DNA polymerase from bacteriophage T7 undergoes large, substrate-induced conformational changes that are thought to account for high replication fidelity, but prior studies were adversely affected by mutations required to construct a Cys-lite variant needed for site-specific fluorescence labeling. Here we have optimized the direct incorporation of a fluorescent un-natural amino acid, (7-hydroxy-4-coumarin-yl)-ethylglycine, using orthogonal amber suppression machinery in Escherichia coli. MS methods verify that the unnatural amino acid is only incorporated at one position with minimal background. We show that the single fluorophore provides a signal to detect nucleotide-induced conformational changes through equilibrium and stopped-flow kinetic measurements of correct nucleotide binding and incorporation. Pre-steady-state chemical quench methods show that the kinetics and fidelity of DNA replication catalyzed by the labeled enzyme are largely unaffected by the unnatural amino acid. These advances enable rigorous analysis to establish the kinetic and mechanistic basis for high-fidelity DNA replication.

Homologous recombination (HR) repairs DNA double-strand breaks using intact homologous sequences as template DNA. Broken DNA and intact homologous sequences form joint molecules (JMs), including Holliday junctions (HJs), as HR intermediates. HJs are resolved to form crossover and noncrossover products. A mismatch repair factor, MLH3 endonuclease, produces the majority of crossovers during meiotic HR, but it remains elusive whether mismatch repair factors promote HR in nonmeiotic cells. We disrupted genes encoding the MLH3 and PMS2 endonucleases in the human B cell line, TK6, generating null MLH3−/− and PMS2−/− mutant cells. We also inserted point mutations into the endonuclease motif of MLH3 and PMS2 genes, generating endonuclease death MLH3DN/DN and PMS2EK/EK cells. MLH3−/− and MLH3DN/DN cells showed a very similar phenotype, a 2.5-fold decrease in the frequency of heteroallelic HR-dependent repair of restriction enzyme–induced double-strand breaks. PMS2−/− and PMS2EK/EK cells showed a phenotype very similar to that of the MLH3 mutants. These data indicate that MLH3 and PMS2 promote HR as an endonuclease. The MLH3DN/DN and PMS2EK/EK mutations had an additive effect on the heteroallelic HR. MLH3DN/DN/PMS2EK/EK cells showed normal kinetics of γ-irradiation–induced Rad51 foci but a significant delay in the resolution of Rad51 foci and a 3-fold decrease in the number of cisplatin-induced sister chromatid exchanges. The ectopic expression of the Gen1 HJ re-solvase partially reversed the defective heteroallelic HR of MLH3DN/DN/PMS2EK/EK cells. Taken together, we propose that MLH3 and PMS2 promote HR as endonucleases, most likely by processing JMs in mammalian somatic cells.

The Phillies continued to bolster their infield depth on Friday by signing versatile veteran Sean Rodriguez to a Minor League contract with an invite to big league Spring Training, MLB.com has learned.

On this opening week of Spring Training, all 30 Major League teams have one thing in common: optimism. Here's an optimism cheat sheet for each of them.

Phillies manager Gabe Kapler has a little advice for the players who could be impacted most if the team signs Bryce Harper or Manny Machado.

The Angels agreed to terms with right-hander reliever Daniel Hudson on a Minor League deal to add bullpen depth, a source confirmed to MLB.com on Friday.

Since debuting in 2011, center fielder Mike Trout has been far and away the best player in the Majors, but the Angels have reached the postseason just once in his eight-year career.

Shohei Ohtani remains a must-watch player for Angels fans in 2019, and his recovery from Tommy John surgery will be worth monitoring throughout the season as he prepares to pitch again in '20.

The Angels announced their Minor League coaching staffs on Saturday, including former Major League catcher Lou Marson being named the new manager of Triple-A Salt Lake and former big leaguer David Newhan as the new skipper at Double-A Birmingham.

The Angels added a veteran lefty reliever, as Dan Jennings officially signed a Minor League deal on Saturday and joined the club for workouts at the club's Spring Training complex. Jennings will earn $1 million, plus incentives, if he makes the club.

On this opening week of Spring Training, all 30 Major League teams have one thing in common: optimism. Here's an optimism cheat sheet for each of them.

Zimbabwe Ahead of the Elections: Political and Economic Challenges 8 May 2018 — 10:00AM TO 11:00AM Anonymous (not verified) 3 May 2018 Chatham House, London

The upcoming elections in Zimbabwe will be the first since 2000 in which former president Robert Mugabe and long-time opposition leader Morgan Tsvangirai are not on the ballot paper. A key electoral issue for many voters will be the economy: recent years have been marked by high unemployment rates, chronic cash shortages and mounting public debt. Although this has traditionally been a strong campaigning issue for the opposition, President Emmerson Mnangagwa has fast-tracked comprehensive economic reforms.

At this event, Nelson Chamisa, MDC Alliance presidential candidate, will discuss his efforts to build a united opposition coalition with a strong message, the steps needed to ensure a free and fair election can take place, and the role that international partners can play in Zimbabwe’s democratic process.

Improving Economic Management for Sustainable Growth in Zambia 13 July 2018 — 9:00AM TO 10:00AM Anonymous (not verified) 19 June 2018 Chatham House, London

THIS EVENT IS POSTPONED.

High levels of infrastructure investment funded by commercial loans, against a backdrop of subdued economic growth, resulted in an increase in Zambia’s public external debt from $8.7 billion in 2017 to $9.3 billion in March 2018.

In June 2018 Zambia’s Ministry of Finance announced new austerity measures aimed at reducing the country’s debt burden, as part of an ongoing reform agenda that is hoped to stabilise the economy.

In the meantime Zambia grapples with severe social and development challenges. Decreased spending in health, education and social protection, and poor access in rural areas, have already left Zambia ranked 139th out of 188 countries in the UNDP’s 2016 human development index.

At this meeting Margaret Mwanakatwe, minister of finance, discusses the government’s financial reform agenda, its engagement with creditors and IFIs, and plans for generating sustainable growth and job creation.

Economic Reform and Recovery in Zimbabwe 8 October 2018 — 2:30PM TO 3:30PM Anonymous (not verified) 4 October 2018 Chatham House, London

Zimbabwe Futures 2030: Policy Priorities for Economic Expansion 28 February 2019 — 9:00AM TO 1:00PM Anonymous (not verified) 7 February 2019 Harare, Zimbabwe

This roundtable draws on current best practice and senior level expertise to identify policy options for long term economic expansion in Zimbabwe and pathways for inclusive development.

Participants discuss the necessary policies and business strategies to enable and support the effective implementation of the Transitional Stabilization Programme and longer term national development plans.

The discussions highlight requisite conditions for a business-driven and inclusive process towards Zimbabwe’s long-term economic recovery.

This event was held in partnership with the Zimbabwe Business Club and Konrad Adenauer Stiftung.

Mine Action in Angola: Clearing the Legacies of Conflict to Harness the Potential of Peace Other resource sysadmin 14 June 2019

This publication draws on and updates the briefing note published following a meeting of the All- Party Parliamentary Group (APPG) on Angola on 26 April 2017. It also incorporates insights from a Chatham House Africa Programme conference session on the legacies of the Angolan Civil War, held on 23 March 2018; and draws on the Africa Programme’s research into conservation-driven development models in Southern Africa.

Almost two decades after the end of its civil war, Angola remains one of the most heavily landmine-contaminated countries in the world. The Angolan government has committed to clearing its landmines by 2025, and there is constructive collaboration between the government and mine clearing agencies in this endeavour, but the target will be achievable only if a decline in funding from international donors is reversed. International funding for mine clearance in Angola fell by more than 80 per cent between 2005 and 2017, and this sharp drop in external support has compounded the impact on domestic funding for national clearance efforts as a result of the downturn in prices for Angola’s main export commodities.

The national mine action agency, the Comissão Nacional Intersectorial de Desminagem e Assistência Humanitária (CNIDAH), is supported by the Mines Advisory Group (MAG), Norwegian People’s Aid (NPA) and the HALO Trust. By 2017, 15 years after the end of the civil war, these organizations had collectively helped clear 56 per cent of known landmine-contaminated land. State-led demining has focused principally on clearing areas designated for infrastructure projects. Now, it is critical that humanitarian demining in largely agricultural and conservation areas is prioritized to bring to an end the daily threat to Angola’s rural poor – as well as to the country’s livestock and wildlife – of injury or death as a result of landmine accidents.

Angola has some of the world’s most important remaining wilderness, including the tributary system for the unique Okavango Delta, and the country has the potential to host one of the most diverse wildlife populations on the continent. However, the presence of landmines and other remnants of the civil war render large areas of the country unsafe both for wildlife and for the local people, whose ability to derive a sustainable livelihood from their natural environment is fundamental to its protection.

Wildlife and tourism provide important economic opportunities for diversification beyond an oil-dominated economy. Critically, Angola’s economic diversification and development objectives can only be achieved if the landmines that prohibit access to land for agriculture, mining, tourism and wildlife are cleared.

There are economic opportunities for released land in the most heavily mined provinces of Cuando Cubango and Moxico. Already, some new funding for mine action in Angola, if upscaled or matched by international donors, could be transformative for its people, and for the conservation of the region’s vital biodiversity.

Zimbabwe Futures 2030: A Vision for Inclusive Long-Term Economic Recovery 10 October 2019 — 10:00AM TO 12:15PM Anonymous (not verified) 5 September 2019 Harare, Zimbabwe

In its Vision 2030, the government of Zimbabwe committed itself to facilitating an open market and stable economy through strategies such as the Transitional Stabilization Programme (TSP) and new industrialization policy. The private sector is pivotal to these objectives and creating an environment conducive to inclusive and job-creating economic growth. Economic growth can only be achieved with a conducive policy environment and government support to underpin markets with provision of public goods, entrepreneurial incentives and protect contract enforcement and dispute resolution mechanisms.

This event will launch a new Chatham House Africa Programme publication on Zimbabwe’s Vision 2030. The paper is the culmination of an inclusive research process that has drawn on senior private sector expertise, civil society, academics, technocratic elements of government and other experts to develop policy recommendations that will support inclusive economic growth in Zimbabwe.

This event is held in partnership with the Zimbabwe Business Club and Konrad Adenauer Stiftung (KAS). It is supported by KAS and the Dulverton Trust.

Economic Recovery and Anticorruption in South Africa: Assessing Progress on the Reform Agenda 4 December 2019 — 3:00PM TO 4:00PM Anonymous (not verified) 25 November 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

South Africa has significant economic potential based on its resource endowment, quality human capital and well-developed infrastructure compared to the region. However, the country’s economic growth rate has not topped 2 per cent since 2013, and in 2018, was below 1 per cent. This has put a strain on citizens and communities in a country that still suffers from structural inequality, poverty and high unemployment. Economic recovery and anti-corruption were the central pillars of President Cyril Ramaphosa’s 2019 electoral campaign and he has set an investment target of $100 billion. However, voters and investors alike are demanding faster and more visible progress from the country’s enigmatic leader who has a reputation for caution and calculation.

At this event, Professor Nick Binedell will discuss the progress of and opposition to the president’s economic reform agenda and the opportunities for international investment to support long term inclusive and sustainable growth in South Africa.

Attendance at this event is by invitation only.

Angola's Business Promise: Evaluating the Progress of Privatization and Other Economic Reforms 21 January 2020 — 2:30PM TO 3:30PM Anonymous (not verified) 16 January 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE

Minister Nunes Júnior will discuss the progress of the Angolan government’s economic stabilization plans and business reform agenda including the privatization of some state-owned enterprises. These reforms could expand Angola’s exports beyond oil and stimulate new industries and more inclusive economic growth.

THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED.

POSTPONED: Pursuing Economic Reform and Growth in South Africa: the view from the African National Congress 18 March 2020 — 10:30AM TO 11:30AM Anonymous (not verified) 3 March 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE

The government of South Africa is pursuing a programme of reform to revitalize the economy, strengthen institutions and combat corruption. The State of the Nation Address (SONA) on 13 February and the budget speech of 26 February represent the most significant articulation of the government’s economic strategy. Central to this is the government’s plans for the energy sector, which is fundamental for reviving the economy, and the reform of State Owned Enterprises (SOEs). But questions remain about possible divergence of the approach taken by government ministers from the policy position of the ruling party, the African National Congress (ANC), and what this might mean for the sustainability and progress of reform.

At this event, Paul Mashatile, Treasurer General of the ANC, will discuss the party’s assessment of reform efforts to date and priorities for delivering on inclusive growth.

PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE.

Webinar: South Africa's Economic Recovery Beyond COVID-19 27 May 2020 — 1:00PM TO 2:00PM Anonymous (not verified) 18 May 2020

South Africa's Economic Outlook 20 August 2020 — 12:00PM TO 1:00PM Anonymous (not verified) 11 August 2020 Online

South Africa’s long mooted economic reforms have been slow to materialize. The economy had fallen into recession even before the COVID-19 pandemic, and had been stripped of its international investment grade rating. The reserve bank is now forecasting a contraction in GDP of over seven percent for 2020.

There are significant questions around the role of the state in the economy, the level of intervention, and its affordability, with key government figures sceptical of rapid market reforms. The mandate and independence of the South African Reserve Bank has also been a subject of public debate. The IMF has approved a US$4.3 billion emergency financial assistance package to help mitigate the health and economic shock to the country. But it has also made clear that there is a pressing need to ensure debt sustainability and implement structural reforms to support recovery and achieve sustainable and inclusive growth.

At this event, Lesetja Kganyago, the governor of the South African Reserve Bank (SARB), gives his assessment of the expected trajectory of the South African economy in the short and medium term. He discusses the IMF package and the implications for economic reform, and the role of the reserve bank in delivering sustainable and inclusive growth.

Zimbabwe's Economy During the Coronavirus Pandemic and Beyond 8 September 2020 — 10:00AM TO 11:30AM Anonymous (not verified) 26 August 2020

COVID-19 has had a devastating effect on Zimbabwe’s already floundering economy. Important foreign currency earning industries have virtually stopped, and across the country livelihoods are at risk and an increasing number of people are reliant on government grants.

Businesses are having to become more flexible but are constrained by a weak policy environment and lack of confidence in the economy. Since 2017, the government has been pursuing an economic reform agenda and Transitional Stabilization Programme (TSP), which was scheduled for completion by the end of 2020. The deepening challenges highlight the need to accelerate economic reform and build confidence in order to achieve sustainable and inclusive growth.

At this webinar, speakers discuss the measures that government, businesses, and individuals are adopting in response to the COVID-19 economic challenge, and the policies required for recovery.

Read a meeting summary

This webinar is held in partnership with the Konrad Adenauer Stiftung.

South Africa's Economic Reform and Employment in the Context of the Coronavirus Pandemic 3 September 2020 — 3:00PM TO 4:00PM Anonymous (not verified) 26 August 2020 Online

President of COSATU, Zingiswa Losi, discusses the organization’s priorities for protecting jobs and workers, and working with other stakeholders to build a sustainable post-pandemic economy.

Employment in South Africa fell by an estimated 18 per cent between February and April 2020. The measures imposed to control the spread of COVID-19 suffocated an already weak economy and unemployment has hit a new high.

The stated aims of the government’s economic reform plans include the support of job creation in labour intensive industries, but the reform of the state and rebalancing of the economy and fiscus could lead to further job losses in state agencies and enterprises.

Protecting jobs while ensuring the health and safety of workers are dual priorities, and require the joint commitment and ‘social compact’ of labour, business and government.

Zimbabwe’s Economic Governance and Regional Integration 17 November 2020 — 12:00PM TO 1:30PM Anonymous (not verified) 6 November 2020 Online

Panellists discuss policy and governance for long-term economic prosperity in Zimbabwe, reflecting on the role of institutional change and regional integration in the context of the shocks caused by the coronavirus pandemic.

At this virtual event, panellists and participants will discuss policy and governance for long-term economic prosperity in Zimbabwe, reflecting on the role of institutional change and regional integration.

The government of Zimbabwe has emphasized its commitment to economic reform and its ambition to achieve upper-middle-income status by 2030, but there are considerable challenges to overcome.

The COVID-19 pandemic has exacerbated existing economic fragility. Improving the business climate to attract international private-sector investment will be contingent on clear, consistent and coherent policy and implementation, including targeting abuse and corruption.

Zimbabwe has, in recent years, successfully strengthened its regional trade integration, although some trade frictions remain. This is an important factor not only for catalysing economic growth in Zimbabwe, but for supporting regional prosperity and post-COVID recovery.

This webinar is the second in a series of events held in partnership with the Konrad Adenauer Stiftung on Zimbabwe’s economic reform and recovery.

Read a meeting summary

This event will also be broadcast live on the Africa Programme Facebook page.

Angola Forum 2021: Policy options to support economic recovery in Angola 7 October 2021 — 2:00PM TO 5:00PM Anonymous (not verified) 22 September 2021 Online

Speakers discuss policy options to support economic recovery in Angola as the country transitions away from a state-led oil economy to a private-sector-led growth model.

The government of Angola has made some progress on a range of policies targeting macroeconomic stability and structural reform. However, the country has been suffering from a recurring economic recession for six consecutive years, with the last positive annual GDP growth rate posted in 2015 at 0.9 per cent.

The national budget remains dependent on oil revenue, leaving the country highly exposed to volatile oil prices particularly during the COVID-19 pandemic. While revenues collapsed, increased spending was needed to respond to the health crisis and estimates of Angola’s debt spike range from 130 to 150 per cent of its GDP by the close of 2020.

At this virtual Angola Forum, speakers discuss policy options to support economic recovery in Angola as the country transitions away from a state-led oil economy to a private-sector-led growth model.

The Forum launches the English translation of the Angola Economic Report 2019-20 by the Centro de Estudos de Investigação (CEIC) of the Catholic University of Angola in partnership with the Konrad-Adenauer-Stiftung (KAS), and the findings of Afrobarometer’s first ever survey in Angola, Ovilongwa – Estudos de Opinião Pública, which interviewed 2,400 adult Angolans and sampled individual perceptions on democracy and economic reform in Angola.

This event will be held in English and Portuguese with simultaneous interpretation.

The Forum will also be broadcast live on the Africa Programme Facebook page.

Zambia’s political and economic reform and recovery 5 November 2021 — 11:30AM TO 12:30PM Anonymous (not verified) 2 November 2021 Chatham House and Online

At this event, HE Hakainde Hichilema, president of the Republic of Zambia, discusses his vision for Zambia’s development and long-term political and economic reform and recovery.

Zambia’s new administration, following the general elections of August 2021, faces a daunting challenge of reversing economic contraction, lowering income-eroding inflation, and addressing the unsustainable national debt.

The country has been one of the few to seek debt restructuring under the G20’s new Common Framework for Debt Treatments, and its immediate priorities include a prospective agreement with the International Monetary Fund (IMF).

Young Zambians are eager for jobs and improved living standards. But the government’s ambition to create more jobs and achieve middle-income status will depend on both attracting new investment into its copper sector and pursuing a programme of economic diversification supporting growth beyond the mining industry.

Addressing these economic concerns will also need to be supported by a programme of political reform and rehabilitation of citizens’ trust in the state.

Angola forum 2022: Prospects for Angola's social and economic future 15 December 2022 — 1:00PM TO 4:30PM Anonymous (not verified) 28 November 2022 Online

At this online Angola forum, experts will discuss Angola’s social and economic future, and what to expect from 2023.

At this virtual Angola Forum, speakers will discuss Angola’s social and economic future and what to expect from 2023.

Angola experienced positive economic momentum in 2022 allowing it to exit its six-year recession, with the economy taking centre stage in the August national multiparty elections. Increased oil prices and high levels of production have driven Angola’s economic growth and improved macroeconomic conditions, as well as helping the country to reduce its public debt to 56.5 per cent of Gross Domestic Product (down from 79.7 per cent in 2021).

However, a global economic downturn in 2023, with increased inflation, means Angola’s re-elected MPLA government will need to focus on job creation, greater economic inclusivity and diversifying away from an oil-led economy. It will also require Angola to navigate its international partnerships more effectively in this era of heightened geopolitical rivalries.  

At this online Angola forum, experts will discuss Angola’s social and economic future and what to expect from 2023. Speakers will reflect on the social and economic trends seen in 2021-22 and explore election trends, human rights and international relations.

This Angola Forum is supported by the Konrad-Adenauer-Stiftung.

American democracy in 2022: Trump, insurrection, and midterm elections 31 October 2022 — 2:00PM TO 3:00PM Anonymous (not verified) 7 October 2022 Online

How much has Donald Trump changed US politics and democracy, and will Trump and ‘Trumpism’ be more or less significant in the years ahead?

America’s democracy is divided, polarized and fragmenting. Inequality and internal division have a long history. But Trump’s lasting influence on the Republican party, and politics more broadly, continues to leave a mark. Repeated denials of President Joe Biden’s 2020 election win, wrapped in claims of electoral fraud, have eroded faith in the democratic institutions.

The memories of 6 January are still fresh, reminding all of the dangers posed by such actions. All told, America’s democracy has taken a beating in recent years.

To help make sense of the events over recent years and consequences for the coming mid-terms, Peter Baker and Susan Glasser (authors of The Divider: Trump in the White House 2017–2021) walk through in detail how the American politics of today has been arrived at.

Key questions discussed include:

• What has been learned from the January 6 Committee?

• Is there a likelihood of a similar event in the future?

• When and how will Trump lose his influence over the Republican party? 

• What are the broader ramifications of the Trump era?

• What did the events of 6 January mean for America’s relationships globally?

 As with all Chatham House member events, questions from members drive the conversation.

Read the transcript. 

Middle East and great power competition 28 November 2022 — 12:00PM TO 1:00PM Anonymous (not verified) 25 October 2022 Chatham House and Online

Experts discuss how the Middle East is changing in a fast-moving geopolitical environment.

The war in Ukraine and great power competition define not only global politics but also regional ones. The Middle East is a microcosm for observing how the great power rivalry informs regional affairs.

OPEC+’s decision to reduce oil supply to international markets and many regional states’ balancing act between the West and Russia, for that matter China as well, are only a few recent policy choices that clearly illustrate how the global and regional levels interact with each other.

Plus this is now a region in which the US has downsized its security commitments, whereas Russia has increased its footprint in regional security and China in economy.

This event tries to unpack how the great power rivalry and the war in Ukraine affect regional politics and how the Middle East adjusts itself to this new phase in global politics.