ace Fresno residents adjust to first day of mandatory face masks By news.yahoo.com Published On :: Thu, 07 May 2020 21:17:01 -0400 You can now add Fresno to the growing list of cities that are now requiring people to wear face masks in public places. Full Article
ace Reopened restaurant tells workers: Don't wear face masks — or don't work By news.yahoo.com Published On :: Sat, 09 May 2020 07:51:42 -0400 Restaurant workers in a reopened Dallas eatery say they are being asked to weigh their safety against their jobs. Full Article
ace Police stop fewer black drivers at night when a 'veil of darkness' obscures their race By www.eurekalert.org Published On :: Wed, 06 May 2020 00:00:00 EDT (Stanford School of Engineering) After analyzing 95 million traffic stop records, filed by officers with 21 state patrol agencies and 35 municipal police forces from 2011 to 2018, a Stanford-led research team concluded that 'police stops and search decisions suffer from persistent racial bias.' Full Article
ace Planting trees is no panacea for climate change, ecologist writes in Science commentary By www.eurekalert.org Published On :: Thu, 07 May 2020 00:00:00 EDT (University of California - Santa Cruz) Restoration ecologist Karen Holl has a simple message for anyone who thinks planting 1 trillion trees will reverse the damage of climate change: 'We can't plant our way out of climate change.' Full Article
ace Complementary and Integrative Medicine: Emerging Therapies for Diabetes, Part 1: Preface By spectrum.diabetesjournals.org Published On :: 2001-08-01 Cynthia PayneAug 1, 2001; 14:Preface Full Article
ace Transforming LEDVANCE: Lighting for the Smart Home and Global IoT Marketplace By www8.gsb.columbia.edu Published On :: Fri, 28 Feb 2020 17:19:09 +0000 What strategic direction should LEDVANCE take to optimize the opportunities presented by the proliferation of Smart Home products and the prospect of integrating its lighting products to the Internet of Things? Full Article
ace What Next After the Facebook and Cambridge Analytica Revelations? By feedproxy.google.com Published On :: Wed, 23 May 2018 11:00:00 +0000 Research Event 2 July 2018 - 6:00pm to 7:30pm Chatham House, London Event participants Silkie Carlo, Director, Big Brother WatchProfessor David Kaye, UN Special Rapporteur on the Promotion and Protection of the Right to Freedom of Opinion and Expression, University of California, Irvine, School of Law Professor Lorna McGregor, Principal Investigator and Co-Director of the ESRC, Human Rights, Big Data and Technology ProjectJames Williams, Oxford Internet InstituteChair: Harriet Moynihan, Associate Fellow, International Law Programme, Chatham House Please note this event was originally scheduled on 13 June 2018 and has been postponed to 2 July 2018.Technology companies, social media platforms and other internet intermediaries dominate the digital age, and harnessing data in algorithmic and artificial intelligence systems is widespread, from political campaigns to judicial sentencing.The recent Facebook and Cambridge Analytica revelations provide a sharp illustration of the risks to human rights and democracy posed by data-mining and "platform capital".These revelations have focused public and policy debate on two key issues. First, they raise questions of how accountability and remedies can be effectively achieved, particularly where companies close in the wake of such revelations. Second, key questions arise on what regulation should look like.Facebook has pledged to respect privacy of its users better, but how effective is self-regulation? There has been heavy emphasis on the role that the EU General Data Protection Regulation (GDPR) can play to improve the protection of privacy and data protection, but will it be enough? What are the implications for international law - how can the established standards in human rights and data protection respond to these challenges?This event, co-hosted with the ESRC, Human Rights, Big Data and Technology Project, will be followed by a drinks reception.Read the meeting summary on the Human Rights, Big Data and Technology Project website. Department/project International Law Programme, International Law Discussion Group Full Article
ace Power Politics Could Impede Progress on Responsible Regulation of Cyberspace By feedproxy.google.com Published On :: Tue, 03 Dec 2019 14:34:13 +0000 3 December 2019 Harriet Moynihan Senior Research Fellow, International Law Programme @HarrietMoyniha9 A new Chatham House paper examines the prospects of countries reaching agreement on issues of sovereignty and non-intervention in cyberspace in the face of persistent, low-level, state-to-state cyber attacks. 2019-11-29-Intl-Law-Cyberattacks.jpg A computer hacked by a virus known as Petya. The Petya ransomware cyberattack hit computers of Russian and Ukrainian companies on 27 June 2017. Photo: Getty Images. In discussions to date about how international law applies in cyberspace, commentators have tended to focus their attention on how the rules on the use of force, or the law of armed conflict, apply to cyber activities conducted by states that give rise to physical damage, injury or death.But in practice, the vast majority of state cyberattacks fall below this threshold. Far more common are persistent, low-level attacks that may leave no physical trace but that are capable of doing significant damage to a state’s ability to control its systems, often at serious economic cost.Such cyber incursions might include network disruptions in the operation of another government’s websites; tampering with electoral infrastructure to change or undermine the result; or using cyber means to destabilize another state’s financial sector.For these kinds of cyber operation, the principle of sovereignty, and the principle of non-intervention in another state’s internal affairs, are the starting point.A UN Group of Government Experts (GGE) agreed in 2013 and 2015 that the principles in the UN Charter, including sovereignty and the prohibition on intervention in another state’s affairs, apply to states’ activities in cyberspace. The 2015 GGE also recommended eleven (non-binding) norms of responsible state behaviour in cyberspace.However, states have not yet reached agreement on how to apply these principles. Until recently, there has also been very little knowledge of what states actually do in cyberspace, as they usually conduct cyber operations covertly and have been reluctant to put their views on record.A new Chatham House research paper analyses the application of the principles of sovereignty and non-intervention to state cyberattacks that fall below the principle of use of force. As well as analysing the application of the law in this area, the paper also makes recommendations to governments on how they might best make progress in reaching agreement in this area.Existing rules or new rules?As the research paper makes clear, there is currently some debate, principally between countries in the West, about the extent to which sovereignty is a legally binding rule in the context of cyberspace and, if so, how it and the principle of non-intervention might apply in practice.In the last few years, certain states have put on record how they consider international law to apply to states’ activities in cyberspace, namely the UK, Australia, France and the Netherlands. While there may be some differences in their approaches, which are discussed in the paper, there also remains important common ground: namely, that existing international law already provides a solid framework for regulating states’ cyber activities, as it regulates every other domain of state-to-state activity.There is also an emerging trend for states to work together when attributing cyberattacks to hostile states, enabling them to call out malign cyber activity when it violates international law. (See, for example, the joint statements made in relation to the NotPetya cyber attack and malicious cyber activity attributed to the Russian government).However, other countries have questioned whether existing international law as it stands is capable of regulating states’ cyber interactions and have called for ‘new legal instruments’ in this area.This includes a proposal by the Shanghai Cooperation Organization (led by Russia and China) for an International Code of Conduct on Information Security, a draft of which was submitted to the UN in 2011 and 2015, without success. The UN has also formed a new Open-Ended Working Group (OEWG) under a resolution proposed by Russia to consider how international law applies to states’ activities in cyberspace.The resolution establishing the OEWG, which began work earlier this year, includes the possibility of the group ‘introducing changes to the rules, norms and principles of responsible behaviour of States’ agreed in the 2013 and 2015 GGE reports. In the OEWG discussions at the UN in September, several countries claimed that a new legal instrument was needed to fill the ‘legal vacuum’ (Cuba) or ‘the gap of ungoverned areas’ (Indonesia).It would be concerning if the hard-won consensus on the application of international law to cyberspace that has been reached at past GGEs started to unravel. In contrast to 2013 and 2015, the 2017 meeting failed to reach an agreement.On 9 December, a renewed GGE will meet in New York, but the existence of the OEWG exploring the same issues in a separate process reflects the fact that cyber norms have become an area of geopolitical rivalry.Aside from the application of international law, states are also adopting divergent approaches to the domestic regulation of cyberspace within their own territory. The emerging trend towards a ‘splinternet’ – i.e. between states that believe the internet should be global and open on the hand, and those that favour a ‘sovereignty and control’ model on the other – is also likely to make discussions at the GGE more challenging.Distinct from the international law concept of sovereignty is the notion of ‘cybersovereignty’, a term coined by China to describe the wide-ranging powers it assumes under domestic law to regulate its citizens’ access to the internet and personal data within its territory. This approach is catching on (as reflected in Russia’s recently enacted ‘Sovereign Internet Law’), with other authoritarian states likely to follow suit.The importance of non-state actorsIn parallel with regional and UN discussions on how international law applies, a number of initiatives by non-state actors have also sought to establish voluntary principles about responsible state behaviour in cyberspace.The Global Commission on the Stability of Cyberspace, a multi-stakeholder body that has proposed principles, norms and recommendations to guide responsible behaviour by all parties in cyberspace, recently published its final report. The Cybersecurity Tech Accord aims to promote collaboration between tech companies on stability and resilience in cyberspace. President Macron’s ‘Paris Call for Trust and Security in Cyberspace’ has to date received the backing of 67 states, 139 international and civil society organizations, and 358 private-sector organizations.It remains to be seen in the long term whether the parallel processes at the UN will work constructively together or be competitive. But notwithstanding the challenging geopolitical backdrop, the UN GGE meeting next week at the least offers states the opportunity to consolidate and build on the results of past meetings; to increase knowledge and discussion about how international law might apply; and to encourage more states to put their own views of these issues on the record. Full Article
ace POSTPONED: Supporting Civic Space: The Role and Impact of the Private Sector By feedproxy.google.com Published On :: Wed, 22 Jan 2020 17:05:01 +0000 Invitation Only Research Event 16 March 2020 - 11:00am to 5:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE A healthy civic space is vital for an enabling business environment. In recognition of this, a growing number of private sector actors are challenging, publicly or otherwise, the deteriorating environment for civic freedoms.However, this corporate activism is often limited and largely ad hoc. It remains confined to a small cluster of multinationals leaving potential routes for effective coordination and collaboration with other actors underexplored.This roundtable will bring together a diverse and international group of business actors, civil society actors and foreign policy experts to exchange perspectives and experiences on how the private sector can be involved in issues around civic space. The meeting will provide an opportunity to explore the drivers of – and barriers to – corporate activism, develop a better understanding of existing initiatives, identify good practice and discuss practical strategies for the business community.This meeting will be the first of a series of roundtables at Chatham House in support of initiatives to build broad alliances for the protection of civic space. Attendance at this event is by invitation only. PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE. Department/project International Law Programme, Global Governance and the Rule of Law, Rights, Accountability and Justice Jacqueline Rowe Programme Assistant, International Law Programme 020 7389 3287 Email Full Article
ace Glucocerebrosidases catalyze a transgalactosylation reaction that yields a newly-identified brain sterol metabolite, galactosylated cholesterol [Glycobiology and Extracellular Matrices] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 β-Glucocerebrosidase (GBA) hydrolyzes glucosylceramide (GlcCer) to generate ceramide. Previously, we demonstrated that lysosomal GBA1 and nonlysosomal GBA2 possess not only GlcCer hydrolase activity, but also transglucosylation activity to transfer the glucose residue from GlcCer to cholesterol to form β-cholesterylglucoside (β-GlcChol) in vitro. β-GlcChol is a member of sterylglycosides present in diverse species. How GBA1 and GBA2 mediate β-GlcChol metabolism in the brain is unknown. Here, we purified and characterized sterylglycosides from rodent and fish brains. Although glucose is thought to be the sole carbohydrate component of sterylglycosides in vertebrates, structural analysis of rat brain sterylglycosides revealed the presence of galactosylated cholesterol (β-GalChol), in addition to β-GlcChol. Analyses of brain tissues from GBA2-deficient mice and GBA1- and/or GBA2-deficient Japanese rice fish (Oryzias latipes) revealed that GBA1 and GBA2 are responsible for β-GlcChol degradation and formation, respectively, and that both GBA1 and GBA2 are responsible for β-GalChol formation. Liquid chromatography–tandem MS revealed that β-GlcChol and β-GalChol are present throughout development from embryo to adult in the mouse brain. We found that β-GalChol expression depends on galactosylceramide (GalCer), and developmental onset of β-GalChol biosynthesis appeared to be during myelination. We also found that β-GlcChol and β-GalChol are secreted from neurons and glial cells in association with exosomes. In vitro enzyme assays confirmed that GBA1 and GBA2 have transgalactosylation activity to transfer the galactose residue from GalCer to cholesterol to form β-GalChol. This is the first report of the existence of β-GalChol in vertebrates and how β-GlcChol and β-GalChol are formed in the brain. Full Article
ace The DNA sensor cGAS is decorated by acetylation and phosphorylation modifications in the context of immune signaling By feedproxy.google.com Published On :: 2020-04-28 Bokai SongApr 28, 2020; 0:RA120.001981v1-mcp.RA120.001981Research Full Article
ace A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients By feedproxy.google.com Published On :: 2020-04-01 Dorte B. Bekker-JensenApr 1, 2020; 19:716-729Technological Innovation and Resources Full Article
ace Create a Global Code of Conduct for Outer Space By feedproxy.google.com Published On :: Thu, 06 Jun 2019 12:24:56 +0000 12 June 2019 Dr Patricia Lewis Research Director, Conflict, Science & Transformation; Director, International Security Programme @PatriciaMary The rules governing human activity in space have been in place for only a few decades, and yet they are already out of date. They need to be built on and extended to reflect the dramatic and rapid changes in the use of space. 2016-09-27-Space2.jpg Nighttime view of the strait of Gibraltar. Photo by NASA. The 1967 Outer Space Treaty (OST) is the mainframe for space law. It recognizes the importance of the use and scientific exploration of outer space for the benefit and in the interests of all countries. It also prohibits national sovereignty in space, including of the Moon and other celestial bodies.The OST prohibits all weapons of mass destruction in space – in orbit or on other planets and moons – and does not allow the establishment of military infrastructure, manoeuvres or the testing of any type of weapon on planets or moons. As the treaty makes clear, outer space is for peaceful purposes only. Except of course, it is not – nor has it ever been so.The very first satellite, Sputnik, was a military satellite which kicked off the Cold War space race between the US and the USSR. The militaries of many countries followed suit, and space is now used for military communication, signals intelligence, imaging, targeting, arms control verification and so on.However, in keeping with international aspirations, space is also being used for all kinds of peaceful purposes such as environmental monitoring, broadcast communications, delivering the internet, weather prediction, navigation, scientific exploration and – very importantly – monitoring the ‘space weather’ (including the activity from the Sun).There are several other international agreements on space, such as on the rescue of astronauts, the registration of satellites and liability for damage caused by space objects. There is also the Moon Treaty, which governs activities on the Moon and other moons, asteroids and planets.[i]More recently, states at the UN Committee on the Peaceful Uses of Outer Space (COPUOS) in Vienna have agreed on guidelines to deal with the worrying situation of space debris which is cluttering up orbits and posing a danger to satellites, the space station and astronauts.The problem the international community now faces is that the use of space is changing dramatically and rapidly. There are more satellites than ever – well over 1,000 – and more owners of satellites – almost every country uses information generated from space. Increasingly, however, those owners are not countries, militaries or international organizations but the commercial sector. Very soon, the owners will even include individuals.Small ‘mini-satellites’ or ‘cube-sats’ are poised to be deployed in space. These can act independently or in ‘swarms’, and are so small that they piggy-back on the launching of other satellites and so are very cheap to launch. This is changing the cost–benefit equation of satellite ownership and use. Developing countries are increasingly dependent on space for communications, the internet and information on, for example, weather systems, coastal activities and agriculture. Another major development is the advent of asteroid mining. Asteroids contain a wide range of metals and minerals – some asteroids are more promising than others, and some are closer to Earth than others. Several companies have been set up and registered around the world to begin the exploitation of asteroids for precious metals (such as platinum) and compounds (such as rare-earth minerals).Legally, however, this will be a murky venture. The current international treaty regime prohibits the ownership of a celestial body by a country – space is for all. But does international law prohibit the ownership or exploitation of a celestial body by a private company? The law has yet to be tested, but there are space lawyers who think that companies are exempt. Luxembourg and Australia are two countries that have already begun the registration of interest for space-mining companies.As humanity becomes more dependent on information that is generated in or transmitted through space, the vulnerability to the manipulation of space data is increasing. The demands on the use of communications frequencies (the issue of spectrum availability and rights), managed by the International Telecommunication Union (ITU),[ii] need to be urgently addressed.There are now constant cyberattacks in space and on the digital information on which our systems rely. For example, position, navigation and timing information such as from GPS or Galileo is not only vital for getting us safely from A to B, but also for fast-moving financial transactions that require accurate timing signals.Almost all of our electronic systems depend on those timing signals for synchronization and basic functioning. Cyber hacks, digital spoofing and ‘fake’ information are now a real possibility. There is no rules-based order in place that is fit to deal with these types of attacks.Cyberweapons are only part of the problem. It is assumed that states, if they haven’t already done so, will be positioning ‘defensive’ space weaponry to protect their satellites. The protection may be intended to be against space debris – nets, grabber bars and harpoons, for example, are all being investigated.All of these ideas, however, could be used as offensive weapons. Once one satellite operator decides to equip its assets with such devices, many others will follow. The weaponization of space is in the horizon.There are no international rules or agreements to manage these developments. Attempts in Geneva to address the arms race in space have floundered alongside the inability of the Conference on Disarmament to negotiate any instrument since 1996.Attempts to develop rules of the road and codes of conduct, or even to begin negotiations to prohibit weapons in space, have failed again and again. There are no agreed rules to govern cyber activity. The Tallinn Manuals[iii] that address how international law is applicable to cyberwarfare also address the laws of armed conflict in space, but data spoofing and cyber hacking in space exist in far murkier legal frameworks.The current system of international space law – which does not even allow for a regular review and consideration of the OST – is struggling to keep up. Space is the inheritance of humankind, yet the current generation of elders – as they have done with so many other parts of our global environment – have let things go and failed to shepherd in the much-needed system of rules to protect space for future generations.It is not too late, but it will require international cooperation among the major space players: Russia, the US, China, India and Europe – hardly a promising line-up of collaborators in the current political climate.Filling the governance gapsNorms of behaviour and rules of the road need to be established for space before it becomes a 21st-century ‘wild west’ of technology and activity. Issues such as cleaning up space debris, the principle of non-interference, and how close satellites can manoeuvre to each other (proximity rules) need to be agreed as a set of international norms for space behaviour.A cross-regional group of like-minded countries (for example Algeria, Canada, Chile, France, India, Kazakhstan, Malaysia, Nigeria, Sweden, the UAE and the UK) should link up with UN bodies, including the Office for Outer Space Affairs (UNOOSA), COPUOS and ITU, and key private-sector companies to kick-start a new process for a global code of conduct to establish norms and regulate behaviour in space.The UN could be the host entity for this new approach – or it could be established in the way the Ottawa process for landmines was established, by a group of like-minded states with collective responsibility for, and collective hosting and funding of, the negotiations.A new approach should also cover cybersecurity in space. The UN processes on space and cyber should intersect more to find ways to create synergies in their endeavours. And the problems ahead as regards spectrum management – particularly given the large number of small satellites and constellations that are to be launched in the near future – need urgent attention in ITU.What needs to happenThe international rules-based order for space – enshrined in particular in the 1967 Outer Space Treaty – has not kept pace with the rapid and dramatic changes in the use of space. New norms of behaviour and rules of the road are needed.These norms and rules need to address a host of contemporary or prospective developments, including asteroid mining, increased numbers of satellite owners, the emergence of ‘mini-satellites’, cyberwarfare, and the potential deployment of ‘defensive’ space weaponry to protect satellites.A cross-regional group of like-minded countries should link up with UN bodies – including UNOOSA, COPUOS and ITU – and key private-sector companies to kick-start a new process for developing a global code of conduct.Problems related to radio spectrum management – given the large number of small satellites and constellations to be launched in the near future – need urgent attention in ITU.Notes[i] All of these treaties and other documents can be found at UN Office for Outer Space Affairs (2002), United Nations Treaties and Principles on Outer Space, http://www.unoosa.org/pdf/publications/STSPACE11E.pdf.[ii] ITU (undated), ‘ITU Radiocommunication Sector’, https://www.itu.int/en/ITU-R/Pages/default.aspx.[iii] The NATO Cooperative Cyber Defence Centre of Excellence (CCDCOE), ‘Tallinn Manual 2.0’, https://ccdcoe.org/research/tallinn-manual/.This essay was produced for the 2019 edition of Chatham House Expert Perspectives – our annual survey of risks and opportunities in global affairs – in which our researchers identify areas where the current sets of rules, institutions and mechanisms for peaceful international cooperation are falling short, and present ideas for reform and modernization. Full Article
ace Cybersecurity of NATO’s Space-based Strategic Assets By feedproxy.google.com Published On :: Tue, 25 Jun 2019 15:38:20 +0000 1 July 2019 Almost all modern military engagements rely on space-based assets, but cyber vulnerabilities can undermine confidence in the performance of strategic systems. This paper will evaluate the threats, vulnerabilities and consequences of cyber risks to strategic systems. Read online Download PDF Dr Beyza Unal Senior Research Fellow, International Security Programme @beyzaunal Google Scholar 2019-06-25-Space-Cybersecurity.jpg The radar domes of RAF Menwith Hill, reported to be the biggest spy base in the world, dominate the skyline on 30 October 2007 in Harrogate, UK. Photo: Getty Images SummaryAll satellites depend on cyber technology including software, hardware and other digital components. Any threat to a satellite’s control system or available bandwidth poses a direct challenge to national critical assets.NATO’s missions and operations are conducted in the air, land, cyber and maritime domains. Space-based architecture is fundamental to the provision of data and services in each of these contexts. The critical dependency on space has resulted in new cyber risks that disproportionately affect mission assurance. Investing in mitigation measures and in the resilience of space systems for the military is key to achieving protection in all domains.Almost all modern military engagements rely on space-based assets. During the US-led invasion of Iraq in 2003, 68 per cent of US munitions were guided utilizing space-based means (including laser-, infrared- and satellite-guided munitions); up sharply from 10 per cent in 1990–91, during the first Gulf war. In 2001, 60 per cent of the weapons used by the US in Afghanistan were precision-guided munitions, many of which had the capability to use information provided by space-based assets to correct their own positioning to hit a target.NATO does not own satellites. It owns and operates a few terrestrial elements, such as satellite communications anchor stations and terminals. It requests access to products and services – such as space weather reports and satellite overflight reports provided via satellite reconnaissance advance notice systems – but does not have direct access to satellites: it is up to individual NATO member states to determine whether they allow access.Cyber vulnerabilities undermine confidence in the performance of strategic systems. As a result, rising uncertainty in information and analysis continues to impact the credibility of deterrence and strategic stability. Loss of trust in technology also has implications for determining the source of a malicious attack (attribution), strategic calculus in crisis decision-making and may increase the risk of misperception. Department/project International Security Programme, Cyber and Space Full Article
ace Cyber Governance in the Commonwealth: Towards Stability and Responsible State Behaviour in Cyberspace By feedproxy.google.com Published On :: Mon, 05 Aug 2019 14:05:02 +0000 Invitation Only Research Event 7 October 2019 - 10:30am to 5:30pm Addis Ababa, Ethiopia This roundtable is part of a series under the project, 'Implementing the Commonwealth Cybersecurity Agenda', funded by the UK Foreign and Commonwealth Office (FCO). The roundtable aims to provide a multi-stakeholder, pan-Commonwealth platform to discuss how to implement the Commonwealth Cyber Declaration with a focus on its third pillar 'To promote stability in cyberspace through international cooperation'.In particular, the roundtable focuses on points 3 and 4 of the third pillar which revolve around the commitment to promote frameworks for stability in cyberspace including the applicability of international law, agreed voluntary norms of responsible state behaviour and the development and implementation of confidence-building measures consistent with the 2015 report of the UNGGE. The workshop also focuses on the commitment to advance discussions on how existing international law, including the Charter of the United Nations and applicable international humanitarian law, applies in cyberspace.The roundtable addresses the issue of global cyber governance from a Commonwealth perspective and will also include a discussion around the way forward, the needed capacity of the different Commonwealth countries and the cooperation between its members for better cyber governance.Participants include UNGGE members from Commonwealth countries in addition to representatives to the UN Open-Ended Working Group from African countries as well as members from academia, civil society and industry. Department/project International Security Programme Calum Inverarity Research Analyst and Coordinator, International Security Department +44 (0) 207 957 5751 Email Full Article
Calum Inverarity Research Analyst and Coordinator, International Security Department +44 (0) 207 957 5751 Email
ace The Future of EU–US Cooperation in Space Traffic Management and Space Situational Awareness By feedproxy.google.com Published On :: Mon, 19 Aug 2019 10:09:54 +0000 29 August 2019 As more space activities develop, there is an increasing requirement for comprehensive space situational awareness (SSA). This paper provides an overview of the current landscape in SSA and space traffic management as well as possible scenarios for EU–US cooperation in this area. Read online Download PDF Alexandra Stickings Research Fellow for Space Policy and Security, RUSI 2019-08-19-SpaceTrafficManagement.jpg Deployment of the NanoRacks-Remove Debris Satellite from the International Space Station. Photo: Getty Images. SummarySpace situational awareness (SSA) and space traffic management (STM) are essential for sustainable near-Earth orbit. International cooperation in SSA and STM is vital with the growing number of satellite operators and the increasingly complex space environment.The various definitions of SSA and STM are ambiguous. Understanding the activities that fall under each term can better assist in finding areas for cooperation and collaboration.SSA has historically been a military activity, leading to an incomplete public catalogue of its use and barriers to sharing information with other states and the commercial sector. The rise in private space actors has increased the number of commercial STM providers and, with plans in the US to move responsibility for STM to civilian control, there will likely be more opportunities for international collaboration, particularly through the EU Space Surveillance and Tracking (SST) programme.Individual EU member states possess developed STM capabilities, but overall these are still some way behind those of allies such as the US. Further investment in STM infrastructure and programmes is required for the EU and individual European states to be an essential partner to the US and add value to the global effort.There are worldwide challenges, both political and technical, to providing STM coverage, which may lead to a lack of collaboration and gaps in understanding of activities in orbit. Existing sensors have limitations in terms of the size of objects that can be detected and the precision with which their movements can be predicted. These capability gaps represent opportunities for the EU to contribute.The EU can build on its tradition of support for openness and civil society by creating a system that fosters an environment of cooperation and collaboration involving industry, commercial STM providers and the wider international community.Although collaboration in STM is vital, the EU should also aim to tackle issues within the wider definition of SSA including space weather, intelligence and the security of ground stations.The EU is well placed to become a global leader in SSA and STM. However, it needs to take into consideration the current political and technical landscape when making decisions regarding investment in capabilities and the pursuit of international partnerships. Department/project International Security Programme, Cyber and Space Full Article
ace Examining Measures to Mitigate Cyber Vulnerabilities of Space-based Strategic Assets By feedproxy.google.com Published On :: Tue, 03 Sep 2019 08:45:02 +0000 Invitation Only Research Event 30 October 2019 - 9:30am to 4:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Beyza Unal, Senior Research Fellow, International Security Department, Chatham HousePatricia Lewis, Research Director, International Security Department, Chatham House Strategic systems that depend on space-based assets, such as command, control and communication, early warning systems, weapons systems and weapons platforms, are essential for conducting successful NATO operations and missions. Given the increasing dependency on such systems, the alliance and key member states would therefore benefit from an in-depth analysis of possible mitigation and resilience measures.This workshop is part of the International Security Department’s (ISD) project on space security and the vulnerability of strategic assets to cyberattacks, which includes a recently published report. This project aims to create resilience in NATO and key NATO member states, building the capacity of key policymakers and stakeholders to respond with effective policies and procedures. This workshop will focus on measures to mitigate the cyber vulnerabilities of NATO’s space-dependent strategic assets. Moreover, participants will discuss the type of resilience measures and mechanisms required.Attendance at this event is by invitation only. Department/project International Security Programme Calum Inverarity Research Analyst and Coordinator, International Security Department +44 (0) 207 957 5751 Email Full Article
Calum Inverarity Research Analyst and Coordinator, International Security Department +44 (0) 207 957 5751 Email
ace Smart Peace By feedproxy.google.com Published On :: Thu, 12 Sep 2019 08:59:39 +0000 With the number of violent conflicts increasing, there is a worldwide need to respond more effectively. Dialogue and mediation are proven to be effective in preventing and resolving conflicts, which are often complex, political and frequently-changing. But there is more to be done to understand how these approaches can adapt – responding quickly to changing politics and overcoming obstacles that block progress.Smart Peace is a global initiative led by Conciliation Resources, which combines the varied expertise of different consortium partners to address the challenges of building peace – focusing on the Central African Republic, Nigeria and Myanmar.This work combines peacebuilding techniques, conflict analysis, rigorous evaluation and behavioural insights. The resulting lessons will help communities, international organisations and governments to implement peace strategies with greater confidence.This project is funded with UK aid from the UK government.Smart Peace PartnersBehavioural Insights TeamConciliation ResourcesChatham HouseInternational Crisis GroupThe Asia FoundationThe Center for Security Studies at ETH ZurichThe Centre for Humanitarian Dialogue Department contact Nilza Amaral Project Manager, International Security Programme Email Latest (1) Research Event The Smart Peace Initiative: An Integrated and Adaptive Approach to Building Peace 12 May 2020 Full Article
ace The Smart Peace Initiative: An Integrated and Adaptive Approach to Building Peace By feedproxy.google.com Published On :: Tue, 11 Feb 2020 10:55:01 +0000 Invitation Only Research Event 12 May 2020 - 10:00am to 11:30amAdd to CalendariCalendar Outlook Google Yahoo Smart Peace brings together global expertise in conflict analysis and research, peacebuilding and mediation programming, and behavioural science and evaluation. Together, Smart Peace partners are developing integrated and adaptive peace initiatives, working with local partners to prevent and resolve complex and intractable conflicts in Central African Republic, Myanmar and northern Nigeria. This roundtable is an opportunity for Smart Peace partners to share the Smart Peace concept, approach and objectives, and experiences of the first phases of programme implementation. Roundtable discussions among participants from policy, practice and research communities will inform future priorities and planning for Smart Peace learning, advocacy and communication. Smart Peace partners include Conciliation Resources, Behavioural Insights Team, The Centre for Humanitarian Dialogue, Chatham House, ETH Zurich, International Crisis Group and The Asia Foundation. Nilza Amaral Project Manager, International Security Programme Email Department/project International Security Programme, Smart Peace Full Article
ace Positron lymphography via intracervical 18F-FDG injection for pre-surgical lymphatic mapping in cervical and endometrial malignancies By jnm.snmjournals.org Published On :: 2020-01-10T04:59:09-08:00 Rationale: The presence of metastasis in local lymph nodes (LNs) is a key factor influencing choice of therapy and prognosis in cervical and endometrial cancers; therefore, the exploration of sentinel LNs (SLNs) is highly important. Currently, however, SLN mapping requires LN biopsy for pathologic evaluation, since there are no clinical imaging approaches that can identify tumor-positive LNs in early stages. Staging lymphadenectomy poses risks, such as leg lymphedema or lymphocyst formation. Furthermore, in 80% to 90% of patients, the explored LNs are ultimately tumor free, meaning the vast majority of patients are unnecessarily subjected to lymphadenectomy. Methods: Current lymphoscintigraphy methods only identify the anatomic location of the SLNs but do not provide information on their tumor status. There are no non-invasive methods to reliably identify metastases in LNs before surgery. We have developed positron lymphography (PLG), a method to detect tumor-positive LNs, where 18F-fluoro-2-deoxy-D-glucose (18F-FDG) is injected interstitially into the uterine cervix the day of surgery, and its rapid transport through the lymphatic vessels to the SLN is then visualized with dynamic positron emission tomography/computed tomography (PET/CT). We previously showed that PLG was able to identify metastatic LNs in animal models. Here, we present the first results from our pilot clinical trial (clinical trials identifier NCT02285192) in 23 patients with uterine or cervical cancer. On the morning of surgery, 18F-FDG was injected into the cervix, followed by an immediate dynamic PET/CT scan of the pelvis and a delayed 1-h whole body scan. Results: There were 3 (15%) node-positive cases on final pathologic analysis, and all LNs (including one with a focus of only 80 tumor cells) were identified by PLG except one node with an 11-mm micrometastasis. There were 2 (10%) false-positive cases with PLG, in which final pathology of the corresponding SLNs was negative for tumor. Methods: Current lymphoscintigraphy methods only identify the anatomic location of the SLNs but do not provide information on their tumor status. There are no non-invasive methods to reliably identify metastases in LNs before surgery. We have developed positron lymphography (PLG), a method to detect tumor-positive LNs, where 18F-fluoro-2-deoxy-D-glucose (18F-FDG) is injected interstitially into the uterine cervix the day of surgery, and its rapid transport through the lymphatic vessels to the SLN is then visualized with dynamic positron emission tomography/computed tomography (PET/CT). We previously showed that PLG was able to identify metastatic LNs in animal models. Here, we present the first results from our pilot clinical trial (clinical trials identifier NCT02285192) in 23 patients with uterine or cervical cancer. On the morning of surgery, 18F-FDG was injected into the cervix, followed by an immediate dynamic PET/CT scan of the pelvis and a delayed 1-h whole body scan. Results: There were 3 (15%) node-positive cases on final pathologic analysis, and all LNs (including one with a focus of only 80 tumor cells) were identified by PLG, except for one node with an 11-mm micrometastasis. There were 2 (10%) false-positive cases with PLG, in which final pathology of the corresponding SLNs was negative for tumor. Conclusion: This first-in-human study of PLG in women with uterine and cervical cancer demonstrates its feasibility and its ability to identify patients with nodal metastases, and warrants further evaluation in additional studies. Full Article
ace Projection-space implementation of deep learning-guided low-dose brain PET imaging improves performance over implementation in image-space By jnm.snmjournals.org Published On :: 2020-01-10T04:59:09-08:00 Purpose: To assess the performance of full dose (FD) positron emission tomography (PET) image synthesis in both image and projection space from low-dose (LD) PET images/sinograms without sacrificing diagnostic quality using deep learning techniques. Methods: Clinical brain PET/CT studies of 140 patients were retrospectively employed for LD to FD PET conversion. 5% of the events were randomly selected from the FD list-mode PET data to simulate a realistic LD acquisition. A modified 3D U-Net model was implemented to predict FD sinograms in the projection-space (PSS) and FD images in image-space (PIS) from their corresponding LD sinograms/images, respectively. The quality of the predicted PET images was assessed by two nuclear medicine specialists using a five-point grading scheme. Quantitative analysis using established metrics including the peak signal-to-noise ratio (PSNR), structural similarity index metric (SSIM), region-wise standardized uptake value (SUV) bias, as well as first-, second- and high-order texture radiomic features in 83 brain regions for the test and evaluation dataset was also performed. Results: All PSS images were scored 4 or higher (good to excellent) by the nuclear medicine specialists. PSNR and SSIM values of 0.96 ± 0.03, 0.97 ± 0.02 and 31.70 ± 0.75, 37.30 ± 0.71 were obtained for PIS and PSS, respectively. The average SUV bias calculated over all brain regions was 0.24 ± 0.96% and 1.05 ± 1.44% for PSS and PIS, respectively. The Bland-Altman plots reported the lowest SUV bias (0.02) and variance (95% CI: -0.92, +0.84) for PSS compared with the reference FD images. The relative error of the homogeneity radiomic feature belonging to the Grey Level Co-occurrence Matrix category was -1.07 ± 1.77 and 0.28 ± 1.4 for PIS and PSS, respectively Conclusion: The qualitative assessment and quantitative analysis demonstrated that the FD PET prediction in projection space led to superior performance, resulting in higher image quality and lower SUV bias and variance compared to FD PET prediction in the image domain. Full Article
ace Clinical Translation of a 68Ga-labeled Integrin {alpha}v{beta}6-targeting Cyclic Radiotracer for PET Imaging of Pancreatic Cancer By jnm.snmjournals.org Published On :: 2020-02-21T14:46:23-08:00 The overexpression of integrin αvβ6 in pancreatic cancer makes it a promising target for noninvasive positron emission tomography (PET) imaging. However, currently, most integrin αvβ6-targeting radiotracers are based on linear peptides, which are quickly degraded in the serum by proteinases. Herein, we aimed to develop and assess a 68Ga-labeled integrin αvβ6-targeting cyclic peptide (68Ga-cycratide) for PET imaging of pancreatic cancer. Methods: 68Ga-cycratide was prepared, and its PET imaging profile was compared with that of the linear peptide (68Ga-linear-pep) in an integrin αvβ6-positive BxPC-3 human pancreatic cancer mouse model. Five healthy volunteers (two women and three men) underwent whole-body PET/CT imaging after injection of 68Ga-cycratide, and biodistribution and dosimetry calculations were determined. PET/CT imaging of two patients was performed to investigate the potential role of 68Ga-cycratide in pancreatic cancer diagnosis and treatment monitoring. Results: 68Ga-cycratide exhibited significantly higher tumor uptake than did 68Ga-linear-pep in BxPC-3 tumor-bearing mice, owing—at least in part—to markedly improved in vivo stability. 68Ga-cycratide could sensitively detect the pancreatic cancer lesions in an orthotopic mouse model and was well tolerated in all healthy volunteers. Preliminary PET/CT imaging in patients with pancreatic cancer demonstrated that 68Ga-cycratide was comparable to 18F-fludeoxyglucose for diagnostic imaging and post-surgery tumor relapse monitoring. Conclusion: 68Ga-cycratide is an integrin αvβ6-specific PET radiotracer with favorable pharmacokinetics and dosimetry profile. 68Ga-cycratide is expected to provide an effective noninvasive PET strategy for pancreatic cancer lesion detection and therapy response monitoring. Full Article
ace Development and evaluation of interleukin-2 derived radiotracers for PET imaging of T-cells in mice By jnm.snmjournals.org Published On :: 2020-02-28T13:52:17-08:00 Recently, N-(4-18F-fluorobenzoyl)-interleukin-2 (18F-FB-IL2) was introduced as PET tracer for T-cell imaging. However, production is complex and time-consuming. Therefore, we developed two radiolabeled interleukin-2 (IL-2) variants, namely aluminum 18F-fluoride-(restrained complexing agent)-IL-2 (18F-AlF-RESCA-IL2) and 68Ga-gallium-(1,4,7-triazacyclononane-4,7-diacetic acid-1-glutaric acid)-IL-2 (68Ga-Ga-NODAGA-IL2) and compared their in-vitro and in-vivo characteristics with 18F-FB-IL2. Methods: Radiolabeling of 18F-AlF-RESCA-IL2 and 68Ga-Ga-NODAGA-IL2 was optimized and stability was evaluated in human serum. Receptor binding was studied with activated human peripheral blood mononuclear cells (hPBMCs). Ex-vivo tracer biodistribution in immunocompetent BALB/cOlaHsd (BALB/c) mice was performed at 15, 60 and 90 min after tracer injection. In-vivo binding characteristics were studied in severe combined immune-deficient (SCID) mice inoculated with activated hPBMCs in Matrigel. Tracer was injected 15 min after hPBMCs inoculation and a 60-min dynamic PET scan was acquired, followed by ex-vivo biodistribution studies. Specific uptake was determined by co-injection of tracer with unlabeled IL2 and by evaluating uptake in a control group inoculated with Matrigel only. Results: 68Ga-Ga-NODAGA-IL2 and 18F-AlF-RESCA-IL2 were produced with radiochemical purity >95% and radiochemical yield of 13.1±4.7% and 2.4±1.6% within 60 and 90 min, respectively. Both tracers were stable in serum, with >90% being intact tracer after 1h. In-vitro, both tracers displayed preferential binding to activated hPBMCs. Ex-vivo biodistribution studies in BALB/c mice showed higher uptake of 18F-AlF-RESCA-IL2 than 18F-FB-IL2 in liver, kidney, spleen, bone and bone marrow. 68Ga-Ga-NODAGA-IL2 uptake in liver and kidney was higher than 18F-FB-IL2 uptake. In-vivo, all tracers revealed uptake in activated hPBMCs in SCID mice. Low uptake was seen after a blocking dose of IL2 or in the Matrigel control group. In addition, 18F-AlF-RESCA-IL2 yielded highest contrast PET images of target lymph nodes. Conclusion: Production of 18F-AlF-RESCA-IL2 and 68Ga-Ga-NODAGA-IL2 is simpler and faster than 18F-FB-IL2. Both tracers showed good in-vitro and in-vivo characteristics with high uptake in lymphoid tissue and hPBMC xenografts. Full Article
ace Digital Solid-State SPECT/CT Quantitation of Absolute 177Lu-Radiotracer Concentration: In Vivo/In Vitro Validation By jnm.snmjournals.org Published On :: 2020-02-28T13:52:17-08:00 The accuracy of lutetium-177 (177Lu) radiotracer concentration measurements using quantitative clinical software was determined by comparing in vivo results for a digital solid-state cadmium-zinc-telluride SPECT/CT (single photon emission computed tomography / x-ray computed tomography) system to in vitro sampling. First, image acquisition parameters were assessed for an International Electrotechnical Commission (IEC) body phantom emulating clinical count rates loaded with a "lung" insert and 6 hot spheres with a 12:1 target-to-background ratio of 177Lu solution. Then, the data of 28 whole-body SPECT/CT scans of 7 patients who underwent 177Lu prostate membrane antigen (177Lu-PSMA) radioligand therapy was retrospectively analyzed. Three users analyzed SPECT/CT images for in vivo urinary bladder radiotracer uptake using quantitative software (Q.Metrix, GE Healthcare). In vitro radiopharmaceutical concentrations were calculated using urine sampling obtained immediately after each scan, scaled to standardized uptake values (SUVs). Any in vivo/in vitro identity relations were determined by linear regression (ideally slope=1, intercept=0), within a 95 % confidence interval (CI). Phantom results demonstrated lower quantitative error for acquisitions using the 113 keV 177Lu energy peak rather than including the 208 keV peak, given that only low-energy collimation was available in this camera configuration. In the clinical study, 24 in vivo/in vitro pairs were eligible for further analysis, having rejected 4 as outliers (via Cook’s distance calculations). All linear regressions (R2 ≥ 0.92, P<0.0001) provided identity in vivo/in vitro relations (95 % CI), with SUV averages from all users giving a slope of 1.03±0.09, an intercept of –0.25±0.64 g/mL, and an average residual difference of 20.4 %. Acquiring with the lower energy 177Lu energy peak, solid-state SPECT/CT imaging provides an accuracy to within ~20 % for in vivo urinary bladder radiotracer concentrations. This non-invasive in vivo quantitation method can potentially improve diagnosis, improve patient management and treatment response assessment, and provide data essential to 177Lu dosimetry. Full Article
ace Kinetic modeling and test-retest reproducibility of 11C-EKAP and 11C-FEKAP, novel agonist radiotracers for PET imaging of the kappa opioid receptor in humans By jnm.snmjournals.org Published On :: 2020-03-13T14:12:30-07:00 The kappa opioid receptor (KOR) is implicated in various neuropsychiatric disorders. We previously evaluated an agonist tracer, 11C-GR103545, for PET imaging of KOR in humans. Although 11C-GR103545 showed high brain uptake, good binding specificity, and selectivity to KOR, it displayed slow kinetics and relatively large test-retest variability (TRV) of distribution volume (VT) estimates (15%). Therefore we set out to develop two novel KOR agonist radiotracers, 11C-EKAP and 11C-FEKAP, and in nonhuman primates, both tracers exhibited faster kinetics and comparable binding parameters to 11C-GR103545. The aim of this study was to assess their kinetic and binding properties in humans. Methods: Six healthy subjects underwent 120-min test-retest PET scans with both 11C-EKAP and 11C-FEKAP. Metabolite-corrected arterial input functions were measured. Regional time-activity curves (TACs) were generated for 14 regions of interest. One- and two-tissue compartment models (1TC, 2TC) and the multilinear analysis-1 (MA1) method were applied to the regional TACs to calculate VT. Time-stability of VT values and test-retest reproducibility were evaluated. Levels of specific binding, as measured by the non-displaceable binding potential (BPND) for the three tracers (11C-EKAP, 11C-FEKAP and 11C-GR103545), were compared using a graphical method. Results: For both tracers, regional TACs were fitted well with the 2TC model and MA1 method (t*=20min), but not with the 1TC model. Given unreliably estimated parameters in several fits with the 2TC model and a good match between VT values from MA1 and 2TC, MA1 was chosen as the appropriate model for both tracers. Mean MA1 VT values were highest for 11C-GR103545, followed by 11C-EKAP, then 11C-FEKAP. Minimum scan time for stable VT measurement was 90 and 110min for 11C-EKAP and 11C-FEKAP, respectively, compared with 140min for 11C-GR103545. The mean absolute TRV in MA1 VT estimates was 7% and 18% for 11C-EKAP and 11C-FEKAP, respectively. BPND levels were similar for 11C-FEKAP and 11C-GR103545, but ~25% lower for 11C-EKAP. Conclusion: The two novel KOR agonist tracers showed faster tissue kinetics than 11C-GR103545. Even with slightly lower BPND, 11C-EKAP is judged to be a better tracer for imaging and quantification of KOR in humans, based on the shorter minimum scan time and excellent test-retest. Full Article
ace First-in-Human Trial of Dasatinib-Derivative Tracer for Tumor Kinase-Targeted Positron Emission Tomography By jnm.snmjournals.org Published On :: 2020-03-13T14:12:30-07:00 We developed a first-of-kind dasatinib-derivative imaging agent, 18F-SKI-249380 (18F-SKI), and validated its use for noninvasive in vivo tyrosine kinase-targeted tumor detection in preclinical models. In this study, we assess the feasibility of using 18F-SKI for PET imaging in patients with malignancies. Methods: Five patients with a prior diagnosis of breast cancer, renal cell cancer, or leukemia underwent whole-body PET/CT imaging 90 min post-injection of 18F-SKI (mean: 241.24 ± 116.36 MBq) as part of a prospective study. In addition, patients underwent either a 30-min dynamic scan of the upper abdomen including, at least partly, cardiac left ventricle, liver, spleen, and kidney (n = 2) or three 10-min whole-body PET/CT scans (n = 3) immediately post-injection and blood-based radioactivity measurements to determine the time course of tracer distribution and facilitate radiation dose estimates. A subset of three patients had a delayed whole-body PET/CT scan at 180 min. Biodistribution, dosimetry, and tumor uptake were quantified. Absorbed doses were calculated using OLINDA/EXM 1.0. Results: No adverse events occurred after injection of 18F-SKI. A total of 27 tumor lesions were analyzed with median SUVpeak 1.4 (range, 0.7–2.3) and tumor-to-blood ratios of 1.6 (range, 0.8–2.5) at 90 min post-injection. Intratumoral drug concentrations calculated for four reference lesions ranged from 0.03–0.07 nM. In all reference lesions, constant tracer accumulation was observed between 30–90 min post-injection. Blood radio-assay indicated that radiotracer clearance from blood and plasma was initially rapid (blood half-time 1.31 ± 0.81 min, plasma 1.07 ± 0.66 min; n = 4), followed variably by either a prolonged terminal phase (blood half-time 285 ± 148.49 min, plasma 240 ± 84.85 min; n = 2) or a small rise to plateau (n = 2). Like dasatinib, 18F-SKI underwent extensive metabolism post-administration, as evidenced by metabolite analysis. Radioactivity was predominantly cleared via the hepatobiliary route. The highest absorbed dose estimates (mGy/MBq) in normal tissues were to the right colon (0.167 ± 0.04) and small intestine (0.153 ± 0.03). The effective dose was 0.0258 (SD 0.0034) mSv/MBq. Conclusion: 18F-SKI demonstrated significant tumor uptake, distinct image contrast despite low injected doses, and rapid clearance from blood. Full Article
ace Design and development of 99mTc labeled FAPI-tracers for SPECT-imaging and 188Re therapy. By jnm.snmjournals.org Published On :: 2020-03-13T14:12:30-07:00 The majority of epithelial tumors recruits fibroblasts and other non-malignant cells and activates them into cancer-associated fibroblasts. This often leads to overexpression of the membrane serine protease fibroblast-activating protein (FAP). It has already been shown that DOTA-bearing FAP inhibitors (FAPIs) generate high contrast images with PET/CT scans. Since SPECT is a lower cost and more widely available alternative to PET, 99mTc-labeled FAPIs represent attractive tracers for imaging applicable in a larger number of patients. Furthermore, the chemically homologous nuclide 188Re is available from generators, which allows FAP-targeted endoradiotherapy. Methods: For the preparation of 99mTc tricarbonyl complexes, a chelator was selected whose carboxylic acids can easily be converted into various derivatives in the finished product. This enabled a platform strategy based on the original tracer. The obtained 99mTc complexes were investigated in vitro by binding and competition experiments on FAP-transfected HT-1080 (HT-1080-FAP) and/or on mouse FAP expressing (HEK-muFAP) and CD26-expressing (HEKCD26) HEK cells and characterized by planar scintigraphy and organ distribution studies in tumor-bearing mice. Furthermore, a first-in-man application was done in two patients with ovarian and pancreatic cancer, respectively. Results: 99mTc-FAPI-19 showed specific binding to recombinant FAP-expressing cells with high affinity. Unfortunately, liver accumulation, biliary excretion and no tumor uptake were observed in the planar scintigraphy of a HT-1080-FAP xenotranplanted mouse. To improve the pharmacokinetic properties hydrophilic amino acids were attached to the chelator moiety of the compound. The resulting 99mTc-labeled FAPI tracers revealed excellent binding properties (up to 45 % binding; above 95 % internalization), high affinity (IC50 = 6.4 nM to 12.7 nM), and significant tumor uptake (up to 5.4 %ID/g) in biodistribution studies. The lead candidate 99mTc-FAPI-34 was applied for diagnostic scintigraphy and SPECT of patients with metastasized ovarian and pancreatic cancer for follow-up to therapy with 90Y-FAPI-46. 99mTc-FAPI-34 accumulated in the tumor lesions also shown in PET/CT imaging using 68Ga-FAPI-46. Conclusion: 99mTc-FAPI-34 represents a powerful tracer for diagnostic scintigraphy, especially in cases where PET imaging is not available. Additionally, the chelator used in this compound allows labeling with the therapeutic nuclide 188Re which is planned for the near future. Full Article
ace 11C-PABA as a Novel PET Radiotracer for Functional Renal Imaging: Preclinical and First-in-Human Studies By jnm.snmjournals.org Published On :: 2020-03-20T13:59:23-07:00 para-Aminobenzoic acid (PABA) has been previously used as an exogenous marker to verify completion of 24-hour urine sampling. Therefore, we hypothesized that radiolabeled PABA with 11C could allow high-quality dynamic PET of the kidneys while reducing the radiation exposure due to its short biological and physical half-lives. We evaluated if 11C-PABA could visualize renal anatomy and quantify function in healthy rats, rabbits, and first-in-human studies in healthy volunteers. Methods: Healthy rats and rabbits were injected with 11C-PABA intravenously. Subsequently, a dynamic PET was performed, followed by post-mortem tissue biodistribution studies. 11C-PABA PET was directly compared with the current standard, 99mTc-MAG3 in rats. Three healthy human subjects also underwent dynamic PET after intravenous injection of 11C-PABA. Results: In healthy rats and rabbits, dynamic PET demonstrated a rapid accumulation of 11C-PABA in the renal cortex, followed by rapid excretion through the pelvicalyceal system. In humans, 11C-PABA PET was safe and well tolerated. There were no adverse or clinically detectable pharmacologic effects in any subject. The cortex was delineated on PET, and the activity gradually transited to the medulla and then renal pelvis with high spatiotemporal resolution. Conclusion: 11C-PABA demonstrated fast renal excretion with very low background signal in animals and humans. These results suggest that 11C-PABA could be used as a novel radiotracer for functional renal imaging, providing high-quality spatiotemporal images with low radiation exposure. Full Article
ace 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
ace Molecular imaging of PD-L1 expression and dynamics with the adnectin-based PET tracer 18F-BMS-986192 By jnm.snmjournals.org Published On :: 2020-05-01T11:16:57-07:00 18F-BMS-986192, an adnectin-based human programmed cell death ligand 1 (PD-L1) tracer, was developed to non-invasively determine whole-body PD-L1 expression by positron emission tomography (PET). We evaluated usability of 18F-BMS-986192 PET to detect different PD-L1 expression levels and therapy-induced changes of PD-L1 expression in tumors. Methods: In vitro binding assays with 18F-BMS-986192 were performed in human tumor cell lines with different total cellular and membrane PD-L1 protein expression levels. Subsequently, PET imaging was executed in immunodeficient mice xenografted with these cell lines. Mice were treated with interferon gamma (IFN) intraperitoneally for 3 days or with the mitogen-activated protein kinase kinase (MEK1/2) inhibitor selumetinib by oral gavage for 24 hours. Thereafter 18F-BMS-986192 was administered intravenously, followed by a 60-minute dynamic PET scan. Tracer uptake was expressed as percentage injected dose per gram tissue (%ID/g). Tissues were collected to evaluate ex vivo tracer biodistribution and to perform flow cytometric, Western blot, and immunohistochemical tumor analyses. Results: 18F-BMS-986192 uptake reflected PD-L1 membrane levels in tumor cell lines, and tumor tracer uptake in mice was associated with PD-L1 expression measured immunohistochemically. In vitro IFN treatment increased PD-L1 expression in the tumor cell lines and caused up to 12-fold increase in tracer binding. In vivo, IFN did neither affect PD-L1 tumor expression measured immunohistochemically nor 18F-BMS-986192 tumor uptake. In vitro, selumetinib downregulated cellular and membrane levels of PD-L1 of tumor cells by 50% as measured by Western blotting and flow cytometry. In mice, selumetinib lowered cellular, but not membrane PD-L1 levels of tumors and consequently no treatment-induced change in 18F-BMS-986192 tumor uptake was observed. Conclusion: 18F-BMS-986192 PET imaging allows detection of membrane-expressed PD-L1, as soon as 60 minutes after tracer injection. The tracer can discriminate a range of tumor cell PD-L1 membrane expression levels. Full Article
ace The effects of monosodium glutamate on PSMA radiotracer uptake in men with recurrent prostate cancer: a prospective, randomized, double-blind, placebo-controlled intra-individual imaging study. By jnm.snmjournals.org Published On :: 2020-05-08T13:18:58-07:00 The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer (PCa). However, PSMA-targeted radioligand therapy can cause undesirable effects due to high accumulation of PSMA radiotracers in salivary glands and kidneys. This study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA targeting radiotracer. Methods: This prospective, double-blind, placebo-controlled study enrolled 10 biochemically recurrent PCa patients. Each subject served as his own control. [18F]DCFPyl PET/CT imaging sessions were performed 3 – 7 days apart, following oral administration of either 12.7 g of MSG or placebo. Data from the two sets of images were analyzed by placing regions of interest on lacrimal, parotid and submandibular glands, left ventricle, liver, spleen, kidneys, bowel, urinary bladder, gluteus muscle and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the ROI data. Results: A total of 142 pathological lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in maximal standardized uptake values corrected for lean body mass (SULmax) on images obtained following MSG administration in the parotids (24 ± 14%, P = 0.001), submandibular glands (35 ± 11%, P<0.001) and kidneys (23 ± 26%, P = 0.014). Significant decreases were also observed in lacrimal glands (49 ± 13%, P<0.001), liver (15 ± 6%, P<0.001), spleen (28 ± 13%, P = 0.001) and bowel (44 ± 13%, P<0.001). Mildly lower blood pool SULmean was observed after MSG administration (decrease of 11 ± 13%, P = 0.021). However, significantly lower radiotracer uptake in terms of SULmean, SULpeak, and SULmax was observed in malignant lesions on scans performed after MSG administration compared to the placebo studies (SULmax median decrease 33%, range -1 to 75%, P<0.001). No significant adverse events occurred and vital signs were stable following placebo or MSG administration. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney and other normal organ PSMA radiotracer uptake in human subjects, using [18F]DCFPyL as an exemplar. However, MSG caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications. Full Article
ace Prospects for Peace and Stability in South Sudan By feedproxy.google.com Published On :: Tue, 29 Oct 2019 15:20:01 +0000 Research Event 11 November 2019 - 5:00pm to 6:15pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Alan Boswell, Senior Analyst for South Sudan, International Crisis GroupMiklos Gosztonyi, Conflict Analyst, South Sudan, Norwegian Refugee CouncilNaomi Pendle, Research Fellow, Firoz Lalji Centre for Africa, London School of EconomicsGolda Abbé, Founding Member, Ghidam (Via Skype)Chair: Teohna Williams, CEO, Business Plan for Peace South Sudan’s prolonged peace process is approaching a critical juncture. There is uncertainty about whether the country’s political leaders will meet the 12 November 2019 deadline to form a transitional government of national unity – a process already delayed after a revitalized power-sharing deal was signed in September 2018. A political impasse has been caused by a lack of progress on outstanding issues such as deciding on the number of states and reunifying the security forces. The latter issue is seen as critical to preventing the reoccurrence of large-scale violence which would exacerbate already considerable humanitarian needs. Continued mediation by regional and international partners remains important to finding a way forward and preventing a return to widespread conflict.At this event, a panel of speakers will examine the status of the peace deal, the issue of federalism and subdivision, measures needed to prevent the humanitarian crisis from worsening and opportunities to foster greater security and unity in the country.THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED. Department/project Africa Programme, African Peace and Security, Horn of Africa Sahar Eljack Programme Administrator, Africa Programme + 44 (0) 20 7314 3660 Email Full Article
ace Realizing South Sudan's Peace Deal By feedproxy.google.com Published On :: Wed, 19 Feb 2020 15:45:01 +0000 Invitation Only Research Event 24 February 2020 - 5:00pm to 6:15pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Miklos Gosztonyi, Conflict Analyst, South Sudan, Norwegian Refugee CouncilMatthew F. Pritchard, Research and Policy Specialist, McGill UniversityJoshua Craze, Writer and ResearcherTeohna Williams, CEO, Business Plan for Peace South Sudan’s new power sharing government must be formed by 22 February 2020, as specified in the Revitalized Agreement on the Resolution of the Conflict in the Republic of South Sudan (R-ARCSS). There have been two extensions to this process already, reflecting the continued distrust among leaders and the complexity of the conflict.The lack of progress in several contentious areas has delayed the formation of the Revitalized Transitional Government of National Unity (R-TGoNU) for nine months, but the recent decision taken by President Salva Kiir Mayardit to re-establish 10 states has been welcomed by opposition groups, regional mediators and international partners.It is seen as the breakthrough needed for an agreement to be reached, despite some outstanding concerns. Further meaningful compromises and difficult decisions will be needed to implement a lasting peace agreement.At this event, a panel of speakers will examine the status of the peace deal following the February deadline and the steps needed to progress the key issues underlying implementation. Event attributes Chatham House Rule Department/project Africa Programme, African Peace and Security, Horn of Africa Sahar Eljack Programme Administrator, Africa Programme + 44 (0) 20 7314 3660 Email Full Article
ace POSTPONED: UN Peacekeeping in Africa: Insights from Successes and Failures of the Past By feedproxy.google.com Published On :: Thu, 20 Feb 2020 14:30:01 +0000 Research Event 10 March 2020 - 3:00pm to 4:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Alan Doss, President, Kofi Annan Foundation With Africa hosting half of the UN peacekeeping missions currently in operation and more than 80 per cent of the UN’s peacekeepers, it is clear that crisis management and conflict resolution on the continent remain key priorities. However, traditional international supporters, notably Canada and the United States, have reduced their financial support for peacekeeping in recent years. Together with frequent reports on peacekeeping abuse, declining support is proving disruptive for the maintenance and predictability of UN missions.At this event, which will launch the book A Peacekeeper in Africa: Learning from UN Interventions in Other People’s Wars, Alan Doss will reflect on past UN peacekeeping missions in Africa and will consider how lessons learned might help to improve future UN peace operations.PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE. Department/project Africa Programme, African Peace and Security, Foreign Relations and Africa’s Agency in the International System Sahar Eljack Programme Administrator, Africa Programme + 44 (0) 20 7314 3660 Email Full Article
ace Profiling the Surfaceome Identifies Therapeutic Targets for Cells with Hyperactive mTORC1 Signaling [Research] By feedproxy.google.com Published On :: 2020-02-01T00:05:30-08:00 Aberrantly high mTORC1 signaling is a known driver of many cancers and human disorders, yet pharmacological inhibition of mTORC1 rarely confers durable clinical responses. To explore alternative therapeutic strategies, herein we conducted a proteomics survey to identify cell surface proteins upregulated by mTORC1. A comparison of the surfaceome from Tsc1–/– versus Tsc1+/+ mouse embryonic fibroblasts revealed 59 proteins predicted to be significantly overexpressed in Tsc1–/– cells. Further validation of the data in multiple mouse and human cell lines showed that mTORC1 signaling most dramatically induced the expression of the proteases neprilysin (NEP/CD10) and aminopeptidase N (APN/CD13). Functional studies showed that constitutive mTORC1 signaling sensitized cells to genetic ablation of NEP and APN, as well as the biochemical inhibition of APN. In summary, these data show that mTORC1 signaling plays a significant role in the constitution of the surfaceome, which in turn may present novel therapeutic strategies. Full Article
ace Guidance Document: Validation of a High-Performance Liquid Chromatography-Tandem Mass Spectrometry Immunopeptidomics Assay for the Identification of HLA Class I Ligands Suitable for Pharmaceutical Therapies [Commentary] By feedproxy.google.com Published On :: 2020-03-01T00:05:26-08:00 For more than two decades naturally presented, human leukocyte antigen (HLA)-restricted peptides (immunopeptidome) have been eluted and sequenced using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Since, identified disease-associated HLA ligands have been characterized and evaluated as potential active substances. Treatments based on HLA-presented peptides have shown promising results in clinical application as personalized T cell-based immunotherapy. Peptide vaccination cocktails are produced as investigational medicinal products under GMP conditions. To support clinical trials based on HLA-presented tumor-associated antigens, in this study the sensitive LC-MS/MS HLA class I antigen identification pipeline was fully validated for our technical equipment according to the current US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. The immunopeptidomes of JY cells with or without spiked-in, isotope labeled peptides, of peripheral blood mononuclear cells of healthy volunteers as well as a chronic lymphocytic leukemia and a bladder cancer sample were reliably identified using a data-dependent acquisition method. As the LC-MS/MS pipeline is used for identification purposes, the validation parameters include accuracy, precision, specificity, limit of detection and robustness. Full Article
ace A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients [Technological Innovation and Resources] By feedproxy.google.com Published On :: 2020-04-01T00:05:32-07:00 State-of-the-art proteomics-grade mass spectrometers can measure peptide precursors and their fragments with ppm mass accuracy at sequencing speeds of tens of peptides per second with attomolar sensitivity. Here we describe a compact and robust quadrupole-orbitrap mass spectrometer equipped with a front-end High Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) Interface. The performance of the Orbitrap Exploris 480 mass spectrometer is evaluated in data-dependent acquisition (DDA) and data-independent acquisition (DIA) modes in combination with FAIMS. We demonstrate that different compensation voltages (CVs) for FAIMS are optimal for DDA and DIA, respectively. Combining DIA with FAIMS using single CVs, the instrument surpasses 2500 peptides identified per minute. This enables quantification of >5000 proteins with short online LC gradients delivered by the Evosep One LC system allowing acquisition of 60 samples per day. The raw sensitivity of the instrument is evaluated by analyzing 5 ng of a HeLa digest from which >1000 proteins were reproducibly identified with 5 min LC gradients using DIA-FAIMS. To demonstrate the versatility of the instrument, we recorded an organ-wide map of proteome expression across 12 rat tissues quantified by tandem mass tags and label-free quantification using DIA with FAIMS to a depth of >10,000 proteins. Full Article
ace Brisbane City Council IT contract faces potential $60 million blow-out By www.smh.com.au Published On :: Wed, 25 Jan 2017 05:49:06 GMT A $122 million Brisbane City Council IT contract will be renegotiated after a systems replacement program was delayed by 18 months, with a potential cost blow-out of up to $60 million. Full Article
ace Face scanning falls flat as part of digital credentials push By www.smh.com.au Published On :: Thu, 18 Jul 2019 01:14:02 GMT State government's facial recognition ID check is now required for those seeking solar rebates, but it failed 40 per cent of the time during the first two weeks. Full Article
ace Rethinking 'The Economic Consequences of the Peace' By feedproxy.google.com Published On :: Mon, 07 Oct 2019 15:10:01 +0000 Members Event 25 November 2019 - 1:00pm to 2:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Professor Michael Cox, Associate Fellow, US and the Americas Programme, Chatham House; Director, LSE IDEASProfessor Margaret MacMillan, Professor of History, University of Toronto; Emeritus Professor of International History, University of OxfordDr Geoff Tily, Senior Economist, TUC; Author, Keynes Betrayed: The General Theory, the Rate of Interest and 'Keynesian' EconomicsChair: Dr Jessica Reinisch, Reader in Modern European History, Birkbeck University of London John Maynard Keynes' The Economic Consequences of the Peace has long been a key reference point in discussions about the Treaty of Versailles and its impact on Germany and Europe’s rehabilitation. A century after its publication, the relevance of Keynes’ thinking – not least the influence it had on public perception of the treaty itself – offers an insight into the impact of expert analysis on how political decisions are received in public and academic spheres.This panel discusses the author, the book and the controversy they have generated up to the present day. How relevant is Keynes’ polemic and how applicable is his European economic recovery plan to our current period of global dislocation? What is the role of experts in the formation and scrutiny of international politics? And how can contemporary politicians use Keynes’ comprehensive assessment of the intersection between political, social and economic realities and national idealism to inform their approaches to international relations? Members Events Team Email Full Article
ace Commentary on SSO and other putative inhibitors of FA transport across membranes by CD36 disrupt intracellular metabolism, but do not affect fatty acid translocation By feedproxy.google.com Published On :: 2020-05-01 Henry J. PownallMay 1, 2020; 61:595-597Commentary Full Article
ace Accessibility of cholesterol at cell surfaces By feedproxy.google.com Published On :: 2020-04-23 Kristen A. JohnsonApr 23, 2020; 0:jlr.ILR120000836v1-jlr.ILR120000836Images in Lipid Research Full Article
ace UK Tech Weekly Podcast - Episode Three: The Internet of Sex Robots - Facebook likes, AI and Trump By play.acast.com Published On :: Fri, 26 Feb 2016 17:02:04 GMT In this week's UK Tech Weekly Podcast host Matt Egan is joined by PC Advisor staff writer Chris Minasians chats about Facebook's new like buttons, the team has contracted smartphone fever from the Mobile World Conference in Barcelona and finally, acting editor of Macworld UK David Price, discusses Donald Trump boycotting Apple. See acast.com/privacy for privacy and opt-out information. Full Article
ace Episode 12 - The Internet of Voodoo Streaming Services (IoVSS) Apple & Facebook results, Nintendo NX By play.acast.com Published On :: Fri, 29 Apr 2016 11:50:59 GMT This week host Matt Egan is joined by regular podder David Price, acting editor of Macworld.co.uk, to discuss Apple's not so awesome results and stalling iPhone sales. Then online editor Scott Carey jumps in to discuss Facebook's far better results and how it has come to dominate the mobile advertising market (15:00) Finally, producer Chris comes out from behind the glass to discuss Nintendo's secretive NX console and having to wait for the new Zelda game (28:00). See acast.com/privacy for privacy and opt-out information. Full Article
ace Episode 42 - The Internet of Chinese Boogie Men (IoCBM) Black Friday, Facebook and Autumn Statement By play.acast.com Published On :: Fri, 25 Nov 2016 07:00:00 GMT Matt Egan is in the presenter chair this week as he chats about Black Friday and the changing face of online retail with acting editor at Macworld UK, David Price. Then online editor at Techworld.com Scott Carey talks Facebook and its recent issues with fake news and Chinese censorship (12:00). Finally, online editor at Computerworld UK Tamlin Magee brings us up to date with the Government's Autumn Statement and what it means for the technology sector (26:00). See acast.com/privacy for privacy and opt-out information. Full Article
ace Episode 63 - The Internet of the French (IotF) New Surface Pro and Netflix vs Cannes By play.acast.com Published On :: Fri, 26 May 2017 11:15:53 GMT This week we dive into the new Surface Pro with Digital Arts' Neil Bennett. Who is it for and is it that different to the last one? And are 2 in 1 devices really the future of computing? Then Techworld's Scott Carey, fresh back from Cannes, discusses why the French film industry booed at a Netflix film - why was it there in the first place? Is the film industry being that affected by tech giants like Amazon? Tech Advisor's Dom Preston chimes in to let us know. Finally, we all quickly nerded out about Alien: Covenant. Mild spoiler alert! See acast.com/privacy for privacy and opt-out information. Full Article technology film tech funny
ace Episode 73 - The Internet of Electric Sheep (IoES) Facebook's blunder, the new Kindle and Blade Runner 2049 By play.acast.com Published On :: Fri, 13 Oct 2017 11:48:50 GMT Episode 73 sees David Price lead Scott Carey, Miriam Harris and Henry Burrell into a critique of Mark Zuckerberg's decision to go into a VR tour of Puerto Rico. Disaster tourism at its finest/worst.Henry then discusses the new Kindle Oasis, which for the firs time is waterproof - but very expensive and quietly released.Finally we all chip in to ask why Blade Runner 2049 is quite so overtly sexist in its portrayal of women. There be spoilers. See acast.com/privacy for privacy and opt-out information. Full Article
ace Episode 74 - The Internet of KRACK (IoK) Wi-Fi flaws, Pixel 2 and Facebook vs cyberbullying By play.acast.com Published On :: Fri, 20 Oct 2017 09:50:29 GMT David Price is back to host this week, with Christina Mercer breaking down what all the fuss about KRACK is and why you should take precautions with your Wi-Fi. Henry Burrell reviewed the Google Pixel 2 this week so gives us his thoughts on the device. You might want to avoid the larger XL though. We then discuss Facebook's idea to counterattack cyberbullying. Charlotte Jee recently spoke with the company to see what they are doing, but will it work? See acast.com/privacy for privacy and opt-out information. Full Article technology podcast krack KRACK wifi wi-fi security google pixel 2 google pixel 2 android facebook cyberbullying
ace Episode 82 - The Internet of Cars in Space (IoCiS) Falcon Heavy, Bitcoin bubble and Apple earnings By play.acast.com Published On :: Fri, 09 Feb 2018 00:00:00 GMT Back with a bang as Computerworld editor Scott Carey leads the squad into the cauldron of convo. Christina Mercer explains why her beau Elon Musk took a car into space, Sean Bradley on that bursting Bitcoin bubble, and David Price to tell us all how Apple can charge even more for its stuff and keep on making record profit. See acast.com/privacy for privacy and opt-out information. Full Article
ace Episode 89 - The Internet of Pirates (IoP) Hacker pirates, face recognition ethics and Elon Musk By play.acast.com Published On :: Wed, 16 May 2018 11:01:06 GMT Back once again like the Renegade Master, the UK Tech Weekly Podcast is coming to you from its new, earlier-in-the-week time slot.Host Scott Carey is joined by Tamlin Magee to talk about pirate-obsessed Nigerian hacking syndicates, and Charlotte Jee is on board to discuss the ethics of facial (and racial) recognition technology.We wrap things up with an Elon Musk news roundup, from his latest bae to building bricks. See acast.com/privacy for privacy and opt-out information. Full Article
