text:
All About of Volvo XC60
Sitting at just 5 for each cent of the complete product sales in the High end SUV section, the XC60 is one particular of the segment's greatest-stored secrets. That's a shame since it is a great vehicle that deserves far more interest than it presently receives.
So with a horde of makers releasing expense-successful, fuel effective entrance-wheel generate SUVs, previously this yr it was Volvo's flip to introduce us to its XC60 T5 & attempt to seize some of the entry-level consumers.
Making use of the exact same drivetrain as the V60 T5 we tested last week, the XC60 T5 functions a 177kW two.-litre turb0charged four-cylinder petrol matched to a 6-pace twin-clutch transmission, which powers the entrance wheels only.
Whilst it could seem odd to have a 4-wheel push which is genuinely only a entrance-wheel push, you'd have to say that almost all of these types of cars stay on the blacktop – the exception is quite unusual without a doubt. The Volvo XC60 specs will make everyone fal in love with the car. The attributes that buyers want are area, a greater seating placement, and – let us be brutally sincere here – the prestige issue.
A 2WD SUV matches that bill completely, and with less relocating components to get treatment of, servicing is simpler and fuel usage is down on the AWD ~equal, not acquiring the drain of added pushed wheels to take care of. In the case of the XC60 T5, fuel use is detailed at eight.seven litres/100km – curiously, precisely the identical figure as the V60 T5.
Review the excess weight of the two – the V60 is 1580kg & the XC60 is 1740kg. The 160kg heavier XC60 also will take an further .4 seconds to get to 100km/h, which signifies that reaching the identical fuel usage is no indicate feat.
Throughout the week of our operating all around, we saw constant minimal 10s in the regular fuel usage, however, provided the possibility to stretch its legs, we've no question the ADR figure would be achievable.
The motor has to operate tougher in the XC60 & it reveals, with turbo lag a lot more noticable than in the V60 T5 as it winds up to get into its stride. Although going, the engine is superb, sleek to rev & with ample grunt for daily use. The Powershift dual-clutch transmission also functions in opposition to the further bodyweight with a a bit shunty really feel as it engages absent from lights, but on the roll is sufficiently easy & like the V60 has fast, decisive modifications.
Volvo does have its background in security as well, and with Town Safety, which either minimizes the severity of, or removes rear-finish collisions altogether, the XC60 is surely the best choice for individuals who want to preserve their family members well protected.
As a practical loved ones vehicle with an edge of indulgence, the XC60 is nicely well worth a search. It is straightforward to get in and out of, has sufficient place and has an interior that will impress. Now that it arrives in T5 guise, it's affordable, generating it available to a entire new realm of clients.
Tags: Auto, Car, SUV, Volvo, Volvo XC60, Volvo XC60 specs


text:
'What will someone feel here?'
That question is at the crux of all our work, a touchstone for every stage of every project you see here.
We have what is on the face of it a straightforward approach to the discipline of architecture. This says that we need to include decisions about the physical impression of the project in its conceptual foundation. It is not good enough to have a concept and hope it can be maintained through the rigours of the RIBA Work Stages. We need to be sure that what we draw can be built, and that what we build will evoke appropriate feelings in the people which use it.
As this is about the technology of enclosing and modifying and filtering a volume of space, it necessarily includes the big issue of sustainability and the small matter of human comfort. Often we find ourselves working with fluid shapes which seem organically to connect people to uses.
So the projects here explore these preoccupations in different ways through very different projects – and after a time we feel we are beginning to understand what all this might mean.

subset: commoncrawl


text:
Series: Flashpoint #2
Published by Janus Publishing on November 21st 2017
Pages: 350
Buy on Amazon
When a food storage depot in famine-struck South Sudan is torched, American aid worker Brie Stewart flees, only to land in a market where she's the next item up for auction. Is the attack on the aid facility another assault upon the war-torn fledgling democracy, or has her family set her up as a pawn in their quest for oil rights?
Chief Warrant Officer Sebastian Ford crossed paths with Brie years ago when she was a shill for her family's company, pushing a pipeline that threatened his tribe's land. Determined to lead the rescue operation to save her, he won't let her abduction—or the attraction that flares between them—get in the way of settling their unfinished business.
The Green Beret's skills are put to the test in the flooded grasslands of South Sudan, where they must battle nature and dangerous factions who are after more than oil. Bastian and Brie put their hearts on the line as they find themselves embroiled in a conflict that extends beyond country and continent. Together they must douse the spark before it reaches the flashpoint and engulfs everything they hold dear.
I've always thought of Rachel Grant as the romantic suspense author who goes where good authors of this sub-genre go, then where most books actually end, takes it a breath-stealing mile further. Where entire books would have been written around a sex-trafficking plot, Grant integrates hers with a smartly-written overview of cultural anthropology, native American issues and the knife-edge balance of the socio-political situation in Africa that makes her Flashpoint series beyond excellent.
'Catalyst' is written pretty much in the same vein as its predecessor: thrilling, engaging and entirely absorbing, particularly if you love the kind of geopolitical background (with some corporate dirt thrown in) that Grant painstakingly unravels—which I do—in a part of the world that's hardly written about in such books. For that alone, I can't wax lyrical enough about this series, which is akin to seeing a complex chess-piece that's put together in a narrative arc that makes it feel as though there's yet unfinished business to conclude.
It's also almost a given that her characters are equally multifaceted, and it's my own fault that I didn't quite warm to Brie and Bastian at all, with the former being more manipulatively needy and self-pitying because of her past than I expected, while the latter was too careless with people and unashamedly being Bastian the bastard about it. The games they later played with each other because neither of them could get a handle on commitment also didn't help my ability to like Brie/Bastian as a pairing while as Brie's 'rich girl's woe-is-me penance' got tiring after a while. That said, the first half of 'Catalyst' enthralled me more than the second, where I found I needed to suspend disbelief a bit more when it seemed that many of the mysterious threads laid out so intricately in the first half were actually tied together by an obsessive man in Brie's past.
The action and suspense are nonetheless very well-done and I was especially taken by the hostile tension between Savannah James and Cal whose book I hope Grant tackles next, as much as I loved the appearance of one of Grant's best heroes in the Evidence series here.


text:
Fruity King Casino
Read The Terms And Conditions Here
Important Features
- Established in 2014
- Exciting collection of games by Progress Play
- Welcome match deposit bonus of 100% up to £200 for new customers
- Fun filled promotional offers
First Impression
Fruity King Casino has a colorful website and a fantastic collection of games. It calls itself "the King of Mobile Casino Games" and is compatible with all the major mobile platforms like android, iOS etc. The sleek website is user friendly and the casino offers numerous exciting promotional offers to its players.
Fruity King Casino was established in 2014 and is owned by Progress Play Limited.
Games and Software
An attractive suite of games powered by Progress Play is the chief attraction at the Fruity King Casino. Slot games like Irish Eyes, Game of Thrones, Miss Midas and Tomb Raider are present here. Numerous high paying progressive Jackpot games like Tunzamunni, Thunderstruck II and Cashapillar tempt you to play in this casino.
Table game enthusiasts can check out games like American Roulette or HD Roulette, Multi-Hand Blackjack etc. You can communicate with a charming live dealer as you try out games such as Live Baccarat, Live Roulette, Live Multiplayer Roulette, Baccarat and Blackjack.
Fruity King Casino is licensed by the UK Gambling Commission and the Gaming Authority of Malta. These licenses assure players that the casino is a secure place to try their luck.
Bonuses and Promotions
Customers are welcomed with a 100% first match deposit bonus up to £200 on opening an account with the casino. Exciting fun filled promotional offers such as Monday Madness, Spin the Slots, Game of the Day, Weekly Surprise, Cash back Day and Big Weekend Cash Race manage to enchant players and reward them gloriously at the Fruity King Casino.
Customer Support
Players can contact the customer support officials at the Fruity King Casino between 6:00 AM and 23:00 GMT. They can make use of methods like live chat or email to contact the team. When the officials are offline, players can leave a message with their queries and get a response.
Deposit and Withdrawal Methods
Customers can choose from a vast array of options to place deposits in the Fruity King Casino. These involve methods like Visa, Visa Debit, Visa Electron, Visa Delta, Solo, JCB, Diners Club, Switch, Discover, Neteller and Skrill.
Withdrawal methods comprise of options like Visa, Master Card, Maestro, Neteller, Skrill, Ukash, iDeal, Cheques and Bank Transfers.
Country Restrictions
Players from Belgium, Belize, British Virgin Islands, Bulgaria, Cyprus, Croatia, Denmark, Estonia, France, Finland, Germany, Greece, Hungary, Italy, Ireland, Israel, Lithuania, Luxembourg, Serbia, Portugal, Romania, Slovenia, Spain, Turkey and the United States of America are forbidden from playing at the Fruity King Casino.
Review Summary
Review Name: Fruity King Casino
Posted On: 19/04/2016
Author: Dean Moors


text:
As it was, I treated the puzzle like a themeless, despite the oddly cut-off corners betraying significant constraints on the fill. The puzzle itself took me the 8 minutes recorded below. I then looked at the answers to the asterisked clues and noticed the abbreviations for the months within a couple of minutes.
The symmetrical arrangement of the theme answers, and their correct ordering, impressed me and I can see that the difficulties of having juxtaposed answers like Sephora and no votes resulted in relatively poor integration of the six main parts of the puzzle - each containing two months.
20a psst! {Cheater's utterance} was a challenge during solving, but I think I've got it now: psst! is what a schoolkid (or maybe an ACPT competitor) would utter to get a neighbor to help with answers, right? Anyway, I assume that's the intended context ... readers?
I was also held up a bit with 34a junction {Roundabout, for one}, thinking roundabout wasn't understood in the USA. Aren't roundabouts called traffic circles over here?
Solving time: 8 mins (solo, no solving aids)Solution
Clue of the puzz: 49d corer {Apple implement}
Grid art by Sympathy [about the grid colors]
The 12 symmetrically disposed answers with starred clues start with abbreviations for months of the year, in the correct order:
1a Janets {Reno and 38-Across, for two}Crucimetrics [about Crucimetrics]
15a Febreze {Procter & Gamble deodorizer}
16a Marsala {Sweet Italian wine}
17a apropos {Fitting}
33a Mayer {The second "M" of MGM}
34a junction {Roundabout, for one}
43a Juliette {Actress Lewis of "Natural Born Killers"}
45a Augie {Hanna-Barbera's ___ Doggie}
55a Sephora {Cosmetics chain whose name comes from the Greek for "beauty"}
59a Octomom {Nadya Suleman, mother of 14, familiarly}
64a no votes {Nays}
67a declaw {Remove nails from}
Video of the Day
Compilers Jose Chardiet / Will Shortz Grid 15x15 with 40 (17.8%) black squares Answers 78 (average length 4.74) Theme squares 80 (43.2%) Scrabble points 334 (average 1.81) Letters used ABCDEFGHIJKLMNOPQRSTUVWXYZ
45a Augie {Hanna-Barbera's ___ Doggie}. Augie Doggie and Doggie Daddy are Hanna-Barbera cartoon characters who debuted on The Quick Draw McGraw Show and appeared in their own segment of that show. The segments centered around the misadventures of a dachshund father-and-son team. Doggie Daddy (voiced by Doug Young impersonating Jimmy Durante) tried to do the best he could at raising his rambunctious son Augie (voiced by Daws Butler). Augie, who loved his father, would often refer to him as "dear old Dad." Their mutual admiration included Daddy gently chiding, "Augie, my son, my son", when he would disappoint his father; and when his son would say or do something that inspired pride, Daddy would turn to the audience and say with a grin, "Dat's my boy who said dat!" Augie Doggie and Doggie Daddy were animated by famous animator Al Bertino, best known for his work for Disney. The character Augie was named after Bertino's son Augustine Bertino.
The Doctor is IN
18a STP {Indy initials}. Reference to STP ("Scientifically Treated Petroleum"), their stickers often being seen at the Indianapolis Motor Speedway.
52a non- {Stop start?}. Reference to non- as a prefix in "non-stop".
3d nar. {Not wide: Abbr.}. nar., short for "narrow".
4d ehs {Canadian query closers}. See eh.
8d abra {Start of a spell}. The full spell being abracadabra.
20d pajamas {Sleepers}. sleeper(s) = "children's pajamas usually with feet — usually used in plural" [MWCD11].
27d gyrated {Did the watusi, e.g.}. The watusi is a solo dance that enjoyed brief popularity during the early 1960s.
31d St. Joe {Missouri city, informally}. I.e. Saint Joseph, MO (informally St. Joe or Joe Town).
36d sol {G string?}. sol corresponds to the note G in solfège.
56d EOE {Want ad abbr.}. EOE = Equal Opportunity Employment in this context.
60d OTC {Like some stocks, for short}. OTC = over-the-counter, i.e. off-exchange trading.
61d mil {1,000 G's}. A million dollars being a 1,000 lots of $1,000.
Image of the Day
49a cobra {Mongoose's foe}. Mongooses (Herpestidae) are a family of 33 species of small carnivorans from southern Eurasia and mainland Africa. Four additional species from Madagascar in the subfamily Galidiinae, which were previously classified in this family, are also frequently referred to as "mongooses". Genetic evidence indicates that the Galidiinae are more closely related to other Madagascar carnivorans in the family Eupleridae, which is the closest living group to mongooses.
Mongooses mostly feed on insects, crabs, earthworms, lizards, snakes, chickens, and rodents. However, they also eat eggs and carrion. The Indian Mongoose and others are popularly used to fight and kill venomous snakes, including vipers. They can do this because of their agility and cunning, and their thick coat. They typically avoid the cobra and have no particular affinity for consuming its meat. Some species can learn simple tricks. They can be domesticated and are kept as pets to control vermin. However, they can be more destructive than desired: when imported into the West Indies to kill rats and snakes, they destroyed most of the small, ground-based fauna. For this reason, it is illegal to import most species of mongoose into the United States, Australia, and other countries. Mongooses were introduced to Hawaii in 1883, and have had a significant negative effect on native species.
Other Clues
7a lab rat {Maze runner}; 13a in a heap {All piled up}; 19a Kea {Mauna ___}; 20a psst {Cheater's utterance}; 24a saber {Cavalry blade}; 26a MGMT {Band with the 2008 song "Electric Feel"}; 30a ah yes {"It's all coming back to me now"}; 32a dad {Parental palindrome}; 36a Sierra {___ Nevada}; 37a ate {Downed}; 38a Jackson {See 1-Across}; 40a AIG {Bailed-out co. in 2009 news}; 41a Mormon {Latter-day Saint}; 46a Jon {Stewart of "The Daily Show"}; 47a steed {Knight's need}; 48a Styx {Dead river?}; 51a eddy {Small vortex}; 53a ore {Lode deposit}; 65a fertile {Productive}; 66a Lecter {Hannibal of "The Silence of the Lambs"}.
1d Jim {Halpert of "The Office"}; 2d Ana {Santa ___}; 5d teas {Oolong and others}; 6d salts {Puts (away), as for safekeeping}; 7d leper {Outcast}; 9d bro {Dude}; 10d rep {Workout unit}; 11d azo {___ dye}; 12d tes {Parisian possessive}; 14d Papa Doc {Nickname of the dictator who said "I know the Haitian people because I am the Haitian people"}; 15d faked {Like some U.F.O. sightings}; 21d shut-out {Game in which only one team scores}; 22d synergy {Working well together}; 23d 'tec {Private eye}; 25d bank job {Heist of a sort}; 26d Mae {Fannie ___}; 28d merited {Deserved}; 29d tragedy {"Coriolanus" or "Richard III"}; 33d minis {Some skirts}; 35d Ian {Actor Holm}; 39d sun-roof {Car option that slides open}; 42d mix {Mingle}; 44d été {Summer on the Seine}; 46d Jonas {Pop's ___ Brothers}; 49d corer {Apple implement}; 50d arced {Rainbowlike}; 52d note {Part of a melody}; 54d être {Raison d'___}; 55d SNL {"___ Digital Shorts"}; 57d PVC {Common pipe material, briefly}; 58d hot {Trendy}; 62d -ola {Suffix with pay or plug}; 63d mew {Cat call}.


text:
Energy and Environment Management System++
The Energy Marketplace is constantly changing which makes it critical for Municipalities to implement a solution that not only tracks energy performance and costs but also incorporates the unique environment and economic impact of Municipal Operations. Although there are many off-the-shelf software products available today, these solutions do not adequately address the unique needs of Municipalities. York Region contracted Inovex to build a brand new application utilizing the latest technology. The new EEMS++ Application provides Municipalities with an "all-in-one" gateway to track & report on energy consumed in Municipal Operations (including fleet vehicles), plus the ability to track and report on the emissions generated by municipal operations. By using EEMS++, Municipalities can easily meet mandatory Municipal Energy Reporting requirements. EEMS++ Licensees include six (6) Ontario municipalities: Waterloo Region, Halton Region, Town of Oakville, Norfolk County, City of Brantford, and the City of Greater Sudbury.
The EEMS++ Energy & Environmental Management System is a robust, flexible, and scalable web based application built using the latest Microsoft .NET technologies.
EEMS++ is a comprehensive energy management tool that boasts the following features for municipalities.
As seen in the screenshot above, the dashboard allows you to see dynamically created charts as soon as you log into the system which serve to give you an overview of the municipality's energy use. Each user of the system can have their own unique dashboard and can drag-and-drop new charts onto the dashboard. The map interface can also be used to filter the charts on your dashboard to apply only to the assets in the selected view. (Assets are any municipal facility that consumes energy, such as a pumping station, street light, splash pad, etc.)
Easily search, create, and edit assets and their energy accounts via an intuitive navigational structure.
Setup emission factors and view emissions per asset, department, region or energy type.
Apply weather correction to charts within the system. Perhaps there was a warmer than usual summer one year which required higher electricity consumption for air conditioning; however, there was a building retrofit that should have shown improvement in energy consumption. Weather correction allows you to normalize the data and provides an unbiased comparison.
Customize KPIs for reporting to look at specific metrics (such as electricity consumption per square foot of a building). Associate user-defined or automatically-generated benchmarks with these metrics.
Automatically import your municipality's energy bills into the system on a regular basis, and define which fields need to be imported (such as cost, consumption and demand). The system also allows for quality control mechanisms to be set in place that will highlight warnings such as zero demand, missing bills, values outside of a baseline deviation threshold, etc.
Import or enter fleet fuel consumption for your municipality and report on emissions, fuel consumption, cost, and more.
For more information about this solution, please contact email@example.com


text:
Students' beliefs about how learning works can also
undermine learning, said Stephen L. Chew, PhD, who chairs the
psychology department at Samford University in Birmingham,
Alabama. Research shows that the typical college student
is inadequately prepared for college but nonetheless over-confident. And there's lots of evidence that students' favorite
study strategy — re-reading material — is also the least effective.
Teachers themselves may have false beliefs about teaching
and learning, said Chew. Instead of basing their pedagogy on
science, he said, they are relying "on untested intuitions, biases
and assumptions." Even among ELC participants, not all could
identify the most important ingredient of successful learning
on a list of learning strategies, despite the fact that researchers
have known for nearly half a century that the answer is the deep
processing that takes place when students link new information
with their prior experience.
What's needed is to replace untested assumptions with
research-based principles boiled down in a way teachers can
easily use, said Chew. That's the idea behind Chew's new series
of You Tube videos. Available at bit.ly/1EGm7f W, the five brief
videos outline the cognitive principles of effective teaching.
APA's Coalition for Psychology in Schools and Education is
also working to ensure that psychological science gets used to
improve education at all levels.
As one example, the coalition is developing "High 5," a
brochure for parents who are trying to choose high-quality
early childhood education programs for their children. "What
the research shows over and over is that it's not just any early
childhood education program that matters; it's high-quality
programs," said Roseanne L. Flores, PhD, an associate professor
of psychology at Hunter College.
APA honored four individuals with Cynthia D. Belar
Education Advocacy Distinguished Service Awards at its
2015 Education Leadership Conference:
• Mark A. Reinecke, PhD, a professor of psychiatry
and behavioral science at Northwestern University,
received an award for his advocacy on behalf of the
Graduate Psychology Education program, especially
his ongoing contact with the Illinois congressional
• Paul M. Robins, PhD, a
professor of clinical psychology
in psychiatry at the University
of Pennsylvania's Perelman
School of Medicine, received
an award for not just being a
committed advocate himself but
for mentoring interns to develop
advocacy skills of their own.
• Jill Brimmer, a legislative
assistant to Sen. Jack Reed
(D-R.I.), and Tim Medeiros, a legislative assistant to
Rep. David Jolly (R-Fla.), won awards for their work on
the Garrett Lee Smith Memorial Act reauthorization of
2015. These "friends of psychology" awards recognize
congressional staffers who as "unsung heroes" work
tirelessly behind the scenes, said Tammy Hughes, PhD,
chair of APA's Board of Educational Affairs.
Dr. Roseanne Flores Dr. Jim Diaz-Granados


text:
Molvi khajimiya is one of the best Astrologer in World.
He has 35years experience.
Lots of people around the world call and meet him and get solution of there problems.
We provide these services.
1:- Marriage Solution
2:- Business Solution
3:- Lost Love Back
4:- Spiritual Power
5:- Do or Remove Black Magic
6:- Success Solution
7:- Education Solution
8:- Childless Solution
9:- Love Problems Solution
10:- Job solution
11:- Family Problems Solution.
12:- Black Magic Specialist
13:- Astrology Or Numerology Expert
14:- Horoscope Or Hypnotism Expert.ETC..
Call him and get solution of your problems
Call Now :—- 9910724640
WEBSITE :—————- https://goo.gl/OQcgHo
India, New Delhi, Delhi


text:
Until recently, a sudden trauma to a bone, joint or muscle meant unnecessary hours of waiting in an emergency room, and a temporary fix until seeing your orthopedist. Specialists at the Central Orthopedic Group saw the need for a viable alternative . . . more
By Teri Ann Loeser | 5/23/19
Mama Theresa's is a name known to many, as there are three thriving locations in Nassau County. We dined in East Meadow, which houses the newest. more
By Terry Biener | 4/26/19
While Peter Kambitsis opened his first Long Island bakery on Feb. 1, he is far from a novice. His other culinary ventures include . . . more
By Teri Ann Loeser | 4/12/19
While Mango Indian Cuisine only opened several weeks ago, management behind it is quite well seasoned. Sewa Singh, who also owns . . . more
By Terry Biener | 3/15/19
According to owner Leon Yakubov, Artistic Men's Grooming is a "collaboration between barbering and hair dressing for men." more
By Teri Ann Loeser | 3/14/19
What sets The Long Island Living Center apart from many other assisted living facilities is the fact that they offer a unique Assisted Living Program. more
By Teri Ann Loeser | 3/1/19
Open since last August, Pure Shore Kitchen was a passion project for its owner, Kevin Donnelly. With the input of chef Chad Pagano and General Manager Lisa Newman . . . more
By Terry Biener | 1/18/19
If you're looking for a cozy spot to relax with brunch on a Sunday, Hemingway's has plenty to offer. A section of this multi-level bar and grill is transformed into . . . more
By Terry Biener | 1/4/19
It isn't surprising that Barbatsuly Furs — family-owned, founded in 1936 and still in its original building — has been cited as the oldest existing store in Garden City. more
By Teri Ann Loeser | 12/21/18
Over a year of hard work and major renovations have paid off, resulting in the lovely, intimate bar and restaurant, The Smith's Modern. more
By Terry Biener | 12/7/18


text:
Original blend of burdock, turkey rhubarb, slippery elm and sheep sorrel.
Premium herbs Certified Organic.
Ojibway Tea History
Ojibway Tea has a history dating back over 100 years. The tea was originally prepared by the Ojibway Indians of Ontario, Canada. Rene Caise a nurse who procured the recipe from the Ojibway Medicine Man helped make the tea famous when she renamed it by its now patented name of Essiac (her name spelled backwards). Our Ojibway Tea is a tea concocted of four organic herbs: Sheep Sorrel, Burdock Root, Slippery Elm and Turkey Rhubarb.
A note on Turkey Rhubarb vs Indian Rhubarb:
Nurse Rene Caisse the maker of Essiac used to purchase Turkey rhubarb for the making of the formula. Rene apparently did use Indian rhubarb at one point, but later changed to Turkey rhubarb, claiming that it was less bitter and more palatable.
Ojibway Tea is currently being consumed throughout the United States, Canada Mexico, Europe, Australia, and Africa and is marketed under many different names...
This packet contains the correct ratio of herbs to combine with one gallon/4 liters of water.


text:
Saturday could go down in Whitwell history, for a cricketing achievement never to be forgotten, and a party never to be remembered.
Both of Whitwell Cricket Club's Bassetlaw League sides are top of their respective tables going into the final game of the season.
The firsts are aiming to capture the Division One title, and with it a return to the Championship for the first time in over 25 years.
While the second string need just five points to be crowned Division Five champions.
Andrew Shaw has been at the club since 2000, and has never known the club to be on the verge of double glory.
"We've (firsts) been in the same league since I arrived in 2000," he said.
"In all the years I've been playing, I've never known both sides to be involved in title races going into the final day."
Although the second team have already earned a promotion spot, the firsts require eight points just to guarantee a place in the top flight.
To win the title outright, the target is 15 points.
Understandably, nerves are kicking in ahead of the visit of Blidworth Colliery Welfare in the season finale.
"I think it will be very tense on Saturday," said Shaw.
"It's a tough game against Blidworth, we've got a good rivalry between us and they won't want to see us go up, they'll put up a fight."
It was always the Derbyshire village club's desire to be up near the top come the business end of the 2015 season, but to conclude the campaign in first place would spark wild celebrations – especially if the seconds also win a title.
"It would be a massive achievement for the club.
"The firsts have had a very good season, there's a great team spirit and no outstanding individuals.
"A few years ago we started trying to bring a load more Whitwell youngsters into the club, and they've come through, some of them in the seconds and some through to the first team.
"They're all Whitwell lads and that makes it special.
"If we did the double I think the party would go into Sunday, it would be great to have trophies in the cabinet."


text:
I already posted about Associated Content politely telling Non-US writers they don't want us there. I basically spent the day before yesterday trying to figure out where I'm standing and where I want to go.
Since I'm currently freelancing only part-time, I prefer to write more for sites that can offer me some passive income, so I can build up on my portfolio and not stress about having to write something or I won't be able to pay the bills.
Still, I don't like putting all my eggs in one basket. That was the only reason while, even though I'm writing for Helium, and I quite enjoy it, I started to write for Associated Content. I didn't want to get all my revenue from one place, in case something happened. Well guess what, something happened. Just not with Helium.
Since AC gave me a choice to keep writing for free until I can apply for their Feature Writer possition, or I can move on.
I decided to move on.
Suite101 is a website I ran across back in 2008 when I was just starting writing articles for the Internet. It was a bit scary, required me to submit two writing samples and threatened with editors and weird submission policies. Back then I went with Helium, which seemed much more newbie friendly.
But two years later, with numerous clips and a lot of experience, I decided to see if Suite101 would make for a good home. I revised their hiring policy, and how one could actually earn with them. Because, let's be honest, I might love writing, but this I do for money.
And so, yesterday, I created a profile, and wrote my very first article for Suite101. Because I know a lot about studying aborad, that is exactly what my article was about. I wrote about finding good study abroad programs. We'll see how it will go.
According to Suite101 rules, I have to write 10 articles every three months, more if I'd like to become a Feature Writer. What's new for me, is the fact that I'm being paid a percentage of the ad-click revenue. Meaning the page views aren't as important. It's people clicking on ads on my articles that will be bringing me money. I don't know how I feel about it. I know I won't be earning huge amounts right away, I've read both incredible earning stories and those more depressing ones.
For now, I'm a bit shy about this new place, I want to try it out, see what works there and what doesn't. I'll definitely keep you updated.
4 May 2010
Discovering Suite101 - First Impressions
No comments:
Subscribe to: Post Comments (Atom)


text:
Anastasia Pavlychenkova won her final match of her WTA campaign, clinching the Kremlin Cup with a 6-4 5-7 6-1 triumph over Romanian Irina-Camelia Begu on home soil in Moscow.
Speaking exclusively to GiveMeSport, the Russian says she has enjoyed her celebrations and is now looking to prepare for the 2015 season, targeting January's Australia Open as the tournament to be fit for.
Pavlyuchenkova admits that her 2014 season hasn't been the best it could be, but is fully confident that she can build on her Kremlin Cup victory next campaign and climb the rankings.
"I couldn't have ended my season better than this, winning this title," she said.
"It's still a very busy week after the tournament but I'm trying to spend time with my family and friends too.
"I'm looking forward to flying out for my holidays and recovering for the next season. I need to be fresh and ready for hard work during my pre season!"
Related Articles
- Pavlyuchenkova: Top 10 world ranking achievable
- US Open title challenge a target - Pavlyuchenkova
- Anastasia Pavlyuchenkova insists singles are the priority
The 23-year-old currently sits 25th in the WTA Rankings and will be looking to go better than her career high ranking of 13 next year, but highlights the importance of pre-season training in completing a successful campaign.
"I have to make sure I'm ready for Australia 2015."
"First of all, with my team we are planning and preparing for my pre season," she added. "As my last year's pre season wasn't ideal, I need to work very hard and still improve on a lot of things in my tennis and my physical parts.
"I have to make sure I'm ready for Australia 2015."
Pavlyuchenkova will be fighting for her first Grand Slam title at the Australian Open in Melbourne, where she will look to carry her Kremlin Cup form through to next year.


text:
After being released in 2002, LinkedIn was seen as an unstoppable force in social media. It had a strong tug among professionals with a simple, straightforward design, which led to having hundreds of millions of subscribers. Now, after years of slowly being overshadowed by other social media giants, it is being considered by many marketers and entrepreneurs as a phased out marketing tool.
Here at Ozment Media, we are always asked by our clients which social media platform is the best fit for their needs. Having a solid Facebook page and an attractive and user-friendly website is definitely important, but don't discredit LinkedIn just yet. Below are some of the reasons why this site can still be seen as a dark horse in the marketing arena.
Quantity Over Quality: With Facebook's whopping 1.7 billion active users, LinkedIn only has a staggering tally of 106 million. However, the social media platform boasts that most of its active users are ripe audiences that are ready for picking. Most of its users remain to be either working professionals or business-minded individuals, hence, you can find a huge pool of people in your industry who can be potential clients, partners, or employees.
If you want to further streamline your search, LinkedIn's Advance People Search lets you target a specific audience based on their job position, company, location, industry, and even skill sets.
Solid Relationships: One of the best features of LinkedIn is its groups which boast of thousands of members in the same industry as you who actively engage in exchanging quality content. Since most people enter this platform to connect with professionals, it is crucial that you first build a profile that will showcase your and your company's services, unique selling points, and recognitions.
Utilizing Employees and Overall Brand Experience: With the current marketing trend is mainly about selling the experience rather than the actual product or service, you can utilize LinkedIn's various tools to your advantage.
One is by publishing blog articles. Though this may seem simple and doable in other platforms, bear in mind that more people in the same industry as yours can be reached and will likely read and appreciate your content.
Second is by having your employees spread your brand identity throughout their connections. By carrying the name of your company, they are actively spreading how you positively handle customer and employee relations.
Learn more about how LinkedIn, Facebook, and other social media sites will boost your marketing and sales by visiting our blog from time to time. Thank you and have a nice day!


text:
When it comes to Sunday Riley products, there's no need to preach—we are believers! The Texas-born makeup artist has been obsessed with anti-aging since the age of 12, giving her at least a ten-year head start on the rest of us—and it shows. Her skincare and makeup line is in a class all of its own and has earned fans in the fashion world like The Row, Helmut Lang, Stella McCartney and Acne—all of whom have had Sunday Riley create their runway looks for one show or another.
We went backstage at the recent Acne Resort presentation in New York to chat with Sunday and makeup artist Lisa Butler about the look they created. Everything you need to recreate the look at home is at Barneys New York—shop the products below.
Video by Scott Goodman. Edited by Katia Vannoy.
Barneys New York: What makes Sunday Riley cosmetics different from other brands?
Sunday Riley: Results are really our number one concern, and I'm impatient. I like things to work immediately—the faster, the better. If a woman doesn't see a change in her appearance right away, she'll never be a loyal client, which is unacceptable. She has to be able to see that change. For skincare, we achieve this by creating formulas that are a perfect union between advanced chemistry and pure, potent botanicals, so that you see immediate results.
When it comes to color, we put skincare ingredients in all of our makeup so that there is a treatment quality to each product. Makeup artists have flocked to the brand because of the amazing textures, color palettes and high performance formulas that are lightweight and breathable.
BNY: What colors are you loving for fall? What beauty look should every woman try in the coming season?
SR: The trends from our F/W 2012 shows provided some great insight into what we can expect to see for the fall season. A red lip we achieved with our lip color Persuasive was recreated everywhere. A red lip is always on trend, but I particularly love the deep mulled wine colors for fall.
I also think we will be seeing a lot of bold, defined eyes, especially purples and greens (I love Burnt Eggplant and Olive Branch) mixed with different shades of brown.
There has also been a resurgence in different shades of blue mascara. I love our Influencer in Midnight Sapphire, which has been popular now as a summer alternative to black for an evening out. Its navy-black hue really brightens the whites of the eyes and looks flattering on anyone who tries it.
BNY: What three products should every woman have in her cosmetics case?
SR: I think every woman needs to have a go-to lip color, whether it's a statement red or a subtle, blush-toned nude. I have really fair skin and dark hair so I like a pop of color, particularly in the summer. My current go-to shade is Stereotype, a vibrant (but wearable!) hot pink.
Sunscreen is always critical, especially where I live since the summers are so brutal. I carry Cashmere SPF 30+ in my cosmetics case, my car, in the entryway in my home, so it's at arm's length wherever I may be.
I also think every woman needs to have a blush that lights up her face and makes her appear healthy and vibrant, without really noticing that she has cheek color on. Our sell-out shades are Blushing and Honest because they provide that flushed radiance that makes a woman look like she's just fallen in love—and who doesn't love summer romance?
Shop The Look—Sunday Riley at Acne Resort 2013:
1. Juno Transformative Lipid Serum 2. Modern Lip Color in French Nude 3. Blush in Honest 4. Good Genes Treatment 5. Primasilk Eye Color in Little Black Dress 6. Liquid Light Breathable Perfecting Foundation


text:
The 1980s
Upon Balanchine's death in 1983, Peter Martins becomes chairman of faculty at SAB and co-ballet master in chief (with Jerome Robbins) at New York City Ballet. One year later, the School celebrates its 50th anniversary with a gala performance at the New York State Theater. In May 1987, SAB becomes the eleventh constituent of Lincoln Center for the Performing Arts and begins to plan an expansion into a new building adjacent to Juilliard. Now 82 years old, Lincoln Kirstein retires in 1989 as president of SAB and general director of New York City Ballet. SAB and NYCB alumnae Kay Mazzo, Garielle Whittle and Susan Pilarre join the School's faculty during this period, and notable students of the decade include Ethan Stiefel, Wendy Whelan and Damian Woetzel.


text:
30 Aug 2011
8/29/11: Department of State Notice Regarding Temporary Suspension of Hague Accreditation for US Agency Working in Ecuador
Yesterday, the Department of State posted a notice related to Ecuadorian adoptions. They said that one adoption agency, Joshua Tree Adoptions, Inc., has been temporarily suspended by the Council on Accreditation for "failing to to maintain substantial compliance with the Hague accreditation standards." The full notice is on the Department of State website; link below.
From the Department of State website. Full link: http://adoption.state.gov/country_information/country_specific_alerts_notices.php?alert_notice_type=alerts&alert_notice_file=ecuador_1


text:
Malvern Walkpast – Saturday 6th July
- 13th June 2013
The Malvern Hills are always a popular for walking, and the third in our Walkpast series will be here on the afternoon Saturday 6th July. Starting from The Wyche, the 4 mile walk will go along the famous Shire Ditch into parkland. Walking along ancient holloways through a wooded landscape dotted with quarries, you will see a variety of archaeological features and visit some very well preserved limekilns.
Aisling Nash, who'll be leading the walk, said, "The Malverns is a really popular place for walks, but people don't always recognise or understand the archaeology that they walk past, so this is a great opportunity to discover more."
Places are limited and need to be booked in advance. Please email email@example.com or ring 01905 765576 to reserve your place, or e-mail email@example.com if you'd like to ask any questions about the walk.
The event is also part of the Geofest, Highlighting and celebrating the Abberley and Malvern Hills Geopark. For more details about other events please visit http://www.earthheritagetrust.org/pub/wp-content/uploads/GeoFest-2013-programme-pdf-download.pdf


text: PrevNextThis stunning dog named Glacier is a brilliant white dog with glacier blue eyes. She is a mix of Louisiana Catahoula Leopard Dog and something else. Glacier also happens to be stone deaf. You would never know it though. Glacier's owner has worked out a system with a collar he can vibrate by remote control to get his dog's attention and hand signals to communicate. Glacier might be deaf, but when you watch him playing ball in the water and working with his owner, you would never know it. By Jay StebbinsDogs of Boston TwittertweetFacebookshareGoogle+sharePinterestpin it


text:
- There are enough verbal annotations to make the book hard to read for non-German readers. In particular this is the case for the long introduction (almost 60 pages).
- As far as I can see, all the games from the first edition are still there - mostly in the same order. One has been moved and one has had the name of a player corrected.
- I have not yet been able to determine to which extent the annotations of the older games have been updated but obviously some new game references have been added.
- There is a list of complete games, but surprisingly the games from the introduction can not be found there.
- There is no complete index of variations, but at the end of each chapter there is a summary of important lines with references to relevant complete games.
- The book seems to be only very lightly updated after 2004. I have so far only found four game references to 2005 games (Pogorelov-Moskalenko, Salou 2005; note to game 10. Feller-Petrisor, Herceg Novi 2005; note to game 10. Mamedjarova-Gleizerov, Abu Dhabi 2005; note to Game 17. Rogers-Jasim, Gibraltar 2005; note to game 67) but no doubt there are some more hidden in the notes.
- It seems that the new games are somewhat better annotated than the older ones, but this is only my first impression.
Mainline 7.b3
Game 5: Farago-Ulibin, Obervart 2001 (1/2-1/2)
Game 13: Korotylev-Ulibin, Genf 2001 (1/2-1/2)
Game 17: Romanov-Gleizerov,
Game 20: Agdestein-Straeter, Germany 2001 (1/2-1/2)
Mainline 7.Bf4
Game 29: Hanley-Williams, Port Erin 2001 (1-0)
Game 31:
Game 34: Barkhagen-Jussupow, Stockholm 2002 (1/2-1/2)
White's Rare 7th
Game 51: Schandorff-Sandner, Germany 2004 (1-0)
Game 53: Schandorff-L.B.
Game 58: Dreev-Radjabov, Tallinn 2004 (1/2-1/2)
Game 63: Anand-Schmittdiel, Germany 2004 (1-0)
Game 70: Kempinski-Radjabov, Antalaya 2004 (1/2-1/2)
Lines with an Early e3
Game 83: Cu. Hansen-Hillarp Persson, Copenhagen 2004 (1-0)
Game 85: Sasikiran-Krasenkow, Calvia Ol 2004 (1-0)
Game 89: Bareev-Jussupow,
Game 90:Yakovich-Kharlov, Elista 2001 (0-1)
Game 93: Bareev-Grischuk, Enghien-les-Bains 2001 (0-1)
PS: For the Table of Content see my entry of August 8th.
Another 2005 reference: Lomineischvili-Tereladze, Georgia 2005; note to game 61. I will add more here if I come by anything.


text:
Note: If you are a Raiser's Edge NXT or Financial Edge NXT client please refer to how to restore NXT database .
For your database security and protection, we require an authorization form be completed by a primary contact, site administrator, or other authorized representative. If your database integrates with another application, please also review the following information: What to consider before restoring your database to a previous backup.
- Request a backup of your Blackbaud Hosting Services database
- Contact Support to request that your database be restored.
- Important: All users should log out of all Blackbaud Applications and the Blackbaud Hosting Services environment until confirmation has been received that the restoration process has been complete.
- A support analyst will contact you when the process has been completed and users can log back into the Application.
- Verify the database information is correct.
Note: If a backup of the database is required and you do not want to lose information that has been entered in your database after a certain time, it is possible to request a backup copy of the database which you can attach to a standalone workstation:
- Refer to How to request a backup of your Blackbaud Hosting Services database to obtain a copy of the data.
- Set up a stand alone workstation.
- Attach the database via the Blackbaud Management Console


text:
Drake Says Nobody Robbed Him After Over $2 Million in Jewelry Was Stolen From His Tour Bus [WATCH]
Despite official police reports and news that a suspect has been arrested, Drake says nobody robbed him.
Earlier this week, it was reported that his tour bus had been robbed and over $2 million worth of jewelry had been lifted in the process during the Summer Sixteen tour stop in Phoenix. Technically, Drake is correct when he says he wasn't robbed—the jewels belonged to his DJ, Future The Prince. A 21 year-old man, Travion King was later arrested for the robbery.
But when Drake was stopped by TMZ and asked about the robbery, Drake said he wasn't "robbed," and all in all, seemed pretty dismissive about the entire thing, which was puzzling because he was caught on video looking pretty upset about the incident directly following the robbery. Maybe he was downplaying the entire thing because he was out with Rihanna? Or maybe he just doesn't want to give future thieves any ideas. Who knows.
Either way, Drake is probably feeling okay, all things considered. It was just revealed that along with Jay Z, Diddy and Dr. Dre, the Toronto rapper made Forbes' annual Hip Hop Cash Kings list, pulling in $38 million last year. It was also announced that he'll be collaborating with Kanye West on a yet-to-be-titled joint album, so no worries for Drizzy.
Check the video encounter above.


text:
- Research
- Open Access
The yeast mitogen-activated protein kinase Slt2 is involved in the cellular response to genotoxic stress
- María Soriano-Carot1,
- M Carmen Bañó1 and
- J Carlos Igual1Email author
© Soriano-Carot et al; licensee BioMed Central Ltd. 2012
- Received: 5 October 2011
- Accepted: 1 February 2012
- Published: 1 February 2012
The maintenance of genomic integrity is essential for cell viability. Complex signalling pathways (DNA integrity checkpoints) mediate the response to genotoxic stresses. Identifying new functions involved in the cellular response to DNA-damage is crucial. The Saccharomyces cerevisiae SLT2 gene encodes a member of the mitogen-activated protein kinase (MAPK) cascade whose main function is the maintenance of the cell wall integrity. However, different observations suggest that SLT2 may also have a role related to DNA metabolism.
This work consisted in a comprehensive study to connect the Slt2 protein to genome integrity maintenance in response to genotoxic stresses. The slt2 mutant strain was hypersensitive to a variety of genotoxic treatments, including incubation with hydroxyurea (HU), methylmetanosulfonate (MMS), phleomycin or UV irradiation. Furthermore, Slt2 was activated by all these treatments, which suggests that Slt2 plays a central role in the cellular response to genotoxic stresses. Activation of Slt2 was not dependent on the DNA integrity checkpoint. For MMS and UV, Slt2 activation required progression through the cell cycle. In contrast, HU also activated Slt2 in nocodazol-arrested cells, which suggests that Slt2 may respond to dNTP pools alterations. However, neither the protein level of the distinct ribonucleotide reductase subunits nor the dNTP pools were affected in a slt2 mutant strain. An analysis of the checkpoint function revealed that Slt2 was not required for either cell cycle arrest or the activation of the Rad53 checkpoint kinase in response to DNA damage. However, slt2 mutant cells showed an elongated bud and partially impaired Swe1 degradation after replicative stress, indicating that Slt2 could contribute, in parallel with Rad53, to bud morphogenesis control after genotoxic stresses.
Slt2 is activated by several genotoxic treatments and is required to properly cope with DNA damage. Slt2 function is important for bud morphogenesis and optimal Swe1 degradation under replicative stress. The MAPK Slt2 appears as a new player in the cellular response to genotoxic stresses.
- Slt2
- genotoxic stress
- DNA damage
- checkpoint
- Saccharomyces cerevisiae
Genome stability and integrity maintenance are fundamental tasks in the cellular function. The DNA in each cell is under constant attack: genomic transactions, spontaneous chemical changes in DNA constituents, replication defects, and endogenous and exogenous agents, inflict damage to DNA. An efficient response to DNA damage is crucial to maintain cellular viability and to prevent diseases like cancer. Eukaryotic cells have developed surveillance mechanisms to respond to genotoxic stresses. These are the DNA damage and DNA replication checkpoints (referred to as DNA integrity checkpoints), a complex signaling network that coordinates cell cycle progression with DNA repair in response to DNA damage or defects in DNA replication to avoid genomic instability [1].
Checkpoint machinery is highly conserved in eukaryotes. The major regulators of the DNA-damage response are the PI3K-related protein kinases ATM (ataxia-telangiectasia mutated) and ATR (ATM and RAD3-related) kinases, Tel1 and Mec1, respectively in S. cerevisiae [2–5]. Tel1 and Mec1 have overlapping yet distinct functions in maintaining yeast genome integrity. Tel1 is specific in signaling double-strand breaks (DSBs). In contrast, Mec1 plays a more general role by functioning in the response to different types of damage, including DSBs, base adducts or crosslinks, and functions during the S phase to regulate the firing of replication origins. Early in the response, Mec1 and Tel1 are recruited to the sites of DNA damage together with accessory proteins that provide platforms on which damage response components are assembled. A final consequence is that Mec1 and Tel1 phosphorylate and activate the checkpoint effector kinases Chk1 and Rad53 [6]. Rad53 mediates most of the response in budding yeast cells. Once phosphorylated, Rad53 is released from chromatin to act on critical targets that promote cell cycle arrest. Additionally, Rad53 targets factors to induce the expression of DNA repair genes, stimulates deoxyribonucleotide triphosphate (dNTP) production, suppresses the replication origins firing and stabilizes replication forks.
In most eukaryotic cells, cell cycle progression is blocked in response to DNA damage or replication stress mainly by stimulating inhibitory phosphorylation of cyclin-dependent kinases (Cdc28 in S. cerevisiae). This inhibition is controlled by the balance between the inhibitory Wee1 kinases (Swe1 in S. cerevisiae) and the opposite effect of the Cdc25 phosphatases (Mih1 in S. cerevisiae) [7]. Budding yeast is an exception because this biochemical switch does not play a role in replication stress or DNA damage-induced cell cycle arrest. Instead, this control is the basis of the morphogenesis checkpoint, a mechanism that delays the mitotic activation of Cdc28 in response to many environmental stresses that provoke a transient depolarization of the actin cytoskeleton, which affects bud construction [8, 9]. However, more recent observations have also connected Swe1 regulation to some aspects of the response to interrupted DNA synthesis. Swe1 accumulates in hydroxyurea-treated cells in a DNA-damage checkpoint independent manner preventing Cdc28-associated mitotic activities. Later on Swe1 degradation is required for proper recovery from hydroxyurea-induced arrest [10]. Swe1 degradation is triggered by the Mec1-Rad53 DNA-damage checkpoint cascade and plays also a crucial role in the control of morphogenetic events during DNA replication stress [11]. In particular, the DNA-damage checkpoint triggers the switch from apical to isotropic bud growth to maintain proper bud morphogenesis. Actin cytoskeleton dynamics along the cell cycle is controlled by different cyclin-Cdc28 kinases [12, 13]. The switch from apical to isotropic bud growth requires activation of the mitotic Clb1,2-Cdc28 kinases in the G2 phase. During the response to DNA damage, Mec1-Rad53 activation causes Swe1 degradation, which allows to build up Clb1,2-Cdc28 activity to switch off apical bud growth.
Mitogen-activated protein kinases (MAPK) are at the core of many signal transduction pathways, orchestrating specific cellular responses to a wide range of stimuli [14]. S.cerevisiae cells contain five MAPK that regulate mating (Fus3), pseudohyphal/invasive growth (Kss1), sporulation (Smk1), response to high osmolarity (Hog1) and response to cell wall stress (Slt2) [15]. Slt2 is the MAPK of the cell wall integrity pathway [16, 17]. Slt2 is a functional homolog of human ERK5 [18], a MAPK that is activated in response to not only growth factors, but also physical and chemical stresses [19, 20]. In yeast, Slt2 is activated under conditions that stress the cell surface, such as growth at high temperatures, hypo-osmotic shock, polarized growth, actin perturbation, or the presence of compounds or mutations that interfere with cell wall biosynthesis [21]. Once activated, Slt2 controls the expression of the genes involved in cell wall biosynthesis through the regulation of transcription factors Rlm1 and SBF (Swi4-Swi6) to maintain cell integrity [22–24]. In addition to gene expression control, Slt2 is also related to the regulation of actin cytoskeleton polarization [25] and contributes, although partially, to the mitotic delay induced by Ca2+ or actin cytoskeleton perturbation as part of the morphogenesis checkpoint mechanism [26, 27]. Slt2 is also involved in the cellular response to oxidative stress through the control of cyclin C degradation [28]. Cross-talks between MAPK pathways are common. Thus, the Hog1 kinase (the functional homolog of mammalian p38 MAPK) has been recently described to operate with Slt2 in the adaptation to zymolyase-mediated cell wall stress [29].
MAPKs have been related to the response to DNA damage. Mammalian MAPKs are grouped into the ERK, JNK/SAPK and p38 families [30, 31]. Different genotoxic treatments activate p38, which contributes to the establishment of cell cycle checkpoints [32]. Activation of p38 involves the ATM/ATR checkpoint pathway, along with other mechanisms which are yet to be established. Activation of ERK and JNK kinases is also induced by multiple DNA damage stimuli [33–38]. Moreover, both ERK1 and ERK2 kinases are required for the proper checkpoint activation by facilitating activation of ATM and ATR [39–42]. Regarding S. cerevisiae, we previously showed that Slt2 is activated by hydroxyurea and that the slt2 mutant is sensitive to this drug [43]. Furthermore, genetic interactions have connected Slt2 to DNA-damage checkpoint proteins and the response to MMS [43, 44]. Here, we extend our work by carrying out a comprehensive analysis of the connection of Slt2 MAPK with the cellular response to different types of DNA damage caused by a wide range of genotoxic agents.
The slt2 mutant strain is hypersensitive to genotoxic agents
Slt2 is activated by genotoxic stresses
Analysis of Slt2 activation in DNA-damage checkpoint mutants
The cellular response to genotoxic stress is governed by the DNA integrity checkpoint pathway. We wondered whether Slt2 activation by genotoxic stresses was mediated by the DNA damage checkpoint. To investigate this, activation of Slt2 by HU or MMS was analyzed in the mutant strains in checkpoint upstream kinases Mec1 and Tel1 or in the effector kinase Rad53 (Figure 4). Rad53 and Mec1 are essential genes so we used in these cases strains containing the sml1 mutation, which is known to suppress rad53 and mec1 lethality. It is noteworthy that strong Slt2 activation took place in the absence of genotoxic agents in rad53 and mec1 tel1 mutant strains. This is in agreement with previously reported results and is probably a response to the cell morphology and cell wall defects characteristic of these checkpoint kinase mutants [11]. Another important aspect is that incubation with HU or MMS brought about higher levels of activated Slt2 in the tel1, mec1, mec1 tel1 or rad53 mutant cells. A similar result was obtained with the tetO 7 :RAD53 mutant strain. These results demonstrate that Slt2 activation by genotoxic stress is not mediated by the DNA damage checkpoint.
Slt2 is activated by HU in post-replicative cells
As the response to genotoxic stress varies depending on the cell cycle stage [45–48], we wondered whether Slt2 activation in response to genotoxic agents depends on the cell cycle stage. Accordingly, Slt2 activation by HU, MMS and UV radiation was analyzed in cells arrested in G1 with α-factor and cells arrested in G2/M by inactivating the CDC20 gene (Figure 5A). A mild Slt2 activation was observed in G1 cells treated with HU. By contrast, no significant increase in phosphorylated Slt2 due to incubation of cells with MMS or UV irradiation was detected in G1 cells; however, it has to be noted that α-factor caused Slt2 activation, which could preclude genotoxic-induced Slt2 activation. In G2/M cells, no activation was observed in the presence of MMS or after UV irradiation in contrast to what was detected in cycling cells. These results suggest that Slt2 activation by MMS or UV radiation probably occurs during the S phase. On the contrary, Slt2 was activated by HU in G2/M cells. We wondered whether Slt2 activation by HU could be related to mitochondrial DNA replication; however, the fact that Slt2 activation is also observed in a rho 0 derived strain ruled out this possibility (Figure 5B). HU is an inhibitor of ribonucleotide reductase, which catalyzes the limiting step in dNTP biosynthesis. Incubation of cells with HU causes a reduction of dNTP pools and a consequent blockage of S phase progression. The fact that HU affects Slt2 activity in post-replicative cells suggests that Slt2 activation could be, at least in part, a direct response to an alteration of the nucleotide pools, which also could indicate that Slt2 might be involved in the control of dNTP pools.
Analysis of dNTP pools in the absence of Slt2
Analysis of DNA-integrity checkpoint activation in the slt2 mutant strain
We also analyzed cell cycle arrest after inducing DNA damage with MMS. In this case, there was no homogenous terminal morphology, but cell cycle arrest was revealed by the DNA content analysis, showing a clear accumulation of cells with non-replicated DNA after a 1-hour incubation in the presence of MMS. Importantly, this accumulation was observed in both the wild-type and the slt2 mutant strains (Figure 7B). Thus, MMS-induced cell cycle arrest occurs in the absence of Slt2.
Finally, we also investigated whether checkpoint activation normally occurs in the absence of Slt2. To test this, slt2 mutant cells were subjected to replicative stress or DNA damage by incubation with HU or MMS, respectively, and the presence of phosphorylated Rad53, as indicative of checkpoint activation, was analysed by Western blot. The results showed that phosphorylated Rad53 accumulated at similar levels in the wild-type and slt2 mutant strains after genotoxic treatments (Figure 7C). Thus, the DNA damage checkpoint is functional in the absence of Slt2, at least until the Rad53 activation step.
Slt2 has a pseudo-kinase paralog in yeast, protein Mlp1. Mlp1 shares a function with Slt2 in transcriptional activation [23]. Therefore, it is possible that Mlp1 could be functionally redundant with Slt2, and that it could activate the DNA integrity checkpoint in the absence of Slt2. However, we detected a proper activation of Rad53 by HU and MMS in the mlp1 and slt2 mlp1 mutant strains (Figure 7C). This observation confirms that Slt2 kinase and its relative Mlp1 protein are not required for proper Rad53 activation.
Increasing evidence indicates there are cross-talks between the MAPK cascades in yeast. Hog1, the MAPK involved in the response to osmotic stress, is especially interesting because recent works have related the Slt2 and Hog1 functions in the activation of the cell wall gene expression [29]. Furthermore, Hog1 is the yeast homolog to mammalian p38 MAPK. As mentioned above, p38 plays an important role in cell cycle checkpoints in response to DNA damage. Therefore, we investigated whether Hog1 was involved in Rad53 activation. However, this was not the case because phosphorylated Rad53 normally accumulated after HU and MMS treatments in the absence of Hog1 (Figure 7C). Moreover, no defect in Rad53 activation was detected in a slt2 hog1 double mutant, which ruled out any functional redundancy between Slt2 and Hog1 in checkpoint activation.
Slt2 is required for the proper degradation of Swe1 after DNA damage
Activation of cell-cycle checkpoints in response to various types of DNA damage is essential for the maintenance of genomic stability in eukaryotic cells. This work describes how the Slt2 MAP kinase is activated in response to DNA damage and that Slt2 is essential to properly cope with genotoxic stresses. Slt2 is involved in cell wall assembly and is activated by cell wall damage, so it could be possible that slt2 mutant hypersensitivity to genotoxic treatments or Slt2 activation simply result from increased cell wall permeability or unknown cell wall damage caused by the treatments. This possibility is unlikely, however, because hypersensitivity to genotoxic treatments is also observed in the presence of sorbitol, which indicates that cell death is not related to cell wall defects. Most remarkably, Slt2 activation after induction of a single DSB in the GAL1:HO strain, a process that has a specific effect on DNA integrity and is not related to cell wall, strongly supports a genuine role for Slt2 in the response to genotoxic stress. This conclusion is also reinforced by a recent genetic interaction network analysis that connected Slt2 to the cellular response to MMS [44]. It is important to note that both Slt2 activation and hypersensitivity of the slt2 mutant are observed in response to a wide range of genotoxic stresses, which result in different types of DNA damage: e.g., DSB, thymidine dimers, nucleotide alkylation or replicative forks stalling. This reinforces the importance of Slt2 in the response to genotoxic stresses and suggests that Slt2 could play a common role in the response to different types of damage.
Response to DNA damage is primarily governed by the activation of the DNA-integrity checkpoints. However, Slt2 is activated even in the absence of a functional checkpoint, indicating that genotoxic stress is transduced to the Slt2 kinase by a checkpoint-independent mechanism. In fact, Slt2 activation and Rad53 activation after inducing DNA damage occur independently of each other. Thus, both kinases appear to fulfill complementary functions necessary for cell survival in parallel independent DNA-damage signaling pathways. This indicates that the response of yeast cells to genotoxic stresses could be more complex than previously suspected, and may involve new crucial players like Slt2 MAPK. In mammalian cells, p38 MAPK activation in response to DNA damage has been reported to be dependent on ATM/ATR checkpoint kinases in some cases; however, in addition to the checkpoint pathway, other mechanisms still to be established activate p38 MAPK in response to DNA damage [32]. Thus, a mechanism directly linking MAPK activation to DNA damage could be conserved in eukaryotic cells.
It is not clear how genotoxic stresses could activate Slt2. We have observed that upregulation of Slt2 is mostly, if not totally, mediated by a post-translational mechanism. As commented above, Slt2 activation occurs in osmotically supported cells or in cdc42 mutant cells that cannot bud [43] and it was observed after specific induction of a single DSB, which strongly suggests that Slt2 activation is not an indirect effect. The observed Slt2 activation could be a direct result of DNA lesions. Remarkably, however, Slt2 activation by MMS and UV is cell cycle-regulated since it does not occur in the cells arrested in G2/M. This suggests that Slt2 does not respond to primary damage and should be related to alterations that appear as damaged cells progress through the cell cycle.
Activation by HU seems to be a different case since HU induced Slt2 activation, even in G2/M-arrested cells. It could be expected that HU stress would only affect cells that were actively replicating DNA. The fact that HU induced activation is also observed in post-replicative cells, i.e., cells that do not consume dNTP pools, suggests that Slt2 could respond directly to the inhibition of ribonucleotide reductase activity and the reduction in dNTP pool levels. Very recently, Slt2 has been suggested to repress the expression of the RNR1,2,3 genes, as deduced from the increase in mRNAs observed in the slt2 mutant strain [44]. However, we detected no change in the protein level in any ribonucleotide reductase subunit after Slt2 inactivation in both untreated and MMS-treated cells. More importantly, dNTP pools, which reflect the physiological function of ribonucleotide reductase activity, were not altered in the slt2 mutant under any analyzed condition. Thus, our results argue against a role of Slt2 in controlling ribonucleotide reductase and dNTP pools.
Our findings show that Slt2 plays an important part in the general cellular response to genotoxic stress. Slt2 could mediate a defensive mechanism developed by yeast cells to overcome treatments affecting DNA integrity. Primary cellular defense to DNA damage involves cell cycle arrest to facilitate DNA repair prior to progression through the S phase or mitosis. It is known that Slt2 contributes to the delay of the G2/M transition in response to actin stress [26, 27]. However, this is not the case in the response to genotoxic stress since cell cycle arrest occurs in the absence of Slt2. Alternatively, it is tempting to speculate that Slt2 could directly favour DNA damage repair. On the other hand, involvement of Slt2 in the response to genotoxic stress could be related with its known function in cell morphogenesis, the actin cytoskeleton and cell integrity. Although this idea may seem surprising, there is increasing evidence for a direct cross-talk between the DNA checkpoint pathway and cellular morphogenesis. Thus, various checkpoint proteins contribute to cell wall architecture and maintenance of cell polarity [11], Cdk1 regulates Rad53 to orchestrate cellular morphogenesis during cell cycle [49], Rad53 interacts with septins in the bud neck and directs filamentous differentiation in response to genotoxic stress [50], Rad53 phosphorylates Slt2 to control the Slt2-dependent expression of the cell wall FKS2 gene in response to caffeine [51], the Mdt1 protein has partially separable functions in both the cell wall and genome integrity pathways [52], and we have observed a synthetic lethality between slt2 and rad53 mutations that is suppressed by sorbitol, which suggests that lethality is caused by a morphogenetic defect. In fact, bud morphogenesis control has been described as an output of DNA replication checkpoint activation [11], which clearly demonstrates the link between genome maintenance and cell morphogenesis. We have observed that Slt2 is related to the morphogenetic aspects of the replicative stress response. In budding yeast cells, actin cytoskeleton polarization has to be regulated during DNA damage-induced cell cycle arrest to maintain bud morphogenesis. Thus during the response to DNA damage, checkpoint activation has been described to cause degradation of the Swe1 kinase [11], which is the main protein involved in the morphogenesis checkpoint controlling bud growth [8, 9]. This leads to the activation of the Clb1,2-Cdc28 kinases, which are responsible for the switch from apical to isotropic bud growth, an essential switch for proper bud morphogenesis [12, 13]. We have observed that Swe1 degradation after replicative stress is partially impaired in the absence of Slt2, causing altered bud morphogenesis in slt2 cells. Defects in Swe1 degradation has been related to HU sensitivity [10], which could explain slt2 phenotype. However, HU and other genotoxic treatments caused a reduced viability of slt2 mutant cells even in the absence of Swe1, which indicates that Slt2 must affect cell viability by a Swe1-independent mechanism. How Slt2 influences Swe1 stability is intriguing, and even more so if we consider that this effect is apparently contradictory to the results previously described in the morphogenesis checkpoint context [26] or in response to Ca2+ [53]. In these cases, Slt2 acts by activating Swe1 or by repressing Mih1 to inhibit Cdc28 kinase activity, whereas in the response to replicative stress, Slt2 seems to act by inactivating Swe1 to induce Cdc28 kinase activity. Elucidating the molecular basis of the Slt2 function in the response to genotoxic stresses will help explain this apparent contradiction and to gain insight into the molecular link between cellular morphogenesis and integrity with genome integrity maintenance.
Our results support a function of MAPK Slt2 in the maintenance of DNA integrity. Inactivation of Slt2 results in hypersensitivity to many types of genotoxic treatments. Moreover, Slt2 is activated by several genotoxic stresses. These results suggest that Slt2 play an important role in the cellular response to DNA damage. Slt2 activation by MMS and UV, but not HU, requires cell cycle progression. Slt2 is not involved in dNTP pools regulation and is not required for DNA-damage induced cell cycle arrest or checkpoint activation. Nevertheless, Slt2 function is important for bud morphogenesis control and optimal Swe1 degradation under replicative stress. The results described here point to the MAPK Slt2 as a new player in the cellular response to genotoxic stresses.
Strains and growth conditions
Yeast strains
MATa ade2-1 trp1-1 leu2-3,112 his3-11,15 ura3-52 can1 rad5-535
MATa ade2-101 trp1-Δ902 leu2-3,112 his3-Δ200 ura3-52 RAD5
MATa ade1-100 trp1-1 leu2-3,112 lys5 ura3-52 trp1::hisG hoΔ hml::ADE1 hmr::ADE1 ade3::GAL-HO RAD5
slt2::LEU2 in SEY6211
rad53::HIS3 sml1-1 in W303-1a
mec1::TRP1 sml1::HIS3 in W303-1a
slt2::TRP1 in W303-1a
sml1::kanMX6 in W303-1a
tTR'::LEU2 tetO 7 ::RAD53-kanMX4 in W303-1a
tel1:: kanMX6 in W303-1a
tel1:: kanMX6 in JCY1039
SWE1-HA-kanMX6 in W303-1a
SWE1-HA-kanMX6 in JCY1062
mlp1::kanMX6 in W303-1a
mlp1::kanMX6 in JCY1062
hog1::kanMX4 in W303-1a
hog1::kanMX4 in JCY1062
swe1::kanMX6 in W303-1a
swe1::kanMX6 in JCY1062
GAL1:CDC20-TRP1 in W303-1a
Western blot analysis
Approximately 108 cells were collected, resuspended in 100 μl water and, after adding 100 μl 0.2 M NaOH, they were incubated for 5 min at room temperature. Cells were collected by centrifugation, resuspended in 50 μl sample buffer and incubated for 5 min at 95°C. Extracts were clarified by centrifugation, and equivalent amounts of protein were resolved in an SDS-PAGE gel and transferred onto a nitrocellulose membrane. The primary antibodies used in this study include anti-fosfo-44/42 Map kinasa Thr200/Tyr204 (Cell Signalling) to detect activated Slt2, anti Mpk1-yC20 (Santa Cruz Biotechnology) to detect total Slt2 protein, anti Rad53-YC19 (Santa Cruz Biotechnology), anti-HA 3F10 monoclonal antibody (Roche), and anti Rnr1, Rnr2, Rnr3 and Rnr4 (kindly provided by M. Huang, University of Colorado). Blots were developed with HRP-labeled secondary antibodies using the ECL Advance Western Blotting Detection Kit (GE Healthcare Life Sciences). Bands were quantified with a ImageQuant™ LAS 4000mini biomolecular imager (GE Healthcare).
dATP, dCTP and dGTP measurements
Approximately 2 × 108 cells were harvested, washed with water, resuspended in 200 μL of cold 60% methanol, and extracts obtained by vigorous shacking in the presence of glass beads. Then, cell debris was pelleted at 27000 g for 1 min, and the supernatant was held at -20°C for 2 h. The samples were boiled for 3 min, and followed by centrifugation at 13000 g for 10 min at 4°C. The supernatant was taken to dryness under vacuum and resuspended in 40 μL of water. The dATP, dCTP and dGTP levels were determined by the DNA polymerase-based enzymatic assay [54]. Briefly, the incorporation by the Klenow DNA polymerase of dATP, dCTP and dGTP into specific oligonucleotides containing poly(AAAT), poly(AAAG) or poly(AAAC) sequences respectively, was determined in the presence of excess [3H]dTTP.
We are very grateful to Dr. I. Quilis for her collaboration. Dr. J. Torres, Dr. J.E. Haber Dr. E. Herrero and Dr. J.R. Pringle for supplying strains and plasmids. We also thanks Dr. M. Huang for kindly provide anti-Rnr antibodies. This work was supported by Grants BFU2007-67929-C02-02 and BFU2010-20927 from Ministerio de Ciencia e Innovación of the Spanish Government (co-financed by ERDF from European Union) and ACOMP/2010/134 from Generalitat Valenciana. M.S. was recipient of a F.P.I: Predoctoral Fellowship from the Spanish Governement.
Authors' Affiliations
- Harper JW, Elledge SJ: The DNA damage response: ten years after. Mol Cell 2007,28(5):739–745.View ArticlePubMedGoogle Scholar
- Cimprich KA, Cortez D: ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol 2008,9(8):616–627.View ArticlePubMed CentralPubMedGoogle Scholar
- Harrison JC, Haber JE: Surviving the breakup: the DNA damage checkpoint. Annu Rev Genet 2006, 40: 209–235.View ArticlePubMedGoogle Scholar
- Navadgi-Patil VM, Burgers PM: The unstructured C-terminal tail of the 9–1-1 clamp subunit Ddc1 activates Mec1/ATR via two distinct mechanisms. Mol Cell 2009,36(5):743–753.View ArticlePubMed CentralPubMedGoogle Scholar
- Shiloh Y: The ATM-mediated DNA-damage response: taking shape. Trends Biochem Sci 2006,31(7):402–410.View ArticlePubMedGoogle Scholar
- Melo J, Toczyski D: A unified view of the DNA-damage checkpoint. Curr Opin Cell Biol 2002,14(2):237–245.View ArticlePubMedGoogle Scholar
- Raleigh JM, O'Connell MJ: The G(2) DNA damage checkpoint targets both Wee1 and Cdc25. J Cell Sci 2000,113(Pt 10):1727–1736.PubMedGoogle Scholar
- Lew DJ: The morphogenesis checkpoint: how yeast cells watch their figures. Curr Opin Cell Biol 2003,15(6):648–653.View ArticlePubMedGoogle Scholar
- Kellogg DR: Wee1-dependent mechanisms required for coordination of cell growth and cell division. J Cell Sci 2003,116(Pt 24):4883–4890.View ArticlePubMedGoogle Scholar
- Liu H, Wang Y: The function and regulation of budding yeast Swe1 in response to interrupted DNA synthesis. Mol Biol Cell 2006,17(6):2746–2756.View ArticlePubMed CentralPubMedGoogle Scholar
- Enserink JM, Smolka MB, Zhou H, Kolodner RD: Checkpoint proteins control morphogenetic events during DNA replication stress in Saccharomyces cerevisiae. J Cell Biol 2006,175(5):729–741.View ArticlePubMed CentralPubMedGoogle Scholar
- Pruyne D, Bretscher A: Polarization of cell growth in yeast. J Cell Sci 2000,113(Pt 4):571–585.PubMedGoogle Scholar
- Pruyne D, Bretscher A: Polarization of cell growth in yeast. I. Establishment and maintenance of polarity states. J Cell Sci 2000,113(Pt 3):365–375.PubMedGoogle Scholar
- Qi M, Elion EA: MAP kinase pathways. J Cell Sci 2005,118(Pt 16):3569–3572.View ArticlePubMedGoogle Scholar
- Chen RE, Thorner J: Function and regulation in MAPK signaling pathways: lessons learned from the yeast Saccharomyces cerevisiae. Biochim Biophys Acta 2007,1773(8):1311–1340.View ArticlePubMed CentralPubMedGoogle Scholar
- Lesage G, Bussey H: Cell wall assembly in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 2006,70(2):317–343.View ArticlePubMed CentralPubMedGoogle Scholar
- Levin DE: Cell wall integrity signaling in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 2005,69(2):262–291.View ArticlePubMed CentralPubMedGoogle Scholar
- Truman AW, Millson SH, Nuttall JM, King V, Mollapour M, Prodromou C, Pearl LH, Piper PW: Expressed in the yeast Saccharomyces cerevisiae, human ERK5 is a client of the Hsp90 chaperone that complements loss of the Slt2p (Mpk1p) cell integrity stress-activated protein kinase. Eukaryot Cell 2006,5(11):1914–1924.View ArticlePubMed CentralPubMedGoogle Scholar
- Abe J, Kusuhara M, Ulevitch RJ, Berk BC, Lee JD: Big mitogen-activated protein kinase 1 (BMK1) is a redox-sensitive kinase. J Biol Chem 1996,271(28):16586–16590.View ArticlePubMedGoogle Scholar
- Yan C, Luo H, Lee JD, Abe J, Berk BC: Molecular cloning of mouse ERK5/BMK1 splice variants and characterization of ERK5 functional domains. J Biol Chem 2001,276(14):10870–10878.View ArticlePubMedGoogle Scholar
- Harrison JC, Zyla TR, Bardes ES, Lew DJ: Stress-specific activation mechanisms for the "cell integrity" MAPK pathway. J Biol Chem 2004,279(4):2616–2622.View ArticlePubMedGoogle Scholar
- Baetz K, Moffat J, Haynes J, Chang M, Andrews B: Transcriptional coregulation by the cell integrity mitogen-activated protein kinase Slt2 and the cell cycle regulator Swi4. Mol Cell Biol 2001,21(19):6515–6528.View ArticlePubMed CentralPubMedGoogle Scholar
- Kim KY, Truman AW, Levin DE: Yeast Mpk1 mitogen-activated protein kinase activates transcription through Swi4/Swi6 by a noncatalytic mechanism that requires upstream signal. Mol Cell Biol 2008,28(8):2579–2589.View ArticlePubMed CentralPubMedGoogle Scholar
- Watanabe Y, Takaesu G, Hagiwara M, Irie K, Matsumoto K: Characterization of a serum response factor-like protein in Saccharomyces cerevisiae, Rlm1, which has transcriptional activity regulated by the Mpk1 (Slt2) mitogen-activated protein kinase pathway. Mol Cell Biol 1997,17(5):2615–2623.PubMed CentralView ArticlePubMedGoogle Scholar
- Guo S, Shen X, Yan G, Ma D, Bai X, Li S, Jiang Y: A MAP kinase dependent feedback mechanism controls Rho1 GTPase and actin distribution in yeast. PLoS One 2009,4(6):e6089.View ArticlePubMed CentralPubMedGoogle Scholar
- Harrison JC, Bardes ES, Ohya Y, Lew DJ: A role for the Pkc1p/Mpk1p kinase cascade in the morphogenesis checkpoint. Nat Cell Biol 2001,3(4):417–420.View ArticlePubMedGoogle Scholar
- Mizunuma M, Hirata D, Miyahara K, Tsuchiya E, Miyakawa T: Role of calcineurin and Mpk1 in regulating the onset of mitosis in budding yeast. Nature 1998,392(6673):303–306.View ArticlePubMedGoogle Scholar
- Krasley E, Cooper KF, Mallory MJ, Dunbrack R, Strich R: Regulation of the oxidative stress response through Slt2p-dependent destruction of cyclin C in Saccharomyces cerevisiae. Genetics 2006,172(3):1477–1486.View ArticlePubMed CentralPubMedGoogle Scholar
- Garcia R, Rodriguez-Pena JM, Bermejo C, Nombela C, Arroyo J: The high osmotic response and cell wall integrity pathways cooperate to regulate transcriptional responses to zymolyase-induced cell wall stress in Saccharomyces cerevisiae. J Biol Chem 2009,284(16):10901–10911.View ArticlePubMed CentralPubMedGoogle Scholar
- Raman M, Chen W, Cobb MH: Differential regulation and properties of MAPKs. Oncogene 2007,26(22):3100–3112.View ArticlePubMedGoogle Scholar
- Cargnello M, Roux PP: Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev 75(1):50–83.Google Scholar
- Thornton TM, Rincon M: Non-classical p38 map kinase functions: cell cycle checkpoints and survival. Int J Biol Sci 2009,5(1):44–51.View ArticlePubMed CentralPubMedGoogle Scholar
- Persons DL, Yazlovitskaya EM, Pelling JC: Effect of extracellular signal-regulated kinase on p53 accumulation in response to cisplatin. J Biol Chem 2000,275(46):35778–35785.View ArticlePubMedGoogle Scholar
- Lee SW, Fang L, Igarashi M, Ouchi T, Lu KP, Aaronson SA: Sustained activation of Ras/Raf/mitogen-activated protein kinase cascade by the tumor suppressor p53. Proc Natl Acad Sci USA 2000,97(15):8302–8305.View ArticlePubMed CentralPubMedGoogle Scholar
- Wang X, Martindale JL, Holbrook NJ: Requirement for ERK activation in cisplatin-induced apoptosis. J Biol Chem 2000,275(50):39435–39443.View ArticlePubMedGoogle Scholar
- Tang D, Wu D, Hirao A, Lahti JM, Liu L, Mazza B, Kidd VJ, Mak TW, Ingram AJ: ERK activation mediates cell cycle arrest and apoptosis after DNA damage independently of p53. J Biol Chem 2002,277(15):12710–12717.View ArticlePubMedGoogle Scholar
- Pippin JW, Durvasula R, Petermann A, Hiromura K, Couser WG, Shankland SJ: DNA damage is a novel response to sublytic complement C5b-9-induced injury in podocytes. J Clin Invest 2003,111(6):877–885.View ArticlePubMed CentralPubMedGoogle Scholar
- Dent P, Yacoub A, Fisher PB, Hagan MP, Grant S: MAPK pathways in radiation responses. Oncogene 2003,22(37):5885–5896.View ArticlePubMedGoogle Scholar
- Wei F, Xie Y, He L, Tao L, Tang D: ERK1 and ERK2 kinases activate hydroxyurea-induced S-phase checkpoint in MCF7 cells by mediating ATR activation. Cell Signal 2011,23(1):259–268.View ArticlePubMedGoogle Scholar
- Wei F, Xie Y, Tao L, Tang D: Both ERK1 and ERK2 kinases promote G2/M arrest in etoposide-treated MCF7 cells by facilitating ATM activation. Cell Signal 2010,22(11):1783–1789.View ArticlePubMedGoogle Scholar
- Yan Y, Black CP, Cowan KH: Irradiation-induced G2/M checkpoint response requires ERK1/2 activation. Oncogene 2007,26(32):4689–4698.View ArticlePubMedGoogle Scholar
- Mogila V, Xia F, Li WX: An intrinsic cell cycle checkpoint pathway mediated by MEK and ERK in Drosophila. Dev Cell 2006,11(4):575–582.View ArticlePubMed CentralPubMedGoogle Scholar
- Queralt E, Igual JC: Functional connection between the Clb5 cyclin, the protein kinase C pathway and the Swi4 transcription factor in Saccharomyces cerevisiae. Genetics 2005,171(4):1485–1498.View ArticlePubMed CentralPubMedGoogle Scholar
- Bandyopadhyay S, Mehta M, Kuo D, Sung MK, Chuang R, Jaehnig EJ, Bodenmiller B, Licon K, Copeland W, Shales M, et al.: Rewiring of genetic networks in response to DNA damage. Science 2010,330(6009):1385–1389.View ArticlePubMed CentralPubMedGoogle Scholar
- Pellicioli A, Lee SE, Lucca C, Foiani M, Haber JE: Regulation of Saccharomyces Rad53 checkpoint kinase during adaptation from DNA damage-induced G2/M arrest. Mol Cell 2001,7(2):293–300.View ArticlePubMedGoogle Scholar
- Ira G, Pellicioli A, Balijja A, Wang X, Fiorani S, Carotenuto W, Liberi G, Bressan D, Wan L, Hollingsworth NM, et al.: DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1. Nature 2004,431(7011):1011–1017.View ArticlePubMed CentralPubMedGoogle Scholar
- Leroy C, Mann C, Marsolier MC: Silent repair accounts for cell cycle specificity in the signaling of oxidative DNA lesions. EMBO J 2001,20(11):2896–2906.View ArticlePubMed CentralPubMedGoogle Scholar
- Tercero JA, Longhese MP, Diffley JF: A central role for DNA replication forks in checkpoint activation and response. Mol Cell 2003,11(5):1323–1336.View ArticlePubMedGoogle Scholar
- Diani L, Colombelli C, Nachimuthu BT, Donnianni R, Plevani P, Muzi-Falconi M, Pellicioli A: Saccharomyces CDK1 phosphorylates Rad53 kinase in metaphase, influencing cellular morphogenesis. J Biol Chem 2009,284(47):32627–32634.View ArticlePubMed CentralPubMedGoogle Scholar
- Smolka MB, Chen SH, Maddox PS, Enserink JM, Albuquerque CP, Wei XX, Desai A, Kolodner RD, Zhou H: An FHA domain-mediated protein interaction network of Rad53 reveals its role in polarized cell growth. J Cell Biol 2006,175(5):743–753.View ArticlePubMed CentralPubMedGoogle Scholar
- Truman AW, Kim KY, Levin DE: Mechanism of Mpk1 mitogen-activated protein kinase binding to the Swi4 transcription factor and its regulation by a novel caffeine-induced phosphorylation. Mol Cell Biol 2009,29(24):6449–6461.View ArticlePubMed CentralPubMedGoogle Scholar
- Traven A, Lo TL, Pike BL, Friesen H, Guzzo J, Andrews B, Heierhorst J: Dual functions of Mdt1 in genome maintenance and cell integrity pathways in Saccharomyces cerevisiae. Yeast 27(1):41–52.Google Scholar
- Mizunuma M, Hirata D, Miyaoka R, Miyakawa T: GSK-3 kinase Mck1 and calcineurin coordinately mediate Hsl1 down-regulation by Ca2+ in budding yeast. EMBO J 2001,20(5):1074–1085.View ArticlePubMed CentralPubMedGoogle Scholar
- Mathews CK, Wheeler LJ: Measuring DNA precursor pools in mitochondria. Methods Mol Biol 2009, 554: 371–381.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


text:
Welcome to the As Fall Leaves Illustration website! This is where you can follow the news on the various jobs and projects of artist Joshua Werner. Be sure to also visit the Facebook page at www.facebook.com/asfallleaves! For those looking for Josh's books and comics, you can find those items available at www.SourcePointPress.com.
Friday, February 8, 2013
Deadpool and B-MO
Posted by As Fall Leaves Illustration at 9:14 AM
Labels: adventure time, artist trading cards, as fall leaves illustration, b-mo, bmo, cartoon network, cartoons, comic books, deadpool, joshua werner, marvel, sketch cards, x-force, x-men
2 comments:
Subscribe to: Post Comments (Atom)


text: The Independent Community Advisory Association (ICAA) exists for the purpose of: Advising Bonvera on any issues affecting the community of associates Promoting, protecting and representing individual business interests for future generations Advocating to Bonvera on behalf of the community Providing a systematic way to gather feedback from individual associates so that their voice can be heard Each associate will pay $8 annually to be a part of the ICAA. Membership is optional and only for current Bonvera members. The association authorizes Bonvera to offer and collect the dues on behalf of the ICAA on the registration form or on the Bonvera website www.icaaboard.com


text:
A print of the destroyed sunflower painting by Vincent van Gogh has recently been discovered. The Six Sunflowers work was painted in 1888 and destroyed by the American war machine in Japan in 1945. Let's hope all the art has already been looted and smuggled out of Syria as that psychopathic war machine has an itchy trigger finger again.
I was just watching the psychopaths putting forward their argument to kill more innocents. How we haven't started a revolution yet just blows my mind. Are we this docile and submissive?!
Anyway, back to the point, sunflowers! I should start a new blog about the system and how mad it makes me!
So, the arts writer Martin Bailey was doing research for a book he has written called The Sunflowers are Mine: The Story of Van Gogh's Masterpiece, when he discovered the print in a Japanese museum.
Vincent really loved his complementary colors. The newly discovered print shows how the artist wanted the Sunflowers framed in contrasting orange. It's said that the Japanese owner had to leave the painting behind as the frame was too big and heavy, so it must have been framed in a big ugly gilt frame. If only he had framed it as Vincent had wanted
There's more on the story at the Independent and the Guardian.


text:
Mercury would be a challenging planet to terraform (though not as challenging as Venus) It has many features that are positive for terraforming, including a low surface gravity (about the same as Mars' [0.38 G]), an internal dynamo that produces a magnetic field (which is especially important as a radiation shield so close to the Sun) and considerable stores of water-ice and organic compounds in its polar craters.
Initial human habitats could be built mostly underground, to allow the establishment of a continuing human presence on the planet before terraforming. However, the above-ground parts of these colonies would need to be rigorously self-contained and the insides pressurized, like a space station. This is because Mercury's surface pressure is close to zero, a result of a combination of low gravity and proximity to the Sun.
If it were determined that fully terraforming Mercury would be uneconomical or technologically impractical, the other option would be building enormous, transparent, geodesic domes across the planet's surface and terraforming the space contained inside them (as proposed by Wikipedia). This would mirror a method proposed to allow terraforming of the Earth's Moon.
Fully terrarforming Mercury would require first shielding the planet from excessive Solar Radiation, before beginning the construction of an atmosphere on the planet. Mercury's native magnetic field is 1/100th the strength of Earth's. This is small; however, between the magnetosphere and the comparable gravity, Mercury in many ways should have an atmosphere comparable in thickness to Mars. However, Mercury's close proximity to the Sun means that it experiences a much more intense pressure of Solar Wind, three times greater than that experienced by the Earth. The intense Solar Wind has prevented Mercury from accumulating an atmosphere thick enough to be relevant to humans.
Accordingly, construction of an atmosphere would only be possible once a shielding unit (such as solar shades) has directed some of the radiation pressure away from the planet's surface. There is a chance that gases from Solar Wind would begin naturally accumulating to form a thin sort of atmosphere around Mercury; but human terraformers would undoubtedly want to thicken that atmosphere to make the surface of the planet more comfortable for colonists.
Unlike Mars, which contains frozen gases locked up in rocks across it's surface, the gaseous components of Mercury's rocks have long been baked away. Gases to build an atmosphere would have to be brought to Mercury from elsewhere in the Solar System. Since excess heat is an acute problem for a planet so close to the Sun, greenhouse gases like methane or carbon dioxide would have to be kept to a bare minimum. Nitrogen for such an atmosphere could come from Titan. Icy comets could be redirected to Mercury to flood the low elevations with water to create oceans. A supply of oxygen would be needed as well, most likely from the Asteroid Belt.
Another problem with terraforming Mercury is that the length of it's solar day is ~4223 hours, or the equivalent of 176 Earth days. Today, temperatures on Mercury are extremely different between the day side and the night side of the planet. Recent research has shown that an atmosphere thick enough to sustain humans might serve to even out the planet's overall temperatures; however, Earth plants would still have a very difficult time adapting to such an extreme day/night cycle.
As of right now, it is technologically unfeasible to alter the rotational speed of a planet and this will continue to be impossible for the foreseeable future. One possible workaround to this would be to expand the terraformed world's solar shielding into a band of mirrors encircling the planet. This would enable the Sun's light to be redirected to light one side of the planet's surface, simulating a shorter day/night cycle than would actually exist.
If terraformed, Mercury will face the problems of a Mountain Planet.
See also:


text:
Monday, June 13, 2011
The Lunch Hour
let's go to lunch and talk about our problems.
Something fashiony i've been working on in my free time.
This week marks a huge change in my life - i'm moving out to the city in seven days and also starting a part-time job! Wish me luck. I cannot stop smiling - it's going to be amazing to be back in the world and close to my friends.
p.s. congrats to Sianne who won the purple tights from my giveaway post.
10 comments:
thats amazing! you can have more exhibitions that are closer to the action ;D what are you doing for a part time job?ReplyDelete
Hopefully i can go to see more galleries now and get in on the action, yeah.
& I'll be working at an art supply store! quite appropriate, i guess.
An art supply store, you say? I'd say that sounds just about perfect! Good luck in your new life, Dear! I'm sure it'll be lots of fun. C:ReplyDelete
Oh my that is beautiful!!ReplyDelete
And good luck with your new job - hope you get a good staff discount!! <3
Gaby xo
Congrats on the move! I'm sure you'll love being near your friends and all those galleries. <3ReplyDelete
Also, I've been loving all your recent work. Been quietly snooping on Flickr. This one has to be my favorite. Such great pattern, texture, and emotion! Well done.
Good luck with your new job!ReplyDelete
This is so beautiful... Your work is perfect!
I really like that! You are so talented.ReplyDelete
Congratulations with your move and new job!
The outfits are so perfect! Lovely painting!ReplyDelete
And best of luck with your move!
Caitlin this is brilliant :)ReplyDelete
love their eyes.... stunning xReplyDelete


text:
Happy Holidays to everyone! Although the holidays are busy for all, François and I are probably busier for we are in the throws of developing four new Collections for Pavé Tile. The first of our new collections soon to be available is called South Beach 1930. How I would love to go into detail about this Collection - but we will do it correctly with the bells and whistles of what each line deserves to have - a fabulous header to let you "feel" the ambiance of the tile, the incredible photography and the detailed specs. Just know it's a gorgeous European terra cotta tile collection that will fill a void in the industry for the outdoor lifestyle of elegance and nostalgia of historic South Beach 1930.
In the meantime, I decided to blog on another lovely tile line we offer - The Old World Crackle Collection in Charcoal. I designed this line while pregnant with my daughter Isabelle. I wanted to see pattern in a more elegant form - yet still reaching across cultures and time periods. Onto a hand made European terra cotta tile with a crazed creme glaze - we hand decorate each piece followed by a ramp kiln fire. The result looks like jewelry. The craze intermingles with the charcoal glaze giving it an almost reflective quality like a tree silhouette onto a placid lake.
And because it's a pattern, the design blooms to infinity, allowing one to cover entire back splashes or shower surrounds in elegance.
The colors - creme and charcoal - with the varying degrees of light and dark values of charcoal - make this collection suitable for the elegant American home decor. Although the patterns are reminiscent of old world European and Moorish decor - the monochromatic color scheme lends this collection to a modern edge. Placing this tile next to a dark granite or concrete countetop is glorious - not to mention the sleek stainless steel of the refrigerator and oven.
One of my favorite designs is the one below entitled "Versailles". It reminds me of a French garden with the pattern being intricate and complicated yet ethereal all at once.
I find it fascinating how one decorative can become so many patterns!
In the end, François and I strive for beauty - so for those of you who love pattern, perhaps you will find beauty in our Old World Crackle Tile Collection.
After the holidays, be sure to view our first of four new Collections - South Beach 1930 - which will be a floor and wall tile collection..with of course..decoratives.
Have a wonderful holiday.
À bientôt,
Emmi Micallef
Pavé Tile & Stone, Inc.


text:
Kim Florence
(304) 231-1839
Charity poker events proceeds will benefit local charity groups
WHEELING, W.Va.— Wheeling Island Racetrack & Gaming Center announces they will host two charity poker events on Monday, October 15 and Tuesday, October 16, 2007 from 4pm-8pm in their newly constructed Poker Room.
All proceeds will benefit The Wheeling Island WISH Foundation, Family Services Upper Ohio Valley, Wheeling Health Right, YWCA, The United Way-Upper Ohio Valley and Soup Kitchen of Greater Wheeling.
Bob Marshall, President and General Manager of Wheeling Island said the charity poker events will serve two purposes; first, to give our local charities an opportunity to raise money for their organizations and second, to provide additional hands-on training for dealers and simulate the poker room operations as it pertains to the approved lottery regulations prior to our official grand opening.
"It is really exciting to see our Poker Room and Poker dealers in action," said Marshall. "The next two days will be a soft opening to fine-tune operational details as we prepare to open our new Poker Room to our guests. If all goes well, we will be ready to open within the week," said Marshall.
Guests who pay a $20 charitable donation at the Poker Room door will receive $100 in play chips, complimentary refreshments and an entry for daily door prize drawings.
Please RSVP for on site parking for satellite trucks to Kim Florence at 304-231-1839.