Dick Jauron2008BUF25 Bill BelichickNE1621+164+761 COACHTEAMSEASONSPLAYOFF WINSBEFORE 2015DURING 2015CHANCE OF FIRING Ron RiveraCAR51+145+1543 Pete CarrollSEA67+276-37<1 Chuck PaganoIND43+173-316 Mike ZimmerMIN20+4+995 Dan QuinnATL10—+6<1 Dave Campo2001DAL39 Jim TomsulaSF10—-103<1 Jason GarrettDAL61+141-11735 John Mackovic1985KC28 Mike McCarthyGB107+136+202 Mike PettineCLE20+32-8319 Herman Edwards2007KC47% Chan Gailey2011BUF28 The idea here is to measure what sort of team performance, somewhat devoid of context, would get a typical coach fired. You’ll notice in the table that Marvin Lewis — a coach pretty unlikely to be fired — is third on this list; that’s mainly because he’s been with the Bengals for 13 years and has zero playoff wins. The real world context is that while that is a broadly undesirable outcome, the Bengals being the Bengals, the team has more than exceeded the existential target of being Not The Browns. (You can see the lasting improvement that Lewis has brought to Cincinnati in the “before 2015″ column, which shows how much the team’s Elo rating improved between the time he got the job and the beginning of this season.) So Marv, like Chip, is probably fine, for reasons that are very different but just as amusing.As for Kelly, he’s in his third year of his tenure with a club, after winning zero playoff games in Years 1 and 2 — a scenario that has traditionally been the death zone for NFL coaches. Coaches in that predicament must show progress to keep their jobs: Roughly two-thirds of surviving coaches improved their team’s Elo rating (relative to preseason expectations) in Year 3, while nearly three-quarters of those fired oversaw an Elo decline from the preseason. So the Eagles’ 86.4-point Elo drop this season doesn’t look good for Kelly — since 1970, only 15 of the 128 coaches in Kelly’s position (Year 3 with a team, no previous playoff victories) oversaw a bigger drop-off in Elo through 11 games of the schedule, and two-thirds of them were fired before the following season began. John FoxCHI10—+50<1 Sometimes coaches still survive odds like Kelly’s. This table shows the coaches whose jobs were in the most jeopardy 11 games into a season yet went on to keep the job. But if Kelly does manage to stick with Philly beyond this season, he would set a new mark for unlikely job retention.Kelly’s trajectory wasn’t always so negative. After Philly beat Dallas in early November to make their record 4-4, there was only about a 5 percent chance that Kelly would be fired according to the model. But the Eagles’ current three-game losing streak has caused his probability of being fired to skyrocket: Things look bad for Chip Kelly and his Eagles. Fans are calling for his head; discord is rampant in the locker room; Kelly seems to be linked to every college job not nailed down or on fire; and the Eagles have found themselves on the receiving end of consecutive beatdowns so humiliating that mayor-turned-governor-turned-commentator Ed Rendell — a man last seen in public supplication outside a McDonald’s, begging for a McRib — was so ashamed that he hid his head in a bag. If Kelly is the NFL’s mad scientist, the lab is on fire.In the short term, Kelly is probably safe. He has two years left on his contract after 2015, and his newfound authority over Philadelphia’s roster — wrestled away from Howie Roseman in a power struggle in January — makes him a little more entrenched than your typical head coach. But the Eagles have also been one of the NFL’s most disappointing teams, by both the eye test and fancier metrics. So while Kelly the personnel czar still has some rope, we can entertain ourselves with a thought exercise wondering just how often such a disastrous season traditionally leads to a coaching change.To measure just what it takes for a coach to get fired in the NFL, I trained a classification model on data for every NFL coach since the 1970 AFL-NFL merger, looking for the factors that predict whether he’ll return the following season. The best model, in terms of having the lowest “out-of-bag error,” accounts for how long a coach has been with his team, the team’s outlook going into the season, and how many playoff wins the coach has recorded during his tenure with the team. Coaches are typically given more leeway early, with firings peaking three to six years into their tenures, and unsurprisingly, playoff wins buy more job security. We used our Elo ratings as a proxy for team outlook; whatever you think of its predictive capabilities, Elo is a fantastic gauge of team perception and expectations.According to that historical rubric, no current coach1So, excluding Joe Philbin and Ken Whisenhunt, both of whom were fired earlier this season. should be feeling the heat more than Kelly, whose indicators have traditionally led to termination a shade over half the time (through 11 games): Gus BradleyJAX30+8-1851 Mike McCoySD31+32-1055 Neill Armstrong1980CHI22 Sean PaytonNO96+94-7619 Bill O’BrienHOU20+120+10<1 Jack Del RioOAK10—+37<1 Gary KubiakDEN10—+66<1 Sam Wyche1994TB30 Jim CaldwellDET20+66-645 John Mazur1971NE29 Rex RyanBUF10—-22<1 Jeff FisherSTL40+124-5613 Chip KellyPHI30+144-8652% Lovie SmithTB20-59+4517 COACHYEARTEAMCHANCE OF FIRING John HarbaughBAL810+117-741 Marvin LewisCIN130+184+10140 Dave McGinnis2002ARI21 Bruce AriansARI30+120+125<1 Tom CoughlinNYG128+81+217 Andy ReidKC30+185+841 Todd BowlesNYJ10—+34<1 Jay GrudenWAS20-28+55<1 Mike TomlinPIT95-6+24 Jim Hanifan1983CRD26 ELO CHANGE There’s still time for Kelly to turn things around. For one, the average coach who was fired since 1970 was assigned a 76 percent probability by the model at this stage of the season, so Kelly, at 52 percent, has some room left to fall. Second, despite their abiding awfulness, the Eagles somehow have a 15 percent chance of winning the NFC East, which would put a little shine on the turd. Although one of the most similar coaching seasons to Kelly’s2In terms of the arc his probability of being fired has taken each week. resulted in Wade Phillips being fired by the Denver Broncos in 1994, other similar years belonged to coaches who held on for another year (Bruce Coslet with the 1993 Jets) or even unexpectedly went to a Super Bowl a year later (Jim Fassel with the 2000 Giants).However the season plays out, Kelly will probably hang onto his job — particularly given the personnel control matter we mentioned earlier. But based on what typically gets coaches fired, Kelly should be thankful that he’ll (probably) remain employed when the smoke clears on this garbage fire, because historical precedent says it should pretty much be a coin flip whether he gets swept out with the ashes. read more

first_img United Airlines Adds Service to Providenciales from Houston this Summer Facebook Twitter Google+LinkedInPinterestWhatsApp American Airlines flights stuck Related Items:american airlines, tokyo Facebook Twitter Google+LinkedInPinterestWhatsAppAmerican Airlines on Tuesday (August 18, 2015) started its Boeing 787-8 Dreamliner service from Japan between Tokyo Narita and Chicago O’Hare, its first international 787 service from Chicago. Showcasing the new modern American Airlines, the aircraft features 28 lie-flat business class seats, 48 Main Cabin Extra seats with a further 150 seats in Main Cabin. The aircraft departs Tokyo as flight AA154 at 6.10 p.m. and arrives in Chicago at 4.20 p.m. the same day.Art Torno, American Airlines’ Senior Vice President for International said: “Our Japanese customers are going to love this aircraft when they see the modern interiors we have on board, as part of the more than $2 billion investments in customer improvements we delivering.”Derek DeCross American Airlines’ Vice President, Global Sales comments: “Our goal is for our customers to experience a product that’s better than our competitors and that includes more Japanese speaking staff, better Japanese food options and entertainment. I’m confident that the combination of American Airlines and Japan Airlines makes us a winning formula for Japanese customers.”Arranged in a two-class cabin configuration, American’s 787-8 features 28 fully lie-flat Business Class seats arranged in a 1-2-1 configuration. The custom-designed forward-and rear-facing seats provide direct-aisle access for every Business Class customer for more mobility throughout the cabin and comes equipped with satellite Wi-Fi capability to keep customers connected while traveling internationally. The premium cabin also features inflight entertainment selections on a 16 inch HD Panasonic touchscreen monitor positioned in each seat with up to 250 movies and 180 TV programs. Business Class customers will also be offered Bose® QuietComfort® Acoustic Noise Cancelling® headphones and ear buds. Each seat is equipped with universal AC power outlets and a USB jack.The Main Cabin has 48 Main Cabin Extra seats in a 3-3-3 configuration, offering customers up to six inches of additional legroom plus 150 Main Cabin seats also arranged in a 3-3-3 configuration. Every seat offers a 9-inch HD Panasonic touchscreen monitor with an assortment of movies, TV programs, games and audio selections. Each Main Cabin seat is also equipped with universal AC power outlets and a USB jack.Other advanced features on the Dreamliner include larger dimmable windows, improved cabin humidity and improved sound quality. American’s 787-8s will also feature a walk-up bar stocked with snacks and refreshments for customers traveling in the premium cabin. Currently American has placed firm orders for 42 Boeing 787 aircraft, with the fleet becoming even younger, more modern and more efficient as additional aircraft are delivered into service.American already has the youngest fleet of the U.S. global network carriers, with an average aircraft age of 12.3 years. In 2015, American is taking delivery of an average of two new aircraft per week. Meanwhile, American is in the midst of more than $2 billion in planned improvements to give customers a superior travel experience around the world. Recommended for you US Airways no more, last flight to TCI ‘emotional’last_img read more

first_imgMcGovern began his career in publishing in 1959 with a part-time editorial job at Computers and Automation magazine where he ultimately became associate editor and associate publisher.McGovern founded the International Data Corporation in 1964, which is now a subsidiary company of IDG. By 1967 he launched IDG’s flagship publication, Computerworld. And in 1972 he exported the concept to Asia with the launch of Shukan Computer in Japan.His push for global IT is underscored by his investments in the People’s Republic of China where he was recognized with the International Investment Achievement Award at the CCTV 2007 China Economic Leadership Awards.McGovern has also received other honors including lifetime achievement awards from American Business Media, the Magazine Publishers of America and the American Society of Business Publications Editors.IDG will remain a privately held company overseen by its board with Kirk Campbell, president and CEO of IDC and Michael Friedenberg, CEO of IDG Communications Worldwide, remaining at their posts.“Pat always believed that each of IDG’s business units should run like independently managed companies and that structure and process will continue,” says Ted Bloom, IDG’s president and CFO, in a statement. “The best way we can all honor Pat is for us to continue being successful with the structure he set up 50 years ago.”You can view the full IDG announcement of McGovern’s passing here. International Data Group (IDG) founder and chairman Patrick J. McGovern passed away on March 19 at Stanford Hospital in Palo Alto, Calif., according to a company announcement Thursday. “IDG has lost a true visionary,” says newly elected IDG Board Chairman Walter Boyd in a statement, “and the IT community has lost one of its most exceptional citizens.”The lauded information technology media pioneer and generous philanthropist spent 50 years developing, championing and expanding IDG’s network of magazines, digital properties and events. Ultimately, he oversaw IDG’s launch of roughly 300 magazines and newspapers, 460 websites, 200 mobile bile apps and 700 events in 97 countries.“Pat’s foremost desire was for IDG to make the world a better place through the medium of information technology,” Boyd says. “We have an outstanding leadership team in place to ensure that the company he created will continue to grow and prosper.”last_img read more

first_img See It Read Google Home Hub review Galaxy’s Edge from every angle: We take you along for… Rylo 5.8K 360 Video Camera: $250 (save $250) $59 at eBay Mentioned Above Apple iPhone XS (64GB, space gray) Post a comment Other Labor Day sales you should check out Best Buy: In addition to some pretty solid MacBook deals that have been running for about a week already, Best Buy is offering up to 40% off major appliances like washers, dryers and stoves. There are also gift cards available with the purchase of select appliances. See it at Best BuyDell: Through Aug. 28, Dell is offering an extra 12% off various laptops, desktops and electronics. And check back starting Aug. 29 for a big batch of Labor Day doorbusters. See it at DellGlassesUSA: Aug. 29 – Sept. 3 only, you can save 65% on all frames with promo code labor65. See it at GlassesUSALenovo: The tech company is offering a large assortment of deals and doorbusters through Labor Day, with the promise of up to 56% off certain items — including, at this writing, the IdeaPad 730S laptop for $700 (save $300).See it at LenovoLensabl: Want to keep the frames you already love and paid for? Lensabl lets you mail them in for new lenses, based on your prescription. From now through Sept. 2 only, you can save 20% on the blue light-blocking lens option with promo code BLOCKBLUE. See it at LensablSears: Between now and Sept. 7, you can save up to 40% on appliances (plus an additional 10% if you shop online), up to 60% on mattresses, up to 50% on Craftsman products and more. The store is also offering some fairly hefty cashback bonuses. See it at SearsNote: This post was published previously and is continuously updated with new information.CNET’s Cheapskate scours the web for great deals on tech products and much more. For the latest deals and updates, follow the Cheapskate on Facebook and Twitter. Questions about the Cheapskate blog? Find the answers on our FAQ page, and find more great buys on the CNET Deals page. Amazon Best laptops for college students: We’ve got an affordable laptop for every student. Best live TV streaming services: Ditch your cable company but keep the live channels and DVR. Rylo $520 at HP Tidal 3-month family subscription: $5.99 (save $54) 0 The Cheapskate $999 Sarah Tew/CNET $999 Share your voice Spotify and most other streaming services rely on compressed audio, which robs the listener of full fidelity. Enter Tidal, the only “major” service that delivers lossless audio — meaning at least on par with CD quality, if not better. Want to see (er, hear) the difference for yourself? Grab this excellent extended trial while you can. It’s just $6 for three months, and it’s good for up to six listeners. $155 at Google Express I thought this might be a mistake, but, no, the weirdly named HP Laptop 15t Value is indeed quite the value at this price. Specs include an Intel Core i7 processor, 12GB of RAM, a 256GB solid-state drive and a 15.6-inch display. However, I strongly recommend paying an extra $50 to upgrade that display to FHD (1,920×1,080), because you’re not likely to be happy with the native 1,366×768 resolution. Studio Ghibli’s Totoro and The Catbus at MCM London Comic Con. Ollie Millington/WireImage/Getty A Studio Ghibli theme park is being built in Japan, reports say.The park, based on the Tokyo anime studio’s films, will be in Expo 2005 Aichi Commemorative Park near Nagoya, according to Variety, and will open in fall 2022.It’s expected to have five themed areas, including Princess Mononoke and Howl’s Moving Castle. My Neighbor Totoro will also be featured in the park, IGN reported. Academy Award-winning film Spirited Away was not mentioned in either report.During a press conference Friday, Studio Ghibli producer Toshio Suzuki reportedly said film creator Hayao Miyazaki is working on the park’s creative side.”[Miyazaki] can’t leave anything up to other people. He’s a meddlesome old man,” Variety reported Suzuki as saying. “[He] is not the type to look on supportively from a distance. He starts in right away with ‘do this’ and ‘don’t do that.'” $261 at Daily Steals via Google Express Read DJI Osmo Action preview The problem with most entry-level laptops: They come with mechanical hard drives. That makes for a mighty slow Windows experience. This Lenovo model features a 128GB solid-state drive, so it should be pretty quick to boot and load software, even with its basic processor. Plus, it has a DVD-burner! That’s not something you see in many modern laptops, especially at this price. Read Lenovo Smart Clock review Culture TV and Movies,I’m shocked — shocked! — to learn that stores are turning Labor Day into an excuse to sell stuff. Wait — no, I’m not. As much as I respect the original intent of the holiday (which became official back in 1894), to most of us, it’s just a bonus day off — one that’s blissfully tacked onto a weekend. So, yeah, stores; go ahead, run your sales. I’m listening. Perhaps unsurprisingly, Labor Day doesn’t bring out bargains to compete with the likes of Black Friday (which will be here before you know it), but there are definitely some sales worth your time.For example:We’ve rounded up the best Labor Day mattress deals.We’ve also gathered the best Labor Day laptop deals at Best Buy.The 2019 Vizio P Series Quantum is back under $999.Be sure to check out Amazon’s roughly three dozen Labor Day deals on TVs and audio. Google Express is having a big sale as well, one that includes deals on game consoles, AirPods, iPhones, laptops and more.Below I’ve rounded up a handful of individual items I consider to be the cream of the crop, followed by a handy reference guide to other Labor Day sales. Keep in mind, of course, that products may sell out at any time, even if the sale itself is still running. Note that CNET may get a share of revenue from the sale of the products featured on this page. Sprint $999 Angela Lang/CNET Formerly known as the Google Home Hub, Google’s Nest Hub packs a wealth of Google Assistant goodness into a 7-inch screen. At $59, this is within a buck of the best price we’ve seen. It lists for $129 and sells elsewhere in the $89-to-$99 range.This is one item of many available as part of eBay’s Labor Day Sale (which, at this writing, doesn’t specifically mention Labor Day, but that’s how it was pitched to us). See at Turo Preview • iPhone XS is the new $1,000 iPhone X Best Buy Sarah Tew/CNET Comments Now playing: Watch this: What’s cooler: A snapshot of a firework exploding in front of you, or full 360-degree video of all the fireworks and all the reactions to seeing them? Oooh, ahhh, indeed. At $250, the compact Rylo dual-lens camera is selling for its lowest price yet. And for an extra $50, you can get the bundle that includes the waterproof housing.This deal runs through Sept. 3; it usually costs $500. 15:04 Turo: Save $30 on any car rentalcenter_img Share your voice Free Echo Dot with an Insignia or Toshiba TV (save $50) See It Lenovo Smart Clock: $59.99 (save $20) Lenovo 130-15AST 15.6-inch laptop: $210 (save $90) Apple iPhone XS Tags $90 at Daily Steals via Google Express Tags Chris Monroe/CNET An Echo Dot makes a fine match for any Fire edition TV, because you can use the latter to say things like, “Alexa, turn on the TV.” Right now, the 24-inch Insignia Fire TV Edition starts at just $100, while the 32-inch Toshiba Fire TV Editions is on sale for $130. Just add any Fire TV Edition to your cart, then add a third-gen Echo Dot, and presto: The latter is free. Turo Turo is kind of like Uber meets Airbnb: You borrow someone’s car, but you do all the driving. I’ve used it many times and found it a great alternative to traditional car-rental services — in part because you get to choose exactly the vehicle you want (not just, say, “midsize”) and in part because you can often do pickup and dropoff right outside baggage claim.Between now and Sept. 1, the first 300 people to check out can get $30 off any Turo rental with promo code LDW30. Read the AirPods review DJI’s answer to GoPro’s action cameras is rugged little model that’s shockproof, dustproof and waterproof down to 11 meters. It normally runs $350, but this deal drops it to $261 when you apply promo code 19LABOR10 at checkout. $299 at Amazon $999 Google Nest Hub: $59 (save $70) See it JBL Soundgear wearable speaker: $90 (save $160) Use promo code 19LABOR10 to get an unusually good deal on JBL’s interesting hybrid product — not quite headphones, and not quite a traditional speaker, but something you wear like neckphones to listen to music on the go. See at Amazon 7 See It $210 at Best Buy Review • iPhone XS review, updated: A few luxury upgrades over the XR DJI Osmo Action camera: $261 (save $89) TVs Speakers Mobile Accessories Cameras Laptops Automobiles Smart Speakers & Displays Sarah Tew/CNET Sarah Tew/CNET Boost Mobile $60 at Best Buy Apple AirPods with Wireless Charging Case: $155 (save $45) CNET may get a commission from retail offers. Though not technically a Labor Day sale, it’s happening during Labor Day sale season — and it’s too good not to share. Nationwide Distributors, via Google Express, has just about the best AirPods deal we’ve seen (when you apply promo code ZBEDWZ at checkout). This is for the second-gen AirPods with the wireless charging case. Can’t imagine these will last long at this price, so if you’re interested, act fast. Read the Rylo camera preview $6 at Tidal HP Laptop 15t Value: $520 (save $780) Recently updated to include digital-photo-frame capabilities, the Lenovo Smart Clock brings Google Assistant goodness to your nightstand. It’s a little smaller than the Amazon Echo Show 5, but also a full $30 less (and tied with Prime Day pricing) during this Best Buy Labor Day sale.last_img read more

first_imgNicolas MaduroPresident Nicolas Maduro’s government won a landslide victory in closely watched regional elections in Venezuela on Sunday, according to official results that the opposition said were “suspicious.”Maduro’s socialist party won governorships of 17 of the 23 states with the opposition Democratic Union Roundtable (MUD) coalition taking only five, according to the results announced by the National Elections Council.The official turnout was 61.14 percent.Maduro said his government had scored an “emphatic victory” over its rivals.”The opposition has five,” Maduro underscored in a speech to supporters, adding that his party could win one further state where the results were still in dispute.Public opinion surveys had predicted that the opposition would win a majority of state governorships despite alleged government dirty tricks to suppress a high turnout.Sunday’s vote came against the backdrop of an International Monetary Fund report in which it sees Venezuela’s economic downturn, and the suffering of its population, continuing.Venezuela “remains in a full-blown economic, humanitarian, and political crisis with no end in sight,” the Fund said in a report on Latin American economies.International powers accuse Maduro of dismantling democracy by taking over state institutions in the wake of an economic collapse caused by a fall in the price of oil, its main source of revenue.Sunday’s polls were the first contested by the opposition since legislative elections in 2015 that gave it a majority in the National Assembly.The MUD has seen Maduro’s hand strengthened after he faced down four months of protests that killed 125 people, forming a Constituent Assembly packed with his own allies and wresting legislative power from the opposition-dominated National Assembly.For Maduro, the polls were an opportunity to counter allegations of dictatorship leveled at him at home and abroad after forming the Constituent Assembly.last_img read more

first_img Journal information: Proceedings of the National Academy of Sciences (Phys.org) — In a tale worthy of Sherlock Holmes, scientists in the School of Chemistry at the University of Bristol, UK have solved a biochemical mystery that had previously proven elusive for 70 years: How the fungus Talaromyces stipitatus produces stipitatic acid (6), which is a tropolone, one of an atypical group of fungal natural products – that is, small molecules produced by genetically encoded pathways – with a seven-carbon ring. (Most natural products, such as cholesterol or phenylalanine, have five or six carbons in rings.) The researchers used a two-part biosynthetic approach – gene deletion and alternate genetic expression – to investigate the molecular pathway in question. Professor Russell J. Cox, Postgraduate student Jack Davison and other researchers engaged in the study faced several long-standing obstacles to showing that 3-methylorcinaldehyde is the direct product of a fungal nonreducing polyketide synthase (NR-PKS) which most likely appends the methyl group from S-adenosyl methionine during biosynthesis of the tetraketide, and which uses a reductive release mechanism to produce the observed aldehyde. “Gene knockouts have been one of the most useful tools in the toolkit of the biosynthetic chemist,” Cox tells Phys.org, “but knockouts can’t answer complex questions like these. We now make extensive use of heterologous expression – that is, moving the gene to a ‘clean’ host and switching it on.”The scientists then monitor the host organism for the production of new compounds which we isolate and identify. The chemical structure of the new compound tells them a great deal about the chemistry which must have been used to make it. “In this case,” Cox continues, “we showed that the TropA gene encodes a polyketide synthase which makes 3-methylorcinaldehyde. Expression also allows us to do more complex experiments – for example, by truncating or mutating the gene – and in this way we discovered the reductive release mechanism and the fact that the programmed methylation occurs during chain extension rather than after chain-building and ring formation.”Tropolone biosynthesis was one of the longest-standing problems in the field of biosynthesis and some of the most distinguished organic chemists of the last century were fascinated by it, but progress had been very limited. “We realized that combining chemical knowledge with genome sequence data could give us the start we needed,” Cox explains. “We already knew a lot about polyketide biosynthesis in fungi, and this allowed us to narrow down the potential genes involved to just four. We then used chemical knowledge to narrow this further to a single gene cluster.” Proof then came from the knockout and expression studies. Explore further Copyright 2012 Phys.Org All rights reserved. This material may not be published, broadcast, rewritten or redistributed in whole or part without the express written permission of PhysOrg.com. More information: Genetic, molecular, and biochemical basis of fungal tropolone biosynthesis, PNAS May 15, 2012 vol. 109 no. 20 7642-7647, doi: 10.1073/pnas.1201469109 Involvement of tspks1 (tropA) in the biosynthesis of methylorcinaldehyde and tropolones in T. stipitatus. PKS domains: SAT, starter unit acyl transferase; KAS, ketosynthase; AT, acyl transferase; PT, product template; ACP, acyl carrier protein; CMeT, C-methyl transferase; R, acyl CoA thiolester reductase. HPLC analysis of tspks1 KO: (A) UV chromatogram at 260 nm for WT T. stipitatus; (B) UV chromatogram at 260 nm for T. stipitatus tspks1 KO. HPLC analysis of tspks1 expression in A. oryzae: (C) UV chromatogram at 293 nm for untransformed A. oryzae; (D) UV chromatogram at 293 nm for A. oryzae expressing aspks1; (E) UV chromatogram at 293 nm for A. oryzae expressing tspks1. Copyright © PNAS, doi: 10.1073/pnas.1201469109 Looking ahead, the team is currently working on systematic methods to express many genes in fungi. “At present this is easy in bacteria, because in bacteria a single promoter can switch on lots of genes in parallel,” notes Cox. “In fungi, however, each gene needs its own promoter, so this has limited progress. In collaboration with our colleagues in the School of Biological Sciences at Bristol we’re developing systems which can express a dozen or so fungal genes in parallel. This will allow the researchers to investigate much more complex systems in the future.In addition, Cox adds, “I do believe that computational biology and chemistry will eventually provide answers to complex questions like this – but at the moment, while computational methods allow us to formulate good questions, lab work is still needed to find the answers. We’re working in an area with very many unknowns, so it’s difficult for computational methods which rely on current knowledge to act predictively with any accuracy. In fact,” notes Cox, “this is a powerful reason why fundamental discoveries are still so important: they’ll form the basis for future predictions.”Cox points out that he and his team will also continue to study the TropB-D enzymes in vitro. “Chemical methods of classical enzymology will allow us to determine their precise mechanisms.”Cox also articulates how comparing the T. stipitatus tropolone biosynthetic cluster with other known gene clusters allows clarification of important steps during the biosynthesis of other fungal compounds, including the xenovulenes, citrinin, sepedonin, sclerotiorin, and asperfuranone. “Fungal genomes generally are much bigger than their bacterial counterparts by roughly 10 times, and they contain many more genes and gene clusters encoding the biosynthesis of complex compounds” he explains. “Barely any of the known fungal gene clusters have been linked to the molecules they must encode. Our work now allows the understanding of a set of genes which encodes the biosynthesis of polyketides followed by oxidative modifications and these occur frequently in fungi. Until now these clusters were mysterious, but now we can – at least partially – begin to understand what they may do. Secondly, knowledge of the gene clusters will allow us to go hunting for new clusters more effectively.” For example, puberulic acid is a potent antimalarial compound, but its gene cluster is unknown – and the team predicts that the cluster should be very similar to the T. stipitatus tropolone gene cluster.In terms of other research and applications that might benefit from their findings, Cox says that understanding biosynthetic pathways is a key strand of the new science of Synthetic Biology. “One can think of the gene clusters and biosynthetic enzymes they encode as building blocks of new biological entities. In the future,” he concludes, “it will be possible to combine the genetic and chemical knowledge of biosynthetic pathways to produce bioactive compounds – such as drugs and agrochemicals – using biology rather than chemistry. This offers huge advantages in terms of sustainability.” Citation: Friendly Fungi: Elucidating the fungal biosynthesis of stipitatic acid (2012, May 18) retrieved 18 August 2019 from https://phys.org/news/2012-05-friendly-fungi-elucidating-fungal-biosynthesis.html How tropolones synthesized in fungi: 70-year-old chemical mystery solved 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.last_img read more

first_imgKolkata: A 35-year-old woman was killed after she was hit by a private bus near Chiriamore at Barrackpore in North 24-Parganas on Tuesday.Police said the incident took place when the woman was taking her child to her school on Tuesday morning. The seven-year-old child also received injuries and is admitted to hospital.A police officer said the victim, Nitu Gupta, was a local resident. Police came to know after speaking to locals that the accident took place because two buses were racing between each other to get more passengers. Also Read – Speeding Jaguar crashes into Merc, 2 B’deshi bystanders killedOne of the buses failed to control the speed and hit the woman while she was crossing the road. Locals took the woman to a hospital where she was declaredbrought dead.The offending bus was seized but the driver had managed to flee.In two road accidents in Birbhum, one was killed when a motorbike collided head on with a truck at Mohammad Bazar.The road remained close after the accident. In another road accident in Birbhum, a toto collided head on with a truck at Abdarpur and it claimed the life of one person, who was travelingin the toto.The driver of the toto also received severe injuries.last_img read more