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

Spend enough time talking with entrepreneurs, product people, designers, and anyone charged with proving something, and you’ll bump into questions about validation. “How do you validate if it’s going to work?”“How do you know if people will buy it to not?”“How do you validate product market fit?”“How do you validate if a feature is worth… 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

For more A.F. Branco cartoons, go to WesternJournal.com/cartoons.

The post Ditch Mictch Clones appeared first on The Western Journal.

Retired Gen. Mark Milley is afraid of retribution. The former chairman of the Joint Chiefs of Staff and a four-star Army general made no bones about his feelings about former […]

The post Mark Milley Fears He Will Face a Court-Martial When Trump Enters White House appeared first on The Western Journal.

One of the greatest pass rushers in NFL history appears to be taking a pass himself when it comes to directly addressing a raging controversy. Pro Football Hall of Famer […]

The post NFL Analyst Michael Strahan Speaks Out After Becoming Embroiled in National Anthem Controversy appeared first on The Western Journal.

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

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

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

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

Pro-Trump businessmen Elon Musk (the richest man in the world) and Vivek Ramaswamy have officially joined the incoming Trump administration. President-elect Donald Trump announced in a statement published Tuesday that […]

The post Breaking: Musk, Ramaswamy Officially Join Trump Administration - Their Job Is to Destroy Bureaucracy appeared first on The Western Journal.

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.

By Cynthia Farahat On Friday 27th, 2023 at 11:00 am EST, my sweet dear younger brother Amir Farahat passed away. Amir was the most loving father I have ever seen, a great brother, son, husband, and brother-in-law. My little Miró, my little prince, my soul is shattered by your loss. I will forever mourn your […]

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 […]

3.6 million will pay with crypto in US; payment value to spike 70% in 2022   April 20, 2022 (New York, NY) – Cryptocurrency usage will continue its meteoric rise, […]

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

A feminist and postcolonial approach to nuclear politics Expert comment NCapeling 20 July 2022

The July issue of International Affairs includes eight articles on the global nuclear order and eight more covering Chinese lending, abortion rights, and global security.

Disarmament and arms control has been a consistent area of debate in this journal for the past century, as underscored in our recent archive collection of research on a century of war and conflict.

The July edition moves this debate forward with a collection of papers guest-edited by Shine Choi and Catherine Eschle. The section ‘Feminist interrogations of global nuclear politics’ includes work by nine authors exploring seven global case-studies that help rethink nuclear politics and feminism.

As the guest editors note in their introduction, the section brings together research on nuclear power and nuclear weaponry to ‘begin the process of decentring 1980s white, western experiences of the global nuclear order in feminist IR’.

The articles speak to three core themes: they provide evidence of the ongoing destructive nature of nuclear technologies, extend understanding of the gendered, racialized, and colonial dimensions of nuclear discourses, and unearth the impact of colonialism on the global nuclear order.

Global nuclear politics

Anne Sisson Runyan examines the gendered effects of uranium mining and nuclear waste dumping on North American Indigenous women, showing how the nuclear cycle tends to have a disproportionate effect on certain communities but also that the area of disposal remains problematic.

This is a global problem – for example, the Royal Navy has yet to successfully dispose of a single redundant nuclear-powered submarine and is rapidly running out of space to store further vessels.

Hebatalla Taha goes back to the early years of nuclear development and, using Egypt as a case-study, her article argues the early visualizations of the atomic age were fluid and ambivalent. She concludes – perhaps controversially – that feminizing nuclear politics and nuclear images will not lead to disarmament but rather reinforce the nuclearized world. The piece is a welcome addition to the emerging field of visuality within international relations.

Anand Sreekumar brings together feminist and Gandhian thinking to suggest a way for Narendra Modi’s government to move beyond the possession of nuclear weapons as symbols of power. In doing so, he also critiques the binary labels of ‘West’ and ‘non-West’ that often frame our understanding of the world.

Lorraine Bayard de Volo revisits the Cuban missile crisis – a point in time where nuclear war looked likely. She compares the actions of Khrushchev, Castro, and Kennedy and finds the pursuit of masculinity led to the rejection of approaches considered more feminine, such as diplomacy and negotiation – the crisis was exacerbated by what might be referred to now as toxic masculinity.

Sweden’s and Finland’s recent application to join the nuclear alliance NATO lends a particular urgency to Emma Rosengren’s article on the original Swedish decision to renounce the development of nuclear weapons during the Cold War. Her article concludes much of the emphasis on power in international relations has contributed to a gendered and racialized nuclear order.

Similarly, Laura Rose Brown and Laura Considine’s article on the Non-Proliferation Treaty finds that ‘gender-sensitive’ approaches focus almost exclusively on women’s inclusion as opposed to feminist policy analysis. They end by making recommendations for future policymaking.

Finally, Rebecca Hogue and Anais Maurer look at the anti-nuclear poetry of Pacific women. This article raises fundamental questions about what is currently considered to constitute evidence. They point to the role of oral history in many communities and the tendency of policymakers and social scientists to ignore this source of understanding.

National politics with international implications

This edition’s ‘Editor’s Choice’ is Jeffrey A. Friedman’s article which questions whether US grand strategy is dead in a post-Trump world. Running counter to much of the existing literature, he suggests there is a strong bilateral commitment to existing partnerships and alliances within the US political establishment.

Following the US Supreme Court decision over Roe vs Wade, it is important to note the issue of abortion rights can have an international dimension. Megan Daigle, Deirdre N. Duffy, and Diana López Castañeda reveal that, although Colombia now has the most progressive legal framework for abortion in Latin America, intense backlash persists as legacies of the civil war overshadow the issue and lead to barriers to safe abortion care.

China

Ric Neo and Chen Xiang look at Chinese public opinion and finds that citizens can be upset by foreign policies of other states even when they have no impact on their daily lives. It reminds us of the potency of nationalism and the importance of who controls the prevailing narrative.

Deborah Brautigam examines China’s role in creating Zambia’s debt crisis, arguing this has not been brought about by a centralized master plan which would give China control over Zambia. Instead, the crisis has been caused by the failure of Chinese bureaucracy with too many state organs offering funding in an uncoordinated fashion.

Security and defence

Using Iran as a case-study, Henrik Stålhane Hiim argues the development of nuclear-capable ballistic missiles is a key indicator when looking for potential nuclear proliferators.

Eray Alim demonstrates the impact of an external great power interacting with local states. Russia’s involvement in the Syrian civil war has allowed it – sometimes through restrictive and punitive measures – to ensure Turkey and Israel do not harm its interests in the region.

Nina Wilén draws on fieldwork in Niger to study how Security Force Assistance (SFA) impacts on Niger’s security sector and compares this to global trends in security. She finds these developments contribute to blurred borders and confusion regarding labour division in the security sector and points to wider questions for intervenors in developing local units.

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.

In conversation with David Miliband: Finding a new approach to tackle conflict, climate and extreme poverty 11 September 2024 — 5:00PM TO 5:45PM Anonymous (not verified) 15 August 2024 Chatham House and Online

David Miliband discusses how the climate crisis, extreme poverty and conflict are becoming inextricably linked and how the global community must respond.

Combatting the climate crisis, ending protracted conflicts, and alleviating poverty are three of the greatest priorities for international action. However, these three challenges become increasingly concentrated in a handful of countries. The subsequent feedback loop makes addressing these challenges even more complex.

The International Rescue Committee’s (IRC’s) work in crisis-affected communities highlights this new geography of crisis. Just 16 countries, which are both climate-vulnerable and conflict-affected. This represents 43% of all people living in extreme poverty, 44% of all people affected by natural disasters and 79% of all people in humanitarian need. This trend towards the concentration of crisis is only deepening. In three decades, the number of conflict-affected, climate-vulnerable states has increased from 44% to more than two-thirds.

Affected countries - like Sudan, Myanmar, and Syria - are also among the least supported financially. Debt burdens are siphoning away critical resources needed for adaptation and resilience. Humanitarian aid budgets are being slashed by donor governments. The private sector refuses to invest in these communities they view as too risky. And the international financial institutions meant to alleviate poverty and spur climate action are not well-designed to work with crisis-affected states or local communities. With the upcoming COP29 Summit in Azerbaijan focused on the New Collective Quantified Goal for climate finance, vulnerable communities will be watching closely whether they will get support in their fight against the worst impacts of the climate crisis.

Conflict, the climate crisis, and extreme poverty are taking their toll. But how can the world best respond?

Key questions to be discussed during the session include:

• At a time of political disruption, how does the West engage with vulnerable countries? What actions should be prioritised in providing support to such countries?
• Can global institutions evolve to better protect vulnerable and displaced people from conflict and climate-risk, particularly as geopolitical rivalries reduce space for cooperation?
• What is the UK’s role in supporting climate action in fragile states and how does this align with its agenda on the Sustainable Development Goals and extreme poverty?

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

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

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

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

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

This raises several questions:

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

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

How can young people in MENA thrive despite economic and political insecurity? 24 September 2024 — 2:00PM TO 3:00PM Anonymous (not verified) 30 August 2024 Online

Experts share insights on how young people navigate challenges and find opportunities in a changing domestic and regional landscape.

Across the Middle East and North Africa young people between the ages of 15 and 29 comprise around 24 per cent of the population in the region. As the complex regional geopolitical developments unfold, the majority of these young people are living in a time of economic and political insecurity, with many, such as Iraqis and Libyans, also growing up during conflict and uncertainty.

Enhanced education and employment programs are key opportunities for development and stability in the region. Despite this, limited resources and competing priorities have meant that governments often struggle to deliver competitive educational and employment opportunities and lack the capacity and funding for education reform and active labour market policy development. Key tensions that pit modernity and autonomy against tradition and control continue to frame the education and skills development landscape.

This webinar will address:

• The challenges young people within the MENA region face in different contexts;
• The role education and employment play in developing skills for 21st century challenges;
• Spaces for young people to practice citizenship and participate in political processes;
• Youth’s economic prospects while navigating the tumultuous backdrop of enduring conflict and authoritarianism. 

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

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

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

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

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

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

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

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

Further background information is available on the initiative website.

More speakers to be announced.

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

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

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

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

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

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

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

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

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

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

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

Please join us for this critical session to discuss:

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

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

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

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

Is the world ready for the next pandemic? 29 October 2024 — 6:00PM TO 7:00PM Anonymous (not verified) 9 October 2024 Chatham House and Online

In a joint event with The Elders, Helen Clark, Ban Ki-moon and other experts discuss the policies needed to prevent the next health catastrophe. A drinks reception will follow this event.

The world faces multiple interlinked existential threats such as pandemics and the climate crisis, exacerbated by conflict and extreme poverty. However, the multilateral system is failing to respond with sufficient urgency or impact. As the fifth anniversary of the COVID-19 pandemic approaches, Chatham House and The Elders will discuss the risk of a general slide into complacency. 

Amid the expanding outbreak of mpox in Africa, rich countries continue to withhold stockpiled mpox vaccines. The failure to release the required amount is contributing to the diseases spread across the continent. 

Meanwhile, the Pandemic Accord negotiations are in overtime, with nations unable to reach agreement over concerns around sovereignty and resource distribution in any future pandemic. Similarly, a proposal to include a UN Emergency Platform in the recent Summit of the Future to strengthen the multilateral response to complex global shocks was shelved due to political deadlock.

Can the world learn from past mistakes and break the cycle of panic and neglect? In today’s fractious and polarized geopolitical context, what would it take for leaders to do what’s necessary? And why is it so critical to have equity at the heart of any sustainable global response?

Join Chatham House for this event in which the panel discuss key questions including:

• Five years on from COVID-19, who is showing global leadership today in preparing for future pandemics?
• Are international organizations and institutions fit for purpose to respond to pandemics in a multipolar geopolitical environment? How can they best adapt?
• What can be done to clarify and detoxify current debates around sovereignty to improve global pandemic prevention, preparedness and response?

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

The human cardiovascular system has adapted to function optimally in Earth's 1G gravity, and microgravity conditions cause myocardial abnormalities, including atrophy and dysfunction. However, the underlying mechanisms linking microgravity and cardiac anomalies are incompletely understood. In this study, we investigated whether and how calpain activation promotes myocardial abnormalities under simulated microgravity conditions. Simulated microgravity was induced by tail suspension in mice with cardiomyocyte-specific deletion of Capns1, which disrupts activity and stability of calpain-1 and calpain-2, and their WT littermates. Tail suspension time-dependently reduced cardiomyocyte size, heart weight, and myocardial function in WT mice, and these changes were accompanied by calpain activation, NADPH oxidase activation, and oxidative stress in heart tissues. The effects of tail suspension were attenuated by deletion of Capns1. Notably, the protective effects of Capns1 deletion were associated with the prevention of phosphorylation of Ser-345 on p47phox and attenuation of ERK1/2 and p38 activation in hearts of tail-suspended mice. Using a rotary cell culture system, we simulated microgravity in cultured neonatal mouse cardiomyocytes and observed decreased total protein/DNA ratio and induced calpain activation, phosphorylation of Ser-345 on p47phox, and activation of ERK1/2 and p38, all of which were prevented by calpain inhibitor-III. Furthermore, inhibition of ERK1/2 or p38 attenuated phosphorylation of Ser-345 on p47phox in cardiomyocytes under simulated microgravity. This study demonstrates for the first time that calpain promotes NADPH oxidase activation and myocardial abnormalities under microgravity by facilitating p47phox phosphorylation via ERK1/2 and p38 pathways. Thus, calpain inhibition may be an effective therapeutic approach to reduce microgravity-induced myocardial abnormalities.

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

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

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

After a thorough read of this paper (1), we wish to clarify that the authors' anaerobic method of synthesis for the production of nitrocobalamin results in the transient formation of nitrosylcobalamin, an unstable intermediate upon exposure to air. We concur that the authors' method results in the production of nitrocobalamin based on the UV-visible data as shown. The authors' adapted anaerobic method consists of mixing hydroxocobalamin hydrochloride with diethylamine NONOate diethylammonium salt in aqueous solution. Of concern, the UV spectrum of nitric oxide overlaps that of all cobalamin species under anaerobic conditions, making any assignments of the binding of nitric oxide to hydroxocobalamin suspect (2). Additionally, the use of acetone to precipitate the authors' product causes precipitation of diethylamine NONOate, resulting in an impure product. As a result, its utility for drawing experimental conclusions is faulty.The product from the authors' anaerobic synthetic method has not been assessed for purity, and the synthetic method itself has not been validated using a stability-indicating method as required by the International Conference on Harmonization (ICH) (ICH Q2B, Validation of Analytical Procedures) methodology, which is a hallmark for analytical characterization. Our nitrosylcobalamin synthesis involves reacting nitric oxide gas with hydroxocobalamin acetate as a heterogeneous mixture in a non-electron-donating solvent followed by rotary evaporation. Our nitrosylcobalamin product is stable in air, releases nitric oxide gas in situ (3), and meets ICH stability guidelines (4). Additionally, our nitrosylcobalamin product demonstrates biological activity, which has not been observed for nitrocobalamin (3, 5).

Arguments Over Innovation Capacity Miss How Much the US and China Are Intertwined Expert comment sysadmin 30 May 2018

Most discussions of current US–China trade tensions fundamentally misrepresent the globalized nature of innovation.

Among the many issues at play in the ongoing economic and trade tensions between the US and China are questions of technological capability and innovation.

Two of the main complaints in the US Section 301 report were that American companies have been forced to transfer technology to China and been the subject of cyber espionage. The presentation of the issues in this report has been disputed, but behind it lies concern in the US that Chinese innovative and technological capability is catching up with that in the US, thanks partly to the support of state policies set out in the Made in China 2025 initiative.

One important feature of the package of measures announced by the US last month is that it was designed to contain China’s technological development as much as to reduce the trade deficit, even though the latter has been the focus of President Donald Trump’s rhetoric.

(Some have cast doubt on this picture of Chinese innovation, suggesting that China is more of a ‘fat tech dragon’ whose massive inputs into research and development do not translate into real innovative capacity.)

The problem with the debate comparing Chinese and American technological capability is that it misunderstands or misrepresents the globalized nature of innovation in today’s world.

Contrary to the economic nationalist rhetoric emanating mainly from Washington, and to a lesser extent from Beijing, the US and China are not two separate economies competing for economic hegemony. As part of the globalization of manufacturing and production over the last 40 years and the more recent globalization of consumption, the shape and structure of innovation has also changed.

As we argue in a new paper, the key to understanding this is to think of innovation as being carried out through global or transnational networks linking economic actors, not within separated economies. What the recent phase of globalization has demonstrated is that innovation is achieved most effectively and efficiently when those engaged in innovation are connected not just within national borders but across them.

China has become integrated into these global innovation networks in ways which reflect its relative strengths and weaknesses in research and development. China’s extensive manufacturing ecosystem has enabled its companies to perform well in production-related and efficiency-driven innovation. Moreover the rapid growth in its large and dynamic consumer market provides fertile ground for consumer-related innovation by Chinese and foreign-invested enterprises alike. The rapidly increasing talent pool in China also provides additional human capital for innovation and technology.

Apart from the increased emphasis by Chinese enterprises on innovation, multinationals have also been stepping up their research and development (R&D) efforts in China. These now consitute a significant part of China’s R&D landscape, and are an increasingly important part of the global innovation by multinationals.

Things are of course changing. China’s overall innovation capacity is improving, and there are concerns in both in the US and Europe that Chinese policy is moving backwards towards the promotion of ‘indigenous innovation’ – or self-reliant innovation – and away from openness. In other words, we may be seeing a more ‘techno-nationalist’ China as well as a protectionist US.

China has also been criticized for inadequate protection of intellectual property rights, though the establishment of special courts for such disputes marks a commitment to improve – and the rights of Chinese companies increasingly need protection too.

As the benefits of globalization increasingly come under question, and with some degree of nationalist political pressure in both the West and China, it is not going to be possible – or politically desirable – to do away with national borders when it comes to innovation. But at the same time, the extent to which businesses and consumers have globalized means that fully ‘indigenous’ innovation is not possible, even if it were politically desirable.

EU-China innovation relations, as well as those between Washington and Beijing, therefore need careful management. But both Americans and Europeans should have more confidence in their innovation capability, given the relative strengths and weaknesses of Chinese innovation.

Americans and Europeans should acknowledge and promote the opportunities that come from globally networked innovation processes. Taking advantage of the comparative advantage of all the players in these networks means working with China as an innovation partner.

How Women are Transforming Indonesia Interview sysadmin 20 May 2019

In a series exploring women in international affairs, Isabel Dunstan speaks to Gitika Bhardwaj about the rise of the women’s movement in Indonesia.

Southeast Asia has one of the highest records of gender-based violence in the world and Indonesia was recently ranked as the second most dangerous place for women in the Asia-Pacific. What is the state of women’s rights and gender equality in Indonesia?

It is true that Indonesia has high rates of violence against women, however, it’s difficult to know the realities of women’s experiences because in the past the data has been somewhat unreliable. This has been due to reasons such as a lack of reporting mechanisms available to survivors of violence and the fact that discussing sexual violence is a taboo and, if reported, can result in stigmatization which limits the number of survivors who have come forward.

However, the first reliable nationwide survey on gendered violence in Indonesia was conducted in 2017 by the Indonesian Ministry of Women and Child Protection and the United Nations Population Fund. Interestingly, it showed that Indonesia’s rates of violence against women are on par with the global rate which is that 1 in 3 women are affected by sexual violence in their lifetime.

It’s therefore difficult to generalize that Indonesia is an unsafe place for women because it’s an extremely diverse country. There is a growing middle class while there is pervasive poverty. There is religious diversity where the eastern-most province of Aceh is the only province in the country where Sharia law is enforced, whereas in the western-most province of West Papua, the dominant religion is Christianity and the ways of life are completely different.

Nevertheless, violence against women is high in Indonesia and can happen in all places – rich or poor, east or west – and has different manifestations from street harassment and trafficking to domestic violence and workplace harassment.

In some parts of the country there are high rates of child marriage too and, according to UNICEF, 14 per cent of girls in Indonesia are married by the time they turn 18 which is shocking when we think about how child marriage limits girls’ access to education and makes them more vulnerable to sexual violence and therefore restricts their futures.

Child marriage is high in Indonesia in part due to rooted gender norms, low levels of education and discriminating legislation, such as the marriage law, which states that, although it is legal to marry at 21, girls can marry at 16 and boys can marry at 19 with parental consent. But this can be even lower meaning parents could get their daughters married at as young as 13. So the law is fundamentally unfair between girls and boys and the women’s movement in Indonesia has been fighting extremely hard to reform legislation that discriminates against women and girls.

From the country’s first female president, Megawati Sukarnoputri​, to incumbent finance minister Sri Mulyani Indrawati – who was voted ‘Best Minister in the World’ in 2018 – and maritime​ and fisheries minister Susi Pudjiastuti – who has become notorious for her tough stance against illegal fishing activities – how are women progressing in Indonesian politics?

Indonesia has come a long way since becoming a democracy in 1998. Before that, the second president and dictator, Suharto, ruled the country for almost 32 years and increased the inequality gap between men and women during his reign.

Since the fall of Suharto, however, gender equality is explicitly enshrined in Indonesia’s constitution and the country has ratified the Convention on the Elimination of Violence Against Women.

The country has also been undergoing a process of democratization which has involved slowly decentralizing its power. This means that greater authority has been distributed to the 34 provincial governments outside of the capital of Jakarta.

Furthermore, to aid gender equality, a quota system requiring political parties to be made up of 30 per cent women has been put in place, although remnants of Suharto’s old system of cronyism remain, limiting the impact of the quotas translating to more women in provincial parliaments.

But the defining approach to furthering gender equality in Indonesia has been through gender mainstreaming and gender-responsive budgeting which can be seen throughout provincial administrations in the country.

This means there is the intention to ensure infrastructure, health and education outcomes include results that address specific gender equality gaps. The challenge for effective gender mainstreaming, however, is the political will to translate the approach into well-resourced programmes from one province to another.

Nevertheless, we have just seen Indonesia go through the most incredible presidential and legislative elections last month – won by the current president, Joko Widodo, who has often been called the ‘Barack Obama of Southeast Asia’ and whose existing cabinet has the highest number of women in the country’s history. This is not simply a matter of filling seats in the cabinet with women – such as the wives and sisters of male politicians – because it’s required by law. But, rather, there are some incredible female political figures who are there because they are strong, smart and capable.

You’ve rightly mentioned Minister of Maritime Affairs and Fisheries, Susi Pudjiastuti, who is a fabulous role model for a lot of women particularly women who have not had tertiary education because she entered politics through an unorthodox route.

Then there’s Minister of Finance, Sri Mulyani Indrawati, who is also the former leader of the World Bank and is such an inspiration to a lot of women who are looking to work in public life because of her experience as well as her work to include gender mainstreaming in state budgets.

There is also Minister of Women’s Empowerment and Child Protection, Yohana Susana Yembise, who is a Papuan woman, as well as many more female public figures.

Virtual Roundtable: The Economic Implications of COVID-19 on Asia 2 April 2020 — 11:00AM TO 12:00PM Anonymous (not verified) 27 March 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE

The COVID-19 pandemic is likely to have a damaging economic impact on Asia, potentially the most serious since the financial crisis two decades ago. While early estimates suggest that a recession is inevitable, differing countries in Asia are generally deploying modest fiscal and monetary measures. This is true even in China, compared with the ‘whatever it takes’ approach pursued by Europe and America.

How effective will these measures be in reviving growth and in easing the pain, particularly on the poor in developing countries in Asia? Is Asia witnessing a sudden but temporary halt in economic activity rather than a prolonged slowdown? At this virtual roundtable, the speakers will consider the likelihood of a recovery for trade in the region and will explore what lessons can be learned from countries like Singapore, who seem to be successfully managing the health and economic aspects of COVID-19.

This event is online only. After registering, you will receive a follow-up confirmation email with details of how to join the webinar.

China's Evolving Economic Relations with North Africa: Before and After COVID-19 10 September 2020 — 12:00PM TO 1:30PM Anonymous (not verified) 20 August 2020 Online

China’s economic presence across North Africa has grown in recent years. The global power has forged close economic relationships with Egypt and Algeria, while also continuing to develop ties with Morocco and Tunisia.

Beijing, which views the region as a geostrategic intersection between Mediterranean, Middle East, and Africa, has primarily focused its efforts on developing bilateral relations, while also working within the Forum on China–Africa Cooperation (FOCAC) and the China–Arab States Cooperation Forum (CASCF).

All countries of the region have agreed to participate in China’s Belt and Road initiative (BRI), which has raised concerns among Western powers. As North African countries grapple with fiscal constraints as part of the fallout from COVID-19 (and the oil price drop for hydrocarbon exporters such as Algeria), it is yet to be seen whether China’s ambitions and relations within the region will continue to develop at the same pace going forward.

In this webinar, organized by Chatham House’s MENA and Asia-Pacific Programmes, experts will discuss the evolving economic relationship between China and North African states, and explore the impact of China’s pandemic diplomacy across the region.

How asymmetric are economic relations between China and North African states? Which sectors are most important, and what are the prospects for China to develop the region’s digital and healthcare infrastructure? Will China’s increasing economic interests necessitate an increasing political and security engagement? Should North African states be wary of Chinese loans? What is the public opinion of China’s economic presence in North Africa? Have Chinese ‘soft power’ efforts helped to bolster economic (and political) ties? What will be the likely fallout of COVID-19 on BRI and infrastructure projects in the region?

You can express your interest in attending by following this link. You will receive a Zoom confirmation email should your registration be successful. Alternatively, you can watch the event live on the MENA Programme Facebook page.

Why America’s midterm elections matter for the world The World Today mhiggins.drupal 28 September 2022

The outcome could threaten the fight against climate change and the future of democracy itself, warns Leslie Vinjamuri.

As the November 8 midterm elections in the United States approach, the sense of urgency among the Democrats and Republicans is escalating. Early voter turnout is on track to surpass the 2018 midterms, when a record 122 million Americans voted ahead of election day. The midterms – when congressional, state and local seats are determined – used to pass almost unnoticed, especially outside the US.

Since 2018, though, they have become a matter of global concern. The 2022 midterm elections will be the first major elections in the US since the January 6 insurrection at the US Capitol. As such, they will be the first real litmus test for the continued relevance of Donald Trump and Trumpism.

For both parties, winning is more important than ever and it is not only a matter of policy. Today, a majority of members of both parties – 72 per cent of Republicans and 63 per cent of Democrats – see those belonging to the opposing party as immoral, according to a Pew Research Center poll in September, representing a significant rise since 2016.

In many states, the midterms will have a direct impact on the 2024 presidential elections, influencing who decides how voting takes place, how votes are counted and, especially, who controls the certification of election results.

Given this context, the stakes in elections are especially high. The winners will have the upper hand not only in defining many procedural rules but also the values that constitute the nation, such as on abortion rights, education and healthcare.

Republicans and Democrats align on most key foreign policy

Though foreign policy will bear a strong resemblance to its former self even if Republicans gain a majority in the House of Representatives, as many anticipate, the outcome of the elections on US global influence could impact efforts to combat climate change and to support the defence of Ukraine.

The Republican Party has become known for its embrace of climate deniers and the radicalized anti-immigrant rhetoric of many of its party’s most established figures. The failure to address rampant gun violence – and, instead, to defend a historically suspect interpretation of the right to bear arms – and the push for a national abortion ban mean that the party is imposing a version of America onto itself that is out-of-step with virtually all other rich democratic countries.

The choices voters make in November are likely to shape the values that come to the fore in the US, and with this the affinity that America’s closest partners feel for it.

Domestic policy is likely to be more heavily affected by the elections. A Republican majority in the House would stall progress on President Joe Biden’s domestic agenda and undercut his ability to raise the taxes he needs to pay for his spending plans. The drive to hold the former President Trump accountable will also be affected by the choices voters make in November.

A Republican majority in the House would spell an end to congressional investigations of Donald Trump. Instead, Republicans would use their electoral gains to launch their investigations into the Democrats.

One anti-Trump Republican on the January 6 committee investigating the storming of the Capitol building last year warned of a vengeful and obstructive turn against Biden from his Republican colleagues if they took the House. ‘They’re going to demand an impeachment vote on President Biden every week,’ said congressman Adam Kinzinger. It is under this shadow that the January 6 Committee is pressing ahead to finish its proceedings and publish its report.

On foreign policy, the parties are more aligned than divided on most of the key issues. Their differences are a matter of diplomacy, which matters, and degree. Support for Ukraine has had bipartisan backing, but in recent weeks the issue has become politicized. Some congressional Republicans are more hawkish than their Democratic counterparts in their ambition to support Ukraine. Yet, the congressman set to be Speaker of the House if Republicans gain a majority, Kevin McCarthy, is leading an effort to exercise far stronger oversight of any additional funds for Ukraine.

Ultimately, though, the president and his advisers maintain considerable control over foreign policy.  

Bipartisan support for a tougher stance on China was consolidated under Trump. He mobilized US voters by blaming China for the loss of manufacturing jobs. Later he held China responsible for the outbreak of Covid and for covering it up. China’s crackdown on democracy in Hong Kong, its assertiveness in the South China Seas, tensions over Taiwan and reports of human rights abuse against the Uighur in Xinjiang have cemented a bipartisan consensus on America’s China policy. But a more empowered Republican base looks likely to lead to a more ideologically driven anti-China rhetoric. 

The ground has also shifted over Russia. During President Trump’s tenure, Republican attitudes towards Vladimir Putin softened. But the Russian president’s aggressive invasion of Ukraine has entrenched American opposition to him and bolstered support for NATO.

Democrats and Republicans are also more aligned on policy towards Iran today than they were before Trump abandoned the Iran Deal negotiating the Middle Eastern country’s nuclear programme. On some contentious issues, such as immigration reform, progress is already stalled and that is unlikely to change.

US climate change policy may depend on the results

The upshot of all this is that the president is unlikely to make radical changes to US foreign policy regardless of the results of the midterms. The most important exception to this is climate change, which continues to be the unwanted stepchild of the Republican Party. Domestic infighting in the US would inevitably detract even further from the bold policy that is needed.

Republicans are unlikely to get the two-thirds majority needed to pass legislation that would undermine President Biden’s climate bill. Republican control of House committees, however, would add more politically driven oversight of any climate spending, including what has already been authorized by the Inflation Reduction Act. 

Policy convergence and clear executive authority cannot mitigate the sheer disruption that would be unleashed if the Republicans were to gain majorities in both the Senate and the House, however. For the rest of the world, and especially within Europe, this would send warning signs about the future trajectory of US foreign policy commitments and set off alarm bells that an ‘America First’ president might return to the White House after 2024.

A Republican majority in the House with a Democratic majority in the Senate would be disruptive, if less so, but would probably spell the end of business as usual, unsettling people, states and markets. All of this is unfolding at a time when many of the world’s rich democracies face internal divisions, rising inequality and populist challenges at home and so are ill-equipped to lead.

Democracies face a trust deficit. This is especially apparent in the US where only 43 per cent of Americans have trust in US institutions, according to the 2022 Edelman Trust Barometer.

Internal threats to democracy also unsettle the promise of US global leadership at a time when concerted and determined leadership is needed to maintain a strong and united response to Russia, and to tackle global food insecurity and the energy, climate and debt crises. In addition, the failure to lead a global response that can help developing countries is feeding a trust deficit between rich and poor countries.

The midterms will reveal a greater truth about the future of the Republican Party. Even more so, it will reveal the values held by the American electorate. In the run-up to the 2020 US presidential elections, Europeans frequently said that they would not give Americans a pass if they voted for Donald Trump twice – and indeed only 17 per cent of those in European Union countries would have cast a vote for Trump if they could.

A Republican midterm victory in both the Senate and the House of Representatives would have ripple effects across the Atlantic at a time when the threat from Russia has intensified.

The US is judged around the world for what it does, but also for who it is. The perception that democracy is failing in America creates a permissive environment for aspiring autocrats. At a time when democracy has been in decline around the world for more than 15 years, it is essential that the US fix its own democracy and that it demonstrates to the rest of the world that democracy can deliver.

The midterms will signal to the world what Americans value, sending a message about what it can expect from the US.

This article was updated on October 31, 2022 to reflect developments such as early voting turnout, and the impact of the midterms on the 2024 presidential election, support for Ukraine and climate change spending.

US midterms: What to expect? Expert comment LJefferson 4 November 2022

The 2022 midterms have a heightened importance with long-term implications for the future of American democracy.

US voters will head to the polls on 8 November 2022 to cast their ballots for the midterm elections, which will see 35 of 100 Senate seats and all 435 seats in the House of Representatives up for re-election.

Midterm elections serve as a benchmark on voter’s approval of the sitting president’s party, but following a turbulent 2020 presidential election, with claims of a stolen election and voter fraud, the midterms have taken on a heightened importance with the processes and results having long-term implications for the future of democracy in the US.

When will we see results?

While many US voters expect to see results the night of an election, the complex voting process in the US often makes it difficult to ascertain the success of candidates in certain states after the polls close.

In Arizona, state laws allow 20 days for election officials to certify results while Nevada allows for additional time to count mail-in ballots following election day. Pennsylvania state laws prevent mail-in ballots from being counted before 7am on election day and the combined effect of counting in-person and mail-in ballots simultaneously, as well as the need to present votes to a state canvassing board could delay official results for weeks, and votes will not be officially certified by the state until 28 November.

In Georgia, the presence of a third-party candidate may lead to a run-off election if neither the Democrat or Republican contender receives over 50 per cent of the vote, which would take place on 6 December with results expected soon after.

Delays in determining election results may bolster claims made by Republican candidates that election results were fraudulent, especially if races are tight, as delays  counting mail-in ballots might cause results to differ over time. Early results favouring Republican candidates may also differ from the final tally as more mail-in ballots get counted, creating a ‘red mirage’, as the majority of Republican voters are expected to vote in-person, as seen in 2020.

In the vast majority of elections since World War II, the president’s party has often lost seats in the first midterm elections after taking office. While there have been exceptions and instances of the sitting party avoiding major losses during wartime, such as after the Gulf War and the 9/11 attacks, it’s unlikely Russia’s war in Ukraine will create the same rally around the flag effect.

Issues influencing voters

There are signs that US support for Ukraine on both sides of the aisle is starting to waver, as evidenced by the now recalled letter by the House Democratic Progressive Caucus pushing for a ceasefire and Republican House Leader, Kevin McCarthy’s recent comments about limiting US financial support for Ukraine.

US voters in general are more concerned with domestic issues rather than foreign policy, and both Democrats and Republicans have shaped their messaging around issues that will resonate with voters in key battleground states, with Democrats focusing heavily on abortion and reproductive rights and Republicans pushing the issues of crime and safety.

Democrats are hoping their focus on reproductive rights will motivate a higher turnout at the polls and have likely been encouraged by a recent referendum in Kansas where voters chose to protect abortion rights in the traditionally conservative state. In 2020, 52 per cent of the electorate in the swing state of Pennsylvania were female, and while not a huge majority, the difference could be enough to push the Democrats ahead.

Though the issue of abortion has gained more focus among Democratic voters, with 75 per cent of registered Democrats saying the issue was very important, 92 per cent of Republican voters rank the economy as their top issue.

The Senate race in Wisconsin, for example, was initially considered one of the Democrat’s most likely prospects for unseating an incumbent Republican senator, following US President Joe Biden’s win in the state in 2020.

Despite heavy fundraising from the Democratic party and a campaign visit by former US president Barack Obama, incumbent Senator Ron Johnson is now four points ahead of Democrat contender, Lieutenant Governor Mandela Barnes. A potential victory by Johnson, who has accused Barnes of being soft on crime and has shaped his messaging around growing the economy, may indicate whether  Democrats need to reshape their messaging ahead of the 2024 presidential election.

Threats of political violence

The risk of political violence in the US has increased in recent years, with many key officials under threat, as evidenced by the recent attack on US Speaker of the House, Nancy Pelosi’s, husband. A bulletin sent out by US agencies, including the Department of Homeland Security and the FBI, warned of attacks against not only political figures in the US, but also of attacks at locations like polling places, ballot box locations and voter registration sites.

The myth of a stolen election

Electoral integrity in 2022 has become especially significant, with over 300 candidates who believe the 2020 election was stolen up for election in various races across the United States.

The role of governors, secretaries of states and attorneys general (state officials charged with approving election results) has become a key issue in 2022. Proposals to give state legislatures the ability to certify election results, a role typically occupied by state officials, have already been made in Wisconsin, Pennsylvania and Arizona, all of which have Republican legislature majorities.

While these measures have not been successful thus far, a number of election deniers who would have the ability to influence how election results are certified are on the ballot for 2022. In Arizona, for example, Republican candidate for governor, Kari Lakes, and for attorney general, Abe Hamadeh have both been endorsed by Trump and have also supported his claims that the 2020 elections were fraudulent.

The Republican candidate for Arizona secretary of state, Mark Finchem publicly made calls to decertify Arizona’s electors, and was placed at receiving 49 per cent of votes in a poll conducted by CNN in early October. If Republicans are successful in both the state governor and secretary of state races, the role of the attorney general in certifying the election results in a state Biden closely won in 2020 becomes ever more crucial given their ability to govern how elections are run in the state, as well as their ability to challenge certification in court.

Japan’s G7 leadership: Defending the liberal order amid crisis 28 February 2023 — 9:00AM TO 10:00AM Anonymous (not verified) 20 February 2023 Online

How G7 countries should best respond to global economic and security challenges in order to defend the liberal international order.

In May 2023 Japan hosts the G7 summit in Hiroshima, where leaders of the US, UK, Canada, France, Germany and Italy come to discuss the most urgent challenges facing the world.

This year’s summit takes place against a backdrop of continued global economic and political instability from the war in Ukraine to intensifying competition between China and the West.

The speakers discuss Japanese Prime Minister Fumio Kishida’s priorities at the summit and consider how G7 countries should best respond to global economic and security challenges in order to defend the liberal international order.

This event is the third of a three-part series held in partnership with Japan House London.

Watch the first event which looked at Africa-Japan relations here, and the second event, on the UK and Japan’s engagement with Southeast Asia, here.

World in brief: Ukraine and nuclear proliferation to dominate G7 The World Today mhiggins.drupal 28 March 2023

Following Russia’s ongoing intimidation, Japan will use its presidency of the G7 – and its history – to prioritize the dangers of nuclear threats, writes James Orr.

Two issues are expected to dominate the agenda as Japan hosts the G7 summit in Hiroshima from May 19-21. Central to talks will be the conflict in Ukraine, with member states eager to highlight a message of unity and resolve in the face of Russia’s continuing aggression.

Fumio Kishida, Japan’s prime minister, made an unannounced visit to Kyiv on March 21, meeting the Ukrainian president Volodymyr Zelenskyy.  This coincided with a visit to Moscow by China’s leader Xi Jinping, who described Russian president Vladimir Putin as a friend and partner.

‘Absolutely unacceptable’

Hosting the G7 summit in Hiroshima is significant, too, with Kishida expected to emphasize the ‘absolutely unacceptable’ threat of nuclear proliferation. Ongoing tensions between China and Taiwan, together with recent North Korean ballistic missile tests, have heightened fears of a breakdown in security in the region.

Meanwhile, President Vladimir Putin’s menacing references to the use of nuclear weapons in Ukraine has raised the prospect of a potentially devastating conflict with NATO. ‘Kishida’s principal goal for the presidency of the G7 is to try to draw the world away from the path of destruction that is another nuclear conflict,’ said Duncan Bartlett, a research associate at SOAS, the School of Oriental and African Studies, in London.

‘Early last year, Putin warned of terrible consequences if NATO and the West interfered in the Ukraine conflict, and that was widely seen as being a nuclear threat. North Korea is also pursuing its nuclear weapons programme, and in February an intercontinental ballistic missile went into the sea just near the northern Japanese island of Hokkaido,’ said Bartlett.

After Russia invaded Ukraine in February 2022, Kishida has taken a firm position on Putin, in line with his G7 peers. President Zelenskyy has addressed the Japanese parliament via video link and Dmytro Kuleba, Ukraine’s minister of foreign affairs, was invited by his Japanese counterpart to a G7 meeting held during the Munich Security Conference earlier this year.

Kishida committed $600 million in financial support to Ukraine and his government may well announce the provision of further non-lethal assistance to Zelenskyy at the summit. The country’s constitution effectively outlaws the export of deadly weapons to foreign forces. On his visit to Kyiv, Kishida promised a further $30 million to Ukraine.

‘Kishida has revised key defence documents and is pursuing a radical and controversial expansion of Japan’s defence budget and capabilities,’ said Hugo Dobson, Professor of Japan’s International Relations at the University of Sheffield.

‘He and his G7 partners have signed historic defence agreements, pledged to strengthen ties or declared the inseparability of their security in light of actual conflict in Ukraine and potential conflict in East Asia. Kishida has linked the two by emphasizing that Ukraine today may be East Asia tomorrow,’ said Dobson.

Aside from security matters, Kishida will at the summit address issues on clean energy, climate change, global health and boosting multilateral cooperation to drive post-pandemic economic recovery.

Invitation to Nagasaki

He is understood to have invited President Joe Biden to visit Nagasaki, where the second of America’s two atomic bombs is estimated to have killed 60,000 people in August 1945. No sitting US president has ever visited the city, and Kishida, who grew up in Hiroshima, may see the visit as an opportunity to boost his flagging domestic approval ratings. It may also serve as a timely reminder to Russia and others that the G7 opposes any future nuclear weapon use.

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