Extracellular vesicle (EV) proteins from acute myeloid leukemia (AML) cell lines were analyzed using mass spectrometry. The analyses identified 2450 proteins, including 461 differentially expressed proteins (290 upregulated and 171 downregulated). CD53 and CD47 were upregulated and were selected as candidate biomarkers. The association between survival of patients with AML and the expression levels of CD53 and CD47 at diagnosis was analyzed using mRNA expression data from The Cancer Genome Atlas database. Patients with higher expression levels showed significantly inferior survival than those with lower expression levels. Enzyme-linked immunosorbent assay results of the expression levels of CD53 and CD47 from EVs in the bone marrow of patients with AML at diagnosis and at the time of complete remission with induction chemotherapy revealed that patients with downregulated CD53 and CD47 expression appeared to relapse less frequently. Network model analysis of EV proteins revealed several upregulated kinases, including LYN, CSNK2A1, SYK, CSK, and PTK2B. The potential cytotoxicity of several clinically applicable drugs that inhibit these kinases was tested in AML cell lines. The drugs lowered the viability of AML cells. The collective data suggest that AML-derived EVs could reflect essential leukemia biology.

Open searching has proven to be an effective strategy for identifying both known and unknown modifications in shotgun proteomics experiments. Rather than being limited to a small set of user-specified modifications, open searches identify peptides with any mass shift that may correspond to a single modification or a combination of several modifications. Here we present PTM-Shepherd, a bioinformatics tool that automates characterization of PTM profiles detected in open searches based on attributes such as amino acid localization, fragmentation spectra similarity, retention time shifts, and relative modification rates. PTM-Shepherd can also perform multi-experiment comparisons for studying changes in modification profiles, e.g. in data generated in different laboratories or under different conditions. We demonstrate how PTM-Shepherd improves the analysis of data from formalin-fixed paraffin-embedded samples, detects extreme underalkylation of cysteine in some datasets, discovers an artefactual modification introduced during peptide synthesis, and uncovers site-specific biases in sample preparation artifacts in a multi-center proteomics profiling study.

The goal of clinical proteomics is to identify, quantify, and characterize proteins in body fluids or tissue to assist diagnosis, prognosis, and treatment of patients. In this way, it is similar to more mature omics technologies, such as genomics, that are increasingly applied in biomedicine. We argue that, similar to those fields, proteomics also faces ethical issues related to the kinds of information that is inherently obtained through sample measurement, although their acquisition was not the primary purpose. Specifically, we demonstrate the potential to identify individuals both by their characteristic, individual-specific protein levels and by variant peptides reporting on coding single nucleotide polymorphisms. Furthermore, it is in the nature of blood plasma proteomics profiling that it broadly reports on the health status of an individual – beyond the disease under investigation. Finally, we show that private and potentially sensitive information, such as ethnicity and pregnancy status, can increasingly be derived from proteomics data. Although this is potentially valuable not only to the individual, but also for biomedical research, it raises ethical questions similar to the incidental findings obtained through other omics technologies. We here introduce the necessity of - and argue for the desirability for - ethical and human rights-related issues to be discussed within the proteomics community. Those thoughts are more fully developed in our accompanying manuscript. Appreciation and discussion of ethical aspects of proteomic research will allow for deeper, better-informed, more diverse, and, most importantly, wiser guidelines for clinical proteomics.

Deep proteome coverage in bottom-up proteomics requires peptide-level fractionation to simplify the complex peptide mixture before analysis by tandem mass spectrometry. By decreasing the number of co-eluting precursor peptide ions, fractionation effectively reduces the complexity of the sample leading to higher sample coverage and reduced bias towards high abundance precursors that are preferentially identified in data-dependent acquisition strategies. To achieve this goal, we report a bead-based off-line peptide fractionation method termed CIF or Carboxylate modified magnetic bead-based isopropanol gradient peptide fractionation. CIF is an extension of the SP3 (single-pot solid-phase-enhanced sample preparation) strategy and provides an effective but complementary approach to other commonly used fractionation methods including strong cation exchange (SCX) and reversed phase (RP)-based chromatography. We demonstrate that CIF is an effective offline separation strategy capable of increasing the depth of peptide analyte coverage both when used alone or as a second dimension of peptide fractionation in conjunction with high pH RP. These features make it ideally suited for a wide range of proteomic applications including the affinity purification of low abundance bait proteins.

Cells continually degrade and replace damaged proteins. However, the high energetic demand of protein turnover generates reactive oxygen species (ROS) that compromise the long-term health of the proteome. Thus, the relationship between aging, protein turnover and energetic demand remains unclear. Here, we used a proteomic approach to measure rates of protein turnover within primary fibroblasts isolated from a number of species with diverse lifespans including the longest-lived mammal, the bowhead whale. We show that organismal lifespan is negatively correlated with turnover rates of highly abundant proteins. In comparison to mice, cells from long-lived naked mole rats have slower rates of protein turnover, lower levels of ATP production and reduced ROS levels. Despite having slower rates of protein turnover, naked mole rat cells tolerate protein misfolding stress more effectively than mouse cells. We suggest that in lieu of rapid constitutive turnover, long-lived species may have evolved more energetically efficient mechanisms for selective detection and clearance of damaged proteins.

High performance liquid chromatography has been employed for decades to enhance detection sensitivity and quantification of complex analytes within biological mixtures. Among these analytes, glycans released from glycoproteins and glycolipids have been characterized as underivatized or fluorescently tagged derivatives by HPLC coupled to various detection methods. These approaches have proven extremely useful for profiling the structural diversity of glycoprotein and glycolipid glycosylation but require the availability of glycan standards and secondary orthogonal degradation strategies to validate structural assignments. A robust method for HPLC separation of glycans as their permethylated derivatives, coupled with in-line MSn fragmentation to assign structural features independent of standards, would significantly enhance the depth of knowledge obtainable from biological samples. Here, we report an optimized workflow for LC-MS analysis of permethylated glycans that includes sample preparation, mobile phase optimization, and MSn method development to resolve structural isomers on-the-fly. We report baseline separation and MSn fragmentation of isomeric N- and O-glycan structures, aided by supplementing mobile phases with Li+, which simplifies adduct heterogeneity and facilitates cross-ring fragmentation to obtain valuable monosaccharide linkage information. Our workflow has been adapted from standard proteomics-based workflows and, therefore, provides opportunities for laboratories with expertise in proteomics to acquire glycomic data with minimal deviation from existing buffer systems, chromatography media, and instrument configurations. Furthermore, our workflow does not require a mass spectrometer with high-resolution/accurate mass capabilities. The rapidly evolving appreciation of the biological significance of glycans for human health and disease requires the implementation of high-throughput methods to identify and quantify glycans harvested from sample sets of sufficient size to achieve appropriately powered statistical significance. The LC-MSn approach we report generates glycan isomeric separations, robust structural characterization, and is amenable to auto-sampling with associated throughput enhancements.

Alpha-1-acid glycoprotein (AGP) is an acute phase glycoprotein in blood, which is primarily synthetized in the liver and whose biological role is not completely understood. It consists of 45% carbohydrates that are present in the form of five N-linked complex glycans. AGP N-glycosylation was shown to be changed in many different diseases and some changes appear to be disease-specific, thus it has a great diagnostic and prognostic potential. However, AGP glycosylation was mainly analyzed in small cohorts and without detailed site-specific glycan information. Here, we developed a cost-effective method for a high-throughput and site-specific N-glycosylation LC-MS analysis of AGP which can be applied on large cohorts, aid in search for novel disease biomarkers and enable better understanding of AGP’s role and function in health and disease. The method does not require isolation of AGP with antibodies and affinity chromatography, but AGP is enriched by acid precipitation from 5 μl of bloodplasma in a 96 well format. After trypsinization, AGP glycopeptides are purified using a hydrophilic interaction chromatography based solid-phase extraction and analyzed by RP-LC-ESI-MS. We used our method to show for the first time that AGP N-glycan profile is stable in healthy individuals (14 individuals in 3 time points), which is a requirement for evaluation of its diagnostic potential. Furthermore, we tested our method on a population including individuals with registered hyperglycemia in critical illness (59 cases and 49 controls), which represents a significantly increased risk of developing type 2 diabetes. Individuals at higher risk of diabetes presented increased N-glycan branching on AGP’s second glycosylation site and lower sialylation of N-glycans on AGP’s third and AGP1’s fourth glycosylation site. Although this should be confirmed on a larger prospective cohort, it indicates that site-specific AGP N-glycan profile could help distinguish individuals who are at risk of type 2 diabetes.

Giardia lamblia (G. lamblia) disease is a zoonosis with a-infection rate affecting the general population of the world. Despite the constant possibility of damage due to their own metabolism, G. lamblia have survived and evolved to adapt to various environments. However, research on energy-metabolism conversion in G. lamblia is limited. This study aimed to reveal the dynamic metabolism-conversion mechanism in G. lamblia under sugar starvation by detecting global lysine acetylation and 2-hydroxyisobutyrylation sites combined with quantitative proteome analyses. A total of 2999 acetylation sites on 956 proteins and 8877 2-hydroxyisobutyryl sites on 1546 proteins were quantified under sugar starvation. Integrated Kac and Khib data revealed that modified proteins were associated with arginine biosynthesis, glycolysis/gluconeogenesis, and alanine, aspartate, and glutamate metabolism. These findings suggested that lysine acetylation and 2-hydroxyisobutyrylation were ubiquitous and provided deep insight into the metabolism-conversion mechanism in G. lamblia under sugar starvation. Overall, these results can help understand the biology of G. lamblia infections and reveal the evolution rule from prokaryote to eukaryote.

Recent advances in MS-based proteomics have vastly increased the quality and scope of biological information that can be derived from human samples. These advances have rendered current workflows increasingly applicable in biomedical and clinical contexts. As proteomics is poised to take an important role in the clinic, associated ethical responsibilities increase in tandem with the impact on the health, privacy, and well-being of individuals. Here we conducted and report a systematic literature review of ethical issues in clinical proteomics. We add our perspectives from a background of bioethics, the results of our accompanying paper extracting individual-sensitive results from patient samples, and the literature addressing similar issues in genomics. The spectrum of potential issues ranges from patient re-identification to incidental findings of clinical significance. The latter can be divided into actionable and unactionable findings. Some of these have the potential to be employed in discriminatory or privacy-infringing ways. However, incidental findings may also have great positive potential. A plasma proteome profile, for instance, could inform on the general health or disease status of an individual regardless of the narrow diagnostic question that prompted it. We suggest that early discussion of ethical issues in clinical proteomics is important to ensure that eventual regulations reflect the considered judgment of the community as well as to anticipate opportunities and problems that may arise as the technology matures further.

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

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

Summary

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

Prices, Products and Priorities: Meeting Refugees’ Energy Needs in Burkina Faso and Kenya Other resource sysadmin 24 January 2018

As the number of displaced people increases, and aid budgets come under further pressure, the imperative to identify cost-effective and sustainable solutions for delivering energy to refugees is more pressing than ever.

This paper examines the issue of energy and displacement in detail, using insights from refugees in camps in Burkina Faso and Kenya. It seeks to promote a better understanding of their energy needs, priorities and preferences, and explores how increased access to energy might help to achieve lasting impact in the two camps surveyed. The paper is based on primary research from the Goudoubo camp in Burkina Faso and the Kakuma I camp in Kenya, but the analysis and conclusions are pertinent in the wider context of camps for forcibly displaced people.

Summary points

• There is a low level of energy access in the refugee camps of Kakuma I and Goudoubo, which contributes to poverty and hampers relief and development efforts. Trying to meet basic cooking, lighting and phone-charging needs is costly for refugees, consuming a significant share of stretched monthly budgets.
• The predominant cooking solution consists of basic improved cookstoves burning wood and charcoal. The ‘three-stone fire’ method also remains commonplace. Three out of five families in Kakuma I report health problems due to smoke from cookstoves.
• Street lighting is a high priority for residents, due to concerns about security and safety in camps. In Goudoubo, 86 per cent of survey respondents said that more household members would go out after dark if there were better public lighting.
• A significant proportion of refugees would pay for cleaner and more efficient energy technologies, but many lack the financial resources required, and the development of markets for such products remains partially contingent on sustained financial support.
• There is a need for a diversity of energy technologies that give varying levels and qualities of service; a ‘one size fits all’ approach is inappropriate if universal access to sustainable energy is to be achieved.
• Clean cookstoves and fuels (LPG, ethanol, biogas, etc.) are in high demand, but require much greater investment if they are to be introduced at scale. Solid biomass and improved cookstoves will continue to be important cooking solutions in Kakuma I and Goudoubo, as well as in other refugee camps. A shift to more efficient cooking can be achieved at little or no extra cost for the significant proportion of people who still cook on three-stone fires.
• Users of quality-verified household solar products spend dramatically less on light and power than do people using inferior technologies. Strong brand recognition and a high willingness to pay indicate a large market and a significant opportunity for the solar private sector.
• Centralized electricity supply solutions – mini-grids or grid connections – are more economic than multiple standalone diesel generators. The current piecemeal and ad hoc approach, with each facility managing its own power supply, is inherently wasteful. Greater coordination among humanitarian clusters is required so that centralized solutions can be assessed, designed, financed and implemented.
• Collecting data on energy expenditure and use, as well as quantification of the wide ranging impacts of improved technologies, is necessary to build a compelling case for investment in electricity infrastructure. In addition, engaging refugees on their needs, preferences and willingness to pay can improve the sustainability and impact of energy interventions.
• Private-sector and market development approaches offer long-term, cost-effective solutions for refugees and can also benefit host communities. As the number of displaced people in the world increases, and as aid budgets come under further pressure, the imperative to identify cost-effective and sustainable solutions is more pressing than ever.

Chatham House is a part of the Moving Energy Initiative, a consortium working towards clean energy for refugees. For more information visit movingenergy.earth

Drones and the European Union: Prospects for a Common Future Research paper sysadmin 30 January 2018

The debate over the use of drones is an opportunity for states to identify elements of military practice that their publics find uncomfortable or troubling, and to explain these areas of military operations in context.

Summary

• The debate over the use of drones is an opportunity for states to identify elements of military practice that their publics find uncomfortable or troubling, and to explain these areas of military operations in context.
• Countries would benefit from working together to identify accountability gaps arising from fundamental elements of military cooperation, including the role of intelligence transfers in joint operations, and the distribution of responsibility for lethal actions in the context of coalition operations.
• Transparency in investigation procedures, as well as devoting sufficient resources towards ensuring that mistakes are identified, will improve the perception of drone use among domestic audiences.
• Identifying and communicating common standards and practices of mitigating complicity should be a priority for countries to ensure that they do not unwittingly become complicit in unlawful lethal operations.
• Although operational safety may hinder the ability of states to be completely transparent, understanding among the general public could be improved through the communication of policies and procedures regarding non-lethal assistance to partner states conducting lethal operations, both inside and outside the context of an armed conflict.

Libya’s War Economy: Predation, Profiteering and State Weakness Research paper sysadmin 9 April 2018

As Libya’s war economy persists, prospects for the restoration of functioning central governance become more distant.

Summary

• Libya suffers from interlinked political, security and economic crises that are weakening state institutions, damaging its economy and facilitating the continued existence of non-state armed groups. As rival authorities continue to compete for power, the resulting fragmentation and dysfunction have provided a fertile environment for the development of a pervasive war economy dependent on violence.
• This war economy is dynamic and constantly in flux. Relative to earlier problems, there were signs of progress on several fronts in 2017: a reduction in human smuggling, a tripling in oil revenues, and increased local action against fuel smuggling. Yet the dynamics that have supported the war economy’s rise remain.
• Libya’s war economy is highly damaging for the future of the state for three reasons:
  • First, it provides an enabling environment for networks of armed groups, criminal networks, corrupt businessmen and political elites to sustain their activities through illicit sales and predatory practices. Their operations are closely linked to the dispensation of violence, and are thus a spur for further conflict.
  • Second, the war economy perpetuates negative incentives for those who profit from the state’s dysfunction. Only effective governance, supported by a durable political settlement, can tackle the foundations of Libya’s war economy. But neither a return to functioning central governance nor the development of a security sector that is fit for purpose is in the interests of war economy profiteers, who are therefore motivated to act as powerful spoilers of reform.
  • Third, the political contestation and resource predation practised by those engaged in the war economy are having a disastrous impact on Libya’s formal economy, undermining what remains of its institutions. As the war economy persists, therefore, the prospects for the restoration of functioning central governance become more distant. This threatens to create a vicious cycle that accelerates further state collapse.
• Due to the limited capacity for coercion available to any actor or entity connected with the state, a strategy of co-opting networks of war economy profiteers has almost exclusively prevailed. This has failed. Drawing on the lessons from these attempts, a more successful policy must pursue targeted measures to combat the enabling structures of Libya’s war economy where possible, and to co-opt war economy profiteers only where necessary.
• In this, state authorities can do more to utilize what power they have to name and shame war economy profiteers in order to weaken the local legitimacy critical to profiteers’ survival. The state must present credible alternative livelihood opportunities to those engaged in, or benefiting from, the war economy. Progress will depend in part on the creation of positive incentives to abandon such activity. Where profiteers cannot be incentivized to move towards more legitimate economic activities, greater and more effective efforts must be made to reduce the profit margins of illicit schemes.
• The international community can do more to support Libyan efforts in countering the war economy. Cooperation over the targeting of criminal groups’ overseas assets, support for increased transparency over the dispensation of state funds, and measures to reduce the viability of illicit activities can all help to strengthen the position of state authorities.

Further reading

Discover the six things you need to know about Libya’s war economy

Dance of the Trillions: Developing Countries and Global Finance Book sysadmin 6 July 2018

David Lubin tells the story of what makes money flow from high-income countries to lower-income ones; what makes it flow out again; and how developing countries have sought protection against the volatility of international capital flows.

Selected by the Financial Times as one of the best economics books of 2018, Dance of the Trillions traces an arc from the 1970s, when developing countries first gained access to international financial markets, to the present day.

Underlying this story is a discussion of how the relationship between developing countries and global finance appears to be moving from one governed by the ‘Washington Consensus’ to one more likely to be shaped by Beijing.

This book is part of the Insights series.

Praise for Dance of the Trillions

About the author

David Lubin is managing director and head of emerging markets economics at Citi, an American bank, where he is responsible for a team of more than 30 economists in 15 locations globally.

Purchase

• UK (via Amazon)
• Rest of world (via Brookings Institution Press)
• Students (via Browns Books)

Tackling Illegal Wildlife Trade in Africa: Economic Incentives and Approaches Research paper sysadmin 5 October 2018

Combating illegal wildlife trade and further pursuing conservation-development models could help generate considerable economic benefits for African countries, while ensuring the long-term preservation of Africa’s wealth of natural capital.

Summary

• The illegal wildlife trade (IWT) significantly impacts African economies by destroying and corroding natural, human and social capital stocks. This hinders the achievement of the Sustainable Development Goals (SDGs) and has an impact on national budgets. Illicit financial flows from IWT deny revenue to governments where legal wildlife product trade exists and perpetuate cash externalization. IWT diverts national budgets away from social or development programmes, increases insecurity and threatens vulnerable populations.
• In expanding wildlife economies and pursuing conservation-driven development models, governments can protect their citizens, derive revenue from wildlife products, and establish world class tourism offerings. The illegal exploitation of wildlife is often due to a failure to enforce rights over those resources, where rights are unclearly defined or not fully exercised. Southern African countries have defined these rights in various ways, contributing to regional differences in conservation practices and the socio-economic benefits derived from wildlife resources. Combating IWT is an important step towards allowing legitimate business and communities to develop livelihoods that incentivize stewardship and connect people to conservation.
• The Southern African Development Community (SADC) has several framework policies for the establishment of transfrontier conservation areas (TFCAs). These promote local stewardship across multiple land-use areas to conserve biodiversity and increase the welfare and socioeconomic development of rural communities. Private-sector partnerships also increase skills transfer, improve access to investment finance, and expand economic opportunities, including through the promotion of local procurement. The economic benefits of TFCAs extend beyond tourism.
• The economic value of African ecosystems is often under-recognized because they remain unquantified, partly due to the lack of available data on the broader economic costs of IWT. Improved monitoring and evaluation with key performance indicators would help governments and citizens to appreciate the economic value of combating IWT.

Exploring Public International Law and the Rights of Individuals with Chinese Scholars - Part One Other resource sysadmin 29 October 2018

As part of a roundtable series, Chatham House and China University of Political Science and Law (CUPL) jointly organized this four-day meeting at Chatham House for international lawyers to discuss a wide range of issues related to public international law and the rights of individuals.

The specific objectives were to:

• create a platform for Chinese international law academics working on international human rights law issues to present their thinking and exchange ideas with counterparts from outside China;
• build stronger understanding within the wider international law community of intellectual debates taking place in China about the international human rights system and China’s role within it;
• support networking between Chinese and non-Chinese academics working on international human rights and related areas of international law.

The roundtable forms part of a wider Chatham House project exploring China’s impact on the international human rights system and was inspired by early discussions with a burgeoning community of Chinese academics thinking, writing (mainly in Chinese) and teaching about international human rights law.

For China University of Political Science and Law, one of the largest and most prestigious law schools in China and perhaps the only university in the world with an entire faculty of international law, the initiative is part of a drive to forge partnerships beyond China in the international law field.

The roundtable had a total of 22 participants, 10 Chinese (from universities and other academic institutions in Beijing and Shanghai) and 12 non-Chinese (from Australia, Germany, the Netherlands, Switzerland, the United Kingdom and the United States).

All discussions were held in English under the Chatham House Rule.

Exploring Public International Law and the Rights of Individuals with Chinese Scholars - Part Two Other resource sysadmin 30 October 2018

As part of a roundtable series, Chatham House and China University of Political Science and Law (CUPL) held a two-day roundtable meeting in Beijing on public international law and the rights of individuals.

The specific objectives were to:

• create a platform for Chinese international law academics working on international human rights law issues to present their thinking and exchange ideas with counterparts from outside China;
• build stronger understanding within the wider international law community of intellectual debates taking place in China about the international human rights system and China’s role within it;
• support networking between Chinese and non-Chinese academics working on international human rights and related areas of international law.

The roundtable forms part of a wider Chatham House project exploring China’s impact on the international human rights system and was inspired by early discussions with a burgeoning community of Chinese academics thinking, writing (mainly in Chinese) and teaching about international human rights law.

For CUPL, one of the largest and most prestigious law schools in China and perhaps the only university in the world with an entire faculty of international law, the initiative is part of a drive to forge partnerships beyond China in the international law field.

The meeting in Beijing was hosted by CUPL and involved 20 participants, 10 Chinese (from universities and other academic institutions in Beijing) and 10 non-Chinese (from Australia, the Netherlands, South Africa, Switzerland, the United Kingdom and the United States).

To ensure continuity while also expanding the experts network being built, the second meeting included a mix of participants from the first meeting and some new participants.

All discussions were held in English under the Chatham House Rule.

Exploring Public International Law and the Rights of Individuals with Chinese Scholars - Part Three Other resource sysadmin 30 October 2018

As part of a roundtable series, Chatham House, China University of Political Science and Law (CUPL) and the Graduate Institute Geneva held a two-day roundtable meeting in Geneva on public international law and the rights of individuals.

The specific objectives were to:

• create a platform for Chinese international law academics working on international human rights law issues to present their thinking and exchange ideas with counterparts from outside China;
• build stronger understanding within the wider international law community of intellectual debates taking place in China about the international human rights system and China’s role within it;
• support networking between Chinese and non-Chinese academics working on international human rights and related areas of international law.

The roundtable forms part of a wider Chatham House project exploring China’s impact on the international human rights system and was inspired by early discussions with a burgeoning community of Chinese academics thinking, writing (mainly in Chinese) and teaching about international human rights law.

For CUPL, one of the largest and most prestigious law schools in China and perhaps the only university in the world with an entire faculty of international law, the initiative is part of a drive to forge partnerships beyond China in the international law field.

The meeting in Geneva was co-hosted by the Graduate Institute Geneva and involved 19 participants, 9 Chinese (from six research institutions in Beijing and Shanghai) and 11 non-Chinese (from eight research institutions in Australia, Germany, the Netherlands, Switzerland, the United Kingdom and the United States).

To ensure continuity while also expanding the expert network being built, the third meeting included a mix of participants from the first two meetings and some new participants

All discussions were held in English under the Chatham House Rule.

The Role of Sub-state and Non-state Actors in International Climate Processes: Civil Society Research paper sysadmin 27 November 2018

Given today’s challenging geopolitical conditions and the evolving nature of the international climate regime since Paris, civil society must now once again recalibrate its strategies to ensure continued and increasing relevance.

This is one of four background papers feeding into a synthesis paper entitled The Role of Sub-state and Non-state Actors in International Climate Processes.

Summary

• Following the failure of the 15th Conference of the Parties (COP 15) in Copenhagen in 2009, there was a step change in the sophistication and unity of civil society engagement on climate policy. This ensured that, subsequently, civil society was more effective in exercising multiple channels of influence around the negotiations for the Paris Agreement in 2015.
• Civil society proved to be particularly effective at harnessing the twin narratives of climate science and economics, and at leveraging an emerging multi-level governance architecture, to create political space for climate leadership.
• Given today’s challenging geopolitical conditions and the evolving nature of the international climate regime since Paris, civil society must now once again recalibrate its strategies to ensure continued and increasing relevance.
• In particular, the shift to a more ‘nationally grounded’ implementation regime focusing on individual states’ climate commitments will require civil society to become more effective at influencing domestic politics. At the same time, civil society will need to continue to seek strategic synergies at the international level.
• Civil society has a central role to play in ensuring that the first key test of the Paris ‘ratchet’ mechanism – revising countries’ pledged climate actions, or Nationally Determined Contributions (NDCs), by 2020 – is robust, science-informed and strongly rooted in domestic politics.

The Role of Sub-state and Non-state Actors in International Climate Processes: Corporate Sector Research paper sysadmin 27 November 2018

Given the challenging political contexts since 2015, the corporate sector will have a key role to play in persuading national governments how technologies and expertise have moved on since the pledges were made.

This is one of four background papers feeding into a synthesis paper entitled The Role of Sub-state and Non-state Actors in International Climate Processes.

Summary

• The corporate sector has traditionally engaged governments at national rather than international level in lobbying for action related to climate change. Where it has engaged at an international level, this has often been to restrain regulation and ambition, such as in air transport. Over time, many businesses have increasingly understood that there is more commercial opportunity in a strong, consistent approach to tackling climate mitigation and adaptation, and an increasing number are willing to speak up on the issue. The Paris Climate Conference in 2015 demonstrated this positive engagement.
• Businesses are more powerful when engaging directly with national governments on detailed policies – by demonstrating what is possible and indirectly influencing national governments’ international pledges. Traditional trade/industry sector associations and groups have tended to suffer from the ‘lowest common denominator’ effect of their least progressive members. Progressive business groups coalescing around climate ambition can help to counter this.
• Unlike at the Copenhagen climate talks in 2009, the business community provided a positive, supportive backdrop to the 2015 Paris talks, mindful of the public relations opportunities in taking a progressive stance and of the benefits of targets that reflected the science. The carbon market was a particular focus for corporates, which succeeded in getting emissions trading options and market mechanisms included in Article 6 of the Paris Agreement.
• Given the challenging political contexts since 2015, the corporate sector will have a key role to play in persuading national governments how technologies and expertise have moved on since the pledges were made. With increasing awareness of resource scarcity, businesses are pursuing ever more creative solutions.
• Wide recognition that the avoidance of future emissions is increasingly dependent on developing and emerging economies means that business voices from these countries will potentially be more influential in the next few years.

The Role of Sub-state and Non-state Actors in International Climate Processes Research paper sysadmin 27 November 2018

In the current international political environment of rising populism, the role of sub- and non-state actors may become more important than ever.

Summary

• Climate action from sub-state and non-state actors such as subnational governments, cities, corporations and NGOs has very significant potential to enhance national efforts to curb CO2 emissions, close the so-called ‘emissions gap’ – between current commitments and the action necessary to meet climate targets – and help move the world on to a ‘1.5°C pathway’ that would limit global warming to 1.5°C above pre-industrial levels by 2100.
• In addition to their own climate action, sub-state/non-state actors can contribute to climate governance by developing new policies and business models to support emissions cuts and build resilience. Knowledge exchange and capacity-building have a role to play in helping these innovations to spread internationally.
• Politically, measures implemented by sub-state/non-state actors can help national governments to implement existing targets faster and more effectively, while helping to build political support for more ambitious climate action.
• The post-Paris climate regime of the United Nations Framework Convention on Climate Change (UNFCCC) reflects the growing importance of sub- and non-state actors, and has featured the creation of institutional structures to engage and coordinate them.
• In the current international political environment of rising populism, the role of sub- and non-state actors may become more important than ever. However, more questions about the robustness of sub- and non-state action are also likely to be raised.
• With the 2020 deadline approaching for countries to submit details of enhanced Nationally Determined Contributions (NDCs), long-term climate strategies and other means of raising policy ambition, the next two years are set to provide significant opportunity for sub- and non-state action. Many governments are already developing ways to engage with sub- and non-state actors to identify opportunities to strengthen action by 2020.
• Key questions in this respect include (a) whether sub- and non-state actors can mobilize across sectors; and (b) whether action can be extended beyond the ‘usual suspects’ to include contributions from less familiar sources, such as business sectors with limited opportunities for climate action or corporations in the Global South.

The Role of Sub-state and Non-state Actors in International Climate Processes: Financial Institutions Research paper sysadmin 20 December 2018

The trillions of dollars needed to secure the sustainable, climate-compatible pathway outlined in the 2015 Paris Agreement have focused attention on private finance and investment.

This is one of four background papers feeding into a synthesis paper entitled The Role of Sub-state and Non-state Actors in International Climate Processes.

Summary

• The trillions of dollars needed to secure the sustainable, climate-compatible pathway outlined in the 2015 Paris Agreement have focused attention on private finance and investment, and on the role of the financial sector as a potentially powerful non-state actor in the international climate debate.
• Leading individual financial institutions reacted to the Paris Agreement by framing it in terms of what it would mean for markets – i.e. risks and opportunities – and by underlining the importance of national implementation of climate change commitments.
• Key recent developments signal that the financial sector actively supports Paris-compatible government action on climate change, as well as company-level action to understand the physical and ‘transition’ risks and opportunities associated with climate change and policy responses. Financial sector engagement is taking place through well-organized and well-supported international initiatives and platforms. A critical part of this process entails robust activity by financial institutions to embed climate change and broader sustainability factors into strategies and operations.
• At country level, attention to implementation of Nationally Determined Contributions (NDCs) and associated sector-level policy development has been largely separate from the broader ‘sustainable finance’ dynamic. National-level action has not benefited from the same level of organized financial sector involvement evident in international action. One of the reasons for this is that, with some notable exceptions, international financial initiatives lack the capacity and resources to participate in the granular detail of national policy processes. Policymakers in turn often lack the internal capacity to consult or engage with the financial sector domestically.
• This paper includes some thoughts on further international and national climate actions. Ensuring that messages from successful international financial sector initiatives are heard in regional and non-climate forums offers one avenue for building a stronger foundation for greater climate ambition. Building the resource base for stronger national climate policy engagement, as a counter-voice to incumbent interests and to ensure that the quality of policy is ‘investment grade’, is another. This will be critical to the delivery of policy outcomes. Other key elements include the need to pool knowledge across relevant parts of the finance sector, build alliances, and shift action towards joint problem-solving with policymakers. A ‘Talanoa 2.020’-type initiative offers one potentially promising approach to advancing dialogue in this respect.

The Role of Sub-state and Non-state Actors in International Climate Processes: Subnational Governments Research paper sysadmin 23 January 2019

This paper looks at the role of subnational governments in influencing global climate ambition, and makes recommendations for how these actors can increase their influence in the future.

Summary

• ‘Subnational governments’ – including municipal, regional and provincial authorities – lack the formal status of negotiating parties to the United Nations Framework Convention on Climate Change (UNFCCC). But they have a vital role to play in informing and helping to shape international climate action, as they are often the key delivery partners for on-the-ground policies.
• Subnational governments are often closer to climate problems than the UNFCCC parties themselves, and have experience, expertise and peer influence that can support the development of progressive policies and increased ambition.
• Many subnational governments have joined or formed various groupings to share information and experience, and to increase their collective profile and voice. Notable initiatives and collaborations include the Under2 Coalition, ICLEI, C40 and the Global Covenant of Mayors for Climate & Energy.
• Subnational governments are highly diverse. In some cases, politically high-profile administrations – the US state of California being a notable example – have exploited their visibility and policy successes to engage in wider climate debates. Equally, however, subnational agendas can encounter resistance from national governments anxious to ensure the primacy of their negotiating positions in the UNFCCC system.
• One of the advantages that subnational governments enjoy, subject to resources, is their ability to join with peer groups to take a fresh approach to mitigation or adaptation policies. Groups of cities or subnational regions can, through collaborative organizations, explore new approaches that might be less attractive within a national context.
• To maintain and build on their current achievements and influence, subnational governments need, among other things, to: improve the credibility of their experience through evaluation of the success of their climate policies; use membership of appropriate international groups to share experience and boost their leverage; continue to create collaborative relationships with progressive businesses to increase influence at a national level; build on cross-regional relationships in climate adaptation and resilience; and work with other subnational actors to build momentum ahead of the first post-Paris revision of climate commitments in 2020.

Artificial Intelligence Prediction and Counterterrorism Research paper sysadmin 6 August 2019

The use of AI in counterterrorism is not inherently wrong, and this paper suggests some necessary conditions for legitimate use of AI as part of a predictive approach to counterterrorism on the part of liberal democratic states.

Summary

• The use of predictive artificial intelligence (AI) in countering terrorism is often assumed to have a deleterious effect on human rights, generating spectres of ‘pre-crime’ punishment and surveillance states. However, the well-regulated use of new capabilities may enhance states’ abilities to protect citizens’ right to life, while at the same time improving adherence to principles intended to protect other human rights, such as transparency, proportionality and freedom from unfair discrimination. The same regulatory framework could also contribute to safeguarding against broader misuse of related technologies.
• Most states focus on preventing terrorist attacks, rather than reacting to them. As such, prediction is already central to effective counterterrorism. AI allows higher volumes of data to be analysed, and may perceive patterns in those data that would, for reasons of both volume and dimensionality, otherwise be beyond the capacity of human interpretation. The impact of this is that traditional methods of investigation that work outwards from known suspects may be supplemented by methods that analyse the activity of a broad section of an entire population to identify previously unknown threats.
• Developments in AI have amplified the ability to conduct surveillance without being constrained by resources. Facial recognition technology, for instance, may enable the complete automation of surveillance using CCTV in public places in the near future.
• The current way predictive AI capabilities are used presents a number of interrelated problems from both a human rights and a practical perspective. Where limitations and regulations do exist, they may have the effect of curtailing the utility of approaches that apply AI, while not necessarily safeguarding human rights to an adequate extent.
• The infringement of privacy associated with the automated analysis of certain types of public data is not wrong in principle, but the analysis must be conducted within a robust legal and policy framework that places sensible limitations on interventions based on its results.
• In future, broader access to less intrusive aspects of public data, direct regulation of how those data are used – including oversight of activities by private-sector actors – and the imposition of technical as well as regulatory safeguards may improve both operational performance and compliance with human rights legislation. It is important that any such measures proceed in a manner that is sensitive to the impact on other rights such as freedom of expression, and freedom of association and assembly.

Delivering Sustainable Food and Land Use Systems: The Role of International Trade Research paper sysadmin 20 September 2019

This paper explores a set of core trade-related issues affecting the food and land use system, and proposes constructive ways forward in reconfiguring the global trading system towards delivering a more sustainable and healthy diet for all.

• Meeting future global food security requirements is not just about quantity; it is also about meeting growing needs in a way that safeguards human as well as planetary health. But national priorities and policies often remain out of sync with aspirations for more sustainable and healthy food systems.
• International trade and trade policies play an ambiguous role in the current food system. With 80 per cent of the world’s population depending on imports to meet at least part of their food and nutritional requirements, trade has a unique function in offsetting imbalances between supply and demand. However, in the absence of effective regulatory frameworks or pricing frameworks that internalize environmental, social or health costs, trade can exacerbate and globalize challenges associated with food production and land use trends such as deforestation, land degradation, greenhouse gas emissions, biodiversity loss and the shift to unhealthy diets.
• Over the last two decades, trade in agricultural products (excluding intra-EU flows) has more than tripled in value, to reach $1.33 trillion. The geography of global food trade flows has also shifted, primarily towards South–South trade, which now accounts for roughly a quarter of total agricultural trade flows. The nature of global trade has changed drastically, with traditional exports such as wheat and coffee growing slowly at around 2 per cent per year, while products such as palm oil, fruit juice, soft drinks and other processed products have grown at 8 per cent or more annually.
• This overall increase in trade in agricultural products raises questions about the growing utilization of resources, such as water or soil nutrients, that are embedded in those products through production and processing. Trade itself also causes negative environmental impacts, starting with greenhouse gas emissions associated with transport and storage. If the environmental cost associated with production and trade is not reflected in the final price of goods, trade may accelerate the depletion of resources or their unsustainable use.
• It is critical to ensure that trade policy options pursued by producing and consuming countries alike will support a transition to more sustainable and healthier food and land use systems. The first step in addressing trade-related food systems challenges must involve rebuilding trust among policy actors. There is a need for new spaces for informal dialogue among actors, and ‘soft’ governance mechanisms that can help rebuild consensus on the best ways forward. Meeting these challenges also requires an appreciation of the complex interactions between sectoral policies (e.g. on water, land, food, etc.) and their multiple interfaces with trade policies.
• Conditioning the use of subsidies on their sustainability and/or health impacts encourages the delivery of essential public goods in ways that are consistent with sustainability and health goals. A first step therefore is the removal of perverse incentives (e.g. subsidies encouraging the overuse of fertilizers or pesticides or the overproduction of certain commodities, as well as certain biofuels subsidies) and replacing them with market-correcting subsidies.
• Trade facilitation measures for fruits and vegetables that are aimed at easing transit at the border, by cutting unnecessary bureaucracy and reducing waiting times, can improve their availability, reduce costs and improve food quality and safety for consumers. Similarly, measures aimed at improving sustainable cold storage and upgrading value chains can support better diets and consumption by increasing the availability of fresh produce on markets, especially in developing countries.
• A global food stamps programme developed through the G20 and facilitated by the UN’s food agencies could address purchasing power imbalances and tackle malnutrition in developing countries. If carefully designed, such ‘safety net’ schemes can not only contribute to improving calorific intakes but also help deliver more balanced and healthier diets. Careful attention must be given to how such a scheme would work in practice, building on experience to date with similar initiatives.
• Integrating the notion of sustainable food and inputs trade in the post-2020 global biodiversity framework can help to deliver more sustainable and healthier food and land use systems. This could be achieved by likeminded countries introducing a set of goals or targets aimed at mitigating the role of trade in placing indirect pressure on biodiversity, and to encourage trade in biodiversity-based products including natural ingredients produced ethically and following sustainability principles and criteria.
• An SDG-oriented agenda for agricultural trade is needed. It could be formed by countries seeking to remove perverse incentives, guaranteeing a safe harbour for market-correcting measures, clarifying existing rules and establishing plurilateral negotiations among subsets of the WTO membership, or sectoral approaches, to address specific challenges.
• Greenhouse gas emissions resulting from trade need to be addressed. Governments could seek to achieve this through ensuring the carbon neutrality of existing and new trade deals, either by connecting carbon markets among contracting parties or by developing joint initiatives to tax international maritime and air transport emissions.

Online Disinformation and Political Discourse: Applying a Human Rights Framework Research paper sysadmin 5 November 2019

Although some digital platforms now have an impact on more people’s lives than does any one state authority, the international community has been slow to hold to account these platforms’ activities by reference to human rights law.

This paper examines how human rights frameworks should guide digital technology.

Summary

• Online political campaigning techniques are distorting our democratic political processes. These techniques include the creation of disinformation and divisive content; exploiting digital platforms’ algorithms, and using bots, cyborgs and fake accounts to distribute this content; maximizing influence through harnessing emotional responses such as anger and disgust; and micro-targeting on the basis of collated personal data and sophisticated psychological profiling techniques. Some state authorities distort political debate by restricting, filtering, shutting down or censoring online networks.
• Such techniques have outpaced regulatory initiatives and, save in egregious cases such as shutdown of networks, there is no international consensus on how they should be tackled. Digital platforms, driven by their commercial impetus to encourage users to spend as long as possible on them and to attract advertisers, may provide an environment conducive to manipulative techniques.
• International human rights law, with its careful calibrations designed to protect individuals from abuse of power by authority, provides a normative framework that should underpin responses to online disinformation and distortion of political debate. Contrary to popular view, it does not entail that there should be no control of the online environment; rather, controls should balance the interests at stake appropriately.
• The rights to freedom of thought and opinion are critical to delimiting the appropriate boundary between legitimate influence and illegitimate manipulation. When digital platforms exploit decision-making biases in prioritizing bad news and divisive, emotion-arousing information, they may be breaching these rights. States and digital platforms should consider structural changes to digital platforms to ensure that methods of online political discourse respect personal agency and prevent the use of sophisticated manipulative techniques.
• The right to privacy includes a right to choose not to divulge your personal information, and a right to opt out of trading in and profiling on the basis of your personal data. Current practices in collecting, trading and using extensive personal data to ‘micro-target’ voters without their knowledge are not consistent with this right. Significant changes are needed.
• Data protection laws should be implemented robustly, and should not legitimate extensive harvesting of personal data on the basis of either notional ‘consent’ or the data handler’s commercial interests. The right to privacy should be embedded in technological design (such as by allowing the user to access all information held on them at the click of a button); and political parties should be transparent in their collection and use of personal data, and in their targeting of messages. Arguably, the value of personal data should be shared with the individuals from whom it derives.
• The rules on the boundaries of permissible content online should be set by states, and should be consistent with the right to freedom of expression. Digital platforms have had to rapidly develop policies on retention or removal of content, but those policies do not necessarily reflect the right to freedom of expression, and platforms are currently not well placed to take account of the public interest. Platforms should be far more transparent in their content regulation policies and decision-making, and should develop frameworks enabling efficient, fair, consistent internal complaints and content monitoring processes. Expertise on international human rights law should be integral to their systems.
• The right to participate in public affairs and to vote includes the right to engage in public debate. States and digital platforms should ensure an environment in which all can participate in debate online and are not discouraged from standing for election, from participating or from voting by online threats or abuse.

AI-driven Personalization in Digital Media: Political and Societal Implications Research paper sysadmin 2 December 2019

The fallout from disinformation and online manipulation strategies have alerted Western democracies to the novel, nuanced vulnerabilities of our information society. This paper outlines the implications of the adoption of AI by the the legacy media, as well as by the new media, focusing on personalization.

Summary

• Machine learning (ML)-driven personalization is fast expanding from social media to the wider information space, encompassing legacy media, multinational conglomerates and digital-native publishers: however, this is happening within a regulatory and oversight vacuum that needs to be addressed as a matter of urgency.
• Mass-scale adoption of personalization in communication has serious implications for human rights, societal resilience and political security. Data protection, privacy and wrongful discrimination, as well as freedom of opinion and of expression, are some of the areas impacted by this technological transformation.
• Artificial intelligence (AI) and its ML subset are novel technologies that demand novel ways of approaching oversight, monitoring and analysis. Policymakers, regulators, media professionals and engineers need to be able to conceptualize issues in an interdisciplinary way that is appropriate for sociotechnical systems.
• Funding needs to be allocated to research into human–computer interaction in information environments, data infrastructure, technology market trends, and the broader impact of ML systems within the communication sector.
• Although global, high-level ethical frameworks for AI are welcome, they are no substitute for domain- and context-specific codes of ethics. Legacy media and digital-native publishers need to overhaul their editorial codes to make them fit for purpose in a digital ecosystem transformed by ML. Journalistic principles need to be reformulated and refined in the current informational context in order to efficiently inform the ML models built for personalized communication.
• Codes of ethics will not by themselves be enough, so current regulatory and legislative frameworks as they relate to media need to be reassessed. Media regulators need to develop their in-house capacity for thorough research and monitoring into ML systems, and – when appropriate –proportionate sanctions for actors found to be employing such systems towards malign ends. Collaboration with data protection authorities, competition authorities and national electoral commissions is paramount for preserving the integrity of elections and of a political discourse grounded on democratic principles.
• Upskilling senior managers and editorial teams is fundamental if media professionals are to be able to engage meaningfully and effectively with data scientists and AI engineers.

Subsidies and Sustainable Agriculture: Mapping the Policy Landscape Research paper sysadmin 10 December 2019

Agricultural subsidies shape production and consumption patterns, with potentially significant effects on poverty, nutrition and other sustainability concerns. This paper maps the different types of support provided by governments to the agricultural sector, and highlights some of the complex political economy dynamics that underpin the relevant policies.

Summary

• Agricultural subsidies, a mainstay of government policy, have a large part in shaping production and consumption patterns, with potentially significant effects as regards poverty, food security, nutrition, and other sustainability concerns such as climate change, land use practices and biodiversity.
• There are multiple types of direct and indirect support provided by governments to various actors in the agricultural sector; and in terms of political economy, there are complex dynamics underpinning the policies that sustain these subsidies.
• Overall, subsidies targeting producers have the most significant effect on production, and the greater trade-distorting effect. These subsidies promote domestic production and discourage imports, leading to overproduction that is largely disposed of on the international market, with the help of export subsidies. This can tend to intensify negative environmental agricultural practices, such as cultivating marginal land, unsustainable types of intensification, or incentivizing excessive pesticide and fertilizer use.
• On the other hand, producer subsidies that are not tied to output of a specific commodity (i.e. delinked) have far fewer distorting impacts and could help to deliver sustainable outcomes. For example, this type of subsidies can require crop diversification or be linked to conservation of permanent grassland.
• Subsidies that enable transfers to consumers, for example through food stamp programmes, also serve to delink production from consumption, can foster healthier diets, can play an important role in delivering food accessibility and security among low-income groups, and can represent one of the less trade-distorting subsidies.
• If subsidies are to be reformed to help promote healthier diets and encourage more sustainable production, it is essential to understand not only the type and amount of support that key countries provide, but also the domestic dynamics that can shape such policies.
• While price support, input subsidies or investment aids remain the central pillars of programmes in large developing countries such as Brazil, China or India, other economies – notably including the EU and Japan – focus on direct payments, support for general services and set-aside schemes, as well as significant border protection. The US, for its part, has tended to focus on subsidized insurance schemes and food programmes for poorer consumers.
• If subsidies are to deliver policy objectives, their design and implementation should delink production from consumption. For example, consumer subsidies designed to deliver nutrition and food security, or payments for environmental services to enable more environmentally friendly production systems, could prove to be the most effective, least trade-distorting means of achieving more sustainable and equitable agricultural production.
• The political economy of food means that the removal of subsidies is often highly sensitive, and tends to be met with significant resistance. However, reform that delinks support from production through a gradual transition process could ultimately prove successful in delivering effective subsidy schemes.
• Effective subsidy schemes must by design be truly result- and performance-based, supported by robust and objective indicators. At the same time, engaging multiple actors along key commodity value chains – including leading importing and exporting countries, traders and transporters – could lead to the development of international, commodity-specific arrangements that are able to deliver effective nutrition and sustainability goals.

Secrets and Spies: UK Intelligence Accountability After Iraq and Snowden Book sysadmin 15 January 2020

How can democratic governments hold intelligence and security agencies to account when what they do is largely secret? Jamie Gaskarth explores how intelligence professionals view accountability in the context of 21st century politics.

Using the UK as a case study, this book provides the first systematic exploration of how accountability is understood inside the secret world. It is based on new interviews with current and former UK intelligence practitioners, as well as extensive research into the performance and scrutiny of the UK intelligence machinery.

The result is the first detailed analysis of how intelligence professionals view their role, what they feel keeps them honest, and how far external overseers impact on their work.

The UK gathers material that helps inform global decisions on such issues as nuclear proliferation, terrorism, transnational crime, and breaches of international humanitarian law. On the flip side, the UK was a major contributor to the intelligence failures leading to the Iraq war in 2003, and its agencies were complicit in the widely discredited U.S. practices of torture and ‘rendition’ of terrorism suspects. UK agencies have come under greater scrutiny since those actions, but it is clear that problems remain.

Secrets and Spies is the result of a British Academy funded project (SG151249) on intelligence accountability. The book is published as part of the Insights series.

Praise for Secrets and Spies

About the author

Jamie Gaskarth is Professor of Foreign Policy and International Relations at The Open University. He was previously senior lecturer at the University of Birmingham where he taught strategy and decision-making. His research focused on the ethical dilemmas of leadership and accountability in intelligence, foreign policy, and defence. He is author/editor or co-editor of six books and served on the Academic Advisory panel for the 2015 UK National Security Strategy and Strategic Defence and Security Review.

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Gender, think-tanks and international affairs: A toolkit Other resource NCapeling 9 February 2021

Encouraging a more gender-sensitive approach for think-tank activities such as convening and debate, research and analysis, and communications and publishing.

Compiled by staff at Chatham House, the Centre for Feminist Foreign Policy and the British American Security Information Council, the toolkit provides think-tanks with guidance on ways of adapting organizational structures, activities and practices in order to embed greater awareness of gender issues and adopt gender-sensitive approaches throughout their work.

The toolkit is designed for all people working in international affairs think-tanks, regardless of role, experience or level of seniority. It will be particularly useful for those think-tanks that are just beginning the process of raising greater awareness of gender issues internally, as well as for those that have already begun to make changes but wish to expand this work further.

The work to develop the toolkit came as a response to the commonly gendered nature of think-tanks and their activities. The toolkit recognizes the discrimination and under-representation that women often experience within the sector, as well as the relative absence of women among executive leadership, governance structures and senior researcher positions in many think-tanks.

The toolkit’s focus on gender is a starting point for wider intersectional analysis and action within the think-tank community. Embedding inclusive research, convening and communication practices is not just ‘the right thing to do’. When diversity and inclusion initiatives succeed, organizations are more resilient, innovative and better at decision-making.

While there has already been incremental change within think-tanks, the toolkit’s authors intend that their work will build on the important body of research and practices that already exist by encouraging think-tanks to examine their own processes and develop ways of working that focus not just on women’s representation, but on the structures and systems that perpetuate biases and inequalities.

War Time: Temporality and the Decline of Western Military Power Book dora.popova 22 February 2021

In War Time the Western way of war, its pace and timing, are discussed and analysed by experts who question the West’s ability to maintain its military superiority given the political and strategic failures of interventions in Iraq and Afghanistan.

In War Time, war studies experts examine the trajectory of Western military power. They discuss conflicting perceptions of time anchored within Western political and military institutions, and the Western attachment to fast-paced warfare at the expense of longer-term political solutions.

Divided into three sections, the book covers ‘civic militarism’ and the trajectory of Western power, Western perceptions of time and the international normative order, and military operations and temporality. War Time explains why the West has been overwhelmingly powerful on the battlefield and yet strategically and politically weak as exemplified by the return of the Taliban and the hasty evacuation of troops and personnel from Afghanistan.

The book identifies policies that decision-makers must adopt to stave off the decline of Western military dominance.

This book is part of the Insights series.

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A special event was held in March 2021 to mark the launch of the book. View the event here.

Praise for War Time

About the editors

Sten Rynning is professor of war studies at the University of Southern Denmark.

Olivier Schmitt is professor with special responsibilities at the Center for War Studies, University of Southern Denmark, and currently director of research and studies at the French Institute for Higher National Defence Studies.

Amelie Theussen is assistant professor at the Center for War Studies, University of 
Southern Denmark.

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COP26: What happened, what does this mean, and what happens next? Chatham House briefing NCapeling 15 November 2021

Analysing a crucial opportunity for enhancing ambitions on climate finance, adaptation, and ‘loss and damage’, and the implementation of the Paris Agreement.

Key findings

Raising the ambition of national emission reduction targets (nationally determined contributions – NDCs) was a critical task for COP26. On this front, governments fell short: although over 120 parties have submitted new or updated NDCs, the new targets only narrow the gap to 1.5°C by 15–17 per cent, and are, if fully implemented (and this is far from certain), projected to result in warming of 2.4°C by the end of the century.

If warming is to be limited to 1.5°C above pre-industrial levels, additional emissions reductions before 2030, over and above current NDC pledges, will need to equate to reducing emissions by the equivalent of two years of current annual emissions. To keep warming to 2°C, the equivalent reductions would be needed of one year’s total emissions.

The Glasgow Climate Pact – the main political outcome of COP26 – requests governments to revisit and strengthen their NDCs before the end of 2022 to bring these in line with the Paris Agreement’s temperature goal. To keep 1.5°C within reach, it will be absolutely essential that governments return to the table with significantly enhanced offers ahead of COP27, which will take place at Sharm El-Sheikh, Egypt, in 2022.

Another key feature of the Glasgow Climate Pact is the reference to ‘accelerating efforts towards the phasedown of unabated coal power and phase-out of inefficient fossil fuel subsidies’. Although the language was watered down over the course of the negotiations, COP26 marks the first time ever reducing fossil fuels is mentioned in a COP decision.

Discussions around climate finance, adaptation, and loss and damage were centre stage in Glasgow, and were critical points of contention. Although the Glasgow Climate Pact urges developed countries to ‘fully’ deliver on the $100 billion annual climate finance pledge through to 2025, it remains unclear when this sum will actually be raised in full – and if a total of $500 billion will be mobilized between 2020 and 2025 to make up for initial shortfalls.

And while the Pact urges developed countries to double their adaptation finance by 2025, and establishes a dialogue on loss and damage finance, much more will need to be done to address the needs of climate-vulnerable developing countries. 

COP26 saw a flurry of plurilateral deals on key issues such as phasing out various forms of fossil fuels and ending deforestation. These initiatives have the potential to accelerate decarbonization, but monitoring their implementation and holding governments and other institutions to account will be critical. Future COPs provide a platform for doing this, and governments should seek to incorporate the pledges made outside the formal remits of the UNFCCC process in their NDCs.

While some progress was made at COP26, the next 12 months will be crucial in determining if the formal agreements reached in Glasgow provide grounds for optimism that 1.5°C remains firmly in sight, and are sufficient to build trust between countries and between citizens and governments.

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There is nothing quite like the excitement of discovery in science—of finding something no one else knew and seeing a story unfold. One has to be part of an emerging picture to feel the elation. These moments in a lifetime are few and far between, but they fuel enthusiasm and keep one going. They are embedded in struggles and joys of everyday life, years of establishing what Louis Pasteur called “the prepared mind,” working with mentors, trainees, and colleagues, failures and successes. This article recalls 1) how I got to be a biochemist; 2) my contributions as an educator and researcher, especially regarding meprin metalloproteases; and 3) my participation in communities of science. Perhaps my reflections will help an aspiring scientist see how fulfilling a career in science can be.

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

The faithful segregation, or “partition,” of many low-copy number bacterial plasmids is driven by plasmid-encoded ATPases that are represented by the P1 plasmid ParA protein. ParA binds to the bacterial nucleoid via an ATP-dependent nonspecific DNA (nsDNA)-binding activity, which is essential for partition. ParA also has a site-specific DNA-binding activity to the par operator (parOP), which requires either ATP or ADP, and which is essential for it to act as a transcriptional repressor but is dispensable for partition. Here we examine how DNA binding by ParA contributes to the relative distribution of its plasmid partition and repressor activities, using a ParA with an alanine substitution at Arg351, a residue previously predicted to participate in site-specific DNA binding. In vivo, the parAR351A allele is compromised for partition, but its repressor activity is dramatically improved so that it behaves as a “super-repressor.” In vitro, ParAR351A binds and hydrolyzes ATP, and undergoes a specific conformational change required for nsDNA binding, but its nsDNA-binding activity is significantly damaged. This defect in turn significantly reduces the assembly and stability of partition complexes formed by the interaction of ParA with ParB, the centromere-binding protein, and DNA. In contrast, the R351A change shows only a mild defect in site-specific DNA binding. We conclude that the partition defect is due to altered nsDNA binding kinetics and affinity for the bacterial chromosome. Furthermore, the super-repressor phenotype is explained by an increased pool of non-nucleoid bound ParA that is competent to bind parOP and repress transcription.

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

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

The origin recognition complex (ORC), composed of six subunits, ORC1–6, binds to origins of replication as a ring-shaped heterohexameric ATPase that is believed to be essential to recruit and load MCM2–7, the minichromosome maintenance protein complex, around DNA and initiate DNA replication. We previously reported the creation of viable cancer cell lines that lacked detectable ORC1 or ORC2 protein without a reduction in the number of origins firing. Here, using CRISPR-Cas9–mediated mutations, we report that human HCT116 colon cancer cells also survive when ORC5 protein expression is abolished via a mutation in the initiator ATG of the ORC5 gene. Even if an internal methionine is used to produce an undetectable, N terminally deleted ORC5, the protein would lack 80% of the AAA+ ATPase domain, including the Walker A motif. The ORC5-depleted cells show normal chromatin binding of MCM2–7 and initiate replication from a similar number of origins as WT cells. In addition, we introduced a second mutation in ORC2 in the ORC5 mutant cells, rendering both ORC5 and ORC2 proteins undetectable in the same cells and destabilizing the ORC1, ORC3, and ORC4 proteins. Yet the double mutant cells grow, recruit MCM2–7 normally to chromatin, and initiate DNA replication with normal number of origins. Thus, in these selected cancer cells, either a crippled ORC lacking ORC2 and ORC5 and present at minimal levels on the chromatin can recruit and load enough MCM2–7 to initiate DNA replication, or human cell lines can sometimes recruit MCM2–7 to origins independent of ORC.

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

Timely repair of DNA double-strand breaks (DSBs) is essential to maintaining genomic integrity and preventing illnesses induced by genetic abnormalities. We previously demonstrated that the E3 ubiquitin ligase SMURF2 plays a critical tumor suppressing role via its interaction with RNF20 (ring finger protein 20) in shaping chromatin landscape and preserving genomic stability. However, the mechanism that mobilizes SMURF2 in response to DNA damage remains unclear. Using biochemical approaches and MS analysis, we show that upon the onset of the DNA-damage response, SMURF2 becomes phosphorylated at Ser384 by ataxia telangiectasia mutated (ATM) serine/threonine kinase, and this phosphorylation is required for its interaction with RNF20. We demonstrate that a SMURF2 mutant with an S384A substitution has reduced capacity to ubiquitinate RNF20 while promoting Smad3 ubiquitination unabatedly. More importantly, mouse embryonic fibroblasts expressing the SMURF2 S384A mutant show a weakened ability to sustain the DSB response compared with those expressing WT SMURF2 following etoposide treatment. These data indicate that SMURF2-mediated RNF20 ubiquitination and degradation controlled by ataxia telangiectasia mutated–induced phosphorylation at Ser384 constitutes a negative feedback loop that regulates DSB repair.

The Phillies acquired All-Star catcher J.T. Realmuto from the Marlins on Thursday for catcher Jorge Alfaro, right-hander Sixto Sanchez, left-hander Will Stewart and $250,000 in international bonus slot money, the latest move in a busy and ambitious offseason for a team eager to return to the postseason.

Phillies manager Gabe Kapler believes the two most important spots in a lineup are the Nos. 2 and 4 holes. Rhys Hoskins and Carlos Santana hit there most of last season. But with J.T. Realmuto, Andrew McCutchen and Jean Segura joining the Phillies in the offseason, Kapler has more options.

Cesar Hernandez scored 91 runs last season, the Phillies' highest mark since Rollins scored 102 in 2012. Now the luster is no longer there for players who score 100 runs or post 100 RBIs, but Hernandez should score at least 100 runs this season, if he stays healthy and if the Phillies' offense improves as expected.

Right-hander Matt Harvey sustained a glute strain while participating in agility drills on Wednesday and will be out for roughly a week and a half, Angels manager Brad Ausmus said Thursday.