Tyrone Mings became the first Englishman to concede a penalty on his Champions League debut in bizarre fashion as Aston Villa lost to Brugge.

"I realised I could sustain the writing life, whether anyone reads it or not. It’s what separates writers from civilians. It’s probably a mental disorder."

With school on break, along with all the homework, tests and early start times that come with it, parents often assume that young people’s stress and anxiety will take a pause as well. However, that’s not always the case, especially as the novelty of summer dwindles. Without the daily structure of school and extracurricular activities, kids may struggle with boredom or restlessness. Maintaining a routine during the summer can be a powerful tool for supporting children’s mental health, and parents can play a crucial role in establishing and reinforcing this structure.

Pandemic academic recovery in both reading and math is lagging notably behind pre-COVID achievement trends for students in grades 4-8 during the 2022-23 school year, according to a new report by NWEA analyzing MAP Growth test scores of 6.7 million students across 20,000 public schools. Third-graders were the only group who saw improvements, and they were slight, according to NWEA, an educational research organization recently acquired by learning technology company HMH.

Some things you should never do on a dog walk include approaching unfamiliar pets, using an extendable leash, and not picking up waste, experts said.

Taylor Swift has made a habit of cheering for the Kansas City Chiefs since she began dating NFL star Travis Kelce.

The best early Black Friday MacBook deals include all-time low prices on the latest MacBook Air models.

Taylor Swift is known for her glamorous red-carpet looks and sparkling stage outfits. But she's also fashionable in her everyday life.

PORT LOUIS, Nov 10 - Mauritius was holding a parliamentary election on Sunday with Prime Minister Pravind Kumar Jugnauth and his main rivals all promising to tackle a cost of living crisis in the Indian Ocean archipelago.

Over the past decade, parent advocacy groups led a grassroots movement resulting in most states adopting dyslexia-specific legislation, with many states mandating the use of the Orton-Gillingham (OG) approach to reading instruction. Orton-Gillingham is a direct, explicit, multisensory, structured, sequential, diagnostic, and prescriptive approach to reading for students with or at risk for word-level reading disabilities (WLRD). Evidence from a prior synthesis and What Works Clearinghouse reports yielded findings lacking support for the effectiveness of OG interventions.

Texts classified according to guided reading levels (GRL) are ubiquitous in U.S. beginning reading classrooms. This study examined features of texts across three grade bands (kindergarten, early first grade, final first grade) and the 10 GRLs within these bands. The 510 texts came from three programs with different functions in beginning reading instruction: core, intervention, and content areas.

Recently, I posted commentary on Emily Hanford’s reporting and the critical response it received from some in the literacy community. I defended the major thrust of her work and called out criticisms I thought to be illogical, ill conceived, or ill intended — criticism more aimed at maintaining status quo than promoting literacy.

If you are the type of person that likes to spoil a game from the off then Brighter Shores is… Continue reading Brighter Shores infinite money glitch – get cash rich with all the money you will ever need

The post Brighter Shores infinite money glitch – get cash rich with all the money you will ever need appeared first on ReadWrite.

Earlier today, Bitcoin’s market cap briefly overtook that of silver, as the world’s first cryptocurrency reached never-before-seen heights. CoinMarketCap data… Continue reading Bitcoin’s market cap briefly overtakes silver’s at $89,000 level

The post Bitcoin’s market cap briefly overtakes silver’s at $89,000 level appeared first on ReadWrite.

The country is set to experience varied weather conditions, with several impact-based warnings issued across various provinces, according to the South African Weather Service.

I’m worried about AI. I’m not worried about it taking my job. I believe AI is a genuine productivity tool. By which I mean it can make developers produce more. The question is whether those developers are producing something good or not. The difference between an experienced developer and a junior is that an experienced […]

October 1 was officially "International Raccoon Appreciation Day," for those of you who love to love the adorable trash panda. Around here, honestly, every day is raccoon appreciation day, so it's an "International Day" I can genuinely get behind.

National Day Calendar explains the origins of the day:

In 2002, a young girl in California wanted to highlight the good points about the raccoon instead of the bad ones.

— Read the rest

The post Every day should be raccoon appreciation day appeared first on Boing Boing.

Steve Vonder Haar recently released an outstanding research report about the online webcasting event services business.

He states that consumers of webcasting services have been motivated by two priorities: 1) the desire to keep costs low; and 2) the desire to keep involvement of their own IT departments to a minimum. For this reason, major webcasting event service providers, like ON24, have enjoyed their greatest success at the ends of the market spectrum: low cost self-provisioning services and high touch premium webcasting services.

The premium end of the market has been bolstered by the complexity of the client's needs, which has kept fees high and competition at bay. The low end of the market had become increasingly commoditized.

He concludes that service providers are going to have to push more to the middle of that spectrum and identify more companies that require well-produced webcasts for the market to continue growing.

He also mentions that the complexity of webcast events that has traditionally protected the major service providers is no longer a significant barrier to entry. Sophisticated webcasting software offered on a Software as a Service (SaaS) basis allows any number of production companies, agencies, and event companies to compete on an equal footing with the ON24s and the OnStreams.

According to Hoovers, the US marketing and services industry includes about 35,000 companies with combined annual revenue of about $80 billion. The industry is fragmented because the top 50 companies generate less than 40 percent of that revenue. In other words, there are a large number of potential buyers of enterprise webcasting software that want to compete for online event services business at a time when traditional advertising revenues are falling and internet advertising revenues are growing. Internet communications are definitely going to become a greater point of emphasis for these companies.

I am unable to attached the report, but you can request a copy at the Interactive Media Strategies website.

An article about Hybrid Flash Multicasting that features MediaPlatform's CTO, Greg Pulier, recently appeared in the Flex Developer's Journal.  Click here to link to the article

Here is the opening paragraph:

Hybrid Flash multicasting is the second and decisive wave of innovation that will enable enterprises to stream video without overtaxing their network infrastructures. It eliminates the usual tradeoffs between video consumption and network investment, regardless of increased video traffic in budget-constrained corporate networks. Hybrid Flash multicasting also solves the cost and complexity challenges of IP multicasting. By combining a new form of multicasting, known as application multicasting, which leverages a peer-assisted model of video sharing with an IP multicast network, a video stream can reach virtually everyone on the network using existing bandwidth and infrastructure. Hybrid multicasting finally unlocks the full potential for video within the enterprise by combining IP and application multicasting to deliver streaming media using the most efficient algorithms within a dynamic self-optimizing topology.

Interactive Media Strategies (IMS) is a market research firm that follows streaming media. They discuss the news of Microsoft’s $8.5 billion acquisition of Skype, and the prospects for Skype to emerge as a viable platform for business video communications. 

Their research compares usage levels for a range of social media and communications applications, including Skype, YouTube and Facebook. Here is a link to the video.

They report that personal use of Facebook and YouTube is relatively high but that has not yet translated into comparable levels of corporate use. They believe this raises the question of whether YouTube and Facebook will be able to outgrow their focus on the consumer side of the business to compete in the enterprise market.

Usage levels for Skype are significantly lower overall, but Skype’s penetration in business communications is higher than they see for other communications apps online among young users most likely to experiment with emerging technologies.

IMS puts forth the opinion that if Microsoft could make it easier for technology laggards to embrace Skype - i.e. integrate Skype with the Microsoft Office suite - then Skype could achieve significant enterprise adoption.

The following article, Steve Bannon Issues 90-Second WARNING To Deep State At Trump Victory Party (Video), was first published on Conservative Firing Line.

(Natural News) Steve Bannon, one of Donald Trump’s most fired-up supporters and allies all throughout the former president’s tumultuous political career, delivered a powerful speech after Trump’s victory warning the deep state that justice is coming. Fresh out of federal prison for his involvement in the events of Jan. 6, 2021, Bannon took the stage to deliver …

Continue reading Steve Bannon Issues 90-Second WARNING To Deep State At Trump Victory Party (Video) ...

The following article, Forty-Seven Percent Of Harris Voters Believe Trump Will Not Be A Legitimate President; 54 Percent Want To Leave The Country, was first published on Conservative Firing Line.

I really wish that everyone would just calm down.  Emotions always run high immediately after an election, but what we are witnessing this time around is truly frightening.  We live at a time when people feel free to express their deepest, darkest emotions on social media, and right now “freak out video” after “freak out …

Continue reading Forty-Seven Percent Of Harris Voters Believe Trump Will Not Be A Legitimate President; 54 Percent Want To Leave The Country ...

MPU 046: Workflows with Merlin Mann II « Mac Power Users

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I have the life that I have because I've made a lot of weird decisions, and they've worked out well.

Not gonna lie to you. I'm a huge nerd. Surprised?

Yep. I can recite big chunks of The Big Lebowski from memory. I can argue for an hour on the merits of Dick York over Dick Sargent. And, I can—and frequently do—catch myself thinking Catwoman, Batgirl, Princess Leia, and Emma Peel should have a light-hearted pillow fight that ends with an hour of genial french-kissing.

Pretty much like you, probably. I dunno, maybe your version includes Kitty Pryde. Po-tay-to/Po-taht-o, right?

Perhaps most saliently, by virtue of having spent a solid 2,399 days as a Fake Productivity Guru, I have been provided with an unquestionably Janusian monkey's paw of a gift; I now know a lot about workflows. Nerdy, nerdy workflows.

I can tell you a few things that almost always work, I can tell you a handful of things that almost never work, and—best or worst of all—I can tell you thousands of things that might work. Sometimes. Maybe. Kinda. For some people. For now.

And, at the risk of gay-marrying my arrogance to my hypocrisy, I can tell you that I also know enough about the unholy diarrhea of potential options for Theoretical Productivity to share two big patterns:

1. Getting your workflow right matters.
2. Getting your workflow right to the exclusion of the actual work is a fool's game.

But. Managing to get the most useful and most elegant and least fiddly mix of 1 and 2 right is super-hard. Especially for nerds. Especially for me.

So, as I type this today, I believe there can be no greater testament to these claims—or, at least, no greater place to test the veracity of these claims for yourself—than in this TWO AND A HALF HOUR-long interview for Mac Power Users.

It is reeeeeeeeally nerdy. Almost intolerably nerdy. Just…overwhelmingly nerdy.

But, man, is it ever really good, and really fat with the most insanely granular details of How I Work.

Lo, even these 928.5 days after officially retiring from productivity pr0n, my desire to not "vend stroke material for your joyless addiction to puns about procrastination and systems for generating more taxonomically satisfying meta-work" is tempered by a (widely under-reported) practical streak.

Yes: I continue to despise empty advice about rearranging deck chairs on The Titanic. But, yes: I do also still very much enjoy talking about how all the tips and tricks can or can't work in the context of work you care about. That matters. It really does.

So. Here goes. A one hundred and forty six minute-long, Joyce-ian amble through the Big Stuff and the Little Stuff. David and Katie were very patient.

How I name text files. Why I break iOS apps. Why I love the letter "x." Why I won't row out to islands any more. How a 115,000 word book manuscript is "like a house full of confederate money." How "The Cloud" broke in New Zealand. How I use MultiMarkdown, Scrivener, TextExpander, OmniFocus, TextMate, Notational Velocity, Dropbox, and an explosive combination of Elements, Notesy, Nebulous, Simplenote, CF Outliner, iThoughts, Instacast, Good Reader, and wow wow wow.

How I try not to fiddle—how I sometimes succeed and often don't. But, how I try.

Anyhow. There you go. A perfectly nerdy bookend to last year's first Magnum Opus MPU interview on these same topics, Mac Power Users Episode 46 is just insanely nerdy. And, what have you.

I hope you like it. I hope it's useful. I hope you don't use it to replace real work.

And, as ever, I really hope Batgirl starts having more sexy pillow fights.

Enjoy. And, God save you.

MPU 046: Workflows with Merlin Mann II « Mac Power Users

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The advertising world is uncomplicated at its core, and utterly bewildering when seen from the outside. The easy bit stems from a simple axiom: Wherever you can find the attention of potential customers, you pay to get your message in front of them. That’s the essence of advertising: paying for attention. It gets complicated by … Continue reading "Ads, Ads Everywhere"

There's a reason Hitler holds a special place of disgrace in public memory. He combined the ambition and destruction of Attila The Hun with the personal malice of a serial killer.

The post The REAL Harm Done By Calling Everyone You Don’t Like ‘Hitler’ Is BIGGER Than Lefties Think appeared first on Clash Daily.

Whichever candidate is sworn into office this January is the President who will be making decisions about how America and her legacy is remembered.

The post AMERICA’S BIG BIRTHDAY: An Election Argument Everyone Seems To Be Missing appeared first on Clash Daily.

There appeared to be a definite frost between first lady Jill Biden and Vice President Kamala Harris during a Veterans Day event at Arlington National Cemetery on Monday. A close-up […]

The post Footage of Jill Biden and Kamala Harris Sitting Side-by-Side at Veterans Day Event Goes Viral appeared first on The Western Journal.

Just because you’re paranoid, it doesn’t mean you’re wrong. And for any supporters of President-elect Donald Trump who feel that they’ve been unfairly targeted by the government, but were summarily […]

The post Fired FEMA Worker Reveals Discrimination Against Trump Supporters Was Even Worse Than First Reported appeared first on The Western Journal.

Sir Kenny Dalglish hailed nine-time Major champion Gary Player and expressed his delight at Liverpool's position at the top of the Premier League during his visit to South Africa this weekend.

Presented by the Middle East Forum on Nov. 18, 2022 Panel discussion with Daniel Pipes, Cynthia Farahat, and Jonathan Schanzer:

Worldwide revenues will triple in 2022   April 11, 2022 (New York, NY) – TikTok’s worldwide ad revenues will triple this year and surpass that of two competitors combined, according […]

Alexander Kupers and Oscar Randal-Williams
J. Amer. Math. Soc. 38 (), 63-178.
Abstract, references and article information

Nonphotochemical quenching (NPQ) is a mechanism of regulating light harvesting that protects the photosynthetic apparatus from photodamage by dissipating excess absorbed excitation energy as heat. In higher plants, the major light-harvesting antenna complex (LHCII) of photosystem (PS) II is directly involved in NPQ. The aggregation of LHCII is proposed to be involved in quenching. However, the lack of success in isolating native LHCII aggregates has limited the direct interrogation of this process. The isolation of LHCII in its native state from thylakoid membranes has been problematic because of the use of detergent, which tends to dissociate loosely bound proteins, and the abundance of pigment–protein complexes (e.g. PSI and PSII) embedded in the photosynthetic membrane, which hinders the preparation of aggregated LHCII. Here, we used a novel purification method employing detergent and amphipols to entrap LHCII in its natural states. To enrich the photosynthetic membrane with the major LHCII, we used Arabidopsis thaliana plants lacking the PSII minor antenna complexes (NoM), treated with lincomycin to inhibit the synthesis of PSI and PSII core proteins. Using sucrose density gradients, we succeeded in isolating the trimeric and aggregated forms of LHCII antenna. Violaxanthin- and zeaxanthin-enriched complexes were investigated in dark-adapted, NPQ, and dark recovery states. Zeaxanthin-enriched antenna complexes showed the greatest amount of aggregated LHCII. Notably, the amount of aggregated LHCII decreased upon relaxation of NPQ. Employing this novel preparative method, we obtained a direct evidence for the role of in vivo LHCII aggregation in NPQ.

Interview: Steve Brooking The World Today mhiggins.drupal 27 September 2022

The Afghanistan expert tells Mike Higgins the Taliban are reneging on their promises and that the region’s powers must intercede.

Steve Brooking is the former chargé d’affaires at the British Embassy in Kabul and was special adviser to the UN Assistance Mission in Afghanistan from 2015 to 2021.

How has day-to-day life become worse for Afghans since the United States and its allies withdrew abruptly from Afghanistan in the late summer of 2021?

That depends on where those Afghans are living and what they were doing. Life for lots of ordinary rural Afghans hasn’t changed much, it is still subsistence farming. Until last year, the success stories of girls in education, new hospitals, schools and clinics were concentrated in the towns and cities.

In fact, there has been a shortage of teachers and medics for years. Many Afghans left those jobs to work for the coalition forces or the international development presence in the country. When the Americans left last year, along with them was a mass exodus of the educated middle class from the country, which affected the cities and towns. The emerging middle class was also hit by the disappearance of the jobs that went with those foreign troops.

Spending power has collapsed. Many Afghans in cities support a dozen or more extended family members, but now they don’t have the money. Afghans are relying on external humanitarian aid but the agencies are only getting about half what they are asking for because there are competing humanitarian crises – in the Horn of Africa, Syria, Ukraine.
 
In September, Washington announced it would transfer $3.5 billion into a Swiss-based trust fund to try to stabilize Afghanistan. How far will that money go and are the US wise to avoid Afghanistan’s central bank?

It is enough to make a significant humanitarian difference. Bypassing the Afghan central bank indicates that the US government is keen the money does not fall into the hands of the Taliban, or international terrorists. The American assassination of the Al-Qaeda leader, Ayman al-Zawahiri, in Kabul in July showed the Taliban have not kept to their promise to prevent the country being used as a terrorist base.

Also, it is clear the US doesn’t want to be seen to be supporting the Taliban government or to start recognizing it or getting anywhere near recognizing it. It remains concerned about all sorts of violations of basic rights – the most egregious being girls not allowed in secondary schools and women not being allowed to work except in certain sectors.

The Americans and other donor countries were paying teachers’ salaries through the UN but that stopped when the new Afghan school year began in March and girls still weren’t allowed back to school.

The Taliban need to show a responsible level of governance and ability before people will trust them with their money. But it’s difficult to see the Taliban making the necessary concessions to move beyond humanitarian aid to receive development funding.

As the attention of the US is focused on Ukraine and further eastwards towards China, what will be the cost if the West doesn’t engage with Afghanistan seriously?

You could argue the costs will be minimal. The Americans tried a lot over 20 years, they failed and then left overnight. It caused complete shock around the region. To be fair, though, the Americans warned the region’s powers that they were leaving and that this would be a problem in the region unless they got help from those same powers.

Europe and the UK are more likely to experience the fallout from a deteriorating Afghanistan. The refugee flows will continue. To stem that, they want to persuade the Taliban to make a more inclusive government.

There are few levers to pull with the Taliban, unfortunately. They complain about sanctions, travel restrictions for various leaders, the freezing of assets. But they haven’t made any attempt to speak to the political opposition or honour the terms of the Doha Agreement, let alone engage in other issues.

I think the onus to act falls on the regional powers because they will feel the first effects of instability in Afghanistan.

China, Russia, India and other regional powers are members of the Shanghai Cooperation Organization (SCO), which had its summit in Samarkand last month. Some have been arguing that the SCO should take a more active role in Afghanistan, which has SCO observer status.

Iran is worried about the persecution of Shia minorities in Afghanistan, but they are trying to have constructive relations with the Taliban because they need water from Afghanistan to feed the southeast of Iran, which is very dry.

Pakistan has not been able to control the Taliban, but has succeeded in establishing a regime in Kabul that is hostile to India. China would like to see stability in Afghanistan to access its natural resources, but otherwise it largely follows Pakistan’s lead. Russia is preoccupied with Ukraine, but is worried about the spread of narcotics and Islamic extremism up through central Asian states.

None of those regional powers, it should be said, is willing to recognize a Taliban government.

How secure is the Taliban government?

Cross-border trade continues, with revenues from mining, timber, coal and natural resources. The Taliban are still involved in heroin production, which they tax heavily despite having said they would suppress it.

They don’t want to upset the poppy farmers who helped return them to power. There is a level of security that has bought the Taliban some time. Previously, in the south there was a lot of fighting and there were daily car bombs and attacks in some cities.

Now, on the whole, mothers know they can send their kids to the water pump. A friend, a senior Afghan female in the country, told me recently: ‘We feel more secure, but less certain about our future than ever before.’ They can see that the economy is going downhill.

One scenario is a disintegration of the country along regional lines, in which, say, the people of Badakhshan decide they will no longer let the central government take all the revenue from their lapis lazuli and ruby mines. Local warlords may re-emerge whom the Taliban would find it more difficult to deal with.

As for the terrorist threat in Afghanistan, the Taliban never broke their ties to Al-Qaeda, and at one point the Americans were saying that there were more than two dozen terrorist groups in Afghanistan. I’m sure the Taliban will be able to rein in most of these, the exception being Islamic State – that is a battle of extreme ideologies. Another problem is a lot of these international terrorists have married Afghans and are now well enmeshed into local society.
 
You paint a bleak picture of Afghanistan’s future. What, if anything, gives you hope for the country?

Ordinary Afghans are resilient and entrepreneurial. They also have a strong sense of being Afghan and that their country is one of the longest-existing countries in that part of the world. But the Taliban need to make people feel they are included in that national identity.

Sadly, I think it will take war, famine, plague and disaster in order for the Taliban to unbend sufficiently to realize that they need better ethnic and gender representation in government, as well as economic expertise. I hope the Afghan diaspora will be asked to come together to forge a better future for the country.

Making the circular economy work for global development: how the UN Summit of the Future can deliver 23 September 2024 — 6:15PM TO 9:00PM Anonymous (not verified) 5 September 2024 Online

This policy roundtable focusses on how to advance implementation of a global approach and collaboration to an inclusive circular economy for an updated post-2030 SDG framework.

As the world looks beyond the Sustainable Development Goals (SDGs) towards the post-2030 era, integrating the principles of the circular economy into the future global development agenda becomes imperative.  

A new Chatham House research paper about the role of the circular economy for the SDGs and their possible extension into the post-2030 development agenda will be launched in September 2024 during the UN Summit of the Future and the New York Climate Week. The paper outlines the rationale for the integration of circular economy goals into for the next crucial phase of international development and how to meet net-zero 2050 targets. It provides actionable recommendations on international cooperation mechanisms for policymakers and stakeholders at the UN Summit for the Future in 2024 and beyond.

The aim of the roundtable is to bring together stakeholders and leaders from intergovernmental organisations, business, governments and civil society. The focus of the roundtable meeting is: 

• Reflections on the Summit of the Future and the role of circularity for an updated post-2030 SDG framework.
• Discussion on key aspects of the institutional arrangements and international coordination that are needed for a globally coordinated approach to achieve an inclusive circular economy that supports SDG implementation. 
• Development of joint strategies on how to advance implementation of a global approach and collaboration to an inclusive circular economy as a follow-up from the Summit of the Future.

The objective is to emerge from the roundtable with a clearer roadmap for translating the recommendations for international coordination into concrete actions, with a shared commitment to driving meaningful change on the international level.

The event is co-hosted by Chatham House and partners from the Global Circular Economy Roadmap initiative including the African Circular Economy Network, the African Development Bank, Circular Change, Circular Innovation Lab, Circle Economy, EU CE Stakeholder Platform, Hanns Seidel Foundation, Institute of Global Environmental Strategies, Sitra, UNIDO, World Business Council on Sustainable Development, World Economic Forum and the Wyss Academy for Nature.

Further background information is available on the initiative website.

More speakers to be announced.

The main protease (3CL Mpro) from SARS–CoV-2, the etiological agent of COVID-19, is an essential enzyme for viral replication. 3CL Mpro possesses an unusual catalytic dyad composed of Cys145 and His41 residues. A critical question in the field has been what the protonation states of the ionizable residues in the substrate-binding active-site cavity are; resolving this point would help understand the catalytic details of the enzyme and inform rational drug development against this pernicious virus. Here, we present the room-temperature neutron structure of 3CL Mpro, which allowed direct determination of hydrogen atom positions and, hence, protonation states in the protease. We observe that the catalytic site natively adopts a zwitterionic reactive form in which Cys145 is in the negatively charged thiolate state and His41 is doubly protonated and positively charged, instead of the neutral unreactive state usually envisaged. The neutron structure also identified the protonation states, and thus electrical charges, of all other amino acid residues and revealed intricate hydrogen-bonding networks in the active-site cavity and at the dimer interface. The fine atomic details present in this structure were made possible by the unique scattering properties of the neutron, which is an ideal probe for locating hydrogen positions and experimentally determining protonation states at near-physiological temperature. Our observations provide critical information for structure-assisted and computational drug design, allowing precise tailoring of inhibitors to the enzyme's electrostatic environment.

Development Prospects in the Asia-Pacific: The Role of the Asian Development Bank 25 September 2019 — 12:30PM TO 1:30PM Anonymous (not verified) 4 September 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

The speaker will discuss development prospects in the Asia-Pacific and their implications for Europe and the UK. He will outline prospects for the region’s growth, the impact of the current US-China trade conflict as well as other challenges faced by the region. He will also discuss the future role of the Asian Development Bank and how it plans to support the further development of the region.

Alfred C. O. Vertegaal
Dec 1, 2006; 5:2298-2310
Research

Boris Macek
Feb 1, 2008; 7:299-307
Research

Steven A. Carr
Mar 1, 2014; 13:907-917
Technological Innovation and Resources

Michal Bassani-Sternberg
Mar 1, 2015; 14:658-673
Research

Mitsunori Fukuda
Jun 1, 2008; 7:1031-1042
Research

Tamar Geiger
Mar 1, 2012; 11:M111.014050-M111.014050
Special Issue: Prospects in Space and Time

Yi Zhang
Sep 1, 2005; 4:1240-1250
Research

Timothy J. Griffin
Apr 1, 2002; 1:323-333
Research

Sebastian A. Wagner
Oct 1, 2011; 10:M111.013284-M111.013284
Research

Staphylococcus aureus adhesion to the host's skin and mucosae enables asymptomatic colonization and the establishment of infection. This process is facilitated by cell wall-anchored adhesins that bind to host ligands. Therapeutics targeting this process could provide significant clinical benefits; however, the development of anti-adhesives requires an in-depth knowledge of adhesion-associated factors and an assay amenable to high-throughput applications. Here, we describe the development of a sensitive and robust whole cell assay to enable the large-scale profiling of S. aureus adhesion to host ligands. To validate the assay, and to gain insight into cellular factors contributing to adhesion, we profiled a sequence-defined S. aureus transposon mutant library, identifying mutants with attenuated adhesion to human-derived fibronectin, keratin, and fibrinogen. Our screening approach was validated by the identification of known adhesion-related proteins, such as the housekeeping sortase responsible for covalently linking adhesins to the cell wall. In addition, we also identified genetic loci that could represent undescribed anti-adhesive targets. To compare and contrast the genetic requirements of adhesion to each host ligand, we generated a S. aureus Genetic Adhesion Network, which identified a core gene set involved in adhesion to all three host ligands, and unique genetic signatures. In summary, this assay will enable high-throughput chemical screens to identify anti-adhesives and our findings provide insight into the target space of such an approach.

HIV Type 1 (HIV-1) and simian immunodeficiency virus (SIV) display differential replication kinetics in macrophages. This is because high expression levels of the active host deoxynucleotide triphosphohydrolase sterile α motif domain and histidine-aspartate domain–containing protein 1 (SAMHD1) deplete intracellular dNTPs, which restrict HIV-1 reverse transcription, and result in a restrictive infection in this myeloid cell type. Some SIVs overcome SAMHD1 restriction using viral protein X (Vpx), a viral accessory protein that induces proteasomal degradation of SAMHD1, increasing cellular dNTP concentrations and enabling efficient proviral DNA synthesis. We previously reported that SAMHD1-noncounteracting lentiviruses may have evolved to harbor RT proteins that efficiently polymerize DNA, even at low dNTP concentrations, to circumvent SAMHD1 restriction. Here we investigated whether RTs from SIVmac239 virus lacking a Vpx protein evolve during in vivo infection to more efficiently synthesize DNA at the low dNTP concentrations found in macrophages. Sequence analysis of RTs cloned from Vpx (+) and Vpx (−) SIVmac239–infected animals revealed that Vpx (−) RTs contained more extensive mutations than Vpx (+) RTs. Although the amino acid substitutions were dispersed indiscriminately across the protein, steady-state and pre-steady-state analysis demonstrated that selected SIVmac239 Vpx (−) RTs are characterized by higher catalytic efficiency and incorporation efficiency values than RTs cloned from SIVmac239 Vpx (+) infections. Overall, this study supports the possibility that the loss of Vpx may generate in vivo SIVmac239 RT variants that can counteract the limited availability of dNTP substrate in macrophages.

AUKUS reveals much about the new global strategic context Expert comment NCapeling 17 September 2021

The new AUKUS partnership as well as the furore in Paris surrounding its announcement says a lot about the new geopolitical landscape.

The growing diplomatic drama surrounding the announcement of the new Australia-UK-US (AUKUS) risks concealing rather than highlighting what the deal reveals about profound changes in the global strategic context. Several elements stand out.

First, Australia’s decision to break off the $66 billion contract it signed with France in 2016 to purchase a new fleet of diesel electric submarines underscores the heightened level of concern in Canberra about China’s growing naval capabilities.

Despite all the industrial, legal, and diplomatic disruption, the Australian government has decided only the stealthy nuclear-powered submarines developed by Britain with US support can provide the genuine naval capability it needs long-term.

Next, in helping Australia resolve this conundrum, the British government has revealed the versatility of its new foreign policy. Part of the reason UK prime minister Boris Johnson eschewed the concept of a formal foreign policy and security treaty in the post-Brexit deal with the European Union (EU) was to pursue freely new ventures such as the recent ‘G7-plus’ summit in Cornwall, and enhanced cooperation among the Five Eyes allies. AUKUS reveals that this approach can produce real results.

Europe or the Indo-Pacific

During this week’s Polish-British Belvedere Forum in Warsaw, one of the main Polish concerns was that this ‘tilt’ to the Indo-Pacific could overstretch Britain’s scarce resources when it should be focusing on Europe, where they are most needed.

But AUKUS does not over-extend Britain. There is no military commitment involved in the agreement. The UK also remains outside the Quad – made up of the US, India, Japan, and Australia. And the ongoing stately voyage of its new aircraft carrier from the Mediterranean into the South China Sea provides better insight into the substance of the UK’s Indo-Pacific tilt.

Much derided for not carrying enough of its own aircraft – and for depending on US and Dutch escort vessels – the UK has in fact managed to coalesce a flexible group of allies around the Queen Elizabeth while enabling it to fly the British flag in Asian waters and strengthening interoperability with its allies for future joint operations.

Despite the hype, Britain’s main defence investments and deployments remain firmly focused in Europe, as laid out by the recent Integrated Review. And the decision to draft a new NATO Strategic Concept – midwifed by Britain at the 70th anniversary NATO summit hosted in London in December 2019 and confirmed during Joe Biden’s visit to NATO headquarters in June – will give Britain’s role in European security a new purpose and focus in the coming years.

Alone on the strategic landscape

For France, of course, the cancellation of its submarine deal is a painful humiliation, and a severe blow to thousands of workers in its hi-tech defence industry. It also comes at a sensitive moment politically, with Emmanuel Macron keen to demonstrate his international standing ahead of the 2022 presidential election. Instead, France now looks rather lonely on the strategic landscape alongside the more homogeneous and collectively powerful AUKUS trio.

But, rather than take the high road, a furious French reaction has compared Biden to Donald Trump and argued that this defence industrial failure for France should drive an acceleration towards European – for which, read EU – strategic autonomy.

This implies France sees European strategic autonomy as protecting and extending its own sovereign power and industrial interests rather than as a process for EU members to achieve more together in security and foreign policy than they can alone – thereby undermining rather than enhancing its case.

The gap between European strategic rhetoric and practical action was further highlighted by the AUKUS partnership being announced the evening before the EU launched its own Indo-Pacific strategy, and on the same day as China refused to allow a German frigate its first planned port visit to Shanghai.

America is still back

There is still a long way to go before the new submarine deal becomes reality. Australia needs to extricate itself from the French deal, decide how to secure the highly enriched uranium to power its new nuclear submarines, decide with the US and UK the division of labour and technology transfer of production, and assuage the International Atomic Energy Agency’s concerns about the precedent this deal sets. The fruits of this dramatic announcement will, therefore, be a long time in coming.

But, however the details play out, 15 September 2021 was a consequential day. The AUKUS announcement showed that China’s growing hard power is now eliciting a genuinely tough and structural political-military reaction.

Across the Atlantic, it also allowed President Biden – flanked ‘virtually’ by the British and Australian prime ministers – to send the global message that America is indeed back, just three weeks after the ignominious retreat from Afghanistan and chaotic exit from Kabul. And it offered him the opportunity to remind the world that the Indo-Pacific is where the US will be putting its main effort in the future.

For many in China, AUKUS now confirms their belief that the US and its principal allies are determined to contain China’s rise in its own ‘backyard’, where it believes it has the right to flex its muscles. For others, it will confirm Xi Jinping has overreached and China is now paying the price of his more assertive strategy. Either way, the Chinese are on notice that the ambivalent nature of the Obama pivot to Asia has given way to a more determined pivot under Biden.

While the US is stepping up, the UK has shown it is in the mix, leveraging opportunities as they arise. For example, the goodwill the UK has generated in Tokyo with this new partnership with Australia could help its case as it pursues membership of the Transpacific Partnership trade area in 2022.

The EU looks like a bystander in comparison and ill-equipped for the geopolitical competition inherent in this new strategic context. It is essential, therefore, once the dust has settled from these fraught few days, that the US and UK reach out to find ways to involve France and its EU partners in a meaningful, shared transatlantic approach to the Indo-Pacific.

COP27: What was achieved, and what needs to happen now Expert comment NCapeling 20 November 2022

Chatham House environment experts give their initial reaction to the end of COP27, examining how much progress was achieved, and the key issues still to be worked on.

Loss and Damage fund is a historic moment

Anna Aberg

COP27 will go down in history as the UN climate change conference where the Loss and Damage fund was agreed. After decades of pushing, this is a momentous victory for climate-vulnerable developing countries.

The shift in the conversation – and in the positions of developed countries – since COP26 is remarkable. It is critical parties continue to build on the positive momentum created in Sharm as challenging discussions on how the new loss and damage fund will work – and who will contribute to it financially – ensue.

Tim Benton

Overall COP27 was a hectic, sometimes chaotic, event. The COP advanced some matters but on others failed to drive ambition towards the sort of climate action required to keep alive the possibility of restricting climate change within the envelope of the Paris agreement.

Loss and Damage progressed but, especially in week two, the risk was of going backwards in this COP relative to COP26 in Glasgow. The final cover declaration managed to avoid the worst, but also avoided the best.

Notably disappointing was that, although food systems were much in debate unlike in previous COPs, there was still significant political resistance to fully adopting a systems approach. Globally, food systems emit about one-third of all greenhouse gasses, while poor diets – in rich and poor countries alike – are arguably the single biggest factor in ill-health and early death.

COP27 maintained a firm focus on supply-side solutions to tackle food insecurity, avoiding the politically more contentious demand-side issues of ensuring nutritious and sustainable diets for all.

Start of implementation phase demands renewed urgency

Bernice Lee

It has often been said climate action is moving from target-setting into the implementation phase. What COP27 shows is that, as the implementation phase begins, integrity and accountability will be ever more critical, as the voices of the vulnerable economies and the youth remind the world time and time again.

This compromised outcome is also a reminder that the delivery of climate action begins at home, as does the bread-and-butter politics of money and influence. It is significant the link between fossil energy and climate impacts has now been openly made in the international arena, regardless of whether it appeared in the final cover agreement.

As the dust settles, there will be many questions and reflection over tactics chosen by different parties and actors, and much to be learned that can help those pushing for more breakthrough moments at COP28.

Antony Froggatt

There was insufficient progress on the energy transition both in and around COP27. Few countries followed through on their promises to increase the ambition of their nationally determined contributions (NDCs), although Australia and the European Union (EU) were rare exceptions among the developed countries.

Higher fossil fuel prices, due to Russia’s invasion of Ukraine, can and should have resulted in an accelerated energy transition. Yet the language in the final decision around carbon reductions and energy at best repeats the language of COP26 and does not reflect the renewed urgency of the situation, stemming from accelerating climate impacts and the weaponization of fossil fuels in Russia’s conflict.

At COP28, parties to the UNFCCC will finalize a Global Stock Take which will include a review of national progress in meeting carbon abatement targets. This will be a key moment and unfortunately is likely to highlight once again how much faster the world needs to reduce its dependency on fossil fuels.

Fossil fuel discussions show failure of imagination

Glada Lahn

Overshadowed by the pain of developing country fuel importers and European attempts to replace Russian gas, discussion of fossil fuels was fraught. The text, which called for accelerating the ‘phasedown of unabated coal’ use for the first time only last year, failed to expand to include oil and gas, despite calls to do so from India, the US, EU, and UK. Gas use also appeared to gain a pass via the inclusion of ‘low emission’ energy alongside renewables.

Given that extracting and burning oil and gas accounts for 40 per cent of all annual greenhouse gas emissions (GHGs), and leaders agree on the need for ‘deep, rapid and sustained’ emission cuts, that language is beyond logical argument. However, current dependencies, fears of stranded investments, and a failure of imagination won out.

Stronger than usual oil and gas industry presence led to a higher number of meetings focused on decarbonization of the sector. Major producer countries such as Canada and Saudi Arabia were keen to emphasize technologies to ‘clean up’ rather than phase down their fuels as the future.

Not all developing country governments with hydrocarbon reserves see the ‘phase down’ text as conflicting with their economic interests. Large oil and gas exporter Colombia supported the inclusion of ‘all fossil fuels’ and Kenya, a country which had been pursuing oil and coal prospects, became a friend of the high ambition Beyond Oil and Gas Alliance which seeks a ‘managed phase out of oil and gas supply’.

A vocal contingent of African civil society meanwhile railed against health and ecology-damaging oil and gas projects and investments that would lock them into a high emissions future.

With stronger resolve to reorient finance towards net zero both in Sharm el-Sheikh and at the concurrent G20 summit in Bali, the practicalities of economic adaptation to the shift out of fossil fuels – including just transition for workers – rose up the agenda. These issues will overtake the wrangle over wording in the run up to COP28.

Adaptation must now move to the forefront

Ruth Townend

There are three pillars of climate action: mitigation, adaptation, and loss and damage. This year progress was made on mitigation and loss and damage but, to avoid wild spiralling of the latter, adaptation must have its day in the sun in the United Arab Emirates (UAE) at COP28 next year.

Adaptation lacks a concrete goal, akin to the 1.5 degree limit, and few countries have set out plans to adapt to climate change. Momentum will come when the promised ‘global goal on adaptation’ (GGA) is finally defined, to help mobilize finance and spur implementation.

The Glasgow-Sharm-el-Sheikh (GLASS) work programme to achieve this has so far lacked focus. At COP27, parties decided to define a framework to measure the goal’s achievement and enable reviews of progress over the next year.

Some concrete progress on adaptation was seen at the COP: UN Secretary-General Antonio Guterres called for worldwide extreme weather early warning systems within the next five years, while the Adaptation Fund received more than $230 million for the most climate-vulnerable in 2022.

The call from Glasgow to double adaptation finance was repeated, but overall, progress was muted, when parties really needed to come together for implementation of this crucial element of climate action.

Not enough done for agriculture and food security

Richard King

It is welcome that the Koronivia Joint Work on Agriculture – adopted in 2017 as the first and only formal UNFCCC agenda item focusing on agriculture and food security – has concluded in a decision to implement a new four-year work programme focused on implementing solutions.

While this has an objective of promoting holistic approaches to addressing climate impacts both on and from agriculture and food security, it disappointingly falls short of taking a food systems lens that includes all activities and actors from farm to fork.

There is now a small window of opportunity until March 2023 for governments and civil society to shape and broaden this agenda for the next four years. If not in the negotiating halls, then certainly in the myriad side events and discussions focusing on the issue, this year’s COP has clearly demonstrated a growing appreciation of the imperative of tackling food systems in their entirety.

An overarching and integrated approach to sustainable food production, distribution, and retail; nutrition and dietary shifts; and addressing food loss and waste will be vital to making comprehensive headway in addressing climate change and other planetary and social challenges.

It is important the parties at COP28 in the UAE seize this rising momentum to become the first climate negotiations to make tangible progress on transforming food systems towards sustainability, equitability, and resilience.

Rainforest leadership challenges traditional aid

Thiago Kanashiro Uehara

COP27 served well as a business fair for entrepreneurs wishing to benefit from new carbon markets. But forests, peatlands, and nature-based solutions did not receive the attention they deserve in guaranteeing climate security.

The good news is the COP26 pledges on forest finance, for the Congo basin, and for indigenous peoples (IP) and local communities’ (LC) forest tenure are pretty much alive, with disbursement rates at decent levels, albeit rarely directly to IP and LC-led organizations. The bad news is the financialization of forest governance and voluntary sustainability standards in global supply chains are solution ‘myths’ and were exposed by scientists as such at the conference.

On the second day of COP27, there was a last-minute launch led by the Global North, with Rishi Sunak and Emmanuel Macron announcing the ‘forests and climate leaders’ partnership’. One week later, at the G20 Bali summit, ministers from Indonesia, DR Congo, and Brazil announced a South-South rainforest leadership alliance – referred by some as the ‘OPEC of forests’ – challenging traditional forms of top-down international aid.

The climate crisis is one symptom of the inequality crisis engulfing our world at present. The African COP represented a step forward in addressing climate justice, an improvement over COP26 in Glasgow, where the issue was virtually denied.

The time has come for Global North constituents to work together with self-fashioned ‘solution countries’, such as the DRC now and Brazil after 2023. An ‘implementation COP’ will be successful only after establishing a new framework of co-leadership in climate action based on principles of justice and strong sustainability.

Outcomes of an African COP

Christopher Vandome

Africa’s contribution to the global energy transition cannot be at the expense of its own industrialization.

While pledges of increased financing for adaptation and the landmark establishment of a fund for loss and damage are important steps, the reality of under-disbursement and delivery of promised funds is causing many African leaders to rethink their engagement with multilateral climate initiatives.

African leaders are intent on advancing their own strategies for energy generation and adaptation that deliver on national priorities of job creation, sustainable growth, and environmental protection.

Many countries strategies involve exploiting gas reserves. But with mounting global pressures against further hydrocarbon extraction, African leaders need to demonstrate to international partners that these operations are part of a long-term transition away from other fossil fuels and contribute towards poverty alleviation.

Leaders need to be coordinated in their demands to international partners on how to phase out over time as well as de-risk potential stranded assets. President Ramaphosa’s unveiling of the investment plan for the South African Just Energy Transition Partnership (JETP) was a significant mark of progress to unlocking the $8.5 billion pledge for lowering the economy’s reliance on coal.

While progress has at times faltered over the past year, it has been critical that South Africa articulate its own needs and desired energy mix, rather than this be internationally prescribed. It has also demonstrated to other African nations that bilateral not multilateral initiatives may offer a fast-track route to green finance.