a c 9 Things You Cannot Do On A Cruise Any More ! By tips4travellers.libsyn.com Published On :: Mon, 17 Jun 2019 04:00:00 +0000 There are (at least) 9 things that you used to be able to do on a cruise that you are not able to do any more. Discover what things cruisers are not allowed to do on a cruise ship. Whilst some may be obvious, there are quite a few surprises. These cruise tips, secrets and facts will, hopefully, entertain as well as inform you. How many things did you not know you are not allowed to do on your cruise and cruising vacation now? Full Article
a c French Polynesia Cruise: Should It Be On Your Travel Bucket List ? By tips4travellers.libsyn.com Published On :: Mon, 29 Jul 2019 04:00:00 +0000 Do you have a cruise or travel bucket list? If so, should a French Polynesia cruise be on that list? In this I discuss the Tahiti and French Polynesia region and review what I think are the 4 pros and the 4 cons of cruising that I believe you should consider as you consider this as a cruising vacation option. I travelled to the region, which is pretty remote to explore. It takes well over 8 hours to fly from Los Angeles and the trip from Europe is 21 hours. It is very unique, different and beautiful. But, is it worth going all the way there? Find out what to expect and if I think you should add this to your travel and cruise bucket list - especially when there are so many other things you could have on your travel and cruise bucket list. Note: Some of the costs of my trip to French Polynesia were covered by Paul Gauguin Cruises and Air Tahiti Nui before making this video. ** Subscribe to my channel: http://bit.ly/TFT_YouTube2 ** Buy one of my unique Cruise T-shirts: http://bit.ly/TFTStore ** Get great cruise deals via CRUISEDIRECT.COM: http://bit.ly/TFTBookCruise Gary Bembridge's Tips For Travellers aims to help you make more of your precious travel time and money on land and when cruising the oceans or rivers of the world. To help you, in every video I draw on my first-hand tips and advice from travelling every month for over 20 years and 60+ cruises. Follow Tips For Travellers on: - Instagram: http://www.instagram.com/garybembridge - Facebook: http://www.facebook.com/tipsfortravellers - Twitter: http://www.twitter.com/garybembridge Full Article
a c Saga Cruises Spirit of Discovery Ship : 8 Must-Knows And A Key Watch-Out By tips4travellers.libsyn.com Published On :: Mon, 12 Aug 2019 04:00:00 +0000 Saga Cruises launched Spirit of Discovery in July 2019, the first of two sister cruise ships (Spirit of Adventure in 2020). These are the first new-build ships for cruising ever for Saga, why had previously bought and refurbished existing cruise ships. The Spirit of Discovery holds 999 passengers and in this I discuss the 8 things that I think are best about the ship, and show and explain why. I also talk about one major watch-out and issue that could stop you from cruising. Note: I travelled as a guest of the cruise line on a pre-naming cruise before making this video. Saga Cruises had no input in the video and content. ** Subscribe to my channel: http://bit.ly/TFT_YouTube2 ** Buy one of my unique Cruise T-shirts: http://bit.ly/TFTStore ** Get great cruise deals via CRUISEDIRECT.COM: http://bit.ly/TFTBookCruise Gary Bembridge's Tips For Travellers aims to help you make more of your precious travel time and money on land and when cruising the oceans or rivers of the world. To help you, in every video I draw on my first-hand tips and advice from travelling every month for over 20 years and 60+ cruises. Follow Tips For Travellers on: - Instagram: http://www.instagram.com/garybembridge - Facebook: http://www.facebook.com/tipsfortravellers - Twitter: http://www.twitter.com/garybembridge Full Article
a c 10 Things Not To Do On A Cruise Ship Balcony (Ever!) By tips4travellers.libsyn.com Published On :: Mon, 09 Sep 2019 04:00:00 +0000 Discover the 10 things that you should never do on a cruise ship balcony. Some of them are rules from the cruise line, which if you break you could find yourself thrown off your cruising vacation (or even banned by the cruise line for life!). Some are things that will make your and the other cruisers around you have a more enjoyable cruise. And some even could save you a lot of embarrassment.... ** Buy my Cruise T-shirts: http://bit.ly/TFTStore ** USA cruisers get great cruise deals CRUISEDIRECT.COM: http://bit.ly/TFTBookCruise ** UK Cruisers get great cruise deals with CRUISE.CO.UK: http://bit.ly/BookCruiseUK Gary Bembridge's Tips For Travellers aims to help you make more of your precious travel time and money on land and when cruising the oceans or rivers of the world. To help you, in every video I draw on my first-hand tips and advice from travelling every month for over 20 years and 60+ cruises. Follow Tips For Travellers on: - Instagram: http://www.instagram.com/garybembridge - Facebook: http://www.facebook.com/tipsfortravellers - Twitter: http://www.twitter.com/garybembridge Full Article
a c 6 Things You Can Get Free On A Cruise (By Asking) By tips4travellers.libsyn.com Published On :: Mon, 07 Oct 2019 04:00:00 +0000 How can you get free things on your next cruise, and get much more bang for your cruising bucks? I discuss the 6 main areas of cruise freebies that are available, if you go and ask for them or seek them out. They are not things that cruise brochures and websites usually reveal, or talk about. I tell you the things to focus on and how to get as many free things as you possibly can, including drinks, special food, gifts, spa treatments, better and improved cabins and more. ** Buy my Cruise T-shirts: http://bit.ly/TFTStore ** USA cruisers get great cruise deals CRUISEDIRECT.COM: http://bit.ly/TFTBookCruise ** UK Cruisers get great cruise deals with CRUISE.CO.UK: http://bit.ly/BookCruiseUK Gary Bembridge's Tips For Travellers aims to help you make more of your precious travel time and money on land and when cruising the oceans or rivers of the world. To help you, in every video I draw on my first-hand tips and advice from travelling every month for over 20 years and 60+ cruises. Follow Tips For Travellers on: - Instagram: http://www.instagram.com/garybembridge - Facebook: http://www.facebook.com/tipsfortravellers - Twitter: http://www.twitter.com/garybembridge Full Article
a c Sneaking Alcohol On A Cruise By tips4travellers.libsyn.com Published On :: Mon, 21 Oct 2019 04:00:00 +0000 I am not suggesting, or recommending, you should sneak booze on your next next cruising vacation as you could, in worst case, risk being refused boarding if caught. However despite this, there are cruisers who use surprising and unusual techniques to smuggle alcohol on to a cruise ship to avoid having to buy drinks on board. In this video I explore the different ways that people are using to sneak their alcohol onto their cruise ship. The cost of drinking on a cruise is increasing, and with some of the drinks packages you could be spending almost as much as the cruise itself costs and some travellers are resorting to innovative methods to bring their own alcohol onto cruise ships. There are even companies making products, devices and accessories specifically designed to assist. Full Article
a c Saga Cruises Need-to-knows By tips4travellers.libsyn.com Published On :: Mon, 27 Jan 2020 05:00:00 +0000 Is Saga Cruises the best cruise line for your cruise vacation? In this I explore what I think Saga Cruises do better, the same or worse than other premium cruise lines. I also look at who they are and who they are most suited for and why. Saga Cruises is a UK-based line with a different take on a number of areas of cruising, which you will discover... Note: I travelled as a guest of the cruise line a number of times over the last few years before making this video SUPPORT THE CHANNEL BY: Buying my Cruise T-shirts: http://bit.ly/TFTStoreBooking your next cruise with CRUISEDIRECT.COM: http://bit.ly/TFTBookCruise Gary Bembridge's Tips For Travellers aims to help you make more of your precious travel time and money on land and when cruising the oceans or rivers of the world. To help you, in every video I draw on my first-hand tips and advice from travelling every month for over 20 years and 60+ cruises. Follow Tips For Travellers on: - Instagram: http://www.instagram.com/garybembridge- Facebook: http://www.facebook.com/tipsfortravellers - Twitter: http://www.twitter.com/garybembridge Full Article
a c If even France can’t figure out a climate policy, what hope is there for the U.S.? By www.washingtonpost.com Published On :: Thu, 20 Jun 2019 22:15:15 +0000 There are ways to curb the pain of economic and political changes. Full Article
a c This ‘dreamer’ is saving lives during this pandemic. She wants a chance at normal life. By www.washingtonpost.com Published On :: Thu, 16 Apr 2020 23:21:02 +0000 Young medical students and health-care workers simply want to keep contributing in the only home they know. Full Article
a c strataconf: A roundup from the data journalism beat http://t.co/y8RVUwHO4G Global open data, scholarships, mapping a civil war & more #strataconf By twitter.com Published On :: Thu, 06 Jun 2013 21:36:47 +0000 strataconf: A roundup from the data journalism beat http://t.co/y8RVUwHO4G Global open data, scholarships, mapping a civil war & more #strataconf Full Article
a c strataconf: Innovative ways journalists are using data to tell stories http://t.co/y8RVUwHO4G Global open data, scholarships, mapping a civil war & more By twitter.com Published On :: Sun, 09 Jun 2013 11:25:28 +0000 strataconf: Innovative ways journalists are using data to tell stories http://t.co/y8RVUwHO4G Global open data, scholarships, mapping a civil war & more Full Article
a c strataconf: The Future Is Graph Databases http://t.co/BVxOZwtoKS A Conversation with @EmilEifrem, founder of @Neo4J #strataconf By twitter.com Published On :: Tue, 11 Jun 2013 18:25:30 +0000 strataconf: The Future Is Graph Databases http://t.co/BVxOZwtoKS A Conversation with @EmilEifrem, founder of @Neo4J #strataconf Full Article
a c Fin24.com | Icasa wants companies to lower data cost during coronavirus outbreak By www.fin24.com Published On :: Fri, 20 Mar 2020 07:26:40 +0200 The communications regulator is asking telecom companies to consider lowering the cost of data in a bid to ensure productivity during the period the coronavirus outbreak. Full Article
a c One-Pan Paprika Chicken with Potatoes and Tomatoes By feedproxy.google.com Published On :: Sun, 03 May 2020 21:00:00 +0000 This one-pan chicken dinner is made with potatoes, onions, garlic, cherry tomatoes, and an easy paprika sauce. Dairy-free, gluten-free. 1 hour start to finish. Continue reading "One-Pan Paprika Chicken with Potatoes and Tomatoes" » Full Article
a c velocityconf: @tsantero @garethr No, there's just a lot that goes into producing #velocityconf. Plus the chairs are getting ready for Santa Clara + NY! :) By feedproxy.google.com Published On :: Mon, 20 May 2013 16:50:15 +0000 velocityconf: @tsantero @garethr No, there's just a lot that goes into producing #velocityconf. Plus the chairs are getting ready for Santa Clara + NY! :) Full Article
a c News24.com | Bleak future for young people if Ramaphosa can't deliver on his promises By www.news24.com Published On :: Wed, 19 Feb 2020 18:19:26 +0200 With the working class resorting to online vouchers for groceries and the poor eating less bread than before, is it not impractical for the president to expect ordinary citizens to tighten their belts when MPs, Ministers and government officials' well-fed bellies belie the trouble the economy is in? Full Article
a c News24.com | Don't be a Covid-19 criminal By www.news24.com Published On :: Mon, 23 Mar 2020 17:01:53 +0200 South Africans would do well to verify information which they receive through social media channels, and avoid re-posting or forwarding information which they have not properly verified. Full Article
a c AT#67 - Travel to Edmonton and Jasper, Alberta Canada By traffic.libsyn.com Published On :: Mon, 20 Nov 2006 03:40:00 +0000 Edmonton and Jasper, Alberta Canada Full Article
a c AT#68 - Travel to Lake Louise, Banff and Calgary, Alberta Canada By traffic.libsyn.com Published On :: Mon, 27 Nov 2006 04:53:00 +0000 Lake Louise, Banff and Calgary, Alberta Canada Full Article
a c AT#103 - Travel to Baja California By traffic.libsyn.com Published On :: Mon, 27 Aug 2007 03:35:00 +0000 Baja California Full Article
a c AT#492 - Trekking the Annapurna Circuit in Nepal By asia.amateurtraveler.com Published On :: Sat, 28 Nov 2015 15:30:00 +0000 Hear about Trekking the Annapurna Circuit in Nepal as the Amateur Traveler talks to the Su Family from sufamilyadventures.com about tackling this well known route. Full Article
a c AT#545 - Travel to Oklahoma City By usa.amateurtraveler.com Published On :: Sat, 21 Jan 2017 18:13:54 +0000 Hear about travel to Oklahoma City as the Amateur Traveler talks to Sheila Scarborough from Tourism Currents about what she calls a "tremendously underrated destination". Full Article
a c Huge Group of California Churches Announces Plan To Defy Governor Newsom’s Order By www.westernjournal.com Published On :: Sat, 09 May 2020 02:21:33 +0000 An evangelical church network in California will ignore Democratic Gov. Gavin Newsom’s executive prohibitions this month, opening sanctuary doors for communal worship despite the ongoing coronavirus pandemic. According to Fox News, California Church United, representing roughly 3,000 churches and 2.5 million congregants statewide, announced Thursday that it will return to conducting in-person services by Pentecost… The post Huge Group of California Churches Announces Plan To Defy Governor Newsom’s Order appeared first on The Western Journal. Full Article News California Christianity Coronavirus Culture Faith Politics US News
a c ‘The Voice’ Contestant Alexa Cappelli Treats Neighbors to Weekly Performance in Her Cul-de-Sac By www.westernjournal.com Published On :: Sat, 09 May 2020 15:39:49 +0000 It’s not good for people to be alone. Quarantining has been difficult for many people who have gotten used to socializing daily, and because of that, some have found ways to follow the rules but feel a little less isolated. Some neighborhoods have decided to be social while maintaining the suggested distance apart, whether that’s… The post ‘The Voice’ Contestant Alexa Cappelli Treats Neighbors to Weekly Performance in Her Cul-de-Sac appeared first on The Western Journal. Full Article Lifestyle Celebrity Entertainment Music Uplifting
a c Four Providers’ Houston Data Centers Online, but Access Roads Flooded By feedproxy.google.com Published On :: Mon, 28 Aug 2017 19:50:15 +0000 Full Article Colocation Manage Uptime
a c Hurricane Harvey: Delivering Managed IT Services During a Catastrophe By feedproxy.google.com Published On :: Tue, 29 Aug 2017 15:00:00 +0000 Full Article Manage North America Uptime
a c How to Design a Data Center in a Norwegian Fjord By feedproxy.google.com Published On :: Wed, 30 Aug 2017 12:00:00 +0000 Full Article Design Europe Featured
a c A Campaign of Disappearances in Syria Leaves Thousands Missing By feedproxy.google.com Published On :: Thu, 05 Nov 2015 18:54:46 EST At least 65,116 individuals have been "forcibly disappeared" by the Syrian government, according to a new report by Amnesty International. Full Article
a c WATCH: A Conversation With Teens in Training as ISIS Suicide Bombers By feedproxy.google.com Published On :: Mon, 16 Nov 2015 14:34:40 EST As ISIS expands its reach into Afghanistan, it is training children and teenagers to become the next generation of jihadis. Full Article
a c This isn't a checkers board, it's actually a musical instrument— Future Blink By feedproxy.google.com Published On :: Fri, 08 May 2020 19:45:11 +0000 Striso is a digital instrument with pressure-sensitive buttons that plays a variety of acoustic-like sounds. Read more...More about Tech, Music, Mashable Video, Innovation, and Future Blink Full Article Tech Music Mashable Video Innovation Future Blink
a c Try your hand at becoming a cybersecurity superhero for just $40 By feedproxy.google.com Published On :: Sat, 09 May 2020 09:00:00 +0000 TL;DR: Get trained in cybersecurity with The Ultimate 2020 White Hat Hacker Certification Bundle for $39.90, a 97% as of May 9. When you think of superheroes, you probably picture capes and some sort of otherworldly powers. But in the digital world, superheroes are actually normal people like you and me. They just happen to know a thing or two about stopping cybercriminals in their tracks. These superheroes are in short supply across the world. In fact, there are over half a million cybersecurity job openings in the U.S. alone. That just means this could be your chance to swoop in, superhero style, and save the day. But first things first, you need to learn the ropes and the Ultimate 2020 White Hat Hacker Certification Bundle is a great place to start. Read more...More about Cybersecurity, Online Learning, Mashable Shopping, Tech, and Consumer Tech Full Article Cybersecurity Online Learning Mashable Shopping Tech Consumer Tech
a c A classical flutist listens to Ian Anderson in 1969 and 1976 By feedproxy.google.com Published On :: Sat, 09 May 2020 10:22:49 PDT I have a love/hate relationship with musical reaction videos. There are kids reacting to heavy metal (or The Beatles), vocal teachers and opera singers reacting to rock vocalists, millennials reacting to classic rock, and on and on. Some of these are quite moving, for instance, a 20-something hearing Zep's "Since I've Been Loving You" for the first time or a vocal teacher reacting to a Black Metal vocalist's cookie monster growl. In these two videos, Heline, a classical flutist and music teacher, listens to Jethro Tull's Ian Anderson performing "Bouree" at a 1969 concert and then she listens and reacts to a performance from 1976. I didn't realize that Anderson had only been playing the flute for a year and had no formal training at the time of the 69 video (their first tour). Heline can appreciate his chutzpah in the first performance and the fact that he's only been playing for a year(!), but is perhaps predictably critical of his playing. She is more impressed with what she sees and hears in the 76 performance. Personally, I always thought his playing was inspired and his playing, vocalizing, singing and playing, and his other stage antics (the goofy one-legged stance) were a perfect example of "the street finding its own uses for things," using technology in ways in which it was never intended. As with all things artistic, your mileage may vary. Image: YouTube Read the rest Full Article Post flute music appreciation Reaction video Rock n Roll
a c Sport24.co.za | Cycling's Vuelta a Espana cuts Portugal from itinerary By www.sport24.co.za Published On :: Sat, 09 May 2020 14:45:58 +0200 The Vuelta a Espana organisers have confirmed that a race already rescheduled and shortened would also now cut its foray into neighbouring Portugal from the 2020 itinerary. Full Article
a c Police find 8-foot boa constrictor while investigating Oppenheimer Park fight By bc.ctvnews.ca Published On :: Fri, 8 May 2020 18:36:00 -0700 Police officers responding to a call about a man with a machete in Oppenheimer Park Friday afternoon found what they were looking for, and then some. Full Article
a c 'Where is that compassion?': Closing tent cities a chance to change housing policy, advocates say By bc.ctvnews.ca Published On :: Fri, 8 May 2020 06:49:00 -0700 T.J. Lovell had just 30 minutes to pack up his belongings from the tent city in Oppenheimer Park if he wanted access to a hotel room that he could share with his father. Full Article
a c Donald Trump Jr. Offers To Walk Bride-to-Be Down The Aisle After Liberal Parents Refuse To Attend Her Wedding Because Fiance Is A Conservative By 100percentfedup.com Published On :: Wed, 06 May 2020 02:26:06 +0000 The following article, Donald Trump Jr. Offers To Walk Bride-to-Be Down The Aisle After Liberal Parents Refuse To Attend Her Wedding Because Fiance Is A Conservative, was first published on 100PercentFedUp.com. TDS or Trump Derangement Syndrome brings out the worst in a lot of people. One young Texan girl’s story of her intolerant parents who refuse to attend her wedding because she’s marrying a conservative, however, is a new low. Lawyer and conservative civil rights activist, Rogan O’Handley tweeted a Tik Tok video of a Texan […] Continue reading: Donald Trump Jr. Offers To Walk Bride-to-Be Down The Aisle After Liberal Parents Refuse To Attend Her Wedding Because Fiance Is A Conservative ... Full Article Featured Political Correctness Politics
a c Legal Immigrant in Michigan Sends a Message to MI Gov Whitmer and Media Criticizing Freedom-Loving Protesters By 100percentfedup.com Published On :: Wed, 06 May 2020 22:43:02 +0000 The following article, Legal Immigrant in Michigan Sends a Message to MI Gov Whitmer and Media Criticizing Freedom-Loving Protesters, was first published on 100PercentFedUp.com. The media and even some governors are trying to paint the Americans who are protesting to open businesses up as racists and even Nazis. The Governor of Michigan recently made a derogatory statement about the protesters implying they are racists. Painting a negative picture of the people who want their freedom and businesses demonizes our […] Continue reading: Legal Immigrant in Michigan Sends a Message to MI Gov Whitmer and Media Criticizing Freedom-Loving Protesters ... Full Article Featured Left News Political Correctness Politics
a c Video: Dallas Salon Owner Shelley Luther Gets Surprise Visit from Sen Ted Cruz for a Celebratory Haircut By 100percentfedup.com Published On :: Sat, 09 May 2020 13:19:16 +0000 The following article, Video: Dallas Salon Owner Shelley Luther Gets Surprise Visit from Sen Ted Cruz for a Celebratory Haircut, was first published on 100PercentFedUp.com. When Dallas, Texas salon owner Shelley Luther opened her salon in defiance of the lockdown order in Texas, she was visited numerous times by the local police and then sentenced to 7 days in jail with a fine of $7,000. After public outrage at her punishment, the Texas Supreme Court stepped in to demand her […] Continue reading: Video: Dallas Salon Owner Shelley Luther Gets Surprise Visit from Sen Ted Cruz for a Celebratory Haircut ... Full Article Breaking Featured Government News Politics
a c A comprehensive evaluation of a typical plant telomeric G-quadruplex (G4) DNA reveals the dynamics of G4 formation, rearrangement, and unfolding [Plant Biology] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Telomeres are specific nucleoprotein structures that are located at the ends of linear eukaryotic chromosomes and play crucial roles in genomic stability. Telomere DNA consists of simple repeats of a short G-rich sequence: TTAGGG in mammals and TTTAGGG in most plants. In recent years, the mammalian telomeric G-rich repeats have been shown to form G-quadruplex (G4) structures, which are crucial for modulating telomere functions. Surprisingly, even though plant telomeres are essential for plant growth, development, and environmental adaptions, only few reports exist on plant telomeric G4 DNA (pTG4). Here, using bulk and single-molecule assays, including CD spectroscopy, and single-molecule FRET approaches, we comprehensively characterized the structure and dynamics of a typical plant telomeric sequence, d[GGG(TTTAGGG)3]. We found that this sequence can fold into mixed G4s in potassium, including parallel and antiparallel structures. We also directly detected intermediate dynamic transitions, including G-hairpin, parallel G-triplex, and antiparallel G-triplex structures. Moreover, we observed that pTG4 is unfolded by the AtRecQ2 helicase but not by AtRecQ3. The results of our work shed light on our understanding about the existence, topological structures, stability, intermediates, unwinding, and functions of pTG4. Full Article
a c ER stress increases store-operated Ca2+ entry (SOCE) and augments basal insulin secretion in pancreatic beta cells [Molecular Bases of Disease] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Type 2 diabetes mellitus (T2DM) is characterized by impaired glucose-stimulated insulin secretion and increased peripheral insulin resistance. Unremitting endoplasmic reticulum (ER) stress can lead to beta-cell apoptosis and has been linked to type 2 diabetes. Although many studies have attempted to link ER stress and T2DM, the specific effects of ER stress on beta-cell function remain incompletely understood. To determine the interrelationship between ER stress and beta-cell function, here we treated insulin-secreting INS-1(832/13) cells or isolated mouse islets with the ER stress–inducer tunicamycin (TM). TM induced ER stress as expected, as evidenced by activation of the unfolded protein response. Beta cells treated with TM also exhibited concomitant alterations in their electrical activity and cytosolic free Ca2+ oscillations. As ER stress is known to reduce ER Ca2+ levels, we tested the hypothesis that the observed increase in Ca2+ oscillations occurred because of reduced ER Ca2+ levels and, in turn, increased store-operated Ca2+ entry. TM-induced cytosolic Ca2+ and membrane electrical oscillations were acutely inhibited by YM58483, which blocks store-operated Ca2+ channels. Significantly, TM-treated cells secreted increased insulin under conditions normally associated with only minimal release, e.g. 5 mm glucose, and YM58483 blocked this secretion. Taken together, these results support a critical role for ER Ca2+ depletion–activated Ca2+ current in mediating Ca2+-induced insulin secretion in response to ER stress. Full Article
a c Biosynthesis of depsipeptides with a 3-hydroxybenzoate moiety and selective anticancer activities involves a chorismatase [Metabolism] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Neoantimycins are anticancer compounds of 15-membered ring antimycin-type depsipeptides. They are biosynthesized by a hybrid multimodular protein complex of nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS), typically from the starting precursor 3-formamidosalicylate. Examining fermentation extracts of Streptomyces conglobatus, here we discovered four new neoantimycin analogs, unantimycins B–E, in which 3-formamidosalicylates are replaced by an unusual 3-hydroxybenzoate (3-HBA) moiety. Unantimycins B–E exhibited levels of anticancer activities similar to those of the chemotherapeutic drug cisplatin in human lung cancer, colorectal cancer, and melanoma cells. Notably, they mostly displayed no significant toxicity toward noncancerous cells, unlike the serious toxicities generally reported for antimycin-type natural products. Using site-directed mutagenesis and heterologous expression, we found that unantimycin productions are correlated with the activity of a chorismatase homolog, the nat-hyg5 gene, from a type I PKS gene cluster. Biochemical analysis confirmed that the catalytic activity of Nat-hyg5 generates 3-HBA from chorismate. Finally, we achieved selective production of unantimycins B and C by engineering a chassis host. On the basis of these findings, we propose that unantimycin biosynthesis is directed by the neoantimycin-producing NRPS–PKS complex and initiated with the starter unit of 3-HBA. The elucidation of the biosynthetic unantimycin pathway reported here paves the way to improve the yield of these compounds for evaluation in oncotherapeutic applications. Full Article
a c By enabling formal trade, Nigeria can unleash its vast potential By feedproxy.google.com Published On :: Mon, 07 Dec 2015 16:18:19 +0000 3 December 2015 20151207Nigeriabooming.jpg Nigeria’s booming informal trade is costly for society, business and government, yet a critical opportunity exists to formalize such trade and drive more sustainable and less volatile growth, argues a new report from Chatham House.According to one estimate, informal activity accounts for up to 64 per cent of Nigeria’s GDP. Nigeria's Booming Borders: The Drivers and Consequences of Unrecorded Trade finds that this is a result of obstacles that impede trading through formal channels. These drivers include bureaucratic burdens and other factors, such as:The need for Nigerian businesses to produce at least nine documents in order to send an export shipment and at least 13 in order to bring in an import consignment.Rigid and dysfunctional foreign-exchange regulations that push most smaller traders into the incompletely regulated parallel exchange market.Corruption and unofficial ‘taxation’, especially on major border highways, which delegitimize formal channels and encourage the use of smuggling routes.As a result, the state loses direct tax revenues that would be generated by formal cross-border trade. This is not just siphoned into the informal economy; some is lost entirely. For example, many shippers opt to dock in neighbouring countries rather than deal with the expense and difficulty of using Nigeria’s ports.Informal trade also undermines the social contract between the private sector and government. The state lacks tax revenues to pay its officials, improve infrastructure or implement reforms, while traders feel the government provides no services in return for any taxes they might pay.‘Every day tens of thousands of unofficial payments are made, none destined for the government. Policy-makers need to create an environment that encourages trade to flow through formal channels and capture lost revenue’, says co-author Leena Koni Hoffmann.‘Formalization would assist Nigeria to pursue more high-quality, high-tech economic activity at a time when rising labour costs in Asia are creating scope for Nigerian manufacturers to compete’, she adds.The report makes a number of recommendations for how Nigeria could encourage more formal trade, including:Strengthening the resources and capacity of the Federal Ministry of Industry, Trade and Investment to coordinate action across key government ministries, departments and agencies, as well as public and private stakeholders.Prioritizing engagement in the development of Economic Community of West African States (ECOWAS) trade policies and fully implementing the ECOWAS Protocol on Free Movement of Persons to reduce harassment at borders.Allowing banks to operate simple services for small and medium-sized businesses to make trade payments directly from Nigerian naira to CFA francs and vice versa.Improving basic facilities that support traders, including improving the efficiency of border posts, installing truck parks and all-weather surfacing on market access roads, and introducing online booking for trucks to enter ports.Separating responsibilities for assessing duty and tariff liabilities from revenue collection in order to reduce opportunities for corruption, an approach already tested with success by the Lagos State Internal Revenue Service.Increasing funding and technical support for the National Bureau of Statistics, which has a significant role to play in measuring and capturing more of Nigeria’s external trade.Interviews conducted for the report reveal that business people would welcome the opportunity to pay taxes, but only if they received assurance that these payments would represent a contract with government guaranteeing that conditions for business would be improved.‘As Africa’s largest economy, formalizing external trade would allow Nigeria to fulfil its potential as the trading engine of the West and Central African economy and shape the business landscape across the region,’ says co-author Paul Melly. Editor's notes Read Nigeria's Booming Borders: the Drivers and Consequences of Unrecorded Trade (embargoed until 17:00 GMT on Monday 7 December).To request an interview with the authors, contact the press office.Nigeria’s recorded external trade for 2014 was $135.8 billion.Estimate of informal activity as a percentage of GDP from Jonathan Emenike Ogbuabor and Victor A. Malaolu, ‘Size and Causes of the Informal Sector of the Nigerian Economy: Evidence from Error Correction Mimic Model’, Journal of Economics and Sustainable Development, Vol. 4, No. 1, 2013. Contacts Press Office +44 (0)20 7957 5739 Email Full Article
a c Transatlantic Strategy Group on the Future of US Global Leadership: Transatlantic Security Policy Towards a Changing Middle East By feedproxy.google.com Published On :: Thu, 05 Mar 2015 11:45:02 +0000 Invitation Only Research Event 6 February 2015 - 8:45am to 4:30pm Residence of the British Ambassador to France, Paris Meeting Summarypdf | 95.65 KB With the Middle East in chaos and the future of many states increasingly uncertain, there is a large amount of attention as to how policy-makers in Europe and the US should respond. In particular, many in Europe are unsure of long-term US policy in light of competing American priorities, budgetary constraints and a public adverse to committing further resources abroad. In this context, it is important that European and American policy-makers understand each other’s positions.At this all-day event, a group of experts will discuss how US policy towards the Middle East is changing, what this means for Europe and, subsequently, how Europe should respond. Attendance at this event is by invitation only.The workshop is held as part of the Transatlantic Strategy Group on the Future of US Global Leadership run jointly with the German Marshall Fund of the United States. Over the course of a year, this group will discuss how US policy is changing on key issues and the implications for Europe. This project is supported by the Fritz Thyssen Foundation, with support for this event provided by the Delegation of Strategic Affairs of the French Ministry of Defence and the British Embassy in Paris. Event attributes External event Department/project US and the Americas Programme Full Article
a c Transatlantic Rifts: Averting a Turkey/Russia Conflict By feedproxy.google.com Published On :: Thu, 04 Aug 2016 09:27:37 +0000 5 August 2016 Based on a workshop which played out a scenario of rising tensions between Turkey and Russia, this paper finds that the situation would have to escalate dramatically to threaten transatlantic unity. Download PDF Xenia Wickett @xeniawickett LinkedIn Former Head, US and the Americas Programme; Former Dean, The Queen Elizabeth II Academy for Leadership in International Affairs Dr Jacob Parakilas Former Deputy Head, US and the Americas Programme 2016-08-04-transatlantic-rift-russia-turkey.jpg A protester waves Turkey's national flag in front of the Russian consulate during a demonstration against Russia's Syria policy on 24 November 24 2015 in Istanbul, Turkey. Photo: Getty Images. SummaryChatham House brought together 22 participants over a two-day period in May 2016 to discuss US and European responses to a potential conflict between Turkey and Russia. This was the third of four scenario roundtables (the first two involved a conflict between China and Japan and a potential breakdown in the Iran nuclear deal, respectively).The scenario was designed and the roundtable took place before a number of crucial subsequent developments, including the partial restoration of Turkish/Russian relations, the British vote to leave the European Union (EU), and the attempted coup against Turkish President Recep Tayyip Erdoğan. This paper should be read and understood in that context.In our simulation, the United States and Europe worked closely together, with cooperation particularly in evidence between the US and Germany. While the US was slightly more willing than Europe to threaten sanctions against Russia, transatlantic unity was not seriously threatened by a Turkey/Russia conflict.Western states were wary of bringing NATO into the picture for fear that this would be perceived as militarizing an already tense situation. The EU was also sidelined in favour of more ad hoc negotiating strategies.Russia was effective in using international law to defend its position, even as it took steadily more aggressive action in Syria. Neither the West nor Turkey deployed an effective countermeasure to this tactic. Department/project US and the Americas Programme Full Article
a c South Africa Can Easily Afford National Health Insurance By feedproxy.google.com Published On :: Mon, 09 Dec 2019 06:07:40 +0000 9 December 2019 Robert Yates Director, Global Health Programme; Executive Director, Centre for Universal Health @yates_rob Countries with much lower per capita GDP have successfully implemented universal healthcare. 2019-12-06-NMCH.jpg Builders work on an outside yard at the Nelson Mandela Children's Hospital in Johannesburg in 2016. Photo: Getty Images. At the United Nations general assembly in September, all countries, including South Africa, reaffirmed their commitment to achieving universal health coverage by 2030. This is achieved when everybody accesses the health services they need without suffering financial hardship.As governments outlined their universal health coverage plans, it was noticeable that some had made much faster progress than others, with some middle-income countries outperforming wealthier nations. For example, whereas Thailand, Ecuador and Georgia (with national incomes similar to South Africa) are covering their entire populations, in the United States, 30 million people still lack health insurance and expensive health bills are the biggest cause of personal bankruptcy.The key factor in financing universal health coverage is, therefore, not so much the level of financing but rather how the health sector is financed. You cannot cover everyone through private financing (including insurance) because the poor will be left behind. Instead, the state must step in to force wealthy and healthy members of society to subsidise services for the sick and the poor.Switching to a predominantly publicly financed health system is, therefore, a prerequisite for achieving universal health coverage.The National Health Insurance (NHI) Bill, recently presented to parliament, is President Cyril Ramaphosa’s strategy to make this essential transition. In essence, it proposes creating a health-financing system in which people pay contributions (mostly through taxes) according to their ability to pay and then receive health services according to their health needs.Surprisingly, these reforms have been dubbed 'controversial' by some commentators in the South African media, even though this is the standard route to universal health coverage as exhibited by countries across Europe, Asia, Australasia, Canada and much of Latin America.In criticising the NHI other stakeholders (often with a vested interest in preserving the status quo) have said that the government’s universal health coverage strategy is unaffordable because it will require higher levels of public financing for health.Evidence from across the world shows that this is patently false. South Africa already spends more than 8% of its national income on its health sector, which is very high for its income level. Turkey, for example (a good health performer and slightly richer than South Africa), spends 4.3% of its GDP and Thailand (a global universal health coverage leader) spends only 3.7%. Thailand shows what can be accomplished, because it launched its celebrated universal health coverage reforms in 2002 when its GDP per capita was only $1 900 — less than a third of South Africa’s today.In fact, Thailand’s prime minister famously ignored advice from the World Bank that it could not afford publicly financed, universal health coverage in the aftermath of the Asian financial crisis when it extended universal, tax-financed healthcare to the entire population. When these reforms proved a great success, a subsequent president of the World Bank, Dr Jim Kim, congratulated the Thai government for ignoring its previous advice.Similarly the United Kingdom, Japan and Norway all launched successful universal health coverage reforms at times of great economic difficulty at the end of World War II. These should be salutary lessons for those saying that South Africa can’t afford the NHI. If anything, because universal health reforms generate economic growth (with returns 10 times the public investment), now is exactly the time to launch the NHI.So there is enough overall funding in the South African health sector to take a giant step towards universal health coverage. The problem is that the current system is grossly inefficient and inequitable because more than half of these funds are spent through private insurance schemes that cover only 16% of the population — and often don’t cover even this population effectively.Were the bulk of these resources to be channelled through an efficient public financing system, evidence from around the world shows that the health sector would achieve better health outcomes, at lower cost. Health and income inequalities would fall, too.It’s true that in the long term, the government will have to increase public financing through reducing unfair subsidies to private health insurance and increasing taxes. But what the defenders of the current system don’t acknowledge is that, at the same time, private voluntary financing will fall, rapidly. Most families will no longer feel the need to purchase expensive private insurance when they benefit from the public system. It’s this fact that is generating so much opposition to the NHI from the private insurance lobby.This is the situation with the National Health Service in the UK and health systems across Europe, where only a small minority choose to purchase additional private insurance. Among major economies, only the United States continues to exhibit high levels of private, voluntary financing.As a consequence, it now spends an eye-watering 18% of its GDP on health and has some of the worst health indicators in the Organisation for Economic Co-operation and Development, including rising levels of maternal mortality. If South Africa doesn’t socialise health financing this is where its health system will end up — a long way from universal health coverage.What countries celebrating their universal health coverage successes at the UN have shown is that it is cheaper to publicly finance health than leave it to the free market. This is because governments are more efficient and fairer purchasers of health services than individuals and employers. As Dr Gro Harlem Brundtland, the former director general of the World Health Organization, said in New York: 'If there is one lesson the world has learnt, it is that you can only reach UHC [universal health coverage] through public financing.'This is a step South Africa must take — it can’t afford not to.This article was originally published by the Mail & Guardian. Full Article
a c The Hurdles to Developing a COVID-19 Vaccine: Why International Cooperation is Needed By feedproxy.google.com Published On :: Thu, 23 Apr 2020 09:26:36 +0000 23 April 2020 Professor David Salisbury CB Associate Fellow, Global Health Programme LinkedIn Dr Champa Patel Director, Asia-Pacific Programme @patel_champa While the world pins its hopes on vaccines to prevent COVID-19, there are scientific, regulatory and market hurdles to overcome. Furthermore, with geopolitical tensions and nationalistic approaches, there is a high risk that the most vulnerable will not get the life-saving interventions they need. 2020-04-23-Covid-Vaccine.jpg A biologist works on the virus inactivation process in Belo Horizonte, Brazil on 24 March 2020. The Brazilian Ministry of Health convened The Technological Vaccine Center to conduct research on COVID-19 in order to diagnose, test and develop a vaccine. Photo: Getty Images. On 10 January 2020, Chinese scientists released the sequence of the COVID-19 genome on the internet. This provided the starting gun for scientists around the world to start developing vaccines or therapies. With at least 80 different vaccines in development, many governments are pinning their hopes on a quick solution. However, there are many hurdles to overcome. Vaccine developmentFirstly, vaccine development is normally a very long process to ensure vaccines are safe and effective before they are used. Safety is not a given: a recent dengue vaccine caused heightened disease in vaccinated children when they later were exposed to dengue, while Respiratory Syncytial Virus vaccine caused the same problem. Nor is effectiveness a given. Candidate vaccines that use novel techniques where minute fragments of the viruses’ genetic code are either injected directly into humans or incorporated into a vaccine (as is being pursued, or could be pursued for COVID-19) have higher risks of failure simply because they haven’t worked before. For some vaccines, we know what levels of immunity post-vaccination are likely to be protective. This is not the case for coronavirus. Clinical trials will have to be done for efficacy. This is not optional – regulators will need to know extensive testing has taken place before licencing any vaccine. Even if animal tests are done in parallel with early human tests, the remainder of the process is still lengthy. There is also great interest in the use of passive immunization, whereby antibodies to SARS-CoV-2 (collected from people who have recovered from infection or laboratory-created) are given to people who are currently ill. Antivirals may prove to be a quicker route than vaccine development, as the testing requirements would be shorter, manufacturing may be easier and only ill people would need to be treated, as opposed to all at-risk individuals being vaccinated.Vaccine manufacturingDevelopers, especially small biotechs, will have to make partnerships with large vaccine manufacturers in order to bring products to market. One notorious bottleneck in vaccine development is getting from proof-of-principle to commercial development: about 95 per cent of vaccines fail at this step. Another bottleneck is at the end of production. The final stages of vaccine production involve detailed testing to ensure that the vaccine meets the necessary criteria and there are always constraints on access to the technologies necessary to finalize the product. Only large vaccine manufacturers have these capacities. There is a graveyard of failed vaccine candidates that have not managed to pass through this development and manufacturing process.Another consideration is adverse or unintended consequences. Highly specialized scientists may have to defer their work on other new vaccines to work on COVID-19 products and production of existing products may have to be set aside, raising the possibility of shortages of other essential vaccines. Cost is another challenge. Vaccines for industrialized markets can be very lucrative for pharmaceutical companies, but many countries have price caps on vaccines. Important lessons have been learned from the 2009 H1N1 flu pandemic when industrialized countries took all the vaccines first. Supplies were made available to lower-income countries at a lower price but this was much later in the evolution of the pandemic. For the recent Ebola outbreaks, vaccines were made available at low or no cost. Geopolitics may also play a role. Should countries that manufacture a vaccine share it widely with other countries or prioritize their own populations first? It has been reported that President Trump attempted to purchase CureVac, a German company with a candidate vaccine. There are certainly precedents for countries prioritizing their own populations. With H1N1 flu in 2009, the Australian Government required a vaccine company to meet the needs of the Australian population first. Vaccine distributionGlobal leadership and a coordinated and coherent response will be needed to ensure that any vaccine is distributed equitably. There have been recent calls for a G20 on health, but existing global bodies such as the Coalition for Epidemic Preparedness Innovations (CEPI) and GAVI are working on vaccines and worldwide access to them. Any new bodies should seek to boost funding for these entities so they can ensure products reach the most disadvantaged. While countries that cannot afford vaccines may be priced out of markets, access for poor, vulnerable or marginalized peoples, whether in developed or developing countries, is of concern. Developing countries are at particular risk from the impacts of COVID-19. People living in conflict-affected and fragile states – whether they are refugees or asylum seekers, internally displaced or stateless, or in detention facilities – are at especially high risk of devastating impacts. Mature economies will also face challenges. Equitable access to COVID-19 vaccine will be challenging where inequalities and unequal access to essential services have been compromised within some political systems. The need for global leadership There is an urgent need for international coordination on COVID-19 vaccines. While the WHO provides technical support and UNICEF acts as a procurement agency, responding to coronavirus needs clarity of global leadership that arches over national interests and is capable of mobilizing resources at a time when economies are facing painful recessions. We see vaccines as a salvation but remain ill-equipped to accelerate their development.While everyone hopes for rapid availability of safe, effective and affordable vaccines that will be produced in sufficient quantities to meet everyone’s needs, realistically, we face huge hurdles. Full Article
a c Lysine Acetylation Is a Highly Abundant and Evolutionarily Conserved Modification in Escherichia Coli By feedproxy.google.com Published On :: 2009-02-01 Junmei ZhangFeb 1, 2009; 8:215-225Research Full Article
a c Toward a Comprehensive Atlas of the Physical Interactome of Saccharomyces cerevisiae By feedproxy.google.com Published On :: 2007-03-01 Sean R. CollinsMar 1, 2007; 6:439-450Research Full Article
a c Parts per Million Mass Accuracy on an Orbitrap Mass Spectrometer via Lock Mass Injection into a C-trap By feedproxy.google.com Published On :: 2005-12-01 Jesper V. OlsenDec 1, 2005; 4:2010-2021Technology Full Article
a c Noncatalytic Bruton's tyrosine kinase activates PLC{gamma}2 variants mediating ibrutinib resistance in human chronic lymphocytic leukemia cells [Membrane Biology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Treatment of patients with chronic lymphocytic leukemia (CLL) with inhibitors of Bruton's tyrosine kinase (BTK), such as ibrutinib, is limited by primary or secondary resistance to this drug. Examinations of CLL patients with late relapses while on ibrutinib, which inhibits BTK's catalytic activity, revealed several mutations in BTK, most frequently resulting in the C481S substitution, and disclosed many mutations in PLCG2, encoding phospholipase C-γ2 (PLCγ2). The PLCγ2 variants typically do not exhibit constitutive activity in cell-free systems, leading to the suggestion that in intact cells they are hypersensitive to Rac family small GTPases or to the upstream kinases spleen-associated tyrosine kinase (SYK) and Lck/Yes-related novel tyrosine kinase (LYN). The sensitivity of the PLCγ2 variants to BTK itself has remained unknown. Here, using genetically-modified DT40 B lymphocytes, along with various biochemical assays, including analysis of PLCγ2-mediated inositol phosphate formation, inositol phospholipid assessments, fluorescence recovery after photobleaching (FRAP) static laser microscopy, and determination of intracellular calcium ([Ca2+]i), we show that various CLL-specific PLCγ2 variants such as PLCγ2S707Y are hyper-responsive to activated BTK, even in the absence of BTK's catalytic activity and independently of enhanced PLCγ2 phospholipid substrate supply. At high levels of B-cell receptor (BCR) activation, which may occur in individual CLL patients, catalytically-inactive BTK restored the ability of the BCR to mediate increases in [Ca2+]i. Because catalytically-inactive BTK is insensitive to active-site BTK inhibitors, the mechanism involving the noncatalytic BTK uncovered here may contribute to preexisting reduced sensitivity or even primary resistance of CLL to these drugs. Full Article