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Iran Nuclear Deal

Pamela Falk, CBS News Foreign Affairs Analyst, discusses a diplomatic deal reached to stop Iran from making a nuclear bomb and avoid a possible war with a regional power in the Middle East.




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Modified Nucleic Acids

Location: Electronic Resource- 




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Toward consistent design evaluation of nuclear power piping by nonlinear finite element analysis

Location: Engineering Library- TK9211.7.Z46 2015




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Earthquake risks and rising costs: The price of operating California's last nuclear plant

The plant supplies 6% of California's power, yet critics charge the facility is too expensive and too dangerous to continue operating.




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To find masked mob members who attacked UCLA camp, police are using Jan. 6 tactics

Campus police are scanning hundreds of images and using facial-recognition technology to identify the attackers. Similar tools were used to identify Jan. 6 attackers.




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Amazon, Google tap into nuclear power to fuel data centers and AI push

E-commerce giant Amazon joins Google and other tech companies in investing in nuclear power they plan to use in the race to build new AI-powered products.




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Gene Proximity to Nuclear Speckles Drives Efficient mRNA Splicing

Nuclear architecture investigation provides insights into the role of nuclear bodies in RNA processing.



  • News
  • News & Opinion

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A Small Genome Editing Nuclease Packs a Big Punch

For the past decade, scientists have relied almost exclusively on CRISPR-Cas systems for genome editing. Now, a smaller but equally efficient nuclease is here to compete. 



  • News
  • News & Opinion

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Chris Hall: There's no path to net-zero without nuclear power, says O'Regan

Minister of Natural Resources Seamus O'Regan says Canadians have to be open to more nuclear power generation if this country is to meet the carbon emissions reduction targets it agreed to five years ago in Paris.



  • Radio/The House

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Suing Facebook over hate speech, nuclear fusion in sci-fi, invasive Strep A, British 'pantos', Tantura & more

Facebook faces a $2 billion lawsuit over hate speech; Expanse co-author Ty Franck on the role of nuclear fusion in sci-fi universes and the real world; making sense of the connection between respiratory virus outbreaks and invasive Strep A bacterial infections; a theatre director's bid to bring British holiday 'pantos' to Canada; Israeli documentary Tantura confronts an alleged massacre in a Palestinian village; and more.



  • Radio/Day 6

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Microsoft, Google and Amazon turn to nuclear energy to fuel the AI boom




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SPIA exhibit and programming are directing attention to nuclear weapons as a scholarly and policy issue

“Close Encounters: Facing the Bomb in a New Nuclear Age” is on display at SPIA’s Bernstein Gallery through Oct. 25. 




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Which rural area will take the UK’s nuclear waste?

The UK's nuclear waste needs a permanent home - but finding a community willing to take it is tricky.




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Nuclear-powered aircraft carriers would give China's growing navy new reach, and researchers say it's working on the reactor to power one

A nuclear-powered aircraft carrier, like American carriers, would be a major jump for China, giving its navy a global reach.




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News24 Business | Google to use small nuclear reactors for AI-intensive data centres

Google is investing in the development of the next generation of nuclear power, backing a company that’s building small modular reactors and agreeing to purchase energy once the sites start supplying US grids.




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A feminist and postcolonial approach to nuclear politics

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.

Gendered images, symbols and metaphors play a key role in narrating, imagining and criticizing, but also sustaining, the nuclear-armed world.

Hebatalla Taha, Assistant Professor of International Relations, Department of Political Science, American University in Cairo

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.

Bipartisan support for deep engagement is at least as strong today as it has been at any other point since the end of the Cold War.

Jeffrey A. Friedman, Associate Professor of Government, Dartmouth College; Visiting Fellow at the Institute for Advanced Study, Toulouse

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.

It was not the Chinese party-state’s grand strategy, or even a purposeful effort, to indebt Zambia.

Deborah Brautigam, Bernard L. Schwartz Professor of International Political Economy and Director, China Africa Research Initiative, Johns Hopkins University School of Advanced International Studies (SAIS)

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.




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The new geopolitics of nuclear power

The new geopolitics of nuclear power The World Today mhiggins.drupal 27 September 2022

States may be looking to build or restore nuclear plants, but they will need to bypass Chinese and Russian sector dominance, says Sung-Mi Kim.

Against the backdrop of a worldwide energy crisis, the global nuclear market may be seeing a renaissance with growing interest in nuclear energy.

Sceptics are being compelled to rethink the trade-off calculus of nuclear power for the first time since the 2011 Fukushima disaster, which prompted countries to postpone or phase out nuclear power. The nuclear option is again being seen as a way of boosting a nation’s energy autonomy and its ability to weather the volatility caused by unpredictable Russian gas supplies.

Russia supplies more than a third of global nuclear fuel-related services


Adoption or expansion of nuclear energy capability will not allow a country to be free of Russian influence entirely given its dominant presence in the global nuclear sector. Rosatom, Russia’s state-controlled power corporation, and its subsidiaries, make Russia the leading exporter of nuclear power plants. Russia also supplies more than a third of the global fuel-related services, namely uranium conversion and enrichment. Notably, Russia has been capable of building these into an attractive financial package for importing countries, backed by generous state support.

Like Russia, Chinese government-owned nuclear corporations have started to make forays into export markets as part of its Belt and Road Initiative and ‘Go Out’ policy, which encourages companies to invest overseas. Both China and Russia have a strong comparative advantage in offering competitive state-backed financing schemes for nuclear products and services.


In the meantime, nuclear investment in advanced economies in the West have tended to remain stagnant. The International Energy Agency reports that of the 31 reactors built in the past five years, 27 are of Russian or Chinese design.

Given current market conditions and the technological complexity of the nuclear fuel cycle, new entrants will find it difficult to acquire energy autonomy through nuclear power. They will have to rely on foreign suppliers to build, operate and maintain their nuclear plants and supporting infrastructure. It typically takes a decade to build a nuclear plant and start generating electricity, and nuclear plant deals are built on a decades-long commitment of the parties to forge a political, technical, regulatory and scientific partnership that goes beyond purely commercial terms.

Nuclear export, therefore, is often a long-term, whole-of-the-government effort involving diplomatic skills and geopolitical calculations, and is subject to global oversight to ensure the peaceful use of nuclear energy.

The US is building strategic nuclear partnerships

In response to the Russian and Chinese dominance of the civilian nuclear sector, American nuclear industries are asking the government to streamline the export-licensing process and provide them with support. The US government is also establishing strategic partnerships with nuclear-capable allies such as South Korea to win procurement contracts. South Korea has recently made a U-turn in its nuclear policy. Its new president Yoon Suk-yeol intends to revive the role of nuclear power to help meet the country’s climate targets and has vowed to export 10 nuclear power plants by 2030.

In Japan, where nuclear energy production was halted after the Fukushima nuclear meltdown, a new policy platform was launched in 2019 to enhance public-private collaboration for nuclear research and development.

Intensifying geopolitical tensions between the US and its allies on one side, and Russia and China on the other, will inevitably affect nuclear market dynamics. Domestic economic slowdowns and international sanctions will be a stress test for the export potential of Russia and China.

For instance, in May 2022, Finland eliminated Rosatom from its consortium to build a nuclear power plant, citing delays and increased uncertainties stemming from the invasion of Ukraine. In 2020, Romania cancelled its nuclear deal with China, instead securing an agreement with the US to build two more reactors for its Cernavoda plant. The decision was seen as a move to align Romania with US intentions to sideline China.


 In March 2022, when the Czech Republic officially launched a tender to build a new reactor at the Dukovany nuclear plant, Rosatom and Chinese state-controlled nuclear exporter CGN have been excluded from the tender on security grounds.

As countries try to wean themselves off price-volatile gas and decarbonize their economies to meet climate targets, new commercial opportunities are opening up for the nuclear industry. At least 15 countries are building reactors, according to the World Nuclear Association. Some, such as China, are building more than one.

More than 30 countries are considering, planning or starting a nuclear programme. There is also a growing need for replacing or extending the lives of ageing reactors. It is in this context that the commercial, geopolitical and regulatory aspects of nuclear energy will play an increasing role in the  geopolitical contest for money and influence.




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Nuclear proliferation in a fragmenting world

Nuclear proliferation in a fragmenting world 13 September 2022 — 1:00PM TO 2:00PM Anonymous (not verified) 5 September 2022 Online

Where does the Treaty on the Non-Proliferation of Nuclear Weapons (NPT) stand in 2022?

With the war in Ukraine and China–US tensions rising, the threat of a nuclear arms race has never been as high since the Cold War.

Global efforts to control the appropriation and use of nuclear weapons are strained with the war in Ukraine, US–Russia and US–China tension, Iran on the nuclear threshold, instability in Pakistan and the ongoing threat from North Korea.

The Review Conference of the NPT that took place in New York this August sought to deal with the multiple nuclear threats, but new missile technology such as hypersonic glide vehicles and torpedoes are not covered by a treaty.

Russia and the US are in a development phase for a host of new technologies and delivery systems, especially after both withdrew from various arms-control treaties in the 2000s and 2010s. Now the nuclear stockpile is growing again and major superpowers are adopting confrontational geostrategic positions.

As the world’s established orders and system fragment, there is a possibility the nine countries with confirmed nuclear weapons could grow. Events in Ukraine highlight the need for a new, modern agreement on nuclear weapons control, needed today more than ever.

The panel of experts discuss key questions including:

  • What did ‘RevCon’ in New York tell us about the adoption or update to the NPT?

  • Will the war in Ukraine deter or prevent any agreement between nations or does nuclear weapons control represent an area of potential multilateral harmony?

  • Are we likely to see a new arms race akin to the Cold War? Where does China fit into this race?

  • How has technology changed the arms control landscape?

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




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Nuclear stability for all put at risk by Putin's speech

Nuclear stability for all put at risk by Putin's speech Explainer NCapeling 22 February 2023

Explaining the risks of Russia’s decision to suspend the New START nuclear treaty with the US, and the wider implications for international relations.

Why is New START important?

Following the collapse of the Intermediate-range Nuclear Forces treaty (INF), New START is the only remaining nuclear arms control treaty between the US and Russia.

This means that without it there would be no limits on numbers or the type of Russian and US deployed nuclear warheads. The limits set under New START are lower than those set under its predecessor, the Strategic Arms Reduction Treaty (START).

It is also important for maintaining some form of strategic arms control between Russia and the US. The treaty provides the US and Russia with mechanisms for transparency and confidence-building, for instance through regular biannual data exchanges, as well as measures for verification.

What is Russia able to do next after suspending participation?

President Vladimir Putin’s decision to suspend its participation could pave the way for Russia to increase the number of deployed warheads, delivery vehicles and launchers, potentially exceeding the limits placed on numbers under the new START.

Putin stated he would resume testing of nuclear weapons if the US resumed – Russia is a full state party to the nuclear Comprehensive Test Ban Treaty (CTBT) negotiated in 1996, as is the UK and France. The US has signed, as has China, but neither state has yet ratified the treaty.

This is likely to have wider implications for progress on nuclear non-proliferation under the Treaty on the Non-Proliferation of Nuclear Weapons (NPT), as well as the wider international security treaty regime.

Other countries required to ratify the treaty for it to enter into force include Egypt, India, Iran, Israel, North Korea, and Pakistan.

Although the US is modernizing its nuclear weapons forces, there is no need – or plan – for the US to test nuclear warheads, and it is the same for the UK and France.

Concerns are now rising that Russia could point to no-fissionable yield experiments – which are allowed under the treaty and which the US and other nuclear weapons possessors conduct primarily for safety purposes – and then falsely declare those to be nuclear weapons tests, thus paving the way for a narrative to justify the resumption of nuclear testing by Russia.

Conducting a nuclear weapons test would be seen clearly as a further step on the escalation scale towards nuclear use for Russia.

While inspections of nuclear weapons sites had not resumed since COVID-19, Russia’s suspension of its participation could result in the further halting of other transparency and verification measures under New START, including the regular mutual data exchanges between the US and Russia – for example on warhead numbers, locations, and technical information on weapons systems and their sites – which are conducted through the Bilateral Consultative Commission (BCC).

What is the difference between withdrawing from New START and ‘suspending’ participation?

In his speech, Putin announced the suspension of Russian participation in New START. While this does not mean Russia has formally withdrawn from the treaty, the suspension could enable Russia to continue preventing the US from inspecting its nuclear weapons sites and halt Russia’s participation in other obligations, such as the routine reporting and data exchanges on nuclear weapons as well as meetings of the BCC.

The decision to suspend participation rather than withdraw from the treaty means Russia retains the option to return to compliance at a later point. However, it is not yet clear under what conditions Russia would opt to return to compliance with the treaty, or whether this means the US will, in turn, suspend their own obligations.

The treaty text itself does not provide for a suspension of participation by parties to the treaty. However, the Vienna Convention on the Law of Treaties does address the mechanisms for suspension of participation in a treaty. Russia is a full state party to the Vienna Convention, but the US has remained a signatory without ratification since 1970.

There is a precedent of Russia suspending its membership in arms control treaties rather than withdrawing, which is when Russia suspended its participation in the original Treaty on Conventional Armed Forces in Europe (CFE) in 2007.

The US does not recognize Russia’s suspension of its participation in the CFE treaty, but this does not make a material difference to Russian actions.

What does the suspension mean for the wider international treaty regime?

Russia’s suspension of the New START could signal the end of strategic arms control between the two countries. There is now virtually no regular scheduled arms control communication between the two countries bilaterally – this is a dangerous position to be in, especially in times of crisis.

By announcing Russia’s suspension of the treaty in his main address on the anniversary of the invasion of Ukraine, Putin is sending a signal about Russia’s intent for the future

The suspension of New START further erodes limited recourse for communication between the two countries, by suspending information exchange and meetings of the BCC under the treaty.

This is likely to have wider implications for progress on nuclear non-proliferation under the Treaty on the Non-Proliferation of Nuclear Weapons (NPT), as well as the wider international security treaty regime.

Will this increase the nuclear threat or the likelihood of nuclear use?

New START provides both the US and Russia with a degree of transparency surrounding nuclear weapons systems. Without an avenue for regular data exchange and notification, and mechanisms for verification through mutual nuclear weapons site inspections, the risk of misperception or misunderstanding could increase and fuel uncertainty which could increases the perception of threat between Russia and the US.

What are Putin’s reasons for suspending Russia’s participation?

Putin and various members of his government have been linking the future of New START to the war in Ukraine rhetorically for several months now, threatening that Russia may not be willing to negotiate a follow-on treaty for when New START expires in Feb 2026 because of US support for Ukraine.

By announcing Russia’s suspension of the treaty in his main address on the anniversary of the invasion of Ukraine, Putin is sending a signal about Russia’s intent for the future.

Russia’s new hypersonic glide vehicle Avangard was already counted under New START and it is likely follow-on negotiations would have focused on some of Russia’s other hypersonic capabilities or other new nuclear systems.

Without the treaty, Russia might be less inhibited in its development of new nuclear systems.

Have both the US and Russia been compliant with the treaty until now?

Both the US and Russia have remained within the central limits of the treaty since its entry into force in 2011. Following the outbreak of COVID-19, both sides agreed to suspend in-person inspections due to restrictions on travel, and attempts to recommence in-person inspections in 2022 were unsuccessful.

In August 2022, Russia prevented US on-site inspections under New START and a November 2022 meeting of the BCC was called off by Russian officials. Russia has blamed both the ongoing COVID-19 pandemic and the sanctions burden on Russia as reasons for not wanting to resume inspections.




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World in brief: Ukraine and nuclear proliferation to dominate G7

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.

A North Korean ballistic missile recently went into the sea near the Japanese island of Hokkaido

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.

We are witnessing a shift in the identity and purpose of the G7

Tristen Naylor, University of Cambridge

‘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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Molecular Composition of IMP1 Ribonucleoprotein Granules

Lars Jønson
May 1, 2007; 6:798-811
Research




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Can the world avoid a new nuclear arms race?

Can the world avoid a new nuclear arms race? 18 November 2024 — 6:00PM TO 7:00PM Anonymous (not verified) Chatham House and Online

Leading experts discuss how states are expanding nuclear arsenals amid rising geopolitical challenges.

Leading experts discuss how states are expanding nuclear arsenals amid rising geopolitical challenges.

The Doomsday Clock stands at 90 seconds to midnight – the closest to global catastrophe it has ever been. As geopolitical competition intensifies, nuclear risks are resurging at an alarming rate. The collapse of key arms control agreements, such as the Intermediate-Range Nuclear Forces (INF) Treaty, has removed crucial safeguards against arms races. Efforts to extend or replace existing treaties face significant hurdles in the current geopolitical climate.

Nuclear rhetoric has become more aggressive, as evidenced by Russian and North Korean nuclear threats. Several nuclear-armed states are also engaging in extensive modernization programmes of their nuclear arsenals, potentially fuelling a new arms race.

Despite these pressures, the number of nuclear possessor states has held steady so far. The ongoing Iranian efforts to build nuclear weapons is the closest attempt by a new state to acquire nuclear weapons. As the global security environment becomes more and more tense, existing nuclear possessor states increasingly rely on their nuclear weapons. This might threaten the global consensus against nuclear proliferation.

This session examines these competing pressures and propose strategies to reduce the risks of nuclear weapons use and proliferation. Our expert panel explores diplomatic initiatives, technical measures, and policy innovations to address these critical challenges.

This expert panel discusses key questions including:

  • Are we already in the middle of a global nuclear arms race?
  • How can international arms control treaties be negotiated in the current geopolitical environment?
  • Does a new US president change the nuclear calculus? Is the US still able to reassure allies of its ‘extended deterrence’?
  • How can we reduce the risk of additional proliferation? Which states might want to acquire nuclear weapons and what can we do about it?

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




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Talking to North Korea: Ending the Nuclear Standoff?




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Hepatocyte nuclear factor 1{beta} suppresses canonical Wnt signaling through transcriptional repression of lymphoid enhancer-binding factor 1 [Molecular Bases of Disease]

Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is required for normal kidney development and renal epithelial differentiation. Mutations of HNF-1β produce congenital kidney abnormalities and inherited renal tubulopathies. Here, we show that ablation of HNF-1β in mIMCD3 renal epithelial cells results in activation of β-catenin and increased expression of lymphoid enhancer–binding factor 1 (LEF1), a downstream effector in the canonical Wnt signaling pathway. Increased expression and nuclear localization of LEF1 are also observed in cystic kidneys from Hnf1b mutant mice. Expression of dominant-negative mutant HNF-1β in mIMCD3 cells produces hyperresponsiveness to exogenous Wnt ligands, which is inhibited by siRNA-mediated knockdown of Lef1. WT HNF-1β binds to two evolutionarily conserved sites located 94 and 30 kb from the mouse Lef1 promoter. Ablation of HNF-1β decreases H3K27 trimethylation repressive marks and increases β-catenin occupancy at a site 4 kb upstream to Lef1. Mechanistically, WT HNF-1β recruits the polycomb-repressive complex 2 that catalyzes H3K27 trimethylation. Deletion of the β-catenin–binding domain of LEF1 in HNF-1β–deficient cells abolishes the increase in Lef1 transcription and decreases the expression of downstream Wnt target genes. The canonical Wnt target gene, Axin2, is also a direct transcriptional target of HNF-1β through binding to negative regulatory elements in the gene promoter. These findings demonstrate that HNF-1β regulates canonical Wnt target genes through long-range effects on histone methylation at Wnt enhancers and reveal a new mode of active transcriptional repression by HNF-1β.




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Nuclear Energy in a Post-Brexit Europe

Nuclear Energy in a Post-Brexit Europe 11 October 2019 — 8:30AM TO 10:00AM Anonymous (not verified) 18 September 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

Brexit will significantly change the balance within the EU in relation to nuclear energy. Apart from France and Finland, both of whose nuclear development programmes are behind schedule, the UK is the only member state in northern or western Europe currently investing in new nuclear capacity. Brexit will therefore leave the supporters of nuclear energy within the EU27 and the European Commission in a weaker position.

The speaker will argue that at a time when the energy industry needs to accelerate its shift away from fossil fuels, and when the electricity generation industry must cut its carbon emissions faster than it has ever managed to do in the past, this change is unhelpful.

The workshop will also address the need for additional interconnector capacity and the future of carbon-trading outside the EU emission trading system and how this relates to potential nuclear energy capacity.

Attendance at this event is by invitation only.




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Nuclear, gas and green finance taxonomies in the EU and UK

Nuclear, gas and green finance taxonomies in the EU and UK 23 February 2022 — 10:00AM TO 11:00AM Anonymous (not verified) 20 January 2022 Online

Experts discuss EU, UK, and international perspectives on green taxonomy.

This event will address the controversial additions to the EU green finance taxonomy, including the labelling of some nuclear and gas power sources as “green”. Hear perspectives from the UK, EU and international experts.

The UK has committed to creating a green taxonomy to provide a shared understanding of which economic activities count as sustainable. It should be robust and evidence-based, taking an objective and science-based approach to assessing sustainability.

Technical Screening Criteria (TSCs) for the climate change mitigation, and climate change adaptation objectives within the UK green taxonomy will be based on those in the EU Taxonomy. The Government is currently reviewing these and expects to consult on UK draft TSCs in the first quarter of 2022, ahead of legislating by the end of 2022.

In recent weeks the European Commission has proposed controversial additional TSCs for the EU taxonomy, most notably the inclusion of nuclear and natural gas in power generation, which are currently being discussed by Member States and the European Parliament.

The inclusion of controversial power sources not only risks affecting investment and deployment patterns in the net-zero transition, but may also be a threat to the authority of the taxonomy as a whole

Key questions for the UK now include whether and how to address these issues in its own taxonomy, and how to promote a science-based ‘race to the top’ between jurisdictions that can lead to robust international standards.

This Environment and Society Discussion Series event brings expert voices together to discuss EU, UK, and international perspectives, and is co-organized with E3G.




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Guidance and best practices for nuclear cardiology laboratories during the coronavirus disease 2019 (COVID-19) pandemic: An Information Statement from ASNC and SNMMI




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Impact of the ISCHEMIA Trial on Stress Nuclear Myocardial Perfusion Imaging




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Intraarterial Administration of Peptide Receptor Radionuclide Therapy in Patients with Advanced Meningioma: Initial Safety and Efficacy

Visual Abstract




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Stoichiometry of Nucleotide Binding to Proteasome AAA+ ATPase Hexamer Established by Native Mass Spectrometry

Yadong Yu
Dec 1, 2020; 19:1997-2014
Research




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Fibrillar {alpha}-synuclein toxicity depends on functional lysosomes [Cell Biology]

Neurodegeneration in Parkinson's disease (PD) can be recapitulated in animals by administration of α-synuclein preformed fibrils (PFFs) into the brain. However, the mechanism by which these PFFs induce toxicity is unknown. Iron is implicated in PD pathophysiology, so we investigated whether α-synuclein PFFs induce ferroptosis, an iron-dependent cell death pathway. A range of ferroptosis inhibitors were added to a striatal neuron-derived cell line (STHdhQ7/7 cells), a dopaminergic neuron–derived cell line (SN4741 cells), and WT primary cortical neurons, all of which had been intoxicated with α-synuclein PFFs. Viability was not recovered by these inhibitors except for liproxstatin-1, a best-in-class ferroptosis inhibitor, when used at high doses. High-dose liproxstatin-1 visibly enlarged the area of a cell that contained acidic vesicles and elevated the expression of several proteins associated with the autophagy-lysosomal pathway similarly to the known lysosomal inhibitors, chloroquine and bafilomycin A1. Consistent with high-dose liproxstatin-1 protecting via a lysosomal mechanism, we further de-monstrated that loss of viability induced by α-synuclein PFFs was attenuated by chloroquine and bafilomycin A1 as well as the lysosomal cysteine protease inhibitors, leupeptin, E-64D, and Ca-074-Me, but not other autophagy or lysosomal enzyme inhibitors. We confirmed using immunofluorescence microscopy that heparin prevented uptake of α-synuclein PFFs into cells but that chloroquine did not stop α-synuclein uptake into lysosomes despite impairing lysosomal function and inhibiting α-synuclein toxicity. Together, these data suggested that α-synuclein PFFs are toxic in functional lysosomes in vitro. Therapeutic strategies that prevent α-synuclein fibril uptake into lysosomes may be of benefit in PD.




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Murine GFP-Mx1 forms nuclear condensates and associates with cytoplasmic intermediate filaments: Novel antiviral activity against VSV [Immunology]

Type I and III interferons induce expression of the “myxovirus resistance proteins” MxA in human cells and its ortholog Mx1 in murine cells. Human MxA forms cytoplasmic structures, whereas murine Mx1 forms nuclear bodies. Whereas both HuMxA and MuMx1 are antiviral toward influenza A virus (FLUAV) (an orthomyxovirus), only HuMxA is considered antiviral toward vesicular stomatitis virus (VSV) (a rhabdovirus). We previously reported that the cytoplasmic human GFP-MxA structures were phase-separated membraneless organelles (“biomolecular condensates”). In the present study, we investigated whether nuclear murine Mx1 structures might also represent phase-separated biomolecular condensates. The transient expression of murine GFP-Mx1 in human Huh7 hepatoma, human Mich-2H6 melanoma, and murine NIH 3T3 cells led to the appearance of Mx1 nuclear bodies. These GFP-MuMx1 nuclear bodies were rapidly disassembled by exposing cells to 1,6-hexanediol (5%, w/v), or to hypotonic buffer (40–50 mosm), consistent with properties of membraneless phase-separated condensates. Fluorescence recovery after photobleaching (FRAP) assays revealed that the GFP-MuMx1 nuclear bodies upon photobleaching showed a slow partial recovery (mobile fraction: ∼18%) suggestive of a gel-like consistency. Surprisingly, expression of GFP-MuMx1 in Huh7 cells also led to the appearance of GFP-MuMx1 in 20–30% of transfected cells in a novel cytoplasmic giantin-based intermediate filament meshwork and in cytoplasmic bodies. Remarkably, Huh7 cells with cytoplasmic murine GFP-MuMx1 filaments, but not those with only nuclear bodies, showed antiviral activity toward VSV. Thus, GFP-MuMx1 nuclear bodies comprised phase-separated condensates. Unexpectedly, GFP-MuMx1 in Huh7 cells also associated with cytoplasmic giantin-based intermediate filaments, and such cells showed antiviral activity toward VSV.




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Nuclear translocation ability of Lipin differentially affects gene expression and survival in fed and fasting Drosophila

Stephanie E. Hood
Dec 1, 2020; 61:1720-1732
Research Articles




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Nuclear translocation ability of Lipin differentially affects gene expression and survival in fed and fasting Drosophila [Research Articles]

Lipins are eukaryotic proteins with functions in lipid synthesis and the homeostatic control of energy balance. They execute these functions by acting as phosphatidate phosphatase enzymes in the cytoplasm and by changing gene expression after translocation into the cell nucleus, in particular under fasting conditions. Here, we asked whether nuclear translocation and the enzymatic activity of Drosophila Lipin serve essential functions and how gene expression changes, under both fed and fasting conditions, when nuclear translocation is impaired. To address these questions, we created a Lipin null mutant, a mutant expressing Lipin lacking a nuclear localization signal (LipinNLS), and a mutant expressing enzymatically dead Lipin. Our data support the conclusion that the enzymatic but not nuclear gene regulatory activity of Lipin is essential for survival. Notably, adult LipinNLS flies were not only viable but also exhibited improved life expectancy. In contrast, they were highly susceptible to starvation. Both the improved life expectancy in the fed state and the decreased survival in the fasting state correlated with changes in metabolic gene expression. Moreover, increased life expectancy of fed flies was associated with a decreased metabolic rate. Interestingly, in addition to metabolic genes, genes involved in feeding behavior and the immune response were misregulated in LipinNLS flies. Altogether, our data suggest that the nuclear activity of Lipin influences the genomic response to nutrient availability with effects on life expectancy and starvation resistance. Thus, nutritional or therapeutic approaches that aim at lowering nuclear translocation of lipins in humans may be worth exploring.




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{alpha}-Synuclein facilitates endocytosis by elevating the steady-state levels of phosphatidylinositol 4,5-bisphosphate [Membrane Biology]

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




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Stoichiometry of Nucleotide Binding to Proteasome AAA+ ATPase Hexamer Established by Native Mass Spectrometry [Research]

AAA+ ATPases constitute a large family of proteins that are involved in a plethora of cellular processes including DNA disassembly, protein degradation and protein complex disassembly. They typically form a hexametric ring-shaped structure with six subunits in a (pseudo) 6-fold symmetry. In a subset of AAA+ ATPases that facilitate protein unfolding and degradation, six subunits cooperate to translocate protein substrates through a central pore in the ring. The number and type of nucleotides in an AAA+ ATPase hexamer is inherently linked to the mechanism that underlies cooperation among subunits and couples ATP hydrolysis with substrate translocation. We conducted a native MS study of a monodispersed form of PAN, an archaeal proteasome AAA+ ATPase, to determine the number of nucleotides bound to each hexamer of the WT protein. We utilized ADP and its analogs (TNP-ADP and mant-ADP), and a nonhydrolyzable ATP analog (AMP-PNP) to study nucleotide site occupancy within the PAN hexamer in ADP- and ATP-binding states, respectively. Throughout all experiments we used a Walker A mutant (PANK217A) that is impaired in nucleotide binding as an internal standard to mitigate the effects of residual solvation on mass measurement accuracy and to serve as a reference protein to control for nonspecific nucleotide binding. This approach led to the unambiguous finding that a WT PAN hexamer carried – from expression host – six tightly bound ADP molecules that could be exchanged for ADP and ATP analogs. Although the Walker A mutant did not bind ADP analogs, it did bind AMP-PNP, albeit at multiple stoichiometries. We observed variable levels of hexamer dissociation and an appearance of multimeric species with the over-charged molecular ion distributions across repeated experiments. We posit that these phenomena originated during ESI process at the final stages of ESI droplet evolution.




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Detection of multiple autoantibodies in patients with ankylosing spondylitis using nucleic acid programmable protein arrays [11. Microarrays/Combinatorics/Display Technology]

Ankylosing Spondylitis (AS) is a common, inflammatory rheumatic disease, which primarily affects the axial skeleton and is associated with sacroiliitis, uveitis and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine if plasma from patients with AS contained autoantibodies and if so, characterize and quantify this response in comparison to patients with Rheumatoid Arthritis (RA) and healthy controls. Two high-density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis in order to determine patterns of signalling cascades or tissue origin. 44% of patients with Ankylosing Spondylitis demonstrated a broad autoantibody response, as compared to 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The AS patients autoantibody responses were targeted towards connective, skeletal and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic Acid Programmable Protein Arrays constitute a powerful tool to study autoimmune diseases.




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Nuclear Disarmament and the Protection of Cultural Heritage

Nuclear Disarmament and the Protection of Cultural Heritage Research paper sysadmin 6 October 2017

States possessing nuclear weapons should be called upon to consider and publish the risks posed to cultural heritage, and their mitigation strategies, in their nuclear-weapons doctrines and policies.

A woman walks on the roof of the Great Mosque of Djenné, a World Heritage Site, after praying. Photo: United Nations.

Summary

  • Renewed risk assessments for nuclear weapons and policies are taking place around the world in light of nuclear modernization and the changing geostrategic environment that is making the use of nuclear weapons more likely. As such the humanitarian impacts of nuclear weapons and tests have received increased attention. However, the effect on cultural heritage has so far been neglected.
  • The potential for armed conflict to destroy cultural heritage has been recognized in international law since 1954. There is significant evidence on the impact of nuclear weapons on cultural heritage including the consequences of their use in Hiroshima and Nagasaki and the effect of nuclear-testing programmes in places of cultural significance since 1945. States that possess nuclear weapons have increased liabilities and responsibilities to protect cultural heritage and cultural rights. The need to protect cultural heritage should strengthen the case for reducing and eliminating nuclear weapons.
  • Failure to take into account the protection of heritage in the development of nuclear weapons policies – including disarmament, non-proliferation and arms-control negotiations – significantly undermines states’ existing commitments to protecting heritage threatened by conflict.
  • Risk assessments of the impact of nuclear weapons on cultural heritage and important cultural artefacts – and methods of preventing such catastrophic damage – should be part of protecting cultural heritage in every country and the subject of informed public debate. A new body of knowledge on the full range of nuclear weapons impacts would introduce a fresh perspective to inform decision-makers, international organizations and the public in thinking about nuclear weapons policies and practices.
  • Risk and resilience frameworks, which provide sets of solutions for risk assessments, would allow assessments of nuclear weapons threats to heritage and highlight vulnerabilities that need to be addressed. Such frameworks would provide a basis for policymakers to identify the world’s cultural heritage most at risk and help develop mitigation strategies to ensure that it is protected. In particular, states possessing nuclear weapons should be called upon to consider and publish the risks posed to cultural heritage, and their mitigation strategies, in their nuclear weapons doctrines and policies, as a contribution to transparency and confidence-building, and as a responsibility to the world’s shared heritage. International organizations, such as the UN Educational, Scientific, and Cultural Organization (UNESCO), have a role to play in bridging security perspectives with protecting cultural heritage.




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Mycobacteria excise DNA damage in 12- or 13-nucleotide-long oligomers by prokaryotic-type dual incisions and performs transcription-coupled repair [Genomics and Proteomics]

In nucleotide excision repair, bulky DNA lesions such as UV-induced cyclobutane pyrimidine dimers are removed from the genome by concerted dual incisions bracketing the lesion, followed by gap filling and ligation. So far, two dual-incision patterns have been discovered: the prokaryotic type, which removes the damage in 11–13-nucleotide-long oligomers, and the eukaryotic type, which removes the damage in 24–32-nucleotide-long oligomers. However, a recent study reported that the UvrC protein of Mycobacterium tuberculosis removes damage in a manner analogous to yeast and humans in a 25-mer oligonucleotide arising from incisions at 15 nt from the 3´ end and 9 nt from the 5´ end flanking the damage. To test this model, we used the in vivo excision assay and the excision repair sequencing genome-wide repair mapping method developed in our laboratory to determine the repair pattern and genome-wide repair map of Mycobacterium smegmatis. We find that M. smegmatis, which possesses homologs of the Escherichia coli uvrA, uvrB, and uvrC genes, removes cyclobutane pyrimidine dimers from the genome in a manner identical to the prokaryotic pattern by incising 7 nt 5´ and 3 or 4 nt 3´ to the photoproduct, and performs transcription-coupled repair in a manner similar to E. coli.




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Kinetic investigation of the polymerase and exonuclease activities of human DNA polymerase ϵ holoenzyme [DNA and Chromosomes]

In eukaryotic DNA replication, DNA polymerase ε (Polε) is responsible for leading strand synthesis, whereas DNA polymerases α and δ synthesize the lagging strand. The human Polε (hPolε) holoenzyme is comprised of the catalytic p261 subunit and the noncatalytic p59, p17, and p12 small subunits. So far, the contribution of the noncatalytic subunits to hPolε function is not well understood. Using pre-steady-state kinetic methods, we established a minimal kinetic mechanism for DNA polymerization and editing catalyzed by the hPolε holoenzyme. Compared with the 140-kDa N-terminal catalytic fragment of p261 (p261N), which we kinetically characterized in our earlier studies, the presence of the p261 C-terminal domain (p261C) and the three small subunits increased the DNA binding affinity and the base substitution fidelity. Although the small subunits enhanced correct nucleotide incorporation efficiency, there was a wide range of rate constants when incorporating a correct nucleotide over a single-base mismatch. Surprisingly, the 3'→5' exonuclease activity of the hPolε holoenzyme was significantly slower than that of p261N when editing both matched and mismatched DNA substrates. This suggests that the presence of p261C and the three small subunits regulates the 3'→5' exonuclease activity of the hPolε holoenzyme. Together, the 3'→5' exonuclease activity and the variable mismatch extension activity modulate the overall fidelity of the hPolε holoenzyme by up to 3 orders of magnitude. Thus, the presence of p261C and the three noncatalytic subunits optimizes the dual enzymatic activities of the catalytic p261 subunit and makes the hPolε holoenzyme an efficient and faithful replicative DNA polymerase.




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A new nuclear order

A new nuclear order 7 February 2023 — 6:00PM TO 7:00PM Anonymous (not verified) 26 January 2023 Chatham House and Online

In conversation with Rafael Mariano Grossi.

For more than half a century, the global nuclear non-proliferation framework has supported international security and facilitated the expansion of the many peaceful applications of nuclear science and technology. 

What is happening today in Ukraine, Iran and North Korea, not only challenges the way we deal with the existential threat of nuclear weapons, but also the impact it could have on addressing another existential threat – climate change.

Russia’s invasion of Ukraine is the biggest test to global resolve both in avoiding nuclear conflict and in ensuring the safety of one of the biggest nuclear power programmes in Europe.

Rafael Mariano Grossi of the International Atomic Energy Agency discusses key questions on global nuclear cooperation including:

  • The impact of the war in Ukraine and issues with Iran and North Korea on countries’ risk assessment with regards to nuclear non-proliferation.

  • What the IAEA’s on-the-ground presence and the director general’s missions to Ukraine, particularly the Zaporizhzhia Nuclear Power Plant, tells us about what is necessary – now and in the long term – to ensure the safety and security of nuclear material under all circumstances.

  • The role of ensuring nuclear energy can play its vital part in mitigating climate change now and in the future.

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

Read the transcript.




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[68Ga]Ga-PSMA-11 PET/CT-Positive Hepatic Inflammatory Pseudotumor: Possible PSMA-Avid Pitfall in Nuclear Imaging




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The Emission of Internal Conversion Electrons Rather Than Auger Electrons Increased the Nucleus-Absorbed Dose for 161Tb Compared with 177Lu with a Higher Dose Response for [161Tb]Tb-DOTA-LM3 Than for [161Tb]Tb-DOTATATE

Preclinical data have shown that 161Tb-labeled peptides targeting the somatostatin receptor are therapeutically more effective for peptide receptor radionuclide therapy than are their 177Lu-labeled counterparts. To further substantiate this enhanced therapeutic effect, we performed cellular dosimetry to quantify the absorbed dose to the cell nucleus and compared dose–response curves to evaluate differences in relative biological effectiveness in vitro. Methods: CA20948 cell survival was assessed after treatment with [161Tb]Tb- and [177Lu]Lu-DOTATATE (agonist) and with [161Tb]Tb- and [177Lu]Lu-DOTA-LM3 (antagonist) via a clonogenic assay. Cell binding, internalization, and dissociation assays were performed up to 7 d to acquire time-integrated activity coefficients. Separate S values for each type of particle emission (Auger/internal conversion [IC] electrons and β particles) were computed via Monte Carlo simulations, while considering spheric cells. Once the absorbed dose to the cell nucleus was calculated, survival curves were fitted to the appropriate linear or linear-quadratic model and corresponding relative biological effectiveness was evaluated. Results: Although the radiopeptide uptake was independent of the radionuclide, [161Tb]Tb-DOTATATE and [161Tb]Tb-DOTA-LM3 delivered a 3.6 and 3.8 times higher dose to the nucleus, respectively, than their 177Lu-labeled counterparts on saturated receptor binding. This increased nucleus-absorbed dose was mainly due to the additional emission of IC and not Auger electrons by 161Tb. When activity concentrations were considered, both [161Tb]Tb-DOTATATE and [161Tb]Tb-DOTA-LM3 showed a lower survival fraction than did labeling with 177Lu. When the absorbed dose to the nucleus was considered, no significant difference could be observed between the dose–response curves for [161Tb]Tb- and [177Lu]Lu-DOTATATE. [161Tb]Tb-DOTA-LM3 showed a linear-quadratic dose response, whereas [161Tb]Tb-DOTATATE showed only a linear dose response within the observed dose range, suggesting additional cell membrane damage by Auger electrons. Conclusion: The IC, rather than Auger, electrons emitted by 161Tb resulted in a higher absorbed dose to the cell nucleus and lower clonogenic survival for [161Tb]Tb-DOTATATE and [161Tb]Tb-DOTA-LM3 than for the 177Lu-labeled analogs. In contrast, [161Tb]Tb-DOTATATE showed no higher dose response than [177Lu]Lu-DOTATATE, whereas for [161Tb]Tb-DOTA-LM3 an additional quadratic response was observed. Because of this quadratic response, potentially caused by cell membrane damage, [161Tb]Tb-DOTA-LM3 is a more effective radiopeptide than [161Tb]Tb-DOTATATE for labeling with 161Tb.




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Nuclear Imaging of Bispecific Antibodies on the Rise

Bispecific antibodies (bsAbs) are engineered to target 2 different epitopes simultaneously. About 75% of the 16 clinically approved bsAbs have entered the clinic internationally since 2022. Hence, research on biomedical imaging of various radiolabeled bsAb scaffolds may serve to improve patient selection for bsAb therapy. Here, we provide a comprehensive overview of recent advances in radiolabeled bsAbs for imaging via PET or SPECT. We compare direct targeting and pretargeting approaches in preclinical and clinical studies in oncologic research. Furthermore, we show preclinical applications of imaging bsAbs in neurodegenerative diseases. Finally, we offer perspectives on the future directions of imaging bsAbs based on their challenges and opportunities.




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U.S., South Korea agree to greater cooperation on civil nuclear energy

Earlier this month, the United States and the Republic of Korea reached an agreement on greater cooperation on civil nuclear energy projects, the U.S. Department of Energy said this week.





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Barker, Betts lead No. 5 UCLA women over Pepperdine 91-54

Janiah Barker had 18 points and 11 rebounds, Lauren Betts had 17 points and 12 rebounds and the No. 5 UCLA women rolled past Pepperdine 91-54 on Tuesday. The Bruins (3-0) started the game with an 18-0 run. Ornela Muca, who led Pepperdine (1-2) with 20 points, made a 3-pointer to stop the run.




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Neuregulin1 Nuclear Signaling Influences Adult Neurogenesis and Regulates a Schizophrenia Susceptibility Gene Network within the Mouse Dentate Gyrus

Prithviraj Rajebhosale
Oct 23, 2024; 44:e0063242024-e0063242024
Cellular




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Brief and Diverse Excitotoxic Insults Increase the Neuronal Nuclear Membrane Permeability in the Neonatal Brain, Resulting in Neuronal Dysfunction and Cell Death

Neuronal cytotoxic edema is implicated in neuronal injury and death, yet mitigating brain edema with osmotic and surgical interventions yields poor clinical outcomes. Importantly, neuronal swelling and its downstream consequences during early brain development remain poorly investigated, and new treatment approaches are needed. We explored Ca2+-dependent downstream effects after neuronal cytotoxic edema caused by diverse injuries in mice of both sexes using multiphoton Ca2+ imaging in vivo [Postnatal Day (P)12–17] and in acute brain slices (P8–12). After different excitotoxic insults, cytosolic GCaMP6s translocated into the nucleus after a few minutes in a subpopulation of neurons, persisting for hours. We used an automated morphology-detection algorithm to detect neuronal soma and quantified the nuclear translocation of GCaMP6s as the nuclear to cytosolic intensity (N/C ratio). Elevated neuronal N/C ratios occurred concurrently with persistent elevation in Ca2+ loads and could also occur independently from neuronal swelling. Electron microscopy revealed that the nuclear translocation was associated with the increased nuclear pore size. The nuclear accumulation of GCaMP6s in neurons led to neocortical circuit dysfunction, mitochondrial pathology, and increased cell death. Inhibiting calpains, a family of Ca2+-activated proteases, prevented elevated N/C ratios and neuronal swelling. In summary, in the developing brain, we identified a calpain-dependent alteration of nuclear transport in a subpopulation of neurons after disease-relevant insults leading to long-term circuit dysfunction and cell death. The nuclear translocation of GCaMP6 and other cytosolic proteins after acute excitotoxicity can be an early biomarker of brain injury in the developing brain.




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Neuregulin1 Nuclear Signaling Influences Adult Neurogenesis and Regulates a Schizophrenia Susceptibility Gene Network within the Mouse Dentate Gyrus

Neuregulin1 (Nrg1) signaling is critical for neuronal development and function from fate specification to synaptic plasticity. Type III Nrg1 is a synaptic protein which engages in bidirectional signaling with its receptor ErbB4. Forward signaling engages ErbB4 phosphorylation, whereas back signaling engages two known mechanisms: (1) local axonal PI3K-AKT signaling and (2) cleavage by -secretase resulting in cytosolic release of the intracellular domain (ICD), which can traffic to the nucleus (Bao et al., 2003; Hancock et al., 2008). To dissect the contribution of these alternate signaling strategies to neuronal development, we generated a transgenic mouse with a missense mutation (V321L) in the Nrg1 transmembrane domain that disrupts nuclear back signaling with minimal effects on forward signaling or local back signaling and was previously found to be associated with psychosis (Walss-Bass et al., 2006). We combined RNA sequencing, retroviral fate mapping of neural stem cells, behavioral analyses, and various network analyses of transcriptomic data to investigate the effect of disrupting Nrg1 nuclear back signaling in the dentate gyrus (DG) of male and female mice. The V321L mutation impairs nuclear translocation of the Nrg1 ICD and alters gene expression in the DG. V321L mice show reduced stem cell proliferation, altered cell cycle dynamics, fate specification defects, and dendritic dysmorphogenesis. Orthologs of known schizophrenia (SCZ)-susceptibility genes were dysregulated in the V321L DG. These genes coordinated a larger network with other dysregulated genes. Weighted gene correlation network analysis and protein interaction network analyses revealed striking similarity between DG transcriptomes of V321L mouse and humans with SCZ.