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FrightFest 2016 - Horror goes West
This time two weeks ago we were half-way through the 17th annual Christmas for horror fans - FrightFest.
As a regular, who has been going since 2007, I was more than a little anxious about the move West, but I have to admit that having spent five full days inside the Vue Shepherd's Bush, I was pleasantly surprised. This year I was there both as a film-goer and to work on a premiere (of my partner's film The Chamber), so it was interesting to see how the venue worked for both purposes.
Collecting passes on the first night was a doddle - having a mezzanine level for the box office (with plenty of space) worked out really well. I even had time for a quick drink with friends before the first film.
We then skipped Cell to go to the opening night party at The Bull - one thing that struck me on the first night was how many decent bars and restaurants were just a stone's throw away from the Vue (which is just what you need when you're about to spend the best part of a week in that one location).
I was working all day on Friday for The Chamber premiere - seeing first-hand how manic it is to organise just one film screening (as well as all of the interviews in between), I now have a much greater appreciation and understanding of what all of the people who work behind the scenes at FrightFest (and other film festivals) do. I can't imagine what it is like to have to organise what I experienced on Friday times 66, and still have the energy to socialise with festival-goers afterwards.
The rest of the weekend I enjoyed as a FrightFest regular - it was great to see old faces and lots of new ones too. The female-to-male ratio of festival goers/ filmmakers is increasing every year and I hope it continues to do so. The panels were a great addition to the lineup this year - I managed to attend two of them (Dan Martin's SFX demonstration and the Women In Horror panel); both really interesting and provided a lot of discussion for people after the panels ended.
The film line-up was great this year - a real diverse mix of body horrors, sci-fis, thrillers, slashers, comedy horrors and more. As FrightFest continues to grow, it's important for the festival and it's films to keep evolving - this may mean more international films or more genre-diverse films (horror doesn't have to mean 'gore' anymore - horror is anything that is horrifying). Some of my favourites of the weekend were Train to Busan, The Master Cleanse, Monolith and Beyond The Gates.
This year, more than in recent years (at the Vue Leicester Square), it really felt like the family atmosphere I remember from my first FrightFest at the Odeon West End back in 2007 - the large foyer and corridor leading to all screens were big enough for people to meet and chat between screenings, and I never found it too difficult to find people (despite the larger than ever numbers attending FrightFest this year).
Despite my initial ribbing of Wetherspoons, it was actually a pretty decent place to go to in between screenings to grab a quick pint and catch up with people - so, sorry Wetherspoons, I take it all back.
It was also great to meet some of the filmmakers attending the festival - one thing I really love about FrightFest is that everyone mingles with everyone. There is no class system with filmmakers or actors vs festival-goers - something that sets the horror genre/ horror festivals apart from all others.
And after all that - when I caught up with Alan, Greg, Paul and Ian (throughout various parts of the weekend), they were all chatty, upbeat and had smiles on their faces!
So guys, I'm not sure if you've decided what's happening next year in terms of location for the festival, but I am a huge fan of FrightFest moving permanently to Shepherd's Bush (despite the schlep from North East London), and I've heard a lot of other people saying positive things about the new venue too.
Let's see what FrightFest 2017 has in store for us - 348 days to go....
Hopefully see you all at the Halloween all-dayer!


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(Reuters) - The Detroit Tigers scored three runs in the first inning and that was all they needed to beat the Oakland Athletics 3-2 in Game One of their American League Division Series on Friday.
Ace Detroit pitcher Max Scherzer threw six scoreless innings before giving up a towering two-run homer to Yoenis Cespedes in the bottom of the seventh with none out that briefly brought the largest Oakland crowd in nearly a decade to life.
Scherzer, who recorded the most wins (21) for any major league pitcher in the regular season, showed his class to get through the rest of the inning without further damage.
The Athletics did not seriously threaten to score again as the Tigers held on to record a precious road win in the best-of-five series.
Scherzer, who accrued 11 strikeouts, gave up just three hits — two of them in the seventh — in the win while Bartolo Colon took the loss after conceding 10 hits in six innings.
After Scherzer had completed his work, Todd Smyly pitched 2/3 of an inning before Joaquin Benoit threw a four-out save, finishing off the game in style for the Tigers by striking out Josh Reddick.
"When you're pitching you just go on your instincts and we had a gameplan what we wanted to do early in the game but when you get in the game sometimes it changes," Scherzer said.
"Today my fastball seemed pretty good and my change-up seemed pretty good and early in the game I was pitching those two pitches a lot.
"I thought I did a good job of attacking the zone and throwing first pitch strikes and was able to get deep into the game and because of that I was able to pass the baton onto the bullpen ... and they pitched lights out."
Cuban slugger Cespedes was the only Oakland batter to worry Scherzer, recording a three-base hit in addition to his home run. Brandon Moss was the only other batter to record a hit.
It was a different story for the Tigers, as seven batters combined for 10 hits, although Miguel Cabrera was restricted to just one hit in four at-bats.
Game Two will be played in Oakland on Saturday, before the series moves to Detroit.
Reporting by Andrew Both in Cary, North Carolina; editing by Amlan Chakraborty

subset: commoncrawl


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This original French style is all about being sensual and not to try too hard. Low key make up, don't look at me sense of style and a splash of a bedraggled look.
A monotone look is perfect for is this style : a tuxedo jacket, a nude cashmere jumper and a silk blouse (worn as a t shirt) are basic must haves .
Décolletage is good for any body shape, draws attention and makes you look slimmer.
Skinny black pants or a classic jean are perfect basic trousers : a pencil skirt has the same effect.
|Ines de la Fressange
|Isabel Marant
|Carine Roitfeld


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Find More Images of Siya Ke Ram 24th October Episode on the end of the post.
Siya Ke Ram 24th October Episode starts with
Sita coming to Janak. Janak is praying. She says Pita ji. He gets surprised and says Sita, you here at this time, is everything fine. She says I came to meet and thank you. He asks why thanks. She says for everything I got from you, you made me independent and giving me good values, and making me Sita. He asks why did you come to say this to me suddenly. She says I had wish to meet you and speak my heart out, now permit me to leave. He takes his blessings and disappears. Janak gets shocked and shouts Sita. He calls Shathanand and asks him to get horse chariot, Sita took some decision by which big danger is going to come on her, we have to leave for Valmiki ashram without any delay. Shathanand gets shocked and says sure. He rushes. Janak prays to Mahadev to protect Sita.
Ram recalls his bad dream and Guru Vashisht's words. He thinks is this bad happening related to that bad dream, I have to meet Sita now itself, she promised to come with me, how can she go away from me. Ram rushes to meet Sita. He looks inside the hut and sees Sita praying. He gets relieved seeing her fine and shuts door. He thinks it was his fear to lose Sita again, and that's why he felt so. Hanuman comes to him. He asks is everything fine. Ram says I was worried for Sita, so I came to see her, everything is fine. Hanuman says I can understand your sorrow, pain and emotions, this good time came after many sorrowful years, I m praying for this night to end, and Ram and Sita re-unite, and I see you both sitting on Ayodhya throne. Ram says yes, just a night left and then no one can separate Siya and Ram.
Its morning, everyone wait for Sita outside the hit. Sita gets ready in her bridal clothes. Bhoomija Janak……plays………….. She wears her jewelry. Lav says I will go and get Sita. Ram says no need, Sita will come out of hut herself, we have to wait here. Sita applies her sindoor. Sita opens the door and comes out. Everyone smile seeing her in her bridal wear. Everyone proceed to her. Kaikeyi asks Sita to come. Sita gets tearful eyes. She walks to Ram. Ram smiles. Sita walks along with Ram.
Ram gets glad and walks ahead of her, thinking she is coming along. Sita stops. Ram turns to Sita and asks what happened, why did you stop. Sita says I can't go ahead of here. Everyone get shocked. It starts thundering and gets dark. Ram asks why are you saying this. Sita says its not possible for me to return to Ayodhya again. Everyone get shocked.
Ram asks Sita not to say this. Sita says my decision is final. Badra says no Mata, don't say this and requests her. Lav and Kush look on. Badra says I m that unfortunate Badra, because of whom you are bearing all this, I have questioned wrongly on your purity and character, its my crime, I pressurized Ram to abandon you, give me death punishment, but return to Ayodhya, accept my request. Sita says no Badra, there is no question to forgive you, because you are not culprit, the society is the culprit who gave you this direction to your mind, and filled such thoughts, where you were not learnt to respect women, where society finds woman's fault in injustice with women, you are just representing society, that mindset will not end by punishing you.
Kaushalya says we all came to apologize to you, for doing injustice with you, we all are culprits, forgive us, why are you refusing to come to Ayodhya. Janak is on the way and asks Shathanand about the way. Shathanand says its 10 miles away. Janak says its looking long distance. Shathanand asks him not to worry.
Sita says today everyone is apologizing to me and came to take Sita, what about all those Sita whose problems and sufferings are not known to anyone, no one will go to take them, I m not just Ram's wife, Lav and Kush's mum, and Ayodhya's Queen, I m also a woman, its my firstmost duty to protect my identity, if I return to Ayodhya, it will be injustice to all those suffering women who don't know their crime, do you think I should not think of women's respect and return to Ayodhya along with you. Everyone cry.
siya ke ram 24th october siya ke ram 24th october siya ke ram 24th october
Precap :
Sita says my character was stained and my purity was doubted, its not possible for me to return to that society, today I swear by water, earth, fire, air, sky, that I was born by the earth, today I will return to that earth's lap forever. Ram gets shocked.
siya ke ram 24th october siya ke ram 24th october siya ke ram 24th october siya ke ram 24th october
** Jai Shree Ram **


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Remember this post about Pluto? I found the perfect illustration for it:
P.S. Did you know now that it's officially no longer a planet, Pluto is technically a "dwarf planet?" That poor little guy just breaks my heart.
That's a great graphic.
I got my husband this shirt a few months ago and when people see it, they always talk about "poor Pluto".
Ha! Love it.


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As I have already mentioned in my previous post, about going home for Diwali (the festival of lights as its aptly called) and 2 homes this time making it double fun. Its a month long stay in India!! so it got to be fun and nothing else, apart from me putting on few more kilos of weight. ;) I am not sure whether I would gather anytime to blog in the middle of all the enjoyment & fun with family, friends and food not to forget. But I wish to bring back lots of memories and experiences with pics to share. Till then wishing you all a super Diwali filled with love, happiness, lots of family time and obviously prosperity - thats what the festival is all about, remember Goddess Lakshmi! :)
These are some pictures from last years diwali at my home in Dubai.
Thursday, October 13, 2011
It's that time of the year again!
Labels: Deepawali, Diwali, diyas, Festivals, Indian Festivals, lamps, lights, photography, Prosperity
Location: Dubai - United Arab Emirates
7 comments:
Hi PracheeReplyDelete
The pics are truly fantastic. Your post reminds me to get set for my trip as well!
Take care
Happy & a safe journey and in advance wish you, Raghu & your entire family a very happy, safe & prosperous Diwali:)
Enjoy !
hey prach great pics! congratulations to you for being so consistent and blogging all the great stuff!!ReplyDelete
enjoy you trip and stay in India!!enjoy being with parents and yes don't forget meeting up with friends!! have a very happy Diwali!! full of lights!!
Thanks both of you and the wish the same for u guys :)ReplyDelete
Simply beautifully captured shots...lovely!ReplyDelete
hope you had a wonderful Diwali!ReplyDelete
Thanks again Kalyan & Neha :)ReplyDelete
Those are very nice clicksReplyDelete
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Preparing teens for our nation's workforce
CareerLaunch encourages Club members ages 13 to 18 to assess their skills and interests, explore careers, make sound educational decisions and prepare to join our nation's work force. Club staff or volunteers help teens build their job-search skills and job readiness by using the CareerLaunch Facilitator Guide and working with teens individually or in small groups. The CareerLaunch page provides Club teens, staff and volunteers with online career exploration, college and job search information and interactive activities. Mentoring, job shadowing and training opportunities round out the program.
What are you going to do after high school?
College Prep program for teens.
Junior Staff is a small-group program that is both practical and user friendly.
Assists Club members ages 13 to 18 in exploring a career in youth or human services, particularly Boys & Girls Club work. Young people prepare for future roles as human services professionals by participating in career development activities, discovering the importance of community service, building customer service skills and completing a Club apprenticeship. Clubs that implement this program make an investment in the development of Club members' interpersonal skills, work ethic and sense of community responsibility.
Keystoning is the Boys & Girls Club Movement's ultimate teen program
This unique leadership development experience provides opportunities for young people ages 14 to 18. Youth participate, both in and out of the Club, in activities in three focus areas: academic success, career preparation and community service. With the guidance of an adult advisor, Keystone Clubs aim to have a positive impact on members, the Club and community.


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If you have tuned in before then you will know that I'm a huge fan of wireless charging and have reviewed more than a few charging products in the past. Well I finally think I have found the best looking wireless chargers out there. These Bamboo Qi chargers arrive from Fonesalesman and are definitely worth a look. If you like what you see then be sure to enter our giveaway, all instructions below the video.
If you want to win yourself a selection of these awesome pucks then just CLICK HERE.
The following two tabs change content below.
Ryan Oneill
Editor In Chief
I live in Scotland UK and have been blogging about technology for a long time. I started BeginnersTech as I wanted even the total novice to be able to enjoy it as much as I do. If you ever need help or want to ask a question you have come to right place.
Latest posts by Ryan Oneill (see all)
- My Gaming Setup – November 12, 2017
- Win Some Cooler Master Swag (International) – July 6, 2016
- Corsair Lapdog Review – Lounge Gaming At It's Best – July 1, 2016


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Welcome to TLC South Africa
Nestle S26 celebrates Mums
Posted by supriya.singh | 04 August
In celebration of Mother's Day across the GCC, NESTLE S26 PROGRESS GOLD wanted to reward mums for being mums! Sometimes it's not easy feat, and Mum's require some time out to themselves. That's why when consumers who purchased any promotional Nestle Wyeth Nutrition S26 Progress Gold Milk or S26 ProKids Gold Milk received a free pampering session. Consumers were requested to enter the unique code found on pack on the dedicated microsite www.progressgoldrewards.com . Once validated, the consumer could proceed to select a pamper session of their choice ranging from manicures to massages. Every validated code was entered into a draw to win free Tuition worth AED 30,000.


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At a little bit more than 2 weeks from the start of the 71th edition of the Sturgis (or Black Hills) Rally, both sides continue to fight over the STURGIS RALLY and other trademarks associated with the motorcycle event. On one side the SMRI (Sturgis Motorcycle Rally Inc.), a not for profit organization, requesting a fee from vendors for use of the name STURGIS RALLY and other trademarks on all merchandise, threatening or suing opponents violating its intellectual property acquired February 22, 2011 from the United States Patent & Trademark Office (USPTO) On the other side, a group led by the Neiman family of Rushmore Photos & Gifts, alleging that the trademark(s) can't be enforced because SMRI made the misrepresentation of "substantially exclusive and continuous use" of the term Sturgis as a mark for 5 years before the filing of the claim, knowingly and with the intent to defraud the US Patent & Trademark Office.
Regarding this conflict, it seems that both parties enjoy using my Blog to express their multiple point of views. Because of the legal aspect and not knowing all the facts, I limit myself to reproducing the documents spontaneously sent to me by both sides. If you are interested by this issue, the 2 following documents contain interesting information to form your judgment. At the end you will read the answers that Brian Neiman made to me when I asked for a couple of clarifications.
1- Letter Dated 2001 From Sturgis Chamber Of Commerce Applying for Sturgis and Black Hills Rally.
2- Letter From SMRI Dated July 15, 2011.
3- Brian Neimann from Rushmore Photos & Gifts answering my questions.
1- Cyril Huze. Why did the Chamber Of Commerce filed this document in 2001. Brian Niemann. They filed it because of the opposition from Black Hills Harley Davidson, Good Sports/Hot Leathers, and Sturgis Bike Week. They were about to lose the battle if they could not come up with a valid reason to own Sturgis.
2- Cyril Huze. Was a trademark given to the Chamber Of Commerce? Brian Niemann. It was never obtained by the Sturgis Chamber Of commerce. They fought the battle and when they were about to go bankrupt, Jim Burgess (Black Hills Harley Davidson), and Jerry Berkowitz (Good Sports, Inc./Hot Leather) joined with Dean Kinney (Home Slice, Load American Roadhous) and John Johnson (First Interstate Bank) created SMRI that took the intellectual Property from the Chamber and took over the registrations of "Sturgis" and "Black Hills". Then Jim and Jerry with Sturgis Bike Week going out of business pulled their opposition to "Sturgis" and "Black Hills" resulting in them being issued to SMRI, now ran by Dean, Jerry, Jim, and John.
3- Cyril Huze. If the trademark was not given to the Sturgis Chamber Of Commerce, it could not be enforced. Right? Brian Neiman. Even though the trademark was not ever issued to the Sturgis Chamber, Dean Kinney and John Johnson decided to have the Chamber sue Sturgis, Kentucky and a rally contained within for a children's Charity. SMRI settled this battle after they took ownership by crushing the charity because they needed to get rid of the bad press.
4- Cyril Huze. Why did you tell me (sending me a copy of the 2001 trademark request by the Sturgis Chamber) "Here is the disputed Document that was used fraudulently to obtain "STURGIS RALLY" and "BLACK HILLS RALLY" trademarks"? Please, explain. Brian Niemann. My public statement is that SMRI obtained its trademarks by making a sworn statement to the U.S. Trademark office that STURGIS was exclusively used by the Sturgis Chamber of Commerce from 1987-2001. It's a lie. (note from Cyril: SMRI states that such statement was never made by SMRI's predecessor to the U.S.P.T.O)
Response from Dean Kinney of SMRi
The Chamber historically owned the intellectual property and had the sponsorship and promotion trail back to the origin of the event in 1938. Basically, the Gypsies transferred management over to the Black Hills Motorcycle Classic Board in the 70's and in 1984 (taking this off the top of my head) that board made a formal request to become a part of the Sturgis Chamber… that is when the Chamber inherited the historical rights. They had several common law brands as well as the federal registration of the Sturgis logo, Sturgis Bike Week and Take the Ride to Sturgis and the federal applications for STURGIS and BLACK HILLS. Ultimately, they transferred all of these rights to SMRi and earlier this year the STURGIS and BLACK HILLS marks registered.


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Daily Archives: January 14, 2018
Video Can Improve Conversion Rates
Embedded videos have become a popular online marketing tactic and many business owners report significantly improved conversion rates. Videos can quickly and convincingly showcase a product or service and allow the use of humor much better than text. And funny videos may go viral, just think of the Squatty Potty or Old Spice videos.
There're a few things to keep in mind. On average it takes about 5 seconds for a viewer to decide whether to watch a video or not. Make sure that your video captures the viewer's attention right away! For example, it can be emotionally appealing and relatable, or it can offer instructions and teach new skills. It's important to inform in a unique and exciting way what the video is going to be about in just a few seconds. When this is out of the way, and you know how to inspire interest, think of the technical aspects. High quality is important, so consider location, light, sound and good editing tools. There's no perfect formula for a great marketing video, just try different things and be creative.
There are some free options to embed videos on a web page, such as utilizing YouTube. This is perfectly fine for small businesses with a very limited marketing budget. However, using a custom video player like BOSS would be ideal. It is not the cheapest option, but it allows for much better customization, such as embedding links, which in turn could yield the best results in terms of conversions. Also, for high-end brands and products, using YouTube videos would look cheap and clash with an upscale brand's image.
And as always when it comes to conversions, testing different versions of an ad or a video is crucial. There is no way of knowing which version converts better until you actually test it. Among other things, you should test the length of the video and the call to action.


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Virtual Assistant Services
With us crafting beautiful documents and handling admin tasks for you, your clients will start to think you're a superhero. And who doesn't want to be a superhero?
Don't let your business overwhelm you. Focus more on the parts of your business you love while we take care of the rest.


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Peer-to-peer rentals
Be a renter ● Be an owner
Or be both
About Us
The EZMonk, Inc. website is a peer-to-peer rental marketplace that provides the interface for users (Owners and Renters) to make and save money. With today's economy, EZMonk was designed to enable registered users the ability to increase residual income from renting items already owned or save money by renting items in-lieu of buying them for limited use. The website is an intermediary for bringing Owners and Renters together in a virtual marketplace, allowing all registered users the ability to be an Owner, a Renter, or both.
EZMonk is focused on reaching the general public, established businesses and startup companies, giving everyone the opportunity to earn and save money. To support diverse money earning and saving opportunities, the rental marketplace has a wide array of categories to post and search items for rent. This is all provided in a marketplace focused on being a user friendly environment, allowing for easy tracking of rental items in a secure setting.
The founders of EZMonk are focused on providing consumers the services they need in a peer-to-peer marketplace. User satisfaction is extremely important, hence consumers are provided with the opportunity to rate their experiences.
EZMonk, thanks you for visiting and taking the time to learn about the company.


text: Posted by: jsharpe on April 13, 2016 in Industry News Leave a comment Fraudulent gas safety checks put tenants' lives at risk A man has been given an 18 month suspended sentence and was ordered to pay £2,000 in costs after arranging fraudulent gas safety checks. Gary Lynch, aged 36, arranged for Neil Walker to undertake the landlords' gas safety checks at tenanted properties on 14 separate occasions between February 2013 and May 2015 despite Neil Walker not being a registered gas engineer. Gas safety records produced used a false Gas Safe Register registration number and a fictitious address for Neil Walker. Gary Lynch claimed to have met Neil Walker in a pub and instructed him to undertake the landlords' gas safety checks for him, as the agent for the landlords, but Gary Lynch did not undertake any checks on whether Neil Walker was registered to legally undertake such work. One gas boiler that Neil Walker passed as safe was subsequently found to be 'Immediately Dangerous' and was potentially leaking poisonous carbon monoxide into the tenants' property. The tenants had been suffering from headaches and dizziness and contacted Wales and West Utilities who isolated the gas supply to the boiler and contacted the Health and Safety Executive (HSE) who investigated Gary Lynch's activities. During that investigation Gary Lynch was not able to provide any information or contact details for Neil Walker. Gary Lynch was sentenced at Plymouth Crown Court. He had previously been warned by HSE in 2014 about undertaking gaswork whilst not registered following previous concerns. Gary Lynch of Fletemoor Road, Plymouth, pleaded guilty to breaching Regulation 4 of the Gas Safety (Installation and Use) Regulations 1998 and Section 3(2) of the Health and Safety at Work etc Act 1974 and was sentenced to 12 months imprisonment for each offence suspended for 18 months and was ordered to pay £2,000 in costs. HSE Inspector Simon Jones, speaking after the hearing, said: "Gary Lynch's negligence could have cost lives. All landlord's gas safety checks must be done by registered Gas Safe engineers to ensure the highest standards are met to prevent injury and loss of life. Mr Lynch knew this but carried on instructing an unregistered man and put the lives of tenants at serious risk from deadly carbon monoxide poisoning. Further information about gas safety can be found at http://www.hse.gov.uk/gas/ Share ! tweet


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Can Indocin raise BG #s?
I am type 2 since Dec. 09. I normally have my numbers under control 80-120. I am losing weight (finally). My only diabetes med is Glimepiride 2mg twice per day. Today my blood glucose spiked at 157. The highest in a long time. I took an indocin for gout symptoms. Could that have caused the spike??
6 replies
after doing a search on known side effects of indocin blood sugar spikes are not a listed side effect.
that being said, stress and pain are both known to cause bs spikes… so what exactly is causing the spike is hard to identify exactly, but it is very possible that its a side-effect.
If in doubt ask your doctor or pharmacist to see if the benefits out-weigh the risks :)
Next Discussion: Type 1/Type 2 »


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Zenith Infotech Hosts IT Services Open House in Harrisburg, Pennsylvania
Interactive showcase gives IT service providers hands-on experience with the latest technology solutions
Jan 07, 2010, 12:29 ET
HARRISBURG, Penn., Jan. 7 /PRNewswire/ -- Zenith Infotech Ltd., an international company serving over 4,000 IT service providers worldwide, will host an interactive technology showcase Jan. 13, 2010 from 2:30 - 7:30 p.m. at the Hilton Garden Inn Hershey, located at 550 East Main Street. Snacks and drinks will be provided. The event, one of 124 U.S. open houses scheduled for the first quarter of 2010, is sponsored by Autotask, the leading provider of web-based IT services management software, used by thousands of IT service professionals worldwide.
(Logo: http://www.newscom.com/cgi-bin/prnh/20091228/LA30713LOGO)
IT service providers attending the open house will see live demonstrations of 'managed services' infrastructure and business continuity products and services. Together, these solutions enable small- and-midsized companies to automate IT processes and more efficiently run their business operations. Those attending will also receive a free 45-day trial of Zenith's managed services offering or a 30-day trial of its business continuity solution.
"We developed these open house events to demonstrate how services like backup and disaster recovery and outsourced networking can help IT services providers generate recurring revenue," said Barb Burk, Zenith Infotech senior director of marketing. "By migrating from a traditional break/fix to a managed services business model, they can better forecast revenue and resource requirements. And when these solutions are delivered via the Web, they can scale their business offering quickly, conveniently and cost effectively."
"I was drawn to Zenith's technology offering, mainly because I liked how all of the tools were remotely hosted, and that everything was Web-based," said Eric Shorr, president of PC Troubleshooters. "I also liked that I didn't have to be concerned about hosting a management server at my office, which my techs would have to monitor. With the Zenith model, I can instead have the techs out in the field, serving customers, rather than back at the office, managing a server."
For more information or to register for this event, visit www.zenithinfotech.com/register.
About Zenith Infotech
Zenith Infotech Ltd. is a leading provider of remote monitoring and management (RMM), backup and disaster recovery, and virtual help-desk solutions for managed services providers worldwide. The company's award-winning solutions enable its technology partners to scale their business without increasing their overhead.
SOURCE Zenith Infotech


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Re "Letters: What has become of the Republican Party?" (sacbee.com, Letters, Nov. 27) I am a former Republican who has to agree with letter writer Powell Svendsen's statement that the only families Republicans value are the rich ones. There is nothing more evident of this than President Donald Trump's stated goal of eliminating the estate tax, which provides about enough money to run the Veterans Administration. Proponents of this cut call it the "death tax," and try to snow us by asking if we want to give most of our inheritance to the government after the fact. In the real fact world, the tax does not even apply until a married couple has received over $10.6 million, and is progressive above that. About 5,500 families, some with hundreds of millions and even billions of dollars, have to pay as it now stands. To my knowledge, no wealthy Democrat has ever pushed this legislation. This is payoff to the pay-for-play gang, ironically the very thing that they accused others of doing during the campaign. Only one Republican Senator, Susan Collins of Maine, has spoken up on this issue. At some point, one has to inquire which party really believes in self-responsibility.
Bob Brauns, Folsom
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"The Woolworth Building @ 100"
Grand Central isn't the only NYC icon turning 100 this year. Just two months after it opened in 1913, President Woodrow Wilson flipped on a ceremonial switch to illuminate the new Woolworth Building, at the time the tallest office building in the world, on April 24. This exhibit spotlights the elegant green building, from the initial stages of architect Cass Gilbert's design and an up-close look at the building's gorgeous terra cotta ornaments to an examination of the building's pop cultural significance. All ages.
|Event website:


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Turbospoke – Bicycle "exhaust" system
So here we go again, something to add to my list of reasons I want to be a kid again. I remember my first bike, a purple and white Schwinn with the streamers on the handlebars and a bell. Eventually I needed more, so my dad added playing cards by clothes pinning them to the spokes, I waited for the sound of raw power. Okay, so it wasn't quite what I had hoped for…
Meet Turbospoke, the bicycle "exhaust" system that makes your bike look and sound like a motorcycle. Turbospoke is a cool new bicycle accessory that transforms any bike, except for maybe a purple Schwinn with streamers, into a super cool street machine. Using only the power of your bike's pedals, Turbospoke produces pretty nifty engine sounds from chopper to dirt bike, and then amplifies them for a realistic rider experience.
While Turbospoke certainly wasn't attracting the attention of the police, it sure was head and shoulders above the card in the spokes trick, it comes with three different motor sounds to choose from and it's definitely something that you don't see on every kid's bike. Check out the video:
At around $20.00 bucks, what kid wouldn't want one? I'm guessing it's gonna look stupid on my 10 speed, but then again, I look really stupid on my 10 speed anyway. Available at amazon.com
Source: www.schylling.com
Related Posts
4 reviews or comments
Arky Says: February 10, 2011 at 11:59 am
ha yeah i used to use bits of cardboard and pegs for this.,… i remember my first bike also (bright red bmx with plastic black 5spoke wheels :D), only thing was it got stolen and then i was sad… obviously
Mike B Says: February 11, 2011 at 3:18 am
I like the cards in the spoke better. Sure they wear out quickly, but you're making the sound. Here, you create the power, but electronics makes the sounds. You lose that connection. It's like driving a stick shift compared to an automatic.
John Q Says: February 11, 2011 at 5:18 am
This also uses cards and no electronics 🙂 Take a good look at the presentation video…
Julie Says: February 11, 2011 at 1:00 pm
Nope, no electronics… just pedal power, and cards… but not your average playing card! and louder.. to a kid louder is almost always better 😉


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The Block recap: Honk if you love old people (13.09.16)
The Block's real winner last night was alcohol, the cause of and solution to all life's problems.
It was challenge night on The Block, with the teams tasked with taking two pieces of furniture salvaged from the building in its art deco heyday and restoring one to its former glory while repurposing the other. They had seven hours to complete the restoration and repurpose, and had to use at least one of the pieces in their apartment.
The prize on offer was $5,000 cash and a bonus point the winning team can add to their score at any time. Block alums Kara and Kyal of "Fans vs Faves" were set to judge the challenge.
Shelley, Kara, Kyal and Scott inspect the couples pieces. Source: 9now.com.au
As the teams got off to their task, Sasha and Julia had a particularly rough start. The two were barely on speaking terms after Sasha ignored Julia's wishes when ordering wallpaper and curtains. Could we be headed toward another Block breakup, à la Whitney and Andrew or Chantelle and Steve? Of all the things demolished on The Block, relationships seem to be the hardest to rebuild.
However, the two seemed to smooth things over when Sasha agreed to let Julia return the unsanctioned purchases. The pair enlisted the aid of Scott Cam for help with their project.
The repurposed and restored pieces by Kim and Chris. Source: 9now.com.au
Now came time to present the final products. In addition to driving relationships to the breaking point, The Block appears to be driving our teams to drink, as alcohol seemed to be the dominant theme of the challenge.
Julia and Sasha repurposed a bedside table as a drinks cart, Carleen and Dan turned a set of shelves into a drinks cart while Karlie and Will went double duty by both restoring a drinks cabinet and turning a dining table into a bar. Party at their place, apparently.
Breaking from the theme, Kim and Chris turned an old desk into a vanity, while Andy and Ben went the intellectual route by turning a set of dining chairs into a bookcase.
However, booze was the winner as Kara and Kyal judged Carleen and Dan's project the best. The couple will get an additional $5,000 and an extra point to keep the Chump Jacket at bay.
Ben and Andy's restoration and repurpose pieces. Source: 9now.com.au
While the boomers may be able to fend off the Chump Jacket, they can't fend off pranksters Andy and Ben. Once the teams returned to The Block, the pair continued their campaign of psychological torture by surreptitiously placing a sticker on Carleen and Dan's back windscreen that read, "The Block retirement village. Honk if you love old people". Carleen spent a full day fielding honks from fellow motorists before discovering the boys' chicanery. Good thing they have that drinks cart.
While last night saw its share of drama, the real drama appears to be in store tonight. Nine has been teasing a Block bombshell all week. Who will walk out of the competition in frustration? Watch tonight, or come back tomorrow to find out.


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Camptothecin‐induced locking of topoisomerase 1 on DNA generates a physical barrier to replication fork progression and creates topological stress. By allowing replisome rotation, absence of the Tof1/Csm3 complex promotes the conversion of impending topological stress to DNA catenation and causes camptothecin hypersensitivity. Through synthetic viability screening, we discovered that histone H4 K16 deacetylation drives the sensitivity of yeast cells to camptothecin and that inactivation of this pathway by mutating H4 K16 or the genes SIR1‐4 suppresses much of the hypersensitivity of tof1∆ strains towards this agent. We show that disruption of rDNA or telomeric silencing does not mediate camptothecin resistance but that disruption of Sir1‐dependent chromatin domains is sufficient to suppress camptothecin sensitivity in wild‐type and tof1∆ cells. We suggest that topoisomerase 1 inhibition in proximity of these domains causes topological stress that leads to DNA hypercatenation, especially in the absence of the Tof1/Csm3 complex. Finally, we provide evidence of the evolutionarily conservation of this mechanism.
Camptothecin traps topoisomerase on DNA, which generates DNA damage and topological chromosomal stress in S phase. Synthetic viability screening reveals that Sir2 deacetylase activity drives topology‐mediated camptothecin sensitivity in yeast and human cells.
Genetic suppressor screening and whole‐genome sequencing provide a rapid and effective approach to identify drug resistance mechanisms.
Loss of chromatin factors Sir1, Sir2, Sir3 or Sir4 rescues camptothecin hypersensitivity of yeast tof1∆ cells and reduces camptothecin toxicity in wild‐type cells.
Sirtinol‐mediated Sir2 inhibition suppresses camptothecin toxicity in cultured human epithelial cells.
Separation of the two parental DNA strands during DNA replication creates positive supercoiling ahead of the replication fork. Such over‐winding hinders replisome progression and must be removed for DNA replication to be completed. In eukaryotes, two DNA topoisomerases, Top1 and Top2, cooperate to allow DNA replication and segregation. The main DNA topoisomerase that relaxes positive supercoiling during DNA replication is considered to be Top1, a type‐IB topoisomerase, while Top2 activity seems to be concentrated behind replication forks [1], [2], [3]. Despite the importance of DNA uncoiling for replication, Saccharomyces cerevisiae cells lacking Top1 can fully replicate their genome because in the absence of Top1, positive supercoils can either be relaxed directly by Top2 [4], [5] or indirectly by rotation of replication forks along their axes, converting impending positive supercoiling into intertwines/catenation between the two daughter DNA strands [6]. The catenation generated in this way is an obstacle to chromosome segregation and must be resolved by Top2, a type II topoisomerase, before the onset of mitosis [3], [7]. In contrast to Top1, Top2 is essential in yeast cells because a certain amount of catenation is generated even in wild‐type cells, possibly because Top1 cannot relieve topological stress between replisomes converging towards replication termination zones [8]. Consistent with this model, increased fork rotation has been observed when replication forks approach stable fork‐pausing structures, such as centromeres, tRNA genes, inactive replication origins [9], and potentially retrotransposon long terminal repeats (LTRs) and transcriptionally repressed chromatin [10], [11].
To reduce the requirement for decatenation, replisome rotation is normally restricted by the Tof1/Csm3 complex [9], the yeast homolog of the mammalian Timeless/Tipin complex. Tof1 and Csm3 are also crucial for proper pausing of replication forks at replication fork barriers present in the tandem arrays that form the large ribosomal DNA (rDNA) locus [12]. Independently of these functions, the Tof1/Csm3 complex also interacts with Mrc1 [13], which functions as an adaptor to transmit signals from the apical replication‐checkpoint kinase Mec1 to the transducer kinase Rad53 during replication stress induced by nucleotide depletion [14]. The fact that tof1∆ strains, similar to mrc1∆ strains, show synergistic phenotypes in combination with loss of Rad9—the other major checkpoint adaptor protein in S. cerevisiae—suggests that the Tof1/Csm3 complex recruits Mrc1 for the purpose of Rad53 activation [12], [15]. In this regard, it is noteworthy that Mrc1 also has checkpoint‐independent functions and can be recruited to replication forks independently of Tof1/Csm3 [14], [16], [17].
Despite the above findings, certain results have remained unexplained, and the precise roles of the Tof1/Csm3 complex have remained elusive. For instance, tof1∆ and csm3∆ yeast strains were shown to be hypersensitive to high doses of camptothecin [18], a drug that induces DNA double‐strand DNA breaks (DSBs) during S phase by trapping Top1 in a covalent complex with DNA. These strains, however, are not hypersensitive to other agents that induce DSBs, such as ionising radiation, or to drugs such as hydroxyurea that affect S phase progression [18], suggesting that the camptothecin hypersensitivity of tof1∆ and csm3∆ strains might arise through topologically stressed DNA structures generated by Top1 inhibition rather than from DNA damage per se [19], [20].
Here, we show that histone H4 K16 deacetylation by the yeast sirtuin complex drives the sensitivity of wild‐type cells to camptothecin. Our results also show that the disruption of chromatin domains bearing deacetylated H4 K16 rescues the camptothecin hypersensitivity of tof1∆ and csm3∆ cells, suggesting that the increased sister chromatid catenation generated in the absence of these proteins promotes camptothecin toxicity. Finally, we show that the role of sirtuins in driving camptothecin sensitivity in S. cerevisiae is evolutionarily conserved in the yeast Schizosaccharomyces pombe and in human cells.
To better understand the roles of the Tof1/Csm3 complex during DNA replication, we investigated the basis for the camptothecin hypersensitivity of TOF1‐ or CSM3‐deleted cells. This hypersensitivity arises from the well‐established trapping of Top1 in a covalent complex with DNA, as shown by the fact that it was rescued by TOP1 deletion (Fig 1A). Notably, mrc1∆ strains were not hypersensitive to camptothecin (Fig 1A; [18]), indicating that a defect in replication‐checkpoint activation does not explain the camptothecin hypersensitivity of tof1∆ or csm3∆ strains. Moreover, this hypersensitivity does not appear to arise from issues connected to fork pausing at the replication fork barrier on rDNA, as pausing‐deficient fob1∆ strains were not hypersensitive to camptothecin, and FOB1 deletion did not alleviate the camptothecin hypersensitivity of a csm3∆ strain (Fig 1B).
SIR gene mutations suppress camptothecin hypersensitivity of tof1∆/csm3∆ cells
To understand the origin of the hypersensitivity of tof1∆ and csm3∆ strains to camptothecin, we carried out a synthetic viability genomic screening [21] to identify mutations capable of suppressing such hypersensitivity (Fig 1C). We plated approximately 1 × 107 cells on a YPD plate supplemented with 20 μM camptothecin (Fig EV1A), isolated sixteen resistant colonies, and verified that they indeed displayed both resistance to camptothecin and to the antibiotic G418, a readout for TOF1 deletion, which was later confirmed by whole‐genome sequencing (Figs 1D and EV1B). This validation ensured that the cells isolated did not merely survive camptothecin treatment, but carried genetic (or epigenetic) marks conferring camptothecin resistance. We then sequenced their genomic DNAs to identify candidate mutations responsible for the suppression phenotype (all the mutations identified in each strain are listed in Table EV1). Two of the sixteen strains—the most resistant ones—carried mutations that inactivated TOP1, which encodes the drug target. Three strains carried either of two nonsense mutations that inactivated SIR3, while eight of the remaining strains carried a nonsense mutation inactivating SIR4 (Fig 1D; premature stop codons are designated by a ∆ following the position of the last amino acid residue encoded by the truncated gene). Importantly, we validated these putative drivers of camptothecin resistance by directly introducing deletions of SIR3 and SIR4 in tof1∆ and csm3∆ strains and establishing that SIR3 or SIR4 inactivation suppressed camptothecin hypersensitivity (Fig 2A). In the three remaining suppressor strains—the weakest suppressors—we could not identify any mutation responsible for the suppression. In one of these, no mutations were detected, while the other two carried point mutations in IME2 (inducer of MEiosis, which is not expressed in exponentially growing cells) or IRC15. However, ensuing studies established that neither IME2 nor IRC15 deletion suppressed the camptothecin hypersensitivity of tof1∆ cells (Fig EV1C and D; the reasons for the decreased camptothecin sensitivity of these three strains therefore remain to be defined).
Sir3 and Sir4 form a ternary protein complex with the histone deacetylase catalytic subunit Sir2 (reviewed in [22]), with removal of any of the three subunits inactivating the transcriptional silencing functions of the complex [23]. Significantly, we established that loss of Sir2 alleviated the camptothecin hypersensitivity of tof1∆ cells to a similar extent as conferred by Sir3 or Sir4 loss (Figs 2B and EV2B, lower panel). Furthermore, by increasing the concentration of camptothecin, we found that deletion of SIR2, SIR3, and SIR4 also promoted camptothecin resistance in a wild‐type yeast background (Figs 2B and EV2B, upper panel). Interestingly, in wild‐type cells, deletion of SIR2 suppressed camptothecin sensitivity to a similar extent as conferred by TOP1 deletion, and combining the deletions did not further increase resistance to camptothecin (Fig EV1E). By contrast, SIR2 deletion did not alleviate the strong camptothecin hypersensitivity of a rad51∆ strain, which is severely defective in repairing DSBs induced by camptothecin (Fig 2C). These data indicated that the SIR complex is a major mediator of camptothecin sensitivity, but crucially, inactivation of the SIR complex does not act as a general suppressor of camptothecin toxicity, for example by reducing Top1 activity, cell permeability to camptothecin, or DSB induction by camptothecin.
SIR proteins mediate camptothecin sensitivity via histone H4‐K16 deacetylation
To assess whether loss of the deacetylase activity of the Sir complex was responsible for the suppression of tof1∆ hypersensitivity to camptothecin, we used the small‐molecule Sir2 inhibitor, sirtinol [24]. This work established that addition of 20 μM sirtinol strongly suppressed the camptothecin sensitivity of a tof1∆ strain (Fig 2D). While Sir2 homologs in higher eukaryotes have been implicated in deacetylating proteins involved in DNA repair, such as PARP1, Ku70, and CtIP [25], [26], [27], the prime target for S. cerevisiae Sir2 is histone H4 lysine 16 (H4‐K16), which is found in an acetylated state through much of the transcriptionally active yeast genome. In S. cerevisiae, deacetylation of this residue by Sir2 allows binding of Sir3, thus recruiting further Sir2 that removes acetylation marks from flanking H4‐K16 residues, a process that is then propagated to produce a transcriptionally silent heterochromatic state [22]. To explore whether the relevant target for Sir2 in relation to its effects on the camptothecin sensitivity of tof1∆ cells was H4‐K16, we mutated this residue to glutamine (Q), a residue that mimics a constitutively acetylated lysine and abrogates Sir3 binding [28]. Strikingly, this hhf‐K16Q mutation suppressed the camptothecin hypersensitivity of a tof1∆ strain, and at higher doses also reduced the camptothecin sensitivity of a wild‐type strain (Fig 2E). Similarly, mutation of H4‐K16 to glycine (G), which prevents binding by Sir3 [28], strongly counteracted the camptothecin sensitivity of both tof1∆ and wild‐type cells. Taken together, these results highlighted a correlation between chromatin association of the SIR complex and camptothecin sensitivity.
A deacetylated H4‐K16 template promotes camptothecin‐induced mitotic arrest
To further explore how TOF1 or CSM3 deletion causes camptothecin hypersensitivity, we took advantage of the fact that camptothecin treatment of synchronised wild‐type cells released from G1 into S phase leads to a prolonged G2/M cell cycle delay [29]. We first assessed the effect of TOF1 and CSM3 deletion on this particular phenotype by arresting wild‐type, tof1∆ and csm3∆ cultures in G1 by alpha‐factor treatment, and then releasing them from this arrest either in the presence or in the absence of camptothecin. As expected, wild‐type cells treated in this way with camptothecin did not delay bulk DNA replication compared to strains released in the absence of camptothecin, although they did exhibit delayed exit from the subsequent mitosis (Fig 3A). Significantly, compared to wild‐type controls, cells deleted for TOF1 or CSM3 arrested for longer periods of time in G2/M following camptothecin treatment (Fig 3A bottom panels), a phenotype that correlated with persistence of the mitotic cyclin, Clb2 (Fig 3B). Nevertheless, these cells eventually re‐entered the cell cycle and continued proliferating, consistent with the fact that tof1∆ and csm3∆ strains were not killed by acute camptothecin treatment (Fig 3C; note that a repair‐defective rad51∆ strain was hypersensitive even to acute camptothecin treatment).
Source Data for Figure 3 [embr201643560-sup-0006-SDataFig3.tif]
Collectively, the data we had obtained supported a model in which the mechanism by which the SIR complex yields camptothecin sensitivity is via effects on H4‐K16 deacetylation. In this regard, we reasoned that the SIR complex might impart camptothecin sensitivity either by deacetylating newly incorporated histone H4 during DNA replication, or by it broadly promoting a condensed chromatin template that impairs DNA replication in the presence of camptothecin. If Sir2 deacetylation activity during S phase promoted camptothecin sensitivity, one would expect that addition of sirtinol after the release from G1 would circumvent the extended mitotic delay induced by camptothecin in tof1∆ cells. Conversely, if broad acetylation of the chromatin template was required to rescue the tof1∆ phenotype, sirtinol should lead to suppression of extended mitotic delay only if tof1∆ cells were pre‐grown in the presence of sirtinol. To discriminate between these two hypotheses, we grew hml and hml, tof1∆ cells either in the presence or in the absence of sirtinol, and then synchronised them in G1 by addition of alpha‐factor (Fig 3D). We used a mutant hml background because sirtinol makes wild‐type cells insensitive to alpha‐factor by derepressing the HML/R (HM) loci [24] (importantly, as shown in Fig EV1F, HML mutation did not affect camptothecin sensitivity). We then released the G1‐synchronised cells into S phase in the presence of camptothecin alone, or in the presence of camptothecin plus sirtinol. While addition of sirtinol after the G1 release was not sufficient to rescue the mitotic delay of tof1∆ cells (Figs 3D and EV1G), pre‐growing tof1∆ cells in the presence of sirtinol suppressed their mitotic delay, whether or not sirtinol was present during the subsequent camptothecin treatment. A similar effect, albeit smaller, could be observed in a wild‐type strain (Figs 3D and EV1G). Taken together, these findings supported a model in which camptothecin leads to replication‐associated problems that arise within chromatin regions containing deacetylated H4‐K16, with cells lacking Tof1 or Csm3 being particularly sensitive to such problems.
Multiple HM‐like chromatin regions govern camptothecin sensitivity
The yeast genome contains three well‐studied heterochromatic regions that are transcriptionally silenced by SIR proteins: the rDNA array, subtelomeric regions and the cryptic mating‐type loci (Fig 4A–C). To establish whether loss of rDNA silencing mediated the suppression of tof1∆ camptothecin hypersensitivity upon SIR protein loss, we used a strain carrying a deletion of the entire rDNA locus complemented by a multi‐copy plasmid containing the rDNA repeat unit [30]. We found that deletion of the rDNA locus did not reduce the hypersensitivity of tof1∆ cells to camptothecin (Fig 4A), indicating that this genomic region is not the prime target of the SIR complex that mediates camptothecin toxicity in tof1∆ cells. This notion was also supported by the fact that, while we observed suppression of camptothecin sensitivity with sir2∆, sir3∆, or sir4∆, silencing of the rDNA locus only requires Sir2, with SIR4 deletion actually increasing rDNA silencing by delocalising Sir2 from telomeres [31].
To determine if loss of subtelomeric silencing could rescue the camptothecin hypersensitivity of tof1∆ cells, we employed a strain carrying a C‐terminal truncation of Rap1 (rap1∆663), the so‐called rap1‐17 allele. This mutation completely disrupts transcriptional silencing at telomeres (telomere position effect) and partially affects silencing of the cryptic mating‐type locus HML [32]. While strains carrying the rap1∆663 allele grew slower than wild‐type strains, presumably due to the role of Rap1 in regulating transcription of genes involved in ribosome formation and glycolysis [33], [34], they did not display altered sensitivity to camptothecin (Fig 4B). The rap1∆663 mutation also failed to suppress the camptothecin hypersensitivity of tof1∆ cells (Fig 4B), indicating that loss of telomere position effect does not promote survival in the presence of this drug.
At the cryptic mating‐type loci HML and HMR, silencing is established by replication origin recognition complex (ORC)‐mediated recruitment of Sir1, which then attracts the SIR complex via an interaction with Sir4 [35], [36]. Sir4 binding is also stabilised by an interaction with Rap1, which binds to its DNA consensus sequence located next to the ORC binding site ACS (ARS consensus sequence, Fig 4C). For these reasons, deletion of SIR1 results in partial loss of silencing at the cryptic mating‐type loci, but does not affect telomeric or rDNA silencing [37]. Strikingly, we found that SIR1 deletion strongly alleviated the camptothecin hypersensitivity of a tof1∆ strain (Fig 4C). Importantly, SIR1 deletion did not further improve the survival of tof1∆sir2∆ strains, suggesting that Sir1 mediates camptothecin sensitivity entirely via its connection to the Sir2/3/4 complex (Fig 4D). Furthermore, similar to what we had observed for SIR2, SIR3, or SIR4 deletion, disruption of SIR1 also decreased the sensitivity of a wild‐type strain to high levels of camptothecin but it did not rescue the camptothecin hypersensitivity of a rad51∆ strain (Figs 4C and EV2A and B). These data were thus consistent with our conclusions that camptothecin sensitivity is not mainly generated via the rDNA or telomeric loci. Moreover, they indicated that the features of the chromatin template that are toxic to tof1∆ and wild‐type cells in the presence of camptothecin are generated in a Sir1‐dependent manner.
Various SIR‐bound genomic regions mediate camptothecin sensitivity
Our findings suggested that loss of the SIR complex might promote camptothecin resistance via effects on the HM loci. To test whether this might be connected to changes on the HM chromatin template itself or associated expression of genetic information from the normally silenced HML locus, we analysed the sensitivity of diploid tof1∆/tof1∆ cells that simultaneously express the genetic information encoded by HMR and HML. If transcription of genetic information from the HML locus reduced the camptothecin hypersensitivity of MATa tof1∆ strains, one would expect a homozygous tof1∆ diploid strain to be less camptothecin sensitive than the corresponding haploid strain; however, this was not the case (Fig 4E). Moreover, the camptothecin hypersensitivity of diploid tof1∆/tof1∆ cells was also rescued by sirtinol, clearly establishing that chromatin alterations, rather than expression of HM genetic information, are responsible for suppression of camptothecin hypersensitivity (Fig 4E).
While the above findings suggested that the chromatin status of the HM locus governs camptothecin sensitivity, when we deleted the HML and HMR loci, we were surprised to observe that this did not rescue the camptothecin hypersensitivity of tof1∆ cells (Fig 5A). This observation therefore strongly suggested the existence of other genomic loci targeted by Sir1‐4 as governing camptothecin sensitivity. To attempt to identify such loci, we analysed chromatin immunoprecipitation‐sequencing (ChIP‐seq) data for Sir2, Sir3, Sir4, GFP, acetylated histone H4‐K16, and histone H3 [38], [39]. In these datasets, we searched for genomic regions displaying higher association with Sir2, Sir3, and Sir4 compared to neighbouring regions. From the ensuing list, we then removed regions displaying increased GFP binding to exclude ChIP bias towards highly expressed genes [39]. We also removed regions where we did not observe decreased histone H4‐K16 acetylation (the consequence SIR complex binding) compared to neighbouring regions, as well as regions also displaying reduced histone H3 ChIP signals suggesting depletion of nucleosomes. Genomic regions identified in this manner localised to confirmed open reading frames (ORFs; Figs 5B and EV2C).
We then defined a "SIR‐binding score" (the fraction of nucleotides for which the above conditions held) for every ORF in the yeast genome. While the majority of all ORFs essentially had a null SIR score (indicative of no enrichment of SIR complex binding), we found that 82 of them showed an enrichment of Sir2/3/4 and concomitant loss of H4‐K16 acetylation along more than 20% of their sequence (Table EV4). Of these 82 ORFs, 28 were localised in subtelomeric regions or in regions proximal to the HM loci (Fig 5C, small grey dots), while the remaining 54 hits were positioned along chromosome lengths (Fig 5C, green dots). Although the majority of the identified ORFs are expressed at high levels during exponential growth, high expression was not sufficient for a high SIR score (Fig EV2D based on data from [40]). Taken together, these findings highlighted how, in addition to functioning at its well‐defined target loci, the SIR complex may also act at a variety of loci scattered throughout the genome, and suggested that these loci might also promote camptothecin toxicity in wild‐type and tof1∆ cells.
Recruitment of Sir1 at HM loci requires its interaction with the bromo‐adjacent domain (BAH) region of Orc1 [36], [41], [42]. We therefore assessed whether any of the loci we identified above were also positioned in proximity to a site bound by ORC. Thus, we calculated the distance between the centre of each ORF and the nearest ORC binding site [43]. This revealed that ~50% of SIR‐enriched ORFs were located less than ~750 bp from a site of ORC binding (Fig 5D), a distance considerably shorter than the median value of 7.7 kbp for all yeast ORFs. We therefore reasoned that, if ORC has a functional role in recruiting the SIR complex to these genomic loci, it should be possible to suppress the camptothecin hypersensitivity of tof1∆ cells by preventing ORC‐mediated recruitment of Sir1. In line with this hypothesis—and in contrast to what we had observed upon deleting the HM locus—deleting the BAH domain of Orc1 markedly suppressed the camptothecin hypersensitivity of tof1∆ cells (Fig 5E; effects of ORC1 deletion could not be studied because it is an essential gene). In agreement with the proposed role of Orc1 BAH domain in recruiting the SIR complex, deletion of SIR2 did not further enhance camptothecin resistance of orc1∆BAH cells, either in a wild‐type or a tof1∆ background (Fig 5F and G). These findings thus suggested that the chromatin substrates that become toxic to tof1∆ cells exposed to camptothecin are at least partially formed in an ORC‐dependent manner.
Evidence for an evolutionarily conserved connection between sirtuin function and camptothecin sensitivity
Consistent with a model in which SIR proteins might promote camptothecin sensitivity in other organisms, we found that sir2∆ S. pombe strains were more resistant to camptothecin than control sir2+ strains (Fig 6A). Moreover, in line with our findings in budding yeast, addition of sirtinol to the growth medium reduced the camptothecin sensitivity of wild‐type S. pombe cells (Fig 6B).
Next, we tested whether sirtinol affected the camptothecin sensitivity of hTERT‐immortalised, non‐transformed human RPE‐1 cells. In line with previous studies [44], [45], we found that sirtinol induced a dose‐dependent killing of human cells (Fig 6C). However, when the cells were pre‐incubated with sirtinol for 24 h prior to camptothecin addition, a protective effect on the survival to camptothecin was observed (Fig 6D). As expected, flow cytometry analysis based on DNA content showed that camptothecin induced a replication‐dependent cell cycle arrest, with the majority of cells in G2/M after 24 h of camptothecin treatment. By contrast, camptothecin‐induced G2/M accumulation was much less pronounced when cells had been pre‐treated with sirtinol (Fig 6E). Importantly, when we used EdU pulse‐labelling to quantify DNA replication, we found that neither the proportion of EdU‐incorporating cells nor the average intensity of EdU per cell was significantly affected by sirtinol (Fig 6F), indicating that replication was not inhibited by the sirtinol concentration used in our experimental setting. Collectively, these results supported a model in which cell killing induced by camptothecin is to a large degree mediated by the action of sirtuins, via a mechanism that is conserved from yeast to human cells.
By using a synthetic viability screening approach [21], we identified the SIR3 and SIR4 genes as major mediators of the sensitivity of both wild‐type and tof1∆ cells to camptothecin. We subsequently established that SIR2 and SIR1 also function in a similar way (these genes were likely not found in our initial screen because of the relatively small number of suppressor strains analysed). We established that, rather than by reducing camptothecin action, deletion of these SIR genes removes a factor that hinders cell proliferation in the presence of camptothecin in wild‐type cells and that is particularly toxic to cells lacking the Tof1‐Csm3 replication‐pausing complex. Camptothecin promotes the accumulation of positive supercoiling during DNA replication by locking topoisomerase 1 on DNA in a non‐functional state [19], [20]. Since Tof1 and Csm3 function to restrict replisome rotation during DNA replication [9], and since an important factor driving fork rotation is positive supercoiling [19], we hypothesise that an excess of camptothecin‐induced positive supercoiling is the factor that is alleviated by deletion of SIR genes.
While camptothecin is a Top1 inhibitor, lack of Top1 activity is not sufficient to explain the hypersensitivity of tof1∆ and csm3∆ cells, as deletion of TOP1 is not toxic to tof1∆ cells. Instead, camptothecin‐mediated locking of Top1 on DNA could be the source of topological stress, either directly by creating topologically closed domains, or indirectly by preventing Top2 action—similar to what is thought to happen when a catalytically inactive Top2 that still retains an ability to bind DNA is expressed [46].
Lack of Sir2, Sir3, or Sir4 leads to loss of histone H4 lysine 16 (H4‐K16) deacetylation and subsequent impairment in heterochromatin formation. We have observed that inhibition of Sir2 deacetylase activity or mutation of H4‐K16 to glutamine (a residue that mimics an acetylated lysine) also increases the camptothecin resistance of both wild‐type and tof1∆ cells. Importantly, we have established that the cell cycle delay observed in camptothecin‐treated tof1∆ cells can only be suppressed if Sir2 activity is inhibited prior to camptothecin treatment, suggesting that it is the state of the chromatin template itself that becomes toxic to cells when replicated in the presence of camptothecin.
Yeast genomes contain three well‐characterised regions of transcriptionally silenced chromatin: the ribosomal DNA, subtelomeric regions and the cryptic mating‐type loci HML and HMR; and of these, only the cryptic mating‐type loci require Sir1 for their silencing [37]. The fact that SIR1 deletion also suppresses the camptothecin sensitivity of tof1∆ cells initially suggested to us that HML and HMR represent the chromatin templates that are toxic to tof1∆ cells in the presence of camptothecin. However, we did not observe a reduction in tof1∆ sensitivity to camptothecin by deleting HML and HMR, meaning that these two genomic loci alone are not responsible for the strong camptothecin sensitivity phenotype displayed by tof1∆ cells.
Analysis of publicly available ChIP‐seq data allowed us to identify various genomic loci that exhibit enhanced localisation of Sir2, Sir3 and Sir4 as well as H4‐K16 under‐acetylation. Notably, we found that these genomic loci colocalise with confirmed ORFs and are located closer to sites of ORC binding than the average yeast ORF. Indeed, we found that many of these sites colocalise with genomic loci that were previously shown to bind ORC despite not having replication origin activity [43]. Importantly, we note that some of the SIR‐enriched loci also colocalise with sites of replication fork pausing and sites enriched in binding of Rrm3, a DNA helicase that relieves replication fork pauses [47], [48], suggesting that SIR‐enriched loci are inherently difficult to replicate even in the absence of camptothecin. The fact that these ORFs are amongst the most highly expressed yeast genes and yet exhibit enhanced recruitment of the SIR silencing complex and markers of histone H4 deacetylation is enigmatic. One possibility is that strong transcription could prevent heterochromatin formation despite the presence of the SIR complex. Indeed, it has been shown that promoter strength affects the efficiency of silencing [49]. In this regard, the sensitivity of yeast cells to camptothecin might stem from DNA catenation that is generated when replication forks approach barriers created by the Sir2/3/4 complex, a phenotype that would be exacerbated by the absence of the Tof1/Csm3 complex. We note that increased catenation would likely require time to be resolved, thereby potentially accounting for the M/G1 delay observed following camptothecin treatment in wild‐type cells and more strongly in tof1∆ cells. Another possibility is that SIR‐mediated genomic loci could be particularly prone to replication‐induced topological stress and would therefore be more frequently targeted by Top1 and more susceptible to camptothecin‐induced DNA damage. In this context, replisome instability caused by TOF1 deletion would increase the chance of fork breakdown or failure to rescue fork reversal events.
We have also provided evidence that the role of sirtuins in driving camptothecin sensitivity is evolutionarily conserved from yeast to humans. In the case of S. pombe, either loss or inhibition of Sir2, the fission yeast SIR2 ortholog, results in camptothecin resistance. As in S. cerevisiae, fission yeast Sir2 is involved in the heterochromatin assembly within the mating‐type locus, subtelomeric regions and centromeric DNA [50], [51] by deacetylating histone H3‐K9 and histone H4‐K16. Furthermore, we have found that sirtinol protects non‐transformed human RPE‐1 cells from killing by camptothecin via a mechanism that does not appear to reflect effects on DNA replication per se. As in yeast, human SIRT1 and SIRT2 deacetylate H3‐K9 and H4‐K16, among other substrates, and promote heterochromatin formation and gene silencing [52], [53]. This suggests that the role of sirtuins in camptothecin‐mediated lethality in human cells may be similar to that in yeast, although alternative mechanisms cannot be ruled out due to the considerable number of sirtuin‐dependent pathways documented in mammalian systems.
Inhibition of topoisomerase 1 is a widely used therapeutic strategy to selectively kill proliferating cancer cells, with camptothecin analogues being part of the standard of care provided by many cancer clinics worldwide. Various mechanisms of camptothecin resistance have been observed, ranging from overexpression of drug‐efflux transporters, which actively reduce intracellular drug concentration [54], to specific Top1 mutations that prevent its interaction with camptothecin [55], [56]. On the other hand, several sirtuin inhibitors have been shown to exhibit cytotoxic activity against various cancer cell lines (reviewed in [57]) and are currently being assessed for their potential clinical applicability [58], [59]. Using budding yeast as a model system, we have found that inhibition of histone H4‐K16 deacetylation by inactivation of the SIR protein complex represents an additional mechanism of camptothecin resistance and that this mechanism is likely conserved in fission yeast and in human cells. Further studies will be required to determine the precise mechanism‐of‐action of sirtinol in both transformed and non‐transformed human cells and whether sirtuins play a role in the emergence of resistance to camptothecin analogues in cancers.
Materials and Methods
Yeast strains and plasmids
Yeast strains used for this work are haploid derivatives of W303 unless otherwise indicated and are listed in Table EV1. All deletions were introduced by one‐step gene disruption/tagging [60]. Strains carrying histone H4 mutations were obtained by plasmid shuffling, transforming the strain JHY6 (hht1‐hhf1∆::KanMX6 hht2‐hhf2∆::HPH) with plasmids obtained by site‐directed mutagenesis of plasmid pMR206 (HHT2‐HHF2; TRP1). Isolation of suppressor strains was carried out as previously described [21]. The number of colonies sequenced was determined by reason of economics. S. pombe strains used were 49 (h+ ade6‐M210 leu1‐32 ura4‐D18) and 34 (h+ sir2::kanMX6 ade6‐M216 leu1‐32 ura4‐D18).
Whole‐genome paired‐end DNA sequencing and data analysis
Whole‐genome paired‐end DNA sequencing and data analysis were performed as previously described [21]. All raw sequencing data are available from the European Nucleotide Archive (ENA) under the accession codes detailed in Table EV2. SNPs and indels were identified by using the SAMtools (v0.1.19) mpileup function, which finds putative variants and indels from alignments and assigns likelihoods, and BCFtools that performs the variant calling [61]. The following parameters were used: for SAMtools (v0.1.19) mpileup "‐EDS ‐C50 ‐m2 ‐F0.0005 ‐d 10000" and for BCFtools (v0.1.19) view "‐p 0.99 –vcgN". Functional consequences of the variants were produced by using the Ensembl VEP [62].
Drug sensitivity assays
Overnight‐grown saturated cultures of the indicated strains were serially diluted (10 fold) in water; 10‐μl drops of each dilution were deposited on each plate. Images were scanned 2–3 days after plating and growth at 30°C. Each experiment was repeated at least twice (n ≥ 2).
Analysis of yeast cell cycle progression and Western blotting
Exponentially growing cultures (30°C) were synchronised in G1 by addition of 5 μg/ml alpha‐factor for 2 h. G1‐synchronised cultures were then transferred to fresh YPD and released into S phase in the presence or in the absence of camptothecin and/or sirtinol; 45 min after the release, 20 μg/ml alpha‐factor was added to allow quantification of G1 cells by preventing re‐entry into the cell cycle. To detect Clb2, trichloroacetic acid protein extracts were separated on 10% polyacrylamide gels and Clb2 detection was carried out using anti‐Clb2 antibodies (Santa Cruz sc9071).
Analysis of ChIP‐seq data
Reads were aligned using BWA‐MEM, and duplicates marked with Picard. For each genomic coordinate, coverage was calculated using samtools and bedtools (samtools view ‐q10 ‐b $filename|genomeCoverageBed ‐d ‐ibam stdin ‐g) and normalised using the genomewide median of each sample. For each coordinate, the enrichment (E) was calculated as the ratio of the normalised coverages of IP and input samples. Every genomic position showing Esir2 > 1.75 and Esir3 > 1.5 and Esir4 > 2 and EGFP < 3 and EH4‐K16ac < 0.3 and EH3 > 0.75 was exported to a bed file. These values were determined empirically, and small adjustments did not substantially alter the final results. For every ORF, the total number (T) of positions (nucleotides) for which the above conditions held was calculated by querying the bed file. The final SIR score was obtained by dividing this number (T) by the length of the ORF.
Human cell culture
hTERT RPE‐1 cells were cultured in Dulbecco's modified Eagle's (DME)/F12 1:1 medium (Sigma‐Aldrich) supplemented with 10% foetal bovine serum (BioSera), 2 mM L‐glutamine, 100 units/ml penicillin and 100 μg/ml streptomycin (Sigma‐Aldrich) and buffered with 0.2% Na(CO3)2.
Clonogenic survival assays
Cells were treated for 48 h with 50 μM sirtinol (Tocris), with camptothecin 30 nM for 24 h or pre‐treated with sirtinol for 24 h and then incubated with camptothecin and sirtinol for another 24 h as indicated. Cells were then washed three times with PBS and left to form colonies for 7–14 days. Colonies were stained with 0.1% (w/v) crystal violet in 20% (v/v) ethanol for counting. Results were normalised to plating efficiencies of untreated cells.
Human flow cytometry assays
Flow cytometry assays were performed as described in [63]. A 1‐h pulse of 10 μM EdU was performed after 48 h of the indicated treatment. After fixation and permeabilisation, Alexa Fluor 488 azide (Invitrogen) was used for the click reaction to detect the incorporated EdU. Finally, cells were resuspended in FACS buffer with DAPI and analysed in a BD LSRFortessa™ cell analyser.
Author contributions
The initial project was conceived by FP, VC and SPJ. Screening for suppressors and DNA extractions were carried out by FP and NJG. Analysis of whole‐genome sequencing data was carried out by MH and FP. Subsequent in vivo experiments and analyses of ChIP‐seq data were designed and carried out by FP; experiments in S. pombe and human cells were carried out by IS. The manuscript was largely written by FP, IS and SPJ, with contributions made by all the other authors.
Conflict of interest
The authors declare that they have no conflict of interest.
Expanded View
Expanded View Figures PDF [embr201643560-sup-0001-EVFigs.pdf]
Table EV1 [embr201643560-sup-0002-TableEV1.xlsx]
Table EV2 [embr201643560-sup-0003-TableEV2.xlsx]
Table EV3 [embr201643560-sup-0004-TableEV3.xlsx]
Table EV4 [embr201643560-sup-0005-TableEV4.xlsx]
We thank Jasper Rine, Catherine A. Fox, Takehiko Kobayashi, and Tony Kouzarides for the gift of strains and plasmids, all the members of the SPJ laboratory for helpful discussions, and Helena Santos‐Rosa for advice with designing histone point mutations. Research in the Jackson laboratory is funded by Cancer Research UK [C6/A11224, C6/A18796, C6946/A14492] and the Wellcome Trust [WT092096]; FP was supported by the Associazione Italiana per la Ricerca sul Cancro [10932] and the European Molecular Biology Organization [ALTF1287‐2011]; IS, MH, and NJG were supported by the Wellcome Trust [101126/Z/13/Z (Strategic Award—COMSIG)] and [098051 to MH];VC is supported by the Armenise‐Harvard Foundation and the Fondazione Telethon.
FundingCancer Research UKhttp://dx.doi.org/10.13039/501100000289 C6/A11224C6/A18796C6946/A14492
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license


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PLAINSBORO, New Jersey (WABC) --Strong storms loomed across the area on Saturday, bringing torrential downpours, and sending people scrambling for safety in flash floods. A State Of Emergency was declared in West Windsor Township. Nearly six inches of rain fell in just a few hours, and water quickly rose in low-lying areas.
Here's a look at the radar from 3-6 p.m., showing why so much rain fell in Middlesex County:
Flooding at a New Jersey Transit underpass tunnel was waist-high.
Flooding at NJ Transit underpass tunnel waist high. Witness says it was to the top earlier. pic.twitter.com/sFQAhFUATJ— CeFaan Kim (@CeFaanKim) July 31, 2016
AJ Ross had more on conditions from South Brunswick:
The rain was so heavy in Princeton Junction, that one viewer said he couldn't leave Princeton Junction station because of flash flooding.
#FlashFlood right now @ #Princton Junction in #NJ! Can't leave the station. @ABC7NY @LeeGoldbergABC7 @JeffSmithABC7 pic.twitter.com/nW24792dlD— Mathieu Blue (@MrMathieuBlue) July 30, 2016
There are also reports of up to 4 inches of rain in the Plainsboro area.
@ABC7NY Plainsboro NJ pic.twitter.com/C8AsxFf3nE— paul elian (@spte1905) July 30, 2016
Another video from Plainsboro shows streets completely flooded, with cars unable to move.
As of 5:30 p.m., Jersey Central Power and Light report 2,726 power outages in Morris County, and 1,036 in Somerset County.
Click to watch the 7-day AccuWeather forecast and get the all the weather any time at abc7NY.com/weather.


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Gerard Doustraat
- Address: Gerard Doustraat, De Pijp
- Article in De Parool (Dutch)
In a recent article in the Parool newspaper, the Gerard Doustraat in the bustling neighborhood of De Pijp was mentioned as "The Jordaan's 9 Streets in One!". With so many nice little places to shop and eat on just one street, we have to agree! But then, we are biased....we are just a few minutes walk away. ;)


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It's perhaps one of the most controversial topics and widely debated subjects in modern history: Does intelligent alien life exist? It seems people around the world have always speculated the existence of aliens, asserted government cover-ups, and shared their versions of alien encounters. In the 1960s, the U.S. experienced a surge in the interest of extraterrestrial life after a weather balloon fell over Roswell, New Mexico and subsequently incited a rash of theories linking aliens, top secret government facilities and general fandom. Crop circles, the mysterious Area 54, alleged sightings and meetings are parts of a complex puzzle.
While it can be easy to dismiss some claims made by staunch believers in other-worldly life, if the universe is so vast and humans have inhabited Earth for so long, why haven't we encountered aliens yet? Or maybe even stranger: what if we are the aliens? Check out this playlist to get at the heart of the debate and decided for yourself: What else is really out there?


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(Reuters) - Planned Parenthood said on Tuesday that the leading U.S. breast-cancer charity would no longer provide new funding to the group, which performs abortions and other services at clinics around the country.
In a statement, Planned Parenthood said the Susan G. Komen Foundation had "succumbed to political pressure" from anti-abortion groups in cutting the funding.
Komen had begun notifying local Planned Parenthood affiliates that their breast cancer prevention programs will no longer be eligible for new grants from the charity, it said.
Planned Parenthood said Komen had not responded to requests to meet and talk about the decision to cut the funding, which it said had helped thousands of women in rural and underserved communities get breast health education, screenings, and mammogram referrals.
But it said the Komen Foundation had been "repeatedly threatened" in recent years by anti-abortion groups upset with its affiliation with Planned Parenthood.
The Komen Foundation, best-known for the Race for the Cure fundraisers it sponsors around the country each year, did not immediately respond to a request for comment from Reuters.
The foundation said it raised more than $1.9 billion for breast cancer research and programs and has affiliates in more than 100 U.S. cities and 50 countries. Its symbol - the pink ribbon - is widely recognized.
Planned Parenthood said Komen's funding had helped pay for 170,000 of the more than 4 million clinical breast exams the group had performed over the past five years, as well as more than 6,400 of the 70,000 mammogram referrals it has made during that time.
Planned Parenthood has come under attack by lawmakers in several states over the past year, including North Carolina, Indiana and Kansas, who have attempted to block any government funding of the group.
In Kansas, county prosecutors outside Kansas City are pressing criminal charges against Planned Parenthood, alleging the group failed to maintain required paperwork related to the abortions it provided.
Under current law, Planned Parenthood cannot use federal funds to provide abortions though it receives federal money to provide family aid to low-income women.
Reporting by James Kelleher; Editing by Greg McCune


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Kenan Thompson Biography
Born in Atlanta, Georgia, on May 10, 1978, Kenan Thompson starred on the kids' shows All That and Kenan and Kel before branching off into film roles. Since 2003, he has been a cast member of Saturday Night Live.
Early Life
Born on May 10, 1978, in Atlanta, Georgia, Kenan Thompson is an actor and comedian known widely for his work on Saturday Night Live. As a child, his mother, Elizabeth Ann Thompson, encouraged him to take acting classes. His work was rewarded in his teens when he won a role as a film reviewer for the Turner Broadcasting Station and, at age 16, worked with Emilio Estevez in the 1994 film D2: The Mighty Ducks. That same year, he began appearing on the popular Nickelodeon show All That. In 1996, he and All That co-star Kel Mitchell began starring on a highly successful spin-off, Kenan and Kel, which lasted four seasons and helped earn Thompson a Kids' Choice Award in 1998.
Professional Success
After leaving Nickelodeon, Thompson appeared in a number of films, including Rocky and Bullwinkle (2000), Love Don't Cost a Thing (2003), Barbershop 2 (2004) and Snakes on a Plane (2006). In 2004, he also starred in the film adaptation of Fat Albert, working alongside his childhood idol, Bill Cosby. "That was awesome, that was like a dream come true!" Thompson later said about the experience. "He's the first comedian that I knew that I could watch as a kid. Other comedians were too dirty, I couldn't watch them. But Bill Cosby, I could watch him all the time."
In 2003, Thompson won a role on Saturday Night Live and has appeared on the show for more than eight seasons. Well-known for his impression of Bill Cosby and Whoopi Goldberg, he has joked that he was originally brought on to replace Tracy Morgan.
In late 2012, Thompson was reportedly developing a television comedy with TV producer, Lorne Michaels, in which Thompson would star as a young man who gives up life in the Big Apple and moves to the suburbs to live with his in-laws.
Personal Life
In 2011, Thompson married model Christina Evangeline at the Georgia Aquarium in Atlanta. Spending time between Los Angeles and New York, Thompson has remarked that he would like to start his own production company one day: "The things I do are fun; it's hard to call it a job, even though I do take it seriously."
Fact Check
We strive for accuracy and fairness. If you see something that doesn't look right, contact us!


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What Is Crowdsourcing? Making Money From Your Social Networks and Shares
You Are Already Crowdsourcing! Learn How To Use Your Social Networks for Crowd Sourcing to Increase Sales and Make More Profits and Income Earnings!
Crowdsourcing: A Brief History and Instruction Video
Have You Heard of Crowdsourcing? You Are Probably Already Using It!
You may have heard of "Crowd Sourcing" lately and even if you haven't, you soon will!
In fact, you are already Crowdsourcing just about every day if you use Social Networking Sites such as Twitter, Zurker, Facebook and Pinterest!
Every time you share an article on your Social Networks you hope that your followers will read your work and share it with their friends and followers. When they do, you are sourcing the crowd! That is Crowdsourcing!
This article will explore what crowdsourcing is and how you can use it to earn more money online as an article publisher or product vendor. Getting others to promote your products and services without direct pay or overhead is the "Going Concern" of your business. Money spent is the difference between "Outsourcing" and "Crowdsourcing".
Simply put, if people are searching for a product, service or solution that You can provide, and if you have the best products and solutions, people will naturally find your product. They will Buy it and Recommend it! This is the nature of business. You don't always have to spend a lot to acquire a lot. You should spend more time than money on any of your projects. That will lead to success.
Crowdsourcing: A Definition
Wikipedia defines Crowdsourcing as:
"Crowdsourcing is a process that involves outsourcing tasks to a distributed group of people. This process can occur both online and offline. The difference between crowdsourcing and ordinary outsourcing is that a task or problem is outsourced to an undefined public rather than a specific body, such as paid employees."
Isn't that exactly what we are doing when we socially share our articles on our social networks? If you have a Targeted Audience that is likely to read and share your articles as well as click your Ads, then you are already Crowdsourcing!
Learn More About Crowdsourcing
Crowdsourcing is the Future of Business!
Let's face it. People like what their friends like, not what corporations tell them what they should like. That used to work in the early 1900's but we have become smarter and better advised consumers.
If your friend tells you about a horrible experience at a particular restaurant, would you visit the restaurant or would you trust your friend's advice? That is the key to how crowdsourcing works! Warm Market Referrals (aka "Word of Mouth")
If you own your own business than you know this single truth: If customers are happy, they will not only come back for your products and services, but they will also tell their friends and will recommend you! That philosophy is the backbone to your business' success!
If you get good referrals you will do well. The opposite will happen if you get bad feedback and negative press. Your business and products are only as good as their reputation!
Are You Aware of Crowdsourcing?
What Do You Know About Crowdsourcing?
Stand Out In The Crowd! Be The Leader!
Ways to Take Advantage of Crowdsourcing To Make More Money for your Business: Beyond Online Social Networks
As noted, Crowdsourcing is the best way to promote your products and services to a wider audience. Getting people to "push" your products and services is not as hard as you think. You will have to work hard at first, setting up your networks with a targeted audience, but once the ball gets rolling, it will continue to bring you an increasing amount of traffic and sales.
Here are some Tips and Guidelines for making the most out of Crowdsourcing:
- Best Tip Ever: NEVER PAY MONEY for referrals or so-called "Guaranteed Traffic and Backlinks"! These are SCAMS and will earn you a reputation as a SPAMMER online!
- The best way to get traffic and backlinks is to Create Quality and share it with a Targeted Audience; customers who are already searching for your products and services!
- A Fact of Life: Most of the time, your family and friends will not be your best referrals! Over time when they see your success they can be valuable but when you are just starting out trying to promote a new product, don't be upset when they have doubts or lack of interest! Move on and find a Targeted Audience!
- Let your Products Work For You! If you have great products they will sell! Yes, you need to get the word out, but once you do, your great product or service will "Go Viral"! It's a natural process that occurs under the right conditions.
- Start A Campaign.
- Write Down Your Goals! What do you expect from your Campaign? Create a Marketing and Business Plan that is Realistic. Don't overshoot your goals.
- Deal with Disappointment! Sometimes deals fall through or you don't make your Quotas and Goals. That's OK...Forward Progress!
- Find Like-minded Individuals that are willing to Promote Your Products and you should Return the Favor.
- Consider sending out Mailings to Local Business to form Relationships and Referrals.
- No matter where you are, Look Around You for Potential Sales and Relationships.
- Remember that this is a Numbers Game; Most People Are Not Interested in Your product and you have to Sell Yourself to Sell Your Product! Never Lie or be deceitful by making false promises.
- Hand Out Business Cards
- Give Free Samples or Discounts to First Time Clients
- All of these ideas can help you to expand your Crowdsource and Networks!
Use Crowdsourcing To Keep Your Business Moving!
I'm a freelancer and social media marketer and never heard of this. Honestly it sounds like a fancy word for what we're already doing and I'm still a little confused- it sounds like a combination of a few marketing approaches. It's good to know though and food for thought.
Great advice, Matthew. UP and shared. The trick of course is not to be a spammer, nor to appear as one :-)
I am so glad you posted your hub on Facebook or I never would have found this article. It has so much valuable information. I am back after two years off. My family thought I was just wasting my time, lying to myself and that I would never be successful. They went so far as to say they didn't want to hear one more word about on line marketing, blogging or Hub Pages. It was my life... They talk about work to me all the time... I even went so far as to create a different Facebook account so I could say and do whatever I wanted without bothering them. Now, having received a check from HP after doing nothing for two years, it was a real wake up call. I have to ask myself how big that check would have been if I hadn't given up. I kept telling them that it generally takes two years, in any business, to know if you will be successful or not. I wish I could have had this article two years ago. It's a real boost to have you say to ignore what family and friends have to say. Great read, great info. I am sharing it and rating you up. Thanks!
A very interesting hub on a subject that I was completely unaware of before reading this hub....I think I will give some of your suggestions a chance....especially with my hub views diminishing every day...thanks for posting....voted up and very useful.
I think I understand the concept, but I'm unclear about the application. My target audience is people who like to read what I write but don't know it yet. I have a targeted audience and I have products that are the best quality I can make them -- a published novel and a growing number of HubPages, nonfiction and fiction. But they aren't connecting. Now what?
Anyway -- Up, Useful, Interesting, and shared.
Hi JS, and what a powerful and useful hub this one is!
I've learn quite a bit from reading your hubs about social networking and I thank you.
Voted up - useful
JS - I didn't know it was called crowdsourcing. I was actually thinking about this concept, though, as I was driving this morning. I feel like family and friends (i.e. MY family and friends) will share my stuff and people will buy more from my online store when I have put a lot of time, effort, volume and professionalism into my craft. Well done! Thanks for sharing this.
Hi J.S.
Thanks for sharing. I have learned something new.
Voted up and awesome
Sharing this one
Take care :)
Very good article. Crowd sourcing is the dream of every marketeer. It talks about a situation where your brand ambassadors are your customers/audience. They get emotionally attached to your product so much so that they think it is worth talking about. voted up and most definitely shared :) :)
Crowdsourcing rhymes with Outsourcing, doesn't it.....?
In point of fact, do you use it (outsourcing) ?
Hi, J.S., very interesting article, I had never actually heard the term crowd sourcing, but I'm very familiar with word of mouth and I always thought it extremelly important. Me and my husband run our own business and that has always been the backbone of the business. Anyway, you are quite right about friends and family, it is quite frustating, isn't it? Well, what can we do... You made the explanation very simple and have nice tips... Voted up and useful and sharing!
thanks for sharing this JS!
I never heard the term crowd sourcing but its what we've been doing all along huh? Intersting how you point out that a person's best referrals are not going to be from family. I found the same to be true - gotta wonder why! Anyways, excellent article JS =) Glad to see you writing more.
Inspiring. Thanks for taking the time.
Same here JSMatthew!!
You are so welcome JS Matthew and thank you again!!
Thanks for the valuable information about Crowd Sourcing. Have voted this up and shared!!!


text: Frannie, over at the Mary Jane's Farm Farmgirl Connection has generously offered to teach a group of us gals to make rag dollies. I couldn't wait to get started, so I embroidered a few little aprons for my "girls." Fabric is unbleached muslin. I just used regular old DMC embroidery floss. Went to WalMart today to buy some other dolly making stuff--some cotton osnaberg (like a loose-weave muslin), more muslin (unbleached and "tea dyed"), a bit of burlap (never worked with it before--don't know if I'll like it), and stuffing. Also scored some $2.00/yard poly/cotton for cowboy shirts. Yay!


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This article was originally posted on rainbowromancewriters.com/node/760 on 6/9/14
***Please visit RainbowRomanceWriters.com for more informative LGBT articles every week***
As we all know, June is gay pride month and that means a chance for
every member of the LGBTQA community to shine like a fabulous rainbow.
LOL Of course, there is also a lot of serious work happening as well,
both in politics and education. Even in the virtual world, there is
celebrating with publishers having sales, and writers hosting blog tours
and giveaways.
But the truth is, most of my friends are busy losing weight, getting tan, selecting hot outfits, and getting ready to par-tay
for Pride. In fact, that word, "Pride" holds enough weight in the
LGBTQA community that it's like saying Christmas to anyone else. Not
only is it a feeling but it is the EVENT of the summer.
I've had the privilege of attending multiple Prides, Motor City Pride in Detroit, Stonewall Columbus Pride, and my hometown Pride, Toledo Pride,
which isn't until Aug 22-24. Each festival has had its own special way
for the community within a community to show their city that LGBTQA is
more than just a social identifier. It is a vastly diverse group of
people from the everyday folk to the fabulous.
Pssst!! Did you notice that today I am including the Questioning and the Allies into the LGBT alphabet soup? Wanna know why?
Because it is Pride season and I am proud to be an A!
right, I'm an Ally. When I go to Pride I'm not an outsider or a mere
observer. This middle-age straight women—God I hate saying that
middle-age part, LOL—is a part of the alphabet.
While most of us do not like labels or stereotypes, darn it, I love being an A!
IMO, there's a big difference between being an Ally and merely saying
that you support gay rights. To me, mere talk won't earn you the
privilege of being in the LGBTQA alphabet. I'm not getting into too many
deets on the subject, but I blogged about the topic once with a post
entitled: "I'm cool that you're gay, BUT....", so if you're curious you can check that out. I not an Ally simply because I write gay romance, either. Deep in my bones I believe
in equality and I've been known to be quite vocal in defending my gay
bros and sistas. Have I offended some? Yes. Do I care? No. On an upbeat
note (this post is all about the positive) I've also changed some minds
and made others think about their words, too. The small victories are
still wins.
That's even our motto here at RRW—Changing minds one heart at a time.
Now I'm not here to list off my volunteer work or give myself props, I am just here to say:
I'm proud to be an A!
next weekend, when I get my bags packed to go to Columbus Pride with my
favorite A and G, we're gonna grab a deep-dish pizza at Fabian's in the
Short North before we head off to a drag show with a cute pair of Ls.
Then we're gonna party like rock stars and regret it all in the morning,
LOL Some of my fellow alphabet peeps will even get to see George Takei—Oh Myyy!—because
he's the Grand Marshall this year for the Columbus Pride parade
#awesome. I'm thinking about getting a pedicure with little rainbows
painted on my toes. Yeah, that's how I roll.
Whatever we do, one
thing is for certain, we are all excited about the chance to be
surrounded by our happy and united community. That's what Pride is
about, after all.
Celebrating our beautifully diverse alphabet.
you find the time this summer, I hope you can attend a Pride event near
you. LGBTQA events are, by far, full of the most loving and accepting
people you will ever meet. Like going to GRL or Rainbow Con with fellow
writers, Pride is a spectacular way to get immersed in our fabulous
Happy Pride!
~Deanna—proud to be an A!
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