It's all over but the crying for a campaign that was supposed to be characterized by 'joy'. There will be no concession speech tonight. At little before 1 am, Kamala is running like a scared rabbit.

The post Cowardly Kamala Pulls A Hillary — Refuses To Concede As Trump Paints The Country Red appeared first on Clash Daily.

Republican primary opponents like Ron DeSantis said that every time they announced another indictment, his poll numbers got better. They should have known better. But they were blinded by hate.

The post BOOM: Trump Prosecutors React To New Post-Election Realities… Here’s Their Plan appeared first on Clash Daily.

It was just a couple of weeks ago that the media was bragging about Kamala's HUGE fundraising haul.

The post YIKES: Kamala’s Failed Campaign Finished DEEP In Debt — Here’s The 411 appeared first on Clash Daily.

If anyone could accuse Trump of being on 'defense' during his witch-hunt trials, he's going on full offense now.

The post BOOM: Trump’s Lawyers SAVAGE Letitia James… Threaten PRISON If She Plays More Of Her Games appeared first on Clash Daily.

Claims that FEMA specifically skipped homes with Trump signs were blown off as 'hoaxes'... until they were proven true. Now the fallout of that story is spreading FAR beyond the official responsible.

The post FEMA FAIL: The Claim, The Lie, & The Consequences appeared first on Clash Daily.

One of the best parts about the first days after a Trump win is how the left has begun to devour themselves.

The post WATCH: Carville Has NO ‘Effs’ Left To Give — Blasts ‘Woke’ In Epic ‘I Told You So’ Rant appeared first on Clash Daily.

Without a consequence-free hook-up culture, Planned Parenthood's business model collapses. The left's response to Trump's election is an existential threat... to itself!

The post OOPS: Planned Parenthood Sounds Alarm As Lefties Weaponize Abstinence appeared first on Clash Daily.

A.F. Branco Cartoon – The Media (CBS, MSNBC, CNN, ABC, etc. are showing their complete bias in support of Kamala..

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.

In a surprise move that broke in the early hours of Tuesday morning, President-elect Donald Trump has reportedly picked South Dakota Gov. Kristi Noem as his nominee to head the […]

The post Trump Makes His Pick for Secretary of the Department of Homeland Security Secretary: Report appeared first on The Western Journal.

It was one of the high points in the early days of the Kamala Harris campaign, the honeymoon period where the vice president — newly minted as the Democratic nominee […]

The post Watch: Oprah Pressed Over Claims That Kamala Harris' Campaign Paid Her $1M for Political Endorsement appeared first on The Western Journal.

Melania Trump will not be traveling with her husband to Washington on Wednesday when President-elect Donald Trump and President Joe Biden have a formal transition meeting, according to multiple reports. […]

The post Melania Trump to Give Jill Biden the Cold Shoulder This Week: 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.

Shortly after President-elect Donald Trump appointed Tom Homan as “border czar,” the immigration hardliner’s hilarious 2019 smackdown of Democratic Rep. Alexandria Ocasio-Cortez of New York went viral on social media. […]

The post Flashback: Video of Tom Homan Taking Down AOC Resurfaces, Showing Why Trump Picked Him appeared first on The Western Journal.

To a large extent, President-elect Donald Trump’s winning coalition came together around one absolute truth. In sum, Americans do not have a self-governing constitutional republic if we also have a […]

The post Trump Shares His 10-Step Plan to 'Shatter the Deep State' and It Will Give You Chills appeared first on The Western Journal.

Americans will only achieve healthy public discourse when we agree on basic principles and start telling the truth. As it stands, however, too many elected officials engage in hypocrisy by […]

The post Dem Lawmaker Says the Quiet Part Out Loud as She Suddenly Changes Her Tune on the Senate Filibuster appeared first on The Western Journal.

A Louisiana law that sought to post the Ten Commandments in every schoolroom in the state has been shelved by a federal judge. U.S. District Court Judge John W. deGravelles, […]

The post Obama-Appointed Federal Judge Temporarily Blocks Ten Commandments Law appeared first on The Western Journal.

CNN reportedly will be making more cuts in the near future, including to its highly paid on-air personalities, following poor election ratings. The New York Post reported that Fox News […]

The post On-Air Talent Will Not Be Spared as CNN Prepares Mass Layoffs in Wake of Election: Report 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.

In his latest Rucking with Rob newsletter, Rob Houwing argues that for England to have any hopes of beating the Springboks, they'll have to be on the ball in the final stages.

Sri Lanka's cricket board named former South African batsman Neil McKenzie as a consultant coach ahead of their Test tour of South Africa.

As captain, Aiden Markram is allowed a long rope from a wonky form perspective, but how long can that rope be as the run river continues to shrivel, asks Khanyiso Tshwaku.

Bafana Bafana coach Hugo Broos has welcomed the number of young players who are given a chance and backed in the premier division, but has warned that to build on their progress, agents must prioritise players' development over their personal enrichment.

The Springboks will continue to evolve their attack, but they must do so within the framework of what has made them so successful, says attack coach Tony Brown.

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.

The race to succeed Bill Beaumont as chairman of World Rugby comes to a conclusion in a vote in Dublin at the governing body's headquarters on Thursday.

The first battle cry has sounded ahead of the showdown at Twickenham on Saturday, with English winger Tommy Freeman reckoning that the Springboks are 'still human' and 'still playing the same game'.

Wednesday's third T20 between South Africa and India at SuperSport Park in Centurion is shaping up to be a run-drenched one, especially if the weather holds and SA's bowling centre doesn't.

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.

By SADF – Nov. 30, 2022 Online conversation on The West, a New Haven for the ‘Muslim Brotherhood’s Planetary Nebula’? On November the 29th at 16H.00 (CET), SADF promoted an online conversation in the web platform StreamYard titled ‘The West, a New Haven for the ‘Muslim Brotherhood’s Planetary Nebula’?’ The conversation included the Member of the European Parliament (EPP, […]

TikTok will have more US users than Snapchat and Pinterest in 2022   January 24, 2022 (New York, NY) – YouTube is the “OG” of influencer marketing platforms, and it’s […]

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 […]

June 22, 2022 (New York, NY) – Will Apple’s entry into the buy now, pay later (BNPL) space upend the already competitive industry? That’s the question many are trying to […]

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

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.

Beijing briefing: China bets on warmer EU relations The World Today mhiggins.drupal 30 January 2023

With the Sino-US Xi relationship cooling, Xi Jinping is sending a new diplomatic team to Europe – but his ties to Putin may mean slow progress, writes Yu Jie.

It has been a momentous year for Beijing. Twelve months after Russia’s invasion of Ukraine, its relations with the West have become more strained than ever. And after President Xi Jinping secured an unprecedented third term in office at the 20th Party Congress, the country has embarked on a chaotic exit from the Covid lockdown amid hopes the economy will rebound quickly.

Some are already asking if Beijing will set a course correction in its diplomatic priorities to spare itself some of the setbacks it incurred in 2022. But when it comes to foreign affairs, China’s priorities rarely change. 

The Chinese leadership seeks to create a stable external environment to allow its domestic economic development. This conservative maxim was adopted in the 1980s by Deng Xiaoping, and President Xi is likely to follow it as a time-honoured recipe for diplomatic reconciliation.

China’s awkward position

Beijing’s close relationship with Moscow and its failure to oppose Russia’s invasion of Ukraine have put China in an awkward position. Xi and his colleagues have begun to realize that cooperation with Russia comes with substantial limits to avoid undermining China’s own political priorities and longer-term economic interests.

Interestingly, pundits interpreted the omission of ‘pursuing new types of great power relations’ in the 20th Party Congress report as an acceptance by the party leadership that its fraught relationship with advanced developed nations is likely to remain, with little prospect of improvement in the short term.

Chinese diplomatic literature has always presented Russia as a great power, but the abandonment of such terms signals that Beijing is keen to put clear daylight between itself and Vladimir Putin, although international commentators may argue this is not enough and nothing has changed.

There has been little sign of China using its influence to help resolve the Ukraine conflict. Facing, as it feels it now does, a ‘collective West’ and not the Americans alone, Beijing has concluded there are few reasons not to move closer to Russia.

But a reset would appear necessary if China is to tackle its domestic economic woes. So far, Beijing’s main political tactic has been to reassure European countries that it is willing to use its ties with Russia to restrain Putin from entertaining the deployment of nuclear weapons. That was the message conveyed during the visit of Olaf Scholz, the German Chancellor, and it will be said again when both President Emmanuel Macron of France and Giorgia Meloni, Italy’s prime minister, each visit later this year.

Economically, China has traditionally relied on its relationships with the European Union and the United States to support innovation and growth. So, a perceived isolation from ‘a collective West’ is not an attractive option given Xi’s hopes of achieving a robust economic rebound after dropping the country’s ‘zero-covid’ policy. A precarious bilateral tie with the US has already reduced Beijing’s choice of partners and consumers. Worsening Sino-US relations and a tightening of access to overseas markets for Chinese companies have prompted Beijing not only to reconsider the country’s sources of economic growth but to reconfigure its approach to foreign affairs.

China is making a renewed push to strengthen ties with the Global South, which does not see the war in Ukraine as black and white as the West does. Such a move is only possible because five decades of engagement with the ‘collective West’ has allowed China to emerge from poverty and become a global economic powerhouse.

A new diplomatic team

In an attempt to reset the tone of China’s relations with the EU, its largest trading partner, Xi has formed a new diplomatic team headed by Qin Gang, as Minister of Foreign Affairs, who is returning from his post in Washington as ambassador to the US and who has a background in European affairs. Achieving warmer relations will be easier said than done, however, as China has maintained its ‘neutrality’ at Russia’s aggression since February 2022.

China is attempting a precarious balancing act Expert comment NCapeling 9 March 2023

In its efforts to maintain ties with both Russia and Europe, China is having to wade through conflicting interests and rapidly changing sentiments.

Precisely how far China will go in supporting Russia has been one of the most important questions of the war in Ukraine.

On 20 February, US secretary of state Antony Blinken warned China may soon provide arms (‘lethal support’) to Moscow. But then, on 24 February – the anniversary of Russia’s invasion – China released a position paper calling for a political settlement to end the conflict, tellingly omitting any mention of its ‘no-limits partnership’ with Russia.

China’s goal was to present itself as a neutral mediator. In fact, Beijing’s ties with Russia remain unchanged, even if this relationship has grown more exasperating for Chinese diplomats over the past year.

Their job is to continue striking a delicate balance, a task that is becoming increasingly difficult as Russian president Vladimir Putin doubles down on nuclear brinkmanship and reckless rhetoric.

Staying out of the Ukraine war

With Putin extolling the law of the jungle in its most brutal form, China must be careful not to involve itself too much in the conflict. After all, Russia is clearly losing, and China has high hopes of repairing ties with major European economies.

But Putin is of course keen to signal that China has his back. That is why he recently rolled out the red carpet for China’s top diplomat Wang Yi and then alluded to an (unconfirmed) upcoming visit by Chinese president Xi Jinping.

Such diplomatic developments allow him to present China’s ambivalent position as, in fact, an endorsement of the invasion. While the costs of aligning with Russia could easily outweigh the benefits for China, one must remember that China’s reasons for maintaining good relations with the Kremlin go beyond the war in Ukraine.

For starters, the two countries share a 2,672-mile (4,300-kilometer) border – roughly equivalent to the width of Europe – and the frontier’s exact location was not even finally settled until the beginning of this century, after generations of negotiations that included some 2,000 meetings.

Yet to this day, the spectre of the Sino-Soviet split in the 1950s and 1960s looms large on both sides and it is not likely to be exorcised anytime soon. With China focused on moves by the US and its allies in East Asia and the Indo-Pacific, it simply cannot afford sabre-rattling or unrest on its other borders.

Moreover, unlike the collective West, China’s foreign policy has always been shaped by interests rather than by values. Even with respect to Russia, the two countries’ bond is based mainly on shared resentment of US hegemony. By deepening their bilateral cooperation in recent years, they have been able to achieve a level of great-power status with which to counterbalance America.

But Putin’s misadventure in Ukraine has forced Xi and China’s newly minted Politburo to manage a new set of economic, financial, and political risks.

Russia’s war has left the West more firmly united than it has been in years. As China’s relations with the US have reached new lows, Chinese leaders want to avoid also alienating the European Union (EU), which is one of the country’s biggest trading partners.

This is why Xi and Chinese diplomats have been so careful not to accept the Kremlin’s talking points in full. Being isolated from the ‘collective West’ is not an attractive option for China, given its hopes of achieving a robust economic rebound after years of the zero-COVID policy.

Balancing Europe with the Global South

In seeking to keep diplomatic and trade channels open, China’s main tactic has been to reassure European countries that it will use its own ties with Russia to restrain Putin from deploying nuclear weapons.

At the same time, China is making a renewed push to strengthen its ties with the Global South where many countries do not see the war in Ukraine in the same stark moral terms as the West does.

The emphasis on energy and food security in China’s recent position paper may have struck a chord with developing countries that have been reeling from the war’s negative knock-on effects on their economies.

India-China relations: Is the Quad the answer? Interview NCapeling 28 March 2023

The threat of China’s military aggression is being felt across the world, but this is a phenomenon India has been contending with for decades.

India’s border with China became the site of tense conflict in 2020, which led to India reinvesting in the Quad. Arzan Tarapore discusses key issues from his International Affairs article, such as how India is responding to increased aggression at the border and how a reinvigorated Quad may hold answers to balancing China in the Indo-Pacific.

What have India-China relations been like in the past?

Relations between India and China have varied over the decades. In the years following World War Two there was some hope they would find common cause in their international outlooks but that was quite quickly extinguished with their border war of 1962.

Since then, the two countries have oscillated between detente and tension. It took decades for them to normalize their relations and slowly build trust through several confidence-building agreements.

More recently it seemed the two countries were both willing to set aside their border dispute in order to profit from their burgeoning economic relationship – as, for both, there is no question development and economic growth is the primary national objective.

The question has been the extent to which their unresolved sovereignty and security issues undermine those goals as, at the same time, they both began paying more attention to the security of their territorial claims.

China in particular matched its explosive economic growth with startling military modernization and assertiveness. Its long-standing military doctrine and terrain advantages means it relies heavily on quality military infrastructure on the Tibetan plateau and it has accelerated the pace of those infrastructure upgrades and expansion.

In the 2010s, India belatedly began to improve its own transport infrastructure near the border, which threatened to reduce China’s military advantages. The earlier quiet on the border began to crack and China began launching border incursions with increasing frequency and scale.

This was a dynamic, iterative process, with incursions prompting India to accelerate its infrastructure development, which in turn probably prompted more incursions by China.

What happened around 2020 to change their relationship?

The cycle of competitive security policies on the border reached a tipping point in 2020 with Chinese incursions at multiple points simultaneously in Ladakh, apparently designed to establish a new status quo on the Line of Actual Control (LAC) separating Indian and Chinese-controlled territory.

The Indian political leadership played down the incursions but both Indian and Chinese militaries rushed to reinforce their positions near the border. They held multiple rounds of military talks which made halting progress.

On 15 June 2020, a skirmish resulted in the loss of 20 Indian troops, and an unknown number of Chinese troops. In the weeks that followed, both sides further reinforced their positions in a scramble to gain positional advantage.

How has India responded to China’s increasing military might?

The Indian government’s response to the Chinese landgrab was to threaten the entire bilateral relationship. In a reversal of decades of policy, it argued China had demolished the painstakingly constructed confidence-building measures on the border, and so the relationship could not continue as normal until the border crisis was resolved.

It imposed new restrictions on Chinese investment in India – even as overall trade continued to increase – and adopted a more assertive diplomatic posture.

Strategically, the 2020 border crisis had two major effects. First, it reinforced the Indian proclivity to see its northern borders as the primary threat to Indian national security.

India has heavily reinforced the border, reassigning some major formations and making numerous new investments in military capability to manage the threat. The significance of this however is that, in the context of budget scarcity, these military improvements come at the cost of potential increases in India’s capability in the Indian Ocean region – ultimately a more consequential zone of competition in the Indo-Pacific.

The Indian government may yet change course and reallocate resources for power projection but, at this stage, I see no evidence of that.

The second major strategic effect of the crisis was to unleash Indian cooperation with its partners, especially the US and the reinvigorated Quad grouping of Australia, India, Japan and the US.

India has generally avoided formal international alliances, and the Quad was in hiatus for years – why has India invested in it now?

India had always been mindful not to embrace external partners too closely so as to maintain its freedom of action and to not provoke a Chinese reaction. But since the Ladakh crisis, New Delhi has a newfound willingness to work more closely with the US, Japan, and Australia – because it calculates correctly that these partnerships enhance its freedom to act, and that China has already adopted the aggressive posture India feared.

It is important to note however that the border crisis was not the only driver of India’s strategic adjustment. The crisis coincided with the COVID-19 pandemic which highlighted to India the ineffectiveness of existing international institutional arrangements.

For New Delhi, then, the twin crises of Ladakh and the pandemic stressed the need for new international arrangements, and the Quad offered the best combination of agility and capability to meet the most pressing challenges of the Indo-Pacific region.

What do the Quad partners hope to achieve in their renewed partnership?

Beginning in 2021, the Quad assumed far greater significance. The first national leader summits happened – which have since continued at regular intervals – and its members have all agreed to a continually expanding agenda of work.

It seeks to provide international public goods, and everything from climate action to telecommunications regulations. Critically, it has limited its security role to some niche and relatively unprovocative areas, such as humanitarian assistance and maritime domain awareness – issues which benefit the Indo-Pacific as a whole and do not intensify security competition. It has certainly eschewed military cooperation.

Interestingly, the four Quad countries have also separately accelerated their military cooperation, bilaterally, trilaterally, and even quadrilaterally. But that cooperation lies outside the formal mechanisms of the Quad.

What impact will these Quad actions have on Chinese aggression and the Indo-Pacific region?

This Quad approach, which I call ‘zone balancing’ in my article, is specifically designed to build the capacity and resilience of regional states, and to not inflame dyadic security competition.

The relatively uncompetitive character of these activities helps to deflate Chinese claims that the Quad is an antagonistic new bloc, and to ameliorate southeast Asian states’ concerns over the potential intensification of strategic competition.

But the Quad’s agenda is not fixed and not bounded. It has expanded year on year and may continue to extend into new areas. This gives it a degree of flexibility and coercive leverage as Beijing cannot be confident about the Quad’s future direction.

This slate of activities has a lot of utility in building the Quad’s regional legitimacy and habits of cooperation among its members. But it conspicuously does not address the region’s most pressing security challenges.

It is not, in its current form, equipped to manage the challenge of territorial disputes or aggression. So the Quad will not address India’s unresolved border dispute with China, potential crises over Taiwan, or the South China Sea.

I would argue, however, that the four members of the Quad have unparalleled advantages of capacity and geography. With further military cooperation, even outside the formal structures of the Quad, they have the potential to deter Chinese aggression, but that remains subject to their political preferences.

Will other countries in different parts of the world adopt similar balancing strategies?

Zone balancing could be an attractive strategy for other countries which want to either avoid the costs of hard military balancing, or to not provoke their rivals.

It has been used in the past – such as the Marshall Plan during the early Cold War – and I would not be surprised if other countries competing with China, or even China itself, use it.

Chinese supply chains could tip the balance in Ukraine Expert comment NCapeling 29 March 2023

Disrupting supply chains of critical minerals to those supporting Ukraine could give China a key advantage in its wider international trade competition.

Direct military intervention from China into the war on Ukraine, with Chinese troops and airmen appearing at the front line, would be highly escalatory and highly unlikely.

Equipping Russia with weapons and equipment is much more likely – if indeed it hasn’t already happened – and considering the West is supplying armaments to Ukraine, a joust with western technologies would be an interesting development to follow.

But if Chinese weapons underperform in the heat of battle, this may have implications for the current situation with Taiwan and the US, as a poor outcome on the Ukraine front could give the West more confidence over the tensions in the South China Sea. And the use of Chinese weapons in Ukraine would also be a feast for Western technical intelligence to capture.

Creating economic disruption

A much more likely development for China is to put in place export controls on critical minerals for Western powers supplying arms to Ukraine. This is a significant lever which China has used before during its fishing dispute with Japan in 2010 when hi-tech industrial production in Japan was affected by shortages of China-sourced critical minerals. Once normal supplies were resumed, Japan started to stockpile critical mineral reserves.

In October 2020, the Chinese Communist Party (CCP) passed a new statute enabling – when necessary – restriction of critical mineral supplies to third party nations intending to use them for defence and security applications, adding a ‘versatile weapon to Beijing’s arsenal’ in its trade competition with the US.

That legal control has been applied to Lockheed Martin production of Taiwan-bound F-35s and it applies not only to critical minerals mined on the Chinese mainland, but also to Chinese-controlled enterprises within international supply chains, of which there are many.

Responding to any such restrictions by opening up new mines and setting up new supply chains can take more than a decade, so the countries involved may need to start stockpiling critical materials as Japan has been doing since 2010.

Commodity markets also need to be ready for some interesting price wobbles – a persistent problem in critical minerals extractives investment as is overcoming environmental, social, and governance (ESG) challenges in this new game of global supplies.

In addition, those markets include the London Metal Exchange, now owned by Hong Kong Exchanges & Clearing whose biggest shareholder is the Hong Kong government which is struggling to operate with complete independence from Beijing.

Splitting the West’s consensus

By extending the thinking on China’s potential to throttle global critical mineral supply chains and the ensuing latency of extraction from new mining resources, progress to the Paris Agreement 2050 goals on climate change will inevitably be affected.

Given there are no supply chain assurance mechanisms, such as distributed ledger technologies, in place within global mining supply chains, a key issue to overcome would be how the West assures China that critical mineral supplies are not destined for military applications.

But if China’s default position becomes a total refusal to supply client nations unless end-to-end assurances can be achieved to prove non-military use, the West’s aspirations regarding the Paris 2050 goals will certainly be put in jeopardy, or even made unachievable.

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.

Epoxide hydrolases (EHs) have been characterized and engineered as biocatalysts that convert epoxides to valuable chiral vicinal diol precursors of drugs and bioactive compounds. Nonetheless, the regioselectivity control of the epoxide ring opening by EHs remains challenging. Alp1U is an α/β-fold EH that exhibits poor regioselectivity in the epoxide hydrolysis of fluostatin C (compound 1) and produces a pair of stereoisomers. Herein, we established the absolute configuration of the two stereoisomeric products and determined the crystal structure of Alp1U. A Trp-186/Trp-187/Tyr-247 oxirane oxygen hole was identified in Alp1U that replaced the canonical Tyr/Tyr pair in α/β-EHs. Mutation of residues in the atypical oxirane oxygen hole of Alp1U improved the regioselectivity for epoxide hydrolysis on 1. The single site Y247F mutation led to highly regioselective (98%) attack at C-3 of 1, whereas the double mutation W187F/Y247F resulted in regioselective (94%) nucleophilic attack at C-2. Furthermore, single-crystal X-ray structures of the two regioselective Alp1U variants in complex with 1 were determined. These findings allowed insights into the reaction details of Alp1U and provided a new approach for engineering regioselective epoxide hydrolases.

Mitochondria are specialized compartments that produce requisite ATP to fuel cellular functions and serve as centers of metabolite processing, cellular signaling, and apoptosis. To accomplish these roles, mitochondria rely on the genetic information in their small genome (mitochondrial DNA) and the nucleus. A growing appreciation for mitochondria's role in a myriad of human diseases, including inherited genetic disorders, degenerative diseases, inflammation, and cancer, has fueled the study of biochemical mechanisms that control mitochondrial function. The mitochondrial transcriptional machinery is different from nuclear machinery. The in vitro re-constituted transcriptional complexes of Saccharomyces cerevisiae (yeast) and humans, aided with high-resolution structures and biochemical characterizations, have provided a deeper understanding of the mechanism and regulation of mitochondrial DNA transcription. In this review, we will discuss recent advances in the structure and mechanism of mitochondrial transcription initiation. We will follow up with recent discoveries and formative findings regarding the regulatory events that control mitochondrial DNA transcription, focusing on those involved in cross-talk between the mitochondria and nucleus.

The QT interval is a recording of cardiac electrical activity. Previous genome-wide association studies identified genetic variants that modify the QT interval upstream of LITAF (lipopolysaccharide-induced tumor necrosis factor-α factor), a protein encoding a regulator of endosomal trafficking. However, it was not clear how LITAF might impact cardiac excitation. We investigated the effect of LITAF on the voltage-gated sodium channel Nav1.5, which is critical for cardiac depolarization. We show that overexpressed LITAF resulted in a significant increase in the density of Nav1.5-generated voltage-gated sodium current INa and Nav1.5 surface protein levels in rabbit cardiomyocytes and in HEK cells stably expressing Nav1.5. Proximity ligation assays showed co-localization of endogenous LITAF and Nav1.5 in cardiomyocytes, whereas co-immunoprecipitations confirmed they are in the same complex when overexpressed in HEK cells. In vitro data suggest that LITAF interacts with the ubiquitin ligase NEDD4-2, a regulator of Nav1.5. LITAF overexpression down-regulated NEDD4-2 in cardiomyocytes and HEK cells. In HEK cells, LITAF increased ubiquitination and proteasomal degradation of co-expressed NEDD4-2 and significantly blunted the negative effect of NEDD4-2 on INa. We conclude that LITAF controls cardiac excitability by promoting degradation of NEDD4-2, which is essential for removal of surface Nav1.5. LITAF-knockout zebrafish showed increased variation in and a nonsignificant 15% prolongation of action potential duration. Computer simulations using a rabbit-cardiomyocyte model demonstrated that changes in Ca2+ and Na+ homeostasis are responsible for the surprisingly modest action potential duration shortening. These computational data thus corroborate findings from several genome-wide association studies that associated LITAF with QT interval variation.