bit Griffin Canning pitches two good innings, but Angels fall to Dodgers in exhibition game By www.latimes.com Published On :: Wed, 26 Feb 2020 20:52:41 -0500 The Angels lost 9-4 to the Dodgers on Wednesday at Camelback Ranch in Phoenix. Full Article
bit Kings showed this fan they had a lot of bite By www.latimes.com Published On :: Thu, 13 Feb 2020 12:54:57 -0500 For one night, the hapless Kings show it's not the size of the dog in the fight, but the size of the fight in the dog that matters. Full Article
bit Dodgers beat Angels behind good pitching and offense in spring training exhibition By www.latimes.com Published On :: Wed, 26 Feb 2020 19:38:08 -0500 The Dodgers mount a comeback to beat the Angels 9-4 on Wednesday at Camelback Ranch to improve their spring training record 3-1. Full Article
bit Kenley Jansen looks sharp in Dodgers' exhibition loss to Rangers By www.latimes.com Published On :: Sun, 1 Mar 2020 19:29:45 -0500 Dodgers closer Kenley Jansen retires the three batters he faces and shows off his new slider grip in spring training loss to Texas Rangers. Full Article
bit Alex Wood and Tony Gonsolin are sharp in Dodgers' exhibition rout of the Padres By www.latimes.com Published On :: Mon, 9 Mar 2020 20:18:48 -0400 Left-hander Alex Wood and right-hander Tony Gonsolin combined to allow one run in six innings of the Dodgers' 14-2 exhibition win over the San Diego Padres. Full Article
bit Korean soccer league prohibiting players from spitting, talking on field By www.nydailynews.com Published On :: Fri, 08 May 2020 01:56:39 +0000 Korea's top soccer league will be banning players from talking and excessive spitting on the pitch. Full Article
bit From controversial to awards darling, down the rabbit hole with 'Jojo' By www.latimes.com Published On :: Wed, 29 Jan 2020 09:00:39 -0500 Taika Waititi's irreverent but humanist look at a boy in the Hitler Youth has been a major presence this awards season — for good and bad. Full Article
bit 'Jojo Rabbit,' 'Knives Out,' 'Schitt's Creek' win big at Costume Designers Guild Awards By www.latimes.com Published On :: Wed, 29 Jan 2020 14:15:32 -0500 Find out if your favorite film, TV show or commercial won at the 22nd CDGAs, which were hosted by Mindy Kaling. Also honored were Charlize Theron, Adam McKay, Michael Kaplan and Mary Ellen Fields. Full Article
bit 'Jojo Rabbit's' Mayes Rubeo 'euphoric' as first Latina costume designer to be nominated By www.latimes.com Published On :: Thu, 30 Jan 2020 10:30:30 -0500 'Jojo Rabbit' costume designer Mayes C. Rubeo made her mark with Mel Gibson's 'Apocalypto.' For Taika Waititi, she turned to history and art for inspiration. Full Article
bit Sniping at airlines for a soundbite doesn't fly By www.independent.co.uk Published On :: 2020-04-01T07:05:00Z Plane Talk: Many airlines have erred during the coronavirus crisis, but so have some politicians Full Article
bit Review: Like a teenage spin on Todd Haynes, 'To the Stars' delivers bittersweet take on the past By www.latimes.com Published On :: Wed, 22 Apr 2020 16:00:36 -0400 "To the Stars" sensitively explores forbidden love and small minds with a supporting cast that includes Jordana Spiro, Shea Whigham, Malin Akerman and Tony Hale. Full Article
bit Celtic hero Chris Sutton bites back at Robbie Savage trolling as Hoops leapfrog Rangers By www.express.co.uk Published On :: Sun, 20 Oct 2019 15:06:00 +0100 Celtic legend Chris Sutton has bitten back Robbie Savage on Twitter, as the Hoops finished the week top of the Scottish Premiership table, after Rangers’ 1-1 draw against Hearts. Full Article
bit Martin Lewis breaks down new ISA rules: ‘Now this is a bit complicated’ By feedproxy.google.com Published On :: Fri, 08 May 2020 07:37:00 +0100 MARTIN LEWIS, 47, appeared on his Money Show Live last night to discuss the latest news on all things finance and coronavirus. He responded to one viewer who had questions on their ISA options. Full Article
bit Over 50% of people plan not to reinstate direct debits post lockdown – expert gives advice By feedproxy.google.com Published On :: Sat, 09 May 2020 04:00:00 +0100 CORONAVIRUS has forced people to re-evaluate their finances as income takes a hit and budgets are stretched. One of the first port of calls for change has been direct debits and new research reveals that some people may find themselves with more cash available once this all ends. Full Article
bit Bitcoin surges as cryptocurrency jumps $13 BILLION in huge rally By feedproxy.google.com Published On :: Fri, 08 May 2020 09:44:00 +0100 A SURGE in bitcoin prices has seen the cryptocurrency market jump by over $13 billion overnight. Full Article
bit Shock at two million bits of plastic in just a square metre of Mediterranean Sea By www.express.co.uk Published On :: Fri, 01 May 2020 09:06:00 +0100 ALARMING levels of plastic have been found on the Mediterranean seabed, scientists revealed yesterday. Full Article
bit Exoplanets shock: Pioneering research expands definition of habitable planets By www.express.co.uk Published On :: Sat, 09 May 2020 07:00:00 +0100 PIONEERING new research has indicated life can thrive on planets with hydrogen-rich atmospheres, opening up a whole new area of exploration for astrobiologists. Full Article
bit The Hobbit live reading: How to watch Andy Serkis 12-hour charity reading of The Hobbit By feedproxy.google.com Published On :: Thu, 07 May 2020 15:10:00 +0100 THE HOBBIT is exactly the story we need to escape from normal life - and now Andy Serkis will take on a mammoth reading. Full Article
bit Lord of the Rings: Gollum star Andy Serkis to read The Hobbit in ONE sitting live online By feedproxy.google.com Published On :: Thu, 07 May 2020 15:44:00 +0100 LORD OF THE RINGS Gollum actor Andy Serkis has announced he will read JRR Tolkien's The Hobbit in one sitting live online for charity. Full Article
bit Samsung To Launch a Samsung Pay Debit Card This Summer By rss.slashdot.org Published On :: 2020-05-08T23:10:00+00:00 In a blog post yesterday, Samsung announced plans to launch a Samsung Pay debit card this summer. The Verge reports: Samsung will launch the card, which will be backed by a cash management account, in partnership with personal finance company SoFi, Ahn said. Samsung is also developing a "mobile-first money management platform," according to Ahn. His blog doesn't detail what features that money management platform or the upcoming debit card may have, but he does say that Samsung will share more details "in the coming weeks." Samsung joins Apple in offering a branded payment card. Google is reportedly working on its own branded payment card as well, though Google's will apparently be a debit card, like Samsung's. Google will also supposedly offer spending-tracking tools for the card. Read more of this story at Slashdot. Full Article
bit John Mellencamp will collect Woody Guthrie Prize as Rock Hall exhibit shifts to Oklahoma By rssfeeds.indystar.com Published On :: Tue, 17 Jul 2018 23:32:00 +0000 Woody Guthrie Center will honor John Mellencamp's career of spotlighting "the everyday man and woman, the less fortunate and the forgotten." Full Article
bit Coronavirus: Lockdown bites poor as France eases grip By www.bbc.co.uk Published On :: Thu, 07 May 2020 15:20:10 GMT France is eyeing a lifting of strict coronavirus measures on Monday but for many the damage is done. Full Article
bit These biting cartoons tell the story of the impeachment fight this week By www.washingtonpost.com Published On :: Fri, 01 Nov 2019 15:14:06 +0000 Did Pelosi or Trump gain the upper hand? Full Article
bit 12 Bad Cruise Habits That Annoy Other Cruise Passengers By tips4travellers.libsyn.com Published On :: Mon, 01 Jul 2019 04:00:00 +0000 Discover 12 habits and things cruisers do on a cruise that annoy other cruise passengers the most. Things I have seen on my many cruises, watch cruise fans discussing on cruising forums and reading complaints about. 12 common practices, habits and things cruise guests do that drive other passengers crazy. Are you guilty of any of these? Do some or all of these drive you crazy? Or, do you not see why they upset other cruise guests? Full Article
bit Tools You Should Know To Protect Bitcoin Transactions By spyrestudios.com Published On :: Tue, 28 Apr 2020 02:17:25 PDT The option of cryptocurrencies or electronic currencies for websites is increasingly stronger as a mechanism for the purchase of products and services, not only on the Internet but also in some businesses that have begun to accept this means of payment. If you’re working on a crypto-related project or a client who accepts cryptocurrency payments, […] The post Tools You Should Know To Protect Bitcoin Transactions appeared first on SpyreStudios. Full Article Tools bitcoin cryptocurrency
bit Fin24.com | WATCH: Documents show Huawei role in shipping prohibited US gear to Iran By www.fin24.com Published On :: Thu, 05 Mar 2020 11:09:30 +0200 China’s Huawei, which for years has denied violating American trade sanctions on Iran, produced internal company records in 2010 that show it was directly involved in sending prohibited US computer equipment to Iran’s largest mobile-phone operator. Full Article
bit Fin24.com | WATCH | Facebook tries again with its Bitcoin rival By www.fin24.com Published On :: Mon, 20 Apr 2020 12:44:32 +0200 Facebook's Libra cryptocurrency could now launch in mid-November after a revamp aimed at mollifying its many critics. Full Article
bit BitTorrent Debuts P2P-Powered Social One-Click Hosting By feedproxy.google.com Published On :: Thu, 12 May 2011 12:38:37 -0700 BitTorrents new Project Chrysalis client now makes it possible to share files of unlimited size with your friends even when youre not online. The company is caching files and using a revamped UI to make the facilitation of BitTorrent downloads much easier than before. Continue reading on NewTeeVee.Tags: BitTorrent, Chrysalis Full Article File sharing
bit Sneak peak: BitTorrent expands live streaming tests By feedproxy.google.com Published On :: Mon, 3 Oct 2011 17:22:07 -0700 BitTorrent founder Bram Cohen and his company are moving forward with its P2P live streaming project, expanding field trials and courting indie bands to stress test Cohens algorithms. However, it could still take months before BitTorrent Live is ready for prime time. Continue reading on NewTeeVee. Tags: NewTeeVee, BitTorrent Full Article Misc
bit What you need to know about Bitcoin halving By feedproxy.google.com Published On :: Fri, 08 May 2020 19:22:32 +0000 Bitcoin will “halve” for the third time next week, slowing down the discovery of new bitcoins and preventing disruptions from new miners. Read more...More about Tech, Internet, Mashable Video, Money, and Bitcoin Full Article Tech Internet Mashable Video Money Bitcoin
bit Inhibition of the erythropoietin-producing receptor EPHB4 antagonizes androgen receptor overexpression and reduces enzalutamide resistance [Molecular Bases of Disease] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Prostate cancer (PCa) cells heavily rely on an active androgen receptor (AR) pathway for their survival. Enzalutamide (MDV3100) is a second-generation antiandrogenic drug that was approved by the Food and Drug Administration in 2012 to treat patients with castration-resistant prostate cancer (CRPC). However, emergence of resistance against this drug is inevitable, and it has been a major challenge to develop interventions that help manage enzalutamide-resistant CRPC. Erythropoietin-producing human hepatocellular (Eph) receptors are targeted by ephrin protein ligands and have a broad range of functions. Increasing evidence indicates that this signaling pathway plays an important role in tumorigenesis. Overexpression of EPH receptor B4 (EPHB4) has been observed in multiple types of cancer, being closely associated with proliferation, invasion, and metastasis of tumors. Here, using RNA-Seq analyses of clinical and preclinical samples, along with several biochemical and molecular methods, we report that enzalutamide-resistant PCa requires an active EPHB4 pathway that supports drug resistance of this tumor type. Using a small kinase inhibitor and RNAi-based gene silencing to disrupt EPHB4 activity, we found that these disruptions re-sensitize enzalutamide-resistant PCa to the drug both in vitro and in vivo. Mechanistically, we found that EPHB4 stimulates the AR by inducing proto-oncogene c-Myc (c-Myc) expression. Taken together, these results provide critical insight into the mechanism of enzalutamide resistance in PCa, potentially offering a therapeutic avenue for enhancing the efficacy of enzalutamide to better manage this common malignancy. Full Article
bit Structure-based discovery of a small-molecule inhibitor of methicillin-resistant Staphylococcus aureus virulence [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton–Valentine leukocidin (PVL) and α-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and α-toxin in their soluble, monomeric, and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C14PC). The structures revealed two evolutionarily conserved phosphatidylcholine-binding mechanisms and their roles in modulating host cell attachment, oligomer assembly, and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and α-toxin and hence may serve as the basis for the development of an antivirulence agent for managing MRSA infections. Full Article
bit Pro-515 of the dynamin-like GTPase MxB contributes to HIV-1 inhibition by regulating MxB oligomerization and binding to HIV-1 capsid [Microbiology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Interferon-regulated myxovirus resistance protein B (MxB) is an interferon-induced GTPase belonging to the dynamin superfamily. It inhibits infection with a wide range of different viruses, including HIV-1, by impairing viral DNA entry into the nucleus. Unlike the related antiviral GTPase MxA, MxB possesses an N-terminal region that contains a nuclear localization signal and is crucial for inhibiting HIV-1. Because MxB previously has been shown to reside in both the nuclear envelope and the cytoplasm, here we used bioinformatics and biochemical approaches to identify a nuclear export signal (NES) responsible for MxB's cytoplasmic location. Using the online computational tool LocNES (Locating Nuclear Export Signals or NESs), we identified five putative NES candidates in MxB and investigated whether their deletion caused nuclear localization of MxB. Our results revealed that none of the five deletion variants relocates to the nucleus, suggesting that these five predicted NES sequences do not confer NES activity. Interestingly, deletion of one sequence, encompassing amino acids 505–527, abrogated the anti-HIV-1 activity of MxB. Further mutation experiments disclosed that amino acids 515–519, and Pro-515 in particular, regulate MxB oligomerization and its binding to HIV-1 capsid, thereby playing an important role in MxB-mediated restriction of HIV-1 infection. In summary, our results indicate that none of the five predicted NES sequences in MxB appears to be required for its nuclear export. Our findings also reveal several residues in MxB, including Pro-515, critical for its oligomerization and anti-HIV-1 function. Full Article
bit Inhibition of the polyamine synthesis enzyme ornithine decarboxylase sensitizes triple-negative breast cancer cells to cytotoxic chemotherapy [Molecular Bases of Disease] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Treatment of patients with triple-negative breast cancer (TNBC) is limited by a lack of effective molecular therapies targeting this disease. Recent studies have identified metabolic alterations in cancer cells that can be targeted to improve responses to standard-of-care chemotherapy regimens. Using MDA-MB-468 and SUM-159PT TNBC cells, along with LC-MS/MS and HPLC metabolomics profiling, we found here that exposure of TNBC cells to the cytotoxic chemotherapy drugs cisplatin and doxorubicin alter arginine and polyamine metabolites. This alteration was because of a reduction in the levels and activity of a rate-limiting polyamine biosynthetic enzyme, ornithine decarboxylase (ODC). Using gene silencing and inhibitor treatments, we determined that the reduction in ODC was mediated by its negative regulator antizyme, targeting ODC to the proteasome for degradation. Treatment with the ODC inhibitor difluoromethylornithine (DFMO) sensitized TNBC cells to chemotherapy, but this was not observed in receptor-positive breast cancer cells. Moreover, TNBC cell lines had greater sensitivity to single-agent DFMO, and ODC levels were elevated in TNBC patient samples. The alterations in polyamine metabolism in response to chemotherapy, as well as DFMO-induced preferential sensitization of TNBC cells to chemotherapy, reported here suggest that ODC may be a targetable metabolic vulnerability in TNBC. Full Article
bit The major subunit of widespread competence pili exhibits a novel and conserved type IV pilin fold [Protein Structure and Folding] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Type IV filaments (T4F), which are helical assemblies of type IV pilins, constitute a superfamily of filamentous nanomachines virtually ubiquitous in prokaryotes that mediate a wide variety of functions. The competence (Com) pilus is a widespread T4F, mediating DNA uptake (the first step in natural transformation) in bacteria with one membrane (monoderms), an important mechanism of horizontal gene transfer. Here, we report the results of genomic, phylogenetic, and structural analyses of ComGC, the major pilin subunit of Com pili. By performing a global comparative analysis, we show that Com pili genes are virtually ubiquitous in Bacilli, a major monoderm class of Firmicutes. This also revealed that ComGC displays extensive sequence conservation, defining a monophyletic group among type IV pilins. We further report ComGC solution structures from two naturally competent human pathogens, Streptococcus sanguinis (ComGCSS) and Streptococcus pneumoniae (ComGCSP), revealing that this pilin displays extensive structural conservation. Strikingly, ComGCSS and ComGCSP exhibit a novel type IV pilin fold that is purely helical. Results from homology modeling analyses suggest that the unusual structure of ComGC is compatible with helical filament assembly. Because ComGC displays such a widespread distribution, these results have implications for hundreds of monoderm species. Full Article
bit Pro-515 of the dynamin-like GTPase MxB contributes to HIV-1 inhibition by regulating MxB oligomerization and binding to HIV-1 capsid [Microbiology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Interferon-regulated myxovirus resistance protein B (MxB) is an interferon-induced GTPase belonging to the dynamin superfamily. It inhibits infection with a wide range of different viruses, including HIV-1, by impairing viral DNA entry into the nucleus. Unlike the related antiviral GTPase MxA, MxB possesses an N-terminal region that contains a nuclear localization signal and is crucial for inhibiting HIV-1. Because MxB previously has been shown to reside in both the nuclear envelope and the cytoplasm, here we used bioinformatics and biochemical approaches to identify a nuclear export signal (NES) responsible for MxB's cytoplasmic location. Using the online computational tool LocNES (Locating Nuclear Export Signals or NESs), we identified five putative NES candidates in MxB and investigated whether their deletion caused nuclear localization of MxB. Our results revealed that none of the five deletion variants relocates to the nucleus, suggesting that these five predicted NES sequences do not confer NES activity. Interestingly, deletion of one sequence, encompassing amino acids 505–527, abrogated the anti-HIV-1 activity of MxB. Further mutation experiments disclosed that amino acids 515–519, and Pro-515 in particular, regulate MxB oligomerization and its binding to HIV-1 capsid, thereby playing an important role in MxB-mediated restriction of HIV-1 infection. In summary, our results indicate that none of the five predicted NES sequences in MxB appears to be required for its nuclear export. Our findings also reveal several residues in MxB, including Pro-515, critical for its oligomerization and anti-HIV-1 function. Full Article
bit 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
bit {gamma}-Hydroxybutyrate does not mediate glucose inhibition of glucagon secretion [Signal Transduction] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Hypersecretion of glucagon from pancreatic α-cells strongly contributes to diabetic hyperglycemia. Moreover, failure of α-cells to increase glucagon secretion in response to falling blood glucose concentrations compromises the defense against hypoglycemia, a common complication in diabetes therapy. However, the mechanisms underlying glucose regulation of glucagon secretion are poorly understood and likely involve both α-cell–intrinsic and intraislet paracrine signaling. Among paracrine factors, glucose-stimulated release of the GABA metabolite γ-hydroxybutyric acid (GHB) from pancreatic β-cells might mediate glucose suppression of glucagon release via GHB receptors on α-cells. However, the direct effects of GHB on α-cell signaling and glucagon release have not been investigated. Here, we found that GHB (4–10 μm) lacked effects on the cytoplasmic concentrations of the secretion-regulating messengers Ca2+ and cAMP in mouse α-cells. Glucagon secretion from perifused mouse islets was also unaffected by GHB at both 1 and 7 mm glucose. The GHB receptor agonist 3-chloropropanoic acid and the antagonist NCS-382 had no effects on glucagon secretion and did not affect stimulation of secretion induced by a drop in glucose from 7 to 1 mm. Inhibition of endogenous GHB formation with the GABA transaminase inhibitor vigabatrin also failed to influence glucagon secretion at 1 mm glucose and did not prevent the suppressive effect of 7 mm glucose. In human islets, GHB tended to stimulate glucagon secretion at 1 mm glucose, an effect mimicked by 3-chloropropanoic acid. We conclude that GHB does not mediate the inhibitory effect of glucose on glucagon secretion. Full Article
bit The focal adhesion protein kindlin-2 controls mitotic spindle assembly by inhibiting histone deacetylase 6 and maintaining {alpha}-tubulin acetylation [Signal Transduction] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Kindlins are focal adhesion proteins that regulate integrin activation and outside-in signaling. The kindlin family consists of three members, kindlin-1, -2, and -3. Kindlin-2 is widely expressed in multiple cell types, except those from the hematopoietic lineage. A previous study has reported that the Drosophila Fit1 protein (an ortholog of kindlin-2) prevents abnormal spindle assembly; however, the mechanism remains unknown. Here, we show that kindlin-2 maintains spindle integrity in mitotic human cells. The human neuroblastoma SH-SY5Y cell line expresses only kindlin-2, and we found that when SH-SY5Y cells are depleted of kindlin-2, they exhibit pronounced spindle abnormalities and delayed mitosis. Of note, acetylation of α-tubulin, which maintains microtubule flexibility and stability, was diminished in the kindlin-2–depleted cells. Mechanistically, we found that kindlin-2 maintains α-tubulin acetylation by inhibiting the microtubule-associated deacetylase histone deacetylase 6 (HDAC6) via a signaling pathway involving AKT Ser/Thr kinase (AKT)/glycogen synthase kinase 3β (GSK3β) or paxillin. We also provide evidence that prolonged hypoxia down-regulates kindlin-2 expression, leading to spindle abnormalities not only in the SH-SY5Y cell line, but also cell lines derived from colon and breast tissues. The findings of our study highlight that kindlin-2 regulates mitotic spindle assembly and that this process is perturbed in cancer cells in a hypoxic environment. Full Article
bit EU Security Ambitions Are Hostage to the Brexit Process By feedproxy.google.com Published On :: Fri, 21 Jun 2019 11:46:55 +0000 25 June 2019 Professor Richard G Whitman Associate Fellow, Europe Programme @RGWhitman Google Scholar The EU faces a fundamental contradiction in its goals to become more strategically autonomous in defence matters. 2019-06-20-Eurocorps.jpg Soldiers of a Eurocorps detachment raise the EU flag at the European Parliament in Strasbourg. Photo: Getty Images. Three years ago, as the UK was holding its referendum on Brexit, the EU was rolling out its Global Strategy for a more cohesive and effective security and defence policy. Since then, EU member states have set impressive goals and, as significantly, taken important practical steps to make an EU defence capability a tangible proposition, despite differing collective defence commitments, traditions of neutrality among some member states and very different strategic cultures.All of these developments have taken place with the UK as reluctant observer. The UK has been traditionally hostile to a deepening of defence collaboration within the EU (and consistent of the view that Europe’s military security was best provided through NATO). But the Brexit referendum vote has placed the UK as a bystander as EU security and defence initiatives have been pursued which have overridden the past red lines of British governments.There is, however, a Brexit-related paradox in all these developments.A central goal of the security and defence-related aspects of the EU Global Strategy is for the EU to have the capacity to act independently of the United States and, through indigenous defence industries, the ability to produce the means to make that possible.With the UK outside the EU, and its opposition absent, it is easier to create a political consensus to push for more defence integration. But without the UK there are diminished collective defence capabilities which would make European strategic autonomy much harder to achieve. The May government has been an enthusiast for preserving close security and defence cooperation with the EU. The Withdrawal Agreement and the Political Declaration both seek to provide for a close EU–UK relationship post-Brexit.However, the Article 50 negotiations have made clear that the EU’s institutions are hostile to special treatment for the UK beyond that normally accorded to a third country. Disagreements over the terms of the UK’s continuing participation in the Gailleo dual-use satellite system, which has a significant security and defence utility, have signalled that there is a strong lobby in Brussels and some national capitals seeking to significantly circumscribe collaboration with Britain.The scale and capabilities of the UK’s military, its defence expenditure (notably on defence research and development) and its defence industrial base make any British decoupling from the EU’s security and defence a major issue. Disconnecting the UK from EU developments entirely would be a costly political choice for both sides.And excluding the UK from new initiatives in defence R&D and new defence procurement arrangements would be suboptimal in delivering a stronger European defence, technological and industrial base. Duplicating existing UK capabilities, especially strategic enablers such as strategic airlift, target acquisition and intelligence, surveillance and reconnaissance capabilities, would be an unnecessary squandering of already hard-pressed European defence budgets.At present the common procurement and defence industry plans driven by the EU Global Strategy are embryonic. And significant defence capability decisions are taking place detached from the EU’s plans, which could reinforce a divide between the UK and other member states.As illustrative, the formal agreement this week between France, Germany and Spain on the Future Combat Air System (FCAS) to develop a next-generation stealth fighter is competing with the UK-supported Tempest project that shares the same objective. The 20-year timescales for the delivery of the FCAS and Tempest projects are a reminder that defence procurement decisions are of multi-decade significance.As the EU’s ambitions are nascent, it is too early to fully assess what might be the impact of any decision by the EU and the UK to keep each other at an arms-length in security and defence cooperation. With a more detached relationship, the UK will have significant concerns if it sees the EU’s common procurement arrangements develop in a manner that actively discriminates against the UK defence industry.Outside of procurement and defence issues there may be other areas of future concern for the UK – for example, the extent to which the EU might deepen and broaden cooperation with NATO in a manner that makes the collective influence of EU member states within NATO more apparent, or to which the footprint of future EU conflict and security activities in third countries starts to overshadow the activities of the UK.As the UK has been grappling with Brexit domestically, the EU has been evolving its security and defence policy ambitions. These are developments that will impact on the UK and in which, therefore, it has a stake but as a departing member state it has a weakening ability to shape.Any aspect of future EU–UK cooperation is hostage to the vagaries of how the Brexit endgame concludes. Full Article
bit 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
bit 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
bit Unfulfilled Ambitions: the State of Democracy in Africa By feedproxy.google.com Published On :: Mon, 04 Jun 2018 00:00:00 +0100 Full Article
bit The Challenge of Ambition? Unlocking Climate Action and the Outcomes of COP24 By feedproxy.google.com Published On :: Fri, 01 Mar 2019 00:00:00 +0000 Full Article
bit The Climate Briefing: Episode 2 - European Climate Ambitions By feedproxy.google.com Published On :: Fri, 03 Apr 2020 00:00:00 +0100 Full Article
bit Structural basis of specific inhibition of extracellular activation of pro- or latent myostatin by the monoclonal antibody SRK-015 [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Myostatin (or growth/differentiation factor 8 (GDF8)) is a member of the transforming growth factor β superfamily of growth factors and negatively regulates skeletal muscle growth. Its dysregulation is implicated in muscle wasting diseases. SRK-015 is a clinical-stage mAb that prevents extracellular proteolytic activation of pro- and latent myostatin. Here we used integrated structural and biochemical approaches to elucidate the molecular mechanism of antibody-mediated neutralization of pro-myostatin activation. The crystal structure of pro-myostatin in complex with 29H4-16 Fab, a high-affinity variant of SRK-015, at 2.79 Å resolution revealed that the antibody binds to a conformational epitope in the arm region of the prodomain distant from the proteolytic cleavage sites. This epitope is highly sequence-divergent, having only limited similarity to other closely related members of the transforming growth factor β superfamily. Hydrogen/deuterium exchange MS experiments indicated that antibody binding induces conformational changes in pro- and latent myostatin that span the arm region, the loops contiguous to the protease cleavage sites, and the latency-associated structural elements. Moreover, negative-stain EM with full-length antibodies disclosed a stable, ring-like antigen–antibody structure in which the two Fab arms of a single antibody occupy the two arm regions of the prodomain in the pro- and latent myostatin homodimers, suggesting a 1:1 (antibody:myostatin homodimer) binding stoichiometry. These results suggest that SRK-015 binding stabilizes the latent conformation and limits the accessibility of protease cleavage sites within the prodomain. These findings shed light on approaches that specifically block the extracellular activation of growth factors by targeting their precursor forms. Full Article
bit Structure-based discovery of a small-molecule inhibitor of methicillin-resistant Staphylococcus aureus virulence [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton–Valentine leukocidin (PVL) and α-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and α-toxin in their soluble, monomeric, and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C14PC). The structures revealed two evolutionarily conserved phosphatidylcholine-binding mechanisms and their roles in modulating host cell attachment, oligomer assembly, and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and α-toxin and hence may serve as the basis for the development of an antivirulence agent for managing MRSA infections. Full Article
bit Breaking the Habit: Why Major Oil Companies Are Not ‘Paris-Aligned’ By feedproxy.google.com Published On :: Mon, 07 Oct 2019 14:50:01 +0000 Invitation Only Research Event 23 October 2019 - 8:30am to 10:00am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Andrew Grant, Carbon Tracker InitiativeChair: Siân Bradley, Research Fellow, Energy, Environment and Resources, Chatham House The investment community is increasingly seeking to assess the alignment of their portfolios with the Paris Agreement. In a recent update to their Two Degrees of Separation report, Carbon Tracker assessed the capital expenditure of listed oil and gas producers against ‘well below’ 2C targets, and for the first time, against short-term actions at the project level.The speaker will present the key findings of the report and will argue that every oil major is betting heavily against a low-carbon world by investing in projects that are contrary to the Paris goals.This roundtable discussion will further explore the report findings and consider what investors, regulators and oil and gas companies can do to encourage alignment with the Paris Agreement ahead of 2020. Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Energy, Environment and Resources Programme Full Article
bit COP26 Diplomatic Briefing: Climate Ambition in Europe and its Potential Global Impact By feedproxy.google.com Published On :: Fri, 03 Apr 2020 14:05:01 +0000 17 February 2020 - 8:30am to 10:00am Chatham House | 10 St James's Square | London | SW1Y 4LE Jacob Werksman, Principal Adviser to Directorate General for Climate Action, European CommissionImke Lübbeke, Head of EU Climate and Energy Policy, WWF European Policy Office Simon Petrie, Head of International Climate Strategy - Europe, UK Department for Business, Energy and Industrial StrategyJen Austin, Policy Director, We Mean Business CoalitionChair: Jill Duggan, Associate Fellow, Chatham House The President of the European Commission, Ursula von der Leyen, has declared that she wants Europe to become ‘the first climate-neutral continent by 2050’, and in December 2019, the Commission presented the European Green Deal in order to achieve this objective. However, even though greenhouse gas emissions from the EU have fallen by more than 20 per cent since 1990, the Union remains the third largest emitter in the world, after the United States and China.What are the opportunities and challenges for raising climate ambition in Europe? Will the EU increase its Nationally Determined Contribution and what impact might this have globally? How might Brexit affect climate action in the EU and the UK? The second event in the Chatham House COP26 Diplomatic Briefing Series will address these critical questions. Read meeting summarypdf | 118.6 KB Anna Aberg Research Analyst, Energy, Environment and Resources Programme 020 7314 3629 Email Department/project Energy, Environment and Resources Programme, COP26 Diplomatic Briefing Series Full Article
bit Episode 17: The Hobbit Review & Christmas Movies By feedproxy.google.com Published On :: Mon, 24 Dec 2012 07:13:00 +0000 The Hobbit ReviewChristmas MoviesWhat We Watched: Sunshine/Silver Lining's Playbook/The Grey/ArgoDownload the episode here (right click to save). Full Article