ucl Perspectives on Nuclear Deterrence in the 21st Century By feedproxy.google.com Published On :: Sun, 19 Apr 2020 19:32:28 +0000 20 April 2020 Nuclear deterrence theory, with its roots in the Cold War era, may not account for all eventualities in the 21st century. Researchers at Chatham House have worked with eight experts to produce this collection of essays examining four contested themes in contemporary policymaking on deterrence. Read online Download PDF Dr Beyza Unal Senior Research Fellow, International Security Programme @beyzaunal Google Scholar Yasmin Afina Research Assistant, International Security Programme @afinayasmin LinkedIn Dr Patricia Lewis Research Director, Conflict, Science & Transformation; Director, International Security Programme @PatriciaMary Dr John Borrie Associate Fellow, International Security Programme Google Scholar Dr Jamie Shea Associate Fellow, International Security Programme LinkedIn Peter Watkins Associate Fellow, International Security Programme LinkedIn Dr Maria Rost Rublee Associate Professor of International Relations, Monash University Cristina Varriale Research Fellow in Proliferation and Nuclear Policy, RUSI Dr Tanya Ogilvie-White Adjunct Senior Fellow, Griffith Asia Institute, Griffith University Dr Andrew Futter Associate Professor of International Politics, University of Leicester Christine Parthemore Chief Executive Officer, Council on Strategic Risks (CSR) 2020-04-20-NuclearDeterrence.jpeg Royal Navy Vanguard Class submarine HMS Vigilant returning to HMNB Clyde after extended deployment. The four Vanguard-class submarines form the UK's strategic nuclear deterrent force. Photo: Ministry of Defence. SummaryThis collection of essays explores, from the perspectives of eight experts, four areas of deterrence theory and policymaking: the underlying assumptions that shape deterrence practice; the enduring value of extended deterrence; the impact of emerging technologies; and the ‘blurring’ of the lines between conventional and nuclear weapons.Nuclear deterrence theory, with its roots in the Cold War era, may not account for all eventualities in security and defence in the 21st century, given the larger number of nuclear actors in a less binary geopolitical context. It is clear that a number of present factors challenge the overall credibility of ‘classical’ nuclear deterrence, meaning that in-depth analysis is now needed.Uncertainty as to the appetite to maintain the current nuclear weapons policy architecture looms large in discussions and concerns on global and regional security. The demise of the Intermediate-Range Nuclear Forces Treaty, doubts over the potential extension of the New Strategic Arms Reduction Treaty, heightened regional tensions in Northeast and South Asia, together with the current and likely future risks and challenges arising from global technological competition, making it all the more urgent to examine long-held assumptions in the real-world context.Extended deterrence practices differ from region to region, depending on the domestic and regional landscape. Increased focus on diplomatic capabilities to reduce risks and improve the long-term outlook at regional level, including by spearheading new regional arms-control initiatives, may be a viable way forward. Addressing the bigger picture – notably including, on the Korean peninsula, Pyongyang’s own threat perception – and the links between conventional and nuclear missile issues will need to remain prominent if long-term and concrete changes are to take hold.Most states have long held nuclear weapons to be ‘exceptional’: their use would represent a dramatic escalation of a conflict that must never be attained. Latterly, however, some officials and scholars have made the case that the impact of the use of a low-yield nuclear weapon would not be entirely distinct from that of a large-scale conventional attack. This blurring of lines between conventional and nuclear deterrence strips nuclear weapons of their exceptional nature, in a context in which states are faced with diverse, complex and concurrent threats from multiple potential adversaries that are able to synchronize non-military and military options, up to and including nuclear forces. The use of nuclear weapons risks becoming a ‘new normal’, potentially reducing the threshold for use – to cyberattacks, for example. This has direct implications for discussions around strategic stability. While emerging technologies may offer tremendous opportunities in the modernization of nuclear weapons, they also present major risks and destabilizing challenges. Artificial intelligence, automation, and other developments in the cyber sphere affect dynamics on both the demand and supply sides of the nuclear deterrence equation. States and alliance such as NATO must adapt their deterrence thinking in light of these technological developments, and define their primary purpose and priorities in this shifting security context. Resilience planning, adaptation to the evolving security environment, threat anticipation, and consistent crisis management and incident response – as well as thinking about the mitigation measures necessary to prevent conflict escalation should deterrence fail – will all be critical in upholding nuclear deterrence as both policy and practice. Department/project International Security Programme, Deterrence Perspectives in the 21st Century Full Article
ucl Nuclear Tensions Must Not Be Sidelined During Coronavirus By feedproxy.google.com Published On :: Fri, 01 May 2020 11:18:35 +0000 1 May 2020 Ana Alecsandru Research Assistant, International Security Programme @anaalecs LinkedIn Although the pandemic means the Nuclear Non-Proliferation Treaty (NPT) Review Conference (RevCon) is postponed, the delay could be an opportunity to better the health of the NPT regime. 2020-05-01-Iran-Peace-Nuclear Painted stairs in Tehran, Iran symbolizing hope. Photo by Fatemeh Bahrami/Anadolu Agency/Getty Images. Despite face-to-face diplomatic meetings being increasingly rare during the current disruption, COVID-19 will ultimately force a redefinition of national security and defence spending priorities, and this could provide the possibility of an improved political climate at RevCon when it happens in 2021.With US presidential elections due in November and a gradual engagement growing between the EU and Iran, there could be a new context for more cooperation between states by 2021. Two key areas of focus over the coming months will be the arms control talks between the United States and Russia, and Iran’s compliance with the 2015 Joint Comprehensive Plan of Action (JCPOA), also known as the Iran Nuclear Deal.It is too early to discern the medium- and longer-term consequences of COVID-19 for defence ministries, but a greater focus on societal resilience and reinvigorating economic productivity will likely undercut the rationale for expensive nuclear modernization.Therefore, extending the current New START (Strategic Arms Reduction Treaty) would be the best, most practical option to give both Russia and the United States time to explore more ambitious multilateral arms control measures, while allowing their current focus to remain on the pandemic and economic relief.Continuing distrustBut with the current treaty — which limits nuclear warheads, missiles, bombers, and launchers — due to expire in February 2021, the continuing distrust between the United States and Russia makes this extension hard to achieve, and a follow-on treaty even less likely.Prospects for future bilateral negotiations are hindered by President Donald Trump’s vision for a trilateral arms control initiative involving both China and Russia. But China opposes this on the grounds that its nuclear arsenal is far smaller than that of the two others.While there appears to be agreement that the nuclear arsenals of China, France, and the UK (the NPT nuclear-weapons states) and those of the states outside the treaty (India, Pakistan, North Korea, and Israel) will all have to be taken into account going forward, a practical mechanism for doing so proves elusive.If Joe Biden wins the US presidency he seems likely to pursue an extension of the New START treaty and could also prevent a withdrawal from the Open Skies treaty, the latest arms control agreement targeted by the Trump administration.Under a Biden administration, the United States would also probably re-join the JCPOA, provided Tehran returned to strict compliance with the deal. Biden could even use the team that negotiated the Iran deal to advance the goal of denuclearization of the Korean peninsula.For an NPT regime already confronted by a series of longstanding divergences, it is essential that Iran remains a signatory especially as tensions between Iran and the United States have escalated recently — due to the Qassim Suleimani assassination and the recent claim by Iran’s Revolutionary Guard Corps to have successfully placed the country’s first military satellite into orbit.This announcement raised red flags among experts about whether Iran is developing intercontinental ballistic missiles due to the dual-use nature of space technology. The satellite launch — deeply troubling for Iran’s neighbours and the EU countries — may strengthen the US argument that it is a cover for the development of ballistic missiles capable of delivering nuclear weapons.However, as with many other countries, Iran is struggling with a severe coronavirus crisis and will be pouring its scientific expertise and funds into that rather than other efforts — including the nuclear programme.Those European countries supporting the trading mechanism INSTEX (Instrument in Support of Trade Exchanges) for sending humanitarian goods into Iran could use this crisis to encourage Iran to remain in compliance with the JCPOA and its NPT obligations.France, Germany and the UK (the E3) have already successfully concluded the first transaction, which was to facilitate the export of medical goods from Europe to Iran. But the recent Iranian escalatory steps will most certainly place a strain on the preservation of this arrangement.COVID-19 might have delayed Iran’s next breach of the 2015 nuclear agreement but Tehran will inevitably seek to strengthen its hand before any potential negotiations with the United States after the presidential elections.As frosty US-Iranian relations — exacerbated by the coronavirus pandemic — prevent diplomatic negotiations, this constructive engagement between the E3 and Iran might prove instrumental in reviving the JCPOA and ensuring Iran stays committed to both nuclear non-proliferation and disarmament.While countries focus their efforts on tackling the coronavirus pandemic, it is understandable resources may be limited for other global challenges, such as the increasing risk of nuclear weapons use across several regions.But the potential ramifications of the COVID-19 crisis for the NPT regime are profound. Ongoing tensions between the nuclear-armed states must not be ignored while the world’s focus is elsewhere, and the nuclear community should continue to work together to progress nuclear non-proliferation and disarmament, building bridges of cooperation and trust that can long outlast the pandemic. Full Article
ucl Nuclear Tensions Must Not Be Sidelined During Coronavirus By feedproxy.google.com Published On :: Fri, 01 May 2020 11:18:35 +0000 1 May 2020 Ana Alecsandru Research Assistant, International Security Programme @anaalecs LinkedIn Although the pandemic means the Nuclear Non-Proliferation Treaty (NPT) Review Conference (RevCon) is postponed, the delay could be an opportunity to better the health of the NPT regime. 2020-05-01-Iran-Peace-Nuclear Painted stairs in Tehran, Iran symbolizing hope. Photo by Fatemeh Bahrami/Anadolu Agency/Getty Images. Despite face-to-face diplomatic meetings being increasingly rare during the current disruption, COVID-19 will ultimately force a redefinition of national security and defence spending priorities, and this could provide the possibility of an improved political climate at RevCon when it happens in 2021.With US presidential elections due in November and a gradual engagement growing between the EU and Iran, there could be a new context for more cooperation between states by 2021. Two key areas of focus over the coming months will be the arms control talks between the United States and Russia, and Iran’s compliance with the 2015 Joint Comprehensive Plan of Action (JCPOA), also known as the Iran Nuclear Deal.It is too early to discern the medium- and longer-term consequences of COVID-19 for defence ministries, but a greater focus on societal resilience and reinvigorating economic productivity will likely undercut the rationale for expensive nuclear modernization.Therefore, extending the current New START (Strategic Arms Reduction Treaty) would be the best, most practical option to give both Russia and the United States time to explore more ambitious multilateral arms control measures, while allowing their current focus to remain on the pandemic and economic relief.Continuing distrustBut with the current treaty — which limits nuclear warheads, missiles, bombers, and launchers — due to expire in February 2021, the continuing distrust between the United States and Russia makes this extension hard to achieve, and a follow-on treaty even less likely.Prospects for future bilateral negotiations are hindered by President Donald Trump’s vision for a trilateral arms control initiative involving both China and Russia. But China opposes this on the grounds that its nuclear arsenal is far smaller than that of the two others.While there appears to be agreement that the nuclear arsenals of China, France, and the UK (the NPT nuclear-weapons states) and those of the states outside the treaty (India, Pakistan, North Korea, and Israel) will all have to be taken into account going forward, a practical mechanism for doing so proves elusive.If Joe Biden wins the US presidency he seems likely to pursue an extension of the New START treaty and could also prevent a withdrawal from the Open Skies treaty, the latest arms control agreement targeted by the Trump administration.Under a Biden administration, the United States would also probably re-join the JCPOA, provided Tehran returned to strict compliance with the deal. Biden could even use the team that negotiated the Iran deal to advance the goal of denuclearization of the Korean peninsula.For an NPT regime already confronted by a series of longstanding divergences, it is essential that Iran remains a signatory especially as tensions between Iran and the United States have escalated recently — due to the Qassim Suleimani assassination and the recent claim by Iran’s Revolutionary Guard Corps to have successfully placed the country’s first military satellite into orbit.This announcement raised red flags among experts about whether Iran is developing intercontinental ballistic missiles due to the dual-use nature of space technology. The satellite launch — deeply troubling for Iran’s neighbours and the EU countries — may strengthen the US argument that it is a cover for the development of ballistic missiles capable of delivering nuclear weapons.However, as with many other countries, Iran is struggling with a severe coronavirus crisis and will be pouring its scientific expertise and funds into that rather than other efforts — including the nuclear programme.Those European countries supporting the trading mechanism INSTEX (Instrument in Support of Trade Exchanges) for sending humanitarian goods into Iran could use this crisis to encourage Iran to remain in compliance with the JCPOA and its NPT obligations.France, Germany and the UK (the E3) have already successfully concluded the first transaction, which was to facilitate the export of medical goods from Europe to Iran. But the recent Iranian escalatory steps will most certainly place a strain on the preservation of this arrangement.COVID-19 might have delayed Iran’s next breach of the 2015 nuclear agreement but Tehran will inevitably seek to strengthen its hand before any potential negotiations with the United States after the presidential elections.As frosty US-Iranian relations — exacerbated by the coronavirus pandemic — prevent diplomatic negotiations, this constructive engagement between the E3 and Iran might prove instrumental in reviving the JCPOA and ensuring Iran stays committed to both nuclear non-proliferation and disarmament.While countries focus their efforts on tackling the coronavirus pandemic, it is understandable resources may be limited for other global challenges, such as the increasing risk of nuclear weapons use across several regions.But the potential ramifications of the COVID-19 crisis for the NPT regime are profound. Ongoing tensions between the nuclear-armed states must not be ignored while the world’s focus is elsewhere, and the nuclear community should continue to work together to progress nuclear non-proliferation and disarmament, building bridges of cooperation and trust that can long outlast the pandemic. Full Article
ucl 177Lu-NM600 targeted radionuclide therapy extends survival in syngeneic murine models of triple-negative breast cancer By jnm.snmjournals.org Published On :: 2019-12-20T13:25:42-08:00 Triple negative breast cancer (TNBC) remains the most aggressive subtype of breast cancer leading to the worst prognosis. Because current therapeutic approaches lack efficacy, there is a clinically unmet need for effective treatment alternatives. Herein, we demonstrate a promising strategy utilizing a tumor-targeting alkylphosphocholine (NM600) radiolabeled with 177Lu for targeted radionuclide therapy (TRT) of TNBC. In two murine syngeneic models of TNBC, we confirmed excellent tumor targeting and rapid normal tissue clearance of the PET imaging analog 86Y-NM600. Based on longitudinal PET/CT data acquired with 86Y-NM600, we estimated the dosimetry of therapeutic 177Lu-NM600, which showed larger absorbed doses in the tumor compared to normal tissues. Administration of 177Lu-NM600 resulted in significant tumor growth inhibition and prolonged overall survival in mice bearing syngeneic 4T07 and 4T1 tumors. Complete response was attained in 60% of 4T07 bearing mice, but animals carrying aggressive 4T1 tumor grafts succumbed to metastatic progression. The injected activities used for treatment (9.25 and 18.5 MBq) were well tolerated, and only mild transient cytopenia was noted. Overall, our results suggest that 177Lu-NM600 TRT has potential for treatment of TNBC and merits further exploration in a clinical setting. Full Article
ucl In vivo instability of 177Lu-DOTATATE during peptide receptor radionuclide therapy By jnm.snmjournals.org Published On :: 2020-01-31T13:36:41-08:00 Peptide receptor radiotherapy using 177Lu-labeled somatostatin ligand analogs is a well-established treatment for neuroendocrine tumors (NET), with 177Lu-DOTATATE having acquired marketing authorization in Europe and the USA. The investigation of the pharmacokinetics of those radiopharmaceuticals in vivo in humans is crucial for personalized treatment management and understanding of treatment effects. It requires input data on the in vivo stability of the radiopharmaceuticals in blood and plasma. The work presented here is devoted to the investigation of in vivo stability of 177Lu-DOTATATE in humans affected by NET. Unexpectedly, fast metabolism of the radiopharmaceutical was observed, with fraction of intact 177Lu-DOTATATE in plasma decreasing rapidly to 23±5% (mean ± SD) at 24 h and 1.7±0.9% at 96 h after injection. Full Article
ucl Efficacy of Peptide Receptor Radionuclide Therapy for Esthesioneuroblastoma By jnm.snmjournals.org Published On :: 2020-01-31T13:36:41-08:00 Objectives: Esthesioneuroblastoma (ENB) is rare with limited therapeutic options when unresectable or metastatic; however, expression of somatostatin receptors qualifies it for peptide receptor radionuclide therapy (PRRT). We report outcomes of PRRT in ENB from two referral centers. Methods: Using PRRT databases at two European Neuroendocrine Tumour Society Centers of Excellence, case finding was undertaken between 2004-2018 for patients who had PRRT with recurrent/metastatic ENB deemed unsuitable for further conventional therapies. Evaluations of response using a composite reference standard and for survival were performed. Results: Of seven patients, four had partial response, two had disease stabilization and one had early progression. Possible side effects include worsening CSF-leaks. Median progression-free survival was 17 months (range, 0-30), and median overall survival was 32 months (range, 4–53). Conclusion: PRRT shows promising efficacy and moderate survival duration in unresectable locally advanced or metastatic ENB warranting larger cohort studies incorporating measures of quality of life. Full Article
ucl Early prostate-specific antigen changes and clinical outcome following 177Lu-PSMA radionuclide treatment in patients with metastatic castration-resistant prostate cancer By jnm.snmjournals.org Published On :: 2020-02-28T13:52:17-08:00 Background: Prostate-specific antigen (PSA) is widely used to monitor treatment response in patients with metastatic castration-resistant prostate cancer (mCRPC). However, PSA measurements are considered only after 12 wk of treatment. We aimed to evaluate the prognostic value of early PSA changes following 177Lu-labelled prostate specific membrane antigen (LuPSMA) radionuclide treatment in mCRPC patients. Methods: Men who were treated under a compassionate access program with LuPSMA at our institution and had available PSA values at baseline, at 6 wk after treatment initiation were included in this retrospective analysis. Patients were assigned to three groups based on PSA changes: 1) response: ≥30% decline, 2) progression: ≥25% increase and 3) stable: <30% decline and <25% increase. The co-primary endpoints were overall survival and imaging-based progression-free survival. The secondary end points were PSA changes at 12 wk and PSA flare-up. Results: We identified 124 eligible patients with PSA values at 6 wk. A ≥30% decline in PSA at 6 wk was associated with longer overall survival (median 16.7 mo; 95%CI 14.4–19.0) compared with patients with stable PSA (median: 11.8 mo; 95%CI 8.6–15.1; P = 0.007) and progression (median: 6.5 mo; 95%CI 5.2–7.8; p<0.001). Patients with ≥30% decline in PSA at 6 wk also had a reduced risk of imaging-based progression compared with patients with stable PSA (HR: 0.60; 95%CI 0.38–0.94; P = 0.02), while patients with PSA progression had a higher risk of imaging-based progression compared with those showing stable PSA (HR: 3.18; 95%CI 1.95–5.21; p<0.001). The percentage changes of PSA at 6 wk and 12 wk were highly associated (r=0.90; p<0.001). 29 of 31 (94%) patients who experienced early PSA progression at 6 wk achieved biochemical progression at 12 wk. Overall, only 1 of 36 (3%) patients with PSA progression at 6 wk achieved any PSA decline at 12 wk (1% of the entire cohort). Limitations of the study included its retrospective nature and the single center experience. Conclusion: PSA changes at 6 wk after LuPSMA initiation are an early indicator of long-term clinical outcome. Patients progressing by PSA after 6 wk of treatment could benefit from a very early treatment switch decision. PSA flare-up during LuPSMA treatment is very uncommon. Prospective studies are now warranted to validate our findings and potentially inform clinicians earlier on the effectiveness of LuPSMA. Full Article
ucl OpenDose: open access resources for nuclear medicine dosimetry By jnm.snmjournals.org Published On :: 2020-03-13T14:12:30-07:00 Background: Radiopharmaceutical dosimetry depends on the localization in space and time of radioactive sources and requires the estimation of the amount of energy emitted by the sources deposited within targets. In particular, when computing resources are not accessible, this task can be carried out using precomputed tables of Specific Absorbed Fractions (SAFs) or S values based on dosimetric models. The OpenDose collaboration aims to generate and make freely available a range of dosimetric data and tools. Methods: OpenDose brings together resources and expertise from 18 international teams to produce and compare traceable dosimetric data using 6 of the most popular Monte Carlo codes in radiation transport (EGSnrc/EGS++, FLUKA, GATE, Geant4, MCNP/MCNPX and PENELOPE). SAFs are uploaded, together with their associated statistical uncertainties, in a relational database. S values are then calculated from mono-energetic SAFs, based on the radioisotope decay data presented in the International Commission on Radiological Protection (ICRP) publication 107. Results: The OpenDose collaboration produced SAFs for all source regions and targets combinations of the two ICRP 110 adult reference models. SAFs computed from the different Monte Carlo codes were in good agreement at all energies, with standard deviations below individual statistical uncertainties. Calculated S values were in good agreement with OLINDA 2 (commercial) and IDAC 2.1 (free) software. A dedicated website (www.opendose.org) has been developed to provide easy and open access to all data. Conclusion: The OpenDose website allows the display and download of SAFs and the corresponding S values for 1252 radionuclides. The OpenDose collaboration, open to new research teams, will extend data production to other dosimetric models and implement new free features, such as online dosimetric tools and patient-specific absorbed dose calculation software, together with educational resources. Full Article
ucl Prognostic Value of 18F-FDG PET/CT in a Large Cohort of 495 Patients with Advanced Metastatic Neuroendocrine Neoplasms (NEN) Treated with Peptide Receptor Radionuclide Therapy (PRRT) By jnm.snmjournals.org Published On :: 2020-03-13T14:12:30-07:00 The objective of this retrospective study was to determine the role of 18F-FDG PET/CT in a large cohort of 495 patients with metastatic neuroendocrine neoplasms (NENs) who were treated with peptide receptor radionuclide therapy (PRRT) with a long-term follow-up. Methods: The 495 patients were treated with 177Lu- and/or 90Y- DOTATOC/DOTATATE PRRT between 2/2002 and 7/2018. All subjects received both 68Ga-DOTATOC/TATE/NOC and 18F-FDG PET/CT prior to treatment and were followed 3-189 months. Kaplan-Meier analysis, log-rank test (Mantel-Cox), and Cox regression analysis were performed for overall survival (OS) and progression-free survival (PFS). Results: 199 patients (40.2%) presented with pancreatic NEN, 49 with CUP (cancer of unknown primary), 139 with midgut NEN, whereas the primary tumor was present in the rectum in 20, in the lung in 38, in the stomach in 8 and other locations in 42 patients. FDG-PET/CT was positive in 382 (77.2%) patients and 113 (22.8%) were FDG-negative before PRRT, while 100% were 68Ga-DOTATOC/TATE/NOC positive. For all patients, the median PFS and OS, defined from start of PRRT, were 19.6 mo and 58.7 mo, respectively. Positive FDG predicted shorter PFS (18.5 mo vs 24.1 mo; P = 0.0015) and OS (53.2 mo vs 83.1 mo; P < 0.001) than negative FDG. Amongst the pancreatic NEN, the median OS was 52.8 mo in FDG positive and 114.3 mo in FDG negative subjects (P = 0.0006). For all patients with positive 18F-FDG uptake, and a ratio of the highest SUVmax on 68Ga-SSTR PET to the most 18F-FDG-avid tumor lesions >2, the median OS was 53.0 mo, compared to 43.4 mo in those patients with a ratio <2 (P = 0.030). For patients with no 18F-FDG uptake (complete "mismatch" imaging pattern), the median OS was 108.3 mo vs 76.9 mo for SUVmax >15.0 and ≤15.0 on 68Ga-SSTR PET/CT, respectively. Conclusion: The presence of positive lesions on 18F-FDG PET is an independent prognostic factor in patients with NEN treated with PRRT. Metabolic imaging with 18F-FDG PET/CT compliments the molecular imaging aspect of 68Ga-SSTR PET/CT for the prognosis of survival after PRRT. High SSTR expression combined with negative 18F-FDG PET/CT imaging is associated with the most favorable long-term prognosis. Full Article
ucl The Changing Face of Nuclear Cardiology: Guiding Cardiovascular Care towards Molecular Medicine By jnm.snmjournals.org Published On :: 2020-04-17T08:32:41-07:00 Radionuclide imaging of myocardial perfusion, function, and viability has been established for decades and remains a robust, evidence-based and broadly available means for clinical workup and therapeutic guidance in ischemic heart disease. Yet, powerful alternative modalities have emerged for this purpose, and their growth has resulted in increasing competition. But the potential of the tracer principle goes beyond the assessment of physiology and function, towards the interrogation of biology and molecular pathways. This is a unique selling point of radionuclide imaging, which has been under-recognized in cardiovascular medicine until recently. Now, molecular imaging methods for the detection of myocardial infiltration, device infection and cardiovascular inflammation are successfully gaining clinical acceptance. This is further strengthened by the symbiotic quest of cardiac imaging and therapy for an increasing implementation of molecular-targeted procedures, where specific therapeutic interventions require specific diagnostic guidance towards the most suitable candidates. This review will summarize the current advent of clinical cardiovascular molecular imaging and highlight its transformative contribution to the evolution of cardiovascular therapy beyond mechanical interventions and broad "blockbuster" medication, towards a future of novel, individualized molecular targeted and molecular imaging-guided therapies. Full Article
ucl The role of Nuclear Medicine for COVID-19 - Time to act now. By jnm.snmjournals.org Published On :: 2020-04-17T08:32:41-07:00 Full Article
ucl Time for a Next-Generation Nuclear Medicine Gamma Camera? [NEWSLINE] By jnm.snmjournals.org Published On :: 2020-05-08T13:18:58-07:00 Full Article
ucl Human Hepatocyte Nuclear Factor 4-{alpha} Encodes Isoforms with Distinct Transcriptional Functions [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 HNF4α is a nuclear receptor produced as 12 isoforms from two promoters by alternative splicing. To characterize the transcriptional capacities of all 12 HNF4α isoforms, stable lines expressing each isoform were generated. The entire transcriptome associated with each isoform was analyzed as well as their respective interacting proteome. Major differences were noted in the transcriptional function of these isoforms. The α1 and α2 isoforms were the strongest regulators of gene expression whereas the α3 isoform exhibited significantly reduced activity. The α4, α5, and α6 isoforms, which use an alternative first exon, were characterized for the first time, and showed a greatly reduced transcriptional potential with an inability to recognize the consensus response element of HNF4α. Several transcription factors and coregulators were identified as potential specific partners for certain HNF4α isoforms. An analysis integrating the vast amount of omics data enabled the identification of transcriptional regulatory mechanisms specific to certain HNF4α isoforms, hence demonstrating the importance of considering all isoforms given their seemingly diverse functions. Full Article
ucl Nuclear Tensions Must Not Be Sidelined During Coronavirus By feedproxy.google.com Published On :: Fri, 01 May 2020 11:18:35 +0000 1 May 2020 Ana Alecsandru Research Assistant, International Security Programme @anaalecs LinkedIn Although the pandemic means the Nuclear Non-Proliferation Treaty (NPT) Review Conference (RevCon) is postponed, the delay could be an opportunity to better the health of the NPT regime. 2020-05-01-Iran-Peace-Nuclear Painted stairs in Tehran, Iran symbolizing hope. Photo by Fatemeh Bahrami/Anadolu Agency/Getty Images. Despite face-to-face diplomatic meetings being increasingly rare during the current disruption, COVID-19 will ultimately force a redefinition of national security and defence spending priorities, and this could provide the possibility of an improved political climate at RevCon when it happens in 2021.With US presidential elections due in November and a gradual engagement growing between the EU and Iran, there could be a new context for more cooperation between states by 2021. Two key areas of focus over the coming months will be the arms control talks between the United States and Russia, and Iran’s compliance with the 2015 Joint Comprehensive Plan of Action (JCPOA), also known as the Iran Nuclear Deal.It is too early to discern the medium- and longer-term consequences of COVID-19 for defence ministries, but a greater focus on societal resilience and reinvigorating economic productivity will likely undercut the rationale for expensive nuclear modernization.Therefore, extending the current New START (Strategic Arms Reduction Treaty) would be the best, most practical option to give both Russia and the United States time to explore more ambitious multilateral arms control measures, while allowing their current focus to remain on the pandemic and economic relief.Continuing distrustBut with the current treaty — which limits nuclear warheads, missiles, bombers, and launchers — due to expire in February 2021, the continuing distrust between the United States and Russia makes this extension hard to achieve, and a follow-on treaty even less likely.Prospects for future bilateral negotiations are hindered by President Donald Trump’s vision for a trilateral arms control initiative involving both China and Russia. But China opposes this on the grounds that its nuclear arsenal is far smaller than that of the two others.While there appears to be agreement that the nuclear arsenals of China, France, and the UK (the NPT nuclear-weapons states) and those of the states outside the treaty (India, Pakistan, North Korea, and Israel) will all have to be taken into account going forward, a practical mechanism for doing so proves elusive.If Joe Biden wins the US presidency he seems likely to pursue an extension of the New START treaty and could also prevent a withdrawal from the Open Skies treaty, the latest arms control agreement targeted by the Trump administration.Under a Biden administration, the United States would also probably re-join the JCPOA, provided Tehran returned to strict compliance with the deal. Biden could even use the team that negotiated the Iran deal to advance the goal of denuclearization of the Korean peninsula.For an NPT regime already confronted by a series of longstanding divergences, it is essential that Iran remains a signatory especially as tensions between Iran and the United States have escalated recently — due to the Qassim Suleimani assassination and the recent claim by Iran’s Revolutionary Guard Corps to have successfully placed the country’s first military satellite into orbit.This announcement raised red flags among experts about whether Iran is developing intercontinental ballistic missiles due to the dual-use nature of space technology. The satellite launch — deeply troubling for Iran’s neighbours and the EU countries — may strengthen the US argument that it is a cover for the development of ballistic missiles capable of delivering nuclear weapons.However, as with many other countries, Iran is struggling with a severe coronavirus crisis and will be pouring its scientific expertise and funds into that rather than other efforts — including the nuclear programme.Those European countries supporting the trading mechanism INSTEX (Instrument in Support of Trade Exchanges) for sending humanitarian goods into Iran could use this crisis to encourage Iran to remain in compliance with the JCPOA and its NPT obligations.France, Germany and the UK (the E3) have already successfully concluded the first transaction, which was to facilitate the export of medical goods from Europe to Iran. But the recent Iranian escalatory steps will most certainly place a strain on the preservation of this arrangement.COVID-19 might have delayed Iran’s next breach of the 2015 nuclear agreement but Tehran will inevitably seek to strengthen its hand before any potential negotiations with the United States after the presidential elections.As frosty US-Iranian relations — exacerbated by the coronavirus pandemic — prevent diplomatic negotiations, this constructive engagement between the E3 and Iran might prove instrumental in reviving the JCPOA and ensuring Iran stays committed to both nuclear non-proliferation and disarmament.While countries focus their efforts on tackling the coronavirus pandemic, it is understandable resources may be limited for other global challenges, such as the increasing risk of nuclear weapons use across several regions.But the potential ramifications of the COVID-19 crisis for the NPT regime are profound. Ongoing tensions between the nuclear-armed states must not be ignored while the world’s focus is elsewhere, and the nuclear community should continue to work together to progress nuclear non-proliferation and disarmament, building bridges of cooperation and trust that can long outlast the pandemic. Full Article
ucl Detection of multiple autoantibodies in patients with ankylosing spondylitis using nucleic acid programmable protein arrays [11. Microarrays/Combinatorics/Display Technology] By feedproxy.google.com Published On :: 2010-02-01T14:51:46-08:00 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. Full Article
ucl Perspectives on Nuclear Deterrence in the 21st Century By feedproxy.google.com Published On :: Sun, 19 Apr 2020 19:32:28 +0000 20 April 2020 Nuclear deterrence theory, with its roots in the Cold War era, may not account for all eventualities in the 21st century. Researchers at Chatham House have worked with eight experts to produce this collection of essays examining four contested themes in contemporary policymaking on deterrence. Read online Download PDF Dr Beyza Unal Senior Research Fellow, International Security Programme @beyzaunal Google Scholar Yasmin Afina Research Assistant, International Security Programme @afinayasmin LinkedIn Dr Patricia Lewis Research Director, Conflict, Science & Transformation; Director, International Security Programme @PatriciaMary Dr John Borrie Associate Fellow, International Security Programme Google Scholar Dr Jamie Shea Associate Fellow, International Security Programme LinkedIn Peter Watkins Associate Fellow, International Security Programme LinkedIn Dr Maria Rost Rublee Associate Professor of International Relations, Monash University Cristina Varriale Research Fellow in Proliferation and Nuclear Policy, RUSI Dr Tanya Ogilvie-White Adjunct Senior Fellow, Griffith Asia Institute, Griffith University Dr Andrew Futter Associate Professor of International Politics, University of Leicester Christine Parthemore Chief Executive Officer, Council on Strategic Risks (CSR) 2020-04-20-NuclearDeterrence.jpeg Royal Navy Vanguard Class submarine HMS Vigilant returning to HMNB Clyde after extended deployment. The four Vanguard-class submarines form the UK's strategic nuclear deterrent force. Photo: Ministry of Defence. SummaryThis collection of essays explores, from the perspectives of eight experts, four areas of deterrence theory and policymaking: the underlying assumptions that shape deterrence practice; the enduring value of extended deterrence; the impact of emerging technologies; and the ‘blurring’ of the lines between conventional and nuclear weapons.Nuclear deterrence theory, with its roots in the Cold War era, may not account for all eventualities in security and defence in the 21st century, given the larger number of nuclear actors in a less binary geopolitical context. It is clear that a number of present factors challenge the overall credibility of ‘classical’ nuclear deterrence, meaning that in-depth analysis is now needed.Uncertainty as to the appetite to maintain the current nuclear weapons policy architecture looms large in discussions and concerns on global and regional security. The demise of the Intermediate-Range Nuclear Forces Treaty, doubts over the potential extension of the New Strategic Arms Reduction Treaty, heightened regional tensions in Northeast and South Asia, together with the current and likely future risks and challenges arising from global technological competition, making it all the more urgent to examine long-held assumptions in the real-world context.Extended deterrence practices differ from region to region, depending on the domestic and regional landscape. Increased focus on diplomatic capabilities to reduce risks and improve the long-term outlook at regional level, including by spearheading new regional arms-control initiatives, may be a viable way forward. Addressing the bigger picture – notably including, on the Korean peninsula, Pyongyang’s own threat perception – and the links between conventional and nuclear missile issues will need to remain prominent if long-term and concrete changes are to take hold.Most states have long held nuclear weapons to be ‘exceptional’: their use would represent a dramatic escalation of a conflict that must never be attained. Latterly, however, some officials and scholars have made the case that the impact of the use of a low-yield nuclear weapon would not be entirely distinct from that of a large-scale conventional attack. This blurring of lines between conventional and nuclear deterrence strips nuclear weapons of their exceptional nature, in a context in which states are faced with diverse, complex and concurrent threats from multiple potential adversaries that are able to synchronize non-military and military options, up to and including nuclear forces. The use of nuclear weapons risks becoming a ‘new normal’, potentially reducing the threshold for use – to cyberattacks, for example. This has direct implications for discussions around strategic stability. While emerging technologies may offer tremendous opportunities in the modernization of nuclear weapons, they also present major risks and destabilizing challenges. Artificial intelligence, automation, and other developments in the cyber sphere affect dynamics on both the demand and supply sides of the nuclear deterrence equation. States and alliance such as NATO must adapt their deterrence thinking in light of these technological developments, and define their primary purpose and priorities in this shifting security context. Resilience planning, adaptation to the evolving security environment, threat anticipation, and consistent crisis management and incident response – as well as thinking about the mitigation measures necessary to prevent conflict escalation should deterrence fail – will all be critical in upholding nuclear deterrence as both policy and practice. Department/project International Security Programme, Deterrence Perspectives in the 21st Century Full Article
ucl Nuclear Weapons: Trident is the Answer, Now What was the Question? By feedproxy.google.com Published On :: Tue, 21 Apr 2020 15:43:46 +0000 1 February 2007 , Number 3 Next month, parliament will vote on whether to replace Britain’s Trident nuclear missile submarines with a new and similar system. There is little doubt the proposal will be approved with support from the Conservative opposition. But the facts used to back the government’s favourite option raise as many questions as answers. The future of Britain’s defence is in doubt. Andrew Norman Senior Lecturer, Defence Studies, King's College London GettyImages-51273218.jpg Trident Submarine USS Georgia Full Article
ucl Chemical, Biological, Radiological and Nuclear Terrorism: Tomorrow's Threat By feedproxy.google.com Published On :: Mon, 27 Apr 2020 13:23:42 +0000 1 March 2007 , Number 11 In early November, the retiring head of Britain’s Security Service MI5, Dame Eliza Manningham-Buller, warned that the danger of a terror attack was ‘serious’ and ‘growing’, with as many as thirty plots underway. Traditional terrorism of the sort practised by the Irish Republican Army has given way to the possibility, if not the expectation, that groups such as Al Qaeda might make use of chemical, biological, radiological and nuclear weapons and materials in an attack in Britain. So what are the dangers? GettyImages-200457787-001 copy.jpg Syrian Special Forces in gas masks, Saudi Arabia 1990 Full Article
ucl Two- and three-color STORM analysis reveals higher-order assembly of leukotriene synthetic complexes on the nuclear envelope of murine neutrophils [Computational Biology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Over the last several years it has become clear that higher order assemblies on membranes, exemplified by signalosomes, are a paradigm for the regulation of many membrane signaling processes. We have recently combined two-color direct stochastic optical reconstruction microscopy (dSTORM) with the (Clus-DoC) algorithm that combines cluster detection and colocalization analysis to observe the organization of 5-lipoxygenase (5-LO) and 5-lipoxygenase–activating protein (FLAP) into higher order assemblies on the nuclear envelope of mast cells; these assemblies were linked to leukotriene (LT) C4 production. In this study we investigated whether higher order assemblies of 5-LO and FLAP included cytosolic phospholipase A2 (cPLA2) and were linked to LTB4 production in murine neutrophils. Using two- and three-color dSTORM supported by fluorescence lifetime imaging microscopy we identified higher order assemblies containing 40 molecules (median) (IQR: 23, 87) of 5-LO, and 53 molecules (62, 156) of FLAP monomer. 98 (18, 154) molecules of cPLA2 were clustered with 5-LO, and 77 (33, 114) molecules of cPLA2 were associated with FLAP. These assemblies were tightly linked to LTB4 formation. The activation-dependent close associations of cPLA2, FLAP, and 5-LO in higher order assemblies on the nuclear envelope support a model in which arachidonic acid is generated by cPLA2 in apposition to FLAP, facilitating its transfer to 5-LO to initiate LT synthesis. Full Article
ucl Correction: Mitochondrial and nuclear genomic responses to loss of LRPPRC expression. [Additions and Corrections] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 VOLUME 285 (2010) PAGES 13742–13747In Fig. 1E, passage 10, the splicing of a non-adjacent lane from the same immunoblot was not marked. This error has now been corrected and does not affect the results or conclusions of this work.jbc;295/16/5533/F1F1F1Figure 1E. Full Article
ucl Nuclear Tensions Must Not Be Sidelined During Coronavirus By feedproxy.google.com Published On :: Fri, 01 May 2020 11:18:35 +0000 1 May 2020 Ana Alecsandru Research Assistant, International Security Programme @anaalecs LinkedIn Although the pandemic means the Nuclear Non-Proliferation Treaty (NPT) Review Conference (RevCon) is postponed, the delay could be an opportunity to better the health of the NPT regime. 2020-05-01-Iran-Peace-Nuclear Painted stairs in Tehran, Iran symbolizing hope. Photo by Fatemeh Bahrami/Anadolu Agency/Getty Images. Despite face-to-face diplomatic meetings being increasingly rare during the current disruption, COVID-19 will ultimately force a redefinition of national security and defence spending priorities, and this could provide the possibility of an improved political climate at RevCon when it happens in 2021.With US presidential elections due in November and a gradual engagement growing between the EU and Iran, there could be a new context for more cooperation between states by 2021. Two key areas of focus over the coming months will be the arms control talks between the United States and Russia, and Iran’s compliance with the 2015 Joint Comprehensive Plan of Action (JCPOA), also known as the Iran Nuclear Deal.It is too early to discern the medium- and longer-term consequences of COVID-19 for defence ministries, but a greater focus on societal resilience and reinvigorating economic productivity will likely undercut the rationale for expensive nuclear modernization.Therefore, extending the current New START (Strategic Arms Reduction Treaty) would be the best, most practical option to give both Russia and the United States time to explore more ambitious multilateral arms control measures, while allowing their current focus to remain on the pandemic and economic relief.Continuing distrustBut with the current treaty — which limits nuclear warheads, missiles, bombers, and launchers — due to expire in February 2021, the continuing distrust between the United States and Russia makes this extension hard to achieve, and a follow-on treaty even less likely.Prospects for future bilateral negotiations are hindered by President Donald Trump’s vision for a trilateral arms control initiative involving both China and Russia. But China opposes this on the grounds that its nuclear arsenal is far smaller than that of the two others.While there appears to be agreement that the nuclear arsenals of China, France, and the UK (the NPT nuclear-weapons states) and those of the states outside the treaty (India, Pakistan, North Korea, and Israel) will all have to be taken into account going forward, a practical mechanism for doing so proves elusive.If Joe Biden wins the US presidency he seems likely to pursue an extension of the New START treaty and could also prevent a withdrawal from the Open Skies treaty, the latest arms control agreement targeted by the Trump administration.Under a Biden administration, the United States would also probably re-join the JCPOA, provided Tehran returned to strict compliance with the deal. Biden could even use the team that negotiated the Iran deal to advance the goal of denuclearization of the Korean peninsula.For an NPT regime already confronted by a series of longstanding divergences, it is essential that Iran remains a signatory especially as tensions between Iran and the United States have escalated recently — due to the Qassim Suleimani assassination and the recent claim by Iran’s Revolutionary Guard Corps to have successfully placed the country’s first military satellite into orbit.This announcement raised red flags among experts about whether Iran is developing intercontinental ballistic missiles due to the dual-use nature of space technology. The satellite launch — deeply troubling for Iran’s neighbours and the EU countries — may strengthen the US argument that it is a cover for the development of ballistic missiles capable of delivering nuclear weapons.However, as with many other countries, Iran is struggling with a severe coronavirus crisis and will be pouring its scientific expertise and funds into that rather than other efforts — including the nuclear programme.Those European countries supporting the trading mechanism INSTEX (Instrument in Support of Trade Exchanges) for sending humanitarian goods into Iran could use this crisis to encourage Iran to remain in compliance with the JCPOA and its NPT obligations.France, Germany and the UK (the E3) have already successfully concluded the first transaction, which was to facilitate the export of medical goods from Europe to Iran. But the recent Iranian escalatory steps will most certainly place a strain on the preservation of this arrangement.COVID-19 might have delayed Iran’s next breach of the 2015 nuclear agreement but Tehran will inevitably seek to strengthen its hand before any potential negotiations with the United States after the presidential elections.As frosty US-Iranian relations — exacerbated by the coronavirus pandemic — prevent diplomatic negotiations, this constructive engagement between the E3 and Iran might prove instrumental in reviving the JCPOA and ensuring Iran stays committed to both nuclear non-proliferation and disarmament.While countries focus their efforts on tackling the coronavirus pandemic, it is understandable resources may be limited for other global challenges, such as the increasing risk of nuclear weapons use across several regions.But the potential ramifications of the COVID-19 crisis for the NPT regime are profound. Ongoing tensions between the nuclear-armed states must not be ignored while the world’s focus is elsewhere, and the nuclear community should continue to work together to progress nuclear non-proliferation and disarmament, building bridges of cooperation and trust that can long outlast the pandemic. Full Article
ucl Why wealthy countries must not drop nuclear energy: coal power, climate change and the fate of the global poor By feedproxy.google.com Published On :: Thu, 12 Mar 2015 11:37:45 +0000 12 March 2015 , Volume 91, Number 2 Reinhard Wolf Full Article
ucl Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents By diabetes.diabetesjournals.org Published On :: 1999-08-01 G PerseghinAug 1, 1999; 48:1600-1606Articles Full Article
ucl Cholecystokinin 2 Receptor Agonist 177Lu-PP-F11N for Radionuclide Therapy of Medullary Thyroid Carcinoma: Results of the Lumed Phase 0a Study By jnm.snmjournals.org Published On :: 2020-04-01T06:00:28-07:00 Treatment of patients with advanced medullary thyroid carcinoma (MTC) is still a challenge. For more than 2 decades, it has been known that the cholecystokinin 2 receptor is a promising target for the treatment of MTC with radiolabeled minigastrin analogs. Unfortunately, kidney toxicity has precluded their therapeutic application so far. In 6 consecutive patients, we evaluated with advanced 3-dimensional dosimetry whether improved minigastrin analog 177Lu-DOTA-(d-Glu)6-Ala-Tyr-Gly-Trp-Nle-Asp-PheNH2 (177Lu-PP-F11N) is a suitable agent for the treatment of MTC. Methods: Patients received 2 injections of about 1 GBq (~80 μg) of 177Lu-PP-F11N with and without a solution of succinylated gelatin (SG, a plasma expander used for nephroprotection) in a random crossover sequence to evaluate biodistribution, pharmacokinetics, and tumor and organ dosimetry. An electrocardiogram was obtained and blood count and blood chemistry were measured up to 12 wk after the administration of 177Lu-PP-F11N to assess safety. Results: In all patients, 177Lu-PP-F11N accumulation was visible in tumor tissue, stomach, and kidneys. Altogether, 13 tumors were eligible for dosimetry. The median absorbed doses for tumors, stomach, kidneys, and bone marrow were 0.88 (interquartile range [IQR]: 0.85–1.04), 0.42 (IQR: 0.25–1.01), 0.11 (IQR: 0.07–0.13), and 0.028 (IQR: 0.026–0.034) Gy/GBq, respectively. These doses resulted in median tumor-to-kidney dose ratios of 11.6 (IQR: 8.11–14.4) without SG and 13.0 (IQR: 10.2–18.6) with SG; these values were not significantly different (P = 1.0). The median tumor-to-stomach dose ratio was 3.34 (IQR: 1.14–4.70). Adverse reactions (mainly hypotension, flushing, and hypokalemia) were self-limiting and not higher than grade 1. Conclusion: 177Lu-PP-F11N accumulates specifically in MTC at a dose that is sufficient for a therapeutic approach. With a low kidney and bone marrow radiation dose, 177Lu-PP-F11N shows a promising biodistribution. The dose-limiting organ is most likely the stomach. Further clinical studies are necessary to evaluate the maximum tolerated dose and the efficacy of 177Lu-PP-F11N. Full Article
ucl Nuclear Energy in a Post-Brexit Europe By feedproxy.google.com Published On :: Wed, 18 Sep 2019 14:45:01 +0000 Invitation Only Research Event 11 October 2019 - 8:30am to 10:00am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Tim Yeo, Chairman, The New Nuclear Watch InstituteChair: Antony Froggatt, Senior Research Fellow, Energy, Environment and Resources, Chatham House 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. Event attributes Chatham House Rule Department/project Energy, Environment and Resources Programme, Sustainable Transitions Series Chloé Prendleloup Email Full Article
ucl Impact of 1,N6-ethenoadenosine, a damaged ribonucleotide in DNA, on translesion synthesis and repair [Enzymology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2. Full Article
ucl UCLA dental school researchers create nanoparticle that could improve bone defect treatment By www.ada.org Published On :: Tue, 05 May 2020 10:25:00 -0500 A team of researchers at the University of California, Los Angeles School of Dentistry has developed a nanoparticle that could improve treatment for bone defects. Full Article
ucl Two- and three-color STORM analysis reveals higher-order assembly of leukotriene synthetic complexes on the nuclear envelope of murine neutrophils [Computational Biology] By www.jbc.org Published On :: 2020-04-24T06:08:45-07:00 Over the last several years it has become clear that higher order assemblies on membranes, exemplified by signalosomes, are a paradigm for the regulation of many membrane signaling processes. We have recently combined two-color direct stochastic optical reconstruction microscopy (dSTORM) with the (Clus-DoC) algorithm that combines cluster detection and colocalization analysis to observe the organization of 5-lipoxygenase (5-LO) and 5-lipoxygenase–activating protein (FLAP) into higher order assemblies on the nuclear envelope of mast cells; these assemblies were linked to leukotriene (LT) C4 production. In this study we investigated whether higher order assemblies of 5-LO and FLAP included cytosolic phospholipase A2 (cPLA2) and were linked to LTB4 production in murine neutrophils. Using two- and three-color dSTORM supported by fluorescence lifetime imaging microscopy we identified higher order assemblies containing 40 molecules (median) (IQR: 23, 87) of 5-LO, and 53 molecules (62, 156) of FLAP monomer. 98 (18, 154) molecules of cPLA2 were clustered with 5-LO, and 77 (33, 114) molecules of cPLA2 were associated with FLAP. These assemblies were tightly linked to LTB4 formation. The activation-dependent close associations of cPLA2, FLAP, and 5-LO in higher order assemblies on the nuclear envelope support a model in which arachidonic acid is generated by cPLA2 in apposition to FLAP, facilitating its transfer to 5-LO to initiate LT synthesis. Full Article
ucl WNBA Draft Profile: UCLA guard Japreece Dean ready to lead at the next level By sports.yahoo.com Published On :: Fri, 10 Apr 2020 16:40:28 GMT UCLA guard Japreece Dean is primed to shine at the next level as she heads to the WNBA Draft in April. The do-it-all point-woman was an All-Pac-12 honoree last season, and one of only seven D-1 hoopers with at least 13 points and 5.5 assists per game. Full Article video Sports
ucl UCLA's Natalie Chou on her role models, inspiring Asian-American girls in basketball By sports.yahoo.com Published On :: Tue, 05 May 2020 21:33:42 GMT Pac-12 Networks' Mike Yam has a conversation with UCLA's Natalie Chou during Wednesday's "Pac-12 Perspective" podcast. Chou reflects on her role models, passion for basketball and how her mom has made a big impact on her hoops career. Full Article video Sports
ucl Statistical aspects of nuclear mass models. (arXiv:2002.04151v3 [nucl-th] UPDATED) By arxiv.org Published On :: We study the information content of nuclear masses from the perspective of global models of nuclear binding energies. To this end, we employ a number of statistical methods and diagnostic tools, including Bayesian calibration, Bayesian model averaging, chi-square correlation analysis, principal component analysis, and empirical coverage probability. Using a Bayesian framework, we investigate the structure of the 4-parameter Liquid Drop Model by considering discrepant mass domains for calibration. We then use the chi-square correlation framework to analyze the 14-parameter Skyrme energy density functional calibrated using homogeneous and heterogeneous datasets. We show that a quite dramatic parameter reduction can be achieved in both cases. The advantage of Bayesian model averaging for improving uncertainty quantification is demonstrated. The statistical approaches used are pedagogically described; in this context this work can serve as a guide for future applications. Full Article
ucl Microbial cyclic di-nucleotide signaling By dal.novanet.ca Published On :: Fri, 1 May 2020 19:44:43 -0300 Callnumber: OnlineISBN: 9783030333089 Full Article
ucl Low-dose radiation effects on animals and ecosystems : long-term study on the Fukushima Nuclear Accident By dal.novanet.ca Published On :: Fri, 1 May 2020 19:44:43 -0300 Callnumber: OnlineISBN: 9789811382185 (electronic bk.) Full Article
ucl A handbook of nuclear applications in humans' lives By dal.novanet.ca Published On :: Fri, 1 May 2020 19:44:43 -0300 Author: Tabbakh, Farshid, author.Callnumber: OnlineISBN: 9781527544512 (electronic bk.) Full Article
ucl Astrocytes Modulate Baroreflex Sensitivity at the Level of the Nucleus of the Solitary Tract By www.jneurosci.org Published On :: 2020-04-08 Svetlana MastitskayaApr 8, 2020; 40:3052-3062Systems/Circuits Full Article
ucl Astrocytes Modulate Baroreflex Sensitivity at the Level of the Nucleus of the Solitary Tract By www.jneurosci.org Published On :: 2020-04-08T09:30:18-07:00 Maintenance of cardiorespiratory homeostasis depends on autonomic reflexes controlled by neuronal circuits of the brainstem. The neurophysiology and neuroanatomy of these reflex pathways are well understood, however, the mechanisms and functional significance of autonomic circuit modulation by glial cells remain largely unknown. In the experiments conducted in male laboratory rats we show that astrocytes of the nucleus of the solitary tract (NTS), the brain area that receives and integrates sensory information from the heart and blood vessels, respond to incoming afferent inputs with [Ca2+]i elevations. Astroglial [Ca2+]i responses are triggered by transmitters released by vagal afferents, glutamate acting at AMPA receptors and 5-HT acting at 5-HT2A receptors. In conscious freely behaving animals blockade of Ca2+-dependent vesicular release mechanisms in NTS astrocytes by virally driven expression of a dominant-negative SNARE protein (dnSNARE) increased baroreflex sensitivity by 70% (p < 0.001). This effect of compromised astroglial function was specific to the NTS as expression of dnSNARE in astrocytes of the ventrolateral brainstem had no effect. ATP is considered the principle gliotransmitter and is released by vesicular mechanisms blocked by dnSNARE expression. Consistent with this hypothesis, in anesthetized rats, pharmacological activation of P2Y1 purinoceptors in the NTS decreased baroreflex gain by 40% (p = 0.031), whereas blockade of P2Y1 receptors increased baroreflex gain by 57% (p = 0.018). These results suggest that glutamate and 5-HT, released by NTS afferent terminals, trigger Ca2+-dependent astroglial release of ATP to modulate baroreflex sensitivity via P2Y1 receptors. These data add to the growing body of evidence supporting an active role of astrocytes in brain information processing. SIGNIFICANCE STATEMENT Cardiorespiratory reflexes maintain autonomic balance and ensure cardiovascular health. Impaired baroreflex may contribute to the development of cardiovascular disease and serves as a robust predictor of cardiovascular and all-cause mortality. The data obtained in this study suggest that astrocytes are integral components of the brainstem mechanisms that process afferent information and modulate baroreflex sensitivity via the release of ATP. Any condition associated with higher levels of "ambient" ATP in the NTS would be expected to decrease baroreflex gain by the mechanism described here. As ATP is the primary signaling molecule of glial cells (astrocytes, microglia), responding to metabolic stress and inflammatory stimuli, our study suggests a plausible mechanism of how the central component of the baroreflex is affected in pathological conditions. Full Article
ucl Seven examples of nuclear technology improving food and agriculture By www.fao.org Published On :: Wed, 27 Sep 2017 00:00:00 GMT Some of the most innovative ways being used to improve agricultural practices involve nuclear technology. Nuclear applications in agriculture rely on the use of isotopes and radiation techniques to combat pests and diseases, increase crop production, protect land and water resources, ensure food safety and authenticity, and increase livestock production. FAO and the International Atomic Energy Agency (IAEA) have been expanding [...] Full Article
ucl Innovation in a crisis Q&A series: UCL-Ventura breathing aid (CPAP) By www.raeng.org.uk Published On :: Tue, 19 May 2020 14:00:00 +01:00 Full Article
ucl Staining Nucleic Acids By cshprotocols.cshlp.org Published On :: 2020-02-03T06:30:10-08:00 This introduction describes the features and uses of ethidium bromide, methylene blue, and SYBR dyes for staining nucleic acids. Full Article
ucl A Simple Method To Detect Point Mutations in Aspergillus fumigatus cyp51A Gene Using a Surveyor Nuclease Assay [Analytical Procedures] By aac.asm.org Published On :: 2020-03-24T08:01:15-07:00 One of the main mechanisms of azole resistance of Aspergillus fumigatus is thought to be a reduction in the drug’s affinity for the target molecule, Cyp51A, due to its amino acid mutation(s). It is known that the azole resistance pattern is closely related to the mutation site(s) of the molecule. In this study, we tried to develop a simple and rapid detection method for cyp51A mutations using the endonuclease Surveyor nuclease. The Surveyor nuclease assay was verified using several azole-resistant strains of A. fumigatus that possess point mutations in Cyp51A. For validation of the Surveyor nuclease assay, blind tests were conducted using 48 strains of A. fumigatus (17 azole-resistant and 31 azole-susceptible strains). The Surveyor nuclease assay could rapidly detect cyp51A mutations with one primer set. Also, all the tested strains harboring different cyp51A single point mutations could be clearly distinguished from the wild type. The Surveyor nuclease assay is a simple method that can detect cyp51A mutations rapidly. Full Article
ucl Fin24.com | Govt still pursuing plans for more nuclear power By www.fin24.com Published On :: Fri, 08 May 2020 12:37:44 +0200 Mineral Resources and Energy Minister Gwede Mantashe says that if there is appetite for nuclear power in the market, the SA government will pursue it over the next five years. Full Article
ucl Fetal and Maternal Candidate Single Nucleotide Polymorphism Associations With Cerebral Palsy: A Case-Control Study By pediatrics.aappublications.org Published On :: 2012-01-30T00:06:43-08:00 Candidate genes involved in thrombophilia, inflammation, and preterm birth have previously been associated with cerebral palsy. Most studies to date have included small cohorts, did not allow for multiple testing, and require replication.This study of children with cerebral palsy and their mothers did not confirm previously reported candidate gene associations. Prothrombin gene mutation was associated with hemiplegia in children born at term to mothers with a reported infection during pregnancy. (Read the full article) Full Article
ucl Incidence of Rash After Amoxicillin Treatment in Children With Infectious Mononucleosis By pediatrics.aappublications.org Published On :: 2013-04-15T00:06:42-07:00 Antibiotics-induced rash in Epstein-Barr virus acute infectious mononucleosis, especially the aminopenicillins-induced type, was first described during the 1960s, with a reported incidence of 80% to 100%. This phenomenon was not further investigated but is well-established in pediatric textbooks.The main observation of this study is that rash induced by amoxicillin in confirmed Epstein-Barr virus acute infectious mononucleosis was found at a rate of ~30%, which is much lower than previously reported. (Read the full article) Full Article
ucl #UCLFutsal main round report By www.uefa.com Published On :: Sun, 07 Oct 2018 14:30:00 GMT The elite round line-up is complete with the likes of holders Inter FS, Barça, Benfica, Sporting, Ugra and Kairat making progress. Full Article general
ucl Coaches on #UCLFutsal finals draw By www.uefa.com Published On :: Fri, 01 Feb 2019 16:30:00 GMT UEFA.com hears from the four coaches after the semi-final draw was made for the matches on 26 April at Almaty Arena. Full Article general
ucl Sporting pip Kairat for #UCLFutsal title By www.uefa.com Published On :: Sun, 28 Apr 2019 16:53:00 GMT Sporting CP beat hosts Kairat Almaty 2-1 to win the title, while Barça edged Inter FS for bronze. Full Article general
ucl Public Advocate Calls on White House to Deny Subsidies for Coal and Nuclear Plants By news.delaware.gov Published On :: Thu, 03 May 2018 20:29:35 +0000 Delaware’s Public Advocate today issued a letter to the White House asking the Trump administration to deny a request for emergency bailouts for aging coal and nuclear power plants owned by a large regional energy supplier. Full Article Department of State News energy efficiency PJM Public Advocate public utilities white house
ucl China should TRIPLE nuclear arsenal to deter ‘warmongering’ US, editor of state-run Global Times argues By www.rt.com Published On :: Fri, 08 May 2020 12:55:17 +0000 China should drastically increase its stockpile of nuclear warheads to dissuade the United States from pursuing its strategic ambitions abroad, the editor of the Global Times has urged. Read Full Article at RT.com Full Article
ucl There’s too much hype about Pakistan’s nuclear capability: Anil Kakodkar By www.financialexpress.com Published On :: 2020-01-05T01:46:00+05:30 Nuclear physicists Kakodkar and Gangotra believe India’s nuclear industry “lost time” due to liability regime that followed 2008 nuclear deal, say country should aim for 50% nuclear energy, and insist that the space programme is about “national pride”, not jingoism Full Article India
ucl Exodus from Kiev: aftermath of Chernobyl nuclear accident - archive, 5 May 1986 By www.theguardian.com Published On :: 2020-05-05T04:30:27Z 5 May 1986: Moscow has seen many Russians arriving by train from Kiev in the disaster area MoscowThe first real signs of alarm among the Soviet public began to emerge over the weekend as Russians arriving by train from Kiev in the Chernobyl disaster area, began saying frankly that they were worried by radiation.In the last two days large numbers of unescorted children have been arriving here from the city by train, to be met by relatives and grandparents. Related: From the archive, 30 April 1986: Russia admits blast as death fears rise Related: Revisiting Chernobyl: 'It is a huge cemetery of dreams' Continue reading... Full Article Chernobyl nuclear disaster Russia Nuclear power
