If killjoy leftists can wear their self-parodying and ridiculous 'Handmaid's Tale' outfits, then they can't complain when a MAGA voter plays the same game... only better.

The post MUST-WATCH: MAGA Voter Finds Hilarious Way To Sidestep Election Clothing Rules appeared first on Clash Daily.

Kamala was right about one thing: this election really DID deliver 'joy'... just not the way she expected.

The post EPIC: The ‘Songify’ Trend Of Clipping Speeches To Music Is Back… And AWESOME! appeared first on Clash Daily.

He learned some hard lessons from his first kick at the can. This time, he's not making the same mistakes. Personnel IS policy.

The post Left Already Losing It As Trump Announces His Starting Lineup (VIDEO) appeared first on Clash Daily.

A.F Branco Cartoon – The choice in this election is clear: Sleight-of-hand leftist Tricks or the abrasive truth in the..

A.F. Branco Cartoon – Gov. Tim Walz lost his own Blue Earth County in Minnesota. Trump also flipped three other..

Bob Moesta is a dear friend, mentor, and all around original thinker. He’s helped me see around corners, shine lights on things I didn’t know were there, and approach product development from unusual angles. Every time we talk, I come away inspired and full of optimism. So when he asked me to help him with… keep reading

Earlier this year, we announced that Basecamp was committing to getting to carbon negative for our cumulative history and moving forward. Today, I want to share an update on that commitment. Note: I edited this post on Nov 5, 2020 to include the prices paid for all carbon offsets and explain a little more about the… keep reading

Chairman Klein and members of the Senate Industry, Business and Labor Committee- My name is David Heinemeier Hansson, and I’m the CTO and co-founder of Basecamp, a small internet company from Chicago that sells project-management software and email services. I first testified on the topic of big tech monopolies at the House Antitrust Subcommittee’s field… keep reading

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.

Even after her loss on Nov. 5, Vice President Kamala Harris’ election campaign is still hounding donors for money. Harris’ campaign has bombarded supporters with fundraising messages following her election […]

The post Kamala's Campaign Is Still Aggressively Shaking Down Supporters For Cash appeared first on The Western Journal.

President-elect Donald Trump is expected to nominate Florida Sen. Marco Rubio as his secretary of state, reports late Monday indicate. According to The Wall Street Journal, while the nomination isn’t […]

The post Trump to Pick Senator Marco Rubio for Crucial Cabinet Position: Report appeared first on The Western Journal.

President-elect Donald Trump will begin his second term by putting pieces of his first one back in place, according to incoming White House Chief of Staff Susie Wiles. Wiles made […]

The post Trump's New Chief of Staff Susie Wiles Discloses His Day One Plans: Report appeared first on The Western Journal.

President-elect Donald Trump has chosen the next director of the CIA. Trump tapped former Texas congressman and director of national intelligence John Ratcliffe for the job. According to a statement […]

The post 'Warrior for Truth': Trump Has Chosen His Next CIA Director, Crediting Pick for 'Exposing Russian Collusion' Hoax appeared first on The Western Journal.

Now that there is a Republican majority in the next Congress, it’s time for the party to bare its internal fault lines. That is likely to take place Wednesday, according […]

The post Another House Speaker Battle? Mike Johnson's Position May Be at Risk as Conservative Anger Heats Up appeared first on The Western Journal.

Springbok coach Rassie Erasmus wants a tour whitewash and, with the Scotland win, he's a third of the way there. He didn't say it would be pretty, as Sunday's success at Murrayfield showed.

Jannik Sinner hit the accelerator at the end of each set as he cruised past Taylor Fritz 6-4, 6-4 on Tuesday to close in on a semi-final spot at the ATP Finals in Turin.

Rassie Erasmus' 7-1 variation of the Bomb Squad used against Scotland on Sunday set off a few tremors in the north, with Times writer Stephen Jones the latest to criticise the "dangerous" and "arrogant" tactic.

Late injection Johan Grobbelaar may find himself more than simply an “extra” on the Bok tour, writes Rob Houwing.

Cairo, Egypt Oct. 28, 2022 On Egyptian TV show, “Headlines,” Dr. Hossam Farouk dedicated an episode to discussing national and international coverage of the Secret Apparatus: The Muslim Brotherhood’s Industry of Death. It was a great honor having the book featured on this great show.

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

Originally published in Gatestone Institute on Nov. 25, 2022 By Cynthia Farahat Bahgat Saber, a member of the Muslim Brotherhood, operates from his New York apartment and often streams live videos from Times Square. During his multi-hour videos, Saber routinely incites terrorism, assassinations, kidnapping and torture in an extremely graphic manner. The calls for violence […]

Spotify still No. 1 by wide margin February 24, 2022 (New York, NY) – Pandora, once the dominant player in terms of digital music streaming, will be eclipsed by Amazon […]

Total media ad spend in Russia to drop nearly 50%   March 30, 2022 (New York, NY) – Insider Intelligence expects the ongoing war in Ukraine to have a significant […]

Richard Moeckel and Richard Montgomery
J. Amer. Math. Soc. 38 (), 225-241.
Abstract, references and article information

Marcelo Campos, Matthew Jenssen, Marcus Michelen and Julian Sahasrabudhe
J. Amer. Math. Soc. 38 (), 179-224.
Abstract, references and article information

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

Russia–China defence and security relations: Insights from the expert community 13 September 2022 — 3:00PM TO 4:00PM Anonymous (not verified) 31 August 2022 Online

Experts share insights on Russia–China military, defence, and security relations. 

In the defence and security realms, Russia–China relations resemble more pragmatic cooperation based on shared, calculated interests than an alliance.

This event presents and discusses key findings from a recent expert survey conducted by Chatham House with the aim to gather insights on Russia–China military, defence, and security relations.

Survey responses helped identify areas of bilateral cooperation but also crucial friction points and obstacles that prevent the relationship from developing further, as well as policy pathways for the West.

Russia-China Defence and Security Relations

This project explores the military and security linkages between Russia and China.

The project seeks to provide a nuanced understanding of Russia-China relations in the defence and security realms.

It also seeks to understand Russian political and security perceptions regarding Chinese inroads into what Russia considers its ‘near abroad’, as well as other sources of irritation and tension in the bilateral relationship. It offers recommendations to guide NATO policy responses.

China’s high-stakes incursion in the heights of Bhutan The World Today mhiggins.drupal 28 September 2022

Why is Beijing establishing settlements over the Bhutanese border? To undermine India’s strategic security, say John Pollock and Damien Symon.

A confrontation is fomenting on the roof of the world in a country that rarely warrants international attention.

In the tiny Kingdom of Bhutan, China is building villages in isolated, mountainous regions, upping the pressure on the capital Thimphu to yield contested areas to Beijing. In doing so, China risks a collision with South Asia’s largest state and Bhutan’s principal security guarantor, India.

Sitting on top of fragile geopolitical fault lines in the Himalayas, China’s Central Military Commission has seemingly authorized a series of incursions into the Bhutanese regions of Doklam, Jakarlung, and Pasamlung. Beijing has also announced fresh claims in the east towards Sakteng. Taken together, these amount to 12 per cent of Bhutan’s total territory according to Nathan Ruser, an analyst at the Australian Strategic Policy Institute.

India is wary of Beijing’s increased assertiveness in the Himalayas following a large-scale incursion by the Chinese People’s Liberation Army (PLA) into Ladakh two years ago when dozens of Indian and Chinese soldiers were killed in a stand-off.

The appearance of Chinese roads, villages and a host of other infrastructure projects within largely uninhabited areas of Bhutan close to Tibet, have, for sections of India’s national security establishment, confirmed their worst fears – Beijing is altering the status quo across the Himalayas in a bid to undermine India’s strategic security through territorial alterations.

As a country of only 780,000 people, Bhutan is greatly influenced by New Delhi when it comes to its foreign affairs. In exchange, India guarantees the defence of the kingdom and trains the Royal Bhutanese Army. The appearance of Chinese villages on its territory risks Bhutan becoming a victim of the wider regional tensions.

The trauma of China-Bhutan border relations

Bhutan is no stranger to the territorial aspirations of its northern neighbour. Thousands of refugees fled into the country after China annexed Tibet, damaging longstanding cultural and religious links between the Tibetan and Bhutanese people – a trauma still being felt today.

Now, Beijing is laying claim to three areas within Bhutan, including Doklam in the west. This plateau is close to the Siliguri Corridor which connects to the ‘Seven Sister’ states in northeast India. Indeed, such is India’s concern over any Chinese presence near Doklam that in 2017 local Indian commanders sent troops into Bhutan to prevent PLA engineers building a road near the Doka La pass, resulting in a 72-day stand-off on Bhutanese soil between India and China, an experience Thimphu is unwilling to repeat.

Once again, China is looking to force the border issue unilaterally, altering the status quo and building villages and outposts on Bhutanese soil. On the available evidence, it has been doing so for at least three years.

The presence of Chinese villages in uninhabited areas of Bhutan serves a strategic purpose. They appear to be intended to pressure Bhutan into accepting an earlier version of a border deal that concedes Doklam to the Chinese.

Bhutan’s increasing concern is that China now views the Sino-Bhutanese border dispute as a way of unravelling India’s strategic position by stealth. Here we see a growing pattern of behaviour across the Himalayas. China is testing the boundaries in isolated and contested areas of India to attain local advantages that ensure New Delhi’s gaze remains fixed on the Himalayas.

The costly choice facing Bhutan

Bhutan for its part has very deliberately opted to remain silent, despite clear violations of its border deal with Beijing. Thimphu has made no public comment on any of the Chinese incursions.

The choice now facing Bhutan is a costly one. To concede Doklam would devastate relations with India, its closest partner. But to ignore China’s ambitions would be to risk further violations of its sovereign territory.

Bhutan may yet agree in principle to a land swap but then delay its implementation in the hope China limits any further advances. Thus Bhutan, India and China stand at a crossroads, with an impending confrontation that has not yet arrived and one that through Thimphu’s delicate diplomacy, Bhutan hopes never does.

China’s incursions into Bhutan

1. Pangda

The most high-profile incursion is in the disputed areas in Doklam. Running adjacent to the previous Doka La stand-off site, a series of Chinese projects are visible, following the Amo Chu River that runs from the Chumbi Valley in Tibet into Bhutan.

The most well-known of these xiaokang – meaning peaceful and prosperous – border projects is Pangda, a village of 124 people that sits roughly two kilometres within Bhutan from the border. First spotted by open-source intelligence analysts in October-November 2020, Chinese state media says that 27 households were moved from the Shangdui village to Pangda in September of that year and that the village is located in Yadong County, Tibet. Pangda, however, lies on territory internationally recognized as belonging to Bhutan.

Since Pangda was first identified, two more villages and an additional excavation site have been noted through satellite photographs taken in March this year, steadily following the river further into Bhutanese territory. In recent reporting by journalist Vishnu Som, a connecting road is also visible that runs 9km into Bhutan.

Given the geopolitical sensitivities of the area vis-a-vis India, speculation points to Chinese attempts to increase pressure on the Jampheri ridge overlooking the 2017 stand-off site, which according to journalist Tenzing Lamsang, is currently occupied by a small Royal Bhutanese Army detachment. As ever in the Himalayas, small tactical alterations have strategic implications. Chinese control of the Jampheri ridge would command views towards Sikkim, increase the scope of China’s surveillance operations near the border and place India’s Eastern Theatre Command at a terrain disadvantage were it to intervene as it did at Doka La.

2. Dramana and Shakhatoe

Further north of Doklam, at Dramana and Shakhatoe, more villages have been identified, with recent photographs taken in November 2021 showing a collection of structures nestled between snow-capped mountains. Varying in size, the largest village identified by journalist Devjyot Ghoshal comprises more than 84 buildings with construction having been started in December 2020 and seemingly completed by December 2021.

Little is known about the nature of these villages or their occupants other than their size and location. However, the Chinese PLA has patrolled these areas aggressively, warning away Bhutanese herders and challenging counter patrols by the Royal Bhutanese Army.

A permanent PLA presence in the area would be a significant change to the status quo. Informed speculation suggests that these may house either civilian contractors brought in from Tibet to oversee construction projects in the area, Tibetan or Chinese citizens brought across the border, or they could even be barracks for the PLA to help facilitate increased patrols in these contested areas.

3. Menchuma Valley

Amid the sustained activity in the west of Bhutan, we are seeing similar levels of activity mirrored in the northern contested areas in Jakarlung, Pasumlung and the Menchuma Valley, a well-known entry point into Tibet for Bhutanese pilgrims.

In May 2021, a team of researchers led by Robert Barnett from the London School of Oriental and African Studies discovered three additional villages in these contested areas, alongside a series of infrastructure projects, sitting between 3km and 5km south of the Chinese border in Bhutan. Barnett identified what appears to be police and military posts near these villages, as well as a communications tower.

While the building efforts at Doklam are seen as having a geopolitical intent towards India, these villages and their locations are seemingly aimed to maximize China’s leverage over Bhutan. They are considered sacred in Tibetan Buddhist teachings as the birthplace of ancient Himalayan cultural heroes, with strong links to the Bhutanese royal family. Today they are the home to holy sites and temples, such as the Singye Dzong.

For China to intrude on this area, and in some cases even deny entry to parts of it, is suppression of Bhutanese history, culture and traditions. By design or by default, Beijing is managing Tibetan religion and culture beyond the borders of the Tibetan Administrative Region.

Russia and China in Antarctica: Implications for the Five Eyes 15 December 2022 — 11:00AM TO 12:00PM Anonymous (not verified) 2 December 2022 Online

This event explores Russia’s and China’s postions on the Antarctic and offers a critical assessment of their actions in the region.

Ever since the 1959 Antarctic Treaty System (ATS), signed at the height of Cold War, Antarctica has remained a demilitarized continent.

Today, even though the ATS is not in immediate danger of collapse, Antarctica and the Southern Ocean are no longer insulated from wider geopolitical tension, with China and Russia posing challenges to regional governance. 
 
This event also discusses key recommendations for the Five Eyes regarding Russian and Chinese current and future efforts at undermining the ATS and Antarctic governance. 

The discussion is informed by Mathieu Boulègue’s paper ‘Russia and China in Antarctica and the Southern Ocean: Implications for the Five Eyes’ published by the Sea Power Centre of the Royal Australian Navy.

An important mechanism of resistance to β-lactam antibiotics is via their β-lactamase–catalyzed hydrolysis. Recent work has shown that, in addition to the established hydrolysis products, the reaction of the class D nucleophilic serine β-lactamases (SBLs) with carbapenems also produces β-lactones. We report studies on the factors determining β-lactone formation by class D SBLs. We show that variations in hydrophobic residues at the active site of class D SBLs (i.e. Trp105, Val120, and Leu158, using OXA-48 numbering) impact on the relative levels of β-lactones and hydrolysis products formed. Some variants, i.e. the OXA-48 V120L and OXA-23 V128L variants, catalyze increased β-lactone formation compared with the WT enzymes. The results of kinetic and product studies reveal that variations of residues other than those directly involved in catalysis, including those arising from clinically observed mutations, can alter the reaction outcome of class D SBL catalysis. NMR studies show that some class D SBL variants catalyze formation of β-lactones from all clinically relevant carbapenems regardless of the presence or absence of a 1β-methyl substituent. Analysis of reported crystal structures for carbapenem-derived acyl-enzyme complexes reveals preferred conformations for hydrolysis and β-lactone formation. The observation of increased β-lactone formation by class D SBL variants, including the clinically observed carbapenemase OXA-48 V120L, supports the proposal that class D SBL-catalyzed rearrangement of β-lactams to β-lactones is important as a resistance mechanism.

Business Briefing: Assessing the geopolitical implications of EU AI regulation 17 September 2024 — 4:00PM TO 5:00PM Anonymous (not verified) 8 August 2024 Chatham House

Join us for this critical discussion of how the EU AI Act will shape the world’s approach to the technology.

Join us for this critical discussion of how the EU AI Act will shape the world’s approach to the technology

Governments, technology companies and civil society groups across the world are now advocating firmer AI regulation. Machine learning algorithms have changed the way we interact with technology and powered much of our online lives for decades: why has this pendulum swung back so far toward greater control, and why now?

In 2023 the UK government seized the initiative with its Bletchley AI Safety Summit. The event attempted to address the so called ‘frontier risks’ associated with AI development. Global competition on AI is reflected in AI governance efforts in China, US, the Gulf and beyond. But to date, it is the EU that has led the West in passing AI legislation. The EU AI Act, has separated AI systems into graded risk categories carrying different regulatory requirements, and it remains to be seen whether global AI will feel the Brussels effect.

This conversation will cover the following questions:

• Critics have painted regulation including the AI Act as anti-innovation. Is this a fair assessment?
• What lessons can we learn from the successes and shortcomings of GDPR?
• How do we tackle the challenge of low public trust in AI and low public trust in government technology projects, particularly in Western democracies?
• Does the proliferation of safety institutes, and the AI office, point to the emergence of a new type of technical governance institution? What is its future?

Islamic radicalisation in Central Asia 18 September 2024 — 10:00AM TO 11:30AM Anonymous (not verified) 20 August 2024 Chatham House and Online

Experts analyse rising foreign recruitment, current counter-radicalisation efforts and challenge past Chatham House predictions made of the Central Asia region.

In 2014, Chatham House released a report titled The Myth of Post-Soviet Muslim Radicalisation in the Central Asian Republics. At that time, a significant, Western-funded counter-radicalisation industry was addressing what was believed to be a major issue of Islamic violent extremism in the region.

Over the past decade, two key developments have occurred. First, Western interest in the region has declined in favour of traditional geopolitical concerns. Second, while violent extremism incidents within Central Asia remain rare, there has been a notable recruitment of Central Asians by foreign groups, with several attacks carried out by Central Asians overseas.

In this event, the original report’s authors, John Heathershaw and David Montgomery, will discuss whether the report’s arguments are still valid and how we might answer these questions today.

This raises several questions:

• What did the report accurately predict, and where did it fall short?
• How can we explain the lack of violent extremist organisations (VEOs) within Central Asia but the presence of Central Asians in VEOs abroad?
• Could repression by Central Asian states both domestically and transnationally have contributed to this issue?
• What, if anything, can the counter-radicalisation industry do today to address this problem more effectively?

Please note that in-person places are limited. Please wait for confirmation before participating. 

A world in transition and the future of the global workforce 15 October 2024 — 9:00AM TO 10:00AM Anonymous (not verified) 22 August 2024 Chatham House and Online

How are migration and global megatrends shaping international labour?

As the fallout of 2024’s ‘Election Super-Year’ becomes clearer, international policymakers and business leaders must now equip themselves to face the challenges and opportunities of the three key transitions that will dominate the next few decades: the journey toward a greener and healthier world; the transition to a more technologically adept society; and the development of a secure and productive economy for all.

The adaption and evolution of the global workforce is an essential component of all three of these transitions and therefore a prescient analysis of how migration, workforce policies and modern technology trends will impact this ecosystem is essential.

Upskilling the workforce will no doubt remain a key focus for stakeholders. But the question remains, how do these plans move beyond the ‘ideas-phase’ and become policies that will keep pace in the fast-paced, modern and digital workplace?

It may prove harder than ever for these ideas to come to fruition, with the rise of populist and nationalist political thinking fragmenting the balance between local and international labour. Indeed, this often leads to reduced attractiveness of skilled foreign labour in domestic markets.

This puts global business in a very powerful position though, as companies can play an important role in readdressing these narratives, shaping the future of workforce policies and using examples of best practice to improve access, mobility and ultimately economic productivity, for the benefit of all.

Through this event, in partnership with EY, the panel analyses how migration, skills development agendas and global megatrends, such as technology, sustainability and the global economy, will shape developments in the years to come.

A networking breakfast precedes this event, served between 0800 and 0900 BST.

Director’s Briefing: Assessing foreign policy challenges for the next US president 5 September 2024 — 2:00PM TO 3:00PM Anonymous (not verified) 27 August 2024 Chatham House and Online

This briefing will explore what challenges might await the winner of 2024 US presidential election.

As the 2024 US Presidential election draws closer, the future direction of American foreign policy seems ever more uncertain. Kamala Harris, the Democratic presidential candidate, appears to be embracing many of Biden’s policies, but she brings a different background, and most likely a different team, so change is likely.  Donald Trump has more well-known views on foreign policy, but the context for a second Trump administration would be very different than the first.

The next U.S. President will be confronted a world in need of leadership with two major wars, a more assertive and capable China, a climate crisis, ungoverned technological change, emerging powers that demand a seat at the table, and debt distress across much of the developing world.

Please join us for this critical conversation covering:

• How will US-China strategic competition and the threat of conflict over Taiwan challenge US policy makers?
• What are the risks and challenges posed by Russia’s illegal full-scale invasion of Ukraine?
• How does war in the Middle East and the threat of regional escalation shape US foreign policy?

Member’s question time: Is Russia losing the South Caucasus? 22 October 2024 — 1:00PM TO 1:30PM Anonymous (not verified) 2 September 2024 Online

Join us and ask Chatham House Senior Research Fellow, Natalie Sabanadze anything about the situation in the Caucasus. Submit your questions in advance.

Whilst Russia focuses on its illegal invasion of Ukraine, the situation at its southern border is evolving. Relations between the three states in the South Caucasus and Moscow have never been easy as Russia tried to maintain its dominance by leveraging vulnerabilities, playing one side against another to keep conflicts simmering and even engaging in open military aggression.  Although the violence seen in the 1990s and early 2000s has abated, the war in Ukraine has had an indirect impact on the region, bringing a change to the status quo.

Russia abandoned its long-standing support for Armenia, allowing for the collapse of Nagorny-Karabakh and the restoration of the territorial integrity of Azerbaijan with the backing of Turkey. As a result, Azerbaijan has emerged as a dominant regional player with Baku recently declaring its interest to join BRICS.  Turkey’s influence has grown, while Armenia frustrated by Russia’s change of heart has been turning cautiously towards the EU and the US.

In Georgia, meanwhile, the ruling party has been consolidating its grasp on power, rolling back democratic reforms and pivoting away from the West. Georgia’s long-awaited European integration process has been suspended, following the adoption of the Russian-style foreign agents legislation.

Join us as our Senior Research Fellow in the Russia and Eurasia Programme answers your questions in this quick-fire session assessing the extent to which the Russian influence has changed since the start of the invasion of Ukraine and who is there to fill the vacuum; how geopolitical contestation in the region is going to impact aspirations of Armenia, Azerbaijan and Georgia; and much more.

Submit your questions to Natalie Sabanadze in advance of the event. Your questions will drive the conversation.

Fostering inclusive health systems amidst geopolitical instability 13 October 2024 — 9:00AM TO 10:00AM Anonymous (not verified) 11 September 2024 Sheraton Berlin Grand Hotel Esplanade

How can we build trust and inclusivity in the health sector in a fractured geopolitical environment?

Building trust in government, service provision and delivery are crucial considerations for policymakers who aim to make local, national and international health systems more inclusive. In the health space, trust can be a matter of life and death. Understanding and modulating policies that account for the trust factor, alongside the geopolitical determinants of health, can lead to more inclusive decision making and thus better health outcomes for larger proportions of a population.

International unity is key to addressing the challenges posed by geopolitical instability, which include disinformation campaigns, rising nationalism and growing divisions between states. If countries can find common ground through an inclusive approach to health, the effects could be transformative in achieving global health and equity targets.

This discussion, held in partnership with Haleon, will examine what it takes to foster trust and resilience in the health sector, achieve global inclusivity aims and chart a path for the public and private spheres to come together to navigate a fractured geopolitical environment.

• In what ways can localised health inclusivity data help policymakers to alleviate gaps in healthcare provision and why is this an essential element in instilling trust across the system?
• What role should multilateral organizations play in setting precedents for health inclusivity around the world?
• How do health inclusivity policies empower the service user and help reduce the burden placed on public healthcare systems?
• How can the health sector come together to ensure individuals are included within their own health decisions, are able to access services regardless of demographics and geography and trust their healthcare providers?

This event will be held at the Sheraton Hotel, Grand Esplanade, Berlin in the margins of the World Health Summit. You do not need a ticket for the World Health Summit to attend this event.

US domestic polarization and implications for the presidential election 30 September 2024 — 5:00PM TO 6:00PM Anonymous (not verified) 19 September 2024 Online

This webinar explores the rise of polarization amongst the US public and implications for the upcoming election.

Domestic polarization has been on the rise in the US in recent years, with Democrats and Republicans moving further away from the centre on key policy issues. As polarization increases, so too do concerns about the state of US democracy and prospects of political violence surrounding the upcoming presidential election. 

This expert panel discusses key questions including:

• What are the driving forces of the growing political divide in the US?
• How far apart are voters on key election issues, from healthcare to immigration to national security?
• How is partisan polarisation altering the effectiveness of US foreign policy and influencing America’s role in the world?

In conversation with Speaker Emerita Nancy Pelosi 14 October 2024 — 12:00PM TO 1:00PM Anonymous (not verified) 19 September 2024 Chatham House and Online

The former Speaker of the House of Representatives discusses challenges to American democracy and the importance of leadership in an election year.

As the US gears up for the 2024 Presidential election, the importance of leadership in politics has come to the fore. As the Harris and Trump campaigns move towards election day, the heightened sense of strong leadership is central to the position of both candidates.

Following her first election to the House in 1987, Speaker Emerita Nancy Pelosi has been central to American political leadership for over two decades. Serving as the 52nd Speaker of the House of Representative, Speaker Pelosi rose to become one of the most powerful and consequential Speakers in American political history.

Following the release of her recent book The Art of Power, Speaker Pelosi will discuss how she became a master legislator, working with numerous presidents, her political legacy in the house and her leadership during a contentious time in US politics.

Business Briefing: US election geopolitical and economic risk scenarios 10 October 2024 — 11:45AM TO 1:00PM Anonymous (not verified) 23 September 2024 Chatham House

Please join us for this critical discussion of the US Election related global business risks.

The outcome of the US presidential election will have significant, intersecting implications for global as well as American business. At stake will be the degree of continuity and stability on both the domestic and international fronts, with a Harris presidency pursuing policies building broadly on the Biden Administration and a second Trump Administration departing sharply from them—with both shaped and limited by control of Congress.

An already volatile geopolitical environment and global economy may become even more unpredictable in the face of potential American political instability and uncertain leadership in the international community.

Please join us for this critical session to discuss:

• How might trade policy differ between a Harris and Trump presidency? Will national security pressures, especially over China, lead to greater policy commonalities than expected?

• What might differing approaches to decarbonization and the energy transition mean for the future of policy toward EVs, critical mineral supply chains, and ‘green’ industrial subsidy?

• How might each Administration approach fiscal policy? Will either push for a tightening to the current loose policy—and what may be implications for US debt and the dollar?

• What economic effects can we expect in the case of a disputed election result or non-peaceful transfer of power—and will Corporate America be compelled to make public statements?

Looking ahead to the 2024 US Presidential Election 2 October 2024 — 6:00PM TO 7:00PM Anonymous (not verified) 23 September 2024 Chatham House and Online

This panel explores the state of the US presidential election following the vice presidential debate.

With only weeks to go, this panel looks at the state of the 2024 US presidential election.

Harris and Trump are campaigning to drive up voter enthusiasm and bring undecided voters to their side.

What are the key issues shaping voter’s preferences and how may this impact voter turnout? What can we expect in the weeks ahead?

Israel-Palestine: Is peace possible? 7 October 2024 — 6:00PM TO 7:00PM Anonymous (not verified) 30 September 2024 Chatham House and Online

As Israel’s war in Gaza reaches the year mark, and with war spreading, what can the world expect in the Middle East?

A year on from the 7 October Hamas attacks on Israel which sparked a deadly war in Gaza, significant escalation in Lebanon and regional instability, Chatham House will host experts to explore the profound impacts of the conflict and what lies ahead.

The conversation will look at the humanitarian toll in Gaza and Lebanon, the international community’s response and the spreading of the conflict beyond Israel and Palestine. Regional players, including Iran and Saudi Arabia, will be discussed as well as their influence and involvement in these dynamics.

Looking forward, the discussion will focus on potential pathways to peace and stability in Gaza and the broader Middle East.

Key questions considered by the panel include:

• What is the state of Israeli and Palestinian leadership one year on?
• What would it take for Israel to stop its military campaign in Lebanon?
• How are regional powers’ responses changing?
• How likely is a Palestinian state in the future? What must happen to realise it?
• What is the role of the international community?
• What is Iran’s role in the crisis and how should policymakers respond?

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Numerous iron-sulfur (Fe-S) proteins with diverse functions are present in the matrix and respiratory chain complexes of mitochondria. Although [4Fe-4S] clusters are the most common type of Fe-S cluster in mitochondria, the molecular mechanism of [4Fe-4S] cluster assembly and insertion into target proteins by the mitochondrial iron-sulfur cluster (ISC) maturation system is not well-understood. Here we report a detailed characterization of two late-acting Fe-S cluster-carrier proteins from Arabidopsis thaliana, NFU4 and NFU5. Yeast two-hybrid and bimolecular fluorescence complementation studies demonstrated interaction of both the NFU4 and NFU5 proteins with the ISCA class of Fe-S carrier proteins. Recombinant NFU4 and NFU5 were purified as apo-proteins after expression in Escherichia coli. In vitro Fe-S cluster reconstitution led to the insertion of one [4Fe-4S]2+ cluster per homodimer as determined by UV-visible absorption/CD, resonance Raman and EPR spectroscopy, and analytical studies. Cluster transfer reactions, monitored by UV-visible absorption and CD spectroscopy, showed that a [4Fe-4S]2+ cluster-bound ISCA1a/2 heterodimer is effective in transferring [4Fe-4S]2+ clusters to both NFU4 and NFU5 with negligible back reaction. In addition, [4Fe-4S]2+ cluster-bound ISCA1a/2, NFU4, and NFU5 were all found to be effective [4Fe-4S]2+ cluster donors for maturation of the mitochondrial apo-aconitase 2 as assessed by enzyme activity measurements. The results demonstrate rapid, unidirectional, and quantitative [4Fe-4S]2+ cluster transfer from ISCA1a/2 to NFU4 or NFU5 that further delineates their respective positions in the plant ISC machinery and their contributions to the maturation of client [4Fe-4S] cluster-containing proteins.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma membrane anion channel that plays a key role in controlling transepithelial fluid movement. Excessive activation results in intestinal fluid loss during secretory diarrheas, whereas CFTR mutations underlie cystic fibrosis (CF). Anion permeability depends both on how well CFTR channels work (permeation/gating) and on how many are present at the membrane. Recently, treatments with two drug classes targeting CFTR—one boosting ion-channel function (potentiators) and the other increasing plasma membrane density (correctors)—have provided significant health benefits to CF patients. Here, we present an image-based fluorescence assay that can rapidly and simultaneously estimate both CFTR ion-channel function and the protein's proximity to the membrane. We monitor F508del-CFTR, the most common CF-causing variant, and confirm rescue by low temperature, CFTR-targeting drugs and second-site revertant mutation R1070W. In addition, we characterize a panel of 62 CF-causing mutations. Our measurements correlate well with published data (electrophysiology and biochemistry), further confirming validity of the assay. Finally, we profile effects of acute treatment with approved potentiator drug VX-770 on the rare-mutation panel. Mapping the potentiation profile on CFTR structures raises mechanistic hypotheses on drug action, suggesting that VX-770 might allow an open-channel conformation with an alternative arrangement of domain interfaces. The assay is a valuable tool for investigation of CFTR molecular mechanisms, allowing accurate inferences on gating/permeation. In addition, by providing a two-dimensional characterization of the CFTR protein, it could better inform development of single-drug and precision therapies addressing the root cause of CF disease.

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.

Dilated cardiomyopathy (DCM) is associated with mutations in cardiomyocyte sarcomeric proteins, including α-tropomyosin. In conjunction with troponin, tropomyosin shifts to regulate actomyosin interactions. Tropomyosin molecules overlap via tropomyosin–tropomyosin head-to-tail associations, forming a continuous strand along the thin filament. These associations are critical for propagation of tropomyosin's reconfiguration along the thin filament and key for the cooperative switching between heart muscle contraction and relaxation. Here, we tested perturbations in tropomyosin structure, biochemistry, and function caused by the DCM-linked mutation, M8R, which is located at the overlap junction. Localized and nonlocalized structural effects of the mutation were found in tropomyosin that ultimately perturb its thin filament regulatory function. Comparison of mutant and WT α-tropomyosin was carried out using in vitro motility assays, CD, actin co-sedimentation, and molecular dynamics simulations. Regulated thin filament velocity measurements showed that the presence of M8R tropomyosin decreased calcium sensitivity and thin filament cooperativity. The co-sedimentation of actin and tropomyosin showed weakening of actin-mutant tropomyosin binding. The binding of troponin T's N terminus to the actin-mutant tropomyosin complex was also weakened. CD and molecular dynamics indicate that the M8R mutation disrupts the four-helix bundle at the head-to-tail junction, leading to weaker tropomyosin–tropomyosin binding and weaker tropomyosin–actin binding. Molecular dynamics revealed that altered end-to-end bond formation has effects extending toward the central region of the tropomyosin molecule, which alter the azimuthal position of tropomyosin, likely disrupting the mutant thin filament response to calcium. These results demonstrate that mutation-induced alterations in tropomyosin–thin filament interactions underlie the altered regulatory phenotype and ultimately the pathogenesis of DCM.

In their comment (1) on our publication (2), the authors make two points: (i) they raise concerns about the possible effect of residual NONOate in our study, and (ii) they promote nitrosylcobalamin (NOCbl) supplied by their own company. Both points lack merit for the following reasons. The authors make the astonishing claim that the spectra of nitric oxide (NO•) and cobalamins overlap. Unlike NO•, cobalamin absorbs in the visible region, permitting unequivocal spectral assignment of NOCbl as reported (3). We demonstrated that whereas NOCbl is highly unstable in solution, it is stabilized by the B12 trafficking protein CblC. So even if present, residual NONOate (which is unstable at neutral pH and is removed during the work-up (3)) could not account for the observed difference.The authors then misrepresent our synthetic method, claiming that anaerobic conditions were used to generate nitrocobalamin (NO2Cbl), which results in the transient formation of NOCbl. We synthesized NO2Cbl aerobically using nitrite as described (4); NOCbl is not an intermediate in this ligand exchange reaction. The aerobic instability of NOCbl has been rigorously described by inorganic chemists (3, 5) and raises obvious questions about its purported biological effects as exemplified by the authors' own 2003 JBC publication, which was later withdrawn.As to promoting NOCbl from their company, the authors refer to a synthetic route from a mixture of NO• gas and aquocobalamin. The authors' method (6) has been described as “dubious” by chemists (5). Whereas DEAE NONOate used in our method is widely known as an NO• donor,...