eps 4 Steps of Cognitive Restructuring to Help You Think Clearly By feedproxy.google.com Published On :: Tue, 05 May 2020 15:00:03 +0000 Humans are guilty of having less than rational thoughts. We do it all the time. We might assume the worst is going to happen or jump to conclusions before we have all the information. Cognitive restructuring helps people become aware of their irrational thoughts so that they can correct them and replace them with more [...]Read More... Full Article
eps PeepShow.tv: Cy By feeds.queerclick.com Published On :: Sat, 09 May 2020 04:18:21 +0000 Cy rubs one out for us! See more at Peepshow.tv. The post PeepShow.tv: Cy appeared first on QueerClick. Full Article Porn Site Updates PeepShow.tv
eps False Claim Targets Gates Using Epstein Connection By www.factcheck.org Published On :: Wed, 06 May 2020 21:19:37 +0000 There's no evidence that Bill Gates ever visited Jeffrey Epstein's private island in the Caribbean, contrary to a viral Facebook post claiming he went there numerous times. The "flight records" cited do not show that. The post False Claim Targets Gates Using Epstein Connection appeared first on FactCheck.org. Full Article Debunking False Stories
eps 04 – The Internet Musician – 8 Steps to Create a Music Website By feedproxy.google.com Published On :: Tue, 14 Feb 2012 20:19:46 +0000 Show Notes for Episode 4: Subscribe to the Internet Musician Podcast with iTunes: As a musician, you need a good website. You know that. But you really don’t need to spend years trying to understand the technology. You also don’t want to spend tons of time working on your site without knowing if you’re doing things […] Full Article Podcast create a music website create a website music website design
eps Prepaid Legal Leads - 3 Easy Steps to Generate an Absolute Abundance of Them By EzineArticles.com Published On :: Wed, 02 Dec 2009 07:47:15 -0600 Generating Prepaid Legal Leads can be difficult right? How about frustrating? Or how about all the above! Well, you are not the only one who may find it hard my friend. If you know how to harness the power of the internet and how to position yourself right you will generate more Prepaid Legal Leads than you can handle. In fact I am going to give you 3 easy steps to follow to truly prosper. Full Article
eps Learn the Best Online Marketing Strategy Using Articles - 2 Simple Steps! By EzineArticles.com Published On :: Fri, 29 Jan 2010 21:31:58 -0600 What is the best on-line marketing strategy? How can articles really help you? Well if you follow these simple tips you will find out why so many people are using it. Full Article
eps Street fight gets communities attention when a citizen steps up to help guide young men By chimac.net Published On :: Wed, 06 May 2020 16:31:22 +0000 Full Article Videos
eps Five Steps to Better Security Working from Home By feedproxy.google.com Published On :: Sat, 02 May 2020 15:00:30 +0000 Security threats for people working from home are increasing. I'll review steps you need to take to keep yourself, your company, and your job safe. Five Steps to Better Security Working from Home from Ask Leo!. Get the newsletter: https://newsletter.askleo.com Full Article Security automatic update Featured multi-factor authentication password reuse password vault Phishing phishing attacks two-factor authentication VPN windows update
eps Walking in My Own Footsteps in Singapore By www.travelblog.org Published On :: My friend Mizzi who lives in Melbourne Australia and I had decided to meet somewhere halfway between Germany and Australia for a holiday. I had suggested Borneo since I had wanted to go there during my year in Singapore but had never made it there. Mizz Full Article
eps Derbyshire 101 Chesterfield 7000 steps by 9.30 from frost to blue skiesSkype. Risk assessments and telekits will life ever be the same again By www.travelblog.org Published On :: Surfacing this morning was difficult . It is a work day today . Last night we had a frost . Not a heavy one . Not the sort of frost you get in the Winter . Not the sort of frost that you have to scrape off the car windscreen. But a frost nevertheless . The Full Article
eps Utah Reps. John Curtis and Chris Stewart to serve on GOP ‘China task force’ By www.sltrib.com Published On :: Fri, 08 May 2020 02:31:44 +0000 Full Article
eps Robert Kirby: This year just keeps getting worse, but screaming won’t help By www.sltrib.com Published On :: Fri, 08 May 2020 12:15:41 +0000 Full Article
eps Banjo CEO steps down after news of past KKK membership By www.sltrib.com Published On :: Sat, 09 May 2020 03:16:10 +0000 Full Article
eps How To Target Your Ideal Buyer in 6 Steps By feedproxy.google.com Published On :: Mon, 01 Jun 2015 12:37:27 +0000 When you’re trying to reach a particular audience, your success depends on how thoroughly you’re able to target them. It also depends on your market positioning and segmentation, but to achieve both of those you need, first and foremost, to know who your ideal buyer is – and how to reach him (or her). These 6 steps will give you a clear road map for how to target your ideal buyer. Identify Your Customer Profile This is more complex ... The post How To Target Your Ideal Buyer in 6 Steps appeared first on RSS Feed Converter. Full Article eBusiness Tips Internet marketing make money online online sales tips
eps How Leitrim ascended the steps to heaven in the 1990s By www.rte.ie Published On :: Wed, 06 May 2020 09:43:35 +0000 Leitrim's historic 1994 Connacht championship success was the culmination of a building process initiated five years earlier Full Article GAA
eps RTÉ Sport Classics: Briggs steps back into the unknown By www.rte.ie Published On :: Thu, 07 May 2020 13:09:14 +0000 Ireland's historic 2013 Women's Six Nations Grand Slam victory is the latest of our RTÉ Sport Classics which you can watch on RTÉ2 and the RTÉ Player at 9.30pm tonight. Niamh Briggs, who played a key role in that triumph relives the glory day before she watches it back for the first time. Full Article Rugby
eps Despite rough week, USC keeps tournament hopes alive with win over Washington By www.latimes.com Published On :: Fri, 14 Feb 2020 02:09:27 -0500 The situation practically begged for the young and inconsistent Trojans to fall apart. But instead, USC beat Washington, the Pac-12's last-place team 62-56. Full Article
eps Your favorite souvenirs: Readers share their wildest and wackiest travel keepsakes By www.latimes.com Published On :: Fri, 17 Apr 2020 10:00:24 -0400 We all bring home reminders of our trips. Now is the time to savor them. Full Article
eps 10 steps to take to start becoming plastic-free By www.latimes.com Published On :: Fri, 6 Mar 2020 09:00:48 -0500 Don't get overwhelmed. Start with doable goals in your quest to cut back on plastics. Full Article
eps Brigade response to Government announcement on further steps to reform the building safety system By www.london-fire.gov.uk Published On :: Thu, 02 Apr 2020 18:59:35 +0100 A Government announcement on further steps to reform the building safety system has been welcomed by London Fire Brigade, but senior firefighters also have concerns it has not gone far enough Full Article
eps Surviving the Shutdown: Brodard Restaurant keeps feeding Little Saigon By www.latimes.com Published On :: Thu, 23 Apr 2020 12:00:21 -0400 Sales are down at one of Orange County's most famous Vietnamese restaurants, but Brodard is adapting to survive Full Article
eps Deputy chief medical officer warns Boris’ next lockdown steps are ‘extremely painstaking’ By feedproxy.google.com Published On :: Sat, 09 May 2020 16:56:00 +0100 BORIS Johnson's deputy chief medical officer has warned the next coronavirus lockdown steps could prove to be extremely painstaking. Full Article
eps Rangers star Alfredo Morelos keeps the pressure on Celtic with late winner By www.express.co.uk Published On :: Sun, 23 Dec 2018 11:37:00 +0000 ALFREDO MORELOS powered Rangers to victory with a second half double to keep the pressure on Celtic. Full Article
eps Deputy chief medical officer warns Boris’ next lockdown steps are ‘extremely painstaking’ By feedproxy.google.com Published On :: Sat, 09 May 2020 16:56:00 +0100 BORIS Johnson's deputy chief medical officer has warned the next coronavirus lockdown steps could prove to be extremely painstaking. Full Article
eps How to build your own patio steps By feedproxy.google.com Published On :: Thu, 07 May 2020 10:21:00 +0100 DIY STORES across the UK have flung open their doors again, delighting housebound Brits. How do you build your own patio steps? Full Article
eps Mrs Hinch fan's cleaning hack will leave windows smear-free with easy to follow steps By feedproxy.google.com Published On :: Thu, 07 May 2020 03:00:00 +0100 MRS HINCH - also known as Sophie Hinchcliffe - is an Instagram cleaning sensation who has inspired millions to clean their home. She is known for her cheap cleaning hacks and quick easy methods. A Hinch fan has recently revealed how she got her windows gleaming with minimal effort. Full Article
eps Letters: Trump keeps campaign promises by building a robust economy By rssfeeds.indystar.com Published On :: Thu, 06 Feb 2020 10:00:22 +0000 Keeping him in office prevents the left from destroying America with their socialistic ideology, a letter to the editor says. Full Article
eps Coronavirus took their final milestones. Now, high school seniors are planning next steps By rssfeeds.indystar.com Published On :: Thu, 16 Apr 2020 09:00:06 +0000 With schools and campuses closed, high school seniors are planning for college just like they are finishing their high school careers: virtually. Full Article
eps Preps Podcast: What's happening in recruiting, concerns about fall sports By rssfeeds.indystar.com Published On :: Tue, 28 Apr 2020 20:37:14 +0000 Kyle Neddenriep and Matt Glenesk discuss sports after the coronavirus hits, what is happening in recruiting, concerns about fall sports and more. Full Article
eps Preps podcast: Kyle Neddenriep talks basketball with 3 guests By rssfeeds.indystar.com Published On :: Tue, 05 May 2020 14:32:27 +0000 High school basketball players Sincere McMahon and Connor Hickman, and coach Jeremy Rauch talk with IndyStar's Kyle Neddenriep Full Article
eps This Indianapolis burger restaurant keeps winning best burger awards By rssfeeds.indystar.com Published On :: Thu, 28 Jun 2018 14:21:23 +0000 Every burger on the Flamme Burger menu is cooked over a live fire. Full Article
eps Coronavirus: Why Denmark is taking steps to open up again By www.bbc.co.uk Published On :: Sat, 11 Apr 2020 23:25:30 GMT Danish schools will reopen soon, but curbs will only be lifted gradually. Full Article
eps Wearable technology started by tracking steps. Soon, it may allow your boss to track your performance. By www.washingtonpost.com Published On :: Fri, 28 Jun 2019 16:01:14 +0000 A team of researchers from Dartmouth say they’ve created a mobile sensing system — consisting of fitness bracelets, sensors and a custom app — that can measure employee performance with about 80 percent accuracy. Full Article
eps Alex Acosta gave a pass to Epstein years ago. He’s still at it as labor secretary. By www.washingtonpost.com Published On :: Mon, 08 Jul 2019 23:53:00 +0000 His department has ignored visas for trafficking victims. Full Article
eps Stop Losing Sleep: 7 Steps for Stress-free Decision-making By feedproxy.google.com Published On :: Mon, 27 Apr 2020 12:30:49 +0000 Decision-making can be tough especially when the best choice isn’t glaringly obvious. We’re faced with this process every minute of the day. When do I wake up? What’s for lunch? Do I want to go out on a date with this person? What do I want to do with my life? Can I stay in […] The post Stop Losing Sleep: 7 Steps for Stress-free Decision-making appeared first on Dumb Little Man. Full Article Stress Success
eps 3 Easy Steps to Save Money for Travel By everintransit.com Published On :: Thu, 30 May 2019 21:45:27 +0000 Finding ways to save money is much easier than you think, because you’re probably spending money you don’t have to spend. The article 3 Easy Steps to Save Money for Travel originated at EverInTransit.com Full Article Points + Miles Travel Tips credit card points food saving money
eps Oman’s New Sultan Needs to Take Bold Economic Steps By feedproxy.google.com Published On :: Thu, 16 Jan 2020 11:20:41 +0000 16 January 2020 Dr John Sfakianakis Associate Fellow, Middle East and North Africa Programme The country is in a good regional position, but the economy is at a crossroads. 2020-01-16-SultanHaitham2.jpg Sultan Haitham bin Tariq speaks during a swearing in ceremony as Oman's new leader. Photo: Getty Images. The transition of power in Oman from the deceased Sultan Qaboos to his cousin and the country’s new ruler, Sultan Haitham bin Tariq, has been smooth and quick, but the new sultan will soon find that he has a task in shoring up the country’s economic position.Above all, the fiscal and debt profile of the country requires careful management. Fiscal discipline was rare for Oman even during the oil price spike of the 2000s. Although oil prices only collapsed in 2014, Oman has been registering a fiscal deficit since 2010, reaching a 20.6 per cent high in 2016. As long as fiscal deficits remain elevated, so will Oman’s need to finance those deficits, predominately by borrowing in the local and international market.Oman’s Debt-to-GDP ratio has been rising at a worrying pace, from 4.9 per cent in 2014 to an IMF-estimated 59.8 per cent in 2019. By 2024, the IMF is forecasting the ratio to reach nearly 77 per cent. A study by the World Bank found that if the debt-to-GDP ratio in emerging markets exceeds 64 per cent for an extended period, it slows economic growth by as much as 2 per cent each year.Investors are willing to lend to Oman, but the sultanate is paying for it in terms of higher spreads due to the underlying risk markets are placing on the rising debt profile of the country. For instance, Oman has a higher sovereign debt rating than Bahrain yet markets perceive it to be of higher risk, making it costlier to borrow. Failure to address the fiscal and debt situation also risks creating pressure on the country’s pegged currency.If oil revenues remain low, Sultan Haitham will have to craft a daring strategy of diversification and private sector growth. He is well placed for this: Sultan Haitham headed Oman’s Vision 2040, which set out the country’s future development plans and aspirations, the first Gulf country to embark on such an assessment. However, like all vision documents in the Gulf, Oman’s challenge will be implementation.In the age of climate change, renewable energy is a serious economic opportunity, which Oman has to keep pursuing. If cheap electricity is generated it could also be exported to other Gulf states and to south Asia. In Oman, the share of renewables in total electricity capacity was around 0.5 per cent in 2018; the ambition is to reach 10 per cent by 2025.However, in order to reach this target, Oman would have to take additional measures such as enhancing its regulatory framework, introducing a transparent and gradual energy market pricing policy and integrating all stakeholders, including the private sector, into a wider national strategy.Mining could provide another economic opportunity for Oman’s diversification efforts, with help from a more robust mining law passed last year. The country has large deposits of metals and industrial minerals and its mountains could have gold, palladium, zinc, rare earths and manganese.Oman’s strategic location connecting the Gulf and Indian Ocean with east Africa and the Red Sea could also boost the country’s economy. The Duqm special economic zone, which is among the largest in the world, could become the commercial thread between Oman, south Asia and China’s ‘Belt and Road Initiative.’Oman has taken important steps to make its economy more competitive and conducive to foreign direct investment. Incentives include a five-year renewable tax holiday, subsidized plant facilities and utilities, and custom duties relief on equipment and raw materials for the first 10 years of a firm’s operation in Oman.A private sector economic model that embraces small- and medium-sized enterprises as well as greater competition and entrepreneurship would help increase opportunities in Oman. Like all other Gulf economies, future employment in Oman will have to be driven be the private sector, as there is little space left to grow the public sector.Privatization needs to continue. Last year’s successful sale of 49 per cent of the electricity transmission company to China’s State Grid is a very positive step. The electricity distribution company as well as Oman Oil are next in line for some form of partial privatization.The next decade will require Oman to be even more adept in its competitiveness as the region itself tries to find its new bearings. Take tourism for instance; Oman hopes to double its contribution to GDP from around 3 per cent today to 6 per cent by 2040 and the industry is expected to generate half a million jobs by then. Over the next 20 years, Oman will most likely be facing stiff competition in this area not only by the UAE but by Saudi Arabia as well.The new sultan has an opportunity to embark on deeper economic reforms that could bring higher growth, employment opportunities and a sustainable future. But he has a big task. Full Article
eps 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
eps Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3 By feedproxy.google.com Published On :: 2000-09-01 Mohamad NavabSep 1, 2000; 41:1495-1508Articles Full Article
eps Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: step 1 By feedproxy.google.com Published On :: 2000-09-01 Mohamad NavabSep 1, 2000; 41:1481-1494Articles Full Article
eps The Failed Marshall Plan: Learning from US Foreign Policy Missteps By feedproxy.google.com Published On :: Mon, 10 Sep 2018 00:00:00 +0100 Full Article
eps CBD Communiqué: The Biodiversity Family Stands in Solidarity with the People and Government of the Historic Nagoya Biodiversity Summit: CBD Secretariat steps up to support disaster relief efforts in Japan. By www.cbd.int Published On :: Thu, 07 Apr 2011 00:00:00 GMT Full Article
eps CBD Press Release: Biodiversity Awareness Keeps Rising among Consumers and Business. By www.cbd.int Published On :: Thu, 05 May 2011 00:00:00 GMT Full Article
eps CBD News: Governments have agreed to a series of actions that will further bolster the Nagoya Protocol on Access and Benefit Sharing, facilitate its effective implementation, and ensure that countries have the necessary resources to take the next steps to By www.cbd.int Published On :: Fri, 17 Oct 2014 00:00:00 GMT Full Article
eps Biosynthesis of depsipeptides with a 3-hydroxybenzoate moiety and selective anticancer activities involves a chorismatase [Metabolism] By www.jbc.org 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
eps Can you reuse a disposable mask? Yes, if you follow these steps By news.yahoo.com Published On :: Thu, 07 May 2020 15:22:00 -0400 Disposable masks can be used more than once, but it's important to make sure the mask isn't carrying coronavirus. Full Article
eps Oman’s New Sultan Needs to Take Bold Economic Steps By feedproxy.google.com Published On :: Thu, 16 Jan 2020 11:20:41 +0000 16 January 2020 Dr John Sfakianakis Associate Fellow, Middle East and North Africa Programme The country is in a good regional position, but the economy is at a crossroads. 2020-01-16-SultanHaitham2.jpg Sultan Haitham bin Tariq speaks during a swearing in ceremony as Oman's new leader. Photo: Getty Images. The transition of power in Oman from the deceased Sultan Qaboos to his cousin and the country’s new ruler, Sultan Haitham bin Tariq, has been smooth and quick, but the new sultan will soon find that he has a task in shoring up the country’s economic position.Above all, the fiscal and debt profile of the country requires careful management. Fiscal discipline was rare for Oman even during the oil price spike of the 2000s. Although oil prices only collapsed in 2014, Oman has been registering a fiscal deficit since 2010, reaching a 20.6 per cent high in 2016. As long as fiscal deficits remain elevated, so will Oman’s need to finance those deficits, predominately by borrowing in the local and international market.Oman’s Debt-to-GDP ratio has been rising at a worrying pace, from 4.9 per cent in 2014 to an IMF-estimated 59.8 per cent in 2019. By 2024, the IMF is forecasting the ratio to reach nearly 77 per cent. A study by the World Bank found that if the debt-to-GDP ratio in emerging markets exceeds 64 per cent for an extended period, it slows economic growth by as much as 2 per cent each year.Investors are willing to lend to Oman, but the sultanate is paying for it in terms of higher spreads due to the underlying risk markets are placing on the rising debt profile of the country. For instance, Oman has a higher sovereign debt rating than Bahrain yet markets perceive it to be of higher risk, making it costlier to borrow. Failure to address the fiscal and debt situation also risks creating pressure on the country’s pegged currency.If oil revenues remain low, Sultan Haitham will have to craft a daring strategy of diversification and private sector growth. He is well placed for this: Sultan Haitham headed Oman’s Vision 2040, which set out the country’s future development plans and aspirations, the first Gulf country to embark on such an assessment. However, like all vision documents in the Gulf, Oman’s challenge will be implementation.In the age of climate change, renewable energy is a serious economic opportunity, which Oman has to keep pursuing. If cheap electricity is generated it could also be exported to other Gulf states and to south Asia. In Oman, the share of renewables in total electricity capacity was around 0.5 per cent in 2018; the ambition is to reach 10 per cent by 2025.However, in order to reach this target, Oman would have to take additional measures such as enhancing its regulatory framework, introducing a transparent and gradual energy market pricing policy and integrating all stakeholders, including the private sector, into a wider national strategy.Mining could provide another economic opportunity for Oman’s diversification efforts, with help from a more robust mining law passed last year. The country has large deposits of metals and industrial minerals and its mountains could have gold, palladium, zinc, rare earths and manganese.Oman’s strategic location connecting the Gulf and Indian Ocean with east Africa and the Red Sea could also boost the country’s economy. The Duqm special economic zone, which is among the largest in the world, could become the commercial thread between Oman, south Asia and China’s ‘Belt and Road Initiative.’Oman has taken important steps to make its economy more competitive and conducive to foreign direct investment. Incentives include a five-year renewable tax holiday, subsidized plant facilities and utilities, and custom duties relief on equipment and raw materials for the first 10 years of a firm’s operation in Oman.A private sector economic model that embraces small- and medium-sized enterprises as well as greater competition and entrepreneurship would help increase opportunities in Oman. Like all other Gulf economies, future employment in Oman will have to be driven be the private sector, as there is little space left to grow the public sector.Privatization needs to continue. Last year’s successful sale of 49 per cent of the electricity transmission company to China’s State Grid is a very positive step. The electricity distribution company as well as Oman Oil are next in line for some form of partial privatization.The next decade will require Oman to be even more adept in its competitiveness as the region itself tries to find its new bearings. Take tourism for instance; Oman hopes to double its contribution to GDP from around 3 per cent today to 6 per cent by 2040 and the industry is expected to generate half a million jobs by then. Over the next 20 years, Oman will most likely be facing stiff competition in this area not only by the UAE but by Saudi Arabia as well.The new sultan has an opportunity to embark on deeper economic reforms that could bring higher growth, employment opportunities and a sustainable future. But he has a big task. Full Article
eps Demarcation of Sepsis-Induced Peripheral and Central Acidosis with pH-Low Insertion Cyclic (pHLIC) Peptide By jnm.snmjournals.org Published On :: 2020-01-31T13:36:41-08:00 Acidosis is a key driver for many diseases, including cancer, sepsis, and stroke. The spatiotemporal dynamics of dysregulated pH across disease remains elusive and current diagnostic strategies do not provide localization of pH alterations. We sought to explore if PET imaging using hydrophobic cyclic peptides that partition into the cellular membrane at low extracellular pH (denoted as "pHLIC") can permit accurate in vivo visualization of acidosis. Methods: Acid-sensitive cyclic peptide c[E4W5C] pHLIC was conjugated to bifunctional maleimide-NO2A and radiolabeled with copper-64 (t1/2 = 12.7 h). C57BL/6J mice were administered LPS (15 mg/kg) or saline (vehicle) and serially imaged with [64Cu]Cu-c[E4W5C] over 24 h. Ex vivo autoradiography was performed on resected brain slices and subsequently stained with cresyl violet to enable high-resolution spatial analysis of tracer accumulation. A non- pH-sensitive cell-penetrating control peptide (c[R4W5C]) was used to confirm specificity of [64Cu]Cu-c[E4W5C]. CD11b (macrophage/microglia) and TMEM119 (microglia) immunostaining was performed to correlate extent of neuroinflammation with [64Cu]Cu-c[E4W5C] PET signal. Results: [64Cu]Cu-c[E4W5C] radiochemical yield and purity was >95% and >99% respectively, with molar activity >0.925 MBq/nmol. Significantly increased [64Cu]Cu-c[E4W5C] uptake was observed in LPS-treated mice (vs. vehicle) within peripheral tissues including blood, lungs, liver, and small intestines (P < 0.001-0.05). Additionally, there was significantly increased [64Cu]Cu-c[E4W5C] uptake in the brains of LPS-treated animals. Autoradiography confirmed increased uptake in the cerebellum, cortex, hippocampus, striatum, and hypothalamus of LPS-treated mice (vs. vehicle). Immunohistochemical (IHC) analysis revealed microglial/macrophage infiltrate, suggesting activation in brain regions containing increased tracer uptake. [64Cu]Cu-c[R4W5C] demonstrated significantly reduced uptake in the brain and periphery of LPS mice compared to the acid-mediated [64Cu]Cu-c[E4W5C] tracer. Conclusion: Here, we demonstrate that a pH-sensitive PET tracer specifically detects acidosis in regions associated with sepsis-driven pro-inflammatory responses. This study suggests that [64Cu]Cu-pHLIC is a valuable tool to noninvasively assess acidosis associated with both central and peripheral innate immune activation. Full Article
eps 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
eps Oman’s New Sultan Needs to Take Bold Economic Steps By feedproxy.google.com Published On :: Thu, 16 Jan 2020 11:20:41 +0000 16 January 2020 Dr John Sfakianakis Associate Fellow, Middle East and North Africa Programme The country is in a good regional position, but the economy is at a crossroads. 2020-01-16-SultanHaitham2.jpg Sultan Haitham bin Tariq speaks during a swearing in ceremony as Oman's new leader. Photo: Getty Images. The transition of power in Oman from the deceased Sultan Qaboos to his cousin and the country’s new ruler, Sultan Haitham bin Tariq, has been smooth and quick, but the new sultan will soon find that he has a task in shoring up the country’s economic position.Above all, the fiscal and debt profile of the country requires careful management. Fiscal discipline was rare for Oman even during the oil price spike of the 2000s. Although oil prices only collapsed in 2014, Oman has been registering a fiscal deficit since 2010, reaching a 20.6 per cent high in 2016. As long as fiscal deficits remain elevated, so will Oman’s need to finance those deficits, predominately by borrowing in the local and international market.Oman’s Debt-to-GDP ratio has been rising at a worrying pace, from 4.9 per cent in 2014 to an IMF-estimated 59.8 per cent in 2019. By 2024, the IMF is forecasting the ratio to reach nearly 77 per cent. A study by the World Bank found that if the debt-to-GDP ratio in emerging markets exceeds 64 per cent for an extended period, it slows economic growth by as much as 2 per cent each year.Investors are willing to lend to Oman, but the sultanate is paying for it in terms of higher spreads due to the underlying risk markets are placing on the rising debt profile of the country. For instance, Oman has a higher sovereign debt rating than Bahrain yet markets perceive it to be of higher risk, making it costlier to borrow. Failure to address the fiscal and debt situation also risks creating pressure on the country’s pegged currency.If oil revenues remain low, Sultan Haitham will have to craft a daring strategy of diversification and private sector growth. He is well placed for this: Sultan Haitham headed Oman’s Vision 2040, which set out the country’s future development plans and aspirations, the first Gulf country to embark on such an assessment. However, like all vision documents in the Gulf, Oman’s challenge will be implementation.In the age of climate change, renewable energy is a serious economic opportunity, which Oman has to keep pursuing. If cheap electricity is generated it could also be exported to other Gulf states and to south Asia. In Oman, the share of renewables in total electricity capacity was around 0.5 per cent in 2018; the ambition is to reach 10 per cent by 2025.However, in order to reach this target, Oman would have to take additional measures such as enhancing its regulatory framework, introducing a transparent and gradual energy market pricing policy and integrating all stakeholders, including the private sector, into a wider national strategy.Mining could provide another economic opportunity for Oman’s diversification efforts, with help from a more robust mining law passed last year. The country has large deposits of metals and industrial minerals and its mountains could have gold, palladium, zinc, rare earths and manganese.Oman’s strategic location connecting the Gulf and Indian Ocean with east Africa and the Red Sea could also boost the country’s economy. The Duqm special economic zone, which is among the largest in the world, could become the commercial thread between Oman, south Asia and China’s ‘Belt and Road Initiative.’Oman has taken important steps to make its economy more competitive and conducive to foreign direct investment. Incentives include a five-year renewable tax holiday, subsidized plant facilities and utilities, and custom duties relief on equipment and raw materials for the first 10 years of a firm’s operation in Oman.A private sector economic model that embraces small- and medium-sized enterprises as well as greater competition and entrepreneurship would help increase opportunities in Oman. Like all other Gulf economies, future employment in Oman will have to be driven be the private sector, as there is little space left to grow the public sector.Privatization needs to continue. Last year’s successful sale of 49 per cent of the electricity transmission company to China’s State Grid is a very positive step. The electricity distribution company as well as Oman Oil are next in line for some form of partial privatization.The next decade will require Oman to be even more adept in its competitiveness as the region itself tries to find its new bearings. Take tourism for instance; Oman hopes to double its contribution to GDP from around 3 per cent today to 6 per cent by 2040 and the industry is expected to generate half a million jobs by then. Over the next 20 years, Oman will most likely be facing stiff competition in this area not only by the UAE but by Saudi Arabia as well.The new sultan has an opportunity to embark on deeper economic reforms that could bring higher growth, employment opportunities and a sustainable future. But he has a big task. Full Article