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 […]

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State of the Union has lessons for transatlantic unity Expert comment NCapeling 8 February 2023

Analysing key foreign policy aspects of President Joe Biden’s annual address, and what it means for the upcoming Munich Security Conference and the year ahead.

Trade and economics are key areas to watch

Daniel W. Drezner

Russia’s absence from the Munich Security Conference will allow US and European policymakers to brag about their flourishing partnership. The past year has seen repeated predictions of a fracturing transatlantic relationship – only to see repeated agreement on how to sanction Russia and which arms to ship to Ukraine.

Putin invaded because he thought the West was divided. Events have proven him wrong. When one takes a step back, however, and examines the Biden administration’s embrace of geoeconomics, Putin’s assumption becomes easier to comprehend.

The strongest throughline between the Trump and Biden administrations has been their shared mindset on weaponized interdependence. Both administrations have been wary of US interdependence with an increasingly autocratic China.

The primary difference has been that, while the Trump administration talked a good game, the Biden administration has passed laws and issued executive orders making the pivot away from trade liberalization a reality.

The passage of the CHIPS and Science Act, Bipartisan Infrastructure Law, and the Inflation Reduction Act (IRA) amount to the most ambitious US attempt at industrial policy in decades, accompanied by multiple executive orders examining US supply chain resilience and imposing unprecedented export controls targeting China.

The Biden administration’s restrictions on exchange with China’s semiconductors includes the use of the ‘foreign direct product rule’, essentially a means of applying US export controls in an extraterritorial manner.

The Biden administration’s angry response to the WTO panel ruling against US steel and aluminum tariffs makes it clear the US will apply an expanded definition of national security to restrict trade. In many ways, the sanctions on Russia are a continuation of a US foreign economic policy grounded in geoeconomics.

Several of these measures have rankled European officials. The IRA massively subsidizes the North American production of environmentally-friendly cars, discriminating against European producers. And continued US hostility to the WTO leaves European officials wondering if they are the last bastion of multilateralism left in the world. In Washington and Davos last month, European policymakers made their displeasure clear.

The sanctions against Russia and export controls against China threaten to be additional sore subjects. During the strategic embargo of the Soviet Union, US officials wanted to maximize restrictions while European allies wanted more trade opportunities. Since then, Europeans have suspected that the US uses multilateral export controls regimes to advance its commercial interests, while Americans worry Europe underestimates the risks of business-as-usual with China.

The Biden administration has tried to finesse these trade tensions, and was successful at persuading the Netherlands to join the US in the export controls on China. More generally, Biden officials talk about ‘friendshoring’ and propose mechanisms for greater policy coordination, such as the US-EU Trade and Technology Council. But even in these gestures, US officials have taken greater market access off the table.

In the State of the Union address, Biden bragged about how the US ‘came together to defend a stronger and safer Europe’ as well as defending his ‘buy American’ plans and pledging to make sure the ‘supply chain for America begins in America’. At the upcoming Munich Security Conference, attention should be on how much officials talk about trade and economic issues. The more that topic comes up, the clearer it will be that both sides are subtweeting each other about the future of the transatlantic economic relationship.

Division on China now would bring a high price

Dr Leslie Vinjamuri

President Biden has made unity his guiding principle and chief objective, but it is a tall order. His State of the Union address touted past bipartisan backing for investments in infrastructure, climate-friendly technologies, and semiconductor chips, along with a focus on creating jobs for working-class Americans, especially in manufacturing.

Little was said that was explicitly about China, but the Biden administration has said that China is its pacing challenge, and competing with China has shaped the ambition behind these legislative successes.

In fact, the hallmark of the address was its foreign policy minimalism. Biden hailed unity in the US defence of democracy in Ukraine in the face of Russia’s aggression. And in defending US sovereignty in the face of China’s violations, this time with a balloon.

But the presidents temporary minimalism on foreign policy will be short-lived. And unity with America’s partners and allies will continue to be at the centre of Biden’s strategy. In the past 12 months, it is the yardstick by which he has measured America’s success with respect to Ukraine.

Russia’s invasion of Ukraine has so far served as a lubricant for the NATO alliance, and for the US relationship with its non-NATO allies.

This has not automatically sprung from the well of Russia’s aggression. NATO’s success, and transatlantic unity, has been achieved through the sheer force of diplomatic effort, not least by the US.

Now Biden is looking for unity on China. His administration has identified China as its pacing threat. While Ukraine will continue to demand and deserve attention, the US will be looking beyond the urgent to focus on other less urgent but crucially important challenges. That means China.

China’s balloon helps ensure unity will be an easy victory at home. For several days, the balloon floated across the US, captivating the American public, seizing the headlines, and hardening US attitudes towards its only peer competitor.

Republican leaders in Congress are determined to scrutinize US policy to ensure it is tough on China, especially on technology and deterrence. This intense domestic focus on China could put Biden in a bind as he seeks to resume diplomacy. It also explains why he was careful not to inflate the China threat in his address. Secretary Blinken’s visit to Beijing has already been postponed.

As the Munich Security Conference approaches, the president’s unity agenda will turn to Europe, but the timing is difficult. China is opening and a charm offensive across Europe is likely. Europe is vulnerable as it seeks to recover its economies, continue to hold Russia back, and inhibit greater alignment between Russia and China.

The risk for the US is that domestic pressure to take a harder line on China escalates and Europe refuses to keep up. But dividing on China would come at a high price, both for Europe and the US, so to avoid this, they should take a pragmatic and sequenced approach to cooperation.

The goal for now should be policy coordination, as success is vital to momentum and managing expectations in the current environment is critical. Alignment may be possible with discrete partners on specific topics. But the perfect should not be the enemy of the good.

The US has postponed, not cancelled, Blinken’s trip while Europe is preparing to ramp up its diplomacy with China. A collective but temporary and shared transatlantic pause on diplomacy would offer low hanging fruit to give momentum to transatlantic cooperation.

It would also signal to China a unity that has a power of its own. A clear and coordinated signal, soon, that Europe and the US are moving forward with diplomacy is essential.

Munich can move the talk into action on Ukraine

James Nixey

Russia’s excommunication from this year’s Munich Security Conference is an opportunity. The principle of inclusivity may have pros and cons, but the cons have been evident since at least 2007 – its use as a platform for Russia’s leadership to launch broadsides about ‘western injustice’ and a reflexive default to increasingly inappropriate and harmful diplomatic courtesies and allowances.

Without the distraction of listening to Russian lies, there is at least now the remote possibility of a more unified West agreeing to specific action beyond the talk. As at the recent Ramstein talks, it is unlikely Munich will result in an agreement to send F-16 fighter jets to Ukraine. That may prove a step too far for the West or it will need further Russian atrocities inflicted upon Ukrainians on a scale horrendous enough to prick consciences once again.

However, although President Biden’s State of the Union address has promised nothing new or innovative regarding Ukraine or Russia, it did re-establish the fundamentals of US support and so can serve as a ‘pre-read’ for a newfound resolve.

Although some European countries are a lost cause, others – Germany for example – have proved able to be guilted into action. The key lesson for everyone to understand is that Ukraine is sovereign. Or at least ‘nothing about Ukraine, without Ukraine’. The difference is moot but, from these simple precepts, all else flows.

Ukrainians will be their impassioned selves at Munich. But although publicly gracious and thankful, privately they are distraught at the West’s collective failure to affirm these principles and back them with the necessary support, not just to force a stalemate or a ‘frozen conflict’ but to engineer victory.

Most Ukrainian officials would privately argue that the danger to their country comes more from the West and forums such as the Munich Security Conference than it does from Russia, which can be defeated with the requisite tangible assistance. In Munich, beyond fine words of support – watertight from some, ambiguous from others – there lurks the ever-present danger of the politician who simply wants it all to go away by offering Putin an off-ramp.

The irony of the host city of this forum is that many times over the past year compromise ‘solutions’ have been described as having ‘a whiff of Munich’ about them – a reference of course to appeasement in 1938, which still haunts.

As it should, because the failure to ensure Ukraine’s victory with an outcome the Ukrainian government and people are content with and which convinces Russia it was a disastrous mistake to escalate, will lead to a global security collapse too catastrophic to contemplate.

Middle East security challenges must be dealt with

Dr Sanam Vakil

A trifecta of security concerns – Iran’s advancing nuclear programme, the export of unmanned aerial vehicles (UAVs) to support Russia in the war in Ukraine, and a heavy-handed response towards protests in Iran – has raised alarm bells in Washington, Europe and the UK. These intersecting challenges lay bare the lack of a broader Iran strategy and the deprioritization of Middle East security among transatlantic partners.

This downgrading of the Middle East was evident in President Biden’s State of the Union speech as, for the first time in decades, the region was not even mentioned. The upcoming Munich Security conference provides a much needed opportunity for the transatlantic community to align on next steps and multilateral policy responses.

Transatlantic partners have long relied on the prism of the JCPOA negotiations as the pathway to both separate and manage nuclear tensions from broader regional challenges associated with Iran’s export of lethal aid and sponsorship of proxy groups.

Despite repeated negotiation efforts led by the Biden administration since April 2021, the JCPOA has languished due to Tehran’s fears over another US retreat. The promise of sanctions relief has also failed to incentivise Iran’s return to the deal. Tehran’s nuclear programme has accelerated without the consistent IAEA oversight which was part of the initial deal and is now at a level where it can produce enough uranium enrichment for four nuclear weapons.

Tehran’s decision to send drones to support Moscow’s war effort has further elevated transatlantic concerns, and reports have circulated that Tehran may also export its missile capabilities and build a drone factory in Russia. In tandem, the two sanctioned states have begun to strengthen their economic arrangements.

Digital governance must not marginalize smaller states Expert comment LToremark 19 May 2021

For effective and inclusive digital governance, multi-stakeholderism must raise its game.

Last month, the G7 announced it is to work towards a trusted, values-driven digital ecosystem. While this is commendable, the G7 must recognize that key international digital governance decisions should involve all states whose populations will be affected. Not doing so is to deny the legitimate interests of those populations and may cause a lack of trust in international digital governance that embeds longer-term instability.

While a multi-stakeholder approach to digital governance is important, it must be structured in a way that allows for meaningful representation of states’ interests and ensures their representatives have the opportunity and capacity to take part. As the internet becomes fundamental to life in every country of the world, international digital governance is increasingly important to all governments and excluding some states’ perspectives may engender wider risks to international security and governance.

The ‘glitter ball’ of digital governance

International digital governance is playing catch-up with the digital sphere it needs to govern. Its starting point is a ‘glitter ball’ of governance initiatives: a large number of complex facets with overlapping impacts – and an almost impenetrable core. Governance initiatives (see infographic) include governance of the internet itself and its uses, international cybersecurity, international human rights, data management, as well as the impact of digital developments in areas such as armed conflict, trade and health.

Many of the bodies involved – such as the Internet Governance Forum, the Internet Corporation for Assigned Names and Numbers (ICANN) and technical standards bodies – include a wide range of stakeholders, yet there is no one accessible, central body. Furthermore, certain key issues, such as the role and responsibilities of tech platforms, are barely touched upon by international governance mechanisms. There is also currently only a limited role for traditional UN multilateral decision-making, a process which builds in a role for smaller states.

The sheer number of forums involved, each with a different set of working methods and rules on participation, makes it difficult to fully grasp what digital governance looks like as a whole. The UN secretary-general’s High-level Panel on Digital Cooperation recognized the complexity of digital cooperation arrangements and the barriers to inclusion facing small and developing countries as well as under-represented groups. In response, the June 2020 UN Roadmap on Digital Cooperation accepts the need to streamline digital governance while ensuring marginalized voices are heard.

The UN is considering potential models for future governance, each of which would – reassuringly – involve multi-stakeholder participation, dedicated funds to boost participation, consolidation of discussions currently split between different forums and a minor coordinating role for the UN.  

Building in roles for smaller states

As the UN designs new digital governance architecture, it is particularly important to build in roles for small and medium states. Core constituencies affected by decisions should be at the centre and governments – as guardians of public interest – should have a key say in the decision-making process. The distrust generated by built-in power imbalances needs to be addressed, as does the dominance of voices from the Global North in bodies such as ICANN.   

There has been some progress made to increase participation. For example, the Freedom Online Coalition includes a number of developing countries and the 2020 Internet Governance Forum included input from 175 states.

However, participation is not only a matter of having a seat at the table. As discussed at the March 2021 UN Open-ended Working Group on ICTs in the context of international security, capacity-building is vital. The group’s conclusions include the suggested development of a global cyber capacity-building agenda with information sharing and norms guidance under the auspices of the UN. Representatives of small and medium states need a roadmap to understand in which forums they can defend and pursue their interests, and the financial help to do so if necessary.

Managing multi-stakeholder participation

A multi-stakeholder approach has been fundamental to digital governance from the start and has played a vital role in helping to secure the openness and universality of the internet. This approach is rightly seen as essential to effective governance because it introduces diverse expertise, allows the interests of all impacted sectors to be taken into account and helps ensure decisions are accepted by those affected.

However, as identified in a Chatham House report on inclusive global governance, multi-stakeholderism needs to raise its game. One of its downsides is that in the cacophony some important voices may not be heard because they lack resource or capacity to speak up. There is a perennial risk of debate and decision-making being captured by the wealthiest companies or the most powerful states. At present, small and medium states are under-represented in multi-stakeholder forums and it is important that those managing such forums seek to identify and include previously excluded voices.

Multi-stakeholderism should not come at the expense of efficiency. While it does not have to mean huge, inefficient meetings or endless discussion, it should also not mean that smaller, less well-funded voices are not heard. Instead, such processes should enable representation of appropriate interest groups, complemented by wider meetings (such as regional meetings, or sector-specific meetings) as needed. While inclusivity and transparency are key, synergies between regional and global forums can work well –  for example, some countries have adopted national versions of the Internet Governance Forum –  and so too can hybrid models such as the Freedom Online Coalition, which meets both as government members and for regular multi-stakeholder dialogue.

A multi-stakeholder approach should also not lose sight of the key role of states – and where mandated, sub-state entities – in making public policy decisions.

An important role for the UN

For 75 years, the UN has acted as a bulwark of international security and shared values, and a promoter of economic and social development. If misused, technology has the potential to undermine this bulwark, to facilitate conflict, erode rights and undermine development. The UN must encourage the harnessing of technology for society’s benefit, while leading a collective effort to guard against the risks through the retention and growth of a universal, open internet – particularly in the face of growing digital authoritarianism exacerbated by COVID-19.

The UN can also help protect against a commercial culture that threatens to trample fundamental freedoms of privacy and autonomy in its pursuit of wealth and to widen economic and social gulfs by leaving large swathes of the world behind. If the UN is to play this role effectively – and for the benefit of all its members ­– it requires the active participation of all states, large and small.

Expert

What's next for environmental peacebuilding? Lessons learned and opportunities from conflict-affected states 17 February 2021 — 3:00PM TO 4:00PM Anonymous (not verified) 8 February 2021 Online

 This event explores lessons and opportunities from conflict-affected states.

In the field of peacebuilding, scholars and policymakers increasingly recognize the importance of environmental restoration, afforestation and infrastructural renewal for creating the sustainable livelihoods necessary for successful peacebuilding efforts.

Featuring academics writing for International Affairs on environmental peacebuilding in Colombia, Yemen and the Sahel, this webinar discusses the policy implications of the turn to environmental peacebuilding.

This event is part of the Chatham House’s Environment and Society Discussion Series in which the Energy Environment and Resources Programme brings together leading academics and policymakers to discuss key issues in environmental policy.

In particular, this event focuses on the role of environmental peacebuilding in creating sustainable livelihoods. From the impact the destruction of infrastructure can have on poverty as a driver of conflict, to the role environmental peacebuilding can play in bringing communities together by creating sustainable shared spaces of employment, the importance of the environmental livelihood creation is difficult to overstate.

Panellists focus on how policymakers can best encourage inclusive and sustainable livelihood creation and on addressing the key challenges such approaches face in the context of environmental peacebuilding efforts.

Frederic Heihoff
Proc. Amer. Math. Soc. 152 (), 5229-5247.
Abstract, references and article information

Intrinsically disordered protein domains often have multiple binding partners. It is plausible that the strength of pairing with specific partners evolves from an initial low affinity to a higher affinity. However, little is known about the molecular changes in the binding mechanism that would facilitate such a transition. We previously showed that the interaction between two intrinsically disordered domains, NCBD and CID, likely emerged in an ancestral deuterostome organism as a low-affinity interaction that subsequently evolved into a higher-affinity interaction before the radiation of modern vertebrate groups. Here we map native contacts in the transition states of the low-affinity ancestral and high-affinity human NCBD/CID interactions. We show that the coupled binding and folding mechanism is overall similar but with a higher degree of native hydrophobic contact formation in the transition state of the ancestral complex and more heterogeneous transient interactions, including electrostatic pairings, and an increased disorder for the human complex. Adaptation to new binding partners may be facilitated by this ability to exploit multiple alternative transient interactions while retaining the overall binding and folding pathway.

11 August 2020

Purpose: The ⁶⁸Ga-PSMA PET/CT is a commonly used imaging modality in prostate cancers. However, few studies have compared the diagnostic efficiency between ⁶⁸Ga-PSMA and ¹⁸F-FDG PET/CT and evaluated whether a heterogeneous metabolic phenotype (especially PSMA-FDG+ lesions) exists in patients with castration-resistant prostate cancer (CRPC). We determined the added value of ¹⁸F-FDG PET/CT compared to ⁶⁸Ga-PSMA PET/CT in CRPC patients and identified CRPC patients who may benefit from additional ¹⁸F-FDG PET/CT. Methods: Data of 56 patients with CRPC who underwent both ⁶⁸Ga-PSMA and ¹⁸F-FDG PET/CT from May 2018 to February 2021 were retrospectively analysed. Patients were classified into two groups with or without PSMA-FDG+ lesions. The differences in patient characteristics between the two groups and predictors of patients who having at least one PSMA-FDG+ lesion were analysed. Results: Although both the detection rate (75.0% vs. 51.8%, P = 0.004) and positive lesion number (135 vs. 95) of ⁶⁸Ga-PSMA PET/CT were higher than ¹⁸F-FDG PET/CT, there were still 13/56 (23.2%) patients with at least one PSMA-FDG+ lesion. The prostate-specific antigen (PSA) and Gleason score were both higher in the patients with PSMA-FDG+ lesions than in those without PSMA-FDG+ lesions (P = 0.04 and P<0.001, respectively). Multivariate regression analysis showed that the Gleason score (≥8) and PSA (≥7.9 ng/mL) were associated with the detection rate of patients who had PSMA-FDG+ lesions (P = 0.01 and P = 0.04, respectively). The incidences of having PSMA-FDG+ lesions in low-probability (Gleason score<8 and PSA<7.9 ng/mL), medium-probability (Gleason score≥8 and PSA<7.9 ng/mL or Gleason score<8 and PSA≥7.9 ng/mL), and high-probability (Gleason score≥8 and PSA≥7.9 ng/mL) groups were 0%, 21.7%, and 61.5%, respectively (P<0.001). Conclusion: Gleason score and PSA are significant predictors for PSMA-FDG+ lesions, and CRPC patients with high Gleason score and PSA may benefit from additional ¹⁸F-FDG PET/CT.

Visual Abstract

Visual Abstract

Visual Abstract

Visual Abstract

Visual Abstract

The kinesin-3 family contains the fastest and most processive motors of the three neuronal transport kinesin families, yet the sequence of states and rates of kinetic transitions that comprise the chemomechanical cycle and give rise to their unique properties are poorly understood. We used stopped-flow fluorescence spectroscopy and single-molecule motility assays to delineate the chemomechanical cycle of the kinesin-3, KIF1A. Our bacterially expressed KIF1A construct, dimerized via a kinesin-1 coiled-coil, exhibits fast velocity and superprocessivity behavior similar to WT KIF1A. We established that the KIF1A forward step is triggered by hydrolysis of ATP and not by ATP binding, meaning that KIF1A follows the same chemomechanical cycle as established for kinesin-1 and -2. The ATP-triggered half-site release rate of KIF1A was similar to the stepping rate, indicating that during stepping, rear-head detachment is an order of magnitude faster than in kinesin-1 and kinesin-2. Thus, KIF1A spends the majority of its hydrolysis cycle in a one-head-bound state. Both the ADP off-rate and the ATP on-rate at physiological ATP concentration were fast, eliminating these steps as possible rate-limiting transitions. Based on the measured run length and the relatively slow off-rate in ADP, we conclude that attachment of the tethered head is the rate-limiting transition in the KIF1A stepping cycle. Thus, KIF1A's activity can be explained by a fast rear-head detachment rate, a rate-limiting step of tethered-head attachment that follows ATP hydrolysis, and a relatively strong electrostatic interaction with the microtubule in the weakly bound post-hydrolysis state.

α-Synuclein (α-Syn) is a protein implicated in the pathogenesis of Parkinson's disease (PD). It is an intrinsically disordered protein that binds acidic phospholipids. Growing evidence supports a role for α-Syn in membrane trafficking, including, mechanisms of endocytosis and exocytosis, although the exact role of α-Syn in these mechanisms is currently unclear. Here we investigate the associations of α-Syn with the acidic phosphoinositides (PIPs), phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2). Our results show that α-Syn colocalizes with PIP2 and the phosphorylated active form of the clathrin adaptor protein 2 (AP2) at clathrin-coated pits. Using endocytosis of transferrin as an indicator for clathrin-mediated endocytosis (CME), we find that α-Syn involvement in endocytosis is specifically mediated through PI(4,5)P2 levels on the plasma membrane. In accord with their effects on PI(4,5)P2 levels, the PD associated A30P, E46K, and A53T mutations in α-Syn further enhance CME in neuronal and nonneuronal cells. However, lysine to glutamic acid substitutions at the KTKEGV repeat domain of α-Syn, which interfere with phospholipid binding, are ineffective in enhancing CME. We further show that the rate of synaptic vesicle (SV) endocytosis is differentially affected by the α-Syn mutations and associates with their effects on PI(4,5)P2 levels, however, with the exception of the A30P mutation. This study provides evidence for a critical involvement of PIPs in α-Syn–mediated membrane trafficking.

After successful completion of the Human Genome Project (HGP), HUPO has recently officially launched a global Human Proteome Project (HPP) which is designed to map the entire human protein set. Given the presence of about 30% undisclosed proteins out of 20,300 protein gene products, a systematic global effort is necessary to achieve this goal with respect to protein abundance, distribution, subcellular localization, interaction with other biomolecules, and functions at specific time points. As a general experimental strategy, HPP groups employ the three working pillars for HPP: mass spectrometry, antibody capture, and bioinformatics tools and knowledge base. The HPP participants will take advantage of the output and cross-analyses from the ongoing HUPO initiatives and a chromosome-based protein mapping strategy, termed C-HPP with many national teams currently engaged. In addition, numerous biologically-driven projects will be stimulated and facilitated by the HPP. Timely planning with proper governance of HPP will deliver a protein parts list, reagents and tools for protein studies and analyses, and a stronger basis for personalized medicine. HUPO urges each national research funding agency and the scientific community at large to identify their preferred pathways to participate in aspects of this highly promising project in a HPP consortium of funders and investigators.

The complexity and dynamics of the immensely heterogeneous glycoproteome of the prostate cancer (PCa) tumour micro-environment remain incompletely mapped, a knowledge gap that impedes our molecular-level understanding of the disease. To this end, we have used sensitive glycomics and glycoproteomics to map the protein-, cell- and tumour grade-specific N- and O-glycosylation in surgically-removed PCa tissues spanning five histological grades (n = 10/grade) and tissues from patients with benign prostatic hyperplasia (n = 5). Quantitative glycomics revealed PCa grade-specific alterations of the oligomannosidic-, paucimannosidic- and branched sialylated complex-type N-glycans, and dynamic remodelling of the sialylated core 1- and core 2-type O-glycome. Deep quantitative glycoproteomics identified ~7,400 unique N-glycopeptides from 500 N-glycoproteins and ~500 unique O-glycopeptides from nearly 200 O-glycoproteins. With reference to a recent Tissue and Blood Atlas, our data indicate that paucimannosidic glycans of the PCa tissues arise mainly from immune cell-derived glycoproteins. Further, the grade-specific PCa glycosylation arises primarily from dynamics in the cellular makeup of the PCa tumour microenvironment across grades involving increased oligomannosylation of prostate-derived glycoproteins and decreased bisecting GlcNAcylation of N-glycans carried by the extracellular matrix proteins. Further, elevated expression of several oligosaccharyltransferase subunits and enhanced N-glycoprotein site occupancy were observed associated with PCa progression. Finally, correlations between the protein-specific glycosylation and PCa progression were observed including increased site-specific core 2-type O-glycosylation of collagen VI. In conclusion, integrated glycomics and glycoproteomics have enabled new insight into the complexity and dynamics of the tissue glycoproteome associated with PCa progression generating an important resource to explore the underpinning disease mechanisms.

Libya’s War Economy: Predation, Profiteering and State Weakness Research paper sysadmin 9 April 2018

As Libya’s war economy persists, prospects for the restoration of functioning central governance become more distant.

Summary

• Libya suffers from interlinked political, security and economic crises that are weakening state institutions, damaging its economy and facilitating the continued existence of non-state armed groups. As rival authorities continue to compete for power, the resulting fragmentation and dysfunction have provided a fertile environment for the development of a pervasive war economy dependent on violence.
• This war economy is dynamic and constantly in flux. Relative to earlier problems, there were signs of progress on several fronts in 2017: a reduction in human smuggling, a tripling in oil revenues, and increased local action against fuel smuggling. Yet the dynamics that have supported the war economy’s rise remain.
• Libya’s war economy is highly damaging for the future of the state for three reasons:
  • First, it provides an enabling environment for networks of armed groups, criminal networks, corrupt businessmen and political elites to sustain their activities through illicit sales and predatory practices. Their operations are closely linked to the dispensation of violence, and are thus a spur for further conflict.
  • Second, the war economy perpetuates negative incentives for those who profit from the state’s dysfunction. Only effective governance, supported by a durable political settlement, can tackle the foundations of Libya’s war economy. But neither a return to functioning central governance nor the development of a security sector that is fit for purpose is in the interests of war economy profiteers, who are therefore motivated to act as powerful spoilers of reform.
  • Third, the political contestation and resource predation practised by those engaged in the war economy are having a disastrous impact on Libya’s formal economy, undermining what remains of its institutions. As the war economy persists, therefore, the prospects for the restoration of functioning central governance become more distant. This threatens to create a vicious cycle that accelerates further state collapse.
• Due to the limited capacity for coercion available to any actor or entity connected with the state, a strategy of co-opting networks of war economy profiteers has almost exclusively prevailed. This has failed. Drawing on the lessons from these attempts, a more successful policy must pursue targeted measures to combat the enabling structures of Libya’s war economy where possible, and to co-opt war economy profiteers only where necessary.
• In this, state authorities can do more to utilize what power they have to name and shame war economy profiteers in order to weaken the local legitimacy critical to profiteers’ survival. The state must present credible alternative livelihood opportunities to those engaged in, or benefiting from, the war economy. Progress will depend in part on the creation of positive incentives to abandon such activity. Where profiteers cannot be incentivized to move towards more legitimate economic activities, greater and more effective efforts must be made to reduce the profit margins of illicit schemes.
• The international community can do more to support Libyan efforts in countering the war economy. Cooperation over the targeting of criminal groups’ overseas assets, support for increased transparency over the dispensation of state funds, and measures to reduce the viability of illicit activities can all help to strengthen the position of state authorities.

Further reading

Discover the six things you need to know about Libya’s war economy

The Role of Sub-state and Non-state Actors in International Climate Processes: Civil Society Research paper sysadmin 27 November 2018

Given today’s challenging geopolitical conditions and the evolving nature of the international climate regime since Paris, civil society must now once again recalibrate its strategies to ensure continued and increasing relevance.

This is one of four background papers feeding into a synthesis paper entitled The Role of Sub-state and Non-state Actors in International Climate Processes.

Summary

• Following the failure of the 15th Conference of the Parties (COP 15) in Copenhagen in 2009, there was a step change in the sophistication and unity of civil society engagement on climate policy. This ensured that, subsequently, civil society was more effective in exercising multiple channels of influence around the negotiations for the Paris Agreement in 2015.
• Civil society proved to be particularly effective at harnessing the twin narratives of climate science and economics, and at leveraging an emerging multi-level governance architecture, to create political space for climate leadership.
• Given today’s challenging geopolitical conditions and the evolving nature of the international climate regime since Paris, civil society must now once again recalibrate its strategies to ensure continued and increasing relevance.
• In particular, the shift to a more ‘nationally grounded’ implementation regime focusing on individual states’ climate commitments will require civil society to become more effective at influencing domestic politics. At the same time, civil society will need to continue to seek strategic synergies at the international level.
• Civil society has a central role to play in ensuring that the first key test of the Paris ‘ratchet’ mechanism – revising countries’ pledged climate actions, or Nationally Determined Contributions (NDCs), by 2020 – is robust, science-informed and strongly rooted in domestic politics.

The Role of Sub-state and Non-state Actors in International Climate Processes: Corporate Sector Research paper sysadmin 27 November 2018

Given the challenging political contexts since 2015, the corporate sector will have a key role to play in persuading national governments how technologies and expertise have moved on since the pledges were made.

This is one of four background papers feeding into a synthesis paper entitled The Role of Sub-state and Non-state Actors in International Climate Processes.

Summary

• The corporate sector has traditionally engaged governments at national rather than international level in lobbying for action related to climate change. Where it has engaged at an international level, this has often been to restrain regulation and ambition, such as in air transport. Over time, many businesses have increasingly understood that there is more commercial opportunity in a strong, consistent approach to tackling climate mitigation and adaptation, and an increasing number are willing to speak up on the issue. The Paris Climate Conference in 2015 demonstrated this positive engagement.
• Businesses are more powerful when engaging directly with national governments on detailed policies – by demonstrating what is possible and indirectly influencing national governments’ international pledges. Traditional trade/industry sector associations and groups have tended to suffer from the ‘lowest common denominator’ effect of their least progressive members. Progressive business groups coalescing around climate ambition can help to counter this.
• Unlike at the Copenhagen climate talks in 2009, the business community provided a positive, supportive backdrop to the 2015 Paris talks, mindful of the public relations opportunities in taking a progressive stance and of the benefits of targets that reflected the science. The carbon market was a particular focus for corporates, which succeeded in getting emissions trading options and market mechanisms included in Article 6 of the Paris Agreement.
• Given the challenging political contexts since 2015, the corporate sector will have a key role to play in persuading national governments how technologies and expertise have moved on since the pledges were made. With increasing awareness of resource scarcity, businesses are pursuing ever more creative solutions.
• Wide recognition that the avoidance of future emissions is increasingly dependent on developing and emerging economies means that business voices from these countries will potentially be more influential in the next few years.

The Role of Sub-state and Non-state Actors in International Climate Processes Research paper sysadmin 27 November 2018

In the current international political environment of rising populism, the role of sub- and non-state actors may become more important than ever.

Summary

• Climate action from sub-state and non-state actors such as subnational governments, cities, corporations and NGOs has very significant potential to enhance national efforts to curb CO2 emissions, close the so-called ‘emissions gap’ – between current commitments and the action necessary to meet climate targets – and help move the world on to a ‘1.5°C pathway’ that would limit global warming to 1.5°C above pre-industrial levels by 2100.
• In addition to their own climate action, sub-state/non-state actors can contribute to climate governance by developing new policies and business models to support emissions cuts and build resilience. Knowledge exchange and capacity-building have a role to play in helping these innovations to spread internationally.
• Politically, measures implemented by sub-state/non-state actors can help national governments to implement existing targets faster and more effectively, while helping to build political support for more ambitious climate action.
• The post-Paris climate regime of the United Nations Framework Convention on Climate Change (UNFCCC) reflects the growing importance of sub- and non-state actors, and has featured the creation of institutional structures to engage and coordinate them.
• In the current international political environment of rising populism, the role of sub- and non-state actors may become more important than ever. However, more questions about the robustness of sub- and non-state action are also likely to be raised.
• With the 2020 deadline approaching for countries to submit details of enhanced Nationally Determined Contributions (NDCs), long-term climate strategies and other means of raising policy ambition, the next two years are set to provide significant opportunity for sub- and non-state action. Many governments are already developing ways to engage with sub- and non-state actors to identify opportunities to strengthen action by 2020.
• Key questions in this respect include (a) whether sub- and non-state actors can mobilize across sectors; and (b) whether action can be extended beyond the ‘usual suspects’ to include contributions from less familiar sources, such as business sectors with limited opportunities for climate action or corporations in the Global South.

The Role of Sub-state and Non-state Actors in International Climate Processes: Financial Institutions Research paper sysadmin 20 December 2018

The trillions of dollars needed to secure the sustainable, climate-compatible pathway outlined in the 2015 Paris Agreement have focused attention on private finance and investment.

This is one of four background papers feeding into a synthesis paper entitled The Role of Sub-state and Non-state Actors in International Climate Processes.

Summary

• The trillions of dollars needed to secure the sustainable, climate-compatible pathway outlined in the 2015 Paris Agreement have focused attention on private finance and investment, and on the role of the financial sector as a potentially powerful non-state actor in the international climate debate.
• Leading individual financial institutions reacted to the Paris Agreement by framing it in terms of what it would mean for markets – i.e. risks and opportunities – and by underlining the importance of national implementation of climate change commitments.
• Key recent developments signal that the financial sector actively supports Paris-compatible government action on climate change, as well as company-level action to understand the physical and ‘transition’ risks and opportunities associated with climate change and policy responses. Financial sector engagement is taking place through well-organized and well-supported international initiatives and platforms. A critical part of this process entails robust activity by financial institutions to embed climate change and broader sustainability factors into strategies and operations.
• At country level, attention to implementation of Nationally Determined Contributions (NDCs) and associated sector-level policy development has been largely separate from the broader ‘sustainable finance’ dynamic. National-level action has not benefited from the same level of organized financial sector involvement evident in international action. One of the reasons for this is that, with some notable exceptions, international financial initiatives lack the capacity and resources to participate in the granular detail of national policy processes. Policymakers in turn often lack the internal capacity to consult or engage with the financial sector domestically.
• This paper includes some thoughts on further international and national climate actions. Ensuring that messages from successful international financial sector initiatives are heard in regional and non-climate forums offers one avenue for building a stronger foundation for greater climate ambition. Building the resource base for stronger national climate policy engagement, as a counter-voice to incumbent interests and to ensure that the quality of policy is ‘investment grade’, is another. This will be critical to the delivery of policy outcomes. Other key elements include the need to pool knowledge across relevant parts of the finance sector, build alliances, and shift action towards joint problem-solving with policymakers. A ‘Talanoa 2.020’-type initiative offers one potentially promising approach to advancing dialogue in this respect.

The Role of Sub-state and Non-state Actors in International Climate Processes: Subnational Governments Research paper sysadmin 23 January 2019

This paper looks at the role of subnational governments in influencing global climate ambition, and makes recommendations for how these actors can increase their influence in the future.

Summary

• ‘Subnational governments’ – including municipal, regional and provincial authorities – lack the formal status of negotiating parties to the United Nations Framework Convention on Climate Change (UNFCCC). But they have a vital role to play in informing and helping to shape international climate action, as they are often the key delivery partners for on-the-ground policies.
• Subnational governments are often closer to climate problems than the UNFCCC parties themselves, and have experience, expertise and peer influence that can support the development of progressive policies and increased ambition.
• Many subnational governments have joined or formed various groupings to share information and experience, and to increase their collective profile and voice. Notable initiatives and collaborations include the Under2 Coalition, ICLEI, C40 and the Global Covenant of Mayors for Climate & Energy.
• Subnational governments are highly diverse. In some cases, politically high-profile administrations – the US state of California being a notable example – have exploited their visibility and policy successes to engage in wider climate debates. Equally, however, subnational agendas can encounter resistance from national governments anxious to ensure the primacy of their negotiating positions in the UNFCCC system.
• One of the advantages that subnational governments enjoy, subject to resources, is their ability to join with peer groups to take a fresh approach to mitigation or adaptation policies. Groups of cities or subnational regions can, through collaborative organizations, explore new approaches that might be less attractive within a national context.
• To maintain and build on their current achievements and influence, subnational governments need, among other things, to: improve the credibility of their experience through evaluation of the success of their climate policies; use membership of appropriate international groups to share experience and boost their leverage; continue to create collaborative relationships with progressive businesses to increase influence at a national level; build on cross-regional relationships in climate adaptation and resilience; and work with other subnational actors to build momentum ahead of the first post-Paris revision of climate commitments in 2020.

VOLUME 279 (2004) PAGES 33438–33446For Fig. 1B, the second, third, and fifth panels were mistakenly duplicated during article preparation as no yeast colonies were observed in these conditions. The corrected images are presented in the revised Fig. 1B. This correction does not affect the results or conclusions of the work. The authors apologize for the error.jbc;295/50/17382/F1F1F1Figure 1B.

War on Ukraine: The state of the global response 17 October 2022 — 6:30PM TO 7:30PM Anonymous (not verified) 3 October 2022 Chatham House and Online

Implications of the war for the future of multilateralism.

Russia’s war on Ukraine has tested the capacity for a unified global response to grave violations of the UN Charter. The world is in unchartered territory as a nuclear member of the United Nations Security Council attacks a non-nuclear country. 

Multilateral institutions that were born out of an effort to prevent war are struggling to prove their relevance in the face of growing existential threats to humanity. The war is exacerbating divisions within the global community, disrupting food and energy supplies worldwide and contributing to a profound crisis of multilateralism.

The longer these divisions last, the longer the war in the middle of Europe and the harder it will be to respond to the interconnected global crises that threaten everyone.

This discussion offers a unique insight into the macro-geopolitical questions in relation to the war in Ukraine with members of the Elders and other experts:

The panel considers:

• How can a more united global response to Russian aggression be built?

• What stands in the way of an effective multilateral response based on international norms?

• In what ways are divisions between UN member states influencing the trajectory of the war or prospects for peace?

• How is the conflict changing geopolitics and the ability of the multilateral system to address global challenges?

As with all members events, questions from the audience drive the conversation. This event is organised in partnership between Chatham House and The Elders, the group of independent global leaders founded by Nelson Mandela who work for peace, justice and human rights.

Read the transcript.

The state of the union? US foreign policy and a new US Congress 30 January 2023 — 5:30PM TO 6:30PM Anonymous (not verified) 11 January 2023 Chatham House and Online

As a new Congress takes shape, what is the impact for US foreign policy?  

The recent US 2022 midterm elections have led to a split with Republicans in command of the US House of Representatives and Democrats retaining a slim majority in the Senate.

Following a gruelling selection process for the new Speaker of the House, the new Congress took its seats in January 2023, but President Joe Biden no longer enjoys single-party control of Congress.

• What will be the implications of this for US leadership and US foreign policy?
• How will domestic politics constrain foreign policy objectives?
• Can policymakers across government set aside political differences to tackle global challenges?

This panel also unpacks insights into the following questions:

• What will this Congress view as foreign policy priorities?
• Will policies that are tough on China ramp up?
• Can the US continue its support for Ukraine with a split Congress?
• Will the next two years lead to any considerable foreign policy pivots with a general election on the horizon?

As with all members events, questions from the audience drive the conversation.

Read the transcript.

Disruptive technologies by nation states and malign cyber actors – the US response 16 February 2023 — 1:00PM TO 2:00PM Anonymous (not verified) 2 February 2023 Chatham House and Online

Lisa Monaco, the US deputy attorney general, discusses how autocratic governments and malign cyber actors use disruptive technologies to project power and engage in illicit activity.

Weaponizing data, ransomware attacks and other illicit cyber activity represent significant threats to national security. 

Governments and malicious cyber actors around the world exploit disruptive technology to engage in criminal activity, track citizens and coerce other countries thereby weakening the rules-based order and fundamental principles of democracy. 

Lisa Monaco discusses how the world is at an inflection point when it comes to meeting this challenge and describes how the US and partner nations are responding to protect their citizens and the broader international community.

Key questions to discuss include:

• What steps does the US government need to take to properly address this threat?
• How are countries coordinating policies to confront the problem?
• To what extent does this challenge go beyond US-China competition?

As with all member events, questions from the audience drive the conversation.

Read the transcript.

Virtual breakfast: The state of the EU in 2023 3 May 2023 — 8:30AM TO 9:30AM Anonymous (not verified) 5 April 2023 Online

In this breakfast discussion, we will explore the current state of play in the EU with one the most prominent experts on European politics.

While the European Union has come together in its response to the invasion of Ukraine, significant divisions remain on other issues. East-West tensions remain high and troublesome German-French relations are hampering the bloc’s traditional engine of integration.
 
Furthermore, the EU is pushing through legislation at breakneck speed, including in its attempts to kickstart green industrial policy with its responses to the American Inflation Reduction Act. At the same time, the main players within the EU continue to disagree on what the bloc’s fiscal rules should look like.

• What are the implications of the recent wave of protests in France against President Macron’s pension reforms?
• What is the outlook of EU-UK relations following the successful completion of the Windsor Framework?
• Where are the fiscal rules likely to land and when will they be back in place?
• Are we seeing the emergence of a new Central and Eastern European power bloc within the EU?

In short, despite having avoided an energy crisis over the winter, the EU continues to face significant challenges. In this breakfast event, we will explore the current state of play in the EU with one of the most prominent experts on European politics.

Unspecific bone uptake (UBU) related to [¹⁸F]PSMA-1007 PET/CT imaging represents a clinical challenge. We aimed to assess whether a combination of clinical, biochemical, and imaging parameters could predict skeletal metastases in patients with [¹⁸F]PSMA-1007 bone focal uptake, aiding in result interpretation. Methods: We retrospectively analyzed [¹⁸F]PSMA-1007 PET/CT performed in hormone-sensitive prostate cancer (PCa) patients at 3 tertiary-level cancer centers. A fourth center was involved in performing an external validation. For each, a volume of interest was drawn using a threshold method to extract SUV_max, SUV_mean, PSMA tumor volume, and total lesion PSMA. The same volume of interest was applied to CT images to calculate the mean Hounsfield units (HU_mean) and maximum Hounsfield units. Clinical and laboratory data were collected from electronic medical records. A composite reference standard, including follow-up histopathology, biochemistry, and imaging data, was used to distinguish between PCa bone metastases and UBU. PET readers with less (n = 2) or more (n = 2) experience, masked to the reference standard, were asked to visually rate a subset of focal bone uptake (n = 178) as PCa metastases or not. Results: In total, 448 bone [¹⁸F]PSMA-1007 focal uptake specimens were identified in 267 PCa patients. Of the 448 uptake samples, 188 (41.9%) corresponded to PCa metastases. Ongoing androgen deprivation therapy at PET/CT (P < 0.001) with determination of SUV_max (P < 0.001) and HU_mean (P < 0.001) independently predicted bone metastases. A composite prediction score, the bone uptake metastatic probability (BUMP) score, achieving an area under the receiver-operating-characteristic curve (AUC) of 0.87, was validated through a 10-fold internal and external validation (n = 89 bone uptake, 51% metastatic; AUC, 0.92). The BUMP score’s AUC was significantly higher than that of HU_mean (AUC, 0.62) and remained high among lesions with HU_mean in the first tertile (AUC, 0.80). A decision-curve analysis showed a higher net benefit with the score. Compared with the visual assessment, the BUMP score provided added value in terms of specificity in less-experienced PET readers (88% vs. 54%, P < 0.001). Conclusion: The BUMP score accurately distinguished UBU from bone metastases in PCa patients with [¹⁸F]PSMA-1007 focal bone uptake at PET imaging, offering additional value compared with the simple assessment of the osteoblastic CT correlate. Its use could help clinicians interpret imaging results, particularly those with less experience, potentially reducing the risk of patient overstaging.