Russian President Vladimir Putin will visit India on October 4 for the annual bilateral meet with Prime Minister Narendra Modi. Defence deals including the purchase of the five S-400 air defence systems between India and Russia are likely to top the agenda during Putin’s two-day visit.The Rs 39,000 crore deal is for acquiring five S-400 air defence systems and would be signed during Putin’s annual bilateral meet with Prime Minister Narendra Modi, Defence Ministry officials said.During the meeting, the two countries will discuss ways of further expanding the strategic partnership and exchange opinions on current international and regional issues. Apart from Modi, Putin will also meet with President Ram Nath Kovind.The Cabinet Committee on Security headed by Prime Minister Narendra approved the program earlier this week.When asked about India’s decision in relation to US objections over the purchase, a top Ministry of Defence official said, “We already have communicated our stand on the subject to Washington.”A formal government-to-government contract is expected to be announced during the 19th India-Russia summit on October 5.With inputs from Manjeet Singh NegiRead | Vladimir Putin to visit India for summit with PM Modi on October 5Watch | Indo-Russian friendship on full display during sports competitions
Dipa Karmakar bagged a bronze medal in the vault event on the third day of Artistic Gymnastics World Cup in Cottbus, Germany on Saturday, in another return from injury.Earlier this year, Dipa had returned from an almost two-year injury lay-off to win gold in the vault event at the FIG Artistic Gymnastics World Challenge Cup at Mersin, Turkey.She had become the first Indian gymnast to win a gold at the World Challenge Cup.However, she then endured an injury-marred Asian Games campaign and returned without a medal.On Saturday, Dipa scored 14.316 in the vault discipline to secure a bronze medal in the tournament, which is also a part of the eight-event qualifying system for the 2020 Tokyo Olympics. Dipa had qualified for the vault finals on Friday, scoring 14.100 to finish at the sixth place out of 16 gymnasts in the qualification.Brazil’s Rebeca Andrade won the gold with a score of 14.728, while USA’s Jade Carey (14.516) bagged the silver.With this performance, the Indian, who had finished fourth at the Rio Olympics, inched closer to qualifying for the 2020 Olympics.”Dipa has done well in the first tournament. She will be travelling to two more events out of Australia, Doha and Baku. But this event was the toughest. Congratulations to her coach Bisweshwar Nandi. They have made the country proud. Now Olympics is not far,” said Riyaz Ahmed Bhati, Vice-President of Gymnastic Federation of India (GFI).”I am also thankful to the sports ministry and SAI for showing faith.”On the other hand, Dipa said that she felt overwhelmed after competing with such top class gymnasts and this bronze was no less than gold for her.advertisementBronze medal in vault eventto finish my campaign at 2018 Cottibus World Cup. It was overwhelming to compete against some of the best athletes in the world!! Aaj ye bronze bhi gold lag raha hai! pic.twitter.com/WOZS3lSRZM Dipa Karmakar (@DipaKarmakar) November 24, 2018She further thanked her coach, her parents, her physio, Sports Ministry and the Gymnastics Federation for their support.Thank you to my coach Nandi Sir, ma baba, my physio, @Media_SAI, @IndiaSports Gymnastics Federation of India, @GoSportsVoices @merakiconnect Dipa Karmakar (@DipaKarmakar) November 24, 2018In the balance beam event, Dipa scored 11.066 (4.8 + 6.266) for a lowly finish out of the 32 competing gymnasts.Rakesh Patra was ranked 16th out of 29 gymnasts in parallel bar qualification round with a score of 13,033 (5.3 + 7.733).In the qualification round of men’s vault, Ashish Kumar finished at the 23rd place out of 27 gymnasts after scoring 12.866.Aruna Reddy, however, couldn’t participate in floor due to the knee injury she suffered on the opening day.The Cottbus meet is part of an eight-event qualifying system for the 2020 Olympics, under which the gymnasts will make the cut based on the their top three scores.(With PTI inputs)Watch – Mary Kom becomes first female boxer to win 6 golds at Worlds
Tottenham boss Pochettino: This not the best squad I’ve hadby Paul Vegasa month agoSend to a friendShare the loveTottenham boss Mauricio Pochettino has had a dig at his players.After two transfer windows without signing a single player, Spurs returned to business this summer and secured the services of Ryan Sessegnon, Giovani Lo Celso, Tanguy Ndomele and Jack Clarke.And although only a handful of key players left, with Kieran Trippier and Fernando Llorente moving on, Pochettino remains unsure just how good the side can be.”We will see at the end of the season. At the moment I don’t believe this is the best squad,” Pochettino said.”But I think if you only see the results, playing in the final of the Champions League, it’s easy to say the better squad was last season’s squad because we got to the final.”We will see if we can repeat, or if we win some trophy maybe we can talk about this being the best squad.” About the authorPaul VegasShare the loveHave your say
zoom Frontline has bought four Very Large Crude Carrier (VLCC) newbuilds from Greek Metrostar Management Corporation, according to the latest data provided by VesselsValue. The resale deal covers 308,000 DWT quartet under construction at South Korean shipbuilder Hyundai Heavy Industries. As disclosed, Frontline is paying USD 84.75 million for each ship.The ships in question, said to be bought on June 2nd, are Crude Hope, Crude Horn, Crude Med and Crude Progress.The first two out of the batch are set for delivery in 2016 whereas the remaining two are scheduled for completion in 2017.Metrostar ordered the ships in 2015, paying USD 95 million for each ship. Euronav was interested in purchasing the quartet, however the resale deal was never realized.The information emerges as Frontline teams up with Euronav NV and Diamond S Management LLC to set up a joint venture focusing on chartering of Suezmax vessels.The join venture will be named Suezmax Chartering and will have a large fleet of 43 Suezmaxes, including newbuildings, operated on the spot market, as disclosed by the companies.World Maritime News Staff
New Delhi: Mark Zuckerberg is determined to converge all his platforms — Facebook, WhatsApp, Messenger and Instagram — for a unified experience for billions of users and India which is the largest market for some of its services, including WhatsApp, is going to play a critical role in the success of social networking giant’s new montetisation mission. According to the company, more than 2.1 billion people now use Facebook, Instagram, WhatsApp or Messenger (its ‘Family’ of services) every day on average, and more than 2.7 billion people use at least one of its ‘Family’ of services each month. Also Read – Thermal coal import may surpass 200 MT this fiscal In India, Facebook has over 300 million users, WhatsApp another 400 million and Instagram over 70 million (millennials are the largest user group). In recent communications, Zuckerberg has talked about merging many of its services so that people can message seamlessly across platforms. About one-fourth of WhatsApp’s 1.5 billion users are in India. It is, therefore, no surprise, that Facebook chose the Indian market to test-run its digital payment service, before rolling out similar experiments in other countries. Also Read – Food grain output seen at 140.57 mt in current fiscal on monsoon boost After about one and a half years of test run, WhatsApp is now close to launch its Pay service later this year which could dominate the payment economy, given the fact that almost every Indian who has a smartphone or a Jio phone seems to have taken a liking for WhatsApp despite all the flak it received for its failure to effectively contain the spread of fake news. WhatsApp also launched a separate app for businesses last year and while the company is yet to disclose the exact number of businesses using the service, they are in millions globally. While WhatsApp for Business app is free to download, Facebook is trying to find ways to monetise this service by bringing traffic from its other platforms. “We helped businesses make the shift to mobile and now we are helping them shift to Stories, video and eventually messaging,” Facebook Chief Operating Officer Sheryl Sandberg said during the earnings call with analysts after the second quarter results. An integrated messaging ecosystem plus a payment service may open the doors for various other services, including shopping, for Facebook in India in the near future. With its photo-sharing app Instagram, Facebook has, in fact, dabbled into shopping in a limited way. “It’s early days for shopping on Instagram, but we’re excited about this over the long run,” Sandberg revealed. “In the future, we’ll enable people to use the same payments account to send money to friends and businesses on WhatsApp, shop on Instagram, or make transactions on Facebook,” Zuckerberg said. The challenge for Facebook, would be to get the next billion users to its platform as about 2.7 billion people today use the Facebook app, or the Facebook-owned Instagram, WhatsApp, or Messenger each month out of about 3.8 billion people who are connected to the Internet in the world. Zuckerberg knows it well that it cannot get the next billion users if it ignores India as more than half a billion people in the country are yet to go online. Another challenge would be to retain the people who are already in its network, especial in view of the growing popularity of the Chinese short video-sharing app TikTok in India. The good news for Facebook is that it has continued to grow despite all the challenges it has faced in the past 15 years of its existence, including the Cambridge Analytica scandal. Even its revenue has grown, so has its expenses, especially due to the historic $5 billion settlement that it has reached with US Federal Trade Commission (FTC) due to privacy concerns. Facebook expects its full-year 2019 expenses to grow to 61 per cent compared to last year and the expense linked to FTC settlement alone accounts for close to 16 percentage points of this anticipated expense growth. In fact, besides increasing expenses, the focus on privacy could slow the process of rolling out new products for the social networking giant. For Facebook, the need to create a new robust market is now. India, being the largest market for many of its services, is set to inspire some of the innovations coming from the Facebook camp.
Quebec junior health minister Lionel Carmant is refusing to bend on legislation that seeks to increase the legal age of cannabis consumption from 18 to 21 and ban the product from all public areas across the province.Carmant wasn’t even willing to accept amendments to his legislation during public consultations on the bill Tuesday in Quebec City. His stance led the Opposition Liberals to call the consultations — which are scheduled to end Wednesday — a “masquerade.”Despite calls to modify the bill from some of the 10 organizations that have so far testified in front of the legislature’s health committee, Carmant has refused to budge.“For one week, what I’ve heard is ‘psychosis’, ‘depression’, ‘motivation problems,’ ‘bad decision-making,’” Carmant said in the legislature. “Yes, I hear the groups: all the groups who support us in increasing the age to 21. Who are they? They are those taking care of patients on the ground.”Liberal health critic Andre Fortin said the groups who came Tuesday to testify in front of the health committee “have a greater chance of getting a sunburn than of convincing the minister to change his bill.” The Liberals used six questions in the legislature Tuesday to denounce what they called the government’s failure to listen and its incoherence on the cannabis file.Carmant also resisted calls from Montreal and Gatineau to modify his bill in order to permit the cities to maintain bylaws allowing the consumption of cannabis in most public areas. Montreal Mayor Valerie Plante said Carmant’s bill violates the principal of municipal autonomy. Her city currently allows citizens to smoke marijuana in most places where tobacco is permitted.Plante added that roughly 60 per cent of Montrealers are renters, who would be disproportionately affected if the government’s bill limiting cannabis consumption to private property becomes law. The city’s renters would be barred from smoking marijuana in public and in their home, if their landlords don’t permit cannabis.Alexandre Cusson, the president of Quebec’s union of municipalities, called on the minister “to respect the autonomy and the jurisdiction of local governments.”Caroline Plante, The Canadian Press
Emmy-award winning actress and St. Jude celebrity ambassador, Sofia Vergara will once again join forces with Buca di Beppo, the authentic, family-style Italian restaurant, for the second installment of Meatballs 4 Niños, a charitable campaign that supports St. Jude Children’s Research Hospital.Sofia Vergara & Buca Di Beppo to kick-off second installment of Meatballs 4 NinosMeatballs 4 Niños launched nationwide Sept. 26, 2016.Sharing a common mission, Vergara and Buca are dedicated to making an impact, boosting awareness and raising funds to support St. Jude. Drawing upon its commitment to the family experience, Buca di Beppo will donate $1 to St. Jude for every lunch and dinner meatball meal purchased.As a St. Jude celebrity ambassador, Ms. Vergara is passionate about health and wellness for children and families. Because of supporters like Buca di Beppo, families never receive a bill from St. Jude for treatment, travel, housing or food because all a family should worry about is helping their child live.“We’re honored to be partnering again with Sofia to raise money for such an important organization,” said Robert Earl, chairman and founder of Planet Hollywood International. “St. Jude Children’s Research Hospital does everything possible to save the lives of children fighting cancer, and they freely share their research breakthroughs with other doctors around the world, which helps save kids in communities everywhere. Every donation matters, so why not help raise money for pioneering research and treatments for kids with cancer and other life-threatening diseases while enjoying a meal.”“It means so much to me that one of my favorite restaurants is supporting a cause so dear to me,” said Sofia Vergara. “We were able to help so many families with the success of the first ‘Meatballs 4 Niños’ program, it’s an honor to be able to help even more families in need! I hope everyone will visit Buca di Beppo to experience their amazing meatballs and support St. Jude.”Made from the highest-quality ingredients and slow-cooked in fresh marinara sauce, Buca di Beppo is best known for their half-pound, mouth-watering meatballs, which are made fresh daily.To make reservations or to find the closest Buca di Beppo location, please click here.
(Protestors from Six Nations, Ont., and Barriere Lake, Que., demonstrate oustide the Crown-First Nations Gathering in Ottawa Tuesday. APTN/Photo)APTN National NewsOTTAWA–In speeches to open the Crown-First Nations Gathering in Ottawa Tuesday, Prime Minister Stephen Harper and Assembly of First Nations National Chief Shawn Atleo painted starkly differently visions of the paths ahead for Canada and its Indigenous population.Their two speeches diverged significantly over the issue of the Indian Act.While Harper called the Indian Act a tree with roots too deep to be uprooted at the moment, Atleo compared the 136 year-old legislation to a boulder blocking the path of First Nations.Harper said his government had no plans to scrap the Indian Act, choosing instead to find “creative ways” to work within and outside the over century-old legislation.“Our government has no grand scheme to repeal or unilaterally re-write the Indian Act. After 136 years, that tree has deep roots. Blowing up the stump would just leave a big hole,” said Harper.Atleo, however, said the legislation needed scrapping because it was “a painful obstacle to re-establishing any form of meaningful partnership. Atleo said the legislation, enacted in 1876, was a “complete abrogation” in the partnership between First Nations and Canada.“Like a rock that sits in the middle of the road, a boulder that blocks the path of collaboration, remains the Indian Act,” said Atleo. “Along with the age-old structures and policies that administer it and steadfastly resist change.”Their speeches also diverged on the pace needed for change.Harper spoke of incremental change.“There are ways, creative ways, collaborative ways, ways that involve consultation between our government, the provinces and First Nations leadership and communities,” said Harper. “Ways that provide options within the Act, or outside of it, for practical, incremental and real change.”Atleo spoke of urgency.“We need only to look at Attawapiskat, Marten Falls, Pikangikum and St. Theresa Point, among dozens of other communities, on reserve or in our cities, to see the impact of broken promises, the pain of broken lives, the tragedy of lost opportunity,” said Atleo. “Our people cannot wait.”Both leaders, however, said they believed Canada and First Nations had reached a new stage in their relationship.Harper declared a “new day” had dawned.“In past conversations, we have talked about symbolism and respect and trust. Certainly in the past lack of trust on both sides has held us back,” said Harper. “But this is a new day.”Atleo said the relationship had reached a “historic” moment.“Today must mark the beginning of renewal, the beginning of realizing our shared potential foretold in the visions of our ancestors,” said Atleo. “The step we take today, recalling the words of my late grandmother, and ability to see one another, is the first step,”The two leaders also highlighted the damage Canada had done to First Nations.Harper said Canada’s relationship with First Nations had been tainted by events like the Indian residential school system which was “an explicit attempt to destroy Aboriginal culture.”The prime minister said one of his “most rewarding days in office” was when he delivered the government’s apology for residential schools in the House of Commons in 2008.“Every relationship has its ups and downs, moments of consensus and of disagreement,” said Harper. “I believe it is important to build a narrative of any relationship based on its highest points.”Atleo said the damage inflicted on First Nations have left many First Nations sceptical of any goodwill the federal government may offer.“I understand those feelings, I respect that scepticism. It would be disrespectful of the suffering of our peoples over two centuries of agreements follows by broken promises,” said Atleo. “It is well past time that we began to undo the damage of the (Indian)Act…From it grew the reserve system, the tragedy of residential schools and offensive prohibitions on our cultural and spiritual practices, a breach of faith that has devastated families and communities ever since.”Harper, however, stuck to the theme he had developed in media interviews in the run-up to the gathering saying that his government was focused on incremental steps, not grand leaps.Harper said his government would continue with the so-called Joint Action Plan with the Assembly of First Nations which targets education, economic development, accountability and treaty relationships.“We have only just begun,” said Harper.Atleo continued his theme to “smash this status-quo” and propel First Nations people into a new realm.“Our people can make an enormous contribution to Canada if we tackle these obstacles,” said Atleo. “Next must come new fiscal relationships…We struggle under layer upon layer of wasteful bureaucratic interference, useless and expensive controls are piled upon our people squandering tax dollars and frustrating change.”
HALIFAX — A clearer picture is emerging of the young man at the centre of the mysterious demise of one of Canada’s largest cryptocurrency exchanges.Gerald Cotten, a Nova Scotia resident originally from Ontario, was 30 years old when he died suddenly while travelling in India on Dec. 9 — leaving his virtual company, QuadrigaCX, without access to $180 million in Bitcoins and other digital assets.His widow, Jennifer Robertson, has said in court documents that Cotten was the only person with access to his laptop, which is thought to contain the digital keys to the so-called cold wallets containing the missing cryptocurrency.The circumstances surrounding Cotten’s death — and the way he conducted his business from the couple’s home in Fall River, N.S. — has led to a flurry of speculation and allegations in internet chat rooms, with some former QuadrigaCX users coming forward to raise questions about the $250 million in cash and cryptocurrency owed to 115,000 of them.Cotten signed his will on Nov. 27, 2019 — less than two weeks before he died at a private hospital in Jaipur, the capital and largest city in the northern Indian state of Rajasthan.In an application to probate the will, filed on Dec. 21, 2018, Robertson confirmed that the gross value of Cotten’s personal property — all of which was left to her — was $9.6 million. She was granted the right to administer his estate as executor on Jan. 2.The will specifically states that Robertson was authorized to access his digital assets and “obtain, access, modify, delete and control (his) passwords and other electronic credentials.”Robertson, in an affidavit filed Jan. 31, said she was not involved in the business, and she insisted Cotten — as QuadrigaCX’s CEO and sole director — was the only person with access to the private digital keys.The will includes a few details about Cotten’s assets, but those items are limited to a section dealing with property that would have been bequeathed to friends and relatives should Robertson die within 30 days of his death.The list includes: a large home in Kelowna, B.C.; a property on Nova Scotia’s western shore; an undeveloped property in Fall River, N.S.; a 2017 Lexus; an “airplane;” a 2015 Mini Cooper and a 50-foot Jeanneau 51 sailboat.There was also a plan in place to provide $100,000 to Cotten’s in-laws to help them cover the costs of caring for the couple’s pet Chihuahuas, Nitro and Gully.Court documents attached to the will include a statement of death from the J.A. Snow Funeral Home in Halifax, dated Dec. 12, which says Cotten died in Jaipur on Dec. 9. The cause of death is not listed.In her affidavit, Robertson says she has been subjected to online threats, slanderous comments and speculation about Cotten’s death, “including whether he is really dead.”Robertson said Cotten was diagnosed with Crohn’s disease at the age of 24, about a year after he co-founded QuadrigaCX with his partner Mike Patryn.She said Cotten died from complications linked to the disease, which disrupts digestion by causing inflammation of the bowels.Fortis Escorts hospital in Jaipur issued a statement Thursday confirming that Cotten was admitted on Dec. 8, 2018, at 9:45 p.m. and died from a cardiac arrest at 7:26 p.m. the next night, according to CoinDesk, an online publication that tracks the cryptocurrency industry.Cotten was in septic shock when he was admitted and suffered two cardiac arrests before he died, CoinDesk reported.Meanwhile, industry critics have come forward to say the QuadrigaCX debacle has proven to be a major embarrassment for Canada’s cryptocurrency industry, which includes more than a dozen exchanges across the country.Some industry insiders have said provincial and federal officials should move quickly to do something about a business that is largely unregulated and has no independent oversight.The Canadian Securities Administrators, an umbrella organization representing provincial securities regulators, issued a statement Thursday urging Canadians to be cautious when buying crypto-assets through trading platforms.“As highlighted in recent CSA investor alerts and awareness campaigns over the past year, this means that key investor protections may not be in place,” the agency said.QuadrigaCX and its affiliated companies are registered in British Columbia, but it has no offices, no bank accounts and no employees, aside from a handful of contractors.The B.C. Securities Commission issued a statement Thursday saying it has been aware of QuadrigaCX’s operations since 2017. The agency said QuadrigaCX was not subject to regulation because it did not operate as a marketplace or exchange under B.C. securities laws.“The BCSC … (has) been urging investors to exercise caution with regard to crypto-assets,” the agency said Thursday.On Tuesday, the Nova Scotia Supreme Court granted QuadrigaCX protection from its creditors and a 30-day stay of proceedings to given the insolvent company time to find the missing currency and draft a plan to restructure or sell the business.Michael MacDonald, The Canadian Press
Rabat – The secretary of state for higher education, Khalid Samadi, has said that people who have degrees from vocational training schools are most likely to find jobs.Like King Mohammed VI, the head of government, and other officials, Samadi emphasized the importance of vocational training during a meeting at the House of Representatives on Monday.Samadi said that a field study by the Ministry of Education found that 63 percent of students with vocational training degrees find a job within nine months of graduation. The official said that the study, which sampled 20,000 students enrolled in vocational training, showed that after three years, the rate of professional integration is more than 80 percent.Read Also: Morocco’s Unemployment on the Rise 2018-2028: ReportSamadi said that a new strategy was developed in the field of vocational training, in accordance with King Mohammed VI’s instructions during his August 20 speech on the Day of the Revolution of the King and the People.The official said that the strategy aims to set up a new offer adapted to the changes that Morocco is experiencing in terms of direct investment abroad, particularly in renewable energies, the automotive industry and many other opportunities offered in the labor market.During a working session in October, King Mohammed VI ordered the government to create a committee to elaborate specific solutions to curb youth unemployment.Read Also: King Mohammed VI Gives El Othmani More Time to Tackle Youth UnemploymentThe King instructed that the committee should find solutions to youth unemployment. He also called for new vocational training programs, new training centers, and to reinforce youth entrepreneurship programs.The unemployment rate remains relatively high among youth aged 15-24 (27.5 percent). The rate among women and those with degrees is 13.8 percent and 17.1 percent, respectively.The unemployment rate of those with a vocational training certificate is 23.9 percent: 36.5 percent for women and 19.3 percent for men, according to Morocco’s High Commission for Planning (HCP).A survey from the Moroccan marketing agency Sunergia found that 4 out of 10 Moroccans would emigrate if they could due to the high unemployment rate or difficulty finding jobs and difficult social and economic situations.
The relationship between NBA players and referees has arguably never been more strained than it is right now.In January, Golden State forward Draymond Green — who is never shy about complaining and already has a league-high 14 technical fouls — said that too many refs carry personal vendettas against players and that the NBA should consider replacing its entire crop of referees. Kevin Durant, who is Green’s teammate and started the season with one ejection in his entire 10-year career, leads the NBA this year, with four early exits. And this week, Paul George and LeBron James have both outlined what they perceive to be biases in how games are officiated.1The players and officials met during the All-Star break to talk about their differences, but it’s unclear how much that has helped, if at all. One report suggested that some officials were disappointed by the lack of star-player turnout at the meeting.When the NBA’s biggest names are complaining about something, it’s obviously going to get a lot of attention. But that doesn’t necessarily mean those voices have the biggest reason to complain. That honor belongs to the Brooklyn Nets. Through Wednesday, Brooklyn had seen more blown foul calls than any other club this season, according to our analysis of The Pudding’s compilation of the NBA’s “Last Two Minute” reports. In those, the league evaluates the accuracy of calls and non-calls made by officials at the end of close games.2Specifically, in the NBA’s words: “officiated events that occurred in the last two minutes of games that were within 3 points at any time in the last two minutes of the fourth quarter or the last two minutes of any overtime period.” 1Spencer DinwiddieNets11011– Sources: NBA ‘Last Two Minute’ Reports, The Pudding 5DeMar DeRozanRaptors066– 7Dennis SchroderHawks145– 5Kristaps PorzingisKnicks066– 7J.J. BareaMavericks145– Through Wednesday, the Nets had been disadvantaged by an official’s incorrect call or incorrect non-call 28 times this season. In second place is Dallas, with 26.To get a sense of the sorts of plays that have hurt the Nets, watch the clips below, which highlight several sequences that the league later determined should have drawn whistles in Brooklyn’s favor. One involves Nets swingman Allen Crabbe, who managed to score a tough bucket despite being bumped by one defender and being fallen upon by another at the conclusion of the play. Two other examples show forward DeMarre Carroll being bumped or swiped across the arm while trying to get a shot off during the last 20 seconds of play. After many of the plays, you can see Brooklyn players turn to officials in disbelief over the fact that no foul was called.Video Playerhttps://fivethirtyeight.com/wp-content/uploads/2018/03/netsfouls.mp400:0000:0000:36Use Up/Down Arrow keys to increase or decrease volume.There are a handful of interesting takeaways from this data. For starters, it seems to provide evidence to support comments made by Brooklyn guard Spencer Dinwiddie in January suggesting that this young Nets team gets less respect from officials than other clubs.“To see the same type of respect not reciprocated is very frustrating for us,” Dinwiddie said after the Nets fell 87-85 to the Boston Celtics. “The other thing that’s very frustrating as well: We have these meetings as teams, or with [the players’ association], about respect, so we want to treat everybody with respect, right? Because everybody’s doing their job, and they’re trying their best, including us, [even if] we turn the ball over or calls are missed or whatever it is. But when you approach somebody, and they shush you or they wave you off like you’re not a man, or something of that nature, that’s also very frustrating.”On an individual level, Dinwiddie’s frustration may be justified. The 11 blown calls that left him disadvantaged led the league as of Wednesday and is a very high number considering there’s still more than a month left in the campaign. In fact, that figure is already tied for the highest number of calls that left a player disadvantaged in a single year since the NBA first began publishing these reports during the 2014-15 season. (The National Basketball Referees Association, which has long pushed for an end to the public reports, recently called them “pointless.” The union argues that publishing the corrections, which ultimately have no impact on the standings, only creates more division, despite the transparency that the NBA is aiming for.) 7Nikola JokicNuggets325– 2Will BartonNuggets178– 7Kemba WalkerHornets055– 7Marcus SmartCeltics055– These players have the most legitimate complaintsThe NBA players who had the most blown calls against them (incorrect calls and incorrect non-calls) in the last two minutes of 2017-18 games when the score was within 3 points, through Feb. 28 PlayerTeamBad CallsBad Non-CallsTotal 3Dennis Smith Jr.Mavericks077– 3LeBron JamesCavaliers077– 7Josh RichardsonHeat055– In the Jan. 23 Nets-Thunder game, according to the report, Dinwiddie was disadvantaged twice — smacked on offense (with no call) and then bulldozed on defense (also with no call) — within a two-second span during the final 10 seconds. By swallowing the whistle both times, the officials likely sealed a loss for the Nets — in particular, the second non-call would have triggered an offensive foul on George, which would have kept Russell Westbrook from making a game-winning basket seconds later. (Worth noting: Going back to the 2014-15 season, we found that incorrect non-calls occur about 8.4 times more frequently than incorrect calls, suggesting that referees would rather risk missing a call than calling a phantom foul that ends up deciding a game.)Said Dinwiddie of the play: “It’s like, that’s Russell Westbrook and Paul George … and I’m Spencer Dinwiddie.”Video Playerhttps://fivethirtyeight.com/wp-content/uploads/2018/02/pgdinwiddie.mp400:0000:0000:11Use Up/Down Arrow keys to increase or decrease volume.Whether it’s a respect issue or just a mere coincidence, five of the six NBA teams that have seen the most blown calls this season — Brooklyn, Dallas, Denver, Atlanta and Chicago — each lack a bona-fide, go-to star in the most traditional sense. None possesses a 20-point-per-game scorer, perhaps making it tougher for officials to anticipate who’d be most likely to draw a foul in a given situation.While Brooklyn has almost certainly dropped at least a game or two as a result of these missed calls — this ultimately benefits the Cavs, since the Nets don’t own their first-round pick anyway — some additional details around this subject are helpful in understanding the full picture here.First off: The Nets have played a relatively large number of games that went down to the wire, meaning that officials may have been forced to make more decisions — both correct and incorrect ones — in situations involving Brooklyn than with most other teams. The Nets have the fourth-highest of rate of incorrect calls against them this season, at 9.8 percent — meaning that nearly 10 percent of all possible calls in the Last Two Minute reports that could have gone against them did. That’s a high number, but not astronomically so compared with the leaguewide average of 6.8 percent this season.Another detail that suggests officiating equity: That a team as awful as Orlando — in contention for the top overall draft pick — has the second-lowest blown-call rate in the league (4.1 percent, ahead of only Detroit) is a relatively strong counterexample to the notion that a team needs a star to get late-game calls to go its way.Taking the opposite approach from Dinwiddie, Carroll said he wanted his teammates to stop focusing so much on how the games were being officiated.“Hollering at the refs, screaming at them — that isn’t going to do us justice,” said Carroll, who was grabbed on the wrist while going up for a shot in the closing seconds of an overtime loss to New Orleans but got no call. “They’re human just like we are, so at the end of the day, we’ve got to try something different, maybe. Hopefully it works.”CORRECTION (March 2, 7:05 p.m.): The analysis in this article originally miscounted “bad calls”/incorrect calls — in which refs made a call that shouldn’t have been made. Those calls were counted as disadvantaging the opponent of the team they were made against but should have been counted as hurting the team whistled for an infraction. The text and charts have been updated throughout. In correcting the analysis, the number of 2017-18 games that were included in the analysis was extended, from Feb. 15 to Feb. 28.Check out our latest NBA predictions.
Junior guard Sam Thompson takes a shot during a game against Penn State Jan. 29 at the Schottenstein Center. OSU lost, 71-70.Credit: Shelby Lum / Photo editorBig Ten basketball — especially this season — can mess with any team’s confidence because of the conference’s competitiveness.The Ohio State Buckeyes are no exception to difficulties and frustrations the conference can provide, having won their first two Big Ten contests before dropping five out of six.Now, OSU (18-5, 5-5) has won back-to-back road games against top 20 opponents — a 59-58 win against then-No. 14 Wisconsin Feb. 1 followed by a 76-69 victory against No. 17 Iowa Tuesday — and the feelings around the team have been a bit on the lighter side.“The mood is way better. I mean in the gym, we go to the weight room … the mood is better,” junior forward LaQuinton Ross said Friday. “In the locker room, everybody’s laughing, where like a week ago, you come in there and it’s sad in there. You can almost put on some gloomy music in there, it’s been real bad in there for us.”The two wins against ranked opponents on the road, though, has gotten things back to where they should be, Ross said.“I think winning — winning cures all,” Ross said. “We was down, we was at our lowest point this season when we lost those couple games, but I think right now, it’s looking good for us.”While the team’s confidence might be on the upswing, its coach doesn’t want the team to head into a Saturday matchup with Purdue (14-9, 4-6) with the attitude that just because the Buckeyes are returning home, a win is guaranteed.“The fact that you’ve won two games on the road and you’re coming home, I know in this league means absolutely nothing if you’re not ready to play at the level you need to play at,” coach Thad Matta said Friday. “There’s no rhyme or reason with why teams are winning right now. It’s just, ‘Hey, whoever plays best for that 40 minutes.’”OSU was able to hold off the Boilermakers, 78-69, in West Lafayette, Ind., Dec. 31, but had its hands full with sophomore center A.J. Hammons, who scored 18 points and snatched 16 rebounds. Hammons also blocked five shots, doing his best to clog up the lane.OSU junior center Amir Williams will likely shoulder the bulk of the responsibility of containing the 7-footer, but taking him out of the game is a team effort, Ross said.“He clogs up the lane. So we’re going to have to find ways to spread him out, get him out of there,” Ross, who scored a game-high 25 points in the win against Purdue on New Year’s Eve, said. “He’s a real big dude. So we gotta work on getting him off the block, and we also gotta give Amir help down there.”A big reason for the Buckeyes’ recent success could be the change in their starting lineup, as junior guard Shannon Scott has been replaced with junior forward Sam Thompson. Scott has come off the bench to average 10 points in the Buckeyes last two games, seeming to be more aggressive than before and give OSU another option offensively.“I think I got my edge back a little bit. I know coming off the bench gotta bring a spark to the team, so I feel like now that’s my role,” Scott said Friday. “And if I’m able to do that by being aggressive, I gotta keep doing that every game.”The Buckeyes have been able to finish off the two close victories on the road by making big plays down the stretch as well as hitting their free throws. That late game confidence for the Buckeyes was missing during their tough run of losses, Matta said.“We’ve been right there in every game that we haven’t won and shots haven’t fell for us in the timely fashion that we needed them to,” Matta said. “I’ve always told our guys and I’m telling them now in late game situations: Be as confident as you possibly can. Take and make a great shot. We’re perfectly fine with it.”Tipoff between the Boilermakers and Buckeyes is set for 6 p.m. at the Schottenstein Center.
Nicolas Sarkozy veut relancer la politique spatiale françaiseLe chef de l’Etat, Nicolas Sarkozy a donné un discours à l’occasion du 50e anniversaire de la création du Centre national d’études spatiales (Cnes). Devant de nombreux invités et membres de l’organisation, il a promis “un nouvel élan” à la politique spatiale de la France. Cette année, le Centre national d’études spatiales (Cnes) célèbre les 50 ans de sa création. L’occasion pour l’établissement placé sous la tutelle des ministères de la Recherche et de la Défense d’organiser une série d’évènements mais aussi de célébrer l’espace et les compétences françaises en la matière. Mardi à Toulouse, c’était ainsi au tour du président de la République Nicolas Sarkozy de rendre hommage à l’aventure spatiale française et européenne lors d’un discours qu’il a prononcé devant un parterre d’invités et de membres du CNES. Mais si le chef de l’Etat a notamment évoqué le lancement du premier satellite français Astérix en 1965, il a également exposé les enjeux et la situation actuels du secteur. Il a ainsi promis de donner “un nouvel élan” à la politique spatiale de la France, domaine qui est selon ses dires, vital à l’économie du pays comme à son avenir. “Alors que la crise fait peser de lourdes contraintes sur nos finances publiques, la solution de facilité aurait été de réduire nos investissements. C’eut été sacrifier le futur”, a t-il estimé poursuivant : “si l’espace est pour nous une priorité, c’est parce qu’il n’y a pas de souveraineté française en ignorant cet enjeu”. “La France possède la première industrie spatiale en Europe (…) ce serait folie que de ne pas donner à cette filière les moyens de se développer”, a poursuivi Nicolas Sarkozy, précisant que “l’emploi dans ce secteur s’est développé de 6% sur ces quatre dernières années”. Ajouté à cela, il a également rappelé que “le budget spatial de la France (civil) aura augmenté de 16% entre 2007 et 2012”, passant de 1,4 à 1,6 milliard d’euros, “alors qu’il avait stagné jusque-là” et qu’une enveloppe d'”un demi milliard d’euros” avait été dédiée au secteur spatial parmi les 35 milliards débloqués dans le cadre du grand emprunt pour les “investissements d’avenir”, relaie l’AFP.Lanceurs et satellites comme principaux objectifs D’après Nicolas Sarkozy, l’une des priorités du gouvernement est aujourd’hui de “préparer l’avenir des futurs lanceurs européens pour continuer de garantir notre accès autonome à l’espace”. Ainsi, l’Etat français a déjà investi quelque 83 millions d’euros pour le successeur du lanceur lourd Ariane 5, baptisé Ariane 6, pour un investissement total d’une valeur d’1,5 milliard d’euros. La France s’est engagée à verser la moitié de la somme mais les premiers financements européens prévus pour combler le reste de la facture tardent à être décidés.Autre objectif : “conforter la filière française des satellites de télécommunications” et “d’observation” de la Terre, aussi bien civils que militaires avec pour exemple le succès du programme européen Galileo de géolocalisation, le concurrent du GPS américain. Enfin, le chef de l’Etat a également insisté sur “l’exploration de l’espace”, assurant : “notre objectif prioritaire n’est pas d’envoyer des astronautes au-delà de l’orbite terrestre dans un futur proche mais d’amplifier l’exploration scientifique de notre système solaire” avec pour exemples les satellites Herschel et Planck et le vaisseau cargo européen ATV, piloté depuis Toulouse. À lire aussiSpaceX : un satellite d’Elon Musk manque d’entrer en collision avec un satellite de l’ESAFace à la concurrence grandissante de la Chine et de l’Inde, Nicolas Sarkozy a plaidé pour des “grands projets fédérateurs” européens en matière spatiale, affirmant : “il faut que l’Europe ne baisse pas la garde”.Pour voir l’intégralité du discours de Nicolas Sarkozy, rendez-vous sur le site du CNES. Le 23 novembre 2011 à 12:03 • Maxime Lambert
KUSI Newsroom Posted: July 31, 2019 KUSI Newsroom, Two abandoned homes in Grant Hill used for drug-use will be rehabilitated July 31, 2019 Updated: 10:42 PM 00:00 00:00 spaceplay / pause qunload | stop ffullscreenshift + ←→slower / faster ↑↓volume mmute ←→seek . seek to previous 12… 6 seek to 10%, 20% … 60% XColor SettingsAaAaAaAaTextBackgroundOpacity SettingsTextOpaqueSemi-TransparentBackgroundSemi-TransparentOpaqueTransparentFont SettingsSize||TypeSerif MonospaceSerifSans Serif MonospaceSans SerifCasualCursiveSmallCapsResetSave SettingsSAN DIEGO (KUSI) – These two properties have been abandoned for twenty-three years, so the city announced it is getting involved in the clean up. This is called receivership and the property owner is not happy about it. KUSI’s Ashlie Rodriguez has more on the story. Categories: Local San Diego News FacebookTwitter
Looking to tap into publishers’ growing need to expand their revenue channels, print-to-mobile solutions firm GossRSVP says its mobile phone integration service offers publishers an additional option for monetizing advertisements by allowing readers to scan as well as text message special codes for expanded content and promotional offers.“GossRSVP was founded (in July 2008) on making print interactive and to provide tools that enhance print’s value,” director Roger Belanger told FOLIO:. “The two-way interaction then provides real-time metrics.”Belanger differentiates GossRSVP from the competition—including third party integration tools services like SnapTell and SnapNow, which utilize multimedia services so consumers can take a photo of a promotional code—by the virtue of its texting functionality. “[Using SnapTell or SnapNow] is more costly to the end user since in addition to having short message service [texting], they must pay for multimedia services,” Belanger said. “That is a niche market. Our aim is to make print common to all interactive services.” The GossRSVP service is compatible with all text-enables cell phone models and all U.S. mobile service providers, including Sprint, AT&T, Verizon and T-Mobile.How It WorksGossRSVP offers publishers and advertisers the ability to create branded promotions that include a short code specific to the promotion (publishers can also sell text ads to run alongside the promotions). Readers text the code to a special number and are texted back with more information, hyperlinks, or the option to enter contests and/or sign up for texted breaking news alerts, depending on the promotion. GossRSVP can also create a scannable barcode. According to Belanger, there are “at least five ways” publishers can monetize the service. “They can resell the service to their advertisers, in the sense that they can make their static print ad interactive,” he said. “They can also upcharge the pay/click rate, reuse and/or sell demographic data, sell third party text ads and earn residual commissions for referral accounts brought on.”Clients include Questex Media, Study Breaks and Teen Ink. Study Breaks, a monthly college lifestyle title with a circulation of 42,500, has been using the GossRSVP service since last November. “We needed to expand our products and services for our advertising clients,” publisher Steve Viner told FOLIO:. “The college demographic is extremely savvy and we had to offer a service that kept up with the mobile student.”One of the magazine’s goals through using the GossRSVP technology is to expand its customer list. “We plan to roll out a text alert program to our readers (SBVIP text alerts) and build our lists through giveaway promotions and events,” said Viner. “A significant list will allow us to offer our advertising clients opportunities to send out exclusive specials, discounts and services.”Viner expects as many as 2,500 people will opt-in for the text alert program by the end of 2009. “We should be able to more than double that in 2010,” he says.GossRSVP offers three subscription packages. One covers mobile text promotions and “text-to-win” messaging. The second covers text alert opt-in/opt-out programs and the third covers interactive media links. Each individual package costs $50 per month and includes 250 free clicks, then a “low” pay-per-click rate. Accounts include 50 customers then a $50 surcharge per each additional 50 customers is added.
Don’t Hold Your Breath For Noah Hawley’s ‘Doctor Doom&…How ‘Legion’ Uses Superpowers to Explore Mental Illness Stay on target This week, Legion realized there are other characters on this show besides David and Syd. Better still, it noticed that they haven’t received nearly as much attention this season. The overall story didn’t move forward much, which is weird for the third-to-last hour of an 11-episode season. But it’s exactly what the series needed.The show picks up with a recap of what happened at the end of last week’s episode. Clark wakes up, walks through the hall, presumably to help David, and Melanie smacks him over the head. As she drags his unconscious body away, we flash back 13 days to when David first came back. We hear Oliver say “we have her.” So The Shadow King did influence her mind. We see the same conversation from the first episode of the season about how men use absence to control women. Only this time, it’s different. This time, we know she’s compromised, or at least she’s about to be. This conversation feels much more suspect, more sinister. She’s still not wrong, but her motives for having this conversation with Syd are definitely in question. As she finishes and Syd leaves the room, the camera stays on her. So, we finally get to see what Melanie’s been doing all season long. About time.Jean Smart (Photo via FX)Farouk’s hold over her has been going on for a while. It’s not long after David first shows up that Oliver appears to Melanie in the night. He tries to reminisce with her, and she reminds him of how everything’s changed. She’s not the same girl he left, she says. He tells her that’s not true, and shows Melanie her younger self in the mirror. Throughout the conversation, brief flashes of Farouk’s face are cut into the scene. It makes the whole thing even more unsettling, and doesn’t let you forget who Melanie’s really talking to here. After the artsy late title card, there’s no middleman. She’s talking to Farouk directly while Oliver stands in the background. He tells her to find the Mi Go monk and find his body. How much did you know, Melanie?Melanie has spent the entire season so far in her room, and we spend the bulk of this episode on what she’s been up to all this time. It’s a lot of sitting in her room, smoking. On its own, that would make for a pretty boring episode. She does have one interesting conversation with Kerry, though. She calls her (and Cary’s) identity into question. What if only one of them is real, and the other is a delusion? What if, instead of them formerly sharing a body, Cary is only a projection of who Kerry wishes she could be? That’s certainly not the case, but this season has explored the idea of delusions a lot. We’ve seen how powerful they can be. Ptonomy died for one. Just the suggestion that any one of these characters is actually a delusion is unsettling.Amber Midthunder, Bill Irwin (Photo via FX)It gets to Kerry, that’s for sure. It still seems to be weighing on her when she and Cary get David’s message about his plan to kill Farouk. Together, they figure out how David planted instructions in their heads, and drive off to follow them. As they pull up to the motel with the sign of the electric octopus, Kerry is still questioning what all this is for. Cary, not having had his entire existence called into question (not while he was in earshot, anyway), is confident that David has a plan. Kerry thinks it’s a stupid plan and opts to get a drink at the nearby bar. That’s going to make things interesting once Lenny shows up to collect the gun they delivered.Speaking of Lenny, hers is easily the best story of this week’s episode. Her arc this week is everything that made us love Legion in its first season. Lenny is now free of Division 3 after David’s visit last week, and she’s taking full advantage of her new body. She visits her old hangout, where people are doing what looks like the same drug Melanie’s been on this whole season. There, she’s treated like a queen, and her old friends throw a huge party in her return. That’s when things start to get weird. As the drug-fueled party goes on, we’re treated to an overwhelming torrent of image and sound. The camera kaleidoscopes the view, so we can’t quite tell what’s going on. A strange woman stares directly at Lenny, which means she also stares directly at us. The camera breaks up her body in a way that makes the whole thing just a little disturbing. As her body comes together, we realize it’s Amy Haller.Aubrey Plaza (Photo via FX)Legion might be the only show where characters get their best episodes after they die. First, we got an awesome journey through Division 3’s mainframe after Ptonomy died. Now, were getting more one-on-one time with Amy than we ever did when she still had her own body. And in the process, we learn so much more about Lenny. Despite her hard exterior, she does love David. She doesn’t show it in the same way that Syd does, but she’d still do anything for him. Even if she doesn’t want to admit it to herself without a little prodding from Amy. And boy, does Amy prod. She constantly appears to Lenny, freaking her out while she’s trying to eat breakfast or sleep. Lenny also sees The World’s Angriest Boy from Season One, which is still the scariest image this show has produced. Amy’s constant analysis and spooking of Lenny, and Lenny’s begrudging acceptance of her own feelings, is so much fun to watch in this episode. We only have a couple left in this season, but I’m hoping for a whole lot more of this.Thanks to Amy playing the part of Lenny’s conscience, she stops ignoring the plan David put into her head. She follows Amy’s directions to the electric octopus and enters the car… while the Loudermilks watch from the diner. I was looking forward to a confrontation, but what actually happened was even better. As soon as Lenny gets in the car, it starts glowing green and disappears. The look on Cary and Kerry’s faces is priceless. How did David plan for that? Hopefully, we find out next week. For now, Lenny is in position (after managing to take the gun from the trunk before the car fully caught fire), and the Loudermilks are tracking the weapon to figure out what’s going on.(Photo via FX)That might complicate David’s plan some, but not as much as Melanie. The episode ends just a little after the last one did. After ironically lamenting that everything ends in violence, she knocks out Clark and drags his body away. Then, she finally gets what she wants. Well, what she thinks she wants. She tells Oliver what she knows of David’s plan, which… it’s still unclear how much he told anyone at Division 3. We get to see all of this week to week, and even we don’t know. As she touches Oliver’s face though, her words to Syd, reiterated at the start of this episode, take on a new meaning. Melanie’s loneliness made her vulnerable. Farouk took control of Oliver and used his absence to control her. That’s one chillingly poetic way to end an episode.It’s strange to see an entire episode of Legion without David in it. In some ways, it almost feels a little like filler. We basically spend the entire time seeing what all the other characters were doing during last week’s episode. The overall story doesn’t move forward, but we’re given much more context. Really, this is exactly what this season of Legion needed. It’s natural that a show would follow its main character almost exclusively, but David’s been on his own a lot this season. That means we don’t get to see the other characters as much, and that’s a shame. There are some great characters on this show not named David or Syd. It took too long for this season to let us get to know them.I’m glad it did, though. Melanie’s actions (or lack thereof) make so much more sense now that we know what she’s been going through. Likewise, the Loudermilks’ conversation was the deepest the show has ever gone into either character. In the first season, they were fairly simply defined. Cary was the smart one, Kerry was the tough one. Forcing them apart this season has done wonders for both characters, and this episode really lets us know how Kerry sees the world. She doesn’t just dislike it; she’s scared of it. She doesn’t like change and rejects the idea completely, going so far as to say she’ll kill Death to keep her brother around. With only two episodes left, the rest of the season will be spent with David and whatever his plan turns out to be. And I’m excited about that. I just wish there had been more episodes like this.Let us know what you like about Geek by taking our survey.
Prof. Steven A. Benner discussed the paper that he, Dr. Kwame Sefah and their co-authors published in Proceedings of the National Academy of Sciences – starting with the main challenges they faced. One such challenge was overcoming the limitation of chemical theory by directly designing binders through in vitro recreation of the Darwinian processes that nature uses to molecular binders. “Current chemical theory is quite able to do broad brush design,” Benner tells Phys.org. Indeed, Benner notes, the scientists used current chemical theory to design the additional nucleotides in their AEGIS technology. “However,” he continues, “both at the highest level of quantum mechanics as well as the more practical level of molecular dynamics, the assumptions in models of reality are not good enough to allow energy output to be accurate to better than, say, 5 kcal per mole – the difference between success and failure in, as an example, a pharmaceutical.”Conversely, Benner adds, while Darwinism is incapable of doing what he calls big design, it is capable of fine tuning. The whole idea behind this strategy, he explains, is to construct by coarse design a system that is better able to support Darwinism and the laboratory environment. “This publication,” he points out, “represents the first case in which this combination has been fully successful.” (Benner notes that development of this technology was funded by the Defense Threat Reduction Agency, which consolidates a variety of US Defense Department functions to deal more effectively with the threats posed by nuclear, chemical, or biological weapons.)A second challenge, says Benner, was demonstrating the first example of SELEX using AEGIS to produce a molecule that binds to cancer cells. “Molecular biological and genetic engineering tools, which have advanced so far over the past half-century, and which have led to several Nobel Prizes, have been advanced for use with natural genetic systems, not our artificially expanded systems. Therefore, we needed to develop analogous molecular biological tools for AEGIS. These included tools to manufacturer the AEGIS components, chemistry to synthesize AEGIS oligonucleotides, enzymes to do AEGIS PCR amplification, procedures to sequence AEGIS DNA, and so on.” Incremental research and improvements in technology have allowed AEGIS DNA to be manipulated almost the same level as natural DNA is by classical molecular biology. Explore further © 2014 Phys.org. All rights reserved. Citation: The ties that bind: Recreating Darwinian ligand evolution in vitro (2014, January 24) retrieved 18 August 2019 from https://phys.org/news/2014-01-ties-recreating-darwinian-ligand-evolution.html Schematic of the AEGIS cell–SELEX used here. A GACTZP DNA library, consisting of randomized sequences and primer sites, was first incubated with the target cells. Unbound sequences were then removed by washing. Bound sequences having affinity to the target cells were collected. “Survivors” in the enriched collection were amplified using a FITC-labeled 5´-primer and a biotinylated 3´-primer by GACTZP six-nucleotide PCR (22). Enriched FITC-conjugated single-stranded DNA obtained from PCR products was used for the next round of selection. The binding affinity of survivors from 9th round up to 12th round of selection was monitored by flow cytometer. The survivors from 12th round selection were subjected to deep sequencing. Credit: Copyright © PNAS, doi:10.1073/pnas.1311778111 More information: In vitro selection with artificial expanded genetic information systems, PNAS Published online before print December 30, 2013, doi:10.1073/pnas.1311778111Related: 1Toward the Combinatorial Selection of Chemically Modified DNAzyme RNase A Mimics Active Against all-RNA Substrates, ACS Combinatorial Science 2013 15 (4), 174-182, doi:10.1021/co3001378 A tighter fit with artificial DNA Journal information: Proceedings of the National Academy of Sciences To address these challenges, the scientists had to develop chemical pipelines to synthesize AEGIS components on multi-gram scales; develop DNA and RNA polymerase to make DNA and RNA that contain AEGIS components; and create tools to restrict decomposition of DNA containing AEGIS components.Benner points out that because SELEX, as originally proposed by Larry Gold two decades ago, follows a simple recipe, their findings could possibly generate receptors, ligands, and catalysts having sequence diversities nearer to that displayed by proteins. Specifically, that recipe entails: 1. Synthesizing a library of xNA (xeno-nucleic acid, or synthetic DNA) molecules, typically containing 1011-1014 members. 2. Placing the library in contact with the target in order to separate molecules in the library that bind to the target from molecules that do not. (To select catalysts, xNA libraries are put in an environment where an ability to catalyze a reaction separates them from xNA molecules that cannot.) 3. Survivors are enriched in a pool of xNA molecules that bind to the target (or catalyze a reaction), and then amplified in a polymerase chain reaction (PCR). 4. After a sufficient number of rounds of selection, individual aptamers (oligonucleic acid or peptide molecules that bind to a specific target molecule) are recovered, sequenced, re-synthesized and characterized as molecular species having defined molecular structures.”As with many new technologies,” Benner explains, “SELEX was initially regarded as having high potential, and aptamers were hoped to eventually rival antibodies as binders. This potential has been fulfilled in part. xNA aptamers are known for many targets, including carbohydrates, small molecules, and peptides.” In fact, he adds, some aptamers have already entered the clinic – although only after extensive modification of the aptamers originally selected.”However, as SELEX evolved as a field,” Benner continues, “it became clear that the binding diversity and catalytic power of xNA aptamers built from standard nucleotides (G, A, C, and T/U) were not able to match the diversity and power of proteins, including antibodies. At the same time, targets for the best aptamers had a natural propensity to bind to xNA, yielding aptamers with nanomolar dissociation constants.” Dissociation constants are a specific type of equilibrium constant that measure the propensity of a larger object to reversibly separate, or dissociate, into smaller components. Ligands having nanomolar (nM) dissociation constants bind more tightly to a particular protein than those with micromolar (μM) dissociation constants. (A molar is a measure of amount-of-substance concentration.)”For example, Benner illustrates, “aptamers selected to bind to nucleocapsid proteins, reverse transcriptase and HIV integrase had affinities of 2 nM, 0.3-20 nM, and 10-800 nM, respectively. In contrast, aptamers against small molecules were generally selected to have poorer affinities in the micromolar range. For example, dissociation constant values reported for aptamers selected to bind citrulline and arginine ranged from 0.3 to 65 μM, while the values for specific aptamers that bind ATP and xanthine were only 3.3 and 6 μM, respectively.”Benner point out that similar disappointment was also the rule for xNAzymes (xNA molecules that catalyze a preselected reaction). “While many xNAzymes have been reported, the best again performed well only for reactions of nucleic acids themselves, including phosphate hydrolysis, transesterification (the process of exchanging the organic group R″ of an ester with the organic group R′ of an alcohol), xNA ligation, and xNA polymerization. Even here, however, the rates of reactions were not impressive, and certainly not impressive when compared to natural enzymes that have evolved over millions of years to catalyze a specific reaction.” He adds that they also did not perform orders of magnitude better than designed protein catalysts or antibody-based catalysts.”In retrospect,” Benner points out, “we might have expected xNA aptamers to not perform as well as proteins, since the latter are built from 20 different units and carry a wide range of chemical functionalities.” These include positively-charged nitrogens (on lysine and arginine), anionic groups (aspartate and glutamate), hydrophobic groups (valine, leucine and others), polarizable groups (such as the tryptophan indole and the methionine thioether), catalytic units (including histidine), and metal coordinating groups (cysteine and histidine). In contrast, he adds, standard xNA nucleotides carry little of this functionality. “Accordingly,” Benner continues, “the Benner group and others added functionality to the four standard nucleotides in an attempt to get better performing xNA molecules – and this too has had some success.” Examples include:Prof. David Perrin and his coworkers1 made DNA where each of the four standard xNA building blocks (GACT) carried a different functional group; applying these to select for DNA catalysts, they saw an improvement in the catalytic power of the emerging DNAzymes (DNA molecules that have the ability to perform a chemical reaction, such as catalytic action)SomaLogic modifies the 5-position of pyrimidines with benzyl, naphthyl, tryptamino, and isobutyl groups, inter alia, generating SOMAmers (Slow Off-rate Modified Aptamers); the company reports a set of these that detect ∼800 different human proteins in blood volumes as small as 15 microliters (μL), with affinities in the 0.1 picomolars (pM) – 1 μM rangeBenner also tells Phys.org that AEGIS–SELEX would be improved by the following investigations being developed in their laboratories:Strains of E. coli cells that can propagate plasmids containing GACTZP DNA (a form of xNA), which he notes is the core of their current activitiesA technology for directly sequencing single molecule Z:P pairsPolymerases with still higher levels of fidelity and efficiencyMoving forward, Benner tells Phys.org, the scientists are developing E. coli strains that can propagate plasmids containing GACTZP DNA, and are improving sequencing. “We also hope to also develop the chemistry and enzymology of the xNA S:B pair, as well as the xNA K:X and V:J pairs, in this order.”Benner notes that there are other areas of research that might benefit from their study. “Nearly everything in medicine involves the binding of molecules to other molecules,” he tells Phys.org. “This is true in the research laboratory, in clinical diagnostics, and even within patients. Medicine needs drugs that bind to therapeutic targets to cure diseases; diagnostics needs molecules that bind to markers to indicate the presence of the diseased state; and researchers need molecules that bind to functional molecules to track their movement within cells.” For this reason, he says, binding to and between targets is key to essentially all work done under the auspices of the National Institutes of Health (NIH), even when that binding is not the explicit focus of that work.”Accordingly,” Benner concludes, “biomedical researchers, diagnosticians and clinicians have long sought a technology that delivers binding molecules and catalysts on demand. In this vision, the technology would deliver binders quickly, reliably and inexpensively, to any researcher who has in hand some of the target. AEGIS-SELEX will be, we hope, this technology.” (Phys.org) —A key feature of certain chemicals is their ability to bind to other molecules – a property that emerged through evolution – but current chemical theory lacks the ability to design binders from first principles. To resolve this dilemma, scientists at the University of Florida and the Foundation for Applied Molecular Evolution have recreated these Darwinian processes in vitro (that is, in the laboratory). Their approach extracts nucleic acids as binders from DNA/RNA libraries to evolve through a process called Systematic Evolution of Ligands by Exponential Enrichment, or SELEX. (A ligand is a substance, usually a small molecule, that forms a complex with a biomolecule to serve a biological purpose,) However, natural DNA/RNA has only four nucleotides as building blocks, and so often yields poor binding molecules. By integrating synthetic biology, sequencing tools, and polymerase chain reaction (PCR) amplification, and additional DNA/RNA building blocks from an Artificially Expanded Genetic Information Systems (AEGIS), the scientists successfully demonstrated the first example of SELEX using AEGIS, producing a molecule that binds to cancer cells. This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
US Consul General Meets Agents1US Consul General Meets Agents at Visit USA Expo BrisbanePrizes, presentations and a celebrity vibe brought Brisbane travel agents out in droves to the Visit USA Expo in Brisbane last night with over 250 agents attending.Held at Howard Smith Wharves, travel agents chanted throughout the prize rounds, celebrating the prize-winners announced by I’m A Celebrity Get Me Out of Here winner and MC Mr Richard Reid.US Consul General Sharon Hudson-Dean also made a surprise visit to mix with the agents commenting,“The energy and enthusiasm at the Visit USA Expos 2019 is really impressive.”“The USA has an endless list of top class tourist destinations and we’re thrilled that Australian travellers come for long visits to explore and experience as much as they can, frequently more than once,” commented Ms Hudson-Dean. “Our doors are open and we love to host Australian visitors.”The roadshow moves on to Sydney tonight 20 February at the Hilton Hotel.Details at www.usatraveltrade.org.auSource = Visit USA
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