Jürgen Cox
Sep 1, 2014; 13:2513-2526
Technological Innovation and Resources

Shao-En Ong
May 1, 2002; 1:376-386
Research

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

Candida albicans and Aspergillus fumigatus are dangerous fungal pathogens with high morbidity and mortality, particularly in immunocompromised patients. Innate immune-mediated programmed cell death (pyroptosis, apoptosis, necroptosis) is an integral part of host defense against pathogens. Inflammasomes, which are canonically formed upstream of pyroptosis, have been characterized as key mediators of fungal sensing and drivers of proinflammatory responses. However, the specific cell death pathways and key upstream sensors activated in the context of Candida and Aspergillus infections are unknown. Here, we report that C. albicans and A. fumigatus infection induced inflammatory programmed cell death in the form of pyroptosis, apoptosis, and necroptosis (PANoptosis). Further, we identified the innate immune sensor Z-DNA binding protein 1 (ZBP1) as the apical sensor of fungal infection responsible for activating the inflammasome/pyroptosis, apoptosis, and necroptosis. The Zα2 domain of ZBP1 was required to promote this inflammasome activation and PANoptosis. Overall, our results demonstrate that C. albicans and A. fumigatus induce PANoptosis and that ZBP1 plays a vital role in inflammasome activation and PANoptosis in response to fungal pathogens.

Lys234 is one of the residues present in class A β-lactamases that is under selective pressure due to antibiotic use. Located adjacent to proton shuttle residue Ser130, it is suggested to play a role in proton transfer during catalysis of the antibiotics. The mechanism underpinning how substitutions in this position modulate inhibitor efficiency and substrate specificity leading to drug resistance is unclear. The K234R substitution identified in several inhibitor-resistant β-lactamase variants is associated with decreased potency of the inhibitor clavulanic acid, which is used in combination with amoxicillin to overcome β-lactamase–mediated antibiotic resistance. Here we show that for CTX-M-14 β-lactamase, whereas Lys234 is required for hydrolysis of cephalosporins such as cefotaxime, either lysine or arginine is sufficient for hydrolysis of ampicillin. Further, by determining the acylation and deacylation rates for cefotaxime hydrolysis, we show that both rates are fast, and neither is rate-limiting. The K234R substitution causes a 1500-fold decrease in the cefotaxime acylation rate but a 5-fold increase in kcat for ampicillin, suggesting that the K234R enzyme is a good penicillinase but a poor cephalosporinase due to slow acylation. Structural results suggest that the slow acylation by the K234R enzyme is due to a conformational change in Ser130, and this change also leads to decreased inhibition potency of clavulanic acid. Because other inhibitor resistance mutations also act through changes at Ser130 and such changes drastically reduce cephalosporin but not penicillin hydrolysis, we suggest that clavulanic acid paired with an oxyimino-cephalosporin rather than penicillin would impede the evolution of resistance.

Time to accelerate the sustainability pivot Expert comment NCapeling 26 May 2021

Higher stakes make it more important than ever to safeguard the integrity of sustainability commitments, and ensure high quality in delivery and implementation.

Regular headlines reaffirm the rise of sustainability on the global stage. Political momentum behind climate action has not been derailed by COVID-19, sustainability is increasingly central to national political debates, and what once might have been confined to scientific pursuits and UN conferences has now percolated through to international financial affairs and the wider political summits.

Much is made of the scale of the challenge, from climate change, water stresses, and biodiversity loss to the looming spectre of environment-induced societal breakdown triggering unprecedented civilizational challenges on the back of decades of systemic neglect over the true cost of social and environmental imbalances and unencumbered consumption.

But the good news is that talk of sustainability solutions is picking up pace and growing in its reach into the mainstream. The Wall Street Journal recently charted the shift of sustainable finance from being a niche interest of socially conscious investors into a sustainable ‘gold rush’, further bolstering its financial credentials with trillions of dollars designated for the global energy transition.

Assets in investment funds with links to the environment came to almost $2 trillion globally in the first quarter of 2021, more than tripling in just three years, and investors are putting some $3 billion a day into these funds while bonds and loans worth $5 billion looking to bankroll green initiatives are issued every day.

Climate ambitions and power diplomacy

Should the number of zeros fail to persuade, other signs of a sustainability pivot abound. Climate ambition was the driving force in major power diplomacy as France, Germany, China, and the US jostled for leadership positions in a high octane theatre of ‘climate one upmanship’ in the run-up to the Climate Summit hosted by US president Joe Biden. The G7 has agreed to stop international financing of coal projects, and an International Energy Agency report says delivering net zero emissions by 2050 means no new coal, oil, or gas development from now on.

Governments are sending unmistakable policy signals which are redrawing multiple frontiers of the real economy, such as the banning of single use plastic in multiple jurisdictions from Europe, China, and more than 30 African states as well as New York and California. The sale of internal combustion engine vehicles is also set to end by 2035 or sooner in the EU, the UK, and California, and China is expected to follow suit with similar plans. France has proposed a ban on domestic flights when there are less carbon intensive alternatives on the ground.

But these signals did not spring out of a political vacuum. A global climate poll conducted by the United Nations (UN) in 50 countries showed two-thirds of the 1.2 million people polled thought there is a global climate emergency, and most indicated their support for stronger climate action even in countries with strong fossil energy interest.

Real economy responses to noticeable changes in risk calculus and political appetite will likely underpin further rapid shifts in market sentiment as investors begin to fully factor in the scale of the challenge and escalate their interrogation of company-level climate action plans.

Rapid pace of change still needed

But despite this ever-clearer direction of travel and growing availability of new technology and policy options, the need for speed remains. The rationale for moving fast in the next decade and a half to avoid the clear and present threats of environmental and breakdown is increasingly clear.

Getting up to scale is an ongoing and daunting challenge not least because exponential growth has brought growing pains. The recent spat over the definition and the usefulness of net zero targets for corporations and investors as seen in the shareholder votes over the climate plans put forward by Shell and other companies are all testimony to the challenge of mainstreaming.

While some have characterized these debates as political infighting, the reality is higher stakes simply mean it is more important than ever to safeguard the integrity of sustainability commitments as well as the quality of their delivery and implementation.

The move from ‘what’ to ‘how’ points to a clear demand for new, innovative collaborative efforts to help mitigate myriad political economy challenges associated with the upcoming great transition and ensure this sustainability pivot will deliver the promised outcomes. Launching the Chatham House Sustainability Accelerator in support of these once-in-a-generation efforts is a proud moment for the institute, and a clear sign that this pivot to sustainability is here to stay.

Independent Thinking: Iran protests, Iraq's invasion legacy Audio NCapeling 17 November 2022

Episode five of our new weekly podcast has a Middle East focus with insights into what is driving the ongoing protests in Iran, and the progress of Iraq in the years since the fall of Saddam Hussein.

Since September, Iran has been swept by thousands of women-led protests, demanding an end to the morality police and the even calling for the fall of the Islamic Republic.

Meanwhile at Chatham House this week saw our Iraq Initiative conference 2022, which delved heavily into the multiple challenges facing Iraq two decades on from the invasion which toppled Saddam Hussein.

Joining Bronwen Maddox on the podcast this week are the Chatham House Middle East and North Africa programme deputy director Dr Sanam Vakil and senior research fellow Dr Renad Mansour, who is also project director of the Iraq Initiative. They are joined by Sanya Burgess, digital investigations journalist with Sky News.

Independent Thinking: China protests, North Korea missile tests Audio NCapeling 1 December 2022

Episode seven of our new weekly podcast examines the civil unrest in China and the ongoing development of North Korea’s nuclear weapons programme.

Anti-lockdown protests are sweeping the cities of Beijing, Shanghai, and Guangzhou. What does the unrest say about China’s response to COVID-19? How serious a challenge is it to Xi Jinping’s legitimacy so soon after the Party Congress?

Meanwhile, 2022 has been a record year for Pyongyang’s ballistic missile launches. How far has North Korea’s nuclear programme and its missile systems developed, and what does it mean for the country’s neighbours?

Joining Bronwen Maddox in the studio this week from the Chatham House Asia-Pacific programme are its director Ben Bland and senior research fellow Dr Yu Jie. Joining the panel is special guest Ankit Panda, the Stanton senior fellow at the Carnegie Endowment for International Peace, and editor-at-large for The Diplomat magazine.

About Independent Thinking

A weekly podcast hosted by Chatham House director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.

Health not independence is focus for Sturgeon successor Expert comment NCapeling 15 February 2023

Nicola Sturgeon’s star may have been fading, but Rishi Sunak and Keir Starmer will be relieved at the exit of one of the UK’s most influential politicians.

Nicola Sturgeon has left at the right time, maybe even a bit late. Although one of the most influential politicians the UK has seen in recent times, she was also one of the most divisive.

Her ability to fan Scotland’s sense of difference from England brought new hope to the independence movement, but this cause – by which she measured herself above all others – has been losing ground and for now, looks to be in abeyance.

Neat and disciplined, Sturgeon could not have presented a greater contrast to Boris Johnson in the first months of the pandemic. That was one of her finest moments.

She used the powers of the devolved government to make different lockdown decisions for Scotland – never all that different from those in England but often announced just a few hours earlier.

Although analysts surmise that these made little difference to the death rate – although poverty and other health support factors make comparisons hard – she used the platform, with the cameras on her, to ram home the point that Scotland could set its own rules.

Rallying young voters to independence

Her second greatest moment was in the aftermath of Brexit. Scots voted overwhelmingly to stay in the European Union (EU) and so, she argued, they should have the right to leave the UK to join that other union. Younger voters in particular responded, rallying to the independence cause.

But two recent setbacks showed her star was fading. She lost the Supreme Court battle to hold a second independence referendum in November, when she was told Scotland simply did not have the powers to hold one on its own if Westminster said no – and the UK government did just that. It was hard to see how her campaign for independence could move forwards.

And her planned reforms to the gender recognition process in Scotland have been blocked by the UK government – but unease about her reforms within Scotland meant this rebuff did not win her the support at home she hoped for. She was also accused of playing politics by pressing ahead with unpopular reforms simply because of their potential to discomfit the UK government.

Health, education, and public services need attention

Other challenges were also building up and, even if less eye-catching, her successor is likely to focus on health and education above the birth of a new nation. Sturgeon’s critics have long argued that under Scottish National Party rule, health, education, and other public services have declined.

In elections, these factors can be eclipsed by passions about independence but it is rare in political life for a leader to be insulated from public anger on this front. This is almost certainly where her successor will want to focus first.

Independent Thinking: Nigeria votes, Northern Ireland deal Audio NCapeling 2 March 2023

Episode 17 of our weekly podcast examines the outcome of Nigeria’s presidential election and the new deal for Northern Ireland negotiated by the UK and EU.

On 24 February, millions of Nigerians went to the polls in an election widely seen as crucial for the direction of the country, with the winner Bola Ahmed Tinubu declared the new president-elect. The panel discusses the state of Nigeria’s democracy and what lies ahead for the new administration.

In addition, UK prime minister Rishi Sunak and European Commission president Ursula von der Leyen announced a new deal for Northern Ireland with implications for all the UK. Three years after the UK formally left the European Union (EU), has Rishi Sunak now got Brexit done?

Joining Bronwen Maddox are Leena Koni Hoffman, associate fellow with the Chatham House Africa programme, Aanu Adeoye, West African correspondent for the Financial Times and an academy associate at Chatham House, and Charles Grant, director of the Centre for European Reform.

About Independent Thinking

A weekly podcast hosted by Chatham House director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.

Independent Thinking: UK Integrated Review, Georgia protests Audio NCapeling 16 March 2023

Episode 19 of our weekly podcast examines the AUKUS deal, UK defence priorities, and the state of Georgia’s democracy following anti-government protests.

The UK and Australia will soon be building nuclear submarines together, but is the UK’s tilt to the Indo-Pacific sustainable? Two years on from the last Integrated Review, has the UK finally clarified its foreign policy priorities on Russia, China, and on defence? And is the money there to do it all?

Also on the show, the panel discusses Georgia following recent anti-government protests in Tbilisi. Following the Rose revolution in 2003, Georgia seemed to be on a path towards closer ties with NATO and the European Union (EU). But the country’s government has recently moved closer to Russia and Vladimir Putin. What is the state of Georgia’s democracy and where is the country heading?

Joining Bronwen Maddox from Chatham House is Creon Butler, director of our Global Economy and Finance programme, Professor Andrew Dorman, editor of the International Affairs journal, and Alice Billon-Galland, research fellow in our Europe Programme.

They are joined by Natia Seskuria, associate fellow with the Royal United Services Institute (RUSI) and Arthur Snell, former diplomat and host of the podcast Doomsday Watch.

About Independent Thinking

A weekly podcast hosted by Chatham House director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.

Accumulation of the microtubule-associated protein tau is associated with Alzheimer's disease (AD). In AD brain, tau is abnormally phosphorylated at many sites, and phosphorylation at Ser-262 and Ser-356 plays critical roles in tau accumulation and toxicity. Microtubule affinity–regulating kinase 4 (MARK4) phosphorylates tau at those sites, and a double de novo mutation in the linker region of MARK4, ΔG316E317D, is associated with an elevated risk of AD. However, it remains unclear how this mutation affects phosphorylation, aggregation, and accumulation of tau and tau-induced neurodegeneration. Here, we report that MARK4ΔG316E317D increases the abundance of highly phosphorylated, insoluble tau species and exacerbates neurodegeneration via Ser-262/356–dependent and –independent mechanisms. Using transgenic Drosophila expressing human MARK4 (MARK4wt) or a mutant version of MARK4 (MARK4ΔG316E317D), we found that coexpression of MARK4wt and MARK4ΔG316E317D increased total tau levels and enhanced tau-induced neurodegeneration and that MARK4ΔG316E317D had more potent effects than MARK4wt. Interestingly, the in vitro kinase activities of MARK4wt and MARK4ΔG316E317D were similar. When tau phosphorylation at Ser-262 and Ser-356 was blocked by alanine substitutions, MARK4wt did not promote tau accumulation or exacerbate neurodegeneration, whereas coexpression of MARK4ΔG316E317D did. Both MARK4wt and MARK4ΔG316E317D increased the levels of oligomeric forms of tau; however, only MARK4ΔG316E317D further increased the detergent insolubility of tau in vivo. Together, these findings suggest that MARK4ΔG316E317D increases tau levels and exacerbates tau toxicity via a novel gain-of-function mechanism and that modification in this region of MARK4 may affect disease pathogenesis.

Synapse loss is associated with motor and cognitive decline in multiple neurodegenerative disorders, and the cellular redistribution of tau is related to synaptic impairment in tauopathies, such as Alzheimer's disease and frontotemporal dementia. Here, we examined the cellular distribution of tau protein species in human tau overexpressing line 66 mice, a transgenic mouse model akin to genetic variants of frontotemporal dementia. Line 66 mice express intracellular tau aggregates in multiple brain regions and exhibit sensorimotor and motor learning deficiencies. Using a series of anti-tau antibodies, we observed, histologically, that nonphosphorylated transgenic human tau is enriched in synapses, whereas phosphorylated tau accumulates predominantly in cell bodies and axons. Subcellular fractionation confirmed that human tau is highly enriched in insoluble cytosolic and synaptosomal fractions, whereas endogenous mouse tau is virtually absent from synapses. Cytosolic tau was resistant to solubilization with urea and Triton X-100, indicating the formation of larger tau aggregates. By contrast, synaptic tau was partially soluble after Triton X-100 treatment and most likely represents aggregates of smaller size. MS corroborated that synaptosomal tau is nonphosphorylated. Tau enriched in the synapse of line 66 mice, therefore, appears to be in an oligomeric and nonphosphorylated state, and one that could have a direct impact on cognitive function.

Alzheimer's disease (AD) is characterized by neuronal loss and accumulation of β-amyloid-protein (Aβ) in the brain parenchyma. Sleep impairment is associated with AD and affects about 25–40% of patients in the mild-to-moderate stages of the disease. Sleep deprivation leads to increased Aβ production; however, its mechanism remains largely unknown. We hypothesized that the increase in core body temperature induced by sleep deprivation may promote Aβ production. Here, we report temperature-dependent regulation of Aβ production. We found that an increase in temperature, from 37 °C to 39 °C, significantly increased Aβ production in amyloid precursor protein-overexpressing cells. We also found that high temperature (39 °C) significantly increased the expression levels of heat shock protein 90 (Hsp90) and the C-terminal fragment of presenilin 1 (PS1-CTF) and promoted γ-secretase complex formation. Interestingly, Hsp90 was associated with the components of the premature γ-secretase complex, anterior pharynx-defective-1 (APH-1), and nicastrin (NCT) but was not associated with PS1-CTF or presenilin enhancer-2. Hsp90 knockdown abolished the increased level of Aβ production and the increased formation of the γ-secretase complex at high temperature in culture. Furthermore, with in vivo experiments, we observed increases in the levels of Hsp90, PS1-CTF, NCT, and the γ-secretase complex in the cortex of mice housed at higher room temperature (30 °C) compared with those housed at standard room temperature (23 °C). Our results suggest that high temperature regulates Aβ production by modulating γ-secretase complex formation through the binding of Hsp90 to NCT/APH-1.

Grassroots to global: Young changemakers against violence 24 October 2024 — 3:00PM TO 4:00PM Anonymous (not verified) 11 October 2024 Chatham House

As part of Black History Month, this event will look at how youth activism against violence can influence change.

To address the alarming increase knife crime, a 10% rise in knife-related homicides between April 2022 and March 2023, the UK government launched a coalition of community leaders, campaigners and policy makers to tackle this tragic loss of life.

With people under 25 disproportionately affected, the ‘knife crime epidemic’ represents an example of how youth activist groups are central to tackling the problem. Organisations for and operated by young people form a key part of the strategy to ensure people are better protected from violent crime.

Around the world, a network of youth groups are similarly striving to make a difference and build a better life for future generations. Operating in different political and economic conditions, there are learnings to be found in groups working across the world.

This session will discuss how grassroot activism and youth organisations can influence governments to prevent young people falling into crime, the role of race and religion, and whether organisations are improving in their effectiveness around the world.

This event is a collaboration with Integrate UK.

Sinwar’s death does not make Hamas–Fatah reconciliation more likely, whoever his successor may be Expert comment jon.wallace 22 October 2024

The killing may aid Hamas recruitment – but it will not make agreement with Fatah any easier to achieve.

Western political leaders were quick to argue that Israel’s killing of Hamas leader Yahya Sinwar on 17 October presented an opportunity for a ceasefire in Gaza and the return of Israeli hostages.

US President Joe Biden immediately called on Israeli prime minister Benjamin Netanyahu to seize the moment to negotiate, now that Israel has achieved one of its war aims.

However, that ‘moment’ has already passed. Israel’s military assault on Gaza has intensified since Sinwar was killed, leading UN Peace Process Co-ordinator Tor Wennesland to say that ‘nowhere is safe in Gaza’. It is abundantly clear Netanyahu is intent on further degrading Hamas, resetting a new ‘power balance’ and carving out a buffer zone, no matter the cost in Palestinian lives or Israeli hostages. 

But there are other implications of Sinwar’s assassination beyond the zero-sum analysis of will there or won’t there be a ceasefire.

Hamas’s ability to fight

At present, everyone has an opinion on how Sinwar’s killing will affect Hamas and its ability to resist and respond to Israel’s military. His death will have been a major blow – symbolically, operationally, and psychologically. Hamas has been downgraded and its capacity to respond compromised.

But it will recover, regenerate and retaliate in time – and Sinwar’s death will have been no surprise to Palestinians in Gaza or elsewhere. Hamas is accustomed to seeing its leaders assassinated. Since its formation in 1987, it has been ‘decapitated’ many times, only to continue with its mission to ‘liberate Palestine’.

Hamas’s portrayal of Sinwar dying in his fatigues, head wrapped in a keffiyeh and resisting until the end will persuade many young Palestinians that he died as a martyr serving the Palestinian cause. Many will be inspired to join and fortify the ranks of Hamas as a result.

The IDF’s release of drone footage showing Sinwar’s last moments will have done nothing to undermine his credibility. 

On the contrary, it will serve as a rallying call to disaffected and disenfranchised young Palestinians horrified by Israel’s bombing of civilian targets in Gaza and disaffected with Fatah’s inability to prevent Israeli settler expansion and violence in the West Bank.

Reconciliation

Some hope that if Sinwar is replaced by a more ‘moderate’ leader, his killing may smooth the path to Hamas–Fatah reconciliation – and that this could provide a foundation for a patchwork political solution when Israel and Gaza arrive at the ‘day after.’  

But the idea that a downgraded and ‘leaderless’ Hamas will be susceptible to international pressure to reconcile with Fatah is divorced from reality.  

Prospective new Hamas leaders such as Khaled al Meshaal and Khalil al-Hayya are based in Qatar. 

They may be more pliable to external pressure to reconcile with Fatah in search of a political outcome, but their ability to influence events on the ground in Gaza will be limited. That was demonstrated by the Sinwar-orchestrated attacks on 7 October 2023, which took place without the blessing of the exiled leadership in Doha.

Hamas has long gone to ground in Gaza and become far more decentralized than it was before 7 October. It is now more typical of an insurgency, where Hamas cadres exercise a great degree of operational autonomy.

In other words, the disconnect between Hamas in Gaza and its political leadership in Qatar has only grown wider since this round of conflict started.

International efforts

That will undermine international efforts made by Qatar, Egypt, Saudi Arabia, China, Russia and others to bring about a reconciliation. Moscow and Beijing already hosted reconciliation talks in February and April early this year but made no progress in closing the chasm between the two parties. Saudi Arabia has also hosted talks.

The three Arab states, none of which have so far commented publicly on Sinwar’s killing, will likely view his death as an opportunity to bolster the political wing of Hamas – backing it with pledges of political, diplomatic and financial support.

Saudi Arabia and Egypt will have next to no influence over the succession process, but Qatar’s long-established relationship with the political wing of Hamas affords it leverage over the organization, albeit limited. They may be able to strengthen the hand of those based in Doha by promising to work harder at securing a ceasefire, guaranteeing the provision of humanitarian relief, and working towards a political solution.

How to revive Europe’s economy and unlock its potential 7 November 2024 — 6:00PM TO 7:00PM Anonymous (not verified) 22 October 2024 Chatham House and Online

Enrico Letta, former prime minister of Italy, and other experts discuss how the European Union’s economy must adapt to a challenging world.

Amid a fractured geopolitical environment, global trade volatility and hardening protectionist policies in many countries, the European economy must adapt fast. The single market is a key driver of European integration, but it was designed in a very different global economic context.

Launched in April, Enrico Letta’s Much more than a market report set out how the European Union should adapt the arrangements of the single market to ensure it delivers prosperity and economic security for EU citizens in the 21st century. The report resonates with ongoing debates over the future of European competitiveness, industrial strategy and how to respond to an apparently deglobalizing world. In this event, Letta and other experts on the European economy and integration will discuss the prospect of meaningful reform of the single market, and what the incoming Commission can do to ensure the EU unlocks the potential of its economy for all its citizens.

Key questions will include:

• What dynamics are shaping the Europe’s economic landscape?
• What opportunities are there to enhance the strength and competitiveness of the single market
• How can the EU’s leaders ensure the single market is aligned with other strategic objectives such as security and enlargement?
• What political hurdles may prevent progress on single market reform? And how can these be overcome?

The institute occupies a position of respect and trust, and is committed to fostering inclusive dialogue at all events. Event attendees are expected to uphold this by adhering to our code of conduct.

Mary G. McCoy
Jun 1, 2002; 43:921-929
Research Articles

Margrit Schwarz
Sep 1, 1998; 39:1833-1843
Articles

W Gamble
Nov 1, 1978; 19:1068-1070
Articles

M el-Saadani
Apr 1, 1989; 30:627-630
Articles

David A. Mitchell
Jun 1, 2006; 47:1118-1127
Thematic Reviews

Mohamad Navab
Jun 1, 2004; 45:993-1007
Thematic Reviews

WS Harris
Jun 1, 1989; 30:785-807
Reviews

Nica M. Borradaile
Dec 1, 2006; 47:2726-2737
Research Articles

Mohamad Navab
Sep 1, 2000; 41:1495-1508
Articles

Mohamad Navab
Sep 1, 2000; 41:1481-1494
Articles

M. Burstein
Nov 1, 1970; 11:583-595
Articles

M. Mahmood Hussain
Jan 1, 2003; 44:22-32
Reviews

JL Dixon
Feb 1, 1993; 34:167-179
Reviews

Gijs den Besten
Sep 1, 2013; 54:2325-2340
Reviews

S Eisenberg
Oct 1, 1984; 25:1017-1058
Reviews