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Personnel Committee
Monday 8 June 2009 6:30 PM
Walton Room, Guildhall, Winchester
Dave Shaw
Position: Principal Democratic Services Officer
Telephone: 01962 848221
Email: firstname.lastname@example.com
Business Items
1 - View minutes of this meeting
Minutes 8 June 2009 46KB
7 - Organisational Development – Outturn Report 2008/09
8 - Winchester City Council Establishment 2009/10
PER164 plus Appendices 1-3 112KB
Appendix 4A 25KB
Appendix 4B 21KB
Appendix 4C 23KB
Appendix 4D 22KB
Appendix 4E 23KB
Appendix 4F 20KB
Appendix 4G 20KB
Appendix 4H 30KB
Appendix 4I 22KB
Appendix 4J 25KB
Appendix 4K 24KB
Appendix 4L 27KB
Appendix 4M 21KB
Appendix 4N 34KB
Appendix 4O 30KB
Appendix 4P 26KB
Appendix 4Q 29KB
Appendix 4R 23KB
Appendix 5 33KB
Exempt Business
In accordance with the Local Government Act 1972 the Committee will decide whether it wishes to consider the following items under Exempt Business. If it decides to do this, the public will be asked to leave the meeting whilst consideration of these items takes place. For this reason the reports are not available on the website. Please contact the Committee Administrator for further details.
10 - Exempt Minutes of previous meeting held on 23 February 2009
Exempt Minutes 23 February 2009
11 - Revenues Partnership working with Test Valley Borough Council


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VIDEO: Victoria Beckham Slams Divorce Rumors
Victoria Beckham is shutting down those divorce rumors! The 41-year-old former Spice Girl says she has never listened to or commented on any rumors, until now. After 16 years of marriage, Victoria says she and her soccer star hubby David have nothing to prove. She adds, "We love each other, look out for each other and are strong as both partners and parents. My husband constantly inspires me and guides me." And with that, the cupid gods are still working.
[grabpress_video video_id="5449887″ auto_play="true" width="500″ height="281″ guid="c871c2faeaa77415b7aabe47c7f68adc3fa5ec15″]Thanks for checking us out. Please take a look at the rest of our videos and articles.
To stay in the loop, bookmark our homepage.

subset: commoncrawl


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The Wallabies will unleash tenacious flanker Sean McMahon on an injury-ravaged Wales as they go into Saturday's World Cup shootout with top spot in Pool A on the line.
The fiery Rebels star, who will occupy the No.7 jersey at Twickenham in place of suspended vice-captain Michael Hooper, beat fellow back-rower Ben McCalman to the starting lineup against Wales in one of three changes from the team that thrashed England last Saturday.
In the only change not forced by injury or suspension, lock Dean Mumm joins Kane Douglas in the Wallabies' second-row with Rob Simmons dropped.
Joining him in the starting XV is winger Drew Mitchell, Australia's most prolific World Cup tryscorer with 12, who takes the left wing spot from the injured Rob Horne (shoulder).
Star backs Israel Folau and Matt Giteau have overcome ankle and rib injuries respectively to be named.
Coach Michael Cheika has made it clear throughout the tournament how impressed he is with young McMahon – who has won man-of-the-match honours in his past two games, against Uruguay a fortnight ago and the USA in a pre-World Cup warm-up clash.
McMahon's selection also minimises the selection shake-up for the Wallabies – had Cheika gone with McCalman, it would've likely forced David Pocock out of the No.8 jersey.
While the openside flanker role is Pocock's preferred position, he's grown immensely in the No.8 role and will certainly end up back there when Hooper returns from his one-game ban in time for the quarter-finals.
Wales have deployed a starting backrow that includes their own ball-hunting duo of Sam Warburton and Justin Tipuric to counter the Wallabies' fearsome backrow.
"Tipuric is a fantastic player," Cheika said.
"We respect their players massively and we have to make sure we isolate and try to get onto our ball."
The Wallabies intend to use the Wales clash to further refine their approach before the knock-out games.
"Every match in this tournament has required our team to step up to another level and we'll need to do that again against an undefeated Welsh team," Cheika said.
"Every player in our squad knows the improvements required, and we still have two days to continue to make them, both individually and as a team.
"Saturday night at Twickenham is another opportunity for us to put in a solid performance and continue to build towards the next stage of the tournament."
Israel Folau, Adam Ashley-Cooper, Tevita Kuridrani, Matt Giteau, Drew Mitchell, Bernard Foley, Will Genia, David Pocock, Sean McMahon, Scott Fardy, Dean Mumm, Kane Douglas, Sekope Kepu, Stephen Moore (capt), Scott Sio. Res: Tatafu Polota-Nau, James Slipper, Greg Holmes, Rob Simmons, Ben McCalman, Nick Phipps, Matt Toomua, Kurtley Beale.
Gareth Anscombe; Alex Cuthbert, George North, Jamie Roberts, Liam Williams; Dan Biggar, Gareth Davies; Taulupe Faletau, Justin Tipuric, Sam Warburton (capt); Alun Wyn Jones, Luke Charteris; Samson Lee, Scott Baldwin, Paul James. Res: Ken Owens, Aaron Jarvis, Tomas Francis, Jake Ball, Ross Moriarty, Lloyd Williams, Rhys Priestland, James Hook.


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- Description
- View Full Specifications
Fresh Water Beauty!
- Year:
- 1977
- Length:
- 42'
- Engine/Fuel Type:
- Twin / diesel
- Located In:
- Muskegon, MI
- Hull Material:
- Fiberglass
- 1863-2986259
- Last Listed Price:
- Sold
Traditional flush-deck motor yacht introduced in 1973, the BERTRAM 42' MY gets high marks for build quality, ride, comfort and lasting popularity. Convenient floorplan layout has mid-level galley forward, companionway to starboard with a large locker for storage on the starboard side of the companionway forward.
Generous forward cabin (Vee Berth) and private head closed off from salon. Excellent arrangement for two couple cruising or to segregate kids for privacy.
Master stateroom aft has two twin and a half berths (very generous), private head, stall shower and storage in lockers, drawers and cabinets.
This model is loaded with storage through out.
Salon features a hid-a-bed couch, chairs, opening windows, air/heat and engine room access.
Large aft deck has lower centermounted helm, screened in aft deck, "wing doors" (rare), and access to swim platform.
Wide walk arounds allow easy access forward and aft, easy line handling and comfortable one couple cruising.
NOTHING COMPARES TO BERTRAM'S SEA-KEEPING ABILITY and the 42' MotorYacht is no exception. A great heavy weather vessel!
Amazing condition from it's 2nd owner of 21 years! All gel coat glistens, bottom clean & ready, mechanically up to date, all systems and equipment in proper operating condition.
Change in life style necessitates sale. This BERTRAM 42' MOTORYACHT is an amazing value!
Contact STARBOARD YACHTS, INC.
ERIC ROBINSON or JEREMY PEARSON
Please contact Eric Robinson at 616 796 0505
Additional Specs, Equipment and Information:
Boat Name
LOA: 42 ft 6 in
Beam: 14 ft 10 in
Maximum Draft: 4 ft 0 in
Bridge Clearance: 17 ft 11 in
Headroom: 6 ft 5 in
Deadrise: 17 ° at Transom
Dry Weight: 39000 lbs
Total Power: 670 HP
Engine 1:
Engine Brand: Detroit Diesel Allison
Year Built: 1977
Engine Model: 6-71
Engine Type: Inboard
Engine/Fuel Type: Diesel
Location: Starboard
Engine Hours: 1985
Propeller: 3 blade propeller
Drive Type: Direct Drive
Engine Power: 335 HP
Engine 2:
Engine Brand: Detroit Diesel Allison
Year Built: 1977
Engine Model: 6-71
Engine Type: Inboard
Engine/Fuel Type: Diesel
Location: Port
Engine Hours: 1985
Propeller: 3 blade propeller
Drive Type: Direct Drive
Engine Power: 335 HP
Cruising Speed: 16 knots
Maximum Speed: 24 knots
Fresh Water Tanks: Fiberglass (150 Gallons)
Fuel Tanks: Fiberglass (400 Gallons)
Holding Tanks: Fiberglass (60 Gallons)
Number of twin berths: 2
Number of double berths: 2
Number of cabins: 2
Number of heads: 2
Seating Capacity: 14
Radar - RayMarine
Depthsounder - AutoHelm
Log-speedometer - AutoHelm
Autopilot - AutoHelm
Inside Equipment
Electric bilge pump
Battery charger
Microwave oven
Refrigerator - Full size
Air conditioning - Reverse cycle/heat
Deep freezer
Heating - 110 volt plus reverse cycle
Electric head - 2- Vac
Hot water
Electrical Equipment
Shore power inlet
Electrical Circuit: 240V
Outside Equipment/Extras
Swimming ladder
Electric windlass
*Large salon that features opening screened windows, air/heat and enough room for gatherings on those cool evenings or rainy days. Forward of the salon and one step down is a full width galley, that can be an easy snack center, bar for entertainment or full meal preparation.
*Salon has hid-a-bed couch on starboard side, end tables and barrel style chairs
*Storage and both electrical panels are located on the port & starboard side of the salon. Easy access to both.
*Light airy and full beam this area is for all to enjoy
*Storage in drawers, shelves and cabinets, enough for a weekend or weeks of cruising
*Full size frig/freezer
*SS sink w/hot and cold pressure water
*Cook top, three burner
*Dish Washer
*Micro-wave oven
*Large "in floor" pantry
Master Stateroom
*Aft with twin and a half berths the MSR offers a huge getaway area. It has loads of storage in two large lockers, drawers, cupboards and shelves
*Private head, electric toilet and separate shower, storage and room
*Opening ports, screened, air/heat controls
Forward Stateroom/Head
*Large forward stateroom features a generous Vee Berth
*Storage in lockers, drawers and cupboards
*Screened opening ports
*Forward head is privately separated from salon by a companionway that twists from salon to the port side. It can be used for a "day head" or private facility for the forward stateroom, very unique and practical layout!
Enclosed Aft Deck
*Enclosed aft deck offers a full additional "room" screened in with furniture for enjoying cool evenings watching the sun go down, dining al-fresco or taking that well deserved nap out of the direct sunshine
*Wet Bar on port side, ice maker, water and storage
*Furniture; chairs and couch
*Lower helm or "main helm" centered for handling ease
*Dual wing doors port and starboard
*Stern access through gate to swim platform on the starboard side out of the way
*Enter thru port side ladder to compact flybridge
*Captains/helm chair and mates chair
*Generous bench aft seating for 6
*Center mount helm station w/electronics repeaters
*Storage under bridge cowling port and starboard side
*Excellent visibility for those lazy, sunny cruising days when you want to have a commanding view
*Generous walk around areas that feature high rails for safety, port & starboard wing doors from the enclosed aft deck, and port and starboard entry gates
*Windlass, anchor, chain & rode
*Wide swim platform w/fold down safety ladder
*Gel Coat on the super structure shines like new!
The Company offers the details of this vessel in good faith but cannot guarantee or warrant the accuracy of this information nor warrant the condition of the vessel. A buyer should instruct his agents, or his surveyors, to investigate such details as the buyer desires validated. This vessel is offered subject to prior sale, price change, or withdrawal without notice.
Visit Website


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By Peg Rosen
If your child has dyscalculia, he may be getting supports and services in school to help with his math issues. But he may also benefit from tutoring outside of school. Are there tutors who can specifically help kids with dyscalculia? Learn about the options.
Tutors who help kids with dyslexia have specific reading programs they can be trained in. They can also get certification in those programs. The same doesn't really exist for tutors who help kids with dyscalculia.
There hasn't been as much research done on dyscalculia as on some other learning issues. So there are few evidence-based programs designed to help students who have it.
That doesn't mean you can't find a good tutor for your child, however. Or that there aren't teaching methods that benefit kids who struggle with math. The research that has been done suggests that a multisensory structured approach can help kids with dyscalculia.
One math program that uses this approach is Stern Structural Arithmetic. It appears to be effective, though there are not large studies to confirm its effectiveness. The Stern method is similar to some effective dyslexia reading programs.
You can try to find a tutor who uses the Stern system. But what's most important is that the tutor you hire uses elements like those found in Stern Structural Arithmetic. That means that the tutor's approach should be:
As the tutor works with your child, she should set goals for him. She should also provide you with regular updates about his progress.
Not many people call themselves a "dyscalculia tutor." So what type of professional can help your child with dyscalculia? The best options include:
Your child's school is the best place to start. His special education teacher, math teacher or caseworker may even have a list of qualified tutors.
Referrals from other parents who have kids with dyscalculia are another good option.
You can also contact the Association of Educational Therapists or the National Institute for Learning Development. Both organizations keep lists of certified educational therapists.
Most commercial tutoring centers won't have the specialized instruction your child needs. One exception is the Lindamood–Bell Program. It's best known for its reading program. But it also offers math tutoring that may be helpful for kids with dyscalculia. Lindamood–Bell has many centers throughout the United States.
The best teaching approach for dyscalculia may be multisensory. So online tutoring might not be a great option.
There's no real time frame for when tutoring should start or how long kids will need it. It's ideal to find outside help as soon as your child is identified as having dyscalculia. This is true even if he has an IEP or a 504 plan and is getting math support in school.
At first, intensive instruction is the best way for your child to learn to grasp basic math concepts. That gives him the best shot at catching up with his peers.
But new concepts are constantly introduced in math. So if he's not keeping up as new concepts are introduced, he may need ongoing outside support. He may be able to scale back how often he sees the tutor, however.
Parents usually have to pay out of pocket for private tutoring. The costs can be considerable: Rates can range from $25 to $80 an hour. They may be much higher in large cities.
Private tutoring can require a major commitment of time and money. But it can help your child develop a better understanding of math and math concepts. Learn more about questions to ask potential tutors. And find out what steps you can take to offset tutoring expenses.
Peg Rosen writes for digital and print, including ParentCenter, WebMD, Parents, Good Housekeeping and Martha Stewart.
Brendan R. Hodnett, M.A., is a special education teacher in Middletown, New Jersey.
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FAQs About Tutoring for Kids With Learning and Attention Issues
How Different Types of Tutoring Can Help Kids With Learning and Attention Issues
The Difference Between Tutoring and Academic Coaching
Is Online Tutoring a Good Option for My Child?
At a Glance: Skills Educational Therapists Work On
Tutoring Kids With Dyslexia: What You Need to Know
See a unique collection of articles on music and learning and attention issues.
Looking for the right college for your child? Get expert advice on common mistakes parents make.
Find out when and how to have your child reevaluated by the school.
Hear from an expert on the genetics behind reading and math issues.
Jerome Schultz
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Kern County: Take a Closer Look
Kern Economic Development Foundation
KEDF is a research and education-based 501(c)(3) organization that supports Kern County businesses and communities in reaching their full economic potential.
News & Press
Bakersfield MSA No. 2 for Most Diversified Large Metro Economy
June 21, 2017
The Bakersfield MSA was ranked the No. 2 large metros in the nation by WalletHub.com for most diversified economies.
Bakersfield No. 5 in U.S. for Affordable Home Ownership for Teachers, First Responders & Restaurant Workers
June 21, 2017
Trulia's study on affordable housing in the United States found that over 75% of teachers and first responders are able to afford a home in Bakersfield, compared to approximately 65% in Fresno, 45% in Riverside, 22% in Los Angeles, and just 14% in San Diego.


text: Market Vectors Emerging Markets Local Currency Bond ETF (EMLC) is not sponsored, endorsed, sold or promoted by J.P. Morgan and J.P. Morgan makes no representation regarding the advisability of investing in EMLC. J.P. Morgan does not warrant the completeness or accuracy of the J.P. Morgan GBI-EMG Core Index. "J.P. Morgan" is a registered service mark of JPMorgan Chase & Co. © 2010. JPMorgan Chase & Co. All rights reserved.Fund shares are not individually redeemable and will be issued and redeemed at their NAV only through certain authorized broker-dealers in large, specified blocks of shares called "creation units" and otherwise can be bought and sold only through exchange trading. Creation units of Market Vectors Africa Index ETF and Market Vectors Egypt Index ETF are issued and redeemed principally in cash. Creation units of Market Vectors Emerging Markets Local Currency Bond ETF are issued and redeemed principally in kind. Shares may trade at a premium or discount to their NAV in the secondary market. Investing involves risk, including possible loss of principal. Investors may call 1.888.MKT.VCTR or visit vaneck.com for a free prospectus or summary prospectus. They should consider the investment objective, risks, and charges and expenses of the investment company carefully before investing. The prospectus and summary prospectus contains this and other information. Please read the prospectus carefully before investing. Van Eck Securities Corporation, Distributor, 335 Madison Avenue, New York, NY 10017


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This property in Marseillan in the South of France enjoys a superb setting on the historic harbour quay in the village. Built in authentic style and with only three loft-style apartments available for sale, it is fair to say that this small and exclusive development, referred to as La Vermoutherie, is a truly a unique opportunity.
Each of the 3-bedroom loft apartments feature spacious and open living areas, oak flooring, private outdoor space and not least, the always present harbour and the lagoon at the end of the road.
Ranging in size from 112m² to 179m² and with private terraces up to 97m² the homes are a perfect escape to carefree lifestyle in Languedoc in the south of France.
The Marseillan apartments come fully equipped with quality kitchens and bathrooms with NEFF appliances, Gessi faucets, Arnould switches and Farrow & Ball paint, private parking and storage areas.
For extra convenience, the holiday homes are also fitted with air conditioning and smart home automation. And if you want to have your loft completely move-in ready, there is a complete furniture pack available along with a media pack from Loewe at an additional cost.
When you have paid for your home and moved in, you are in most cases left on your own but buying a home in La Vermoutherie is different. As a homeowner, there is a range of additional services available to you such as key handover and cleaning if you want to rent out you loft when not using it yourself. There is even a complete property management service who take full control of renting your property on your behalf and you can be fully assured that when you come down next time, you will come to clean and well managed home that is at least in just as good order as when you left it last time.
And when 'at home', a concierge service is available to help with everything from ordering a taxi to booking a restaurant.
And as an extra bonus, if you decide to rent out your apartment in Marseillan, you can save 20% on the purchase price as you can claim back the VAT (conditions apply).
Marseillan, Languedoc
Owning a home in Marseillan will give you easy access to everything that make living in South of France so amazing. The charming old seaside harbour town with its bustling quay and old town is laid back, beautiful and there is wealth of cafes, bars and restaurants. The Mediterranean beaches are close by and inland you will find sprawling vineyards, authentic villages, lakes and mountains.


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Ja, ich weiß! – New Video
Here's a quick cut, filmed on Friday, edited over the weekend and posted on Monday. This is why spring time in Vienna is pretty epic; the wind is good, the weather is warm and the people are awesome!
Be sure to follow all the latest updates on: www.facebook.com/adamsimsk72
Going downnn
Ok so a quick one on what's going downnn as I noticed this evening that I haven't updated in quite a while. Soooo..
PWA Fuerteventura
Great event but I destroyed myself 6 days before the competition, I'm still suffering from the ligament damage at the moment. Actually if I'm honest I feel like a cripple on the water right now but just getting on with it. Practising a lot of regular stance stuff because switch sucks, that has resulted in double culos becoming fairly dialled, yep a move update claim!
Pre and post PWA Fuerte
Basically I've just been training full power and enjoying windsurfing and everything that surrounds it. A lot of my friends came out this year and it was awesome to catch up with them, Tim Cowen was shredding the guitar every moment he got. And living with the groms is an 'experience' haha! It's a lot of fun and pushing them to send it everytime we hit the water is funny, today Nic went for his first pushloops after seeing me trying them off the smallest 'waves' in the world, somewhere between those centre 2 wave riders!!
Yep threw out the move claim earlier but here are a couple of videos I uploaded recently. We also did a lot of filming and these are pretty far from the best shots we have. I've been sessioning this tiny lagoon which is pretty much a puddle and can't wait to release the video. We (the groms, myself and Hanna) are working on this one now. Here are the videos…
Move tips – The kono
So hopefully one or two people tuned in a couple days ago for the forward loop technique, if not, take a look at my last post and follow the link. I've now completed the Kono and once again I hope there is something in there of use. I would focus mainly on ducking the sail because you need to be able to do this everytime anyway, so that is the first 'move' to master. Also it will help when it comes to the culo and other moves I start uploading.
For now here is THE KONO – CLICK HERE
Any questions or move requests please leave a comment or get in touch, my details are on the contact page.
Cape Town Video
So it's been a while in the making but I think the wait has been worth it. Bartek Jankowski who has already released a few epic clips put this one together for me. Feel free to like, rate, share, enjoy, etc…
The title is simply – Adam Sims Freestyling in Cape Town 2012
A massive thanks to BJ for producing it and also Hanna and Sam for doing a lot of the filming.
On another note there are a few changes going on my end with sponsors, etc… so feel free to hazard a guess and all will be reveled shortly!


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|Message view
|« Date » · « Thread »
|« Date » · « Thread »
|Jon Stevens <...@latchkey.com>
|Re: [jBoss-Dev] Re: jboss on tomcat update
|Sun, 29 Oct 2000 00:58:21 GMT
on 10/28/2000 5:41 PM, "Aaron Mulder" <firstname.lastname@example.com> wrote: > Overall, the most unfortunate thing here is that I don't believe > either party is trying to lock out code from the other. But the fact that > the licenses are not compatible means that one group or the other has to > change licenses in order to enable true sharing of code, which is one of > the greatest promises of open source. And it doesn't sound like either > party is willing. > > Aaron The amazing thing here is that the APL 1.1 license is one of the least restrictive licenses out there and definitely much less restrictive than the GPL. So, we are asking to not go to a MORE restrictive license, but to a LESS restrictive license. How can that be a bad thing? -jon -- http://scarab.tigris.org/ | http://noodle.tigris.org/ http://java.apache.org/ | http://java.apache.org/turbine/ http://www.working-dogs.com/ | http://jakarta.apache.org/velocity/ http://www.collab.net/ | http://www.sourcexchange.com/
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Top Posts by Category WordPress Plugin Added
Last week I added 4 WordPress plugins – "Share This", "Subscribe to Comments", "PageBar" and "Akismet".
Today I added another applicable plugin for k-director.com – Top Posts by Category Plugin.
According to liewcf,  Top Posts by Category Plugin allows you to display best posts which determined by the number of visits to the post or number of comments. Top posts list is recommended to increase blog traffic and new readers.
You can download the plugin at http://www.macalua.com/2007/02/01/top-posts-by-category-plugin/.
Subscribe to get free latest updates by email. Like our Facebook Page.
LIKE It & Leave A Comments
2 Responses to Top Posts by Category WordPress Plugin Added
It's test. This site was probably down…
This what i looking for. Thank for the info.
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Valor Wealth Management is a member of the Estate Planning Team (EPT). EPT is a team of professionals trained in the principles and strategies of business planning and wealth succession planning of the Deferred Sales Trust. EPT is a professional group of highly trained advisors comprised of top tax attorneys and advisors committed to assisting clients with business transitions. The Deferred Sales Trust is a tax-deferred strategy under IRS rule 453. Over the next twenty years it is estimated that 20 trillion dollars will transition to the next generation in the United Sates. Many of these individuals want to minimize their potential tax liability by deferring tax, the Estate Planning Team believes that we engineer the liability as well as increase income for the beneficiary. According to Pew Research Center, roughly 10,000 baby boomers will turn 65 every day for the next 15 years.
Our goal is to establish professional relationships by developing solutions that solve business and estate transfer situations. The Estate planning Team (EPT) is comprised of experts in multiple disciplines focused on developing viable solutions for all of our clients. EPT membership consists of C.P.As, tax professionals, tax attorneys, real estate professionals and investment professionals.
We believe in a tactical approach to preserving and growing wealth, building a business and/or planning for retirement. We have yet to meet an investor who enjoys the rollercoaster experience associated with a "buy and hope" investment strategy. We work with individuals as well as private and corporate clients. It is our belief that an effective wealth management strategy should include 3 key foundational elements: financial planning, healthcare expense mitigation and estate planning. Whether you are in the middle of your career, approaching retirement or already relaxing on the beach, we assure you that together we can make a significantly positive impact on your future and the legacy you leave to future generations.
Apparel and Accessory Stores, Automotive Dealers, Bars/Taverns, Blding Mat., Hardware, Garden, Convenience Stores, Florists, Gasoline Service Stations, General Merchandise Stores, Home Furniture & Furnishings, Liquor Stores, Marine Dealers & Equipment, Miscellaneous Retail, Other Eating & Drinking Places, Other Food Stores, Pet Shops & Supplies, Restaurants, Supermarkets, Vending Machines, Agents & Brokers, Amusement & Recreation, Auto Repair, Parts & Services, Beauty Salons, Barber Shops, Computer & Software Services, Drycleaning/Laundry Services, Educational Services, Engineering & Accounting Svcs, Finance, Banking, Loans, etc., Freight, Moving/Delivery, Health, Medical & Dental, Hotels & Other Lodging Places, Landscaping & Yard Services, Legal Services, Marine Repair, Parts & Services, Membership Organizations, Miscellaneous Repair Services, Miscellaneous Services, Motion Pictures, Museums, Art Galleries, Zoos, Other Business Services, Other Personal Services, Other Travel & Transportation, Passenger Transportation, Pet Care & Grooming, Social Services, Storage & Warehousing, Travel Agencies, Business Services (B2B), Consumer Services (B2C), Domain Name/Basic Site, General Internet, ISP/ASP Services, Software, Web Design/Tech Services, Apparel & finished fabrics, Chemicals & Allied Products, Electronic & Electrical Equip., Fabricated Metal Products, Food and Kindred Products, Furniture and Fixtures, Industrial & Comm. Machinery, Leather and Leather Products, Lumber and Wood Products, Measuring & Analyzing Instr., Miscellaneous Manufacturing, Paper & Allied Products, Petroleum Refining, Primary Metal Industries, Printing, Publishing, Rubber and Plastic Products, Stone, Clay, Glass, Concrete, Textile Mill Products, Tobacco Products, Transportation Equipment, Durable Goods, Nondurable Goods, Building, Heavy, Special Trades, For Sale


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Friday 10 July 1914
It was Friday, under the sign of Cancer. The US president was Woodrow Wilson (Democratic).
Famous people born on this day include Joe Shuster and Rempo Urip.
The King of the Beggars, directed by , was one of the most viewed movies released in 1914
But much more happened that day: find out below..
You can also have a look at the whole 1914 or at July 10 across the years.
Old Newspapers
Have a look at the old newspapers from 10 July 1914 and get them!
Which were the most popular movies released in the last months ?
Find out your future
Get a FREE Numerology report based on the digits of 10 July 1914!
Wish him/her..
Historical Events
Which were the important events of 10 July 1914 ?
- Mauritania - Armed Forces Day
- Bahamas - Independence Day
- Silence Day - celebrated by followers of Meher Baba
- Ancient Latvia - Septinu Bralu Diena observed
Famous Birthdays:
- Joe Shuster: Canadian comic book artist, and co-creator of Superman (b.
- Rempo Urip: Indonesian film director.
- Boston Red Sox purchase Babe Ruth from the Baltimore Orioles.
- Mr. Hartwig, Russian Minister to Serbia, dies suddenly at the Austrian Legation in Belgrade.
Music Charts
Which were the top hits in that special week of July 1914 ?
Top #1 songs in the USA
- In the Town Where I was Born - Owen McCormack
Search For Your Ancestors
Subscribe to our Newsletter
Don't miss our monthly news, no spam guarantee Click here to Subscribe
...and if 10 July 1914 was your Birth Date then Join our Birthday Club!
Make this date unforgettable
Genealogy: find out your family heritage
Which were the most popular books released in the last weeks ?
Remember when
What videogames would you be playing back in the days ?


text:
Competera is Ukrainian IT company, founded in 2013. We believe in the power of data-driven decision, so we have developed several successful SaaS for e-commerce and online retailers.
Our products are Price Intelligence and Brand Intelligence platforms, that help our clients to make decisions and be competitive on the market.
Our clients are top players of e-commerce market all over the world.
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>> at union bank, our relationship managers work hard to know your business, offering specialized solutions and capital to help you meet your growth objectives. we offer expertise and tailored solutions for small businesses and major corporations. what can we do for you? >> and now, "bbc world news america." >> this is bbc world news america. reporting from washington, i'm kathy kaye. the white house says it will push from -- for tighter gun control days after the school shooting shattered new town. they tried to help children and five women are shot dead in pakistan simply for distributing polio vaccines.
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jansing into the future decades ne o one electronic superhighway long before many even knew he was being built. welcome to our viewers on public television in america and elsewhere around the globe. four days after the mass shootings in newtown, conn., the funerals continue for the 22 becomes lost their lives. and while the town mourns, the white house issued its strongest indication yet it will be pushing for tighter gun controls, including reinstating the assault weapons ban. from newtown, we begin our coverage. >> she loved or go wales and horses. a beautiful girl, her parents said. 6-year-old jessica was buried. another victim in america.
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that terrible friday as parents waited to hear what happened in the school, their pastor was with them. >> one parent, one mother in desperation cried out "are there any survivors?" there was violence. there were officials looking at one another and then they said, no, there are no survivors. i do not know that i will ever forget the noise as people wept, wales, eelam -- wailed, yelled. it was horrible noise. suddenly, reality hit. there are no survivors. >> this horror has changed the mood in america, for now at least. there of been those who have demonstrated against guns, but not a manufacturer of the weapon used to murder the children is
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under pressure. it was advertised as a prop to masculinity now the company within 95% stake in the firm is selling out because of this watershed event. just outside town, there are four rows of empty shelves. they have taken the guns off the market out of respect. but more important, it is part of a chain of around 200 jobs throughout the u.s. they all stopped selling the modern sporting rifles, as they're called. changes the law might be more difficult. >> there is no chance of a ban on handguns. the supreme court has ruled plans to outlaw them in chicago and washington d.c. are unconstitutional. the most likely move would be to ban military-style assault rifles, magazines holding numerous bullet. the president has backed such a
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bill. >> while he supports strongly an assault weapons ban and other measures, he wants to expand the conversation beyond those specific areas of legislation. >> i'm joe manchin -- >> the group of the gun hand -- of the gun ban will be loosened a little. even west virginia senator joe manchin, whose campaign had focused on gun rights, has changed his mind. he is not alone kerpen >> when my daughters ask me on friday night, dad, you are in the senate, why can't we put reasonable restrictions on assault weapons or rapid-fire ammunition clips, i did not have a good answer for them. enough is enough. >> america is in a reflective mood, which may not last. weapons of war should not be available to take the lives of children. >> the white house came out
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today with steps they would take toward tougher gun control. the national rifle association has released a statement saying they are prepared to offer meaningful contributions to help make sure this never happens again. for more on that part of the store, i spoke earlier with the bbc's paul adams. >> it has taken a while, and people have been wondering whether they were just shocked into a kind of silence. it does say they are prepared to offer what they call meaningful contributions to make sure this never happens again and they also are saying it will hold a major news conference in washington on friday. it will be interesting to see whether in the wake of this mounting series of calls for changes to america's gun legislation they have anything constructive to say about that. will they recognize that somehow some kind of tide has turned? >> meanwhile, the white house has issued a statement saying that president obama will try to push to tighter -- for tighter access to guns in america. he has said this before.
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nothing has actually happened. this time is different, perhaps? >> it feels different, and it feels different for the reason we are all talking about, because of a particular horror that was visited on newtown last week. the president did talk about it very briefly in the election campaign, and after his reelection, sales of assault weapons skyrocketed. they skyrocketed again on friday for the same reason, that people are conscious, nervous perhaps, gun enthusiasts, that new legislation may, indeed, come. this is a path that americans have been down before. bayville existed for 10 years and was deemed not to be successful -- a bill existed for 10 years and was deemed not to be successful. >> the president does not have to run for reelection anymore, so that may change the equation. as well as senior figures who have a good relationship with the gun lobby saying that this
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has to change now. >> i think the latter seems to be the thing that is very different you are getting publications publishing the list of 10 most influential supporters of the nra who are now in favor of some kind of change, names like harry reid, senator manchin common -- senator manchin. these are people whose nra record is impeccable. and they are all turning around and saying essentially the same thing, that assault weapons have no place in the kind of hunting culture that they espouse. it is something that makes it feel in washington as if we might be about to have something more than just a meaningful conversation. >> pala items they're remembering newtown. now to pakistan where five female health workers there to help with the country's anti- polio drive have been shot. their deaths come just one day after another polio program worker was also killed. the taliban has said the
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vaccination drive is part of a western plot. >> it is hard to explain why women would be shot dead for providing children care. that is what has happened in pakistan. four female health workers killed in different parts of karachi, another in a different city as they tried to vaccinate against polio. police say the -- it is clear these were coordinated attacks. the taliban are in charge of this area, says the mother of one of the victims. they say this polio-polio program was planned by america ftoish off our nation. they shot my daughter in the head. in the 1990's, about 20,000 people and here in pakistan were affected by polio. that came down to just 28 in 2005. but the numbers have risen since then and there is a risk they could rise further.
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what changed was propaganda from the pot -- the pakistani taliban. bay said the health workers were spies from western agencies and that they would sterilize children. began the program in some areas and workers were beaten out in others. then the militants found another justification for their position. when american -- america try to use a pakistani doctor and a fixed -- fake a vaccination program to get information about the home of bin laden. >> unfortunately, and in advisedly, they employed a health a vaccination campaign as a cover activity. this is really quite surprising that they would have put the entire helping campaign and at risk. -- health campaign at risk. >> the government says it simply cannot give security to the tens of thousands of health workers under threat.
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the vaccination program has been suspended, and children here are at risk of getting a crippling disease. bbc news, islamabad. the >> for more on these extraordinary attacks, i spoke earlier with a former u.s. ambassador to pakistan, wendy chamberlin. she is now president of the middle east institute. does it just looked like it, or are we seeing an increase in targeted attacks against women and children in pakistan? >> it does look like it, but long before mullock was attacked -- >> the girl that was trying to promote education for girls. >> that is right. the spokesman was attacked in a bird away by the pakistani taliban. but they have been attacking innocent people for a long time. and today is very brutal attack is just a dramatic -- symptomatic of the campaign against innocent people in pakistan. >> they have not cleaned these attacks, but they have set in the past that the campaign to eradicate polio in pakistan as
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part of a western plot. >> not only that, and i know it is hard to believe, but they have been able to convince many of the more uneducated people in the northwest and along the border that it is actually a cia plot to sterilize their children. this has been going on long before mulala and long before the doctor connected with the osama bin laden attacks. >> what has happened to these people is awful. one of them was only 17 years old. tragic, but also in the light of the fact that pakistan is so close to eradicating polio. it is hard to fathom that a group might not want that to happen in the country. >> i know. and you raise a very good point. the taliban has been encouraging people not to inoculate their children for years. but they have suffered some setbacks. and actually, because of the
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mullahs that have supported the taliban and the religious leaders stood up against this and inoculated their own children and encouraged villagers to inoculate against polio. they turned it around. in 2011, 200 pakistani children came down with polio. this year, only a little more than 50. it was a successful campaign. that is one of the victims in addition to these wonderful u.n. world health organization aid workers. the other victims are the 280,000 children have not get vaccinated now. >> what is being done to protect health workers and what is happening with a pakistani public opinion when it comes to attacks on civilians like this? >> the nature of these tax and the attack on mulala and the aid workers is terror. people need heroes. that is why the world rallied
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around mulala, because she stood up. she was a champion of education before she was attacked. these aid workers have gone forward with the polio campaign in the face of f taliban threat. they are heroes, and unfortunately, victims as well. >> ambassador, thank you for joining us. five very brave woman shot dead in pakistan. for more news about the world, chief correspondent for nbc, richard engel, and members of his production crew have been freed from syria after being held captive for five days. they came under fire at a rebel checkpoint on monday. he said his captors talked openly about their loyalty to president assad. under hospital care after 4 -- after a stroke.
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there is discussion about whether to fly president talabani abroad for treatment appeared correct -- portrait and. -- for treatment. and pres. zuma and won comfortably, but many people question his role following allegations of corruption. jonathan edwards report. >> it could be the first world -- clean, tidy, prosperous. south africa's black middle class is now 3 million strong. this place is where the anc was founded a century ago. today, its leaders enjoy all the trappings of the area as they turn up for their conference. the anc remains remarkably relaxed, not even the discovery of a white extremist bomb plot
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has upset them. still, all is not well with the party. the president, jacob zuma, is being challenged by his deputy. president zuma himself has been strongly accused of corruption, raised here in his speech. >> we can stop corruption in its tracks. >> one anc figure believes the correction comes because the movement has attracted the wrong sort of people. >> it has become one of the means through which people feel that they can accumulate wealth and great -- create opportunities for themselves and their families. and that is to the detriment of the movement. >> it is 18 years since the historic district -- the agreement between nelson mandela and the anc and the de
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klerk regime. today, declerck speaks about mandela with affection and respect. not so about president zuma. >> corruption is out of hand. the first five years have been bad for south africa. the unresolved allegations of corruption has made him unsuitable as the leader for the next seven years in south of the crop. -- south africa. >> only a short drive from the anc's conference call is this place, a depressing squatter camp. a single tap serves 700 people here. corruption is not the anc's only failing. it has failed also to sort out key problems like this one. squatter camps are supposed to be phased out in just two years, but it is obviously not going to happen. no one from the anc has been near this place.
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>> we do suffer living in this place. we suffer with water. we have got nothing here. >> does not how the founding father of the new south africa wants things to be. but nelson mandela poses a real achievement is the normality, the ordinariness of everything here. people used to be afraid that when he died, a country might fall apart. there is real anxiety about his health now, but nobody thinks south africa is in danger. bbc news. >> a group that had so much promise when it was first elected is struggling with running the country. your watching bbc world news america. still to come on tonight's program, striking gold for a second time. it is proving quite a treasure trove of. rk fax --
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of the very heart attacks. britain's queen elizabeth spent her morning in a meeting with the government's senior ministers. nicholas majora reports on an extremely rare event. >> there was a time when this is how britain was run, by the mark with his or her minister record that has not been the way of things for roughly 300 years. the prime minister has been studying historical records. the queen sat in the chair which is normally occupied by the prime minister. she did what she has done for so many generations of politicians. she watched and she listened. she said very little. but did she detect any cabinet rivalries? any tensions, perhaps, between the coalition partners? of course, whatever secrets of the cabinet table the queen may have picked up during this short visit will never be known. that is the essence of having a constitutional monarch.
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she has the right to be consulted, to encourage, and to warn, but never to interfere in politics. today, there was a moment for something else, a celebration of the end of her diamond jubilee and a gift from the cabinet. what did they get hurt? a side of the chancellor reminded the queen of the gold bars she had been shown up in of england pipa -- at the bank of england. but there were no gold bars today. instead, the cabinet had had a with a round, which produced just enough to buy between 60 placemats to mark her 60 years of service. the foreign office announce something of a grander. it announced that 160,000 square miles of british antarctic territory is to be renamed queen elizabeth land. and so, the monarchs went home, and ice cream and keeper of a few more cabinet secrets.
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-- an ice queen and keeper of a few more cabinet secrets. >> now to a story of archaeologists striking treasure for a second time. it was three years ago that britain's largest port of anglo- saxon metalwork was found in a field and staff for chyron. they found -- in staffordshire. they found 19 more pieces. jeremy could have a look. >> anglo-saxon treasurer, 90 artifacts dating back some 1400 years. just the latest fine from a location where the huge staffordshire hall was unearthed in three years ago. but why was so much a valuable stuff. in a field near warsaw? -- buried in a field near warsaw? to one theory is someone under threat had to leave town in a hurry. >> you rode away from your house and found a nice, quiet place, a place that you can remember and you come back for it.
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>> but they never did. >> no. >> the original, finding included 3900 mainly gold and silver items, up 3.3 million pounds worth. experts thought they had recovered everything. it turns out they had missed a bit. the theory at behind why some of the treasure was met -- was left in the ground was that was buried so deep that it was beyond the range of metal detectors. what has changed now that the crown has recently been proud -- been plowed, bringing these fresh items to the surface. -- the crown has recently been plowed company's fresh items to the surface. -- ground has recently been plowed contracts in my view, is the most important find that has ever been seen. it ranks along with totten common's treasure critical -- to dock a mean --
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.otankamen's treasure >> for archaeologists, it opens a unique window on our anglo- saxon past. >> beautiful. from an ancient find to the speed of modern technology, these days, transmitting data with a few keystrokes seems like second nature. but in the 1960's when the korean-born visual artist envision it, he was definitely ahead of his time. considered the father of video art, he died in 2006 and now there is a new exhibition devoted to his work. >> this is how he imagine the future. the electronic superhighway uses movie clips and newsreels to illustrate how media underpins our understanding of the world. hardly a revelation today, but
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at the time the technology was deion and the idea of revolutionary -- the technology was young and the idea of revolutionary. even earlier, he predicted a paperless society and inflation sharing on a global scale. >> he imagine a world in which the videos could be sent around the world and cultures could interconnect around the globe to communicate better, learn from each other. it is an inspired idea, and he had in 1968. the date of that piece blows my mind. >> he was born in north korea in 1932 -- in korea in 1932. when the north invaded, he and his family fled to japan. but in new york at the epicenter of new technology and ideas, that eventually became his home. and at a time when people were not expected to interact with technology, he invited
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participation. >> we have his random access, which shows the artist having read -- the constructed a real to real audio decker he invites the audience to interact with the trucks on our own with the device. >> why did he do this? and how is it relevant today? >> he was the first artist to the construct technology and give it back to west. it is a metaphor for what we're going through today with the internet and the technology that we deal with on a day-to-day basis. >> he knew that television would change the world. and his art embraces it, sometimes playfully, sometimes obscure. he defined a new visual medium that is now at the center of our to the 21st century. he was really the first person
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to use technology in ways that today, we take for granted. he predicted the power of television, how electronic media could bring us all together, and what you see here are his ideas. decades later compaq now reality. -- decades later, now a reality. >> that is very cool. it brings a show to it -- our show to a) you can watch for updates -- to a close. and you can watch for updates anytime on our website. >> makes sense of international news at bbc.com/news. >> funding of this presentation was made possible by the freeman foundation of new york, stowe, vermont, and honolulu, newman's own foundation,
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and union bank. >> at union bank, our relationship managers work hard to understand the industry you operate in, working to nurture new ventures and help provide capital for key strategic decisions. we offer expertise and tailored solutions in a wide range of industries. what can we do for you? >> "bbc world news" was presented by kcet, los angeles.
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captioning sponsored by wpbt >> this is n.b.r. >> susie: good evening, everyone. i'm susie gharib. tom is off tonight. the white house knocks down house speaker john boehner's back-up plan to avoid the fiscal cliff. we'll have details on his "plan b." we get an insider's perspective on those talks from roger altman. he was a key adviser in the clinton administration and now, as head of investment firm evercore, he's plugged in to corporate america and wall street. and are apple's hot-selling products cooling off? is the competitwi
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text:
Easy Kidney Bean and Cheese Casserole
READY IN: 40mins
Recipe by Kittencalrecipezazz
If you prefer spicy then add in a finely chopped jalapeno pepper. The chili powder can be increased or decreased to suit taste.Also you can add in some navy beans with the kidney beans. This is a very simple but good bean recipe.
Top Review by maxwelltrenton
I used 1 can of petite tomotoes and 1 can of Rotel. It gives it a little more kick but not super spicy. Reheats well... tastes better the second day so I make on the weekend for lunches the next week.
See Discussion:4 Reviews
Ingredients Nutrition
- 3 cups grated cheddar cheese (or to taste)
- 1 large onion, chopped
- 1 tablespoon chopped fresh garlic (to taste)
- 1 small green bell pepper, coarsley chopped (optional)
- 3 -4 tablespoons oil
- 3 -4 teaspoons chili powder (to taste)
- 1 (28 ounce) can red kidney beans, drained and rinsed
- 1 (28 ounce) can whole tomatoes, drained and coarsley chopped
- salt and pepper
Directions See How It's Made
- Set oven to 350 degrees.
- Grease a 2-quart casserole dish.
- Heat a large skillet with oil over medium heat.
- Add in onion, garlic and green bell pepper (if using) saute until the onions are just golden.
- Add in the chili powder, salt and pepper; cook stirring for 1 minute.
- Add in the red kidney beans and drained chopped tomatoes; cook, stirring for 20 minutes, seasoning with more chili powder, salt and pepper to taste.
- Spread half of the mixture into the bottom of the baking dish.
- Sprinkle with about 1-1/2 cups cheese.
- Top with remaining bean mixture.
- Then top with remaining 1-1/2 cups cheddar cheese (or to taste).
- Bake uncovered for about 25 minutes, or until the cheese is browned.
- Serve hot.


text:
I am making a tiered cake with silk flowers between the tiers. I will use the separator plates with columns. But.....I really don't want to be able to see the plates. So can I put the cake on covered cake boards..the size of the cake....and then use a plate that is a size smaller than the cake?
1 reply
Yes. The exception would be if the top tier is too small and separator plates aren't available in that size.


text:
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Cytech Europe
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Cytech Europe Limited is the UK distributor of the Comfort Intelligent Home System incorporating an advanced intruder alarm system, a home automation system that can control lighting (including KNX, C-Bus and Dynalite), appliances, heating and airconditioning, an 8 mailbox voicemail system, voicemail and doorphone intercom system. Comfort products include designer scene control switches, hand-held remote controls, talking keypads.
Cytech iPhone Apps Available
15 June, 2011
Free iPhone apps have been made available from Cytech Europe with keypad emulation and alarm events display
Intelligent Home Automation On Show in Manchester
27 September, 2010
UK Distributor for Cytech Europe's Comfort system for home automation and domestic security will be displaying the system at Manchester City Football Club
Stylish Keypad Controller For Home Security Systems
24 August, 2010
The KT03 from Cytech Europe has been designed for flexibility and ease of use for home users of the Comfort security system
Brochure Available on Comfort to KNX Bus
21 April, 2010
Cytech Europe has introduced a brochure available on the company's website detailing the intruder alarm signal mapping to the Comfort Intelligent Home System
Portuguese Installers Undergo Home Security Training Course
10 February, 2010
Cytech Europe has visited Portuguese town to train system installers on home security and management systems
Cytech Home Automation benefits for assistive living
09 December, 2009
The Comfort System for home automation and security from Cytech Europe has a number of benefits relating to Assistive Living and the building industry's Sustainable Homes targets
Comfort Home Security Systems gain Italian language support
10 November, 2009
Cytech Europe has added Italian language support to its other European and Asian languages on the Comfort Home Security System
Installer training available for KNX integration
23 October, 2009
Course in January focuses on integrating the Comfort Intelligent Home System with the KNX building control standard
Comfort integrated interface with KNX standard
18 August, 2009
Support for the KNX standard for home and building control now available on the Comfort Intelligent Home System from Cytech Europe
Comfort intelligent home system on display at BRE innovation park
06 August, 2009
Test out the Comfort Intelligent Home System from Cytech Europe at the interactive display now in operation at the Building Research Establishment's Innovation Park in Watford
Smart home training program for Ireland
17 June, 2009
Cytech distributor in Ireland to hold training course in July for the Comfort home automation and security system
Door station intercoms for home security
09 June, 2009
Intercoms for the Comfort Intelligent Home System can enable call diversion to mobile phones to prevent users from knowing the home is unoccupied
Upgrade available for home security users
13 May, 2009
Path available for upgrade to Comfort II for home security users to benefit from modifications including improved intercom system
Intelligent home system gains new user interface
26 March, 2009
Downloadable Comfigurator 3 programming software available for home automation and security system
Smart home security for the Irish market
27 February, 2009
Cytech Europe launches IDAS as distributor of Comfort Intelligent Home security systems in Ireland
Smart keypad for intelligent home security systems
03 February, 2009
Cytech's Comfort intelligent home system gains new addition with the flush fitting KP04 keypad with microphone, speaker, voicemail and infrared activation capabilities
Smart home security system training course
20 January, 2009
Training course available for installers of Cytech's Comfort smart home system including latest Comfigurator 3 software
Home security system on specifinder
09 December, 2008
Cytech's Comfort home security system is now featured on the Specifinder site detailing building products
Browser and mobile access to home security systems
05 December, 2008
Webserver and GSM module enables users to access home security and automation systems remotely through browsers or mobile phones


text:
For a Limited Time Buy this US Army Carver One Paintball Gun MEGA Set and get 100 Paintball Rounds for FREE. Hurry while supplies last! Here for a limited time only at an unheard of price. This packages includes:
Introducing the latest in Tippmann's popular US Army line of paintball markers. The Carver One paintball gun brings added customization and affordability to the design and function of the Tippmann 98 Custom inline bolt system. the versatile design of the Carver One allows for a variety of add-ons including: bipods, foregrips, sights, scopes, tactical flashlights, cameras, and other accessories to provide look and function that is unique to your needs. Take a look at some of the Carver One kits we put together below The Tippmann team designed the US Army Carver One to come standard with a horizontal foregrip allowing for tighter prone shooting and a more traditional stance. The all-metal receiver and airline hose ensures durability and quality when making those hard bunker slides. The Carver One accepts all standard US Army and Tippmann 98 shoulder stocks allowing even further customization to give a more stable firing platform. Built in sling mounts allow easy attachment to tactical vests, which frees you up to move easier across the field, provides quick storage if you want to carry a sidearm, or simply a handy place to hang your marker between games. Now that is cool! At under $100, the US Army Carver One is a great value for the entry player, and provides a firm platform for players to build on as their experience develops. If you're looking for the most realistic way to get in the game, just remember… Play Smart, Play Strong, US Army Paintball.
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Copyright Punishers Paintball Supply © 2003-2016 All Rights Reserved
All photography and text on this site is the original work of Punishers Paintball Supply and manufacturers.
Contents may not be used for any commercial or non-commercial purpose without prior written consent from www.punisherspb.com.


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The Battle of Písek was a final pummeling of the eastern Habsburg forces that had sought to ouster Wallenstein from Bohemia with the initial siege of Tabor, which became the Battle of Tabor.
Under direct leadership of Wallenstein and Gustav Adolphus, Bohemian and Swedish troops attacked and drove back the Austrian invaders. In a series of skirmishes in and around Písek, it became clear to Gustavus Adolphus that Wallenstein would not be allowed to remain neutral for the duration of the war, should the Habsburgs not be taught a sound lesson.
Following stringent negotiations, the two armies proceeded on to Vienna, for while the Habsburgs had thought the war to be on a winter hiatus, their foolhardy foray to the north had stirred the proverbial hornets nest. While Habsburg forces were otherwise occupied in the west of Germany, they were about to be trounced on their home territory at the Sack of Vienna.


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In previous reports from this study, measurements of pulmonary inflammation, bronchoalveolar lavage cell cytokine production and nuclear factor-κB activation, cytotoxic damage, and fibrosis were detailed. In this study, we investigated the temporal relationship between silica inhalation, nitric oxide (NO), and reactive oxygen species (ROS) production, and damage mediated by these radicals in the rat. Rats were exposed to a silica aerosol (15 mg/m3 silica, 6 h/day, 5 days/wk) for 116 days. We report time-dependent changes in 1) activation of alveolar macrophages and concomitant production of NO and ROS, 2) immunohistochemical localization of inducible NO synthase and the NO-induced damage product nitrotyrosine, 3) bronchoalveolar lavage fluid NOx and superoxide dismutase concentrations, and 4) lung lipid peroxidation levels. The major observations made in this study are as follows: 1) NO and ROS production and resultant damage increased during silica exposure, and 2) the sites of inducible NO synthase activation and NO-mediated damage are associated anatomically with pathological lesions in the lungs.
- silicosis
- fibrosis
- oxidant injury
- nitrotyrosine
silica inhalation in humans has been linked to the pulmonary disease silicosis, which is generally characterized by a severe decline in respiratory function and premature death (3). Because silicotic lungs are known to be in a state of oxidative stress (35), it has been proposed that oxidant-mediated lung damage may participate in the development of silica-induced pulmonary disease (21).
Alveolar macrophages (AM) become activated after exposure to silica, and this activation results in the production of reactive oxygen species (ROS), which can be measured by chemiluminescence (8). The production of ROS by AM contributes to the cytotoxic damage to the lung, indicated by increased lactate dehydrogenase activity and total protein in the bronchoalveolar lavage (BAL) fluid of silica-exposed rats (15).
Other studies have suggested that nitric oxide (NO) may also participate in silica-induced pulmonary inflammation, damage, and fibrosis. mRNA levels for inducible NO synthase (iNOS), an inducible enzyme that produces NO, are increased in BAL cells after intratracheal instillation of silica in rats (4, 17). Furthermore, pharmacological evidence suggests that NO production by AM is increased after intratracheal instillation (4) or inhalation (8) of silica.
A recent workshop on poorly soluble particles concluded that a significant gap in our knowledge exists concerning the temporal sequence of molecular, cellular, and histopathological changes that occur after exposure to poorly soluble particles, such as silica (18). Indeed, although providing substantial mechanistic information concerning silica-induced production of NO and ROS, previous studies did not establish the detailed temporal relationship between silica inhalation, NO and ROS production, and damage mediated by these radicals, and the development of pulmonary fibrosis. Thus we initiated a study with the comprehensive goal to investigate the temporal relationship between silica inhalation, NO and ROS production, and the resultant pulmonary damage in the rat model. Specifically, we report the time course of 1) AM activation and production of NO and ROS, 2) BAL fluid NOx and superoxide dismutase (SOD) levels, and 3) immunohistochemical localization of iNOS and nitrotyrosine (NT) in silica-exposed rat lungs.
Silica chemical analyses.
The silica used in this study was MIN-U-SIL 5 (US Silica, Berkeley Springs, WV). The bulk silica was analyzed for inorganic contaminants and desorbable organic carbon compounds, and aerosolized silica samples were analyzed for trace inorganic elements and elemental and organic carbon. The results of these analyses have been reported elsewhere (27).
Silica aerosol exposure of rats.
Pathogen-free male Fischer 344 rats (strain CDF, 75–100 g; Charles River, Raleigh, NC) were housed in an American Association for Accreditation of Laboratory Animal Care-accredited animal facility in individual cages in two 5-m3 Hinners-type inhalation chambers. One chamber was used for filtered air exposures (control) and the other for exposure to 15 mg/m3 silica. Exposures were conducted for 6 h/day, 5 days/wk for a total of 116 exposure days. Water was available ad libitum, and food was available at all times except during exposures. The rats were subjected to a 12:12-h light-dark schedule and were exposed during the dark cycle to coincide with their most active period.
The silica aerosol concentration was monitored using two independent methods: an RAS-2 particle sensor allowed real-time monitoring, and gravimetric determinations were made at hourly intervals during each day of exposure. The gravimetric determinations indicated that the silica aerosol concentration was 14.9–15.5 mg silica/m3 during the study (27). Silica particle size averaged ≤2 μm as determined with an Anderson eight-stage cascade impactor, and the mass median aerodynamic diameter of the silica particles was 1.47–1.86 μm (27). Further details of the silica chemical composition analyses and the silica aerosol particle characterization, generation, and exposure system have been described elsewhere (27).
The silica lung burden of rats ranged from 0.42 ± 0.05 mg SiO2/lung after 1 day of exposure to 6.27 ± 0.15 mg SiO2/lung after 116 days of exposure (27). On the basis of the volumetric model described by Oberdorster and colleagues (26), the percentage of AM volume occupied by silica in this study was below overload levels (27). Furthermore, the silica burden-exposure duration relationship exhibited equilibrium between 79 and 116 days of exposure, suggesting that the silica-exposed animals were not in pulmonary overload (27).
Rats were euthanized with an injection of pentobarbital sodium (≥100 mg/kg body wt ip) after 5, 10, 16, 20, 30, 41, 79, and 116 days of exposure. BAL with Ca2+- and Mg2+-free phosphate-buffered saline (pH 7.4) with 5.5 mM d-glucose added and the isolation of acellular first BAL fluid and BAL cells were conducted as described previously (27). BAL cells were resuspended in HEPES-buffered medium (10 mM HEPES, 145 mM NaCl, 5 mM KCl, 1 mM CaCl2, 5.5 mM d-glucose, pH 7.4) and counted using an electronic cell counter equipped with a cell sizer (Multisizer II, Coulter Electronics, Hialeah, FL) as described previously (6).
BAL fluid SOD activity.
BAL fluid SOD activities were determined by monitoring the reduction of cytochrome c at 550 nm as previously described (34,35) with a Cobas Fara II Analyzer (Roche Diagnostic Systems, Montclair, NJ).
BAL fluid NOx concentrations.
We define NOx as the total of nitrite (NO ) plus nitrate (NO ) in a sample. To determine BAL NOx, it was necessary to reduce NO to NO in the BAL sample. To reduce NO , a previously described NO reduction assay (14) was modified. The NO reduction reaction consisted of 50 mM HEPES, 5 mM flavin adenine dinucleotide, 0.1 mM reduced nicotinamide adenine dinucleotide phosphate, 0.2 unit of nitrate reductase (Roche Molecular Biochemicals, Indianapolis, IN), and BAL fluid in a total volume of 1.0 ml. This reaction was incubated with gentle mixing at 37°C for 30 min. At the end of the incubation, the reaction was diluted with water, and NO was determined by flow injection analysis colorimetry at 540 nm using the Griess reaction (Quick-Chem 8000, Lachat Instruments, Milwaukee, WI).
AM zymosan-stimulated and NO-dependent chemiluminescence.
AM chemiluminescence was determined in a total volume of 0.25 ml of HEPES-buffered medium. Resting AM chemiluminescence was determined by incubating 1.0 × 106 AM/ml at 37°C for 20 min, adding 5-amino-2,3-dihydro-1,4-phthalazinedione (luminol) to a final concentration of 0.08 μg/ml, and then measuring chemiluminescence. To determine zymosan-stimulated chemiluminescence, unopsonized zymosan (2 mg/ml) was added immediately before the measurement of chemiluminescence. All chemiluminescence measurements were made with an automated luminometer (Berthold Autolumat LB 953, EG & G, Gaithersburg, MD) at 390–620 nm for 15 min. The integral of counts per minute vs. time was calculated. Zymosan-stimulated chemiluminescence was calculated as counts per minute in the zymosan-stimulated assay minus counts per minute in the resting assay. NO-dependent chemiluminescence was determined by subtracting zymosan-stimulated chemiluminescence from cells preincubated with 1 mM nitro-l-arginine methyl ester from zymosan-stimulated chemiluminescence from cells without nitro-l-arginine methyl ester. The use of unopsonized zymosan in the chemiluminescence assay allowed only AM chemiluminescence to be measured, because unopsonized zymosan stimulates AM chemiluminescence (7) but not polymorphonuclear (PMN) chemiluminescence (1, 16).
Lung lipid peroxidation.
Rats, separate from those used for BAL, were euthanized with an injection of pentobarbital sodium (≥100 mg/kg body wt ip) after 10, 20, 41, 79, and 116 days of exposure. Lungs were removed en bloc, washed with ice-cold 0.9% (wt/vol) NaCl, blotted dry, and weighed. Lung tissue was processed, and lipid peroxidation was measured using a colorimetric assay at 586 nm (BIOXYTECH LPO-586, Oxis International, Portland, OR) following the protocol provided by the manufacturer.
Silica- and air-exposed control rats, separate from those used for BAL, were euthanized with an injection of pentobarbital sodium (≥100 mg/kg body wt ip) after 10, 20, 41, 79, and 116 days of exposure. The left lobe was inflated transpleurally with 2–3 ml of formalin, processed within 24 h, and embedded in paraffin. Paraffin sections were cut at 5 μm, deparaffinized in xylene, and rehydrated. Slides were placed in citrate buffer (pH 6.0) and microwaved (32). After endogenous peroxidase was blocked in a 1:1 mixture of 3% H2O2 and methanol, slides were placed in 10% bovine serum albumin for 30 min at room temperature and then incubated overnight at 4°C in the primary antibody [monoclonal anti-iNOS, 1:50 dilution (N32020, Transduction Laboratories, Lexington, KY); polyclonal anti-NT, 1:100 dilution (06-284, Upstate Biotechnology, Lake Placid, NY)]. A kit (K0609, LSAB-2 kit, Dako, Carpenteria, CA) for rat specimens was used to label the antibody, with diaminobenzidine (Zymed Laboratories, South San Francisco, CA) as the chromogen. Sections were counterstained briefly with Mayer's hematoxylin and dehydrated, and coverslips were applied.
Positive controls for iNOS were lung sections from rats that had been exposed to lipopolysaccharide (LPS, 10 mg/kg body wt) by intratracheal instillation 24 h before death; the AM in these animals were highly positive for iNOS using the above procedures. In control slides with 10% bovine serum albumin and no antibody, the mast cells were positive (in air- and silica-exposed animals), but there was no other staining. NT controls included an absorption control, in which the antibody was mixed with 10 mM NT before it was added to the sections, and a positive control, in which the sections were incubated in 1 mM sodium nitrite before application of the antibody. In the absorption control, no staining for NT appeared in the lung sections.
Statistical analyses.
The difference between air- and silica-exposed rats at each time point was tested using appropriate contrasts in the two-way analysis of variance model with interaction (30). A logarithmic transformation of the response variable was used to satisfy assumptions of normality and constant variance. To characterize toxicity changes over time, data were fit to a linear regression model that included any statistically significant polynomial terms up to a cubic. Predicted values and associated confidence intervals from the regression model (25) were used to identify significant differences between exposure times (i.e., time points with nonoverlapping confidence intervals) within the silica-exposed animals. This approach was preferable to pairwise tests of mean values, inasmuch as the regression model fits a single curve to the dose-response relationship over the entire range of data. Statistical significance was set at P≤ 0.05.
NO-dependent AM chemiluminescence.
Except at 5 days of exposure, NO-dependent AM chemiluminescence was significantly higher for AM isolated from silica-exposed animals than from air-exposed controls (Fig. 1). Furthermore, NO-dependent AM chemiluminescence for AM isolated from silica-exposed rats from 10 to 116 days of exposure was significantly higher than that determined for AM isolated after 5 days of exposure (Fig. 1).
BAL fluid NOx concentrations.
Silica-exposed rats had significantly higher BAL fluid NOx concentrations than air-exposed controls at every exposure time measured from 16 to 116 days of exposure (Fig.2). For silica-exposed rats, BAL fluid NOx concentrations at 79 days of exposure were significantly higher than those determined from 5 to 41 of days exposure. A further significant increase occurred at 116 days of exposure (Fig. 2).
Pathological changes, specifically histiocytic and suppurative alveolitis, alveolar epithelial cell hypertrophy and hyperplasia, and alveolar lipoproteinosis, were observed in all silica-exposed rat lungs after 79 and 116 days of exposure. Granulomatous inflammation was also seen in the bronchus-associated lymphoid tissue (BALT) at these time points. Cellular debris or possibly apoptotic bodies were observed in some of the alveoli, especially in regions of alveolitis and lipoproteinosis, after 41, 79, or 116 days of silica exposure. Similar pathological changes were previously described and quantified in air- and silica-exposed rat lungs from different animals in a previous report from this silica inhalation study (27).
The pattern of iNOS staining corresponded to the areas of inflammation within lung parenchyma (Fig. 3,A and B). There was very little staining with the iNOS antibody in animals exposed to silica or air for 10, 20, and 41 days. After 79 days of exposure, very little staining was present in the air-exposed controls, but in the silica-exposed animals, many regions of the lung stained positively, especially subpleural areas (Fig. 3 A). The staining for iNOS was localized primarily in the periphery of the lung after 79 days, while after 116 days of exposure many of the central areas were positive as well.
AM and alveolar epithelial cells that appeared to be type II cells were positive for iNOS after 79 days of exposure to silica, while these cells were negative in air controls (Fig. 3, C andD). Neutrophils were unstained or only weakly positive. Intense iNOS staining was localized in silicotic granulomas in the parenchyma after 79 days of silica exposure (Fig. 3 E). The areas of granulomatous inflammation in the BALT were positive for iNOS in three of five animals exposed to silica for 79 days (Fig.3 F) and in all the animals after 116 days. Lipoprotein, present in peripheral areas after 79 days of exposure and in almost all alveoli after 116 days of exposure, was not stained.
The pattern of NT staining was very similar to that of iNOS and corresponded to the areas of inflammation within the lung (Fig.4, A and B). There were no major differences in NT staining between silica- and air-exposed animals after 10, 20, and 41 days of exposure. After 79 and 116 days of exposure, however, there was very pronounced staining in the silica-exposed animals (Fig. 4 A), with positive areas primarily in the periphery of the lung after 79 days of silica exposure and throughout the lung after 116 days of exposure. AM and alveolar epithelial cells that appeared to be type II cells were positive for NT after 79 days of silica exposure but were negative or weakly positive in the controls (Fig. 4, C and D). Some of the AM in silica-exposed and control animals were positive at all time points. The alveolar lipoprotein was positive for NT in one of five animals after 79 days of silica exposure and in four of five animals after 116 days (Fig. 4 C). Histiocytic aggregates in lipoprotein-rich regions were positive for NT (Fig. 4 E). The areas of granulomatous inflammation in the BALT were positive for NT in one animal after 79 days and in four of five animals after 116 days of silica exposure (Fig. 4 F).
Zymosan-stimulated AM chemiluminescence.
Zymosan-stimulated AM chemiluminescence was significantly higher for AM isolated from silica-exposed rats than from air-exposed controls at every exposure time examined (Fig. 5). For silica-exposed rats, AM chemiluminescence from 10 to 79 days of exposure was significantly higher than that determined for AM isolated after 5 days of exposure, and a further significant increase occurred at 116 days of exposure (Fig. 5).
BAL fluid SOD activity.
SOD activity was significantly higher in BAL fluid from silica-exposed rats than from air-exposed controls at every exposure time except 5 days (Fig. 6). BAL fluid SOD activity in silica-exposed rats was significantly lower from 5 to 41 days of exposure than at 79 and 116 of days exposure (Fig. 6).
Lung lipid peroxidation.
Lung lipid peroxidation levels were significantly higher in silica-exposed rats from 41 to 116 days of exposure than in air-exposed controls (Fig. 7). Lung lipid peroxidation levels in silica-exposed rats were significantly higher at 41 days of exposure than at 10 and 20 days of exposure; further significant increases occurred at 79 and 116 days of exposure (Fig. 7).
In two previous reports from this silica inhalation study, we presented data on the temporal relationships between silica exposure, pulmonary inflammation and damage, and the development of fibrosis (27, 28). In the present report from this inhalation study, we examined the oxidative mechanisms underlying the development of silica-induced pulmonary disease, primarily focusing on NO and ROS.
The first step in our investigation of the relationship between NO and silica-induced pulmonary inflammation and damage was to characterize NO production in the lung. AM production of NO was measured by NO-dependent chemiluminescence and indicated NO-dependent chemiluminescence levels that were 46-fold higher in AM isolated from rats exposed to silica for 10 days than in AM from air-exposed controls, and by 116 days of exposure this value had increased to 71-fold. On the basis of this observation, it might be expected that the pulmonary NO concentration may increase as the silica exposure progresses. Indeed, BAL NOx concentration, which represents NO production not only from AM but also other cell types present in the lung, was significantly higher in silica-exposed rats than in air-exposed controls from 16 to 41 of days exposure and explosively increased thereafter.
To examine the anatomic association between NO production and pulmonary inflammation, damage, and fibrosis, immunohistochemical studies were conducted. The pattern of iNOS and NT staining corresponded very well to the localization of pathological changes observed in silica-exposed animals. Specifically, areas of granulomatous inflammation of BALT, lipoproteinosis, type II cell hyperplasia, and alveolitis were sites for iNOS or NT positivity. The staining in regions of inflammation was very apparent in silica-exposed animals after 79 and 116 days of exposure and was absent in air-exposed animals.
Peroxynitrite, produced by a reaction between superoxide anion and NO (2), reacts with tyrosine residues on proteins to form NT. In this study, NT localization is highly congruent with iNOS localization. Localization of NT indicates that peroxynitrite is being produced in the immediate vicinity. This would also account for positive staining for NT in the lipoprotein, probably from increased iNOS activity in AM, or in type II cells, when surfactant is being produced.
Despite the significant effect of silica exposure from 16 to 41 days on BAL fluid NOx and AM NO production (as measured by NO-dependent AM chemiluminescence), immunohistochemistry detected no significant iNOS or NT staining in the AM or epithelial cells at these early times. This apparent inconsistency is probably due to the difference in the sensitivity of the NO-dependent AM chemiluminescence and immunohistochemistry assays, the chemiluminescence assay being more sensitive. At 79 and 116 days of exposure, BAL NOx concentrations from silica-exposed rats further increased. During this period, AM NO production remained significantly higher than control for silica-exposed rats but was not different from that determined at earlier silica exposure times, as measured by NO-dependent AM chemiluminescence. However, the number of lavagable AM increased significantly vs. control at these exposure times (28), and thus this increase in the number of AM may contribute to the increase in BAL NOx. At these same exposure times, 79 and 116 days, immunohistochemistry detected significant iNOS and NT staining in the AM and pulmonary epithelial cells. These data suggest that AM, as well as pulmonary epithelial cells, contribute to BAL fluid NOxconcentrations. Interestingly, the time when the BAL fluid NOx increases dramatically coincides with the rapid increase in pulmonary inflammation, cytotoxic damage, and fibrosis previously described (27, 28).
Some investigators have reported that human AM fail to express iNOS and induced production of NO in response to various stimulants and, therefore, question the relevance of silica-induced NO in rats to human disease. However, recent evidence indicates that, after in vivo stimulation, human AM can produce NO and that the level of NO production correlates with the degree of human pulmonary pathology.
Similar to rats, human pulmonary NO, measured as the concentration of NO in epithelial lung lining fluid and exhaled NO concentration, is highly correlated with iNOS expression in AM isolated from subjects with primary lung cancer (22). Increased NO production has also been reported in humans with silica-induced lung disease. Specifically, iNOS mRNA levels and NO production from BAL cells were determined from a silica-exposed coal miner with an abnormal chest X-ray, a silica-exposed coal miner with a normal chest X-ray, and an unexposed control. iNOS mRNA was higher from BAL cells isolated from the two coal miners than from BAL cells from the unexposed control, and iNOS mRNA was higher in the miner with the abnormal chest X-ray than in the miner with the normal chest X-ray (5). AM NO production was measured by NO-dependent chemiluminescence, and the coal miners with normal and abnormal chest X-rays had 15- and 31-fold higher NO-dependent chemiluminescence, respectively, than the unexposed control (5).
Further examination of the data suggests some possible mechanisms through which NO may contribute to silica-induced pulmonary disease. In this study, the cellular debris observed in the alveoli at 41, 79, and 116 days of silica exposure, especially in regions of lipoproteinosis, corresponded to foci of apoptotic cells detected using the TdT-mediated dUTP nick end labeling assay (24). The apoptotic cells were limited to the air spaces, were not in the interstitium, and increased significantly in number after 41, 79, and 116 days of silica exposure (23). It was also noted that the apoptotic cells were not highly loaded with silica particles (23). Because we localized iNOS and NT in the same regions, it is possible that NO and/or peroxynitrite is having a direct effect on AM, perhaps stimulating apoptosis. The observation that the time course for elevation of AM apoptosis (23,31) correlates well with pulmonary NO concentrations as measured by BAL fluid NOx further supports this hypothesis. Thus it is proposed that AM apoptosis may be regulated by pulmonary NO concentrations and not by AM phagocytosis of silica particles.
Another mechanism through which NO may influence silica-induced disease is regulation of nuclear factor-κB (NF-κB) activation. The effect of NO on NF-κB activation is controversial. Studies using the mouse monocyte-macrophage cell line RAW 264.7 have indicated that exogenous NO inhibits silica- and LPS-induced NF-κB activation (11). However, a later study that also used RAW 264.7 cells demonstrated that exogenous NO can stimulate NF-κB activation (19). Furthermore, NF-κB activation is stimulated in rat primary AM exposed to silica and LPS in vitro, and iNOS inhibitors reduced this NF-κB activation (19). The contradictory results of these studies may reflect differences in NO concentrations, the duration of NO exposure, and/or the basal activity of macrophages (19), since these have been shown to alter the effect of NO on NF-κB activation in other studies (12, 33).
We previously reported that NF-κB is activated in BAL cells isolated from silica-exposed rats in this inhalation study and that the level of activation progressively increased throughout the silica exposure (28). Data presented in this report demonstrate that the NO concentration in the lung, evidenced by the BAL fluid NOx concentration, was significantly increased in silica-exposed rats but was relatively constant through the first 41 days of exposure before steadily increasing thereafter. Thus the duration and NO concentration to which the BAL cells were exposed changed during this study. This makes it difficult to determine the effect NO may have had on the progressive increase in NF-κB activation previously reported for the BAL cells (28). To further investigate the relationship between NO and NF-κB activation in BAL cells in vivo, it will be necessary to conduct additional experiments in which the duration and concentration of NO in the lung are controlled.
Similar to rats, and equally controversial, one of the proposed mechanisms through which NO may regulate pulmonary disease in humans is regulation of NF-κB activation. In vitro, LPS-induced NF-κB activation in human primary AM is decreased in a dose-dependent manner by NO (29). Furthermore, in vivo studies of humans with asthma or primary pulmonary hypertension indicate an inverse relationship between NF-κB activation and airway NO concentrations (29). In contrast, human AM isolated from patients with pulmonary tuberculosis have enhanced NO production and NF-κB activation, and inhibition of NO byN G-monomethyl-l-arginine decreased NF-κB activation, indicating a positive correlation between NO production and NF-κB activation (36).
Oxidative damage, not mediated by NO but by other forms of ROS, was monitored in this study by measuring lung lipid peroxidation levels. We determined that lung lipid peroxidation increased steadily in the lungs of silica-exposed rats. This indicated that the lungs were in a state of oxidative stress, which is consistent with previous studies of silica-exposed rat lungs (35). SOD catalyzes the conversion of superoxide to H2O2, which is subsequently converted to water and oxygen by catalase. It has been suggested that SOD is produced in proportion to the oxidant stress in the lung as a defensive response (34). However, the increase in BAL SOD activity does not appear to be sufficient to protect the lung from ROS-mediated damage, since lung tissue lipid peroxidation levels continued to increase throughout the silica exposure.
Several significant observations were made in this study. First, immunohistochemistry studies determined that the sites of iNOS activation and NT damage are associated anatomically with pathological lesions in the lungs of silica-exposed rats. Second, the data suggest that AM and epithelial cells of the lung contribute to NO production in the lung. Finally, there is an apparent positive association between the pulmonary NO concentration reported in this study and increased AM apoptosis (23, 31) and BAL cell NF-κB activation (28) previously described in other reports from this study. The regulatory interactions between NO, NF-κB, and apoptosis are complex and remain to be completely eludicated, but the data from this study suggest that AM NO production and NF-κB activation in BAL cells occur when pulmonary NO concentration and silica lung burden are low, whereas AM apoptosis peaks at 79 days (23, 31), when the pulmonary NO concentration and silica lung burden are higher. Although this does not assist in determining the regulatory interactions between NO, NF-κB, and apoptosis, it does indicate that NF-κB activation and NO production by AM are much earlier events than AM apoptosis in response to silica exposure.
Finally, one should consider the human relevance of this rat model. Previously reported data from this silica inhalation study demonstrated that silica-exposed rats developed lipidosis and diffuse pulmonary fibrosis (27), characteristics similar to those observed in humans with accelerated silicosis (10). Unlike accelerated silicosis in humans, BAL PMN yield from rats exposed to silica exhibited a nonlinear, 61-fold increase over controls after 116 days of exposure (28). However, this difference in the PMN response of the two species to silica may not be physiologically significant for three reasons: 1) It has previously been demonstrated that pulmonary damage, as measured by BAL protein, lactate dehydrogenase, and N-acetyl-β-glucosaminidase, is not dependent on PMN infiltration into the lung (13).2) Immunohistochemical data in this study indicate that rat PMN have little to no iNOS protein and, thus, would make a negligible contribution to pulmonary NO production. 3) Histological examination of silica-exposed rat lungs in this study indicated that AM are the predominant inflammatory cell (27), but this was not reflected in BAL AM yields, because activated AM are difficult to lavage, and thus their numbers are underestimated in exposed rats (9). Thus similarities in silica-induced AM NO production and NO-dependent regulatory mechanisms in rats and humans suggest that the proposed role of NO in the initiation and progression of silica-induced pulmonary disease in this rat model may also be operating in humans with accelerated silicosis. Furthermore, data from our silica inhalation study were used to model the relationship between lung burden and pulmonary response in the rat and have also been used to model the human response using coal miner data (20). Results of this modeling indicate that the rat exposed to silica is a relevant model for human pneumoconiosis.
Address for reprint requests and other correspondence: D. W. Porter, Pathology and Physiology Research Branch, Health Effects Laboratory Div., National Institute for Occupational Safety and Health, 1095 Willowdale Rd., M/S 2015, Morgantown, WV 26505 (E-mail: DPorter{at}cdc.gov).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
March 15, 2002;10.1152/ajplung.00427.2001
- Copyright © 2002 the American Physiological Society