh, og er en litt mindre parallell til Brandbukampen lenger nord. Platået på toppen av Sølvsberget dekker ca. 15 dekar, og er avgrenset med store voller av jord og stein mot sør og vest. "
- 1 local recommends
Beer Garden
"Wednesday and Thursday 18:00–23:00. Friday 18:00–02:30. Saturday 14:00–02:30. Sunday 18:00–23:00. Quiz and concerts"
- 4 locals recommend


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|For the record, the "Vulcan" name here is more closely related to Britain's loud Cold War-era bombers than to the notoriously logical aliens in "Star Trek". Nonetheless, the Vulcan is Aston Martin's entry into the hypercar market, and there will only be 24 of these track-only vehicles built. Those lucky enough to accept the offer of purchase will find 800 hp ready to thrill from the race-inspired V12. The asking price? Somewhere north of $2 million, but the uncanny lines and performance should inspire the appropriately logical responses of longing stares and envious eyes.
— Official description [1]
The 2016 Aston Martin Vulcan, abbreviated as AM Vulcan and Aston Vulcan, is a front-engined hypercar by Aston Martin that debuted in Forza Horizon 3 as part of The Smoking Tire Car Pack and is featured in all subsequent Forza titles.
It appears as a Showcase reward in Forza Motorsport 7.
Based on the Aston Martin One-77, the Vulcan is a track-only hypercar by Aston Martin. Its name is a reference to the British Cold War-era bombers of the same name. Aston Martin produced only 24 examples of the car worldwide, each priced at US$2.3 million, with all but one of them not road legal.[2]
The Vulcan is powered by Aston Martin's most powerful version of their 7.0 L (6,949 cc) naturally aspirated V12 engine, with 820 hp (611 kW) at 7,750 rpm and 590 ft·lb (800 N·m) of torque at 6,500 rpm. There is a selector knob inside the car that selects power from three options: the first option delivers 500 hp (373 kW); the second option brings more power at 675 hp (503 kW); and the third option unleashes the full 820 hp (611 kW) of the engine.
The Vulcan is also fitted with carbon ceramic brakes, magnesium torque tube with a carbon fiber propeller shaft, and limited-slip differential. Tires used are Michelin Pilot Sport Cup 2s. The carbon ceramic brakes which also increase braking performance, measure 15 in (380 mm) at the front and 14 in (360 mm) at the rear.
The Vulcan makes use of a six-speed Xtrac sequential transmission delivering power to the rear wheels. With a weight of 2998 lb (1360 kg), the Vulcan has a power-to-weight ratio of 603 hp (450 kW) per tonne.
The Vulcan is capable of 0 to 60 mph (97 km/h) in 3 seconds, 0 to 100 mph (161 km/h) in 5.7 seconds, and a top speed of 205 mph (330 km/h), which is downgraded to 194 mph (313 km/h) in Forza Horizon 3.
The Vulcan is the hypercar equivalent of the Dodge Viper ACR, with a focus on grip and braking. It generates huge amounts of downforce to help it corner very sharply and brake to cornering-appropriate speeds very quickly. Unlike the Viper ACR, though, it has a stronger emphasis on acceleration, handling, and top speed.
The Vulcan is considerably quicker than other production Aston Martins, as it is the only production Aston Martin with the ability to reach 100 mph (161 km/h) in less than six seconds. Just like the Viper ACR, though, its top speed is held back by its gearing and downforce to 194 mph (313 km/h) (205 mph (330 km/h) in Forza Motorsport 7), making it suitable for handling-focused tracks. It is noted for being the fastest Hypercar division car around tracks that are not focused on top speed, even faster than the Ferrari FXX K.
Forza Edition
The Forza Edition - abbreviated as AM Vulcan FE - is a special variant in Forza Horizon 4 featuring a Clean Skills boost and an S2 998 upgrade preset.
It is unlockable as a Wheelspin prize, but was also available as a Forzathon Shop car during the Series 9 Summer Season.
|Speed 7.5
|Handling 7.3
|Acceleration 8.9
|Braking 7.2
|Unlock: Complete the Passing Challenge - Aston Martin Vulcan Showcase event
|Price: ? CR
|Collection Tier: 5 - Legendary (+1,820)
|Top Speed: 201.9 mph (324.9 km/h)
|Division: Hypercar
|Acceleration 0-60 mph (0-97 km/h): 3.000 secs.
|0-100 mph (0-161 km/h): 5.700 secs.
|Braking 60-0 mph (97-0 km/h): 122.3 ft (37.3 m)
|100-0 mph (161-0 km/h): 273.5 ft (83.4 m)
|Lateral G's 60 mph (97 km/h): 1.45 g
|120 mph (193 km/h): 1.78 g
|1/4 Mile: missing data
|Speed 7.5
|Handling 7.6
|Acceleration 8.9
|Braking 7.5
|Unlock: Complete the Passing Challenge - Aston Martin Vulcan Showcase event
|Price: ? CR
|Collection Tier: 5 - Legendary (+1,820)
|Top Speed: 202.8 mph (326.3 km/h)
|Division: Hypercar
|Acceleration 0-60 mph (0-97 km/h): 2.921 secs.
|0-100 mph (0-161 km/h): 5.569 secs.
|Braking 60-0 mph (97-0 km/h): 120.4 ft (36.7 m)
|100-0 mph (161-0 km/h): 270.4 ft (82.4 m)
|Lateral G's 60 mph (97 km/h): 1.51 g
|120 mph (193 km/h): 1.85 g
|1/4 Mile: missing data
|Speed 7.2
|Handling 9.2
|Acceleration 9.0
|Launch 8.3
|Braking 10
|Unlock: Purchase from the Autoshow
|Price: 1,500,000 CR or ? T
|DLC: Requires the The Smoking Tire Car Pack
|Top Speed: 190.9 mph (307.2 km/h)
|Championship: Hypercars
|Acceleration 0-60 mph (0-97 km/h): 3.012 secs.
|0-100 mph (0-161 km/h): 5.700 secs.
|Braking 60-0 mph (97-0 km/h): 110.8 ft (33.8 m)
|100-0 mph (161-0 km/h): 257.3 ft (78.4 m)
|Lateral G's 60 mph (97 km/h): 1.32 g
|120 mph (193 km/h): 1.70 g
|Forza Edition
|Speed 8.4
|Handling 10
|Acceleration 7.7
|Launch 9.2
|Braking 10
|Unlockable as Wheelspin prize, seasonal reward or from an Auction House purchase
|Value: 1,750,000 CR
|Rarity: Forza Edition
|Boost: Clean Skills
|Top Speed: 229.8 mph (369.7 km/h)
|Championship: Extreme Track Toys
|Acceleration 0-60 mph (0-97 km/h): 2.721 secs.
|0-100 mph (0-161 km/h): 5.219 secs.
|Braking 60-0 mph (97-0 km/h): 91.3 ft (27.8 m)
|100-0 mph (161-0 km/h): 207.1 ft (63.1 m)
|Lateral G's 60 mph (97 km/h): 1.59 g
|120 mph (193 km/h): 1.96 g
|Conversion - Engine
|Racing V12
|Conversion - Drivetrain
|AWD Drivetrain
|AWD Drivetrain
- The 7.0L V12 engine swap originates from this car.
- Vulcan is the god of fire in Roman mythology, and his Greek counterpart is Hephaestus. It also refers to the Avro Vulcan Cold War-era bombers of the same name.
- ↑ "The Smoking Tire Car Pack". forzamotorsport.net. Retrieved 08-17-2018.
- ↑ "Aston Martin Vulcan - Road-legal hypercar revealed". express.co.uk. Retrieved 08-17-2018.
|Aston Martin
|DB4 GT Zagato · DB5 (DB5 JB) · DBS JB '69
|V8 Vantage
|V8 Vantage V600
|#007 DBR9, #008 DBR9, #009 DBR9 · DB7 Zagato · DB9 Coupe · DBS '08 (DBS JB '08) · V12 Vanquish
|#009 AMR One · #007 - #6 Lola · #7 V12 Vantage GT3 · Vanquish (Limited Collector Edition) · Cygnet · DB10 JB · DB11 · One-77 · Rapide · V12 Vantage · V12 Vantage S · V12 Zagato · Vantage · Vantage GT12 · Virage · Vulcan (Forza Edition)


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DeLauro Statement on ORR Cancelling Basic Services for Unaccompanied Children
WASHINGTON, DC (June 5, 2019) — Congresswoman Rosa DeLauro (CT-03), Chair of the House Appropriations Subcommittee on Labor, Health and Human Services, and Education, today released the following regarding reports that the Office of Refugee Resettlement (ORR) is cancelling programs for unaccompanied children.
"Basic educational, recreational, and legal services for unaccompanied children are imperative for their physical and mental well-being. ORR's cancelling of these services will inflict further harm on children, many of whom continue to languish for months without being placed safely and expeditiously into a sponsor's care. That is not only unacceptable, it could be in violation of the law. Congressional Republicans need to stop holding up the emergency supplemental negotiations and agree to necessary and reasonable protections to ensure the health and safety of the thousands of unaccompanied children."


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Praise Choir
Rehearsals have begun, but new members are always welcome. Contact Sarah for more information.
The Praise Choir is an ensemble of singers and instrumentalists. This choir rehearses on Tuesday evenings from 6:15-7:15 pm and leads music at the 5 pm liturgies twice a month. The music styles sung by this group include: Contemporary Christian, Praise & Worship, Gospel, & Traditional. The group loves music with lots of harmonies & a variety of instrumentation. Interested in joining? Contact Sarah in the Parish Office.


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According to Amazon, former Jorney singer Steve Perry will release a new solo album titled "Traces" on October 5.
Perry apparently teased his return to activity yesterday by launching what appears to be an official web site and social media accounts. The initial posting on the sites contained a simple message: "I know it's been a long time comin'."
"Traces" track listing, according to Amazon:
01. No Erasin'
02. We're Still Here
03. Most Of All
04. No More Cryin'
05. In The Rain
06. Sun Shines Gray
07. You Belong To Me
08. Easy To Love
09. I Need You
10. We Fly
It has been reported that Perry will appear on the October 7 edition of "CBS Sunday Morning", presumably to promote his new solo disc and discuss his plans for the future.
Last year, Perry told ABC Radio that his next solo album was inspired by a personal tragedy. He explained: "I met someone and I feel in love with this person. And I lost this person to breast cancer four years ago. In the midst of that, I had written some songs, and before I met her, I had sketched some. And so about a year ago, I started recording."
He continued: "Basically the record is an emotional expression, and a reason to make one. It's been a real cathartic experience going back to that emotional place that I thought I would never go back to. And we really have been doing our very best to capture what I think are some timeless songs."
Perry last released a solo album in 1994. That effort, "For The Love Of Strange Medicine", was certified gold in the U.S. for sales in excess of half a million copies.


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Budget travel: How to save enough for your wanderlust wish list
Wondering how to attain your travel bucket list? Here are traveling tips on how to budget for your holiday abroad
Wondering how to attain your travel bucket list? Here are traveling tips on how to budget for your holiday abroad
Ensure that you have all the documents you need before leaving on a trip abroad. Here's the best way to keep your paperwork in check
Dreaming of a vacation? Here are 8 simple steps to plan the perfect trip. Follow this guide to sort the admin before the real fun begins.
An introduction to Reunion Island, a French department in the Indian Ocean, plus how they will be celebrating the festive season
All the things South Africans who have immigrated to the UK wish they brought with them, and what to consider taking if you're next
Every month, more than a billion people use Google Maps, and they're not just looking for directions. Here's how to get the most benefit from Google Maps' Local Guides.
Even with crowds, overpriced souvenirs, and a rather ordinary, highly-promoted pastry specialty called Schneeball, Rothenburg is still an absolute treasure.
Below are destinations that require either no visa or offer free visas.
If you're a traveller who spends your time reflecting on the fact that your carbon footprint melts thousands of pounds of glacier ice, keep reading.
You can either max out your credit card when planning your next travel adventure. Or, follow these guidelines and save before you hit the road.
Safety should always take priority. Be prepared with these travel safety tips, because it's better to be safe than sorry.
Which vehicle to use? How much to spend? Here are a few things to consider before packing up your life and embarking on that road trip.
A quick guide to help you pack light and keep warm while still looking good on your travels.
Tips for South Africans to stretch those rands.
Tired of waiting at the baggage carousal? Blame it on the shape of your bag.
Switzerland may seem relatively small compared to other European nations and is often overlooked when choosing where to travel to, but it doesn't fall short on its offerings. Fondues, scenic train rides, unparalleled landscapes, chocolates, and ski trips of a lifetime are just some of the reasons why you must ...
Fitting all your travel essentials into one small bag sounds daunting, I know, but minimalism packing really isn't that hard.
For centuries, hot sulphuric water has been flowing through this Pyrénées town.
Forget Bali, and head to the pink beaches of Indonesia.
Luxembourg. Say what? Where is that?
Forget Thailand, Mauritius and Bali.
Dirco has moved to remind South Africans how to properly prepare for overseas travel, after one of our own was kidnapped in Burkina Faso.
From Worcester to Montreal, check out the names of these countries and cities you've more than likely been mispronouncing all along.
A U.S. scientist mapped out the ultimate road trip for your perusal. Fancy a Euro-trip?
Top tips for making the most of the beach... there's it.
Have a look at some of the kiffest places to grab a dop, and satisfy your wanderlust.
The departments of home affairs and tourism have finally announced that the controversial visa laws – which required all minors travelling to or going out of SA to have an unabridged birth certificates – will be replaced in favour of an updated passport for minors with printed details of both ...
South Africa may not be the first destination that pops into your mind when considering your next family holiday. However, it is a fantastic place to consider for a relaxing -- and more affordable -- vacation; with something for everyone.
Silly season is here and with it comes some silly people. If you are traveling these holidays, try not to be an asshole, be it at the airport or when you are wandering through a foreign city. It's really not that hard. Follow these tips and avoid being an asshat, ...
If you're thinking of heading off for the holidays, here are some pretty neat tips for making it last that extra bit longer.
With 24 James Bond films under the belt, here are some of the best, most beautiful destinations 007 has visited.
Sleeping pills, yogurt, bananas, turkey meat and even nuts; folks have tried everything and there's an old wives tale for almost every scenario. Here's what might actually work though.


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Dogs and apps both tend to make life better. Does a prospective match need to be happy sharing you with a furry feline? Is it a must that any potential partner loves dogs? If you're an animal lover looking for. Sniffr is the original social network that brings dog people the best people together!
Netflix news Log in. Owning a dog is a big part of your life, so it makes sense that you'd like to meet a significant other who also loves dogs. Enter dog dating apps. These are online. Judy Stanley, an advertising account executive from Calgary, cites as the ultimate nightmare date the time she invited a man she had met at a professional singles club to her home for a pre-dinner drink.
Just type and press 'enter'. Sniffr is the original social network that brings dog people (the best people) together in your neighbourhood or set your pup up on that much needed play date. Jump to navigation.
A new study suggests American singles are taking their search for love into the wild. The American Veterinary Medical Association AVMA says there has been a major rise in pet ownership among singles since as they look to fill a sense of love and family in their lives. It seems these little creatures are serving as creatures of comfort for singles. While it's still more common for a pet to be owned by a family, the increase in pet ownership by singles far exceeds the growth of pet ownership for familieswhich has only grown by 1.
Published: March 18, Recently, You Must Love Dogs Dating garnered media attention when an Orlando, Fla., couple who met on the site announced their. Jump to navigation.
Email dmz ryerson. That's when I decided that in future I would only consider dating 'dog people.'" " There are millions of single pet owners in Canada," says Robert Yau, who. The Safety Harbor, Fla.
A couple of evenings ago, Mum was quite excited to try dog-owners speed dating that was held at the dog-friendly Marmara Hotel — organised by DigDates. A new study suggests American singles are taking their search for love into the wild. The American Veterinary Medical Association (AVMA).
That notion is something that Pam McCarthy wants to explore, and is why she's launching a dating website called Must Love Dogs this fall.


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Hospice of Lenawee:
On Saturday, September 7, 2019, South Michigan Wheels will once again be hosting the "Ride for Hospice of Lenawee" with all proceeds from this event to benefit Hospice of Lenawee's Hospice Heart Endowment Fund. This year the event will again be an "All Wheel Ride" allowing for anyone to jump on their bike or in their car and support our organization. It will begin in Adrian at The Grasshopper/ El Chapulin and end in Tipton at South Michigan Wheels. Registration will begin at 11:00 with the last bike/ vehicle out at Noon. Drivers- $20; passengers- $15. Come early for breakfast! The Grasshopper/ El Chapulin will open at 10:00.
Our mission is to promote and enhance professional and member interests and to
increase the general welfare and prosperity of the Tecumseh area.
Tecumseh Area Chamber of Commerce ~ 132 W. Chicago Blvd. ~ Tecumseh, MI 49286 ~517-423-3740


text: Poetry 25 June 2017 Madeleines A new poem by Gary Allen. Photo: Getty Sign UpGet the New Statesman's Morning Call email. Sign-up Gary Allen was born in Northern Ireland and has published 14 collections, most recently Jackson's Corner (Greenwich Exchange) › Wilderness and wastelands in Rick Bass's hypnotic short stories Subscribe £1 per month This article appears in the 22 June 2017 issue of the New Statesman, The zombie PM


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West Texas A&M University is hosting a gala celebrating the release of WT 125: From the Panhandle to the World on Feb. 2. It is a generational plan that is supposed to set achievements for WTAMU by the year 2035.
The Texas A&M University System Chancellor, John Sharp, the president of WTAMU, Walter Wendler, and other local leaders will be hosting the gala.
WTAMU is expected to have a number of doctoral programs by WT's 125th anniversary in 2035.
The WT 125 is set to celebrate the future of the leading institution for higher education in the Texas Panhandle.
The task force for WT 125 included more than 300 community members making 10 theme groups focused on the connectivity of WT and the surrounding communities.
The gala will take place at 6:30 p.m. in downtown Amarillo at Embassy Suites, 550 South Buchanan Street.


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The HN878 strain of Mycobacterium tuberculosis is regarded as "hypervirulent" due to its rapid growth and reduced survival of infected mice when compared with other clinical isolates. This property has been ascribed due to an early increase in type I IFNs and a failure to generate TH1-mediated immunity, induced by a response to an unusual cell wall phenolic glycolipid expressed by the HN878 isolate. We show, however, that although type I IFN does play an inhibitory role, this response was most apparent during the chronic disease stage and was common to all M. tuberculosis strains tested. In addition, we further demonstrate that the HN878 infection was associated with a potent TH1 response, characterized by the emergence of both CD4 and CD8 T cell subsets secreting IFN-γ. However, where HN878 differed to the other strains tested was a subsequent reduction in TH1 immunity, which was temporally associated with the rapid emergence of a CD4+CD25+FoxP3+CD223+IL-10+ regulatory T cell population. This association may explain the paradoxical initial emergence of a TH1 response in these mice but their relatively short time of survival.
It is becoming apparent that a significant percentage of new clinical isolates of Mycobacterium tuberculosis are of high virulence (1, 2). Initial studies by Manca et al. (3, 4) demonstrated that the HN878 strain is of unusually high virulence, wherein mice failed to induce a strong TH1 T cell and cytokine response early in infection and died more rapidly in comparative survival studies. This "hypervirulence" was hypothesized to be associated with induction of increased production of type I IFN (4), and further work has subsequently shown that HN878 expresses a TH2 cytokine inducing biologically active phenolic glycolipid Ag in its cell wall, removal of which ablates its lethality (5).
The role of type I IFNs in the protective immune response to M. tuberculosis infection is not well understood. More recent reports from Manca et al. (3, 4) demonstrated that wild-type HN878-infected mice treated with anti-IFN-αβ Ab results in higher TH1 cytokine response and increased survival of animal without concomitant differences in bacterial growth. Taken together, these studies suggested that the increased type I IFNs during infection with HN878 may be deleterious for survival of M. tuberculosis-infected mice, which was associated with reduced TH1 immunity (3, 4).
Cell-mediated immunity is responsible for control of tuberculosis (6, 7). After pulmonary infection of the mouse with M. tuberculosis (∼50–100 CFU), alveolar macrophages and dendritic cells (DCs)3 phagocytose the bacilli and DCs carry Ags to draining lymph nodes where recognition by T cells generates cell-mediated immunity (6, 7, 8, 9). The generation of prolonged immunity to the products of the phagocytosed bacteria have Ags that are presented by macrophages, as Ag bound to class I MHC molecules to CD8+, class II MHC molecules to CD4+, and non-MHC molecules to γδ+ T cells (10, 11, 12, 13). The presentation of these molecules to T cells causes the secretion of IFN-γ, IL-12, and the subsequent signaling from TNF-α results in the activation of other macrophages to phagocytose and kill the intracellular organism (8, 12, 13). The additional influx of monocytes, macrophages, B cells, and neutrophils form the granulomatous lesion at the site of mycobacterial replication (14, 15, 16, 17) in the lung to contain multiplication and further dissemination of the bacteria to other cells. Although there is an initial presence of a strong TH1 Ag-specific response in mice, which leads to the control of M. tuberculosis growth, these responses may also increase inflammation and lung immunopathology. Although the immunosuppressive cytokines such as TGF-β, IL-4, and IL-10 (9, 18, 19) are generally considered to increase the susceptibility to intracellular pathogens, their expression with a bacterial strain of higher virulence may be necessary to attenuate the potentially tissue-damaging inflammatory response (18, 19, 20). An example, of reduction of inflammatory tissue damage is the development of a CD4 T regulatory population that expresses CD25, CD223, and FoxP3, which down-regulates inflammation and protective TH1 responses (21, 22).
Materials and Methods
Specific pathogen-free female C57BL/6 mice were purchased from The Jackson Laboratory. Mice lacking the IFN-αβ receptor on a 129 background were bred in-house at Colorado State University (Fort Collins, CO) from breeders provided by Dr. P. Marrack (National Jewish Medical and Research Center, Denver, CO). Mice were used at ∼6–8 wk of age. Mice were maintained in the Biosafety Level 3 biohazard facility at Colorado State University, and were given sterile water, mouse chow, bedding, and enrichment for the duration of the experiments. The specific pathogen-free nature of the mouse colonies was demonstrated by testing sentinel animals. All experimental protocols were approved by the Animal Care and Use Committee of Colorado State University.
Experimental infections
Mice were challenged by low-dose aerosol exposure with M. tuberculosis using a Glas-Col aerosol generator calibrated to deliver 50–100 CFU of bacteria into the lungs. Information regarding preparation of bacterial stocks and growth characteristics of the various bacterial strains (n = 5) used were as previously described (1, 2). Strain H37Rv was originally obtained from the Trudeau Institute Collection; HN878 was provided by Dr. B. Kreiswirth (Public Health Research Institute Center, Newark, NJ); CSU 123 was provided by Dr. R. Cho, (Seoul, South Korea); CDC1551 (CSU 93) was provided by Dr. T. Shinnick (Centers for Disease Control and Prevention, Atlanta, GA); and Erdman-KO1 was obtained from Mycos Research, with permission from the Aeras Foundation.
Bacterial counts in the lung (n = 5 represents 5 mice and 5 lung samples) were determined by plating serial dilutions of organ homogenates on nutrient 7H11 agar and counting CFU after 3 wk incubation at 37°C. Lungs from mice (n = 5) in the same groups were harvested for histological analysis, and lung cell suspensions were used for flow cytometric analysis at indicated time points. In survival studies, animals showing substantial weight loss with no evidence of weight rebound were euthanized. The results shown in the survival studies are based upon 10 mice per group.
Histological analysis
The accessory lung lobe from each mouse was fixed with 10% Formalin in PBS. Sections from these murine tissues were stained using H&E, and by acid fast staining to detect mycobacteria.
Lung cell digestion
To prepare single-cell suspensions the lungs were perfused with a solution containing PBS and heparin (50 U/ml; Sigma-Aldrich) through the pulmonary artery and aseptically removed from the pulmonary cavity, placed in medium, and dissected. The dissected lung tissue was incubated with complete DMEM containing collagenase XI (0.7 mg/ml; Sigma-Aldrich) and type IV bovine pancreatic DNase (30 μg/ml; Sigma-Aldrich) for 30 min at 37°C. The digested lungs were further disrupted by gently pushing the tissue through a cell strainer (BD Biosciences). RBC were lysed with ACK buffer, washed, and resuspended in complete DMEM. Total cell numbers per lung were determined using a hemocytometer.
Flow cytometric analysis of cell surface markers
Cells suspensions from each individual mouse were incubated with mAbs labeled with FITC, PE, PerCP, or allophycocyanin at 4°C for 30 min in the dark. After washing the cells with deficient RPMI 1640 (Irvine Scientific) containing 0.1% sodium azide (Sigma-Aldrich), the cells were incubated with mAbs. Monoclonal Abs against CD4+low vs side light scatter (SSC)low or FSCmid/high vs SSCmid/high region, respectively. Analyses were performed with an acquisition of at least 100,000 or 500,000 total T cell events and a minimum of 10,000 CD11c+ events.
Intracytoplasmic cytokine staining
Inflammatory cytokine measurement
A cytometric bead array kit (BD Biosciences) was used to measure inflammatory cytokines of lung cell suspensions incubated for 72 h at 37°C with culture filtrate proteins at 2 μg/ml and then frozen at −80°C. After thawing the supernatants, the cytometric bead array mouse inflammatory cytokine assay procedure was performed according to kit instructions. Assays were completed with duplicate samples and results are expressed as the mean of two experiments. Values are represented by the mean cytokine in picograms per milliliter minus the noninfected medium control. The beads were analyzed on a BD Biosciences FACSCalibur flow cytometer.
Statistical analysis
Data are presented using the mean values (n = 5) using replicated samples and duplicate or triplicate assays. The parametric Student t test was used to assess statistical significance between groups of data.
Comparison of survival and lung bacterial loads in the lungs of C57BL/6 and IFN-αβ receptor KO mice infected with virulent strains of M. tuberculosis
In a first study we compared the growth of each of the five test strains in the lungs of mice exposed to low-dose aerosol infection (Fig. 1⇓A). In the case of H37Rv, CSU 123, and Erdman-KO1, all showed evidence of slowing when reaching ∼106 bacteria in the lungs, whereas levels of CSU 93 continued to rise, peaking at 107 after day 50. In contrast, HN878 grew faster than the other strains, reaching a lung bacterial load of 107 by as early as day 15 before showing evidence of containment.
A second study comparing the survival times of mice infected with the panel of laboratory and clinical strains was consistent with the resulting data and confirmed earlier reports (4, 5), illustrating the much higher virulence of the HN878 strain (Fig. 1⇑B).
These studies also addressed the previous hypothesis (4) that this virulence reflected the production of type I IFN by comparing the growth of HN878 in control mice with IFN-αβ receptor gene disrupted knockout (KO) mice. We found this hypothesis to be the case, with better control of the bacterial load in mice unable to make type I IFN (Fig. 1⇑A). However, this possibility was not restricted to HN878, but was a common observation with all five strains tested. Moreover, whereas an earlier report (4) implied that these cytokines had an early influence, the data obtained from the IFN-αβ KO mice showed that the inhibitory effects of these cytokines was predominantly expressed during the chronic stage of the disease process.
Differences in the granulomatous response in the lungs
We then examined the lung pathology in the HN878 mice and compared it with pathology found in mice with the other infections. Lesions were ranked in order of severity from 1 to 5 and scored for granuloma formation, alveolitis, perivasculitis, and peribroncholitis. All parameters were added for a total score. As shown in Fig. 2⇓, the rapid growth of HN878 was associated with substantial lung damage, whereas the pathology scores rose much more slowly in lungs with the other infections. Interestingly, lung damage in the HN878-infected mice clearly slowed after day 30.
Lung pathology is also illustrated in Fig. 3⇓, which shows the appearance of the lung tissues in mice infected with HN878 compared with animals infected with H37Rv or CSU 93. Examination of the lungs of C57BL/6 mice 15 days after being given a low-dose aerosol infection showed small aggregates of cells (Fig. 3⇓A). By day 30, moderately sized lesions present, which consisted predominantly of macrophages and large aggregates of lymphocytes, were seen within the epithelioid macrophage fields. The development of organized multifocal granulomas containing lymphocytes and macrophages progressed through day 100 (Fig. 3⇓C). Infections with CSU 123 and Erdman-KO1 showed similar pathology (data not shown).
The development of pathology in the lungs of mice given CSU 93 was similar but more exaggerated. During early infection lesions tended to be larger than those seen with H37Rv and again consisted of aggregates of lymphocytes and some macrophages (Fig. 3⇑D). Evidence for worsened lung pathology was apparent by day 30 (Fig. 3⇑E) characterized by an increased number of lymphocytes and highly vacuolated cells infiltrating into the lung tissues resulting in large lesions. By day 100, however, the frequency of lesions and lung consolidation had appeared to stabilize (Fig. 3⇑F).
Marked differences in pathology were seen in mice infected with M. tuberculosis HN878. Early in infection, moderately sized lesions were already developing, denoted by increased lymphocytic and phagocytic cellular infiltration, and thickening of the parenchymal walls indicative of inflammation in excess to the other strains tested (Fig. 3⇑G). These lesions continued to increase in size as the infection progressed (Fig. 3⇑H), characterized by coalescing inflammatory granulomas that were larger than those seen in the other groups. Most lesions contained a large number of highly vacuolated "foamy" macrophages containing a large number of acid fast bacilli. By day 100, most of the lung tissues were consolidated, with some lesions showing evidence of necrosis (Fig. 3⇑I).
Differences in the influx of CD4+ and CD8+ T cells in the lungs of infected mice
Given the clear differences seen in cell influx indicated by the histological analysis, we conducted a comparative flow cytometric analysis of CD4+ and CD8+ T cell populations in lung cell digests from each group of infected mice. T cells were gated with a primary gate on viable FSClow vs SSClow lymphocytes and then on CD3+ T cells, and analyzed for changes in the total percentage of CD3+CD4+ and CD3+CD8+ cells over the course of infection (Fig. 4⇓).
In mice infected with HN878, there were rapid influxes of both CD4 and CD8 cells (Fig. 4⇑, A and B), reaching higher levels on day 15 of the infection compared with the other four strains. This stabilized by day 30 and then declined at a similar rate in all groups. These observations were consistent with histological data from day 15, in which much larger lymphocytic lesions were observed in the animals infected with HN878 (Fig. 4⇑C).
Differences in the influx of DCs and plasmacytoid DCs (pDCs) in the lungs of infected mice
DCs and pDCs are major producers of type I IFNs that are involved in inflammation, immunoregulation, and T cell responses during bacterial and viral infections (43, 44, 45). Given earlier reports implicating increased type I IFN in mice infected with M. tuberculosis HN878, we decided to monitor the number of pDCs and DCs infiltrating the lungs over the course of the disease.
The number of CD11b−CDllc+B220−Gr1− DCs and CD11b−CDllc+B220+Gr1+ pDCs was determined by primarily gating on FSChigh vs SSChigh granulocytes (Fig. 5⇓A) and then detecting DCs in the CD11c+ region containing CD11b−CD11c+ cells (Fig. 5⇓B), which also were B220−GR1−. Thereafter, pDCs were present in the region containing CD11b−CD11c+GR1+CD11b+ cells (Fig. 5⇓C).
As shown in Fig. 5⇑D, the total number of pDCs in the lungs obtained from M. tuberculosis HN878-infected mice increased in much larger numbers from day 15 to day 60 of the infection compared with the number of pDCs in mice infected with other strains. Similarly, the total number of DCs in the lungs of HN878-infected mice steadily increased with time at a higher rate than seen in the other strains (Fig. 5⇑E). In previous studies we have found evidence of DC markers on highly vacuolated foamy macrophages in granulomatous lesions (46), and so it was interesting to note in the current study that many more cells of this type appeared early in lesions in lungs of HN878-infected mice compared with H37Rv infection (Fig. 5⇑F) and that these contained a large number of acid fast-positive bacteria (Fig. 5⇑F).
Differential production of IFN-γ, TNF-α, MCP-1, IL-10, and IL-6 cytokines by cells from infected lungs
As shown in Fig. 6⇓A, we were able to demonstrate that T cells harvested from the lungs of all infected groups and stimulated in vitro with culture filtrate proteins were able to produce IFN-γ, thus questioning earlier reports that HN878-infected mice could not generate a TH1 response. Further analysis of supernatants also revealed similar amounts of TNF-α, MCP-1, and IL-6 (Fig. 6⇓, B–E). Interestingly, and consistent with further results described below, IL-10 production was considerably elevated in the HN878 group after day 30.
Characterization of CD4+ and CD8+ cells in the lungs of C57BL/6 mice exposed to M. tuberculosis strains H37Rv or HN878 reveals the appearance of regulatory T cells in the latter group
It was interesting to note that despite the rapid growth of the HN878 strain it was rapidly controlled by host immunity and quickly showed evidence of entering a chronic state. An initial rapid worsening of lung pathology also began to apparently stabilize, and these mice somewhat paradoxically showed evidence of increased IL-10 production. To try to understand these early events we performed studies in which we reexamined the early T cell response. Fig. 7⇓ shows a representative dot plot of lung cells from a representative mouse after 21 days of infection with H37Rv or HN878 primarily gated on viable FSClow vs SSClow lymphocytes and then on CD3+ T cells (Fig. 7⇓A) and then gated on CD4+IFN-γ+ cells (Fig. 7⇓B). Fig. 7⇓C shows the bacterial load in the lungs over the first 21 days and the number of IFN-γ-secreting CD4 or CD8 found in the lungs at that time. Fig. 7⇓, D and E, shows an increased number of IFN-γ-secreting CD4 or CD8 T cells in the HN878-infected mice, but also evidence of a drop at day 21. We found evidence that initially HN878 induces a strong TH1 response characterized by significant IFN-γ production, which by day 14 begins to decline.
In view of this observation, we performed a much more comprehensive examination of the phenotypes of the CD4 and CD8 cells present in the lungs using multiparameter flow cytometry. The number of T cells was gated with a primary gate on viable FSClow vs SSClow lymphocytes (Fig. 8⇓A) and then a gate on CD4+ T cells (Fig. 8⇓B) coexpressing CD25 and FoxP3 (Fig. 8⇓C) and CD223 and IL-10 (Fig. 8⇓D). Changes in the total percentage of these cells were monitored over the course of infection. To our surprise, we not only found evidence of CD4 cells expressing the regulatory T cell markers CD25, FoxP3, and CD223 in the lungs, but also evidence of a rapid expansion of these cells by day 21 (Fig. 8⇓E). Moreover, many of these cells were also positive for intracellular IL-10 (Fig. 8⇓F). A very low number of such cells was seen in the H37Rv-infected mice but with no evidence of any expansion (in our unpublished observations, we monitored mice infected with H37Rv for over 300 days and found no evidence for any expansion of CD4 cells with a regulatory T cell phenotype).
To further validate the presence of immunosuppressive T regulatory cells during infection with the HN878 strain, we evaluated expression of the mouse GITR. GITR interaction with its ligand augments T cell activation, proliferation, and IL-2, IFN-γ, and IL-4 cytokine secretion and abrogates regulatory T cell suppression (47, 48, 49). C57BL/6 mice infected with HN878 demonstrated an increased number of CD4+CD25+GITR+ T cells in the lungs during the early course of infection compared with M. tuberculosis H37Rv-infected mice (Fig. 8⇑G). However, C57BL/6 mice infected with M. tuberculosis H37Rv showed a substantial increase in CD4+CD25+GITR+ T cells in the lungs after 21 days of the infection. By this time, this population was declining in the HN878-infected mice indicative of reduced CD4+ T cell proliferation and activation. GITR plays a key role in regulating the immunosuppressive function mediated by regulatory T cells. Therefore the increased expression of GITR by M. tuberculosis H37Rv-infected mice indicates a state of T cell activation and prevents the development of immunosuppressive T cells. In contrast, decreased expression of GITR by M. tuberculosis HN878-infected mice indicates removal of GITR signaling, which leads to the development of immunosuppressive T cells.
The results of this study show that the M. tuberculosis strain HN878 is clearly more virulent for mice than other strains, growing much faster in the lungs and inducing severe lung damage and consolidation. After 20–30 days or more, the infection is contained and the lung pathology apparently slows, but animals still die more quickly than other virulent strains. The reason for this paradox can hypothetically be explained by our observation that the HN878 infection rapidly induces progressive lung pathology during a time when the protective TH1 response declines, which was associated with the appearance of a regulatory T cell response. In our study, we show these forementioned events occurred during the same time frame and do not demonstrate a causal link between the lung pathology and the appearance of a regulatory T cell population during HN878 infection.
In this regard, we found evidence that initially HN878 induces a strong TH1 response, contrary to the hypothesis of Manca and colleagues (4, 5) who have argued that the hypervirulence of HN878 reflects its ability to avoid a TH1 response, an ability ascribed to its possession of a cell wall polyketide synthase-derived phenolic glycolipid that induces cytokines known to block TH1 responses (5). However, in our hands, HN878 induced a potent TH1 response characterized by significant IFN-γ and TNF-α production; this peaked by day 14 and then declined. It is possible that the differences in our results and the earlier reports from Manca and colleagues (4, 5) could be due to differences in the experimental methods used, as we tracked the early phenotypical cellular kinetics and cytokine responses by flow cytometry compared with their reports using RT-PCR for cytokine mRNA in the animals lungs. Furthermore, our report depended heavily on the animals lung pathology induced by the HN878 strain, whereas their studies were devoid of pathological analyses (4, 5).
Earlier studies also found evidence for an increased production of type I IFN and hypothesized that this interfered with the ability of the animal to control the infection (4). To test this further, we compared normal and IFN-αβ receptor KO mice, reasoning that inability to respond to these cytokines would improve protection. This effect indeed seemed to be the case, but was only evident for most strains well into the chronic phase of the disease.
A steady increase in both pDCs and DCs was observed in the lungs of all the infection groups, and these cells are known to be rich sources of type I IFN (43, 50). The apparent lack of TH1 immunity during HN878 infection in earlier reports was associated with increases in IFN-α but changes in the levels of IFN-β were not evaluated. This observation is important because other reports have shown that infection of C57BL/6 mice with Listeria induces IFN-β expression and suppresses the accumulation of CD11b+ macrophages secreting TNF-α cells at the sites of infection (51). In contrast IFN-αβ receptor KO mice were more resistant to Listeria infection and had a greater number of CD11b+ cells producing TNF-α and IL-12p70 cells at the site of infection (51). In the present study, pDCs and DCs were very prominent in the early response to HN878, and were found to be harboring a large number of acid fast bacilli. In addition, foamy cells, which express the DC marker DEC-205, were also prominent; these cells down-regulate molecules involved in Ag presentation and may potentially provide safe niches for M. tuberculosis survival (46).
In our evaluation of the early T cell response in the HN878-infected mice, we observed that both CD4 and CD8 cells secreting IFN-γ were rapidly induced, but these began to decline at 21 days, whereas at the same time a rapid increase in IL-10+ CD4 cells was observed. These latter cells stained positive for CD25, CD223, and FoxP3, which are all known markers of immunosuppressive regulatory T cells (27, 28). A recent report showed cotransferred CD4+CD25+ T regulatory cells from naive C57BL/6 mice into C57BL/6J-Rag1−/− mice infected with M. tuberculosis H37Rv resulted in suppression of protective immunity, which was not associated with IFN-γ, inducible NO synthase, nor increased IL-10 (52). Our current study evaluated the early T regulatory cell response during M. tuberculosis H37Rv infection and supports the notion that the presence of T regulatory cells was not associated with inhibition of the early acquired immune response by reduced IFN-γ. It is probable that differences in the virulence and kinetics of the immunopathology induced by these two bacterial strains are associated with the degree to which functional characteristics of T regulatory cells are expressed.
In addition we evaluated the expression of GITR on T regulatory cells by M. tuberculosis HN878-infected mice, which was down-regulated by day 21 and associated with the appearance of immunosuppressive regulatory T cells (47, 48, 49). GITR is expressed at low levels on responder T cells and is up-regulated in T regulatory cells and in activated T cells (47). Activation of GITR enhances costimulation of responder T cells and suppressor activity is abrogated, resulting in enhanced immune responses (47, 48, 49). It is plausible that the reduced expression of GITR in M. tuberculosis HN878-infected mice evident by day 21 and coincided with reduced IFN-γ represents lack of GITR signaling and less potent T cell activation. In contrast M. tuberculosis H37Rv showed increased GITR expression, which was associated with increased IFN-γ expression (47).
Whether the speed of the emerging TH1 response was the stimulus for the induction of the regulatory T cell subset is unknown, but it was clearly much faster than that seen in the other M. tuberculosis infections, and indeed we have yet to detect this latter subset in these other cases (even high dose i.v. models). A second possibility is that regulatory T cells responded to the acute lung damage caused by the HN878 infection, consistent with our previous observation that IL-10, a product of regulatory T cells as well as macrophages, may play a role in maintaining the stability of chronic lung disease in the face of increasing necrosis (19). A similar observation has been made in the case of Bordetella pertussis infection (53). Moreover there is evidence that patients with active tuberculosis have raised levels of circulating regulatory T cells (22, 54). More importantly these tuberculosis patients demonstrated T regulatory cells were expanded at sites of active tuberculosis disease in parallel with high local concentrations of M. tuberculosis-specific TH1-type IFN-γ-secreting T cells and in areas of immunopathology (22). Future studies are warranted sorting these T regulatory cells and using adoptive cell transfer into C57BL/6J-Rag1 mice to show a causal link between the aggressive TH1 response and the appearance of immunosuppressive T regulatory cells during HN878 infection.
The authors have no financial conflict of interest.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵1 This work was supported by Grants AI-44072 and AI-40488 from the National Institutes of Health.
↵2 Address correspondence and reprint requests to Dr. Diane Ordway, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682. E-mail address: D.Ordway-Rodriguez{at}colostate.edu
↵3 Abbreviations used in this paper: DC, dendritic cell; pDC, plasmacytoid DC; FSC, forward light scatter; SSC, side light scatter; GITR, glucocorticoid-induced TNF-related receptor; KO, knockout.
- Received January 26, 2007.
- Accepted April 25, 2007.
- Copyright © 2007 by The American Association of Immunologists


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