The Eastside does family fun with flair! There are so many fun family events around town that it's easy to feel overwhelmed! The good news is that most of these events are free, or at least low cost, so you can try them all out and see which ones are the best fit for your family. Here's a rundown of the events that make creating family traditions fun!
Act fast! This is a weekend event special, happening on December 1-2. It's a free event held in downtown Redmond. The progressive event starts at City Hall with a tree lighting ceremony and fireworks show. From there, stroll down a lighted pathway dotted with carolers and performers. Your trail ends in Redmond Town Center where you'll find more entertainers, shops, treats, and family fun.
This event is the priciest on my list. But it does offer a fun experience that the kids will love. You board an Argosy ship at one of many docks around Lake Washington or in Seattle and set sail! Along the way, you'll be serenaded by choirs and subject to beautiful views. Many local yacht and boat owners follow the parade of boats and have their vessels decorated as well. If you have kids, try to snag a ticket on the lead boat, since Santa is on board and there is a dedicated kid space for coloring and crafts. There are adult beverages available for purchase as well. The event will almost always sell out, so book tickets well in advance! If the ship isn't for you, plan to take the family to designated beaches to view the parade of boats from land!
Another annual family tradition for many Eastside families, there just aren't enough words to describe how magical this event is. Marching drummers, dancing snow fairies, and even ice queens. You'll also experience "snow" falling every night. (It's really a foam machine, but the kids won't care. It's still magical!) The event features a parade, music, dancing, and free candy handed out by the character cast. It's a popular event, though, so be sure to get there early. The event is free and kicks off nightly at 7 pm.
This annual play features local child actors. It's a tradition for many families and offers a glimpse into theatre life for children. Recommended for ages 4 and up, the show is only offered on weekends. Tickets are $20 per person for all ages.
An outdoor lights display, this one is just north of the Eastside. Put on by Bothell's Evergreen Church, this is a free event. Take advantage of free cookies and cider while you're there, too.
Finally, let's talk outside of the Eastside. One of the benefits to living here is the close proximity to Seattle. If you feel like making the trip across the bridge to the big city, here are my favorite holiday events in the city.
New to the city this year, this is a traveling display of lights that features the world's largest Christmas light maze. You'll find an ice skating trail, as opposed to a rink, which winds you by live entertainment and right to your visit with Mr. and Mrs. Claus. You need to pre-book your time in the event. Here's a Groupon for tickets to help save you some cash!
Now in its 26th year, this is an impress ive display of gingerbread houses. Many have moving parts and most are taller than your child! It's simply magical. Every year they have a different theme — this year is Dr. Seuss. Always a must see!!
There are so many activities here! From the Winter Train Village to an ice skating rink and carousel to live ice sculpting demonstrations and live performances all season long. Be sure to check the website before heading down as the schedule changes daily.
These are all amazing activities in our very own backyard. Many of which I have started as traditions in my family!! What are your favorite traditions during this magical time of year!?


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Arapaimidae (Beentongvissen) zijn een familie van straalvinnige vissen uit de orde van beentongvissen (Osteoglossiformes).

Taxonomie
De familie kent de volgende geslachten:
 Arapaima Müller, 1843
 Heterotis Rüppell, 1828

redpajama_set_name: RedPajamaWikipedia


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Q: Finding a $C^*$-subalgebra of $B(H)$ for $c_0$? Let $c_0$ denote the set of all complex sequences that converge to zero.
We can show that $c_0$ is a $C^*$-algebra with the $*$-involution defined as complex conjugate and norm $$\|x\| = \max_j |x_j|$$ for every $x \in c_0$.
I know that every $C^*$-algebra is $*$-isomorphic to a $C^*$-subalgebra of $B(H)$ for some Hilbert space $H$.
How do I go about finding this $C^*$-subalgebra of $B(H)$ for $c_0$?
Any help pointing me in the right direction would be much appreciated.

A: The other answer is obviously the canonical one. I just wanted to mention that it can be obtained via the GNS construction, if one uses its generalized form for weights (and not states).
Indeed, we can define a faithful weight $\varphi:c_0\to\mathbb C$ by
$$
\varphi(x)=\sum_jx_j
$$
(recall that a weight is a priori only defined on positive elements, and it can be infinite). If we do GNS for this weight, no quotient is necessary (because $\varphi$ is faithful) and the inner product  is given by
$$
\langle x,y\rangle=\varphi(y^*x)=\sum_j x_j\overline{y_j}.
$$
This inner product is defined on a dense subspace of $c_0$ (the sequences with finitely many nonzero elements) and its completion is $\ell^2(\mathbb N)$, with $c_0$ acting as multiplication operators.

A: Let's begin with $\ell_\infty$: every bounded sequence induces an operator on the sequence space $\ell_2$ by multiplication. That is, $x\in \ell_\infty$ corresponds to the multiplication operator $M_x(y) = (x_ky_k)_{k=1}^\infty$ on $\ell_2$.  These are all diagonal operators with respect to the standard basis of $\ell_2$.
Restricting to $c_0$, we get only operators with diagonal entries that tend to $0$. These are precisely compact diagonal operators. Indeed, being compact is equivalent to being the limit of finite-rank operators; on the other hand, being in $c_0$ is equivalent to being the limit of sequences that have finitely many nonzero terms.

redpajama_set_name: RedPajamaStackExchange


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Pendragon suitor Lithia Motors in 'advanced' talks over £300m Jardine acquisition
23/01/2023 in Acquisitions and deals
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Lithia Motors has revealed that it views Jardine Motors as "a platform for future growth in the UK" after it emerged the US-based car retailer was in advanced talks to acquire the AM100 group.
Lithia, which made a bid to acquire Pendragon last year, is understood to be lining up a takeover worth about £300 million, according to a report published by Sky News today (January 23).
The AM100's ninth-placed car retail group, with a turnover of £1.61 billion, Jardine employs around 2,700 people at 50 sites across the UK and counts brands including Aston Martin, Audi, BMW, Ferrari, Jaguar Land Rover (JLR), Porsche and Pininfarina among its franchise partners.
In a statement issued to Sky News, $22.8bn (£19bn) turnover New York Stock Exchange-listed Lithia Motors said it had previously stated its "desire to expand into the UK market" and confirmed that it had held discussions with Jardine Motors Group owner, Hong Kong-based Jardine Matheson, with a view to investing in the car retail business.
It added: "Jardine Motors Group UK is one of the UK's leading automotive retailers and Lithia firmly believes that a combination of the two businesses will help to deliver significant value for employees, partners and customers.
"Lithia views the potential acquisition of Jardine Motors as a platform for future growth in the UK and plans to invest in the business, working with Jardine Motors' market-leading management team to build on the strong momentum the Group has generated in recent years.
"Discussions around a potential transaction are ongoing and a further update will be issued in due course."
Lithia's bid to acquire Pendragon was revealed by Sky News back in August.
It came in-between two approaches by Hedin Automotive for the former AM100-topping retail group, the latter of which was withdrawn after the Swedish car retail group entered the UK market through the acquisition of dealerships from Mercedes-Benz Retail Group.
If completed, Lithia's acquisition of Jardine Motors Group would be larger than other recent large-scale M&A deals in the UK's automotive retail sector – Marshall's acquisition of Motorline and Vertu's takeover of Helston Garages – in the shade.
A news insight report published by AM late last year found that the climate for car retail M&A was "hotting-up" in the UK, with overseas investors in pole position.
Alistair Cassels, head of automotive advisory at MHA, said: "Over the past five years we have seen a number of overseas entrants, including Motus, Super Group and Group 1, and we know there is still a lot of appetite from those overseas businesses to acquire more.
"As for other newcomers, like Hedin, some might have grown as much as they can in their home territory and be looking for a new opportunity. Others could be looking to make the most of what is – in some ways – quite a favourable climate for M&A activity."
Automotive Management Live 2023
The UK's leading event for motor retailers - November 2023.
Automotive Management Live welcomes motor retail managers from across the UK to shape the future of the industry and network with peers and suppliers.
Venue: NEC, Birmingham
Author: Tom Sharpe Tom Sharpe
News and features editor
tom.sharpe@bauermedia.co.uk
A multi-award-winning news journalist, Tom is news and features editor for Bauer Media's AM brand. His role demands he keep abreast of all industry and business news to provide coverage of the franchised automotive retail sector and the wider automotive industry, while assisting in the management of the magazine's production and AM events.
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07 Nights / 08 Days Tour Package In Sri Lanka
Colombo / Habarana Tropical Life Resort & Spa or Similar
Habarana Tropical Life Resort & Spa or Similar
Habarana / Kandy Thilanka Hotel or Similar
Kandy Thilanka Hotel or Similar
Kandy / Nuwara Eliya Araliya Red or Similar
Nuwara Eliya / Beruwala The Palms or Similar
Beruwala The Palms or Similar
Beruwala / Airport Departure
Book your unforgettable Trip in Sri Lanka, Experience Heritage, Adventure and Beach. Including Half Board Basis and Transfers.
Seductive beaches and tempting water sports, magnificent landscapes featuring lazy lagoons, fertile wetlands, ecologically-wondrous types of forest, imposing mountains, bounteous rivers and waterfalls, an abundance of wildlife - much of it endemic unique ecosystems, inspiring heritage sites from ancient cities to colonial forts, a vibrant culture including fine arts and crafts and grand festivals, and people of diverse ethnicity and religious persuasion, charming and hospitable.
Map of Sri Lanka.
One 500ML bottle of water per day per person.
Free upgrades on availability.
Complimentary Head & Shoulder massage in the Spice Garden.
Complimentary witness the Cultural dance show in Kandy
Meet & assistance at the Airport.
Accommodation on HB Basis
English speaking chauffeur guide
Transfers on private basis in A/C vehicle
Wheel Chair for People with a disability (On Request during the confirmation).
Spice Garden visit
Gem Museum visit
Complimentary witness the Cultural dance at Kandy
Entrance tickets of
Pinnawala Elephant Orphange
Tooth Relic Temple
Turtle Farm
Dambulla Cave Temple
Gregory Lake
Minneriya Park
Village Trek
Any compulsory room supplement during the tour.
Video and Camera permits at sights.
Meals Outside of the stated meal plan.
Use of vehicle other than the specified itinerary.
Expenses of personal nature.
Any other services not specified above.
Early check in & Late check out at the hotels (Check in & Check out time 14.00 to 12.00 Noon)
Any compulsory supplements
Sights mentioned as optional
Departure PCR – US $ 40.00
Package Type: Culture Adventure
Locations: Dambulla Golden Rock Temple - Minneriya National Park - Half Day Jeep Safari - Pinnawala Elephant Orphanage - Sigiriya Rock Fortress - Temple Of The Tooth Relic
Colombo / Habarana
Upon arrival you will be greeted by our Travel Lanka Connection representative and proceed to the Habarana. Transferred to the hotel and In the evening, you can visit the Minneriya National Park.
Minneriya National Park is located between Habarana and Polonnaruwa. Covered an area of 8890 hectares park is an ideal place for elephant and leopard watching. The vegetation of this park is mixed evergreen and scrub areas. The important feature of this park is that 3rd century built Minneriya Tank is located in the park. During the dry season Minneriya tank becomes the ideal place to observe its natural wild life. Minneriya National Park is home to 24 species of mammals,160 species of birds , 75 species of butterflies, 9 species of amphibians, 26 species of fish and 25 species of reptiles.
Transfer back to the hotel. Dinner and overnight stay at the hotel-Habarana
Hotel: Tropical Life Resort & Spa or Similar
After having the breakfast at the hotel, proceed to visit the Sigiriya.
Sigiriya This UNESCO World Heritage Site, a spectacular Rock Fortress, is one of Sri Lanka's major attractions. The most impressive facets of the unique complex are the Water Gardens, the Frescoes of beautiful maidens, the Mirror Wall with ancient graffiti, the Lion platform and the Summit of 1.6 hectares, which was completely covered by buildings during the period of Sigiriya's glory. Built by King Kashyapa (477-495 A.D), the "Lion Rock" is a citadel of unusual beauty rising 200m from the scrub jungle.
Village Trek, Trek through this archetypal Sri Lankan village. The trek begins with a scenic walk along a bund of a Wewa (man-made reservoir). The amazing birdlife, butterflies and possible sightings of crocodile only add to the charm of the trek. Sight the villagers as they go about their early morning tasks of fishing or washing clothes at the periphery of the lake. Initially one wades through a shallow stream and thereafter crosses a wider tributary in a catamaran of an obliging farmer to Inspect Chena cultivation (slash and burn agriculture) Enjoy the farmer's humble hospitality. With the guidance of the farmer, pick some fresh vegetables from the plot.
Habarana / Kandy
After having the breakfast at the hotel, proceed to the Kandy and en route visit the Pinnawala elephant Orphanage and the Dambulla Cave Temple.
Pinnawala Elephant Orphanage is an orphanage, nursery and captive breeding ground for wild Asian elephants located at Pinnawala village, 13 km northeast of Kegalle town in Sabaragamuwa Province of Sri Lanka. Pinnawala has the largest herd of captive elephants in the world.
Dambulla Cave Temple Located in the north central province this UNESCO World Heritage Site which dates back to the 01st century BC, is an amazing complex of 05 caves, first used as a refuge by an ancient king who on regaining his throne, commissioned magnificent carved images within the living rock, Later kings made further improvements and the caves contain over 150 images of the Buddha of which the largest is a colossal figure spanning 15 meters. Cave inscriptions from the 2nd Century BC are found and on the walls are many paintings most of which belong to the Kandy period (early 19th century).
Then proceed to Kandy Enroute visit Matale, visit a spice garden where you will witness many spices and herbs in Sri Lanka, (Distance from Dambulla to Matale – 66KMs – Approx. 1 ½ Hours)
Spice Garden , The Island had been famous for its spices since the medieval times and is considered as one of the main reasons for the Europeans to conquer the Island and for the Arabs to trade upon from the 14th century onwards. The most interesting feature would be the opportunity you'll get to identify the real plants of spices you are so familiar with in your day to day life. A qualified guide will do a conducted tour of the garden and a presentation of its products. and Enjoy a special head and shoulder massage at the spice garden.
Check in to the hotel. Dinner and overnight stay at the hotel-Kandy
Hotel: Thilanka Hotel or Similar
After having the breakfast at the hotel, Proceed to visit the the Royal Botanical Garden.
Royal Botanic Gardens, Peradeniya are about 5.5 km to the west of the city of Kandy in the Central Province of Sri Lanka. It attracts 2 million visitors annually. It is near the Mahaweli River. It is renowned for its collection of orchids.
Transfer back to the hotel.
In the evening conduct a sightseeing tour of Kandy. Visit a Batik Factory, a Gem Museum and a visit to the Kandy "Tooth Relic Temple''.
A lovely exotic city, the Hill Capital and last stronghold of the Sinhala Kings is a UNESCO World Heritage Site which retains an aura of grandeur, time has not affected. Encircled by hills, with a tranquil lake in its centre, it is the site of the renowned temple that enshrines the Tooth Relic of the Buddha and the Royal Botanical gardens – home to one of the world's best collections of Orchids. A cultural sanctuary where many legends, traditions and folklore are still lovingly kept alive, Kandy and its satellite villages are the centre of the islands handicraft industry (items of wood, brass & silver) exquisite silver or gold jewellery and precious gems of many varieties including the world's best blue and star sapphires. The highlight of the city's calendar is the Esala Perahera, when a replica of the casket enclosing the Tooth is taken in procession for ten glittering nights in July/August by exotically costumed dancers, drummers and approximately 100 Elephants.
In the evening, you can be a witness of Cultural Dance show. Transfer back to the hotel. Dinner & overnight stay at the hotel
Kandy / Nuwara Eliya
After the breakfast at the hotel, proceed to the Nuwara Eliya and en route you can visit the Tea Factory and get an experience of walking among the mushy tea plantation.
Sri Lanka is one of the world's largest exporters of tea with a roaring tea industry that dominates the island's central highlands. Introduced to the country by British tea planter James Taylor in 1867, tea irreversibly changed the topography, and even the demography of the country.
Check-in to the hotel and evening walk around the Gregory lake and Bazzar in Nuwara Eliya town,
Transfer back to the hotel. Dinner & overnight stay at the hotel-Nuwara Eliya.
Hotel: Araliya Red or Similar
Nuwara Eliya / Beruwala
After the breakfast at the hotel, Proceed to the Beruwala. and Check-in to the hotel.
Dinner & overnight stay at the hotel- Beruwala.
Hotel: The Palms or Similar
After having the breakfast at the hotel, spend your day leisurely at the hotel. In the evening, visit the Turtle Hatchery.
The Turtle Hatchery Project at Bentota Beach is another important attraction. Up to five endangered species of turtles have been frequenting a stretch on this undisturbed beach for a long time now. The turtles are allowed to hatch and thrive in a protected area before being set free.
Transfer back to the hotel. Dinner & Overnight stay at the hotel – Beruwala.
Beruwala / Airport
After Breakfast proceed to the airport .
Please note that you need to be at the airport before 03 hrs prior to the departure


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West Valley teen serves as Rep. Norm Johnson's page in state House of Representatives
Ian Vickers, a West Valley High School student from Yakima, recently served as a page in the Washington State House of Representatives during the first week of the 2018 legislation session. He was sponsored by Rep. Norm Johnson, R-Yakima.
As a page, Ian observed the Legislature in action and was responsible for delivering messages and documents to legislators in their offices, committee meetings and the House chamber during floor sessions. Paging presents students with a unique educational opportunity to participate in the legislative process, such as presenting the flags, to operational chores like distributing amendments during legislative sessions.
To become a page, applicants must have a legislative sponsor and be between the ages of 14 and 16. Additionally, pages are required to obtain written permission from their parents and school.
Ian's favorite sports include skiing, swimming, hiking, golf and snow shoeing. He is the 16-year-old son of Robert and Lisa Vickers of Yakima.
For more information about the legislative page program, visit: http://leg.wa.gov/House/Pages/HousePageProgram.aspx


Multi-purpose use - Oil sprayer Fill this sprayer with your favorite Seasoning (liquid), vinegars, lemon and lime juice, sherry, or Marsala wine.
High quality deign- BPA free made from glass with stainless steel. This oil sprayer can not clogged.
Its perfect for spraying ingredients instead of using a brushes when roasting, sauteing, baking, cooking.
Transparent glass bottle easy to see the capacity and dosage, easy to clean.
Easy to use - Simple pumping action that produces a fine mist, more uniform in spraying and control the amount of oil per time used in cooking.
2 Pack Oil Sprayer Dispenser is your good assistant in kitchen.
Multi-purpose use- It is perfect oil sprayer bottle for sunflower oil, vinegar, soy sauce, lemon and lime juice, sherry, or marsala wine in it.
Good for cooking- This sprayer is designed to home cooks who like to control the amount of oil they use.
Transparent glass bottle, you can recognize the seasoning(oil/ vinegar/ sauce) quickly.
Easily to clean, unscrew the lid, rinse with water.


Vietnam a century ago was occupied by the French but still retained many of its former traditions.
The Dan Nguyet or "Moon Guitar" was a popular instrument played in Vietnam before guitars were introduced in the 20th century.
Part 3: John Doan's Southeast Asia Tour – Penang, Malaysia, Where Nature Grows Out of Buildings, People Dine From the Trunk of Their Cars and He Perform On the Top of a Birthday Cake!
Although Penang is an island just off to the north east of peninsular Malaysia it seems like a world apart. Unlike Malaysia's capitol of Kuala Lumpur, there are many streets that have been left just as they were over a century ago.
Coming to Malaysia from Oregon was almost like entering a fairytale world of endless summer (95 degrees every day of the year!), palm trees, and exotic foods and products reflecting a multicultural and multi-ethnic people.
I returned to Xi'an China for the second time this year and was received at the airport by the concert promoter Yilin Wang and our guitarist friend Adam Varjavandi.
There is nothing quite like being greeted with a bouquet of flowers (even though I had to fight to get into the picture).


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Home»Culture»Rich Paul's Klutch Sports Begins Its MLB Takeover
CultureMLBSports Business
Rich Paul's Klutch Sports Begins Its MLB Takeover
With roughly 60 NBA, NFL and MLB clients, Rich Paul continues to break cultural ground while expanding the Klutch Sports dynasty.
J.R. Gamble April 27, 2020
The coronavirus pandemic has paralyzed the sports world…well everybody except super agent Rich Paul who has cornered the NBA market, quietly accumulated a roster of potent NFL talent and recently focused his energies on building his Major League Baseball roster.
These major moves make Paul's burgeoning sports agency an official triple threat. It also solidifies the 38-year-old G as the Micheal Jackson of this sports agent sh*t.
With his venture into MLB, where less than 8 percent of the players are African-American, two out of the league's 30 teams have African-American managers and none of the agents or owners are Black, Paul continues to disprove the notion that he's a one trick pony.
This month, Klutch announced the completion of its Tidal Sports acquisition and finalized a deal with baseball agent Brodie Scofield to join the Klutch family as its lead baseball agent.
While everyone was still patting Paul on the back for his hoops exploits, Klutch Sports was doing what it does best and changing the culture. In a few short months, Paul has been able to expand into football and now baseball.
Klutch Sports has added 13 MLB players to the mix, including perennial MVP candidate Alex Bregman (Houston Astros), and pitching sensation Marcus Stroman (Mets).
It was also recently announced that United Talent Agency, one of the top leading representation firms in Hollywood, has teamed up with Paul to create a sports division for the entertainment company.
The kid from Ohio who used to sell throwback jerseys now runs the most powerful sports agency in the world.
Klutch has 23 NFL players on its roster, including All-Pro running backs Alvin Kamara and Melvin Gordon, Cleveland's Jarvis Landry, and Ohio State defensive stud Chase Young, who's expected to go no lower than No. 2 in the 2020 NFL Draft.
Klutch's NBA roster is already loaded with 22 players led by power names like LeBron James, Anthony Davis, John Wall, Ben Simmons, Eric Bledsoe and three-time NBA Champion Draymond Green.
Most people still equate Paul's success with the NBA, because his gold star client LeBron is one of his best friends and the biggest name in the sport. Paul's power move to first lure Anthony Davis away from his old agent and then strong arming the trade to LA, was proof that he was changing the culture, helping to empower players and elevating to the top spot in a game that once excluded Black men from participating.
Haters continue to downplay Paul's genius, saying that he has an advantage with signing the young Black players in the NBA because he's African-American. There might be some validity to that and if so, then we also have to credit Paul with changing perceptions — even among brainwashed Black folks — that white agents were superior, more business savvy, more numbers crafty.
AD TO LA WAS A WARNING SHOT
The AD deal was the backbreaker. Paul became a threat to the white hierarchy of sports agents who have long dominated the game by keeping the "game of business" separated from the players. Paul not only brings tribal energy to the conversation, but he genuinely cares for his athletes and provides them with the jewels and nuggets for personal and professional growth.
So threatened by Paul's business savvy and growing control, the NCAA tried to switch up the game plan and reverse some of the diversity inroads Paul has made in the business by implementing the so-called "Rich Paul Rule," which required agents looking to represent student-athletes to have obtained at least a bachelor's degree, among other criteria.
It was a rule that in theory would have stopped another young brother like Rich Paul, who didn't have a degree, from also defying the odds and becoming the king of basketball business.
After much pressure from social media, superstar players of color and social and civil rights groups, the NCAA rescinded the rule, but the point was made very clear; The powers that be don't want Paul at the table messing up a good thing.
Unfortunately for the old regime, it's too late.
KLUTCH SPORTS GOT IT ALL COVERED
From the court, to the gridiron, to the diamond, Klutch Sports has it covered. And after seeing the kind of genius and prophetic deals Rich Paul negotiated for his elite NBA clients, there's not an athlete in any sport that wouldn't want this man to handle their finances and help elevate their brand.
The icing on the cake, as far as cementing Paul's superiority over other agents came with the coronavirus pandemic that suspended the NBA season and put the players' finances in doubt.
It was reported that if the season is finally canceled, as rumors have suggested in recent days, the NBA could withhold 1.08 percent of each player's 2019/20 salary for every game missed. With 17 games still left to play, plus the playoffs, some guys could take a big hit.
However, a small group of about 12 players received a big percentage of their money upfront, which means they are safe from financial disruption.
Nine of those players are Klutch Sports clients.
Nine who secured these all-you-can-get deals, which pay out 90-plus percent of their 2019-20 salaries by April 1, are represented by Klutch Sports on contracts structured and negotiated by agent Rich Paul and attorney Mark Termini
— Marc Stein (@TheSteinLine) March 31, 2020
The lucky nine are James, John Wall, Kentavious-Caldwell Pope, Dejounte Murray, Miles Bridges, Darius Bazley, Darius Garland, Terrance Ferguson and Trey Lyles. Next season it will be 10 when Draymond Green's contract extension kicks in.
The rest of the league got paychecks last Wednesday but don't know when they will be paid again. With Paul's entrance into MLB, maybe the underpublished Black superstars will join Klutch and enjoy the branding perks of being associated with rising game changers of the sports and entertainment world.
What else is there to say? Paul continues to outmaneuver the competition, stay in tune with the younger generation and expand his corporate dynasty.
(All Photos Courtesy of Klutch Sports)
Alex Bregman agent black MLB agents Klutch Sports Klutch Sports Alex Bregman Klutch Sports Marcus Stroman Klutch Sports MLB Takeover Marcus Stroman agent MLB agents Rich Paul Rich Paul and baseball Rich Paul and MLB
Stop Sanitizing Dr. Martin Luther King, Jr.
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Utah Jazz Offering College Scholarships For Every Win This Season


Hello peoples, this picture is about Jenn-Air Oven – Support Bracket – Oven Roller Rack Could Fall Off ( Off Rack #6). This blog post is a image/jpeg and the resolution of this photo is 1882 x 1059. This attachment's file size is only 260 KB. Wether You desired to save It to Your laptop, you might Click here. You might too see more photos by clicking the following image or see more at this post: Off Rack.
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YOUTH FORCE : Mr. K. Mukudappa President of Ahinda and Former Member of Karnataka Public service Commission, Mr. Raja shekara Doddanna Mourya Founder President, Mr. Veeranna Hale Gowdar Mourya, Working President and others took part in the protest at Freedom Park in Bengaluru.
Bengaluru. Members of the Halu Matha Kurubas, accompanied by a herd of Kuruba , breached police security around the Freedom Park and almost picketed the Park to press for the inclusion of the community in the Scheduled Tribes category and attacked Chief Minister Siddaramaiah for not interested in support of Kuruba Community, and simply lying to Kuruba Community, addicted to lying, remained, and some supporters kept him in a specified state. Wanted him to implement the Reservation from 5% to 13% and Chinnappa Reddy Commission .Said K. Mukudappa President of Ahinda and Former Member of Karnataka Public service Commission.
The members, under the banner of Krantiveera Sangolli Rayanna Yuva Gharjane, had been allotted tent near Freedom Park at the protest venue near the Freedom Park .
They staged a day-long since 29/1/2018 protest at the tent with 'do or die' strengths and slogans In the afternoon, as over 1,000 Kurubas arrived on the national highway, they rushed there.
Over 50 members, raising slogans in support of their demand, then moved towards the Freedom Park, where the winter session of the legislature is over, along with the Kurabas.
The attempt by the Kurubas to picket the Freedom Park took the police off guard.
There was chaos on the national highway as the police tried to stop them. The Protesters staged a protest even as the police made efforts to pacify them.
Traffic movement was severely affected on the highway. The police, without resorting to force, finally managed to chase away the protestors and the community people. Several of them were taken into preventive but staged and sent to the Freedom Park. They were later protested for the Kuruba Community.
Earlier, the protesters said the community had been brought under the ST category in all districts.
The inclusion of the Kurubas in the ST category will not affect the reservation benefits of the tribal people as the Constitution provides for a proportionate increase of reservation benefits based on the population of the community, the protesters said.
Police said the protesters took advantage of the moving flock of community to draw the attention of the government.
Even in all districts, there are some problem in including Kurba community to ST category. The problems will be discussed with the Chief Minister at the earliest. K.Mukudappa said Kuruba community is the second largest community in the state. However, owing to the selfish politics, they could not come up in politics. Assured to provide help for the building of the community and release of more fund from state fund.
Members of Kuruba held a dharna in front of tahsildar's office here on Monday, condemning Chief Minister Siddaramaiah's instruction to tahsildars and deputy commissioners of Bidar, Kalaburagi, Yadgir and Raichur districts to issue ST caste certificate given to Gondas and Rajagondas to Kurubas and Halumata communities. Supporting the move to issue ST certificate to Kurubas and Halumata communities, the agitators submitted a memorandum to the tahsildar.
"Gonda community is found only in Bidar district. The deputy commissioner has submitted a report to the state in this regard. But Chief Minister Siddaramaiah to further his interests, has ordered the deputy commissioners of the aforementioned districts to issue ST certificate, being given to Gondas, to the Kurubas too. This is illegal and will cause injustice to the original ST communities," the agitators complained.
Siddaramaiah had made a controversial statements during his speech addressing the gathering at Halumata cultural festival at Jewargi in Yadgir district, recently. "If he has concerns for his community, let him give separate reservation. He has no right to deprive others their rights," they alleged. The agitators demanded Siddaramaiah to withdraw his statement and instrucions given to tahsildars and deputy commissioners failing which they would stage a statewide protest.
and others took part in the protest.
Thoug CM Siddaramaiah has not made it clear that it was only their communiy protest and function but in reality it is to woo their caste to vote for him to power and to support him for the C.Ms post if Congress wins with majority even JD(S )OR BJP . The state of Karnataka is already doomed and will go to dogs if these leaders encourage caste based politics and the people with merit can never become head of the state .If they encourage such rift based on caste there will be a revolt from other communities who are at present the silent spectators. If these politicians persist politics based on caste in our state the democracy will perish. It is for the people of this state to introspect whether to have people with merrit or the people of a particular caste to rule our state in future.
Mr. Raja shekara Doddanna Mourya Founder President, Mr. Veeranna Hale Gowdar Mourya, Working President and others took part in the protest.


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text:
Bradykinin increases resensitization of purinergic receptor signaling in glioma cells
Héctor E López-Valdés1,
Luis Beltran-Parrazal2,
Kevin C Brennan1 &
Andrew C Charles1
Purinergic receptor-mediated signaling plays an important role in the function of glial cells, including glial tumor cells. Bradykinin is also an important paracrine mediator which is highly expressed in brain tumors and may correlate with their pathological grade. Interaction between bradykinin and purinergic signaling may therefore be involved in the regulation of glial tumor cells.
We examined the effect of bradykinin on glial purinergic signaling in an immortalized glioma cell line. Confocal calcium imaging revealed that ATP evokes an increase in [Ca2+]i in the U87 human astrocytoma cell line. This response was reduced with repetitive application of ATP, likely due to receptor desensitization. However exposure to bradykinin increased the Ca2+ response to a second application of ATP, consistent with increased resensitization. The bradykinin effect on resensitization was similar in the absence of extracellular Ca2+ or in the presence of the PKC activator PMA, but was inhibited by the protein phosphatase inhibitor okadaic acid and the PI3K inhibitor LY294002.
Modulation of protein phosphatases and the PI3K pathway may represent a mechanism by which bradykinin potentiates purinergic signaling in glial cells.
ATP is a primary extracellular signaling molecule for glial cells in the CNS [1, 2]. In astrocytes, ATP is a key messenger for the intercellular communication of calcium waves, in which increases in [Ca2+]i propagate from cell to cell across multiple cells [3–5]. Glial cell calcium waves have been characterized extensively in vitro in a variety of different tissue preparations, and also more recently in vivo in rodent cortex and retina [6–10]. They are thought to play physiological roles in the modulation of neuronal activity and vascular function, in addition to contributing to pathological processes such as cortical spreading depression and seizures [11, 12]. Purinergic signaling is also believed to play an important role in the development and proliferation of glial cells under both physiological and pathological conditions, including those associated with glial tumors [13–15].
Glial cells respond to ATP through P2 purinergic receptors that belong to two families: P2Y G protein-coupled receptors (GPCR) and P2X ligand gated ion channels. Activation of P2Y purinergic receptors triggers G-protein mediated activation of phospholipase C γ (PLCγ) and increases levels of inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG), leading to elevations in intracellular calcium concentration and the activation of protein kinase C (PKC). By contrast, activation of P2X purinergic receptors leads to an increase in intracellular calcium concentration by influx of extracellular calcium through the receptor channel. In glial cells, the sustained increase in [Ca2+]i evoked by ATP is mediated predominantly via activation of P2Y purinergic receptors, although the response to higher concentrations of ATP may also involve Ca2+ influx through P2X receptors [1].
Activation of GPCRs by agonists not only results in the G protein- dependent activation of the effector system, but also triggers coordinated molecular mechanisms governing the ongoing response of the receptors to further stimulation [16, 17]. GPCR receptors show attenuation or loss of responses by repetitive agonist exposure, referred to as desensitization. Reduction of GPCR responsiveness to an agonist over time represents an important physiological feedback mechanism that protects against both acute and chronic receptor overstimulation. After a period of desensitization, receptors recover their responses to agonists (resensitization), which enables receptors to maintain their ability to respond to agonists over time [17].
GPCR desensitization involves multiple distinct events including the uncoupling of receptors from their G proteins, the internalization and sequestration of receptors to endosomes, and down-regulation [16]. Receptor G protein uncoupling in response to receptor phosphorylation is the most rapid means of attenuating GPCR responsiveness and occurs within seconds to minutes following agonist activation. Phosphorylation is mediated by two families of protein kinases: the second messenger dependent protein kinases (e.g. PKA, PKC) and the G protein-coupled receptor kinases GRPKs; [18]. Receptor sequestration is also initiated within seconds to minutes of receptor activation and potentially contributes to receptor desensitization by limiting the number of plasma membrane accessible receptor binding sites. Down-regulation, a decrease in the total cellular complement of GPCRs, occurs in response to longer-term exposure to agonist from minutes to hours [18]. Resensitization of receptors involves the reversal of these processes, namely receptor dephosphorylation by phospatases, recovery of sequestered receptors to the plasma membrane, and increased synthesis and or trafficking of receptors to their sites of function [17].
Bradykinin is a nonapeptide (or kinin) formed from precursors (kininos) through actions of plasma and tissue kallikreins [19]. Kinins are implicated in physiological and pathological processes such as vasodilatation and inflammation [19]. Two kinin-specific GPCR have been reported, B1R and B2R. The B1R mediates the actions of Lys-des-Arg9- bradykinin whereas B2R is activated by the main kinin, bradykinin [19, 20]. Activation of B2R is preferentially coupled to G proteins of the Gα-q subtypes, which in turn activate PLCβ, leading to production of IP3 and release of intracellular calcium [19, 20]. B2R activation also activates PKC, phosphatase A2, phospholipase C, and phosphoinositide 3-kinase (PI3K), and stimulates production of nitric oxide [19, 20]. B2R's are expressed in many different cells including astrocytes [19–25] and human astrocytic tumors [26, 27]. It has been reported that B2 receptors are more highly expressed in glioma cells as compared with normal astrocytes [28] and the level of expression of B2 receptors may be correlated with the grade of human gliomas [29].
Bradykinin and ATP-mediated signaling may interact via multiple pathways. Bradykinin potentiates the ATP response in Xenopus oocytes that express P2X receptors [30]. Meanwhile, ATP causes a desensitization of B2R in a neuroblastoma cell line [31] and bradykinin promotes/induces ATP release from astrocytes [32]. In this work, we explore the effects of bradykinin on purinergic receptor signaling in the U87 human astrocytoma cell line. We show that bradykinin promotes resensitization of P2Y purinergic receptors via activation of PI3K and the phosphatase A2 pathways.
Human astrocytoma U87 cells were grown in DMEM/F12 mixture (50-50) medium supplemented with 10% (V/V) fetal calf serum, 100 units/ml penicillin, and 10 mg/ml streptomycin in humidified air with 5% CO2 at 37°C. 1 × 106 cells were grown to sub-confluent density on Poly-D-lysine treated round glass cover slips (18 mm diameter) for 4-6 days prior to experimentation.
Measurement of [Ca2+]i
Cells were loaded with 5 μM fluo-4-AM for 20 min at room temperature in Hanks Buffered Saline Solution (HBSS) with HEPES (pH 7.38) that was used as the standard experimental solution. All experiments were performed with constant perfusion (2 ml/min) at room temperature (22°C) on a Nikon Diaphot microscope coupled to a custom confocal imaging system as previously described [33]. Briefly, excitation from a 475 nm diode laser was delivered via scanning mirrors to the specimen through a 40× lens. Fluorescence emission was gathered through a dichroic mirror and 535 bandpass filter to a photomultiplier tube (Hamamatsu) and images were acquired at 1 Hz for 6 minutes by an image acquisition board (Bitflow Raven) controlled by Video Savant software. Before application of test substances, cells were continuously perfused for 10 minutes with standard solution. Ligands were added for the duration specified by continuous perfusion. For dose-response relationships of bradykinin, the compound was applied for 5 minutes.
Bradykinin Pretreatment and Repetitive ATP application
After exposure to either control solution or 200 nM bradykinin for 5 minutes, cells were then washed for 10 minutes with HBSS-HEPES, after which ATP (10 μM) was applied for 1 minute, ATP was washed off for 2 minutes, followed by a second 1-minute application of ATP. The PKC activator PMA (1 μM), the BK2R antagonist HOE-140 (1 μM), and the phosphatase and kinase inhibitors (Okadaic acid, 40 nM and LY294002, 50 μM, respectively) were applied for 10 minutes prior to application of bradykinin. All chemicals were dissolved in HBSS-HEPES. For experiments with Ca2+ free medium, ATP was applied in HBSS-HEPES containing no added Ca2+, after which cells were returned to normal HBSS-HEPES.
Regions of interest (30 × 30 pixels) were placed in the center of the cell body of every single cell in each microscopic field, and fluo4 fluorescence vs. time was determined for each cell using ImageJ and Origin 6.0 software (Northampton, MA, USA). Ca2+ responses were characterized based on ΔF/Fo calculated as (F1 - F0)/F0, where F1 is the fluorescence at a given time and F0 is the basal mean fluorescence 1 minute before of application of test substances. Peak Δ/Fo was determined for each individual cell for each ATP application, and these peak responses were compared for individual cells to determine the extent of resensitization. The area under the curve (AUC) for each [Ca2+]i response was also quantified using Origin software and values for AUC were also compared for the 1st and 2nd ATP response as an indication of resensitization. The ratio of the peak Δ/Fo or AUC for the 2nd vs. 1st response to ATP was designated as the % resensitization for each cell, and these values were averaged for all cells. A sigmoidal dose-response curve was fitted by Origin 6.0 (Northampton, MA, USA). Statistical analysis was performed using GraphPad Prizm 4.0 (La Jolla, CA, USA). Data are presented as mean ± SEM; p < 0.05 was considered significant.
Bradykinin [Ca2+]i response
Since activation of B2R leads to release of intracellular calcium [19, 20], we first determined the concentration that evoked the maximum [Ca2+]i response in U-87 cells. Results from those experiments (Figures 1A-B) showed that maximum averaged peak response reached a plateau at 200 nM of bradykinin, we therefore used this concentration to investigate the effects of bradykinin on the response to ATP. [Ca2+]i was monitored for 10 minutes following bradykinin exposure. After the initial response to bradykinin, no further changes in [Ca2+]i were observed over the next 10 minutes.
Response of U-87 cells to Bradykinin. (A) Superimposed line traces show the calcium increase upon exposure to different concentrations of bradykinin. The traces are the fluo4 ΔF/F vs. time for representative cells. (B) Dose-response relationships of bradykinin. Each value represents the average peak value of ΔF/F from 78-276 cells for each concentration tested. The average peak values for each concentration were fitted with sigmoidal dose-response and EC50 obtained was 6.7 nM of bradykinin. The maximum response was reached with 200 nM. (C) Typical Ca2+ response to repetitive application of ATP (10 μM). Line trace shows fluo4 ΔF/F vs. time for a representative cell. Note that the amplitude of the increase in [Ca2+]i in response to the second application ATP is significantly reduced as compared with the first application. (D). Typical Ca2+ response to ATP in a cell pre-treated with bradykinin (200 nM). Pre treatment with bradykinin did not results in any significant change in the response to fist exposure to ATP, however, the second response to ATP showed an increase in the amplitude as compared with untreated cells (C).
Desensitization and Resensitization of ATP receptors
GPCR, including P2Y purinergic receptors, undergo desensitization and resensitization after agonist exposure [18]. We investigated whether bradykinin can affect these processes. When U-87 glioma cells were exposed to repetitive 1 minute application of ATP (10 μM) separated by two minutes, the response for the second application of ATP showed a reduced [Ca2+]i response (Figure 1C). Cells incubated with bradykinin (200 nM for 5 minutes) and then exposed to the same double application of ATP, ten minutes later, also showed a reduced [Ca2+]i response. However, the peak and the AUC for second response to ATP were significantly (p < 0.001) larger than in control cells (Figure 1D), suggesting that previous exposure to bradykinin significantly increased the resensitization of P2Y receptors.
To confirm that the activation of BK2R is necessary for the increase in the resensitization of the ATP receptors, we applied the selective BK2R antagonist, HOE-140 (1 μM) concurrently with bradykinin application. Cells treated with HOE-140 plus bradykinin showed no differences in the responses to ATP with respect to the control cells (standard solution); moreover, the evoked increase in the resensitization of the second response to ATP observed in the group with bradykinin alone was significantly blocked (p < 0.001, Figures 2A-B)
Mechanisms of bradykinin effects on ATP resensitization. Graph A shows the average (± SEM) of ratio of the peak Ca2+ response and graph B shows the average (± SEM) ratio of the area under the curve (AUC) of the Ca2+ response of the second ATP response for all conditions tested. The ratio of the peak Δ/Fo (A) or AUC (B) for the 2nd vs. 1st response to ATP was designated as the % resensitization for each cell, and these values were averaged for all cells. Statistical significance was obtained using one way ANOVA with post-hoc Turkey. ***p < 0.001, **p < 0.01 and *p < 0.05, denotes statistic significance. Note that the enhancement of resensitization persisted on removal of extracellular Ca2+, but is lost on inhibition of phosphatases with okadaic acid, and by inhibition of PI3 kinase with LY294002.
Application of ATP (10 μM) consistently evoked an increase in [Ca2+]i in U87 cells. This response was blocked by pretreatment with the PLC inhibitor U73122 (10 μM) and was not inhibited by the removal of extracellular Ca2+, indicating that the response was mediated primarily by G-protein coupled purinergic (P2Y) receptors as has been previously described [1].
To examine the contribution of extracellular calcium to the ATP resensitization, similar experiments were performed in Ca2+ free medium. When ATP was applied in 0 Ca2+ medium, the amplitude of the first ATP response was not significantly different from those observed in normal Ca2+ medium (figures 3A-B), suggesting that the response was due to release of Ca2 from intracellular stores. The increase in resensitization we observed with bradykinin application was also preserved in 0 Ca2+ medium, although a significantly smaller peak amplitude (39% average resensitization in 0 Ca2+ vs. 55% average resensitization in normal Ca2+ medium, Figure 2A, p < 0.001). These results indicate that Ca2+ influx is important for the resensitization of the response to ATP, likely in part by replenishing intracellular Ca2+ stores. However, Ca2+ influx through P2X receptors or other Ca2+ influx pathways is not required for the increased resensitization of the ATP response that is mediated by bradykinin.
The first ATP response in bradykinin-treated vs. untreated cells. A and B graphs shows the average ratio (± SEM) of the peak Ca2+ response and the average (± SEM) of area under the curve (AUC) of the Ca2+ response of the first ATP response for all conditions tested (n = 47-276 cells per condition). Statistical significance was obtained using one way ANOVA with post-hoc Turkey. ***p < 0.001, **p < 0.01 and *p < 0.05, denotes statistic significance compared with control.
To investigate the role of phosphorylation in the resensitization of GPCR/P2Y in response to bradykinin, we applied the PKC activator phorbol 12-myristate 13-acetate (PMA, 1 μM) for 10 minutes prior to the application of bradykinin (15 minutes before the first ATP application). Treatment with PMA significantly (p <0.001) reduced the peak amplitude of the first ATP response in both bradykinin treated and untreated cells by about 40%, with no significant difference between groups (Figures 3A). PMA treatment also significantly (p < 0.001) reduced resensitization of the ATP response in both groups. However, the bradykinin treated cells still showed significantly (p < 0.05) greater resensitization as compared with untreated cells (Figures 2A-B). These results indicate that activation of PKC significantly inhibits ATP mediated Ca2+ signaling and reduces resensitization of the response to ATP. However, the effect of bradykinin on the resensitization of the ATP response continues to occur following activation of PKC by PMA.
The role of phosphatases in the GPCR/P2Y response was tested with okadaic acid (40 nM), a protein phosphatase 1 and 2A inhibitor. Okadaic acid did not have a significant effect on the initial response to ATP in bradykinin-treated and control cells (Figures 3A-B). However, okadaic acid blocked the bradykinin -evoked increase in resensitization of the second response to ATP (Figures 2A-B).
To determine the potential involvement of the PI3K pathway in the resensitization response to bradykinin, we applied the PI3K inhibitor LY294002 (50 μM) to both control and bradykinin -treated cells. LY294002 significantly (p < 0.001) inhibited both the initial response to ATP (Figures 3A-B) as well as the resensitization of the response to the second application of ATP. Treatment with LY294002 also inhibited the effect of bradykinin on resensitization of the ATP response. (Figures 2A-B)
Purinergic receptor-mediated signaling is critically important for the function of many cell types [1, 2], but relatively little is known about the process by which purinergic signaling interacts with other types of receptor-mediated signaling. Given the potential importance for this kind of interaction, especially in glial tumors, we investigated the role of bradykinin signaling on purinergic signaling in the human glioma cell line.
In U87 astrocytoma cells, the preincubation with bradykinin had no significant effect on the peak amplitude and area under the curve (AUC) in the first response to ATP. However both peak amplitude and AUC of the response to second application of ATP were significantly increased by bradykinin. That this effect was blocked by the bradykinin the specific antagonist HOE 140, confirm that the resensitization phenomenon we observed is mediated by the activation of bradykinin receptors.
The calcium response of U87 cells to ATP is mediated primarily by P2Y purinergic receptors, as shown by the persistence of the response in zero Ca2+ solution, as well as the complete inhibition of the response in cells treated with the PLC inhibitor U73122. The persistence of the bradykinin -induced increase in resensitization of the Ca2+ response to ATP in the absence of extracellular Ca2+ indicates that the entry of calcium through P2X receptors or other Ca2+ influx pathways is not required for the effect of bradykinin on resensitization. Because bradykinin activates PKC, we investigated the effects of the PKC activator phorbol ester on ATP mediated calcium signaling and its modulation by bradykinin. Similar to the reports of others [34], we found that treatment with phorbol ester significantly reduced the initial response to ATP, and increased desensitization of the response. However, the increased resensitization of the ATP response in bradykinin treated cells was maintained, suggesting that PKC did not play a primary role in the bradykinin effect.
The resensitization effect of bradykinin was abolished by the phosphatase 1 and 2A inhibitor okadaic acid, consistent with a key role for dephosphorylation of P2Y purinergic receptors in the increased resensitization induced by bradykinin. Other investigators [34–36] have also found that phophatases are important for the resensitization of P2Y purinergic receptors, and their blockage with okadaic acid decreases receptor resensitization [36].
Our additional finding that the bradykinin effect was prevented by inhibition of PI3K with LY294002 is consistent with previous reports of a role for PI3K in resensitization of P2Y purinergic receptors in guinea pig Muller cells [37]. PI3K has been found to mediate phosphorylation and translocation of phospholipase C-gamma and resultant IP3 production in response to activation of P2Y purinergic receptors - this could be one mechanism by which PI3 kinase inhibitors inhibit both the initial response to ATP and the resensitization of P2Y purinergic receptors [38].
Resensitization of GPCR's may occur both through re-coupling of receptors to G proteins, as well as agonist-dependent endocytosis of the receptor to endosomal compartment followed by dephosphorylation and recycling back to the membrane as a functional receptor [18]. The U87 cells mainly express P2Y1 purinergic receptors [39] and it has recently been reported that agonist-mediated endocytosis of P2Y1 purinergic receptors occurs over a period of 30 minutes, with recycling of endocytosed receptors occurring over a period of approximately 60 minutes [40]. The duration of this process is therefore significantly greater than the 1 minute time period over which we observed increased resensitization of the ATP response in bradykinin treated cells. Thus, the effect of bradykinin that we observed is more likely to be due to a re-coupling of the receptor to G protein prior to recycling through the endosomal compartment.
The effects of bradykinin on ATP-mediated signaling could play multiple functional roles in the nervous system. B2 receptors are highly expressed on glioma cells, and the expression of these receptors may be correlated with tumor grade [29], suggesting that they may play a role in the abnormal growth and migration of these cells [28]. P2Ypurinergic receptors have also been implicated in the growth and migration of glial tumors [41–43]. Thus, potentiation of purinergic receptor signaling by bradykinin could play a role in CNS tumor formation and progression.
B2 receptors have also been a focus of investigation and potential therapies because of their role in opening the blood-tumor-barrier [44]. P2Y purinergic receptors are also highly expressed at the glio-vascular interface, suggesting that an interaction between bradykinin and P2Y purinergic receptors could play a role in the interaction of glioma cells with the vasculature [45]. Bradykinin is also well known as an important inflammatory mediator, with potential roles in the response of the brain to head injury, encephalitis, and ischemia [46]. Significant quantities of ATP may be released in association with these same events, which therefore represent other settings in which interaction between bradykinin and ATP-mediated signaling may be important [47]. Finally, both B2 and P2Y purinergic receptors may be involved in pain transmission. Bradykinin released in the setting of tissue damage or inflammation could therefore influence nociception by increased resensitization of P2Y purinergic receptors [48, 49].
Our results indicate that bradykinin-evoked signaling has a significant influence on purinergic receptor signaling via the PI3 kinase pathway. Potentiation of purinergic signaling by increasing receptor resensitization may represent an important mechanism by which bradykinin modulates glial cell function.
[Ca2+]i:
intracellular calcium concentration
ATP:
adenosine 5' triphosphate
PKC:
phorbol12-myristate 13-acetate
PI3K:
Phosphoinositide 3-kinase.
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Paukert M, Hidayat S, Grunder S: The P2X(7) receptor from Xenopus laevis: formation of a large pore in Xenopus oocytes. FEBS Lett. 2002, 513: 253-258. 10.1016/S0014-5793(02)02324-4.
Czubayko U, Reiser G: Desensitization of P2U receptor in neuronal cell line. Different control by the agonists ATP and UTP, as demonstrated by single-cell Ca2+ responses. Biochem J. 1996, 320: 215-219.
Verderio C, Matteoli M: ATP mediates calcium signaling between astrocytes and microglial cells: modulation by IFN-gamma. J Immunol. 2001, 166: 6383-6391.
Beltran-Parrazal L, López-Valdés HE, Brennan KC, Díaz-Muñoz M, de Vellis J, Charles AC: Mitochondrial transport in processes of cortical neurons is independent of intracellular calcium. Am J Physiol Cell Physiol. 2006, 291: C1193-1197. 10.1152/ajpcell.00230.2006.
Otero M, Garrad RC, Velazquez B, Hernandez-Perez MG, Camden JM, Erb L, Clarke LL, Turner JT, Weisman GA, Gonzalez FA: Mechanisms of agonist-dependent and -independent desensitization of a recombinant P2Y2 nucleotide receptor. Mol Cell Biochem. 2000, 205: 115-123. 10.1023/A:1007018001735.
Santiago-Perez LI, Flores RV, Santos-Berrios C, Chorna NE, Krugh B, Garrad RC, Erb L, Weisman GA, Gonzalez FA: P2Y(2) nucleotide receptor signaling in human monocytic cells: activation, desensitization and coupling to mitogen-activated protein kinases. J Cell Physiol. 2001, 187: 196-208. 10.1002/jcp.1063.
Flores RV, Hernández-Pérez MG, Aquino E, Garrad RC, Weisman GA, Gonzalez FA: Agonist-induced phosphorylation and desensitization of the P2Y2 nucleotide receptor. Mol Cell Biochem. 2005, 280: 35-45. 10.1007/s11010-005-8050-5.
Weick M, Wiedemann P, Reichenbach A, Bringmann A: Resensitization of P2Y receptors by growth factor-mediated activation of the phosphatidylinositol-3 kinase in retinal glial cells. Invest Ophthalmol Vis Sci. 2005, 46: 1525-1532. 10.1167/iovs.04-0417.
Bony C, Roche S, Shuichi U, Sasaki T, Crackower MA, Penninger J, Mano H, Puceat M: A specific role of phosphatidylinoitol 3-kinase gamma. A regulation of autonomic Ca(2)+ oscillations in cardiac cells. J Cell Biol. 2001, 152: 717-728. 10.1083/jcb.152.4.717.
Maier R, Glatz A, Mosbacher J, Bilbe G: Cloning of P2Y6 cDNAs and Identification of a Pseudogene: Comparison of Receptor Subtype Expression in Bone and Brain Tissues. Biochem Biophys Res Commun. 1997, 237: 297-302. 10.1006/bbrc.1997.7135.
Tulapurkar ME, Zundorf G, Reiser G: Internalization and desensitization of a green fluorescent protein-tagged P2Y nucleotide receptor are differently controlled by inhibition of calmodulin-dependent protein kinase II. J Neurochem. 2006, 96: 624-634. 10.1111/j.1471-4159.2005.03594.x.
Morrone FB, Jacques-Silva MC, Horn AP, Bernardi A, Schwartsmann G, Rodnight R, Lenz G: Extracellular nucleotides and nucleosides induce proliferation and increase nucleoside transport in human glioma cell lines. J Neurooncol. 2003, 64: 211-218. 10.1023/A:1025699932270.
Neary JT: Trophic actions of extracellular ATP: gene expression profiling by DNA array analysis. J Auton Nerv Syst. 2000, 81: 200-204. 10.1016/S0165-1838(00)00154-5.
Neary JT, Kang Y, Bu Y, Yu E, Akong K, Peters CM: Mitogenic signaling by ATP/P2Y purinergic receptors in astrocytes: involvement of a calcium-independent protein kinase C, extracellular signal-regulated protein kinase pathway distinct from the phosphatidylinositol-specific phospholipase C/calcium pathway. J Neurosci. 1999, 19: 4211-4220.
Borlongan CV, Emerich DF: Facilitation of drug entry into the CNS via transient permeation of blood brain barrier: laboratory and preliminary clinical evidence from bradykinin receptor agonist, Cereport. Brain Res Bull. 2003, 60: 297-306. 10.1016/S0361-9230(03)00043-1.
Simard M, Arcuino G, Takano T, Liu QS, Nedergaard M: Signaling at the gliovascular interface. J Neurosci. 2003, 23: 9254-9262.
Raidoo DM, Bhoola KD: Pathophysiology of the kallikrein-kinin system in mammalian nervous tissue. Pharmacol Ther. 2006, 79: 105-127. 10.1016/S0163-7258(98)00011-4.
Franke H, Krugel U, Illes P: P2 receptors and neuronal injury. Pflugers Arch. 2006, 452: 622-644. 10.1007/s00424-006-0071-8.
Millan MJ: The induction of pain: an integrative review. Prog Neurobiol. 1999, 57: 1-164. 10.1016/S0301-0082(98)00048-3.
Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Knight GE, Fumagalli M, Gachet C, Jacobson KA, Weisman GA: International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Pharmacol Rev. 2006, 58: 281-341. 10.1124/pr.58.3.3.
This work was supported by NIDA DA05010 and the Johnny Carson Foundation (AC) and Larry L. Hillblom (KCB and AC).
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Héctor E López-Valdés, Kevin C Brennan & Andrew C Charles
Program of Neurobiology, Universidad Veracruzana, Xalapa, Veracruz, México
Luis Beltran-Parrazal
Héctor E López-Valdés
Kevin C Brennan
Andrew C Charles
Correspondence to Héctor E López-Valdés.
HELV and LBP carried out all experiments; KCB and AC contributed to the writing of the manuscript and participated in experimental designs. All authors read and approved the final manuscript.
López-Valdés, H.E., Beltran-Parrazal, L., Brennan, K.C. et al. Bradykinin increases resensitization of purinergic receptor signaling in glioma cells. Cancer Cell Int 10, 35 (2010). https://doi.org/10.1186/1475-2867-10-35
Okadaic Acid
Purinergic Receptor
Purinergic Signaling
Protein Phosphatase Inhibitor Okadaic Acid
Bradykinin Effect


So, sadly I am one for the more obscure websites in the world, recently I was telling my friend about a truly pointless website and he countered with pimpmysnack.com. Hooked instantly I immediately informed my friends, posted on various discussion boards and… told the wife.
Now my wife is a little bit of a cookery nut and it didn't help that she was being egged (sorry) on by her equally insane friend. I myself am more of a partaking than construction person but I have in the past raised my love of meat and hence a giant scotch egg was born.
So as to method… an ostrich egg was mooted though it was eggstremely (I will stop) eggpensive (no really, that's the last). So the mad women (I think a fair description) decided they would make the egg themselves by combining many eggs into a single giant egg.
This would involve separating the whites and the yolk and then somehow (like they had a clue - they were making it up as they went along) combine them into one super egg.
Ok, the story now gets a little complicated (my idea is a little sketchy because my friend and I got a little bored and started playing the xbox360) however from interviewing the main participants I think they did this….
4.	After that filled up the space around the jar with more white.


DentistryIQ Thursday Troubleshooter: "I can't have my hours cut!"
Thanks to DentistryIQ for the chance to contribute to this week's Thursday Troubleshooter. I wish this Office Manager well!
QUESTION: I recently accepted a dental office manager position at an office that had not had a manager. On my third day during my newly implemented morning huddle, one of the front staff members blurted, "Is the doctor going to cut my hours, because I can't have my hours cut, I need 40 hours." I said, "Have you not been getting your hours? I was told you all are overtime and I've been asked to fix that."
She responded, "No, but he promised me 40 hours." She and two other staff members cosigned a promise of 40+ hours a week. I was taken aback by these demands. I've been in the dental field 15 years and I've never demanded 40+ hours. I'm thankful to be employed and to get at least 32 hours. After assessing patients' in-office time, the office's open hours, and the hours the staff stays on the clock, I determined that 40+ hours isn't realistic. I posted a schedule for the staff that lists their days off and lunch times.
I'm not exaggerating when I say I probably should have walked out! They were enraged because they were only scheduled 39.50 hours or 40 hours! What I've observed is that the staff does what they want and they really don't use their time productively, they just get "their hours." There are six female staff members and one male dentist who isn't consistent with policy and rules, hence why he and his wife hired me. Now the resistance and pushback I get from the team is disheartening. Help!
It appears you may have been hired to be the "bad guy," probably because the dentist knows he's gotten himself into a pickle in terms of what he's promised his employees and what the practice can actually afford to deliver.
If the doctor supports you, call the team together and explain that the practice does not have the necessary production to support a 40+ hour workweek for six employees. Explain that the industry norm in a job like theirs is 32 hours per week, and that you have done your best to keep them at or near the 40-hour mark. If you continue to meet resistance, tell them you and the doctor will understand if they need to look elsewhere for employment. Be firm, you are being tested.
If the doctor does not support you, you also have a decision to make as to whether or not this is the right job for you. From what you've said, I don't think you would have trouble finding a better and probably healthier position somewhere else.


text:
5.3 earthquake hits Alberta, Canada.
5.2 earthquake hits Fiji.
5.2 earthquake hits the Pacific-Antarctic ridge.
5.1 earthquake hits the Ryukyu Islands off Japan.
Tropical Storms – Roundup of Tropical Storms:
There are currently no tropical storm systems.
Newsbytes:
Cameroon – A massive landslide struck in the city of Yaoundé, capital of Cameroon, on 27 November 2022. Media report at least 14 fatalities. The landslide occurred late on 27 November in the Antenne Damas neighbourhood in Yaounde, Centre Region. The victims were gathered for a religious service near a soccer pitch at the base of a 20 metre high soil embankment, which then collapsed. The cause of the collapse is not clear. Some media reports speculated that it was triggered by heavy rain.
Salmonella – Norway
Norway's Institute of Public Health, or Folkhälsomyndigheten (FHI) discovered a national outbreak caused by the gastrointestinal bacterium Salmonella Agona. So far, infection has been detected in 31 people living in several counties.
Monkeypox – Chile
The Chile Ministry of Health reported the second monkeypox death in the country. The patient was a older male who was unvaccinated and diagnosed on October 20. He had underlying pathologies and a weakened immune system (immunosuppression).
The World Health Organisation has decided to rename 'monkeypox' as 'mpox' due to a perceived discriminatory connotation in third world societies.
5.2 earthquake hits south of the Kermedec Islands.
5.0 earthquake hits Seram, Indonesia.
Australia fires damaged ozone layer – caused major warming
Australia's fire season in late 2019 and early 2020 was extreme. It blew smoke some 20 miles into the sky, not unlike what a nuclear blast might cause. Smoke from the fires circled the globe and hovered in plumes over the Pacific.
Now, a study published Thursday in the journal Scientific Reports suggests the smoky aerosols caused the highest temperatures in the stratosphere in about three decades and probably damaged the ozone layer — which has been slowly recovering since the substances that deplete it were largely phased out through the 1987 Montreal Protocol.
Hawaii's Mauna Loa, the world's largest active volcano, is erupting for the first time in nearly 40 years.
Dozens of earthquakes — one of them a magnitude 4.2 quake — have swarmed the region after the volcano's Moku'āweoweo summit caldera erupted on Sunday (Nov. 27) night. Officials have issued an ashfall advisory for Hawaii's Big Island and residents have been asked to remain vigilant. So far the eruption's lava flows pose no risk to people living downhill from the eruption and air travel is currently unaffected.
Cholera – Kenya
The Kenya Ministry of Health announced a multicounty cholera outbreak on October 19. The first cases of Vibrio cholerae -01 Ogawa serotype were detected following a wedding festival that was held in Limuru sub-county, Kiambu County October 8, 2022. As of 13 November 2022, a total of 568 cases with 281 confirmed (48 cases by culture and 233 by rapid diagnostic test) and 15 deaths (CFR = 2.6%), have been reported so far. This is the second cholera outbreak to be declared in almost one month this year for Kenya.
Ebola – Uganda
Uganda health officials reported today an additional Ebola Virus Disease (EVD) case and death, the first in eleven days.
5.0 earthquake hits the Pacific Antarctic ridge.
5.0 earthquake hits the Mariana Islands.
Italy – Heavy rainfall triggered massive landslides and floods on the island of Ischia in southern Italy early on 26 November 2022. Houses in northern parts of the island were damaged or destroyed as a torrent of mud, flood water and debris crashed down slopes of Mount Epomeo. Some areas were under mud and debris several metres deep. Dozens of vehicles were swept into the sea in areas of Casamicciola Terme. As of 27 November authorities reported the bodies of 3 victims have been found. Four people are still missing. Poor weather conditions have hampered rescue and damage assessment efforts.
The Dead Sea is Dying
The Dead Sea is the lowest exposed place on Earth. It is 10 times saltier than the ocean. So you don't sink in it. You float. The mud and the waters are full of minerals – great therapeutic for your skin. But the Dead Sea is dying. The lake level is dropping 4 feet every single year. The cause is that in the last several decades, the freshwater sources that feed into the Dead Sea have been diverted for drinking water and irrigation. Also, Israeli and Jordanian companies pump out and evaporate Dead Sea water to harvest its rich minerals for export. Cavities along the shore open up into sinkholes.
Climate change makes this worse. The area is getting hotter. Rainfall is dropping. Populations are growing, and there's not enough water for drinking and irrigation, let alone for saving the Dead Sea.
Dengue Fever – Bangladesh
The Bangladesh Directorate General of Health Services (DGHS) reported an additional 513 dengue fever cases and three fatalities today, bringing the country's total to 56,130 cases and 257 deaths year to date.
5.7 earthquake hits the Kuril Islands.
5.3 earthquake hits Easter Island.
5.1 earthquake hits Taiwan.
5/1 earthquake hits the Banda Sea.
5.1 earthquake hits Vanuatu.
5.0 earthquake hits the Izu Islands off Japan.
5.0 earthquake hits near the coast of Nicaragua.
Trinidad and Tobago – Several parts of Trinidad and Tobago are experiencing flooding as an active low-level tough traverses westward over the country. Affected areas include Biche, Ortoire, Santa Cruz, St Joseph, Maracas, Caparo and Arouca. There have also been reports of landslides.
Wildfires – Europe
Over 20 wildfires raged across Portugal and several burned in western Spain yesterday, menacing villages and disrupting tourists' holidays amid a heatwave that meteorologists expect to push temperatures into the high 40s Celsius.
In Spain's western region of Extremadura bordering Portugal firefighters evacuated a few hundred villagers overnight as a precaution and continued to battle a blaze that on Tuesday swept into Salamanca province in the region of Castile and Leon.
In France too, about 800 firefighters, supported by six water-bomber aircraft, were battling two wildfires in the southwest, which have already prompted the evacuation of thousands of campers. About 2 700 hectares were burned.


Last week, Vice President Joe Biden announced that 25 communities would receive Retrofit Ramp-up awards to help improve energy efficiency in both residential and commercial buildings.
April 26, 2010, 2 p.m.
As a follow-up to the Recovery Through Retrofit report, Vice President Joe Biden recently announced that 25 communities would receive up to $452 million in Recovery Act dollars as part of the new Retrofit Ramp-up program. Retrofitting both residential and commercial buildings will help provide good green jobs to out-of-work Americans while improving the energy efficiency of these buildings. More energy-efficient buildings lowers the nation's overall carbon footprint while at the same time reducing energy bills.
The projects that have received Retrofit Ramp-up funding vary in location and nature. The city of Indianapolis, Ind., has received $10 million. These funds will help launch energy efficiency pilot projects in two urban areas. The retrofits will be made to commercial, residential and industrial buildings but also to schools in the area. Overall, 470 square blocks in the city center will be turned into a more sustainable community.
In Nebraska, the cities of Omaha and Lincoln will benefit from a $10 million grant. In addition to focusing on energy-efficient building retrofits, the funds will also help grow workforce development programs to train city residents for good green jobs.
These are just two of the 25 projects that have received funds from the first round of Retrofit Ramp-up program. Overall, the nearly $452 million investment is expected to create about 30,000 jobs over the next three years while saving Americans nearly $100 million in energy costs each year.
For more information on the specific projects that have been awarded funding, download the Retrofit Ramp-up Selected Projects list (PDF).


"The Assassination" podcast with BBC's Owen Bennett-Jones is nearing its season-finale. If I could recommend one podcast this January, it'd be this one. It is so well-researched and well-produced that it makes you feel the historicity of the moment with new-clips and interviews with people who were right there as Benazir Bhutto was murdered. This week caps off the series and I'd recommend a podcast-binge from the very first one.
The second podcast that I loved this last ten days was the one on Bijlmer by 99% Invisible. Again, Roman Mars and co. are superb and I'd highly recommend checking out their article along with the podcast episode itself.
One of favorite podcasters posted recently, which I am extremely happy about. The Kitchen Sisters are one of the most radically innovative producers and everything they tackle in their podcasts. If you have not listened to the one about the "Bone Records" in Russia, this would be the time to rectify that grave mistake in your life.
This week, though, they had a story about an exiled writer that because of my own research interests, was something that was moving, hilarious and at times, simply enchanting. The interplay of text and voices weave to create something more than an episode about Guillermo Cabrera Infante; it was simply excellent podcasting.
The last podcast from last week is by The Guardian's Book podcast which is an excellent place to listen to and actually discover new podcasts. Last week, in a rather charming interview with a woman who has documented her loss of memory in a book, I was left wondering how I would respond if I had to choose between losing my sense of smell or taste or, say, the memory of my lovers and poems. This was one of the podcast episodes I know I will go back to over time simply because it asks questions that have many complicated entries into the theatre of the mind.


New Curriculum Coming This Fall!
I am so excited to announce a new curriculum for our 4year olds and Kindergarten that we will be doing next year. These classes will be studying U.S. History and Social Studies weekly in their classrooms using a common curriculum based on the Kindergarten Georgia Standards of Excellence for Social Studies. This curriculum, combined with the existing computer class geography curriculum, and the individual classroom celebrations of our national holidays provides a complete history, geography, government, and economics education. Each of these lessons is taught with a variety of media and further enriched with math, science, and language arts hands-on activities. This "student-centered" learning approach provides a variety of methods and opportunities to learn about the subject and can be adapted to meet the needs of each classroom. The students' interests and questions about each week's subject matter will guide how the teacher approaches the lesson, while all of the classrooms will cover the same main teaching points.
Our Kindergarten class has already been focused on History as part of that overall curriculum, but we are adding a more structured program for our 4yr old classes. The children will be learning about the Constitution, U.S. Flag, Declaration of Independence, Statue of Liberty and much, much more! We already say the Pledge of Allegiance to the flag, and the children will learn more about what those words really mean. For more information about each of the lessons, visit our SPECIALS page. Our teachers are excited about teaching this to your 4year and Kindergarten students!


There will be a day when you will be traveling to different places for some backpacking, maybe volunteer work or just a simple vacation that will be a bit more unconventional. There are a lot of reason why you should try and visit Kenya. Kenya is home to one of the most friendly locals in the world, they also have rich history and culture that will be worth experiencing, they also have amazing nature and wildlife. You will not regret choosing Kenya to be the next place to visit or travel to because there are a lot of things you can do and it is also recognized to be one of the most beautiful countries in Africa. It is always important to plan out the itinerary before actually going to Kenya and also plan a couple of things first like understanding their own set of laws and culture so that you will not fall into any problem when you get there.
Before you go to another country, it is important that your vaccinations are updated, when you plan to visit to Kenya, be sure that you are already vaccinated. Before you go to Kenya, there are also new vaccinations that you will need just to make sure. You need to know that your routine vaccinations like MMR will be included. You will not only think about the vaccines for chicken pox, tetanus and polio, you also have to think about the vaccinations all Kenyan visitors will need. The needed vaccines for Kenyan visitors will be typhoid, malaria and hepatitis A. It is better to have your general check up before you go to Kenya or to any country for that matter. You will feel a lot safer when you get to Kenya when you already know that you have all of the vaccines that you will need for Kenya. You should watch out for malaria, it is hard when you get the sickness, there. You need to bring your own stock of mosquito sprays and also bug repellent.
You have to check your visa first before you even plan on traveling. If you come from a different country and you would love to get to Kenya, you will have to prepare something. You will have to have your visa in order to gain entry to Kenya.


Teaching is a form of service that lets you create a direct, positive impact on the lives of young people. Every new year introduces you to students with fresh ideas, unique talents and varied personalities. Our vibrant community comprises of students from all over the globe. Trio cherishes and honours individuals whose vision is to teach, inspire and nurture students.
Teaching is a great way to help children realise their highest potential and gain a deep sense of fulfilment. TRIO understands that our teachers deserve the very best environment to become the best they can be. We continuously improve our training programmes, workshops, technology and related resources to help teachers grow in their careers.
We love to work with passionate and qualified teachers who can thrive in a multicultural environment. If this describes you, then we would love to hear from you!
Trio World Academy is presently following IB PYP, Cambridge Secondary 1, IGCSE and IB Diploma programmes.
NOTE – Candidate should have IB or/and International Curriculum experience.
Join us and ignite the spark of learning in a new generation!


Sporting goods, Fan Shop and Fan Gear Including NFL, MLB, NBA, NHL, NASCAR, NCAA and much more!
Tailgating outfitter featuring NFL helmet snack trays, college team coolers, tents, football gifts, and incentive awards.
Tailgating gear and homegating supplies, team gear, grills and coolers, portable chairs and folding picnic tables, outdoor tailgate games and much more.