Smith grabbed a bat for the first time out of necessity for the first time in his … CLICK HERE if you are having a problem viewing the photos on a mobile deviceSAN FRANCISCO — With the game on the line, there’s no one the Giants would rather have on the mound than closer Will Smith.At the plate? They’ll take Smith, too.“In the second or third inning, we were talking in the dugout about how he needs to get an at-bat.” second baseman Scooter Gennett said. “He was like, ‘I rake.’”
Scientists have created enzymes with enhanced ability to select between left- and right-handed molecules, using an “evolutionary” process, claims Manfred Reetz in a Perspective article in PNAS:1A fundamentally new approach to asymmetric catalysis in organic chemistry is described based on the in vitro evolution of enantioselective enzymes. It comprises the appropriate combination of gene mutagenesis and expression coupled with an efficient high-throughput screening system for evaluating enantioselectivity (enantiomeric excess assay). Several such cycles lead to a “Darwinistic” process, which is independent of any knowledge concerning the structure or the mechanism of the enzyme being evolved. The challenge is to choose the optimal mutagenesis methods to navigate efficiently in protein sequence space. As a first example, the combination of error-prone mutagenesis, saturation mutagenesis, and DNA-shuffling led to a dramatic enhancement of enantioselectivity of a lipase acting as a catalyst in the kinetic resolution of a chiral ester. Mutations at positions remote from the catalytically active center were identified, a surprising finding, which was explained on the basis of a novel relay mechanism. The scope and limitations of the method are discussed, including the prospect of directed evolution of stereoselective hybrid catalysts composed of robust protein hosts in which transition metal centers have been implanted.Basically, researchers built enzymes top-down instead of bottom-up. Instead of the old “rational design” method, trying to construct an active site to perform the function needed, they started with the function they wanted, and iteratively selected any “mutants” that came closest to doing the job, without stipulating how they did it. The “surprising finding” he spoke of was that a distant mutation, far from the active site, actually improved the performance of the enzyme.1Manfred T. Reetz, “Controlling the enantioselectivity of enzymes by directed evolution: Practical and theoretical ramifications,” Proceedings of the National Academy of Sciences USA, 10.1073/pnas.0306866101, published online before print April 12, 2004.He put “Darwinistic” in quotes, because it was not really Darwinistic, it was Designistic. The scientists played the role of designer by carefully selecting the results and directing the outcome. This paper, like others before it, gives two false impressions: (1) that Darwinism achieved the high specificity of proteins in the past, and (2) that Darwinian theory is a boon to science in the present. This is nothing but name-dropping. Charlie had nothing to do with it. If this were Darwinism, there would be no “directed evolution” (an oxymoron), because there would be no direction. Here, the scientists had a goal: they wanted enantioselective enzymes. Their “mutation and selection” process was results-driven by artificial selection, a form of intelligent design. Yet Reetz illogically claims, without any evidence or support (only belief), “Enzymes are products of evolution, and might therefore be expected to function with high enantioselectivity only with natural substrates under physiological conditions.” Then, in the very next breath, he falsifies this evolutionary prediction: “However, it is well known that this is not the case, because a surprisingly large number of unnatural compounds are converted with high enantioselectivity, even in organic solvents.” So does this convert him to ID theory? No, he just waltzes into the problem at hand: “Nevertheless, the problem of substrate specificity persists. In such cases several approaches to enhance enzyme stereoselectivity have been described, including site-specific mutagenesis based on theoretical considerations…” la te da, blah blah, and so on, and so forth, so we’ll design an enzyme with a creative method and give Charlie the glory. The difference between this method and the traditional bottom-up approach Reetz calls “rational design” can be compared to the difference between engineering and management. The engineer knows the physical laws and properties of the widget he is designing, and organizes the parts specifically toward the solution. The manager just says, “Build me a widget that flies.” An upper manager might devise a contest between engineers to see who can come up with the best design. All the manager cares about is the results: will it fly? He weeds out the losers and rewards the winners. The winner gets more resources to refine the design until an optimal design is produced. Even if the engineer uses trial and error and chance, given enough trials a working prototype will emerge as long as intelligence is directing the process toward a goal. In a similar way, these researchers did not need to know all the details of the structure of the enzyme they wanted to create; they just mutated ingredients and selected the few that worked, then iterated the process until the best design was filtered out of the pile. They managed the process rather than engineering it. Only Dilbert would nominate his manager for a Darwin award. Another thing. The “surprising” discovery Reetz made also argues against Darwinism. His team found that a remote amino acid, far from the active site, was essential to the function. He was so surprised by this he called it a paradigm-shifting finding: “This observation leads to a change in paradigm, because all previous attempts to influence enantioselectivity of an enzyme by using site-specific mutagenesis had focused on amino acid substitutions near the active center. Such protein engineering was designed to “carve” an appropriate chiral pocket at the active center, in line with Fischer’s “lock-and-key” hypothesis or modified versions such as Koshland’s induced fit. Later, he adds, “… our studies show that the long-standing dogma regarding the necessity of amino acid substitutions exclusively at the active site to influence enantioselectivity no longer holds.” What this means is that an enzyme is designed all the way through, not just at the active site. The “lock and key” fit of an enzyme to its substrate is amazing enough, but to think that distant amino acids actually affect the workings of the molecular machine calls into question the belief that proteins can be mutated at will, as long as they are far from the active site. This underscores the improbability of getting all the amino acids in the right order, as described in our online book, Evolution: Possible or Impossible? Let’s give credit where credit is due. This experiment is all about design. Calling this “Darwinistic” is like calling Boeing a manufacturer of tornados in junkyards.(Visited 44 times, 1 visits today)FacebookTwitterPinterestSave分享0
To build South Africans’ pride in the country’s natural, cultural and historical heritage, South African National Parks (SANParks) is offering free entry to citizens during SANParks Week. It runs from 12 to 16 September.“When people take pride in the national parks, they will start to understand the importance of conservation,” said SANParks acting head of communications, William Mabasa.#FreeAccess to National Parks starts in 2 weeks. Which Park will you be visiting? https://t.co/LrfOWBBpBL pic.twitter.com/xnfKFLkVGn— SANParks (@SANParks) August 30, 2016Started in 2006, the theme of the week this year is “Know your national parks”. Access to the parks is free to South Africans with a valid identity document; however, entry will also be free to children under the age of 16 without proof of identity.“It should be noted that the free access to the parks will not include accommodation and any commercial activities in the park such as guided safaris in vehicles or guided walks, etc,” said SANParks.Mabasa said this year’s SANParks Week would include exhibitions showcasing the myriad geographical regions of the parks. “The expo will include cultural, conservation, nursery and tourism aspects from the community, rangers and various conservation entities in order to highlight the broader South African biodiversity landscape.”Click here for a detailed list of the parks taking part in the initiative.Source: SANParks and South Africa.info reporterWould you like to use this article in your publication or on your website? See Using SouthAfrica.info material
Japan ex-PM Nakasone who boosted ties with US dies at 101 “I think you will all agree that one year isn’t enough to rebuild a team like this. It would be easier if we had a Kevin Ferrer or an Ed Daquioag, but we don’t. People are expecting us to deliver, but chemistry needs time to jell,” he said.“In a year’s time, those things have to happen with a longer period for us to bond. That’s why I’m saying for next year, give us another year, these guys will be ready.” Kammuri turning to super typhoon less likely but possible — Pagasa “We went on a rebuilding process, and the transition these players had to go through with having different coaches wasn’t easy and we had to start it from there. These players, wherever they end up, I know they will be good people. They won’t get into fights and they won’t start fights. That’s the values of UST that was instilled to us, to just play our game. Even though we’re banged up, we won’t retaliate. That’s the lesson I taught them, to be good people.”Sablan shared that he really tried his best to expose his wards to the best competition he can get in preparation for the season, taking UST to different leagues nationwide just for the team to be tested.FEATURED STORIESSPORTSWATCH: Drones light up sky in final leg of SEA Games torch runSPORTSSEA Games: Philippines picks up 1st win in men’s water poloSPORTSMalditas save PH from shutout“I did my part. I did my best. I took them everywhere just for us to play. Agusan, Davao, Malolos, Baguio, Subic, Pampanga, Cabanatuan, Laguna — we all played there because we knew that we lack in experience and exposure and for us to have that, we have to play,” he said.However, Sablan didn’t get the results he wanted. UST had a habit of losing early leads and faltering in the end as the inexperience showed. Don’t miss out on the latest news and information. Trending Articles PLAY LIST 00:50Trending Articles01:29Robredo to gov’t, after accepting anti drug post: Are you ready for me?00:50Trending Articles01:37Protesters burn down Iran consulate in Najaf01:47Panelo casts doubts on Robredo’s drug war ‘discoveries’01:29Police teams find crossbows, bows in HK university01:35Panelo suggests discounted SEA Games tickets for students02:49Robredo: True leaders perform well despite having ‘uninspiring’ boss02:42PH underwater hockey team aims to make waves in SEA Games Brace for potentially devastating typhoon approaching PH – NDRRMC Stronger peso trims PH debt value to P7.9 trillion CPP denies ‘Ka Diego’ arrest caused ‘mass panic’ among S. Tagalog NPA Photo by Tristan Tamayo/INQUIRER.netIt was a nightmare of a season for University of Santo Tomas but head coach Boy Sablan can sleep well at night knowing he had instilled good values in his players.“Even though we’re 1-13, I’m proud of these boys,” Sablan said on the heels of the Growling Tigers’ 88-85 win over University of the East on Sunday.ADVERTISEMENT For the complete collegiate sports coverage including scores, schedules and stories, visit Inquirer Varsity. LATEST STORIES La Salle shows no quit in comeback win over Ateneo MOST READ QC cops nab robbery gang leader, cohort “We can’t finish games. That’s where maturity and experience comes into play. All of the factors when it comes to our rebuilding process have worked against us,” Sablan lamented.But through it all, Sablan believed the losses will toughen his players in the long run.He is also proud of the progress of his players, who he claimed to have blossomed under his watch.“I’m happy for these players that we got a win. You know why? Because you can see their individual improvement in their time under me,” said Sablan, who raved about the development of some of his players like Marvin Lee and Jeepy Faundo, Eric Caunan and rookies Vaughn Soriano and Martin Romero.Amid talks of his ouster, Sablan pleaded for another chance as he sees a better UST team ahead.ADVERTISEMENT Typhoon Kammuri accelerates, gains strength en route to PH John Lloyd Cruz a dashing guest at Vhong Navarro’s wedding View comments Read Next
MANILA, Philippines—Kate Diaz gave the Philippines’ its first medal in the 2019 Arafura Games after taking home the silver in the women’s weightlifting competition Saturday at Darwin Convention Centre.The 15-year-older weightlifter, who’s the niece of Rio Olympics silver medalist Hidilyn Diaz, lifted a total of 115 kilograms after tallying 50 kg in the snatch and 65 kg in the clean and jerk in the women’s 45 kg division. Hontiveros presses for security audit of national power grid SEA Games hosting troubles anger Duterte Panelo: Duterte ‘angry’ with SEA Games hosting hassles DeMar DeRozan, Spurs prepared for pressure of Game 7 in Denver PH underwater hockey team aims to make waves in SEA Games PLAY LIST 02:42PH underwater hockey team aims to make waves in SEA Games01:44Philippines marks anniversary of massacre with calls for justice01:19Fire erupts in Barangay Tatalon in Quezon City01:07Trump talks impeachment while meeting NCAA athletes02:49World-class track facilities installed at NCC for SEA Games02:11Trump awards medals to Jon Voight, Alison Krauss Duterte wants probe of SEA Games mess Private companies step in to help SEA Games hosting DA eyes importing ‘galunggong’ anew Cayetano: Senate, Drilon to be blamed for SEA Games mess LATEST STORIES MOST READ Chinese-Taipei’s Shi Yue took the gold after lifting a total of 120 kg, 53 kg in the snatch and 67 kg in the clean and jerk. Don’t miss out on the latest news and information. “I learned that whatever happened, my focus and concentration will always be there.”Diaz and Shi were the only ones left to compete after about 30 weightlifters from across all weight categories failed to submit the Anti-Doping Administration and Management System (ADAMS) a document that the International Weightlifting Federation requires.Sports Related Videospowered by AdSparcRead Next “I think God has a reason why I settled for the silver medal so I won’t be too confident if I won the gold,” said Diaz, who failed to lift 70 kg in her second and third attempts in the clean and jerk, in Filipino.ADVERTISEMENT Philippine Arena Interchange inaugurated View comments
TagsTransfersAbout the authorPaul VegasShare the loveHave your say Ex-Newcastle U23 coach Beardsley responds to his football banby Paul Vegasa month agoSend to a friendShare the loveFormer Newcastle United U23 coach Peter Beardsley has responded to his football ban.The 58-year-old has been suspended from all football-related activity after being found guilty of making racist comments by an independent regulatory commission.Beardsley left his role as Newcastle United Under-23 coach earlier this year following an internal investigation. He has now been banned by the FA until April 29 next year.In a statement released on behalf of Beardsley by the player’s representatives, Farleys Solicitors LLP, the ex-England man said: “Peter Beardsley is very surprised and disappointed by the decision of the Regulatory Commission.”It was almost impossible for Peter to clear his name because of the serious flaws and contamination of evidence that occurred in the Disciplinary process before Newcastle United and by the unusual fact that The FA Rules put the burden of proof on him to prove his innocence in the proceedings.”After a long process which has been unnecessarily protracted, Peter feels vindicated that the Commission has expressly found that he is not a racist.”Peter and his legal advisers have been inundated with support from all over the Country, both from fellow professionals of the highest repute including John Barnes, Kevin Keegan, Les Ferdinand and Andrew Cole, as well as other football professionals including managers, coaches, players, and football fans, all of which provided unchallenged evidence to the Commission as to Peter’s good character, the fact that he is not a racist and whatever was said, there was no intent to cause offence.”Peter has had many great years at Newcastle United and despite the circumstances of his dismissal he will always have the Club close to his heart and wishes the fans the success they deserve in the future. Surprisingly, Newcastle United did not provide the relevant training and education for Peter. Peter has always been willing and eager to attend all and any training organised by the Club. “Peter fully appreciates all the support over what has been a difficult period for him and his family, particularly that of previous manager and colleague Arthur Cox.”Peter has categorically denied the allegations throughout whilst continuing to honour the contractual obligations of confidentiality to Newcastle United and maintaining his silence which in itself has been very difficult.”With no avenue left open to him to clear his name Peter has no choice but to acknowledge the decision and now looks forward to moving on with his life and resuming his career.”He shall respect the sanction imposed and looks forward to returning to work in football, which has been his life, at the end of his suspension.”
Don’t even think about poking the Nebraska men’s basketball student section in the eye today, Adam Woodbury. The Huskers have come prepared. In an obvious attempt to mock the Iowa big man, a notorious eye gouger, three Nebraska students are sporting protective eye goggles for the Huskers’ game against the Hawkeyes this afternoon. Check it out: Students in the @HuskerRedZone wearing protective goggles today, just in case Adam Woodbury gets too close. pic.twitter.com/bYM6rnpAGH— Robin Washut (@RobinWashut) February 22, 2015That’s just fantastic. Nebraska (13-13, 5-9 Big Ten) and Iowa (16-10, 7-6 Big Ten) are set to tip off at 3 p.m. E.T. The Huskers will be wearing special throwback uniforms for Legends Weekend.
Beverly AndrewsAPTN NewsThe residential school experience comes to life each time a survivor tells their story.But survivors of St. Anne’s residential school in Fort Albany, Ontario are in a fight to even get their stories out.They held a rally in Toronto where their testimony is being firstname.lastname@example.org
After getting back the recommendations from that review, PRRD staff made several amendments to the bylaw, including adding definitions for ‘cannabis,’ ‘cannabis accessory,’ and ‘cannabis-related business,’ while also amending a reference to the since-repealed Municipal Act.In a report presented to the Board back in February, staff wrote that the intention of the ban on cannabis sales is pre-emptive to prevent cannabis retail stores setting up shop and becoming grandfathered in.“Through the zoning amendment process, the Regional Board would have an opportunity to look at the specific context of the location and consider public input,” said the report.So far, a number of municipalities in Northeast B.C. have passed bylaws or are in the process of passing bylaws allowing recreational cannabis sales, including Fort St. John, Dawson Creek, Chetwynd, and Tumbler Ridge.Earlier this year, the District of Taylor passed a bylaw pre-emptively banning the sale of cannabis in order for District Council to learn more about the provincial government’s regulations and to gather feedback from residents.With the Regional District Board voting in favour of the bylaw passing second reading, the PRRD will hold a public hearing on the proposed bylaw, which will take place at the Regional Board meeting on August 23rd. DAWSON CREEK, B.C. – The Peace River Regional District has moved one step closer to pre-emptively prohibiting the sale of cannabis ahead of the legalization of recreational cannabis this fall.At last week’s meeting, the PRRD Board voted in favour passing second reading on the proposed bylaw, which would disallow not only the sale of recreational cannabis, but also would prohibit the sale of any items that could be used to consume cannabis such as pipes, bongs, vaporizers, or similar accessories.The proposed bylaw passed first reading back on February 22nd, after which it was sent off for a legal review. The full bylaw and discussion at last week’s meeting can be found here (item B-2 under the Bylaws section): http://prrd.bc.ca/board/agendas/2018/2018-23-881821274/AGENDA.html
With apologies to the ESPYS and the WNBA, Wednesday was what has come to be known as the deadest day on the sporting calendar. That’s because the day after Major League Baseball’s All-Star Game (which was held Tuesday) traditionally sees no activity whatsoever from North America’s “Big Four” sports leagues (the NFL, the NBA, the NHL and MLB). This barren day doesn’t always occur on the same date, but the All-Star Game has taken place during the week between July 10 and 16 for more than a decade.In honor of the occasion, we thought we’d chart the average number games per day in those leagues on any given date in a typical year:That noticeable dip in July is what we’re in the midst of, but there’s another time that is, on average, every bit as vacant as ESPYS day: Dec. 24. Christmas Eve is usually an off-day for the NBA and NHL; aside from a stray Friday game in 2004 and Monday Night Football in 2007, the only thing keeping it from complete emptiness is that it fell on a Sunday in 2006 (meaning it had a full compliment of NFL games) and a Saturday in 2005 and 2011 (both years in which the NFL shifted its Week 16 games to Saturday to avoid playing on Christmas Day). Even so, Dec. 24 averaged only four contests per year, lower than any other date over the past 10 years.Christmas itself is always the date of a few notable NBA games, but it has averaged only 4.7 games over the past decade. Combine that with the fact that the MLB All-Star Game is not held on a constant date (July 12 was the most common, seeing an average of 5.1 games), and the holiday season is, statistically, the time in which the fewest games are played per day.